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JAMA_Chen2024

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https://jamanetwork.com/journals/jamadermatology/fullarticle/2811083

A man in his 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The patient also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to his significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen.A, Clinical image demonstrating papulopustules and ovoid ulcerated plaques with elevated, pink borders on the elbows. B, Tzanck smear using Wright-Giemsa staining of specimen demonstrating ballooning of keratinocytes and peripheralization of nuclear material (original magnification ×20). What Is Your Diagnosis?

Herpes simplex virus

Histoplasmosis

Molluscum contagiosum

Mpox

D. Mpox

D

Mpox

The photographs demonstrate a Tzanck smear using Wright-Giemsa stain (Figure, B) with large ballooning keratinocytes with peripheral nuclear staining seen in a patient with subsequently polymerase chain reaction (PCR)-confirmed mpox. Mpox is a member of the pox virus family, which presents with nonspecific symptoms such as fever followed by characteristic skin changes including macules, papules, vesicles, and pustules progressing with cephalocaudal spread or in the genital and/or gluteal region in the most recent outbreak. On histopathologic findings, mpox features vary depending on the stage of the lesion.1,2 Early lesions tend to demonstrate ballooning degeneration, whereas later lesions have few viable keratinocytes.2 The viral cytopathic changes, most often seen in pseudopustular lesions, include multinucleated keratinocytes with ground glass appearance and nuclear contents pushed to the periphery, resulting in a basophilic halo.2 The lack of a true pustule with collections of neutrophils in the stratum corneum have led some to describe these lesions as pseudopustular.Tzanck smear is an inexpensive, rapid, and simple technique to perform cytologic analysis from skin. Initially described in 1947 by Arnault Tzanck for diagnosing vesiculobullous disorders, it is commonly used in diagnosing herpetic infections, which have characteristic features of acantholysis, acute inflammation, and keratinocytic ballooning and specific nuclear changes of molding, multinucleation, and chromatin margination.3 The findings of acantholysis and nuclear cytopathic changes are similarly seen in histopathologic examination of herpes simplex virus (HSV). Herpetic infections may present with clustered vesicles with a pink inflammatory rim, although more verrucous lesions have been described in immunosuppressed patients.In the Tzanck smear from a lesion of mpox in this patient (Figure, B), enlarged keratinocytes were seen with expanded cytoplasm and nuclear material pushed to the periphery, and the nuclear changes associated with HSV were all absent. The observed difference in cytologic features including the nuclear material rimming or pushed to the periphery of the cells is due to the location of viral replication; herpes viruses replicate in the nucleus, whereas mpox replicates in the cytoplasm.4 Although not part of routine practice, Papanicolaou staining was performed in this case to confirm infected cells and provide additional nuclear detail because Tzanck smears in patients with mpox were not previously reported. The findings highlighted the peripheralization of nuclear material in cells with eosinophilic staining, confirming the keratinocyte origin to the cells. A background inflammatory infiltrate was noted and can be seen in most infections.Tzanck smear can also be used to diagnose other viral and fungal infections. Molluscum contagiosum, which presents with multiple umbilicated papules, demonstrates the characteristic large (30-40 µm) ovoid homogenous basophilic staining keratinocytes called Henderson-Patterson bodies that correspond to the identically named intracytoplasmic inclusions seen on histopathologic findings.5,6 Using bedside diagnostics (including Wright Giemsa staining), blastomycosis is diagnosed with 8- to 15-µm spores with broad-based budding, similar in appearance to the organism in histologic examination.5 Histoplasmosis has small (2 to 3 µm) intracellular organisms in macrophages with artifactual clearing (pseudocapsule).5 Both of these fungal infections may manifest clinically as nonhealing ulcerations, verrucous plaques, or multiple papules or nodules and can histologically demonstrate pseudoepitheliomatous hyperplasia with characteristic organisms. The use of the Tzanck smear in diagnosis of any infection depends on the timing of the lesion and is most sensitive with vesicular or pustular lesions.6 Although we only tested 1 stage of lesions, we hypothesize this test will similarly be more sensitive for earlier lesions in patients with mpox.Tzanck smear is a useful technique that can be used to differentiate mpox from other infections at the bedside or in remote settings where PCR or additional culture techniques are not easily accessible. Infection prevention and control precautions are important to help prevent additional spread of this virus with sharp injuries, and caution with unroofing of the lesions is critical to avoid additional spread.7 Knowledge of the cytologic differences of mpox compared with other viral infections is important in the early recognition, diagnosis, and treatment of these patients.

Dermatology

A man in his 30s with AIDS presented with acute-onset painful scattered umbilicated papulopustules and ovoid ulcerated plaques with elevated, pink borders on the face, trunk, and extremities (Figure, A). The patient also had a new-onset cough but was afebrile and denied other systemic symptoms. Due to his significant immunocompromise, the clinical presentation was highly suspicious for infection. For rapid bedside differentiation of multiple infectious etiologies, a Tzanck smear was performed by scraping the base of an ulcerated lesion and inner aspect of a pseudopustule and scraping its base with a #15 blade. These contents were placed on a glass slide, fixed, and stained with Wright-Giemsa and subsequently Papanicolaou staining to further characterize the changes seen.A, Clinical image demonstrating papulopustules and ovoid ulcerated plaques with elevated, pink borders on the elbows. B, Tzanck smear using Wright-Giemsa staining of specimen demonstrating ballooning of keratinocytes and peripheralization of nuclear material (original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Herpes simplex virus

Mpox

Histoplasmosis

Molluscum contagiosum

b

male

31-40

original

https://jamanetwork.com/journals/jama/fullarticle/2810596

An 80-year-old man with stage II bladder carcinoma (T2NXM0) and atrial fibrillation treated with apixaban presented to the emergency department with 1 week of fatigue and 2 days of dyspnea on exertion. One week prior to presentation, he received a fourth cycle of carboplatin/gemcitabine for bladder carcinoma with 6 mg of pegylated granulocyte colony-stimulating factor (G-CSF). The patient reported no anorexia, fever, melena, hematemesis, hematuria, cough, orthopnea, or peripheral edema.His vital signs were normal except for a heart rate of 103/min. His white blood cell count was 22 × 103/μL (reference, 4-11 × 103/μL), increased from 4.8 × 103/μL 8 days prior. His manual differential, which was previously normal, showed 18% bands (0%-10%), 2% metamyelocytes, 7% myelocytes, 7% promyelocytes, and 6% blasts. His hemoglobin level was 5.2 g/dL (reference, 13-17 g/dL), decreased from 7.4 g/dL, and platelets were 25 × 103/μL (reference, 150-420 × 103/μL), decreased from 268 × 103/μL 8 days prior. Ferritin was 1423 ng/mL (reference, 300-400 ng/mL). Mean corpuscular volume, prothrombin time, international normalized ratio, partial thromboplastin time, fibrinogen, haptoglobin, vitamin B12, and methylmalonic acid values were normal, and results of a direct antiglobulin test were negative. A computed tomography (CT) scan of his abdomen and pelvis was normal. He received 2 units of packed red blood cells and was admitted to the hospital. Flow cytometry identified a small population of CD34+/CD117+ cells (Figure).Left, Peripheral blood smear showing normocytic anemia with anisopoikilocytosis and leukocytosis with 6% to 8% blast forms. Right, Flow cytometry of peripheral blood demonstrating a small population of white blood cells that stained positive for CD34 and CD117, which are markers of immature myeloblasts.Esophagogastroduodenoscopy revealed 2 nonbleeding angioectasias in the stomach that were treated with argon plasma coagulation. Three days after admission, his white blood cell count was 27.7 × 103/μL with 4% peripheral blasts, hemoglobin was 7.3 g/dL, and platelet count had increased to 92 × 103/μL without a platelet transfusion.Repeat complete blood cell count with differential in 1 to 2 weeks What Would You Do Next?

Perform a bone marrow biopsy

Prescribe all-trans retinoic acid

Repeat complete blood cell count with differential in 1 to 2 weeks

Start cytoreductive therapy with hydroxyurea

Granulocyte colony-stimulating factor (G-CSF)–induced increase in peripheral blasts

C

Repeat complete blood cell count with differential in 1 to 2 weeks

The key to the correct diagnosis is recognizing that leukocytosis with immature granulocytes and mildly elevated blasts in the peripheral blood can occur after G-CSF administration. Bone marrow biopsy (choice A) is incorrect because his platelet count increased spontaneously 3 days after presentation, making malignant infiltration of his bone marrow unlikely, and recent G-CSF administration can alter bone marrow biopsy results. All-trans retinoic acid and cytoreductive therapy (options B and D) should not be prescribed because the patient did not have biopsy-proven acute promyelocytic leukemia or acute leukemia.Myeloblasts are immature leukocytes that arise from progenitor stem cells in the bone marrow, and their presence in peripheral blood suggests a perturbation of normal hematopoietic differentiation. Myeloblasts are characterized by the presence of CD34 and CD1171 antigens, identified with flow cytometry. A peripheral blood myeloblast count of greater than 20% is diagnostic of acute myeloid leukemia (AML), although AML can occur with a lower myeloblast count.2 Increased peripheral blood myeloblasts with leukopenia may be due to AML, myelodysplastic syndrome (MDS), chemotherapy, or occasionally severe infection. Causes of elevated peripheral blood myeloblasts with leukocytosis include AML, myelodysplastic syndrome, myeloproliferative neoplasms, severe infection, bone marrow damage or infiltration by fibrosis, malignancy or infection,3,4 and administration of G-CSF.G-CSF, which is produced by macrophages, T cells, endothelial cells, and fibroblasts,5 causes proliferation and differentiation of hematopoietic stem cells and progenitor cells, generating polymorphonuclear neutrophils via the precursor stages of myeloblast, promyelocyte, myelocyte, metamyelocyte, and bands. G-CSF therapy stimulates neutrophil production in the bone marrow, causing a rapid increase in peripheral blood neutrophils (emergency granulopoiesis) during severe infections. G-CSF also acts to maintain a neutrophil reserve in the bone marrow and regulates the slow release of neutrophils into the peripheral circulation.3Recombinant human G-CSF (filgrastim) received US Food and Drug Administration (FDA) approval in 1991 for prevention of chemotherapy-induced neutropenia.3,5 In 2002, the FDA approved pegfilgrastim, which is administered once per chemotherapy cycle, with at least 12 days between doses.6,7 G-CSF use is typically recommended during all chemotherapy cycles in which there is greater than 20% risk of febrile neutropenia.7 G-CSF can also be given to prevent infection in patients who experienced neutropenic complications during a prior round of chemotherapy.Patients treated with G-CSF may have peripheral blasts as high as 40% of circulating leukocytes.8 Although the mechanism of action is uncertain, induction of peripheral blasts by G-CSF may be related to differential expression of isoforms or gene variants in the G-CSF receptor. G-CSF–induced transient increase in peripheral blasts, which is most commonly reported in patients with MDS, AML, and other hematologic malignancies, is treated by withholding G-CSF therapy.3,8-10 Peripheral blasts typically resolve 1 to 2 weeks after peak blast count,8,9 at which point G-CSF therapy can be reinitiated with close monitoring of blood counts.After a 3-day hospitalization, the patient had a white blood cell count of 22.7 × 103/μL with 9% bands, 2% metamyelocytes, 2% myelocytes, 2% promyelocytes, and 4% blasts; hemoglobin was 7.3 g/dL, and platelets were 92 × 103/μL. Ten days after hospital discharge, his white blood cell count was 7.4 × 103/μL with a normal differential and no blasts; hemoglobin was 8.9 g/dL, and platelets were 384 × 103/μL. Two months later, he underwent cystectomy and received treatment with nivolumab for 5 months. However, his cancer progressed, and the patient died 5 months after his initial presentation.

General

An 80-year-old man with stage II bladder carcinoma (T2NXM0) and atrial fibrillation treated with apixaban presented to the emergency department with 1 week of fatigue and 2 days of dyspnea on exertion. One week prior to presentation, he received a fourth cycle of carboplatin/gemcitabine for bladder carcinoma with 6 mg of pegylated granulocyte colony-stimulating factor (G-CSF). The patient reported no anorexia, fever, melena, hematemesis, hematuria, cough, orthopnea, or peripheral edema.His vital signs were normal except for a heart rate of 103/min. His white blood cell count was 22 × 103/μL (reference, 4-11 × 103/μL), increased from 4.8 × 103/μL 8 days prior. His manual differential, which was previously normal, showed 18% bands (0%-10%), 2% metamyelocytes, 7% myelocytes, 7% promyelocytes, and 6% blasts. His hemoglobin level was 5.2 g/dL (reference, 13-17 g/dL), decreased from 7.4 g/dL, and platelets were 25 × 103/μL (reference, 150-420 × 103/μL), decreased from 268 × 103/μL 8 days prior. Ferritin was 1423 ng/mL (reference, 300-400 ng/mL). Mean corpuscular volume, prothrombin time, international normalized ratio, partial thromboplastin time, fibrinogen, haptoglobin, vitamin B12, and methylmalonic acid values were normal, and results of a direct antiglobulin test were negative. A computed tomography (CT) scan of his abdomen and pelvis was normal. He received 2 units of packed red blood cells and was admitted to the hospital. Flow cytometry identified a small population of CD34+/CD117+ cells (Figure).Left, Peripheral blood smear showing normocytic anemia with anisopoikilocytosis and leukocytosis with 6% to 8% blast forms. Right, Flow cytometry of peripheral blood demonstrating a small population of white blood cells that stained positive for CD34 and CD117, which are markers of immature myeloblasts.Esophagogastroduodenoscopy revealed 2 nonbleeding angioectasias in the stomach that were treated with argon plasma coagulation. Three days after admission, his white blood cell count was 27.7 × 103/μL with 4% peripheral blasts, hemoglobin was 7.3 g/dL, and platelet count had increased to 92 × 103/μL without a platelet transfusion.Repeat complete blood cell count with differential in 1 to 2 weeks

what would you do next?

What would you do next?

Start cytoreductive therapy with hydroxyurea

Prescribe all-trans retinoic acid

Repeat complete blood cell count with differential in 1 to 2 weeks

Perform a bone marrow biopsy

c

male

71-80

White

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2810537

A 68-year-old man presented with progressive right-sided facial numbness and weakness, vision changes, and headaches. His symptoms began 5 years earlier with right temple numbness, which expanded to include the entire right face and mouth. He then developed progressive right facial weakness with a droop, slurred speech, and eyelid ptosis. Finally, binocular vertical and horizontal diplopia and periorbital headaches began. Trials of gabapentin and steroids provided no relief. His history was significant for a left cheek melanoma completely excised years prior, numerous cutaneous squamous and basal cell carcinomas of the bilateral head and neck removed without issue, type 2 diabetes, and hyperlipidemia. His medications included metformin and simvastatin; he had no history of smoking or drinking.On examination, he had right-sided ptosis and severe right facial weakness in a lower motor neuron pattern with temporal wasting. The right pupil was fixed and dilated. There was no afferent pupillary defect. The left pupil was appropriately sized and reactive. His right-sided vision was impaired (20/250) with blurriness. Vertical and horizontal binocular diplopia was present. Right extraocular movements were significantly limited in all directions and painful, and right-sided facial sensation was diminished to pinprick in all cranial nerve (CN) V distributions. His speech was slightly slurred. Left-sided extraocular movements were intact. His left facial sensation was intact to pinprick, and his strength was without deficit. There were no other neurological abnormalities.Initial magnetic resonance images (MRIs) were unremarkable. A biopsy of CN VII was nondiagnostic. Hemoglobin A1c was 6.8%. Tests for infection and autoimmune disease had negative results. Cerebrospinal fluid (CSF) studies showed mildly elevated protein values. Figure 1 shows the MRI at presentation.T1 turbo spin-echo fat-saturated magnetic resonance images of the brain through the skull base at presentation. What Is Your Diagnosis?

Primary leptomeningeal lymphoma

Tolosa-Hunt syndrome

Perineural spread of cutaneous malignancy

Sphenoid wing meningioma

C. Perineural spread of cutaneous malignancy

C

Perineural spread of cutaneous malignancy

The MRI of the brain and orbits revealed asymmetric enhancement of the right CNs V and VII, with denervation atrophy of the masticator space (Figure 2). Biopsy of the infraorbital nerve revealed squamous cell carcinoma, thought to have originated from a cutaneous source given his history. Immunotherapy was initiated with cemiplimab. MRI findings have remained stable over the past 2 years with no progression of disease or worsening symptoms.Same magnetic resonance image as in Figure 1B with an arrowhead denoting asymmetric enhancement of the right maxillary nerve in the foramen rotundum.The onset of multiple cranial neuropathies presents a diagnostic dilemma. Oncological diagnosis is often difficult in the absence of an obvious lesion and normal or equivocal imaging.1 This can lead to diagnostic delays and worse outcomes. This patient was seen by 20 different physicians over 5 years, including general, autonomic, and neuromuscular neurologists and neuro-ophthalmologists, before a diagnosis of malignancy was made. It can take time for perineural invasion (PNI) to become radiographically apparent, and a high index of suspicion for underlying malignancy must be maintained even with initially negative imaging.Primary leptomeningeal lymphoma (A) is a rare manifestation of primary central nervous system lymphoma that can present with multiple cranial neuropathies.2 CSF results are usually abnormal and progression of symptoms more rapid.2 Tolosa-Hunt syndrome (B) can present with painful ophthalmoplegia and multiple cranial neuropathies; however, steroids are typically effective.3 When located along the sphenoid wing, meningiomas (D) can cause multiple progressive cranial neuropathies.4 Typically visible on MRI as extra-axial homogenously enhancing masses,4 no such lesion was observed here. In this patient, the symptomatology, history, and radiographic findings are best explained by PNI of cutaneous squamous cell carcinoma (cSCC), which a biopsy confirmed.One of the most common cancers in the world, cSCC occurs frequently in the head and neck secondary to sun exposure.5 PNI refers to the process of tumor spread into nerves and the space surrounding them.6 An estimated 2% to 6% of patients with cSCC of the head and neck will have PNI.1,6 Cranial nerves V and VII are most commonly involved given their extensive anatomical distributions.1,5,6 Clinically or radiographically apparent PNI confers a poor prognosis with a reported 5-year absolute survival rate of 50%.5Treatment for cSCC of the head and neck includes surgery (if resectable) and high-dose radiotherapy and systemic therapy as appropriate. Immunotherapy with checkpoint inhibition is being used with increasing frequency and notable effectiveness.5-9 Early-phase studies demonstrated impressive response rates near 50% for advanced, unresectable, and metastatic cSCC of the head and neck, earning US Food and Drug Administration approval for 2 checkpoint inhibitors in this setting.7,8 Recently, a landmark phase 2 trial of neoadjuvant cemiplimab for stage II through IV (M0) cSCC before surgery was published, with 51% complete pathological response rates and 68% objective response rates on imaging.9 Similarly, in a recent report of 11 patients with cSCC of the head and neck with clinical PNI treated with checkpoint inhibitors, radiographic disease control was observed in 9 of 11 patients at extended follow-up.5 Many of these responses are durable and curative.The presence of both CN V and VII symptoms in a patient with a history of head and neck cSCC should raise suspicion for perineural recurrence of disease. While initial MRI may be negative, radiographic manifestation of PNI often occurs over time as the disease progresses and symptoms worsen. Expert review by a neuroradiologist can be helpful in identifying this finding earlier in the disease course. Mounting evidence suggests that immunotherapy is a promising treatment option for this population and should be considered as first-line therapy.

Neurology

A 68-year-old man presented with progressive right-sided facial numbness and weakness, vision changes, and headaches. His symptoms began 5 years earlier with right temple numbness, which expanded to include the entire right face and mouth. He then developed progressive right facial weakness with a droop, slurred speech, and eyelid ptosis. Finally, binocular vertical and horizontal diplopia and periorbital headaches began. Trials of gabapentin and steroids provided no relief. His history was significant for a left cheek melanoma completely excised years prior, numerous cutaneous squamous and basal cell carcinomas of the bilateral head and neck removed without issue, type 2 diabetes, and hyperlipidemia. His medications included metformin and simvastatin; he had no history of smoking or drinking.On examination, he had right-sided ptosis and severe right facial weakness in a lower motor neuron pattern with temporal wasting. The right pupil was fixed and dilated. There was no afferent pupillary defect. The left pupil was appropriately sized and reactive. His right-sided vision was impaired (20/250) with blurriness. Vertical and horizontal binocular diplopia was present. Right extraocular movements were significantly limited in all directions and painful, and right-sided facial sensation was diminished to pinprick in all cranial nerve (CN) V distributions. His speech was slightly slurred. Left-sided extraocular movements were intact. His left facial sensation was intact to pinprick, and his strength was without deficit. There were no other neurological abnormalities.Initial magnetic resonance images (MRIs) were unremarkable. A biopsy of CN VII was nondiagnostic. Hemoglobin A1c was 6.8%. Tests for infection and autoimmune disease had negative results. Cerebrospinal fluid (CSF) studies showed mildly elevated protein values. Figure 1 shows the MRI at presentation.T1 turbo spin-echo fat-saturated magnetic resonance images of the brain through the skull base at presentation.

what is your diagnosis?

What is your diagnosis?

Tolosa-Hunt syndrome

Perineural spread of cutaneous malignancy

Sphenoid wing meningioma

Primary leptomeningeal lymphoma

b

male

61-70

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2810749

A 31-year-old man presented with left cervical and left inguinal masses. He reported intermittent itching and night sweats for 2 years. He denied fever, weight loss, shortness of breath, rashes, diarrhea, and neurological symptoms. On a preemployment evaluation, the patient was told he had a high white blood cell count 2 years ago. On examination, there was left cervical and inguinal lymphadenopathy and no other organomegaly. Complete blood cell count and peripheral blood smear showed marked leukocytosis, with a white blood cell count of 22 340/μL, an absolute neutrophil count of 5360/μL, and 55% eosinophils with an absolute eosinophil count of 12 290/μL (to convert all to cells ×109/L, multiply by 0.001). Vitamin B12 was markedly elevated at more than 4000 pg/mL (to convert to pmol/L, multiply by 0.7378). The erythrocyte sedimentation rate was 5 mm/h. Lactate dehydrogenase was 180 U/L, and alkaline phosphatase was 81 U/L (to convert both to μkat/L, multiply by 0.0167). Evaluations for HIV and hepatitis B and C were all negative. Serum creatinine was 0.76 mg/dL (to convert to μmol/L, multiply by 88.4); alanine aminotransferase and aspartate aminotransferase were 11 U/L and 9.9 U/L, respectively (to convert to μkat/L, multiply by 0.0167); and total bilirubin was 0.35 mg/dL (to convert to μmol/L, multiply by 17.104). Bone marrow biopsy showed hypercellular marrow (cellularity of 100%), myeloid hyperplasia, increased eosinophils with some dysplasia, and a blast count of 2%. Positron emission tomographic–computed tomographic scan showed a left upper cervical lymph node of 2.6 cm and a left inguinal lymph node of 3.1 × 2.3 cm with an standardized uptake value max of 5.7 (Figure, A). Left inguinal lymph node biopsy showed partial involvement by atypical cells with high proliferation index (Ki-67 >95%) that were positive for CD3, CD4, CD8, BCL2, and TDT, suggestive of T-cell lymphoblastic lymphoma/leukemia (Figure, B).A, Positron emission tomographic–computed tomographic (PET/CT) scan of the head and neck at presentation showing a left upper cervical lymph node of 2.6 cm (arrowhead). B, Lymph node biopsy immunohistochemical stain with terminal deoxynucleotidyl transferase. The inset shows interphase fluorescence in situ hybridization for FIP1L1::PDGFRA rearrangement (positive). C, PET/CT 12 weeks after treatment initiation.Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions What Is Your Diagnosis?

Kimura disease

Classic Hodgkin lymphoma

T-cell acute lymphoblastic lymphoma/leukemia

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

D. Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

D

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

The differential diagnoses in young men with eosinophilia and a neck mass can be wide. The typical presentation of Kimura disease is a painless, unilateral swelling of cervical lymph nodes in young adult male patients with peripheral blood eosinophilia and elevated immunoglobulin E levels. Histological evaluation, however, would show hyperplastic reactive follicles with eosinophilic infiltrates in a background of polymorphous inflammatory cells, a picture inconsistent with the presented case. Although Hodgkin lymphoma can present with eosinophilia and neck mass in young adults, the biopsy was inconsistent with the typical morphology of Reed-Sternberg cells in the background of nonneoplastic inflammatory cells. The diagnosis of T-cell acute lymphoblastic lymphoma/leukemia is reasonable given the morphology from lymph node biopsy; however, in the diagnosis hierarchy, myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) would supersede other myeloid and lymphoid cancers.1In the fifth edition of the World Health Organization Classification of Haematolymphoid Tumours, MLN-TK refers to BCR::ABL1–negative myeloid or lymphoid neoplasms with gene rearrangements leading to an activated tyrosine-kinase domain that results in cell-signaling dysregulation.1 This includes PDGFRA, PDGFRB, FGFR1, JAK2, and FLT3 rearrangements, in addition to ETV6::ABL1, ETV6::FGFR2, ETV6::LYN, ETV6::NTRK3, RANBP2::ALK, BCR::RET, and FGFR1OP::RET fusions.1 An increase in vitamin B12 is often found in patients with PDGFRA and PDGFRB disease.2,3 Most patients are male with chronic myeloid neoplasms with eosinophilia; however, patients rarely present with acute myeloid or T-cell leukemia or extramedullary disease.2Fluorescence in situ hybridization (FISH) was positive for FIP1L1::PDGFRA (4q12) fusion in 91% of nuclei, while karyotype was normal (46, XY in 18 cells), as a cryptic loss of the CHIC2 gene causes this fusion. Next, generation sequencing panel for myeloid neoplasms was negative for variants in targeted regions of the genes commonly involved in myeloid neoplasms. Combining imatinib with chemotherapy is acceptable in patients with acute leukemia or extramedullary diseases, although monotherapy with imatinib has shown promising results.4 The patient was concerned about fertility, as he and his partner were starting a family, and decided to avoid chemotherapy. The patient was concomitantly initiated on 1 mg/kg of prednisone for 7 days and imatinib at 600 mg daily. The eosinophil counts normalized after 2 days, and bone marrow evaluation after 4 weeks showed resolution of eosinophilic infiltration; however, FISH results were 3% positive for FIP1L1::PDGFRA fusion. Repeat bone marrow evaluation after 8 weeks showed complete resolution of the FISH abnormality, and the imatinib dose was reduced to 400 mg daily. Although studies have confirmed deep and durable remission with a starting dose of imatinib, 100 mg, we elected to start with a high dose given the patient’s young age and blastic presentation.5,6 Follow-up positron emission tomographic–computed tomographic scan 12 weeks after initiation of imatinib was consistent with complete metabolic remission (Figure, C). Complete hematological remission is achieved in more than 95% of patients with imatinib and is typically seen early (within weeks of treatment initiation). Cytogenetic/molecular response can be achieved within 3 to 6 months of treatment initiation.7 In patients who achieved molecular remission, the imatinib dose can be reduced to 100 thrice weekly or weekly.8 Treatment-free remission as the experience with chronic myeloid leukemia has been tried, although with limited experience. The success rate is around 60%, with most patients relapsing within the first 10 months. Reinitiating of imatinib restores hematological remission in almost all patients.9,10The current patient was in complete remission 12 months from his treatment and receiving imatinib. Evaluating patients suspected of MLN-TK is critical, as treatment and prognosis may drastically change.

Oncology

A 31-year-old man presented with left cervical and left inguinal masses. He reported intermittent itching and night sweats for 2 years. He denied fever, weight loss, shortness of breath, rashes, diarrhea, and neurological symptoms. On a preemployment evaluation, the patient was told he had a high white blood cell count 2 years ago. On examination, there was left cervical and inguinal lymphadenopathy and no other organomegaly. Complete blood cell count and peripheral blood smear showed marked leukocytosis, with a white blood cell count of 22 340/μL, an absolute neutrophil count of 5360/μL, and 55% eosinophils with an absolute eosinophil count of 12 290/μL (to convert all to cells ×109/L, multiply by 0.001). Vitamin B12 was markedly elevated at more than 4000 pg/mL (to convert to pmol/L, multiply by 0.7378). The erythrocyte sedimentation rate was 5 mm/h. Lactate dehydrogenase was 180 U/L, and alkaline phosphatase was 81 U/L (to convert both to μkat/L, multiply by 0.0167). Evaluations for HIV and hepatitis B and C were all negative. Serum creatinine was 0.76 mg/dL (to convert to μmol/L, multiply by 88.4); alanine aminotransferase and aspartate aminotransferase were 11 U/L and 9.9 U/L, respectively (to convert to μkat/L, multiply by 0.0167); and total bilirubin was 0.35 mg/dL (to convert to μmol/L, multiply by 17.104). Bone marrow biopsy showed hypercellular marrow (cellularity of 100%), myeloid hyperplasia, increased eosinophils with some dysplasia, and a blast count of 2%. Positron emission tomographic–computed tomographic scan showed a left upper cervical lymph node of 2.6 cm and a left inguinal lymph node of 3.1 × 2.3 cm with an standardized uptake value max of 5.7 (Figure, A). Left inguinal lymph node biopsy showed partial involvement by atypical cells with high proliferation index (Ki-67 >95%) that were positive for CD3, CD4, CD8, BCL2, and TDT, suggestive of T-cell lymphoblastic lymphoma/leukemia (Figure, B).A, Positron emission tomographic–computed tomographic (PET/CT) scan of the head and neck at presentation showing a left upper cervical lymph node of 2.6 cm (arrowhead). B, Lymph node biopsy immunohistochemical stain with terminal deoxynucleotidyl transferase. The inset shows interphase fluorescence in situ hybridization for FIP1L1::PDGFRA rearrangement (positive). C, PET/CT 12 weeks after treatment initiation.Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

what is your diagnosis?

What is your diagnosis?

T-cell acute lymphoblastic lymphoma/leukemia

Kimura disease

Classic Hodgkin lymphoma

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions

d

male

31-40

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2810850

A 28-year-old woman presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. She denied recent travel, sick contacts, or autoimmune disease. Her medical history was significant for α-thalassemia but otherwise noncontributory.On examination, she had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. She was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over her face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given her persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy.On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies.Well-defined areas of fibrinoid necrosis in paracortical areas (hematoxylin-eosin, original magnification ×20). What Is Your Diagnosis?

Lymphoma

Kikuchi-Fujimoto disease

Systemic lupus erythematosus

Rosai-Dorfman disease

B. Kikuchi-Fujimoto disease

B

Kikuchi-Fujimoto disease

Common diagnostic considerations of lymphadenopathy alongside recurrent fever in young adults include infection, autoimmune disorders, and malignant neoplasms. Failure of conservative management with antibiotics reduces the likelihood of bacterial infection, whereas lack of cutaneous findings is atypical for a patient with classic systemic lupus erythematosus (SLE) (option C). Furthermore, both FNA and bone marrow biopsy results were not concerning for malignancy. Due to her relatively nonspecific and persistent symptoms, excisional biopsy was performed, giving the final diagnosis of Kikuchi-Fujimoto disease (KFD).Kikuchi-Fujimoto disease (also known as Kikuchi-Fujimoto lymphadenopathy, Kikuchi lymphadenitis, and necrotizing lymphadenitis of unknown etiology) is a benign, self-limiting disease that commonly affects young adults. This rare disease was first reported in Japan in 1972, with the highest prevalence in Asia.1 Patients typically present with painful cervical lymphadenopathy alongside fever and leukopenia.2 It commonly affects women younger than 40 years. Recent studies, however, suggest a more equal distribution among men and women.3Although the etiology is unknown, both autoimmune and viral causes are suspected. Involvement of Epstein-Barr and other herpesviruses is controversial and can be distinguished with periodic acid–Schiff, Grocott methenamine silver, and Ziehl-Nielsen stains. An inappropriate immune reaction has been hypothesized, as KFD is a T-cell–mediated response in those with a specific genetic profile.3 Individuals with KFD have a significantly higher incidence of human leukocyte antigen class II genes (specifically, the DPA1*01 and DPB1*0202 alleles, which are more common in Asian individuals).3 Interestingly, KFD has also occurred in conjunction with SLE, preceding its onset in 30% of cases.4The FNA biopsy is not specific in diagnosing KFD, with an accuracy of 56.7%.5 Therefore, excisional biopsy of the affected lymph nodes is often required. Figure 1 shows a typical necrotic phase of Kikuchi lymphadenitis with well-defined areas of fibrinoid necrosis in paracortical areas of affected lymph nodes. The necrotic foci show abundant karyorrhectic and cellular debris, fibrin deposition, and mononuclear cells (Figure 2). There are no intact neutrophils or eosinophils and only rare plasma cells. Crescentic histiocytes with phagocytized debris are seen along with numerous plasmacytoid dendritic cells/monocytes, macrophages, and activated T cells, which can simulate the appearance of a peripheral T-cell lymphoma. Some cases show prominent xanthomatous inflammation with foamy histiocytes.The necrotic foci show abundant karyorrhectic and cellular debris, fibrin deposition, and mononuclear cells. There are no intact neutrophils or eosinophils and only rare plasma cells. Crescentic histiocytes with phagocytized debris as well as plasmacytoid dendritic cells/monocytes are seen (hematoxylin-eosin, original magnification ×100).This disease is self-limited, lasting 1 to 4 months; although recurrence has been reported, the incidence is 3% to 4%.3 The fatality rate is low and has been reported in only 3 patients. Treatment is largely supportive with analgesic agents, antipyretic agents, and corticosteroids. In patients with recurrent symptoms, low doses of corticosteroids may achieve remission.6The differential diagnosis includes lymphoma with necrosis (option A), cat-scratch disease, and lupus lymphadenitis. Cat-scratch disease is confirmed by serologic testing for Bartonella henselae antibodies.5 Patients with lupus present with lymphadenopathy, fever, skin eruption, and hepatosplenomegaly. In contrast, patients with KFD present with predominantly cervical lymphadenopathy alongside fever and skin eruption.6 Although nonspecific, serologic testing may show leukopenia, anemia, thrombocytopenia, or atypical lymphocytes on peripheral blood smear.At last follow-up, this patient’s fever and lymphadenopathy had resolved, but the skin eruption had progressed to her hands and feet. She is currently receiving prednisone therapy and undergoing an autoimmune workup due to high suspicion of disease progression to SLE or myositis. She will continue to follow up with rheumatology, hematology/oncology, infectious disease, and otolaryngology services.

General

A 28-year-old woman presented with a 5-day history of painful cervical lymphadenopathy along with fever, nausea, and vomiting. Treatment with antibiotics and corticosteroids was started, without improvement of symptoms. She denied recent travel, sick contacts, or autoimmune disease. Her medical history was significant for α-thalassemia but otherwise noncontributory.On examination, she had tender lymphadenopathy involving right level V. A computed tomography scan of the neck revealed a collection of enlarged, matted nodes without evidence of an abscess. Fine-needle aspiration (FNA) biopsy showed nondiagnostic reactive lymph nodes. She was subsequently admitted to the hospital, where the lymphadenopathy progressed to the left side of the neck and a skin eruption developed over her face, back, and trunk. Results of an infectious disease and rheumatological workup, including bone marrow biopsy, were negative. Given her persistent symptoms, the ear, nose, and throat service consulted for excisional biopsy.On pathologic examination, the lymph nodes showed extensive coagulative necrosis, apoptosis, and karyorrhectic debris (Figure 1). Cellular components included histiocytes and dendritic cells, with absent neutrophils and hematoxylin bodies.Well-defined areas of fibrinoid necrosis in paracortical areas (hematoxylin-eosin, original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Lymphoma

Systemic lupus erythematosus

Kikuchi-Fujimoto disease

Rosai-Dorfman disease

c

female

21-30

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2810393

A woman in her 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. She had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, she had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and her vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with her previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis.Patient electrocardiogram showing monomorphic regular wide complex tachycardia with a left bundle branch block morphology, with a precordial transition at V3 and inferior axis suggesting right ventricular origin. What Would You Do Next?

Cardiac magnetic resonance imaging

Electrophysiology study

Genetic testing

Implantation of cardiac defibrillator

Cardiac sarcoidosis

A

Cardiac magnetic resonance imaging

The patient underwent cardiac magnetic resonance imaging, which demonstrated areas of nonischemic near-transmural late gadolinium enhancement (LGE) of the interventricular septum and epicardium to midmyocardium of the LV basal to midanterior and basal inferior walls extending to the RV walls and septal papillary muscle (Figure 2A). However, T2 mapping revealed only discrete evidence of edema of a small region of the midanterior LV wall. Taken together, these findings raised the possibility of end-stage cardiac sarcoidosis (CS).A, Cardiac magnetic resonance imaging using phase-sensitive inversion recovery with motion correction demonstrates multiple areas of subepicardial, midmyocardial, and transmural and near-transmural late gadolinium enhancement in the left ventricle (pink arrowhead) and extending to the right ventricular wall and septal papillary muscle (blue arrowhead). B, Selected matched contiguous short-axis rubidium-82 (top row) and fluorodexoyglucose F 18 (FDG) positron emission tomographic images (bottom row) demonstrate reduced perfusion in the midseptum with marked FDG uptake in the septum and inferior wall, sparing the lateral wall.Cardiac fluorodeoxyglucose F 18 (FDG) and rubidium-82 positron emission tomography (PET) for CS was obtained with a strict high-fat, low-carbohydrate diet, followed by 12 hours of fasting prior to the examination per American Society of Nuclear Cardiology recommendations.1 Because the patient was hospitalized, dietary compliance was ensured. Furthermore, FDG uptake was segmental and the LV blood pool maximum standard uptake value was only 1.1, demonstrating adequate suppression of normal myocardial glucose utilization. There was an extensive FDG uptake (Figure 2B), with maximum standard uptake value of 10.4 in the LV septum. There was also extracardiac FDG uptake in hilar and mediastinal lymph nodes and in multiple pulmonary nodules. Rubidium-82 PET showed only mildly reduced perfusion in the basal to apical septal wall.This case highlights multiple learning points in the use of multimodality imaging for evaluation of patients with CS and understanding its complex pathophysiology. First, the utility of T2 mapping for detecting myocardial edema, a potential surrogate for active inflammation, needs to be better understood, as this can be challenging and in this case underrepresented the extensive positive FDG uptake seen on cardiac PET. Despite extensive LV and RV LGE and depressed biventricular systolic function, substantial myocardial inflammation in this patient is consistent with active rather than end-stage CS. Second, determining individual patient prognosis and assessment of immunosuppression response in patients with CS using cardiac imaging remains challenging. It has been demonstrated that patients without LGE are at an extremely low risk of arrhythmic events.2,3 However, although there is increased risk of arrhythmic events in patients with cardiac involvement identified by LGE, only a fraction of these patients experience arrhythmic events. Patients with both RV and LV LGE are at elevated risk of cardiovascular events compared with patients with only LV enhancement.2-4 Last, while CS is extremely rare after 70 years of age, as the oldest patient reported in the literature was 80 years old,5 this patient presented with CS in her 90s, reminding us that CS remains on the differential diagnosis in patients with sustained ventricular arrythmias regardless of age.Heart failure guideline–directed medical treatment, oral amiodarone, and immunosuppressive therapy consisting of a high, tapering dose of prednisone with mycophenolate mofetil were started. The patient remained stable with no more arrythmias. After shared decision discussions with the patient, a cardiac defibrillator was not implanted given the patient’s age and out of respect for her wishes. She will undergo follow-up FDG-PET to monitor her response to therapy and disease activity.

Cardiology

A woman in her 90s presented to the emergency department with symptoms of fever, hemoptysis, and syncopal episodes. She had a history of breast cancer and pulmonary nodules with biopsy findings negative for metastatic disease but positive for granulomatous inflammation. Initial vital signs included blood pressure of 103/66 mm Hg, heart rate of 190 bpm, and temperature of 38.7 °C. Electrocardiogram showed monomorphic ventricular tachycardia with a morphology suggesting right ventricular (RV) origin (Figure 1). In addition to receiving intravenous amiodarone hydrochloride, she had correction of mild hypokalemia (3.1 mEq/L [reference range, 3.5-5.2 mEq/L]; to convert to mmol/L, multiply by 1.0). Successful arrhythmia termination occurred shortly thereafter, and her vital signs remained stable. Chest computed tomographic angiography excluded pulmonary embolism but showed pulmonary nodules and mediastinal lymphadenopathy that had progressed compared with her previous computed tomography. An echocardiogram showed severe RV and left ventricular (LV) systolic dysfunction with multiple areas of hypokinesis.Patient electrocardiogram showing monomorphic regular wide complex tachycardia with a left bundle branch block morphology, with a precordial transition at V3 and inferior axis suggesting right ventricular origin.

what would you do next?

What would you do next?

Implantation of cardiac defibrillator

Electrophysiology study

Cardiac magnetic resonance imaging

Genetic testing

c

female

91-100

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2810455

A 27-year-old woman presented to her primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the patient described a progressively enlarging lesion on her left scalp, which she had initially noted in high school. She denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and she only reported pain with prolonged pressure. On her scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The patient underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains.Coronal T2-weighted (A) and postcontrast T1-weighted (B) fat-saturated images show the large left T2 hyperintense scalp lesion (double arrowheads; A and B), with underlying calvarial thickening (asterisk; A and B) without invasion, prominent vascularity (single arrowhead; A), and enhancement (B). Note the preservation of the overlying skin. Catheter angiography (C) shows the hypervascular scalp lesion being supplied by hypertrophied branches arising from the left superficial temporal and occipital arteries, with marked internal vascularity (arrowheads). R indicates right. What Is Your Diagnosis?

Arteriovenous malformation of the scalp

Solitary fibrous tumor

Diffuse-type neurofibroma

Dermatofibrosarcoma protuberans

C. Diffuse-type neurofibroma

C

Diffuse-type neurofibroma

Neurofibromas, which are common in the head and neck, arise from endoneurium and connective tissues of peripheral nerve sheaths. From a morphologic and imaging perspective, there are 3 main types of neurofibromas: localized, diffuse, and plexiform.1 Diffuse neurofibromas are rare and represent less than 5% to 10% of all neurofibromas. The localized type, which is more common (>90%) and is the most well recognized and documented, is usually not a diagnostic conundrum. Plexiform neurofibromas, the other subtype, also have a pathognomonic imaging appearance and are frequently associated with neurofibromatosis 1, with findings of multiple lesions at different sites, which makes the diagnosis easier. Diffuse neurofibromas, however, are frequently solitary and are mostly sporadic, with few reported cases of associated with neurofibromatosis 1 (NF1).2 These lesions are more often seen in children and young adults. They are unusually large and frequently multispatial, with ill-defined margins, which appear to infiltrate and grow around tissues rather than invade them.On imaging, these are frequently plaquelike infiltrative lesions, unlike the more rounded or nodular appearance of localized neurofibromas, with frequent involvement of the subcutaneous/deep fascia both underlying the skin and overlying the musculature. Another characteristic is preservation of the overall morphologic features of the involved tissue space due to its unusual infiltrative pattern.2 A lesser known feature of these lesions is that many also demonstrate marked internal vascularity with prominent flow voids, arterial feeders, and draining veins, which can sometimes mimic vascular malformations.3 On MRI, these are isointense to mildly hyperintense to muscle on T1-weighted imaging and mild to markedly hyperintense on T2-weighted imaging to muscle, with marked enhancement. The lesions are usually solid without any necrotic or cystic changes, calcification, or hemorrhage.Solitary fibrous tumors (option B) (previously referred to as hemangiopericytomas) are rare mesenchymal-origin lesions, usually in older adults. On MRI, these are homogeneous lesions, with usually low to intermediate signals on both T1- and T2-weighted sequences (relative to muscle), with intense enhancement. They can be plaquelike and are frequently hypervascular, with numerous flow voids.4 Rarely, they may have a heterogeneous appearance secondary to internal hemorrhage or necrosis. They frequently mimic meningiomas when they arise intracranially.Scalp arteriovenous malformations (option A) are rare, and they present in children and young adults. On imaging, a predominant vascular lesion is identified with numerous flow voids due to its high flow state. The imaging features can be variable if there are associated abnormalities as well as other low-flow lesions, such as venous or lymphatic malformations. Vascular imaging, such as computed tomographic and magnetic resonance angiography, ultrasonography, and catheter angiography, is frequently done for both diagnosis and treatment planning.5Dermatofibrosarcoma protuberans (option D) are rare superficial lesions of the dermis, usually presenting in the third to fourth decade of life. These are locally aggressive, infiltrative masses that can arise in the head and neck, including the scalp. They present as a painless, slow-growing, nodular mass–like firm lesion. On imaging, these are markedly enhancing lesions, usually T1 hypointense and T2 hyperintense, with no vascular flow voids, underlying osseous invasion, or perineural spread.6 However, underlying calvarial thinning is seen in a few cases.Given the findings of the large scalp neurofibroma and her age, the patient was advised to undergo comprehensive genetic testing for NF1. Although NF1 is autosomal dominant and the patient had a negative family history, almost half of all individuals with NF1 are the first person in their family to have NF1 (de novo variant).7 The patient tested negative for identifiable pathogenic variants in the NF1 or SPRED1 genes, decreasing her risk of having NF1 and confirming that this was likely a sporadic neurofibroma.

General

A 27-year-old woman presented to her primary care physician with primary complaints of headaches and visual-spatial difficulties when driving at night. In addition, the patient described a progressively enlarging lesion on her left scalp, which she had initially noted in high school. She denied any overlying loss of hair, sharp pain, or bleeding from the scalp lesion, and she only reported pain with prolonged pressure. On her scalp examination, a 7-cm ill-defined spongy and pulsatile mass was noted with an overlying gray patch of hair. Magnetic resonance imaging (MRI) of the brain/orbit was initially performed (Figure, A and B), which demonstrated an ill-defined, diffuse, intensely enhancing scalp lesion in the left frontoparietal region with very prominent vascularity and underlying calvarial thickening. No osseous destruction or intracranial extension was present. Subsequent catheter angiography (Figure, C) confirmed the hypervascular mass, supplied via hypertrophied superficial temporal and occipital arteries with marked internal vascularity without direct involvement of the calvarium or intracranial structures. The patient underwent biopsy under general anesthesia; the specimen showed an ill-defined deep dermal/subcutaneous proliferation of spindle cells without significant nuclear pleomorphism or mitotic activity. The lesions stained positive for S100 and SOX10 immunostains.Coronal T2-weighted (A) and postcontrast T1-weighted (B) fat-saturated images show the large left T2 hyperintense scalp lesion (double arrowheads; A and B), with underlying calvarial thickening (asterisk; A and B) without invasion, prominent vascularity (single arrowhead; A), and enhancement (B). Note the preservation of the overlying skin. Catheter angiography (C) shows the hypervascular scalp lesion being supplied by hypertrophied branches arising from the left superficial temporal and occipital arteries, with marked internal vascularity (arrowheads). R indicates right.

what is your diagnosis?

What is your diagnosis?

Diffuse-type neurofibroma

Dermatofibrosarcoma protuberans

Solitary fibrous tumor

Arteriovenous malformation of the scalp

a

female

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2810452

A woman in her 30s presented for evaluation of asymptomatic erythematous scaly plaques over the face and proximal extremities. The lesions started as an erythematous papule on the face, which had progressed to larger plaques within 10 years. There was involvement of the upper respiratory tract, causing palatal perforation and stridor, necessitating a tracheostomy a year ago. In addition, there was history of wheezing and breathlessness. There was no history of preceding trauma, fever, malaise, joint pain, cough, epistaxis, hemoptysis, or hematuria.Examination revealed multiple well-defined brown erythematous scaly plaques with central scarring measuring 2 × 1 to 8 × 7 cm on the face, arm, and thighs. The patient also had saddle nose deformity, perforation of the hard palate, and necrotic plaques on the ear, causing destruction of ear cartilage (Figure, A and B). There was cervical lymphadenopathy: multiple, nontender, discrete nodes, ranging from 1.5 to 2 cm without any surface changes. The results of sensory examination and peripheral nerve examination were within normal limits. Respiratory examination and chest radiography results were normal. Hemogram showed anemia (hemoglobin, 10.1 g/dL [to convert to g/L, multiply by 10.0]); the results of a kidney function test, a liver function test, a fasting blood glucose test, and routine urinalysis were within normal limits. Serologic analysis results for HIV-1/2, antinuclear antibody, and antineutrophil cytoplasmic antibodies were negative. Punch skin biopsy was obtained for histopathologic analysis and culture (Figure, C).A, Multiple well-defined brown erythematous scaly plaques with central scarring, saddle nose deformity, and necrotic lesions on the ear with loss of ear cartilage. B, Perforation of the hard palate. C, Infiltrate of foamy histiocytes and pigmented yeasts without multiaxial septation (Fontana-Masson). What Is Your Diagnosis?

Chromoblastomycosis

Hyalohyphomycosis

Blastomycosis

Phaeohyphomycosis

D. Phaeohyphomycosis

D

Phaeohyphomycosis

Histopathologic results showed pseudoepitheliomatous hyperplasia, parakeratosis, dense dermal infiltrate of histiocytes, foamy histiocytes, neutrophils, and multinucleate giant cells along with pigmented hyphae. Fungal skin culture showed black yeastlike colonies characteristic of Exophiala spinifera species. Based on clinical presentation, histopathologic analysis, and fungal culture, the diagnosis of phaeohyphomycosis was made. The patient will be treated with intravenous amphotericin B, followed by itraconazole.Phaeohyphomycosis is a rare subcutaneous mycosis caused by dematiaceous fungi found in soil, wood, and decomposing vegetation. The disease, caused by dematiaceous fungi, is classified into 2 types based on fungal forms in the tissue: phaeohyphomycosis (presence of yeasts and hyphae) and chromoblastomycosis (muriform bodies). The literal meaning of phaeohyphomycosis is dark fungus with hyphae. The pigment melanin in the fungus is a virulence factor that inhibits phagocytosis by scavenging free radicals produced by the host. The common etiological agents are Exophiala, Aureobasidium, Cladosporium, Alternaria, Phialophora, Wangiella, and Curvularia.1 Phaeohyphomycosis can affect skin, subcutaneous tissue, paranasal sinuses, and, rarely, the central nervous system. Commonly, it presents as asymptomatic cystic swelling on exposed areas, usually after traumatic inoculation involving the hands, feet, and legs. Facial involvement is uncommon and can extend to involve the upper respiratory tract, causing perforation of the palate and destruction of the nasal bridge, leading to mutilation and disfigurement.2-4 Other rare presentations include verrucous plaques, erythematous papules, and noduloulcerative lesions. The diagnosis can be confirmed by demonstration of pigmented septate hyphae with occasional globose swelling on histopathologic analysis and fungal culture. Panfungal real-time polymerase chain reaction is an emerging tool in the diagnosis of phaeohyphomycosis. Treatment with azole antifungal agents (itraconazole, posaconazole, or voriconazole) is the mainstay of treatment. Other treatment options include amphotericin B, terbinafine, flucytosine, and griseofulvin along with physical modalities, such as excision, heat therapy, and cryotherapy.5The common deep mycoses that can cause mutilation include chromoblastomycosis, hyalohyphomycosis, blastomycosis, and phaeohyphomycosis. Both chromoblastomycosis and phaeohyphomycosis are caused by dematiaceous fungi. Chromoblastomycosis (option A) is commonly caused by Fonsecaea pedrosoi, Fonsecaea monophora, and Cladophialophora carrionii and usually presents with localized, verrucous, hyperkeratotic, irregular plaque on distal extremities with scarring.6 Hyalohyphomycosis (option B) is a rare opportunistic fungal infection caused by various fungi, which produce nonpigmented septate hyphae. It has myriad presentations, which include erythematous macules, papules, vesicles, indurated verrucous plaques, necrotic ulcers, and discharging sinus.7 Blastomycosis (option C) is a suppurative fungal infection caused by Blastomyces dermatitidis, endemic in the Ohio and Mississippi River valleys, the Great Lakes, and the Saint Lawrence River. It presents with papulopustular lesions, violaceous nodules, plaques, abscesses, ulcers, and verrucous or crusted lesions on exposed body parts.8 All these infections can have systemic involvement. Chromoblastomycosis involves lungs, lymph nodes, and bone, and hyalohyphomycosis primarily affects paranasal sinuses and lungs. Blastomycosis involves lymph nodes, bone, prostate, and testis, and phaeohyphomycosis commonly involves lungs and heart.All the differential diagnoses show suppurative granuloma on histopathologic analysis; the establishment of the respective fungal form helps in confirming the diagnosis. Chromoblastomycosis is characterized by thick-walled, multicellular, globe-shaped, cigar-colored inclusion bodies with multiaxial septation called sclerotic bodies (Medlar bodies).6 Hyphae in cross-sections in the index case resembled Medlar bodies, and the absence of septation was a clue indicating phaeohyphomycosis.7 Hyalohyphomycosis is characterized by nonpigmented septate hyphae, and culture helps in confirming the diagnosis.8 Large (8-15 μm) thick-walled yeast cells, prominent broad-based budding, and centrally retracted cytoplasm help in the diagnosis of blastomycosis.9Although many clinical differential diagnoses were considered in the case presented, histopathologic analysis and culture played decisive roles in arriving at a diagnosis of phaeohyphomycosis. This case highlights the importance of recognition of rare presentation of deep mycosis and the value of histopathologic analysis and fungal cultures in establishing the right diagnosis.

Dermatology

A woman in her 30s presented for evaluation of asymptomatic erythematous scaly plaques over the face and proximal extremities. The lesions started as an erythematous papule on the face, which had progressed to larger plaques within 10 years. There was involvement of the upper respiratory tract, causing palatal perforation and stridor, necessitating a tracheostomy a year ago. In addition, there was history of wheezing and breathlessness. There was no history of preceding trauma, fever, malaise, joint pain, cough, epistaxis, hemoptysis, or hematuria.Examination revealed multiple well-defined brown erythematous scaly plaques with central scarring measuring 2 × 1 to 8 × 7 cm on the face, arm, and thighs. The patient also had saddle nose deformity, perforation of the hard palate, and necrotic plaques on the ear, causing destruction of ear cartilage (Figure, A and B). There was cervical lymphadenopathy: multiple, nontender, discrete nodes, ranging from 1.5 to 2 cm without any surface changes. The results of sensory examination and peripheral nerve examination were within normal limits. Respiratory examination and chest radiography results were normal. Hemogram showed anemia (hemoglobin, 10.1 g/dL [to convert to g/L, multiply by 10.0]); the results of a kidney function test, a liver function test, a fasting blood glucose test, and routine urinalysis were within normal limits. Serologic analysis results for HIV-1/2, antinuclear antibody, and antineutrophil cytoplasmic antibodies were negative. Punch skin biopsy was obtained for histopathologic analysis and culture (Figure, C).A, Multiple well-defined brown erythematous scaly plaques with central scarring, saddle nose deformity, and necrotic lesions on the ear with loss of ear cartilage. B, Perforation of the hard palate. C, Infiltrate of foamy histiocytes and pigmented yeasts without multiaxial septation (Fontana-Masson).

what is your diagnosis?

What is your diagnosis?

Blastomycosis

Phaeohyphomycosis

Hyalohyphomycosis

Chromoblastomycosis

b

female

31-40

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2808316

A 64-year-old man with a 2-year history of seizure disorder presented to the emergency department (ED) at an outside hospital with breakthrough seizures. One month prior to his ED visit, he had been treated with oral antibiotics when he presented to an urgent care center with left-sided otorrhea, otalgia, and hearing loss. In the ED, he denied headaches, fever, otalgia, otorrhea, or hearing loss. Magnetic resonance imaging of the brain with contrast showed diffuse enhancement and possible coalescence in the left mastoid process with adjacent dural enhancement and sigmoid sinus occlusion. He received intravenous vancomycin and cefepime and was started on a heparin drip before being transferred to our facility. On presentation at our facility, the patient appeared well with normal vital signs. There was no periauricular swelling or erythema. Otoscopic examination showed no inflammation of the external auditory canals, and the tympanic membranes were translucent without evidence of retraction or effusion. Computed tomographic venogram confirmed occlusion of the left transverse and sigmoid sinuses, and computed tomography of the temporal bone showed coalescence of mastoid air cells with erosion into the sigmoid sinus. Mastoidectomy was performed for biopsy and culture specimens. Histologic findings from the specimens demonstrated cells with oval nuclei and abundant cytoplasm arranged in syncytial clusters with occasional whorls, pseudoinclusions, and psammomatous calcifications (Figure, A). Immunohistochemical stains were positive for epithelial membrane antigen (EMA) and vimentin (Figure, B).Hematoxylin-eosin stain (A) and immunohistochemical stain (B) after mastoidectomy for biopsy and culture specimens. What Is Your Diagnosis?

Langerhans cell histiocytosis

Meningioma

Acute coalescent mastoiditis with sigmoid sinus thrombosis

Cholesteatoma

B. Meningioma

B

Meningioma

This patient presented to the ED with an acute exacerbation of a seizure disorder. The recent history of left-sided otorrhea and otalgia with magnetic resonance imaging enhancement in the mastoid along with dehiscence and occlusion of the adjacent venous sinuses suggested that the seizure may have been triggered by an indolent suppurative complication of mastoiditis. However, because the patient’s otologic symptoms had resolved and he did not appear septic, temporal bone neoplasm was considered. Mastoidectomy revealed solid tumor attached to the sigmoid sinus with no evidence of mastoid suppuration or inflammatory process, and the biopsy was diagnostic for intraosseous meningioma.Meningiomas typically are intracranial neoplasms, but 2% present as extracranial intraosseous lesions.1,2 Extracranial meningiomas present in the middle ear, external auditory canal, petrous bone, squamous temporal bone, and paranasal sinuses.1 Histologic sections in this case showed findings consistent with a meningothelial variant of meningioma World Health Organization grade I.1,3 Immunohistochemistry studies confirmed the diagnosis with positive EMA and vimentin staining.3 However, somatostatin receptor subtype 2A and progesterone receptors are more sensitive for diagnosis. Intraosseous meningiomas originate from arachnoid cap cells associated with the sigmoid sinus or adjacent dura. As was the case with this patient, most patients with temporal bone intraosseous meningiomas are asymptomatic, and observation with serial imaging is appropriate. Surgical debulking or resection is considered when tumors grow and extend into the middle ear causing hearing loss, compromising patency of the external auditory canal, or compressing the facial nerve. Fractionated external-beam radiation therapy or stereotactic radiation therapy are also options for treating growing tumors, but there is a high risk of profound hearing loss.2Coalescent mastoiditis can present with intracranial complications such as sigmoid sinus thrombosis or subperiosteal abscess.4 Typically, patients with acute mastoiditis present with headaches, vomiting, seizures, otalgia, otorrhea, and fever.5 Physical findings include tenderness and swelling inferior to the temporal line, purulent middle ear effusion, and conductive hearing loss. Cholesteatoma can be the source of infection in patients with acute mastoiditis, but otomicroscopic findings would reveal a retraction of the tympanic membrane, scutal erosion, or secondary acquired cholesteatoma associated with a tympanic membrane perforation. The absence of these symptoms and physical findings make these diagnoses less likely, yet it is possible to have an indolent progressive suppurative mastoid infection that remains isolated from the middle ear and erodes the thin bony plate over the sigmoid sinus. Mastoidectomy was critical to differentiate an infectious process from neoplastic pathology. Histologic results for a cholesteatoma would reveal keratinizing stratified squamous epithelium with stromal fibrosis. Biopsy in patients with mastoiditis shows granulation tissue, acute and chronic leukocyte infiltration, and hemorrhage with negative EMA and vimentin staining. Mastoidectomy in patients with acute coalescent mastoiditis provides drainage of the infection and cultures to select intravenous antibiotics. Anticoagulation may be recommended when acute coalescent mastoiditis results in sigmoid sinus thrombosis.6,7Langerhans cell histiocytosis of the temporal bone is extremely rare in older adults. Patients present with otorrhea, subjective hearing loss, otalgia, and soft-tissue postauricular swelling.8 Physical examination shows granulation tissue in the external ear canal, middle ear effusion, conductive hearing loss, and external auditory canal stenosis.8 The absence of these symptoms and physical examination findings make this diagnosis less likely. Computed tomography of the temporal bone shows erosion of mastoid air cells and destruction of the mastoid cortex while the otic capsule is spared.9 Computed tomographic imaging is critical for diagnosing and following Langerhans cell histiocytosis, but biopsy is required to confirm the diagnosis. Histological sections typically demonstrate mononuclear cells with coffee bean nuclei that are CD1a, S100, and langerin positive.8,9 For focal lesions, surgery is recommended, and for multifocal lesions chemotherapy (typically vincristine and steroids) and surgery is recommended.8,10

General

A 64-year-old man with a 2-year history of seizure disorder presented to the emergency department (ED) at an outside hospital with breakthrough seizures. One month prior to his ED visit, he had been treated with oral antibiotics when he presented to an urgent care center with left-sided otorrhea, otalgia, and hearing loss. In the ED, he denied headaches, fever, otalgia, otorrhea, or hearing loss. Magnetic resonance imaging of the brain with contrast showed diffuse enhancement and possible coalescence in the left mastoid process with adjacent dural enhancement and sigmoid sinus occlusion. He received intravenous vancomycin and cefepime and was started on a heparin drip before being transferred to our facility. On presentation at our facility, the patient appeared well with normal vital signs. There was no periauricular swelling or erythema. Otoscopic examination showed no inflammation of the external auditory canals, and the tympanic membranes were translucent without evidence of retraction or effusion. Computed tomographic venogram confirmed occlusion of the left transverse and sigmoid sinuses, and computed tomography of the temporal bone showed coalescence of mastoid air cells with erosion into the sigmoid sinus. Mastoidectomy was performed for biopsy and culture specimens. Histologic findings from the specimens demonstrated cells with oval nuclei and abundant cytoplasm arranged in syncytial clusters with occasional whorls, pseudoinclusions, and psammomatous calcifications (Figure, A). Immunohistochemical stains were positive for epithelial membrane antigen (EMA) and vimentin (Figure, B).Hematoxylin-eosin stain (A) and immunohistochemical stain (B) after mastoidectomy for biopsy and culture specimens.

what is your diagnosis?

What is your diagnosis?

Acute coalescent mastoiditis with sigmoid sinus thrombosis

Meningioma

Cholesteatoma

Langerhans cell histiocytosis

b

male

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2808660

A 62-year-old healthy man with no recent travel history or sick contacts presented with 2 weeks of midline sore throat without systemic signs, such as fever, myalgia, or rash. A physical examination, including flexible laryngoscopy, revealed cobbling, adherent, thick yellow mucus and ulceration of the uvula (Figure 1A).A, Nasopharyngoscopic imaging revealed infected nasal surface of uvula. B, Physical examination showed recurrent skin lesions at incision site and in the surrounding skin.Empirical treatment with augmentin and nystatin oral suspension for possible bacterial or fungal pharyngitis was unsuccessful, with symptoms worsening during the subsequent 2 weeks. Results of laboratory testing for group A Streptococcus, COVID-19, and mononucleosis were negative. A tissue biopsy was performed, and results of pathology revealed epithelial hyperplasia with suppurative granulomatous inflammation without evidence of dysplasia or malignancy. There was no evidence of fungal or acid-fast organisms. Tissue culture revealed only normal respiratory flora. Additional treatment with fluconazole, augmentin, doxycycline, omeprazole, prednisone, and bactrim failed to improve symptoms.Further exploration of the patient’s history revealed that 5 years earlier, he had traveled to Guyana in South America. After that trip, he sought medical care for multiple neck subcutaneous nodules as well as for a 4-cm focus of neck cellulitis. After failed treatment with empirical antibiotics, the largest lesion was excised. Findings of pathologic testing revealed dense granulomatous inflammation. However, results of stains for bacteria, fungus, and acid-fast bacillus were negative (Figure 1B). The remaining cutaneous and subcutaneous nodules had resolved spontaneously. What Is Your Diagnosis?

Leishmaniasis

Tuberculosis

Leprosy

Lethal midline granuloma

A. Leishmaniasis

A

Leishmaniasis

Polymerase chain reaction (PCR) testing of the uvular tissue confirmed the presence of Leishmania braziliensis. A reevaluation of Giemsa (May-Grunwald) stains of the original cutaneous lesion revealed intracytoplasmic organisms, morphologically consistent with Leishmania species (Figure 2). These organisms were not visible in the uvular biopsy specimen. Treatment with 50 mg of miltefosine 3 times daily for 28 days led to complete resolution of the mucosal lesion and associated symptoms.Results of hematoxylin-eosin staining (original magnification, ×60) intracytoplasmic organisms consistent with leishmaniasis.Infection with L (Viannia) complex, particularly L (Viannia) braziliensis, results in cutaneous leishmaniasis, which tends to be persistent and may be complicated by mucosal leishmaniasis (ML).1 Risk factors for development of ML include large and/or multiple cutaneous lesions; male sex; lesions above the waist, head, and neck localization; and long-standing skin lesions for which adequate systemic treatment has not been administered.3The overall lifetime risk of ML from L (Viannia) braziliensis was reported as being 12.8% among a cohort of 3000 patients in Brazil.4 A case series of 145 patients with cutaneous leishmaniasis caused by L (Viannia) braziliensis reported a 41% incidence of ML among untreated patients and 3.3% in patients who had received appropriate treatment.5 The median time to presentation for ML is approximately 8 months after exposure or cutaneous lesion, ranging from concurrent skin lesions to 20 years after untreated lesion or exposure. Likely caused by early hematogenous or lymphatic spread from cutaneous lesions through parasitic infection and replication within macrophages of the naso-oropharyngeal mucosa, ML produces a destructive inflammatory process.For ML diagnosis, PCR is performed as the standard criterion for diagnosis. Biopsy specimens consistently reveal granulomatous inflammation; however, amastigote identification is uncommon.2In the case of this patient, tuberculosis was unlikely given the absence of pulmonary symptoms, no acid-fast bacilli on pathology and culture results, and the nonnecrotizing granulomatous inflammation. Leprosy was also not likely because it is not endemic to the places where this patient traveled, and it tends to affect nasal rather than pharyngeal mucosa. Lastly, natural killer or T-cell lymphomas, which are clinically very aggressive, were also unlikely considering this patient’s relatively indolent disease course as well as the PCR findings.

General

A 62-year-old healthy man with no recent travel history or sick contacts presented with 2 weeks of midline sore throat without systemic signs, such as fever, myalgia, or rash. A physical examination, including flexible laryngoscopy, revealed cobbling, adherent, thick yellow mucus and ulceration of the uvula (Figure 1A).A, Nasopharyngoscopic imaging revealed infected nasal surface of uvula. B, Physical examination showed recurrent skin lesions at incision site and in the surrounding skin.Empirical treatment with augmentin and nystatin oral suspension for possible bacterial or fungal pharyngitis was unsuccessful, with symptoms worsening during the subsequent 2 weeks. Results of laboratory testing for group A Streptococcus, COVID-19, and mononucleosis were negative. A tissue biopsy was performed, and results of pathology revealed epithelial hyperplasia with suppurative granulomatous inflammation without evidence of dysplasia or malignancy. There was no evidence of fungal or acid-fast organisms. Tissue culture revealed only normal respiratory flora. Additional treatment with fluconazole, augmentin, doxycycline, omeprazole, prednisone, and bactrim failed to improve symptoms.Further exploration of the patient’s history revealed that 5 years earlier, he had traveled to Guyana in South America. After that trip, he sought medical care for multiple neck subcutaneous nodules as well as for a 4-cm focus of neck cellulitis. After failed treatment with empirical antibiotics, the largest lesion was excised. Findings of pathologic testing revealed dense granulomatous inflammation. However, results of stains for bacteria, fungus, and acid-fast bacillus were negative (Figure 1B). The remaining cutaneous and subcutaneous nodules had resolved spontaneously.

what is your diagnosis?

What is your diagnosis?

Leprosy

Lethal midline granuloma

Leishmaniasis

Tuberculosis

c

male

61-70

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2808228

A 53-year-old woman with a history of stage IVA1 (T4N1M0B2) mycosis fungoides presented with a new 1-month history of hyperpigmentation of the oral mucosa (Figure 1). Examination of the mouth revealed multiple coalescing painless nonpruritic black macules and patches on the tongue, roof of the mouth, and buccal mucosa. Examination of the skin was notable for erythematous and hyperpigmented patches covering 90% of the body surface area, consistent with her known mycosis fungoides. Other notable findings on examination were 1- to 2-cm lymphadenopathy in the bilateral inguinal folds and axillae. Review of systems was notable for fatigue. The patient had previously received 5 cycles of romidepsin with progression of disease, followed by 4 doses of pegylated liposomal doxorubicin hydrochloride, which was followed by partial response.Black macules and patches on the tongue, roof of the mouth, and buccal mucosa. What Is Your Diagnosis?

Laugier-Hunziker syndrome

Melanoma

Medication adverse effect

Oral involvement of mycosis fungoides

C. Medication adverse effect

C

Medication adverse effect

Oral hyperpigmentation is a rare adverse effect of certain chemotherapy agents, such as doxorubicin. The exact mechanism of this phenomenon is not well understood. One hypothesis is that chemotherapy drugs can trigger increased melanin deposition in the oral mucosa. The risk is thought to be higher in individuals of African descent.1,2 However, this adverse effect is underreported, and it is important for treating physicians to be familiar with this adverse effect to avoid unnecessary testing and undue stress to the patient.Doxorubicin is an anthracycline-based chemotherapy that is frequently used as a single agent or in combination therapy to treat various types of cancer, such as breast cancer, multiple myeloma, and non-Hodgkin lymphoma.3 Doxorubicin directly inhibits topoisomerase II, thereby preventing DNA synthesis.3 There are several formulations, including pegylated liposomal doxorubicin and nonliposomal conventional formulations.3 Single-agent pegylated liposomal doxorubicin is typically used for treatment of advanced mycosis fungoides.4 Although this is often an effective treatment option in cases of refractory and recalcitrant mycosis fungoides, it is also associated with several oral adverse effects, including mucositis, altered taste, and oral hyperpigmentation.5Doxorubicin-induced oral hyperpigmentation is a rare adverse effect that typically presents with multiple coalescing, painless black macules and patches on the tongue, roof of the mouth, and buccal mucosa.2,6,7 The hyperpigmented areas may be uniform in color or have a speckled appearance.2,6,7 These lesions are benign and do not cause any pain or discomfort.2,6,7 However, they may sometimes be accompanied by other oral mucosal changes associated with chemotherapy, such as candidiasis or mucositis.2,6,7 Oral hyperpigmentation usually occurs within the first few weeks of treatment, and it is usually reversible within a few months after discontinuation of doxorubicin.2,6,7Doxorubicin-induced tongue hyperpigmentation is usually a clinical diagnosis based on the patient’s history of chemotherapy and the characteristic appearance of the oral lesions.2,6,7 It is important to rule out other potential causes of oral hyperpigmentation, such as melanoma (choice B) or oral involvement of mycosis fungoides (choice D). Melanoma usually presents as a solitary, asymmetric, and irregularly shaped lesion, in contrast to the multiple black macules and patches seen in this patient.8 Oral involvement of cutaneous lymphoma is a rare complication; prior case reports describe flesh-colored or erythematous plaques and ulcerated nodules that are associated with global disease progression.9 Laugier-Hunziker syndrome (choice A) is a rare idiopathic condition that usually presents with nail hyperpigmentation in addition to mucosal pigmentation.10 This is a diagnosis of exclusion and would not resolve with cessation of medications.As doxorubicin-induced oral hyperpigmentation is benign and self-limiting, the inciting chemotherapy can be continued for treatment of the patient’s primary illness. Additional therapy is not needed, and the hyperpigmentation will slowly resolve during the course of months to years after completion of chemotherapy. In the meantime, the patient should be reassured that the hyperpigmentation is a benign adverse effect of chemotherapy and is unrelated to the underlying cancer.In this case, the patient developed oral mucosal hyperpigmentation after receiving 4 doses of pegylated liposomal doxorubicin. The patient was reassured that mucosal hyperpigmentation is a rare benign adverse effect of pegylated liposomal doxorubicin that is more common in Black women and unrelated to mycosis fungoides. She continued receiving pegylated liposomal doxorubicin for 33 total doses, with an overall good partial response. She did not develop any other types of hyperpigmentation. Once the course of doxorubicin was completed, the oral mucosal hyperpigmentation resolved during the course of the next several months (Figure 2).Resolution of oral pigmentation after cessation of doxorubicin therapy.

Oncology

A 53-year-old woman with a history of stage IVA1 (T4N1M0B2) mycosis fungoides presented with a new 1-month history of hyperpigmentation of the oral mucosa (Figure 1). Examination of the mouth revealed multiple coalescing painless nonpruritic black macules and patches on the tongue, roof of the mouth, and buccal mucosa. Examination of the skin was notable for erythematous and hyperpigmented patches covering 90% of the body surface area, consistent with her known mycosis fungoides. Other notable findings on examination were 1- to 2-cm lymphadenopathy in the bilateral inguinal folds and axillae. Review of systems was notable for fatigue. The patient had previously received 5 cycles of romidepsin with progression of disease, followed by 4 doses of pegylated liposomal doxorubicin hydrochloride, which was followed by partial response.Black macules and patches on the tongue, roof of the mouth, and buccal mucosa.

what is your diagnosis?

What is your diagnosis?

Laugier-Hunziker syndrome

Medication adverse effect

Melanoma

Oral involvement of mycosis fungoides

b

female

51-60

Black

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2809279

A 33-year-old man with no prior ocular problems presented to the emergency department in central Florida with a chief complaint of a “pulling and popping” sensation in his left eye that had occurred the previous night. Ophthalmology was consulted to evaluate for a conjunctival foreign body of the left eye. At the time of the examination, his symptoms had resolved; however, he had a photograph from a cellular phone taken during the episode (Figure 1). The photograph shows an irregular, serpiginous extension from beneath the plica semilunaris toward the corneal limbus with localized conjunctival hyperemia. He reported a similar sensation of movement in his left eye that occurred for 1 night about 5 years ago for which he visited an urgent care center where he was diagnosed with allergic conjunctivitis. He also reported recent swelling of the left side of his face with associated numbness and occasional swelling of his left hand, all of which resolved after a few days. He had immigrated from Nigeria 10 years prior, had not returned since, and was working as a traveling nurse. A slitlamp examination did not reveal any conjunctival hyperemia, foreign bodies, or other abnormalities like those shown in the photograph. His uncorrected visual acuity was 20/20, extraocular movements were full and without pain or abnormal sensation, and intraocular pressure was normal. His dilated fundus examination was unremarkable. A comprehensive blood cell count revealed mild elevation in the relative (but not absolute) eosinophil count (6.9% reference; 6.0% of white blood cells).Patient cellular phone photograph of the left eye shows an irregular serpiginous extension from beneath the plica semilunaris toward the corneal limbus with localized conjunctival hyperemia.Exploration of conjunctiva and removal of foreign body What Would You Do Next?

Treatment with diethylcarbamazine

Peripheral blood smear

Serological testing for onchocerciasis

Exploration of conjunctiva and removal of foreign body

Loa loa infection

B

Peripheral blood smear

In this Nigerian patient with a sensation of movement of the left eye, a photograph showing serpiginous conjunctival elevation, and intermittent swelling of the dorsum of the hand, the most likely diagnosis is Loa loa. Also known as the African eye worm, Loa loa is a filarial nematode transmitted by day-biting flies of the genus Chrysops endemic to Western and Central Africa.1 After a bite from an infected fly, filarial larvae introduced into the subcutaneous tissue mature into adult worms that shed microfilariae that migrate into the spinal fluid, urine, sputum, and peripheral blood.2 Most infections are asymptomatic despite high numbers of circulating microfilaria; however, patients may have characteristic symptoms that include migratory angioedema of the extremities (so-called Calabar swellings) and migration of adult worms into the subconjunctival space as in this patient.3,4The recommended next step in the treatment of this patient is a peripheral blood smear for species identification and quantification of circulating microfilariae (choice B). Blood should be drawn between 10 am and 2 pm during the migration of microfilaria from the lungs into the peripheral circulation; this diurnal pattern coincides with the biting activity of the vector. Diethylcarbamazine is the first-line therapy due to its ability to eradicate both microfilaria and adult worms, while empirical therapy (choice A) can result in intense inflammatory reactions during the rapid death of the nematodes. Due to the risk of fatal encephalopathy in patients with microfilarial concentrations greater than 8000 per mL of blood, it is recommended to first measure the concentration prior to treatment with diethylcarbamazine.4 Treatment with diethylcarbamazine in patients who are coinfected with onchocerciasis can also lead to vision loss and blindness.5 Therefore, in patients from coendemic areas such as Nigeria, serological testing (choice C) should be used to rule out onchocerciasis prior to treatment, but only after identification of microfilariae in peripheral blood.6 Surgical removal of the adult worm from the conjunctiva (choice D) may treat localized symptoms and provide an opportunity for species identification; however, removal is not necessary for diagnosis and treatment with curative antiparasitic medication.Peripheral blood smears with Wright and Geimsa stains (Figure 2) revealed microfilaria (1000/mL) with characteristic morphology of Loa loa that included an approximate length of 250 μm, shortened headspace, a dense nuclear column continuous to the tip of the tail, and the presence of a sheath.7 The patient was prescribed albendazole, which is only effective against adult worms and decreases the load of microfilariae through the reduction in shedding of microfilariae.8 Serologic testing for onchocerciasis was ordered, and the US Centers for Disease Control and Prevention was contacted to obtain diethylcarbamazine, which is no longer US Food and Drug Administration–approved or commercially available in the US due to the low incidence of this disease in the US.9 The results of the onchocerciasis serology were negative, and the patient was given the diethylcarbamazine obtained from the US Centers for Disease Control and Prevention. Three weeks later, he reported no recurrence of his symptoms, and there were no eye worms on examination.Peripheral thick blood smears stained with Wright and Geimsa (main panel [original magnification ×400] and inset panel [original magnification ×200], respectively) revealed microfilaria (1000/mL) with characteristic morphology of Loa loa that included an approximate length of 250 μm, shortened headspace (pink arrowhead), a dense nuclear column continuous to the tip of the tail (blue arrowhead), and the presence of a sheath (black arrowhead).

Ophthalmology

A 33-year-old man with no prior ocular problems presented to the emergency department in central Florida with a chief complaint of a “pulling and popping” sensation in his left eye that had occurred the previous night. Ophthalmology was consulted to evaluate for a conjunctival foreign body of the left eye. At the time of the examination, his symptoms had resolved; however, he had a photograph from a cellular phone taken during the episode (Figure 1). The photograph shows an irregular, serpiginous extension from beneath the plica semilunaris toward the corneal limbus with localized conjunctival hyperemia. He reported a similar sensation of movement in his left eye that occurred for 1 night about 5 years ago for which he visited an urgent care center where he was diagnosed with allergic conjunctivitis. He also reported recent swelling of the left side of his face with associated numbness and occasional swelling of his left hand, all of which resolved after a few days. He had immigrated from Nigeria 10 years prior, had not returned since, and was working as a traveling nurse. A slitlamp examination did not reveal any conjunctival hyperemia, foreign bodies, or other abnormalities like those shown in the photograph. His uncorrected visual acuity was 20/20, extraocular movements were full and without pain or abnormal sensation, and intraocular pressure was normal. His dilated fundus examination was unremarkable. A comprehensive blood cell count revealed mild elevation in the relative (but not absolute) eosinophil count (6.9% reference; 6.0% of white blood cells).Patient cellular phone photograph of the left eye shows an irregular serpiginous extension from beneath the plica semilunaris toward the corneal limbus with localized conjunctival hyperemia.Exploration of conjunctiva and removal of foreign body

what would you do next?

What would you do next?

Exploration of conjunctiva and removal of foreign body

Treatment with diethylcarbamazine

Serological testing for onchocerciasis

Peripheral blood smear

d

male

31-40

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2809480

A 13-year-old boy with a history of sports-related blunt trauma to the left eye was referred for evaluation of an asymptomatic, pigmented iris lesion in the left eye. On examination, his best-corrected visual acuity was 20/20 OU, and intraocular pressures were normal in both eyes. Results of slitlamp examination of the right eye were unremarkable. Slitlamp examination of the left eye revealed a round, pigmented lesion measuring 3 × 3 mm in basal dimension and with gravitational shifting within the anterior chamber fluid with patient head tilt (Video). There was no corneal guttatae or edema. Anterior segment optical coherence tomography depicted the lesion in the anterior chamber angle abutting the corneal endothelium and resting on the iris stroma with no internal fluid level and no solid component. Ultrasound biomicroscopy confirmed the lesion to be cystic with a thickness of 1.6 mm. Dilated fundus examination revealed normal findings in both eyes. What Would You Do Next?

Fine-needle aspiration biopsy with cytology and cytogenetics

Iodine 125 plaque radiotherapy

Observe with no additional testing or intervention

Cyst paracentesis with complete drainage

Free-floating iris pigment epithelium cyst

C

Observe with no additional testing or intervention

A pigmented mass in the anterior chamber could represent a benign entity but also raises suspicion for malignancy, such as iris melanoma. Iris tumors are predominantly characterized as solid (79% of cases) or cystic (21% of cases).1 Solid tumors include melanocytic lesions, with the 3 most common being benign iris nevus (60%), iris melanoma (26%), and iris freckle (4%).1,2 Cystic iris tumors are subclassified based on their tissue layer of origin, arising from either the iris stroma or iris pigment epithelium (IPE). Iris stromal cysts appear translucent, located on the anterior iris surface and with smooth lobulated surface, typically in young children.1,2 By contrast, IPE cysts appear on the posterior iris surface with brown or black color simulating solid melanocytic tumors, such as iris melanoma or IPE adenoma.1,2 For this reason, some IPE cysts have historically been mistaken for melanoma, even leading to enucleation. As iris melanoma is malignant with risk for metastasis, proper treatment for life protection with consideration of the potential for ocular adverse sequelae should be realized. Differentiation of the various iris tumors is paramount to management.Ultrasound biomicroscopy and anterior-segment optical coherence tomography are useful tools in assessing the internal quality of iris tumors and differentiation of solid from cystic tumors.3 These technologies are critical for defining tumor basal dimension and thickness to monitor change over time or response to treatment. In this patient, slitlamp biomicroscopy (Figure) demonstrated the gravitational shifting of the mass (Video), and both ultrasound biomicroscopy (Figure, inset) and anterior-segment optical coherence tomography documented the mass to be cystic with no internal fluid or solid component. The Video demonstrates the superior-to-inferior descent of an IPE cyst across the visual axis, coursing purely through the aqueous humor with gravity, offering insight into the dynamic behavior of this lesion.Slitlamp biomicroscopy of the left eye showing a round, pigmented lesion in the inferior anterior chamber angle abutting the corneal endothelium and resting on the iris stroma measuring 3 × 3 mm in basal dimension. Inset, Ultrasound biomicroscopy scan of the free-floating cyst showing central lucency, no fluid level, and no solid component.Free-floating IPE cysts occur when the cyst becomes separated from the IPE, speculated to occur following ocular trauma, as in this patient.4,5 These free-floating IPE cysts are benign and rarely cause endothelial decompensation or visual sequelae.2,5 Fine-needle aspiration biopsy with cytology and cytogenetics (choice A) was not appropriate because the lesion in question was not solid or within the iris, so iris melanoma was not likely. Iodine 125 plaque radiotherapy (choice B) was not appropriate, as this was a cystic, benign mass that was unlikely to be malignant. Cyst paracentesis with complete drainage (choice D) was not necessary in this case because the cyst did not affect the visual axis and was visually asymptomatic. Additionally, drainage of a free-floating cyst without any portion anchored to the iris would likely prove to be technically difficult.In summary, free-floating IPE cysts are benign epithelial cysts that can dislodge into the aqueous or vitreous following trauma, as in this patient. This form of cyst is benign and rarely leads to adverse sequelae; therefore, conservative observation is advised.This patient was counseled on the benign nature of the free-floating IPE cyst and advised to follow up in 12 months for repeated examination with imaging. There was no expectation that this cyst would grow, rupture, transform into a malignant process, or cause damage to the cornea.

Ophthalmology

A 13-year-old boy with a history of sports-related blunt trauma to the left eye was referred for evaluation of an asymptomatic, pigmented iris lesion in the left eye. On examination, his best-corrected visual acuity was 20/20 OU, and intraocular pressures were normal in both eyes. Results of slitlamp examination of the right eye were unremarkable. Slitlamp examination of the left eye revealed a round, pigmented lesion measuring 3 × 3 mm in basal dimension and with gravitational shifting within the anterior chamber fluid with patient head tilt (Video). There was no corneal guttatae or edema. Anterior segment optical coherence tomography depicted the lesion in the anterior chamber angle abutting the corneal endothelium and resting on the iris stroma with no internal fluid level and no solid component. Ultrasound biomicroscopy confirmed the lesion to be cystic with a thickness of 1.6 mm. Dilated fundus examination revealed normal findings in both eyes.

what would you do next?

What would you do next?

Fine-needle aspiration biopsy with cytology and cytogenetics

Cyst paracentesis with complete drainage

Iodine 125 plaque radiotherapy

Observe with no additional testing or intervention

d

male

11-20

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2808886

A woman in her 60s with long-standing thickening and induration of the legs presented with 1 week of left leg pain. The patient had previously been diagnosed with elephantiasis nostras verrucosa, and she was advised to elevate and compress the leg but was unavailable for follow-up. Her medical history was notable for morbid obesity, hypertension, diabetes, and stroke. She reported no fever, fatigue, weight changes, gastrointestinal symptoms, difficulty concentrating, anxiety, or hyperhidrosis. Physical examination results revealed multiple firm skin-colored papules and nodules coalescing to form a large plaque on the anterior aspect of the left lower leg, whereas the right lower leg had diffuse induration and hyperpigmentation (Figure 1). There was no palpable lymphadenopathy. Laboratory analysis revealed normal complete blood cell count, thyroid function, serum protein electrophoresis, and serum immunofixation. A biopsy of a left leg nodule was performed.Multiple firm skin-colored papules and nodules coalesce to form a large plaque on the anterior aspect of the left lower leg. What Is Your Diagnosis?

Pretibial myxedema

Elephantiasis nostras verrucosa

Lobomycosis

Euthyroid pretibial mucinosis

D. Euthyroid pretibial mucinosis

D

Euthyroid pretibial mucinosis

Histopathologic examination showed an atrophic epidermis, angioplasia with vertically oriented vessels, horizontal fibrosis, hemosiderin deposits, and increased mucin deposition, extending from the papillary to the reticular dermis (Figure 2). Pretibial mucinosis in a patient with euthyroid due to obesity and venous stasis was diagnosed. The patient’s cutaneous mucinosis was complicated by cellulitis, which resolved with a short course of antibiotics. Weight loss was recommended, and compression and leg elevation were suggested for the management of chronic skin changes. Detailed vascular studies to explain the asymmetry were planned, but the patient was unavailable for follow-up after multiple hospital admissions for her comorbidities.A and B, Histologic examination shows atrophic epidermis, angioplasia with vertically oriented vessels, and horizontal fibrosis (hematoxylin-eosin). C, Colloidal iron staining with increased mucin deposition extending from the papillary to the reticular dermis.Classically, accumulation of mucin on the shins is associated with pretibial myxedema (choice A), prompting thyroid function testing. However, in a small percentage of patients with pretibial mucinosis, thyroid dysfunction is not identified.1 Pretibial mucinosis in patients with euthyroid has been described in states of chronic stasis, such as venous insufficiency and obesity with lymphedema, termed pretibial stasis mucinosis and obesity-associated lymphedematous mucinosis (OALM).1,2 These conditions often overlap and share a similar pathogenesis. Chronic venous insufficiency and/or obesity-associated lymphedema have been suggested to induce hypoxia, leading to angiogenesis and plasma protein extravasation, ultimately resulting in increased production and deposition of mucopolysaccharides.3Patients with stasis mucinosis and OALM present with skin-colored to yellow-red papules, plaques, and/or nodules. Symptoms can be bilateral or asymmetric, involving a single extremity. Distinct histopathologic findings, such as epidermal atrophy, angioplasia with vertically oriented capillaries, increased stellate fibroblasts, and hemosiderin deposition, aid in confirming the diagnosis and differentiating it from other forms of cutaneous mucinosis.4 Treatment entails weight loss and modalities that improve lymphatic and venous blood flow, such as compression stockings. Second- and third-line therapeutics include topical corticosteroids or intralesional corticosteroids, pentoxifylline, octreotide, plasmapheresis, and intravenous immunoglobulins.Differential diagnosis of multiple long-standing papules and nodules on the lower legs includes pretibial myxedema and elephantiasis nostras verrucosa (choice B) and lobomycosis (choice C). Clinical and histologic features are essential to differentiate these conditions. Pretibial myxedema in thyroid disease often precedes skin manifestations, and it is commonly associated with coexisting orbitopathy in Graves disease.4 Histologically, it is characterized by mucin deposition in the upper dermis, with a grenz zone present in the superficial dermis.5 Euthyroid pretibial mucinosis lacks this feature, showing mucin deposition throughout the dermis. Elephantiasis nostras verrucosa may be distinguished clinically from pretibial mucinosis, as it develops on the dorsa of the feet and extends proximally over time. It can be differentiated histologically by the presence of pseudoepitheliomatous hyperplasia and exhibits dilated lymph channels in the early stages and extensive dermal fibrosis in the later stages. Mucin is absent.6 Pretibial mucinosis nodules can be mistaken for lobomycosis, an uncommon fungal infection acquired in tropical areas of Central and South America, that is histopathologically is characterized by granulomas containing sclerotic bodies.7

Dermatology

A woman in her 60s with long-standing thickening and induration of the legs presented with 1 week of left leg pain. The patient had previously been diagnosed with elephantiasis nostras verrucosa, and she was advised to elevate and compress the leg but was unavailable for follow-up. Her medical history was notable for morbid obesity, hypertension, diabetes, and stroke. She reported no fever, fatigue, weight changes, gastrointestinal symptoms, difficulty concentrating, anxiety, or hyperhidrosis. Physical examination results revealed multiple firm skin-colored papules and nodules coalescing to form a large plaque on the anterior aspect of the left lower leg, whereas the right lower leg had diffuse induration and hyperpigmentation (Figure 1). There was no palpable lymphadenopathy. Laboratory analysis revealed normal complete blood cell count, thyroid function, serum protein electrophoresis, and serum immunofixation. A biopsy of a left leg nodule was performed.Multiple firm skin-colored papules and nodules coalesce to form a large plaque on the anterior aspect of the left lower leg.

what is your diagnosis?

What is your diagnosis?

Elephantiasis nostras verrucosa

Pretibial myxedema

Euthyroid pretibial mucinosis

Lobomycosis

c

female

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2809085

A female patient in her early 50s presented with multiple (approximately 10) bluish, partially keratotic papules and nodules on the lower legs (Figure, A). Since the age of 24 years, the lesions had been growing very slowly in number and size and had been bleeding occasionally after a trauma. The patient used a wheelchair due to a right-sided hemiparesis and hemianopsia caused by an intracranial hemorrhage. At the age of 4 years, recurrent seizures had led to the diagnosis of cerebral venous malformations. Clinical examination also demonstrated a lipolymphedema of the lower legs that had been attributed to a functional venous insufficiency with insufficient venous pump activity. The patient had been wearing compression stockings for years. The family history was positive for cerebral venous malformations involving the patient’s father and aunt, the father having died of an intracranial hemorrhage in his early 70s.A, Clinical picture. B and C, Hematoxylin-eosin stain.Sonography of the skin lesions demonstrated intradermal slow-flow vascular malformations with a maximum diameter of 1.2 cm. A biopsy of a lower-extremity papule was performed (Figure, B and C). Mutational analysis resulted in the detection of a heterozygous pathogenic KRIT1 variant. What Is Your Diagnosis?

Blue rubber bleb nevus syndrome

Familial cerebral cavernous malformations

Glomuvenous malformations

Verrucous venous malformations

B. Familial cerebral cavernous malformations

B

Familial cerebral cavernous malformations

Skin biopsy revealed a well-circumscribed lesion with hyperkeratosis and acanthosis of the epidermis overlying a conglomerate of dilated venous-like malformations with continuous smooth muscle in the upper dermis, partly showing thrombosis. Histomorphology together with a positive personal and family history of venous malformations and the identification of a pathologic KRIT1 variant led to the diagnosis of familial cerebral cavernous malformations (CCMs) in the current patient.Cerebral cavernous malformations or cavernomas (International Society for the Study of Vascular Anomalies [ISSVA] simple vascular malformations III) are slow-flowing venous malformations that are lined by a single layer of endothelium with no involvement of brain parenchyma.1 They can occur in sporadic (80%) or familial (20%) form, affecting up to 0.5% in the general population.2 Familial CCMs are frequently inherited as multiple lesions in an autosomal dominant manner. Following the Knudson hypothesis, they are caused by germline loss-of-function variants in KRIT1, CCM2, or PDCD10 in association with a somatic “second hit” in the other allele.3 Among patients with CCMs, 40% to 70% present with neurological symptoms, such as seizures, focal deficits, and headaches due to intracranial hemorrhages. Extraneurological manifestations may involve the skin, retina, kidney, and liver. In a study of 417 patients with familial CMMs, 38 patients (9%) had cutaneous venous malformations, which is a higher rate than in the general population (0.3%).4 In this study, the lesions were associated with KRIT1 variants and further classified as hyperkeratotic capillary-venous malformations, capillary malformations, and venous malformations. Prognosis and management are determined by the location, number, and size of the cerebral venous malformations. Recent advances in understanding CCM pathophysiology have revealed new strategies to control disease progression, ie, Rho kinase inhibition by atorvastatin.5Blue rubber bleb nevus syndrome (BRBNS; ISSVA simple vascular malformations III) is another rare disorder characterized by multiple, most commonly cutaneous and gastrointestinal venous malformations.1 Skin lesions present as rubbery, bluish, easily compressible nodules since birth or early childhood.6 Histopathology reveals large, thin-walled vessels with discontinuous or no smooth muscle separated by variable amounts of fibrous tissue scattered through the dermis.7 Gastrointestinal malformations typically cause recurrent hemorrhages resulting in chronic anemia and may occasionally lead to volvulus, intussusception, or perforation. Thirteen percent of patients have central nervous system involvement.8 Familial occurrence is extremely rare, as BRBNS is due to somatic double (cis) variants in TEK, the gene encoding endothelial cell tyrosine kinase receptor TIE2.9Glomuvenous malformations or glomangiomas (ISSVA simple vascular malformations III) are bluish, tender, noncompressible papules and nodules of the cutis that histologically represent venous-like channels surrounded by 1 or 2 layers of glomus cells, and no intracranial involvement is seen.1 Glomuvenous malformations are inherited in over 60% of cases in an autosomal dominant manner and are due to loss-of-function variants in the glomulin gene.7 Verrucous venous malformations (ISSVA simple vascular malformations III) are sporadic congenital hyperkeratotic nodules—mainly on the legs—that show a deep vascular component and no further associations and, in particular, no intracranial involvement.1 Histopathology reveals a compact hyperkeratosis, papillomatosis, and acanthosis overlying dilated vessels extending into the deep dermis and the subcutis.7 A somatic missense MAP3K3 variant has been recently identified.10

Dermatology

A female patient in her early 50s presented with multiple (approximately 10) bluish, partially keratotic papules and nodules on the lower legs (Figure, A). Since the age of 24 years, the lesions had been growing very slowly in number and size and had been bleeding occasionally after a trauma. The patient used a wheelchair due to a right-sided hemiparesis and hemianopsia caused by an intracranial hemorrhage. At the age of 4 years, recurrent seizures had led to the diagnosis of cerebral venous malformations. Clinical examination also demonstrated a lipolymphedema of the lower legs that had been attributed to a functional venous insufficiency with insufficient venous pump activity. The patient had been wearing compression stockings for years. The family history was positive for cerebral venous malformations involving the patient’s father and aunt, the father having died of an intracranial hemorrhage in his early 70s.A, Clinical picture. B and C, Hematoxylin-eosin stain.Sonography of the skin lesions demonstrated intradermal slow-flow vascular malformations with a maximum diameter of 1.2 cm. A biopsy of a lower-extremity papule was performed (Figure, B and C). Mutational analysis resulted in the detection of a heterozygous pathogenic KRIT1 variant.

what is your diagnosis?

What is your diagnosis?

Blue rubber bleb nevus syndrome

Familial cerebral cavernous malformations

Verrucous venous malformations

Glomuvenous malformations

b

female

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2810142

An 81-year-old White woman noted decreased vision in her left eye for 6 months. She was referred to the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, for suspected choroidal melanoma. She disclosed a history of macular degeneration in both eyes and retinal detachment in the left eye that was treated 35 years previously. Medical history revealed cutaneous basal cell carcinoma and squamous cell carcinoma, both treated surgically.On examination, visual acuity was 20/50 OD and 20/400 OS. External examination showed posterior-chamber intraocular lenses in both eyes and conjunctival scarring in the left eye from circumferential scleral buckle surgery with no visible extraocular tumor. Fundus evaluation showed macular drusen in the right eye and a pale optic disc with geographic macular atrophy in the left eye, explaining her visual acuity of 20/400 OS. In addition, a shallow circumferential buckle effect and an inferotemporal mass measuring 15.0 × 10.0 mm in basal dimension and 9.1 mm in thickness (Figure, A) were seen in the left eye. The mass appeared elevated, amelanotic with overlying retinal vasculature, and with chorioretinal atrophy. No retinal detachment or breaks were seen. By ultrasonography the mass was echolucent (Figure, A inset). Magnetic resonance imaging (MRI) revealed a T1, T2-hypointense shallow circumferential band in the left eye. In addition, there was an inferotemporal nodular mass in the left eye showing T1 (gadolinium) hypointense, T2-hyperintense features, underlying the encircling buckle, and with adjacent subtle delineation. There was no enhancement with gadolinium (Figure, B).Fundus photograph and magnetic resonance imaging of the left eye. A, Fundus photograph of left eye showed a pale optic disc, geographic macular atrophy, and an inferotemporal amelanotic mass (white arrowhead); inset shows ultrasonography revealing an echolucent mass (white arrowhead). B, Magnetic resonance imaging (MRI) (T2-weighted axial orientation) revealed a shallow hypointense circumferential band in the left eye (pink arrowheads), inferotemporal hyperintense nodular mass (asterisk), and inward compressed sclera (white arrowhead); inset (T1-weighted coronal orientation with gadolinium) shows hypointense encircling band (pink arrowhead), subtle scleral indentation (white arrowhead), and no gadolinium enhancement of mass (asterisk). What Would You Do Next?

Whole-body positron emission tomography scan

Fine-needle aspiration biopsy

Plaque radiotherapy

Observation

Expanded hydrogel scleral sponge

D

Observation

In this case, based on MRI and the lack of gadolinium enhancement, the final diagnosis was expanded hydrogel sponge from previous retinal detachment repair. This mass did not show MRI features of choroidal melanoma. The mass showed complete ultrasonographic acoustic hollowness, potentially suggestive of choroidal melanoma, but MRI confirmed a subtle delineation on the inner portion of the mass (Figure, B) suggestive of thinned sclera, indicating that the mass was episcleral and indenting the globe. The mass was hypointense on T1-weighted (gadolinium-enhanced) imaging suggesting a nonvascular mass and hyperintense on T2-weighted imaging suggesting a hydrophilic mass, possibly a hydrogel sponge. We suspect that the sponge, over time, had slowly expanded underneath the circumferential buckle, leading to inward indentation of the globe and the appearance of an intraocular tumor (Figure).Scleral buckle is one of the highly effective options for retinal detachment repair with success rates ranging from 63% to 99% between various studies.1 The hydrogel scleral buckle was introduced in the 1980s and was deemed safe with low risk of infection when soaked in antibiotics, owing to the hydrophilic nature. In addition, the buckle slowly expanded over time, a presumed beneficial effect to further buckle the retina.2 However, delayed complications were later recognized as this implant continued expansion disproportionately, leading to extreme scleral buckle effect, resulting in diplopia, dysmotility, pseudotumor formation in the orbit, eyelid, conjunctiva, and globe, occasionally with inflammation and pain.2,3Our group has previously described expanding hydrogel (MIRAgel) scleral sponge mimicking orbital cysts and tumors.4 This patient had no symptom of an enlarging orbital mass but was clinically found to have an asymptomatic intraocular mass, suspicious for uveal melanoma. However, the clinical features of the episcleral mass combined with imaging that demonstrated the nonvascular mass overlying markedly thinned sclera, confirmed our suspicion of a hydrogel sponge that presumably expanded over 35 years.Swollen hydrogel implants can be managed by careful surgical excision or close observation.3,4 Despite various techniques described for excision of this discohesive, distended material, complete excision is challenging and risks include continued swelling of remnant implant, retinal detachment recurrence, and thinned scleral wall leading to perforation.3 In the absence of intervention, continued enlargement of the buckle effect can lead to complications; hence, long-term surveillance is advised. In view of this patient’s age and absence of symptoms, observation (option D) was recommended. On subsequent follow-up, if enlargement, extrusion, or any signs of infection are noted, implant removal may be considered. Since the absence of tumor or malignancy was suggested by MRI, there was no need for positron emission tomography scan (option A), biopsy (option B), or radiotherapy (option C).

Ophthalmology

An 81-year-old White woman noted decreased vision in her left eye for 6 months. She was referred to the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, for suspected choroidal melanoma. She disclosed a history of macular degeneration in both eyes and retinal detachment in the left eye that was treated 35 years previously. Medical history revealed cutaneous basal cell carcinoma and squamous cell carcinoma, both treated surgically.On examination, visual acuity was 20/50 OD and 20/400 OS. External examination showed posterior-chamber intraocular lenses in both eyes and conjunctival scarring in the left eye from circumferential scleral buckle surgery with no visible extraocular tumor. Fundus evaluation showed macular drusen in the right eye and a pale optic disc with geographic macular atrophy in the left eye, explaining her visual acuity of 20/400 OS. In addition, a shallow circumferential buckle effect and an inferotemporal mass measuring 15.0 × 10.0 mm in basal dimension and 9.1 mm in thickness (Figure, A) were seen in the left eye. The mass appeared elevated, amelanotic with overlying retinal vasculature, and with chorioretinal atrophy. No retinal detachment or breaks were seen. By ultrasonography the mass was echolucent (Figure, A inset). Magnetic resonance imaging (MRI) revealed a T1, T2-hypointense shallow circumferential band in the left eye. In addition, there was an inferotemporal nodular mass in the left eye showing T1 (gadolinium) hypointense, T2-hyperintense features, underlying the encircling buckle, and with adjacent subtle delineation. There was no enhancement with gadolinium (Figure, B).Fundus photograph and magnetic resonance imaging of the left eye. A, Fundus photograph of left eye showed a pale optic disc, geographic macular atrophy, and an inferotemporal amelanotic mass (white arrowhead); inset shows ultrasonography revealing an echolucent mass (white arrowhead). B, Magnetic resonance imaging (MRI) (T2-weighted axial orientation) revealed a shallow hypointense circumferential band in the left eye (pink arrowheads), inferotemporal hyperintense nodular mass (asterisk), and inward compressed sclera (white arrowhead); inset (T1-weighted coronal orientation with gadolinium) shows hypointense encircling band (pink arrowhead), subtle scleral indentation (white arrowhead), and no gadolinium enhancement of mass (asterisk).

what would you do next?

What would you do next?

Plaque radiotherapy

Observation

Whole-body positron emission tomography scan

Fine-needle aspiration biopsy

b

female

81-90

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2809657

A woman in her 30s presented with progressive, multiple itchy erythematous to violaceous papules and plaques localized to the left shin for more than 10 years (Figure, A and B). On close inspection, milia and a few erosions with partially detached epidermis were identified. There were no abnormalities of the mucous membranes, nails, hair, or teeth. No extracutaneous involvement was observed.A, Multiple pruritic erythematous to violaceous lichenified papules and plaques on the left shin. B, Close-up of the skin lesions showing an erosion with partially detached epidermis and multiple milia. C, Histopathologic examination revealed dermoepidermal separation (hematoxylin-eosin stain). D, Histopathologic examination revealed several milia (hematoxylin-eosin stain). What Is Your Diagnosis?

Pretibial pruritic papular dermatitis (PPPD)

Hypertrophic lichen planus (HLP)

Epidermolysis bullosa pruriginosa (EBP)

Lichen amyloidosis (LA)

C. Epidermolysis bullosa pruriginosa (EBP)

C

Epidermolysis bullosa pruriginosa (EBP)

We performed a skin biopsy under the impression of prurigo nodularis and to exclude hypertrophic lichen planus. Histopathologic examination revealed a dermoepidermal cleft (Figure, C) and several milia (Figure, D) in the superficial dermis, features that were inconsistent with either PN or HLP but suggestive of epidermolysis bullosa (EB). Whole-exome sequencing using genomic DNA extracted from the patient’s peripheral blood mononuclear cells identified a novel heterozygous missense variant, c.6832G>T, p.Gly2278Trp, in COL7A1 (NM_000094), which was graded as “likely pathogenic” based on American College of Medical Genetics and Genomics guidelines. Further inquiry of the patient led to identification of 2 other affected family members: 1 who had typical EBP (intensely itchy, symmetric, hypertrophic papules and plaques on both shins) and nail dystrophy, and another, who only had dystrophic toenails. Sanger sequencing confirmed cosegregation of this variant with variable phenotypes, supporting its pathogenicity and the patient’s diagnosis of autosomal dominant EBP. The patient had a 2-year old relative who had only very mild nail dystrophy and no skin disease who also harbored this pathogenic variant.Epidermolysis bullosa is an inherited, heterogeneous group of rare genetic dermatoses characterized by mucocutaneous fragility, blister formation, and abnormal wound healing.1 It is categorized into 4 major subtypes, EB simplex, junctional EB, dystrophic EB (DEB), and Kindler EB, based on the ultrastructural level of skin cleavage and inherent molecular pathology.2 Dystrophic EB is caused by pathogenic variants in the COL7A1 gene, which encodes type 7 collagen. Epidermolysis BP is a rare subtype of DEB characterized by intensely pruritic, prurigo-like nodules and plaques affecting the lower legs, thighs, and arms, often associated with nail dystrophy.3 Unlike other forms of EB, except for some localized subtypes of EB simplex and some rare late-onset forms of junctional EB, it is not uncommon for patients with EBP to present beyond the neonatal/childhood period, and sometimes well into adult life.Epidermolysis BP is traditionally considered a rare subtype of DEB, but it seems to be more prevalent in some countries, including Taiwan.4 So far, no clear genotype-phenotype correlation has been established in EBP.5 Epidermolysis BP is also often misdiagnosed as other dermatoses because blisters are often inconspicuous. Diagnostic clues of EBP include nail dystrophy, the most common associated feature of EBP,6 as well as a history of blistering during infancy and family medical history of other subtypes of DEB,1 which makes it distinct from factitial dermatitis. Although the histopathologic features of factitial dermatitis are nonspecific, milia are usually absent. In this case, however, the unilateral, localized presentation of EBP and undisclosed family medical history of EB at the patient’s initial visit made the diagnosis difficult. It was the milia and dermoepidermal separation on histopathologic findings that prompted subsequent genetic investigations. Still, had we been more vigilant, we might have noticed the milia and partially detached epidermis and put DEB in our initial differential diagnoses.The present case needs to be distinguished from PPPD, HLP, and LA. Overall, PPPD is characterized by extremely pruritic, discrete, smooth, flesh-colored to erythematous papules, caused by persistent rubbing of the anterior surface of the legs. Histopathologic features include minimal compact orthokeratosis, mild acanthosis with flattening of the rete ridges, and superficial and middermal perivascular lymphohistiocytic infiltrates with a variable number of eosinophils.7 In most cases, there is evidence of superficial dermal fibrosis, characterized by the presence of multinucleated fibroblasts and thickened collagen bundles arranged in a random pattern, without the dermoepidermal cleft and milia seen in EBP. Hypertrophic lichen planus presents as extremely pruritic, violaceous, hyperkeratotic flat-topped papules and plaques affecting the extremities.8 Histopathologic findings of HLP show compact orthokeratosis, acanthosis, wedge-shaped hypergranulosis, saw-tooth appearance of the undersurface of the epidermis with necrotic keratinocytes, and a band-like infiltrate of lymphocytes at the dermoepidermal junction, which is distinct from EBP. Generally, LA is the most common form of primary localized cutaneous amyloidosis, clinically characterized by pruritic, discrete hyperkeratotic hyperpigmented papules with a predilection for the shins.9 The key component of the histologic findings is the deposition of pink amorphous amyloid material in the papillary dermis, which exhibits a bright apple-green birefringence under polarized light when stained with Congo red. These findings distinguish LA from EBP, despite both conditions presenting similar epidermal changes induced by chronic scratching.10To our knowledge, this is the first case of unilateral EBP ever reported. This case highlights the importance of considering EBP even when the prurigo-like lesions are unilateral and without nail involvement. Milia and erosions provide diagnostic clues for such atypical cases, as in other subtypes of DEB.

Dermatology

A woman in her 30s presented with progressive, multiple itchy erythematous to violaceous papules and plaques localized to the left shin for more than 10 years (Figure, A and B). On close inspection, milia and a few erosions with partially detached epidermis were identified. There were no abnormalities of the mucous membranes, nails, hair, or teeth. No extracutaneous involvement was observed.A, Multiple pruritic erythematous to violaceous lichenified papules and plaques on the left shin. B, Close-up of the skin lesions showing an erosion with partially detached epidermis and multiple milia. C, Histopathologic examination revealed dermoepidermal separation (hematoxylin-eosin stain). D, Histopathologic examination revealed several milia (hematoxylin-eosin stain).

what is your diagnosis?

What is your diagnosis?

Pretibial pruritic papular dermatitis (PPPD)

Lichen amyloidosis (LA)

Hypertrophic lichen planus (HLP)

Epidermolysis bullosa pruriginosa (EBP)

d

female

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2809652

A 13-year-old girl with a 7-day history of painless vision loss and central scotoma in her left eye was referred to the department of ophthalmology. Three weeks prior, she had presented with mild fever and flulike symptoms, associated with a severe frontal headache that was mildly relieved by analgesics. Her medical history was positive for relapsing urinary tract infections since early infancy without adequate follow-up. Findings of an ophthalmological examination 1 year prior were reported as normal.At initial examination, she was conscious but somewhat lethargic. Her best-corrected visual acuity was 20/20 OD and 20/80 OS. Pupillary light responses, extrinsic ocular motility, anterior segment biomicroscopy, and intraocular pressure were normal in both eyes. Dilated fundus examination revealed a bilateral sectorial macular star that was more extended in the left eye, with retinal veins slightly dilated and tortuous, attenuated arterioles, some juxta and peripapillary nerve fiber layer infarcts, and optic disc edema with marked papillary telangiectasia; in addition, some faint, small, tan-yellow dots were observed at the level of the retinal pigment epithelium in the posterior pole, some of them already grayish and with a hypopigmented halo (Figure 1). Optical coherence tomography displayed elevated optic discs and hyperreflective material in the outer plexiform layer temporal to the optic disc in both eyes and a macular neurosensory detachment in the left eye. Results of visual field testing were normal in the right eye and showed a central scotoma in the left eye.Fundus image of the right eye (A) and left eye (B) showing slight dilation of retinal veins (magenta arrowheads), intraretinal lipid deposits in the papillomacular bundle and the inferonasal macular quadrant forming an incomplete macular star (yellow arrowheads), optic disc edema and epipapillary telangiectasia (blue arrowheads), nerve fiber layer infarcts or cotton-wool nodules (green arrowheads) over the inferior margin of the optic disc in the right eye and juxta and parapapillary in the left eye, and paramacular temporal light-pigmented subretinal dots at the level of the retinal pigment epithelium (white arrowheads) in both eyes, with some already scarred (pigmented dot surrounded by a pale halo; gold arrowhead). What Would You Do Next?

Prescribe systemic corticosteroids

Order serologic testing for infectious neuroretinitis

Rule out brain tumor

Check blood pressure

Hypertensive retinopathy

D

Check blood pressure

Option D is the correct approach. The child underwent immediate hospitalization and systemic evaluation. Clinical examination revealed severe systemic hypertension (225/160 mm Hg). Laboratory test results showed leukocytosis, elevated erythrocyte sedimentation rate (35 mm), hypercholesterolemia, hypokalemia, proteinuria, and microalbuminuria.Echocardiography showed left ventricle hypertrophy, and kidney doppler ultrasonography revealed advanced bilateral kidney atrophy with parenchymal scarring that was presumed to be the consequence of undertreated relapsing urinary tract infections. Results of magnetic resonance imaging of the brain and orbits were normal.The most common masquerader for neuroretinitis is malignant hypertension.1 Systemic hypertension in children is rare, potentially underrecognized,2 and its prevalence ranges from 2% to 5%.3 Mostly asymptomatic, pediatric hypertension may manifest by symptoms originating from target organ disease, and most cases present secondary hypertension from kidney disorders, especially kidney parenchymal disease.4 Hypertensive retinopathy occurs in 8% to 18% of children with severe hypertension, figures substantially lower than those observed in adults with hypertension, with the highest prevalence in those with kidney and renovascular disease.5Malignant hypertension is an acute, severe rise of more than 180 mm Hg in systolic pressure and/or more than 120 mm Hg in diastolic pressure, associated with severe hypertensive retinopathy and papilledema. It constitutes a medical emergency, where severe acute increase in blood pressure results in end-organ damage.6 The bilateral retinal disease, the presence of nerve fiber layer infarcts and Elschnig spots (focal signs of choroidal ischemia at the level of the retinal pigment epithelium), and the accompanying neurologic symptoms (severe headache and lethargy) suggested a severe systemic disease and were the presenting signs of malignant hypertension, which is a life-threatening condition in this patient secondary to kidney parenchymal disease from undertreated relapsing urinary tract infections since early infancy.Option A is incorrect. It is not advisable to prescribe corticosteroids before ruling out an infectious condition. Also, corticosteroids are contraindicated in the context of malignant hypertension. For option B, in the presence of the triad unilateral vision loss, macular star, and optic disc swelling in a child, infectious neuroretinitis must be ruled out, with cat scratch disease (CSD) its most frequent cause. However, neuroretinitis is a rare complication of cat scratch disease, occurring in only 1% to 2% of cases, and it generally presents unilaterally and self-limited.1 In this patient, results of serum tests for infective causes were negative. Besides, retinal and optic nerve disease were bilateral, and the child presented with neurologic signs. Option C is incorrect. Although this patient had neurologic symptoms with bilateral optic disc edema, other features, like macular lipid deposits, nerve fiber layer infarcts, and Elschnig spots, are not clinical signs that accompany papilledema from intracranial hypertension.Treatment with amlodipine, 5 mg, every 12 hours, daily losartan, 50 mg, and a hyposodic diet reduced blood pressure drastically and slowly normalized the retinal disease. Visual acuity progressively improved in the left eye, as did the macular star, optic disc edema, and nerve fiber layer infarcts in both eyes. One year later, blood pressure was generally within normal values under treatment but with intermittent episodes of high values. Best-corrected visual acuity was 20/20 OD and 20/25 OS, and optic discs were nonedematous but moderately pale in both eyes (Figure 2). Optical coherence tomography performed during follow-up showed a diffuse thinning of the neurosensory retina and the peripapillary nerve fiber layer.Fundus image of the left eye (panel) and the right eye (insert) at 1-year follow-up showing a pronounced sclerotic appearance of arteries, a complete resolution of both optic discs’ edema and the macular stars, a moderate optic disc pallor, and no evidence of nerve fiber layer infarcts.

Ophthalmology

A 13-year-old girl with a 7-day history of painless vision loss and central scotoma in her left eye was referred to the department of ophthalmology. Three weeks prior, she had presented with mild fever and flulike symptoms, associated with a severe frontal headache that was mildly relieved by analgesics. Her medical history was positive for relapsing urinary tract infections since early infancy without adequate follow-up. Findings of an ophthalmological examination 1 year prior were reported as normal.At initial examination, she was conscious but somewhat lethargic. Her best-corrected visual acuity was 20/20 OD and 20/80 OS. Pupillary light responses, extrinsic ocular motility, anterior segment biomicroscopy, and intraocular pressure were normal in both eyes. Dilated fundus examination revealed a bilateral sectorial macular star that was more extended in the left eye, with retinal veins slightly dilated and tortuous, attenuated arterioles, some juxta and peripapillary nerve fiber layer infarcts, and optic disc edema with marked papillary telangiectasia; in addition, some faint, small, tan-yellow dots were observed at the level of the retinal pigment epithelium in the posterior pole, some of them already grayish and with a hypopigmented halo (Figure 1). Optical coherence tomography displayed elevated optic discs and hyperreflective material in the outer plexiform layer temporal to the optic disc in both eyes and a macular neurosensory detachment in the left eye. Results of visual field testing were normal in the right eye and showed a central scotoma in the left eye.Fundus image of the right eye (A) and left eye (B) showing slight dilation of retinal veins (magenta arrowheads), intraretinal lipid deposits in the papillomacular bundle and the inferonasal macular quadrant forming an incomplete macular star (yellow arrowheads), optic disc edema and epipapillary telangiectasia (blue arrowheads), nerve fiber layer infarcts or cotton-wool nodules (green arrowheads) over the inferior margin of the optic disc in the right eye and juxta and parapapillary in the left eye, and paramacular temporal light-pigmented subretinal dots at the level of the retinal pigment epithelium (white arrowheads) in both eyes, with some already scarred (pigmented dot surrounded by a pale halo; gold arrowhead).

what would you do next?

What would you do next?

Check blood pressure

Order serologic testing for infectious neuroretinitis

Prescribe systemic corticosteroids

Rule out brain tumor

a

female

11-20

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2809348

An otherwise healthy 13-month-old male was scheduled to undergo excisional biopsy of a left anterior tongue submucosal intramuscular mass (Figure 1). This firm-to-palpation mass was noted at birth and remained proportional in size with the child’s somatic growth, measuring approximately 1 cm in diameter on presentation. Preoperative magnetic resonance imaging (MRI) documented the mass to be uniformly solid and well circumscribed without cystic components or flow voids, hypointense on T2, and hyperintense with homogeneous contrast enhancement on T1. His head, neck, and general examination findings were otherwise normal with no cervical lymphadenopathy or additional masses. What Is Your Diagnosis?

Hemangioma

Rhabdomyoma

Rhabdomyosarcoma

Teratoma

B. Rhabdomyoma

B

Rhabdomyoma

Neonatal tongue lesions have a broad differential diagnosis, including cystic, solid, and mixed composite lesions.1 Differentiation of cystic from solid lesions is important, as each warrants a unique differential diagnosis. Ultrasonography, computed tomography, and MRI are modalities that can be used to make this differentiation. If sedation is required, MRI with contrast is preferable given the excellent soft tissue detail without risk of radiation.Common congenital cystic tongue lesions include foregut duplication cysts, dermoid cysts, and ranulas. Foregut duplication cysts and dermoid cysts tend to be midline lesions, the former lined by gastrointestinal mucosa and the latter lined by squamous epithelium with adnexal structures.2 Ranulas and alternative pseudocysts of sublingual gland origin are more commonly unilateral lesions with a floor of mouth rather than tongue focality. Lymphatic and venous vascular malformations need to also be considered.This child’s lesion, based on physical examination and MRI characteristics, was solid. The differential diagnosis of solid tongue masses is broad, but neonatal presentation favors congenital and neoplastic causes. Common benign solid tongue masses in this age group include hemangiomas, hamartomas, choristomas, and teratomas.Hamartomas are benign growths composed of a proliferation of tissue native to the site of the lesion, whereas choristomas are proliferations of tissues not normally found in that anatomical location. Both hamartomas and choristomas can be solid depending on their tissue of origin.The World Health Organization Classification of Tumors lists 4 subtypes of extracardiac rhabdomyoma: fetal, adult, intermediate, and genital.3 Fetal rhabdomyoma may present at any age; however, over 50% of fetal rhabdomyoma cases have been diagnosed in infants and children younger than 3 years, with 25% being congenital.4 Fetal rhabdomyoma is the most common type found in the head and neck.5Although rare, malignant tongue masses should be considered, as delayed diagnosis can have devastating consequences. Rhabdomyosarcoma is the most common pediatric tongue malignant neoplasm, with leiomyosarcoma and fibrosarcoma being additional possibilities.6 Specifically, embryonal rhabdomyosarcoma should be considered, given the location.The pathology findings key to making the diagnosis in this case are highlighted in Figure 2. The histopathology demonstrated a circumscribed lesion composed of irregular bundles of primitive-appearing spindle cells and striated immature skeletal muscle cells, resembling fetal microtubules, within a myxoid background. Minimal mitotic activity was noted; no necrosis or atypia was present. These features supported a diagnosis of fetal rhabdomyoma.A, Histopathology findings of the excised lesion demonstrating irregular bundles of primitive cells and immature striated skeletal muscle fibers (hematoxylin-eosin). B, Desmin immunohistochemical stain highlighting the lesional cells.The myxoid background is important for the diagnosis of a classical fetal-type rhabdomyoma. Rhabdomyomas generally do not show atypia or necrosis, and mitoses are uncommon. Both the spindle cells and rhabdomyoblasts will be positive for myogenin and MyoD1 by immunohistochemistry. Adult rhabdomyoma can also be considered if the characteristic spider cells are present. Embryonal rhabdomyosarcoma is a poorly circumscribed lesion that shows both primitive round-to-spindle cells to differentiating rhabdomyoblasts (“tadpole cells” and/or “strap cells”) to cross-striated myofibers present in zones of hypocellularity to hypercellularity, embedded within a myxoid background. Embryonal rhabdomyosarcoma generally shows increased mitotic activity (sometimes with atypical mitoses), necrosis, and atypia; anaplasia may be seen.Heterotopic fetal rhabdomyoma, similar to choristoma, is managed by surgical excision for diagnosis and therapy.7 A recurrence rate of 4% over a median follow-up of 4 years has been reported for fetal rhabdomyoma of the head and neck.4 Recurrence likely reflects incomplete resection and, rarely, multicentricity.8The decision to wait to perform surgery was purposeful given the benign characteristics of the lesion and anesthesia exposure concerns. The patient was admitted for overnight monitoring with discharge home the following morning. At 6-month postoperative follow-up, the child demonstrated tongue symmetry, no functional impairment, and no evidence of recurrence.

General

An otherwise healthy 13-month-old male was scheduled to undergo excisional biopsy of a left anterior tongue submucosal intramuscular mass (Figure 1). This firm-to-palpation mass was noted at birth and remained proportional in size with the child’s somatic growth, measuring approximately 1 cm in diameter on presentation. Preoperative magnetic resonance imaging (MRI) documented the mass to be uniformly solid and well circumscribed without cystic components or flow voids, hypointense on T2, and hyperintense with homogeneous contrast enhancement on T1. His head, neck, and general examination findings were otherwise normal with no cervical lymphadenopathy or additional masses.

what is your diagnosis?

What is your diagnosis?

Teratoma

Hemangioma

Rhabdomyosarcoma

Rhabdomyoma

d

male

0-10

original

https://jamanetwork.com/journals/jama/fullarticle/2809109

A 42-year-old woman with asthma, seasonal allergies, and invasive ductal breast carcinoma presented to the dermatology clinic for rash and poor wound healing 2 weeks after bilateral mastectomy. Five days after surgery, the patient noted erythema, edema, pain, pruritus, and serous fluid drainage at the mastectomy incision sites (Figure 1). Two days later, she developed an erythematous papulovesicular rash on her trunk and upper and lower extremities. A skin swab was sent for bacterial culture, and she was prescribed cefadroxil (500 mg twice daily for 1 week). The skin swab bacterial culture result was negative, and her skin findings did not improve with antibiotics. The patient reported having a similar episode of rash and delayed wound healing after laparoscopy 1 year prior to presentation.Erythema and crusting along incision sites surrounded by a papulovesicular rash.Perform a skin biopsy at the mastectomy incision sitePrescribe acyclovir (400 mg orally 3 times daily for 7 days)Start topical steroids and perform a skin patch testTreat with doxycycline (100 mg orally twice daily for 7 days) What Would You Do Next?

Perform a skin biopsy at the mastectomy incision site

Prescribe acyclovir (400 mg orally 3 times daily for 7 days)

Start topical steroids and perform a skin patch test

Treat with doxycycline (100 mg orally twice daily for 7 days)

Allergic contact dermatitis due to use of surgical skin glue

C

Start topical steroids and perform a skin patch test

The key to the correct diagnosis is recognizing that an acute pruritic papulovesicular rash involving a surgical incision site is characteristic of allergic contact dermatitis due to use of surgical skin glue. Skin biopsy (choice A) would not be helpful because histopathologic findings of allergic contact dermatitis are nonspecific. Prescribing acyclovir (choice B) is not recommended because the patient did not have typical findings of herpes simplex virus such as grouped vesicles on an erythematous base. Doxycycline (choice D) is not indicated because her bacterial culture result was negative, and she had already been treated with a course of antibiotics.Allergic contact dermatitis (ACD) is a cutaneous type IV (delayed) hypersensitivity reaction caused by activation of allergen-specific T cells that develop after initial exposure to an allergen in contact with the skin.1 Activation of these T cells causes cytokine release and cellular infiltrates that result in the clinical symptoms of ACD.2Acute ACD presents with intense pruritus or burning, and the affected skin typically has a weepy erythematous appearance with surrounding erythematous papulovesicles and honey-colored crusting. Bullae and oozing may arise in severe cases.2,3 Skin findings may occur as early as 1 to 2 days after exposure in sensitized individuals or up to 1 month with initial allergen exposure.4 The differential diagnosis of ACD includes irritant contact dermatitis, atopic dermatitis, seborrheic dermatitis, psoriasis, tinea, mycosis fungoides, and surgical site infection in patients who have undergone recent surgery.2,3ACD affects approximately 72 million individuals in the US annually and is diagnosed more commonly in females than in males.1,2,4 Risk factors for ACD include atopic dermatitis, a family history of ACD, and exposure to acrylates, which are chemical agents commonly used in glues, adhesives, and plastics.1,3 Occupations with increased risk of ACD due to acrylate exposure include medical and dental practitioners, beauticians, chemical plant workers, construction workers, metal workers, and mechanics.1,3Patients who have undergone recent surgery can develop ACD from exposure to tissue adhesives, sutures, staples, antiseptic preparations, topical antibiotics, joint implants, and bone cement5-7 ACD causes inflammation of the skin that may impair wound healing, cause wound dehiscence, and increase the risk of wound infections.5,7ACD due to surgical skin glue occurs in 1.5% to 2.8% of exposed patients,3,4 and the most common allergens are acrylates (methacrylates or cyanoacrylates). ACD caused by one acrylate may lead to cosensitization to another acrylate.1 Surgical skin glue adhesives reside in the dermis and can cause sensitization and skin reactions up to 1 month after application.4 Approximately one-half of patients with allergic contact dermatitis due to surgical skin glue also develop a skin eruption in areas of the body remote from the site of application.4ACD is typically diagnosed with standard skin patch testing performed by an allergist or dermatologist. However, standard patch testing does not include cyanoacrylate, methacrylate, or suture materials and fails to identify approximately 25% of allergens that cause ACD.2,7 A specialized (“open”) patch test can be performed for patients who have exposure to specific known allergens not typically included in standard skin patch testing.2,7Treatment of ACD includes removal of the allergen and daily treatment with topical or systemic steroids for at least 2 to 3 weeks, at which point the skin findings typically resolve.2 However, patients must be informed that ACD will recur with reexposure, so strict avoidance of the specific allergen and cross-reacting allergens is required.2 Patients with a history of ACD due to use of surgical skin glue should inform their surgeon and anesthesiologist prior to surgery to avoid reexposure to an allergen that caused ACD.5An open patch test was performed to assess for an allergic reaction to the sutures and surgical skin glue used during the patient’s mastectomy. At 48 hours, she demonstrated a “strong positive” skin reaction to surgical skin glue (Figure 2). Acetone was used to remove the remaining surgical skin glue on her mastectomy incision sites, and triamcinolone was prescribed (0.1% cream twice daily for 2 weeks). Three days later, the patient noted a substantial decrease in pruritus and erythema at the incision sites. She was advised to avoid future contact with surgical skin glue and other potentially cross-reacting adhesives and was provided a handout detailing safe alternative products. At 2-week follow-up, the skin over her mastectomy incision sites appeared healthy, and the rash on her trunk and upper and lower extremities had resolved.Open skin patch test with materials used during the patient’s mastectomy showed a 2+ (strong positive) reaction to surgical skin glue observed 48 hours after application. No suture reactions occurred.

General

A 42-year-old woman with asthma, seasonal allergies, and invasive ductal breast carcinoma presented to the dermatology clinic for rash and poor wound healing 2 weeks after bilateral mastectomy. Five days after surgery, the patient noted erythema, edema, pain, pruritus, and serous fluid drainage at the mastectomy incision sites (Figure 1). Two days later, she developed an erythematous papulovesicular rash on her trunk and upper and lower extremities. A skin swab was sent for bacterial culture, and she was prescribed cefadroxil (500 mg twice daily for 1 week). The skin swab bacterial culture result was negative, and her skin findings did not improve with antibiotics. The patient reported having a similar episode of rash and delayed wound healing after laparoscopy 1 year prior to presentation.Erythema and crusting along incision sites surrounded by a papulovesicular rash.Perform a skin biopsy at the mastectomy incision sitePrescribe acyclovir (400 mg orally 3 times daily for 7 days)Start topical steroids and perform a skin patch testTreat with doxycycline (100 mg orally twice daily for 7 days)

what would you do next?

What would you do next?

Treat with doxycycline (100 mg orally twice daily for 7 days)

Start topical steroids and perform a skin patch test

Prescribe acyclovir (400 mg orally 3 times daily for 7 days)

Perform a skin biopsy at the mastectomy incision site

b

female

41-50

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2807476

A 56-year-old woman with a history of multiple myeloma complicated by therapy-related acute myeloid leukemia was admitted for myeloablative conditioning in preparation for allogeneic hematopoietic cell transplant. Her course was complicated by severe mucositis, acute kidney injury, and neutropenic fever. During her admission, the patient also developed painful necrotic skin lesions, a nonproductive cough, and altered mental status.Physical examination findings demonstrated dusky, purpuric, and pink papulonodules, some with overlying eschar, scattered on the scalp, neck, trunk, and extremities (Figure, A). Laboratory study results revealed a white blood cell count of 150/μL (reference range, 3500/μL to 10 500/μL), an absolute neutrophil count of 130/μL (reference range, 1500/μL to 7400/μL), and a platelet count of 19 ×103/μL (reference range, 150 ×103/μL to 400 ×103/μL). (To convert the white blood cell and neutrophil counts to cells ×109/L, multiply by 0.001; conversion of the platelet count to cells ×109/L is 1:1.) Blood culture results were negative. The results of a computed tomography (CT) scan of the brain showed no acute intracranial hemorrhage, territorial infarction, or mass effect. The results of a CT scan of the chest demonstrated multifocal bilateral ground-glass patchy opacities, scattered solid bilateral pulmonary nodules, and a moderately sized pericardial effusion. A biopsy specimen from a skin nodule on the left lateral thigh was obtained for histopathologic examination and tissue culture, and wet mount preparation of a tissue culture colony was performed (Figure, B).A, Physical examination findings demonstrate dusky and pink papulonodules, some with overlying eschar, scattered on the scalp, neck, and extremities. B, Lactophenol cotton blue staining of a tissue culture colony reveals septated hyphae and oval microconidia. What Is Your Diagnosis?

Disseminated fusariosis

Invasive aspergillosis

Pseudomonal ecthyma gangrenosum

Sweet syndrome

A. Disseminated fusariosis

A

Disseminated fusariosis

Wet mount preparation of a tissue culture mold colony with lactophenol cotton blue staining revealed septated hyphae and oval microconidia (Figure, B). A fungal culture grew Fusarium solani.Fusarium species are ubiquitous in soil and air, and transmission occurs through inhalation or direct cutaneous inoculation from a contaminated source.1 Localized infections can present as onychomycosis, superficial cutaneous infections, and keratitis in immunocompetent hosts; invasive and disseminated disease is more common in those who are immunocompromised, particularly those with neutropenia.2 In those with hematologic cancer, disseminated fusariosis most frequently involves the skin, blood, lungs, and sinuses.3Although the incidence of fusariosis among patients undergoing hematopoietic transplant is less than 1%, invasive fusariosis has a mortality rate of approximately 80% in individuals with hematologic cancer.4 Thus, early recognition is crucial for prompt treatment of the infection. Purpuric patches or papulonodules in this population should be evaluated urgently with skin biopsy and tissue culture. It is also recommended that patients with hematologic cancer who are about to receive chemotherapy and/or bone marrow transplant first undergo a thorough examination for skin findings of onychomycosis, which has been associated with Fusarium infections.1,3,5The patient’s physical examination findings of scattered and painful purpuric papulonodules are similar to those found in invasive aspergillosis, which has an incidence of 2.7% in patients undergoing hematopoietic stem cell transplant.4 Invasive aspergillosis is an infection caused by the fungal Aspergillus species, which is ubiquitous in the environment.6 As transmission is primarily through inhalation, invasive aspergillus most commonly presents with pulmonary or sinus disease that can then progress to dissemination in immunocompromised individuals. Both Aspergillus and Fusarium may cause elevated serum galactomannan antigen. Chest CT findings of invasive aspergillosis and disseminated fusariosis are similar, and both may show ground-glass opacities, segmental consolidation, cavitary lesions, and the “halo sign” (ground-glass opacities representing hemorrhage surrounding central fungal nodules). Lactophenol cotton blue staining of mold colony can differentiate between the 2 pathogens, as Aspergillus species have septate hyphae and flask-shaped vesicles.1,7Ecthyma gangrenosum is a cutaneous infection caused by hematogenous spread of bacteria, most commonly Pseudomonas aeruginosa. It most frequently occurs in immunocompromised individuals, including those with chemotherapy-induced neutropenia.8 As this represents bacterial angioinvasion, ecthyma gangrenosum presents as purpuric macules that may become pustular or bullous before progressing to ulcers with overlying eschar most commonly in the anogenital and axillary areas. In most cases, Pseudomonas can be detected from tissue specimens, but blood culture results are often negative.9Sweet syndrome, also known as acute febrile neutrophilic dermatosis, is a rare disorder that is commonly associated with hematologic cancers, such as acute myeloid leukemia. Sweet syndrome can also be associated with other states, such as autoimmune disease, or be due to medications, such as granulocyte colony-stimulating factor. Classic Sweet syndrome presents as tender, erythematous, and edematous plaques associated with fever and leukocytosis. Cutaneous involvement generally does not show overlying eschar, as seen in disseminated fusariosis. Skin biopsy histopathologic features can mimic infection with dermal edema and a dense infiltrate of neutrophils; however, the results of infectious stains and tissue culture will be negative. Systemic corticosteroids are often first-line treatments for Sweet syndrome.10The patient was treated with intravenous amphotericin B and voriconazole for disseminated fusariosis, with resolution of her cutaneous lesions over the course of 6 weeks. This case highlights the importance of early diagnosis of disseminated fusariosis, especially for those who are immunocompromised or undergoing immunosuppressive therapy.

Oncology

A 56-year-old woman with a history of multiple myeloma complicated by therapy-related acute myeloid leukemia was admitted for myeloablative conditioning in preparation for allogeneic hematopoietic cell transplant. Her course was complicated by severe mucositis, acute kidney injury, and neutropenic fever. During her admission, the patient also developed painful necrotic skin lesions, a nonproductive cough, and altered mental status.Physical examination findings demonstrated dusky, purpuric, and pink papulonodules, some with overlying eschar, scattered on the scalp, neck, trunk, and extremities (Figure, A). Laboratory study results revealed a white blood cell count of 150/μL (reference range, 3500/μL to 10 500/μL), an absolute neutrophil count of 130/μL (reference range, 1500/μL to 7400/μL), and a platelet count of 19 ×103/μL (reference range, 150 ×103/μL to 400 ×103/μL). (To convert the white blood cell and neutrophil counts to cells ×109/L, multiply by 0.001; conversion of the platelet count to cells ×109/L is 1:1.) Blood culture results were negative. The results of a computed tomography (CT) scan of the brain showed no acute intracranial hemorrhage, territorial infarction, or mass effect. The results of a CT scan of the chest demonstrated multifocal bilateral ground-glass patchy opacities, scattered solid bilateral pulmonary nodules, and a moderately sized pericardial effusion. A biopsy specimen from a skin nodule on the left lateral thigh was obtained for histopathologic examination and tissue culture, and wet mount preparation of a tissue culture colony was performed (Figure, B).A, Physical examination findings demonstrate dusky and pink papulonodules, some with overlying eschar, scattered on the scalp, neck, and extremities. B, Lactophenol cotton blue staining of a tissue culture colony reveals septated hyphae and oval microconidia.

what is your diagnosis?

What is your diagnosis?

Pseudomonal ecthyma gangrenosum

Sweet syndrome

Invasive aspergillosis

Disseminated fusariosis

d

female

51-60

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2807704

A man in his 80s presented to the dermatology clinic with a 3-month history of a violaceous plaque with blackish papules and nodules on his left cheek, neck, and chest. He reported that the lesion had been asymptomatic but was increasing in size, with progression from his face to anterior chest. He received a diagnosis of primary salivary duct carcinoma of the hard palate 1 year prior and had been receiving treatment with oral bicalutamide and radiotherapy. A partially regressive change of the palatal tumor was noted radiographically during regular follow-up 3 months previously. On clinical examination, a hemorrhagic and erythematous plaque with multiple purpuric-to-blackish infiltrative papules and nodules extending from cheek, lateral neck, to the interclavicular area was found (Figure 1). An incisional biopsy from the infiltrative nodule on cheek was performed and submitted for histopathologic analysis.Hemorrhagic and erythematous plaque with multiple infiltrative purpuric-to-blackish papules and nodules with varying sizes extending from left cheek, neck, to chest. What Is Your Diagnosis?

Radiotherapy-induced epithelioid angiosarcoma

Kaposi sarcoma

Acquired angiokeratomas

Carcinoma hemorrhagiectoides

D. Carcinoma hemorrhagiectoides

D

Carcinoma hemorrhagiectoides

Hematoxylin-eosin staining of the lesion revealed a diffuse infiltrate of large, ovoid tumor cells that formed tumor nests and tumor emboli, with marked erythrocytes extravasation in the dermis (Figure 2A). The cells had an abundant eosinophilic cytoplasm and were hyperchromatic, with nuclear pleomorphism and comedonecrosis (Figure 2B). Androgen receptor and GATA3 were diffusely strong positive in the tumor cells, while other endothelial markers, including CD31, CD34, and ERG1, were negative. A diagnosis of carcinoma hemorrhagiectoides due to metastatic salivary duct carcinoma (SDC) was made. Further image study results revealed multiple metastases in the lung, liver, and bone. A combination of oral bicalutamide and chemotherapy with carboplatin and fluorouracil was administered. Four months later, partial regression of the liver and lung metastases was noted radiographically.Hematoxylin-eosin staining of the lesion from the biopsy specimens. A, Scanning magnification showed a diffuse infiltrate of tumor cells with marked erythrocyte extravasation. B, The tumor cells were characterized by an abundant eosinophilic cytoplasm, nuclear atypia, and pleomorphism, with comedonecrosis on higher magnification.Salivary duct carcinoma is an aggressive cancer of the primary salivary gland origin and is generally associated with a high rate of local recurrence and distant metastasis.1 It accounts for 5% to 10% of salivary gland cancer and has a tendency of developing in male individuals older than 50 years. While the most common sites of metastatic SDC are the lungs and bones,2 rare cases of cutaneous metastasis have been reported.3-5 Clinically, metastatic SDC on the skin may present as pink pebble-like papules, subcutaneous nodules, or, rarely, as carcinoma hemorrhagiectoides, as in this case. Carcinoma hemorrhagiectoides is characterized as a purpuric indurated plaque with overlying angiokeratoma-like black keratotic papules and nodules. A shield sign, a term derived from the similarity in shape to a medieval knight’s shield, has been described on the anterior chest of affected individuals.4 Studies have suggested that the pathomechanism of carcinoma hemorrhagiectoides may be associated with direct tumor invasion of blood vessels and lymphatic ducts in the dermis.4 A biopsy was needed for exclusion of other differential diagnoses in this case. The histopathological findings of SDC typically show tumor cells with abundant eosinophilic cytoplasm, large pleomorphic nuclei, and conspicuous nucleoli. Comedonecrosis and a cribriform growth pattern can be variably presented. Immunohistochemically, the tumor cells show a strong and diffuse positive staining for androgen receptor in more than 90% of the cases.1 GATA3 and GCDFP-15 positivity with negative p63 expression can also aid the diagnosis toward SDC. In addition, the histopathologic and immunohistochemical profiles of metastatic SDC may closely resemble invasive ductal carcinoma of the breast; thus, a definite diagnosis is made on a thorough clinicopathological correlation.The differential diagnosis in this case included radiotherapy-induced epithelioid angiosarcoma, Kaposi sarcoma (KS), and acquired angiokeratomas. Radiotherapy-induced angiosarcoma is a late complication of radiotherapy, with a median latency period of 8 years after treatment.6 It occurs mostly in those with breast and gynecological cancers7 and typically presents as a diffuse purplish discoloration in the previously irradiated skin area. Pathologically, crowded atypical endothelial cells with nuclear atypia, necrosis, hemorrhage, occasional formation of intracytoplasmic lumina, and positivity for endothelial cell markers, such as CD31, CD34, and ERG1, can be found. Epithelioid angiosarcoma is a high-grade variant of angiosarcoma with poor prognosis and should be carefully distinguished from this case, given that it is composed of mostly epithelioid cells with minimal vasoformation.8 Additional immunohistochemical features of epithelioid angiosarcoma include positivity of Friend leukemia integration 1 transcription factor and von Willebrand factor, variable positivity for creatine kinase, focal positivity of epithelial membrane antigen A, and negativity of CD34. Kaposi sarcoma is an angioproliferative disorder due to human herpesvirus type 8 infection with intermediate cancer potential. It mostly involves the trunk, limbs, and mucosa as violaceous patches, plaques, or nodules, while craniofacial manifestation is less observed except in AIDS-associated KS.9 The pathological features depend on the different stages of the disease, as characterized by slit-like spaces and a proliferation of bland spindle cells stating positive for CD31 and herpesvirus type 8. Lastly, acquired angiokeratomas are characterized by multiple bluish-to-reddish hyperkeratotic papules with a wide range of anatomic distribution. Microscopically, dilated vascular spaces in the dermis extending into the epidermis with hyperkeratosis, acanthosis, papillomatosis, and elongation of the rete ridges can be found.

Dermatology

A man in his 80s presented to the dermatology clinic with a 3-month history of a violaceous plaque with blackish papules and nodules on his left cheek, neck, and chest. He reported that the lesion had been asymptomatic but was increasing in size, with progression from his face to anterior chest. He received a diagnosis of primary salivary duct carcinoma of the hard palate 1 year prior and had been receiving treatment with oral bicalutamide and radiotherapy. A partially regressive change of the palatal tumor was noted radiographically during regular follow-up 3 months previously. On clinical examination, a hemorrhagic and erythematous plaque with multiple purpuric-to-blackish infiltrative papules and nodules extending from cheek, lateral neck, to the interclavicular area was found (Figure 1). An incisional biopsy from the infiltrative nodule on cheek was performed and submitted for histopathologic analysis.Hemorrhagic and erythematous plaque with multiple infiltrative purpuric-to-blackish papules and nodules with varying sizes extending from left cheek, neck, to chest.

what is your diagnosis?

What is your diagnosis?

Acquired angiokeratomas

Kaposi sarcoma

Radiotherapy-induced epithelioid angiosarcoma

Carcinoma hemorrhagiectoides

d

male

81-90

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2808313

A previously healthy 16-year-old girl presented to our department with a red tumor on her right upper arm that enlarged over 6 months. The lesion initially started as a small cutaneous nodule without obvious triggers that gradually developed and enlarged to form a red-colored tumor with a hard nodule inside. There was no history of local trauma or insect bite. Her personal, past, and family histories were unremarkable.On physical examination, there was a 6 × 6-cm protuberant, thick-walled, and well-defined red bullalike tumor on the right upper arm, which extended 1 to 3 cm from the epidermal surface (Figure, A). Inside the tumor, a nontender, firm-to-hard nodule was palpated. There was no regional lymphadenopathy, and results of the rest of the physical and systemic examinations were normal. Laboratory examinations of hematologic, biochemical, and urinalysis tests were normal. The tumor was excised completely under local anesthesia, and part of the tissue was sent for pathological examination.A, A tumor on the patient’s right shoulder. B, The excisional tumor showed multilocular spaces below the epidermis and a solid tumor present in the deep dermis with a chalky-white cut surface and lobulated appearance. C and D, Histological examination revealed basophilic cells and shadow cells as well as dilated lymphatic vessels (hematoxylin-eosin; original magnification ×100). What Is Your Diagnosis?

Matrical carcinoma

Panfolliculoma

Bullous pilomatricoma

Trichodiscoma

C. Bullous pilomatricoma

C

Bullous pilomatricoma

The gross specimen of excised material showed multilocular spaces below the epidermis and a solid tumor present in the deep dermis with a chalky-white cut surface and lobulated appearance (Figure, B). Histopathological examination revealed basophilic cells and shadow cells in the deep dermis (Figure, C) and dilated lymphatic vessels in the dermis above the tumor (Figure, D).Based on the clinical morphology and histological features, the diagnosis of bullous pilomatricoma was confirmed. The patient is under regular outpatient follow-up, with no recurrence detected in 1 year of follow-up.Bullous pilomatricoma is a rare variant of pilomatricoma with a bullous appearance.1 It most commonly occurs on the shoulder and upper arm but also can be found on the neck, trunk, eyelid, and scalp. The peak age of presentation is 10 to 20 years old, and there is a predilection for female individuals.2 Clinically, bullous pilomatricoma usually presents as a solitary, semitransparent, erythematous, bluish or skin-colored, heavily folded or striaelike, flaccid, thick-walled, bullalike tumor with an underlying palpable hard nodule.1-3 It is rare for patients with bullous pilomatricoma to have multiple lesions.4The present patient’s lesion was increasing in size gradually but always had a clear border. When the bullalike tumor was punctured, a jellylike substance could be seen exuding out.4 Unlike some typical pilomatricomas, bullous pilomatricoma is not associated with Turner syndrome, myotonic dystrophy, Gardner syndrome, or Rubinstein-Taybi syndrome.2The etiopathogenesis of bullous pilomatricoma is not clear. There are 2 proposed theories. In the first, obstruction of lymphatic vessels and congestion of lymphatic fluid caused by the growth of the tumor nodule causes dilatation of lymphatic vessels, leakage of lymphatic fluid, and edema in the dermis surrounding the tumor, which further produces the bullous appearance.2,5 The second theory suggests that the presence of matrix metalloproteinases (MMP-9 and MMP-12), released by fibroblasts and inflammatory cells surrounding the tumor, may be associated with the degradation of elastic fibers and collagen, resulting in the bullouslike/anetodermic appearance.6Histologically, bullous pilomatricoma not only has the hallmarks of pilomatricoma, including basaloid cells and eosinophilic keratinized (shadow) cells, but also shows dilated lymphatic vessels, giant cell reaction, lymphoedema, disruption of collagen fibers, dilated blood vessels, fibrous capsule, calcification, nests of transitional cells, and necrosis.2 The presence of dilated lymphatic vessels and lymphedema have been described as a common pathologic feature in bullous pilomatricomas2,7 and can be used to distinguish bullous pilomatricomas from common pilomatricomas. Moreover, as a low-cost, noninvasive tool, ultrasonography (specifically high-frequency ultrasonography8) has been used as a diagnostic tool and is more appropriate for younger children to demonstrate the superficial position, continuity of the lesion with deeper structures, and degree of calcification.The diagnosis of bullous pilomatricoma may be difficult clinically, due to its atypical presentation. The common differential diagnoses should include matrical carcinoma, panfolliculoma, and trichodiscoma. Matrical carcinoma is a locally aggressive tumor, which is typically featured with a nontender, firm dermal swollen nodule and occurs most commonly in the area of the head and neck. Histologically, both matrical carcinomas and pilomatricomas are composed of nodular aggregates of basaloid keratinocytes that transform into shadow cells.9 Cellular pleomorphism and asymmetry, undefined circumscription, and tumor necrosis can help distinguish these 2 entities. Panfolliculoma typically presents as a slow-growing cystic or dome-shaped nodule, which may develop ulcers and crusts in the center, mainly affecting the face and scalp, though sometimes the limbs, of elderly patients.10 Histologically, cellular aggregates can differentiate into any components of the hair follicle, not just the hair matrix cells and shadow cells. Trichodiscoma, a follicular mesenchymal hamartoma, is characterized by multiple, small, 2- to 4-mm, dome-shaped, skin-colored papules on the face, scalp, ears, or upper trunk. Histopathological examination can show a central zone of fibro-mucinous stroma, with surrounding sebaceous glands in a mittlike configuration. The first-line treatment is surgical excision or curettage, and incomplete resection almost always results in recurrence.

Dermatology

A previously healthy 16-year-old girl presented to our department with a red tumor on her right upper arm that enlarged over 6 months. The lesion initially started as a small cutaneous nodule without obvious triggers that gradually developed and enlarged to form a red-colored tumor with a hard nodule inside. There was no history of local trauma or insect bite. Her personal, past, and family histories were unremarkable.On physical examination, there was a 6 × 6-cm protuberant, thick-walled, and well-defined red bullalike tumor on the right upper arm, which extended 1 to 3 cm from the epidermal surface (Figure, A). Inside the tumor, a nontender, firm-to-hard nodule was palpated. There was no regional lymphadenopathy, and results of the rest of the physical and systemic examinations were normal. Laboratory examinations of hematologic, biochemical, and urinalysis tests were normal. The tumor was excised completely under local anesthesia, and part of the tissue was sent for pathological examination.A, A tumor on the patient’s right shoulder. B, The excisional tumor showed multilocular spaces below the epidermis and a solid tumor present in the deep dermis with a chalky-white cut surface and lobulated appearance. C and D, Histological examination revealed basophilic cells and shadow cells as well as dilated lymphatic vessels (hematoxylin-eosin; original magnification ×100).

what is your diagnosis?

What is your diagnosis?

Trichodiscoma

Panfolliculoma

Matrical carcinoma

Bullous pilomatricoma

d

female

11-20

White

original