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JAMA_Chen2024

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https://jamanetwork.com/journals/jama/fullarticle/2630579

A 27-year-old woman with asthma and obesity recently underwent a laparoscopic cholecystectomy for presumed cholecystitis. One week later, she had new-onset ascites and diffuse abdominal pain. She was a current smoker, was taking oral contraceptives, and delivered a healthy infant (2.5 months prior). The patient was not jaundiced, but her abdomen was distended without rebound or guarding. An ultrasound of her right upper quadrant showed hepatic vein thrombosis that was confirmed by magnetic resonance imaging of the abdomen. A laboratory workup and bone marrow biopsy were performed (Table). How Would You Interpret These Test Results?

The patient has a myeloproliferative neoplasm (MPN).

The patient has paroxysmal nocturnal hemoglobinuria.

The patient has hereditary protein C deficiency.

The patient has hereditary antithrombin III deficiency.

A

The patient has a myeloproliferative neoplasm (MPN).

Janus kinase 2 (JAK2) is a nonreceptor tyrosine kinase expressed by all hematopoetic stem cells that acts as a messenger in the intracellular signaling cascade to induce cellular proliferation in response to external growth factors. The acquired JAK2 V617F mutation results in constitutive phosphorylation of JAK2 and activates the cellular proliferation cascade in the absence of external growth factor signaling. Thus, the JAK2 mutation causes clonal proliferation of hematopoetic cells.1 A single-allele qualitative polymerase chain reaction test is the most common method of identifying a JAK2 mutation. Depending on the assay manufacturer and clinical cutoff used for detecting mutant allele burden in peripheral blood, the assay is sensitive to the detection of as few as 1% to 3% mutant alleles and is nearly 100% specific for clonal hematopoiesis.2-4 The Medicare reimbursement for a JAK2 V617F mutation screen is $144.5According to the 2016 World Health Organization classification system of myeloproliferative neoplasms (MPNs), the presence of a molecular marker (most commonly JAK2 V617F) is a major criterion for a diagnosis of polycythemia vera (PV), essential thrombocythemia, and primary myelofibrosis.6 Although most patients with PV have a JAK2 mutation, only 50% to 60% with essential thrombocythemia or primary myelofibrosis have a JAK2 mutation.6,7 Therefore, additional clinical, laboratory, and histological features are needed to distinguish between PV, essential thrombocythemia, and primary myelofibrosis.6 Lacking criteria for a specific MPN subtype, these patients have unclassifiable MPN.6Among patients without abdominal malignancy or cirrhosis, the prevalence of JAK2 V617F mutations is 41% in those with hepatic vein thrombosis and 27.7% in those with portal vein thrombosis.8 Even among patients without leukocytosis, erythrocytosis, or thrombocytosis, JAK2 V617F mutations are still found in 17.1% of those with hepatic vein thrombosis and 15.4% of those with portal vein thrombosis as blood count abnormalities can sometimes be masked by hypersplenism, blood loss, or hemodilution.8 Accordingly, it is recommended that JAK2 V617F testing be performed in patients with noncirrhotic, nonmalignant hepatic or portal vein thrombosis.8Application of This Test Result to the PatientResults for JAK2 V617F were positive, confirming the presence of clonal hematopoiesis. Because of this patient’s normal complete blood count results, she is among the subset of patients with an unclassifiable MPN who have a positive JAK2 V617F mutation but do not meet the diagnostic criteria for PV, essential thrombocythemia, or primary myelofibrosis. Test results for antiphospholipid antibody syndrome were negative. Flow cytometry identified CD55/59 expression, making the diagnosis of paroxysmal nocturnal hemoglobinuria less likely. Protein C and antithrombin activities were below the lower limit of normal, but these results were more likely due to acquired deficiency from acute thrombosis rather than hereditary thrombophilia. Heparin use can also reduce antithrombin levels. Therefore, testing for hereditary thrombophilia in the setting of anticoagulation or acute thrombosis is not recommended. In isolation, protein C deficiency and antithrombin deficiency are rare (present in <1% of population); it would be unusual for a patient to have both tendencies together.9This patient’s hepatic vein thrombosis was likely related to her underlying JAK2 mutation, but other risk factors for acute thrombosis, such as obesity, recent pregnancy, recent surgery, smoking, and oral contraceptive use may have contributed. Typically, an MPN is suspected based on erythrocytosis, thrombocytosis, or leukocytosis alone or in combination; however, hepatic or portal vein thrombosis can be the first clinical manifestation of an MPN.10 The presence of hepatic vein thrombosis in the setting of an underlying MPN warrants long-term anticoagulation and monitoring for consequences of portal hypertension that increase risk for serious bleeding. In addition, routine complete blood count monitoring is recommended because a distinct MPN phenotype can develop 1 to 10 years after initial presentation and may require treatment.8The patient underwent large-volume paracentesis and subsequently, a transjugular intrahepatic portosystemic shunt procedure. Anticoagulation therapy was initiated and the patient was monitored with serial complete blood cell counts every 3 to 4 months. A specific phenotype became apparent 4 years after presentation when she developed erythrocytosis and thrombocytosis, leading to a diagnosis of PV. Currently, her condition is managed with hydroxyurea, therapeutic phlebotomy, aspirin, and warfarin.Myeloproliferative neoplasms (MPNs), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are associated with JAK2 V617F mutations.Patients with JAK2 V617F mutations may have a masked MPN phenotype and present first with hepatic or portal vein thrombosis without leukocytosis, erythrocytosis, or thrombocytosis.JAK2 V617F mutation testing is recommended in patients who are noncirrhotic, without malignancy, and who present with hepatic or portal vein thrombosis.In the absence of erythrocytosis, leukocytosis and/or thrombocytosis, JAK2 V617F mutation screening is not recommended during evaluation of venous thrombosis involving typical sites (eg, deep vein thrombosis or pulmonary embolism).

Diagnostic

A 27-year-old woman with asthma and obesity recently underwent a laparoscopic cholecystectomy for presumed cholecystitis. One week later, she had new-onset ascites and diffuse abdominal pain. She was a current smoker, was taking oral contraceptives, and delivered a healthy infant (2.5 months prior). The patient was not jaundiced, but her abdomen was distended without rebound or guarding. An ultrasound of her right upper quadrant showed hepatic vein thrombosis that was confirmed by magnetic resonance imaging of the abdomen. A laboratory workup and bone marrow biopsy were performed (Table).

how would you interpret these test results?

How do you interpret these results?

The patient has a myeloproliferative neoplasm (MPN).

The patient has hereditary antithrombin III deficiency.

The patient has hereditary protein C deficiency.

The patient has paroxysmal nocturnal hemoglobinuria.

a

female

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2598513

A young woman presented with multiple arciform to annular plaques on her extremities, favoring the antecubital and popliteal fossae (Figure, A). The patient reported that these asymptomatic lesions had been present since her adolescence, and she was easily bruised with minimal trauma since birth. There was no family history of similar cutaneous findings.Clinically, arciform to annular plaques surround white atrophic patches on the left antecubital fossa (A), and skin atrophy is apparent on the dorsal aspects of the hands (B). C, Histopathologically, a punch biopsy specimen from a papule on the left arm was analyzed with Verhoeff–van Gieson stain (original magnification ×100).On close inspection, the plaques were found to be composed of individual 2- to 4-mm keratotic papules surrounding white atrophic patches. Physical examination also revealed remarkable skin atrophy on the dorsal aspects of her hands (Figure, B) and feet. The patient’s skin was generally pale and translucent with visible veins, especially on the chest and abdomen. The face appeared to be emaciated, with a pinched nose, thin lips, sunken cheeks, and prominent eyes. A punch biopsy specimen from an individual papule from the left arm was obtained and analyzed under Verhoeff–van Gieson stain (Figure, C). What Is Your Diagnosis?

Annular elastolytic giant cell granuloma

Granuloma annulare

Porokeratosis

Vascular Ehlers-Danlos syndrome with elastosis perforans serpiginosa

D. Vascular Ehlers-Danlos syndrome (vEDS) with elastosis perforans serpiginosa

D

Vascular Ehlers-Danlos syndrome with elastosis perforans serpiginosa

Histological examination under Verhoeff–van Gieson staining revealed accumulation and transepidermal elimination of elastic fibers, characteristic pathologically of elastosis perforans serpiginosa (EPS). Given the medical history, cutaneous findings, and characteristic facial appearance, a suspicion of vEDS (OMIM 130050) was raised, which was confirmed by detection of a pathogenic missense mutation c.3535G>C (p.G1179R) in the COL3A1 gene by Sanger sequencing. This mutation was de novo; it was not detected in her parents, which was in accordance with the negative family history. The patient was monitored regularly in local facilities for any vascular and organ complications, and she was advised to avoid collision sports and elective surgery in favor of more conservative management.vEDS (OMIM 130050) is a rare autosomal dominant disorder caused by mutations in the COL3A1 gene that leads to synthesis of abnormal collagen type III.1 Collagen type III is widely distributed in skin, blood vessels, pleuroperitoneal linings, and ligaments.1 In addition to prominent arterial and gastrointestinal complications, patients with vEDS demonstrate characteristic cutaneous findings and facial features, including thin, translucent skin, acrogeria, easy bruising, early-onset varicose veins, thin vermillion of the lips, narrow nose, and prominent eyes.2 Furthermore, vEDS is associated with other dermatologic disorders, including piezogenic papules and EPS.3,4EPS is a rare skin condition of unknown cause characterized histologically by transepidermal elimination of abnormal elastic fibers. EPS has been reported to be induced by drugs, especially penicillamine. In approximately 25% of cases, an underlying systemic disorder can be detected, particularly connective tissue disorders, including EDS, Marfan syndrome, osteogenesis imperfecta, Down syndrome, and pseudoxanthoma elasticum.4 In this case, the skin findings and facial features coexistent with typical EPS manifestations suggested the diagnosis of vEDS, which was confirmed by genetic testing.The clinical severity of vEDS is associated with the types and locations of variants in COL3A1. A variant that results in a substitution for a triple helical glycine residue by a larger residue is more likely to cause a severe vEDS phenotype than variants resulting in haplo insufficiency or nonglycine missense variants located in the C- or N-terminal regions of the protein.5,6 The G1179R glycine substitution mutation detected in our patient was predicted to result in a severe vEDS phenotype, consistent with a previous report of this mutation elsewhere.7The diagnosis of vEDS carries with it the life-threatening risks of vascular and organ rupture leading to sudden death. In a French cohort of 215 individuals with vEDS, the median age at the first major vascular, digestive, or obstetrical complication was 29 years.5 Therefore, a close surveillance of major complications is encouraged in patients with vEDS. The patient described herein was advised to undertake blood pressure monitoring and periodic noninvasive imaging of the arterial vasculature.

Dermatology

A young woman presented with multiple arciform to annular plaques on her extremities, favoring the antecubital and popliteal fossae (Figure, A). The patient reported that these asymptomatic lesions had been present since her adolescence, and she was easily bruised with minimal trauma since birth. There was no family history of similar cutaneous findings.Clinically, arciform to annular plaques surround white atrophic patches on the left antecubital fossa (A), and skin atrophy is apparent on the dorsal aspects of the hands (B). C, Histopathologically, a punch biopsy specimen from a papule on the left arm was analyzed with Verhoeff–van Gieson stain (original magnification ×100).On close inspection, the plaques were found to be composed of individual 2- to 4-mm keratotic papules surrounding white atrophic patches. Physical examination also revealed remarkable skin atrophy on the dorsal aspects of her hands (Figure, B) and feet. The patient’s skin was generally pale and translucent with visible veins, especially on the chest and abdomen. The face appeared to be emaciated, with a pinched nose, thin lips, sunken cheeks, and prominent eyes. A punch biopsy specimen from an individual papule from the left arm was obtained and analyzed under Verhoeff–van Gieson stain (Figure, C).

what is your diagnosis?

What is your diagnosis?

Vascular Ehlers-Danlos syndrome with elastosis perforans serpiginosa

Porokeratosis

Granuloma annulare

Annular elastolytic giant cell granuloma

a

female

11-20

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2592312

An 8-month-old white male was seen for evaluation of a red, bleeding umbilical mass. The lesion had been present since loss of the umbilical stump at 1 week of life. It bled easily with Valsalva maneuver or trauma. The lesion was treated as an infantile hemangioma with timolol by an outside dermatologist and as an umbilical pyogenic granuloma with silver nitrate by the patient’s pediatrician, with minimal improvement. The patient was born at 38½ weeks by normal spontaneous vaginal delivery. His medical history was notable for tongue tie from birth. On examination, he was an alert and healthy-appearing child. The umbilicus demonstrated a bright red, friable, 5-mm papule (Figure, A). A shave biopsy specimen was obtained for histologic examination (Figure, B and C).A, Clinical photograph of the red friable papule in the umbilicus. B and C, Hematoxylin-eosin–stained shave biopsy specimen showing an ulcerated epidermis, colonic mucosa, and granulation tissue (B, original magnification ×2.7; C, original magnification ×10). What Is Your Diagnosis?

Pyogenic granuloma

Umbilical mucosal polyp

Umbilical hernia

Patent urachus

B. Umbilical mucosal polyp

B

Umbilical mucosal polyp

Pathology findings revealed an ulcerated epidermis with underlying normal-appearing colonic mucosa and associated granulation tissue (Figure, B and C). Several prominent lymphoid aggregates with well-developed germinal centers were present. Mild epidermal acanthosis was noted adjacent to the erosion. These histologic features were consistent with a diagnosis of an umbilical mucosal polyp. Serial abdominal ultrasounds at 9 and 18 months of age did not reveal any further anatomic abnormalities of the gastrointestinal tract. The patient has experienced complete healing and no recurrence of the lesion.The differential diagnosis of the umbilical mass in this patient includes an umbilical pyogenic granuloma, umbilical mucosal polyp, patent urachus, and umbilical hernia.1 An umbilical pyogenic granuloma would typically respond to chemical cautery with silver nitrate. However, these lesions can be difficult to distinguish from an umbilical mucosal polyp based on clinical examination findings alone as both can present as a friable, bleeding mass. An umbilical hernia is typically covered entirely by skin. Small hernias (<1 cm) often close spontaneously, whereas larger defects are usually corrected surgically. A patent urachus is a remnant of the allantois, which runs between the urinary bladder and the umbilicus. On clinical examination, these lesions are often found to be draining urine.The omphalomesenteric duct connects the yolk sac to the primitive gut of the developing embryo. This structure normally obliterates between the fifth and eighth week of life.2 Persistence of the duct can result in a range of anatomic abnormalities including Meckel diverticula, sinus tracts, polyps, fistulae, and congenital bands.3 Most of these abnormalities remain asymptomatic, so the true prevalence of a residual omphalomesenteric duct is not known. However, symptomatic duct remnants can present as an acute abdomen, rectal bleeding, or gastrointestinal (GI) tract obstruction. In patients with an umbilical mucosal polyp, estimates of further underlying GI abnormalities range from 30% to 60%.4 Diagnosis of an umbilical mucosal polyp should prompt a search for other underlying anatomic abnormalities, as persistence of the duct can occur in a discontinuous fashion along the GI tract. Ultrasound is appropriate for an initial screening study in these patients to identify sinus tracts. If the patient is symptomatic or has rectal bleeding, a scan for Meckel diverticula could also be considered.3Our case illustrates the salient histologic features of an umbilical mucosal polyp and the importance of maintaining a broad differential diagnosis when considering an umbilical mass in an infant.

Dermatology

An 8-month-old white male was seen for evaluation of a red, bleeding umbilical mass. The lesion had been present since loss of the umbilical stump at 1 week of life. It bled easily with Valsalva maneuver or trauma. The lesion was treated as an infantile hemangioma with timolol by an outside dermatologist and as an umbilical pyogenic granuloma with silver nitrate by the patient’s pediatrician, with minimal improvement. The patient was born at 38½ weeks by normal spontaneous vaginal delivery. His medical history was notable for tongue tie from birth. On examination, he was an alert and healthy-appearing child. The umbilicus demonstrated a bright red, friable, 5-mm papule (Figure, A). A shave biopsy specimen was obtained for histologic examination (Figure, B and C).A, Clinical photograph of the red friable papule in the umbilicus. B and C, Hematoxylin-eosin–stained shave biopsy specimen showing an ulcerated epidermis, colonic mucosa, and granulation tissue (B, original magnification ×2.7; C, original magnification ×10).

what is your diagnosis?

What is your diagnosis?

Patent urachus

Umbilical mucosal polyp

Umbilical hernia

Pyogenic granuloma

b

male

0-10

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2595033

A man in his 80s presented with a 1-year history of purpura, ecchymoses, anorexia, and weight loss. His medical history included alcohol abuse and cognitive impairment. Purpura and ecchymoses, initially periorbital, progressed over the previous 12 months. Elder abuse was excluded. Examination demonstrated waxy yellow papules and plaques with purpura in the periocular, neck, axillary, trunk, and inguinal regions (Figure, A). Investigations revealed anemia, abnormal liver function test results, and renal impairment with moderate proteinuria. The patient’s serum protein electrophoresis (SPEP) and immunofixation urine protein electrophoresis test results were normal. Radiological studies were unremarkable. Subsequently, a 4-mm punch biopsy specimen was obtained (Figure, B-D).A, Waxy yellow discoloration of the skin with papules and purpura in the periorbital region. B, Punch biopsy specimen (hematoxylin-eosin, original magnification × 4). C, Punch biopsy specimen stained with Congo red (original magnification × 10). D, Punch biopsy specimen under polarized microscopy (original magnification × 10). What Is Your Diagnosis?

Myeloma

Metastatic disease

Amyloidosis

Leukemia cutis

C. Amyloidosis

C

Amyloidosis

Hematoxylin-eosin staining showed upper dermal amorphous eosinophilic deposits (Figure, B), Congo red staining results were positive (Figure, C). Polarizing light microscopy demonstrated pale apple-green birefringence (Figure, D). The patient was diagnosed with primary systemic (AL) amyloidosis, with biopsy proven cutaneous amyloidosis and likely renal, hepatic, and cerebral involvement. The patient’s family decided against further investigation or treatment and the patient subsequently died from pneumonia.Amyloidosis is not a single disease but a general term describing several diseases sharing the feature of abnormal extracellular tissue deposition of amyloid, a fibrillar proteinaceous material. Amyloid is classified as systemic or organ limited. Systemic amyloidosis comprises AL and secondary amyloidosis. Primary amyloidosis is associated with plasma cell dyscrasias or may be idiopathic, as in this patient. Secondary amyloidosis complicates chronic inflammatory disease.Presentation is varied, reflecting the wide spectrum of organ involvement. Systemic symptoms, such as fatigue and weight loss, are common.1 Mucocutaneous lesions occur in 30% to 40%,2 manifesting as waxy thickening, ecchymoses, and subcutaneous nodules or plaques. Amyloid purpura, characteristically periorbital, appears in a minority.3Diagnosis of AL amyloid requires demonstration of amyloid fibrils. On hematoxylin-eosin staining, amyloid appears as a pink, amorphous, waxy substance. Amyloid fibrils are confirmed by Congo red staining, In the evaluation for plasma cell dyscrasias, a negative SPEP result does not entirely exclude a monoclonal gammopathy and should be followed by immunofixation electrophoresis, with approximately 10-fold enhanced sensitivity when compared with SPEP.4Differential diagnoses include other forms of amyloidosis, multiple myeloma, cutaneous metastases, and papular mucinosis. The prognosis is poor, with mean survival of 14 months from diagnosis.The diagnosis of AL amyloidosis was delayed owing to nonspecific symptoms and unawareness of the significance of persistent and progressive purpura. Skin lesions may be the sole manifestation of systemic amyloidosis; therefore, prompt recognition and assessment for systemic involvement is important because prognosis is affected by early recognition of the disease.5

Dermatology

A man in his 80s presented with a 1-year history of purpura, ecchymoses, anorexia, and weight loss. His medical history included alcohol abuse and cognitive impairment. Purpura and ecchymoses, initially periorbital, progressed over the previous 12 months. Elder abuse was excluded. Examination demonstrated waxy yellow papules and plaques with purpura in the periocular, neck, axillary, trunk, and inguinal regions (Figure, A). Investigations revealed anemia, abnormal liver function test results, and renal impairment with moderate proteinuria. The patient’s serum protein electrophoresis (SPEP) and immunofixation urine protein electrophoresis test results were normal. Radiological studies were unremarkable. Subsequently, a 4-mm punch biopsy specimen was obtained (Figure, B-D).A, Waxy yellow discoloration of the skin with papules and purpura in the periorbital region. B, Punch biopsy specimen (hematoxylin-eosin, original magnification × 4). C, Punch biopsy specimen stained with Congo red (original magnification × 10). D, Punch biopsy specimen under polarized microscopy (original magnification × 10).

what is your diagnosis?

What is your diagnosis?

Myeloma

Amyloidosis

Metastatic disease

Leukemia cutis

b

male

0-10

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2614284

A 30-year-old man was referred with progressive quadriplegia for 2 months. The muscle weakness started from the right lower limb and gradually spread to the upper limb and contralateral side. Urinary retention developed 1 month later. Because he was suspected of having tubercular meningomyelitis, he received an antituberculosis regimen plus dexamethasone (10 mg daily) for 10 days. The symptoms ameliorated in the first week but thereafter deteriorated with fever. He had no history of central nervous system injury or drug overuse. He was a construction supervisor and had daily contact with moist earth. No relevant family history was reported. On physical examination, he was alert and well oriented. The cranial nerve was intact, but he had quadriplegia with a Medical Research Council muscle scale grade of 0 of 5 power, decreased tendon reflexes, and bilateral positive Babinski sign. Pinprick and vibration sensation were markedly impaired below the nipples. Multiple enlarged cervical lymph nodes could be palpitated. The skin was extraordinarily dry, and a pigmentation of 10 mm in diameter at the T2 vertebrae, just on the midline of the back, was noticed. Total blood T-cell count (CD3+) was 1643/uL (to convert to ×109 per liter, multiply by 0.001), and the patient had a CD4+/CD8+ ratio of 0.89. Results of blood testing for human immunodeficiency virus, syphilis, and tuberculosis were negative. Cerebrospinal fluid testing revealed pleocytosis (72 cells/uL; mononuclear cells, 59 of 72), elevated protein concentration (200 mg/dL), and a decreased glucose level (36.0 mg/dL [to convert to millimoles per liter, multiply by 0.0555]), but no organisms were identified on Gram stain or on stain for acid-fast bacilli. Pulmonary computed tomography showed enlarged lymph nodes in mediastinum and axillary regions. Results from magnetic resonance imaging of the brain were normal, while magnetic resonance imaging of the cervical spine revealed multiple intramedullary lesions with enhancement (Figure 1).Magnetic resonance imaging of the cervical spine. Multiple intramedullary lesions and enlarged lymph nodes with strong enhancement were revealed. A, Lateral view of the cervical cord. The subcutaneous abscess beneath the pigmentation on the back is also shown. Inset, photograph of the skin lesion on the back. B, Coronal view of the cervical cord. What Is Your Diagnosis?

Tubercular meningomyelitis

Mycotic meningomyelitis

Neurosarcoidosis

Central nervous system lymphoma

B. Mycotic meningomyelitis

B

Mycotic meningomyelitis

The patient was a young man presenting with progressive quadriplegia and fever with multiple intramedullary lesions. Together, with multiple enlarged lymph nodes, the diagnosis was narrowed down to a group of diseases, including tubercular meningomyelitis, neurosarcoidosis, lymphoma, metastatic disease, and mycotic meningomyelitis. The quadriplegia quickly deteriorated despite a standard antituberculosis regimen, and results from blood testing for tuberculosis were negative. Neurosarcoidosis can have spinal manifestations, but abnormalities of the cranial nerves are the most common. In patients with systemic non-Hodgkin lymphoma, lymphomatous involvement of the leptomeninges can be seen; in such cases, patients usually respond well to corticosteroids. No indications of malignancy could be identified. Therefore, given the history of exposure to moist dust and the presence of subcutaneous abscess beneath the pigmentation on the back, fungal infection was more likely.Further testing showed that plasma (1-3)-β-D-glucan was elevated to 578.2 pg/mL (normal range, <60 pg/mL). An open biopsy of cervical lymphonode revealed necrotic lymph node structure with numerous multinucleated giant cells and dematiaceous fungal materials in the form of spores and hyphaes. A fungal culture of the pus extracted from the subcutaneous abscess beneath the pigmentation showed entangled black hyphae (Figure 2). Sequencing analysis of the isolate revealed a high degree of homology to Fonsecaea (F pedrosoi, F monophora, and F compacta). Sequencing of the internal transcribed spacer 2 region narrowed the isolate to F pedrosoi. The patient started antifungal treatment (intravenous voriconazole with a loading dose of 400 mg twice daily and a maintenance dose of 200 mg twice daily). Body temperature returned to normal within 2 weeks. Three weeks later, the Medical Research Council muscle scale grade was 2 of 5 in the upper extremities. Six months later, the patient was able to walk with assistance. Oral voriconazole was given at a dose of 200 mg twice daily for another 12 months. At the last follow-up of 24 months, he was able to walk upstairs with assistance.Smear of the culture medium. Entangled black hyphae was found in the fungal culture medium.Multiple lesions to the spinal cord can be diagnostically challenging. In this patient, the mycosis lesions appeared to be of leptomeningeal origin with parenchymal invasion. Mycotic infection of the central nervous system (ie, phaeohyphomycosis) is typically caused by one of the following pathogens: Cladophialophora bantiana, Exophiala dermatitidis, or Rhinocladiella mackenziei.1 On the contrary, infection by F monophora or F pedrosoi is typically confined to the skin and subcutaneous tissue (chromoblastomycosis).2-4 Deep tissue is involved only in rare cases.5 Brain phaeohyphomycosis caused by Fonsecaea has only been reported in several case reports, whereas spinal cord involvement was even rarer.6,7 Notably, unlike other life-threatening mold infections, roughly half of patients with central nervous system phaeohyphomycosis were reported in apparently immune-competent individuals, possibly owing to melanin in the cell walls of Chaetothyriales as a key virulence factor for central nervous system localization.7 The diagnosis could have been established earlier in this patient with a more careful physical examination of the skin lesions.

Neurology

A 30-year-old man was referred with progressive quadriplegia for 2 months. The muscle weakness started from the right lower limb and gradually spread to the upper limb and contralateral side. Urinary retention developed 1 month later. Because he was suspected of having tubercular meningomyelitis, he received an antituberculosis regimen plus dexamethasone (10 mg daily) for 10 days. The symptoms ameliorated in the first week but thereafter deteriorated with fever. He had no history of central nervous system injury or drug overuse. He was a construction supervisor and had daily contact with moist earth. No relevant family history was reported. On physical examination, he was alert and well oriented. The cranial nerve was intact, but he had quadriplegia with a Medical Research Council muscle scale grade of 0 of 5 power, decreased tendon reflexes, and bilateral positive Babinski sign. Pinprick and vibration sensation were markedly impaired below the nipples. Multiple enlarged cervical lymph nodes could be palpitated. The skin was extraordinarily dry, and a pigmentation of 10 mm in diameter at the T2 vertebrae, just on the midline of the back, was noticed. Total blood T-cell count (CD3+) was 1643/uL (to convert to ×109 per liter, multiply by 0.001), and the patient had a CD4+/CD8+ ratio of 0.89. Results of blood testing for human immunodeficiency virus, syphilis, and tuberculosis were negative. Cerebrospinal fluid testing revealed pleocytosis (72 cells/uL; mononuclear cells, 59 of 72), elevated protein concentration (200 mg/dL), and a decreased glucose level (36.0 mg/dL [to convert to millimoles per liter, multiply by 0.0555]), but no organisms were identified on Gram stain or on stain for acid-fast bacilli. Pulmonary computed tomography showed enlarged lymph nodes in mediastinum and axillary regions. Results from magnetic resonance imaging of the brain were normal, while magnetic resonance imaging of the cervical spine revealed multiple intramedullary lesions with enhancement (Figure 1).Magnetic resonance imaging of the cervical spine. Multiple intramedullary lesions and enlarged lymph nodes with strong enhancement were revealed. A, Lateral view of the cervical cord. The subcutaneous abscess beneath the pigmentation on the back is also shown. Inset, photograph of the skin lesion on the back. B, Coronal view of the cervical cord.

what is your diagnosis?

What is your diagnosis?

Neurosarcoidosis

Central nervous system lymphoma

Mycotic meningomyelitis

Tubercular meningomyelitis

c

male

21-30

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2613459

A 7-year-old healthy boy presented to the emergency department with recurrent painless tongue masses since birth. His mother reported that multiple masses would develop and resolve spontaneously over the course of days to weeks. The lesions were usually white and the size of a pinhead, and located on the anterior portion of the tongue. Occasionally they would grow in size and progress to red-filled vesicles that did not burst or bleed. The timing of the lesions was not associated with fever or other rashes. The patient’s history was otherwise unremarkable, he had no recent travel outside the United States, and his vaccinations were up to date.On physical examination, the patient had multiple pale, nontender papules distributed over the anterior third of his tongue (Figure). No other masses were noted to the remainder of his oropharynx. He was afebrile and had no signs or symptoms of airway obstruction.Multiple discolored masses located on the anterior surface of the tongue. What Is Your Diagnosis?

Herpes simplex virus infection

Mucocele

Neurofibromatosis type 1

Oral lymphangioma

D. Oral lymphangioma

D

Oral lymphangioma

Lymphangiomas are benign, hamartomatous tumors of lymphatic vessels. Oral lymphangiomas most commonly affect the dorsal and ventral surfaces of the anterior two-thirds of the tongue.1 Lesions may also affect the palate, gingiva, buccal mucosa, and lips.2 In addition to cosmetic deformity, comorbidities may include hemorrhage, excessive salivation, speech disturbances, difficulty chewing or swallowing, airway obstruction, and orthodontic abnormalities.3 The characteristic appearance is of multiple lymph-filled cysts, which may be clear, white, red, blue, or purple, representing various stages of granulation as well as capillary rupture into the lymphatic space. Deeper lesions may not appear discolored at all. These masses are typically classified as microcystic (lesions smaller than 2 cm3) or macrocystic (lesions larger than 2 cm3). Histologically, lymphangiomas are composed of thin-walled, cystically dilated vascular channels lined by endothelial cells and filled with proteinaceous fluid.4 As with this patient, lesions often regress and recur spontaneously, although definitive treatment typically involves surgical intervention, particularly in cases of airway obstruction, obstructive sleep apnea, recurrent tongue trauma, bleeding, or pain.4 Prior to treatment, advanced imaging is recommended to determine the extent of the lesions, with magnetic resonance imaging being the preferred modality. However, surgical excision is frequently incomplete, resulting in residual disease and high rate of recurrence.5 Other techniques, such as low radiofrequency ablation and sclerotherapy, have been found to be effective in case series.5-7The differential diagnosis for oral lymphangioma includes other congenital malformations, infectious masses, and neoplasms. Congenital malformations, such as arteriovenous malformations, branchial cleft cysts, and mucoceles, may also present with oral lesions. Mucoceles are cysts resulting from the extravasation of mucin from nearby salivary glands. They are anatomically located at the base of the tongue rather than on the anterior surface, as in this patient. The patient does not have other symptoms that suggest an infectious etiology, such as fever or rhinorrhea, and the absence of associated pain makes herpes simplex and varicella virus infection unlikely. Neurofibromatosis type 1 can rarely present with multiple tongue lesions, often representing fleshy neurofibromas along peripheral nerves, but the vesicular nature of the lesions, the recurrent history of the masses, and the lack of other stigmata of neurofibromatosis type 1 makes this diagnosis unlikely.For this patient, the diagnosis of oral lymphangioma was made based on history and physical examination. He had no signs of airway obstruction. He was discharged home from the emergency department with referrals to dermatology and otolaryngology clinics. Outpatient workup included computed tomography of the neck to evaluate the presence of other masses that could potentially compromise his airway. Owing to the recurrent nature of these masses, the patient underwent elective ablation and sclerotherapy with injected bleomycin; despite these interventions, his lymphangiomas continue to recur and he follows up regularly with an otolaryngology clinic.

Pediatrics

A 7-year-old healthy boy presented to the emergency department with recurrent painless tongue masses since birth. His mother reported that multiple masses would develop and resolve spontaneously over the course of days to weeks. The lesions were usually white and the size of a pinhead, and located on the anterior portion of the tongue. Occasionally they would grow in size and progress to red-filled vesicles that did not burst or bleed. The timing of the lesions was not associated with fever or other rashes. The patient’s history was otherwise unremarkable, he had no recent travel outside the United States, and his vaccinations were up to date.On physical examination, the patient had multiple pale, nontender papules distributed over the anterior third of his tongue (Figure). No other masses were noted to the remainder of his oropharynx. He was afebrile and had no signs or symptoms of airway obstruction.Multiple discolored masses located on the anterior surface of the tongue.

what is your diagnosis?

What is your diagnosis?

Neurofibromatosis type 1

Oral lymphangioma

Mucocele

Herpes simplex virus infection

b

male

0-10

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2618379

A 77-year-old institutionalized and bedridden man with severe Alzheimer dementia and long-standing schizophrenia was admitted to the emergency department for bowel obstruction with progressive abdominal distension and tenderness. His family members and caregivers accompanied him. At physical examination the patient was pale, sweaty, peripherally hypoperfused, tachypnoeic, and dehydrated, and the abdomen was extremely distended, diffusely tympanic, and tender at palpation. His blood pressure was 90/70 mm Hg, his heart rate was 114 beats per minute, his oxygen saturation was at 90%, his arterial blood gas pH level was 7.43, his partial pressure of carbon dioxide was 32, his partial pressure of oxygen 68, his laceration lactate level was 5.0, and his white blood cell count was 24 000 mm3. A plain abdominal radiograph showed a huge colonic distension (Figure 1A). A computed tomography scan with multiplanar reconstruction was also performed (Figure 1B).A, A plain abdominal x-ray shows a huge colonic distension and a clear coffee-bean-like or “bent inner tube” sign is visible. B, A computed tomography scan with multiplanar reconstruction. What Is Your Diagnosis?

Cecal volvulus

Aerophagia

Sigmoid volvulus

Colonic ileus/colonic pseudoobstruction (Ogilvie syndrome)

C. Sigmoid volvulus

C

Sigmoid volvulus

A plain abdominal radiograph showed a clear coffee bean-like or “bent inner tube” sign, suggestive for colonic volvulus. A computed tomography scan confirmed a huge colonic volvulus with a twisted mesentery and vascular compromise (Figure 2). Based on the patient’s critical conditions and severe long-standing obstruction with initial signs of ischemia and shock, taking the patient immediately to the operating room was most logical, a choice especially justified in settings without a daily 24-hour interventional endoscopy service. However, the surgical risks of an aggressive treatment such as laparotomy in a frail patient should be carefully considered, along with the potential health care burden of surgery, a prolonged intensive care unit stay, and/or a long recovery of a patient with an irreversible condition/advanced dementia. In the case of sigmoid volvulus, the 2016 American Society of Colon and Rectal Surgeons Guidelines recommend performing an endoscopic derotation, which is less invasive and cheaper than a surgical intervention. It is effective in 60% to 95% of cases, but it has a risk of overall recurrence up to 61%,1 could lead to complications such as perforation, and should not be performed in patients with suspected ischemia or perforation. However, for an endoscopic failure or finding of gangrene, the only possible therapeutic step is performing an emergency laparotomy and sigmoidectomy, which has significant morbidity and mortality rates, especially among high-risk patients (based on their American Society of Anesthesiologists score).A computed tomography scan and a diatrizoate meglumine and diatrizoate sodium enema were performed with a diagnostic and therapeutic purpose, confirming a huge colonic volvulus with a twisted mesentery and a vascular compromise (so-called “whirl-sign” highlighted within the red circle).We successfully performed an emergency colonoscopy for derotation and decompression. However, the mucosa appeared endoscopically dusky. While without such comorbidities and surrogate decisions to limit interventions immediate laparotomy would be appropriate given the ischemic signs and symptoms, because of the patient’s critical conditions and underlying chronic diseases with advanced Alzheimer dementia, and after discussion with his family and guardian, we decided not to proceed with futile therapeutic procedures and give him palliative care with appropriate painless end-of-life comfort.2 The physician in charge should discuss the situation with relatives/guardians, make them aware of a probable therapeutic futility, and listen to their point of view while explaining the reasons and consequences of such action.3,4 Provided the critical conditions of the patient and his severe comorbidities, the final decision making may be influenced by the judgment of not only the surgeon, anesthetist, and physician in charge, but also by the cultural environment and the feelings of the patient’s relatives. Multidisciplinary discussions and joint decisions with families/guardians and health care clinicians is advisable.Decision making when providing care and treatment for a person with dementia who is at the end of life, or generally among patients with a reduced capacity and severe comorbidities, can be complex and challenging3 for clinical and ethical reasons. Institutionalized elderly and mentally impaired, bedridden patients represent a significant burden for health care systems in industrialized countries. Efforts should be implemented to help carers overcome barriers to proxy decision making and to ensure that people with dementia retain their dignity.3Honest discussions with family members should be pursued when the potential harms of surgery outweigh the benefits.2

Surgery

A 77-year-old institutionalized and bedridden man with severe Alzheimer dementia and long-standing schizophrenia was admitted to the emergency department for bowel obstruction with progressive abdominal distension and tenderness. His family members and caregivers accompanied him. At physical examination the patient was pale, sweaty, peripherally hypoperfused, tachypnoeic, and dehydrated, and the abdomen was extremely distended, diffusely tympanic, and tender at palpation. His blood pressure was 90/70 mm Hg, his heart rate was 114 beats per minute, his oxygen saturation was at 90%, his arterial blood gas pH level was 7.43, his partial pressure of carbon dioxide was 32, his partial pressure of oxygen 68, his laceration lactate level was 5.0, and his white blood cell count was 24 000 mm3. A plain abdominal radiograph showed a huge colonic distension (Figure 1A). A computed tomography scan with multiplanar reconstruction was also performed (Figure 1B).A, A plain abdominal x-ray shows a huge colonic distension and a clear coffee-bean-like or “bent inner tube” sign is visible. B, A computed tomography scan with multiplanar reconstruction.

what is your diagnosis?

What is your diagnosis?

Sigmoid volvulus

Cecal volvulus

Aerophagia

Colonic ileus/colonic pseudoobstruction (Ogilvie syndrome)

a

male

71-80

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2622643

A 45-year-old woman presented to the emergency department on the morning after Thanksgiving with sudden, severe, constant epigastric pain that migrated to the right upper quadrant as well as subjective fever and emesis since the previous evening. She reported a failure to pass stool or flatus since the onset of symptoms. She denied hematochezia, melena, or hematemesis. Her medical history was significant for heavy smoking, reflux, and surgical procedures including a right inguinal hernia repair, total abdominal hysterectomy, and bilateral salpingo-oopherectomy, all more than 5 years prior. On examination, she had a distended and tympanic abdomen with tenderness, guarding, and rebound in the epigastrium and right upper quadrant. Vital signs and standard laboratory test results were unremarkable.An upright abdominal plain radiograph showed a distended, thickened stomach and multiple dilated loops of small bowel with air-fluid levels. Contrast-enhanced computed tomography demonstrated a focal area of mixed fat density involving the distal small bowel concerning for a lead point with adjacent mesenteric fat stranding (Figure 1). The scan also revealed multiple bilateral lung nodules.Computed tomography of abdomen. A, Coronal view demonstrating obstructing intraluminal lesion (arrowhead). B, Transverse view demonstrating obstructing intraluminal lesion (arrowhead). The patient was subsequently taken to the operating room for exploratory laparotomy and found to have an obstruction in the distal ileum. What Is Your Diagnosis?

Metastatic lung cancer

Small-bowel intussusception secondary to pelvic adhesions

Phytobezoar

Endometriosis

C. Phytobezoar

C

Phytobezoar

In this patient presenting with a small-bowel obstruction, imaging studies raised concern for intussusception. However, surgical exploration revealed an obstructing, mobile intraluminal mass in the distal ileum 0.3 meters from the ileocecal valve. The mass was milked proximally, and a longitudinal jejunal enterotomy was performed (Video), yielding a phytobezoar confirmed to be a piece of whole corn cob (Figure 2) measuring 3.0 × 1.9 × 1.8 cm on pathological review. The enterotomy was closed transversely and the patient discharged home tolerating a regular diet on postoperative day 3. While an overindulgent holiday meal was suspected, the patient claimed to have no recollection of ever ingesting a whole corn cob.Intraoperative photograph of obstructing lesion. Gentle antegrade pressure on the obstructing lesion through a longitudinal jejunotomy produced a whole, undigested corn cob.Review of the literature on mechanical small-bowel obstruction yields a well-known list of etiologies. Intra-abdominal adhesions are predominant, with a 2000 review reporting involvement in 74% of cases.1 Other etiologies include hernias, malignancies, and inflammatory bowel disease.1 Bezoars are an unusual cause of small bowel obstruction, ranging between 0.4% to 4%2 of cases. Of these, phytobezoars composed of undigested plant matters are most common and can persist in the stomach without ever causing an obstruction.3 While many bezoars remain intragastric, passage through the pylorus into the small intestine can lead to an acute obstruction, usually just proximal to the ileocecal valve.Plain radiography should be obtained whenever a small-bowel obstruction is suspected, with computed tomographic scan serving a useful additional tool. In patients with phytobezoar-related disease, radiographic findings will be similar to those of other causes: a focal transition point with dilated proximal loops of bowel. Pathognomonic findings for bezoars on computed tomography are debatable but may include a mottled intraluminal mass.4 Yet most bezoars are discovered as incidental findings and are not reliably predicted as the source of obstruction on preoperative evaluation.5Bezoars found incidentally or without complete obstruction can often be managed conservatively by dissolution with Coca-Cola6 or endoscopic fragmentation.3 Complete small-bowel obstruction necessitates a surgical approach for removal, most often accomplished by milking the bezoar through a proximal enterotomy to avoid surgical injury to the ileocecal valve.This patient’s history of smoking and lung nodules on computed tomographic scan raise concern for a primary lung malignancy, which can metastasize to the viscera in up to 14% of patients but rarely manifest acute abdominal symptoms and cause perforation more often than obstruction or intussusception.7 This patient had no evidence of intra-abdominal malignancy or lymphadenopathy on exploration. Furthermore, adhesions from her prior gynecologic procedures were minor and did not involve any intraperitoneal organs, a finding belied by adhesive disease’s implication in most small-bowel obstructions.1 Finally, persistent endometriosis after hysterectomy and salphingo-oophorectomy occurs in roughly 10% of patients and presents with nonspecific, gradual symptoms of pelvic pain and dyspareunia.8While other causes of small-bowel obstruction remain more likely, phytobezoars should be considered on the differential of any patient with a small-bowel obstruction, especially in patients with no history of abdominal surgery.

Surgery

A 45-year-old woman presented to the emergency department on the morning after Thanksgiving with sudden, severe, constant epigastric pain that migrated to the right upper quadrant as well as subjective fever and emesis since the previous evening. She reported a failure to pass stool or flatus since the onset of symptoms. She denied hematochezia, melena, or hematemesis. Her medical history was significant for heavy smoking, reflux, and surgical procedures including a right inguinal hernia repair, total abdominal hysterectomy, and bilateral salpingo-oopherectomy, all more than 5 years prior. On examination, she had a distended and tympanic abdomen with tenderness, guarding, and rebound in the epigastrium and right upper quadrant. Vital signs and standard laboratory test results were unremarkable.An upright abdominal plain radiograph showed a distended, thickened stomach and multiple dilated loops of small bowel with air-fluid levels. Contrast-enhanced computed tomography demonstrated a focal area of mixed fat density involving the distal small bowel concerning for a lead point with adjacent mesenteric fat stranding (Figure 1). The scan also revealed multiple bilateral lung nodules.Computed tomography of abdomen. A, Coronal view demonstrating obstructing intraluminal lesion (arrowhead). B, Transverse view demonstrating obstructing intraluminal lesion (arrowhead). The patient was subsequently taken to the operating room for exploratory laparotomy and found to have an obstruction in the distal ileum.

what is your diagnosis?

What is your diagnosis?

Small-bowel intussusception secondary to pelvic adhesions

Metastatic lung cancer

Phytobezoar

Endometriosis

c

female

41-50

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2625159

A 67-year-old white man with a medical history of hypertension presented to the hospital after noting irregular heartbeats on his home blood pressure monitor. He had no palpitations. The electrocardiogram showed several premature ventricular contractions. Results of 30-day Holter monitoring were obtained, and more than 5000 premature ventricular contractions were recorded, including occasional polymorphic ventricular couplets.Transthoracic echocardiography showed normal left ventricular internal dimensions and systolic function. All valves were structurally normal with trace mitral and tricuspid regurgitation. A treadmill exercise stress test demonstrated 2 mm horizontal ST-segment depression in inferior and apical leads with exercise. Cardiac catheterization of the left side of the heart was performed (Figure, A) and can be viewed in the Video.Retrograde filling of the right coronary artery emptying into the main pulmonary artery (A) and a medium-sized area of moderate stress-induced ischemia throughout the right coronary artery territory (B). MC indicates myocardial; Rst, rest; and Str, stress.Results of a regadenoson-stress myocardial positron emission tomographic perfusion test with ammonia labeled with nitrogen N 13 (Figure, B) demonstrated a medium-sized area of moderate stress-induced ischemia throughout the right coronary artery (RCA) territory, with preserved perfusion in the left anterior descending and left circumflex territories.Medical therapy with β-blocker, nifedipine, long-acting nitrate, and flecainide acetateTransposition of the RCA from the pulmonary artery to the aortaLeft internal mammary artery graft to the left anterior descending arteryPercutaneous coronary intervention of the total RCA occlusion What Would You Do Next?

Medical therapy with β-blocker, nifedipine, long-acting nitrate, and flecainide acetate

Transposition of the RCA from the pulmonary artery to the aorta

Left internal mammary artery graft to the left anterior descending artery

Percutaneous coronary intervention of the total RCA occlusion

Anomalous origin of the RCA from the pulmonary artery with a myocardial steal

B

Transposition of the RCA from the pulmonary artery to the aorta

A decision was made to surgically reposition the RCA to the aorta, and the patient underwent a transposition of the RCA from pulmonary artery to the aorta and an autologous patch closure of the pulmonary artery.In 1945, Soloff1 described 4 possible types of anomalies of the coronary arteries originating from the pulmonary artery. Anomalous origin of coronary artery from the pulmonary artery is rare and most frequently involves the left coronary artery, with an incidence rate of 0.008% in the general population compared with a rate of 0.002% involving the RCA. In about 50% of cases, anomalous RCA from the pulmonary artery is associated with other congenital heart defects. Patients with anomalous pulmonary origin of the left coronary artery usually present in infancy with signs of left ventricular ischemia and congestive heart failure, but those with anomalous origin of the RCA may remain asymptomatic until adulthood.2,3Our patient had evidence of reversal of flow in the RCA into the pulmonary artery with no evidence of ostial narrowing and stress-induced ischemia in the RCA territory that is compatible with a myocardial steal. Adults with anomalous origin of the RCA from the pulmonary artery often present with atypical chest pain or are asymptomatic and incidentally diagnosed on coronary angiography. There may be associated ostial stenosis of the RCA that limits the collateral flow and the degree of ischemia.4Congenital coronary malformations are the second leading cause of sudden cardiac death in the young. The presumptive mechanism of sudden death in these patients is ischemia and is generally precipitated by physical exertion. Most patients remain asymptomatic because they have adequate intercoronary collateral vessels to maintain perfusion of the RCA territory with preservation of ventricular function. The collateral vessels can produce a coronary steal phenomenon because of the relative difference in the diastolic pressures between the pulmonary artery and the systemic artery.5The utility of myocardial perfusion imaging in cases of coronary steal remains unclear: Several published reports show the high specificity of demonstrating early ischemia with underlying coronary steal in patients with atherosclerotic disease.6,7 Stress testing can be useful in objectively demonstrating myocardial ischemia if the management strategy remains unclear.Although most patients remain asymptomatic, prophylactic reimplantation of the RCA into the aorta has been recommended to prevent an adverse outcome.8At 1-month follow-up, the patient was recovering well from his surgery with no complaints of palpitations or chest pain.

Cardiology

A 67-year-old white man with a medical history of hypertension presented to the hospital after noting irregular heartbeats on his home blood pressure monitor. He had no palpitations. The electrocardiogram showed several premature ventricular contractions. Results of 30-day Holter monitoring were obtained, and more than 5000 premature ventricular contractions were recorded, including occasional polymorphic ventricular couplets.Transthoracic echocardiography showed normal left ventricular internal dimensions and systolic function. All valves were structurally normal with trace mitral and tricuspid regurgitation. A treadmill exercise stress test demonstrated 2 mm horizontal ST-segment depression in inferior and apical leads with exercise. Cardiac catheterization of the left side of the heart was performed (Figure, A) and can be viewed in the Video.Retrograde filling of the right coronary artery emptying into the main pulmonary artery (A) and a medium-sized area of moderate stress-induced ischemia throughout the right coronary artery territory (B). MC indicates myocardial; Rst, rest; and Str, stress.Results of a regadenoson-stress myocardial positron emission tomographic perfusion test with ammonia labeled with nitrogen N 13 (Figure, B) demonstrated a medium-sized area of moderate stress-induced ischemia throughout the right coronary artery (RCA) territory, with preserved perfusion in the left anterior descending and left circumflex territories.Medical therapy with β-blocker, nifedipine, long-acting nitrate, and flecainide acetateTransposition of the RCA from the pulmonary artery to the aortaLeft internal mammary artery graft to the left anterior descending arteryPercutaneous coronary intervention of the total RCA occlusion

what would you do next?

What would you do next?

Medical therapy with β-blocker, nifedipine, long-acting nitrate, and flecainide acetate

Transposition of the RCA from the pulmonary artery to the aorta

Left internal mammary artery graft to the left anterior descending artery

Percutaneous coronary intervention of the total RCA occlusion

b

male

61-70

White

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2613596

A 47-year-old African American man with a medical history significant for hypertension, type 2 diabetes, and gastroesophageal reflux disease was given atorvastatin at 40 mg daily for a markedly elevated low-density lipoprotein-cholesterol (LDL-C) of 279 mg/dL (millimoles per liter, multiply by 0.0259). He was subsequently tried on various statins, but owing to hip pain thought possibly because of these agents, a rise in liver enzymes, and persistently elevated LDL-C, he was referred to the Boston Medical Center Lipid Clinic Fasting lipid profile in December 2013 on no lipid-lowering agents included an LDL-C level of 232 mg/dL. He restarted atorvastatin at 40 mg daily because it was determined that his hip pain was more likely because of arthritis than statin therapy. The adherence and effectiveness of lipid-lowering therapy were then routinely monitored by measuring direct LDL-C levels, which dropped to 113 mg/dL in June 2014 and 115 mg/dL in October 2015, respectively. Interestingly, his directly measured LDL was 115 mg/dL in October 2015, but a calculated LDL-C was 170 mg/dL in December 2015. Repeat fasting lipid profiles with simultaneously calculated and directly measured LDL-C levels, apolipoprotein B (Apo B), and lipoprotein (a) (Lp[a]) were subsequently assessed in April 2016 and June 2016. They confirmed a marked difference between the direct LDL-C level and calculated LDL-C levels (Table).The marked discordance between the direct and calculated LDL levels is the result of a laboratory error.The patient has familial dysbetalipoproteinemia (type III hyperlipidemia).The marked discordance between the direct and calculated LDL levels is related to the effects of very LDL (VLDL), intermediate-density LDL (IDL), and/or Lp(a).The marked discordance between the direct and calculated LDL levels is the result of excess VLDL cholesterol only. How Do You Interpret These Test Results?

The marked discordance between the direct and calculated LDL levels is the result of a laboratory error.

The patient has familial dysbetalipoproteinemia (type III hyperlipidemia).

The marked discordance between the direct and calculated LDL levels is related to the effects of very LDL (VLDL), intermediate-density LDL (IDL), and/or Lp(a).

The marked discordance between the direct and calculated LDL levels is the result of excess VLDL cholesterol only.

C

The marked discordance between the direct and calculated LDL levels is related to the effects of very LDL (VLDL), intermediate-density LDL (IDL), and/or Lp(a).

The 2013 American College of Cardiology/American Heart Association guidelines on managing blood cholesterol levels recommend a fasting lipid panel to monitor the adherence and effectiveness of statin therapy.1 Although total cholesterol, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) levels are directly measured, LDL-C is calculated by the Friedewald formula in which LDL-C = total cholesterol − HDL-C − (TG/5).2 Among patients with normal TG levels, the Friedewald-calculated LDL level and the directly measured LDL have minimal difference. The formula presupposes that VLDL can be estimated by TG/5, but this is inaccurate when TG is more than 400 mg/dL. The formula has been confirmed to overestimate LDL-C even when TG levels exceed 200 mg/dL.3 Among patients with TG levels more than 200 mg/dL or VLDL levels less than 70 mg/dL, it may be more accurate to measure LDL-C directly.3 The formula is also inaccurate in Friedrickson type III hyperlipidemia (abnormal VLDL and elevated levels of apolipoprotein E [E2/2 phenotype], also known as dysbetalipoproteinemia).4 Elevated Lp(a) levels can also result in higher calculated LDL-C levels, but are not measured with direct methods.2 Non-HDL cholesterol is easily calculated and is a surrogate of all atherogenic particles, especially VLDL and IDL. Apolipoprotein B is the main apolipoprotein of VLDL, IDL, LDL particles, and chylomicrons. Lipoprotein (a) is structurally similar to LDL with the addition of apolipoprotein (a), which is genetically determined and involved in the atherogenic process. When Apo B and LDL-C levels are discordant, atherosclerotic cardiovascular disease risk tracks closer with Apo B.5 The costs of measuring Apo B levels and Lp(a) at a large academic safety-net hospital are $21.11 and $17.63, respectively.Application of the Test Results to This PatientThis patient had a discrepancy between his levels of direct and calculated LDL-C. We initially considered that the difference between the direct and calculated LDL-C levels could be because of type III dysbetalipoproteinemia. Sniderman et al6 have suggested that a ratio of total cholesterol (millimoles per liter)/Apo B (grams per liter) levels greater or equal to 6.2 and TG (millimoles per liter)/Apo B (grams per liter) levels less than 10 are consistent with this condition. However, this patient had a TC/Apo B level of 6.1 and a TG/Apo B level of 3.1, making the diagnosis of type III hyperlipidemia less likely.6We reasoned that this discrepancy was not because of the effects of VLDL and IDL but because of his elevated Lp(a) level. Lipoprotein (a) is not routinely measured directly but is included in the calculated LDL-C equation with IDL and VLDL. Hence, the direct measurement of Lp(a) in this case was useful. Knowledge of an increased Lp(a) level can identify patients with a significant increase for residual atherosclerotic cardiovascular disease risk despite statin therapy. Among these patients, statin therapy will result in a less than predicted decline in LDL-C and may indicate the need for adjunctive therapies to lower LDL-C more aggressively.7 Randomized clinical trials targeting Lp(a) directly are eagerly awaited.Low-density lipoprotein cholesterol can be measured directly as a routine test. Attention might be targeted on using non-HDL-C to assess risk, as this fraction contains all the cholesterol components in atherogenic lipoproteins (LDL, VLDL, IDL, and Lp[a]). Studies using an intravascular ultrasound suggest that atheroma regression tracks closer with changes in non-HDL-C than LDL-C levels.8Based on the finding of increased Lp(a) and elevated residual atherosclerotic cardiovascular disease risk, his atorvastatin dosage was increased to 80 mg daily, and ezetimibe at 10 mg daily was recommended. The expensive copay associated with ezetimibe will force him to defer its use until it becomes available generically in 2017.•The Friedewald calculated LDL-C level obtained through a standard fasting lipid profile has limitations. It is less accurate among patients with high triglycerides (≥200 mg/dL [millimoles per liter, multiply by 0.0113]). When TG ≥ 400 mg/dL, direct LDL measurement should be used.•The marked discordance between direct LDL measurements and calculated LDL levels from the Friedewald formula when TG > 400 mg/dL not only indicate excess VLDL and IDL, but also suggest the possibility of elevated Lp(a) and/or type III hyperlipidemia. In our case, measuring Lp(a) and apolipoprotein B levels was not expensive and provided useful information to evaluate the observed discrepancies in lipid abnormalities. The very elevated Lp(a) informed our risk estimation and suggested that more aggressive LDL-C lowering was reasonable.•The measurement of non-HDL may be a useful way to follow-up patients with elevated TG and an increased atherosclerotic cardiovascular disease risk.

Diagnostic

A 47-year-old African American man with a medical history significant for hypertension, type 2 diabetes, and gastroesophageal reflux disease was given atorvastatin at 40 mg daily for a markedly elevated low-density lipoprotein-cholesterol (LDL-C) of 279 mg/dL (millimoles per liter, multiply by 0.0259). He was subsequently tried on various statins, but owing to hip pain thought possibly because of these agents, a rise in liver enzymes, and persistently elevated LDL-C, he was referred to the Boston Medical Center Lipid Clinic Fasting lipid profile in December 2013 on no lipid-lowering agents included an LDL-C level of 232 mg/dL. He restarted atorvastatin at 40 mg daily because it was determined that his hip pain was more likely because of arthritis than statin therapy. The adherence and effectiveness of lipid-lowering therapy were then routinely monitored by measuring direct LDL-C levels, which dropped to 113 mg/dL in June 2014 and 115 mg/dL in October 2015, respectively. Interestingly, his directly measured LDL was 115 mg/dL in October 2015, but a calculated LDL-C was 170 mg/dL in December 2015. Repeat fasting lipid profiles with simultaneously calculated and directly measured LDL-C levels, apolipoprotein B (Apo B), and lipoprotein (a) (Lp[a]) were subsequently assessed in April 2016 and June 2016. They confirmed a marked difference between the direct LDL-C level and calculated LDL-C levels (Table).The marked discordance between the direct and calculated LDL levels is the result of a laboratory error.The patient has familial dysbetalipoproteinemia (type III hyperlipidemia).The marked discordance between the direct and calculated LDL levels is related to the effects of very LDL (VLDL), intermediate-density LDL (IDL), and/or Lp(a).The marked discordance between the direct and calculated LDL levels is the result of excess VLDL cholesterol only.

how do you interpret these test results?

How do you interpret these results?

The marked discordance between the direct and calculated LDL levels is the result of excess VLDL cholesterol only.

The marked discordance between the direct and calculated LDL levels is the result of a laboratory error.

The patient has familial dysbetalipoproteinemia (type III hyperlipidemia).

The marked discordance between the direct and calculated LDL levels is related to the effects of very LDL (VLDL), intermediate-density LDL (IDL), and/or Lp(a).

d

male

41-50

African American

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2606783

A man in his 50s was referred for a 6-month history of swelling involving the nasal bridge and right eye, accompanied by intermittent ipsilateral epistaxis. His medical history was notable for allergic rhinitis and well-controlled type 2 diabetes mellitus. The prior biopsy diagnosis from the area of swelling was inflammatory nasal polyp. Physical examination revealed tenderness to palpation over the right nasal bridge and mild right proptosis. Flexible and rigid nasal endoscopy demonstrated a right-sided exophytic mass visible between the middle turbinate and nasal septum. Computed tomography showed a large, right-sided mass centered in the ethmoid sinus with expansion into the anterior skull base, anterior cribriform plate, and right medial orbit. Magnetic resonance imaging showed vascularity in the lesion and early intracranial involvement with transdural spread but no evidence of invasion into the meninges or brain. The patient was taken for surgery, and findings from intraoperative frozen section analysis were consistent with a spindle cell neoplasm. Definitive skull base resection of the mass was deferred until final pathological diagnosis was obtained, given the morbidity with skull base resection. The final pathology report showed an infiltrative, low-grade, malignant spindle cell neoplasm with immunoreactivity for BCL2 protein and neural marker, S-100 protein, and focal immunoreactivity for smooth muscle markers SMA and HHF35 (Figure). Cytoplasmic immunoreactivity for β-catenin was noted, and nonreactive immunostains included CD31, CD34, epithelial membrane antigen (EMA), and CD99. In addition, there was minimal mitotic activity, and no tumoral necrosis was present. There was no regional or distant metastasis, and TNM staging was cT4N0M0.Histopathologic photomicrographs of a biopsy specimen from a mass centered in the ethmoid sinus. A and B, Hematoxylin-eosin. A, Spindle cells in fascicular pattern. B, Invagination of respiratory-type epithelium. C, Tissue section showing strong nuclear and cytoplasmic immunologic staining for S-100 protein. D, Immunologic staining for smooth muscle actin showing patchy immunoreactivity in tumor cells. What Is Your Diagnosis?

Low-grade malignant peripheral nerve sheath tumor

Monophasic synovial sarcoma

Biphenotypic sinonasal sarcoma

Glomangiopericytoma

C. Biphenotypic sinonasal sarcoma

C

Biphenotypic sinonasal sarcoma

Biphenotypic sinonasal sarcoma (BSNS), previously termed low-grade sinonasal sarcoma with neurogenic and myogenic features, is a recently described low-grade sinonasal sarcoma.1 BSNS is a hypercellular, unencapsulated infiltrative malignant neoplasm that is most often located within the nasal cavity or ethmoid sinuses. Classically, mitotic activity is low, and no tumoral necrosis is present. Thus, these lesions are classified as low-grade sarcomas despite their bone infiltrative tendencies.1 The tumor has been strongly associated with translocations involving the PAX3 gene, most notably t(2;4)(q35;q31.1) translocation forming a PAX3-MAML3 fusion.2 Other described gene fusions include PAX3-NCOA1 and PAX3-NCOA2.3The differential diagnosis includes cellular spindle cell neoplasm of the sinonasal tract with, namely, glomangiopericytomas, cellular schwannomas, fibrosarcomas, malignant peripheral nerve sheath tumors, and monophasic synovial sarcomas. In this case, findings from interphase fluorescence in situ hybridization for monophasic synovial sarcoma were interpreted as negative. Collectively, these results are consistent with the original literature descriptions of BSNS.1,2,4 Some authors have reported nuclear β-catenin positivity in these tumors. A recent retrospective case series5 demonstrated β-catenin in 91% of BSNS; however, only cytoplasmic staining was identified in the present tumor. With these studies in mind, Rooper and colleagues5 postulated that BSNS can be reliably identified without genetic testing by using an expanded immunohistochemistry panel that includes immunoreactivity for S-100, actin, calponin, nuclear β-catenin, factor XIIIa; patchy immunoreactivity desmin, myogenin, cytokeratins, EMA; and absolute negative transcription factor SOX10.Several cases describe the frequent finding of hyperplastic respiratory epithelium penetrating and surrounded by the tumor, perhaps explaining the pathology report noting components of inflammatory nasal polyps (Figure, B).1,6 The relatively new classification of BSNS and the combination of features found in other neoplasms makes it a difficult pathological diagnosis. It is plausible that before the judicious use of immunohistochemical analysis and molecular studies, BSNS was unknowingly classified in the past as sinonasal fibrosarcoma or malignant peripheral nerve sheath tumor, and cellular schwannomas7 Treatment and prognosis are based on histologic grade, tumor size, and effectiveness of surgical resection.4In all the reported cases of biphenotypic sinonasal sarcoma, there has been only 1 death attributed to this neoplasm.3,5 Recurrence is well-documented following resections.1 Risk factor associations have not been established for BSNS. The patient described herein works as a locksmith, potentially exposing him to metal shavings. He has a remote history of smoking. He is planning to undergo anterior craniofacial resection based on the consensus recommendations of our institution’s multidisciplinary head and neck tumor board.

General

A man in his 50s was referred for a 6-month history of swelling involving the nasal bridge and right eye, accompanied by intermittent ipsilateral epistaxis. His medical history was notable for allergic rhinitis and well-controlled type 2 diabetes mellitus. The prior biopsy diagnosis from the area of swelling was inflammatory nasal polyp. Physical examination revealed tenderness to palpation over the right nasal bridge and mild right proptosis. Flexible and rigid nasal endoscopy demonstrated a right-sided exophytic mass visible between the middle turbinate and nasal septum. Computed tomography showed a large, right-sided mass centered in the ethmoid sinus with expansion into the anterior skull base, anterior cribriform plate, and right medial orbit. Magnetic resonance imaging showed vascularity in the lesion and early intracranial involvement with transdural spread but no evidence of invasion into the meninges or brain. The patient was taken for surgery, and findings from intraoperative frozen section analysis were consistent with a spindle cell neoplasm. Definitive skull base resection of the mass was deferred until final pathological diagnosis was obtained, given the morbidity with skull base resection. The final pathology report showed an infiltrative, low-grade, malignant spindle cell neoplasm with immunoreactivity for BCL2 protein and neural marker, S-100 protein, and focal immunoreactivity for smooth muscle markers SMA and HHF35 (Figure). Cytoplasmic immunoreactivity for β-catenin was noted, and nonreactive immunostains included CD31, CD34, epithelial membrane antigen (EMA), and CD99. In addition, there was minimal mitotic activity, and no tumoral necrosis was present. There was no regional or distant metastasis, and TNM staging was cT4N0M0.Histopathologic photomicrographs of a biopsy specimen from a mass centered in the ethmoid sinus. A and B, Hematoxylin-eosin. A, Spindle cells in fascicular pattern. B, Invagination of respiratory-type epithelium. C, Tissue section showing strong nuclear and cytoplasmic immunologic staining for S-100 protein. D, Immunologic staining for smooth muscle actin showing patchy immunoreactivity in tumor cells.

what is your diagnosis?

What is your diagnosis?

Monophasic synovial sarcoma

Low-grade malignant peripheral nerve sheath tumor

Biphenotypic sinonasal sarcoma

Glomangiopericytoma

c

male

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2611960

A woman in her 60s presented with mild to moderate trismus and swelling on the left side of the face of a few months’ duration. Her medical history was significant for herpes zoster and self-limited vertigo approximately 3 years prior. Her physical examination was remarkable for left-sided facial swelling. No deficits of the facial or trigeminal nerves were detected. Magnetic resonance imaging (MRI) was performed (Figure).Magnetic resonance imaging, axial views. A. T1-weighted image demonstrating a mass lying on the anterior surface of the eroded left mandibular condyle with homogeneous isointensity relative to skeletal muscle. B, Postcontrast T1-weighted image with fat suppression showing homogeneous, avid enhancement of the mass. C, T2-weighted image showing homogeneous moderately hyperintense signal. D, Diffusion-weighted image is significant for marked diffusion restriction. What Is Your Diagnosis?

Plasmacytoma

Ameloblastoma

Osteosarcoma

Venous malformation

A. Plasmacytoma

A

Plasmacytoma

The masticator space mass lies along the anterior surface of the eroded mandibular condyle and is distinguished radiographically by its avid solid enhancement and bland, homogenous signal characteristics. It is approximately isointense to adjacent skeletal muscle on T1-weighted MRI with only moderate T2 hyperintensity and marked restricted diffusion. These signal characteristics point to a highly cellular neoplasm, such as plasmacytoma or lymphoma, “small round blue-cell” tumors with high nucleus-to-cytoplasm ratio. Ameloblastomas are benign but aggressive odontogenic tumors that most commonly arise from the posterior mandibular body. They classically are composed of multiloculated cystic spaces and are considerably more heterogeneous than the displayed lesion.1 Similarly, osteosarcoma appears most commonly as markedly heterogeneous destructive masses that are often with associated osseous matrix and periosteal reaction. Venous malformations occur commonly in the masticator space and are characterized by intramuscular foci of contrast enhancement and marked T2 hyperintensity, often in association with round areas of signal void representing phleboliths.2Plasma cell neoplasms were first described in 1846 by Dalrymple and Bence Jones, who classified them as solitary plasmacytoma of bone (SPB), extramedullary plasmacytoma (EMP), and multiple myeloma (MM). Extramedullary plasmacytomas are extremely rare tumors that are almost entirely composed of plasma cells.3 They most commonly occur in men in the sixth to seventh decades of life.3,4 Eighty percent of EMPs arise in the head and neck,3 most commonly in the upper aerodigestive tract.5 Compared with SPB, EMP has a lower probability of progressing to MM (53%-70% of SPBs vs 10%-36% in EMPs).3,6,7 Tirumani et al8 described 2 radiologic patterns of extramedullary plasmacytomas: contiguous with bone and noncontiguous with bone. They identified many common features, including homogeneity, diffuse enhancement, and marked diffusion restriction with hypointensity to isointensity on T1-weighted images seen in both groups. On T2-weighted imaging, however, EMPs contiguous with bone (as in this case) are more often isointense to hyperintense on T2-weighting, whereas those that are noncontiguous with bone are more likely to be hypointense on T2-weighting, similar to lymphoma.Treatment of solitary plasmacytoma is mainly with surgery and/or external beam radiation.3,8 These tumors are radiosensitive, and typical doses are in the 40 to 60 Gy range.3,4,6 Extramedullary plasmacytomas respond better to surgical treatment with or without radiation than radiation alone.5 Local recurrence occurs in 6% to 10% of treated EMPs.3

General

A woman in her 60s presented with mild to moderate trismus and swelling on the left side of the face of a few months’ duration. Her medical history was significant for herpes zoster and self-limited vertigo approximately 3 years prior. Her physical examination was remarkable for left-sided facial swelling. No deficits of the facial or trigeminal nerves were detected. Magnetic resonance imaging (MRI) was performed (Figure).Magnetic resonance imaging, axial views. A. T1-weighted image demonstrating a mass lying on the anterior surface of the eroded left mandibular condyle with homogeneous isointensity relative to skeletal muscle. B, Postcontrast T1-weighted image with fat suppression showing homogeneous, avid enhancement of the mass. C, T2-weighted image showing homogeneous moderately hyperintense signal. D, Diffusion-weighted image is significant for marked diffusion restriction.

what is your diagnosis?

What is your diagnosis?

Ameloblastoma

Osteosarcoma

Plasmacytoma

Venous malformation

c

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2613592

A white man in his 40s presented with a slowly enlarging, nontender, left-sided neck mass at the angle of the mandible that had been present for 4 years. Fine-needle aspiration was performed twice, each time with inconclusive results. Computed tomography (CT) of the neck showed a heterogeneous mass located immediately adjacent to the tail of the left parotid. No other masses were noted. He underwent a left superficial parotidectomy with en bloc removal of the mass. Pathologic findings revealed a 3.0 × 2.9 × 1.9-cm, encapsulated, tan, soft nodule within the specimen. The nodule had peripheral cystic spaces as well as focal areas of hemorrhage and a 0.5 × 0.4 × 0.4-cm area of calcification within the periphery. The entire tumor was confined within a periparotid lymph node, almost completely replacing it. Histopathologic findings (Figure) showed a mixture of dark, granular, basophilic acinar cells and eosinophilic intercalated ductal cells. The acinar cells contained periodic acid–Schiff–positive, diastase-resistant intracytoplasmic granules, whereas the ductal cells were both fusiform and cuboidal forming small ductlike structures. The neoplasm also exhibited focal areas of hyaline sclerosis without necrosis. What Is Your Diagnosis?

Pleomorphic adenoma

Mucoepidermoid carcinoma

Acinic cell carcinoma

HIV-associated benign lymphoepithelial cyst

C. Acinic cell carcinoma

C

Acinic cell carcinoma

Acinic cell carcinoma (ACC) typically arises in the parotid or minor salivary glands. Although ACC commonly has lymphatic stroma, in this case the tumor appeared to arise completely within a periparotid lymph node with an intact capsule and peripheral lymphoid follicles. This finding suggests a rare case of ACC arising within a periparotid lymph node.1Fine-needle aspiration is typically a reliable tool in characterizing neck masses; however, it is less reliable in providing the precise classification and grade of salivary gland malignant neoplasms. A few malignant neoplasms are particularly prone to diagnostic error. For example, ACC is frequently interpreted as benign or even nonneoplastic, and low-grade lymphomas are often discounted as inflammatory processes.2 The malignant lesions that are most often misdiagnosed as benign are lymphomas (57%), acinic cell carcinomas (49%), low-grade mucoepidermoid carcinomas (43%), and adenoid cystic carcinomas (33%).3The diagnosis of ACC is based on histopathologic findings. Immunohistochemical analysis (IHC) is rarely of diagnostic value, but it can assist in uncertain cases. The present case showed staining for CEA, EMA, calponin, and 2% to 5% Ki-67 positive nuclear staining (an indicator of proliferation).4 IHC for S-100, mammaglobin (both typically positive in mammary analogue secretory carcinoma), and DOG1 (anoctamin-1, typically positive in in ACC) were not performed. While most cases of ACC arise in either the parotid gland or minor salivary glands, a periparotid lymph node was determined to be the primary site of this neoplasm. The possibility of a metastasis was rejected based on the lymph node’s intact peripheral lymphoid follicles and capsule, and the fact that the superficial parotid gland was found to contain no abnormalities. It is also recognized that ACC is frequently associated with encapsulation and lymphoid stroma that can resemble a lymph node.5 This contributes to the difficulty in differentiating a primary tumor from a metastatic origin. Further supporting the conclusion that this represented a primary tumor, the neoplasm was completely confined within its own capsule with intact nodal tissue rather than containing the typical lymphoid stroma associated with ACC.Ectopic salivary gland tissue is often found within intraparotid lymph nodes.5,6 During embryogenesis, parotid buds proliferate and surround lymph nodes, giving rise to the intraglandular lymph nodes.6 It is not unexpected that ACC can arise in residual salivary tissue that is within the intraparotid lymph nodes. Conversely, it is very uncommon to find ectopic salivary tissue within extraglandular lymph nodes.5,6 Abrams et al1 reported a series of 77 ACCs, only 3 of which arose in intraparotid or periparotid lymph nodes. The authors1 did not specify how many were found in periparotid lymph nodes. Perzin and LiVolsi6 described a case in which a primary ACC was found in ectopic salivary gland tissue in a periparotid lymph node. This scenario is likely in the present case.Resection margins in the case were negative. The patient was offered the option of postoperative radiation therapy. He elected to forego radiation therapy and has been followed closely for over 1 year without evidence of recurrence. The literature suggests that a 10-year follow-up is required to adequately determine conclusive treatment outcomes.7,8 While most cases of ACC have a favorable outcome, this tumor has the potential to undergo high-grade transformation (dedifferentiation), which can significantly alter prognosis. Because only 3 such cases have been previously reported, more experience with this neoplasm is needed to refine patient treatment recommendations and prognosis.

General

A white man in his 40s presented with a slowly enlarging, nontender, left-sided neck mass at the angle of the mandible that had been present for 4 years. Fine-needle aspiration was performed twice, each time with inconclusive results. Computed tomography (CT) of the neck showed a heterogeneous mass located immediately adjacent to the tail of the left parotid. No other masses were noted. He underwent a left superficial parotidectomy with en bloc removal of the mass. Pathologic findings revealed a 3.0 × 2.9 × 1.9-cm, encapsulated, tan, soft nodule within the specimen. The nodule had peripheral cystic spaces as well as focal areas of hemorrhage and a 0.5 × 0.4 × 0.4-cm area of calcification within the periphery. The entire tumor was confined within a periparotid lymph node, almost completely replacing it. Histopathologic findings (Figure) showed a mixture of dark, granular, basophilic acinar cells and eosinophilic intercalated ductal cells. The acinar cells contained periodic acid–Schiff–positive, diastase-resistant intracytoplasmic granules, whereas the ductal cells were both fusiform and cuboidal forming small ductlike structures. The neoplasm also exhibited focal areas of hyaline sclerosis without necrosis.

what is your diagnosis?

What is your diagnosis?

Pleomorphic adenoma

HIV-associated benign lymphoepithelial cyst

Mucoepidermoid carcinoma

Acinic cell carcinoma

d

male

41-50

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2616158

A teenage boy was referred with a progressive 2-week history of blurred vision in his right eye and right ear pain, which had worsened in the past 7 days. This change prompted a visit to an optometrist, who found a mild decrease in visual acuity and minor cataract in the right eye. His primary care physician diagnosed his ear pain as acute otitis media and prescribed a course of amoxicillin-clavulanate; however, the young man’s vision continued to deteriorate and became associated with the onset of right eye swelling and forehead tenderness. A repeat eye examination by an ophthalmologist was performed and showed normal peripheral visual acuity with a decrease in central vision and confirmed proptosis. The patient had not experienced nasal congestion, epistaxis, weight loss, fevers, or chills. Physical examination included right eye proptosis and restricted eye movement. A computed tomographic (CT) scan with contrast of the face showed a small relatively homogenous mass in the right anterior nasal cavity invading the right orbit, and a magnetic resonance image (MRI) with contrast showed a right superior nasal cavity mass, with invasion of the right orbit and right ethmoidal sinus with extension to the overlying soft-tissue scalp (Figure). A 30° endoscope was used to visualize the superior nasal cavity and revealed a fleshy red soft-tissue mass. Several biopsy specimens were taken and sent for frozen pathologic evaluation.A, Postintravenous contrast computed tomographic (CT) scan of the face showing a relatively homogenous mass of the right ethmoid complex with invasion of the orbit and extension to the nasal cavity (arrowhead). B, Fast spin echo (FSE) T2 magnetic resonance image (MRI) of the right ethmoidal/orbital soft-tissue mass (arrowhead). C, Positron emission tomographic (PET) scan of the face with fludeoxyglucose F 18 showing increased uptake within the right ethmoid air cells and nasal cavity, and in the medial right orbit. What Is Your Diagnosis?

Esthesioneuroblastoma

Rhabdomyosarcoma

Ethmoid mucocele

Sinonasal undifferentiated carcinoma

B. Rhabdomyosarcoma

B

Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and can occur anywhere in the body. It is a tumor of mesenchymal origin and develops in the striated muscle.1 The 2 most common locations are the genitourinary system and the head and neck (typically spreading to parameningeal spaces and meningeal areas).2 There are 4 histological subtypes of RMS: embryonal, alveolar, spindle cell or sclerosing, and the pleomorphic tumor.Pediatric sinonasal tumors remain difficult to diagnose. Rhabdomyosarcoma usually mimics common allergic symptoms of nasal congestion; however, 53% of patients may present with more serious neuropathic abnormalities.1,3 Reilly et al4 looked at nonorbital tumors of the head and neck and found overall 5-year survival rate of approximately 75%.To diagnose RMS, the clinician must identify and localize the tumors. The best imaging modalities that are currently available are CT and MRI. Gomaa et al5 showed that these imaging modalities are needed to determine the location and the extent of metastases of sinonasal tumors.Magnetic resonance imaging has greater sensitivity than CT to distinguish inflammatory tissue from tumor and to demonstrate intracranial extension as well as a better ability to determine involvement of the neural and vasculature structures of the head and neck region.5,6 Both CT and MRI can be used to determine the extent of involvement of the surrounding tissues and the aggressiveness of the tumor. For example, while bony remodeling indicates a slow benign process, as may occur in mucocele, bony destruction usually indicates a more malignant process.6Certain imaging characteristics, in addition to the patient history and presentation, may be indicative of the type of tumor present. Esthesioneuroblastoma is a tumor of neural crest origin. The presence of a mass in the caudal nasal cavity with extension to the neurocranium is highly suggestive of esthesioneuroblatoma.7 Sinonasal undifferentiated carcinoma (SNUC) is a tumor of paranasal sinuses. It has radiographic features of a soft-tissue mass with heterogenous enhancement on CT. On MRI, SNUC appears isointense to muscle on T1, likely hyperintense on T2, and enhances heterogeneously. Mucoceles have cystic characteristics on both CT and MRI. If not infected, mucoceles are hypodense on CT and show increased T2 signal on MRI. They do not enhance on either CT or MRI. Chronically, mucoceles become hyperdense on CT and hypointense on T2 MRI. Rhabdomyosarcomas, as in the case described herein, are usually seen as a solitary soft-tissue mass. Although perineural, adjacent osseous destruction or metastatic spread can be visualized, imaging characteristics are nonspecific.In this case, the contrast-enhanced CT, as seen in the Figure, A, showed a mass within the right ethmoid complex/nasal cavity with invasion of the right orbit and right frontal sinus. There was invasion of the right frontal scalp (not shown) through the outer cortex of the frontal sinus. The MRI image in the Figure, B, did not show cystic or necrotic components within the mass.Positron emission tomography (PET) (Figure, C) performed after tissue biopsy but before final diagnosis showed increased glucose uptake within the mass, which is highly concerning for a malignant process. Multiple neck nodes and a superficial left femoral node also showed increased glucose uptake, causing concern for metastasis.There are inherent limitations to imaging because the diagnosis of RMS will always need to be made based on a biopsy specimen of the tumor. However, the CT, MRI, and PET scan helped ensure that the biopsy could be safely performed without the risk of bleeding, as would occur with a vascular tumor, and minimized risk of cerebrospinal fluid leak, which could occur with dural invasion from any malignant sinonasal mass.

General

A teenage boy was referred with a progressive 2-week history of blurred vision in his right eye and right ear pain, which had worsened in the past 7 days. This change prompted a visit to an optometrist, who found a mild decrease in visual acuity and minor cataract in the right eye. His primary care physician diagnosed his ear pain as acute otitis media and prescribed a course of amoxicillin-clavulanate; however, the young man’s vision continued to deteriorate and became associated with the onset of right eye swelling and forehead tenderness. A repeat eye examination by an ophthalmologist was performed and showed normal peripheral visual acuity with a decrease in central vision and confirmed proptosis. The patient had not experienced nasal congestion, epistaxis, weight loss, fevers, or chills. Physical examination included right eye proptosis and restricted eye movement. A computed tomographic (CT) scan with contrast of the face showed a small relatively homogenous mass in the right anterior nasal cavity invading the right orbit, and a magnetic resonance image (MRI) with contrast showed a right superior nasal cavity mass, with invasion of the right orbit and right ethmoidal sinus with extension to the overlying soft-tissue scalp (Figure). A 30° endoscope was used to visualize the superior nasal cavity and revealed a fleshy red soft-tissue mass. Several biopsy specimens were taken and sent for frozen pathologic evaluation.A, Postintravenous contrast computed tomographic (CT) scan of the face showing a relatively homogenous mass of the right ethmoid complex with invasion of the orbit and extension to the nasal cavity (arrowhead). B, Fast spin echo (FSE) T2 magnetic resonance image (MRI) of the right ethmoidal/orbital soft-tissue mass (arrowhead). C, Positron emission tomographic (PET) scan of the face with fludeoxyglucose F 18 showing increased uptake within the right ethmoid air cells and nasal cavity, and in the medial right orbit.

what is your diagnosis?

What is your diagnosis?

Rhabdomyosarcoma

Sinonasal undifferentiated carcinoma

Ethmoid mucocele

Esthesioneuroblastoma

a

male

11-20

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2612187

A woman in her 20s was referred to the Massachusetts Eye and Ear Infirmary Neuro-Ophthalmology Service with a 2-month complaint of frequent headaches and 1 week of blurry vision in her left eye. Her ocular history was significant only for refractive error. Her medical history revealed systemic hypertension, depression, and obesity. Her current medications included hydrochlorothiazide and fluoxetine. On review of systems, she endorsed nausea as well as paresthesia in her hands.Neuro-ophthalmic examination revealed visual acuities of 20/20 OD and 20/40 OS, with no pinhole improvement. Color vision (Ishihara pseudoisochromatic plates) was within normal limits bilaterally, although it was noted to be slightly slower in the left eye. With the Amsler grid, she reported significant metamorphopsia in the left eye. Pupils were symmetric with slow responses bilaterally but without afferent defects. Applanation tonometry revealed pressures of 16 mm Hg OD and 17 mm Hg OS. Slitlamp examination revealed no cells in the anterior chamber or the anterior vitreous in either eye. Automated (Humphrey) visual field testing revealed enlargement of the blind spot in the right eye (mean deviation, −2.91 dB) and generalized, nonspecific depression in the left eye (mean deviation, −3.41 dB). Examination of her fundus was notable for bilateral optic disc swelling (Frisén grade 2 in each eye) as well as unilateral macular exudates, subretinal fluid, and subretinal hemorrhages in the left eye (Figure 1). Results from brain magnetic resonance imaging with magnetic resonance venography with and without contrast were normal.A, Color fundus photograph demonstrating Frisén grade 2 optic disc edema. B, Color fundus photograph demonstrating Frisén grade 2 optic disc edema associated with subretinal fluid, exudate, and retinal hemorrhages.Perform a lumbar puncture with opening pressure, routine chemistry, and cell count analysis What Would You Do Next?

Observe the patient and treat headaches conservatively

Consult surgery for immediate surgical intervention

Perform a lumbar puncture with opening pressure, routine chemistry, and cell count analysis

Begin treatment with high-dose corticosteroids

Idiopathic intracranial hypertension, with papilledema complicated by peripapillary choroidal neovascular membrane

C

Perform a lumbar puncture with opening pressure, routine chemistry, and cell count analysis

A lumbar puncture revealed an opening pressure of 30 cm H2O (normal range, 10-25 cm H2O), a glucose level of 67 mg/dL (normal range, 50-75 mg/dL), a total protein level of 21 mg/dL (normal range, 5-45 mg/dL), and no nucleated cells. Fluorescein angiography revealed a lesion adjacent to the optic disc edema with leakage of dye noted in the early-phase frame and a pattern of leakage persistent in the late-phase frames consistent with choroidal neovascularization (Figure 2). Optical coherence tomography demonstrated intraretinal and subretinal fluid with a small pigment epithelial detachment. Based on the findings of elevated cerebrospinal fluid pressure with a normal magnetic resonance imaging with magnetic resonance venography and bland cerebrospinal fluid constituents, a diagnosis of idiopathic intracranial hypertension was made.Late-phase frame of fluorescein angiography showing dye leakage from choroidal neovascularization.Idiopathic intracranial hypertension is a vision-threatening idiopathic disorder characterized by elevated intracranial pressure in the absence of a mass lesion. Patients typically are overweight women of childbearing age who present with headache worsened by recumbence, transient obscurations of vision, and pulsatile tinnitus. Many clinicians follow the modified Dandy criteria, initially developed in 1937, which requires a normal neurological examination except for cranial nerve deficits.1 Neuroimaging, such as with magnetic resonance imaging, is mandated to rule out the possibility of an intracranial lesion or dural venous sinus thrombosis. Next, a lumbar puncture in the recumbent position is obtained to measure the opening pressure, as well as analysis of the cerebrospinal fluid for evidence of inflammatory, infectious, and malignant processes.The goal of therapy is to decrease the intracranial pressure to preserve optic nerve function. This is typically achieved with oral acetazolamide, which decreases cerebrospinal fluid production at the level of the choroid plexus. A short course of oral corticosteroids can be added in the setting of early visual field loss or poor response to initial management. Progression may occur in some patients and require surgical intervention, such as optic nerve sheath fenestration, ventriculoperitoneal, or lumboperitoneal shunt.2Choroidal neovascularization is a rare complication of optic nerve edema.3 However, as in this patient, it can be directly responsible for loss of visual acuity—a deficit that does not typically occur secondary to papilledema alone. Historically, macular photocoagulation, photodynamic therapy, or other surgical options were used as treatment for choroidal neovascularization, but the primary treatment today is intravitreous anti–vascular endothelial growth factor therapy.The patient underwent 2 intravitreous bevacizumab injections, with resolution of leakage from the choroidal neovascularization membranes. She also started first-line medical therapy for idiopathic intracranial hypertension (acetazolamide 500-mg extended-release capsules twice daily by mouth), which provided good symptomatic relief of her headaches, numbness, and tingling. At most recent follow-up 4 months later, the visual acuity had improved to 20/25 OS, with near total resolution of the subretinal fluid.

Ophthalmology

A woman in her 20s was referred to the Massachusetts Eye and Ear Infirmary Neuro-Ophthalmology Service with a 2-month complaint of frequent headaches and 1 week of blurry vision in her left eye. Her ocular history was significant only for refractive error. Her medical history revealed systemic hypertension, depression, and obesity. Her current medications included hydrochlorothiazide and fluoxetine. On review of systems, she endorsed nausea as well as paresthesia in her hands.Neuro-ophthalmic examination revealed visual acuities of 20/20 OD and 20/40 OS, with no pinhole improvement. Color vision (Ishihara pseudoisochromatic plates) was within normal limits bilaterally, although it was noted to be slightly slower in the left eye. With the Amsler grid, she reported significant metamorphopsia in the left eye. Pupils were symmetric with slow responses bilaterally but without afferent defects. Applanation tonometry revealed pressures of 16 mm Hg OD and 17 mm Hg OS. Slitlamp examination revealed no cells in the anterior chamber or the anterior vitreous in either eye. Automated (Humphrey) visual field testing revealed enlargement of the blind spot in the right eye (mean deviation, −2.91 dB) and generalized, nonspecific depression in the left eye (mean deviation, −3.41 dB). Examination of her fundus was notable for bilateral optic disc swelling (Frisén grade 2 in each eye) as well as unilateral macular exudates, subretinal fluid, and subretinal hemorrhages in the left eye (Figure 1). Results from brain magnetic resonance imaging with magnetic resonance venography with and without contrast were normal.A, Color fundus photograph demonstrating Frisén grade 2 optic disc edema. B, Color fundus photograph demonstrating Frisén grade 2 optic disc edema associated with subretinal fluid, exudate, and retinal hemorrhages.Perform a lumbar puncture with opening pressure, routine chemistry, and cell count analysis

what would you do next?

What would you do next?

Observe the patient and treat headaches conservatively

Perform a lumbar puncture with opening pressure, routine chemistry, and cell count analysis

Consult surgery for immediate surgical intervention

Begin treatment with high-dose corticosteroids

b

female

21-30

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2613114

A man in his 50s with an unremarkable ocular history was referred for atypical corneal deposits of the right eye. On examination, visual acuity was 20/25 OD with correction, and the superior cornea showed an intact epithelium, mild stromal thinning, and pannus with faint yellow-white subepithelial deposits at the leading edge (Figure 1A). There were no other abnormalities reported on examination. The patient was treated conservatively with lubrication. Slitlamp photographs of corneal findings. A, Appearance of the cornea at time of the initial presentation. B, Appearance of the cornea 1 year later, with more prominent neovascularization and progression of deposits toward the visual axis.A year later, best-corrected visual acuity had decreased to 20/30 OD with against-the-rule astigmatism. There was progressive corneal thinning and a dense, serpentine network of subepithelial deposits with adjacent neovascularization in the superior cornea, extending toward the visual axis (Figure 1B).Subconjunctival injection of anti–vascular endothelial growth factor medicationRefraction with rigid gas permeable contact lens fitting What Would You Do Next?

Crescent-shaped lamellar keratoplasty

Thorough ocular adnexal evaluation with eyelid eversion

Subconjunctival injection of anti–vascular endothelial growth factor medication

Refraction with rigid gas permeable contact lens fitting

Extranodal marginal zone lymphoma of the conjunctiva with adjacent corneal deposits

B

Thorough ocular adnexal evaluation with eyelid eversion

On eversion of the upper eyelid, a large, elevated subconjunctival mass was noted in the superonasal bulbar conjunctiva extending into the fornix with prominent blood vessels spanning between the mass and the superior cornea (Figure 2). Magnetic resonance imaging of the orbits did not show evidence of orbital extension. The patient underwent an incisional biopsy, which revealed extranodal marginal zone lymphoma of mucosa-associated tissues on histopathology and immunohistochemistry. A staging computed tomography scan showed no adenopathy elsewhere, and radiation therapy of the orbit was therefore recommended. The patient completed a course of radiation for a total dose of 2400 cGy. Subconjunctival mass in the fornix prior to biopsy.Extranodal marginal zone lymphoma is the most frequent type of non-Hodgkin B-cell lymphoma occurring in the conjunctiva. It typically presents in patients 70 years and older as a slow-growing salmon patch lesion in the fornix, with a slight predominance in women. Its pathogenesis is thought to involve chronic inflammation from antigenic stimulation, infection, or autoimmune processes.1Terrien marginal degeneration is a slowly progressive, commonly bilateral, painless degenerative ectasia of the peripheral cornea, occurring most often in men older than 40 years.2 It is most frequently seen in the superior cornea, where stromal thinning or furrowing with lipid deposition at the leading anterior edge is seen. Vision loss due to irregular against-the-rule astigmatism and, in rare cases, perforations can occur. Treatment options generally entail correction of the astigmatism with a rigid gas permeable contact lens, lamellar keratoplasty, or corneal patch graft if perforation is imminent. While the exact mechanism behind the condition is unknown, inflammation is generally not a prominent feature,3 unlike with Mooren ulcer, although some studies suggest an inflammatory variant.4,5 This case was less typical for Terrien degeneration in that it was completely unilateral and that it eventually developed pronounced inflammation and neovascularization.In cases of lipid keratopathy from corneal neovascularization without another known cause, there have been reports of regression of both vessels and lipids after injections of subconjunctival anti–vascular endothelial growth factor agents, such as bevacizumab.6 In this patient, this was not the treatment of choice, as the patient had another, more pressing diagnosis that was likely contributing to the corneal findings.In this patient, it is possible that indolent, chronic inflammation from the cornea served as antigenic stimulation for the formation of extranodal marginal zone lymphoma in the adjacent conjunctiva. On the other hand, a paraneoplastic syndrome or secondary lipid deposition from pathologic neovascularization attributable to the extranodal marginal zone lymphoma can also be considered.7 Regardless of the etiology of this atypical corneal degeneration, results from this case highlight the importance of a thorough examination of the ocular surface and fornices.On repeated examinations 2 and 6 months thereafter, his visual acuity improved to 20/25 OD without any evidence of recurrence of the subconjunctival mass. There was also partial regression of neovascularization and an appreciable decrease in the density of corneal deposits.

Ophthalmology

A man in his 50s with an unremarkable ocular history was referred for atypical corneal deposits of the right eye. On examination, visual acuity was 20/25 OD with correction, and the superior cornea showed an intact epithelium, mild stromal thinning, and pannus with faint yellow-white subepithelial deposits at the leading edge (Figure 1A). There were no other abnormalities reported on examination. The patient was treated conservatively with lubrication. Slitlamp photographs of corneal findings. A, Appearance of the cornea at time of the initial presentation. B, Appearance of the cornea 1 year later, with more prominent neovascularization and progression of deposits toward the visual axis.A year later, best-corrected visual acuity had decreased to 20/30 OD with against-the-rule astigmatism. There was progressive corneal thinning and a dense, serpentine network of subepithelial deposits with adjacent neovascularization in the superior cornea, extending toward the visual axis (Figure 1B).Subconjunctival injection of anti–vascular endothelial growth factor medicationRefraction with rigid gas permeable contact lens fitting

what would you do next?

What would you do next?

Subconjunctival injection of anti–vascular endothelial growth factor medication

Crescent-shaped lamellar keratoplasty

Refraction with rigid gas permeable contact lens fitting

Thorough ocular adnexal evaluation with eyelid eversion

d

male

51-60

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2613349

A man in his early 60s received his initial zoledronic acid (Aclasta, Novartis, Sydney) intravenous infusion (5 mg in 100 mL of solution) for the management of biochemically and radiologically diagnosed Paget disease of the bone. Within 24 hours he developed prodromal flu like myalgias and malaise. After 48 hours, the patient experienced severe bilateral photophobia, conjunctival injection, lacrimation, and blurred vision. His photophobia peaked at 72 hours but had significantly improved by the time of his initial ophthalmic review 4 days after the infusion. His uncorrected visual acuities were 6/5 bilaterally. His intraocular pressures were within normal limits. An anterior segment examination demonstrated symmetric bilateral nasal sectoral subconjunctival hemorrhages (Figure). The corneas were clear. Examination of his anterior chambers revealed a 2+ cell count and 2+ flare count in both eyes without hypopyon or synechiae. The posterior segment was unremarkable, with no evidence of vitritis, retinitis, or macular edema.Routine investigations returned results of an elevated alkaline phosphatase level (230 U/L) and mild-positive (1:160) antinuclear antibody speckled pattern. The complete blood cell count and coagulation profile were normal. The results for extractable nuclear antigen antibodies, antidouble-stranded deoxyribonucleic acid, rheumatoid factor, human leukocyte antigen B27, QuantiFERON-TB Gold (Quest Diagnostics), syphilis serology, elevated serum angiotensin-converting enzyme level, and a chest radiography were all negative. Topical dexamethasone, 0.1%, and homatropine, 2%, were commenced, with complete resolution of uveitic signs within 2 weeks. Dexamethasone frequency was initially once hourly for 3 days and was followed by a standard weekly tapering course. The homatropine frequency was twice daily.Advise the patient’s endocrinologist to request an alternative to a bisphosphonateRechallenge the patient in 12 months with zoledronic acid and manage reactively if uveitis recursPreemptively treat the patient before his next dose of zoledronic acidTreat the problem as an unrelated idiopathic uveitis What Would You Do Next?

Advise the patient’s endocrinologist to request an alternative to a bisphosphonate

Rechallenge the patient in 12 months with zoledronic acid and manage reactively if uveitis recurs

Preemptively treat the patient before his next dose of zoledronic acid

Treat the problem as an unrelated idiopathic uveitis

Bilateral acute anterior uveitis and subconjunctival hemorrhage secondary to the bisphosphonate zoledronic acid acute-phase reaction.

B

Rechallenge the patient in 12 months with zoledronic acid and manage reactively if uveitis recurs

Zoledronic acid (ZA) infusions are generally well tolerated by patients and adverse reactions are usually mild and transient. The most common adverse effect is a systemic acute phase reaction (APR) in the immediate postinfusion period, which usually incites symptoms of fatigue, musculoskeletal pain, gastrointestinal upset, and fever. Ocular inflammation is rarely coexistent, but given the increasing use of this bisphosphonate, all ophthalmologists should be aware of the association. Zoledronic acid–induced uveitis (ZAIU) is rare (≥1 in 10 000).1,2 Patel et al3,4 provided data via a large-scale osteoporosis randomized clinical trial, reporting an incidence of 1.1% (95% CI, 0.5-2.1).4 There have been 32 reported cases of ZAIU worldwide since 2005.3-5 Patients with osteoporosis represent most cases (n = 25), followed by patients with metastatic bone deposition (n = 6). There is a female preponderance with unilateral cases much more common than bilateral.Bisphosphonates are the most effective drug class for treating metastatic and metabolic bone disorders. Paget disease of bone is a common and chronic metabolic bone disease characterized by an increase in focal bone turnover. Zoledronic acid is the most widely used, efficacious, and potent nitrogenous bisphosphonate, able to be given as an annual infusion. It inhibits osteoclast-mediated bone resorption by inhibiting the enzyme farnesyl pyrophosphate synthase that is responsible for protein prenylation within the osteoclast. The result is a disruption of intracellular signaling cascades, altered cytoskeletal arrangement, and disrupted osteoclast function with accelerated cellular apoptosis.6 Nitrogen-containing bisphosphonates can cause a systemic APR in up to 30% of patients receiving their first infusion.6,7 Reid et al7,8 demonstrated a clinical spectrum of the APR and a marked clustering of adverse reactions in the first 3 days following an intravenous administration of ZA. They found that the APR lasted a few days among most individuals and rarely went beyond a week. The incidence was greatly reduced on the redosing of the drug.7 Eye complaints, albeit rare, were significantly associated with ZA and are included as a subcategory within the definition of APR. Postulating pathophysiological associations between ZA and uveitis, bisphosphonates share homologies with γ and δ Tcell ligands by stimulating a cytokine release through activating γ/δ T-cell lymphocytes.8 Inhibiting farnesyl pyrophosphate synthase in monocytes leads to the intracellular accumulation of intermediates, namely isopentenyl pyrophosphate, which may lead to adjacent T cells activating with the release of the proinflammatory cytokines interleukin 6 and tumor necrosis factor α, which results in the APR.5The close temporal relationship between infusion, symptom onset, and improvement before steroid treatment correlate with a bisphosphonate-related APR rather than an unrelated idiopathic uveitis. Because no superior alternative to ZA exists for the management of Paget disease, we would not advise an alternative to a bisphosphonate, but instead suggest that the patient’s physician could continue treatment and treat any uveitis if it recurs. The APR reaction is less likely to occur on successive administrations of ZA.8,9 Preemptive treatment does not seem warranted according to Patel et al.10 In their study, 3 participants who previously experienced ZAIU were administered 2 further infusions 18 months apart. All 3 participants were formally reviewed by an ophthalmologist 3 days after their second infusion. None of the participants had any ocular signs of AAU.The patient reported a complete resolution of ocular symptoms and was discharged to the care of his endocrinologist. He awaits his next dose of ZA.

Ophthalmology

A man in his early 60s received his initial zoledronic acid (Aclasta, Novartis, Sydney) intravenous infusion (5 mg in 100 mL of solution) for the management of biochemically and radiologically diagnosed Paget disease of the bone. Within 24 hours he developed prodromal flu like myalgias and malaise. After 48 hours, the patient experienced severe bilateral photophobia, conjunctival injection, lacrimation, and blurred vision. His photophobia peaked at 72 hours but had significantly improved by the time of his initial ophthalmic review 4 days after the infusion. His uncorrected visual acuities were 6/5 bilaterally. His intraocular pressures were within normal limits. An anterior segment examination demonstrated symmetric bilateral nasal sectoral subconjunctival hemorrhages (Figure). The corneas were clear. Examination of his anterior chambers revealed a 2+ cell count and 2+ flare count in both eyes without hypopyon or synechiae. The posterior segment was unremarkable, with no evidence of vitritis, retinitis, or macular edema.Routine investigations returned results of an elevated alkaline phosphatase level (230 U/L) and mild-positive (1:160) antinuclear antibody speckled pattern. The complete blood cell count and coagulation profile were normal. The results for extractable nuclear antigen antibodies, antidouble-stranded deoxyribonucleic acid, rheumatoid factor, human leukocyte antigen B27, QuantiFERON-TB Gold (Quest Diagnostics), syphilis serology, elevated serum angiotensin-converting enzyme level, and a chest radiography were all negative. Topical dexamethasone, 0.1%, and homatropine, 2%, were commenced, with complete resolution of uveitic signs within 2 weeks. Dexamethasone frequency was initially once hourly for 3 days and was followed by a standard weekly tapering course. The homatropine frequency was twice daily.Advise the patient’s endocrinologist to request an alternative to a bisphosphonateRechallenge the patient in 12 months with zoledronic acid and manage reactively if uveitis recursPreemptively treat the patient before his next dose of zoledronic acidTreat the problem as an unrelated idiopathic uveitis

what would you do next?

What would you do next?

Treat the problem as an unrelated idiopathic uveitis

Rechallenge the patient in 12 months with zoledronic acid and manage reactively if uveitis recurs

Preemptively treat the patient before his next dose of zoledronic acid

Advise the patient’s endocrinologist to request an alternative to a bisphosphonate

b

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2613416

A 64-year-old man with type 2 diabetes mellitus, hypertension, hyperlipidemia, and chronic obstructive pulmonary disease fell 3 days prior to presentation, hitting the right side of his face, sustaining a small eyelid skin laceration for which he did not seek treatment. Over subsequent days, he developed right periorbital erythema, edema, and pain, with blisters appearing on the eyelid skin 1 day prior to presentation.On examination, his pulse was 120 beats per minute, blood pressure was 92/62 mm Hg, and temperature was 38.2°C. The right upper and lower eyelids were warm, erythematous, edematous, and tender, with large fluctuant blisters (Figure, A). Erythema tracked down the cheek, and there was right cervical lymphadenopathy. The patient did not cooperate for a visual acuity assessment, but there was no afferent pupillary defect. Limited penlight examination revealed a normal anterior segment except for 360° conjunctival chemosis. Noncontrast computed tomography of the orbits demonstrated extensive right preseptal soft tissue swelling and slight enlargement of the right lateral rectus muscle with minimal orbital fat stranding. The right globe was slightly proptotic (Figure, B). Laboratory testing revealed a white blood cell count of 32.6 K/µL (to convert to × 109 per liter, multiply by 0.001), with 95% polymorphonuclear lymphocytes.A, External photograph of the right eyelids demonstrates significant erythema and edema with large blisters. B, Noncontrast axial computed tomography scan of the orbits demonstrates slight proptosis of the right globe, marked preseptal edema on the right, and slight enlargement of the right lateral rectus muscle.Begin oral antibiotics and discharge home with follow-up the next dayPerform bedside incision and drainage of the blisters and admit for intravenous antibioticsPerform aggressive debridement of the eyelids in the operating room and give intravenous antibiotics What Would You Do Next?

Begin oral antibiotics and discharge home with follow-up the next day

Admit for intravenous antibiotics

Perform bedside incision and drainage of the blisters and admit for intravenous antibiotics

Perform aggressive debridement of the eyelids in the operating room and give intravenous antibiotics

Periorbital necrotizing fasciitis

D

Perform aggressive debridement of the eyelids in the operating room and give intravenous antibiotics

Periorbital necrotizing fasciitis (PNF) is rare, with an estimated incidence of 1 in 4 million per year, but ideally is diagnosed promptly owing to its potential for rapidly progressive morbidity and mortality.1 Necrotizing fasciitis is less common in periorbital tissues than other parts of the body because of the abundant periorbital blood supply. Men and women are affected equally, and cases have been described in all age groups, with the mean age approximately 45 to 50 years.2-4 Fifty percent of patients have a history of underlying immunosuppression, usually mild, such as diabetes, alcoholism, or rheumatologic disease.2-4 Antecedent trauma is common, including lacerations, abrasions, blunt trauma, puncture wounds, or surgery, with at least 4 cases reported following blepharoplasty; however, 27% to 52% of patients have no prior trauma history.2-4Initially PNF may be difficult to distinguish from preseptal cellulitis because early features include erythema, edema, warmth, fever, and tachycardia.2,3,5 Later features that help distinguish PNF from cellulitis include the formation of bullae, such as those present in this patient, from which dishwater-like fluid may be expressed, as well as violaceous or dusky erythema.2,3,5 Other features of PNF that are variably present include severe pain, crepitus, skin anesthesia, skin necrosis, and black discoloration.2,3,5Monomicrobial infection with group A β-hemolytic Streptococcus causes 50% of PNF cases, with Staphylococcus aureus (5%), Pseudomonas aeruginosa (3%-10%), and polymicrobial infections (20%) also encountered.2,3 Therapy is initiated with broad-spectrum antibiotics, but because Streptococci produce proteases that facilitate rapid spread of infection along avascular tissue planes, debridement is needed in 85% to 100% of cases to control infection at sites that are poorly accessible to antibiotics.2-4Occasional cases of PNF have been treated successfully with antibiotics alone.6,7 Medical treatment, in theory, preserves tissue to minimize postinfectious disfigurement and morbidity; however, the main goal in acute PNF treatment is eradication of infection to prevent mortality, which usually requires debridement.2-4,6,7 The decision to treat with medical treatment alone requires extremely close monitoring, with the surgeon ready to take the patient to the operating room at any time should there be worsening of the clinical condition. Mortality from periorbital PNF is 6% to 14%, lower than in other parts of the body (20%-30%) but not insignificant, and is associated with delayed presentation and infection with group A β-hemolytic Streptococcus.2-4In this case, the presence of large bullae pointed to a clinical diagnosis of PNF. Oral antibiotics with outpatient follow-up would have been inappropriate because the patient was septic. Treatment with intravenous antibiotics was necessary, and bedside debridement of blisters was useful for obtaining cultures but not adequate to halt progression of disease. Extensive surgical debridement in addition to antibiotics was most appropriate given the delayed presentation and the severe clinical appearance.Vancomycin, meropenem, and clindamycin were initiated, and blisters were debrided. The patient’s clinical appearance worsened during the subsequent day, with erythema spreading down the neck, necessitating urgent surgical debridement. Necrotic nonbleeding tissue and thin, gray, dishwater-like fluid were noted intraoperatively. Frozen section pathology revealed gangrenous tissue necrosis, acute and chronic inflammation, and abundant Gram-positive cocci in chains and pairs, consistent with necrotizing fasciitis. Cultures confirmed group A β-hemolytic Streptococcus, and antibiotics were narrowed to penicillin G and vancomycin. He remained hospitalized for 22 days, requiring 3 additional debridements. His globe remained unaffected, with 20/25 visual acuity at discharge. During the subsequent year, he underwent 6 reconstructive procedures, with future surgeries still planned.

Ophthalmology

A 64-year-old man with type 2 diabetes mellitus, hypertension, hyperlipidemia, and chronic obstructive pulmonary disease fell 3 days prior to presentation, hitting the right side of his face, sustaining a small eyelid skin laceration for which he did not seek treatment. Over subsequent days, he developed right periorbital erythema, edema, and pain, with blisters appearing on the eyelid skin 1 day prior to presentation.On examination, his pulse was 120 beats per minute, blood pressure was 92/62 mm Hg, and temperature was 38.2°C. The right upper and lower eyelids were warm, erythematous, edematous, and tender, with large fluctuant blisters (Figure, A). Erythema tracked down the cheek, and there was right cervical lymphadenopathy. The patient did not cooperate for a visual acuity assessment, but there was no afferent pupillary defect. Limited penlight examination revealed a normal anterior segment except for 360° conjunctival chemosis. Noncontrast computed tomography of the orbits demonstrated extensive right preseptal soft tissue swelling and slight enlargement of the right lateral rectus muscle with minimal orbital fat stranding. The right globe was slightly proptotic (Figure, B). Laboratory testing revealed a white blood cell count of 32.6 K/µL (to convert to × 109 per liter, multiply by 0.001), with 95% polymorphonuclear lymphocytes.A, External photograph of the right eyelids demonstrates significant erythema and edema with large blisters. B, Noncontrast axial computed tomography scan of the orbits demonstrates slight proptosis of the right globe, marked preseptal edema on the right, and slight enlargement of the right lateral rectus muscle.Begin oral antibiotics and discharge home with follow-up the next dayPerform bedside incision and drainage of the blisters and admit for intravenous antibioticsPerform aggressive debridement of the eyelids in the operating room and give intravenous antibiotics

what would you do next?

What would you do next?

Admit for intravenous antibiotics

Perform aggressive debridement of the eyelids in the operating room and give intravenous antibiotics

Begin oral antibiotics and discharge home with follow-up the next day

Perform bedside incision and drainage of the blisters and admit for intravenous antibiotics

b

male

61-70

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2606437

A woman in her 30s noticed a painless left neck mass. She had no history of dysphagia, dyspnea, recent upper respiratory tract infection, injury, or surgery. She also had no weight loss, pain, or fever and had no history of tobacco or alcohol use, radiation exposure, family history of thyroid cancer, and no previous thyroid dysfunction. Thyroid function test results were normal. Physical examination revealed a palpable nontender, firm mass and no cervical lymphadenopathy. She had a medical history of high-grade osteosarcoma with areas of leimyosarcoma of the tibia which had been treated with right above-knee amputation and chemotherapy 4 years prior to presentation. She was followed up in the oncology clinic without any recurrence or metastases. Her last visit was 6 months earlier. She was also diagnosed with squamous cell carcinoma of the cervix 2 months earlier and was awaiting surgery. Computed tomography (CT) of the neck revealed a 6.0 × 3.4 × 4.4-cm calcified left thyroid lobe mass (Figure, A). Positron emission tomography–computed tomographic (PET-CT) imaging showed increased uptake in the left thyroid gland. She underwent a left thyroid lobectomy. The neoplastic cells were positive for p53, vimentin, and smooth muscle actin, and negative for S-100, thyroid transcription factor-1 (TTF-1), and CD34 (Figure, B).A, Computed tomographic image reveals a calcified mass (blue arrowhead). B; Left, negative immunostain results for S-100; right, positive immunostain results for vimentin (original magnification ×100). What Is Your Diagnosis?

Thyroid lymphoma

Anaplastic thyroid carcinoma

Osteosarcoma metastasis

Squamous cell carcinoma metastasis

C. Osteosarcoma metastasis

C

Osteosarcoma metastasis

Pathologic analysis revealed metastatic osteosarcoma in a 6.5-cm mass. The mass showed apparent bony tissue.Metastases to the thyroid gland are reported at autopsy in 1% to 24% of metastatic cancer patients.1,2 The most common sites were kidney, lung, breast, esophagus, and uterus.3-5 Some studies showed that the most common primary tumor for thyroid metastases was lung cancer4,6,7; however, some showed renal cell carcinoma.3,8 Review articles concluded that lung and renal cell carcinomas made up more than 80% of total thyroid gland metastases. Unlike uterine cancer, cancer of the cervix is not a common primary source for thyroid metastasis. Unlike the considerable predominance of primary thyroid cancers in women, some studies have found male,1 some have found female,3 and some studies have found no gender predominance4,5 for metastasis to the thyroid gland.The majority of patients presented with clinical complaints, such as new-onset neck swelling, dysphagia, dysphonia, and cough.8 Clinical differential diagnosis for a rapidly enlarging unilateral thyroid mass includes anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), thyroid lymphoma or sarcoma, metastasis to the thyroid gland, and abscess. Differential diagnosis for pathology should include osteosarcoma, sarcomatoid PDTC, ATC with osseous metaplasia, medullary thyroid carcinoma, spindle epithelial tumor with thymus-like differentiation, and synovial sarcoma.9 The cytological image may be ambiguous and requires histopathological confirmation, supported by immunohistochemical examinations.Sarcomas are derived from mesenchymal cells, such as bone, fat, and muscle. Sarcomas of the thyroid, both primary and metastatic, are rare. Osteosarcomas express vimentin; leiomyosarcomas express vimentin, desmin, and smooth-muscle actin. Unlike PDTC, ATC often displays p53 mutations and does not stain for thyroglobulin and often not vimentin. Osteosarcoma may be positive for p53.Metastases of primary tumors can be divided into 2 categories: synchronous and metachronous. Synchronous indicates that the tumors are detected at the same time as the thyroid metastases, whereas metachronous indicates that the thyroid metastases are detected some time after the primary tumor was detected. The mean interval between discovery of the primary tumor and the thyroid metastases was 5.8 years.8 Our patient presented with thyroid gland metastasis after 4 years of disease-free survival without other metastasis apparent on PET-CT examination.We recommend neck ultrasonography for all thyroid enlargement as a first step for imaging. However, in selected cases, CT or PET-CT may be considered initially if clinical suspicion is high for nonthyroid causes such as metastases.In patients with clinically suspected metastasis to the thyroid gland, core-needle biopsy achieved a significantly higher sensitivity than fine-needle biopsy without any false-negative results.10 In cases of known rare primary malignant abnormality, nontypical ultrasonography features of primary thyroid malignant abnormality, and need for an additional immunohistochemical analysis, core-needle biopsy may be primarily considered.10 In this case, we deferred biopsy considering highly calcified tissue on CT imaging and likelihood of osteosarcoma metastasis with previous history of osteosarcoma.The treatment is surgical excision of the lesion with or without lymph node dissection. Chemotherapy or radiotherapy is also considered in selected cases of local recurrence or concomitant metastases. Surgical treatment was associated with improved survival duration.3 The incidence of surgical complications was very low and did not vary by extent of surgical treatment. The most common surgical complications are injury of the recurrent laryngeal nerve and incomplete resection of the metastasis. In 1 review,5 no patients had tumor recurrence when margins were negative. In light of these data, subtotal thyroidectomy may be warranted unless there is concern for involvement of the contralateral lobe. However, another review3 found that recurrence was more likely in patients treated with subtotal thyroidectomies (13.3%) vs total thyroidectomies (4.8%).Metastasis of osteosarcoma to the thyroid gland is rare. It is important to consider thyroid metastases in the differential diagnosis in thyroid nodules, especially in patients with a medical history of malignant abnormality and rapidly enlarging thyroid mass. Immunohistochemistry is important to establish a diagnosis.

Oncology

A woman in her 30s noticed a painless left neck mass. She had no history of dysphagia, dyspnea, recent upper respiratory tract infection, injury, or surgery. She also had no weight loss, pain, or fever and had no history of tobacco or alcohol use, radiation exposure, family history of thyroid cancer, and no previous thyroid dysfunction. Thyroid function test results were normal. Physical examination revealed a palpable nontender, firm mass and no cervical lymphadenopathy. She had a medical history of high-grade osteosarcoma with areas of leimyosarcoma of the tibia which had been treated with right above-knee amputation and chemotherapy 4 years prior to presentation. She was followed up in the oncology clinic without any recurrence or metastases. Her last visit was 6 months earlier. She was also diagnosed with squamous cell carcinoma of the cervix 2 months earlier and was awaiting surgery. Computed tomography (CT) of the neck revealed a 6.0 × 3.4 × 4.4-cm calcified left thyroid lobe mass (Figure, A). Positron emission tomography–computed tomographic (PET-CT) imaging showed increased uptake in the left thyroid gland. She underwent a left thyroid lobectomy. The neoplastic cells were positive for p53, vimentin, and smooth muscle actin, and negative for S-100, thyroid transcription factor-1 (TTF-1), and CD34 (Figure, B).A, Computed tomographic image reveals a calcified mass (blue arrowhead). B; Left, negative immunostain results for S-100; right, positive immunostain results for vimentin (original magnification ×100).

what is your diagnosis?

What is your diagnosis?

Osteosarcoma metastasis

Anaplastic thyroid carcinoma

Thyroid lymphoma

Squamous cell carcinoma metastasis

a

female

31-40

original

https://jamanetwork.com/journals/jama/fullarticle/2627942

A 19-day-old Japanese male infant presented with a 12-day history of fevers and facial rash. He was born by spontaneous vaginal delivery at 36 weeks’ gestational age with a birthweight of 3048 g (6.7 lb) with Apgar scores of 9 and 10. There were no complications during the prenatal and perinatal periods. His mother had no history of ringworm infection, positive IgG antibodies against rubella virus and herpes zoster virus, and serology findings negative for human immunodeficiency virus, hepatitis B virus, and syphilis. His family history was unremarkable.On examination, he had a temperature of 38.0°C, a heart rate of 150/min, and a respiratory rate of 60/min. Slightly scaly annular erythematous plaques with central atrophy and raised margins were present on the forehead and periorbital areas (Figure). The remainder of the physical examination was unremarkable. Laboratory investigation showed a white blood cell count of 10.5 ×103/µL (reference range, 4.8-18.5 ×103/μL); hemoglobin level, 7.2 g/dL (8.7-13.5 g/dL); platelet count, 47 × 104/µL (28-91 ×104/μL); aspartate aminotransferase level, 23 IU/L (20-62 IU/L); alanine aminotransferase level, 9 IU/L (11-45 IU/L); serum creatinine level, 0.27 mg/dL (0.12-0.27 mg/dL); uric acid level, 2.6 mg/dL (1.8-5.3 mg/dL); and C-reactive protein level, 6.94 mg/dL (<0.30 mg/dL).Scattered annular erythematous plaques with central atrophy and raised margin on the forehead and periorbital areas of patient.Provide education on proper facial cleansing and moisturizingOrder antinuclear antibody, anti-Ro/SS-A, and anti-La/SS-B antibody testing for both the infant and his motherOrder a serologic test for syphilis for the infant What Would You Do Next?

Provide education on proper facial cleansing and moisturizing

Administer topical antifungals

Order antinuclear antibody, anti-Ro/SS-A, and anti-La/SS-B antibody testing for both the infant and his mother

Order a serologic test for syphilis for the infant

Neonatal lupus

C

Order antinuclear antibody, anti-Ro/SS-A, and anti-La/SS-B antibody testing for both the infant and his mother

The key to the correct diagnosis is the presence of characteristic erythematous plaques on the face, including the periorbital areas, along with anemia and low-grade fever. The diagnosis of neonatal lupus can be made if a neonate born to a mother with anti-Ro/SS-A or anti-La/SS-B antibodies develops facial annular plaques. Congenital syphilis (choice D) may be considered, but mucosal, periorificial, and palmar and plantar lesions are common in congenital syphilis and not seen in this case. It is important to avoid misdiagnosis, as false-positive syphilis antibody tests can occur in systemic lupus erythematosus. Infantile seborrheic dermatitis (choice A) does not present with annular infiltrated plaques. Tinea faciei (choice B) is unlikely in a newborn without a history of ringworm in the mother.Neonatal lupus occurs in approximately 1 per 20 000 newborns.1 It is defined as a passively acquired autoimmune disease mediated by the transplacental passage of maternal IgG autoantibodies.1 However, other events that have not been fully elucidated are required to cause tissue injury.2 For mothers who have had an infant with neonatal lupus, a subsequent infant has a 25% risk of some form of the disease.3Most infants with neonatal lupus have either skin or cardiac lesions. Other clinical manifestations of neonatal lupus include thrombocytopenia, anemia, neutropenia, and autoimmune hepatitis. A rash appears in 16% of all infants born to mothers with anti-Ro/SS-A antibodies, anti-La/SS-B antibodies, or both.4 It may be present at birth or occur within a few months of life and is characterized by a slightly elevated annular erythema, which resembles subacute cutaneous lupus erythematosus, predominantly on the face.5 The rash, cytopenias, and hepatitis usually spontaneously resolve with the disappearance of maternal IgG. Therefore, for those symptoms, periodic follow-up and supportive care are recommended until about 6 months of life. Thrombocytopenia can lead to severe manifestations such as bleeding, but it responds well to intravenous immunoglobulins and corticosteroids if required.6 Cardiac involvement is potentially life-threatening, with a mortality rate of 17.5% and in utero death rate of 6%. Infants with neonatal lupus are at risk for complete heart block, and up to 20% develop cardiomyopathy, valvular dysfunction, and endocardial fibroelastosis, resulting in a poor prognosis.6 Seventy percent of live-born infants with congenital heart block require pacemakers at some point in life.7 Pregnancies with autoantibodies are estimated to have a 1.7% risk of cardiac neonatal lupus if the mother has had no previously affected pregnancies. However, mothers with a previous infant with cardiac neonatal lupus have a 9-fold higher risk (16%) in subsequent pregnancies, and mothers with a previous history of an infant with cutaneous neonatal lupus have a 7-fold higher risk (13%) than those without this history.8 Pregnant women with autoantibodies may benefit from screening for fetal congenital heart block with weekly or biweekly Doppler fetal echocardiography from the 16th through the 34th week of gestation, when congenital heart block is usually diagnosed.9 In addition, obtaining an electrocardiogram in infants before hospital discharge is recommended. Preemptive treatments to prevent congenital heart block for pregnant women with autoantibodies are under investigation. Dexamethasone and β-agonists may play a role in secondary prevention of complete heart block or heart failure. Hydroxychloroquine may prevent the recurrence of cardiac neonatal lupus in families with a previously affected child.5,7Although some mothers of infants with neonatal lupus have diagnoses of systemic lupus erythematosus or Sjögren syndrome, up to 40% have no symptoms of autoimmune disease at the time of the birth. However, half of asymptomatic mothers will develop an autoimmune disease in the future, most often Sjögren syndrome.10Serologic tests on the infant and his mother were both positive for antinuclear antibodies (speckled pattern; antibody titer, 1:640), Ro/SS-A antibody (>240 U/mL), and La/SS-B antibody (>320 U/mL). His electrocardiogram was normal. His fever, rash, and anemia spontaneously resolved at the first, third, and sixth months of life, respectively. Within 8 months of life, autoantibodies disappeared and no other organ involvement appeared. The mother was seen by a rheumatologist; no additional rheumatologic diagnoses were made.

General

A 19-day-old Japanese male infant presented with a 12-day history of fevers and facial rash. He was born by spontaneous vaginal delivery at 36 weeks’ gestational age with a birthweight of 3048 g (6.7 lb) with Apgar scores of 9 and 10. There were no complications during the prenatal and perinatal periods. His mother had no history of ringworm infection, positive IgG antibodies against rubella virus and herpes zoster virus, and serology findings negative for human immunodeficiency virus, hepatitis B virus, and syphilis. His family history was unremarkable.On examination, he had a temperature of 38.0°C, a heart rate of 150/min, and a respiratory rate of 60/min. Slightly scaly annular erythematous plaques with central atrophy and raised margins were present on the forehead and periorbital areas (Figure). The remainder of the physical examination was unremarkable. Laboratory investigation showed a white blood cell count of 10.5 ×103/µL (reference range, 4.8-18.5 ×103/μL); hemoglobin level, 7.2 g/dL (8.7-13.5 g/dL); platelet count, 47 × 104/µL (28-91 ×104/μL); aspartate aminotransferase level, 23 IU/L (20-62 IU/L); alanine aminotransferase level, 9 IU/L (11-45 IU/L); serum creatinine level, 0.27 mg/dL (0.12-0.27 mg/dL); uric acid level, 2.6 mg/dL (1.8-5.3 mg/dL); and C-reactive protein level, 6.94 mg/dL (<0.30 mg/dL).Scattered annular erythematous plaques with central atrophy and raised margin on the forehead and periorbital areas of patient.Provide education on proper facial cleansing and moisturizingOrder antinuclear antibody, anti-Ro/SS-A, and anti-La/SS-B antibody testing for both the infant and his motherOrder a serologic test for syphilis for the infant

what would you do next?

What would you do next?

Administer topical antifungals

Provide education on proper facial cleansing and moisturizing

Order a serologic test for syphilis for the infant

Order antinuclear antibody, anti-Ro/SS-A, and anti-La/SS-B antibody testing for both the infant and his mother

d

male

0-10

Japanese

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2597888

A white woman in her 60s presented for a routine visit to the outpatient dermatological graft-vs-host disease (GVHD) clinic at Westmead Hospital for review of lichenoid GVHD evolving into sclerodermatous GVHD. The GVHD occurred secondary to a bone marrow transplant in 2014 for treatment of chronic lymphocytic leukemia. At the time of review she was being treated with oral azathioprine (50 mg twice daily), tacrolimus (0.5 mg twice daily), and prednisone (25 mg daily) therapy. She was also receiving monthly intravenous immunoglobulin, prophylactic oral fluconazole, acyclovir, sulfamethoxazole-trimethoprim, and penicillin. One month prior to commencing oral azathioprine therapy, the patient noted the growth of nodules on the genital and perianal region, with 1 ulcerated nodule in the perianal area associated with painless bleeding on trauma. The lesions were otherwise asymptomatic.On examination she had several yellow-colored nodules, some of them ulcerated with extrusion of yellow-colored discharge on the left labia majora and on the perianal area with surrounding inflammatory reaction (Figure 1). Additionally, she had sclerodermatous plaques on the lower legs, scarring alopecia on the scalp with minimal hyperkeratosis, nail dystrophy and lichenoid changes, erythematous changes in both feet, and desquamation in the lower legs and on the back and arms suggestive of eczematous or postlichenoid changes as part of her lichenoid GVHD. Initial investigations revealed a white blood cell count of 13.1 × 103/μL (to convert to billions per liter, multiply by 0.001); however, the results of the rest of her blood tests including the full blood count and electrolytes, urea and creatinine, and liver function tests were otherwise stable and unremarkable.Clinical photographs of cutaneous nodules in a woman with graft-vs-host disease. A, Multiple erythematous eroded nodules in the perianal area. B, yellowish nodules located on the left labia majora. What Is Your Diagnosis?

Atypical mycobacterial infection

Cutaneous malakoplakia

Cryptococcosis

Calcinosis cutis

C. Cutaneous malakoplakia

C

Cryptococcosis

An excisional biopsy was performed, and the specimen was sent for histologic analysis and bacterial, mycobacterial, and fungal culture. Hematoxylin-eosin stain showed a focal ulceration and acute inflammation in the epithelium. Deep to this, there were prominent nodular aggregates of granular histiocytes and neutrophils. Numerous round calcospherites were seen, in keeping with the diagnosis of malakoplakia (Figure 2A). The calcospherites stained positively on von Kossa and periodic acid–Schiff stain (Figure 2B). There was fibrosis noted around some nodular aggregates. No obvious fungi or mycobacteria were seen on silver and Ziehl-Neelsen stain, and there was no evidence of dysplasia or malignancy. The specimen had a positive bacterial culture result showing heavy growth of Escherichia coli. In combined management with hematology and infectious disease specialists, treatment with oral ciprofloxacin was commenced and oral prednisone was slowly reduced. Four months later, she was receiving oral prednisone, 15 mg, daily. The nodules were greatly reduced, but some small lesions remained and azathioprine therapy was subsequently ceased. Nine months later all clinical lesions had resolved.Histopathologic analysis. A, There is a dermal infiltrate deep to the ulcer composed of predominantly granular histiocytes and scattered Michaelis Gutmann bodies (arrowhead) on hematoxylin-eosin stain. B, The Michaelis Gutmann bodies (arrowhead) are highlighted by the periodic acid–Schiff stain.Malakoplakia is a rare condition associated with infections, tumors, and primary or secondary immunodeficiency.1 First described in 1902 by Michaelis and Gutmann, it was termed malakoplakia (“soft plaque”) in 1903 by von Hansemann.2 Cutaneous malakoplakia is rare and was first described in 1972.3Malakoplakia presents as skin-colored nodules, ulcerations, abscesses, erythematous papules, or masses.4 Histologic analysis is essential for diagnosis by identifying characteristic Michaelis Gutmann bodies, which show up with periodic acid–Schiff, Perl (iron), and von Kossa (calcium) stains. These targetoid intracytoplasmic basophilic inclusions found in foamy macrophages are pathognomonic for malakoplakia.5 Culture of biopsy is often positive for bacteria, most often E coli, less often Pseudomonas, Proteus, Klebsiella, Staphylococcus, or Mycobacteria.4 Differential diagnoses include other infectious diseases, neoplastic or reactive process including tuberculosis, cryptococcosis, lepromatous leprosy, and parasites such as leishmaniasis.6The pathogenesis is unknown, but an acquired bactericidal defect of macrophages has been suggested. Patients have defective in vitro bactericidal activity to microorganisms including E coli.4Use of antibiotics that concentrate in macrophages such as ciprofloxacin and sulfamethoxazole-trimethoprim is associated with a high cure rate.1 Directed antibiotic therapy in combination with local surgical excision has shown the highest chance for cure.1,5 Reduction or discontinuation of immunosuppressive drug therapy is also usually required.1The clinical course is often benign, with no deaths directly associated with cutaneous malakoplakia.1,4 Skin lesions often last 4 to 6 months, and mortality is usually due to an underlying condition.1 Early diagnosis and treatment may reduce morbidity.

Dermatology

A white woman in her 60s presented for a routine visit to the outpatient dermatological graft-vs-host disease (GVHD) clinic at Westmead Hospital for review of lichenoid GVHD evolving into sclerodermatous GVHD. The GVHD occurred secondary to a bone marrow transplant in 2014 for treatment of chronic lymphocytic leukemia. At the time of review she was being treated with oral azathioprine (50 mg twice daily), tacrolimus (0.5 mg twice daily), and prednisone (25 mg daily) therapy. She was also receiving monthly intravenous immunoglobulin, prophylactic oral fluconazole, acyclovir, sulfamethoxazole-trimethoprim, and penicillin. One month prior to commencing oral azathioprine therapy, the patient noted the growth of nodules on the genital and perianal region, with 1 ulcerated nodule in the perianal area associated with painless bleeding on trauma. The lesions were otherwise asymptomatic.On examination she had several yellow-colored nodules, some of them ulcerated with extrusion of yellow-colored discharge on the left labia majora and on the perianal area with surrounding inflammatory reaction (Figure 1). Additionally, she had sclerodermatous plaques on the lower legs, scarring alopecia on the scalp with minimal hyperkeratosis, nail dystrophy and lichenoid changes, erythematous changes in both feet, and desquamation in the lower legs and on the back and arms suggestive of eczematous or postlichenoid changes as part of her lichenoid GVHD. Initial investigations revealed a white blood cell count of 13.1 × 103/μL (to convert to billions per liter, multiply by 0.001); however, the results of the rest of her blood tests including the full blood count and electrolytes, urea and creatinine, and liver function tests were otherwise stable and unremarkable.Clinical photographs of cutaneous nodules in a woman with graft-vs-host disease. A, Multiple erythematous eroded nodules in the perianal area. B, yellowish nodules located on the left labia majora.

what is your diagnosis?

What is your diagnosis?

Cryptococcosis

Cutaneous malakoplakia

Atypical mycobacterial infection

Calcinosis cutis

a

female

61-70

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2586162

A black woman in her 50s presented to the clinic with a 3-month history of nontender mildly pruritic verrucous nodules in several areas of a polychromatic tattoo on her right lower leg and foot. She reported that these appeared 1 to 2 months following placement of the tattoo and were restricted to areas where the artist created pink zones by layering white ink over red ink. She denied pain, fevers, and chills and had no history of skin cancer. She reported a distant history of discoid lupus, and was taking 2 antihypertensives but no other oral or topical medications. Physical examination revealed well-demarcated erythematous to violaceous verrucous nodules on the right lateral leg and dorsal foot (Figure 1A). A punch biopsy specimen from a representative nodule was obtained, with an additional biopsy for tissue culture (Figure 1B).A, Verrucous nodules are restricted to zones of pink pigment within the tattoo, sparing other colors present. B, Histologic reaction pattern from punch biopsy specimen of right lower leg nodule (hematoxylin-eosin, original magnification ×4). What Is Your Diagnosis?

Hypertrophic discoid lupus

Eruptive keratoacanthomas

Pseudoepitheliomatous hyperplasia

Sarcoidosis arising in a tattoo

C. Pseudoepitheliomatous hyperplasia

C

Pseudoepitheliomatous hyperplasia

The initial interpretation was invasive squamous cell carcinoma with tattoo pigment, tissue cultures being negative for bacterial or fungal organisms (Figure 1B). Given the clinical/histologic mismatch, a reevaluation of the pathologic specimen found no cellular atypia or atypical nesting of keratinocytes, weighing against invasive squamous cell carcinoma. Excision with secondary intention healing was performed on the remaining involved areas for both treatment and confirmation of diagnosis. Histologic evaluation of the excision revealed the presence of pseudoepitheliomatous hyperplasia (PEH) arising from eccrine glands with granulomatous inflammation due to the presence of tattoo pigment (Figure 2A). Scanning electron microscopy with energy-dispersive x-ray analysis showed dark brown finely granular pigment in the superficial dermis with autofluorescence to filters optimized to Texas red/fluorescein isothiocyanate and pink to blue-white birefringence most consistent with titanium dioxide (TiO2) (Figure 2B). Finely granular red pigment in the dermis showed weak red birefringence and autofluorescence on filters optimized to Texas red, consistent with organic dye (not mercury).A, Histologic reaction pattern from excision of right dorsal foot (hematoxylin-eosin, original magnification ×4). Notable is hyperplasia of the epidermis and adnexal epithelium with granulomatous inflammation and tattoo pigment within the dermis. Atypical nesting of keratinocytes or cellular atypia is not present. B, Scanning electron microscope image of black birefringent particles (original magnification ×800).With fewer than 7 cases reported in the literature, PEH is a relatively rare complication of exposure to tattoo ink. This histologic pattern is typified by irregular hyperplasia of the epidermis involving follicular infundibula and acrosyringia and is a reactive rather than primary disease process.1 Characteristically, PEH occurs secondary to red or purple ink within 3 months after tattoo placement.2-4 This patient matches the timeline of other PEH cases but is unique in that only “white ink” zones of the design (pink zones) were affected. Previous in vitro spectral analysis of commercial tattoo inks indicates that the white inks are based mainly on TiO2 with small amounts of aluminum.5 Scanning electron microscopy demonstrates TiO2, carbon, and smaller amounts of aluminum and silicon in the tissue specimen indicating the typical components of white tattoo ink, supporting a diagnosis of PEH secondary to white tattoo ink. Review of PubMed, ClinicalKey, and Web of Science using the search terms “pseudoepitheliomatous hyperplasia,” “tattoo,” and “white ink” indicates that this case is the initial report of white ink stimulating reactive PEH within a tattoo. It also highlights the importance of clinical/pathologic correlation when evaluating tattoo reactions. For both pathologist and clinician, it represents a benign “lamb” that can easily be mistaken for a malignant “wolf.”

Dermatology

A black woman in her 50s presented to the clinic with a 3-month history of nontender mildly pruritic verrucous nodules in several areas of a polychromatic tattoo on her right lower leg and foot. She reported that these appeared 1 to 2 months following placement of the tattoo and were restricted to areas where the artist created pink zones by layering white ink over red ink. She denied pain, fevers, and chills and had no history of skin cancer. She reported a distant history of discoid lupus, and was taking 2 antihypertensives but no other oral or topical medications. Physical examination revealed well-demarcated erythematous to violaceous verrucous nodules on the right lateral leg and dorsal foot (Figure 1A). A punch biopsy specimen from a representative nodule was obtained, with an additional biopsy for tissue culture (Figure 1B).A, Verrucous nodules are restricted to zones of pink pigment within the tattoo, sparing other colors present. B, Histologic reaction pattern from punch biopsy specimen of right lower leg nodule (hematoxylin-eosin, original magnification ×4).

what is your diagnosis?

What is your diagnosis?

Sarcoidosis arising in a tattoo

Eruptive keratoacanthomas

Hypertrophic discoid lupus

Pseudoepitheliomatous hyperplasia

d

female

51-60

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2593031

A 22-year-old woman with a history of systemic lupus erythematosus was readmitted with fever and a generalized eruption. Six days prior to this admission, she had been hospitalized for a photo-induced flare of acute cutaneous lupus erythematosus (ACLE). At readmission, she was febrile with a temperature of 101.5°F, and on examination, she had a worsening, exquisitely tender rash with several blisters across her right arm. Physical examination revealed erythematous plaques with superficial desquamation in the malar distribution of the face, nose, ears, and medial forehead (Figure, A), as well as bilateral extensor arms, chest, posterior neck, and upper back. Several large bullae were located on the right arm (Figure, B). Numerous flat and raised 2-zoned atypical targets with dusky centers were appreciated on the forearms, abdomen, back (Figure, C), thighs, legs, palms and soles.A, Dusky malar erythema with focal heme crusting. B, Flaccid bullae and target lesions. C, Diffuse typical and atypical target lesions of the back. D, High-power view (original magnification 100×) of punch biopsy obtained from left abdomen demonstrating dyskeratosis with superficial perivascular inflammation and interface changes.Hemogram test results revealed a normocytic anemia (mean corpuscular volume, 99 fL; hemoglobin, 11.7 g/dL [to convert to g/L, multiply by 10.0]; hematocrit, 33.4%), in addition to thrombocytopenia (platelet count, 81 K/μL). Other pertinent laboratories included hypocomplementemia (C3 of 42 mg/dL; C4 of 3 mg/dL), a speckled antinuclear antibody titer of 1:1280, and an antidouble-stranded DNA titer of 1:80, along with positive anti-Smith, antiribonucleoprotein, and SSA/anti-Ro antibodies. Bacterial blood, urine, stool and cerebrospinal fluid cultures, and a hepatitis panel revealed no infectious source. Punch biopsy of an abdominal atypical target lesion was performed (Figure, D). What Is Your Diagnosis?

Pemphigus erythematosus

Generalized fixed drug eruption

Rowell syndrome

Toxic epidermal necrolysis

C. Rowell syndrome

C

Rowell syndrome

Punch biopsy of a left abdominal target lesion revealed dyskeratosis with superficial perivascular inflammation and interface changes resembling erythema multiforme (EM). Additional features of cutaneous lupus erythematosus (LE) were not observed. An acute stratum corneum was present overlying full thickness epithelial necrosis (Figure, C).The constellation of patient history, clinical findings, and histopathology were congruent with a diagnosis of Rowell syndrome. No infectious or drug-related etiology was identified, thus it was thought that her lupus flare was the catalyst for the EM. Pulsed methylprednisone was given in conjunction with topical fluocinonide ointment and Domeboro soaks, and the patient was discharged in dramatically improved condition after 1 week of inpatient management.Rowell syndrome refers to a rare clinical manifestation of lesions resembling EM in patients with LE. This entity has been described in association with all clinical variants of LE. Scholtz first recognized the link between LE and EM in 1922, and it was further delineated by Rowell and colleagues in 1963.1 The majority of reported cases describe concomitant LE and EM but do not strictly adhere to the original description of Rowell syndrome. Thus, Zeutoni et al2 modified the original criteria for Rowell syndrome, proposing 3 major and 1 minor criteria requisite for diagnosis. Major criteria include: (1) systemic lupus erythematosus, discoid LE, or subacute cutaneous LE; (2) EM-like lesions (with or without involvement of the mucous membranes); and (3) speckled pattern of antinuclear antibody. Minor criteria include: (1) chilblains; (2) anti-Ro antibody or anti-La antibody; and (3) positive rheumatoid factor.2Whether or not Rowell syndrome exists (eg, if it constitutes a nosographically distinct clinical entity or simply the incidental concurrence of EM and LE) is controversial.3 Recent literature suggests that certain presentations of Rowell syndrome may actually represent a phenotypical variant of subacute cutaneous LEand/or acute LE, defined as subacute cutaneous LE and/or acute LE with EM-like lesions.4 These cases diverge from EM in that mucosal and acral sites are not preferentially involved. Other presentations of Rowell syndrome, including the case described herein, are thought to represent the acute syndrome of apoptotic panepidermolysis(ASAP), a unifying descriptor for the entire spectrum of conditions characterized by fulminant epidermal cleavage conferred by hyperacute apoptotic injury. The ASAP designation includes, but is not limited to, EM, Steven Johnson syndrome, the toxic epidermal necrolysisspectrum and toxic epidermal necrolysis–like forms of cutaneous injury.5 In cases such as ours, LE, rather than an infection or medication, is the inciting factor for ASAP.Rowell syndrome presents as the raised typical and atypical targets of EM. Typical target lesions are edematous round papules or plaques with discrete borders and 2 outer zones of color change surrounding a central zone of epidermal necrosis. This central zone often appears as a dusky area or blister. Atypical target lesions may occur in conjunction with typical targets, or alternatively represent the primary cutaneous lesions. Atypical targets, like typical targets, are round, palpable and edematous but demonstrate only 2 appreciable zones and/or ill-defined borders.6 The raised character of atypical target EM lesions may distinguish them from the flat lesions of Steven Johnson syndrome and/or toxic epidermal necrolysis.Histopathology in Rowell syndrome reveals changes consistent with EM. Necrotic keratinocytes and perivascular lymphocytic infiltration with exocytosis into the epidermis are seen. Blister formation may occur at varying levels of the epidermis, and superficial epidermal edema is also frequently observed. In cases of subacute cutaneous LE and/or acute LE with EM-like lesions, changes of LE including mucin deposition and interface dermatitis may be appreciated.Many cases of Rowell syndrome have been managed with corticosteroids and/or antimalarials with variable response. In severe cases mimicking Steven Johnson syndrome and/or toxic epidermal necrolysis, patients may benefit from intravenous immunoglobulin.5,7 The condition may be resistant to treatment and is frequently recurrent.3

Dermatology

A 22-year-old woman with a history of systemic lupus erythematosus was readmitted with fever and a generalized eruption. Six days prior to this admission, she had been hospitalized for a photo-induced flare of acute cutaneous lupus erythematosus (ACLE). At readmission, she was febrile with a temperature of 101.5°F, and on examination, she had a worsening, exquisitely tender rash with several blisters across her right arm. Physical examination revealed erythematous plaques with superficial desquamation in the malar distribution of the face, nose, ears, and medial forehead (Figure, A), as well as bilateral extensor arms, chest, posterior neck, and upper back. Several large bullae were located on the right arm (Figure, B). Numerous flat and raised 2-zoned atypical targets with dusky centers were appreciated on the forearms, abdomen, back (Figure, C), thighs, legs, palms and soles.A, Dusky malar erythema with focal heme crusting. B, Flaccid bullae and target lesions. C, Diffuse typical and atypical target lesions of the back. D, High-power view (original magnification 100×) of punch biopsy obtained from left abdomen demonstrating dyskeratosis with superficial perivascular inflammation and interface changes.Hemogram test results revealed a normocytic anemia (mean corpuscular volume, 99 fL; hemoglobin, 11.7 g/dL [to convert to g/L, multiply by 10.0]; hematocrit, 33.4%), in addition to thrombocytopenia (platelet count, 81 K/μL). Other pertinent laboratories included hypocomplementemia (C3 of 42 mg/dL; C4 of 3 mg/dL), a speckled antinuclear antibody titer of 1:1280, and an antidouble-stranded DNA titer of 1:80, along with positive anti-Smith, antiribonucleoprotein, and SSA/anti-Ro antibodies. Bacterial blood, urine, stool and cerebrospinal fluid cultures, and a hepatitis panel revealed no infectious source. Punch biopsy of an abdominal atypical target lesion was performed (Figure, D).

what is your diagnosis?

What is your diagnosis?

Generalized fixed drug eruption

Rowell syndrome

Toxic epidermal necrolysis

Pemphigus erythematosus

b

female

21-30

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2606440

A 21-year-old man was admitted to the hospital owing to recurrent, transient episodes of dysarthria, dysphagia, and limb weakness over the course of 3 days. Although these symptoms had resolved after 3 hours’ rest, they recurred 2 hours prior to hospital admission. In addition, the patient had begun to experience weakness and numbness of his limbs, with more severe symptoms on the right side. The symptoms began to gradually resolve 2 hours following admission, and normal function had returned within 2 days. No significant history of illness was noted in the patient or among family members.Neurological examination on admission revealed normal mental status, and the results of cranial nerve examination were normal. Although the patient had cavus feet, no atrophy was observed in the distal lower limbs (Figure, A). Muscle strength was classified as grade 4 for the left limbs and grade 3 for the right limbs, according to Medical Research Council criteria, and muscle tone was diminished. The sensory examination was unremarkable. Deep reflexes were diminished or absent. However, bilateral positive Babinski signs were observed. Results from laboratory examinations, including blood electrolytes, cerebrospinal fluid, and lactate, were normal. Oligonucleotide bands and aquaporin 4 detection were negative. Craniocervical computed tomographic angiography results were normal. Cerebral magnetic resonance imaging (MRI) revealed abnormal bilateral increases in T2 signal and diffusion restriction in the periventricular areas and the splenium of corpus callosum (Figure, B). Interestingly, a significant reduction of the abnormal signal was noted on MRI 3 months later. Electrophysiological examination of peripheral nerves revealed extensive bilateral nerve conduction abnormalities. Significantly reduced motor nerve conduction velocity was also observed in the median nerves (38.3 m per second in the left and 36.5 m per second in the right).A, Image shows patient’s pes cavus. B, Patient’s brain axial diffusion-weighted image at admission. Demyelinating disease (multiple sclerosis or acute disseminated encephalomyelitis) What Is Your Diagnosis?

Transient ischemic attack

Demyelinating disease (multiple sclerosis or acute disseminated encephalomyelitis)

Periodic paralysis

X-linked Charcot-Marie-Tooth disease 1

D. X-linked Charcot-Marie-Tooth disease 1

D

X-linked Charcot-Marie-Tooth disease 1

Periodic paralysis and transient ischemic attack (TIA) were initially considered. However, levels of serum electrolytes were normal during episodes, and dysarthria and dysphagia are not causal symptoms of periodic paralysis. Diagnosis of TIA seemed reasonable for the transient weakness of limbs and bulbar muscles owing to complete restoration of function after episodes. However, TIA cannot explain the diminished or absent tendon reflex, as well as the extensive peripheral nerve impairment detected by the nerve conduction tests. Thus, TIA was excluded. Abnormally increased signal (including diffusion restriction) revealed in the cerebral MRI may be found in cases of cerebral infarction; however, the clinical course did not support this diagnosis.Lesions in cerebral white matter and recurrent episodes followed by periods of remission led to the consideration of demyelinating disease (multiple sclerosis [MS] or acute disseminated encephalomyelitis). However, in MS, the duration of each episode is more than 24 hours. Typical MRI images of MS depict round or oval lesions of different sizes in white matter. Periventricular lesions are usually elliptical or linear and perpendicular to the lateral ventricle.1 In addition, oligonucleotide bands were negative for this patient. Therefore, MS was unlikely. Furthermore, asymmetric cerebral white matter lesions are usually observed in acute disseminated encephalomyelitis, and the clinical course is usually monophasic. Relapse cannot occur within several days, as seen in this patient.Significant conductive abnormalities of extensive peripheral nerves in the electrophysiological examination were also observed. Cavus can usually be found in Charcot-Marie-Tooth (CMT) disease.2 Of particular interest were the coexistent intracranial white matter lesions, which indicated central nervous system (CNS) involvement and peripheral nerve impairment. Considering the involvement of both the CNS and peripheral nervous system, we suspected a diagnosis of X-linked CMT disease 1 (CMTX1) for the patient.Charcot-Marie-Tooth diseases are a group of hereditary sensorimotor neuropathies characterized by slowly progressing distal muscle atrophy and weakness, initially affecting the lower extremities. X-linked CMT disease is the second most common type of CMT, and CMTX1 accounts for 90% of cases in patients with CMTX.3 The most notable and atypical clinical characteristics of CMTX1 are reversible cerebral white matter lesions.4 Several reports have indicated CNS involvement in patients with CMTX1.5,6 In addition to the typical CMT clinical features, patients with CMTX1 may experience recurrent dysarthria, dysphagia, limb weakness, and paralysis.4 Central nervous system manifestation may be the initial symptom for patients with CMTX1, when symptoms of peripheral nerve impairment are not obvious.7X-linked CMT disease 1 is due to mutations in GJB1, the gene responsible for encoding connexin 32, which is highly present in Schwann cells and oligodendrocytes and forms gap junctions. GJB1 mutations may reduce and disrupt transmission between oligodendrocytes and astrocytes in the cerebral white matter, resulting in dysfunction of the brain and transient paralysis. In this patient, analysis of the connexin 32 gene was performed and revealed a missense mutation c.311A>C. This mutation has been reported in previous cases.8 Thus, the patient was diagnosed as having CMTX1.The present case suggests that, for those with transient CNS involvement and white matter lesions, physical examination and electrophysiological examination of the peripheral neuropathy should be performed to screen for CMTX1.

Neurology

A 21-year-old man was admitted to the hospital owing to recurrent, transient episodes of dysarthria, dysphagia, and limb weakness over the course of 3 days. Although these symptoms had resolved after 3 hours’ rest, they recurred 2 hours prior to hospital admission. In addition, the patient had begun to experience weakness and numbness of his limbs, with more severe symptoms on the right side. The symptoms began to gradually resolve 2 hours following admission, and normal function had returned within 2 days. No significant history of illness was noted in the patient or among family members.Neurological examination on admission revealed normal mental status, and the results of cranial nerve examination were normal. Although the patient had cavus feet, no atrophy was observed in the distal lower limbs (Figure, A). Muscle strength was classified as grade 4 for the left limbs and grade 3 for the right limbs, according to Medical Research Council criteria, and muscle tone was diminished. The sensory examination was unremarkable. Deep reflexes were diminished or absent. However, bilateral positive Babinski signs were observed. Results from laboratory examinations, including blood electrolytes, cerebrospinal fluid, and lactate, were normal. Oligonucleotide bands and aquaporin 4 detection were negative. Craniocervical computed tomographic angiography results were normal. Cerebral magnetic resonance imaging (MRI) revealed abnormal bilateral increases in T2 signal and diffusion restriction in the periventricular areas and the splenium of corpus callosum (Figure, B). Interestingly, a significant reduction of the abnormal signal was noted on MRI 3 months later. Electrophysiological examination of peripheral nerves revealed extensive bilateral nerve conduction abnormalities. Significantly reduced motor nerve conduction velocity was also observed in the median nerves (38.3 m per second in the left and 36.5 m per second in the right).A, Image shows patient’s pes cavus. B, Patient’s brain axial diffusion-weighted image at admission. Demyelinating disease (multiple sclerosis or acute disseminated encephalomyelitis)

what is your diagnosis?

What is your diagnosis?

Demyelinating disease (multiple sclerosis or acute disseminated encephalomyelitis)

Periodic paralysis

X-linked Charcot-Marie-Tooth disease 1

Transient ischemic attack

c

male

21-30

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2610465

A 66-year-old woman with a remote history of a pituitary macroadenoma was referred to the neuro-ophthalmology clinic for intermittent diplopia of several years’ duration. Diplopia was frequently present after repeatedly changing direction of gaze. She also noted mild right ptosis. Her visual acuity was unaffected. There was no associated headache or ocular or periorbital pain. She had not noticed any injection of the sclera. Her family and friends made no comments regarding exophthalmos. She had not noticed any deficits in axial or appendicular strength, rapid fatigability, or dysphagia. Her symptoms did not exhibit diurnal variation. Her weight was stable. She had not noted any changes in her hair, skin, or nails. She had no subjective disturbance of thermoregulation. Her relevant history included a pituitary macroadenoma, which had been resected 30 years prior, followed by radiation. There was no evidence of subsequent recurrence. There was no family history of ptosis, ophthalmoplegia, or myopathy. The patient was a retired English teacher.Examination demonstrated anisocoria (right pupil larger than left), which was accentuated in bright ambient light; mild right ptosis; and mildly restricted supraduction, adduction, and infraduction of the right eye (Video, prepared by N.T.). The second half of the Video (from 24 seconds on) demonstrates marked restriction of elevation, depression, and abduction in the right eye after eccentric gaze. Ductions in the left eye were normal. The patient’s neurological examination demonstrated a normal level of consciousness, fluent speech, normal comprehension, good attention, normal cranial nerve function aside from the aforementioned deficits, full strength, normal sensation to proprioception and temperature, symmetric reflexes, absence of ataxia, and a stable, narrow-based gait. A recent contrast-enhanced brain magnetic resonance image showed a stable intracanalicular vestibular schwannoma on the left, which had been monitored for 8 years. What Is Your Diagnosis?

Ocular myasthenia

Ocular neuromyotonia of the third nerve

Giant cell arteritis

Cavernous sinus syndrome

B. Ocular neuromyotonia of the third nerve

B

Ocular neuromyotonia of the third nerve

Examination initially revealed only a mild third nerve palsy in the right eye, which was due to radiation therapy many years prior. The subsequent development of marked restriction in elevation and depression could be consistent with myasthenia or ocular neuromyotonia, but the development of a marked abduction deficit immediately after adduction suggests ocular neuromyotonia as the correct diagnosis. Ocular neuromyotonia involves tonic overaction of the extraocular muscles innervated by any ocular motor nerve with impaired relaxation following activation.1 The increasingly severe motility deficits seen with continued testing reflect the inability of the third nerve–innervated muscles to relax after their initial activation. Thus, the inability to abduct the eye immediately after adduction provides the critical clue to the diagnosis.Ocular myasthenia also causes motor deficits that worsen with continued testing and should always be included in the differential diagnosis of intermittent diplopia. It can mimic pure oculomotor, trochlear, and abducens palsies. Myasthenia never affects the pupil. Were this myasthenia, one would expect the initial adduction impairment to worsen with continued activation.The manifestations of giant cell arteritis are protean and, like myasthenia, this should always be considered in patients older than age 50 years presenting with intermittent diplopia. Giant cell arteritis may result in transient or static dysfunction of the oculomotor, trochlear, or abducens nerves. It may also cause ischemia to any extraocular muscle. However, the history of intermittent diplopia over several years without any definitive event makes giant cell arteritis implausible, and an evolving abduction deficit with repetitive examination suggests a pathology beyond a static cranial mononeuropathy.If the abduction deficit were mistaken for a VI nerve palsy, the combination of deficits to cranial nerves III and VI might suggest a lesion in the cavernous sinus. Cavernous sinus syndrome can result in any combination of deficits referable to cranial nerves III, IV, V, and VI. Sympathetic dysfunction may also occur, resulting in a Horner syndrome. In this case, the key finding to note is that the abduction deficit developed only after adduction, which is inconsistent with a cranial nerve VI palsy.Ocular neuromyotonia may be seen as a delayed complication of radiation treatment,2 tumors,3 thyroid eye disease,4 or vascular irritation.5 The mechanism by which ocular neuromyotonia occurs is unclear but may relate to ephaptic stimulation of the affected cranial nerve, whereby axons are depolarized via nonsynaptic stimulation.6 This may explain the response seen in some patients to drugs such as carbamazepine.7 Recognition of ocular neuromyotonia is of increasing importance given the increasing age of the population and the possibility of occurrence as a very late complication of radiation treatment. What was previously thought to be a rare disease is encountered on a regular basis in academic medical settings and prompt recognition of this highly characteristic disease can avoid costly and unnecessary testing as well as iatrogenesis when the disease is mistaken for ocular myasthenia and treated incorrectly as such.

Neurology

A 66-year-old woman with a remote history of a pituitary macroadenoma was referred to the neuro-ophthalmology clinic for intermittent diplopia of several years’ duration. Diplopia was frequently present after repeatedly changing direction of gaze. She also noted mild right ptosis. Her visual acuity was unaffected. There was no associated headache or ocular or periorbital pain. She had not noticed any injection of the sclera. Her family and friends made no comments regarding exophthalmos. She had not noticed any deficits in axial or appendicular strength, rapid fatigability, or dysphagia. Her symptoms did not exhibit diurnal variation. Her weight was stable. She had not noted any changes in her hair, skin, or nails. She had no subjective disturbance of thermoregulation. Her relevant history included a pituitary macroadenoma, which had been resected 30 years prior, followed by radiation. There was no evidence of subsequent recurrence. There was no family history of ptosis, ophthalmoplegia, or myopathy. The patient was a retired English teacher.Examination demonstrated anisocoria (right pupil larger than left), which was accentuated in bright ambient light; mild right ptosis; and mildly restricted supraduction, adduction, and infraduction of the right eye (Video, prepared by N.T.). The second half of the Video (from 24 seconds on) demonstrates marked restriction of elevation, depression, and abduction in the right eye after eccentric gaze. Ductions in the left eye were normal. The patient’s neurological examination demonstrated a normal level of consciousness, fluent speech, normal comprehension, good attention, normal cranial nerve function aside from the aforementioned deficits, full strength, normal sensation to proprioception and temperature, symmetric reflexes, absence of ataxia, and a stable, narrow-based gait. A recent contrast-enhanced brain magnetic resonance image showed a stable intracanalicular vestibular schwannoma on the left, which had been monitored for 8 years.

what is your diagnosis?

What is your diagnosis?

Cavernous sinus syndrome

Ocular myasthenia

Giant cell arteritis

Ocular neuromyotonia of the third nerve

d

female

61-70

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2612471

A 58-year-old man presented with a 1-year history of severe and progressive action tremor in his dominant hand when writing. When questioned, he described subtle balance problems without falls developing over the past 3 years. With the exception of profound difficulties with handwriting, motor symptoms did not affect livelihood or activities of daily living. There was no tremor reported in the nondominant hand or other limbs or symptoms of autonomic dysfunction. Neither he nor his wife reported any changes in cognitive function. His medical history comprised surgeries of the hand (laceration repair), leg (fracture repair), knee (reconstruction), and ear (stapedectomy); these were not related to the presenting symptoms. He had a family history of ischemic heart disease (both parents) but no family history of neurological disorder. He exercised regularly (5 times per week) and consumed 2 to 4 standard drinks per week. He was a former smoker with a 2-year pack history and denied any illicit drug use.Cognitive testing revealed deficits in executive function and speed of information processing. Examination of eye movements and speech revealed jerky eye pursuit, saccadic dysmetria, and moderate slurring of speech. Additional motor signs included abnormal handwriting (Figure 1A), bilateral intention tremor, mild rigidity (upper extremities), and moderately impaired heel tapping. Facial expression was normal. There was no head or resting tremor. He demonstrated moderate body sway while standing, was unable to stand on 1 foot for more than 10 seconds, and had impaired tandem walking. Gait, posture, and walking capacities during a timed 6-m walk were normal.A, Handwriting task from the motor examination showing abnormal handwriting. B, T2-weighted fluid-attenuated inversion recovery image from brain magnetic resonance imaging showing white matter hyperintensities in the middle cerebellar peduncles.Routine blood test results were normal. Brain magnetic resonance imaging showed moderate volume loss in the cerebral hemispheres bilaterally as well as the cerebellum and brainstem. Abnormal signal intensity was noted in the cerebral hemispheric white matter bilaterally, the middle cerebellar peduncles (Figure 1B), the cerebellar white matter, and the pons. What Is Your Diagnosis?

Multiple system atrophy

Vascular dementia

Fragile X–associated tremor ataxia syndrome

Essential tremor

C. Fragile X-associated tremor ataxia syndrome

C

Fragile X–associated tremor ataxia syndrome

This patient presented with intention tremor, balance instability, executive dysfunction, and slowed information processing. Brain magnetic resonance imaging revealed bilateral volume loss (Figure 2) and white matter lesions throughout the cerebral cortex and cerebellum. These features are highly suggestive of fragile X-associated tremor ataxia syndrome (FXTAS),1 an X-linked neurodegenerative disorder caused by premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene.2 The diagnosis was confirmed by genetic testing, showing an expanded FMR1 allele with 91 CGG repeats.T1-weighted images from brain magnetic resonance imaging showing bilateral volume loss in the cerebral cortex and cerebellum.Alternate diagnoses included multiple system atrophy, which would be consistent with the age at onset, cerebellar involvement, and magnetic resonance imaging signs. This diagnosis was less likely because there were no signs of autonomic dysfunction, muscle weakness, or falls. Vascular dementia was unlikely because symptoms of tremor and ataxia were more prominent than cognitive deficits, and the patient had no history of hypertension, cerebrovascular, or cardiovascular events. While essential tremor would be consistent with tremor affecting the hands, impaired tandem gait, and executive dysfunction, this diagnosis was less likely because the patient’s balance problems preceded the onset of tremor.Approximately 1 in 209 women and 1 in 430 men in the general population carry premutation expansions of the FMR1 gene.3 Up to 46% of men and 17% of women with the premutation will develop symptoms of FXTAS from 50 years of age.4 Diagnosis is based on a combination of clinical and radiological features, including intention tremor, gait ataxia, parkinsonism, peripheral neuropathy, cortical/cerebellar atrophy, and white matter lesions in the cerebral cortex, cerebellum, and splenium.1 Neuropsychiatric features may include depression, anxiety, apathy, disinhibition, agitation, and irritability.5 The mechanisms by which FXTAS occurs are unclear; the most widely known pathogenic models suggest toxicity of abnormal ribonucleic acid species with expanded CGG repeats.2 Insults to the central nervous system (eg, chemotherapy, environmental toxins, and general anesthesia) may accelerate symptom progression.6Despite the community prevalence of the FMR1 premutation, FXTAS is underrecognized.7 Common misdiagnoses include idiopathic Parkinson disease, essential tremor, and multiple system atrophy. Diagnostic challenges may arise owing to lack of awareness of the disorder and the presence of clinical features similar to those seen in other age-related conditions. A family history of fragile X–associated disorders (FXTAS, fragile X-associated ovarian insufficiency, and fragile X syndrome, the most common form of inherited intellectual disability) may provide an indication for genetic testing. Because this patient did not have a known family history of fragile X–associated disorders, brain MRI and FMR1 genetic testing were crucial in obtaining a diagnosis of FXTAS.Genetic testing for an FMR1 mutation is recommended if a patient has (1) onset of cerebellar ataxia or action tremor of unknown cause with parkinsonism or cognitive decline from the age of 50 years; (2) a previous diagnosis of multiple system atrophy, cerebellar subtype; (3) abnormal signal intensity in the middle cerebellar peduncles and clinical signs consistent with FXTAS; and (4) a known family history of fragile X–associated disorders with plausible inheritance, based on their position in the pedigree.8

Neurology

A 58-year-old man presented with a 1-year history of severe and progressive action tremor in his dominant hand when writing. When questioned, he described subtle balance problems without falls developing over the past 3 years. With the exception of profound difficulties with handwriting, motor symptoms did not affect livelihood or activities of daily living. There was no tremor reported in the nondominant hand or other limbs or symptoms of autonomic dysfunction. Neither he nor his wife reported any changes in cognitive function. His medical history comprised surgeries of the hand (laceration repair), leg (fracture repair), knee (reconstruction), and ear (stapedectomy); these were not related to the presenting symptoms. He had a family history of ischemic heart disease (both parents) but no family history of neurological disorder. He exercised regularly (5 times per week) and consumed 2 to 4 standard drinks per week. He was a former smoker with a 2-year pack history and denied any illicit drug use.Cognitive testing revealed deficits in executive function and speed of information processing. Examination of eye movements and speech revealed jerky eye pursuit, saccadic dysmetria, and moderate slurring of speech. Additional motor signs included abnormal handwriting (Figure 1A), bilateral intention tremor, mild rigidity (upper extremities), and moderately impaired heel tapping. Facial expression was normal. There was no head or resting tremor. He demonstrated moderate body sway while standing, was unable to stand on 1 foot for more than 10 seconds, and had impaired tandem walking. Gait, posture, and walking capacities during a timed 6-m walk were normal.A, Handwriting task from the motor examination showing abnormal handwriting. B, T2-weighted fluid-attenuated inversion recovery image from brain magnetic resonance imaging showing white matter hyperintensities in the middle cerebellar peduncles.Routine blood test results were normal. Brain magnetic resonance imaging showed moderate volume loss in the cerebral hemispheres bilaterally as well as the cerebellum and brainstem. Abnormal signal intensity was noted in the cerebral hemispheric white matter bilaterally, the middle cerebellar peduncles (Figure 1B), the cerebellar white matter, and the pons.

what is your diagnosis?

What is your diagnosis?

Multiple system atrophy

Fragile X–associated tremor ataxia syndrome

Vascular dementia

Essential tremor

b

male

51-60

White

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2606516

An 11-day-old, full-term girl presented for evaluation of multiple skin changes that were noted at birth (Figure). These skin changes included a red patch on the central lower back with a soft nodule located on top of the patch. Additionally, she had a pedunculated red papule positioned on top of the red stain and soft nodule. She was asymptomatic, moving all limbs, urinating, and defecating normally. Her prenatal screens, including 20-week ultrasonography, were normal. Pregnancy was uncomplicated and there was no history of teratogenic exposure or family history of congenital defects. Ultrasonography of the spine obtained prior to the visit showed no abnormalities.Photograph depicting a red patch with overlying soft nodule and red pedunculated papule in the lower midback of a neonate. What Is Your Diagnosis?

Teratoma

Spinal dysraphism

Dermoid cyst

Hemangioma

B. Spinal dysraphism

B

Spinal dysraphism

This patient had a port wine stain/capillary malformation with a lipoma and polypoid skin tag in a single location on the lower spine, placing her in a high-risk classification for spinal dysraphism. Imaging of the spine was ordered to confirm suspicions for underlying spinal cord changes. Magnetic resonance imaging (MRI) with and without contrast revealed an intraspinal lipoma with extension to the lipoma present on the skin. The spinal lipoma spanned from posterior and superior to the tip of the conus, which terminated at L2, through to the spinal canal at the L4-L5 level. Per report, there was normal distribution of the cauda equina roots in the thecal sac. Based on these MRI findings, the patient was referred to neurosurgery for discussion of surgical intervention.Spinal dysraphisms encompass a variety of congenital anomalies that occur due to defects in spinal cord development. This condition is defined by failure of appropriate midline fusion of bony, neural, or mesenchymal elements of the spine.1 Although spinal dysraphism may occur at any level, it is most common in the lumbosacral spine.2 No one etiology for spinal dysraphism has been identified, but rather it is thought to occur as a result of effects from both genetic and environmental factors.2 Owing to their common ectodermal etiology and timings of embryological development, spinal dysraphisms are frequently associated with overlying cutaneous findings. The presence of these visible skin markers, especially in a midline and sacral location, is often considered an indication for further imaging to rule out the presence of underlying spinal defects. Detection of these cutaneous signs at an early stage and prompt referral in some cases can be crucial to prevent future irreversible damage.Cutaneous markers are estimated to be present in 50% to 70% of patients with spinal dysraphism.3,4 Moreover, the presence of multiple cutaneous markers has been found to incur a higher risk for an associated defect.5 Of these skin findings, the most commonly encountered associations include hemangiomas, hyperpigmented or vascular patches, hypertrichosis, lipomas, aplasia cutis congenita, and acrochordons/skin tags.2,5Related changes have been associated with varying risk potentials for underlying spinal defects.1,2,5-7 Using current data, cutaneous markings can be divided into high, intermediate, and low risk. High-risk cutaneous findings include lipoma, acrochordon, tail, aplasia cutis, dermoid cyst or dermal sinus, infantile hemangioma greater than 2.5 cm, and the presence of 2 or more cutaneous defects.1,2 Less than 3% of neonates with these high-risk cutaneous markers have no signs of underlying defects on imaging.5 Intermediate-risk skin findings include atypical dimples more than 5 mm in diameter, infantile hemangioma less than 2.5 cm, and hypertrichosis.7 Finally, low-risk markers include dyschromia, melanocytic nevi, simple dimple less than 5 mm in diameter, teratomas, capillary malformation, and telangiectasis.7 The presence of these cutaneous findings and more specifically their classification based on risk provides useful guidance for imaging of patients with suspected occult spinal dysraphism. A review article by Sewell et al2 recommended MRI as first-line evaluation in patients with high-risk cutaneous findings based on high pretest probability. Patients with intermediate-risk cutaneous findings were recommended to undergo ultrasonography if they were younger than 6 months of age and MRI if they were older than 6 months. Ultrasonography alone is recommended in patients with low-risk cutaneous findings.Spinal dysraphism can have a variety of presentations and closed or occult defects are not always clinically apparent. The presence of associated skin markers, such as those found in this patient, are often an important indication for further workup and imaging. Delayed diagnosis of spinal dysraphism may be associated with delayed development of sphincter control, delay in walking, asymmetry of the legs, and pain in the back or lower extremities.8-10 Therefore, using cutaneous markers stratified by risk category is an invaluable tool in guiding management and early detection.

Pediatrics

An 11-day-old, full-term girl presented for evaluation of multiple skin changes that were noted at birth (Figure). These skin changes included a red patch on the central lower back with a soft nodule located on top of the patch. Additionally, she had a pedunculated red papule positioned on top of the red stain and soft nodule. She was asymptomatic, moving all limbs, urinating, and defecating normally. Her prenatal screens, including 20-week ultrasonography, were normal. Pregnancy was uncomplicated and there was no history of teratogenic exposure or family history of congenital defects. Ultrasonography of the spine obtained prior to the visit showed no abnormalities.Photograph depicting a red patch with overlying soft nodule and red pedunculated papule in the lower midback of a neonate.

what is your diagnosis?

What is your diagnosis?

Spinal dysraphism

Dermoid cyst

Teratoma

Hemangioma

a

female

0-10

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2615256

A 30-year-old woman was diagnosed with primary sclerosing cholangitis (PSC) during pregnancy at age 25 years. She was normocholesterolemic prior to the diagnosis of PSC (total cholesterol [TC], 188 mg/dL [to convert to millimoles per liter, multiply by 0.0259]). Following the diagnosis of PSC, she developed moderate hypercholesterolemia (representative TC, 256 mg/dL). She first noted the appearance of periorbital xanthelasmata 2 years after PSC diagnosis (Figure 1A). Approximately 6 months prior to referral, she developed marked worsening of biliary obstruction, deterioration of liver function, and clinical jaundice (aspartate aminotransferase, 145 U/L; alanine aminotransferase, 111 U/L; alkaline phosphatase, 726 U/L; and bilirubin, 6.7mg/dL), and she noted palmar xanthomata in the creases of her palms and fingers (Figure 1B). Periorbital xanthelasmata (A, arrowheads) and palmar xanthomata (B, arrowheads) in a patient with severe hypercholesterolemia and primary sclerosing cholangitis.At the time of referral, she had severe hypercholesterolemia (TC, 832 mg/dL; triglycerides, 114 mg/dL [to convert to millimoles per liter, multiply by 0.0113]; and high-density lipoprotein cholesterol, 18 mg/dL; low-density lipoprotein cholesterol was not calculated). Medications at the time of referral were 1000 mg per day of ursodeoxycholic acid and 2 g of colestipol twice daily for symptomatic relief of pruritus. The majority of TC (719 mg/dL) consisted of free cholesterol (518 mg/dL) instead of the usual esterified cholesterol. Serum phospholipids levels were high (1186 mg/dL), while triglycerides were normal (97 mg/dL). Fast protein liquid chromatography analysis of serum lipoproteins, after ultracentrifugation to remove very-low-density lipoprotein, indicated the unique composition and distribution of lipid classes in a special form of dyslipidemia known as lipoprotein X (LpX), ie, high unesterified cholesterol and phospholipids in large lipid-containing particles. Based on results of analysis of genomic DNA in a custom targeted lipid gene resequencing panel, she had no rare mutations in 25 genes known to be associated with abnormal lipid traits (including LDLR, APOB, PSCK9, LDLRAP1, APOE, ABCG5, ABCG8, LIPA, and STAP1) and had APOE E3/E3 genotype.1Begin therapeutic plasma exchange plus rosuvastatin, 20 mg per day What Would You Do Next?

Resolve obstructive cholestasis with biliary stent placement

Begin rosuvastatin, 20 mg per day

Begin therapeutic plasma exchange plus rosuvastatin, 20 mg per day

Begin therapeutic plasma exchange

Lipoprotein X secondary to primary sclerosing cholangitis

D

Begin therapeutic plasma exchange

Lipoprotein X accumulates in the plasma in hepatic cholestasis and other rare conditions.2 While the therapeutic goal is relief of cholestasis, management of LpX in patients with long-term cholestasis is indicated to reduce hyperviscosity, neuropathy, and interference with electrolyte and lipid biochemical analyses.3,4 This patient was awaiting liver transplant and had an indefinite period of long-term cholestasis without viable means to alleviate biliary obstruction.Management of LpX in cholestasis has not been well established. Hypercholesterolemia has been reported to resolve with resolution of biliary obstruction, such as with biliary stent placement4 and liver transplant.5 Otherwise, both physical removal of lipids and multiple lipid-modifying drugs have varying effectiveness. Significant reduction in LpX has been achieved with filtration-based semiselective low-density lipoprotein apheresis.6 In a case of PSC, TC was reduced with therapeutic plasma exchanges plus statin and cholestyramine.3 Lipoprotein X particles lack apolipoprotein B; it is not metabolically regulated. This limits the effectiveness of lipid-modifying drugs. Statin therapy has been shown to be insufficient or ineffective in lowering LpX.6,7 In a case of PSC, statin plus cholestyramine was associated with worsening neurological and cutaneous symptoms, although TC was reduced.3 Newer lipid-modifying drugs (eg, ezetimibe and proprotein convertase subtilisin/kexin type 9 antibodies) have not been evaluated in this condition. There was safety concern about using cholesterol-lowering drugs in view of the patient’s severe liver dysfunction. Therefore, we initiated plasma exchange without statins or cholesterol absorption inhibitors. Ursodeoxycholic acid and colestipol, both initiated prior to the patient being referred to our clinic, were continued during plasma exchanges. Therefore, the reduction in cholesterol in this patient reflects the effectiveness of therapeutic plasma exchange.Plasma exchange (1.0 plasma volume exchanged with 5% albumin) was performed weekly initially and biweekly after effective reduction in TC. The first plasma exchange effectively decreased TC to 179 mg/dL, mostly due to reduction in free cholesterol (Figure 2A) in LpX particles. The TC level rebounded before each exchange but has remained stable for 5 months from 387 mg/dL to 500 mg/dL before and approximately 116 mg/dL after (Figure 2B).A, Serum free cholesterol levels before the first plasma exchange and after 4 exchanges. After removing very-low-density lipoprotein by ultracentrifugation, d1.006 bottom fractions of samples were analyzed with fast protein liquid chromatography. B, Serum total cholesterol levels before and after treatment (arrowheads). Postexchange cholesterol on November 8, 2016, was not measured.We report an unusual case of severe dyslipidemia secondary to PSC with palmar xanthomata, a rare form of xanthoma, typically described in type 3 hyperlipoproteinemia.8 Hypercholesterolemia was effectively managed with plasma exchange without statins.Hypercholesterolemia was stabilized for more than 6 months with plasma exchange, and the patient awaits liver transplant.

Cardiology

A 30-year-old woman was diagnosed with primary sclerosing cholangitis (PSC) during pregnancy at age 25 years. She was normocholesterolemic prior to the diagnosis of PSC (total cholesterol [TC], 188 mg/dL [to convert to millimoles per liter, multiply by 0.0259]). Following the diagnosis of PSC, she developed moderate hypercholesterolemia (representative TC, 256 mg/dL). She first noted the appearance of periorbital xanthelasmata 2 years after PSC diagnosis (Figure 1A). Approximately 6 months prior to referral, she developed marked worsening of biliary obstruction, deterioration of liver function, and clinical jaundice (aspartate aminotransferase, 145 U/L; alanine aminotransferase, 111 U/L; alkaline phosphatase, 726 U/L; and bilirubin, 6.7mg/dL), and she noted palmar xanthomata in the creases of her palms and fingers (Figure 1B). Periorbital xanthelasmata (A, arrowheads) and palmar xanthomata (B, arrowheads) in a patient with severe hypercholesterolemia and primary sclerosing cholangitis.At the time of referral, she had severe hypercholesterolemia (TC, 832 mg/dL; triglycerides, 114 mg/dL [to convert to millimoles per liter, multiply by 0.0113]; and high-density lipoprotein cholesterol, 18 mg/dL; low-density lipoprotein cholesterol was not calculated). Medications at the time of referral were 1000 mg per day of ursodeoxycholic acid and 2 g of colestipol twice daily for symptomatic relief of pruritus. The majority of TC (719 mg/dL) consisted of free cholesterol (518 mg/dL) instead of the usual esterified cholesterol. Serum phospholipids levels were high (1186 mg/dL), while triglycerides were normal (97 mg/dL). Fast protein liquid chromatography analysis of serum lipoproteins, after ultracentrifugation to remove very-low-density lipoprotein, indicated the unique composition and distribution of lipid classes in a special form of dyslipidemia known as lipoprotein X (LpX), ie, high unesterified cholesterol and phospholipids in large lipid-containing particles. Based on results of analysis of genomic DNA in a custom targeted lipid gene resequencing panel, she had no rare mutations in 25 genes known to be associated with abnormal lipid traits (including LDLR, APOB, PSCK9, LDLRAP1, APOE, ABCG5, ABCG8, LIPA, and STAP1) and had APOE E3/E3 genotype.1Begin therapeutic plasma exchange plus rosuvastatin, 20 mg per day

what would you do next?

What would you do next?

Begin therapeutic plasma exchange

Begin rosuvastatin, 20 mg per day

Begin therapeutic plasma exchange plus rosuvastatin, 20 mg per day

Resolve obstructive cholestasis with biliary stent placement

a

female

21-30

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2594526

An elderly woman presented with 2 episodes of vertigo lasting a few minutes while stationary over 1 day and a several-year history of right-sided hearing loss. She had not experienced otalgia, otorrhea, or tinnitus. Physical examination revealed a mass obstructing the right external auditory canal and House-Brackmann grade 2 facial nerve weakness on the right. Audiogram revealed right-sided moderate to profound mixed hearing loss. Computed tomography revealed a soft-tissue mass emanating from the middle ear involving the facial canal with surrounding bony erosion, including dehiscence of the tegmen, cochlea, bony labyrinth, lateral semicircular canal, and jugular foramen. The patient underwent transtemporal mastoidectomy and debulking. However, owing to the mass’s vascularity and significant bleeding, the operation was aborted, and she was sent for embolization (Figure, A). Magnetic resonance imaging during embolization revealed intense enhancement in the right middle ear extending from the epitympanum to the hypotympanum with extension into the right external auditory canal (Figure, B). She returned to the operating room, and the vascular mass was found to extend inferiorly to the jugular bulb and carotid and anteriorly into the eustachian tube. The mass was adherent to the underlying bone and had invaded the facial canal but not the nerve itself. Both malleus and incus were eroded. Immunohistochemical stains of the specimen indicated cells positive for synaptophysin with a sustentacular pattern of cells positive for S-100 (Figure, C and D).A, Mastoidectomy, visualization of vascular mass. B, T1-weighted axial magnetic resonance image (MRI) showing enhancement of right middle ear extending to external auditory canal. C, Hematoxylin-eosin, original magnification ×40. Clusters of cells surrounded by vascular tissue. D, Synaptophysin stain, original magnification ×40. Nests of strongly staining neuroendocrine cells separated by vasculature. What Is Your Diagnosis?

Middle ear paraganglioma

Facial nerve hemangioma

Facial nerve schwannoma

Middle ear adenoma

A. Middle ear paraganglioma

A

Middle ear paraganglioma

Middle ear paragangliomas are parasympathetic neoplasms of naturally occurring paraganglionic bodies. Paragangliomas are slow-growing, invasive, vascularized neoplasms arising from either the middle ear or the jugular bulb, with a small percentage derived from the facial nerve.1 Middle ear paragangliomas predominate in women, usually presenting in the fifth and sixth decades with biphasic peaks in the fourth and seventh decades.2,3 Though most go unreported, the incidence of head and neck paragangliomas has been estimated at 1 per 100 000.2,4 Most of these are sporadic, although 10% to 30% are familial and associated with mutations in the succinate dehydrogenase complex.3,5The hallmark presentation for middle ear paraganglioma includes pulsatile tinnitus (81%-90%), hearing loss (77%-81%), and aural fullness (12%-71%).6,7 They often abut or invade nearby cranial nerves, with patients occasionally presenting with facial paresis (0%-3%), dysphasia, hoarseness, and even shoulder or tongue weakness.6,7 Physical examination may reveal a fleshy red mass in the middle ear that blanches secondary to pressure from pneumatic otoscopy (Brown sign). Biopsy is contraindicated owing to the mass’s vascularity and possible catecholamine secretion.Parasympathetic paragangliomas in general have a low incidence of catecholamine secretion, with only 1% to 3% of patients presenting with symptoms of catecholamine excess.3,8 Patients should nevertheless be questioned regarding symptoms of catecholamine secretion such as palpitations, headaches, and hypertension. While all suspicions for middle ear paraganglioma should be tested for urine metanephrine and vanillylmandelic acid preoperatively, positive results should prompt investigation for pheochromocytoma owing to the low incidence of functional glomus tumors.2 Serum epinephrine and norepinephrine levels are also useful in diagnosis, as parasympathetic paragangliomas lack the enzyme phenylethanolamine N-methyltransferase, which converts norepinephrine to epinephrine in their sympathetic counterparts.Computed tomography with contrast classically demonstrates a homogeneous mass with intense enhancement, and is particularly sensitive for signs of bony involvement. Magnetic resonance imaging with gadolinium enhances soft-tissue detail, resulting in a lower false-negative rate9 and better delineating dural and neurovascular involvement. Magnetic resonance images demonstrate T1-isointense signaling and T2-hyperintense signaling with a possible “salt and pepper” pattern in larger lesions owing to flow voids.8 Magnetic resonance angiography can further delineate the relationship to the carotid artery, sigmoid sinus and jugular bulb, and identify potential blood supply—often the ascending pharyngeal artery in the case of jugular bulb paragangliomas. The differential diagnosis for a vascular lesion near the geniculate ganglion includes facial nerve hemangioma, which also presents with significant facial nerve paresis and bony erosion disproportionate to its size.Histologically, paragangliomas present as nests of chief cells—polygonal cells with round nuclei and granular, eosinophilic cytoplasm—surrounded by spindle-shaped sustentacular cells in a Zellballen pattern.3 Higher-grade tumors have been shown to progressively lose the relationship between the 2 cell types.10 Immunohistochemical staining of chief cells demonstrates positive staining for neuroendocrine markers, such as neuron-specific enolase, synaptophysin and/or chromogranin, and negative staining for keratins. This lack of keratin immunostaining in paragangliomas distinguishes them from middle ear adenomas. Sustentacular cells typically stain positive for S-100.Middle ear paragangliomas are often locally destructive but rarely malignant. Although features such as an increase in mitotic activity, central necrosis and vascular invasion may increase suspicion of malignancy, only metastasis to a lymph node or distant organ confirms malignancy.2 Surgical resection is indicated owing to their progressive growth pattern and involvement of major vessels and cranial nerves, although radiotherapy presents a growing option.6 While preoperative embolization may be helpful in reducing bleeding, our practice has also found the use of carbon dioxide laser extremely helpful in achieving hemostasis.

General

An elderly woman presented with 2 episodes of vertigo lasting a few minutes while stationary over 1 day and a several-year history of right-sided hearing loss. She had not experienced otalgia, otorrhea, or tinnitus. Physical examination revealed a mass obstructing the right external auditory canal and House-Brackmann grade 2 facial nerve weakness on the right. Audiogram revealed right-sided moderate to profound mixed hearing loss. Computed tomography revealed a soft-tissue mass emanating from the middle ear involving the facial canal with surrounding bony erosion, including dehiscence of the tegmen, cochlea, bony labyrinth, lateral semicircular canal, and jugular foramen. The patient underwent transtemporal mastoidectomy and debulking. However, owing to the mass’s vascularity and significant bleeding, the operation was aborted, and she was sent for embolization (Figure, A). Magnetic resonance imaging during embolization revealed intense enhancement in the right middle ear extending from the epitympanum to the hypotympanum with extension into the right external auditory canal (Figure, B). She returned to the operating room, and the vascular mass was found to extend inferiorly to the jugular bulb and carotid and anteriorly into the eustachian tube. The mass was adherent to the underlying bone and had invaded the facial canal but not the nerve itself. Both malleus and incus were eroded. Immunohistochemical stains of the specimen indicated cells positive for synaptophysin with a sustentacular pattern of cells positive for S-100 (Figure, C and D).A, Mastoidectomy, visualization of vascular mass. B, T1-weighted axial magnetic resonance image (MRI) showing enhancement of right middle ear extending to external auditory canal. C, Hematoxylin-eosin, original magnification ×40. Clusters of cells surrounded by vascular tissue. D, Synaptophysin stain, original magnification ×40. Nests of strongly staining neuroendocrine cells separated by vasculature.

what is your diagnosis?

What is your diagnosis?

Facial nerve hemangioma

Facial nerve schwannoma

Middle ear paraganglioma

Middle ear adenoma

c

female

71-80

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2597597

A man in his 50s was referred to the department of oral and maxillofacial surgery for evaluation and treatment of an intraoral cystic lesion of the left lower lip. This lesion had developed spontaneously 3 months prior to consultation without an identifiable inciting event. He could recall no trauma and described a slow but progressive increase in the volume of this otherwise asymptomatic lesion. His medical history revealed a long-term history of substance abuse with active alcohol and tobacco consumption, chronic obstructive pulmonary disease, and epilepsy (tonic-clonic seizures, badly controlled owing to a lack of adherence to therapy). Clinical intraoral examination of this fully edentulous patient revealed a nontender, mobile, cystic nodule, approximately 1 × 1 cm on the vestibular side of the lower left lip with outflow of a clear serous fluid on palpation (Figure, A). The lesion was excised surgically and the specimen sent for additional histological examination. After hematoxylin-eosin staining, light microscopy revealed an endophytic growing lesion, which consisted of an acanthotic epidermoid epithelium organized in broad papillary folds, with at its periphery an infiltrating border. At the surface of these papillae, the epithelium was sometimes columnar. Mucocytes were present, individually dispersed throughout the epithelium, but also organized in small tubuloacinar structures emptying onto the surface. The epithelium was infiltrated by neutrophils. Atypia or mitotic figures were absent, and the subepithelial stroma contained normal-appearing seromucous acini (Figure, B and C).A, Clinical presentation of the cystic lesion of the lower left lip. B and C, Histopathologic images, hematoxylin-eosin. The papillary fronds lining the interior of the lesion. The lesion is well demarcated from the subepithelial stroma, and has an infiltrating border. C, Detail at the base of one of the papillae. The cells at the surface of the epithelial folds are columnar. Mucocytes organized in acinar structures empty on the surface epithelium but are also individually dispersed between the epidermoid cells. What Is Your Diagnosis?

Intraductal papilloma

Mucoepidermoid carcinoma

Mucocele

Oral inverted ductal papilloma

D. Oral inverted ductal papilloma

D

Oral inverted ductal papilloma

Benign papillary lesions believed to originate from the ductal system of salivary glands include the inverted ductal papilloma, intraductal papilloma, and sialadenoma papilliferum. These tumors are seldom found in major salivary glands but exhibit a clear predilection for minor salivary glands. The term inverted ductal papilloma was coined by White et al1 in 1982 based on 4 cases that demonstrated a resemblance to the inverted papilloma of the urinary bladder, nasal cavity, and paranasal sinuses.Most inverted ductal papillomas are located in the (lower) lip and in the buccal mucosa/mandibular vestibule. Rare cases have been identified on the palate and in the floor of the mouth. They present as a painless, soft-to-firm, movable, submucosal swelling with a normal-colored mucosa, with maximum dimensions ranging from 0.5 to 1.5 cm. A small dilated pore (representing the ductal opening in the mucosa) may be observed, and occasionally fluid expression from this orifice is present.2The incidence of inverted ductal papilloma is assumed to be extremely low. Waldron et al3 did not identify any such cases in a series of 426 minor salivary gland tumors, and neither did Neville et al4 among 103 labial salivary gland tumors. Regezi et al5 found 4 cases in a series of 238 minor salivary gland tumors. Since 1982, no more than 40 cases have been reported in the literature.Inverted ductal papillomas are believed to arise at the junction of the excretory duct of a minor salivary gland and the surface mucosal epithelium, in contrast to the more common inverted sinonasal papilloma, which arises from the endophytically growing surface epithelium. The exact pathogenesis, however, remains obscure. Some authors have suggested a causal relation with chronic inflammation owing to masticatory trauma and the human papillomavirus (HPV). Whereas for the sinonasal papilloma HPV is identifiable in one-third of cases, this relation has been insufficiently studied for the oral inverted ductal papilloma, with HPV 6/11 DNA detected in only 3 of 6 cases, as reported by Haberland-Carrodeguas et al.6The oral inverted ductal papilloma presents as a nonencapsulated tumor with endophytic growth pattern in which epithelial cells grow outward into the adjacent connective tissue. These cell masses, composed mainly of an epidermoid and basaloid cell population, form thick, bulbous papillary projections and contain scattered goblet cells, occasional microcysts and epithelium-lined ductlike spaces. Considering its excretory duct origin, this tumor exhibits an opening on the mucosal surface where the lining ductal epithelium is in continuity with the epithelium of the oral mucosa.In contrast to the inverted ductal papilloma, the (benign) intraductal papilloma is thought to arise in an interlobular duct, thus at a deeper level relative to the mucosal surface. Its smooth clinical outline without central pore correlates with a large unicystic cavity filled by a papillary growth composed of thin, branching papillary fronds supported by a central fibrovascular core. The mucoepidermoid carcinoma represents a malignant type of salivary gland tumor that usually presents as a painless, fixed, slowly growing swelling. Oral tumors are often indurated or fluctuant and cystic, resembling mucoceles or vascular lesions. Squamous cells, mucus-secreting cells, and intermediate cells define this multicystic, multinodular and infiltrative neoplasm.The oral inverted ductal papilloma exhibits a nonaggressive biological behavior and to date no cases of malignant transformation or recurrence have been reported.2 This contrasts with the sinonasal inverted papilloma, in which an associated 10% carcinoma incidence has been observed.7 A conservative but complete surgical removal, followed by histological analysis, is therefore considered the most appropriate treatment and will often lead to the unexpected diagnosis.2

General

A man in his 50s was referred to the department of oral and maxillofacial surgery for evaluation and treatment of an intraoral cystic lesion of the left lower lip. This lesion had developed spontaneously 3 months prior to consultation without an identifiable inciting event. He could recall no trauma and described a slow but progressive increase in the volume of this otherwise asymptomatic lesion. His medical history revealed a long-term history of substance abuse with active alcohol and tobacco consumption, chronic obstructive pulmonary disease, and epilepsy (tonic-clonic seizures, badly controlled owing to a lack of adherence to therapy). Clinical intraoral examination of this fully edentulous patient revealed a nontender, mobile, cystic nodule, approximately 1 × 1 cm on the vestibular side of the lower left lip with outflow of a clear serous fluid on palpation (Figure, A). The lesion was excised surgically and the specimen sent for additional histological examination. After hematoxylin-eosin staining, light microscopy revealed an endophytic growing lesion, which consisted of an acanthotic epidermoid epithelium organized in broad papillary folds, with at its periphery an infiltrating border. At the surface of these papillae, the epithelium was sometimes columnar. Mucocytes were present, individually dispersed throughout the epithelium, but also organized in small tubuloacinar structures emptying onto the surface. The epithelium was infiltrated by neutrophils. Atypia or mitotic figures were absent, and the subepithelial stroma contained normal-appearing seromucous acini (Figure, B and C).A, Clinical presentation of the cystic lesion of the lower left lip. B and C, Histopathologic images, hematoxylin-eosin. The papillary fronds lining the interior of the lesion. The lesion is well demarcated from the subepithelial stroma, and has an infiltrating border. C, Detail at the base of one of the papillae. The cells at the surface of the epithelial folds are columnar. Mucocytes organized in acinar structures empty on the surface epithelium but are also individually dispersed between the epidermoid cells.

what is your diagnosis?

What is your diagnosis?

Mucoepidermoid carcinoma

Intraductal papilloma

Oral inverted ductal papilloma

Mucocele

c

male

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2600192

A previously healthy young man in his late teens presented to his dentist with a 3-week history of left-sided facial pain, fullness, and trismus. He underwent a third maxillary molar extraction and attempted incision and drainage of the area with no improvement in symptoms. No purulence or clinically significant bleeding was identified. A contrast-enhanced computed tomographic (CT) scan was performed (Figure, A), and the patient was referred to the otolaryngology clinic. On presentation, he also reported decreased acuity in his left lower visual field, continued swelling with increasing pain, and worsening trismus. Physical examination revealed mild tenderness over a mass that extended inferiorly to the zygoma into the buccal cavity and posterolaterally to the left superior molars. The patient also reported hypoesthesia of the left maxillary division of the trigeminal nerve. Fiber-optic scope of the nasopharynx revealed a small lesion posterior to the left middle turbinate. Contrast-enhanced magnetic resonance imaging of his head, neck, and brain was performed (Figure, B and C).A, Computed tomographic (CT) image shows a uniformly hyperdense mass extending into the left infratemporal fossa with slight extension of the mass through the medial aspect of the posterior wall of the maxillary sinus and widening of the sphenopalatine foramen. B, Contrast-enhanced magnetic resonance image (MRI) with fat saturation shows a mass with mild punctuate areas of hypointense signal (suggestive of vascularity) terminating in the left buccinator space with extension into the nasal cavity, maxillary sinus and inferior orbital fissure. C, A heterogenous mass in the left retromaxillary region and infratemporal fossa with hyperintense signal and mild salt-and-pepper appearance consistent with vascularity. D, Gross specimen is in similar orientation as mass seen in panel B. What Is the Diagnosis?

Nasopharyngeal carcinoma

Juvenile nasopharyngeal angiofibroma

Rhabdomyosarcoma

Inverted papilloma

B. Juvenile nasopharyngeal angiofibroma

B

Juvenile nasopharyngeal angiofibroma

Axial contrast-enhanced CT (Figure, A), coronal contrast-enhanced T1-weighted MRI with fat saturation (Figure, B), and axial T2-weighted MRI (Figure, C) showed a large, avidly enhancing mass in the left pterygopalatine and sphenopalatine fossae with extension laterally into the retromaxillary region and infratemporal fossa. There was destruction of the medial aspect of the posterior wall of the maxillary sinus and widening of the sphenopalatine foramen. The mass had small extensions into the nasal cavity, maxillary sinus, and inferior orbital fissure. Mild punctuate areas of hypointense signal on T1-weighted MRI and salt-and-pepper appearance on T2-weighted MRI were consistent with vascularity. These imaging findings in a teenager were strongly suggestive of a juvenile nasopharyngeal angiofibroma (JNA).The differential diagnosis for a heterogenous-appearing mass lateral to the nasopharynx includes nasopharyngeal carcinoma, rhabdomyosarcoma, and inverted papilloma. Nasopharyngeal carcinoma of this size would likely show clinical or radiographic evidence of nodal metastasis.1 Rhabdomyosarcoma can present similarly, but on imaging are bulky in appearance with aggressive features (eg, obliteration of fat planes, central necrosis, cavitation).2 A posterolateral nasal location is also atypical. Inverted papilloma is less likely owing to the lack of convoluted cerebriform pattern on imaging and lack of polypoid mucosal lesion on fiber-optic scope.3JNAs are benign but often locally aggressive tumors that occur almost exclusively in males, most commonly during adolescence.4 These lesions are composed of an irregular network of vasculature with intervening fibroelastic stroma believed to originate from the pterygoid canal.5,6 This patient had minimal nasopharyngeal extension and lacked the most common presenting symptoms of nasal obstruction and unilateral epistaxis.4 He instead presented with symptoms of lateral extension, including facial swelling, cranial nerve deficits, and vision changes. Although the classic patient presentation suggests expansion along a path of least resistance (ie, into the relatively open nasopharynx), JNAs often demonstrate some degree of lateral growth into the constricted pterygopalatine space. Liu et al6 examined the expansive routes of histologically proven JNAs and found almost 60% of cases to have the main body of the tumor behind the pterygoid process corpus, with 48% extending into the infratemporal fossa as seen in the presented case.6 A second retrospective review4 using pooled data of 1047 cases found 29.2% to extend into the infratemporal fossa.Degree of JNA extension beyond the nasopharynx is the basis for the staging system described by Radkowski et al.7 Radkowski stage Ia lesions are limited to the posterior nares and/or the nasopharyngeal vault. Stage Ib lesions have extension into paranasal sinuses. Stage IIa lesions have minimal extension into the pterygomaxillary fossa. Stage IIb lesions have full occupation of pterygomaxillary fossa and may have orbital bone erosion. Stage IIc lesions have extension into the infratemporal fossa or extension posterior to the pterygoids. Stage IIIa lesions have skull base erosion with minimal intracranial extension. Stage IIIb lesions have extensive intracranial or cavernous sinus extension.Treatment of JNA is primarily by surgical excision via endoscopic, endoscopic-assisted, or open surgical approach. Preoperative embolization is often used to decrease intraoperative blood loss and improve visualization of margins. Recurrence after surgical resection ranges from 15% to 20% and is believed to be due to incomplete resection. JNAs trend toward increased intraoperative blood loss and recurrence rates at more advanced Radkowski stages. Untreated, morbidity and mortality are largely related to life-threatening hemorrhage, cranial nerve compression, and intracranial extension.4,7-9This patient’s lesion was embolized preoperatively using Onyx. The mass was then excised en bloc via a combined open and endoscopic approach through a Weber-Ferguson incision (Figure, D). Surgical margins were negative for neoplastic disease, and the patient had no signs of recurrence at his 3-month postoperative visit; however, mild visual symptoms persisted.

General

A previously healthy young man in his late teens presented to his dentist with a 3-week history of left-sided facial pain, fullness, and trismus. He underwent a third maxillary molar extraction and attempted incision and drainage of the area with no improvement in symptoms. No purulence or clinically significant bleeding was identified. A contrast-enhanced computed tomographic (CT) scan was performed (Figure, A), and the patient was referred to the otolaryngology clinic. On presentation, he also reported decreased acuity in his left lower visual field, continued swelling with increasing pain, and worsening trismus. Physical examination revealed mild tenderness over a mass that extended inferiorly to the zygoma into the buccal cavity and posterolaterally to the left superior molars. The patient also reported hypoesthesia of the left maxillary division of the trigeminal nerve. Fiber-optic scope of the nasopharynx revealed a small lesion posterior to the left middle turbinate. Contrast-enhanced magnetic resonance imaging of his head, neck, and brain was performed (Figure, B and C).A, Computed tomographic (CT) image shows a uniformly hyperdense mass extending into the left infratemporal fossa with slight extension of the mass through the medial aspect of the posterior wall of the maxillary sinus and widening of the sphenopalatine foramen. B, Contrast-enhanced magnetic resonance image (MRI) with fat saturation shows a mass with mild punctuate areas of hypointense signal (suggestive of vascularity) terminating in the left buccinator space with extension into the nasal cavity, maxillary sinus and inferior orbital fissure. C, A heterogenous mass in the left retromaxillary region and infratemporal fossa with hyperintense signal and mild salt-and-pepper appearance consistent with vascularity. D, Gross specimen is in similar orientation as mass seen in panel B.

what is the diagnosis?

What is your diagnosis?

Nasopharyngeal carcinoma

Inverted papilloma

Rhabdomyosarcoma

Juvenile nasopharyngeal angiofibroma

d

male

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2603326

A 45-year-old woman initially presented for evaluation of a 6-month history of intermittent left facial swelling and pain. She noted a discretely palpable mass in the left parotid region during these episodes. However, at the time of clinic presentation, she had no palpable masses on physical examination. Ultrasonography performed on the day of initial evaluation revealed no intraparotid masses, lesions, or stones. The patient was encouraged to return if she noticed acute return of swelling so that she could be evaluated when symptomatic. The patient returned days later with acutely worsening left facial swelling, which she noticed while straining. On presentation, she was diagnosed as having malignant hypertension and had a palpable parotid lesion noted on physical examination. When asked to perform a Valsalva maneuver, she was noted to have more pronounced left facial swelling (Figure, A). A short tau inversion recovery (STIR) image is shown in the Figure, B. Magnetic resonance angiogram was obtained (Figure, C and D).A, The patient performed a Valsalva maneuver, with increased left parotid gland and neck swelling. B, Coronal T2-weighted short tau inversion recovery (STIR) image demonstrating a T2 hyperintense lesion measuring 3.7 × 3.4 × 7.4 cm involving the left parotid gland and extending to the left side of the neck. C and D, T1-weighted, fat-suppressed, gadolinium-enhanced angiography. C, Arterial section demonstrating no evidence of significant high flow component. D, Delayed phase demonstrating a homogenous contrast enhancing lesion. What Is Your Diagnosis?

Venous malformation

Lymphatic malformation

Arteriovenous malformation

Chronic sialadenitis

A. Venous malformation

A

Venous malformation

Venous malformations (VMs) are slow-flow lesions characterized by an abnormal venous network. In 1982, Mulliken and Glowacki1 broadly classified endothelial malformations as either vascular tumors or VMs. In 1993, Jackson2 et al modified the classification by subcategorizing VMs into slow-flow (capillary, venous, lymphatic, or combined) or fast-flow (arteriovenous) lesions. The International Society for the Study of Vascular Anomalies (ISSVA) in 2014 established a uniform classification of vascular anomalies, which is the most commonly used classification system today.3Venous malformations are congenital and grow proportionately with human growth. Sixty percent of VMs are not detected at birth and become apparent later in life owing to slow venous pooling and gradual venous dilation.4 Diagnosis is typically made around the fourth decade of life. Grossly, malformations can be single, multiple, focal, or infiltrative across multiple soft-tissue planes. Microscopically, VMs demonstrate irregularly dilated, variably thickened vascular channels lined with mature endothelial cells.4Forty percent of VMs present in the head and neck.5 Parotid VMs account for less than 1% of parotid tumors. When these malformations are present in the parotid gland, phleboliths may be misdiagnosed as sialoliths, further complicating diagnosis.6,7 On clinical examination, VMs are soft, expansible lesions that result in asymmetry. A characteristic increase in size can be detected during Valsalva maneuver.4 Valsalva maneuver was not performed on initial evaluation in our case, but later this maneuver confirmed suspicion that the patient had a VM. Given the rarity of these intraparotid VMs, it is often difficult to reach a diagnosis preoperatively, as demonstrated in the literature.6,7 In this case, the patient initially presented with intermittent symptoms suggesting salivary outflow obstruction and sialadenitis, complicating the diagnosis.Many imaging modalities can define the extent of the lesion, including ultrasonography, computed tomography, and magnetic resonance imaging (MRI). Ultrasonography is often the initial modality used to evaluate VMs and is helpful in characterizing the extent of more superficial lesions.5 Ultrasonography demonstrates heterogeneous, hypoechoic patterns with sinusoidal spaces. The sluggish flow within the sinusoidal spaces can be demonstrated on color Doppler.8 Although 84% of VMs demonstrate monophasic or biphasic flow on Doppler, 16% of VMs will demonstrate no detectable flow, as in our case.9If patient presentation and ultrasonography are suggestive of a low-flow malformation, MRI is typically performed as the imaging modality of choice.5 Magnetic resonance imaging (typically with gadolinium contrast) is highly sensitive and specific, can show the extent of involvement within tissue planes, and can confirm the lack of arterial flow voids. Venous malformations are usually lobulated in appearance, hypointense to isointense on T1, and hyperintense on T2 and demonstrate avid enhancement. They can present with multiple rounded signal intensity voids representing phleboliths.5 Magnetic resonance angiography and formal angiography are rarely performed in the evaluation of VMs.The treatment of choice for VMs is percutaneous sclerotherapy, surgical excision, or a combination of both. Other treatment methods for VMs include cryotherapy, laser surgery (Nd:YAG or KTP), vascular ligation, and corticosteroids.5,10 While infiltrative transspatial VMs are difficult to treat, localized lesions can be generally be treated with surgical excision. Local recurrence is often due to incomplete surgical resection and is more common with diffuse malformations.In this case, the patient underwent an open resection of the left cervicofacial VM, total parotidectomy with facial nerve preservation, and dissection of the left parapharyngeal space/infratemporal fossa. At the last follow-up, approximately 18 months after her initial surgery, she had normal facial nerve function and no evidence of recurrence.Clinical presentation of a VM can mimic inflammatory parotid gland abnormalities. This may be more difficult to characterize on examination or ultrasonography when symptoms are not present. Valsalva maneuver can assist in the clinical diagnosis of a VM. Imaging modalities, such as ultrasonography and MRI, can provide valuable information to clarify the nature of the VM and guide treatment.

General

A 45-year-old woman initially presented for evaluation of a 6-month history of intermittent left facial swelling and pain. She noted a discretely palpable mass in the left parotid region during these episodes. However, at the time of clinic presentation, she had no palpable masses on physical examination. Ultrasonography performed on the day of initial evaluation revealed no intraparotid masses, lesions, or stones. The patient was encouraged to return if she noticed acute return of swelling so that she could be evaluated when symptomatic. The patient returned days later with acutely worsening left facial swelling, which she noticed while straining. On presentation, she was diagnosed as having malignant hypertension and had a palpable parotid lesion noted on physical examination. When asked to perform a Valsalva maneuver, she was noted to have more pronounced left facial swelling (Figure, A). A short tau inversion recovery (STIR) image is shown in the Figure, B. Magnetic resonance angiogram was obtained (Figure, C and D).A, The patient performed a Valsalva maneuver, with increased left parotid gland and neck swelling. B, Coronal T2-weighted short tau inversion recovery (STIR) image demonstrating a T2 hyperintense lesion measuring 3.7 × 3.4 × 7.4 cm involving the left parotid gland and extending to the left side of the neck. C and D, T1-weighted, fat-suppressed, gadolinium-enhanced angiography. C, Arterial section demonstrating no evidence of significant high flow component. D, Delayed phase demonstrating a homogenous contrast enhancing lesion.

what is your diagnosis?

What is your diagnosis?

Lymphatic malformation

Arteriovenous malformation

Chronic sialadenitis

Venous malformation

d

female

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2603480

A 6-year-old girl presented to the ophthalmology emergency service with 4 days of double vision associated with headache and fever. She had a history of upper respiratory tract infection with nasal congestion and discharge being treated with oral antibiotics. She also recently received a diagnosis of migraines. Computed tomographic imaging from an outside hospital 3 weeks prior was reported as unremarkable. The patient had an uncorrected visual acuity of 20/50 OU. Her pupils were round and reactive without an afferent pupillary defect. Confrontation visual fields revealed superotemporal, inferotemporal, and superonasal defects in both eyes. The results of her motility examination showed a complete absence of abduction on both eyes, consistent with bilateral sixth nerve palsy. The results of a fundus examination showed blurred optic nerve margins nasally (Figure 1).Fundus photographs demonstrating blurred nasal margins of the right (A) and left (B) discs. What Would You Do Next?

Continue oral antibiotics

Refer to neurology department

Continue neuroimaging

Proceed with strabismus surgery

Embryonal parameningeal rhabdomyosarcoma

C

Continue neuroimaging

Magnetic resonance imaging of the patient’s brain revealed a sphenoidal mass with bony destruction extending into the nasopharyngeal region, nasal passages, and the cavernous sinus. Posterior transsphenoidal biopsy revealed embryonal parameningeal rhabdomyosarcoma (Figure 2).Axial view of a magnetic resonance image of the brain and orbits, which reveals a large sphenoidal mass with bony destruction extending into the nasopharyngeal region, nasal passages, and the cavernous sinus.Rhabdomyosarcoma is the most common soft-tissue sarcoma, accounting for 4.5% of all childhood cancers.1 Presentation occurs in a bimodal distribution, with peaks between the age range of 2 to 6 years and the age range of 12 to 16 years. The majority of children (60%) receive a diagnosis before 6 years of age.2 The embryonal subtype is the most common, with a greater incidence during childhood. Approximately one-third of pediatric rhabdomyosarcomas will manifest in the head and neck region, with more than half involving a location adjacent to the meninges, such as the infratemporal fossa, paranasal sinuses, nasal cavity, nasopharynx, and middle ear.3 Presenting symptoms may be vague, commonly resembling upper respiratory tract infections, as the tumor’s location in the sinuses and pharyngeal spaces tends to allow significant growth while concealing its presence. When the tumor erodes through these spaces and infiltrates the central nervous system, meningeal signs and cranial nerve palsies become evident. As a consequence, neurologic signs are most commonly found in significantly advanced cases, with the sixth cranial nerve most commonly involved.4,5Cranial nerve palsies in children are more alarming than in adults. In the adult population, microvascular etiologies such as diabetes and hypertension are the most common causes of sixth nerve palsies. However, these etiologies are extremely rare in children. The most common etiology in children is a neoplasm, accounting for 20% to 45% of cases. Other causes include elevated intracranial pressure, trauma, and congenital, inflammatory, idiopathic, and postviral causes.5-8The evaluation of infants and children with sixth nerve palsy depends on whether the palsy is isolated or accompanied by other neurologic abnormalities. When papilledema or neurological abnormalities are present, imaging is required emergently. In light of the high prevalence of associated intracranial lesions, the American Academy of Ophthalmology recommends magnetic resonance imaging, even in the absence of other focal neurologic findings.9In this case, even though the patient presented with symptoms of a viral infection, a history of migraines, and a negative computed tomographic scan, the bilateral sixth nerve palsy and the optic nerve findings are alarming signs that would necessitate neuroimaging. Observation or referral would have significantly delayed the diagnosis. Although alternate patching may be indicated to reduce the risk of amblyopia, determining the cause of the palsy is more urgent in this instance.

Ophthalmology

A 6-year-old girl presented to the ophthalmology emergency service with 4 days of double vision associated with headache and fever. She had a history of upper respiratory tract infection with nasal congestion and discharge being treated with oral antibiotics. She also recently received a diagnosis of migraines. Computed tomographic imaging from an outside hospital 3 weeks prior was reported as unremarkable. The patient had an uncorrected visual acuity of 20/50 OU. Her pupils were round and reactive without an afferent pupillary defect. Confrontation visual fields revealed superotemporal, inferotemporal, and superonasal defects in both eyes. The results of her motility examination showed a complete absence of abduction on both eyes, consistent with bilateral sixth nerve palsy. The results of a fundus examination showed blurred optic nerve margins nasally (Figure 1).Fundus photographs demonstrating blurred nasal margins of the right (A) and left (B) discs.

what would you do next?

What would you do next?

Refer to neurology department

Continue oral antibiotics

Proceed with strabismus surgery

Continue neuroimaging

d

female

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2603892

A white man in his 50s initially presented in the fall of 2015 with “macular changes” noticed by his referring optometrist. The patient was asymptomatic at the time. He had a history of hypertension and non-Hodgkin lymphoma, which was last treated in 2012 without evidence of recurrence. His visual acuity was 20/25 OU, and neither fundus was seen to be abnormal. The vitreous was clear in both eyes. Optical coherence tomography (OCT) revealed vitreomacular adhesion in the right eye and a macular posterior vitreous detachment in the left. The patient was told to follow-up as needed.About 2 months later, the patient called on the telephone to say that he had a new onset of blurry vision and photopsias in the right eye that started about 2 days prior. He denied any recent viral-type illness. An examination revealed that his visual acuity was still 20/25 OU. The anterior segment and the anterior vitreous of his right eye were still clear. However, an examination of the posterior pole of the right eye revealed a light white, deep subretinal/choroidal ring surrounding the optic nerve, with smaller rings around the edge of the larger ring (Figure, A). The left eye still appeared normal. Optical coherence tomography of the right eye revealed loss of the outer retina (more nasal than temporal to the fovea), whereas OCT of the left eye revealed that it was normal (Figure, B). The results of fluorescein angiography and fundus autofluorescence were both unremarkable (data not shown).A, Fundus photograph of the right eye at the time of presentation shows a white-gray ring centered on the optic nerve. B, Optical coherence tomography (OCT) of the right eye reveals significant loss of the outer retina, especially nasal to the fovea. What Would You Do Next?

Treatment with oral prednisone

Full laboratory workup for uveitis

Electrophysiology

Orbital imaging (B-scan or computed tomography)

Acute zonal occult outer retinopathy (AZOOR)

C

Electrophysiology

The patient’s clinical history and examination were highly suggestive of AZOOR. We considered performing a B-scan to rule out a metastatic process to the choroid given the history of lymphoma. However, the OCT did not reveal any thickening, which suggests that a metastatic process was an unlikely possibility. We also contemplated a laboratory workup for uveitis but then thought that this was of little value given the presentation. We did perform electroretinography to obtain a multifocal electroretinogram (ERG) that showed reduced signal in the right eye throughout the macula, consistent with the diagnosis of AZOOR. Steroids are of little value in treating this disease.Acute zonal occult outer retinopathy was first described by Gass in 1993.1 He described 13 patients, mostly young women, who presented with rapid loss of 1 or more zones of outer retinal function and photopsias, with minimal, if any, ophthalmoscopic changes.1 Only later did patients show significant losses of the outer retina and retinal pigment epithelium (RPE). Our patient presented with a rare variant of AZOOR called acute annular outer retinopathy, which was first described in 1994. It is similar to AZOOR in imaging, examination, and follow-up but presents with a large, thin, gray-white ring that disappears over several weeks.2By far, the most consistent symptom with AZOOR is photopsia, especially flashes that appear to have movement. The photopsias can precede, appear concurrently, or succeed visual field loss. The field loss is highly variable, but often has a connection with the blind spot. Progression of the field loss can occur for several weeks to months after initial presentation. Although patients report persistent visual field defects, some patients’ conditions have been shown to improve. The disease affects one eye about 60% of the time, with an occasional delayed presentation in the other eye.3At the time of presentation of AZOOR, a fundus examination would reveal minimal, if any, signs of disease. There are reports describing variable degrees of vitritis, perivascular exudation, and disc edema, all of which develop several weeks after onset of symptoms and are thought to be an inflammatory response to the dead retinal cells.4 Weeks to months later, patients can develop retinal vascular narrowing and retinal pigment migration in the abnormal areas.3With regard to fluorescein angiography, the results of initial testing can be normal. Only later, as patients experience significant loss of the outer retina and RPE, will patients develop hyperfluorescence from transmission defects. Autofluorescence often shows hypoautofluorescence in the areas of RPE dysfunction and occasionally a ring of hyperautofluorescence in the rim of the defect.5Although anatomic changes can be subtle or absent initially, electrophysiology is very useful in making a diagnosis in the early phases of the disease. Full-field ERGs show significant photoreceptor dysfunction in the affected eye compared with the normal eye. Multifocal ERGs are also helpful in documenting the extent and localization of the abnormality.6In terms of etiology, no one has proven the cause of the disease. Gass1 initially attributed it to an inflammatory response to a viral agent within the photoreceptors. It is currently thought to be a combination of genetics and autoimmunity and possibly environmentally triggered.3 Steroids and antivirals have been given to patients in the hope of stopping or reversing the disease. In general, the consensus is that these treatments are of limited value. There are just a few case reports describing visual improvement possibly linked to pulsed steroids.7,8When the patient returned 2 months later, his visual acuity declined to 20/30 OD, and an afferent pupillary defect was present. The right optic nerve had pallor, and the retinal arterioles were noticeably attenuated. The grayish ring had disappeared. Optical coherence tomography revealed further loss of the outer retina, with only the fovea having an intact ellipsoid band.

Ophthalmology

A white man in his 50s initially presented in the fall of 2015 with “macular changes” noticed by his referring optometrist. The patient was asymptomatic at the time. He had a history of hypertension and non-Hodgkin lymphoma, which was last treated in 2012 without evidence of recurrence. His visual acuity was 20/25 OU, and neither fundus was seen to be abnormal. The vitreous was clear in both eyes. Optical coherence tomography (OCT) revealed vitreomacular adhesion in the right eye and a macular posterior vitreous detachment in the left. The patient was told to follow-up as needed.About 2 months later, the patient called on the telephone to say that he had a new onset of blurry vision and photopsias in the right eye that started about 2 days prior. He denied any recent viral-type illness. An examination revealed that his visual acuity was still 20/25 OU. The anterior segment and the anterior vitreous of his right eye were still clear. However, an examination of the posterior pole of the right eye revealed a light white, deep subretinal/choroidal ring surrounding the optic nerve, with smaller rings around the edge of the larger ring (Figure, A). The left eye still appeared normal. Optical coherence tomography of the right eye revealed loss of the outer retina (more nasal than temporal to the fovea), whereas OCT of the left eye revealed that it was normal (Figure, B). The results of fluorescein angiography and fundus autofluorescence were both unremarkable (data not shown).A, Fundus photograph of the right eye at the time of presentation shows a white-gray ring centered on the optic nerve. B, Optical coherence tomography (OCT) of the right eye reveals significant loss of the outer retina, especially nasal to the fovea.

what would you do next?

What would you do next?

Full laboratory workup for uveitis

Treatment with oral prednisone

Orbital imaging (B-scan or computed tomography)

Electrophysiology

d

male

51-60

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2606526

A man in his 50s with a history of hypertension and sleep apnea presented with a 6-week history of progressive, bilateral vision loss while receiving treatment with oral steroids and amoxicillin-clavulanate from his primary care physician. He also had associated ear pain, hearing loss, and severe headaches.On presentation, his visual acuity was light perception OD and 20/600 at 1 m OS. The right eye had a 1+ afferent pupillary defect. He also had ear drainage with inflamed tympanic membranes and ear tubes in place bilaterally. A dilated fundus examination revealed grade 2 optic disc edema with an inferior disc hemorrhage in the right eye and grade 1 edema in the left eye. The remainder of the examination was unremarkable.Laboratory results revealed elevated C-reactive protein levels and erythrocyte sedimentation rates at 78 mg/L and 77 mm/h, respectively, with negative antinuclear antibody test results (to convert C-reactive protein to nanomoles per liter, multiply by 9.524). His white blood cell count was elevated at 14 910/μL without eosinophilia (to convert to × 109/L, multiply by 0.001). Cerebrospinal fluid studies were remarkable only for an elevated white blood cell count of 72/μL (79% lymphocytes) and elevated protein level at 97 mg/L, while Gram stain and culture were negative. Opening pressure was 17 cm H2O.A magnetic resonance venogram with and without contrast ruled out venous occlusions. Finally, magnetic resonance imaging demonstrated diffuse pachymeningeal (dural-arachnoid) enhancement (Figure) without leptomeningeal (pial) enhancement, left-sided mastoiditis, and subtle optic nerve enhancement.Coronal T1 with gadolinium showing dural enhancement (blue arrowhead) and optic nerve enhancement (white arrowheads). What Would You Do Next?

Quantiferon gold

Antineutrophil cytoplasmic antibody testing

Rapid plasma reagin

Angiotensin-converting enzyme level

Granulomatosis with polyangiitis, formerly known as Wegener granulomatosis

B

Antineutrophil cytoplasmic antibody testing

Antineutrophil cytoplasmic antibodies (ANCAs) are a group of IgG antibodies that exist in 2 forms: cytoplasmic ANCA (also known as proteinase 3 antibody) and perinuclear ANCA (also known as myeloperoxidase antibody). Cytoplasmic ANCA positivity is found in approximately 65% of cases of granulomatosis with polyangiitis (GPA), while perinuclear ANCA positivity is found in approximately 20% of cases.1This patient’s ANCA testing revealed an elevated myeloperoxidase antibody at 44, while proteinase 3 was within normal limits. Quantiferon gold, angiotensin-converting enzyme level, and rapid plasma reagin tests all returned within normal limits.In this case, disc edema and an afferent pupillary defect directed the initial workup. Compressive etiologies should be excluded with imaging before obtaining a lumbar puncture with opening pressure and cerebrospinal fluid studies to assess for infectious etiologies, inflammatory etiologies, and intracranial pressure. With an elevated serum white blood cell count and meningeal enhancement, lumbar puncture was performed in this patient.The differential diagnosis of diffuse pachymenigeal enhancement includes benign intracranial hypotension, autoimmune causes such as sarcoidosis, GPA and rheumatoid arthritis, and iatrogenic causes such as craniotomy, shunt placement, and lumbar puncture.2Given the meningeal enhancement noted on magnetic resonance imaging, serum ANCA positivity, hearing loss, chronic sinusitis, and mastoiditis, the diagnosis of GPA was made. We presume the vision loss was owing to optic neuritis or perineuritis. Although magnetic resonance imaging of the orbit was severely limited by motion artifact, subtle optic nerve sheath enhancement was seen on the brain magnetic resonance imaging.Granulomatosis with polyangiitis is a multisystem necrotizing granulomatous inflammation of small to medium vessels classically involving the upper respiratory tract, lower respiratory tract, and kidneys.3 Sinonasal symptoms and paranasal bone erosion can help differentiate orbital inflammation owing to GPA from other etiologies.4 Patients with GPA may present with hearing loss, recurrent otitis media, recurrent mastoiditis, sinusitis, recurrent epistaxis, nasal septum perforation, and saddle nose deformity.5 Ocular symptoms can include vision loss, red eye, and pain. Meanwhile, ocular signs include proptosis, scleritis, and eyelid inflammation.6This case is an unusual presentation of GPA given the meningeal involvement. Ocular involvement is found in 87% of GPA; however, it is the presenting feature in only 8% of patients.7 While neurologic involvement, especially of the optic nerve, is seen in 18% of cases,3 meningeal involvement is present in only 1% to 4% of patients.8Granulomatosis with polyangiitis can present with ocular involvement in association with meningeal enhancement and neurologic symptoms. Patients presenting with acute inflammatory optic neuritis and neurologic symptoms require prompt multidisciplinary treatment and, in the appropriate patient, a diagnosis of GPA should be considered.Given the lack of improvement with empiric antibiotics and a negative cerebrospinal fluid Gram stain and typical markers of infection, intravenous methylprednisolone, 1 g daily, was added on day 2 for possible inflammatory disease prior to ANCA results. Within 48 hours, his visual acuity improved to 20/800 OD and 20/30 OS. He was discharged on day 5 receiving 80 mg of oral prednisone daily with 15 mg of methotrexate weekly. After the initial presentation, he also developed pneumonia with a ground-glass appearance on chest radiography. By 2 months follow-up, his visual acuity had improved to 20/200 OD and 20/30+ OS receiving 20 mg of oral prednisone and 15 mg of weekly methotrexate.

Ophthalmology

A man in his 50s with a history of hypertension and sleep apnea presented with a 6-week history of progressive, bilateral vision loss while receiving treatment with oral steroids and amoxicillin-clavulanate from his primary care physician. He also had associated ear pain, hearing loss, and severe headaches.On presentation, his visual acuity was light perception OD and 20/600 at 1 m OS. The right eye had a 1+ afferent pupillary defect. He also had ear drainage with inflamed tympanic membranes and ear tubes in place bilaterally. A dilated fundus examination revealed grade 2 optic disc edema with an inferior disc hemorrhage in the right eye and grade 1 edema in the left eye. The remainder of the examination was unremarkable.Laboratory results revealed elevated C-reactive protein levels and erythrocyte sedimentation rates at 78 mg/L and 77 mm/h, respectively, with negative antinuclear antibody test results (to convert C-reactive protein to nanomoles per liter, multiply by 9.524). His white blood cell count was elevated at 14 910/μL without eosinophilia (to convert to × 109/L, multiply by 0.001). Cerebrospinal fluid studies were remarkable only for an elevated white blood cell count of 72/μL (79% lymphocytes) and elevated protein level at 97 mg/L, while Gram stain and culture were negative. Opening pressure was 17 cm H2O.A magnetic resonance venogram with and without contrast ruled out venous occlusions. Finally, magnetic resonance imaging demonstrated diffuse pachymeningeal (dural-arachnoid) enhancement (Figure) without leptomeningeal (pial) enhancement, left-sided mastoiditis, and subtle optic nerve enhancement.Coronal T1 with gadolinium showing dural enhancement (blue arrowhead) and optic nerve enhancement (white arrowheads).

what would you do next?

What would you do next?

Rapid plasma reagin

Quantiferon gold

Angiotensin-converting enzyme level

Antineutrophil cytoplasmic antibody testing

d

male

51-60

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2609097

A woman in her teens with no relevant medical history was brought to the hospital for personality changes, headache, and decreased vision bilaterally. Review of systems was remarkable for concomitant hearing loss and vertigo for 1 month. She was alert but confused and disoriented, and she manifested gait imbalance and ataxia. White blood cell count was elevated at 14 600/μL (to convert to ×109 per liter, multiply by 0.001). Results from computed tomography of the head were normal, but magnetic resonance imaging of the brain revealed multifocal punctate areas of restricted diffusion. A lumbar puncture showed lymphocytosis (80%), normal glucose levels, and protein levels greater than 125 mg/dL. Results from cerebrospinal fluid polymerase chain reaction were negative for herpes simplex virus, varicella zoster virus, and cytomegalovirus. Results from laboratory tests for hypercoagulable states, antinucleolar antibodies, antineutrophilic cytoplasmic antibodies, human immunodeficiency virus, Lyme disease, and tuberculosis were unrevealing.Ophthalmology was consulted. Visual acuity was 20/20 OU with normal pupil response, visual fields to finger counting, motility, and intraocular pressure. Anterior segment biomicroscopy was normal without vitreous cell or haze. The optic discs were pink with sharp margins. The macula appeared flat, and there were scattered peripheral retinal hemorrhages and areas of retinal vascular nonperfusion in both eyes. Optical coherence tomography showed inner retinal thinning with preservation of outer retinal architecture. Fluorescein angiography showed multiple retinal arteriolar occlusions with variable leakage (Figure).In this widefield fluorescein angiography, there are multiple areas of retinal artery occlusion not at branch points, with prominent leakage of fluorescein dye at some of the occlusions in each eye.Administer systemic steroids and discuss the potential need for long-term immunosuppression for Susac syndromeGive intravenous acyclovir and intravitreal foscarnet for viral retinitisObserve for acute posterior multifocal placoid pigment epitheliopathy What Would You Do Next?

Initiate dimethyl fumarate for relapsing multiple sclerosis

Administer systemic steroids and discuss the potential need for long-term immunosuppression for Susac syndrome

Give intravenous acyclovir and intravitreal foscarnet for viral retinitis

Observe for acute posterior multifocal placoid pigment epitheliopathy

Susac syndrome

B

Administer systemic steroids and discuss the potential need for long-term immunosuppression for Susac syndrome

Susac syndrome (also called retinocochleocerebral vasculopathy) is an autoimmune endotheliopathy1,2 that classically manifests with branch retinal artery occlusions typically not at branch points, encephalopathy, and sensorineural hearing loss, although the classic triad may be incomplete3 until the disease is fulminant. For this reason, it is important that ophthalmologists consider Susac syndrome in the differential diagnosis of all retinal artery occlusions, as a high level of suspicion can prompt early intervention and improved ophthalmic and systemic outcomes.On ophthalmic examination, patients may have scattered intraretinal hemorrhages and multiple branch retinal artery occlusions in each eye. Fluorescein angiography classically reveals arterial occlusions not at branch points with prominent focal leakage at the point of occlusion, which may be more numerous than clinical examination suggests. Optical coherence tomography can be used to confirm inner retinal thinning secondary to arterial occlusions,4 which correspond to visual field defects.Approximately 80% of patients with Susac syndrome are female, and patients may have a monocyclic, polycyclic, or chronic continuous course.5 Cerebrospinal fluid analysis typically reveals lymphocytosis and elevated protein levels without oligoclonal bands. In contrast to patients with multiple sclerosis, patients with Susac syndrome tend to have punctate white matter lesions, meningeal enhancement, and characteristic central corpus callosal involvement on magnetic resonance imaging.6 Despite treatment with systemic steroids, antimetabolites, cyclophosphamide, plasmapheresis, intravenous immunoglobulin, and/or rituximab, patients risk permanent sequelae.This patient was initially treated with high-dose prednisone at 1 mg/kg and 100 mg daily of azathioprine as well as rituximab, with which she initially stabilized. However, as systemic steroids were tapered, she experienced a flare of cerebral and retinal vasculitis, and the prednisone was increased back to 1 mg/kg daily with a slow taper of 5 mg every 2 weeks. Patients with Susac syndrome should start oral or intravenous systemic steroids immediately and be educated on the potential need for long-term immunosuppression. Dimethyl fumarate is a long-term treatment for patients with relapsing multiple sclerosis,6 which this patient does not have. Intravenous acyclovir and intravitreal foscarnet would be appropriate in the management of acute retinal necrosis, which tends to present with rapid vision loss, vitritis, and peripheral, circumferential vascular occlusions with retinal hemorrhages. Finally, patients with acute posterior multifocal placoid pigment epitheliopathy, a white dot syndrome, classically present with minimal intraocular inflammation and choroidal lesions within the macula, which are absent in this patient. The cause of acute posterior multifocal placoid pigment epitheliopathy is unknown; it is sometimes associated with encephalitis warranting neuroimaging and cerebrospinal fluid analysis. Some patients with acute posterior multifocal placoid pigment epitheliopathy are managed with immunosuppression, although many patients are self-limited and can be observed.Over 1 year of follow-up, this patient experienced multiple flares, each associated with flattening of affect, severe hearing loss, and loss of visual field. She is currently undergoing treatment with cyclophosphamide, rituximab, and intravenous immunoglobulin.

Ophthalmology

A woman in her teens with no relevant medical history was brought to the hospital for personality changes, headache, and decreased vision bilaterally. Review of systems was remarkable for concomitant hearing loss and vertigo for 1 month. She was alert but confused and disoriented, and she manifested gait imbalance and ataxia. White blood cell count was elevated at 14 600/μL (to convert to ×109 per liter, multiply by 0.001). Results from computed tomography of the head were normal, but magnetic resonance imaging of the brain revealed multifocal punctate areas of restricted diffusion. A lumbar puncture showed lymphocytosis (80%), normal glucose levels, and protein levels greater than 125 mg/dL. Results from cerebrospinal fluid polymerase chain reaction were negative for herpes simplex virus, varicella zoster virus, and cytomegalovirus. Results from laboratory tests for hypercoagulable states, antinucleolar antibodies, antineutrophilic cytoplasmic antibodies, human immunodeficiency virus, Lyme disease, and tuberculosis were unrevealing.Ophthalmology was consulted. Visual acuity was 20/20 OU with normal pupil response, visual fields to finger counting, motility, and intraocular pressure. Anterior segment biomicroscopy was normal without vitreous cell or haze. The optic discs were pink with sharp margins. The macula appeared flat, and there were scattered peripheral retinal hemorrhages and areas of retinal vascular nonperfusion in both eyes. Optical coherence tomography showed inner retinal thinning with preservation of outer retinal architecture. Fluorescein angiography showed multiple retinal arteriolar occlusions with variable leakage (Figure).In this widefield fluorescein angiography, there are multiple areas of retinal artery occlusion not at branch points, with prominent leakage of fluorescein dye at some of the occlusions in each eye.Administer systemic steroids and discuss the potential need for long-term immunosuppression for Susac syndromeGive intravenous acyclovir and intravitreal foscarnet for viral retinitisObserve for acute posterior multifocal placoid pigment epitheliopathy

what would you do next?

What would you do next?

Give intravenous acyclovir and intravitreal foscarnet for viral retinitis

Observe for acute posterior multifocal placoid pigment epitheliopathy

Administer systemic steroids and discuss the potential need for long-term immunosuppression for Susac syndrome

Initiate dimethyl fumarate for relapsing multiple sclerosis

c

female

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2606975

A 24-year-old man was brought to the emergency department after a high-speed motor vehicle collision. He was a restrained driver noted to be awake at the scene of the collision and had to be extracted from the vehicle. He was hemodynamically stable on route to the hospital. In the emergency department, the patient was awake but restless and combative and was subsequently intubated. He was hypotensive on arrival but responded transiently to fluid resuscitation. Multiple closed long bone fractures of the upper and lower extremities were noted. The chest radiography (Figure 1A) showed marked elevation of the left hemidiaphragm. The pelvic radiography revealed an unstable fracture involving bilateral pubic rami and the left sacroiliac joint. The pelvis was splinted in the emergency department. He remained transiently responsive to fluid resuscitation and was taken for emergent computed tomography. Computed tomography of the head and cervical spine showed no evidence of injury. A computed tomographic scan of the chest (Figure 1B) and abdomen was then performed, and the patient was taken to the operating room.A, single-view supine chest radiography. B, Axial computed tomographic image of the chest.Diaphragmatic rupture and a traumatic rupture of the descending thoracic aorta What Is Your Diagnosis?

Diaphragmatic eventration with lung collapse

Pneumothorax with elevation of the left hemidiaphragm

Diaphragmatic rupture and a mediastinal hematoma

Diaphragmatic rupture and a traumatic rupture of the descending thoracic aorta

D. Diaphragmatic rupture and a traumatic rupture of the descending thoracic aorta

D

Diaphragmatic rupture and a traumatic rupture of the descending thoracic aorta

The patient’s pelvis was stabilized with an external fixation device. Following this, a laparotomy was performed, and a 7-cm lateral tear in the left hemidiaphragm was repaired. No other intra-abdominal injuries were noted. A temporary abdominal closure device was placed. Upper and lower extremity fractures were reduced and splinted. The patient then underwent emergent endovascular stenting of a blunt thoracic aortic injury (Figure 2).In a 2009 review of the natural history of patients with blunt thoracic aortic injury,1 23% of patients died prior to arrival to hospital or during triage. Associated major abdominal injuries were present in 29% of patients, and a major head injury was present in 31% of patients.1 In patients with blunt aortic injury, 30-day mortality was determined primarily by the severity of associated injuries and was not altered by early aortic repair.2 Blunt aortic injury has been reported to occur in 10% of patients with a traumatic diaphragmatic rupture; however, the overall incidence of either of these injuries is quite low (1.8% and 1.1% in patients with traumatic diaphragmatic rupture and blunt aortic injury, respectively).3 Thoracic endovascular repair has been associated with fewer early postoperative complications when compared with open repair.4-7 Grading of blunt aortic injuries by computed tomography allows for selective nonoperative treatment of low-risk lesions (intimal tears and intramural hematoma).5,6 Medical treatment with β-blockade targeting a systolic blood pressure of 100 to 120 mm Hg with delayed repair may be preferred in patients with high-risk lesions (pseudoaneurysms and rupture) who are stable or have significant associated injuries.5 Factors associated with a high risk of progression in patients with pseudoaneurysms include hypotension, a large pseudoaneurysm, and extensive mediastinal hematoma.5 Thoracic endovascular repair has been associated with a lower mortality when compared with open repair or nonoperative treatment. It is also associated with lower rates of renal failure and spinal cord ischemia.6,7 Guidelines of the Society for Vascular Surgery recommend thoracic endovascular repair as the preferred treatment modality in all patients with suitable anatomic criteria, regardless of age.6,8This patient subsequently underwent abdominal wall closure and definitive repair of his orthopedic injuries. This case highlights the importance of careful imaging in multiple-trauma patients with severe deceleration injuries, with liberal use of computed tomography and the need for careful decision making in these patients who have multiple life-threatening injuries.

Surgery

A 24-year-old man was brought to the emergency department after a high-speed motor vehicle collision. He was a restrained driver noted to be awake at the scene of the collision and had to be extracted from the vehicle. He was hemodynamically stable on route to the hospital. In the emergency department, the patient was awake but restless and combative and was subsequently intubated. He was hypotensive on arrival but responded transiently to fluid resuscitation. Multiple closed long bone fractures of the upper and lower extremities were noted. The chest radiography (Figure 1A) showed marked elevation of the left hemidiaphragm. The pelvic radiography revealed an unstable fracture involving bilateral pubic rami and the left sacroiliac joint. The pelvis was splinted in the emergency department. He remained transiently responsive to fluid resuscitation and was taken for emergent computed tomography. Computed tomography of the head and cervical spine showed no evidence of injury. A computed tomographic scan of the chest (Figure 1B) and abdomen was then performed, and the patient was taken to the operating room.A, single-view supine chest radiography. B, Axial computed tomographic image of the chest.Diaphragmatic rupture and a traumatic rupture of the descending thoracic aorta

what is your diagnosis?

What is your diagnosis?

Diaphragmatic rupture and a traumatic rupture of the descending thoracic aorta

Diaphragmatic eventration with lung collapse

Pneumothorax with elevation of the left hemidiaphragm

Diaphragmatic rupture and a mediastinal hematoma

a

male

21-30

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2611280

A 45-year-old woman with factor 1 deficiency presented to the general surgery clinic with a history of multiple episodes of lower gastrointestinal bleeding. These episodes started approximately 4 years prior, occur approximately every 3 to 4 months, and are associated with crampy abdominal pain. Although she has been hospitalized, she never required a transfusion. Colonoscopies were significant only for diverticulosis without a clear source of bleeding. Her previous abdominal surgery included a hysterectomy for menorrhagia. There is no family history of colon cancer.Physical examination showed no abnormalities. She had computed tomography of the abdomen and pelvis that showed eccentric and irregular masslike thickening of the sigmoid colon of approximately 7 cm with a wall thickness of 1.4 cm (Figure 1). Repeat colonoscopy showed an exquisitely painful nodule at the rectosigmoid junction. There were no stigmata of recent bleed, and biopsy showed normal colonic mucosa.Axial (A) and coronal (B) computed tomography of the pelvis with rectal contrast. The images show thickening and narrowing of the sigmoid colon (arrowheads). What Is Your Diagnosis?

Sigmoid adenocarcinoma

Rectosigmoid polyp

Sigmoid endometriosis

Rectosigmoid leiomyoma

C. Sigmoid endometriosis

C

Sigmoid endometriosis

Intraoperatively there was a large masslike lesion on the serosal surface of the sigmoid colon projecting into the mesentery that correlated with the mass noted on colonoscopy (Figure 2). There were no characteristic serosal abnormalities of endometriosis noted in the vicinity of the lesion.Intraoperative specimen showing extrinsic mass on mesenteric border of sigmoid colon with associated thickening and shortening of the colon.Deep endometriosis is a type of endometriosis that infiltrates more than 5 mm below the peritoneal surface and is being increasingly recognized as a cause of gastrointestinal bleeding in women.1-4 Common locations for deep endometriosis are the ureterosacral ligaments, rectovaginal septum, or rectosigmoid junction. The endometrial tissue acts as an inflammatory nidus that leads to fibrosis and alteration of the pelvic anatomy. Patients with endometriosis often present with dysmenorrhea and dyspareunia, although the clinical presentation varies from asymptomatic lesions to hematochezia and, in extreme cases, bowel obstruction.The diagnosis of colonic endometriosis requires a high clinical suspicion. More common sources of lower gastrointestinal bleeding in patients younger than 60 years old include diverticula, inflammatory bowel disease, and polyps. In the stable patient, anorectal disease, such as hemorrhoids or anal fissure, should also be considered. Malignancy should always be in the differential.5,6The cornerstone for the workup of lower gastrointestinal bleeding is colonoscopy,6 which can provide both diagnostic and therapeutic interventions. If prep quality is poor, other options include mesenteric angiography or radionuclide scintigraphy.5 If there is a suspicion for colonic endometriosis, evaluation should include ultrasonography, computed tomography, and magnetic resonance imaging.4 Ultrasonography is often used to evaluate the ovaries and uterus. Computed tomographic scan shows changes of chronic inflammation such as bowel wall thickening. Magnetic resonance imaging is useful in identifying multifocal disease, with both a sensitivity and specificity of 90% for identifying hemorrhagic foci. While colonoscopy contributes little in the diagnosis of deep endometriosis, as these are usually extrinsically associated with the bowel wall, it is necessary to evaluate for other etiologies. Despite all the imaging adjuncts, the gold standard for diagnosis is diagnostic laparoscopy.1-4Long-term outcomes are favorable for patients who undergo operative intervention, most commonly laparoscopic sigmoidectomy.3,4,7 Complication rates are similar to sigmoidectomy for alternate pathologies.7 These patients should be approached in a multidisciplinary fashion with workup by a gynecologist and operative intervention by both the gynecological surgeon and a colorectal surgeon.3,4,7

Surgery

A 45-year-old woman with factor 1 deficiency presented to the general surgery clinic with a history of multiple episodes of lower gastrointestinal bleeding. These episodes started approximately 4 years prior, occur approximately every 3 to 4 months, and are associated with crampy abdominal pain. Although she has been hospitalized, she never required a transfusion. Colonoscopies were significant only for diverticulosis without a clear source of bleeding. Her previous abdominal surgery included a hysterectomy for menorrhagia. There is no family history of colon cancer.Physical examination showed no abnormalities. She had computed tomography of the abdomen and pelvis that showed eccentric and irregular masslike thickening of the sigmoid colon of approximately 7 cm with a wall thickness of 1.4 cm (Figure 1). Repeat colonoscopy showed an exquisitely painful nodule at the rectosigmoid junction. There were no stigmata of recent bleed, and biopsy showed normal colonic mucosa.Axial (A) and coronal (B) computed tomography of the pelvis with rectal contrast. The images show thickening and narrowing of the sigmoid colon (arrowheads).

what is your diagnosis?

What is your diagnosis?

Rectosigmoid polyp

Rectosigmoid leiomyoma

Sigmoid adenocarcinoma

Sigmoid endometriosis

d

female

41-50

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2601215

A 56-year-old woman with metastatic melanoma receiving ipilimumab and nivolumab every 3 weeks developed headaches during the course of her treatment. In the week following her first treatment, the patient reported a few mild morning headaches that improved with acetaminophen. After receiving 3 cycles of ipilimumab, 3 mg/kg, and nivolumab, 1 mg/kg, and 8 weeks after her first treatment, the patient reported experiencing daily headaches for at least the prior week and a half. The location of her headaches varied, and there was no associated eye or temple pain. At best, with taking nonsteroidal anti-inflammatory drugs, the headache decreased to pain rated 3 on a scale of 1 to 10. Also at this time, the patient reported low energy levels and difficulty reading; however, physical examination showed no gross visual field defects. Laboratory workup conducted 8 weeks after initiating treatment included adrenocorticotropic hormone (ACTH) and cortisol levels that were measured at 25 pg/mL (reference range, 10-60 pg/mL) and 16.8 μg/dL (reference range, 6-24 μg/dL), respectively. Thyroid-stimulating hormone (TSH) level was 0.82 mIU/L (reference range, 0.5-5.0 mIU/L), which was gradually decreasing compared with 1.41 mIU/L 5 weeks earlier and 1.21 mIU/L 2 weeks earlier. Her total triiodothyronine level was measured at 73 ng/dL (reference range, 80-200 ng/dL) and free thyroxine level was 1.0 ng/dL (reference range, 0.9-1.7 ng/dL). Her serum sodium level was measured at 138 mEq/L; 1 week later it was measured at 135 mEq/L (reference range, 135-145 mEq/L). Contrast-enhanced magnetic resonance imaging (MRI) of the brain was performed for further assessment (Figure).Magnetic resonance imaging (MRI) of the brain obtained 8 weeks after initiating ipilimumab (A-C) and nivolumab treatment and at follow-up (D). What Is Your Diagnosis?

Brain metastasis

Immune-related hypophysitis

Pituitary adenoma

Mucocele

B. Immune-related hypophysitis

B

Immune-related hypophysitis

Magnetic resonance images at 8 weeks after initiating ipilimumab and nivolumab therapy demonstrate an enlarged ovoid-shaped pituitary gland and thickening of the infundibulum. Based both on the constellation of imaging, laboratory, and clinical findings and the known association of hypophysitis during immune-checkpoint inhibitor treatment, the diagnosis of immune-related hypophysitis was made in this patient treated with ipilimumab and nivolumab. The laboratory abnormalities associated with hypophysitis can include low or inappropriately normal levels of TSH, low levels of ACTH, thyroid hormones, or gonadal hormones. Disruptions of the pituitary can lead to secondary adrenal insufficiency, hypothyroidism, or hypogonadism. Hypophysitis is one of the many adverse effects that has been related to immunotherapies; posterior reversible encephalopathy syndrome, aseptic meningitis, and other neurologic adverse effects have also been reported.1The patient was started on steroid therapy with 20/10-mg doses (am/pm replacement dose) of hydrocortisone. The treatment of hypophysitis was complicated when at 3 days following her last cycle of ipilimumab and nivolumab she was admitted to the hospital for colitis. She was hospitalized for 3 weeks and treated with Solu-Medrol and infliximab. She was discharged receiving a high-dose of prednisone and later tapered to a maintenance dose of hydrocortisone. In total, she completed 4 cycles of ipilimumab and nivolumab.The patient’s clinical symptoms resolved, including headache and fatigue. A follow-up MRI demonstrated resolution of the pituitary enlargement (Figure). She continues to be monitored for adrenal insufficiency and thyroid abnormalities, and more than a year after initiation of treatment her adrenocorticotropic hormone level was 5 pg/mL (reference range, 10-60 pg/mL) and morning cortisol level was 12.9 μg/dL (reference range, 6-14 μg/dL).Mechanistically, ipilimumab is a monoclonal antibody that binds cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), and nivolumab is a monoclonal antibody directed against programed cell death protein-1 (PD-1). CTLA-4 and PD-1 normally function as immune checkpoints by downregulating pathways involved in T lymphocyte activation. By binding CTLA-4 and PD-1, ipilimumab and nivolumab increase the activation of the immune system by inactivating these immune checkpoints. Immune-checkpoint inhibition has been associated with a unique set of adverse events termed immune-related adverse events (irAEs) that can involve multiple organ systems in the body.2,3 Immune-related hypophysitis during immune-checkpoint inhibitor therapy is an uncommon but increasingly recognized form of irAE. Various studies examining patients treated with monotherapy ipilimumab have reported an incidence of immune-related hypophysitis ranging from 1% to 13%.4-8 The median time of onset for hypophysitis after beginning ipilimumab was found to be 9 weeks (range, 5-36 weeks).7 In a study analyzing nivolumab and ipilimumab combination therapy, 11.7% of patients developed hypophysitis.9The treatment of ipilimumab-induced hypophysitis is often with systemic high-dose corticosteroids, although the supportive-treatment with hormone replacement for hypophysitis-related hormone deficiencies could also be considered as a treatment strategy. It was noted that frequency of hypophysitis resolution and time to resolution did not differ significantly between the 2 treatment strategies, nor did either group recover from persistent adrenal insufficiency.7This case highlights the clinical and radiographic presentation of immune-related hypophysitis during ipilimumab and nivolumab combination therapy for metastatic melanoma. As the use of immune-checkpoint inhibitor therapies rapidly increases in clinical oncology practice, heightened awareness of and familiarity with the manifestations of various forms of irAEs, including hypophysitis, will be important for clinicians involved in immuno-oncology patient care.

Oncology

A 56-year-old woman with metastatic melanoma receiving ipilimumab and nivolumab every 3 weeks developed headaches during the course of her treatment. In the week following her first treatment, the patient reported a few mild morning headaches that improved with acetaminophen. After receiving 3 cycles of ipilimumab, 3 mg/kg, and nivolumab, 1 mg/kg, and 8 weeks after her first treatment, the patient reported experiencing daily headaches for at least the prior week and a half. The location of her headaches varied, and there was no associated eye or temple pain. At best, with taking nonsteroidal anti-inflammatory drugs, the headache decreased to pain rated 3 on a scale of 1 to 10. Also at this time, the patient reported low energy levels and difficulty reading; however, physical examination showed no gross visual field defects. Laboratory workup conducted 8 weeks after initiating treatment included adrenocorticotropic hormone (ACTH) and cortisol levels that were measured at 25 pg/mL (reference range, 10-60 pg/mL) and 16.8 μg/dL (reference range, 6-24 μg/dL), respectively. Thyroid-stimulating hormone (TSH) level was 0.82 mIU/L (reference range, 0.5-5.0 mIU/L), which was gradually decreasing compared with 1.41 mIU/L 5 weeks earlier and 1.21 mIU/L 2 weeks earlier. Her total triiodothyronine level was measured at 73 ng/dL (reference range, 80-200 ng/dL) and free thyroxine level was 1.0 ng/dL (reference range, 0.9-1.7 ng/dL). Her serum sodium level was measured at 138 mEq/L; 1 week later it was measured at 135 mEq/L (reference range, 135-145 mEq/L). Contrast-enhanced magnetic resonance imaging (MRI) of the brain was performed for further assessment (Figure).Magnetic resonance imaging (MRI) of the brain obtained 8 weeks after initiating ipilimumab (A-C) and nivolumab treatment and at follow-up (D).

what is your diagnosis?

What is your diagnosis?

Brain metastasis

Immune-related hypophysitis

Pituitary adenoma

Mucocele

b

female

51-60

original

https://jamanetwork.com/journals/jama/fullarticle/2618600

A 29-year-old woman presented with a 6-month history of yellowing skin on her palms and soles. She was previously healthy, did not consume alcohol, and had no personal or family history of liver disease. She took no prescription medications; however, approximately 6 months prior to the onset of symptoms, she began taking a nutritional supplement (Nature Made Beta Carotene, Otsuka Pharmaceutical) manufactured in Japan and available online in China. This supplement contained 1.8 mg of beta carotene per tablet, and she had been taking 2 tablets daily for the past 6 months. She had no other dietary changes during this period, in particular, no increased intake of carrots or other yellow- or orange-colored fruits or vegetables. Physical examination revealed yellow-orange pigmentation of her palms and soles (Figure). There was no scleral icterus. Results of laboratory tests, including measurement of aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, and total and direct bilirubin levels, ratio of blood urea nitrogen to creatinine, as well as fasting lipid profile and thyroid function tests, were normal.Yellowish orange pigmentation of the patient’s palms and soles, as compared with a nonpigmented palm in the center.Advise the patient to discontinue the nutritional supplement What Would You Do Next?

Perform a biopsy

Order repeat liver function tests

Empirically treat with a topical steroid

Advise the patient to discontinue the nutritional supplement

Carotenemia

D

Advise the patient to discontinue the nutritional supplement

The key to the correct diagnosis in this case is awareness that the skin discoloration on the palms and soles, without scleral icterus and with normal bilirubin levels, is consistent with carotenemia. In the context of the patient’s clinical history, physical examination, and laboratory values, a diagnosis of carotenemia secondary to increased consumption of nutritional supplements containing carotene was made.Carotenemia is a cause of abnormal pigmentation characterized by yellow discoloration of the skin related to carotene ingestion. Because carotene is liposoluble, and corneum has a high lipid content, corneum has an affinity for carotene, whereas mucosa has no such attraction; therefore, yellow skin is most prominently seen on the thick areas of the skin, such as the palms and soles.1 Carotenemia is a benign condition, because the conversion of carotene to vitamin A is so slow that even after massive ingestion of carotene, vitamin A toxicity does not occur.2,3Carotenemia can be caused by 3 types of carotene-related processes: excessive intake, reduced biotransformation, and hyperlipidemia.4 Many green, yellow, and orange fruits and vegetables contain carotene, including carrots, oranges, sweet potatoes, squash, and pumpkins. Excessive intake of these carotene-rich foods or other nutritional supplements containing carotene can lead to carotenemia.5 Carotenemia is more common in infants and young children because of diets rich in pureed vegetables,3,6,7 as well as in young and middle-aged women. More cases are observed in autumn and winter than the other months, possibly because carotene-containing fruits and vegetables are in season.Physiologically, carotene converts to vitamin A in the small intestine, mostly in the duodenum.4,8 Decreased conversion, which can be associated with diabetes mellitus, liver disease, and hypothyroidism, can result in high carotene levels in the blood. In addition, hyperlipidemia and other diseases, including nephritic syndrome and diabetes, can cause carotenemia, since there is a linear relationship between serum lipoprotein and carotene levels.2,4 Although carotenemia can be associated with several diseases and medications,9 it is most often caused by excessive intake of carotene-rich food.The diagnosis of carotenemia is mostly clinical, based on history of excessive intake of carotene and the distribution of yellow discoloration on the palms and soles. It is important to recognize carotenemia and not confuse it with jaundice. The presence of clear sclerae is a major clinical sign that can help differentiate carotenemia from jaundice. Normal bilirubin levels, along with high carotene levels in blood, can confirm the diagnosis.The patient was advised to stop taking the nutritional supplements containing carotene and to decrease carotene-rich foods. With these changes, her skin discoloration had faded at a 10-month follow-up visit.

General

A 29-year-old woman presented with a 6-month history of yellowing skin on her palms and soles. She was previously healthy, did not consume alcohol, and had no personal or family history of liver disease. She took no prescription medications; however, approximately 6 months prior to the onset of symptoms, she began taking a nutritional supplement (Nature Made Beta Carotene, Otsuka Pharmaceutical) manufactured in Japan and available online in China. This supplement contained 1.8 mg of beta carotene per tablet, and she had been taking 2 tablets daily for the past 6 months. She had no other dietary changes during this period, in particular, no increased intake of carrots or other yellow- or orange-colored fruits or vegetables. Physical examination revealed yellow-orange pigmentation of her palms and soles (Figure). There was no scleral icterus. Results of laboratory tests, including measurement of aspartate aminotransferase, alanine aminotransferase, hemoglobin A1c, and total and direct bilirubin levels, ratio of blood urea nitrogen to creatinine, as well as fasting lipid profile and thyroid function tests, were normal.Yellowish orange pigmentation of the patient’s palms and soles, as compared with a nonpigmented palm in the center.Advise the patient to discontinue the nutritional supplement

what would you do next?

What would you do next?

Advise the patient to discontinue the nutritional supplement

Perform a biopsy

Empirically treat with a topical steroid

Order repeat liver function tests

a

female

21-30

original

https://jamanetwork.com/journals/jama/fullarticle/2616370

An 80-year-old man with a history of hypertension, gastroesophageal reflux disease, and stage 4 chronic kidney disease presented with 2 days of anuria. He felt well until 6 days prior, when he awoke with diffuse muscle cramps following a strenuous day of moving boxes. He subsequently developed oliguria that progressed to anuria. His only medication was omeprazole (20 mg daily). His usual fluid intake had not changed.Physical examination was notable for moist mucous membranes, clear lungs, no lower extremity or periorbital edema, and no jugular venous distension. Examination was otherwise unremarkable. Bladder scan showed 50 mL of urine, which was collected via straight catheterization. Three liters of normal saline was administered, with no further urine production.Laboratory testing revealed a blood urea nitrogen level of 90 mg/dL (32.1 mmol/L) (reference range, 7-21 mg/dL [2.5-7.5 mmol/L]) and creatinine level of 14.1 mg/dL (1246.4 μmol/L) (reference range, 0.6-1.17 mg/dL [53.0-103.4 μmol/L]); baseline levels 3 months prior were 37 mg/dL (13.2 mmol/L) and 3.3 mg/dL (291.7 μmol/L), respectively. Hemoglobin level was 10.6 g/dL (reference range, 13-17 g/dL); calcium, 8.1 mg/dL (reference range, 8.5-10.1 mg/dL); potassium, 6.2 mmol/L (reference range, 3.5-4.7 mmol/L); and phosphorous 8.8 mg/dL (2.8 mmol/L) (reference range, 2.5-4.9 mg/dL [0.81-1.58 mmol/L]). Creatine kinase level was within normal limits. Urinalysis showed minimal albuminuria (100 mg/dL); however, spot urine protein to creatinine ratio predicted 11 139 mg/g (reference range, 0-200 mg/g) proteinuria. Renal ultrasound showed no hydronephrosis. Serum protein electrophoresis and immunofixation electrophoresis identified a small monoclonal IgG κ band. Serum κ free light chain (FLC) level was 20 765 mg/L (reference range, 3.3-19.4 mg/L) with a free κ to λ ratio of 296 (reference range, 0.37-3.1).1 Hemodialysis was initiated and a bone marrow biopsy obtained.Bone marrow biopsy showed a normocellular bone marrow with 10% κ-restricted plasma cells (Figure, left panel). Immunohistochemical staining demonstrated positivity for the plasma cell marker CD138 (Figure, right panel).Left, Bone marrow biopsy sample (hematoxylin-eosin, original magnification ×400). Right, Immunohistochemical staining of biopsy sample (immunohistochemical stain for CD138, original magnification ×400). What Would You Do Next?

Continue IV fluids and administer furosemide

Initiate bortezomib-dexamethasone–based therapy

Obtain renal biopsy

Order skeletal survey

Multiple myeloma complicated by cast nephropathy

B

Initiate bortezomib-dexamethasone–based therapy

The key to the correct diagnosis is the markedly elevated serum κ to λ ratio, which is diagnostic of multiple myeloma, regardless of bone imaging results. Acute renal impairment in this setting is highly indicative of cast nephropathy, and renal biopsy should not delay treatment. Although hydration is imperative, furosemide may worsen cast nephropathy and should be avoided.2 Patients presenting with multiple myeloma and acute renal impairment attributed to cast nephropathy should urgently receive bortezomib-dexamethasone–based therapy to suppress light-chain production, with consideration of simultaneous mechanical removal of FLCs, to optimize renal recovery.According to the International Myeloma Working Group (IMWG),3 this patient meets criteria for active multiple myeloma reflected by clonal bone marrow plasma cells 10% or greater and by a serum involved to uninvolved FLC ratio greater than 100, qualifying as a myeloma-defining event. Specifically, evidence of end-organ damage (CRAB criteria: hypercalcemia, renal dysfunction, anemia, bone lesions) is no longer exclusively required to diagnose multiple myeloma.3 For patients previously categorized as having smoldering myeloma, the inclusion of myeloma-defining events allows for earlier recognition of patients at high risk for progression who would benefit from early intervention.Renal impairment is one of the most common complications of multiple myeloma, with risk proportional to urinary FLC concentration.4 In this patient, urinary FLCs could not be confirmed prior to initiation of therapy, although urinalysis at admission did show significant nonalbumin proteinuria. This, along with serum κ FLC concentration greater than 500 mg/L, strongly suggested cast nephropathy, circumventing the need for renal biopsy.5 Acute renal impairment in this setting is a medical emergency, warranting rapid initiation of antimyeloma therapy to reduce circulating FLCs and restore renal function, because dialysis dependence confers increased mortality.6On recognition of multiple myeloma–related renal impairment, aggressive hydration should be initiated, hypercalcemia corrected, and nephrotoxic agents avoided.5 The IMWG recommends prompt initiation of antimyeloma treatment with bortezomib-based regimens, as several studies have demonstrated superior renal recovery and rates of dialysis independence5,7 (grade A recommendation). The IMWG also recommends high-dose dexamethasone for at least the first month of therapy (grade B)5 for more rapid renal responses.7 Although immunomodulatory drugs such as thalidomide, lenalidomide, or pomalidomide are options, these may require renal dosing and can be less effective in this setting.5 Thus, for patients newly diagnosed with multiple myeloma who have acute renal impairment, bortezomib-dexamethasone–based regimens are considered first-line therapy. More recently, bortezomib-dexamethasone plus another agent (triplet therapy) has demonstrated superior renal outcomes, including higher rates of dialysis discontinuation, resulting in improved survival.8Mechanical approaches, such as high-cutoff hemodialysis (HCO-HD) or plasma exchange, are occasionally used in conjunction with systemic antimyeloma therapy to rapidly remove FLCs from circulation. Of these, data supporting HCO-HD, which allows FLC removal through large pores, are more promising for reversal of renal impairment and dialysis independence.9 The evidence supporting plasmapheresis is controversial, limited by small trials with conflicting outcomes.5 Randomized clinical trials are ongoing to better define the role of adjunctive mechanical approaches for patients with myeloma-related renal impairment requiring dialysis. According to IMWG guidelines in 2016, in patients with multiple myeloma and acute renal impairment strongly suspected to have light chain cast nephropathy, HCO-HD should be attempted first (grade B). If unavailable, plasma exchange is a reasonable alternative (grade C).5This case highlights a recent shift in the diagnostic criteria for active multiple myeloma and offers an opportunity to discuss specific management options for myeloma-related renal impairment.The patient received bortezomib-dexamethasone plus 3 cycles of plasmapheresis, with lowering of serum FLC level and improvement in urine output. There was significant recovery of renal function; dialysis was reduced to twice weekly after 3 months of antimyeloma therapy and was no longer required after 6 months.

General

An 80-year-old man with a history of hypertension, gastroesophageal reflux disease, and stage 4 chronic kidney disease presented with 2 days of anuria. He felt well until 6 days prior, when he awoke with diffuse muscle cramps following a strenuous day of moving boxes. He subsequently developed oliguria that progressed to anuria. His only medication was omeprazole (20 mg daily). His usual fluid intake had not changed.Physical examination was notable for moist mucous membranes, clear lungs, no lower extremity or periorbital edema, and no jugular venous distension. Examination was otherwise unremarkable. Bladder scan showed 50 mL of urine, which was collected via straight catheterization. Three liters of normal saline was administered, with no further urine production.Laboratory testing revealed a blood urea nitrogen level of 90 mg/dL (32.1 mmol/L) (reference range, 7-21 mg/dL [2.5-7.5 mmol/L]) and creatinine level of 14.1 mg/dL (1246.4 μmol/L) (reference range, 0.6-1.17 mg/dL [53.0-103.4 μmol/L]); baseline levels 3 months prior were 37 mg/dL (13.2 mmol/L) and 3.3 mg/dL (291.7 μmol/L), respectively. Hemoglobin level was 10.6 g/dL (reference range, 13-17 g/dL); calcium, 8.1 mg/dL (reference range, 8.5-10.1 mg/dL); potassium, 6.2 mmol/L (reference range, 3.5-4.7 mmol/L); and phosphorous 8.8 mg/dL (2.8 mmol/L) (reference range, 2.5-4.9 mg/dL [0.81-1.58 mmol/L]). Creatine kinase level was within normal limits. Urinalysis showed minimal albuminuria (100 mg/dL); however, spot urine protein to creatinine ratio predicted 11 139 mg/g (reference range, 0-200 mg/g) proteinuria. Renal ultrasound showed no hydronephrosis. Serum protein electrophoresis and immunofixation electrophoresis identified a small monoclonal IgG κ band. Serum κ free light chain (FLC) level was 20 765 mg/L (reference range, 3.3-19.4 mg/L) with a free κ to λ ratio of 296 (reference range, 0.37-3.1).1 Hemodialysis was initiated and a bone marrow biopsy obtained.Bone marrow biopsy showed a normocellular bone marrow with 10% κ-restricted plasma cells (Figure, left panel). Immunohistochemical staining demonstrated positivity for the plasma cell marker CD138 (Figure, right panel).Left, Bone marrow biopsy sample (hematoxylin-eosin, original magnification ×400). Right, Immunohistochemical staining of biopsy sample (immunohistochemical stain for CD138, original magnification ×400).

what would you do next?

What would you do next?

Initiate bortezomib-dexamethasone–based therapy

Order skeletal survey

Continue IV fluids and administer furosemide

Obtain renal biopsy

a

male

71-80

original

https://jamanetwork.com/journals/jama/fullarticle/2614164

A 35-year-old man presented to the emergency department with 4 days of fever (temperature up to 39°C), extreme weakness, fatigue, and 1 to 2 days of progressive confusion. He was born in the United States but had traveled to Sierra Leone for a period of 3 weeks and had returned 1 week prior to presentation. He did not take any form of malaria prophylaxis, nor did he use insect repellent while traveling. He previously received the yellow fever vaccine but not hepatitis A or typhoid vaccination.Physical examination revealed a temperature of 39.3°C, heart rate of 120/min, blood pressure of 119/60 mm Hg, respiratory rate of 32/min, and oxygen saturation of 98% on room air. The patient was jaundiced, with scleral icterus, and was alert and oriented, although he had a fluctuating attention span and was unable to complete basic tasks. He was able to localize painful stimuli. No retinal lesions were present on dilated ophthalmologic examination. Laboratory tests were notable for a white blood cell count of 5000/μL with 88% polymorphonuclear leukocytes, 1% bands, 5% lymphocytes, 5% monocytes, and 0% eosinophils; hemoglobin level of 9.5 g/dL, and platelet count of 25 ×103/μL. Sodium level was 132 mEq/L; potassium, 4.0 mEq/L; chloride, 100 mEq/L; carbon dioxide, 15 mEq/L; blood urea nitrogen, 40 mg/dL; and creatinine, 1.5 mg/dL. Total bilirubin level was 23.9 mg/dL; aspartate aminotransferase, 252 U/L; and alanine aminotransferase, 100 U/L. Venous lactate level was 49.6 mg/dL. A computed tomography scan of the head was unremarkable. A thin preparation blood smear was obtained (Figure).Thin preparation smear of blood obtained from patient (Wright-Giemsa, original magnification ×100). What Would You Do Next?

Start artemether-lumefantrine

Start chloroquine

Start intravenous quinidine gluconate and doxycycline

Perform an exchange transfusion

Severe Plasmodium falciparum malaria

C

Start intravenous quinidine gluconate and doxycycline

The key to the correct diagnosis was a thin preparation smear showing numerous normal-sized red blood cells with malarial ring forms, including some red blood cells with multiple parasites consistent with P falciparum. Ring forms included single and double “classic headphone” chromatin dots as well as peripheral applique forms. Banana-shaped gametocytes, which are pathognomonic for P falciparum, were not present. Symptoms and laboratory findings were consistent with severe malaria. The absence of cerebral edema on computed tomography scan and absence of coma or convulsions decreases the likelihood of cerebral malaria, which is more common in children.1The current CDC-recommended treatment for severe P falciparum malaria in the United States is parenteral quinidine and doxycycline to rapidly reduce red blood cell parasitemia.2 Choice A is incorrect because an oral agent is not the treatment of choice in cases of severe malaria. All malaria cases from Africa should be considered chloroquine resistant; therefore, B is not correct. Choice D is incorrect because no benefit has been observed for exchange transfusion in multiple studies.Approximately 1700 cases of malaria are diagnosed in the United States each year, mostly from travelers returning from sub-Saharan Africa, with 61% of cases identified as attributable to P falciparum. Sixteen percent are severe cases, which have a significantly higher attributable mortality.3 Patients with severe malaria are found to have significant anemia, renal insufficiency, thrombocytopenia, elevated transaminase levels, coagulopathy, acidosis, hypoglycemia, and hyperparasitemia (defined as ≥10% by the World Health Organization [WHO] and ≥5% by the CDC). Cerebral malaria may be a component of severe malaria, with symptoms that include coma, seizures, or both.1 Retinopathy can often be observed when cerebral malaria occurs in children; however, retinal changes are not always present in adults. The mortality rate associated with cerebral malaria is 15% to 20% with appropriate therapy and can increase to more than 30% with associated organ dysfunction.1The currently recommended therapy in the United States for severe malaria is parenteral quinidine gluconate. A loading dose (6.25 mg base/kg or 10 mg salt/kg) is initially given to rapidly clear parasitemia and prevent early mortality, followed by a maintenance dose of 0.0125 mg base/kg/min or 0.02 mg salt/kg/min by continuous infusion. Quinidine is known to cause adverse effects including hypotension, hypoglycemia, and cardiotoxicity (QTc and QRS complex prolongation and subsequent ventricular arrhythmias).2 Therefore, such patients are typically monitored in an intensive care unit. In patients with renal insufficiency, measurement of quinidine levels can aid in dose adjustment. Supratherapeutic levels may lead to an increase in adverse events.The WHO guidelines recommend intravenous artesunate (not available for commercial use in the United States) as the treatment of choice for severe malaria, which differs from CDC guidelines.2,4 Artesunate clears circulating parasites faster than other therapies. Randomized clinical trials have shown that adults treated with artesunate have a reduced risk of mortality compared with those treated with quinine (relative risk, 0.61 [95% CI, 0.50-0.75]). Additionally, adverse effects are uncommon with artesunate.5,6 The current criteria for release of artesunate from the CDC in the United States consists of quinidine intolerance or contraindication, persistent parasitemia greater than 10% after 48 hours of treatment with quinidine, or unavailability of quinidine.2After treatment with a parenteral agent for a minimum of 12 hours with subsequent documentation of reduced parasitemia to less than 1%, subsequent oral treatment should be administered. The best option includes continuation of an artemisinin derivative such as artemether-lumefantrine for 3 days.4 Alternatives include atovaquone-proguanil or quinine sulfate with doxycycline for 7 days.2Patients with uncomplicated P falciparum malaria should preferably be treated with oral agents such as artemether-lumefantrine. Atovaquone-proguanil or chloroquine (if the region in which the patient traveled does not have chloroquine resistance) are alternatives. Other options include quinine sulfate plus doxycycline or clindamycin. Mefloquine is an option if other agents are not available; however, this treatment is often limited by adverse events, mainly neuropsychiatric events.7 To prevent relapse of P vivax or P ovale disease, primaquine is added to treat the hypnozoite forms protected within the liver.This patient’s thin smear showed P falciparum with 28.7% parasitemia. The CDC was contacted for assistance with management, and he was promptly treated with intravenous quinidine and doxycycline. After 24 hours, parasitemia decreased to 1.7%, and parasites were not observed at 72 hours. During hospitalization he developed progressive renal failure and required hemodialysis. His quinidine level was elevated at 14.6 μg/mL after 28 hours of therapy; therefore, after 48 hours of parenteral therapy, he was transitioned to oral quinine and doxycycline. His QRS complex progressively widened with oral quinine (from 84 ms to 130 ms); therefore, only oral doxycycline was maintained, for an additional 7 days. He clinically improved and at discharge had no neurologic deficits. After 1 month, he recovered normal renal function.

General

A 35-year-old man presented to the emergency department with 4 days of fever (temperature up to 39°C), extreme weakness, fatigue, and 1 to 2 days of progressive confusion. He was born in the United States but had traveled to Sierra Leone for a period of 3 weeks and had returned 1 week prior to presentation. He did not take any form of malaria prophylaxis, nor did he use insect repellent while traveling. He previously received the yellow fever vaccine but not hepatitis A or typhoid vaccination.Physical examination revealed a temperature of 39.3°C, heart rate of 120/min, blood pressure of 119/60 mm Hg, respiratory rate of 32/min, and oxygen saturation of 98% on room air. The patient was jaundiced, with scleral icterus, and was alert and oriented, although he had a fluctuating attention span and was unable to complete basic tasks. He was able to localize painful stimuli. No retinal lesions were present on dilated ophthalmologic examination. Laboratory tests were notable for a white blood cell count of 5000/μL with 88% polymorphonuclear leukocytes, 1% bands, 5% lymphocytes, 5% monocytes, and 0% eosinophils; hemoglobin level of 9.5 g/dL, and platelet count of 25 ×103/μL. Sodium level was 132 mEq/L; potassium, 4.0 mEq/L; chloride, 100 mEq/L; carbon dioxide, 15 mEq/L; blood urea nitrogen, 40 mg/dL; and creatinine, 1.5 mg/dL. Total bilirubin level was 23.9 mg/dL; aspartate aminotransferase, 252 U/L; and alanine aminotransferase, 100 U/L. Venous lactate level was 49.6 mg/dL. A computed tomography scan of the head was unremarkable. A thin preparation blood smear was obtained (Figure).Thin preparation smear of blood obtained from patient (Wright-Giemsa, original magnification ×100).

what would you do next?

What would you do next?

Start intravenous quinidine gluconate and doxycycline

Start chloroquine

Perform an exchange transfusion

Start artemether-lumefantrine

a

male

31-40

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2584936

A healthy man in his 20s presented with a several-month history of asymptomatic, slightly erythematous cutaneous nodules, measuring 1.5 to 3.0 cm, over the calcanea (Figure, A). Physical examination revealed violaceous plaques, measuring 2 to 3 cm, on the extensor surface of the knees, bilaterally (Figure, B). Excisional biopsy specimens were obtained (Figure, C and D).A, Multiple asymptomatic erythematous nodules measuring 1.5 to 3.0 cm at presentation. B, Multiple violaceous plaques measuring 2 to 3 cm on the extensor surface of the knees. C, Excisional biopsy specimen of a calcaneal nodule (hematoxylin-eosin, original magnification ×20). D, Excisional biopsy specimen of a plaque (hematoxylin-eosin, original magnification ×20).Knee-located erythema elevatum diutinum (EED) with a calcaneal late-stage nodular component What Is Your Diagnosis?

Elastolytic granuloma

Knee-located erythema elevatum diutinum (EED) with a calcaneal late-stage nodular component

Epithelioid sarcoma

Storiform collagenoma

B. Knee-located EED with a calcaneal late-stage nodular component

B

Knee-located erythema elevatum diutinum (EED) with a calcaneal late-stage nodular component

Histopathological examination of the genicular plaques revealed a dense neutrophilic infiltrate within and around small vessels with micro-abscesses in the papillary and reticular dermis; deposits of fibrin and leukocytoclasia were also present. For the calcaneal nodules, in contrast, a central hypocellular dermal proliferation of thickened and hyalinized collagen bundles with a distinctive storiform pattern was surrounded by multiple foci of concentric “onionskin” fibrosis with interspersed neutrophils around small vessels.A rare form of cutaneous vasculitis, EED usually affects adults. According to the stage of the lesions, the clinical and histologic features of the disease vary. Early-stage EED is characterized by symmetrical and persistent papules and plaques located on the extensor surfaces of the extremities; histologic sections commonly reveal vascular infiltration in the upper and mid dermis with predominant neutrophils and lesser numbers of lymphocytes, eosinophils, and plasma cells; leukocytoclasia is commonly observed. Such lesions may be histologically indistinguishable from primary vasculitides. However, the typical clinical localization and the absence of systemic involvement are clue features of EED. Some scholars consider EED and granuloma faciale on a spectrum; however, the different localization and the predominance of neutrophils rather than eosinophils in the present case point to the diagnosis of EED.Late-stage EED has been documented in few reports1-7 and consists of hypocellular dermal sclerosing nodules with minimal inflammatory infiltration easily confused clinically and histologically with several dermatoses including annular granuloma, dermatofibroma, or storiform collagenoma. We describe a rare case of EED combining early- and late-stage appearance, characterized by the unusual presentation of nodular sclerotic lesions. Awareness of this peculiar presentation will help avoid misdiagnosis as a neoplastic process in first instance.2 We recommend performing excisional biopsies whenever possible to avoid misdiagnosis. In addition, early, active lesions that are likely to yield diagnostic results should be preferred.8The present case also highlights the importance of combining therapeutic methods to benefit the patient: dapsone (100 mg/d) to avoid the development of early lesions and surgical excision to treat late-stage lesions.9 Surgical excision is a treatment option that has been recently described10 with excellent results and, in the present case, was aimed to relieve discomfort for the patient and prevent interference with usual activities caused by the calcaneal nodules.

Dermatology

A healthy man in his 20s presented with a several-month history of asymptomatic, slightly erythematous cutaneous nodules, measuring 1.5 to 3.0 cm, over the calcanea (Figure, A). Physical examination revealed violaceous plaques, measuring 2 to 3 cm, on the extensor surface of the knees, bilaterally (Figure, B). Excisional biopsy specimens were obtained (Figure, C and D).A, Multiple asymptomatic erythematous nodules measuring 1.5 to 3.0 cm at presentation. B, Multiple violaceous plaques measuring 2 to 3 cm on the extensor surface of the knees. C, Excisional biopsy specimen of a calcaneal nodule (hematoxylin-eosin, original magnification ×20). D, Excisional biopsy specimen of a plaque (hematoxylin-eosin, original magnification ×20).Knee-located erythema elevatum diutinum (EED) with a calcaneal late-stage nodular component

what is your diagnosis?

What is your diagnosis?

Knee-located erythema elevatum diutinum (EED) with a calcaneal late-stage nodular component

Elastolytic granuloma

Epithelioid sarcoma

Storiform collagenoma

a

male

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2588403

A primigravida woman in her 30s at 35 weeks’ gestation and with a history of Darier disease was admitted with an acute, painful eruption on her face and neck. She reported no history of pregnancy-related complications. Physical examination revealed confluent erythema with keratotic papulovesicles distributed on the face and neck (Figure, A). Honey-colored crusts were present on the left ear and preauricular area. The chest and inframammary area displayed occasional red, crusted papules. Laboratory tests revealed an elevated white blood cell count of 17.18 × 103/μL (reference range, 4.50-11.00 × 103/μL). A shave biopsy specimen and tissue culture were obtained from the center of an umbilicated papule on the neck (Figure, B and C).A, Confluent erythema with papulovesicles on the neck and face. B and C, Histopathological images, hematoxylin-eosin. B, Full-thickness epidermal necrosis with focal areas of suprabasal acantholysis with corp ronds, corp grains, and parakeratosis. C, Multinucleated cells with nuclear molding and margination. What Is Your Diagnosis?

Kaposi varicelliform eruption

Impetigo

Pemphigoid gestationis

Impetigo herpetiformis

A. Kaposi varicelliform eruption

A

Kaposi varicelliform eruption

Histopathological examination revealed full-thickness epidermal necrosis with nuclear molding, margination of chromatin, and multinucleation of cells in areas affected by herpes simplex virus (HSV). Features of Darier disease, including suprabasal acantholysis with corps ronds and corps grains and parakeratosis, were also present. Immunohistochemical stain for HSV 1 and 2 showed positive nuclear staining, confirming the presence of HSV infection. Serologic testing was positive for HSV-1 IgG. Tissue culture produced few Staphylococcus aureus and few coagulase negative staphylococci. The patient was treated with oral clindamycin, 300 mg, every 6 hours and intravenous acyclovir, 5mg/kg, every 8 hours for 10 days. She was subsequently switched to oral valacyclovir, 2000 mg, twice daily for 14 days. A prophylactic dose of valacyclovir, 500 mg twice daily, was continued for the duration of the pregnancy. She delivered a healthy infant at term with no evidence of infection.Darier disease is an autosomal dominant genodermatosis characterized by abnormal keratinization of skin, nails, and mucosal surfaces. The pathogenesis of Darier disease involves mutations in ATP2A2, which encodes a sarcoplasmic reticulum calcium-ATPase pump that normally maintains low levels of intracellular calcium. Clinically, patients with Darier disease present in adolescence with greasy, hyperkeratotic papules coalescing into plaques along seborrheic surfaces. Heat, perspiration, and UV light exposure are common exacerbating factors.Kaposi varicelliform eruption (KVE) is a diffuse viral infection typically caused by HSV type 1 or 2 (eczema herpeticum), or other viruses, such as Coxsackie (eczema Coxsackium) or Vaccinia (eczema vaccinatum), occurring within lesions of a preexisting skin disease. KVE is most commonly seen in patients with atopic dermatitis but has also been reported in association with a number of acantholytic, papulosquamous, and autoimmune bullous dermatoses.1,2 Patients with Darier disease are susceptible to KVE for reasons that remain unclear. The current accepted pathogenic theory is that defects in cell-mediated immunity and skin barrier dysfunction predispose these patients to secondary infection.3Characteristically, patients with KVE present with clusters of monomorphic papulovesicles that progress to painful, hemorrhagic, crusted, punched-out erosions. The eruption is accompanied by fever and regional lymphadenopathy and is classically confined to areas of active skin disease. The head, neck, and chest are the most commonly affected regions. Ocular involvement may occur, and should be considered an ophthalmologic emergency.4Prompt initiation of antiviral therapy is advised with clinical suspicion of KVE. High-dose intravenous acyclovir is the treatment of choice for severe cases, while oral valacyclovir may be appropriate for milder cases not requiring hospitalization. Antibacterial prophylaxis is also recommended.Reports of KVE in the context of pregnancy, especially during the third trimester, are rare and raise interesting questions regarding the risk of maternal-fetal transmission and optimal management of such cases. Historically, early recognition and treatment have resulted in healthy deliveries at term without evidence of neonatal infection.5,6 However, 1 reported case7 of KVE with delayed presentation in the third trimester resulted in initiation of preterm labor and delivery with subsequent neonatal infection. In patients with a history of genital HSV, prophylactic acyclovir beginning at 36 weeks’ gestation has been shown to reduce clinical HSV recurrence at delivery.8 While there is insufficient evidence to support or refute such measures in pregnant patients with a history of KVE, consideration of prophylactic therapy seems prudent. Although avoidance of vaginal delivery and proceeding with a cesarean delivery has clear benefits in patients with active genital HSV infections, the use of this procedure in patients with disseminated cutaneous infections remains unclear.This case highlights the importance of considering KVE in patients with predisposing comorbidities and emphasizes treatment considerations in pregnancy. Prompt diagnosis allows for early and appropriate management and the optimization of maternal and fetal outcomes.

Dermatology

A primigravida woman in her 30s at 35 weeks’ gestation and with a history of Darier disease was admitted with an acute, painful eruption on her face and neck. She reported no history of pregnancy-related complications. Physical examination revealed confluent erythema with keratotic papulovesicles distributed on the face and neck (Figure, A). Honey-colored crusts were present on the left ear and preauricular area. The chest and inframammary area displayed occasional red, crusted papules. Laboratory tests revealed an elevated white blood cell count of 17.18 × 103/μL (reference range, 4.50-11.00 × 103/μL). A shave biopsy specimen and tissue culture were obtained from the center of an umbilicated papule on the neck (Figure, B and C).A, Confluent erythema with papulovesicles on the neck and face. B and C, Histopathological images, hematoxylin-eosin. B, Full-thickness epidermal necrosis with focal areas of suprabasal acantholysis with corp ronds, corp grains, and parakeratosis. C, Multinucleated cells with nuclear molding and margination.

what is your diagnosis?

What is your diagnosis?

Impetigo

Impetigo herpetiformis

Pemphigoid gestationis

Kaposi varicelliform eruption

d

female

31-40

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2588693

A man in his 40s presented with gradual hair loss of the eyelashes, eyebrows, beard, and scalp for 4 years, swelling and painful hand joints for 13 months, and multiple asymptomatic nodules on the upper arms for 40 days. The patient exhibited no associated fever, analgesia or hypesthesia. He reported no previous infections or family or personal medical history of autoimmune diseases or psoriasis. He was previously treated for rheumatoid arthritis, but various arthritis treatments showed no improvements over 1 year. A physical examination showed diffuse infiltration of the face with loss of skin creases and diminished facial hair; all joints of both hands were swollen (Figure, A); multiple asymptomatic nodules without ulceration were present on his upper arms (Figure, B); decreased sensation to pain, temperature and/or touch and neuropathic changes were not found. Laboratory test results showed a slightly elevated erythrocyte sedimentation rate (27 mm/h) and significantly elevated rheumatoid factor (70.1 IU/mL). Additional immunology indicators, including C-reactive protein, anticyclic citrullinated peptide, antinuclear antibodies, and globulin levels were normal. X-ray and joint ultrasound results suggested osteoarthritis, synovitis, flexor tendon tenosynovitis, and bone erosions. Ultrasound results also indicated enlarged axillary, cervical, and inguinal lymph nodes and an enlarged spleen. Fundus fluorescein angiography showed uveitis.A, Joints of both hands were swollen. B, Multiple asymptomatic nodules on the upper arms. C, Skin biopsy from the patient’s upper arm nodule demonstrating diffuse infiltrate of foamy histiocytes in the dermis (hematoxylin-eosin stain, original magnification ×100). D, Numerous acid-fast bacilli (acid-fast stain, original magnification ×400). What Is Your Diagnosis?

Rheumatoid arthritis

Systematic lupus erythematosus

Arthritis associated with other connective tissue diseases

Leprosy

D. Leprosy

D

Leprosy

The primary clinical features include the presence of swollen and painful hand joints, asymptomatic subcutaneous nodules, and gradual hair loss. The skin biopsy showed diffuse infiltrate of foamy histiocytes in the dermis with numerous acid-fast bacilli (Figure, C and D). These characteristics exclude other diagnoses such as rheumatic diseases, arthritis associated with other autoimmune diseases, and lupus. The clinical manifestations and histopathologic findings are consistent with the features of lepromatous leprosy with a type 2 leprosy reaction (T2R). The patient was treated effectively with multidrug therapy (rifampin, clofazimine, and dapsone) and thalidomide in the Leprosy Treatment Center in Shandong Province, China. Skin lesions substantially improved after 2 months of therapy, and the patient is currently receiving maintenance therapy with close follow-up.Leprosy is a chronic infection caused by Mycobacterium leprae that primarily attacks the skin and peripheral nerves. The clinical presentation depends on the genetically determined cellular immunity of the patient. Accordingly, the disease is often categorized as multibacillary or paucibacillary (lepromatous or tuberculoid).1 In most patients, early leprosy presents with macular, hypopigmented lesions, and impaired sensory, motor, and autonomic functions of peripheral nerves.2 The pathogen transmission route is not well understood, and patients with susceptibility genes are prone to the infection.3Leprosy reactions are acute inflammatory episodes that may occur multiple times during the course of the disease or after treatment, manifesting as type 1 reaction (T1R) or T2R. A T1R (or reversal reactions) is clinically characterized by acutely inflamed preexisting skin lesions, the appearance of new lesions, edema of extremities, and/or neuritis.4 Type 1 reactions are delayed hypersensitivity reactions that usually present with edema, an increased number of lymphocytes in the dermis, and loss of normal granuloma organization in the histology.5 A T2R (erythema nodosum leprosum) typically presents as tender or painful subcutaneous nodules on the face or extensor surfaces of the limbs with associated fever and arthralgia in patients with a high bacilli load.6 Type 2 reactions are considered a form of small vessel vasculitis (cutaneous and systemic) owing to immune complex deposition; thus, vasculitis indicators might be increased.7 Therefore, patients with leprosy who have a T2R may often be misdiagnosed with rheumatic diseases, as in this case.A previous study8 confirmed T-cell unresponsiveness to Mycobacterium leprae owing to an increase in inhibitory regulator T (Treg) cells in stable nonreactive lepromatous leprosy patients. It shows that patients with leprosy reactions may have an imbalance in T helper 17 (Th17) cells and Treg populations.8 The reduced Treg suppressor activity is associated with higher Th17 cell activity owing to the combined effects of reduced transforming growth factor β (TGF-β) and increased interleukin (IL)-6 and IL-21 cytokines, contributing to lesional inflammation. Moreover, in T2Rs but not T1Rs, the higher Th17 activity may be owing to down-regulation of Tregs.9 Although the pathogenesis of T2Rs is thought to be related to the deposition of immune complexes, the cytokines produced by Th17 include IL-17, IL-21, and IL-22, which promote neutrophil infiltration and tissue damage.10The diagnosis of leprosy can be confirmed by acid-fast bacilli in skin tissue or detecting the DNA of Mycobacterium leprae using polymerase chain reaction. Currently, no uniformly acceptable laboratory markers exist for leprosy reactions diagnosed by clinical presentation. The histopathology varies depending on the host’s immune response and the bacilli load. Lepromatous leprosy usually presents with epidermal atrophy with a grenz zone and diffuse foamy histiocytes in the dermis.Leprosy treatment requires multiple drug therapy, including dapsone, rifampin, and ofloxacin, along with thalidomide to treat T2Rs.6 Steroid treatment should be prescribed for patients with a T1R.7 A 12-month treatment is recommended for patients with multibacillary leprosy, and long-term follow up is needed in case of relapse.

Dermatology

A man in his 40s presented with gradual hair loss of the eyelashes, eyebrows, beard, and scalp for 4 years, swelling and painful hand joints for 13 months, and multiple asymptomatic nodules on the upper arms for 40 days. The patient exhibited no associated fever, analgesia or hypesthesia. He reported no previous infections or family or personal medical history of autoimmune diseases or psoriasis. He was previously treated for rheumatoid arthritis, but various arthritis treatments showed no improvements over 1 year. A physical examination showed diffuse infiltration of the face with loss of skin creases and diminished facial hair; all joints of both hands were swollen (Figure, A); multiple asymptomatic nodules without ulceration were present on his upper arms (Figure, B); decreased sensation to pain, temperature and/or touch and neuropathic changes were not found. Laboratory test results showed a slightly elevated erythrocyte sedimentation rate (27 mm/h) and significantly elevated rheumatoid factor (70.1 IU/mL). Additional immunology indicators, including C-reactive protein, anticyclic citrullinated peptide, antinuclear antibodies, and globulin levels were normal. X-ray and joint ultrasound results suggested osteoarthritis, synovitis, flexor tendon tenosynovitis, and bone erosions. Ultrasound results also indicated enlarged axillary, cervical, and inguinal lymph nodes and an enlarged spleen. Fundus fluorescein angiography showed uveitis.A, Joints of both hands were swollen. B, Multiple asymptomatic nodules on the upper arms. C, Skin biopsy from the patient’s upper arm nodule demonstrating diffuse infiltrate of foamy histiocytes in the dermis (hematoxylin-eosin stain, original magnification ×100). D, Numerous acid-fast bacilli (acid-fast stain, original magnification ×400).

what is your diagnosis?

What is your diagnosis?

Rheumatoid arthritis

Leprosy

Arthritis associated with other connective tissue diseases

Systematic lupus erythematosus

b

male

41-50

original

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2607490

A young man was referred by his Veterans Affairs (VA) primary care provider to the outpatient mental health clinic due to concerns for posttraumatic stress disorder (PTSD) and depression. He served in the military for 4 years, including a 6-month tour in Iraq. While in Iraq he worked as an assault vehicle operator and was involved in frequent foot patrols. He reported numerous traumatic experiences, including frequent receipt of incoming fire, multiple ambushes, and an explosion by an improvised explosive device (IED) that injured several fellow soldiers (see Theme 1, Fear Conditioning, in related Educational Review).1He denied any psychiatric issues prior to his military service, but reported that since returning home “there ain’t a day that goes by that I don’t think about [these experiences].” The thoughts were highly distressing and he had frequent violent nightmares. He reported intense guilt relating to the belief that he should have detected the IED and been able to protect his colleagues. He reported a number of triggers (eg, walking down a city street; driving by a shooting range) that reminded him of his experiences in Iraq and induced panic-like symptoms (eg, fear, anxiety, racing heart, and feeling shaky). He avoided things that reminded him of these events and was reluctant to discuss his history (see Theme 1, Fear Conditioning, in related Educational Review).1He felt numb and withdrawn from others, reported difficulty sleeping, and was always “on guard.” He startled easily and had angry outbursts. The patient was hopeless at times, but denied suicidal thoughts. He reported difficulty concentrating and had significant fluctuations in his weight. He denied mania, psychosis, or medical problems. He reported drinking more than 12 beers 2 to 3 times per week. He denied any other substance abuse history.The patient was briefly in outpatient treatment while he was still in the military. He was prescribed a selective serotonin reuptake inhibitor (SSRI) but did not find it helpful and so he discontinued it. He was referred for psychotherapy but did not keep his appointments (see the last sentence of Theme 1, Fear Conditioning, in related Educational Review).1The patient grew up in the suburb of a small city. Though the patient initially described his childhood as “great,” later data revealed a history of early traumatic experiences (see Theme 4, Epigenetic Considerations, in related Educational Review).1 What Would You Do Next?

Trauma-focused psychotherapy

Pharmacotherapy with risperidone

Pharmacotherapy with prazosin

Pharmacotherapy with propranolol

Posttraumatic stress disorder requiring therapy

A

Trauma-focused psychotherapy

Trauma-focused therapies such as prolonged exposure therapy (PE) and cognitive processing therapy (CPT) have the best evidence to date in treating PTSD in military and veteran populations with 49% to 70% of patients attaining clinically meaningful symptom improvement.2 Focusing on trauma-related memories or beliefs, both CPT and PE are time-limited, manualized therapies typically consisting of approximately 12 sessions. CPT focuses on reframing cognitive distortions about the trauma and providing skills for emotion regulation while PE provides patients with a graded exposure to trauma reminders and triggers in an attempt to undo a conditioned fear response (see Theme 1, Fear Conditioning, in related Educational Review)1 (Audio).The Department of Veterans Affairs and Department of Defense (VA/DoD) clinical practice guidelines recommend trauma-focused psychotherapies, including CPT and PE, as first-line treatment options for PTSD.3 While trauma-focused therapies are almost universally recommended across treatment guidelines,3,4 recommendations regarding other types of psychotherapy have been mixed. Non–trauma-focused psychotherapies (such as supportive psychotherapy, nondirective counseling, and psychodynamic therapy) are not as effective in treating PTSD symptoms5 but may help by restoring interpersonal relationships and occupational functioning.6Direct head-to-head comparisons of CPT and PE with pharmacotherapy for treatment of PTSD are limited. Two SSRIs, sertraline and paroxetine, are approved by the US Food and Drug Administration for the treatment of PTSD. The VA/DoD guidelines recommend SSRIs as first-line agents3 while the World Health Organization recommends SSRIs only as a second-line treatment after psychotherapy or in the case of comorbid depression. An analysis of VA prescription drug records showed that pharmacologic approaches to treating PTSD are the first-line treatment in the majority of veterans, with SSRIs being the primary agents.7 As with many anxiety-related disorders, the early adverse effects of increased anxiety can be marked with SSRIs in treating PTSD, so “starting low and going slow” with titration is important.Second-generation antipsychotics are not recommended for the treatment of PTSD except in populations with comorbid psychosis. Historically, these medications have been used as an augmentation strategy for individuals with SSRI-resistant illness. However, in a recent double-blind, placebo-controlled trial, risperidone did not lead to improvements in PTSD, anxiety, or depression though patients treated with risperidone did show elevated rates of adverse effects.8Prazosin and propranolol have been studied as a potential treatment based on the hyperadrenergic model of PTSD (see Theme 2, Dysregulated Circuits, in related Educational Review).1 However, prazosin and propranolol have not been effective as primary treatment for PTSD. Prazosin is effective in reducing the frequency and intensity of nightmares in patients with PTSD and is recommended for this limited purpose.9 Propranolol has been explored for preventing the original consolidation of fear learning and/or its potential to block the reconsolidation of fear memories (see Theme 3, Memory Reconsolidation, in related Educational Review).1,10 While both of these ideas are active areas of investigation, neither is currently recommended.PTSD is a heterogeneous and complex disorder. Evidence supports trauma-focused therapy as first-line treatment, but a significant portion of patients do not respond adequately and nonadherence is common.2 Given these limitations, it is critical to expand our understanding of the underlying biological mechanisms that contribute to the development of PTSD in order to identify and develop more effective treatments.The patient's mental health fluctuated considerably over the next several years: he engaged in medication management but consistently declined to engage in trauma-focused psychotherapy. He did well when he was able to engage in recovery-oriented work activities that distanced him from the memory of his traumatic events. However, he struggled with alcohol dependence.He eventually participated in a long-term inpatient program that focused on both alcohol dependence and offered exposure therapy for PTSD. He did well with this treatment and experienced a significant reduction in symptoms. He is currently clinically stable and sober.

Psychiatry

A young man was referred by his Veterans Affairs (VA) primary care provider to the outpatient mental health clinic due to concerns for posttraumatic stress disorder (PTSD) and depression. He served in the military for 4 years, including a 6-month tour in Iraq. While in Iraq he worked as an assault vehicle operator and was involved in frequent foot patrols. He reported numerous traumatic experiences, including frequent receipt of incoming fire, multiple ambushes, and an explosion by an improvised explosive device (IED) that injured several fellow soldiers (see Theme 1, Fear Conditioning, in related Educational Review).1He denied any psychiatric issues prior to his military service, but reported that since returning home “there ain’t a day that goes by that I don’t think about [these experiences].” The thoughts were highly distressing and he had frequent violent nightmares. He reported intense guilt relating to the belief that he should have detected the IED and been able to protect his colleagues. He reported a number of triggers (eg, walking down a city street; driving by a shooting range) that reminded him of his experiences in Iraq and induced panic-like symptoms (eg, fear, anxiety, racing heart, and feeling shaky). He avoided things that reminded him of these events and was reluctant to discuss his history (see Theme 1, Fear Conditioning, in related Educational Review).1He felt numb and withdrawn from others, reported difficulty sleeping, and was always “on guard.” He startled easily and had angry outbursts. The patient was hopeless at times, but denied suicidal thoughts. He reported difficulty concentrating and had significant fluctuations in his weight. He denied mania, psychosis, or medical problems. He reported drinking more than 12 beers 2 to 3 times per week. He denied any other substance abuse history.The patient was briefly in outpatient treatment while he was still in the military. He was prescribed a selective serotonin reuptake inhibitor (SSRI) but did not find it helpful and so he discontinued it. He was referred for psychotherapy but did not keep his appointments (see the last sentence of Theme 1, Fear Conditioning, in related Educational Review).1The patient grew up in the suburb of a small city. Though the patient initially described his childhood as “great,” later data revealed a history of early traumatic experiences (see Theme 4, Epigenetic Considerations, in related Educational Review).1

what would you do next?

What would you do next?

Trauma-focused psychotherapy

Pharmacotherapy with prazosin

Pharmacotherapy with risperidone

Pharmacotherapy with propranolol

a

male

11-20

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2599998

A white, nonobese, 15-year-old girl presented with 1 month of frontal and occipital throbbing headaches, tinnitus, and “whooshing” in the ears. She had 1 week of nonbilious, nonbloody emesis, and “graying out” of her vision only when standing up or sitting down. Examination noted normal visual acuities and swelling of both optic discs (Figure, A). Magnetic resonance imaging and magnetic resonance venography of the head showed no intracranial mass or venous sinus thrombosis. Lumbar puncture showed an opening pressure of 550 mm of water and normal cerebrospinal fluid (CSF) composition. A diagnosis of idiopathic intracranial hypertension was made, and she was treated with acetazolamide. Headaches initially improved but worsened during the following weeks. Three months after initial presentation, she reported a 9.07-kg weight loss (height 1.57 m; body mass index dropped from 21.3 to 16.8 [calculated as weight in kilograms divided by height in meters squared]), postural lightheadedness, worsening fatigue, muscle weakness, salt cravings, loss of axillary hair, and missed periods for 2 months. Physical examination was remarkable for ill appearance, blood pressure of 85/42 mm Hg, and hyperpigmentation of the knuckles, distal fingers, and tongue (Figure, B and C). Repeated ophthalmic examination showed normal visual acuities and worsening optic disc swelling.The patient presented with papilledema bilaterally (A, right eye shown) patchy tongue darkening (B), and darkening of knuckles and distal fingers (C). What Is Your Diagnosis?

Hypervitaminosis A

Postural orthostatic tachycardia syndrome

Primary adrenal insufficiency (Addison disease)

Anorexia nervosa

C. Primary adrenal insufficiency (Addison disease)

C

Primary adrenal insufficiency (Addison disease)

Additional laboratory results demonstrated elevated adrenocorticotropic hormone levels (15 500 000 pg/mL; to convert to picomoles per liter, multiply by 0.22), undetectable morning serum cortisol levels (<0.5 µg/dL; to convert to nanomoles per liter, multiply by 27.588); no response to adrenocorticotropic hormone stimulation test; dehydroepiandrosterone sulfate levels (<15 µg/dL; to convert to micromoles per liter, multiply by 0.027); and elevated 21-hydroxylase antibodies (209.6 U/mL). A diagnosis of primary adrenal insufficiency (Addison disease) was made. Two weeks after starting corticosteroid treatment (hydrocortisone 5 mg thrice daily and fludrocortisone 0.1 mg twice daily), her fatigue, salt cravings, hypotension, myalgia, anorexia, and tongue hyperpigmentation completely resolved. She began to regain weight. Six weeks after steroid replacement therapy, optic disc swelling had completely resolved.Primary adrenal insufficiency (Addison disease) can be acute, causing adrenal crisis, or chronic. The classic manifestation of acute adrenal crisis is shock, often accompanied by vague symptoms such as anorexia, nausea, vomiting, abdominal pain, fatigue, lethargy, and weakness. Chronic adrenal insufficiency presents predominately with chronic malaise and fatigue along with additional vague and insidious symptoms such as abdominal pain and postural hypotension, generalized weakness, anorexia, weight loss, and lassitude. History and examination findings may include hypotension; hyperpigmentation and salt craving are highly specific for the disease.Intracranial hypertension (IH) is a rare manifestation of Addison disease and is especially rare as the initial presentation of this disorder.1-3 Idiopathic intracranial hypertension is a disorder with unknown etiology in which intracranial pressure is increased. It is most common in obese women of childbearing age. The annual incidence is 0.9 in 100 000 persons and 19 in 100 000 in young overweight women.4 Diagnosis is made with the modified Dandy criteria: (1) symptoms and signs of raised intracranial pressure (eg, papilledema, positional headache, and transient visual obscurations); (2) elevated CSF opening pressure (>250 mm of water in adults and 280 mm of water in children) and normal CSF composition; (3) brain imaging without intracranial mass or hydrocephalus; and (4) absence of other identifiable causes of increased intracranial pressure. Differential diagnoses of IH include venous obstruction (eg, thromboses, hypercoagulable states, and superior vena cava syndrome), arachnoid granulation obstruction (eg, scarring from prior inflammation), hypervitaminosis A, arteriovenous malformations, endocrine causes such as Addison disease, hypoparathyroidism, obesity, steroid withdrawal, and growth hormone use among others.5 Treatment options include weight loss pharmacotherapy, most commonly acetazolamide or topiramate, or surgery, commonly optic nerve sheath fenestration or CSF diversion procedures.Besides Addison disease, IH is also associated with other neuroendocrine derangements including hypothalamic-pituitary-adrenal axis dysfunction after glucocorticoid withdrawal, relative glucocorticoid deficiency after surgery for Cushing disease, growth hormone replacement, hypoparathyroidism, and hypocalcaemia. Additionally, IH has been reliably associated with intake of tetracyclines compounds containing vitamin A.As this case shows, Addison disease can be challenging to diagnose when it initially presents as IH. Even if classic presentations of adrenocortical deficiency are absent, Addison disease and other neuroendocrine abnormalities should be strongly considered in patients with elevated intracranial pressure and otherwise unexplained fatigue, headaches, and anorexia. Evaluations for alternative causes of elevated intracranial pressure should be sought when there are atypical demographics or clinical features or papilledema does not improve with adequate medical treatment or weight loss.Although to our knowledge, the actual incidence of IH in Addison disease has never been studied, case reports abound.1-3,6,7 Traditionally, idiopathic IH has been thought to be caused by elevated CSF production and decreased absorption or increased cerebral venous pressure. Recent studies have outlined a potential neuroendocrine basis for IH, previously thought to be idiopathic, suggesting a connection between the pathogenesis of IH and Addison disease.8 Aldosterone and cortisol act on abundant mineralocorticoid receptors in the choroid plexus, regulating CSF sodium balance. Glucocorticoid deficiency has been linked to hyponatremia.9 Cerebrospinal fluid sodium concentration in turn controls water entry into CSF via choroid plexus epithelium aquaporin-1 channels, suggesting a mechanism by which these receptors may affect intracranial pressure. In addition, 11β-hydroxysteroid dehydrogenases are abundant in the choroid plexus epithelium and modulate the local availability of cortisol.8,10

Pediatrics

A white, nonobese, 15-year-old girl presented with 1 month of frontal and occipital throbbing headaches, tinnitus, and “whooshing” in the ears. She had 1 week of nonbilious, nonbloody emesis, and “graying out” of her vision only when standing up or sitting down. Examination noted normal visual acuities and swelling of both optic discs (Figure, A). Magnetic resonance imaging and magnetic resonance venography of the head showed no intracranial mass or venous sinus thrombosis. Lumbar puncture showed an opening pressure of 550 mm of water and normal cerebrospinal fluid (CSF) composition. A diagnosis of idiopathic intracranial hypertension was made, and she was treated with acetazolamide. Headaches initially improved but worsened during the following weeks. Three months after initial presentation, she reported a 9.07-kg weight loss (height 1.57 m; body mass index dropped from 21.3 to 16.8 [calculated as weight in kilograms divided by height in meters squared]), postural lightheadedness, worsening fatigue, muscle weakness, salt cravings, loss of axillary hair, and missed periods for 2 months. Physical examination was remarkable for ill appearance, blood pressure of 85/42 mm Hg, and hyperpigmentation of the knuckles, distal fingers, and tongue (Figure, B and C). Repeated ophthalmic examination showed normal visual acuities and worsening optic disc swelling.The patient presented with papilledema bilaterally (A, right eye shown) patchy tongue darkening (B), and darkening of knuckles and distal fingers (C).

what is your diagnosis?

What is your diagnosis?

Postural orthostatic tachycardia syndrome

Primary adrenal insufficiency (Addison disease)

Anorexia nervosa

Hypervitaminosis A

b

female

11-20

White

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2611929

A 32-year-old, asymptomatic woman with history of tetralogy of Fallot (TOF) presented for evaluation of her congenital heart disease. Surgical history consisted of a Blalock-Taussig shunt in early childhood and subsequent TOF repair at age 3 years. On examination, venous pressure was visualized 4 cm above the clavicle at 45° with a prominent a wave. A parasternal lift was present. Auscultatory findings at the left upper sternal border are provided in the corresponding Audio. An electrocardiogram (Figure 1A) revealed sinus rhythm with a right bundle branch block. Findings from a transthoracic echocardiogram (TTE) are shown in Figure 1B and Video 1. Right ventricular diastolic volume index, quantitated by cardiac magnetic resonance, was 161 mL/m2.A, Electrocardiogram showing sinus rhythm, right bundle branch block, right axis deviation, and premature ventricular contractions. B, Still frame from the transthoracic echocardiogram in parasternal long-axis orientation in diastole. LA indicates left atrium; LV, left ventricular; RVOT, right ventricular outflow tract. What Would You Do Next?

Sildenafil for severe pulmonary hypertension

Balloon valvotomy for severe pulmonary valvular stenosis

Pulmonary valve replacement for severe pulmonary regurgitation

Surgical intervention for residual ventricular septal defect

Pulmonary valve regurgitation

C

Pulmonary valve replacement for severe pulmonary regurgitation

Pulmonary valve regurgitation (PR) is the most frequently encountered complication in adult patients with repaired TOF.1 Recognition requires integration of the physical examination findings and multimodality imaging. Surgery is indicated for severe PR when symptoms develop or, as in our case, in asymptomatic patients with evidence of significant right ventricular (RV) enlargement or dysfunction (Figure 1B).The physical examination findings observed with severe PR in TOF include elevated central venous pressure and a prominent a wave related to right atrial contraction into a noncompliant ventricle. Right ventricular enlargement manifests with a palpable substernal cardiac impulse. A short systolic ejection murmur is often heard (Figure 2A) alongside the diastolic decrescendo murmur (Figure 2A) as the severity of PR increases. Severe PR may be difficult to auscultate without careful attention to this murmur at the left upper sternal border.A, Phonocardiogram recorded from the left, second intercostal space reveals systolic ejection murmur (blue asterisk) and short decrescendo diastolic murmur (yellow asterisk). B, Continuous wave Doppler ultrasonography signal obtained across the pulmonary valve shows a short diastolic reversal with rapid return to baseline (rapid equilibration of diastolic pressure) in mid diastole.The echo-Doppler findings parallel the auscultatory findings as demonstrated by the similarity between the continuous wave Doppler and spectral profile of the phonocardiogram in our case. Continuous wave Doppler in severe PR shows the characteristic profile with short deceleration time and cessation of flow in mid diastole (Figure 2B) owing to the rapid rise in RV diastolic pressure and equalization with pulmonary artery diastolic pressure.2 Color flow imaging can be misleading and severe PR is often missed because the signal is rapid and brief owing to diastolic equalization of RV and pulmonary artery pressure (Video 2).This patient underwent successful pulmonary valve replacement with a bioprosthesis. The utility of cardiac magnetic resonance to assess RV size as part of surgical planning was demonstrated in a prospective, multicenter study.3 Right ventricular size was substantially reduced (by approximately 33% on average) with pulmonary valve replacement, and an RV end-diastolic volume index threshold of less than 160 mL/m2 or RV end-systolic volume index threshold of 82 mL/m2 was associated with normal RV size postoperatively.In contrast to this patient, PR in the setting of severe pulmonary arterial hypertension results in a loud diastolic murmur and is accompanied by an accentuated (and often palpable) pulmonic closure sound. Pulmonary stenosis results in a loud systolic ejection murmur and should be suspected with RV hypertrophy (increased afterload) rather than RV enlargement (increased preload). The absence of significant pulmonary stenosis is further confirmed by the mild elevation in forward-flow velocities across the pulmonary valve (Figure 2B) along with normal RV systolic pressure (estimated RV systolic pressure was 32 mm Hg [not shown]). Lastly, the physical examination was not suggestive of a residual ventricular septal defect (holosystolic murmur at the lower sternal border, frequently accompanied by a thrill).

Cardiology

A 32-year-old, asymptomatic woman with history of tetralogy of Fallot (TOF) presented for evaluation of her congenital heart disease. Surgical history consisted of a Blalock-Taussig shunt in early childhood and subsequent TOF repair at age 3 years. On examination, venous pressure was visualized 4 cm above the clavicle at 45° with a prominent a wave. A parasternal lift was present. Auscultatory findings at the left upper sternal border are provided in the corresponding Audio. An electrocardiogram (Figure 1A) revealed sinus rhythm with a right bundle branch block. Findings from a transthoracic echocardiogram (TTE) are shown in Figure 1B and Video 1. Right ventricular diastolic volume index, quantitated by cardiac magnetic resonance, was 161 mL/m2.A, Electrocardiogram showing sinus rhythm, right bundle branch block, right axis deviation, and premature ventricular contractions. B, Still frame from the transthoracic echocardiogram in parasternal long-axis orientation in diastole. LA indicates left atrium; LV, left ventricular; RVOT, right ventricular outflow tract.

what would you do next?

What would you do next?

Balloon valvotomy for severe pulmonary valvular stenosis

Surgical intervention for residual ventricular septal defect

Sildenafil for severe pulmonary hypertension

Pulmonary valve replacement for severe pulmonary regurgitation

d

female

31-40

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2589830

A man in his late 40s with a 30-pack-year history of smoking and a history of heavy drinking presented following 7 months of right-sided neck tenderness. He also reported progressive dysphagia to solids but no dyspnea, otalgia, or weight loss. Examination revealed very tender right-sided neck fullness of 6 cm. Laryngoscopic findings were unremarkable. Computed tomography (CT) with contrast demonstrated a 4.4 × 3.6 × 4.5-cm heterogeneously enhancing mass in the right side of the neck, splaying and completely surrounding both the internal and external carotid arteries (Figure, A). Scattered lymph nodes were also observed. On magnetic resonance imaging (MRI), the mass was hyperintense on T2 (Figure, B). A second 0.9-cm enhancing mass was visualized at the inferior right jugular foramen. Chest radiography demonstrated no suspicious pulmonary or mediastinal lesions. He underwent excision of the mass with right-sided neck dissection. Cranial nerves XI, X, and XII were identified and preserved. During subadventitial dissection of tumor off the carotid bifurcation, a laceration of the internal carotid artery was noted. Vascular surgery was performed to make an intraoperative repair, and an intraoperative angiogram demonstrated no dissections or thrombi. The lesion was suspected to be benign, and the procedure was aborted. The patient experienced no neurologic sequelae postoperatively. A specimen was taken of the right-sided neck mass (Figure, C and D).A and B, Imaging of the carotid space. A, Computed tomographic (CT) image. B, Postcontrast T1 magnetic resonance image (MRI). C and D, Histopathologic images. C, Hematoxylin-eosin. D, Immunohistochemical staining. What Is Your Diagnosis?

Atypical carcinoid

Malignant carotid body tumor

Medullary thyroid carcinoma

Hemangiopericytoma

B. Malignant carotid body tumor

B

Malignant carotid body tumor

Histologic analysis of the right-sided neck mass specimen (Figure, C and D) revealed metastasis in 2 of 18 ipsilateral neck lymph nodes. The tumor cells were positive for synaptophysin, chromogranin, CD 56, and S-100 (sustentacular cells), confirming the diagnosis. Paragangliomas are rare neuroendocrine tumors derived from the embryonic neural crest.1,2 They are chromaffin negative and typically (in 75% of cases) do not produce catecholamines, distinguishing them from chromaffin-positive pheochromocytomas.1,2 They arise in the abdomen (in 85% of cases), chest (in 12%), and the head and neck (in 3%).3 They are most commonly found (in 60% of cases) in the carotid body and less so in the tympanojugular and vagal regions.2,4 Carotid body tumors (CBTs) present as incidental findings or painless, slowly growing neck masses. Presentation includes otalgia, tinnitus, dysphagia, and facial weakness. They occur bilaterally in sporadic (5%) and familial (30%) cases.5Biopsy is challenging owing to location and vascularity. Because CBTs are typically nonsecreting tumors, they are not associated with hypertensive crisis like pheochromocytomas or less commonly like vagal paragangliomas.6 Imaging with contrast is essential for diagnosis and management, as extension occurs into the skull base and critical surrounding structures.2 On CT, lesions enhance and displace the internal and external carotids. On MRI, lesions are moderately intense on T1 and hyperintense on T2.2,7 Angiography determines the extent of dissection or thrombus formation and assists in planning carotid sacrifice or preoperative embolization. Use of positron emission tomography–CT or iodine I123-labeled metaiodobenzylguanidine (MIBG) to detect metastases have been described with mixed results.3,8 On histologic analysis, the tumor consisted of cells arranged in nests (zellballen), trabeculae, and broad cords within a prominent vascular network1 (Figure, C). The cells had pleomorphic nuclei and abundant lightly eosinophilic, granular cytoplasm. Staining was positive for synaptophysin, chromogranin, neurofilament, and S-100 protein (sustentacular cells), common among this tumor type (Figure, D).1,3,7Malignant and hereditary disease is associated with mutations of the succinate dehydrogenase complex (SHDx) gene.4,8,9 A review of 34 patients with CBTs found 17 (50%) with SDHD mutations and 12 (35%) with SDHB mutations. Patients with SDHB mutations had significantly worse disease-free survival and developed metastasis and recurrence.9 Although these tumors are largely benign, malignant disease occurs in 6% to 19% of cases.3,4 Recognized criteria for malignancy is the presence of regional metastasis to lymph nodes (55%-70%) or distantly, most commonly to the liver, lung, and bone.3,4 There is less consensus on histological characteristics or degree of vascular invasion, as these have not been correlated with malignant disease.1,2,4Surgical resection with neck dissection is considered when there is suspected or evident metastatic disease.2,4 Significant morbidity is associated with surgery owing to the proximity of cranial nerves VII, X, and XII, and cerebrovascular events associated with carotid injury. Shamblin classification is routinely used to describe tumor encapsulation of vessels.5,7 Subadventitial resection through the avascular space assists in preservation of the carotids.5,7 The internal jugular vein and carotid branches may be sacrificed, with estimates of up to 11% and 33%, respectively.5 Complete resection of Shamblin III tumors poses high risk for ischemia and may require reconstruction with synthetic or autologous saphenous vein grafts.5,7Despite that surgery is commonly curative in benign lesions, 5-year mortality for malignant tumors ranges from 50% to 80%.2-4 Although benefits to adjuvant therapy have been described, there is no clear consensus on the use of radiation or chemotherapy for malignant disease. Radiation therapy is considered for unresectable tumors, high-risk patients, or following incomplete resection.3,4Two months following diagnosis, the patient underwent preoperative embolization in preparation for resection and neck dissection. Owing to extensive fibrosis and tumor adherence, the common carotid, its branches, and internal jugular vein were sacrificed. Following surgery he underwent intensity-modulated radiation therapy. His posttreatment course was notable for a T1N0M0 right thyroid lobe papillary thyroid carcinoma treated by lobectomy. After 2.5 years of surveillance he had mild but stable neck pain and xerostomia and no evidence of recurrence on a follow-up CT scan.

General

A man in his late 40s with a 30-pack-year history of smoking and a history of heavy drinking presented following 7 months of right-sided neck tenderness. He also reported progressive dysphagia to solids but no dyspnea, otalgia, or weight loss. Examination revealed very tender right-sided neck fullness of 6 cm. Laryngoscopic findings were unremarkable. Computed tomography (CT) with contrast demonstrated a 4.4 × 3.6 × 4.5-cm heterogeneously enhancing mass in the right side of the neck, splaying and completely surrounding both the internal and external carotid arteries (Figure, A). Scattered lymph nodes were also observed. On magnetic resonance imaging (MRI), the mass was hyperintense on T2 (Figure, B). A second 0.9-cm enhancing mass was visualized at the inferior right jugular foramen. Chest radiography demonstrated no suspicious pulmonary or mediastinal lesions. He underwent excision of the mass with right-sided neck dissection. Cranial nerves XI, X, and XII were identified and preserved. During subadventitial dissection of tumor off the carotid bifurcation, a laceration of the internal carotid artery was noted. Vascular surgery was performed to make an intraoperative repair, and an intraoperative angiogram demonstrated no dissections or thrombi. The lesion was suspected to be benign, and the procedure was aborted. The patient experienced no neurologic sequelae postoperatively. A specimen was taken of the right-sided neck mass (Figure, C and D).A and B, Imaging of the carotid space. A, Computed tomographic (CT) image. B, Postcontrast T1 magnetic resonance image (MRI). C and D, Histopathologic images. C, Hematoxylin-eosin. D, Immunohistochemical staining.

what is your diagnosis?

What is your diagnosis?

Hemangiopericytoma

Atypical carcinoid

Malignant carotid body tumor

Medullary thyroid carcinoma

c

male

41-50

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2590052

A 12-day-old boy presented to the outpatient clinic with respiratory distress. He was born at 37 weeks gestation via cesarean delivery and developed noisy breathing and nasal congestion shortly after birth. Otolaryngological consultation, including fiberoptic nasopharyngolaryngoscopy, was performed, and revealed a right septal deviation. The infant was treated with topical neosynephrine and fluticasone spray and discharged home. On the eighth day of life, the patient returned with noisy breathing, retractions, and poor feeding. Flexible nasopharyngolaryngoscopy revealed a large left inferior turbinate and right septal deviation. On the 12th day of life, he presented with worsening symptoms. Physical examination revealed significant distress, retractions, and cyanosis relieved by crying. A mucosalized mass filling the left nasal cavity was visualized on anterior rhinoscopy, requiring nasal stenting to relieve obstruction. A maxillofacial computed tomographic (CT) scan demonstrated a 2.0 × 1.6-cm mass in the left mid-nasal cavity, compressing the middle turbinate and lamina papyracea (Figure, A). The cribriform plate was slightly widened prompting magnetic resonance imaging (MRI), which confirmed a 2-cm heterogeneous mass, isointense on T2 with small hyperintense areas, without intracranial extension (Figure, B). The patient underwent urgent transnasal endoscopic excision of the mass under general anesthesia. The mass was smooth, epithelialized, and pedunculated at the anterior aspect of the face of the left sphenoid sinus and medial to the middle turbinate (Figure, C). Transnasal delivery was performed with a deep margin achieved by resecting the periosteum of the sphenoid (Figure, D). Histologic examination revealed a lesion characterized by regions of cartilage admixed with irregular areas of chondromyxoid stroma containing spindle cells. What Is Your Diagnosis?

Intranasal glioma

Basal encephalocele

Nasal chondromesenchymal hamartoma

Teratoma

C. Nasal chondromesenchymal hamartoma

C

Nasal chondromesenchymal hamartoma

A hamartoma is a malformation of excessive tissue that is native to the site of origin. While hamartomas are common in skin, lungs, liver, kidneys, and the gastrointestinal tract, they are infrequently identified in the head and neck.1 The term nasal chondromesenchymal hamartoma (NCMH) was coined by McDermott et al2 in 1998 when the histopathological features of nasal masses in 7 children were found to be analogous to mesenchymal hamartoma of the chest wall. Subsequently, there have been reports of approximately 50 cases of NCMH, including the present case.1,3 Most patients with NCMH present in the first year of life, although there have been reports of NCMH in both adolescents and adults.4 Although the pathogenesis of NCMH is not well defined, most cases have common histologic features composed of various mixed mesenchymal and cartilaginous tissues.5 It has been suggested that an aberration in inflammatory response or in developmental signaling pathways of mesenchymal tissue may be the underlying mechanism to the development of these tumors.4 Maxillofacial CT scan is the preferred initial radiological modality to establish the diagnosis, although MRI is superior to evaluate intracranial extension, characteristically absent in these tumors. Surgical excision is indicated as the optimal therapeutic approach for NCMH, with low recurrence rates if complete resection is achieved.2The differential diagnosis for nasal obstruction in infants is broad and includes mucosal edema, choanal atresia, pyriform aperture stenosis, nasolacrimal duct cysts, and congenital nasal masses. Dermoid cyst, glioma, and encephalocele are the most common pediatric sinonasal masses, but identification of a mass should prompt consideration of rare lesions, including teratoma, inverted papilloma, giant cell reparative granuloma, ossifying fibroma, and nasal chondromesenchymal hamartoma.6 In addition to nasal obstruction, a variety of presenting signs and symptoms of NCMH are reported in the literature. These may include facial swelling, ophthalmoplegia, diplopia, maxillary pain, tooth mobility, and frontal headaches.3 This case highlights an unusual presentation of NCMH given that it was identified in a neonate with acute respiratory distress requiring urgent intervention.Although NCMH is rare in infants, this case demonstrates the importance of careful nasal examination, as the mass was not identified on 2 previous fiberoptic examinations by an otolaryngology resident and general otolaryngologist, respectively. It was ultimately recognized by a pediatric otolaryngologist whose evaluation focused on assessing nasal patency, which can be determined noninvasively by placement of a mirror under the nares to assess for fogging or cotton wool to assess for airflow. If obstruction is suspected, it is imperative to carefully inspect bilateral nasal cavities during nasopharyngoscopy to prevent misdiagnosis. Accurate identification of NCMH is particularly important because these tumors, although benign, can be locally destructive and mandate complete surgical excision to prevent recurrence. Clinicians should expand their differential diagnosis to include NCMH when faced with neonatal acute respiratory distress in the setting of a sinonasal mass.

General

A 12-day-old boy presented to the outpatient clinic with respiratory distress. He was born at 37 weeks gestation via cesarean delivery and developed noisy breathing and nasal congestion shortly after birth. Otolaryngological consultation, including fiberoptic nasopharyngolaryngoscopy, was performed, and revealed a right septal deviation. The infant was treated with topical neosynephrine and fluticasone spray and discharged home. On the eighth day of life, the patient returned with noisy breathing, retractions, and poor feeding. Flexible nasopharyngolaryngoscopy revealed a large left inferior turbinate and right septal deviation. On the 12th day of life, he presented with worsening symptoms. Physical examination revealed significant distress, retractions, and cyanosis relieved by crying. A mucosalized mass filling the left nasal cavity was visualized on anterior rhinoscopy, requiring nasal stenting to relieve obstruction. A maxillofacial computed tomographic (CT) scan demonstrated a 2.0 × 1.6-cm mass in the left mid-nasal cavity, compressing the middle turbinate and lamina papyracea (Figure, A). The cribriform plate was slightly widened prompting magnetic resonance imaging (MRI), which confirmed a 2-cm heterogeneous mass, isointense on T2 with small hyperintense areas, without intracranial extension (Figure, B). The patient underwent urgent transnasal endoscopic excision of the mass under general anesthesia. The mass was smooth, epithelialized, and pedunculated at the anterior aspect of the face of the left sphenoid sinus and medial to the middle turbinate (Figure, C). Transnasal delivery was performed with a deep margin achieved by resecting the periosteum of the sphenoid (Figure, D). Histologic examination revealed a lesion characterized by regions of cartilage admixed with irregular areas of chondromyxoid stroma containing spindle cells.

what is your diagnosis?

What is your diagnosis?

Basal encephalocele

Nasal chondromesenchymal hamartoma

Teratoma

Intranasal glioma

b

male

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2592950

A woman in her 30s with no significant medical history presented with progressive sore throat, globus sensation, and dysphagia. She was prescribed multiple rounds of antibiotics without notable improvement. Physical examination revealed a submucosal right retropharyngeal mass extending from the level of the soft palate to the postcricoid. Cranial nerve function and neck range of motion were normal. Contrast-enhanced computed tomography (CT) demonstrated a 4 × 3 × 3-cm right retropharyngeal mass with narrowing of the pharyngeal airway, subtle permeative destruction and cortical breakthrough of the C2 vertebral body. Magnetic resonance imaging (MRI) with contrast showed a T2 hyperintense, enhancing mass in the retropharyngeal and prevertebral spaces with marrow replacement of the C2 vertebral body extending to the odontoid (Figure, A). The patient underwent a combined otolaryngology-neurosurgical procedure with a transoral approach via an inferiorly based myomucosal flap to C1-C3 with microsurgical resection of C2 tumor and corpectomy, placement of the halo device, tracheotomy, and staged interval occiput-C6 posterior spinal fusion (Figure, B). Her postoperative course was uneventful, and she was decannulated prior to hospital discharge. Histopathologic findings showed sheets and cords of tumor cells with eosinophilic granular, clear, or bubbly cytoplasm on a basophilic myxoid stromal background (Figure, C), and scattered physaliphorous cells were also noted. Results from immunohistochemical analysis were positive for brachyury (Figure, D). What Is Your Diagnosis?

Carcinoma ex pleomorphic adenoma

Chordoid meningioma

Chondrosarcoma

Chordoma

D. Chordoma

D

Chordoma

Chordomas are low-grade malignant neoplasms that are thought to arise from transformed undifferentiated notochord remnants.1 This hypothesis is supported by their axial distribution, morphologic similarity to notochordal cells, and molecular phenotyping.1 Approximately 3% to 7% of chordomas arise in the cervical spine, making it a less common site than the clivus or sacrum.2 Chordomas most commonly occur in patients 50 to 60 years of age, and there is a male predominance.1 In the cervical spine, presenting symptoms include dysphagia, sore throat, airway obstruction, and a pharyngeal mass. Bony destruction is a characteristic feature of chordomas on imaging and is best appreciated on CT scan.1 On MRI, chordomas are T2 hyperintense and enhance with gadolinium.1Three histologic patterns of chordomas are recognized: classic or conventional, chondroid, and dedifferentiated.1,2 Conventional chordomas, the most common histologic pattern, are composed of islands and cords of eosinophilic and vacuolated cells set against a basaloid myxoid stroma.2 The physaliphorous cells (from the Greek word meaning “bearer of bubbles”) are characteristic of chordomas.1,2 The appearance of lobules is given by thin fibrous septa.1,2 The chondroid pattern is the second most common and contains elements of chondroid differentiation.2 Its prognostic significance relative to the classic type of chordomas is unclear.2 Dedifferentiated chordomas are the least common subtype and are recognized by their sarcomatous component.3 This subtype is associated with decreased survival.1,2The pathologic differential diagnosis of chordomas includes chondrosarcomas, extraskeletal myxoid chondrosarcomas, chordoid meningiomas, minor salivary gland neoplasms, such as myoepithelial carcinoma or carcinoma ex pleomorphic adenoma, metastatic mucinous adenocarcinomas, and metastatic renal cell carcinoma (if extensive clear cell changes are present).4 When the diagnosis of chordoma is not straightforward from light microscopy, immunohistochemical analysis can aid in the pathologic diagnosis. Chordomas are usually positive for cytokeratin, epithelial membrane antigen, and S-100.3 Brachyury, a nuclear transcription factor, is a sensitive and highly specific marker of notochordal differentiation, including chordomas. Brachyury is consistently expressed in conventional and chondroid chordomas, but is frequently lost in areas of dedifferentiation.3 Work on the molecular genetics of chordomas suggest that loss of the fragile histidine triad (FHIT) tumor suppressor gene,5 cyclin-dependent kinase inhibitor 2A (CDKN2A), and tumor suppressor protein p16 are common in chordomas.6Treatment of chordomas of the cervical spine, like other locations, is generally via gross total surgical resection,1,2 which can be accomplished via a variety of surgical approaches.7 Adjuvant radiation is recommended to increase rates of local control,1,2,8 although some centers advocate for preoperative radiation9 or primary external beam radiation.10 Novel treatment options are emerging and include the cyclin-dependent kinase enzymes CDK4/6-specific inhibitor palbociclib, the mTOR inhibitor rapamycin, epidermal growth factor receptor inhibitors, such as erlotinib, and the vascular endothelial growth factor inhibitor bevacizumab.6,11 Despite aggressive multimodality therapy, recurrence is common and usually occurs locally.1 Local recurrence rates for chordomas of the mobile spine range from 20% to 67%8,10,12 and are higher for chordomas of the C1-2 region relative to the subaxial (C3-7) region.13 Distant metastases are rare but occur most commonly to the lungs, bone, skin, and brain.1

General

A woman in her 30s with no significant medical history presented with progressive sore throat, globus sensation, and dysphagia. She was prescribed multiple rounds of antibiotics without notable improvement. Physical examination revealed a submucosal right retropharyngeal mass extending from the level of the soft palate to the postcricoid. Cranial nerve function and neck range of motion were normal. Contrast-enhanced computed tomography (CT) demonstrated a 4 × 3 × 3-cm right retropharyngeal mass with narrowing of the pharyngeal airway, subtle permeative destruction and cortical breakthrough of the C2 vertebral body. Magnetic resonance imaging (MRI) with contrast showed a T2 hyperintense, enhancing mass in the retropharyngeal and prevertebral spaces with marrow replacement of the C2 vertebral body extending to the odontoid (Figure, A). The patient underwent a combined otolaryngology-neurosurgical procedure with a transoral approach via an inferiorly based myomucosal flap to C1-C3 with microsurgical resection of C2 tumor and corpectomy, placement of the halo device, tracheotomy, and staged interval occiput-C6 posterior spinal fusion (Figure, B). Her postoperative course was uneventful, and she was decannulated prior to hospital discharge. Histopathologic findings showed sheets and cords of tumor cells with eosinophilic granular, clear, or bubbly cytoplasm on a basophilic myxoid stromal background (Figure, C), and scattered physaliphorous cells were also noted. Results from immunohistochemical analysis were positive for brachyury (Figure, D).

what is your diagnosis?

What is your diagnosis?

Chordoid meningioma

Chordoma

Carcinoma ex pleomorphic adenoma

Chondrosarcoma

b

female

31-40

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2594263

A 2-year-old boy presented with his parents for evaluation of unilateral neck swelling that had persisted for 4 months. Examination revealed a firm, immobile, and nontender mass affixed to the underlying right mandible. Magnetic resonance imaging (MRI) showed a 3.7 × 3.6 × 2.6-cm mass arising from the medial aspect of the right mandibular body with cortical destruction (Figure, A-C). The mass extended into the submandibular and sublingual spaces. Magnetic resonance imaging demonstrated a lesion isointense to muscle on T1 sequence, heterogeneously hyperintense with internal foci of decreased intensity on T2 sequence (Figure, D), and homogeneous contrast enhancement. Results from staging studies, including a bone survey, were negative for metastatic disease. Core biopsy revealed spindle cell proliferation with abundant intervening collagen but no anaplasia, mitotic activity, eosinophils, or inflammatory components. Incisional biopsy showed fibroblastic proliferation comprised of slender, uniform spindle cells arranged in fascicles with intervening collagenous stroma and no mitoses. Results from immunohistochemical analysis were positive for β-catenin and negative for CD34, desmin, and smooth muscle actin. No clonal abnormalities were present. The patient was negative for familial adenomatous polyposis (FAP) mutations on genetic testing. Chemotherapy with hydroxyurea, 20 mg/kg/d, was initiated and continued for 2 years. Reconstructive surgery was considered but not pursued given the lesion size. The most recent interval MRI, performed 4 years after initial presentation, showed a decrease in the size of the mass to 1.5 cm in the maximum dimension.A and B, T1 precontrast fat-saturated magnetic resonance imaging (MRI) demonstrating a mass (arrowhead) arising from right aspect of the mandible. C, Axial diffusion weighted imaging of the mass (arrowhead). D, Axial T2 MRI image demonstrating heterogeneously hyperintense mass (arrowhead). What Is Your Diagnosis?

Ewing sarcoma

Eosinophilic granuloma

Desmoid tumor

Lymphoma

C. Desmoid tumor

C

Desmoid tumor

Desmoid tumors, also known as fibromatosis, are a rare tumor affecting 2 to 4 out of 1 000 000 individuals and result from a benign proliferation of myofibroblasts.1,2 Approximately 25% of cases involve individuals younger than 15 years, and a female preponderance has been established.1,3 These tumors typically arise within fascial and musculoaponeurotic tissues and exhibit aggressive local infiltration and destruction.1 Typical sites of origin include the abdomen and abdominal wall. Head and neck involvement is less common, occurring in only 15% of cases.4 The typical clinical presentation entails a rapidly enlarging, nontender mass. Fixation to adjacent structures can occur. Neurovascular and obstructive symptoms can also be observed, leading to various sequelae depending on the affected anatomical region.5The precise etiology of desmoid tumors remains unclear; however, there are several known associations, suggesting that pathogenesis is multifactorial. A genetic component has been suggested because these tumors can occur in the context of FAP, a hereditary cancer predisposition syndrome.6 Hormonal influences have also been proposed as an etiologic factor because women of reproductive age are disproportionately affected, and regression has been observed during menopause and in response to antiestrogenic therapies.7 Antecedent trauma may also play a role in tumor development.5The differential for pediatric neck masses with a similar appearance on radiographic imaging includes etiologies such as lymphoma, myofibroma, Ewing sarcoma, and synovial sarcoma. In desmoid tumors, imaging findings depend on tumor composition and the degree of fibrosis. Echogenicity on ultrasonography can be low, medium, or high.8 Characteristic computed tomographic findings include a well-circumscribed homogeneous mass that varies in density relative to muscle with possible enhancement following contrast administration.9 On MRI, these lesions typically exhibit low signal intensity relative to muscle on T1-weighted images and variable signal intensity on T2-weighted images.8 Imaging results must be correlated with histopathologic findings to establish an accurate diagnosis.The characteristic histologic appearance involves benign-appearing uniformly spindle- or stellate-shaped fibroblastic cells within a collagenous stroma.9,10 Positive immunohistochemical staining for β-catenin is considered to be specific for this diagnosis; however, Sharma et al5 demonstrated that only 40% of desmoid tumors in the head and neck region expressed β-catenin, calling into question the usefulness of this tumor marker in cases of head and neck involvement.7Genetic testing for FAP is recommended in patients with newly diagnosed desmoid tumors because up to 16% will be found to have this syndrome.6 Although this patient tested negative for mutations in the associated adenomatous polyposis coli (APC) and mutY homologue (MYH) genes, genetic counselors at our institution recommended a baseline colonoscopy at age 10 years and a dilated ophthalmology examination to evaluate for congenital hypertrophy of the retinal pigment epithelium because some cases of FAP are not identified through standard genetic testing.Desmoid tumors are benign and do not metastasize; however, they recur in approximately 50% of cases owing to their locally invasive nature.2 Management typically entails wide surgical excision with clear margins; however, there is a subset of tumors that are inoperable owing to their size and/or location, as was the case in this patient. In such instances, medical treatment, including cytotoxic agents (eg, methotrexate, vinblastine, and hydroxyurea), as well as hormonal therapies, including tamoxifen and noncytotoxic modalities (eg, nonsteroidal anti-inflammatory drugs), can be used.1 In cases of residual disease or recurrence, a multimodality approach involving chemotherapy and radiotherapy is often pursued.4 Radiologic follow-up at regular intervals is recommended. Sharma et al5 suggest routine scans every 3 months for the first 6 months followed by 6-month interval imaging for the first 2 years, with annual review thereafter until the mass remains stable.

General

A 2-year-old boy presented with his parents for evaluation of unilateral neck swelling that had persisted for 4 months. Examination revealed a firm, immobile, and nontender mass affixed to the underlying right mandible. Magnetic resonance imaging (MRI) showed a 3.7 × 3.6 × 2.6-cm mass arising from the medial aspect of the right mandibular body with cortical destruction (Figure, A-C). The mass extended into the submandibular and sublingual spaces. Magnetic resonance imaging demonstrated a lesion isointense to muscle on T1 sequence, heterogeneously hyperintense with internal foci of decreased intensity on T2 sequence (Figure, D), and homogeneous contrast enhancement. Results from staging studies, including a bone survey, were negative for metastatic disease. Core biopsy revealed spindle cell proliferation with abundant intervening collagen but no anaplasia, mitotic activity, eosinophils, or inflammatory components. Incisional biopsy showed fibroblastic proliferation comprised of slender, uniform spindle cells arranged in fascicles with intervening collagenous stroma and no mitoses. Results from immunohistochemical analysis were positive for β-catenin and negative for CD34, desmin, and smooth muscle actin. No clonal abnormalities were present. The patient was negative for familial adenomatous polyposis (FAP) mutations on genetic testing. Chemotherapy with hydroxyurea, 20 mg/kg/d, was initiated and continued for 2 years. Reconstructive surgery was considered but not pursued given the lesion size. The most recent interval MRI, performed 4 years after initial presentation, showed a decrease in the size of the mass to 1.5 cm in the maximum dimension.A and B, T1 precontrast fat-saturated magnetic resonance imaging (MRI) demonstrating a mass (arrowhead) arising from right aspect of the mandible. C, Axial diffusion weighted imaging of the mass (arrowhead). D, Axial T2 MRI image demonstrating heterogeneously hyperintense mass (arrowhead).

what is your diagnosis?

What is your diagnosis?

Desmoid tumor

Eosinophilic granuloma

Lymphoma

Ewing sarcoma

a

male

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2597591

A Hispanic man in his late 50s presented with gradual progression of bilateral blepharoptosis for 6 months (Figure), starting in the left eye and subsequently involving the right eye. The ptosis did not worsen or fluctuate throughout the day. He had a strong family history of bilateral ptosis, which included his father, grandfather, uncles, cousins, and 4 of his siblings (he had a total of 13 siblings [7 brothers and 6 sisters]). None of his children or his siblings’ children were affected (the oldest being 31 years of age). He had no history of trauma, crossing or drifting of the eyes, dysarthria, dyspnea, or diplopia. He had noticed mild lightheadedness and trouble swallowing. His medical history was unremarkable except for hypertension.External photograph showing bilateral blepharoptosis with dermatochalasis. Notice the chin-up head position that the patient has to maintain to look in the primary gaze.His visual acuity was 20/25 OU with an intraocular pressure of 11 mm Hg OU. He had a mild decrease in elevation and abduction in both eyes on extraocular motility testing. Pupil reactivity and confrontational visual fields were normal. The results of anterior and posterior segment examinations were normal. The margin to reflex distance was −1 mm OD and −3 mm OS. Levator function was 4 mm OD and 3 mm OS with normal orbicularis function. No lagophthalmos was noted. Goldmann perimetry showed a 30° improvement in the right eye and a 50° improvement in the left eye, with taping of the upper eyelids. What Would You Do Next?

Ptosis repair by Müllerectomy or levator advancement

Genetic testing for GCG triplet repeats

Treatment with prednisone

Observation

Oculopharyngeal muscular dystrophy

B

Genetic testing for GCG triplet repeats

This patient has acquired bilateral and asymmetric blepharoptosis that is inherited autosomal dominantly. The combination of bilateral blepharoptosis starting in the sixth decade with other findings on review of systems is concerning for a systemic process, specifically oculopharyngeal muscular dystrophy. Confirmatory genetic testing for GCG triplet repeats is warranted.Ptosis repair should not be considered until the etiology is defined. Müllerectomy or levator advancement would not be the surgical procedure of choice owing to poor levator function. Instead, a frontalis sling should be used. Treatment with prednisone may improve the patient’s ptosis but would not help elucidate the underlying etiology. Observation is not advisable because the patient is symptomatic from progressive ptosis with associated lightheadedness and dysphasia, which warrants further investigation.A neurological examination showed mild proximal extremity weakness. Serological testing was negative for acetylcholine receptor antibodies, but an electromyogram showed electrodiagnostic evidence for patchy non-necrotizing myopathy. Genetic testing showed expansion of the GCG trinucleotide to 9 repeats within the first exon and 6 repeats within the second exon of the PABPN1 gene, consistent with a diagnosis of oculopharyngeal muscular dystrophy.Oculopharyngeal muscular dystrophy is an autosomal dominant disorder that starts in the fifth or sixth decade of life and leads to progressive proximal muscle, pharyngeal, and levator palpebrae weakness.1,2 Patients can also exhibit a decrease in extraocular motility, as was seen in this patient.The dystrophy appears to be most common in people with French-Canadian ancestry,3 Bukhara Jewish immigrants from Uzbekistan, and Hispanic people from New Mexico.4,5 In a cohort study from New Mexico, 216 cases of oculopharyngeal muscular dystrophy were identified between 1965 and 2001, all of which were found in Hispanic people.5 Proximal muscle weakness and gait abnormalities occur later than the ocular or pharyngeal weakness, but the onset of blepharoptosis can be concurrent with or before the dysphasia.5Diagnosis is usually made clinically, with subsequent confirmatory genetic analysis. For patients with oculopharyngeal muscular dystrophy, there is a 8 to 13 polyalanine triplet repeat (GCG) in the PABPN1 gene on chromosome 14q11.2,5-7 Skeletal muscle biopsy showing filamentous intranuclear inclusions and loss or variation of muscle fibers with increased fat and fibrous tissue also confirms the diagnosis.1,2 Electromyography will reveal mild myopathic changes.2Overall, there is no decrease in life expectancy, but difficulty in swallowing (especially solid foods) could lead to malnutrition and aspiration pneumonia.2 Aside from ptosis and dysphasia, patients can also have ocular duction abnormalities, slight facial muscle weakness, dysphonia, and limbal girdle weakness.2Treatment is largely medical and symptomatic. Surgical treatment is reserved for severe ptosis or dysphagia. For ptosis repair, either a levator aponeurosis resection or frontalis suspension procedure should be performed to aid with vision or when compensatory neck postures become painful (chin-up position). A cricopharyngeal myotomy can help with the symptoms of dysphasia.2The patient underwent a bilateral frontalis sling procedure, and at 1-year follow-up, he continued to do well with significant improvement in his visual field. He has improved margin to reflex distance at 2 mm OD and 2.5 mm OS, and with frontalis muscle use, the palpebral fissures are 9 mm OD and 8 mm OS.

Ophthalmology

A Hispanic man in his late 50s presented with gradual progression of bilateral blepharoptosis for 6 months (Figure), starting in the left eye and subsequently involving the right eye. The ptosis did not worsen or fluctuate throughout the day. He had a strong family history of bilateral ptosis, which included his father, grandfather, uncles, cousins, and 4 of his siblings (he had a total of 13 siblings [7 brothers and 6 sisters]). None of his children or his siblings’ children were affected (the oldest being 31 years of age). He had no history of trauma, crossing or drifting of the eyes, dysarthria, dyspnea, or diplopia. He had noticed mild lightheadedness and trouble swallowing. His medical history was unremarkable except for hypertension.External photograph showing bilateral blepharoptosis with dermatochalasis. Notice the chin-up head position that the patient has to maintain to look in the primary gaze.His visual acuity was 20/25 OU with an intraocular pressure of 11 mm Hg OU. He had a mild decrease in elevation and abduction in both eyes on extraocular motility testing. Pupil reactivity and confrontational visual fields were normal. The results of anterior and posterior segment examinations were normal. The margin to reflex distance was −1 mm OD and −3 mm OS. Levator function was 4 mm OD and 3 mm OS with normal orbicularis function. No lagophthalmos was noted. Goldmann perimetry showed a 30° improvement in the right eye and a 50° improvement in the left eye, with taping of the upper eyelids.

what would you do next?

What would you do next?

Observation

Genetic testing for GCG triplet repeats

Ptosis repair by Müllerectomy or levator advancement

Treatment with prednisone

b

male

51-60

Hispanic

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2598416

A Caucasian male in his 40s was referred by his primary care doctor for evaluation after experiencing blurry vision associated with frontal headaches for a week. Despite his headaches, he denied having eye pain. He was otherwise healthy, with no past medical or ocular history. Prior to referral, his symptoms prompted magnetic resonance imaging of the brain, orbits, and cervical spine which were unremarkable. Laboratory test results for the presence of Lyme disease, rapid plasma reagin, antinuclear antibodies, angiotensin-converting enzymes, and erythrocyte sedimentation rates were normal.The best corrected visual acuity was 20/50 in the right eye and 20/200 in the left eye. Motility, intraocular pressures, and pupillary light reflexes were normal. The anterior segment examination results were normal, and the lenses were clear bilaterally. A fundus examination showed vitreous cells in both eyes, but the optic nerve and retinal vessels were visualized clearly. Also, both eyes had optic nerve hyperemia and multiple shallow serous retinal detachments. The fluorescein angiography of both eyes demonstrated optic disc leakage, multiple pinpoint areas of hyperfluorescence, and fluorescein pooling in the areas of serous detachment (Figure).Start prednisone at 80 mg daily with a slow taper What Would You Do Next?

Surgical decompression of vortex veins

Perform B-scan ultrasonography

Start prednisone at 80 mg daily with a slow taper

Check blood pressure

Vogt Koyanagi Harada (VKH) disease.

C

Start prednisone at 80 mg daily with a slow taper

The clinical examination and fluorescein angiography showed bilateral uveitis with serous retinal detachments. Diagnostic considerations in a patient with bilateral serous retinal detachments include sympathetic ophthalmia, uveal effusion syndrome, posterior scleritis, malignant hypertension, and VKH.Vogt-Koyanagi-Harada disease is a systemic autoimmune inflammatory disease that targets melanin-containing cells in the eyes, auditory system, skin, and meninges. The diagnostic criteria for VKH include ocular, neurologic, and integumentary findings in the absence of a history of ocular trauma or surgery. The disease has 4 stages: prodromal, acute uveitic, convalescent, and chronic recurrent. Ocular symptoms in the acute uveitic stage include bilateral uveitis with serous retinal detachments, and symptoms are frequently preceded by headache and neck pain.1There are no confirmatory serologic tests for VKH, so a careful ophthalmic examination to exclude other causes of serous retinal detachments is important. While ultrasonography is helpful in cases of suspected posterior scleritis in identifying scleral thickening with adjacent echolucent edema in the Tenon's space (T sign), the absence of globe pain and episcleral injection in this case precludes that diagnosis.2 Uveal effusion syndrome may also present with serous retinal detachment and a mild vitreous cellular reaction in either a nanophthalmic or normal-length eye. In these cases, the creation of scleral windows to decompress the vortex veins can lead to resolution.3 However, the presence of optic disc leakage on fluorescein angiography, as noted in this patient, is inconsistent with uveal effusion syndrome. The presence of a vitreous cellular reaction and the absence of choroidal infarction on fluorescein angiography or other hypertensive fundus changes makes malignant hypertension a similarly unlikely cause of this patient's serous retinal detachments.In this case, a diagnostic lumbar puncture could be considered. Eighty percent of patients with VKH will have cerebrospinal fluid pleocytosis,4 but pursuing lumbar puncture is not routinely necessary to make the diagnosis in the setting of typical examinations and angiographic findings.High-dose systemic steroids, such as oral prednisone 1-2 mg/kg/d, are the mainstay of treatment of VKH.5 If used as monotherapy, steroids are typically required for a period of 6 months.6 However, given the long duration of required therapy and the systemic risks of corticosteroids, the consensus opinion suggests concurrent initiation of immunosuppressive agents at disease onset.7Prednisone at 80 mg daily with a slow taper was initiated along with mycophenolate mofetil at 3 g daily at initial presentation. Two months after the initial evaluation, the patient's vision had improved to 20/20 in the right eye and 20/25 in the left eye with resolution of all subretinal fluid. After 3 months, his prednisone use was stopped, and he has been maintained on mycophenolate mofetil at 3 g daily without any clinical or angiographic evidence of disease activity.

Ophthalmology

A Caucasian male in his 40s was referred by his primary care doctor for evaluation after experiencing blurry vision associated with frontal headaches for a week. Despite his headaches, he denied having eye pain. He was otherwise healthy, with no past medical or ocular history. Prior to referral, his symptoms prompted magnetic resonance imaging of the brain, orbits, and cervical spine which were unremarkable. Laboratory test results for the presence of Lyme disease, rapid plasma reagin, antinuclear antibodies, angiotensin-converting enzymes, and erythrocyte sedimentation rates were normal.The best corrected visual acuity was 20/50 in the right eye and 20/200 in the left eye. Motility, intraocular pressures, and pupillary light reflexes were normal. The anterior segment examination results were normal, and the lenses were clear bilaterally. A fundus examination showed vitreous cells in both eyes, but the optic nerve and retinal vessels were visualized clearly. Also, both eyes had optic nerve hyperemia and multiple shallow serous retinal detachments. The fluorescein angiography of both eyes demonstrated optic disc leakage, multiple pinpoint areas of hyperfluorescence, and fluorescein pooling in the areas of serous detachment (Figure).Start prednisone at 80 mg daily with a slow taper

what would you do next?

What would you do next?

Surgical decompression of vortex veins

Check blood pressure

Start prednisone at 80 mg daily with a slow taper

Perform B-scan ultrasonography

c

male

41-50

Caucasian

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2599443

A man in his 30s was referred to the retina clinic with a diagnosis of bilateral branch retinal vein occlusions. He reported flashes and progressive blurry vision in both eyes over a period of 6 days. He had no history of eye problems. His medical history was negative for diabetes and hypertension, and review of systems was positive for recent easy bruising and progressive fatigue. His initial best-corrected visual acuity was 20/25 OD and 20/50 OS. Results from examination of his pupils, motility, intraocular pressures, confrontational visual fields, and anterior segments were normal. A dilated fundus examination was conducted (Figure). He had bilateral flame-shaped and intraretinal hemorrhages in both maculae along the superior arcades and some scattered peripheral hemorrhages. There was no vessel tortuosity, and there were hard exudates in the left macula. Spectral-domain optical coherence tomography showed areas of hyperreflectivity in the middle and outer retina. Fluorescein angiography of both eyes showed blocking in the areas of hemorrhage, good venous filling, no leakage, and no neovascularization.Wide-field scanning laser image of the left eye showed superficial and intraretinal hemorrhages and hard exudates. What Would You Do Next?

Obtain an infectious and inflammatory panel

Observe

Obtain a complete blood cell count

Inject an anti–vascular endothelial growth factor

Leukemic retinopathy

C

Obtain a complete blood cell count

The pattern of the hemorrhages and the absence of delayed venous filling made the diagnosis of bilateral branch retinal vein occlusions unlikely. The examination findings along with the history of easy bruising and progressive fatigue prompted a complete blood cell count for this patient. There were no signs of inflammation in both eyes, which made an infectious or inflammatory etiology unlikely. In addition, the fluorescein angiogram did not show any vasculitis. Observation would not be safe for the patient because of the high suspicion of a blood dyscrasia, given the fundus picture in both eyes. The pattern of the hemorrhages along with the absence of leakage on the fluorescein angiogram was suggestive of a retinopathy related to a blood dyscrasia and not related to a vascular endothelial growth factor–driven process, which would exhibit leakage on the fluorescein associated with macular edema. His complete blood cell count revealed anemia (hemoglobin, 6.7 g/dL [to convert to grams per liter, multiply by 10]), thrombocytopenia (platelets, 140 ×103/μL [to convert to ×109 per liter, multiply by 1]), a white blood cell count of 9740/μL (to convert to ×109 per liter, multiply by 0.001) with neutropenia, and 70% blasts on manual smear. A bone marrow biopsy established the diagnosis of acute promyelocytic leukemia.Leukemic retinopathy has features characteristic of the intrinsic anemia and thrombocytopenia, which can vary from scattered preretinal and intraretinal hemorrhages, cotton wool spots, and white-centered hemorrhage spots to more severe forms with large subhyaloid hemorrhages, choroidal infiltration with serous retinal detachments, vascular occlusions, and leukemic infiltrates. Patients with leukemic retinopathy are managed with observation, as most of the retinal findings will subside once chemotherapy for the leukemia is initiated. One prospective study1 revealed the poor prognostic factor of leukemic retinopathy, as it was associated with a decrease in survival times by about 50%, and the presence of cotton wool spots were associated with 8-fold higher relative odds of mortality.The rate of ocular involvement of leukemia has been reported by multiple independent studies to be between 35% and 64% and is most common in adults with acute myeloid leukemia.2-5 The wide variability of reported prevalence is likely secondary to the variability in study design, as these retrospective studies did not state whether patients were seen by an ophthalmologist before beginning chemotherapy. As patients receive treatment, their symptoms may improve. The most reported ocular finding in leukemia is retinal vascular changes, with one study4 reporting this finding in greater than 89% of patients with ocular lesions, while only 2% had neuro-ophthalmic findings. The findings in acute and long-term leukemias are similar, but eyes affected by long-term leukemia may also develop peripheral microaneurysms and neovascularization.4,6 In some patients, the initial presentation of their malignancy is bilateral central retinal vein occlusion secondary to hyperviscosity and hypercoagulability.4,7,8 In a review of 180 patients with pediatric leukemia, Russo et al9 noted that the findings of papilledema, optic nerve infiltration or pallor, Roth spots, retinal infiltrations, vitreous opacities, leukemic hypopyon, and exophthalmos were associated with higher rates of central nervous system involvement and bone marrow relapses. It is important for patients with a diagnosis of leukemia to be seen by an ophthalmologist to screen for any ocular complications.Observation for his leukemic retinopathy was recommended, and he started receiving all-trans retinoic acid before beginning cytarabine for his acute promyelocytic leukemia.

Ophthalmology

A man in his 30s was referred to the retina clinic with a diagnosis of bilateral branch retinal vein occlusions. He reported flashes and progressive blurry vision in both eyes over a period of 6 days. He had no history of eye problems. His medical history was negative for diabetes and hypertension, and review of systems was positive for recent easy bruising and progressive fatigue. His initial best-corrected visual acuity was 20/25 OD and 20/50 OS. Results from examination of his pupils, motility, intraocular pressures, confrontational visual fields, and anterior segments were normal. A dilated fundus examination was conducted (Figure). He had bilateral flame-shaped and intraretinal hemorrhages in both maculae along the superior arcades and some scattered peripheral hemorrhages. There was no vessel tortuosity, and there were hard exudates in the left macula. Spectral-domain optical coherence tomography showed areas of hyperreflectivity in the middle and outer retina. Fluorescein angiography of both eyes showed blocking in the areas of hemorrhage, good venous filling, no leakage, and no neovascularization.Wide-field scanning laser image of the left eye showed superficial and intraretinal hemorrhages and hard exudates.

what would you do next?

What would you do next?

Obtain a complete blood cell count

Observe

Inject an anti–vascular endothelial growth factor

Obtain an infectious and inflammatory panel

a

male

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2603204

A 58-year-old woman returned from the Ukraine with 3 months of constant blurry vision in the left eye. Her history was significant for glaucoma and breast cancer with brain metastasis treated with CyberKnife and whole-brain radiation. While abroad, she received 2 inferiorly placed periocular steroid injections and was treated with glaucoma drops for elevated pressures of 55 mm Hg. At presentation, her visual acuity was 20/20 OD and 20/50 OS, and intraocular pressures were 18 and 20 mm Hg, respectively. She had a left afferent pupillary defect and left superior visual field deficit. Slitlamp examination of the right eye was unremarkable, while the left eye showed 1+ cell in the anterior chamber and 1+ nuclear sclerosis with pigment on the anterior lens capsule. Posterior examination revealed 2+ whitish vitreous deposits, a cup-disc ratio of 0.8, and inferior retinal detachment with subretinal particulate material (Figure, A). B-scan showed vitreous, subhyaloid, and subretinal opacities without choroidal involvement (Figure, B). A magnetic resonance image of the brain and orbits did not reveal any new metastatic lesions.A, Whitish vitreous deposits, inferior retinal detachment, and subretinal material seen on fundus photography of the left eye. B, B-scan ultrasonography of the left eye confirms retinal detachment and hyperechoic subretinal material without choroidal involvement. What Would You Do Next?

Vitrectomy

Biopsy

Observe and manage glaucoma

Enucleate

Metastatic adenocarcinoma

B

Biopsy

Given the history of breast cancer, we offered her a vitrectomy-assisted biopsy (VAB) to rule out endophytic vitreous seeding. In view of the concomitant macula-on retinal detachment and low suspicion for malignancy, the patient underwent a vitrectomy, scleral buckle, retinectomy, removal of subretinal debris, and silicone oil tamponade of the left eye. Cytopathology from the retina, vitreous, and subretinal aspirate revealed hypercellularity with nuclear enlargement and hyperchromasia, consistent with metastatic adenocarcinoma. After the operation, she continued to have pain with elevated intraocular pressures for which transscleral diode cyclophotocoagulation was performed. The patient underwent a full-body staging scan for consideration of palliative ocular radiation therapy.Metastatic cancer is the most common type of intraocular malignancy, classically located in the choroid, with 47% of primaries originating in the breast.1 The first vitreoretinal metastasis was reported in 1934 as a rare event (<1%).1,2 Most vitreoretinal metastases arise from cutaneous melanoma and rarely from lung or breast carcinoma.3 A larger series of vitreoretinal metastases consisted of 8 patients seen over a 40-year period at Wills Eye Hospital compared with 2076 with uveal metastasis and 382 with orbital metastasis. Most cases presented as unilateral and unifocal without choroidal involvement.4 Common symptoms include blurred vision or floaters, with examination revealing nonpigmented vitreous seeding.3-5 Vitreous tumor cell invasion occurs from a weakened blood-retinal barrier, possibly caused by radiation retinopathy following head or neck radiation therapy.6We initially suspected intraocular penetration of steroids given the patient’s history; however, we decided to perform the VAB, rather than simply treat her glaucoma or perform vitrectomy alone, to avoid potential delay in definitive diagnosis and treatment. Clinicians should have a low threshold for biopsy when considering vitreoretinal metastasis, which masquerades as more common diseases and is often misdiagnosed as infectious or inflammatory retinitis.4 Harvesting tissue or obtaining cells is necessary to confirm the diagnosis. Fine-needle aspiration biopsy (FNAB) can be the first step; however, FNAB is a less reliable diagnostic tool with lesion thickness less than 2 mm. Vitrectomy-assisted biopsy should be performed when there is an indication for vitrectomy, a secondary FNAB, or histopathological rather than cytological interpretations are necessary.7 There is a small risk of extrascleral seeding through previous sclerotomy sites; however, there is no evidence that VAB carries any additional risk over FNAB.8Once vitreoretinal metastasis is confirmed, the patient’s overall health and the visual potential of the eye guide treatment decisions. Neuroimaging should be the initial step because brain metastasis increases from 3%-6% to 28%-46% with ocular metastasis from primary breast cancer.9 In this case, the patient had preoperative imaging that showed no evidence of new metastasis to the brain or orbits. Ultimately, enucleation would be appropriate in the setting of severe ocular pain, secondary glaucoma, and minimal visual potential. Chemotherapy and palliative external beam irradiation may also be considered, but only after additional imaging and cancer staging is complete.Because this patient had a concomitant macula-on retinal detachment and no choroidal involvement, VAB was performed and the retinal detachment was repaired.

Ophthalmology

A 58-year-old woman returned from the Ukraine with 3 months of constant blurry vision in the left eye. Her history was significant for glaucoma and breast cancer with brain metastasis treated with CyberKnife and whole-brain radiation. While abroad, she received 2 inferiorly placed periocular steroid injections and was treated with glaucoma drops for elevated pressures of 55 mm Hg. At presentation, her visual acuity was 20/20 OD and 20/50 OS, and intraocular pressures were 18 and 20 mm Hg, respectively. She had a left afferent pupillary defect and left superior visual field deficit. Slitlamp examination of the right eye was unremarkable, while the left eye showed 1+ cell in the anterior chamber and 1+ nuclear sclerosis with pigment on the anterior lens capsule. Posterior examination revealed 2+ whitish vitreous deposits, a cup-disc ratio of 0.8, and inferior retinal detachment with subretinal particulate material (Figure, A). B-scan showed vitreous, subhyaloid, and subretinal opacities without choroidal involvement (Figure, B). A magnetic resonance image of the brain and orbits did not reveal any new metastatic lesions.A, Whitish vitreous deposits, inferior retinal detachment, and subretinal material seen on fundus photography of the left eye. B, B-scan ultrasonography of the left eye confirms retinal detachment and hyperechoic subretinal material without choroidal involvement.

what would you do next?

What would you do next?

Enucleate

Vitrectomy

Biopsy

Observe and manage glaucoma

c

female

51-60

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2599165

A previously healthy man in his 50s was referred with right upper abdominal pain he had experienced for 20 days, with high-grade fever and chills since the first week. There was no history of trauma or alcohol intake. Clinical examination revealed no icterus or significant lymphadenopathy. There was guarding and tenderness in the right upper quadrant; the liver was firm, smooth, and palpable 3 cm below the right costal margin. Laboratory investigations were remarkable for white blood cell counts of 13 200/μL (to convert to × 109 per liter, multiply by 0.001) and alkaline phosphatase of 259 U/L (to convert to microkatals per liter, multiply by 0.0167). Ultrasonography of the abdomen revealed a large hypoechoic area in the right lobe of the liver along with gallstones. A contrast-enhanced computed tomography (CECT) scan was performed (Figure 1).Sections of the contrast-enhanced computed tomographic scan show a large hypodense area (blue arrowhead) measuring 16 × 11.8 × 12.4 cm, involving segments 4, 5, 6, 7, and 8, along with a gallstone (black arrowhead). The gallbladder fundus (red arrowhead) is seen just caudal to this hypodense area.Acute cholecystitis with intrahepatic perforation of the gallbladder What Is Your Diagnosis?

Liver abscess

Acute cholecystitis with intrahepatic perforation of the gallbladder

Gallbladder cancer with contiguous liver infiltration

Necrotic liver tumor

B. Acute cholecystitis with intrahepatic perforation of the gallbladder

B

Acute cholecystitis with intrahepatic perforation of the gallbladder

The correct diagnosis is intrahepatic perforation of the gallbladder. The short history, fever, and leucocytosis suggest an inflammatory pathology. While liver abscess is a valid differential diagnosis, the preceding history of pain suggests acute cholecystitis leading to perforation of the gallbladder, at which time the patient manifested fever. On CECT, there is clear loss of continuity of the gallbladder fundus with stones floating freely in the liver, confirming the diagnosis beyond doubt. The lack of any mucosal irregularity or mass in the gallbladder rules out a tumor. Although large necrotic liver tumors can present with fever, the imaging in this patient is diagnostic. There is no particular enhancement pattern or solid component to suggest a tumor. Additionally, the perileisonal edema suggests abscess formation.Acute cholecystitis is frequently encountered in surgical practice, but intrahepatic gallbladder perforation with abscess formation is a rare and life-threatening complication, with only a few case reports published to date, to our knowledge.1 Although Niemeier2 originally described pericholecystic abscess following a localized perforation as type II, most reports qualify an intraheptic perforation under the same category with some modification.3 Definitive diagnosis can be made on ultrasonography and CECT. For the diagnosis of perforation, CECT is more sensitive than ultrasound.4 Management depends on the general condition of the patient and the size of the intrahepatic collection. In this patient, a percutaneous catheter was inserted as a temporizing measure; it drained 800 mL of biliopurulent fluid initially. A CT done 5 weeks later showed significant resolution of the abscess cavity (Figure 2). The patient underwent laparoscopic cholecystectomy and was thus successfully managed by a staged approach. This strategy has been reported earlier,5 although such a large abscess following intrahepatic perforation has perhaps not been reported before. The histopathology of the gallbladder showed xanthogranulomatous cholecystitis. Intrahepatic gallbladder perforation is a diagnostic possibility in a patient with gallstone disease who presents with fever, pain, and leucocytosis. Ultrasonography and CECT are confirmatory, and staged management may yield good outcomes.Contrast-enhanced computed tomography performed 5 weeks after presentation showed significant resolution (blue arrowhead). The tip of a percutaneous catheter is seen (black arrowhead). Also seen is the gallbladder with a stone.

Surgery

A previously healthy man in his 50s was referred with right upper abdominal pain he had experienced for 20 days, with high-grade fever and chills since the first week. There was no history of trauma or alcohol intake. Clinical examination revealed no icterus or significant lymphadenopathy. There was guarding and tenderness in the right upper quadrant; the liver was firm, smooth, and palpable 3 cm below the right costal margin. Laboratory investigations were remarkable for white blood cell counts of 13 200/μL (to convert to × 109 per liter, multiply by 0.001) and alkaline phosphatase of 259 U/L (to convert to microkatals per liter, multiply by 0.0167). Ultrasonography of the abdomen revealed a large hypoechoic area in the right lobe of the liver along with gallstones. A contrast-enhanced computed tomography (CECT) scan was performed (Figure 1).Sections of the contrast-enhanced computed tomographic scan show a large hypodense area (blue arrowhead) measuring 16 × 11.8 × 12.4 cm, involving segments 4, 5, 6, 7, and 8, along with a gallstone (black arrowhead). The gallbladder fundus (red arrowhead) is seen just caudal to this hypodense area.Acute cholecystitis with intrahepatic perforation of the gallbladder

what is your diagnosis?

What is your diagnosis?

Necrotic liver tumor

Acute cholecystitis with intrahepatic perforation of the gallbladder

Gallbladder cancer with contiguous liver infiltration

Liver abscess

b

male

51-60

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2601315

A woman in her early 70s underwent laparoscopic right partial nephrectomy for oncocytoma. During workup, she was found to have an asymptomatic cystic lesion in the right iliac fossa. Fifteen months later, a contrast-enhanced computed tomographic (CT) scan of her abdomen showed a progressive 16-mm cystic lesion in close relation to the cecum (Figure 1). The rest of the colon and small intestine, as well as the adenexa, solid organs, and peritoneum, appeared normal. There was no other positive radiologic finding except for right partial nephrectomy. The general physical and abdominal examinations were unremarkable. The results of other investigations such as a hemogram, liver and kidney function tests, and serum tumor markers, including serum carcinoembryonic antigen levels (0.94 ng/mL [to convert to micrograms per liter, multiply by 1.0]), were within the prescribed normal range. She had good exercise tolerance, and the results of cardiopulmonary investigations, as a part of preanesthesia workup, were normal.Contrast-enhanced computed tomographic scan of the abdomen showing a cystic lesion (arrowheads) in the right iliac fossa (axial view [A] and planar reconstruction image [B]). What Is Your Diagnosis?

Mucocele of the appendix

Cecal diverticulum

Meckel diverticulum

Ileal duplication cyst

A. Mucocele of the appendix

A

Mucocele of the appendix

Figure 1A (an axial view of a contrast-enhanced CT scan of the patient’s abdomen) shows a low attenuating, blind-ending, well-circumscribed globular mass with smooth walls arising from the cecum. There was no perilesional soft-tissue stranding. These findings are suggestive of mucocele of the appendix. The planar reconstruction image depicts cystic dilatation (16 mm) of the vermiform appendix extending up to the base (Figure 1B).Of the other entities listed, a Meckel diverticulum arises on the antimesenteric border of the ileum approximately 60 cm proximal to the ileocecal junction. In contrast, an ileal duplication cyst is located on the mesenteric border and shares the smooth muscle wall and vascular supply with the affected segment. A cecal diverticulum is likely to have air in it and show contrast on a CT scan.A subsequent surgical procedure confirmed the initial laparoscopic diagnosis of localized mucocele of the appendix. A laparoscopic right hemicolectomy without direct tumor handling was performed (Figure 2). Histopathology confirmed mucocele of the appendix with diffuse mucinous cystadenoma with low-grade dysplasia and clear margins.Specimen obtained after right hemicolectomy showing mucocele of the vermiform appendix involving the base.Mucocele of the appendix has been defined as “an obstructive dilatation of the appendix by intraluminal accumulation of mucoid material.”1(p680) With the aforementioned diagnostic criteria, the currently available multidetector CT scans can detect mucocele of the appendix with accuracy in excess of 85%.2 Preoperative diagnosis of mucocele of the appendix, together with the extent of involvement of the appendix (particularly the base and in the absence or presence of pseudomyxoma peritonei [PMP]), is vital for treatment planning.The clinical significance of mucocele of the appendix arises from the fact that it is the primary cause for PMP for which there is no effective curative therapy. Therefore, all fit patients with mucocele of the appendix should undergo surgery.The sine qua non of surgery for suspected mucocele of the appendix thus is an R0 resection without iatrogenic peritoneal spillage of mucinous material. For mucocele of the appendix with involvement of the base, therefore, it stands to reason that a right colectomy be performed.1,3A simple appendicectomy in this particular case would have resulted in positive resection margins and possible spillage of mucinous material. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are indicated only for patients with PMP and not when there is localized mucocele of the appendix.Following resection for mucocele of the appendix, the occurrence of PMP remains a distinctive possibility (particularly in perforated mucocele of the appendix) and may occur up to 10 years after initial surgery.4 Complete salvage cytoreductive therapy and hyperthermic intraperitoneal chemotherapy may not be feasible for a substantial number of such patients who present late. Hence, meticulous follow-up for early detection of PMP is mandatory.4

Surgery

A woman in her early 70s underwent laparoscopic right partial nephrectomy for oncocytoma. During workup, she was found to have an asymptomatic cystic lesion in the right iliac fossa. Fifteen months later, a contrast-enhanced computed tomographic (CT) scan of her abdomen showed a progressive 16-mm cystic lesion in close relation to the cecum (Figure 1). The rest of the colon and small intestine, as well as the adenexa, solid organs, and peritoneum, appeared normal. There was no other positive radiologic finding except for right partial nephrectomy. The general physical and abdominal examinations were unremarkable. The results of other investigations such as a hemogram, liver and kidney function tests, and serum tumor markers, including serum carcinoembryonic antigen levels (0.94 ng/mL [to convert to micrograms per liter, multiply by 1.0]), were within the prescribed normal range. She had good exercise tolerance, and the results of cardiopulmonary investigations, as a part of preanesthesia workup, were normal.Contrast-enhanced computed tomographic scan of the abdomen showing a cystic lesion (arrowheads) in the right iliac fossa (axial view [A] and planar reconstruction image [B]).

what is your diagnosis?

What is your diagnosis?

Meckel diverticulum

Cecal diverticulum

Ileal duplication cyst

Mucocele of the appendix

d

female

71-80

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2598490

A primigravid woman in her 20s who had been pregnant for 16 weeks presented with significant abdominal pain. A noncontrast computed tomographic (CT) scan revealed a 15 × 13 × 11-cm heterogeneous cystic mass that appeared to originate from the body of the pancreas and protrude into the gastric wall (Figure 1, A). Results of CT scan also revealed a 3-cm hypodense lesion on the left lobe of the liver, ascites, and splenomegaly. Further evaluation with endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography revealed extrinsic compression of the gastric wall from a large mixed solid/cystic lesion with septations and well-defined margins with no clear involvement of the gastric wall. A thin, reddish-brown fluid (700 mL) was aspirated from the cystic component. Analysis of the aspirate showed no tumor cells or mucinous material, and normal carcinoembryonic antigen, CA19-9, and amylase. Fine-needle aspiration was performed on the solid component of the cystic tumor (Figure 1, B-E).A, Coronal view CT scan showing a 15 × 13 × 11-cm complex heterogeneous mass originating from the body of the pancreas (white arrowhead) and protruding into the gastric wall. A hypodense lesion in segment 3 of the liver is observed (black arrowhead) and also moderate ascites (yellow arrowhead). B, Hematoxylin-eosin stain (original magnification ×20); C, α-smooth muscle actin immunostain (original magnification ×40); D, CD117 immunostain (original magnification ×40); and D, CD34 immunostain (original magnification ×40). What Is Your Diagnosis?

Solid pseudopapillary neoplasia of the pancreas

Atypical mucinous cystic neoplasia of the pancreas

Gastrointestinal stromal tumor

Pancreatic pseudocyst

C. Gastrointestinal stromal tumor

C

Gastrointestinal stromal tumor

A spindle cell neoplasia with positive CD34 and CD117 (c-kit) immunostaining is diagnostic of a gastrointestinal stromal tumor (GIST). A GIST usually harbors a KIT or PDGFRA oncogenic mutation,1 and most commonly arises from the stomach. The patient opted for surgical intervention: laparotomy revealed a cystic tumor adherent to the pancreas and posterior wall of the stomach (Figure 2). The liver had a lesion on segments 2 and 3, and frozen sampling confirmed metastatic GIST. She underwent en bloc resection by total gastrectomy, distal pancreatectomy, splenectomy, and left lateral liver segmentectomy. Pathology revealed a 16-cm, solid/cystic GIST arising from the stomach and invading the pancreas. Mitotic count was less than 5 per 50 high-power field, and 5 of 9 lymph nodes were metastatic for GIST, which is unusual for this disease. KIT and PDGFRA were not mutated, supporting the diagnosis of the so-called wild-type GIST. Her GIST was categorized as high-risk (stage 4, pT4N1M1).Mass (gray arrowhead) arising from the posterior surface of the stomach (black arrowhead), close to the greater curvature, that abuts the gastric mucosa and invades the body of the pancreas (blue arrowhead). The spleen (white arrowhead).A GIST during pregnancy is extremely rare: we found 5 other reports.2-6 Current recommendations for resected, intermediate, or high-risk GIST include adjuvant imatinib for at least 36 months.7 Imatinib is also the primary treatment for unresectable or metastatic GIST. However, safety information of imatinib during pregnancy is limited, and it comes from patients. An analysis of 125 pregnancies with imatinib exposure found that 50% of pregnancies ended with a healthy infant, 28% in elective termination, and 9.6% with malformed fetuses.8 Therefore, it is recommended that patients taking imatinib use contraceptives or discontinue the treatment if they conceive inadvertently. Our patient opted to not take imatinib, and at 37 weeks she delivered a healthy infant. She was started on imatinib 400 mg/d postpartum.Most wild-type GIST are succinate dehydronase-deficient (SDH-deficient),9 which are more frequent in younger patients, more likely to spread to lymph nodes, and commonly resistant to imatinib. Our patient is likely to have SDH-deficient GIST. Follow-up CT scans were negative for recurrence up until 3 years after surgery, when she developed hepatic bilobar recurrent lesions. The dose of imatinib was escalated to 600 mg/d; however, there was progression of the disease, therefore, sunitinib was initiated but was not well tolerated. Currently, 4.5 years after her surgery, her dose of imatinib has been escalated to 800 mg/d and she is pending follow-up imaging.Around 50% of primary resected GIST recur or metastasize at a median time of 2 years with a 5-year survival rate of 50%.10 Metastatic GIST is an incurable disease. Drug resistance is usually the result of secondary imatinib-resistant KIT or PDGFRA mutations and second line therapies include imatinib dose escalation, sunitinib, and regorafenib. Patients who have disease progression despite first- and second-line therapies should be considered for enrollment in a clinical trial. Finally, GIST during pregnancy is a significant clinical challenge with a paucity of published reports, and treatment decision making should be discussed thoroughly between the patient and a multidisciplinary surgical, oncological, and obstetric team.

Oncology

A primigravid woman in her 20s who had been pregnant for 16 weeks presented with significant abdominal pain. A noncontrast computed tomographic (CT) scan revealed a 15 × 13 × 11-cm heterogeneous cystic mass that appeared to originate from the body of the pancreas and protrude into the gastric wall (Figure 1, A). Results of CT scan also revealed a 3-cm hypodense lesion on the left lobe of the liver, ascites, and splenomegaly. Further evaluation with endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography revealed extrinsic compression of the gastric wall from a large mixed solid/cystic lesion with septations and well-defined margins with no clear involvement of the gastric wall. A thin, reddish-brown fluid (700 mL) was aspirated from the cystic component. Analysis of the aspirate showed no tumor cells or mucinous material, and normal carcinoembryonic antigen, CA19-9, and amylase. Fine-needle aspiration was performed on the solid component of the cystic tumor (Figure 1, B-E).A, Coronal view CT scan showing a 15 × 13 × 11-cm complex heterogeneous mass originating from the body of the pancreas (white arrowhead) and protruding into the gastric wall. A hypodense lesion in segment 3 of the liver is observed (black arrowhead) and also moderate ascites (yellow arrowhead). B, Hematoxylin-eosin stain (original magnification ×20); C, α-smooth muscle actin immunostain (original magnification ×40); D, CD117 immunostain (original magnification ×40); and D, CD34 immunostain (original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Pancreatic pseudocyst

Gastrointestinal stromal tumor

Atypical mucinous cystic neoplasia of the pancreas

Solid pseudopapillary neoplasia of the pancreas

b

female

21-30

White

original

https://jamanetwork.com/journals/jama/fullarticle/2612593

A healthy 36-year-old man was referred to the dermatology clinic for a 5-day history of an exquisitely tender rash at the base of his left thumb. One day prior to presentation, he went to a local emergency department, where he was prescribed clindamycin and valacyclovir. The patient works as a plumber and attributed his tender rash to a “spider bite” he had incurred while working in an old building. The patient was afebrile, and physical examination revealed several vesicles with purulent fluid on an erythematous base, at the base of the left thumb (Figure). There was no lymphadenopathy, lymphangitis, or mucous membrane involvement. The rash was not found elsewhere on the body. Vesicular fluid was collected and sent for further analysis.Admit to the hospital for intravenous antiviral therapyInstruct the patient to take only the valacyclovirInstruct the patient to take only the clindamycin What Would You Do Next?

Perform local incision and debridement

Admit to the hospital for intravenous antiviral therapy

Instruct the patient to take only the valacyclovir

Instruct the patient to take only the clindamycin

Herpetic whitlow

C

Instruct the patient to take only the valacyclovir

The key to the correct diagnosis was the patient’s report of intense pain and presentation with grouped vesicles on an erythematous base, which was clinically consistent with herpetic whitlow. Although the patient stated a history of spider bite, there was no necrotic tissue; thus, incision and debridement are not recommended. Rather, incision of vesicles in this case would predispose to viremia and bacterial superinfection.1 In the absence of a witnessed bite and identification of a spider species, other causes should be considered. Many suspected spider bites are actually caused by other conditions, such as methicillin-resistant Staphylococcus aureus infection.2 This may have been why the patient was prescribed clindamycin. However, the clinical presentation of an intensely painful vesicular eruption is more consistent with whitlow than with cellulitis or methicillin-resistant S aureus infection; thus, the patient need not continue clindamycin. The patient had no evidence of disseminated herpes zoster infection and therefore does not need intravenous antiviral therapy.Herpetic whitlow refers to herpes virus infection involving 1 or more digits.3 It is caused by either herpes simplex virus (HSV) type 1 or type 2, which belong to the Alphaherpesvirus subfamily within the herpesvirus family and are clinically indistinguishable.3 Whitlow most commonly occurs in children after autoinoculation of primary oral HSV-1 infection and in adults after genital herpes infection or occupational exposure.3-5 Health care workers in contact with infected secretions are vulnerable to herpetic whitlow if gloves are not worn. The virus is transmitted by direct contact through mucous membranes or broken epidermis. Following an incubation period of 2 to 20 days, cutaneous vesicles appear.4 Vesicles have an erythematous base; contain clear to pale-yellow fluid; are associated with intense, throbbing pain; and may coalesce into a single bulla.3,4 The vesicular fluid may become turbid or hemorrhagic, but this should not be mistaken for purulence.3,4Uncomplicated lesions completely resolve within 3 weeks in a process in which the vesicles unroof, form shallow ulcers, crust, then eventually heal.3 However, the virus remains latent in the host sensory neural ganglia and may be reactivated with stress, fever, sun exposure, temperature extremes, trauma, or immunosuppression.3-5About 30% to 50% of patients experience recurrences, although subsequent attacks are typically milder and shorter in duration than the primary infection.3-5 Patients are most infectious during the first 12 days of infection because of viral shedding and may develop satellite lesions.3-5Herpetic whitlow is a clinical diagnosis, although ambiguous or atypical presentations may be confirmed through a number of diagnostic methods. The method of choice is demonstration of viral DNA in skin or mucous membranes using polymerase chain reaction (PCR) assay or viral culture. Viral culture is a widely accepted method, but it requires more time than PCR testing and is relatively insensitive in lesions beyond the ulcerative stage.6 PCR assays for HSV are rapid, type-specific, and cost-competitive.6 Currently, PCR has largely replaced viral culture, especially for late-stage disease.6 Direct HSV antigen detection with immunofluorescence can also be used but is inferior in terms of sensitivity and specificity.6,7 Another less commonly used method is the Tzanck smear, which is performed by taking scrapings from the base of an unroofed vesicle or an ulceration debrided of crust and examining the contents using light microscopy.4 The presence of multinucleated epithelial giant cells supports the diagnosis of HSV but is not specific, because they can also be seen in varicella zoster infections.4 In this patient, viral culture grew HSV-1, and bacterial cultures were negative.Herpetic whitlow is a self-limited disease; however, antiviral therapy reduces the duration of symptoms of primary infection and recurrences.3-6 The optimal dose and duration of valacyclovir therapy remain unclear.3 Studies have shown that 200 mg of acyclovir taken orally 3 to 4 times daily prevents or greatly decreases recurrence rates in cases of culture-proven herpetic whitlow and other nongenital manifestations of HSV.3 The increased bioavailability of valacyclovir may offer advantages in dosage and perhaps efficacy in treating herpetic whitlow, although this has not been studied in clinical trials.8 Data on topical antiviral therapy and on the effect of newer oral antiviral agents are not available.The patient was treated with valacyclovir for 5 days. He reported resolution of rash and pain at follow-up 1 month later.

General

A healthy 36-year-old man was referred to the dermatology clinic for a 5-day history of an exquisitely tender rash at the base of his left thumb. One day prior to presentation, he went to a local emergency department, where he was prescribed clindamycin and valacyclovir. The patient works as a plumber and attributed his tender rash to a “spider bite” he had incurred while working in an old building. The patient was afebrile, and physical examination revealed several vesicles with purulent fluid on an erythematous base, at the base of the left thumb (Figure). There was no lymphadenopathy, lymphangitis, or mucous membrane involvement. The rash was not found elsewhere on the body. Vesicular fluid was collected and sent for further analysis.Admit to the hospital for intravenous antiviral therapyInstruct the patient to take only the valacyclovirInstruct the patient to take only the clindamycin

what would you do next?

What would you do next?

Perform local incision and debridement

Instruct the patient to take only the clindamycin

Admit to the hospital for intravenous antiviral therapy

Instruct the patient to take only the valacyclovir

d

male

31-40

original

https://jamanetwork.com/journals/jama/fullarticle/2610313

A man with a 3-year history of chronic obstructive pulmonary disease presented with increasing dyspnea on exertion, requiring increasing flow rates of oxygen. He was a former smoker with a 50–pack-year history. He had been diagnosed with stage I low-grade prostate cancer several years previously.Lung examination showed no wheezing. Cardiac examination showed a prominent pulmonary component (P2) of the second heart sound. Noncontrast computed tomography of the chest was unremarkable.An echocardiogram revealed dilated right atrium and ventricle. Spirometry showed mild airway obstruction. Duplex ultrasound showed a nonocclusive thrombus in the left femoral and popliteal veins. Catheterization of the right side of the heart showed a pulmonary arterial pressure of 79/32 mm Hg (mean, 48 mm Hg) with a normal pulmonary capillary wedge pressure. A ventilation-perfusion (V/Q) scan was obtained (Figure, panel A), followed by pulmonary angiography (Figure, panel B).A, Ventilation/perfusion scan, right anterior oblique view. B, Pulmonary angiography.Start heparin treatment followed by an oral anticoagulant for 6 monthsStart anticoagulation and refer the patient for surgical embolectomyStart anticoagulation and refer the patient for evaluation for pulmonary thromboendarterectomy What Would You Do Next?

Start parenteral corticosteroids and nebulized bronchodilators

Start heparin treatment followed by an oral anticoagulant for 6 months

Start anticoagulation and refer the patient for surgical embolectomy

Start anticoagulation and refer the patient for evaluation for pulmonary thromboendarterectomy

Chronic thromboembolic pulmonary hypertension (CTEPH)

D

Start anticoagulation and refer the patient for evaluation for pulmonary thromboendarterectomy

The key to the correct diagnosis is the abnormal V/Q scan findings and the presence of pulmonary hypertension. The scan shows a large mismatched defect corresponding to the superior segment of the right lower lobe (Figure, panel A). The findings of an abnormal V/Q scan combined with pulmonary hypertension support the diagnosis of CTEPH. Pulmonary angiography findings of sudden tapering of enlarged pulmonary arteries (pruning), severely decreased perfusion to the right lower lobe, and irregular vascular wall of the right lower lobe artery confirmed the diagnosis of CTEPH (Figure, panel B). Pulmonary thromboendarterectomy (PTE) is the treatment of choice.Although parenteral corticosteroids and bronchodilators are appropriate for chronic obstructive pulmonary disease, severe pulmonary hypertension is not typical for the disorder. Anticoagulation and surgical embolectomy are accepted treatments for acute pulmonary embolism, suggested by the abnormal V/Q scan findings. However, the chronic symptoms, pulmonary angiogram findings, and severe pulmonary hypertension indicate chronicity consistent with CTEPH.CTEPH is an obliterative pulmonary arterial vasculopathy caused by organized blood clots. It has been considered rare, with prevalence among survivors of pulmonary embolism estimated at 0.1% to 0.5%.1 However recent data suggest that CTEPH develops in as many as 5% of patients after pulmonary embolism, despite appropriate treatment.2,3 Risk factors for CTEPH are history of previous pulmonary embolism (odds ratio [OR], 19.0), idiopathic vs provoked pulmonary embolism (OR, 5.70), large perfusion defect at the time of acute pulmonary embolism (OR, 2.22), and young age (OR, 1.79).2The diagnosis of CTEPH requires evidence of pulmonary arterial hypertension (mean pulmonary arterial pressure greater than 25 mm Hg) and evidence of pulmonary thromboembolic disease.A V/Q scan can differentiate CTEPH from other forms of pulmonary hypertension and is the diagnostic test of choice. Extensive perfusion abnormalities with multiple mismatched lobar or segmental defects are sufficient for the diagnosis in the setting of pulmonary hypertension. A normal V/Q scan excludes CTEPH.4,5Pulmonary angiography may be necessary if less invasive tests do not confirm the diagnosis and helps determine the utility of PTE. The typical pulmonary angiogram findings are irregular vascular walls, eccentric filling defects, abrupt caliber decrease in distal vessels (pruning of the vessels), mosaic oligemia, pulmonary artery webs, and convex cutoff signs (“pouch” defect). In contrast, well-defined, more central emboli (polo mint sign) with smooth vessel wall and preserved vessel caliber are seen in acute embolism.CTEPH had been considered a consequence of mechanical obstruction of the pulmonary arteries by incompletely resolved recurrent clots. However, newer evidence suggests that the age of the organized clots is quite uniform in 72% of patients with CTEPH.6 Pathology studies have demonstrated small-vessel arteriopathy similar to changes observed in pulmonary arterial hypertension.7 These facts suggest that pathophysiology of CTEPH is an active vascular wall remodeling process that extends beyond pure mechanical obstruction. CTEPH typically worsens without treatment, even without evidence of further thromboembolic events.8Pulmonary thromboendarterectomy can result in complete symptom resolution and is the treatment of choice.5 As opposed to embolectomy, PTE involves removing the organized clots along with the affected intima of the vessel. Mortality rate for PTE is 4% to 7%.9 Medical therapy (eg, pulmonary vasodilators) is recommended for nonsurgical candidates.5 Lifelong anticoagulation is indicated for all patients unless the risk of bleeding is unacceptably high. For these patients, an inferior vena cava filter is indicated.Patients with high pulmonary vascular resistance or pressure, poor exercise tolerance, and high surgical risk have a poorer prognosis. PTE coupled with lifelong anticoagulation is effective for 99% of patients with CTEPH.10 Medical therapy improves the patients’ exercise capacity and symptoms, but the effect on survival is unclear.The patient underwent successful PTE. The pulmonary hypertension and hypoxemia resolved, and his exercise tolerance improved significantly.

General

A man with a 3-year history of chronic obstructive pulmonary disease presented with increasing dyspnea on exertion, requiring increasing flow rates of oxygen. He was a former smoker with a 50–pack-year history. He had been diagnosed with stage I low-grade prostate cancer several years previously.Lung examination showed no wheezing. Cardiac examination showed a prominent pulmonary component (P2) of the second heart sound. Noncontrast computed tomography of the chest was unremarkable.An echocardiogram revealed dilated right atrium and ventricle. Spirometry showed mild airway obstruction. Duplex ultrasound showed a nonocclusive thrombus in the left femoral and popliteal veins. Catheterization of the right side of the heart showed a pulmonary arterial pressure of 79/32 mm Hg (mean, 48 mm Hg) with a normal pulmonary capillary wedge pressure. A ventilation-perfusion (V/Q) scan was obtained (Figure, panel A), followed by pulmonary angiography (Figure, panel B).A, Ventilation/perfusion scan, right anterior oblique view. B, Pulmonary angiography.Start heparin treatment followed by an oral anticoagulant for 6 monthsStart anticoagulation and refer the patient for surgical embolectomyStart anticoagulation and refer the patient for evaluation for pulmonary thromboendarterectomy

what would you do next?

What would you do next?

Start anticoagulation and refer the patient for surgical embolectomy

Start parenteral corticosteroids and nebulized bronchodilators

Start anticoagulation and refer the patient for evaluation for pulmonary thromboendarterectomy

Start heparin treatment followed by an oral anticoagulant for 6 months

c

male

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2474999

A man in his 60s presented with new-onset bullae and erosions over sun-exposed areas and bony prominences. His medical history was relevant for acute myeloid leukemia, for which he had received an allogeneic stem cell transplant that was complicated by biopsy-proven grade 3 cutaneous and grade 2 gastrointestinal graft-vs-host disease. As part of his posttransplant infectious prophylaxis, the patient had been prescribed valacyclovir hydrochloride, voriconazole, and trimethoprim/sulfamethoxazole. He was also taking tacrolimus hydrate and prednisone for treatment of his graft-vs-host disease. The patient reported fishing outdoors on a sunny day a few days prior to the onset of these skin lesions. On physical examination, the patient’s skin was diffusely tan and there were flaccid bullae and erosions on the bilateral dorsal hands, elbows, and knees (Figure, A). A punch biopsy specimen from a bulla from the upper extremity was obtained (Figure, B).A, Flaccid bulla and erosions on the left dorsal hand at presentation. B, Biopsy from the left elbow. What Is Your Diagnosis?

Acquired epidermolysis bullosa

Pseudoporphyria

Photoallergic drug reaction

Graft-vs-host disease

B. Pseudoporphyria

B

Pseudoporphyria

Histopathologic examination showed a subepidermal bulla with reepithelialization and a pauci-inflammatory infiltrate in the superficial dermis. There was festooning of the dermal papillae (Figure, B).Laboratory workup revealed negative results on tests of 24-hour urine porphyrin and porphobilinogen levels, hepatitis B and C panels, and human immunodeficiency virus serologic testing. These laboratory findings along with the clinical and histological findings confirmed a diagnosis of pseudoporphyria, thought to be secondary to voriconazole therapy.Voriconazole was discontinued and fluconazole therapy initiated for prophylaxis instead. The patient was advised to use sunscreen and photoprotective clothing while his skin lesions resolved. During the following months, the lesions slowly improved.Pseudoporphyria is a photodistributed bullous eruption that has been attributed to medication use, exposure to UV radiation from tanning beds, psoralen–UV-A, chronic renal failure, hemodialysis, and excessive cola consumption.1 Medications that have been implicated in pseudoporphyria include nonsteroidal anti-inflammatory drugs, diuretics, tetracycline hydrochloride, estrogen, retinoids, cyclosporine, amiodarone hydrochloride, pyridoxine hydrochloride, fluorouracil, and recently voriconazole.2Pseudoporhyria imitates both the clinical and histological findings of porphyria cutanea tarda (PCT). Both diseases present with photosensitivity, bullae, vesicles, scarring, skin fragility, and milia, whereas PCT can present with additional features of hypertrichosis, sclerodermoid changes, hyperpigmentation, and dystrophic calcification.1,3 Porphyria cutanea tarda is triggered by hepatitis C or hemochromatosis whereas medication use is implicated in pseudoporphyria.4 The 2 entities are histologically indistinguishable, and direct immunofluorescence shows granular deposits of IgG and C3 at the dermal-epidermal junction and papillary dermal vasculature. Immunofluorescence findings are not necessary for diagnosis of either entity.1 The lack of elevation of urine and serum porphyrin levels in pseudoporphyria distinguishes it from PCT.1,3Voriconazole is a derivative of fluconazole and is a second-generation extended-spectrum triazole antifungal agent used to treat invasive fungal infections.1 Its use has been reported to cause several cutaneous reactions, including pseudoporphyria, macular erythema, increased photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, chelitis, discoid lupus erythematosus, and accelerated development of nonmelanoma skin cancer, melanoma, and atypical melanocytic lesions.5All reports of voriconazole-induced pseudoporhyria have occurred in the setting of minimal sun exposure.6 The mechanism remains unclear1; it is proposed that photosensitizing drugs may act in the same way as photoactivated endogenous porphyrins.7,8New bullae and vesicles in pseudoporphyria may appear up to months after discontinuation of the presumed offending drug, and the reason for delayed resolution is unclear. Postulated mechanisms include the nonlinear pharmacokinetics of voriconazole and genetic polymorphyisms and subsequent interpatient variability in the cytochrome P450 system, which metabolizes the drug.1,9In patients suspected to have pseudoporphyria, the offending drug should be identified and discontinued. Broad-spectrum sunscreens and sun-protective clothing should be used during treatment and for several months afterward. Our case highlights the importance of an awareness of this adverse effect and of counseling patients on the need to photoprotect while receiving voriconazole.

Dermatology

A man in his 60s presented with new-onset bullae and erosions over sun-exposed areas and bony prominences. His medical history was relevant for acute myeloid leukemia, for which he had received an allogeneic stem cell transplant that was complicated by biopsy-proven grade 3 cutaneous and grade 2 gastrointestinal graft-vs-host disease. As part of his posttransplant infectious prophylaxis, the patient had been prescribed valacyclovir hydrochloride, voriconazole, and trimethoprim/sulfamethoxazole. He was also taking tacrolimus hydrate and prednisone for treatment of his graft-vs-host disease. The patient reported fishing outdoors on a sunny day a few days prior to the onset of these skin lesions. On physical examination, the patient’s skin was diffusely tan and there were flaccid bullae and erosions on the bilateral dorsal hands, elbows, and knees (Figure, A). A punch biopsy specimen from a bulla from the upper extremity was obtained (Figure, B).A, Flaccid bulla and erosions on the left dorsal hand at presentation. B, Biopsy from the left elbow.

what is your diagnosis?

What is your diagnosis?

Graft-vs-host disease

Photoallergic drug reaction

Acquired epidermolysis bullosa

Pseudoporphyria

d

male

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2569292

An African American male in his 50s with a longstanding history of atopic dermatitis presented with a 20- to 30-year medical history of occasionally pruritic erythematous papules involving the trunk and extremities. He denied associated fevers, chills, night sweats, weight loss, joint pain, cough, difficulty breathing, or chest pain.Findings from the physical examination revealed red-brown monomorphic papules coalescing into plaques on the face, trunk, and extremities (Figure, A and B). There were thin erythematous plaques with overlying scale on bilateral extensor upper and lower extremities. A 4-mm punch biopsy specimen from his right upper extremity was obtained and stained with hematoxylin-eosin for histopathologic analysis. Periodic acid–Schiff and acid-fast bacilli stains were also performed.A, Distribution of papules over the chest, abdomen, and upper extremities. B, Diffuse distribution of papules over the back with some papules coalescing into plaques. C, Hematoxylin-eosin stain (original magnification, ×10). What Is Your Diagnosis?

Disseminated granuloma annulare

Erythrodermic sarcoidosis

Mycosis fungoides

Tuberculid

B. Erythrodermic sarcoidosis

B

Erythrodermic sarcoidosis

Histopathologic findings revealed epidermal acanthosis with giant cells and discrete granulomas in the superficial to mid dermis with scant surrounding lymphocytic inflammation (Figure, C). Periodic acid-Schiff and acid-fast bacilli stains revealed negative results, ruling out fungi and tuberculosis, respectively.The patient underwent multiple systemic therapies without improvement, including hydroxychloroquine, thalidomide, methotrexate, and prednisone. In addition, he was prescribed azathioprine, mycophenolate mofetil, allopurinol, 11 treatments of oral psoralen and ultraviolet A radiation (PUVA), 12 weeks of adalimumab, day hospitalization with triamcinolone ointment wet wraps and narrowband ultraviolet B (UV-B) phototherapy, cyclosporine, as well as 4 months of leflunomide, also without improvement. Improvement was noted with chloroquine, 500 mg daily, and minocycline, 100 mg, twice a day; however, owing to retinal toxic effects and hyperpigmentation, respectively, these medications were discontinued. He also underwent a therapeutic trial of infliximab, but after his first infusion he was hospitalized for lower extremity cellulitis. Current therapy consists of dapsone, 200 mg daily, in conjunction with triamcinolone 0.1% ointment to his body, clobetasol 0.05% ointment to posterior neck, and desonide 0.05% ointment to his face, groin, and skin folds. He is followed closely by pulmonology experts for chronic paratracheal adenopathy; however, he remains asymptomatic from a respiratory standpoint.Sarcoidosis is a multisystem disorder characterized by noncaseating granulomas affecting patients at any age, with African Americans having the highest incidence in the United States.1 The skin is the second most common organ affected in sarcoidosis after the pulmonary system. Cutaneous involvement is present in 25% to 30% of cases.1 The morphology of cutaneous sarcoidosis varies greatly, from common presentations of lupus pernio and subcutaneous lesions, to uncommon psoriasiform, ichthyosiform, or atrophic presentations. Rare manifestations of cutaneous sarcoidosis include pigmented purpura, alopecia, photodistributed lesions, or erythroderma.Schaumann first drew attention to erythrodermic sarcoidosis in 1920.2 Characteristics of the lesions vary in color and morphology with erythematous to yellow-brown macules and papules with detachable superficial scale and areas of sparing being described.2 Itching and infiltration are typically absent.2-5 Close resemblance of the erythrodermic lesions of sarcoidosis to those of mycosis fungoides has been noted.4 Tuberculosis, deep fungal infections, rosacea, granuloma annulare, and foreign body granulomas also need to be ruled out using clinical and histopathologic correlation. Systemic evaluation should occur using chest radiographic imaging, ophthalmologic examination, and lymph node biopsy procedures if adenopathy is present, because patients typically have organ involvement with chronic sarcoidosis.6 Diffuse, small noncaseating granulomas in the dermis with a rim of lymphocytes surrounding blood vessels, follicles, and sweat glands are typically present on pathologic examination.2-5 Mast cells, plasma cells, and monocytes may also be present.2-4 Patchy parakeratosis, acanthosis, and intracellular edema have also been described. Asteroid bodies and Schumann bodies may also be seen but are not diagnostic.4,6 Treatments for sarcoidosis include topical therapy with corticosteroids, calcineurin inhibitors, or topical retinoids. Ultraviolet A radiation photochemotherapy and narrowband UV-B phototherapy have also been used. In addition, oral immunomodulatory agents, such as antimalarials, tetracyclines, retinoids, dapsone, thalidomide, and leflunomide have been used. Furthermore, immunosuppressants such as prednisone, methotrexate, azathioprine, mycophenolate mofetil, and tumor necrosis factor inhibitors, such as adalimumab and infliximab can be used.1 For erythrodermic sarcoidosis, all of the above can be tried, although UV-based treatment is usually difficult for these patients to tolerate owing to baseline erythema.To our knowledge there have been no reports of erythrodermic sarcoidosis in darker skin types in the English literature. This report provides an example of erythrodermic sarcoidosis in the African American population.

Dermatology

An African American male in his 50s with a longstanding history of atopic dermatitis presented with a 20- to 30-year medical history of occasionally pruritic erythematous papules involving the trunk and extremities. He denied associated fevers, chills, night sweats, weight loss, joint pain, cough, difficulty breathing, or chest pain.Findings from the physical examination revealed red-brown monomorphic papules coalescing into plaques on the face, trunk, and extremities (Figure, A and B). There were thin erythematous plaques with overlying scale on bilateral extensor upper and lower extremities. A 4-mm punch biopsy specimen from his right upper extremity was obtained and stained with hematoxylin-eosin for histopathologic analysis. Periodic acid–Schiff and acid-fast bacilli stains were also performed.A, Distribution of papules over the chest, abdomen, and upper extremities. B, Diffuse distribution of papules over the back with some papules coalescing into plaques. C, Hematoxylin-eosin stain (original magnification, ×10).

what is your diagnosis?

What is your diagnosis?

Mycosis fungoides

Erythrodermic sarcoidosis

Tuberculid

Disseminated granuloma annulare

b

male

21-30

African American

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2580293

A man in his 50s with diagnoses of human immunodeficiency virus (HIV) infection, hepatitis B, and latent tuberculosis presented with a slow-growing nodule on the left foot. The lesion started 1 year prior as a tender red nodule on the medial aspect of his first metatarsophalangeal joint, which would enlarge and become painful approximately once a month (Figure, A). The patient reported that with manipulation, a clear-to-yellow material drained from the lesion. The patient denied any purulent drainage, additional skin lesions, fever, chills, or other systemic symptoms. His medications included efavirenz–emtricitabine–tenofovir disoproxil fumarate for his HIV, with the most recent absolute CD4-positive cell count of 341 cells/mm3 (reference range, 263-2045 cells/mm3), and recent completion of an 8-month course of isoniazid treatment after being exposed to tuberculosis. Physical examination demonstrated an erythematous papulonodule without warmth or drainage on the dorsal left great toe. No lymphadenopathy was appreciated. A punch biopsy was performed (Figure, B, C, and D) to help establish the diagnosis.A, Clinical photograph of slow-growing red papulonodule on the left toe dorsal foot. B, Biopsy with hematoxylin-eosin (H&E) staining demonstrating acral skin with acute and chronic inflammation within the deep dermis. C, Higher magnification highlights eosinophilic material surrounding small cocci. D, Gram staining of the biopsy supported the diagnosis. What Is Your Diagnosis?

Botryomycosis

Cutaneous tuberculosis

Digital mucous cyst

Foreign-body reaction

A. Botryomycosis

A

Botryomycosis

Histopathologic examination of the biopsy showed a dermal collection of numerous neutrophils, histiocytes, plasma cells, and multinucleated giant cells located in the deep dermis (Figure, B). On higher magnification, there was a focal area of bacterial cocci embedded in an eosinophilic amorphous material (Splendore-Hoeppli phenomenon) (Figure, C). Gram staining was remarkable for gram-positive bacterial cocci consistent with Staphylococcus aureus (Figure, D). In addition, Grocott methenamine silver and acid-fast bacilli stains were negative for fungal and acid-fast organisms. The patient was treated with topical mupirocin, 2%, ointment at the time of biopsy, and the infection was completely excised with the biopsy. At 3-month follow-up, no residual lesion was observed.Botryomycosis is a rare, chronic, slow-growing, indolent bacterial infection that involves the skin and, rarely, visceral organs.1 Although the bacterial nature of botryomycosis was established in 1919 from a lesion in a horse,2 the underlying etiology of this slow-progressing infection still remains largely unknown. Botryomycosis most commonly occurs in the setting of immunosuppression, such as in HIV, diabetes, cystic fibrosis,3 and in cases of foreign-body–related masses in the lung,4 abdomen,3 or other visceral organs. The most common organism observed in botryomycosis is S aureus, but other bacteria also have been reported including Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris, and Streptococcus species.2 Multibacterial involvement of cases of botryomycosis also is possible but rarely detected.1 Unlike invasive infection with these organisms, botryomycosis can present for years as a painless swelling with papulonodules without systemic manifestations. Our patient differed from many reported cases of botryomycosis because of the presence of pain. Diagnosis requires histopathologic and/or microbiologic confirmation. The characteristic histopathologic feature of botryomycosis is the presence of granules composed of bacterial cocci (in cases of S aureus) embedded in a unique radiating eosinophilic debris matrix demonstrating characteristics of Splendore-Hoeppli phenomenon.3The clinical and histopathologic differential diagnosis of botryomycosis includes actinomycetoma and eumycetoma. The granules observed in botryomycosis can resemble the granules commonly seen in these entities; however, histopathologic features and culture can help differentiate.5 Differentiating between actinomycetoma and botryomycosis is possible on the basis of the bacterial forms observed. With actinomycetoma, filamentous bacteria are present, whereas gram-positive cocci are observed in most cases of botryomycosis.5 Eumycetomas are caused by fungi, so large segmented mycelial filaments that stain positive with fungal stains such as Grocott methenamine silver will be observed histopathologically.5 In this case, the clinical differential diagnosis also included digital mucous cyst, ganglion cyst, or foreign-body reactions to traumatic implementations of material such as splinters; however, histopathologic analysis could differentiate these entities. Mycobacterium tuberculosis infection also has been reported with involvement of a single digit that mimics cutaneous botryomycosis.6 A negative result with acid-fast bacilli or Fite staining can exclude this diagnosis.Treatment of botryomycosis varies, and the infection can be difficult to clear, depending on the degree of infection. For cases of S aureus botryomycosis, antibiotic therapy with oral trimethoprim-sulfamethoxazole or oral clindamycin can be used based on bacterial culture results and sensitivity.3,7 The duration of antibiotic therapy can vary from weeks to months depending on the extent of the infection. Surgical excision also may be required to remove the localized infection,3 although this can be complicated for extensive cases. In our patient, the lesion was surgically removed with the biopsy and healed well. With appropriate treatment regimens, patients with botryomycosis can be effectively treated. The presence of osteomyelitis, however, may necessitate more extensive workup and longer antimicrobial therapy.8

Dermatology

A man in his 50s with diagnoses of human immunodeficiency virus (HIV) infection, hepatitis B, and latent tuberculosis presented with a slow-growing nodule on the left foot. The lesion started 1 year prior as a tender red nodule on the medial aspect of his first metatarsophalangeal joint, which would enlarge and become painful approximately once a month (Figure, A). The patient reported that with manipulation, a clear-to-yellow material drained from the lesion. The patient denied any purulent drainage, additional skin lesions, fever, chills, or other systemic symptoms. His medications included efavirenz–emtricitabine–tenofovir disoproxil fumarate for his HIV, with the most recent absolute CD4-positive cell count of 341 cells/mm3 (reference range, 263-2045 cells/mm3), and recent completion of an 8-month course of isoniazid treatment after being exposed to tuberculosis. Physical examination demonstrated an erythematous papulonodule without warmth or drainage on the dorsal left great toe. No lymphadenopathy was appreciated. A punch biopsy was performed (Figure, B, C, and D) to help establish the diagnosis.A, Clinical photograph of slow-growing red papulonodule on the left toe dorsal foot. B, Biopsy with hematoxylin-eosin (H&E) staining demonstrating acral skin with acute and chronic inflammation within the deep dermis. C, Higher magnification highlights eosinophilic material surrounding small cocci. D, Gram staining of the biopsy supported the diagnosis.

what is your diagnosis?

What is your diagnosis?

Cutaneous tuberculosis

Foreign-body reaction

Botryomycosis

Digital mucous cyst

c

male

51-60

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2604755

A 13-year-old girl presented to an emergency department with bilateral hip pain for several months and acute worsening with left-sided limp following a school field trip to a large museum. She stated that her pain worsened with walking and was minimally relieved with salicylic acid. Her parents tried to schedule an outpatient appointment for evaluation of her hip pain but had difficulty owing to a lack of a primary care physician. Review of systems was significant for heavy periods since menarche 6 months ago. It was negative for easy bruising or bleeding. The patient described normal stooling and voiding habits. The patient was described as a shy eighth grader who earns A’s and B’s in school. She was not physically active. On physical examination, the patient was noted to be short for her age (1.3 m [4.4 ft]; height in <third percentile), weight (62.5 kg; 87th percentile), and body mass index (35 [calculated as weight in kilograms divided by height in meters squared]; 99th percentile). She had a relatively short, thick neck with acanthosis nigricans, dry skin, Tanner stage II breasts, and nonpitting edema of her hands (Figure 1A). Her family history was significant for hypothyroidism and coronary artery disease in the father, type 2 diabetes mellitus in the maternal great grandmother, and hypothyroidism in the maternal grandmother. Radiography of the hips was performed (Figure 1B), showing bilateral slipped capital femoral epiphysis (SCFE). Prior to undertaking definitive surgical correction of the hips, it is important to consider the potential underlying condition.A, Plain film of the hips revealing bilateral slipped capital femoral epiphysis. B, Photograph of the patient’s hand, which demonstrates nonpitting edema at time of presentation. What Is Your Diagnosis?

Hyponatremia

Diabetes mellitus

Hypothyroidism

Fatty liver disease

C. Hypothyroidism

C

Hypothyroidism

The patient’s thyrotropin level was 496 mIU/L (reference range, 0.5-4.0 mIU/L). Free thyroxine (FT4) and thyroxine (T4) levels were undetectable. Her total triiodothyronine (T3) level was low at 31 ng/dL (reference range, 68-187 ng/dL).Slipped capital femoral epiphysis is characterized by displacement of the capital femoral epiphysis from the femoral neck through the physeal plate (Figure 2). It is one of the most common causes of hip pain in adolescents and is associated with obesity. It occurs in 1 person per 1000 to 10 000 people, and typically occurs prior to menarche in young women or around the time of peak growth in young men.Patient’s plain film of the hips showing bilateral slipped capital femoral epiphysis, with dotted lines indicating normal placement of capital femoral epiphysis bilaterally.The classic presentation of SCFE is an obese adolescent with dull pain in the hip, groin, thigh, or knee or an altered gait without a history of trauma. A plain radiograph can be used to diagnose most cases of SCFE (anteroposterior and frog leg view). The treatment of SCFE is operative stabilization, with the goal to prevent further slippage and complications. The urgency of treatment depends on the stability of the slip and whether or not the patient can bear weight. Patients with bilateral SCFE require bed rest until surgery. Complications of SCFE include osteonecrosis (avascular necrosis), chondrolysis, femoroacetabular impingement, and development of premature osteoarthritis.Slipped capital femoral epiphysis can be categorized as typical or atypical. A typical patient with SCFE is obese, between 10 and 16 years of age, and presents with unilateral disease. The atypical patients with SCFE has an age outside the typical age range, is normal or underweight, and/or presents with bilateral disease. Patients with atypical presentations merit evaluation for underlying risk factors, including hypothyroidism, growth hormone deficiency, renal failure, history of radiation therapy, and genetic disorders (Down syndrome and Rubenstein-Taybi syndrome).1-3Approximately 7% to 8% of patients with SCFE have primary hypothyroidism.1 Risk factors for hypothyroidism at presentation with SCFE include bilateral disease, height in the less than 10 percentile, and age outside the typical range.1,2 Therefore, many experts advise laboratory evaluation of thyrotropin and FT4 levels when these risk factors are present.1,2This patient had severe primary hypothyroidism, likely longstanding, based on her significantly elevated thyrotropin level, undetectable FT4 and T4 levels, and very low T3 level. She denied any obvious symptoms (fatigue, constipation, or cold intolerance) that would likely be due to the longstanding nature of her hypothyroidism. She did display typical physical examination findings of myxedema, dry skin, and short stature. She had a significantly delayed bone age of 10 years (−4.6 SD). Her vaginal bleeding was likely not true puberty but due to thyrotropin stimulation of the follicle-stimulating hormone receptors on the ovary. Owing to the urgency of the surgery to repair her SCFE, treatment was initiated with intravenous levothyroxine sodium, as well as liothyronine sodium (synthetic T3), with a slow titration to detectable levels of thyroid hormone prior to her procedure.Based on a review of the literature, the hypometabolic state associated with hypothyroidism increases the risk of decreased heart rate and contractility, hypoventilation due to weakness of respiratory muscles, decreased gut motility, reduced drug metabolism, and decreased free water clearance. Case reports describe intraoperative hypotension, cardiovascular collapse, and extreme sensitivity to opioids, sedatives, and anesthesia in undiagnosed hypothyroidism.4Owing to concerns of increased sensitivity to anesthesia of patients with severe hypothyroidism, surgery was deferred until the patient’s thyroid levels were detectable, which required approximately 10 days of therapy. At that time, the patient tolerated anesthesia and surgery well. She was discharged home and received levothyroxine daily.In summary, patients with bilateral SCFE, younger than 10 years of age or older than 16 years of age, or with a height in the less than 10 percentile should have their thyrotropin and FT4 levels tested prior to surgery because of the associated increased sensitivity to anesthesia of patients with untreated hypothyroidism.

Pediatrics

A 13-year-old girl presented to an emergency department with bilateral hip pain for several months and acute worsening with left-sided limp following a school field trip to a large museum. She stated that her pain worsened with walking and was minimally relieved with salicylic acid. Her parents tried to schedule an outpatient appointment for evaluation of her hip pain but had difficulty owing to a lack of a primary care physician. Review of systems was significant for heavy periods since menarche 6 months ago. It was negative for easy bruising or bleeding. The patient described normal stooling and voiding habits. The patient was described as a shy eighth grader who earns A’s and B’s in school. She was not physically active. On physical examination, the patient was noted to be short for her age (1.3 m [4.4 ft]; height in <third percentile), weight (62.5 kg; 87th percentile), and body mass index (35 [calculated as weight in kilograms divided by height in meters squared]; 99th percentile). She had a relatively short, thick neck with acanthosis nigricans, dry skin, Tanner stage II breasts, and nonpitting edema of her hands (Figure 1A). Her family history was significant for hypothyroidism and coronary artery disease in the father, type 2 diabetes mellitus in the maternal great grandmother, and hypothyroidism in the maternal grandmother. Radiography of the hips was performed (Figure 1B), showing bilateral slipped capital femoral epiphysis (SCFE). Prior to undertaking definitive surgical correction of the hips, it is important to consider the potential underlying condition.A, Plain film of the hips revealing bilateral slipped capital femoral epiphysis. B, Photograph of the patient’s hand, which demonstrates nonpitting edema at time of presentation.

what is your diagnosis?

What is your diagnosis?

Hyponatremia

Hypothyroidism

Fatty liver disease

Diabetes mellitus

b

female

11-20

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2598387

A woman in her late 50s with a history of multiple sclerosis, without traditional atherosclerosis risk factors and not taking medications, presented to the emergency department after having 30 minutes of pain in her left shoulder and vague chest pressure that had already resolved. There were no associated symptoms. Her daughter had died unexpectedly a few days before presentation, and the burial service was scheduled for that day. Except for the patient appearing struck with severe grief, the results of an initial physical examination, electrocardiography (ECG), and radiography of the chest and her initial laboratory results were all unremarkable. Her serial troponin T levels were less than 0.01, 0.04, and 0.1 ng/mL (normal range, <0.01 ng/mL [to convert to micrograms per liter, multiply by 1.0]). An emergency transthoracic echocardiographic biplane volumetric assessment of left ventricular (LV) function is shown in Figure 1 (Video 1 and Video 2). She received aspirin, high-intensity statin, and low-dose β-blocker and was given a therapeutic dose of low-molecular-weight heparin subcutaneously. Serial ECGs were unchanged, and the patient was completely asymptomatic; thus, she was permitted to briefly attend her daughter’s burial service as long as she returned immediately for direct hospital admission. Twelve hours after readmission, she was asymptomatic, her troponin level had increased to 2.0 ng/mL, and she again underwent ECG (Figure 1).Transthoracic echo biplane volumetric left ventricular function assessment (A-E). Note the systolic apical akinesis or ballooning in the 4- and 2-chamber systolic still frames (B and D, respectively). E, Note the extensive T-wave inversions and mild inferolateral ST elevation in the 12-lead electrocardiogram. LA indicates left artery; LV, left ventricle; RA, right artery; RV, right ventricle.Echocardiography in 2 weeks to confirm Takotsubo cardiomyopathyMagnetic resonance imaging to rule out myocarditis vs ischemia What Would You Do Next?

Echocardiography in 2 weeks to confirm Takotsubo cardiomyopathy

Magnetic resonance imaging to rule out myocarditis vs ischemia

Coronary angiography

Computed tomographic coronary angiography

Spontaneous coronary artery dissection involving multiple coronary arteries

C

Coronary angiography

Her emergency echocardiogram showed apical ballooning as depicted in the biplane volumetric assessment of LV function (Figure 1; Video 1 and Video 2), with a calculated LV ejection fraction of 49%. In the setting of no risk factors, recent severe emotional stress, troponin leak, and apical LV akinesis, the diagnosis appeared to be a “straightforward” Takotsubo cardiomyopathy. At readmission, the patient remained asymptomatic, but her troponin T level was 2.0 ng/mL after 12 hours in the emergency department, and she developed extensiv e T-wave inversions and mild inferolateral ST elevation detected on an ECG (Figure 1), which raised the question of a condition involving multiple coronaries given the combination of apical akinesis and mild inferolateral ST elevation. In the setting of severe emotional stress and no other risk factors, spontaneous coronary artery dissection (SCAD) involving multiple coronary arteries was suspected. Other differential diagnoses would include multiple coronary artery embolism and primary acute coronary syndrome. Therefore, she was treated with a high dose of clopidogrel bisulfate and underwent urgent coronary angiography. Multiple SCADs affecting the proximal-mid-intermediate branch and mid-distal left anterior descending artery (Figure 2A; Video 3), as well as the distal posterior descending artery (Figure 2B; Video 4), were diagnosed. Conservative management with a β-blocker, aspirin, and heparin infusion was pursued. The patient was observed for 5 days in the hospital, where she remained asymptomatic with downtrending troponin T levels and resolving ST segment changes. A computed tomographic scan of her abdomen and pelvis revealed fibromuscular dysplasia of the renal and iliac arteries, a condition associated with SCAD.1,2 Echocardiography at 6-month intervals revealed an LV ejection fraction of 55% and persistent apical akinesis.Coronary angiographs. A, Right anterior oblique (RAO) caudal view of the left system shows a medium-sized ramus, which begins at normal caliber and then becomes a smooth diffuse stenosis (the first 2 arrowheads from left to right) followed by reconstitution of the lumen. The mid-distal left anterior descending artery shows several areas of stenosis with false lumen staining (last 3 arrowheads). B, RAO cranial view of the right coronary artery (RCA) shows the distal RCA appearing as diffuse atherosclerosis (arrowheads).This case highlights the broad differential diagnosis that must be considered for patients presenting with Takotsubo-like syndromes, as well as the importance of in-hospital observation and pursuing coronary angiography. It is important to note that the typical characteristics of a patients who presents with Takotsubo cardiomyopathy—female, emotional event, symptoms of cardiac ischemia, and absence of typical risk factors—has also been associated with SCAD.1,2 Coronary angiography is the gold standard for diagnosis with intravascular imaging (intravascular ultrasonography and/or optical coherence tomography) used to clarify ambiguous cases.2 The reliability of the computed tomographic angiogram in diagnosing SCAD is still evolving, with no available clear diagnostic criteria.2 Magnetic resonance imaging also needs further study.2 In this case, careful observation with serial measures of troponin level and serial ECGs allowed for urgent coronary catheterization, and the correct diagnosis was made. As long as coronary flow is adequate, conservative management is recommended.1,2 Inpatient observation for 5 to 7 days is suggested because progression of dissection may require urgent percutaneous coronary intervention or coronary artery bypass graft.1-3Although single-vessel involvement is more common, there have been previous reports of 3-vessel SCAD.3,4 In our case, multivessel involvement explains the apical akinesis (left anterior descending artery) and inferolateral ST segment changes (intermediate branch and posterior descending artery). Takotsubo cardiomyopathy tends to have a good prognosis with less than 10% recurrence, whereas SCAD recurrence rates are reported to be up to 29%.1,2,5 This case highlights the need for careful inpatient monitoring with cardiac biomarkers, ECGs, and coronary angiography for patients with suspected Takotsubo cardiomyopathy.The patient was enrolled in cardiac rehabilitation and continues to do well.

Cardiology

A woman in her late 50s with a history of multiple sclerosis, without traditional atherosclerosis risk factors and not taking medications, presented to the emergency department after having 30 minutes of pain in her left shoulder and vague chest pressure that had already resolved. There were no associated symptoms. Her daughter had died unexpectedly a few days before presentation, and the burial service was scheduled for that day. Except for the patient appearing struck with severe grief, the results of an initial physical examination, electrocardiography (ECG), and radiography of the chest and her initial laboratory results were all unremarkable. Her serial troponin T levels were less than 0.01, 0.04, and 0.1 ng/mL (normal range, <0.01 ng/mL [to convert to micrograms per liter, multiply by 1.0]). An emergency transthoracic echocardiographic biplane volumetric assessment of left ventricular (LV) function is shown in Figure 1 (Video 1 and Video 2). She received aspirin, high-intensity statin, and low-dose β-blocker and was given a therapeutic dose of low-molecular-weight heparin subcutaneously. Serial ECGs were unchanged, and the patient was completely asymptomatic; thus, she was permitted to briefly attend her daughter’s burial service as long as she returned immediately for direct hospital admission. Twelve hours after readmission, she was asymptomatic, her troponin level had increased to 2.0 ng/mL, and she again underwent ECG (Figure 1).Transthoracic echo biplane volumetric left ventricular function assessment (A-E). Note the systolic apical akinesis or ballooning in the 4- and 2-chamber systolic still frames (B and D, respectively). E, Note the extensive T-wave inversions and mild inferolateral ST elevation in the 12-lead electrocardiogram. LA indicates left artery; LV, left ventricle; RA, right artery; RV, right ventricle.Echocardiography in 2 weeks to confirm Takotsubo cardiomyopathyMagnetic resonance imaging to rule out myocarditis vs ischemia

what would you do next?

What would you do next?

Magnetic resonance imaging to rule out myocarditis vs ischemia

Coronary angiography

Echocardiography in 2 weeks to confirm Takotsubo cardiomyopathy

Computed tomographic coronary angiography

b

female

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2551870

A young man in his late teens presented to a pediatric otolaryngologist for evaluation of enlarged tonsils and recurrent tonsillitis. The patient reported 2 episodes of streptococcal tonsillitis and infectious mononucleosis over the past 8 months, as well as frequent throat soreness and associated difficulty swallowing throughout the past year. Results from a review of systems were negative for weight loss, fevers, and malaise. On physical examination, he appeared well and had 2+ cryptic tonsils. A lobular mass was noted to be extending from the inferior pole of the right tonsil. There was no cervical lymphadenopathy. The patient was scheduled for tonsillectomy for recurrent tonsillitis and tonsillar asymmetry. His surgery was delayed for several months to accommodate his college schedule. In the operating room, the tonsils were noted to be 3+ bilaterally. The right tonsil had a smooth, pedunculated, flesh-colored mass extending inferiorly. The mass had enlarged since the prior examination. Both tonsils were removed without complication. The right tonsil with the attached mass was submitted to the pathology service fresh to allow evaluation by flow cytometry. Flow cytometry revealed no lymphoid abnormality. Grossly, the polypoid oval mass measured 2 × 1 × 1 cm, weighed 8.7 g, and had a narrow 0.4-cm-long stalk connecting it to the tonsil (Figure, A). Histologic sections revealed a polypoid structure composed of a fibrovascular core covered by stratified squamous epithelium (Figure, B). A subepithelial band of lymphoid tissue was noted (Figure, C) as well as lymphatic channels accentuated by D2-40 antibody (Figure, D). No cellular atypia was identified. What Is Your Diagnosis?

Fibroepithelial polyp

Lymphangioma

Lymphangiomatous polyp

Juvenile angiofibroma

C. Lymphangiomatous polyp

C

Lymphangiomatous polyp

Approximately 90% of all lymphangiomatous lesions are found in the head and neck, but most arise in the skin, subcutaneous tissues, larynx, parotid gland, and subsites of the oral cavity.1,2 Lymphangiomatous polyp (LAP) of the palatine tonsil is an uncommon benign tumor of the oropharynx. Approximately 30 cases of tonsillar LAPs have been reported in the literature. These tumors tend to occur in young adults and children and occur in both sexes equally. They are most often unilateral and have not been associated with other lymphatic lesions occurring elsewhere in the head and neck region.1-5 Common symptoms experienced by patients with LAPs of the palatine tonsil include dysphagia, dyspnea, globus sensation, sore throat, and tonsillitis. These symptoms may be present weeks to years before diagnosis. They may also be asymptomatic and incidentally found on physical examination.Two hypotheses have been developed to explain the pathogenesis of LAPs. The first is that in the setting of chronic tonsillar inflammation, lymphatic channels of the tonsil become irreversibly obstructed, and this leads to polyp formation over time.3,4 This is somewhat unlikely because chronic tonsillar inflammation is a very common entity and LAPs of the palatine tonsil are relatively uncommon. The other theory suggests that LAPs are hamartomatous proliferations of tonsillar tissue because they include components native to tonsillar tissue, but the components are arranged in a different and varied pattern.1,3-5 This is currently the most widely accepted hypothesis for pathogenesis.The differential diagnosis includes fibroepithelial polyp, lymphangioma, juvenile angiofibroma, squamous papilloma, lymphangiectasia, hemangioma, and arteriovenous malformation.1-4 Both simple excision of the polyp and tonsillectomy are reported curative for LAP involving the tonsil. To our knowledge, there have been no reported cases of disease recurrence or malignant transformation of these lesions..1-6The diagnosis of LAP is confirmed with histopathologic findings after surgical excision. Grossly, LAPs of the palatine tonsil tend to have a pedicle attached to the surface of the tonsil and extend into the oropharynx. They can also be more sessile in appearance. They range anywhere from 0.5 to 3.8 cm in greatest dimension, but the average size is 1.6 cm. They appear polypoid with a smooth white, tan, or yellow cut surface.1 Histologically, LAPs have a squamous or respiratory epithelium and the stroma consists of fibrous tissue, adipose tissue, dilated lymphatic channels, and lymphoid tissue without clonal lymphoid neoplasia.1-6 The quality and quantity of the different components differ from tumor to tumor. They consistently show no infiltration of underlying normal tonsillar stroma or extension into nearby pharyngeal tissues.1 To assess for hematolymphoid neoplasia, all tonsillar mass specimens should be sent fresh to the pathology service to allow for special stains and flow cytometry as needed.In summary, this case demonstrates a rare head and neck entity that is important to recognize because it does not require extensive workup and is cured with simple excision or tonsillectomy.

General

A young man in his late teens presented to a pediatric otolaryngologist for evaluation of enlarged tonsils and recurrent tonsillitis. The patient reported 2 episodes of streptococcal tonsillitis and infectious mononucleosis over the past 8 months, as well as frequent throat soreness and associated difficulty swallowing throughout the past year. Results from a review of systems were negative for weight loss, fevers, and malaise. On physical examination, he appeared well and had 2+ cryptic tonsils. A lobular mass was noted to be extending from the inferior pole of the right tonsil. There was no cervical lymphadenopathy. The patient was scheduled for tonsillectomy for recurrent tonsillitis and tonsillar asymmetry. His surgery was delayed for several months to accommodate his college schedule. In the operating room, the tonsils were noted to be 3+ bilaterally. The right tonsil had a smooth, pedunculated, flesh-colored mass extending inferiorly. The mass had enlarged since the prior examination. Both tonsils were removed without complication. The right tonsil with the attached mass was submitted to the pathology service fresh to allow evaluation by flow cytometry. Flow cytometry revealed no lymphoid abnormality. Grossly, the polypoid oval mass measured 2 × 1 × 1 cm, weighed 8.7 g, and had a narrow 0.4-cm-long stalk connecting it to the tonsil (Figure, A). Histologic sections revealed a polypoid structure composed of a fibrovascular core covered by stratified squamous epithelium (Figure, B). A subepithelial band of lymphoid tissue was noted (Figure, C) as well as lymphatic channels accentuated by D2-40 antibody (Figure, D). No cellular atypia was identified.

what is your diagnosis?

What is your diagnosis?

Lymphangiomatous polyp

Juvenile angiofibroma

Lymphangioma

Fibroepithelial polyp

a

male

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2552988

A man in his 50s presented with a 5-year history of a slow-growing mass on the posterior surface of the left auricle. He denied any history of trauma or surgery around the ear, and reported only a cosmetic problem without pain or discharge. His medical history was positive for hypertension, impaired glucose tolerance, dyslipidemia, and hyperthyroidism, and negative for unusual skin pigmentation or cardiac problems. A laboratory examination revealed only slightly elevated thyroid-stimulating hormone levels (4.80 µU/mL). A physical examination showed a solitary, 1-cm, dome-shaped, glistening, flesh-colored mass adherent to the posterior groove of the concha ridge (Figure, A and B). There were no abnormal pigmented skin lesions on the rest of his body, including the face, trunk, and extremities. Neither a palpable thyroid nodule nor enlargement of hands and feet was identified. Surgical excision was performed. Gross total extirpation of the mass from the surrounding tissues was enabled by meticulous dissection. Intraoperatively, the 1-cm mass was noted to be gelatinous and glossy with well-demarcated and smooth border. It was attached to the posterior surface of the concha cartilage but easily separated using blunt dissection. Unexpectedly, low-viscosity mucoid fluid had smeared on the surface. The histopathological examination revealed the tumor to be overall hypocellular and composed of bland spindle cells with no mitotic activity in a slightly basophilic myxoid matrix (Figure, C). The surgical wound uneventfully healed, and no recurrence was noted during the 6-month follow-up period.A, Photograph of a protruding mass on the posterior surface of the auricle. B, A preoperative close-up of the solitary lesion. C, Histopathological image showing overall hypocellular stroma with scattered bland spindle cells in slightly basophilic myxoid matrix without mitotic activity. Numerous blood vessels with collapsed lumina (arrowheads) are also visible. What Is Your Diagnosis?

Epidermoid cyst

Dermoid cyst

Chondroma

Solitary cutaneous myxoma

D. Solitary cutaneous myxoma

D

Solitary cutaneous myxoma

In 1871, Rudolf Virchow first used the term myxoma to describe tumors that histologically resembled the mucinous tissue of the umbilical cord.1 Myxomas are rare benign myxoid tumors of the primitive mesenchyme and are the most common primary tumors of the heart.2 Although cardiac myxomas are histologically benign, they may be lethal because of their symptom triad of embolism, intracardiac obstruction, and constitutional symptoms.2 Myxomas can also occur in the bone and somatic soft tissues of other locations, including the head and neck area, although cases involving the ear are extremely rare.3Cutaneous myxoma (CM), also known as superficial angiomyxoma, of the external ear was recently identified as a manifestation of Carney complex (CC). In 1985, Carney et al4(p270) first described CC as “the complex of myxomas, spotty pigmentation, and endocrine overactivity.” This syndrome is an autosomal dominant disorder and is characterized by multiple myxomas (cardiac, cutaneous, and mammary), multiple endocrine hyperactivities (Cushing syndrome, sexual precocity, testicular tumors, and acromegaly), psammomatous melanotic schwannomas (PMSs), and spotty pigmentations (cutaneous and mucocutaneous).5,6Clinically, most CMs are solitary findings in an otherwise healthy patient.7 However, they can be associated with various syndromes, including CC, NAME (nevi, atrial myxoma, myxoid neurofibromas, and ephelides),8 and LAMB (lentigines, atrial myxoma, mucocutaneous myxomas, and blue nevi) syndromes.7Solitary cutaneous myxomas (SCMs) without other manifestations of CC are uncommon tumors and are usually present as cutaneous or subcutaneous nodules primarily located in the distal skin areas of the limb, head, neck, and, very rarely, auricle.9 Accordingly, its diagnosis may be easily delayed or misdiagnosed as another skin disorder, such as epidermoid cyst, dermoid cyst, or chondroma.Histologically, SCMs are very hypocellular and contain mucopolysaccharides. Their characteristic findings are scattered spindle- and stellate-shaped cells with oval nuclei and ill-defined cytoplasm within the basophilic myxoid stroma.9 Histological examination also revealed the presence of numerous blood vessels with collapsed lumina (Figure, C).The treatment for SCM is total removal of the tumor. Recurrence following surgery has been described in up to 38% of cases, probably owing to incomplete surgical resection or subcutaneous extension of the lesions.After a diagnosis of CM is made, it is incumbent on the clinician to rule out the patient having a syndrome, especially CC, because CM is the third most frequent skin manifestation of CC. Moreover, SCMs can be detected prior to the CC.10 Identification of the characteristic cutaneous manifestations, such as SCMs or spotty skin pigmentation, and the consequent definite diagnosis of CC can help in the early detection of PMSs or life-threatening cardiac myxomas.

General

A man in his 50s presented with a 5-year history of a slow-growing mass on the posterior surface of the left auricle. He denied any history of trauma or surgery around the ear, and reported only a cosmetic problem without pain or discharge. His medical history was positive for hypertension, impaired glucose tolerance, dyslipidemia, and hyperthyroidism, and negative for unusual skin pigmentation or cardiac problems. A laboratory examination revealed only slightly elevated thyroid-stimulating hormone levels (4.80 µU/mL). A physical examination showed a solitary, 1-cm, dome-shaped, glistening, flesh-colored mass adherent to the posterior groove of the concha ridge (Figure, A and B). There were no abnormal pigmented skin lesions on the rest of his body, including the face, trunk, and extremities. Neither a palpable thyroid nodule nor enlargement of hands and feet was identified. Surgical excision was performed. Gross total extirpation of the mass from the surrounding tissues was enabled by meticulous dissection. Intraoperatively, the 1-cm mass was noted to be gelatinous and glossy with well-demarcated and smooth border. It was attached to the posterior surface of the concha cartilage but easily separated using blunt dissection. Unexpectedly, low-viscosity mucoid fluid had smeared on the surface. The histopathological examination revealed the tumor to be overall hypocellular and composed of bland spindle cells with no mitotic activity in a slightly basophilic myxoid matrix (Figure, C). The surgical wound uneventfully healed, and no recurrence was noted during the 6-month follow-up period.A, Photograph of a protruding mass on the posterior surface of the auricle. B, A preoperative close-up of the solitary lesion. C, Histopathological image showing overall hypocellular stroma with scattered bland spindle cells in slightly basophilic myxoid matrix without mitotic activity. Numerous blood vessels with collapsed lumina (arrowheads) are also visible.

what is your diagnosis?

What is your diagnosis?

Chondroma

Dermoid cyst

Solitary cutaneous myxoma

Epidermoid cyst

c

male

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2556212

A well-developed man in his 20s presented to our hospital with a clinically significant elevation in serum calcium level to (14.1 mg/dL [reference range, 8.6-10.2 mg/dL]) found on routine laboratory tests. He was highly functional and denied abdominal pain, dysuria, anxiety, lethargy, and constipation. Findings from his physical examination were within normal limits. He did not have any palpable thyroid nodules or cervical lymphadenopathy. Given his elevated calcium level, parathyroid hormone (PTH) was drawn, and results returned significantly elevated at 1377 pg/mL (reference range, 10-65 pg/mL). Because of the extremely elevated PTH level, a technetium Tc 99m sestamibi single-photon emission computed tomographic/computed tomographic (SPECT/CT) scan was obtained, which identified a lesion in the location of the right inferior parathyroid gland, measured at 2.2 cm (Figure, A). In addition, CT showed associated lytic bone lesions of the left mandibular ramus, left scapula, and C5 vertebra (Figure, B).Preoperative imaging of the neck. A, A technetium Tc 99m sestamibi single-photon emission computed tomographic (SPECT)/computed tomographic (CT) scan. B, A CT image. C, Postoperative CT image of the neck. What Is Your Diagnosis?

Parathyroid carcinoma

Multiple myeloma

Primary bone tumor

Osteitis fibrosa cystica

D. Osteitis fibrosa cystica

D

Osteitis fibrosa cystica

The patient underwent right inferior parathyroidectomy, with intraoperative return to normal PTH levels of 50 pg/mL after removal of the affected gland. He recovered without issues postoperatively. Final pathologic findings demonstrated a parathyroid adenoma weighing 5.9 g. No malignant cells were identified. Follow-up imaging 8 months later revealed interval healing of his lytic bone lesions (Figure, C).In the setting of prolonged hyperparathyroidism, chronic PTH activity results in osteopenia and, in long-standing and severe cases, osteitis fibrosa cystica, manifested by resorption of subperiosteal bone and brown tumors (collections of osteoclasts, fibrous tissue, and demineralized bone with the brown color characterized by hemosiderin deposition).1 Clinically, osteitis fibrosa cystica symptoms include bone swelling, pathological fractures, and bone pain. Imaging studies show brown tumors of osteitis fibrosa cystica as lytic lesions (radiolucent regions of bone resorption on CT) generally located in the facial bones, pelvis, ribs, and femur.2 These lesions may be mistaken for primary bone tumors radiologically; in particular, those in the head and neck may have radiologic features similar to those of sinonasal tumors, sarcomas, salivary gland tumors, and plasmacytomas.3 The incidence of osteitis fibrosa cystica has become less frequent over time, currently occurring in less than 1% of patients, likely due to earlier biochemical detection of hyperparathyroidism.4 Brown tumors are frequently treated pharmacologically, and generally improve by addressing the underlying hyperparathyroidism. However, in some cases surgery is needed, specifically in cases of pathologic fracture or increased pain.Osteitis fibrosa cystica can resemble metastatic parathyroid carcinoma, primary bone tumors, or multiple myeloma, both clinically and radiographically, with extremely elevated PTH levels and lytic bone lesions.2,5,6 Thus, clinicians should entertain a careful differential diagnosis and with consideration of both disease processes. Of note, both primary and secondary hyperparathyroidism can lead to osteitis fibrosa cystica. Key features to distinguish primary from secondary hyperparathyroidism include evidence of renal dysfunction, generally lower calcium levels with correspondingly elevated PTH level, lower vitamin D levels, and decreased urinary calcium excretion. Sestamibi imaging is increasingly being used to identify hyperfunctioning parathyroid glands in cases of secondary hyperparathyroidism, which frequently identifies multiple hyperfunctioning glands.7 While the differential diagnosis between hyperparathyroidism with osteitis fibrosa cystica and parathyroid carcinoma can be difficult, some key clinical clues exist. Notably, the average PTH level in patients diagnosed as having parathyroid adenoma is comparatively lower, often no more than 15% to 30% above the normal range or even within normal range,8 although in rare instances markedly elevated PTH and calcium levels may be noted.9 Patients with parathyroid carcinoma, however, often present with serum PTH levels up to 10 times the normal range.10 In addition, about one-third of these individuals have lymph node, liver, and/or bone lesions; comparatively, patients with parathyroid adenomas should have no pathologic lymph nodes, liver lesions, and a much lower rate of osteitis fibrosa cystica and bone lesions.8Although the extremely elevated PTH level and suspicious [Tc-99m] sestamibi SPECT/CT scan findings in this case gave rise to concern about parathyroid carcinoma, the pathologic findings confirmed the final diagnosis of parathyroid adenoma. This case highlights the need for surgeons to be aware of the potential for primary hyperparathyroidism with brown tumors to present similar clinical features to parathyroid carcinoma.

General

A well-developed man in his 20s presented to our hospital with a clinically significant elevation in serum calcium level to (14.1 mg/dL [reference range, 8.6-10.2 mg/dL]) found on routine laboratory tests. He was highly functional and denied abdominal pain, dysuria, anxiety, lethargy, and constipation. Findings from his physical examination were within normal limits. He did not have any palpable thyroid nodules or cervical lymphadenopathy. Given his elevated calcium level, parathyroid hormone (PTH) was drawn, and results returned significantly elevated at 1377 pg/mL (reference range, 10-65 pg/mL). Because of the extremely elevated PTH level, a technetium Tc 99m sestamibi single-photon emission computed tomographic/computed tomographic (SPECT/CT) scan was obtained, which identified a lesion in the location of the right inferior parathyroid gland, measured at 2.2 cm (Figure, A). In addition, CT showed associated lytic bone lesions of the left mandibular ramus, left scapula, and C5 vertebra (Figure, B).Preoperative imaging of the neck. A, A technetium Tc 99m sestamibi single-photon emission computed tomographic (SPECT)/computed tomographic (CT) scan. B, A CT image. C, Postoperative CT image of the neck.

what is your diagnosis?

What is your diagnosis?

Parathyroid carcinoma

Primary bone tumor

Osteitis fibrosa cystica

Multiple myeloma

c

male

21-30

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2595901

A young boy referred by his local otolaryngologist presented with dysphonia and abnormal laryngeal examination results. His voice quality had always been husky, with recent mild exacerbation. No stridor or shortness of breath was reported, but he admittedly “hated to run” and was relatively sedentary. His parents noted intermittent stertor while he was sleeping but no apnea. He had no dysphagia or aspiration manifestations. He was overweight (body mass index, calculated as weight in kilograms divided by height in meters squared, 27.2); breathed comfortably at rest; and had a dysphonic, breathy voice. Findings from an otolaryngologic examination were normal other than those from flexible laryngoscopy, which demonstrated 2 laryngeal lesions, 1 in the postcricoid interarytenoid region and 1 at the anterior commissure, the latter of which compromised vocal fold approximation. Vocal fold mobility otherwise appeared normal. Operative laryngoscopy confirmed a midline, firm, posterior cricoid mass (Figure, A), and a midline, firm, anterior subglottic mass extending into the anterior commissure (Figure, A). Tracheobronchoscopy revealed a distal tracheal submucosal mass partially obstructing the left mainstem bronchus (Figure, B). Excisional biopsy of the postcricoid and subglottic masses with the carbon dioxide laser was performed (Figure, C). Histopathologic examination demonstrated mucosal infiltration by a monotonous population of cells with round nuclei and abundant granular cytoplasm (Figure, D), positive for S-100 and lightly positive for CD68, with occasional interspersed more darkly staining cells, consistent with histiocytes and giant cells. Sections stained negative for epithelial, muscle, endothelial, and glial cell immunohistologic markers.A, Direct laryngoscopy of the larynx. B, Rigid bronchoscopy of the larynx. C, Direct laryngoscopy of the larynx following endoscopic carbon dioxide laser ablation of the lesions. D, Histopathologic image (hematoxylin-eosin, original magnification ×200). What Is Your Diagnosis?

Sarcoidosis

Respiratory papillomatosis

Multifocal granular cell tumor

Metastatic neuroblastoma

C. Multifocal granular cell tumor

C

Multifocal granular cell tumor

Granular cell tumors (GCTs) typically arise from skin or mucosa but can originate from smooth or striated muscle as well.1 Granular cell tumors typically manifest as unifocal solitary lesions, rarely larger than 3 cm in diameter. Grossly these lesions appear as pale, white-yellow, variably circumscribed, solid nodules. The involved skin or mucosa is frequently thickened and may appear cobblestoned. There is a slight female predominance (3:2 compared with males) and an African American predilection.2 Half of all GCTs arise in the head and neck region, with one-third appearing in the tongue and only 10% of GCTs presenting in the larynx.3 The mean age for laryngeal GCT is 36 years.4 Multifocal lesions are reported in 7% of adult cases and represent a more significant therapeutic challenge.1 Multifocal GCTs also tend to be more highly associated with the larynx and trachea. It is not known whether multifocal GCT is a result of seeding or synchronicity; both theories have been postulated.Laryngeal GCTs, owing to their anatomical location, present with the typical signs and symptoms associated with laryngeal lesions, such as hoarseness, stridor, dysphagia, and, rarely, hemoptysis. Because of the insidious nature of these lesions, patients are often initially mistakenly diagnosed as having lower airway diseases, such as asthma or bronchitis.5 The differential diagnosis for a laryngeal mass in a child includes congenital anomalies, such as laryngoceles and hemangiomas; acquired lesions, such as papilloma; and both malignant and benign neoplasms, the latter category including GCT.Both laryngeal and tracheal GCTs are rare entities in the pediatric population, with approximately 40 cases having been reported in the literature.1 Only 4 cases of multifocal GCT with tracheal involvement have been reported in children.6Malignant transformation represents a rare event, reported in only 2% of adult GTC cases, never, to our knowledge, in a child.7 There have also been no reported cases of malignant laryngeal or tracheal GCT.Histologic and immunohistochemical staining are used to confirm the diagnosis of GCT. Microscopic analysis shows large polyhedral cells containing eosinophilic intracytoplasmic granules as well as eccentric nuclei and absent mitosis. Adult GCTs provide a diagnostic dilemma because 50% to 60% of tumors display pseudoepitheliomatous hyperplasia, a finding seen in squamous papilloma or squamous cell carcinoma, but this phenomenon does not occur in the pediatric population.8 A positive finding of S-100 on immunohistochemical analysis is the key confirmatory finding of GCT.Surgery has proven to be the best primary treatment modality. The extent of surgery depends on the anatomical location and, in the case of laryngotracheal GCT, the degree of airway compromise. The reported recurrence rate approximates 8% when negative margins are obtained, although positive margins are not necessarily an absolute predictor of recurrence.9Endoscopic resection is both adequate and preferred for focal laryngotracheal granular cell tumors, but open airway resection may be a consideration for larger, more extensive lesions.1,4 The risks of the surgical approach with respect to the obtainment of clear margins must be weighed against the morbidity associated with what is otherwise a benign neoplasm. For similar reasons, there is no established role for chemotherapy or radiotherapy, particularly in the pediatric population.There is no standard follow-up algorithm status postlaryngeal or tracheal GTC resection. However, given the risk of recurrence, surveillance is critical. Flexible stroboscopic laryngoscopy performed in the office and operative endoscopic follow-up of this child are being conducted at approximate 6-month intervals. The distal tracheal lesion is of particular concern, with anticipated carbon dioxide laser debulking if there is evidence of progression, or possible tracheal resection with reanastomosis in the case of life-threatening obstruction.

General

A young boy referred by his local otolaryngologist presented with dysphonia and abnormal laryngeal examination results. His voice quality had always been husky, with recent mild exacerbation. No stridor or shortness of breath was reported, but he admittedly “hated to run” and was relatively sedentary. His parents noted intermittent stertor while he was sleeping but no apnea. He had no dysphagia or aspiration manifestations. He was overweight (body mass index, calculated as weight in kilograms divided by height in meters squared, 27.2); breathed comfortably at rest; and had a dysphonic, breathy voice. Findings from an otolaryngologic examination were normal other than those from flexible laryngoscopy, which demonstrated 2 laryngeal lesions, 1 in the postcricoid interarytenoid region and 1 at the anterior commissure, the latter of which compromised vocal fold approximation. Vocal fold mobility otherwise appeared normal. Operative laryngoscopy confirmed a midline, firm, posterior cricoid mass (Figure, A), and a midline, firm, anterior subglottic mass extending into the anterior commissure (Figure, A). Tracheobronchoscopy revealed a distal tracheal submucosal mass partially obstructing the left mainstem bronchus (Figure, B). Excisional biopsy of the postcricoid and subglottic masses with the carbon dioxide laser was performed (Figure, C). Histopathologic examination demonstrated mucosal infiltration by a monotonous population of cells with round nuclei and abundant granular cytoplasm (Figure, D), positive for S-100 and lightly positive for CD68, with occasional interspersed more darkly staining cells, consistent with histiocytes and giant cells. Sections stained negative for epithelial, muscle, endothelial, and glial cell immunohistologic markers.A, Direct laryngoscopy of the larynx. B, Rigid bronchoscopy of the larynx. C, Direct laryngoscopy of the larynx following endoscopic carbon dioxide laser ablation of the lesions. D, Histopathologic image (hematoxylin-eosin, original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Sarcoidosis

Metastatic neuroblastoma

Respiratory papillomatosis

Multifocal granular cell tumor

d

male

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2546528

A full-term 2719-g female infant was transferred to a neonatal intensive care unit (NICU) on day 1 of life after developing respiratory distress requiring endotracheal intubation. Gestation was complicated by polyhydramnios and gestational diabetes. In the NICU, choking and desaturation were noted with oral feeding. Videofluoroscopic swallow study demonstrated aspiration with all consistencies. Microlaryngoscopy and bronchoscopy were conducted, and the patient was diagnosed as having a type II laryngeal cleft. At 2 weeks of age, she decompensated secondary to Klebsiella pneumoniae sepsis and was intubated for persistent left lung collapse. At that time, computed tomographic (CT) imaging was performed, revealing the etiology of her respiratory decompensation (Figure 1).Coronal computed tomographic image of the chest with contrast. What Is Your Diagnosis?

Pulmonary sequestration

Congenital cystic adenomatoid malformation