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Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old White man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The White patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old White woman with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, she found her palms could not make full contact with each other (the “prayer sign”). She had not been able to fully clench her fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on her limbs or trunk. No Raynaud phenomenon had occurred. Her medical and family histories were unremarkable. On examination, she showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The White woman’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old White patient with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, they found their palms could not make full contact with each other (the “prayer sign”). They had not been able to fully clench their fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on their limbs or trunk. No Raynaud phenomenon had occurred. Their medical and family histories were unremarkable. On examination, they showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The White patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Black man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Black patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Black woman with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, she found her palms could not make full contact with each other (the “prayer sign”). She had not been able to fully clench her fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on her limbs or trunk. No Raynaud phenomenon had occurred. Her medical and family histories were unremarkable. On examination, she showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Black woman’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Black patient with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, they found their palms could not make full contact with each other (the “prayer sign”). They had not been able to fully clench their fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on their limbs or trunk. No Raynaud phenomenon had occurred. Their medical and family histories were unremarkable. On examination, they showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Black patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Asian man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Asian patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Asian woman with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, she found her palms could not make full contact with each other (the “prayer sign”). She had not been able to fully clench her fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on her limbs or trunk. No Raynaud phenomenon had occurred. Her medical and family histories were unremarkable. On examination, she showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Asian woman’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Asian patient with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, they found their palms could not make full contact with each other (the “prayer sign”). They had not been able to fully clench their fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on their limbs or trunk. No Raynaud phenomenon had occurred. Their medical and family histories were unremarkable. On examination, they showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Asian patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Hispanic man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Hispanic patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Hispanic woman with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, she found her palms could not make full contact with each other (the “prayer sign”). She had not been able to fully clench her fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on her limbs or trunk. No Raynaud phenomenon had occurred. Her medical and family histories were unremarkable. On examination, she showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Hispanic woman’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Hispanic patient with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, they found their palms could not make full contact with each other (the “prayer sign”). They had not been able to fully clench their fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on their limbs or trunk. No Raynaud phenomenon had occurred. Their medical and family histories were unremarkable. On examination, they showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Hispanic patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Arab man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Arab patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Arab woman with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, she found her palms could not make full contact with each other (the “prayer sign”). She had not been able to fully clench her fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on her limbs or trunk. No Raynaud phenomenon had occurred. Her medical and family histories were unremarkable. On examination, she showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Arab woman’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 31-year-old Arab patient with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, they found their palms could not make full contact with each other (the “prayer sign”). They had not been able to fully clench their fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on their limbs or trunk. No Raynaud phenomenon had occurred. Their medical and family histories were unremarkable. On examination, they showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The Arab patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. </clinical_case> <question> A 31-year-old man with insidious onset of limited mobility of joints visited our clinic for evaluation. Six months prior, he found his palms could not make full contact with each other (the “prayer sign”). He had not been able to fully clench his fists for 2 months or squat for the past 10 days. No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk. No Raynaud phenomenon had occurred. His medical and family histories were unremarkable. On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video). No muscular atrophy or sclerodactyly was found. The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed. Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]). Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable. Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal. Nerve conduction studies performed in all 4 limbs were normal. Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+). Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints. B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated. What Is Your Diagnosis? </question> <options> A. Eosinophilic fasciitis B. Myotonic dystrophy C. Deep morphea (morphea profunda) D. Systemic sclerosis </options>

A. Eosinophilic fasciitis Insidious onset of bilaterally limited joint mobility is infrequently seen by neurologists. EMG showed electrical myotonia, reminiscent of myotonic dystrophy (choice A).1 However, myotonic dystrophy is characterized by abnormally slow or delayed muscle relaxation following a normal muscle contraction,1 which was absent in this patient. Limited joint mobility and the prayer sign can be seen in systemic sclerosis (choice B).2 However, the negative ANA test results and the absence of Raynaud phenomenon, sclerodactyly, and internal organ involvement helped exclude systemic sclerosis.3 Limited mobility of joints, peripheral eosinophilia, and increased ESR and CRP can be found in deep morphea (choice C), a rare subtype of morphea that primarily involves the deep dermis and subcutaneous tissue and may extend to underlying fascia and muscle.4 Nevertheless, the symmetrical distribution of joint involvement, histology displaying preferential fascial inflammation (Figure 2), and the absence of sclerotic skin plaque in this patient point to the diagnosis of eosinophilic fasciitis (EF) over deep morphea.Inflammatory cell infiltrate composed primarily of lymphocytes and eosinophils (arrowheads) in the fascia (hematoxylin and eosin stain).EF is a rare disorder characterized by the induration of fascia and skin, preceded by the abrupt onset of erythema and nonpitting edema, resulting in limited mobility of the underlying joints.3 The disease can have an insidious onset.5 The appearance of orange peel caused by skin induration and the groove sign, which is probably due to the relative sparing of the epidermis and superficial dermis by the fibrotic process, are typical signs of established EF.3 Occasionally, EF can present without skin involvement.6,7 Sclerodactyly and Raynaud phenomenon are usually absent. Laboratory findings of EF include peripheral eosinophilia, increased ESR and CRP level, polyclonal hypergammaglobulinemia, and negative ANA test results.3 The results of biopsy containing skin, fascia, and muscle conducted at the left gastrocnemius of this patient showed inflammatory cell infiltrate mainly in the fascia (composed primarily of lymphocytes and eosinophils) (Figure 2) and some subjacent endomysium and perimysium, but they were minimal in the skin. There were moderate variations in muscle fiber size. Some muscle fibers were atrophic. A scatter of necrotic muscle fibers was seen. The myositis, which is frequently observed in EF, may explain the EMG findings in this patient, as myotonic discharges may be seen in a number of acquired myopathic disorders, including myositis.1 Also, certain drugs (eg, statins) can cause myotonic discharges.1 The clinical characteristics, laboratory findings, and biopsy confirmed the diagnosis of EF.The etiology and exact incidence of EF remain unknown. A variety of etiological factors have been proposed, such as strenuous exercise or trauma preceding disease onset.8 To our knowledge, no randomized trials have evaluated therapies for EF. Usually, treatment is started with systemic glucocorticoids at doses equivalent to prednisone, 0.5 to 1 mg/kg per day.8 Concomitant immunosuppressants (eg, methotrexate) are used by some practitioners as the initial therapy or when patients are steroid resistant or refractory.8,9 For this patient, prednisone and cyclophosphamide were prescribed. Nine months later, his joint mobility was improved. Diagnosing EF is challenging because of its rarity. Bilaterally limited mobility of joints, cutaneous manifestations (eg, groove sign and orange peel appearance), and peripheral eosinophilia are useful clues to the diagnosis of EF.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old White man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the White patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old White woman was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the White woman presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old White patient was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the White patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Black man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Black patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Black woman was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Black woman presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Black patient was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Black patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Asian man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Asian patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Asian woman was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Asian woman presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Asian patient was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Asian patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Hispanic man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Hispanic patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Hispanic woman was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Hispanic woman presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Hispanic patient was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Hispanic patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Arab man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Arab patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Arab woman was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Arab woman presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A 21-year-old Arab patient was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the Arab patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. </clinical_case> <question> A 21-year-old man was referred to our tertiary care hospital with a congenital left hemifacial weakness and a chronic unilateral left-sided hearing loss that evolved since birth. On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted. On physical examination, the patient presented a grade VI peripheral left facial paralysis. Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches. It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium. This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass. B, Temporal bone CT scan showing the mass. Arrowheads indicate the abnormal facial nerve. CT denotes computed tomography, and MRI, magnetic resonance imaging. What Is Your Diagnosis? </question> <options> A. Facial nerve schwannoma B. Neuromuscular choristoma C. Vestibular nerve schwannoma D. Hemangioma </options>

B. Neuromuscular choristoma Informed consent was obtained for a complete resection of the mass. Under general anesthesia, a mixed left translabyrinthine approach extended to the parotid gland anteriorly was performed. A left facial nerve decompression and dissection was done from the internal auditory canal to its 5 main branches. A diffuse thickening of the facial nerve was identified from the cerebellopontine angle to the distal branches of the facial nerve (Figure 2). Therefore, the tumor was resected in macroscopically free negative margins at both ends and sent for routine pathology examination. A thickening was also seen at the level of the left greater superficial petrosal nerve exiting the geniculate ganglion, which was dissected, severed, and cauterized as distally as possible. The postoperative course was unremarkable.Intraoperative image. Arrowheads indicate the exit of the facial nerve (blue) and the third portion of the facial nerve (yellow).Microscopic examination revealed within a fibrous tissue the presence of a tumoral proliferation well circumscribed, multinodular, and not encapsulated. It comprised several lobules consisting of bundles of cells with abundant eosinophilic cytoplasm, most often with visible striations; each was well delimited and sometimes sheathed by a fibrous tissue of variable thickness. At the periphery, compressed nerve filaments were noted.On immunostaining, diffuse positivity was noted for desmin with focal positivity for myogenin. Immunolabelling with S100 revealed peripheral nerve threads but also nerve threads smaller in size, trapped within the fibrous septa, and evidenced by antineurofilament. The anti-epithelial membrane antigen highlighted a few perineurial cells in the capsular zone. The Ki67 proliferation index was low (2%). The final diagnosis was a facial nerve neuromuscular choristoma.A choristoma is a developmental tumor-like growth of histologically normal tissue in an abnormal location. Neuromuscular choristomas (NMCs), also known as benign triton tumors, are extremely rare benign expansile peripheral nerve sheath tumors.1 The exact origin of these uncommon lesions is unknown, and the uncertainty about histogenesis is mirrored in the range of nomenclature and pathogenetic ideas, which postulate either a malformative or a neoplastic cause.1 These NMCs have been reported in large nerves or within nerve plexuses, such as the sciatic nerve and the brachial plexus.2 Cranial nerve NMC in the head and neck region has been described as within the orbit, the vestibular nerve, the cochlear nerve, the trigeminal nerve, and the facial nerve.1,3,4Intracranial NMCs occur mostly in the acoustic canal and cerebellopontine angle and most of the cases reported involve the acoustic and vestibular nerves. These patients will initially be misdiagnosed as having vestibular schwannoma.1 Differential diagnosis also includes facial schwannoma, meningioma, hemangioma, glioma, melanoma, osteoma, and other local or metastatic tumors.4 Hence, an NMC occurring in the internal auditory canal is a diagnostic and therapeutic challenge for the ear-nose-throat surgeon. Only surgical treatment followed by pathologic evaluation can accurately diagnose an internal auditory canal choristoma.4To our knowledge, only 3 cases of intratemporal facial nerve NMCs have been reported in the literature.3,5,6 These lesions have been confined to the internal auditory canal. We report the case of a 21-year-old patient with a massive facial nerve NMC extending from the cerebellopontine angle to the distal branches of the facial nerve. These are slow-growing tumors with a good overall prognosis. Depending on the preoperative hearing state and the likelihood of retaining facial and cochlear function, complete or subtotal excision of the lesion has been proposed. The decision is usually made on an individual basis.4 However, postoperative deafness and facial palsy must be considered. Follow-up was reported in only 1 case of facial nerve NMC with no recurrence noted after 2 years.3 The development of aggressive fibromatosis after the resection of a sciatic nerve or branchial plexus NMC is highlighted in a study by Hébert-Blouin and colleagues.7 The cause of aggressive fibromatosis is unknown, but physical factors such as trauma and surgery may play a role in its progression.7Facial nerve neuromuscular choristoma is an extremely rare diagnosis. The exact pathogenesis is not known, and further studies are needed to determine the natural history and evolution over time of an NMC.

Please analyze the following clinical case and the related question: <clinical_case> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A White man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The White patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The White patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A White woman in her 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The White woman denied any known preceding triggers or trauma to the area of the rash. She had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The White woman’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A White patient in their 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The White patient denied any known preceding triggers or trauma to the area of the rash. They had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The White patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Black man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Black patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Black patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Black woman in her 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Black woman denied any known preceding triggers or trauma to the area of the rash. She had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Black woman’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Black patient in their 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Black patient denied any known preceding triggers or trauma to the area of the rash. They had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Black patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Asian man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Asian patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Asian patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Asian woman in her 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Asian woman denied any known preceding triggers or trauma to the area of the rash. She had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Asian woman’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Asian patient in their 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Asian patient denied any known preceding triggers or trauma to the area of the rash. They had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Asian patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Hispanic man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Hispanic patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Hispanic patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Hispanic woman in her 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Hispanic woman denied any known preceding triggers or trauma to the area of the rash. She had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Hispanic woman’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Hispanic patient in their 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Hispanic patient denied any known preceding triggers or trauma to the area of the rash. They had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Hispanic patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Arab man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Arab patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Arab patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Arab woman in her 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Arab woman denied any known preceding triggers or trauma to the area of the rash. She had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Arab woman’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> A Arab patient in their 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The Arab patient denied any known preceding triggers or trauma to the area of the rash. They had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The Arab patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). </clinical_case> <question> A man in his 60s with anti-RNA polymerase III antibody–positive systemic sclerosis complicated by scleroderma kidney crisis, heart failure, interstitial lung disease, sclerodactyly, and Raynaud phenomenon while receiving mycophenolate mofetil, 1 g twice daily, presented with a pruritic rash that had been present for 3 months. The patient denied any known preceding triggers or trauma to the area of the rash. He had tried treating with topical aloe, without improvement. Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms. The patient’s medical history was otherwise unremarkable. Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B). There was no appreciable skin tightening in the affected areas. Complete blood cell count with differential was unremarkable. Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk. B, Clinical image of nodular plaques on the right shoulder and chest. C and D, Lesional punch biopsy specimens (hematoxylin-eosin). What Is Your Diagnosis? </question> <options> A. Fibroblastic rheumatism B. Sarcoidosis C. Keloidal scleroderma D. Lobomycosis </options>

C. Keloidal scleroderma In light of the patient’s history of scleroderma, the clinical and histopathologic findings were compatible with keloidal scleroderma, also known as nodular scleroderma, pseudokeloidal scleroderma, keloidal morphea, and nodular morphea.1-3 Given the patient’s known systemic sclerosis and clinical and histologic findings akin to keloids, we prefer the term keloidal scleroderma for this case. Keloidal scleroderma is a rare variant of scleroderma in which lesions can be morphologically and histopathologically indistinguishable from hypertrophic scar or keloid.1,3,4 Other times, such as in the present case, lesions can appear scarlike but not entirely classic for keloids. Lesions can occur either in sclerotic or nonsclerotic skin and either before or after a diagnosis of systemic sclerosis is made.1,3,4 It is postulated to represent a keloidal response to skin inflammation inherent to systemic sclerosis in individuals already predisposed to keloid formation.2,3,5,6Histopathologically, keloidal scleroderma can show features of scleroderma only, scleroderma and keloid, or as in this case, be indistinguishable from keloids altogether, making clinicopathologic correlation essential.4,7 Histopathologic findings in scleroderma include sclerotic dermal collagen with perivascular lymphoplasmacytic infiltrates, whereas keloids show homogeneous, brightly eosinophilic collagen bundles often in haphazard array.4,7 In cases with features of both entities, one may see both hyalinized fibers, lymphoplasmacytic infiltrates, and keloidal collagen bundles in the same specimen.4 In the present patient, 2 lesional punch biopsy specimens showed nodular proliferations of thick collagen fibers in large fascicles, with 1 additionally showing homogeneous, brightly eosinophilic collagen bundles in haphazard array (Figure, C and D).Patients with scleroderma who present with these clinical findings should be thoroughly assessed to exclude other conditions that may appear similar clinically, particularly dermal processes. Sarcoidosis can have a similar clinical appearance with red-brown infiltrated plaques but would show well-formed, pauci-inflammatory granulomas on histopathology. Fibroblastic rheumatism will appear similarly on histopathology with thickened collagen in a whorled pattern, though one would expect proliferation of dermal fibroblasts and decrease in or absence of elastic fibers. Furthermore, clinical lesions of fibroblastic rheumatism tend to favor periarticular areas and are usually smaller than those in this case. Because many patients with scleroderma are receiving treatment with long-term systemic immunosuppressive agents, one should consider tissue culture to rule out clinical keloid mimickers such as lobomycosis, which would show granulomatous inflammation with fungal organisms with buds and short chains with refractile cell walls. In the present case, tissue cultures obtained by punch biopsy were negative for bacteria, fungus, and acid-fast bacillus.To our knowledge, fewer than 50 cases of keloidal scleroderma have been reported in the literature, and thus guidance on treatment options is limited to anecdotal experience and case reports.3 Previously reported therapy options for symptomatic localized disease include topical and/or intralesional corticosteroids and surgical removal.3,5,6 Therapeutic options for more widespread disease include systemic immunosuppressive agents, such as prednisone, methotrexate, and/or mycophenolate mofetil.3,5,6 Given the present patient’s history of scleroderma kidney crisis and interstitial lung disease, the addition of prednisone or methotrexate was not a viable therapeutic option. We considered increasing his mycophenolate dose, but the patient declined given that his lesions were clinically stable and only mildly symptomatic. High-dose intralesional corticosteroids provided no relief in pruritus or notable change in appearance, so we are currently treating with topical corticosteroids as needed for pruritus. We present this exceptional case to increase clinician and pathologist awareness of this rare scleroderma variant.

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old White woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old White man presented with a 3-month history of a slow-growing mass in him left cheek. He denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old White patient presented with a 3-month history of a slow-growing mass in them left cheek. They denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Black woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Black man presented with a 3-month history of a slow-growing mass in him left cheek. He denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Black patient presented with a 3-month history of a slow-growing mass in them left cheek. They denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Asian woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Asian man presented with a 3-month history of a slow-growing mass in him left cheek. He denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Asian patient presented with a 3-month history of a slow-growing mass in them left cheek. They denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Hispanic woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Hispanic man presented with a 3-month history of a slow-growing mass in him left cheek. He denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Hispanic patient presented with a 3-month history of a slow-growing mass in them left cheek. They denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Arab woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Arab man presented with a 3-month history of a slow-growing mass in him left cheek. He denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> An 81-year-old Arab patient presented with a 3-month history of a slow-growing mass in them left cheek. They denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). </clinical_case> <question> An 81-year-old woman presented with a 3-month history of a slow-growing mass in her left cheek. She denied having any symptoms, tenderness, numbness, or facial nerve weakness. Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes. A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1). The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component. Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present. Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin. On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative. However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead). What Is Your Diagnosis? </question> <options> A. Solitary fibrous tumor B. Synovial sarcoma C. Myopericytoma D. Neurofibroma </options>

A. Solitary fibrous tumor Solitary fibrous tumors (SFTs) are rare, spindle-cell neoplasms of mesenchymal origin that preferentially arise in serosal membranes, intracranial and spinal cord meninges, and the extremities.1 While pleural SFTs are most common, an estimated 6% to 18% of SFTs occur in the head and neck region, most frequently involving the oral cavity, sinonasal tract, orbit, or salivary glands.2 Peak incidence is in middle-aged adults (median age, 51 years); there is no sex predilection. Patients most commonly present with a small (<5 cm), painless, slow-growing mass, with or without site-related compressive symptoms. Standard of care is wide surgical resection; however, rates of positive surgical margins are high, and postoperative radiation therapy may be considered.2 Under the 2020 World Health Organization Classification of Soft Tissue and Bone Tumors, SFTs are categorized as fibroblastic/myofibroblastic neoplasms with intermediate—rarely metastasizing—biological behavior, and multiple case series have described the indolent nature of SFT.1-3 However, the clinical behavior of individual tumors is notoriously difficult to predict: there is a predilection for late local recurrence in 5% to 40% of patients,1 with varying reports of median time to recurrence between 37 and 120 months.1 Several risk-assessment schema have been proposed to predict the behavior of SFT (ie, risk of metastasis, risk of recurrence, disease-free and overall survival).1,4 These schema consider factors such as patient age, tumor size, depth of location, cellularity, pleomorphism, and mitotic rate/index to stratify SFTs as very low, low, moderate/intermediate, or high risk.1,4Furthermore, establishing the diagnosis of SFT is complex: SFT has a nonspecific clinical picture and a broad histological spectrum. Histologically, SFTs are morphologically heterogeneous, characterized by a patternless distribution of ovoid- and spindle-shaped cells within a variably dense collagenous stroma, often associated with a branching or dilated staghornlike-vascular network.2 Generally, mitotic activity is low.2 On immunohistochemical staining, SFTs characteristically have diffuse, intense CD34 immunoreactivity. They are most often B-cell lymphoma 2 positive and S-100, SMA, and keratin (AE1/AE3) negative.5,6 Recent studies have identified NAB2::STAT6 gene fusions as a highly sensitive and specific marker for SFT, which may serve as an additional marker in the setting of any diagnostic uncertainty. STAT6 immunostaining is highly sensitive and almost perfectly specific for SFT and has become increasingly available, contributing to improved diagnostic accuracy for these tumors.7The differential diagnosis of SFTs, given the variations in cellularity and stromal density, is broad and encompasses a number of benign and malignant entities. Myopericytomas are painless, slow-growing, solitary soft-tissue neoplasms that develop from perivascular smooth muscle cells.8 On light microscopy, myopericytomas demonstrate characteristic concentric, perivascular arrangements of spindled cells. They can be further differentiated from SFT on immunohistochemical staining—unlike SFTs, myopericytomas demonstrate strong and diffuse SMA expression.8 Synovial sarcoma is another mesenchymal tumor that demonstrates spindle cells on histologic examination. However, it rarely occurs in the head and neck (comprising only 2.5%-3.5% of sarcomas in this region),9 infrequently demonstrates a staghorn vascular pattern, and is not CD34 or STAT6 immunoreactive.10In this case, the patient was taken to the operating room for resection. The left buccal mucosa was incised intraorally, and the lesion was identified deep to the masseter. The mass was successfully excised in its entirety without complications. On gross examination, the buccal specimen consisted of 2 different architectural zones/areas: a longitudinal portion of white, rubbery tissue (2.8 × 2.0 × 1.0 cm) with a focus of calcified tissue and an attached velvety, friable mass (1.5 × 1.1 × 0.8 cm). Histologically, the tumor demonstrated areas of predominantly densely sclerotic collagenous stroma with scattered calcifications adjacent to small areas of hypercellular spindle cell proliferation, corresponding to the rubbery tissue and friable mass seen on gross examination, respectively (Figure 2A). High-powered images demonstrated the characteristic ropey collagen appearance of SFT (Figure 2B). Immunophenotypically, the tumor cells were positive for STAT6 (Figure 2C), CD34, CD99, and B-cell lymphoma 2, but negative for AE1/AE3, SMA, and S100. There was low mitotic activity and no atypical or malignant histologic features. These findings confirmed the diagnosis of SFT. The patient’s pathology results were presented at a multidisciplinary tumor board, and observation vs adjuvant radiation therapy was discussed. These options were presented to the patient, and she elected for observation.Histopathologic images showing spindled to ovoid cells containing bland, but relatively uniform, nuclei arranged in a “patternless” pattern; the lesion is surrounded by densely sclerotic collagenous stroma with scattered calcifications (A). A high-powered hematoxylin-eosin–stained section demonstrates a characteristic ropey collagen appearance (B) with strong and diffuse STAT6 positivity on immunohistochemical staining (original magnification x10) (C).

Please analyze the following clinical case and the related question: <clinical_case> A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan </clinical_case> <question> A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan What Would You Do Next? </question> <options> A. Transconjunctival orbital biopsy B. Clinical follow-up for idiopathic recurrent retrobulbar hemorrhage C. Arteriography to look for orbital vascular malformations D. Additional imaging, including a computed tomography and positron emission tomography scan </options>

D. Additional imaging, including a computed tomography and positron emission tomography scan The differential diagnosis of a retrobulbar hemorrhage includes orbital trauma; recent orbital, eyelid, lacrimal, or sinus surgery; orbital vascular anomalies; Valsalva-related hemorrhage in a patient with sinonasal carcinoma; and primary orbital tumor or metastasis.1,2 In this patient, there was no history of recent trauma or orbital or periorbital surgery. This presentation—recurrent retrobulbar hemorrhage associated with orbital mass effect over several weeks and restriction in upgaze—suggests an orbital tumor history but is not specific enough to eliminate an orbital vascular anomaly. At this stage, scheduling a follow-up without further investigation is not acceptable.MRI is needed to differentiate between a vascular or tissular lesion. The isointensity of the lesion in T1- and T2-weighted images (Figure 1) is in favor of a tissular lesion; a vascular or cystic lesion would be hyperintense on T2-weighted images.3 These findings support a retrobulbar tumor surrounding the optic nerve.Additional imaging is needed for disease staging and treatment planning. Computed tomography (CT) imaging of the orbital region can show bony involvement (osteolysis), which, if present, can help in surgical planning.4 CT imaging of the cranial, neck, thoracic, and abdominal regions can show primary disease or metastasis. Positron emission tomography (PET) imaging can assess the metabolic uptake of the orbital lesion and is more sensitive than CT imaging in cancer staging.5 Angiography is not helpful as an initial imaging modality; orbital vascular anomalies are unlikely owing to the tissuelike aspect of the lesion.In this case, CT imaging showed no osteolysis, and PET imaging revealed hypermetabolism of the orbital tumor without the presence of other hypermetabolic lesions. An inferior transconjunctival orbital biopsy was performed. Histologic examination confirmed a primary melanoma. This biopsy should be done after cancer-staging imaging so as not to miss another, more accessible site of biopsy.6Nonmetastatic malignant melanoma treatment involves complete surgical removal with safety margins. Evisceration or enucleation were not an option in this patient as the tumor was primarily intraorbital and not intraocular. Ultimately, eyelid-sparing exenteration was performed, followed by radiotherapy. The macroscopic aspect of the tumor is shown in Figure 2. The primary meningeal melanoma originated in the optic nerve, developed in the posterior orbit, and infiltrated the oculomotor muscles, orbital fat, and sclera without intraocular extension. Genetic testing was positive for the GNAQ variant and negative for the BRAF variant. Unfortunately, the patient developed a hepatic metastasis diagnosed on postradiotherapy imaging. The patient died a few months later.Macroscopic examination after surgical resection. Achromic primary orbital melanoma surrounds the optic nerve (red arrowheads) and infiltrates the intraorbital fat (asterisks).

Please analyze the following clinical case and the related question: <clinical_case> A White patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the White patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the White patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the White patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan </clinical_case> <question> A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan What Would You Do Next? </question> <options> A. Transconjunctival orbital biopsy B. Clinical follow-up for idiopathic recurrent retrobulbar hemorrhage C. Arteriography to look for orbital vascular malformations D. Additional imaging, including a computed tomography and positron emission tomography scan </options>

D. Additional imaging, including a computed tomography and positron emission tomography scan The differential diagnosis of a retrobulbar hemorrhage includes orbital trauma; recent orbital, eyelid, lacrimal, or sinus surgery; orbital vascular anomalies; Valsalva-related hemorrhage in a patient with sinonasal carcinoma; and primary orbital tumor or metastasis.1,2 In this patient, there was no history of recent trauma or orbital or periorbital surgery. This presentation—recurrent retrobulbar hemorrhage associated with orbital mass effect over several weeks and restriction in upgaze—suggests an orbital tumor history but is not specific enough to eliminate an orbital vascular anomaly. At this stage, scheduling a follow-up without further investigation is not acceptable.MRI is needed to differentiate between a vascular or tissular lesion. The isointensity of the lesion in T1- and T2-weighted images (Figure 1) is in favor of a tissular lesion; a vascular or cystic lesion would be hyperintense on T2-weighted images.3 These findings support a retrobulbar tumor surrounding the optic nerve.Additional imaging is needed for disease staging and treatment planning. Computed tomography (CT) imaging of the orbital region can show bony involvement (osteolysis), which, if present, can help in surgical planning.4 CT imaging of the cranial, neck, thoracic, and abdominal regions can show primary disease or metastasis. Positron emission tomography (PET) imaging can assess the metabolic uptake of the orbital lesion and is more sensitive than CT imaging in cancer staging.5 Angiography is not helpful as an initial imaging modality; orbital vascular anomalies are unlikely owing to the tissuelike aspect of the lesion.In this case, CT imaging showed no osteolysis, and PET imaging revealed hypermetabolism of the orbital tumor without the presence of other hypermetabolic lesions. An inferior transconjunctival orbital biopsy was performed. Histologic examination confirmed a primary melanoma. This biopsy should be done after cancer-staging imaging so as not to miss another, more accessible site of biopsy.6Nonmetastatic malignant melanoma treatment involves complete surgical removal with safety margins. Evisceration or enucleation were not an option in this patient as the tumor was primarily intraorbital and not intraocular. Ultimately, eyelid-sparing exenteration was performed, followed by radiotherapy. The macroscopic aspect of the tumor is shown in Figure 2. The primary meningeal melanoma originated in the optic nerve, developed in the posterior orbit, and infiltrated the oculomotor muscles, orbital fat, and sclera without intraocular extension. Genetic testing was positive for the GNAQ variant and negative for the BRAF variant. Unfortunately, the patient developed a hepatic metastasis diagnosed on postradiotherapy imaging. The patient died a few months later.Macroscopic examination after surgical resection. Achromic primary orbital melanoma surrounds the optic nerve (red arrowheads) and infiltrates the intraorbital fat (asterisks).

Please analyze the following clinical case and the related question: <clinical_case> A male patient in his 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the male patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the male patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the male patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan </clinical_case> <question> A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan What Would You Do Next? </question> <options> A. Transconjunctival orbital biopsy B. Clinical follow-up for idiopathic recurrent retrobulbar hemorrhage C. Arteriography to look for orbital vascular malformations D. Additional imaging, including a computed tomography and positron emission tomography scan </options>

D. Additional imaging, including a computed tomography and positron emission tomography scan The differential diagnosis of a retrobulbar hemorrhage includes orbital trauma; recent orbital, eyelid, lacrimal, or sinus surgery; orbital vascular anomalies; Valsalva-related hemorrhage in a patient with sinonasal carcinoma; and primary orbital tumor or metastasis.1,2 In this patient, there was no history of recent trauma or orbital or periorbital surgery. This presentation—recurrent retrobulbar hemorrhage associated with orbital mass effect over several weeks and restriction in upgaze—suggests an orbital tumor history but is not specific enough to eliminate an orbital vascular anomaly. At this stage, scheduling a follow-up without further investigation is not acceptable.MRI is needed to differentiate between a vascular or tissular lesion. The isointensity of the lesion in T1- and T2-weighted images (Figure 1) is in favor of a tissular lesion; a vascular or cystic lesion would be hyperintense on T2-weighted images.3 These findings support a retrobulbar tumor surrounding the optic nerve.Additional imaging is needed for disease staging and treatment planning. Computed tomography (CT) imaging of the orbital region can show bony involvement (osteolysis), which, if present, can help in surgical planning.4 CT imaging of the cranial, neck, thoracic, and abdominal regions can show primary disease or metastasis. Positron emission tomography (PET) imaging can assess the metabolic uptake of the orbital lesion and is more sensitive than CT imaging in cancer staging.5 Angiography is not helpful as an initial imaging modality; orbital vascular anomalies are unlikely owing to the tissuelike aspect of the lesion.In this case, CT imaging showed no osteolysis, and PET imaging revealed hypermetabolism of the orbital tumor without the presence of other hypermetabolic lesions. An inferior transconjunctival orbital biopsy was performed. Histologic examination confirmed a primary melanoma. This biopsy should be done after cancer-staging imaging so as not to miss another, more accessible site of biopsy.6Nonmetastatic malignant melanoma treatment involves complete surgical removal with safety margins. Evisceration or enucleation were not an option in this patient as the tumor was primarily intraorbital and not intraocular. Ultimately, eyelid-sparing exenteration was performed, followed by radiotherapy. The macroscopic aspect of the tumor is shown in Figure 2. The primary meningeal melanoma originated in the optic nerve, developed in the posterior orbit, and infiltrated the oculomotor muscles, orbital fat, and sclera without intraocular extension. Genetic testing was positive for the GNAQ variant and negative for the BRAF variant. Unfortunately, the patient developed a hepatic metastasis diagnosed on postradiotherapy imaging. The patient died a few months later.Macroscopic examination after surgical resection. Achromic primary orbital melanoma surrounds the optic nerve (red arrowheads) and infiltrates the intraorbital fat (asterisks).

Please analyze the following clinical case and the related question: <clinical_case> A female patient in her 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the female patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the female patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the female patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan </clinical_case> <question> A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan What Would You Do Next? </question> <options> A. Transconjunctival orbital biopsy B. Clinical follow-up for idiopathic recurrent retrobulbar hemorrhage C. Arteriography to look for orbital vascular malformations D. Additional imaging, including a computed tomography and positron emission tomography scan </options>

D. Additional imaging, including a computed tomography and positron emission tomography scan The differential diagnosis of a retrobulbar hemorrhage includes orbital trauma; recent orbital, eyelid, lacrimal, or sinus surgery; orbital vascular anomalies; Valsalva-related hemorrhage in a patient with sinonasal carcinoma; and primary orbital tumor or metastasis.1,2 In this patient, there was no history of recent trauma or orbital or periorbital surgery. This presentation—recurrent retrobulbar hemorrhage associated with orbital mass effect over several weeks and restriction in upgaze—suggests an orbital tumor history but is not specific enough to eliminate an orbital vascular anomaly. At this stage, scheduling a follow-up without further investigation is not acceptable.MRI is needed to differentiate between a vascular or tissular lesion. The isointensity of the lesion in T1- and T2-weighted images (Figure 1) is in favor of a tissular lesion; a vascular or cystic lesion would be hyperintense on T2-weighted images.3 These findings support a retrobulbar tumor surrounding the optic nerve.Additional imaging is needed for disease staging and treatment planning. Computed tomography (CT) imaging of the orbital region can show bony involvement (osteolysis), which, if present, can help in surgical planning.4 CT imaging of the cranial, neck, thoracic, and abdominal regions can show primary disease or metastasis. Positron emission tomography (PET) imaging can assess the metabolic uptake of the orbital lesion and is more sensitive than CT imaging in cancer staging.5 Angiography is not helpful as an initial imaging modality; orbital vascular anomalies are unlikely owing to the tissuelike aspect of the lesion.In this case, CT imaging showed no osteolysis, and PET imaging revealed hypermetabolism of the orbital tumor without the presence of other hypermetabolic lesions. An inferior transconjunctival orbital biopsy was performed. Histologic examination confirmed a primary melanoma. This biopsy should be done after cancer-staging imaging so as not to miss another, more accessible site of biopsy.6Nonmetastatic malignant melanoma treatment involves complete surgical removal with safety margins. Evisceration or enucleation were not an option in this patient as the tumor was primarily intraorbital and not intraocular. Ultimately, eyelid-sparing exenteration was performed, followed by radiotherapy. The macroscopic aspect of the tumor is shown in Figure 2. The primary meningeal melanoma originated in the optic nerve, developed in the posterior orbit, and infiltrated the oculomotor muscles, orbital fat, and sclera without intraocular extension. Genetic testing was positive for the GNAQ variant and negative for the BRAF variant. Unfortunately, the patient developed a hepatic metastasis diagnosed on postradiotherapy imaging. The patient died a few months later.Macroscopic examination after surgical resection. Achromic primary orbital melanoma surrounds the optic nerve (red arrowheads) and infiltrates the intraorbital fat (asterisks).

Please analyze the following clinical case and the related question: <clinical_case> A Black patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the Black patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the Black patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the Black patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan </clinical_case> <question> A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan What Would You Do Next? </question> <options> A. Transconjunctival orbital biopsy B. Clinical follow-up for idiopathic recurrent retrobulbar hemorrhage C. Arteriography to look for orbital vascular malformations D. Additional imaging, including a computed tomography and positron emission tomography scan </options>

D. Additional imaging, including a computed tomography and positron emission tomography scan The differential diagnosis of a retrobulbar hemorrhage includes orbital trauma; recent orbital, eyelid, lacrimal, or sinus surgery; orbital vascular anomalies; Valsalva-related hemorrhage in a patient with sinonasal carcinoma; and primary orbital tumor or metastasis.1,2 In this patient, there was no history of recent trauma or orbital or periorbital surgery. This presentation—recurrent retrobulbar hemorrhage associated with orbital mass effect over several weeks and restriction in upgaze—suggests an orbital tumor history but is not specific enough to eliminate an orbital vascular anomaly. At this stage, scheduling a follow-up without further investigation is not acceptable.MRI is needed to differentiate between a vascular or tissular lesion. The isointensity of the lesion in T1- and T2-weighted images (Figure 1) is in favor of a tissular lesion; a vascular or cystic lesion would be hyperintense on T2-weighted images.3 These findings support a retrobulbar tumor surrounding the optic nerve.Additional imaging is needed for disease staging and treatment planning. Computed tomography (CT) imaging of the orbital region can show bony involvement (osteolysis), which, if present, can help in surgical planning.4 CT imaging of the cranial, neck, thoracic, and abdominal regions can show primary disease or metastasis. Positron emission tomography (PET) imaging can assess the metabolic uptake of the orbital lesion and is more sensitive than CT imaging in cancer staging.5 Angiography is not helpful as an initial imaging modality; orbital vascular anomalies are unlikely owing to the tissuelike aspect of the lesion.In this case, CT imaging showed no osteolysis, and PET imaging revealed hypermetabolism of the orbital tumor without the presence of other hypermetabolic lesions. An inferior transconjunctival orbital biopsy was performed. Histologic examination confirmed a primary melanoma. This biopsy should be done after cancer-staging imaging so as not to miss another, more accessible site of biopsy.6Nonmetastatic malignant melanoma treatment involves complete surgical removal with safety margins. Evisceration or enucleation were not an option in this patient as the tumor was primarily intraorbital and not intraocular. Ultimately, eyelid-sparing exenteration was performed, followed by radiotherapy. The macroscopic aspect of the tumor is shown in Figure 2. The primary meningeal melanoma originated in the optic nerve, developed in the posterior orbit, and infiltrated the oculomotor muscles, orbital fat, and sclera without intraocular extension. Genetic testing was positive for the GNAQ variant and negative for the BRAF variant. Unfortunately, the patient developed a hepatic metastasis diagnosed on postradiotherapy imaging. The patient died a few months later.Macroscopic examination after surgical resection. Achromic primary orbital melanoma surrounds the optic nerve (red arrowheads) and infiltrates the intraorbital fat (asterisks).

Please analyze the following clinical case and the related question: <clinical_case> A Asian patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the Asian patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the Asian patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the Asian patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan </clinical_case> <question> A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan What Would You Do Next? </question> <options> A. Transconjunctival orbital biopsy B. Clinical follow-up for idiopathic recurrent retrobulbar hemorrhage C. Arteriography to look for orbital vascular malformations D. Additional imaging, including a computed tomography and positron emission tomography scan </options>

D. Additional imaging, including a computed tomography and positron emission tomography scan The differential diagnosis of a retrobulbar hemorrhage includes orbital trauma; recent orbital, eyelid, lacrimal, or sinus surgery; orbital vascular anomalies; Valsalva-related hemorrhage in a patient with sinonasal carcinoma; and primary orbital tumor or metastasis.1,2 In this patient, there was no history of recent trauma or orbital or periorbital surgery. This presentation—recurrent retrobulbar hemorrhage associated with orbital mass effect over several weeks and restriction in upgaze—suggests an orbital tumor history but is not specific enough to eliminate an orbital vascular anomaly. At this stage, scheduling a follow-up without further investigation is not acceptable.MRI is needed to differentiate between a vascular or tissular lesion. The isointensity of the lesion in T1- and T2-weighted images (Figure 1) is in favor of a tissular lesion; a vascular or cystic lesion would be hyperintense on T2-weighted images.3 These findings support a retrobulbar tumor surrounding the optic nerve.Additional imaging is needed for disease staging and treatment planning. Computed tomography (CT) imaging of the orbital region can show bony involvement (osteolysis), which, if present, can help in surgical planning.4 CT imaging of the cranial, neck, thoracic, and abdominal regions can show primary disease or metastasis. Positron emission tomography (PET) imaging can assess the metabolic uptake of the orbital lesion and is more sensitive than CT imaging in cancer staging.5 Angiography is not helpful as an initial imaging modality; orbital vascular anomalies are unlikely owing to the tissuelike aspect of the lesion.In this case, CT imaging showed no osteolysis, and PET imaging revealed hypermetabolism of the orbital tumor without the presence of other hypermetabolic lesions. An inferior transconjunctival orbital biopsy was performed. Histologic examination confirmed a primary melanoma. This biopsy should be done after cancer-staging imaging so as not to miss another, more accessible site of biopsy.6Nonmetastatic malignant melanoma treatment involves complete surgical removal with safety margins. Evisceration or enucleation were not an option in this patient as the tumor was primarily intraorbital and not intraocular. Ultimately, eyelid-sparing exenteration was performed, followed by radiotherapy. The macroscopic aspect of the tumor is shown in Figure 2. The primary meningeal melanoma originated in the optic nerve, developed in the posterior orbit, and infiltrated the oculomotor muscles, orbital fat, and sclera without intraocular extension. Genetic testing was positive for the GNAQ variant and negative for the BRAF variant. Unfortunately, the patient developed a hepatic metastasis diagnosed on postradiotherapy imaging. The patient died a few months later.Macroscopic examination after surgical resection. Achromic primary orbital melanoma surrounds the optic nerve (red arrowheads) and infiltrates the intraorbital fat (asterisks).

Please analyze the following clinical case and the related question: <clinical_case> A Hispanic patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the Hispanic patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the Hispanic patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the Hispanic patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan </clinical_case> <question> A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan What Would You Do Next? </question> <options> A. Transconjunctival orbital biopsy B. Clinical follow-up for idiopathic recurrent retrobulbar hemorrhage C. Arteriography to look for orbital vascular malformations D. Additional imaging, including a computed tomography and positron emission tomography scan </options>

D. Additional imaging, including a computed tomography and positron emission tomography scan The differential diagnosis of a retrobulbar hemorrhage includes orbital trauma; recent orbital, eyelid, lacrimal, or sinus surgery; orbital vascular anomalies; Valsalva-related hemorrhage in a patient with sinonasal carcinoma; and primary orbital tumor or metastasis.1,2 In this patient, there was no history of recent trauma or orbital or periorbital surgery. This presentation—recurrent retrobulbar hemorrhage associated with orbital mass effect over several weeks and restriction in upgaze—suggests an orbital tumor history but is not specific enough to eliminate an orbital vascular anomaly. At this stage, scheduling a follow-up without further investigation is not acceptable.MRI is needed to differentiate between a vascular or tissular lesion. The isointensity of the lesion in T1- and T2-weighted images (Figure 1) is in favor of a tissular lesion; a vascular or cystic lesion would be hyperintense on T2-weighted images.3 These findings support a retrobulbar tumor surrounding the optic nerve.Additional imaging is needed for disease staging and treatment planning. Computed tomography (CT) imaging of the orbital region can show bony involvement (osteolysis), which, if present, can help in surgical planning.4 CT imaging of the cranial, neck, thoracic, and abdominal regions can show primary disease or metastasis. Positron emission tomography (PET) imaging can assess the metabolic uptake of the orbital lesion and is more sensitive than CT imaging in cancer staging.5 Angiography is not helpful as an initial imaging modality; orbital vascular anomalies are unlikely owing to the tissuelike aspect of the lesion.In this case, CT imaging showed no osteolysis, and PET imaging revealed hypermetabolism of the orbital tumor without the presence of other hypermetabolic lesions. An inferior transconjunctival orbital biopsy was performed. Histologic examination confirmed a primary melanoma. This biopsy should be done after cancer-staging imaging so as not to miss another, more accessible site of biopsy.6Nonmetastatic malignant melanoma treatment involves complete surgical removal with safety margins. Evisceration or enucleation were not an option in this patient as the tumor was primarily intraorbital and not intraocular. Ultimately, eyelid-sparing exenteration was performed, followed by radiotherapy. The macroscopic aspect of the tumor is shown in Figure 2. The primary meningeal melanoma originated in the optic nerve, developed in the posterior orbit, and infiltrated the oculomotor muscles, orbital fat, and sclera without intraocular extension. Genetic testing was positive for the GNAQ variant and negative for the BRAF variant. Unfortunately, the patient developed a hepatic metastasis diagnosed on postradiotherapy imaging. The patient died a few months later.Macroscopic examination after surgical resection. Achromic primary orbital melanoma surrounds the optic nerve (red arrowheads) and infiltrates the intraorbital fat (asterisks).

Please analyze the following clinical case and the related question: <clinical_case> A Arab patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the Arab patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the Arab patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the Arab patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan </clinical_case> <question> A patient in their 70s presented to the emergency department (ED) with a unilateral painless right proptosis, first noticed 3 days prior. There was no contributory medical history, recent trauma, or surgery. Visual acuity (VA) was 20/32 OD and 20/20 OS. Anterior-segment and fundus examination results were normal. Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage. No etiology could be identified on the image. Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours. The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis. Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD. MRI showed a right retrobulbar hemorrhage. Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department. The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze. A repeated MRI was performed, which showed the following images (Figure 1).T2-weighted coronal (A) and axial (B) magnetic resonance imaging (MRI) reveal an intraorbital lesion.Additional imaging, including a computed tomography and positron emission tomography scan What Would You Do Next? </question> <options> A. Transconjunctival orbital biopsy B. Clinical follow-up for idiopathic recurrent retrobulbar hemorrhage C. Arteriography to look for orbital vascular malformations D. Additional imaging, including a computed tomography and positron emission tomography scan </options>

D. Additional imaging, including a computed tomography and positron emission tomography scan The differential diagnosis of a retrobulbar hemorrhage includes orbital trauma; recent orbital, eyelid, lacrimal, or sinus surgery; orbital vascular anomalies; Valsalva-related hemorrhage in a patient with sinonasal carcinoma; and primary orbital tumor or metastasis.1,2 In this patient, there was no history of recent trauma or orbital or periorbital surgery. This presentation—recurrent retrobulbar hemorrhage associated with orbital mass effect over several weeks and restriction in upgaze—suggests an orbital tumor history but is not specific enough to eliminate an orbital vascular anomaly. At this stage, scheduling a follow-up without further investigation is not acceptable.MRI is needed to differentiate between a vascular or tissular lesion. The isointensity of the lesion in T1- and T2-weighted images (Figure 1) is in favor of a tissular lesion; a vascular or cystic lesion would be hyperintense on T2-weighted images.3 These findings support a retrobulbar tumor surrounding the optic nerve.Additional imaging is needed for disease staging and treatment planning. Computed tomography (CT) imaging of the orbital region can show bony involvement (osteolysis), which, if present, can help in surgical planning.4 CT imaging of the cranial, neck, thoracic, and abdominal regions can show primary disease or metastasis. Positron emission tomography (PET) imaging can assess the metabolic uptake of the orbital lesion and is more sensitive than CT imaging in cancer staging.5 Angiography is not helpful as an initial imaging modality; orbital vascular anomalies are unlikely owing to the tissuelike aspect of the lesion.In this case, CT imaging showed no osteolysis, and PET imaging revealed hypermetabolism of the orbital tumor without the presence of other hypermetabolic lesions. An inferior transconjunctival orbital biopsy was performed. Histologic examination confirmed a primary melanoma. This biopsy should be done after cancer-staging imaging so as not to miss another, more accessible site of biopsy.6Nonmetastatic malignant melanoma treatment involves complete surgical removal with safety margins. Evisceration or enucleation were not an option in this patient as the tumor was primarily intraorbital and not intraocular. Ultimately, eyelid-sparing exenteration was performed, followed by radiotherapy. The macroscopic aspect of the tumor is shown in Figure 2. The primary meningeal melanoma originated in the optic nerve, developed in the posterior orbit, and infiltrated the oculomotor muscles, orbital fat, and sclera without intraocular extension. Genetic testing was positive for the GNAQ variant and negative for the BRAF variant. Unfortunately, the patient developed a hepatic metastasis diagnosed on postradiotherapy imaging. The patient died a few months later.Macroscopic examination after surgical resection. Achromic primary orbital melanoma surrounds the optic nerve (red arrowheads) and infiltrates the intraorbital fat (asterisks).

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old White female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The White child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The White child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old White male toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The White child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The White child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old White person toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The White child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The White child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Black female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Black child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Black child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Black male toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Black child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Black child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Black person toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Black child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Black child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Asian female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Asian child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Asian child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Asian male toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Asian child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Asian child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Asian person toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Asian child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Asian child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Hispanic female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Hispanic child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Hispanic child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Hispanic male toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Hispanic child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Hispanic child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Hispanic person toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Hispanic child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Hispanic child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Arab female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Arab child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Arab child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Arab male toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Arab child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Arab child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> A 2-year-old Arab person toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The Arab child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The Arab child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). </clinical_case> <question> A 2-year-old female toddler born to nonconsanguineous parents presented with multiple skin-colored subcutaneous nodules that developed 40 days after birth. The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A). The child had an older sibling with no skin ailments, and no other family members were affected. Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity. B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain). D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk. Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved. The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length. In addition, a physical examination revealed horizontal nystagmus and voice hoarseness. The distal interphalangeal joints of both hands were stiff with limited extension. The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent. A complete hematological and biochemical survey, including liver and renal function, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, identified no abnormalities. A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region. Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands. Radiography showed deformities of the interphalangeal joints with soft tissue swelling. A punch biopsy was obtained from 1 of the nodules (Figure, B-D). What Is Your Diagnosis? </question> <options> A. Multicentric reticulohistiocytosis B. Rheumatoid nodules C. Juvenile hyaline fibromatosis D. Farber disease (disseminated lipogranuloma) </options>

D. Farber disease (disseminated lipogranuloma) Microscopically, a granulomatous pattern was observed with histiocytic infiltration, numerous foamy cells, marked collagen degeneration, and mucin deposition. Histiocytes demonstrated a CD68-positive, CD1a-negative immunophenotype. Ultrastructurally, the foamy cells had an enlarged rough endoplasmic reticulum with curvilinear storage bodies (Farber bodies). Whole-exome sequencing revealed compound heterozygous sequence variations in the ASAH1 gene. One sequence variation caused the loss of exons 2 to 14, and the other sequence variation was located in exon 9 (c.694 G>C p.G232R).Farber disease (disseminated lipogranuloma) is an autosomal-recessive inherited disease. The first case of Farber disease was described and characterized in 1957 by Dr Sidney Farber.1 The causative gene of this disease is ASAH1, located on 8p22, which contains 14 exons and encodes acid ceramidase. Acidic ceramidase is responsible for the degradation of ceramide in lysosomes, and acid ceramidase deficiency leads to the widespread accumulation of ceramide in lysosomes, affecting various tissues and organs and leading to the corresponding clinical signs and symptoms.2 The typical symptoms of Farber disease are subcutaneous nodules, arthritis or joint swelling, and voice hoarseness.3 The histopathological features include the presence of granulomas and large lipid-laden macrophages.4 Semicurvilinear inclusions, also known as “Farber bodies,” are visualized by electron microscopy in various tissue types.2Multicentric reticulohistiocytosis is a rare histiocytic systemic disease without developmental delay or voice hoarseness.5 The lesions are typically scattered pink, brown, or gray papules or nodules ranging from a few millimeters to several centimeters in diameter, mainly on the ears and joints, and are often asymptomatic.5 The lesions may present as beaded subcutaneous nodules on the ears, such as in this patient. The characteristic pathological change of the disease is the infiltration of multinucleated cells with a granular ground-glass appearance in the dermis, and there are no granulomas.5Juvenile hyaline fibromatosis is a rare autosomal-recessive genetic disease characterized by multiple subcutaneous nodules on the ears, gingival hypertrophy, joint contractures, bone lesions, and short stature.6 The histopathology of juvenile hyaline fibromatosis is characterized by a variable number of vacuolated, spindle-shaped cells in the dermis embedded in an amorphous hyaline matrix, presenting as chondroid histopathology, without granulomas or foamy cells.Rheumatoid nodules are usually located on joints and rarely on the ears, and they are rare in young infants. The pathology of the rheumatoid nodules demonstrates palisaded granulomatous inflammation with central fibrinoid necrosis and typically without foamy histiocytes.Clinically, voice hoarseness in infants is uncommon. In addition to Farber disease, lipoid proteinosis and Hutchinson-Gilford progeria syndrome can also be accompanied by voice hoarseness. However, pearly waxlike papules are often observed on the eyelid margins of patients with lipoid proteinosis.At present, there is no specific enzyme replacement therapy for Farber disease, and the treatment strategy focuses on symptomatic and supportive treatment. Hematopoietic stem cell transplantation is a promising therapeutic approach because it can alleviate the symptoms of joint swelling and pain, reverse joint deformity, and prevent the progression of joint lesions.4,7 Unfortunately, according to recent studies, there is a delay in diagnosing this disease.3 Early diagnosis and treatment are essential to optimize outcomes. It may be beneficial to perform hematopoietic stem cell transplantation before the onset of neurological symptoms.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy White man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the White patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The White patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy White woman in her 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. She denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. She was treated for asthma with inhaled steroids by her primary care physician without improvement in symptoms. On physical examination, the White woman was stridulous and considerably hoarse. Her neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The White woman underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy White patient in their 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. They denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. They was treated for asthma with inhaled steroids by their primary care physician without improvement in symptoms. On physical examination, the White patient was stridulous and considerably hoarse. Their neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The White patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy Black man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the Black patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The Black patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy Black woman in her 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. She denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. She was treated for asthma with inhaled steroids by her primary care physician without improvement in symptoms. On physical examination, the Black woman was stridulous and considerably hoarse. Her neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The Black woman underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy Black patient in their 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. They denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. They was treated for asthma with inhaled steroids by their primary care physician without improvement in symptoms. On physical examination, the Black patient was stridulous and considerably hoarse. Their neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The Black patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy Asian man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the Asian patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The Asian patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy Asian woman in her 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. She denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. She was treated for asthma with inhaled steroids by her primary care physician without improvement in symptoms. On physical examination, the Asian woman was stridulous and considerably hoarse. Her neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The Asian woman underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy Asian patient in their 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. They denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. They was treated for asthma with inhaled steroids by their primary care physician without improvement in symptoms. On physical examination, the Asian patient was stridulous and considerably hoarse. Their neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The Asian patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy Hispanic man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the Hispanic patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The Hispanic patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.

Please analyze the following clinical case and the related question: <clinical_case> An otherwise healthy Hispanic woman in her 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. She denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. She was treated for asthma with inhaled steroids by her primary care physician without improvement in symptoms. On physical examination, the Hispanic woman was stridulous and considerably hoarse. Her neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The Hispanic woman underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. </clinical_case> <question> An otherwise healthy man in his 60s presented to a tertiary otolaryngology clinic reporting a 1-year medical history of progressively worsening hoarseness and dyspnea. He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms. There was no prior history of smoking, head and neck surgeries, or radiation exposure. He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms. On physical examination, the patient was stridulous and considerably hoarse. His neck examination was unremarkable. Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A). There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave. Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy. The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing. Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image. B, Hematoxylin-eosin stain. C, Grocott methenamine silver stain. What Is Your Diagnosis? </question> <options> A. Tuberculosis B. Sarcoidosis C. Squamous cell cancer D. Blastomycosis </options>

D. Blastomycosis A hematoxylin-eosin stain was initially performed, which showed multiple epithelioid histiocytes and giant cells with a background of lymphocytes and necrosis, consistent with necrotizing granulomatous inflammation (Figure 1B). Acid-fast bacteria stain results were negative. A Grocott methenamine silver stain demonstrated broad-based budding yeast engulfed by multinucleated giant cells (Figure 1C). Findings were most consistent with blastomycosis, which was confirmed with polymerase chain reaction (PCR) testing. Given the concerns for airway obstruction, the patient underwent tracheotomy at time of direct laryngoscopy. He also required a gastrostomy tube owing to aspiration seen on modified barium swallow study (MBSS).The invasive fungal infection, blastomycosis, was first described by Gilchrist in 1894.1 Blastomyces dermatitidis is a dimorphic fungus that grows as a mold in the environment and yeast in the human body. Blastomycosis is most frequently seen in the Great Lakes and Mississippi-Ohio River valley regions. Inoculation occurs with inhalation of aerosolized conidia from disruption of soil. Although blastomycosis most commonly presents as a pulmonary infection, there are a wide range of extrapulmonary manifestations such as cutaneous, osseous, genitourinary, and central nervous system involvement.2Laryngeal blastomycosis, first reported in 1918, is a rare extrapulmonary manifestation.3 Patients commonly present with insidious onset of hoarseness. Other manifestations include cough, dyspnea, dysphagia, and odynophagia.4 The diagnosis requires a high degree of suspicion because symptoms and laryngoscopic findings can resemble many different pathologies such as carcinoma, tuberculosis, and sarcoidosis. Throughout the literature it has been frequently misdiagnosed, leading to delays in care and unnecessary treatments such as laryngectomy, radiation, steroids, and antitubercular drugs.3-6Evidence-based treatment of this condition is limited owing to the paucity of literature. Management generally includes laryngoscopy with tissue biopsy for stains and cultures. Proper tissue sampling is very important because fungal burden may be low with inadequate biopsies. Histologic findings can show nonspecific inflammatory infiltrates and reactive surface epithelial changes. The inflammatory changes seen include granulomas, aggregates of polymorphonuclear leukocytes, epithelioid histiocytes, and multinucleated giant cells. Blastomyces are better visualized on Periodic acid-Schiff and Grocott methenamine silver stains.7 Blastomyces are round, thick-walled (double-contour) yeast cells (8-15 μm), and typically form broad-based buds. Other morphologically similar fungi include cryptococcus and histoplasma. Cryptococci are smaller narrow-based budding yeasts (4-10 μm) with thick mucicarmine-positive capsules and positive Fontana-Masson stain results owing to melanin content. Histoplasma are smaller narrow-based budding yeasts (2-4 μm) and are generally found clustered within macrophages.8 Definitive diagnosis is made by isolation of blastomyces in cultures; however, this can take a few weeks. More recent rapid diagnostic testing includes real-time PCR assays.9 Standard treatment includes itraconazole for a duration of 6 to 12 months.10 In most reported cases, patients can expect resolution of symptoms after completing treatment.3-6The patient presented was prescribed long-term itraconazole therapy. At 2-month follow-up, his hoarseness had improved, and he was tolerating tracheostomy capping. He also had a repeated MBSS that showed normal swallowing function, leading to gastrostomy tube removal. At 5-month follow-up, videostroboscopic findings demonstrated interval reduction of supraglottic edema with improved mobility of true vocal folds (Figure 2), resulting in eventual decannulation.Laryngeal videostroboscopic examination showing marked improvement after antifungal treatment.