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kenza-ily

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JAMA_Chen2024

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https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2686384

A white man in his early 30s was referred to our hospital after abnormal findings on a routine ophthalmologic examination. He had traveled from Gabon to the United States 2 weeks earlier. He had no significant medical history except use of correctional lens due to myopia; his body mass index was normal. He had worked in Gabon as an engineer for the past 10 months and reported numerous insect bites, but denied other exposures. He was up to date on required vaccinations and had received doxycycline for the past 10 months for malaria prophylaxis. The patient had no symptoms on presentation and denied fevers, headaches, or visual disturbances. Examination of the fundus showed bilateral elevation of the optic nerve head with blurring of the disc margins (Figure); an ocular ultrasonography showed no optic nerve drusen. A magnetic resonance image of the brain with and without gadolinium was normal, and a magnetic resonance venogram showed no evidence of venous sinus thrombosis. A lumbar puncture demonstrated elevated intracranial pressure (ICP) of 35 mm Hg; white cells, 1/μL (to convert to ×109/L, multiply by 0.001); protein, 0.02 g/dL (to convert to g/dL, multiply byt 10.0); glucose, 55 mg/dL (to convert to mmol/L, multiply by 0.0555); and a negative gram stain.Optic disc edema with a circumferential halo (arrowhead). What Would You Do Next?

Begin amphotericin B and 5-flucytosine

Start penicillin intravenously

Initiate acetazolamide

Discontinue doxycycline

Doxycycline-induced increased ICP

D

Discontinue doxycycline

Given increased ICP in the setting of normal imaging and cerebrospinal fluid (CSF) test results, doxycycline-induced ICP was the most likely cause and was immediately discontinued. Treatment with amphotericin B and 5-flucytosine was not preferred since fungal infections, such as Cryptococcus, are unlikely without symptoms and with CSF protein levels within the reference range, and the patient was not immunosuppressed (eg, human immunodeficiency virus). Similarly, although high-dose intravenous penicillin would treat syphilis, it was not recommended given the absence of suggestive symptoms, lack of inflammatory findings (eg, uveitis) or granulomatous features (eg, keratic precipitates) on ocular examination, and CSF cell counts within the reference ranges. Acetazolamide therapy may be useful in reducing intraocular pressure, but removal of the inciting event (ie, use of doxycycline) should be the initial intervention. Noninfectious inflammatory conditions, such as sarcoidosis, were considered, but the absence of lacrimal gland involvement, uveitis, or retinal periphlebitis made these conditions less likely.1 In the present case, CSF and blood cultures (bacterial, fungal, and acid-fast bacilli) and serology test results (Cryptococcus antigen, rapid plasmin reagin, interferon-γ release assay, and angiotensin-converting enzyme level) were negative.The diagnostic evaluation of papilledema includes brain imaging followed by lumber puncture. Elevated ICP can be caused by intracranial masses (eg, tumors), bleeding or fluid around the brain, or inflammation from infectious or inflammatory conditions. In addition, pseudotumor cerebri causes elevated ICP but without evidence of underlying structural intracranial pathology and with normal CSF composition.2,3 Primary pseudotumor cerebri typically occurs in obese women during the third to fifth decades of life3; this case occurred in a normal weight man, making this diagnosis less likely. Secondary forms of pseudotumor cerebri include inciting factors (eg, venous sinus thrombosis) or medications (eg, tetracyclines, vitamin A, corticosteroids, nitrofurantoin, ciprofloxacin, danazol, levonorgestrel, and isotretinoin).2The tetracycline class of antibiotics used for acne treatment has been implicated as a cause of increased ICP in both sexes and without concomitant obesity.4 In this case, doxycycline for antimalarial prophylaxis was believed to be the cause, similar to 2 other published cases.5 The exact mechanism by which tetracyclines lead to intracranial hypertension is unknown, but is postulated to be interference with CSF absorption at the arachnoid granulations by affecting cyclic adenosine monophosphate.3 Increased ICP in select patients receiving tetracyclines may be related to host genetics, as proposed by cases occurring in dizygotic twins.6Symptoms of increased ICP due to the tetracycline class of antibiotics can begin within hours to days of initiation or after months to years of chronic use.2 Symptoms of increased ICP (eg, new or worsening headache, visual obscurations, tinnitus, nausea, vomiting, and photosensitivity) should prompt immediate ophthalmologic evaluation.2,5,7 Educating patients on the potential symptoms of this condition is advocated as early recognition may prevent permanent visual compromise.3,5Treatment approaches include permanent discontinuation of the inciting medication since increased ICP can recur with reintroduction.8 If ICP remains elevated, acetazolamide treatment can be considered.2,7,9 Other options include furosemide, methylprednisolone, further lumbar punctures or lumbar drain placement, and optic nerve sheath fenestration.3,4The outcome of tetracycline antibiotic–induced ICP is usually favorable if recognized early; resolution of the elevated ICP and symptoms often occurs within 2 to 4 weeks after drug discontinuation.3 However, permanent visual deficits may occur including impaired acuity, visual field deficits, optic nerve pallor, and central scotoma.2,5,9Doxycycline was discontinued; however, bilateral papilledema persisted 4 weeks later and acetazolamide, 500 mg extended-release twice daily, was initiated. The patient returned to Africa and was provided atovaquone plus proguanil to replace doxycycline for antimalarial prophylaxis.

Ophthalmology

A white man in his early 30s was referred to our hospital after abnormal findings on a routine ophthalmologic examination. He had traveled from Gabon to the United States 2 weeks earlier. He had no significant medical history except use of correctional lens due to myopia; his body mass index was normal. He had worked in Gabon as an engineer for the past 10 months and reported numerous insect bites, but denied other exposures. He was up to date on required vaccinations and had received doxycycline for the past 10 months for malaria prophylaxis. The patient had no symptoms on presentation and denied fevers, headaches, or visual disturbances. Examination of the fundus showed bilateral elevation of the optic nerve head with blurring of the disc margins (Figure); an ocular ultrasonography showed no optic nerve drusen. A magnetic resonance image of the brain with and without gadolinium was normal, and a magnetic resonance venogram showed no evidence of venous sinus thrombosis. A lumbar puncture demonstrated elevated intracranial pressure (ICP) of 35 mm Hg; white cells, 1/μL (to convert to ×109/L, multiply by 0.001); protein, 0.02 g/dL (to convert to g/dL, multiply byt 10.0); glucose, 55 mg/dL (to convert to mmol/L, multiply by 0.0555); and a negative gram stain.Optic disc edema with a circumferential halo (arrowhead).

what would you do next?

What would you do next?

Initiate acetazolamide

Discontinue doxycycline

Begin amphotericin B and 5-flucytosine

Start penicillin intravenously

b

male

31-40

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2686385

An adolescent boy was referred for a routine eye examination with the following medical history: coarctation of the aorta, aortic stenosis, cerebellar hemorrhage, hydrocephalus treated with ventriculoperitoneal shunt, scoliosis due to hemivertebrae, congenital diaphragmatic and umbilical hernia, and hearing loss. Physical examination showed short stature (height in the third percentile) with mild muscle wasting in both lower extremities. Visual acuity was 20/30 OU. He had an esotropia of 30 prism diopters with mild bilateral inferior oblique muscle overaction. External examination showed hypertelorism, bilateral upper eyelid ptosis, and a broad nasal bridge. Slitlamp biomicroscopy disclosed bilateral posterior embryotoxon, iris stromal hypoplasia, and translucent strands extending from the inferior segment of the iris toward the cornea in both eyes, with right corectopia (Figure, A). Intraocular pressures (IOPs) were 11 mm Hg OD and 10 mm Hg OS. Situs inversus of the optic discs and a cup-disc ratio of 0.2 in both eyes was noted. Results of the retinal examination were otherwise normal. SITA (Swedish Interactive Thresholding Algorithm) 24-2 visual field revealed superior arcuate defects in both eyes. Optical coherence tomography (OCT) showed mild peripapillary retinal nerve fiber layer thinning inferiorly in both eyes. Magnetic resonance imaging of the brain disclosed dysgenesis of the left cerebellar hemisphere and vermis (Figure, B). Family history and examination of other family members disclosed no similar abnormalities.A, Slitlamp biomicroscopy showing posterior embryotoxon, peripheral iris strands (arrowhead), and corectopia of the right eye. B, Axial T2-weighted magnetic resonance image showing dysgenesis of the left cerebellar hemisphere (arrowhead) and vermis (the unpaired median portion of the cerebellum that interconnects the 2 hemispheres [asterisk]). What Would You Do Next?

OCT angiography

Topical ocular hypotensive therapy

Strabismus surgery

Genetic testing

Axenfeld-Rieger syndrome

D

Genetic testing

This constellation of findings is diagnostic of Axenfeld-Rieger syndrome (ARS). Ocular features observed in ARS include iris stromal hypoplasia, iridogoniodysgenesis, posterior embryotoxon, iris strands bridging the iridocorneal angle to the trabecular meshwork, polycoria, and corectopia. 1 Ocular involvement is usually bilateral but can be asymmetrical.2 The absence of corneal abnormalities distinguishes ARS from other anterior segment dysgenesis disorders, such as Peters anomaly, iris hypoplasia/iridogoniodysgenesis anomaly, or primary congenital glaucoma.2 Ocular malformations in ARS contribute to obstruction of aqueous humor outflow, leading to increased IOP.3 Patients with ARS are at a greater than 50% risk of developing primary open-angle glaucoma.3 Systemic features that accompany ARS include craniofacial abnormalities (maxillary hypoplasia, hypertelorism, and telecanthus), dental anomalies, a redundant umbilical skin, cardiac defects, and hearing loss.4 This autosomal dominant condition is attributed to abnormal neural crest migration.5Because of the associated cerebellar malformation, the initial diagnostic test to perform is genetic to look for the Forkhead box C1 transcription factor (FOXC1 [OMIM 601090]) mutation. Neuroimaging findings associated with FOXC1 mutation include cerebellar vermis hypoplasia, mega cisterna magna, and Dandy-Walker malformation.3,5 Multiple lacunar infarcts and patchy white matter signal changes can be also seen and may be accompanied by enlarged perivascular spaces, hemorrhage, and dystrophic calcifications.5Optical coherence tomographic angiography is a new technology that shows attenuated peripapillary and parafoveal vascular density, enlarged foveal avascular zone, and reduced blood flow index in patients with glaucoma. However, whether this retinovascular imaging provides more sensitive information about glaucoma diagnosis or progression is unclear. Ocular hypotensive therapy would not be indicated in the absence of elevated IOP, abnormal cupping, or evidence of progression on visual field or OCT findings. Medications to lower IOP and surgery have a lower success rate in patients with ARS compared with patients with glaucoma without ARS.6 Strabismus surgery would not be advisable because the patient had a long-standing esotropia and was asymptomatic. Genetic testing is the correct choice, because identifying the causative mutation can predict systemic associations and provide additional information regarding glaucoma prognosis. For example, mutations in the paired-liked homeodomain transcription factor 2 (PITX2 [OMIM 601542]) are more often associated with dental and umbilical anomalies, whereas FOXC1 variants often have the ARS phenotype alone or present with other systemic anomalies, including cerebellar malformations, heart anomalies, hearing defects, developmental delay, and growth delay.4Mutations in FOXC1 and PITX2 account for approximately 40% of individuals with ARS.2FOXC1 regulates neural crest cell development, proliferation, migration, and differentiation within the eye, brain, heart, and kidney.2,5 In these regions, chemoreceptor signaling regulates neuronal migration and cell positioning with resultant disruption of patterning in brain, vessels, and bone.5 Glaucoma prevalence among patients with FOXC1 and PITX2 mutations has been estimated at 59%, and the median age at diagnosis was significantly younger for FOXC1 mutation carriers compared with PITX2 carriers.4FOXC1 encodes proteins that appear to be necessary for maintaining PITX2 expression at later stages of eye development.1 Recently, FOXC1 mutations have been shown to affect secretion of myocilin, a protein involved in exocytosis within the trabecular meshwork, and thereby predispose to juvenile glaucoma.3The diagnosis of ARS is established based on a combination of ophthalmologic (biomicroscopy, gonioscopy, and IOP measurement) and systemic findings. After the diagnosis is established, genetic analysis can provide critical prognostic information.This patient was diagnosed with ARS caused by FOXC1 mutation conferring an increased risk for glaucoma and associated cerebellar dysgenesis. Despite this risk, subsequent ophthalmologic examinations during a 10-year follow-up have not shown IOP elevation, visual field deterioration, or retinal nerve fiber layer loss on OCT.

Ophthalmology

An adolescent boy was referred for a routine eye examination with the following medical history: coarctation of the aorta, aortic stenosis, cerebellar hemorrhage, hydrocephalus treated with ventriculoperitoneal shunt, scoliosis due to hemivertebrae, congenital diaphragmatic and umbilical hernia, and hearing loss. Physical examination showed short stature (height in the third percentile) with mild muscle wasting in both lower extremities. Visual acuity was 20/30 OU. He had an esotropia of 30 prism diopters with mild bilateral inferior oblique muscle overaction. External examination showed hypertelorism, bilateral upper eyelid ptosis, and a broad nasal bridge. Slitlamp biomicroscopy disclosed bilateral posterior embryotoxon, iris stromal hypoplasia, and translucent strands extending from the inferior segment of the iris toward the cornea in both eyes, with right corectopia (Figure, A). Intraocular pressures (IOPs) were 11 mm Hg OD and 10 mm Hg OS. Situs inversus of the optic discs and a cup-disc ratio of 0.2 in both eyes was noted. Results of the retinal examination were otherwise normal. SITA (Swedish Interactive Thresholding Algorithm) 24-2 visual field revealed superior arcuate defects in both eyes. Optical coherence tomography (OCT) showed mild peripapillary retinal nerve fiber layer thinning inferiorly in both eyes. Magnetic resonance imaging of the brain disclosed dysgenesis of the left cerebellar hemisphere and vermis (Figure, B). Family history and examination of other family members disclosed no similar abnormalities.A, Slitlamp biomicroscopy showing posterior embryotoxon, peripheral iris strands (arrowhead), and corectopia of the right eye. B, Axial T2-weighted magnetic resonance image showing dysgenesis of the left cerebellar hemisphere (arrowhead) and vermis (the unpaired median portion of the cerebellum that interconnects the 2 hemispheres [asterisk]).

what would you do next?

What would you do next?

OCT angiography

Genetic testing

Topical ocular hypotensive therapy

Strabismus surgery

b

male

11-20

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2679558

A white man in his 50s with a medical history of myelodysplastic syndrome (MDS) refractory anemia with excess blasts, type 2 (RAEB-2) or MDS with excess blasts, type 2 (MDS-EB-2) RAEB-2 reported a 2-month history of nonpruritic infiltrative skin lesions on the left upper chest, which disseminated to the entire chest, back, and right facial areas (Figure, A). The patient was initially diagnosed with MDS 3 years ago and treated with azacitidine followed by CLAG (cladribine, cytarabine, granulocyte-colony stimulating factor). Posttreatment bone marrow biopsy findings at that time showed no evidence of disease. His physical examination on this presentation showed multiple dark brown cutaneous papules measuring at 3.0 to 5.0 cm (Figure, A), but the rest of the examination results were negative for hepatosplenomegaly or lymphadenopathy. Complete blood cell count showed a white blood cell count of 3.3 × 109/L with absolute neutrophil count of 1.0 × 109/L, Hb 12.7g/dL, platelet counts 118 × 109/L and differential counts showed no evidence of circulating blasts. In addition, results of laboratory workup including peripheral blood culture, methicillin-resistant Staphylococcus aureus (MRSA) swab, human immunodeficiency virus test, and flow cytometry performed on his peripheral blood were all negative. Pathologic sampling from the skin lesion showed the presence of monomorphous small to medium cells extending through the dermis and into the subcutaneous fat (Figure, B). Immunohistochemical staining demonstrated CD4-, CD33-, CD43-, CD56-, CD123-, and TCL1-positive neoplastic cells with Ki-67 of 85%, but staining results for TdT, MUM1, CD3, CD20, Bcl-6, CyclinD1, and CD8 were negative (Figure, C). Results of bone marrow biopsy showed normocellular marrow maturing trilineage hematopoiesis with no increase of blasts or other abnormal populations. Cytogenetics results were abnormal, showing del(20)(q11.2q13.3)[8]/46,XY[12].A, Skin image showing a single, brownish nodule and adjacent scar from prior biopsy. B, A section of cutaneous blastic plasmacytoid dendritic cell neoplasm with subepidermic confluent atypical cellular infiltrate composed of medium sized, round to oval, or elongated immature precursors with finely granular to open chromatin, inconspicuous to prominent nucleoli and a small amount of cytoplasm (hematoxylin-eosin stain, original magnification ×600). C, CD56 (immunoperoxidase stain, original magnification ×600). What Is Your Diagnosis?

Leukemia cutis

Primary cutaneous anaplastic large cell lymphoma

Cutaneous blastic plasmacytoid dendritic cell neoplasm

Transformed mycosis fungoides and Sézary syndrome

C. Cutaneous blastic plasmacytoid dendritic cell neoplasm

C

Cutaneous blastic plasmacytoid dendritic cell neoplasm

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare clonal disorder comprising 0.7% of cutaneous lymphomas.1 Blastic plasmacytoid dendritic cell neoplasm is categorized as an independent entity to acute myeloid leukemia (AML)2 and it may occur as an isolated disease or in the presence of other hematologic malignant abnormalities including AML, MDS, chronic myelogenous leukemia (CML), and chronic myelomonocytic leukemia (CMML) in 10% to 20% of cases.1 Blastic plasmacytoid dendritic cell neoplasm typically occurs in the elderly population (median age, 60-70 years), and it is more common in men (2.5-3.5:1.0).3Although BPDCN can involve any body site including lymph node, spleen, and liver, the most common sites are skin and bone marrow.4 Accordingly, patients commonly present with cutaneous lesions as brown or purple nodules (73%), bruise-like patches (12%), disseminated or mixed lesions (14%).4 Cytopenia (thrombocytopenia, 78%; anemia, 65%; neutropenia, 34%) is common in the presence of bone marrow involvment.4 Overt leukemia with circulating BPDCN cells could be the first manifestation in advanced cases.4Cutaneous lesions in BPDCN may mimic lesions of leukemia cutis, cutaneous CMML, cutaneous T-cell lymphoma, or Langerhans cell histiocytosis, rendering it a diagnostic challenge. Notably, BPDCN typically show dense dermal infiltration of small-to-medium sized immature cells with plasmacytoid appearance and elongated cytoplasmic tails. Results of immunohistochemical analyses are typically positive for CD4, CD56, CD45RA, CD123, TCL1, BDCA-2, TCF-4/E2-2, and BDCA-4, and results for CD3, CD11c, CD14, CD19, CD57, CD117, and myeloperoxidase are negative. Results for CD8, CD20, CD34, PAX5, Epstein-Barr virus, and T-cell receptor proteins are uniformly negative.The pathogenesis of BPDCN and its relationship to other hematologic disorders remain elusive. Its immunophenotypic resemblance to plasmacytoid dendritic cells (PDCs) and higher proliferation index suggest that BPDCN originates from PDCs. Recent genetic studies demonstrated BPDCN shares many mutations in common (TET2, 80%; ASXL1, 32%; NRAS, 27.3%; TP53) with other myeloid disorders,5 and abnormal karyotypes such as 5q, 6q, 12p, 13q, and 15q have been reported in 50% to 65% of cases.6The clinical outcome of BPDCN remains dismal, with median overall survival (OS) of 12 to 14 months.3 Advanced age is an adverse prognostic factor, and no survival difference was observed between cutaneous vs systemic BPDCN.7 There is no standard care established given its rarity. A retrospective study3 showed that regimens for acute lymphoblastic leukemia (ALL) or aggressive non-Hodgkin lymphomas such as hyper-CVAD (including course A [cyclophosphamide, vincristine, doxorubicin, dexamethasone] and course B [methotrexate and cytarabine]) or CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) had superior outcomes compared with AML regimens (66.6% vs 26.9% complete remission [CR] rate; P = .02; median OS, 12.3 vs 7.1 months; P = .02). Therefore, ALL-like induction chemotherapies are recommended along with central nervous system prophylaxis or therapy. A recent phase 2 clinical trial of SL-401, a recombinant interleukin 3 genetically fused to a truncated diphtheria toxin, demonstrated an overall response rate (ORR) of 95%, a CR of 79%, and median progression-free survival (PFS) of 9.5 months in the front-line setting, enabling successful bridging to allogeneic stem cell transplant (allo-SCT) in 44% of patients.8 Disease relapse is common (median relapse time 9 months) regardless of types of treatments.4 Therefore, allo-SCT is recommended in patients who achieve CR/partial response after induction therapies. In a large retrospective study, 3-year OS rate was 41% in patients treated with allo-SCT, and there was no relapse observed 27 months after allo-SCT, suggesting that allo-SCT could be potentially curative.9 Another study10 showed significantly higher 3-year OS rate (74% vs 0%, P < .001) in patients who received allo-SCT in their first CR vs not in CR1, further emphasizing the benefit of allo-SCT. The optimal therapy for refractory/relapsed BPDCN is poorly defined. The SL-401 study showed an ORR of 69%, a CR rate of 31%, and median PFS 3.6 months in the refractory/relapsed settings.8 Currently, a variety of agents including BCL-2 inhibitors are under clinical development.This patient was treated with hyper-CVAD with complete resolution of skin lesions; however, the patient developed disease relapse and was subsequently treated with SL-401. Unfortunately, he had progression of disease and died after further chemotherapies.

Oncology

A white man in his 50s with a medical history of myelodysplastic syndrome (MDS) refractory anemia with excess blasts, type 2 (RAEB-2) or MDS with excess blasts, type 2 (MDS-EB-2) RAEB-2 reported a 2-month history of nonpruritic infiltrative skin lesions on the left upper chest, which disseminated to the entire chest, back, and right facial areas (Figure, A). The patient was initially diagnosed with MDS 3 years ago and treated with azacitidine followed by CLAG (cladribine, cytarabine, granulocyte-colony stimulating factor). Posttreatment bone marrow biopsy findings at that time showed no evidence of disease. His physical examination on this presentation showed multiple dark brown cutaneous papules measuring at 3.0 to 5.0 cm (Figure, A), but the rest of the examination results were negative for hepatosplenomegaly or lymphadenopathy. Complete blood cell count showed a white blood cell count of 3.3 × 109/L with absolute neutrophil count of 1.0 × 109/L, Hb 12.7g/dL, platelet counts 118 × 109/L and differential counts showed no evidence of circulating blasts. In addition, results of laboratory workup including peripheral blood culture, methicillin-resistant Staphylococcus aureus (MRSA) swab, human immunodeficiency virus test, and flow cytometry performed on his peripheral blood were all negative. Pathologic sampling from the skin lesion showed the presence of monomorphous small to medium cells extending through the dermis and into the subcutaneous fat (Figure, B). Immunohistochemical staining demonstrated CD4-, CD33-, CD43-, CD56-, CD123-, and TCL1-positive neoplastic cells with Ki-67 of 85%, but staining results for TdT, MUM1, CD3, CD20, Bcl-6, CyclinD1, and CD8 were negative (Figure, C). Results of bone marrow biopsy showed normocellular marrow maturing trilineage hematopoiesis with no increase of blasts or other abnormal populations. Cytogenetics results were abnormal, showing del(20)(q11.2q13.3)[8]/46,XY[12].A, Skin image showing a single, brownish nodule and adjacent scar from prior biopsy. B, A section of cutaneous blastic plasmacytoid dendritic cell neoplasm with subepidermic confluent atypical cellular infiltrate composed of medium sized, round to oval, or elongated immature precursors with finely granular to open chromatin, inconspicuous to prominent nucleoli and a small amount of cytoplasm (hematoxylin-eosin stain, original magnification ×600). C, CD56 (immunoperoxidase stain, original magnification ×600).

what is your diagnosis?

What is your diagnosis?

Cutaneous blastic plasmacytoid dendritic cell neoplasm

Primary cutaneous anaplastic large cell lymphoma

Transformed mycosis fungoides and Sézary syndrome

Leukemia cutis

a

male

51-60

White

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2677629

A 44-year-old African American woman without traditional atherosclerotic risk factors or known coronary artery disease (CAD) presented to the emergency department with chest pain. She had 3 previous pregnancies (2 live births and 1 spontaneous abortion); her last child was born more than 5 years ago. Her chest pain began spontaneously 1 hour prior to presentation and was described as retrosternal with radiation to her upper and middle back.On physical examination, her blood pressure was 128/88 mm Hg, her pulse was regular at 96 beats per minute, her respiratory rate was 16 breaths per minute, and her temperature was 36.9° C. Pulse oximetry was 100% in room air. The chest was nontender. Pertinent physical findings included normal central venous pressures, clear lung fields, normal first and second heart sounds, an audible fourth heart sound, and no murmurs. The electrocardiogram (Figure 1A) demonstrated anterior ST-segment elevations consistent with an anterior acute current of injury. Results from the chest radiography were normal. Initial troponin I concentration was 0.02 ng/mL but rose to 177.76 ng/mL over the ensuing 4 hours (the patient’s chest pain had resolved by this time). Urgent coronary angiography was performed (Figure 1B). Thrombolysis in myocardial infarction flow grade 2 was observed in the left anterior descending artery and second diagonal branch.A, Initial 12-lead electrocardiogram on presentation showing ST-segment elevation on anterior leads. B, Selective coronary angiography of the left coronary system in anterior-posterior cranial projection.Perform PCI to the left anterior descending artery and second diagonal branch with drug-eluting stentsPerform PCI to the left anterior descending artery and second diagonal branch with bioresorbable vascular scaffoldsRefer for emergency coronary artery bypass grafting surgery What Would You Do Next?

Perform PCI to the left anterior descending artery and second diagonal branch with drug-eluting stents

Perform PCI to the left anterior descending artery and second diagonal branch with bioresorbable vascular scaffolds

Defer intervention and continue supportive management

Refer for emergency coronary artery bypass grafting surgery

Spontaneous coronary artery dissection

C

Defer intervention and continue supportive management

The differential diagnosis for acute coronary syndrome (ACS) in a young woman includes traditional ACS due to plaque rupture, spontaneous coronary artery dissection (SCAD), coronary vasospasm, and traumatic coronary dissection. Coronary angiography demonstrated a left anterior descending artery and second diagonal branch type 1 nonatherosclerotic SCAD (NA-SCAD) (Figure 2).Selective coronary angiogram of the left coronary system in the anterior-posterior cranial projection. Note the visible dissection flap (arrowheads) in the mid left anterior descending, extending into the ostium of a large second diagonal branch (type I spontaneous coronary artery dissection), with intramural hematoma further down the second diagonal branch. Dissection of the first diagonal branch with thrombolysis in myocardial infarction 1 distal vessel flow is also seen.Type 1 NA-SCAD is a nontraumatic, noniatrogenic separation of the coronary intima from its medial attachments, leading to intramural hematoma formation either due to the presence of an intimal tear or from rupture (and bleeding) of the vasa vasorum. Contemporary estimates attribute 0.1% to 4.0% of all cases of ACS to NA-SCAD, with 50% of patients presenting with ST-elevation myocardial infarction.1 Among women younger than 60 years, up to 35% of cases of ACS are due to this condition.2,3 The most commonly affected vessel is the left anterior descending artery, with multivessel involvement observed in up to 25% of patients.4 Risk factors for NA-SCAD include pregnancy, puerperium, and multiparity. Several systemic disorders have also been associated with this condition, including fibromuscular dysplasia (up to 75% of cases), systemic lupus erythematosus, polyarteritis nodosa, and Marfan syndrome.4The diagnosis of NA-SCAD is challenging and requires a high index of suspicion, given that ACS in young women, particularly those lacking classical CAD risk factors, is uncommon. Angiography is the diagnostic test of choice, with 3 different angiographic patterns described. Type 1 NA-SCAD occurs because of intimal tear formation, as seen in Figure 2. Type 2 NA-SCAD, the most common variant, appears angiographically as a smooth, tubular luminal narrowing from intramural hematoma formation without the development of an intimal tear. Type 3 NA-SCAD, the least common variant, is a focal or tubular irregular stenosis that is difficult to differentiate from atherosclerotic CAD without the use of intracoronary imaging.2 The use of intravenous ultrasonography and optical coherence tomography allows visualization of the intramural hematoma or false lumen, although the coronary manipulation inherent to the use of these imaging modalities is a high-risk maneuver given the potential to propagate dissections with wiring or contrast injection.5The natural course of NA-SCAD–related coronary injury is spontaneous coronary healing. As such, conservative management with supportive care is preferred unless the patient has unremitting chest pain, persistent ST-elevation, or hemodynamic instability because percutaneous or surgical revascularization carries a high failure and complication rate.6 The use of bioresorbable vascular scaffolds to treat NA-SCAD–related ACS in selected patients has been reported.7 However, the recent withdrawal of a bioresorbable scaffold due to elevated risk of stent thrombosis8,9 has limited the availability of this therapy. Further, there is limited evidence to support the use of traditional post-ACS medical therapies in these patients (ie, dual antiplatelet therapy, statins, β-blockers, and angiotensin-converting enzyme inhibitors), outside those in whom these medications are indicated for underlying atherosclerotic CAD, left ventricular dysfunction, or clinical heart failure.Recurrent NA-SCAD occurs in 10% of patients, with most recurrent events affecting a different coronary artery than the index event. Major adverse cardiac events (ie, death, heart failure, myocardial infarction, or recurrent SCAD) occur in almost 20% of cases.2The patient was treated conservatively and monitored in the coronary care unit for 4 days. Her left ventricular ejection fraction at discharge was 50%. Approximately 18 months later, the patient presented with ST-elevation myocardial infarction due to type 2 SCAD of the right coronary artery. This event was treated with drug-eluting stent implantation because of ongoing symptoms and electrical instability. She recovered uneventfully and continues to be observed as an outpatient, with no further events.

Cardiology

A 44-year-old African American woman without traditional atherosclerotic risk factors or known coronary artery disease (CAD) presented to the emergency department with chest pain. She had 3 previous pregnancies (2 live births and 1 spontaneous abortion); her last child was born more than 5 years ago. Her chest pain began spontaneously 1 hour prior to presentation and was described as retrosternal with radiation to her upper and middle back.On physical examination, her blood pressure was 128/88 mm Hg, her pulse was regular at 96 beats per minute, her respiratory rate was 16 breaths per minute, and her temperature was 36.9° C. Pulse oximetry was 100% in room air. The chest was nontender. Pertinent physical findings included normal central venous pressures, clear lung fields, normal first and second heart sounds, an audible fourth heart sound, and no murmurs. The electrocardiogram (Figure 1A) demonstrated anterior ST-segment elevations consistent with an anterior acute current of injury. Results from the chest radiography were normal. Initial troponin I concentration was 0.02 ng/mL but rose to 177.76 ng/mL over the ensuing 4 hours (the patient’s chest pain had resolved by this time). Urgent coronary angiography was performed (Figure 1B). Thrombolysis in myocardial infarction flow grade 2 was observed in the left anterior descending artery and second diagonal branch.A, Initial 12-lead electrocardiogram on presentation showing ST-segment elevation on anterior leads. B, Selective coronary angiography of the left coronary system in anterior-posterior cranial projection.Perform PCI to the left anterior descending artery and second diagonal branch with drug-eluting stentsPerform PCI to the left anterior descending artery and second diagonal branch with bioresorbable vascular scaffoldsRefer for emergency coronary artery bypass grafting surgery

what would you do next?

What would you do next?

Defer intervention and continue supportive management

Refer for emergency coronary artery bypass grafting surgery

Perform PCI to the left anterior descending artery and second diagonal branch with bioresorbable vascular scaffolds

Perform PCI to the left anterior descending artery and second diagonal branch with drug-eluting stents

a

female

41-50

African American

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2687484

A child younger than 10 years presented with an 8-week history of bilateral cervical lymphadenopathy unresponsive to a 10-day course of Augmentin (GlaxoSmithKline). The patient’s parents denied any associated fevers, chills, night sweats, sore throat, abdominal pain, or weight changes. Medical history was noncontributory.Physical examination showed bilateral, mobile, nontender cervical lymphadenopathy without erythema or swelling. Tonsils were symmetric and not enlarged. There was no noticeable thyromegaly or nodules. Laboratory testing was significant for an elevated erythrocyte sedimentation rate (37 mmol/h). Ultrasonography demonstrated cervical lymphadenopathy bilaterally with the largest node measuring 3.8 cm in maximum dimension. Lymph node needle core biopsy demonstrated increased histiocytes and numerous plasma cells on tissue section (Figure, A). Scattered neutrophils and rare giant cells were also present. Findings of Grocott methenamine silver, acid-fast, and Warthin-Starry stains were negative. The CD-68 immunostain showed numerous histiocytes. The specimen stained positive for CD-30 and S-100 immunostains showing emperipolesis (Figure, B and C). Findings of a CD1a stain were negative. Lymphoid markers by flow cytometry showed a polyclonal mixed B-cell and T-cell population.Lymph node needle core biopsy specimens from the patient. A, Evident are increased histiocytes and numerous plasma cells (original magnification × 10). B, Numerous histiocytes with emperipolesis (original magnification × 40). C, Several histiocytes with emperipolesis under oil immersion (original magnification × 100). What Is Your Diagnosis?

Infectious mononucleosis

Langerhans cell histiocytosis

Reactive sinus histiocytosis

Rosai-Dorfman disease

D. Rosai-Dorfman disease

D

Rosai-Dorfman disease

The causes of cervical lymphadenopathy in a child include infection, autoimmune, reactive processes, and cancer. This patient’s 8-week history of lymphadenopathy and lack of clinical symptoms make infectious mononucleosis unlikely. Furthermore, tuberculosis, cat-scratch disease, and fungal infections were ruled out with negative acid-fast, Warthin-Starry, and Grocott methenamine silver staining results, respectively. Lack of distinct elongated, folded, or grooved nuclei and eosinophilic infiltrate, and lack of CD1a staining makes Langerhans cell histiocytosis unlikely. Reactive histiocytosis shows S-100 negativity, unlike that found in the present patient.1Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, was first described in 1969.1 Much of our current understanding of the disease comes from case studies and original histological descriptions by Drs Rosai and Dorfman. Rosai-Dorfman disease classically presents with lymph node enlargement. The most common sites for nodal involvement include cervical (87%), inguinal (26%), axillary (24%), and mediastinal (15%) lymph nodes. Extranodal involvement occurs in up to 43% of patients, most commonly involving the skin, nasal cavity, and paranasal sinuses.1 Most patients are otherwise asymptomatic, although some cases have reported fever. Erythrocyte sedimentation rate is frequently elevated, as seen in this patient.2Grossly, the lymph nodes form multinodular, firm yellow masses with granular cut surfaces surrounded by fibrosis.2 Microscopically, early involvement manifests as expansion of lymph node sinuses by proliferating histiocytes with large, round-to-oval nuclei, and distinct single, centrally located nucleoli. The cytoplasm is abundant and demonstrates a foamy appearance. More advanced cases present with subtotal effacement of architecture by a diffuse infiltrate of histiocytes with an interspersed lymphoplasmacytic infiltrate and a background of fibrosis. Russell bodies are often present in plasma cells.1The histologic findings in extranodal sites are similar to those in lymph nodes. Some differences include more prominent fibrosis, fewer histiocytes, and more prominent germinal centers.1A classic histological feature in RDD is emperipolesis, the presence of intact cells within the cytoplasm of the histiocytes.1 While the cells within histiocytes are most often lymphocytes, plasma cells, and neutrophils, red cells can also be seen. The cells generally appear to be floating freely in the cytoplasm but occasionally may appear contained within a narrow vacuole.1An immunophenotypic feature of RDD histiocytes is granular, cytoplasmic expression of S-100 protein, which can be patchy and variable and helps highlight the emperipolesis as seen in the Figure, C.1 Langerin staining was not performed in this patient. The absence of CD1a expression and characteristic histologic features indicative of RDD were used to exclude Langerhans cell histiocytosis. Expression of CD-30 can be focally positive in RDD cells, as in this case, but is not diffusely reactive, as seen in anaplastic large cell lymphoma.1Rosai-Dorfman disease is rare, and its prevalence is not well documented. There is a male-to-female ratio of 1.4:1, and it is more frequently found in white and African American patients.1 In 1 study, Rosai et al2 found that of 34 patients, 22 presented with RDD in the first decade of life. Overall, RDD has a good prognosis. In another study of 238 patients, 21 patients died, but only 4 from RDD.1Most patients with RDD require no treatment. Although most cases either resolve spontaneously or demonstrate stable disease, a minority of patients have progressive disease, which can result in death due to mass effect on vital structures.1 Treatments in patients requiring therapy, either because of life-threatening disease or for cosmetic reasons, have included surgical excision, steroids, chemotherapy, and radiation but have shown limited and in some cases no benefit.1,3 Garces et al4 reported KRAS and MAP2K1 gene mutations in 33% of cases, allowing for a potential therapeutic target in some progressive cases.The present patient did not receive any intervention and has not exhibited any signs of disease progression. This case highlights the importance of considering RDD in the differential diagnosis of bilateral painless cervical lymphadenopathy.

General

A child younger than 10 years presented with an 8-week history of bilateral cervical lymphadenopathy unresponsive to a 10-day course of Augmentin (GlaxoSmithKline). The patient’s parents denied any associated fevers, chills, night sweats, sore throat, abdominal pain, or weight changes. Medical history was noncontributory.Physical examination showed bilateral, mobile, nontender cervical lymphadenopathy without erythema or swelling. Tonsils were symmetric and not enlarged. There was no noticeable thyromegaly or nodules. Laboratory testing was significant for an elevated erythrocyte sedimentation rate (37 mmol/h). Ultrasonography demonstrated cervical lymphadenopathy bilaterally with the largest node measuring 3.8 cm in maximum dimension. Lymph node needle core biopsy demonstrated increased histiocytes and numerous plasma cells on tissue section (Figure, A). Scattered neutrophils and rare giant cells were also present. Findings of Grocott methenamine silver, acid-fast, and Warthin-Starry stains were negative. The CD-68 immunostain showed numerous histiocytes. The specimen stained positive for CD-30 and S-100 immunostains showing emperipolesis (Figure, B and C). Findings of a CD1a stain were negative. Lymphoid markers by flow cytometry showed a polyclonal mixed B-cell and T-cell population.Lymph node needle core biopsy specimens from the patient. A, Evident are increased histiocytes and numerous plasma cells (original magnification × 10). B, Numerous histiocytes with emperipolesis (original magnification × 40). C, Several histiocytes with emperipolesis under oil immersion (original magnification × 100).

what is your diagnosis?

What is your diagnosis?

Infectious mononucleosis

Langerhans cell histiocytosis

Rosai-Dorfman disease

Reactive sinus histiocytosis

c

neutral

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2688432

A man in his 30s presented with a slow-growing mass in the upper lip that had developed over several years. He had no history of underlying medical diseases, such as hypertension, diabetes, hepatitis, and tuberculosis. On physical examination, a whitish, firm, painless, nodular mass on the superficial layer of the left upper lip was observed (Figure, A). Given the possibility of a tumorous lesion, complete excision was planned under local anesthesia. In surgery, the 1.5 × 1.2 cm, whitish, firm, nodular, and well-encapsulated mass was excised completely without rupture of the capsule from the surrounding mucosa. On histopathologic examination, an encapsulated salivary gland tumor with epithelial and myoepithelial cells, ductlike structures, and mixed stroma was observed (Figure, B). One month after surgery, the surgical wound on the left upper lip was clean and well healed. One year later, there had been no recurrence, and the patient had no symptoms at the left upper lip.A, Clinical image of the left upper lip. B, Histopathologic image (hematoxylin-eosin, original magnification ×10) showing areas of ductal epithelial components with myxoid stroma. What Is Your Diagnosis?

Mucocele

Lipoma

Pleomorphic adenoma

Mucoepidermoid carcinoma

C. Pleomorphic adenoma

C

Pleomorphic adenoma

Salivary gland tumors compose less than 1% of all tumors and 3% to 5% of all head and neck tumors.1 Salivary gland tumors usually occur in major salivary glands; minor salivary gland tumors are rare and represent 15% to 25% of all salivary gland tumors.1,2 The most common site of minor salivary gland tumors is the hard palate (50%-60%), followed by the upper lip (15%-20%) and buccal mucosa (8%-10%).1-4The most common type of minor salivary gland tumor is pleomorphic adenoma (PA), which makes up 40% to 72% of cases.1,2 Pleomorphic adenoma is a benign, epithelial-type tumor with an estimated annual incidence of approximately 1 in 30 000 to 50 000 persons in the United States.1,5 Pleomorphic adenoma is asymptomatic, has slow-growing characteristics, is more common in females than in males, and is most common in the fourth to sixth decades of life.1,4 Pleomorphic adenoma most often involves the parotid glands (80%), followed by submandibular glands (10%) and minor salivary glands (10%). The histopathologic characteristics of PA include both epithelial and myoepithelial cells and an encapsulated form. The tumor cells can differentiate into many types of cells, such as fibrous, hyalinized, mucoid, myxoid, or lipomatous cells. Accordingly, islands of plasmacytoid cells, ductlike structures, and mixed stroma can be observed on histopathologic examination of epithelial salivary gland tissue.1The standard treatment of PA is complete excision with a sufficient margin, because the tumor could recur with incomplete excision. Pleomorphic adenoma also has a high chance of implantability, so it is important not to rupture the capsule during excision. Pleomorphic adenoma can be transformed to malignant carcinoma ex-PA, which comprises approximately 3% of minor salivary gland tumors. The prognosis of PA is good, and the recurrence rate has been reported as 3.4% after 5 years and 6.8% after 10 years.1When a painless, well-demarcated, cystic or nodular mass lesion is in the upper lip, several possible diagnoses could be considered, including mucocele, fibroma, lipoma, and minor salivary gland tumor. Mucocele, the most common minor salivary gland lesion, is mostly found in the lower lip, but occurs rarely in the upper lip.6 Pleomorphic adenoma and mucocele look similar in that both are smooth painless masses. However, mucocele is usually associated with trauma or lip biting,6-8 appears suddenly, and fluctuates in size.6,8 In addition, the color of a mucocele is bluish or pinkish,6,7 and the diameter of most mucoceles is less than 1.5 cm.6In this patient, the location, shape, and color differed from a typical mucocele, favoring consideration of causes such as other benign and malignant tumors. Canalicular adenoma is the most common benign tumor in the upper lip, and PA is the second.3,7 Almost half of all tumors from minor salivary glands are malignant.2 Among malignant tumors in the upper lip, acinic cell adenocarcinoma is the most common; mucoepidermoid carcinoma is more common in the lower lip.3 Benign tumors occur more often in the upper lip, and malignant tumors predominate in the lower lip.8In this patient, PA in the upper lip was excised completely, and there was no recurrence for 1 year. There are many minor salivary glands in the upper lip, and uncommon but clinically important lesions can arise there. Consequently, when a cystic or nodular mass lesion is observed in the upper lip, a careful approach is needed, because it could be benign or malignant. If the lesion is suspicious for PA, a complete, careful excision should be performed to prevent recurrence from a remnant mass and rupture of the capsule. Histopathologic confirmation after surgery is mandatory, and malignancy should be ruled out.

General

A man in his 30s presented with a slow-growing mass in the upper lip that had developed over several years. He had no history of underlying medical diseases, such as hypertension, diabetes, hepatitis, and tuberculosis. On physical examination, a whitish, firm, painless, nodular mass on the superficial layer of the left upper lip was observed (Figure, A). Given the possibility of a tumorous lesion, complete excision was planned under local anesthesia. In surgery, the 1.5 × 1.2 cm, whitish, firm, nodular, and well-encapsulated mass was excised completely without rupture of the capsule from the surrounding mucosa. On histopathologic examination, an encapsulated salivary gland tumor with epithelial and myoepithelial cells, ductlike structures, and mixed stroma was observed (Figure, B). One month after surgery, the surgical wound on the left upper lip was clean and well healed. One year later, there had been no recurrence, and the patient had no symptoms at the left upper lip.A, Clinical image of the left upper lip. B, Histopathologic image (hematoxylin-eosin, original magnification ×10) showing areas of ductal epithelial components with myxoid stroma.

what is your diagnosis?

What is your diagnosis?

Mucoepidermoid carcinoma

Pleomorphic adenoma

Lipoma

Mucocele

b

male

31-40

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2678681

A 40-year-old healthy woman presented with an 8-year history of a slowly growing erythematous plaque on the left lower eyelid, with occasional discomfort. Physical examination revealed a single erythematous scaling plaque involving the left lower eyelid, including its border. Eyelashes were totally absent (Figure 1A). No other lesions were found after complete physical examination. Dermoscopy showed an erythematous background, telangiectatic vessels, whitish structureless areas, and whitish scales (Figure 1B). A 4-mm punch biopsy specimen was obtained (Figure 1C).A, Erythematous scaling plaque involving the left lower eyelid. B, Dermoscopy shows erythematous background, telangiectatic vessels, structureless whitish areas, and white scales. C, Histopathological analysis (hematoxylin-eosin). What Is Your Diagnosis?

Sarcoidosis

Discoid lupus erythematosus

Basal cell carcinoma

Bowen disease

B. Discoid lupus erythematosus

B

Discoid lupus erythematosus

Histopathologic examination demonstrated an atrophic epidermis with parakeratosis, vacuolar alteration of the basal layer, and dense inflammatory infiltrate both in papillary and reticulate dermis, consistent with discoid lupus erythematosus (DLE) (Figure 1C). Antinuclear antibodies and double-stranded DNA serologic testing were negative. The patient was treated with high-potency topical corticosteroid for 10 days, followed by tacrolimus, combined with oral hydroxychloroquine 400 mg daily. At the 2-month follow-up visit, lesions had completely resolved (Figure 2).Discoid lupus erythematosus is the most common clinical subtype of cutaneous lupus erythematosus. Clinically, it is characterized by erythematous and hyperchromic plaques with follicular plugging, which may lead to atrophy, pigmentary changes, and scarring. It primarily affects the ears, face, scalp, and neck.1 Eyelid involvement occurs in only 6% of cases, and DLE solely affecting the eyelids is exceptionally rare.2,3 Lesions involving areas below the neck, the disseminated form of DLE, occur in less than 20% of cases.4 The risk of DLE progressing to systemic lupus erythematosus is relatively low. Nonetheless, widespread DLE lesions, arthralgia and/or arthritis, nail changes, anemia, leucopenia, high erythrocyte sedimentation rates, and high titers of antinuclear antibodies increase this risk.5Dermoscopy has been described as an additional tool for the diagnosis of DLE, and its findings correlate with histopathology and disease duration. Perifollicular whitish halos and follicular plugs are seen in recently developed lesions, whereas structureless whitish areas, telangiectatic vessels, and honeycomb pigment network are findings of longer-standing DLE. These findings correlate with the scarring process seen in DLE, initially affecting the hair follicle with destruction of the perifollicular elastic sheath followed by dermal involvement. Fibrosis throughout the dermis, the end-stage of DLE lesions, corresponds to the whitish structureless areas on dermoscopy.6Eyelid involvement as the only manifestation of DLE can mimic contact dermatitis, atopic dermatitis, seborrheic dermatitis, psoriasis, sarcoidosis, basal cell or squamous cell carcinoma, and actinic keratosis.7,8 Whenever these conditions are suspected or unresponsiveness despite appropriate treatment, DLE should be considered as a potential differential diagnosis.1,3 All efforts must attempt to diagnosis and treat eyelid DLE early to prevent permanent scarring with eyelash loss, entropion, ectropion, adhesion, trichiasis, and visual dysfunction.9,10

Dermatology

A 40-year-old healthy woman presented with an 8-year history of a slowly growing erythematous plaque on the left lower eyelid, with occasional discomfort. Physical examination revealed a single erythematous scaling plaque involving the left lower eyelid, including its border. Eyelashes were totally absent (Figure 1A). No other lesions were found after complete physical examination. Dermoscopy showed an erythematous background, telangiectatic vessels, whitish structureless areas, and whitish scales (Figure 1B). A 4-mm punch biopsy specimen was obtained (Figure 1C).A, Erythematous scaling plaque involving the left lower eyelid. B, Dermoscopy shows erythematous background, telangiectatic vessels, structureless whitish areas, and white scales. C, Histopathological analysis (hematoxylin-eosin).

what is your diagnosis?

What is your diagnosis?

Discoid lupus erythematosus

Bowen disease

Sarcoidosis

Basal cell carcinoma

a

female

31-40

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2678836

A man in his late 20s presented with mildly itchy, erythematous plaques of 3 months’ duration on both legs. The lesions started to appear on the left pretibial region as small papules, which gradually increased in size and coalesced to form bigger plaques. No history of local trauma, prolonged standing, and occupational exposure to mineral dust or recent drug intake was recollected. He was not diabetic. On examination, large, ill-defined, erythematous plaques were present on the pretibial areas extending onto the lateral aspect of both legs. The plaques were surmounted by multiple, discrete atrophic scars. The periphery of the plaques showed increased vascularity in the form of telangiectasias and venous prominences, along with atrophy of the overlying skin (Figure, A). There were no lesions elsewhere on the body. A skin biopsy sample was obtained from the plaque and sent for histopathological examination (Figure, B and C).A, Clinical photograph on presentation showing ill-defined, erythematous plaques surmounted by multiple atrophic scars. The periphery of the plaques shows telangiectasia. Some areas show venous prominence. B, Skin biopsy showing unremarkable epidermis and multiple epithelioid cell granulomas in the entire dermis. C, Compact, noncaseating, epithelioid cell granulomas with multiple Langhans giant cells. D, Photograph after 6 weeks of treatment showing considerable decrease in erythema and induration. What Is Your Diagnosis?

Granulomatous mycosis fungoides

Pretibial myxedema

Cutaneous sarcoidosis

Necrobiosis lipoidica

C. Cutaneous sarcoidosis

C

Cutaneous sarcoidosis

Skin biopsy revealed multiple, well-formed, compact, noncaseating epithelioid cell granulomas with many multinucleated Langhans type giant cells (Figure, B and C). Special stains for microorganisms including Ziehl-Neelsen and periodic acid–Schiff for acid-fast bacilli and fungus, respectively, had negative results. Intradermal testing with purified protein derivative and mycobacterial culture of the skin biopsy specimen had negative results. Overall features were consistent with a diagnosis of sarcoidosis. A complete blood cell count, biochemistry panel including serum calcium level, and inflammatory markers were normal. A high-resolution computed tomography scan of the chest did not reveal any lymphadenopathy or lung parenchymal changes. Serum angiotensin-converting enzyme level was mildly elevated (69 U/L; reference range, 8-65 U/L; to convert to nanokatals per liter, multiply by 16.667). Electrocardiography, 2-dimensional echocardiography, abdominal ultrasound, Doppler ultrasonography of the lower limbs, and high-frequency ultrasound of the local part did not reveal any abnormality.There was no improvement with the initial treatment of potent topical corticosteroids for 1 month, so therapy was switched to oral prednisolone, 0.5 mg/kg/d, plus oral hydroxychloroquine sulfate, 400 mg/d. Within 1 month, there was a substantial reduction in erythema, induration, and vascularity (Figure, D). Prednisolone was tapered over 6 months and stopped. The patient continued use of oral hydroxychloroquine and emollients.Cutaneous sarcoidosis has myriad clinical presentations and is a “great imitator” of many other cutaneous diseases. Hence, the clinical index of suspicion has to be high. It is characterized by noncaseating granulomas in 1 or more organ systems. Skin lesions are present in at least 20% of sarcoidosis cases and are the initial disease manifestation in nearly one-third.1 Diagnosis of cutaneous sarcoidosis can be challenging, especially when the cutaneous presentation is atypical. All cases should undergo histopathological analysis and other laboratory and radiological tests. Biopsy shows the classic noncaseating granulomatous inflammation with sparse lymphocytes and plasma cells (so-called naked granulomas). A chest x-ray, intradermal test with purified protein derivative of Mycobacterium tuberculosis, high-resolution chest computed tomography, and electrocardiogram are important to screen for systemic involvement. Serum angiotensin-converting enzyme level is a nonspecific marker of acute disease activity. It is elevated in roughly 60% of cases with no diagnostic or prognostic significance. A positron emission tomography scan can be considered to detect asymptomatic systemic involvement, especially cardiac, and can also show enhancement of cutaneous granulomatous inflammation.2 The role of dermoscopy and local part ultrasound has been explored for both diagnosis and monitoring during treatment.3,4Necrobiosis lipoidica is most commonly seen on the lower legs and is characterized by well-defined, reddish-brown indurated plaques with a glazed surface and prominent telangiectasia with yellowish atrophic center. Although considered a differential diagnosis, it was not proven because necrobiosis lipoidica on histopathologic analysis shows full-thickness lymphohistiocytic infiltrate extending into deeper dermis with extensive necrobiosis of collagen. Well-formed granulomas, as seen in this patient, are usually not seen in necrobiosis lipoidica. Interestingly, the 2 conditions have been reported to mimic and also coexist with each other.5,6Granulomatous mycosis fungoides (MF) is a rare form of MF characterized by an infiltrate of atypical lymphocytes, histiocytes, and multinucleated giant cells. It has a slowly progressing course with a worse prognosis than other forms of MF. Absence of atypical lymphoid cells and lack of epidermotropism is helpful in excluding this variant of MF.7Pretibial myxedema presents characteristically at this site with diffuse, nonpitting edema of the shins and is characterized histopathologically by extensive mucin deposition in the reticular dermis. Granulomatous inflammation is never a feature.In conclusion, this patient had an uncommon presentation of plaque sarcoid with atrophy that mimicked other common skin diseases involving the lower leg such as necrobiosis lipoidica and pretibial myxedema. Diagnosis was confirmed histopathologically. The lesions responded well to oral corticosteroids, which were tapered and stopped after 6 months with no evidence of recurrence.

Dermatology

A man in his late 20s presented with mildly itchy, erythematous plaques of 3 months’ duration on both legs. The lesions started to appear on the left pretibial region as small papules, which gradually increased in size and coalesced to form bigger plaques. No history of local trauma, prolonged standing, and occupational exposure to mineral dust or recent drug intake was recollected. He was not diabetic. On examination, large, ill-defined, erythematous plaques were present on the pretibial areas extending onto the lateral aspect of both legs. The plaques were surmounted by multiple, discrete atrophic scars. The periphery of the plaques showed increased vascularity in the form of telangiectasias and venous prominences, along with atrophy of the overlying skin (Figure, A). There were no lesions elsewhere on the body. A skin biopsy sample was obtained from the plaque and sent for histopathological examination (Figure, B and C).A, Clinical photograph on presentation showing ill-defined, erythematous plaques surmounted by multiple atrophic scars. The periphery of the plaques shows telangiectasia. Some areas show venous prominence. B, Skin biopsy showing unremarkable epidermis and multiple epithelioid cell granulomas in the entire dermis. C, Compact, noncaseating, epithelioid cell granulomas with multiple Langhans giant cells. D, Photograph after 6 weeks of treatment showing considerable decrease in erythema and induration.

what is your diagnosis?

What is your diagnosis?

Granulomatous mycosis fungoides

Cutaneous sarcoidosis

Necrobiosis lipoidica

Pretibial myxedema

b

male

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2680738

A miner in his early 40s presented with a 6-month history of asymptomatic, erythematous nodules on his face, his chin, the anterior portion of his neck, and the anterior thorax. Approximately 15 years earlier, he had sustained injuries from an accidental land mine explosion that had lacerated his face, neck, and thorax in several places. The wounds apparently healed without difficulty, leaving only scars of expected severity. Approximately 6 months before presentation, the patient began to notice an increase in the size of these lesions. Physical examination showed multiple firm, erythematous, nontender papules, nodules, and small plaques on his face, his chin, the anterior portion of his neck, and the anterior thorax (Figure 1).Multiple firm, erythematous, nontender nodules and small plaques on the patient’s face. What Is Your Diagnosis?

Sarcoidosis

Cutaneous silica granuloma

Infectious granuloma

Keloid

B. Cutaneous silica granuloma

B

Cutaneous silica granuloma

Histologic examination demonstrated multiple nonfusing, noncaseating granulomas containing irregular, highly refractile yellow fragments (Figure 2A). When examined with polarization microscopy, these particles were birefringent (Figure 2B) and showed characteristic features of silicaceous foreign material. Moreover, energy-dispersive radiographic spectroscopy revealed that the particles contained silicon (Figure 2C). Laboratory examination revealed no abnormal findings suggestive of sarcoidosis, such as an increased serum angiotensin-converting enzyme concentration or abnormal chest computed tomography findings. On the basis of the patient’s clinical history and physical and pathologic examination findings, cutaneous silica granuloma was diagnosed. The lesions gradually resolved during 2½ years of observation.A, Histopathologic findings of a cutaneous silica granuloma. Multiple noncaseating granulomas were observed (hematoxylin-eosin, original magnification ×60). B, Polarization microscopic examination of a cutaneous silica granuloma. The particles were birefringent when observed with polarization microscopy (original magnification ×200). C, Energy-dispersive radiographic spectroscopy revealed that the particles contained silicon. C indicates carbon; N, nitrogen; O, oxygen; and Si, silicon.Cutaneous silica granuloma is a rare condition that occurs many years after accidental trauma or minor wounds contaminated by glass, sand, or other silica-containing particles. Most reported cases of silica or silicon granuloma occurred at scar sites.1-5 Such localization occurred as a result of the introduction of silica material into wounds or administration of silicone injections for cosmetic reasons. Skin lesions, which are often nodular, indurated, and erythematous, develop after an asymptomatic latent period that can range from several weeks to many years. Silica granuloma is a granulomatous reaction to silica or silicate and is considered to be a type of delayed hypersensitivity reaction. The pathological picture of silica granuloma involves an allergic reaction to a foreign body, with a typically tuberculoid pattern consisting of epithelioid cells with or without giant cells and with or without caseation necrosis.6The diagnosis of cutaneous silica granuloma is made largely on the basis of clinical findings, including a history of embedment of silica-containing substances in the skin and the development of papules or nodules on a scar caused by past trauma. Silica granuloma should not be confused with sarcoidosis. The diagnosis can be confirmed by the observation of crystalline particles of varying sizes, mainly in giant cells, using light microscopy and doubly refractile particles using polarization microscopy. However, some authors have suggested that silica granuloma and scar sarcoidosis might be the same disease or that silica granuloma might be a feature of systemic sarcoidosis.7,8The optimal treatment of silica granuloma is not clearly defined. Although spontaneous resolution of silica granuloma is mentioned in several articles, excision is the most commonly reported treatment. Therapy with systemic corticosteroids, irradiation, and antibiotics has cleared some lesions.

Dermatology

A miner in his early 40s presented with a 6-month history of asymptomatic, erythematous nodules on his face, his chin, the anterior portion of his neck, and the anterior thorax. Approximately 15 years earlier, he had sustained injuries from an accidental land mine explosion that had lacerated his face, neck, and thorax in several places. The wounds apparently healed without difficulty, leaving only scars of expected severity. Approximately 6 months before presentation, the patient began to notice an increase in the size of these lesions. Physical examination showed multiple firm, erythematous, nontender papules, nodules, and small plaques on his face, his chin, the anterior portion of his neck, and the anterior thorax (Figure 1).Multiple firm, erythematous, nontender nodules and small plaques on the patient’s face.

what is your diagnosis?

What is your diagnosis?

Cutaneous silica granuloma

Keloid

Infectious granuloma

Sarcoidosis

a

male

41-50

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2680067

A man in his 60s with a known history of a large cyst on the right kidney sustained blunt trauma in a skiing crash. Computed tomography (CT) showed a right-sided grade IV renal injury involving his known renal cyst with active arterial extravasation (Figure, A). The patient underwent selective angioembolization of the renal laceration.A, Abdominal computed tomography (CT) with contrast demonstrating grade IV laceration of the right kidney and active extravasation. B, Abdominal CT obtained on day 2 of hospitalization showing large right-sided retroperitoneal hematoma and grade IV renal laceration displacing the patient’s abdominal viscera to the left, with contrast-filled structure medial to the liver.In the 24 hours after embolization, the patient required 2 U of red blood cells via transfusion for anemia. On examination, the patient reported moderate pain in the abdomen and right side and demonstrated a distended abdomen in the absence of any peritoneal signs. Contrast-enhanced CT of the abdomen and pelvis was performed to assess for a source of continued bleeding (Figure, B). What Is Your Diagnosis?

Hepatic artery injury

Jejunal injury with intraluminal contrast extravasation

Contrast-enhancing gallbladder

Rupture of a peripancreatic pseudoaneurysm

C. Contrast-enhancing gallbladder

C

Contrast-enhancing gallbladder

This patient’s CT showed an abnormal finding adjacent to his duodenum, initially concerning for contrast extravasation. On further review, this CT finding was determined to be an artifact produced by vicarious contrast medium excretion (VCME) into the gallbladder. There was no evidence of active extravasation on postembolization imaging, including no persistence of the contrast blush from the known renal laceration.Vicarious contrast medium excretion is a known but rarely reported imaging phenomenon. In cases of blunt trauma, when CT is often used to diagnose injury, vicarious excretion of iodinated contrast medium can cause diagnostic error and subsequent unnecessary testing or intervention. This report highlights a potentially misleading imaging artifact in a patient with blunt trauma secondary to VCME.The excretion of water-soluble contrast medium via the kidneys is a well-described process. When contrast medium is injected to obtain an intravenous pyelogram or angiogram, such as with protocoled CT for trauma, we expect to see renal excretion of the contrast medium on delayed-phase images. Vicarious contrast medium excretion refers to the excretion of water-soluble contrast medium through a route other than renal secretion.1 This type of excretion is predominantly mediated by the biliary system but may also occur in the small intestine, stomach, and colon.1-6 The image shown above (Figure, B) illustrates VCME by the biliary tract into the gallbladder lumen, which is also described as gallbladder opacification.Gallbladder opacification is defined as a radiograph or CT that demonstrates complete or partial opacification of the gallbladder cavity, which appears as a filled, hyperattenuated, or hyperdense structure.2 Earlier studies have demonstrated that VCME and its most common variant, gallbladder opacification, are associated with increased serum creatinine levels, unilateral renal pathologic findings, high-contrast dosing, frequent contrast loads secondary to multiple imaging studies, hypotension, and gallbladder stasis.1-3,6,7 Other studies have shown VCME and gallbladder opacification to be normal variants that may occur in patients with normal renal function.7-9 This patient had several risk factors for VCME, including unilateral renal disease, elevated serum creatinine levels, multiple contrast loads over a 48-hour period, and mild hypotension. Because of early recognition that the imaging artifact was attributable to VCME rather than to active hemorrhage, the patient was spared errors in diagnosis or misguided interventions.This case highlights how imaging artifacts caused by VCME may be misleading and could result in misdiagnosis or unwarranted procedures. Practicing surgeons should be aware of VCME and be able to recognize the hallmarks of VCME on common imaging studies.

Surgery

A man in his 60s with a known history of a large cyst on the right kidney sustained blunt trauma in a skiing crash. Computed tomography (CT) showed a right-sided grade IV renal injury involving his known renal cyst with active arterial extravasation (Figure, A). The patient underwent selective angioembolization of the renal laceration.A, Abdominal computed tomography (CT) with contrast demonstrating grade IV laceration of the right kidney and active extravasation. B, Abdominal CT obtained on day 2 of hospitalization showing large right-sided retroperitoneal hematoma and grade IV renal laceration displacing the patient’s abdominal viscera to the left, with contrast-filled structure medial to the liver.In the 24 hours after embolization, the patient required 2 U of red blood cells via transfusion for anemia. On examination, the patient reported moderate pain in the abdomen and right side and demonstrated a distended abdomen in the absence of any peritoneal signs. Contrast-enhanced CT of the abdomen and pelvis was performed to assess for a source of continued bleeding (Figure, B).

what is your diagnosis?

What is your diagnosis?

Jejunal injury with intraluminal contrast extravasation

Hepatic artery injury

Rupture of a peripancreatic pseudoaneurysm

Contrast-enhancing gallbladder

d

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2680110

A 63-year-old man was seen with decreased vision in both eyes. He had been diagnosed as having type 2 diabetes for 10 years. His visual acuity was 20/40 OU. Fundus examination showed venous dilatation, retinal hemorrhages, hard exudates, and serous macular detachment (arrowheads) (Figure 1). Optical coherence tomography scans showed intraretinal fluid accumulation with serous macular detachment in both eyes. He was diagnosed as having nonproliferative diabetic retinopathy with macular edema in both eyes. He received 3 intravitreal bevacizumab injections at 4 weekly intervals and 2 intravitreal triamcinalone acetonide injections in both eyes, with minimal resolution of edema. Blood analysis revealed a low hemoglobin level of 8 g/dL, red blood cell count of 3.3 × 106/μL, white blood cell count of 3460/μL (15% neutrophils, 84% lymphocytes, and 1% monocytes), fasting blood glucose level of 120 mg/dL, normal lipid profile, serum urea nitrogen level of 45 mg/dL, and an increased serum creatinine level of 1.4 mg/dL (to convert hemoglobin to grams per liter, multiply by 10.0; red blood cell count to ×1012 per liter, multiply by 1.0; white blood cell count to ×109 per liter, multiply by 0.001; blood glucose to millimoles per liter, multiply by 0.0555; serum urea nitrogen to millimoles per liter, multiply by 0.357; and serum creatinine to micromoles per liter, multiply by 88.4).A and B, Fundus photographs showing retinal venous dilatation, hemorrhages, hard exudates, and serous macular detachment (arrowheads). What Would You Do Next?

Treat with intravitreal dexamethasone implant

Treat with grid photocoagulation

Do plasma electrophoresis and bone marrow analysis

Treat with oral corticosteroids

Paraproteinemic maculopathy

C

Do plasma electrophoresis and bone marrow analysis

This patient’s blood analysis revealed anemia, an increased white blood cell count with lymphocytosis, and an elevated serum creatinine level. All of these pointed to an underlying hyperviscosity syndrome secondary to a systemic disease. Nonresponse to antipermeability agents was also consistent with a nondiabetic etiology. Bone marrow study showed plasmacytosis (30%). Serum electrophoresis revealed an M-protein spike. A diagnosis of multiple myeloma with paraproteinemic maculopathy was made, and the patient was started chemotherapy. However, within weeks of starting the therapy, the patient had a cerebrovascular accident.Paraproteinemia is a monoclonal gammopathy. It encompasses diseases like multiple myeloma, Waldenström macroglobulinemia, and cryoglobulinemia. Excess immunoglobulins in the blood lead to hyperviscosity.1 Multiple myeloma is a plasma cell dyscrasia characterized by high levels of a paraprotein called monoclonal protein, or M protein, in the blood and urine. Major organ systems involved in hyperviscosity syndromes include eye, heart (congestive heart failure), and brain (cerebrovascular accidents).Ocular manifestations include features of venous stasis retinopathy, such as dilated and tortuous veins, retinal hemorrhages, and optic disc edema. Serous macular detachment is a rare manifestation.2 There are many theories to explain the pathogenesis of serous macular detachment in paraproteinemic maculopathy. It has been proposed that hyperviscosity causes stasis and hypoxia of the endothelial cells and weakens the blood-retinal barrier.3 Additional risk factors like type 2 diabetes cause loss of pericytes, further compromising the blood-retinal barrier. This increases the accumulation of immunoglobulins in the subretinal space.4,5 Consequent osmotic gradient leads to serous macular detachment (Figure 2).Optical coherence tomography scan shows intraretinal fluid accumulation and serous macular detachment (asterisk).Decreasing the blood immunoglobulin level is the primary goal. Treatment modalities for paraproteinemia include plasmapheresis, rituximab, and chemotherapy.6 Oral or intravenous corticosteroids are used in conjunction with chemotherapeutic agents in the treatment of multiple myeloma because corticosteroids alone can have significant adverse effects.7 No proven benefit of oral corticosteroids in paraproteinemic maculopathy has been documented in the literature. In a 2013 case report,8 intravitreal dexamethasone implant failed to show substantial anatomical or visual improvement in a patient with serous macular detachment secondary to paraproteinemia (Waldenström macroglobulinemia). Similarly, grid photocoagulation or intravitreal injections of bevacizumab have not shown consistent results in this condition.3 Hence, diagnosing (with bone marrow analysis and serum electrophoresis) and treating the underlying paraproteinemia is the preferred choice. The long-term visual prognosis remains guarded, despite adequate treatment.This case emphasizes the need to consider the possibility of hyperviscosity syndromes in a patient seen with nonresolving macular edema, especially when other features of hyperviscosity retinopathy are present, such as dilated, tortuous veins or a macular detachment of the outer retina. Because ocular manifestations may be the presenting features of paraproteinemias, early diagnosis may be lifesaving to the patient.Ten weeks following initiation of chemotherapy, the height of the macular detachment reduced in both eyes. However, the visual acuity remained the same. Following this, the patient had a cerebrovascular accident, which precluded further optical coherence tomography examinations.

Ophthalmology

A 63-year-old man was seen with decreased vision in both eyes. He had been diagnosed as having type 2 diabetes for 10 years. His visual acuity was 20/40 OU. Fundus examination showed venous dilatation, retinal hemorrhages, hard exudates, and serous macular detachment (arrowheads) (Figure 1). Optical coherence tomography scans showed intraretinal fluid accumulation with serous macular detachment in both eyes. He was diagnosed as having nonproliferative diabetic retinopathy with macular edema in both eyes. He received 3 intravitreal bevacizumab injections at 4 weekly intervals and 2 intravitreal triamcinalone acetonide injections in both eyes, with minimal resolution of edema. Blood analysis revealed a low hemoglobin level of 8 g/dL, red blood cell count of 3.3 × 106/μL, white blood cell count of 3460/μL (15% neutrophils, 84% lymphocytes, and 1% monocytes), fasting blood glucose level of 120 mg/dL, normal lipid profile, serum urea nitrogen level of 45 mg/dL, and an increased serum creatinine level of 1.4 mg/dL (to convert hemoglobin to grams per liter, multiply by 10.0; red blood cell count to ×1012 per liter, multiply by 1.0; white blood cell count to ×109 per liter, multiply by 0.001; blood glucose to millimoles per liter, multiply by 0.0555; serum urea nitrogen to millimoles per liter, multiply by 0.357; and serum creatinine to micromoles per liter, multiply by 88.4).A and B, Fundus photographs showing retinal venous dilatation, hemorrhages, hard exudates, and serous macular detachment (arrowheads).

what would you do next?

What would you do next?

Treat with intravitreal dexamethasone implant

Treat with grid photocoagulation

Do plasma electrophoresis and bone marrow analysis

Treat with oral corticosteroids

c

male

61-70

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2680938

A woman in her early 50s was admitted to the hospital with several days of headaches, bilateral photophobia, and blurry vision. Her medical history was notable for cystic fibrosis, receipt of bilateral lung transplant, cytomegalovirus (CMV) viremia, and chronic kidney disease. Earlier treatment for CMV viremia included valganciclovir hydrochloride therapy that was discontinued because of the development of drug resistance and foscarnet sodium therapy with resultant renal dysfunction. The patient was subsequently treated with intravenous renally dosed cidofovir therapy; however, she again developed a nephrotoxic reaction and required dosage reduction in the weeks before presentation. At admission, cidofovir therapy was discontinued because of acute kidney injury (creatinine level, 5.75 mg/dL) (to convert to micromoles per liter, multiply by 88.4). The findings of a workup for meningitis were unremarkable. Ophthalmic consultation occurred 1 week after admission.The patient’s visual acuity was 20/30 OD and 20/25 OS. Pupils were minimally reactive and without an afferent pupillary defect. Intraocular pressures were 15 mm Hg OD and 12 mm Hg OS. Portable slitlamp examination findings included bilateral posterior synechiae and a shallow anterior chamber in the left eye. No anterior segment cell was appreciable by portable examination. The patient had early nuclear sclerosis and posterior subcapsular cataracts in both eyes. Results of a fundus examination demonstrated bilateral temporal choroidal elevations without vitritis, vascular sheathing, retinitis, or optic nerve abnormalities. B-scan ultrasonography findings demonstrated bilateral choroidal effusions (Figure 1).B-scan ultrasonographic images obtained at initial presentation demonstrating choroidal effusions in a patient with recent exposure to cidofovir.Discontinue cidofovir therapy, and start therapy with topical corticosteroids and cycloplegia What Would You Do Next?

Restart cidofovir therapy to treat CMV retinitis

Discontinue cidofovir therapy, and start therapy with topical corticosteroids and cycloplegia

Administer bilateral subtenon corticosteroid injections

Begin treatment with oral prednisone

Cidofovir-associated uveitis and choroidal effusions

B

Discontinue cidofovir therapy, and start therapy with topical corticosteroids and cycloplegia

Because there was no retinitis, restarting therapy with cidofovir (choice A) is unnecessary. Performing bilateral subtenon corticosteroid injections or beginning treatment with oral prednisone (choices C and D) are inadequate without concurrent withdrawal of cidofovir therapy, because cidofovir therapy was inciting uveitis and a nephrotoxic reaction.Infection with CMV causes morbidity and mortality in immunocompromised individuals, including those with AIDS and organ transplant recipients. Prophylactic therapy with antiviral medications is often pursued to reduce these risks,1 although systemic and ocular adverse effects can develop. Iritis, transient and chronic hypotony, and decreased visual acuity are known ocular complications of cidofovir therapy. The associated uveitis is typically bilateral, anterior, and nongranulomatous with rapid development of posterior synechiae.2Cidofovir-associated uveitis occurs in 21% to 32% of eyes after administration of intravitreal cidofovir3-5 and in 26% of eyes after treatment with intravenous cidofovir.6 Uveitis typically occurs within 1 week after exposure.3,6 Cidofovir-associated hypotony is less common than uveitis and is frequently transient; however, irreversible hypotony can develop as a result of atrophy of the ciliary body.4 Hypotony is typically accompanied by anterior uveitis. Choroidal effusions may develop; one study reported that choroidal effusion occurred in 4.2% of eyes treated with cidofovir.5Treatment consists of topical corticosteroid therapy and cycloplegia. When severe inflammation or hypotony occurs, cidofovir therapy should be discontinued and alternative antiviral therapy should be initiated. Uveitis usually resolves within 3 weeks after initiation of therapy.4 Generally, uveitis itself does not result in a significant loss of vision, although cataract development can decrease vision. Hypotony is a risk factor for permanent vision loss.4-6Uveitis and hypotony may recur if cidofovir therapy is reinitiated.3,6 Intravitreal cidofovir doses greater than 20 μg increase the risk of hypotony, but the dose relationship with uveitis is unknown.3 More treatments with and higher concentrations of intravenous cidofovir increase the risk of uveitis6; however, a threshold dosage has not been determined. Concurrent systemic probenecid therapy decreases the risk of developing uveitis.3 Cidofovir is renally excreted and potentially nephrotoxic, which increases the risk of supratherapeutic cidofovir levels if a nephrotoxic reaction develops.Since antiretroviral therapies for HIV infection became widely available, the incidence of AIDs-associated CMV retinitis has decreased.7 Cytomegalovirus infections are of increasing concern in transplant recipients and other immunosuppressed populations, which has prompted the use of antiviral prophylaxis, including prophylaxis with cidofovir. Cidofovir-associated uveitis has been reported in kidney transplant recipients.8 Clinicians should inquire about the medication history of patients who develop anterior uveitis to avoid missing a drug-related cause.This patient likely accumulated high intraocular levels of the drug secondary to a nephrotoxic reaction. Although her intraocular pressure was within normal limits at the initial assessment, this examination occurred 1 week after the final cidofovir dose was administered. We believe that the patient developed transient hypotony leading to choroidal effusions that had started to resolve by the time of the examination. Medical comorbidities prevented a clinic-based examination from being performed to assess for the presence of anterior segment cells, but on the basis of the patient’s symptoms and synechiae development, treatment with prednisolone and cyclopentolate hydrochloride was started, and the symptoms improved. The choroidal effusions resolved after discontinuation of cidofovir therapy (Figure 2).B-scan ultrasonographic image of the patient’s right eye 1 month after cidofovir exposure. The left eye had similar resolution of choroidal effusions.

Ophthalmology

A woman in her early 50s was admitted to the hospital with several days of headaches, bilateral photophobia, and blurry vision. Her medical history was notable for cystic fibrosis, receipt of bilateral lung transplant, cytomegalovirus (CMV) viremia, and chronic kidney disease. Earlier treatment for CMV viremia included valganciclovir hydrochloride therapy that was discontinued because of the development of drug resistance and foscarnet sodium therapy with resultant renal dysfunction. The patient was subsequently treated with intravenous renally dosed cidofovir therapy; however, she again developed a nephrotoxic reaction and required dosage reduction in the weeks before presentation. At admission, cidofovir therapy was discontinued because of acute kidney injury (creatinine level, 5.75 mg/dL) (to convert to micromoles per liter, multiply by 88.4). The findings of a workup for meningitis were unremarkable. Ophthalmic consultation occurred 1 week after admission.The patient’s visual acuity was 20/30 OD and 20/25 OS. Pupils were minimally reactive and without an afferent pupillary defect. Intraocular pressures were 15 mm Hg OD and 12 mm Hg OS. Portable slitlamp examination findings included bilateral posterior synechiae and a shallow anterior chamber in the left eye. No anterior segment cell was appreciable by portable examination. The patient had early nuclear sclerosis and posterior subcapsular cataracts in both eyes. Results of a fundus examination demonstrated bilateral temporal choroidal elevations without vitritis, vascular sheathing, retinitis, or optic nerve abnormalities. B-scan ultrasonography findings demonstrated bilateral choroidal effusions (Figure 1).B-scan ultrasonographic images obtained at initial presentation demonstrating choroidal effusions in a patient with recent exposure to cidofovir.Discontinue cidofovir therapy, and start therapy with topical corticosteroids and cycloplegia

what would you do next?

What would you do next?

Discontinue cidofovir therapy, and start therapy with topical corticosteroids and cycloplegia

Administer bilateral subtenon corticosteroid injections

Begin treatment with oral prednisone

Restart cidofovir therapy to treat CMV retinitis

a

female

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2681464

A woman in her mid-20s presented with subacute bilateral vision loss that was worse in the left eye. Her medical history was remarkable for type 1 diabetes diagnosed at 16 years of age and proliferative diabetic retinopathy in both eyes that had been treated with panretinal photocoagulation 7 years earlier. She had undergone pars plana vitrectomy with endolaser to treat a tractional retinal detachment in her right eye 2 years before this presentation. She also had a history of hypertension and chronic kidney disease, and she was 15 weeks into pregnancy. Visual acuity was 20/50 OD and 20/100 OS. Intraocular pressure was normal bilaterally, and no relative afferent pupillary defect was detected. Findings of an anterior segment examination were normal. The patient was in no apparent distress and denied any headache, chest pain, or focal weakness.Ophthalmoscopic examination (Figure) revealed mild optic nerve head edema that was greater in the left eye than the right eye with associated nerve fiber layer hemorrhage in the left eye. Nerve fiber layer infarctions, dot and blot hemorrhages, and lesions caused by panretinal photocoagulation also were seen bilaterally. Optical coherence tomography showed macular edema that involved the center of the macula in both eyes (Figure, inset).Fundus photographs obtained at presentation that show bilateral peripapillary hemorrhages and mild optic nerve head edema. Insets show the corresponding optical coherence tomographic image.Determine blood glucose level and perform glycated hemoglobin testMeasure heart rate, respiratory rate, and blood pressure What Would You Do Next?

Obtain a fluorescein angiogram

Determine blood glucose level and perform glycated hemoglobin test

Measure heart rate, respiratory rate, and blood pressure

Perform immediate computed tomography of the head

Malignant hypertension with papillopathy

C

Measure heart rate, respiratory rate, and blood pressure

The patient was found to have hypertension, with a blood pressure of 195/110 mm Hg. Heart and respiratory rates were normal. Measurement of the arterial blood pressure may be performed rapidly in the clinic with a sphygmomanometer and is essential to rule out malignant hypertension, which is a potentially life-threatening cause of vision loss. Although the differential diagnosis for bilateral optic nerve edema is broad, workup should always include assessment of blood pressure when appropriate, because a hypertensive emergency (also known as malignant hypertension) may cause substantial morbidity or mortality if not diagnosed and treated promptly. Findings may include macular star, macular edema, serous retinal detachment, intraretinal hemorrhage, and optic disc edema with or without associated hemorrhage.1,2 Optic nerve head edema may occur with systolic blood pressures as low as 160 mm Hg, with the median onset occurring at 188 mm Hg.3 The macular edema associated with hypertensive retinopathy may be distributed more nasally, as was seen in this patient.4This patient had mild optic nerve edema despite high systemic blood pressure and substantial macular edema. This less-pronounced optic nerve edema likely was attributable to optic nerve atrophy at baseline. Proliferative diabetic retinopathy and panretinal photocoagulation can be associated with optic atrophy, and atrophic optic nerves tend to become less edematous than healthy optic nerves.5-7Regarding the other choices above, a fluorescein angiogram (choice A) would be expected to show leakage from the optic nerve and macula, but such findings are already available from the optical coherence tomography, which showed intraretinal and subretinal fluid. Although assessment of serologic levels of glucose and glycated hemoglobin (choice B) is important in the management of diabetic retinopathy, results from such tests are not immediately available and have less bearing on the immediate management of the case (this patient’s glycated hemoglobin level was 10.5% [to convert to a proportion of total hemoglobin, multiply by 0.01]). Performing computed tomography (choice D) would be a reasonable later step, especially if the patient’s blood pressure was found to be normal, to rule out an intracranial mass.In addition to hypertension, other causes of optic nerve head edema exist. Papilledema (when optic nerve head edema is secondary to increased intracranial pressure) is often bilateral and may be caused by intracranial mass lesions, meningitis, cerebral venous thrombosis, or intracranial hypertension, or it may be idiopathic. Bilateral optic nerve head edema also may be caused by diabetic papillopathy (which is a rare cause of optic disc edema, but which is bilateral in up to 50% of cases8,9) and toxic optic neuropathies. Optic disc drusen are frequently bilateral and may cause so-called pseudopapilledema.10 Severe hypertension resulting in acute retinopathy and optic nerve head edema is considered a hypertensive emergency because of its association with end-organ damage, namely, damage to the retina and optic nerve.This case serves as a reminder that, although the differential diagnosis for optic nerve head edema is broad, immediately assessing the patient’s blood pressure to evaluate for hypertensive emergency in the eye clinic may be critical, because this treatable condition could lead to substantial morbidity or mortality if diagnosis is delayed.The patient was admitted to the medicine service for management of hypertension. At an ophthalmology follow-up examination 3 months later, her blood pressure was 128/73 mm Hg and her visual acuity was 20/40 OD and 20/60 OS, close to her visual acuity before this acute event. On examination, the optic nerve head edema had resolved, and optical coherence tomography showed resolution of macular edema.

Ophthalmology

A woman in her mid-20s presented with subacute bilateral vision loss that was worse in the left eye. Her medical history was remarkable for type 1 diabetes diagnosed at 16 years of age and proliferative diabetic retinopathy in both eyes that had been treated with panretinal photocoagulation 7 years earlier. She had undergone pars plana vitrectomy with endolaser to treat a tractional retinal detachment in her right eye 2 years before this presentation. She also had a history of hypertension and chronic kidney disease, and she was 15 weeks into pregnancy. Visual acuity was 20/50 OD and 20/100 OS. Intraocular pressure was normal bilaterally, and no relative afferent pupillary defect was detected. Findings of an anterior segment examination were normal. The patient was in no apparent distress and denied any headache, chest pain, or focal weakness.Ophthalmoscopic examination (Figure) revealed mild optic nerve head edema that was greater in the left eye than the right eye with associated nerve fiber layer hemorrhage in the left eye. Nerve fiber layer infarctions, dot and blot hemorrhages, and lesions caused by panretinal photocoagulation also were seen bilaterally. Optical coherence tomography showed macular edema that involved the center of the macula in both eyes (Figure, inset).Fundus photographs obtained at presentation that show bilateral peripapillary hemorrhages and mild optic nerve head edema. Insets show the corresponding optical coherence tomographic image.Determine blood glucose level and perform glycated hemoglobin testMeasure heart rate, respiratory rate, and blood pressure

what would you do next?

What would you do next?

Perform immediate computed tomography of the head

Determine blood glucose level and perform glycated hemoglobin test

Obtain a fluorescein angiogram

Measure heart rate, respiratory rate, and blood pressure

d

female

21-30

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2681948

A 14-year-old girl was seen with progressive vision loss in both eyes. Two years before our examination, her visual acuity had been 20/200 OD and 20/60 OS. At our initial evaluation, her visual acuity was 20/300 OD and 20/250 OS. Optic nerve atrophy was noted, with no optociliary collaterals. Imaging of the retinal nerve fiber layer showed thinning in both eyes. Automated perimetry demonstrated general constriction of visual fields and bilateral central scotomas. Ocular motility was full, without pain, and orthotropic. Two years prior, initial magnetic resonance imaging (MRI) of the brain and orbits with and without contrast was read as normal. Retrospectively, those images were reviewed and noted to be limited due to artifact from dental braces and a lack of fat suppression. Two years prior, lumbar puncture revealed normal opening pressure.Complete blood cell count with differential was negative, as were test results for erythrocyte sedimentation rate, fluorescent treponemal antibody absorption, antinuclear antibody, angiotensin-converting enzyme, and serum neuromyelitis optica antibodies. Whole-exome genome sequencing was negative for genes associated with neurofibromatosis type 1 and type 2. After removal of dental braces, MRI of the brain and orbits with and without contrast demonstrated thickening and nodular enhancement of bilateral perioptic nerve sheaths extending up to the orbital apex. Patchy T2-weighted hyperintensity was noted within the bilateral optic nerves (Figure).A, T1-weighted fat-suppressed image demonstrates thick, nodular, circumferential enhancement in the bilateral optic sheaths. B, T1-weighted postcontrast image shows sparing of the optic chiasm. What Would You Do Next?

Observation

Optic nerve sheath biopsy

Radiotherapy (fractionated external beam radiotherapy)

Optic nerve sheath biopsy and radiotherapy

Optic nerve sheath meningioma

C

Radiotherapy (fractionated external beam radiotherapy)

Optic nerve sheath meningioma is a benign neoplasm of the meningothelial cells of the arachnoid tissue around the optic nerve.1 The usual age of presentation is between 30 and 50 years, with a 3:1 female to male ratio.2 Bilateral cases of ONSM are rare but can be seen in 5% of all reported cases.3-6 The optic nerve appearance in patients with ONSM reveals a frank optic atrophy.1-7The ONSM compromises the optic nerve function by causing mass effect on the pial vasculature, ischemic changes, and disruption of the axonal transport along the optic nerve.2 The circumferential relationship between the ONSM and the optic nerve and its vascular supply makes the treatment of ONSM challenging. Surgical excision may result in blindness.2,7 Therefore, fractionated external beam radiotherapy has become preferable, especially when treating bilateral OSNMs, and vision preservation is a priority.8Bilateral ONSMs have an insidious onset, in which vision loss precedes anatomical and radiological findings. The compromise in optic nerve axon function progresses to radiologically evident lesions over the course of months to years. Nickel et al5 reported progressive loss of vision in a 4-year-old child with bilateral ONSMs over a 6-year period. Misra and colleagues6 described bilateral ONSM in a 60-year-old patient who had experienced progressive vision loss since age 7 years and who had been lost to follow-up after radiotherapy.One of the largest ONSM studies was reported by Turbin and associates.8 In that study, 64 adult patients with ONSM comprised the following 4 groups: observation alone, surgery alone, surgery with radiotherapy, and radiotherapy alone. With up to 50 months’ follow-up, 59 of 64 patients (92%) had better than light perception vision: 18 of the 59 (31%) had received radiotherapy alone. For the patients with radiotherapy alone, there was no significant vision loss compared with patients in the other 3 groups.Optic nerve sheath biopsy was not performed due to concern about more severe vision loss. Observation alone for visual acuity and visual field loss was not pursued after tumor board discussion with the patient and her family. A course of radiotherapy was initiated using conformal fractionated techniques (ExacTrac; Brainlab) for maximal normal tissue sparing (fractionated external beam radiotherapy via rapid arc to 50.4 Gy) in 28 fractions administered over a 2-month period. Six months later, her visual acuity was counting fingers OD and 20/300 OS.This case emphasizes the importance of considering ONSM in the differential diagnosis of bilateral optic nerve atrophy in children and teens. It is crucial to understand that the goal of radiotherapy is to halt the progression of the disease. Two years after radiotherapy, the patient’s visual acuity was 20/630 OD and 20/400 OS. Repeated MRI of the brain and orbit showed stability and no further worsening of vision. Attention to low vision needs at school and counseling regarding the psychological implications of low vision have been crucial for this patient.

Ophthalmology

A 14-year-old girl was seen with progressive vision loss in both eyes. Two years before our examination, her visual acuity had been 20/200 OD and 20/60 OS. At our initial evaluation, her visual acuity was 20/300 OD and 20/250 OS. Optic nerve atrophy was noted, with no optociliary collaterals. Imaging of the retinal nerve fiber layer showed thinning in both eyes. Automated perimetry demonstrated general constriction of visual fields and bilateral central scotomas. Ocular motility was full, without pain, and orthotropic. Two years prior, initial magnetic resonance imaging (MRI) of the brain and orbits with and without contrast was read as normal. Retrospectively, those images were reviewed and noted to be limited due to artifact from dental braces and a lack of fat suppression. Two years prior, lumbar puncture revealed normal opening pressure.Complete blood cell count with differential was negative, as were test results for erythrocyte sedimentation rate, fluorescent treponemal antibody absorption, antinuclear antibody, angiotensin-converting enzyme, and serum neuromyelitis optica antibodies. Whole-exome genome sequencing was negative for genes associated with neurofibromatosis type 1 and type 2. After removal of dental braces, MRI of the brain and orbits with and without contrast demonstrated thickening and nodular enhancement of bilateral perioptic nerve sheaths extending up to the orbital apex. Patchy T2-weighted hyperintensity was noted within the bilateral optic nerves (Figure).A, T1-weighted fat-suppressed image demonstrates thick, nodular, circumferential enhancement in the bilateral optic sheaths. B, T1-weighted postcontrast image shows sparing of the optic chiasm.

what would you do next?

What would you do next?

Radiotherapy (fractionated external beam radiotherapy)

Optic nerve sheath biopsy

Observation

Optic nerve sheath biopsy and radiotherapy

a

female

11-20

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2666800

A woman in her 50s with biopsy-proven scalp lichen planopilaris (LPP) presented with an increasing number of slightly pruritic facial papules that coincided with the start of her hair loss condition (Figure, A). She denied a history of severe acne or other inflammatory skin disorders. The patient had no health problems and only had a distant medical history of an appendectomy and an oophorectomy. The only medication she was taking was hydroxychloroquine 200 mg twice daily that was initiated as treatment of her LPP and did not improve the appearance or symptoms of her facial papules. On physical examination, she had numerous 1-mm skin-colored grouped monomorphic noninflammatory papules on the bilateral temples, the bilateral cheeks, and the chin. A 3-mm punch biopsy specimen was obtained for histopathologic examination of a representative lesion on the right chin (Figure, B and C).A, Clinical photograph shows numerous grouped 1-mm skin-colored monomorphic noninflammatory papules on the left cheek and chin. B and C, Histology of a 3-mm punch biopsy specimen of a lesion on the right chin using a hematoxylin-eosin stain. What is Your Diagnosis?

Lichen planopilaris

Trichoepitheliomas

Miliary osteoma cutis

Angiofibromas

C. Miliary osteoma cutis

C

Miliary osteoma cutis

The biopsy specimen from the right chin showed osteoma cutis without inflammation. Once the results of the biopsy were obtained, a second 3-mm punch biopsy was performed on an identical lesion on the left medial cheek to reaffirm the initial diagnosis. Again, the biopsy specimen was consistent with osteoma cutis. Blood tests, including thyroid-stimulating hormone, parathyroid hormone, vitamin D level, calcium, and phosphorus, were tested. All laboratory values were normal except for a slightly elevated parathyroid hormone. The patient was referred to endocrinology where further workup was largely unrevealing. It was recommended that the patient have her parathyroid hormone monitored regularly. Repeated testing of her parathyroid hormone remained slightly elevated without other laboratory abnormalities.Miliary osteoma cutis is a rare condition that involves tiny bone fragments usually present in the facial dermis.1 The condition manifests itself as skin-colored papules that can be accompanied by pruritus or can be asymptomatic. The number of lesions is reported to increase over time.2,3 The onset of miliary osteoma cutis often occurs during middle age and most cases reported have been in women.4 Owing to its benign but rare nature, literature is primarily limited to case reports. To our knowledge, this is the first report of miliary osteoma cutis in a patient with LPP.Miliary osteoma cutis can be classified as a primary or secondary phenomenon. Secondary miliary osteoma cutis is associated with other underlying causes such as neoplastic conditions, as well as inflammatory or endocrine disorders. It is associated with scarring acne vulgaris in 50% of reported cases.4,5 One theory to explain the pathogenesis of miliary osteoma cutis due to inflammatory skin conditions involves the differentiation of mesenchymal fibroblasts into osteoblasts because of underlying inflammation.6 In this patient’s case, there was no other preceding inflammatory skin condition except for LPP, and her subsequent endocrine workup, including serum calcium level, was largely normal. Recommended treatments for miliary osteoma cutis vary, but most reports agree on a variation of retinoic acid, surgical techniques such as curettage and needle excision, dermabrasion, and laser therapy.2,4In a patient with LPP, the clinical presentation of miliary osteoma cutis may be difficult to differentiate from the facial papules of LPP. The facial papules that are typically associated with LPP occur most frequently on the temporal area of the face and have been described as noninflammatory monomorphic follicular papules. Patients often attribute the change in the texture of their skin to aging rather than associate it with the diagnosis of LPP. A variant of LPP, Graham-Little syndrome, which predominately affects postmenopausal women, can also be associated with papules. These papules are follicular in nature and are more commonly found on the trunk and extremities; however, they can also be found on the scalp.7,8Facial papules caused by LPP have been reported to improve with systemic treatment of LPP, and histopathologically the biopsy specimens show features consistent with scalp LPP.9 The biopsy specimens in our patient were consistent with osteoma cutis despite appearing clinically similar to LPP facial papules. Underreporting of facial papules and a shortage of biopsy results for diagnostic purposes contributes to their relative absence in the literature.This case highlights the importance of histologic evaluation of facial papules in patients with LPP that do not respond to treatment to ensure these lesions are being properly diagnosed and effectively treated.

Dermatology

A woman in her 50s with biopsy-proven scalp lichen planopilaris (LPP) presented with an increasing number of slightly pruritic facial papules that coincided with the start of her hair loss condition (Figure, A). She denied a history of severe acne or other inflammatory skin disorders. The patient had no health problems and only had a distant medical history of an appendectomy and an oophorectomy. The only medication she was taking was hydroxychloroquine 200 mg twice daily that was initiated as treatment of her LPP and did not improve the appearance or symptoms of her facial papules. On physical examination, she had numerous 1-mm skin-colored grouped monomorphic noninflammatory papules on the bilateral temples, the bilateral cheeks, and the chin. A 3-mm punch biopsy specimen was obtained for histopathologic examination of a representative lesion on the right chin (Figure, B and C).A, Clinical photograph shows numerous grouped 1-mm skin-colored monomorphic noninflammatory papules on the left cheek and chin. B and C, Histology of a 3-mm punch biopsy specimen of a lesion on the right chin using a hematoxylin-eosin stain.

what is your diagnosis?

What is your diagnosis?

Angiofibromas

Trichoepitheliomas

Miliary osteoma cutis

Lichen planopilaris

c

female

51-60

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2667765

A woman in her 50s with a medical history of hypertension and depression was evaluated by the inpatient dermatology consult service for a 1.5-year history of painful intertriginous wounds. She was previously diagnosed with hidradenitis suppurativa and treated with surgical excision and split-thickness skin grafting of the genitocrural folds with graft failure. Over the past 1.5 years, she had been admitted to the hospital on multiple occasions for cellulitis around the wounds, which responded to intravenous antibiotics, and she had received a diverting sigmoid colostomy and indwelling urinary catheter to decrease wound contamination. Her wound care required a nursing home. Just prior to presentation, she received adalimumab for 3 months without clinical improvement. On physical examination there were linear moist, eroded, exophytic, condyloma-like plaques of the bilateral submammary folds (Figure, A), intergluteal cleft, and under the abdominal apron. There were ulcers of the bilateral genitocrural folds, as well as vulvar edema (Figure, B). The lips, oropharynx, and ostomy were unremarkable. A wedge biopsy specimen of a submammary plaque was obtained, and histopathology was performed (Figure, C and D).A, Clinical photograph shows a submammary representative linear condyloma-like ulcerated plaque, as well as secondary irritant contact dermatitis from application of topical medications. Similar plaques were present in the bilateral submammary fold, under the abdominal apron and in the intergluteal cleft. B, Clinical photograph of linear ulcers of the genitocrural folds, vulvar edema, and an indwelling urinary catheter. C, Hematoxylin-eosin stain of a biopsy specimen from the submammary plaque. D, High-power image from the same specimen. What Is Your Diagnosis?

Hidradenitis suppurativa

Metastatic Crohn disease

Pemphigus vegetans

Linear hypertrophic herpes simplex virus infection

B. Metastatic Crohn disease

B

Metastatic Crohn disease

Histopathologic sections showed pseudoepitheliomatous epidermal hyperplasia and focal superficial erosion overlying a superficial and deep granulomatous inflammatory infiltrate (Figure, C), relatively well-formed, nonnecrotizing granulomas, prominent Langhans-type multinucleated giant cells, epithelioid histiocytes, and a variable lymphoplasmacytic inflammatory cuff (Figure, D). Histochemical stains, with adequate controls, and tissue cultures for bacteria, mycobacteria, and fungus were negative. Polymerase chain reaction for herpes simplex virus was negative. Direct immunofluorescence studies were negative. These features were compatible with cutaneous Crohn disease.The patient had no gastrointestinal symptoms. A computed tomography entereography, upper endoscopy, and colonoscopy were unremarkable. A 17-marker diagnostic test for inflammatory bowel disease (PROMETHEUS IBD sgi Diagnostic [Prometheus Laboratories Inc]) performed on peripheral blood was consistent with Crohn disease and revealed elevation of immunoglobulin G antibodies to Crohn disease–associated antigens (falgellins: Fla-X 53.5 EU/mL [nL < 36] and A4-Fla2 50.6 EU/mL [nL < 32.4]). Of note, her son also had Crohn disease.She was initiated on a regimen of prednisone, 30 mg/d and metronidazole 500 mg every 8 hours. Within 2 weeks, her skin lesions were 50% improved, and within 4 weeks only thin hyperpigmented plaques and 2-cm shallow genitocrural ulcers remained. For long-term therapy, she was started on ustekinumab (520 mg intravenous induction dose followed by 90 mg subcutaneously every 8 weeks thereafter). This interleukin-12/23 inhibitor was selected because she had not responded to a tumor necrosis factor α inhibitor (adalimumab).Metastatic Crohn disease (MCD) is defined by noncaseating granulomatous infiltration of the skin and occurrence at anatomic sites not continuous with the gastrointestinal tract. Since the first description1 and naming2 of MCD, many cases3 have been published and reviewed.4,5 In 70% to 90% of cases, MCD occurs in individuals with an antecedent or concurrent development of gastrointestinal Crohn disease, but in 10% to 30% of cases, there is no gastrointestinal involvement,4 making the diagnosis more challenging. Metastatic Crohn disease typically affects intertriginous areas, the trunk, and legs. Lesion types include edema, ulcers, papules, plaques, nodules, and skin tag–like lesions. “Knife cut” is a morphological term used to describe the characteristic linear intertriginous ulcers of MCD.6 Histopathology, MCD can be indistinguishable from cutaneous sarcoidosis, but eosinophil-rich areas and dermal edema are not expected in sarcoidosis.The PROMETHEUS IBD sgi Diagnostic tool is a blood test that uses 17 serologic, genetic, and inflammatory biomarkers, as well as an algorithm, to predict whether patients have inflammatory bowel disease and whether they have Crohn disease or ulcerative colitis (sensitivity and specificity for Crohn disease is 88% and 86%, respectively). In our case, this test provided diagnostic support and identified Crohn disease biomarkers (flagellin antibodies) that, to our knowledge, have not previously been reported in association with skin-limited MCD. Importantly, the PROMETHEUS IBD sgi Diagnostic tool was not designed for use in patients with MCD without gastrointestinal disease. The primary aims of this report are to increase recognition of this unusual manifestation of Crohn disease and encourage further study of biomarkers for its diagnosis and management.

Dermatology

A woman in her 50s with a medical history of hypertension and depression was evaluated by the inpatient dermatology consult service for a 1.5-year history of painful intertriginous wounds. She was previously diagnosed with hidradenitis suppurativa and treated with surgical excision and split-thickness skin grafting of the genitocrural folds with graft failure. Over the past 1.5 years, she had been admitted to the hospital on multiple occasions for cellulitis around the wounds, which responded to intravenous antibiotics, and she had received a diverting sigmoid colostomy and indwelling urinary catheter to decrease wound contamination. Her wound care required a nursing home. Just prior to presentation, she received adalimumab for 3 months without clinical improvement. On physical examination there were linear moist, eroded, exophytic, condyloma-like plaques of the bilateral submammary folds (Figure, A), intergluteal cleft, and under the abdominal apron. There were ulcers of the bilateral genitocrural folds, as well as vulvar edema (Figure, B). The lips, oropharynx, and ostomy were unremarkable. A wedge biopsy specimen of a submammary plaque was obtained, and histopathology was performed (Figure, C and D).A, Clinical photograph shows a submammary representative linear condyloma-like ulcerated plaque, as well as secondary irritant contact dermatitis from application of topical medications. Similar plaques were present in the bilateral submammary fold, under the abdominal apron and in the intergluteal cleft. B, Clinical photograph of linear ulcers of the genitocrural folds, vulvar edema, and an indwelling urinary catheter. C, Hematoxylin-eosin stain of a biopsy specimen from the submammary plaque. D, High-power image from the same specimen.

what is your diagnosis?

What is your diagnosis?

Pemphigus vegetans

Metastatic Crohn disease

Hidradenitis suppurativa

Linear hypertrophic herpes simplex virus infection

b

female

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2668139

A 4-year-old boy presented to our department of dermatology with a 3-year history of nonhealing crusted scalp lesions. He had previously been treated with various topical glucocorticosteroids and antibiotics without improvement. The physical examination revealed multiple disseminated erythematous papules, petechial hemorrhages, and yellowish crusts on the scalp (Figure, A). The remaining skin and mucosal surfaces, as well as neck, axillary, and inguinal lymph nodes, were unremarkable. The patient did not show any other obvious abnormalities, but his mother reported occasional otitis media. The family history was negative for skin disease. Routine blood examinations revealed no pathological findings. A whole-body magnetic resonance imaging (MRI) scan showed 2 osteolytic lesions on the right frontoparietal skull (Figure, B). A punch biopsy specimen of an erythematous papule on the scalp was obtained and stained with hematoxylin-eosin for histopathological analysis (Figure, C). In addition, immunohistochemical stainings were performed (Figure, D).A, Clinical photograph shows multiple disseminated erythematous papules, petechial hemorrhages and yellowish crusts on the scalp. B, Contrast-enhanced T1-weighted axial magnetic resonance image shows osteolytic lesions in the frontotemporal skull. C, Histopathological analysis of a punch biopsy of the scalp demonstrates a subepidermal infiltrate consisting of large cells with kidney-shaped nuclei, solitary lymphocytes, and eosinophilic granulocytes. D, The infiltrate stained positively for CD1A. What Is Your Diagnosis

Seborrheic dermatitis

Multisystem Langerhans cell histiocytosis

Crusted scabies

Psoriasis vulgaris

B. Multisystem Langerhans cell histiocytosis

B

Multisystem Langerhans cell histiocytosis

The histopathological evaluation of the punch biopsy specimen revealed a subepidermal infiltrate consisting of large cells with kidney-shaped nuclei, solitary lymphocytes, and eosinophilic granulocytes (Figure, C). In immunohistochemistry, the infiltrate stained positively for CD1A (Figure, D). These histopathological and immunohistochemical findings were suggestive for Langerhans cell histiocytosis (LCH). Further workup including ultrasonography of the abdomen and lymph nodes and serum electrophoresis was normal. Whole-body MRI showed 2 osteolytic lesions in the right frontoparietal skull (Figure, B). Based on these findings, the diagnosis of multisystem (MS) LCH was made. Treatment was initiated using systemic chemotherapy with vinblastine and prednisone according to the LCH-IV registry therapy recommendations (course IC-1 and IC-2, continuation therapy until treatment week 52) (NCT02205762). After the IC-1 course, a complete clinical remission was observed with regression of the bone lesions. However, during the last months of maintenance therapy, small crusted scalp lesions reappeared and worsened after cessation of therapy. Hence, the patient was started on LCH-IV second-line initial therapy course consisting of prednisolone, cytarabine, and vincristine.Langerhans cell histiocytosis is a rare clonal disorder that usually affects infants and children at the ages of 0 to 3 years.1 It is characterized by the clonal proliferation of CD1A-positive immature dendritic cells with subsequent accumulation in different organs (eg, in the bones [80% of cases], skin [33% of cases], and pituitary gland [25% of cases]).1,2 The clinical spectrum of LCH ranges from single-system disease (eg, with bone or skin involvement) to multisystem disease (eg, with skin, liver, spleen, and bone marrow involvement) with increased mortality.3 In pediatric patients, the skull is the most often affected bone location and this can lead to hearing loss or otorrhea due to mastoid antrum lesions.4 External otitis was seen in patients who developed MS LCH and even cutaneous involvement is more common in MS LCH than in single-system LCH.5 The spectrum of skin lesions includes erythema, papules, nodules, petechiae, vesicles, and crusted plaques.1 Skin lesions frequently resemble seborrheic dermatitis or eczema and are predominantly found on the scalp or face.6 Often histopathology leads to the diagnosis with positive immunohistochemical staining for CD1A and/or CD207 (Langerin).1 Classification of the disease type further requires complete physical examination, laboratory tests, and radiological examinations. Treatment of LCH depends on the extent of organ involvement. In MS LCH, the most frequently used regime is systemic chemotherapy with vinblastine and prednisone administered for 6 to 12 weeks followed by maintenance therapy in case of clinical response. The maintenance therapy usually consists of prednisone and vinblastine.3,7 In patients who do not respond to first-line therapy, more aggressive salvage therapy may be used, consisting of chemotherapy combinations including vincristine, cytarabine, methotrexate, 6-mercaptopurine, and 2-chlorodeoxyadenosine. Haematopoietic stem cell transplantation has a very limited indication these days.7 Recently, somatic BRAF V600E mutations have been described in 60% of patients with LCH.8 In a recent study,9 patients with severe and refractory BRAF V600E–positive LCH were treated with the specific mutant BRAF inhibitor vemurafenib and showed rapid clinical improvement without severe toxic effects or adverse events.9The 5-year survival rate in children with LCH without involvement of risk organs is well above 90%.10 However, regular follow-up investigations are necessary because 50% of patients with MS LCH develop a relapse within the first 2 years. Long-term morbidities such as central diabetes insipidus, orthopedic and neurological problems, as well as growth-hormone deficiency, should be identified and treated as early as possible.1Cutaneous manifestations of LCH may be misdiagnosed as more common skin diseases such as psoriasis, seborrheic eczema, or atopic eczema. The median time from onset of the symptoms to diagnosis of LCH is often more than 3 months and may even reach years, as in our case.10 Dermatologists should be familiar with the broad clinical spectrum of the LCH as the chronic course of skin lesions and the onset after the third month of life can be potential risk factors for a multisystem disease. Early biopsy of skin lesions resistant to therapy is necessary.

Dermatology

A 4-year-old boy presented to our department of dermatology with a 3-year history of nonhealing crusted scalp lesions. He had previously been treated with various topical glucocorticosteroids and antibiotics without improvement. The physical examination revealed multiple disseminated erythematous papules, petechial hemorrhages, and yellowish crusts on the scalp (Figure, A). The remaining skin and mucosal surfaces, as well as neck, axillary, and inguinal lymph nodes, were unremarkable. The patient did not show any other obvious abnormalities, but his mother reported occasional otitis media. The family history was negative for skin disease. Routine blood examinations revealed no pathological findings. A whole-body magnetic resonance imaging (MRI) scan showed 2 osteolytic lesions on the right frontoparietal skull (Figure, B). A punch biopsy specimen of an erythematous papule on the scalp was obtained and stained with hematoxylin-eosin for histopathological analysis (Figure, C). In addition, immunohistochemical stainings were performed (Figure, D).A, Clinical photograph shows multiple disseminated erythematous papules, petechial hemorrhages and yellowish crusts on the scalp. B, Contrast-enhanced T1-weighted axial magnetic resonance image shows osteolytic lesions in the frontotemporal skull. C, Histopathological analysis of a punch biopsy of the scalp demonstrates a subepidermal infiltrate consisting of large cells with kidney-shaped nuclei, solitary lymphocytes, and eosinophilic granulocytes. D, The infiltrate stained positively for CD1A.

what is your diagnosis

What is your diagnosis?

Psoriasis vulgaris

Seborrheic dermatitis

Multisystem Langerhans cell histiocytosis

Crusted scabies

c

male

0-10

original

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2675369

A 4-year-old boy was referred to the child psychiatry clinic for management of tantrums with aggression and self-injurious behavior. Tantrums were unpredictable and often resulted in severe head-butting. His parents also reported atypical social and language development, disrupted sleep, and persistent impulsivity with attempts to elope.The patient had a complex medical history that was marked by prematurity at 32 weeks, slow postnatal growth, and severe gastroesophageal reflux. Genetic testing following an episode of hypoglycemia revealed microdeletion of the 16p11.2 region of chromosome 16. His pediatrician documented a normal neurological examination without dysmorphology or congenital anomalies.A developmental evaluation revealed delays in motor function and language development notable by age 2 years. He attended a 0 to 3 program with intensive speech therapy and then moved to a self-contained preschool classroom with a 1:1 staff-to-student ratio. He received school-based speech, occupational, and physical therapies. Testing results revealed clinically significant scores on the Autism Diagnostic Observation Schedule. Cognitive testing results showed that his IQ was below average but was likely an underestimate due to noncompliance. The parents stated that he played repetitively, lining up toy cars and spinning their wheels. He did not seek or give comfort to others when distressed. He had tactile hypersensitivity but pain hyposensitivity, flicked light switches repetitively, and mouthed objects.In the office, the patient showed a minimal response to clinicians’ social overtures and poor eye contact. He replayed videos on a smartphone while laughing, spinning around, and flapping his hands. He did not respond to prompts for joint engagement and no imaginative play was observed. When the videos stopped, he repeatedly climbed onto chairs and jumped off. As clinicians attempted to redirect him, he became very agitated and his mother intervened physically to protect him from self-injury.Referral of family members for genetic testing to determine 16p11.2 carrier statusPharmacotherapy with R-baclofen based on the mouse model of 16p11.2 deletionPharmacotherapy with citalopram for rigidity and repetitive behaviorReferral to a behavioral intervention program plus pharmacotherapy with aripiprazole for irritability, agitation, and self-injury What Would You Do Next?

Referral of family members for genetic testing to determine 16p11.2 carrier status

Pharmacotherapy with R-baclofen based on the mouse model of 16p11.2 deletion

Pharmacotherapy with citalopram for rigidity and repetitive behavior

Referral to a behavioral intervention program plus pharmacotherapy with aripiprazole for irritability, agitation, and self-injury

Autism spectrum disorder (ASD) (associated with chromosome 16p11.2 deletion syndrome, level 3 severity, with accompanying intellectual and language impairment) and global developmental delay

D

Referral to a behavioral intervention program plus pharmacotherapy with aripiprazole for irritability, agitation, and self-injury

Children with aggression and self-injury are frequently referred to child psychiatrists for management of acute behavioral issues. Fully treating these problem behaviors in ASD requires a careful evaluation of co-occurring medical and psychiatric disorders, developmental and family history, as well as an assessment for communication difficulties, maladaptive reinforcement patterns, and psychosocial stressors.1The 4-year-old boy described in this case had significantly impairing social communication deficits that arose early in development combined with patterns of restricted interests and repetitive behaviors, the cardinal criteria of ASD (as described in DSM-5, criteria A-D). He demonstrated language impairment, motor skills delay, and suspected cognitive deficits. He also has at least 2 identifiable risk factors for a neurodevelopmental disorder: (1) premature birth and (2) 16p11.2 deletion syndrome.A careful medical evaluation in collaboration with his other clinicians ruled out medical problems that would account for his behavior. His behavior had been quite consistent over the past year and there were no recent psychosocial stressors. In the absence of other medical, psychiatric, or psychosocial factors, his behaviors most likely relate to the diagnosis of ASD with outbursts secondary to (1) deficient communication and (2) decreased tolerance for change and frustration.Behavioral intervention is first-line treatment for aggressive behavior in young children, and therapy based on the principles of applied behavior analysis has extensive empirical support in ASD. Several treatment models exist, including standard applied behavior analysis , pivotal response training, and the Early Start Denver Model. Parallel parent-training components can provide additional benefits. A functional behavioral assessment to identify triggers and understand the function of the behavior can help implement a behavioral intervention plan to decrease the target behavior, in this case, aggression and self-injury. While this patient benefitted from school-based therapies, he had not yet received applied behavior analysis –specific or other behavioral therapies at the time of evaluation. Unfortunately, access to behavioral interventions is often limited by a scarcity of trained clinicians.It is critical to evaluate the immediate safety concerns of each patient and determine whether the risk of injury to the patient or others justifies a trial of a medication to reduce the risk of injury.1 In these cases, medications should be carefully considered. Atypical antipsychotic medications have the best evidence for treating aggression and self-injurious behavior in children with ASD. Based on multiple randomized clinical trials,2 risperidone and aripiprazole were approved by the US Food and Drug Administration for the treatment of “irritability associated with autistic disorder” in children as young as 5 and 6 years old, respectively. The “irritability” target symptom definition was based on the Aberrant Behavior Checklist Irritability/Agitation/Crying subscale, which indexes aggression and self-injury as well as tantrums, crying, mood swings, and irritability. In any child, symptoms must be substantial to merit using this medication in the context of the potential adverse effects, which include sedation and an increased risk for movement disorders. Mixed receptor antagonists, such as risperidone and aripiprazole, are also associated with substantial weight gain and related medical problems, including type 2 diabetes. The addition of metformin has shown efficacy in reducing weight gain in children with ASD who are taking risperidone or aripiprazole.3 Some genetic conditions (including chromosome 16p11.2 deletion syndrome) are also associated with an increased risk of obesity,4 and aripiprazole may therefore be preferred over risperidone. While multiple lines of evidence point to abnormalities of the serotonin system in ASD, serotonin reuptake inhibitors do not show the same pattern of benefit in children with ASD that they provide in obsessive compulsive disorder; for example, a large randomized clinical trial of citalopram for repetitive behavior in ASD showed no overall significant benefits and increased adverse effects.5Autism spectrum disorder is an extremely heterogeneous disorder that appears to be a common final outcome of several factors, including genetic risk alleles, environmental insults, and developmental events.6 While chromosomal microarray testing can identify a clinically relevant genetic change in up to 10% of people with autism,7 in most cases we do not yet have evidence-based guidelines to clinically act on these findings. For these individuals (and those with idiopathic ASD), treatments target behavioral symptoms, such as the irritability and agitation experienced by this child.Our patient had a perinatal risk factor (prematurity) and a genetic risk factor (16p11.2 microdeletion). While there is a markedly increased risk for ASD in 16p11.2 microdeletion carriers, most do not receive a diagnosis of ASD. 16p11.2 deletion carriers are phenotypically diverse (and overlap with the nonclinical population), and they are at risk for several other neurodevelopmental disorders, as well as obesity.8 Family members should always be offered genetic counseling and testing to assess whether they are carriers and to assess the recurrence risk of ASD in any siblings.The finding of a rare genomic variant in this patient could eventually open the door to a precision medicine treatment approach based on studies of 16p11.2 deletion syndrome. As an illustration, mouse models of 16p11.2 deletion suggest that the gamma-aminobutyric acid type B receptor agonist R-baclofen may improve behavior.6,9 R-baclofen affects inhibition by gamma-aminobutyric acid, which is postulated to contribute to the pathophysiology of ASD via excessive excitatory or insufficient inhibitory neurotransmission. A randomized clinical trial of R-baclofen in the general ASD population did not show improvement in irritability and agitation symptoms, although suggestive results on 2 other measures may merit a follow-up study.10

Psychiatry

A 4-year-old boy was referred to the child psychiatry clinic for management of tantrums with aggression and self-injurious behavior. Tantrums were unpredictable and often resulted in severe head-butting. His parents also reported atypical social and language development, disrupted sleep, and persistent impulsivity with attempts to elope.The patient had a complex medical history that was marked by prematurity at 32 weeks, slow postnatal growth, and severe gastroesophageal reflux. Genetic testing following an episode of hypoglycemia revealed microdeletion of the 16p11.2 region of chromosome 16. His pediatrician documented a normal neurological examination without dysmorphology or congenital anomalies.A developmental evaluation revealed delays in motor function and language development notable by age 2 years. He attended a 0 to 3 program with intensive speech therapy and then moved to a self-contained preschool classroom with a 1:1 staff-to-student ratio. He received school-based speech, occupational, and physical therapies. Testing results revealed clinically significant scores on the Autism Diagnostic Observation Schedule. Cognitive testing results showed that his IQ was below average but was likely an underestimate due to noncompliance. The parents stated that he played repetitively, lining up toy cars and spinning their wheels. He did not seek or give comfort to others when distressed. He had tactile hypersensitivity but pain hyposensitivity, flicked light switches repetitively, and mouthed objects.In the office, the patient showed a minimal response to clinicians’ social overtures and poor eye contact. He replayed videos on a smartphone while laughing, spinning around, and flapping his hands. He did not respond to prompts for joint engagement and no imaginative play was observed. When the videos stopped, he repeatedly climbed onto chairs and jumped off. As clinicians attempted to redirect him, he became very agitated and his mother intervened physically to protect him from self-injury.Referral of family members for genetic testing to determine 16p11.2 carrier statusPharmacotherapy with R-baclofen based on the mouse model of 16p11.2 deletionPharmacotherapy with citalopram for rigidity and repetitive behaviorReferral to a behavioral intervention program plus pharmacotherapy with aripiprazole for irritability, agitation, and self-injury

what would you do next?

What would you do next?

Referral of family members for genetic testing to determine 16p11.2 carrier status

Referral to a behavioral intervention program plus pharmacotherapy with aripiprazole for irritability, agitation, and self-injury

Pharmacotherapy with R-baclofen based on the mouse model of 16p11.2 deletion

Pharmacotherapy with citalopram for rigidity and repetitive behavior

b

male

0-10

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2674036

A healthy adolescent girl presented with a prolonged dermatitis of both feet characterized by pruritus and accompanying desquamation (Figure 1). Physical examination revealed well-demarcated desquamative patches with scales on both distal feet, showing a sandal appearance. No local heat, swelling, or discharge from the skin lesions was noted. The patient’s medical history was otherwise unremarkable and she had no known history of atopic dermatitis. A fungal smear skin test with potassium hydroxide preparation was performed on the lesion, which showed negative findings.Well-defined hyperkeratotic desquamation on both feet, representing a sandal appearance. What Is Your Diagnosis?

Tinea pedis

Psoriasis

Pityriasis rubra pilaris

Juvenile plantar dermatosis

C. Pityriasis rubra pilaris

C

Pityriasis rubra pilaris

A skin biopsy was performed at the end of the stem of the lesion. Histopathologic testing revealed alternating orthokeratosis and parakeratosis in a checkerboard pattern and epidermal hyperplasia without neutrophilic infiltration. In combination with the clinical findings of localized plantar keratoderma (keratoderma is a group of disorders characterized by thickening of the skin with hyperkeratosis), pityriasis rubra pilaris (PRP) was diagnosed. Differential diagnoses, including tinea pedis and psoriasis, were ruled out based on negative fungal smear skin tests and absent neutrophilic infiltration on histopathologic examination. Juvenile plantar dermatosis was also ruled out as it frequently affects patients with atopic dermatitis and involves the weight-bearing and frictional areas of the feet, leaving toe webs spared. After treatment with oral, low-dose isotretinoin, 0.3 mg/kg/d, for 2 months, the lesions resolved significantly (Figure 2). No relapse occurred over 5 months with ongoing treatment.After treatment with oral, low-dose isotretinoin, 0.3 mg/kg/d, for 2 months, the lesions showed significant improvement.Pityriasis rubra pilaris is a rare papulosquamous disease with an incidence of 1 in 3500 to 5000 patients in the United States.1 Pityriasis rubra pilaris shows a bimodal age distribution, peaking in the first and fifth to sixth decades. Males and females are equally affected. Griffiths2 originally classified PRP into 5 subtypes.1 Type 1 (classic adult type, >50% of all cases) is the most common subtype characterized by follicular hyperkeratotic papules that spread in a cephalocaudal direction and often progress to a generalized erythroderma with islands of normal skin. A waxy, diffuse, yellowish keratoderma of the palms and soles, the so-called sandal appearance, may occur. This form of PRP carries the best prognosis, showing a remission rate of more than 80% within 3 years. Type 2 (atypical adult type, 5%) is characterized by a duration of 20 years or more as well as by atypical morphologic features. Follicular hyperkeratosis, as well as ichthyosiform scaling, especially on the lower limbs, dominates the clinical picture. Type 3 (classic juvenile type, 10%) seems to be the counterpart of the classic adult type (type I PRP) with the age of onset the only difference, and type 3 PRP spontaneously clears within a year. Type 4 (circumscribed juvenile type, 25%) is characterized by well-demarcated hyperkeratotic erythematous plaques limited usually to the elbows and knees with palmoplantar involvement, showing a 3-year remission rate in approximately one-third of affected patients. Type 5 (atypical juvenile type, 5%) is characterized by an early age of onset and a chronic course. It is distinguished by follicular hyperkeratosis and a scleroderma-like appearance on the hands and feet. Following the initial categorization, human immunodeficiency virus–associated PRP was added as a separate type (type 6), showing clinical features similar to those of type 1.2,3 However, the clinical spectrum of PRP could be diverse, and some cases are not neatly categorized by the classification based on age and body surface involvement.4Therapeutic options for PRP include retinoids, antimetabolites, immunosuppressive agents, antibiotics, UV phototherapy, and biologic agents.1,5 Among these treatments, systemic retinoids, such as isotretinoin, have shown the best outcomes.1,6,7 The short-term use of oral retinoids in otherwise healthy children with PRP seems to be well tolerated and safe. In previous studies, isotretinoin, at dosages of 1 to 2 mg/kg/d for 3 to 6 months, showed favorable results.6,7 More recently, alitretinoin, at dosages of 0.5 mg/kg/d, also yielded a convincing clinical response after 7 months.8 In the present case, the patient responded to low-dose isotretinoin treatment of 0.3 mg/kg/d; this could be a feasible treatment option for pediatric patients without serious adverse events.Differentiation between PRP and other diseases is important because of the difference in treatment and prognosis. The presence of follicular keratotic papules, diffuse palmoplantar keratosis, recalcitrance to topical corticosteroid treatment, and the absence of neutrophilic infiltration and alternating orthokeratosis and parakeratosis on histopathologic examination favor a diagnosis of PRP.9 A waxy erythematous palmoplantar keratoderma can also be helpful in distinguishing psoriasis (scaly and pink-red) from PRP (waxy and pink-orange).

Pediatrics

A healthy adolescent girl presented with a prolonged dermatitis of both feet characterized by pruritus and accompanying desquamation (Figure 1). Physical examination revealed well-demarcated desquamative patches with scales on both distal feet, showing a sandal appearance. No local heat, swelling, or discharge from the skin lesions was noted. The patient’s medical history was otherwise unremarkable and she had no known history of atopic dermatitis. A fungal smear skin test with potassium hydroxide preparation was performed on the lesion, which showed negative findings.Well-defined hyperkeratotic desquamation on both feet, representing a sandal appearance.

what is your diagnosis?

What is your diagnosis?

Juvenile plantar dermatosis

Pityriasis rubra pilaris

Psoriasis

Tinea pedis

b

female

11-20

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2673933

A man in his 30s presented with abdominal pain associated with unintentional weight loss for 6 months. The patient had a history of hyperlipidemia. Results of examination revealed a palpable mass of about 15 cm in the left paraumbilical region. The patient had a normal right testis but a missing left testis. Results of a computed tomography scan of the thorax, abdomen, and pelvis revealed large intraperitoneal and retroperitoneal masses. The intraperitoneal heterogenous mass was 20 × 15 × 11 cm, with linear calcifications (Figure 1). There was a right moderate hydronephrosis. The retroperitoneal mass was homogeneous, with associated lymphadenopathy encircling the aorta, inferior mesenteric artery, and both renal arteries. A large left supraclavicular lymph node and left inguinal lymph node were also detected. There was no metastasis identified elsewhere. Serum lactate dehydrogenase was elevated at 1358 U/L (to convert to microkatals per liter, multiply by 0.0167), β human chorionic gonadotrophin was elevated at 1485 mIU/mL (to convert to international units per liter, multiply by 1.0), and α fetoprotein levels were normal.A computed tomography scan of the thorax, abdomen, and pelvis showing large intraperitoneal and retroperitoneal masses. The intraperitoneal heterogenous mass was 20 × 15 × 11 cm, with linear calcifications. What Is Your Diagnosis?

Colorectal cancer

Testicular cancer

Bladder cancer

Lymphoma

B. Testicular cancer

B

Testicular cancer

Results of percutaneous biopsy of the intraperitoneal mass subsequently revealed tumor cells with uniform vesicular hyperchromatic nuclei and clear cytoplasm, with positive staining for placental alkaline phosphatase, CD117 (proto-oncogene c-Kit), and OCT4 (octamer-binding transcription factor 4), suggestive of seminomatous germ cell origin. The patient was diagnosed with stage IIIB seminoma testicular cancer. Testicular cancer commonly affects males between the ages of 15 and 35 years, and is the most common solid tumor among males in this age range.1 It accounts for 1% of all cancers in men, with 95% of cases presenting as germ cell tumors.1 Cryptorchidism increases the risk of testicular cancer: in a meta-analysis,2 the pooled relative risk of testicular cancer in men with isolated cryptorchidism was 2.9. The treatment options for germ cell tumors differ between seminomatous and nonseminomatous subtypes. Seminoma is highly treatable, with cure rates exceeding 90% for all stages combined.1 The staging of testicular cancer is done in accordance with the 2017 joint staging system of the American Joint Committee on Cancer and the Union for International Cancer Control.3 For patients with advanced disease, prognostic tools by the International Germ Cell Cancer Collaborative Group may be used for risk stratification, prognostication, and selection of appropriate systemic therapy.4 In metastatic seminomatous germ cell tumors, patients may have a good or intermediate risk profile based on the location of the metastases. Those with an intermediate risk profile harbor metastasis to visceral organs other than the lungs or lymph nodes.This patient was diagnosed with metastatic seminoma in the good risk category. As such, the recommended treatment option is cisplatin-based combination chemotherapy. The standard treatment regimen is 3 cycles of bleomycin sulfate, etoposide, and cisplatin (BEP)5 or 4 cycles of etoposide and cisplatin (EP).6 Trials conducted by the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group5 and Groupe d’Etude des Tumeurs Uro-Genital comparing 3 cycles of BEP with 4 cycles of EP7 showed that the EP cohort had similar survival outcomes, but possibly slightly inferior, when treating individuals with a good risk profile. Etoposide and cisplatin should be considered for men with compromised pulmonary function and/or compromised renal function. In men with metastatic seminomas who had a good risk profile, the 5-year progression-free survival rate was 90% and the overall survival rate was 92%.4After systemic therapy, the primary site of the germ cell tumor in the testicle should be removed if not previously done, as the testicular blood barrier impairs effective penetration of chemotherapeutic agents into the testicular parenchyma. There is no role for radiotherapy for metastatic seminomas.This patient received 3 cycles of BEP cytoreductive chemotherapy, with good response. The large intraperitoneal heterogenous mass with calcifications became significantly smaller, measuring 9.8 × 16.7 cm in its transverse diameter. There was also interval resolution of the left supraclavicular adenopathy and left inguinal lymph node. Both the lactate dehydrogenase and β human chorionic gonadotrophin levels normalized after chemotherapy. The patient subsequently underwent laparoscopic left testicular orchidectomy for the residual tumor (Figure 2), and results of histologic testing showed no residual viable disease.

Surgery

A man in his 30s presented with abdominal pain associated with unintentional weight loss for 6 months. The patient had a history of hyperlipidemia. Results of examination revealed a palpable mass of about 15 cm in the left paraumbilical region. The patient had a normal right testis but a missing left testis. Results of a computed tomography scan of the thorax, abdomen, and pelvis revealed large intraperitoneal and retroperitoneal masses. The intraperitoneal heterogenous mass was 20 × 15 × 11 cm, with linear calcifications (Figure 1). There was a right moderate hydronephrosis. The retroperitoneal mass was homogeneous, with associated lymphadenopathy encircling the aorta, inferior mesenteric artery, and both renal arteries. A large left supraclavicular lymph node and left inguinal lymph node were also detected. There was no metastasis identified elsewhere. Serum lactate dehydrogenase was elevated at 1358 U/L (to convert to microkatals per liter, multiply by 0.0167), β human chorionic gonadotrophin was elevated at 1485 mIU/mL (to convert to international units per liter, multiply by 1.0), and α fetoprotein levels were normal.A computed tomography scan of the thorax, abdomen, and pelvis showing large intraperitoneal and retroperitoneal masses. The intraperitoneal heterogenous mass was 20 × 15 × 11 cm, with linear calcifications.

what is your diagnosis?

What is your diagnosis?

Colorectal cancer

Testicular cancer

Bladder cancer

Lymphoma

b

male

31-40

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2675987

A 48-year-old man was admitted to our emergency department 12 hours after a bicycle accident with abdominal pain, nausea, and vomiting. He described abdominal trauma caused by the bicycle handlebar. The patient reported undergoing an appendectomy at age 23 years and having ulcerative colitis since he was aged 30 years. He had received treatment (mesalazine and corticosteroids) for inflammatory bowel disease that had been discontinued.Physical examination revealed paraumbilical ecchymosis (Figure 1A), general abdominal tenderness, and distension. Body temperature, blood pressure, and heart and respiratory rates were normal. Laboratory test findings did not show abnormalities except for the leukocyte count (12 300 cells/μL [to convert to ×109/L, multiply by 0.001]); hemoglobin and hematocrit levels were within the reference ranges. An abdominal computed tomographic (CT) scan, performed immediately, revealed a pneumoperitoneum and free fluid in the lower quadrants of the abdomen (Figure 1B).Preoperative workup. A, Paraumbilical bruising. B, Abdominal computed tomography (CT) scan: coronal cut showing free fluid (white arrowhead) and pneumoperitoneum (red arrowheads). What Is Your Diagnosis?

Pancreas injury

Flaring ulcerative colitis

Rectosigmoid junction rupture

Duodenal injury

C. Rectosigmoid junction rupture

C

Rectosigmoid junction rupture

This patient presented with rectosigmoid junction rupture as shown in Figure 2. Regarding other diagnoses, flaring ulcerative colitis is unlikely after abdominal trauma and should be considered as a differential diagnosis. Pancreas injury and/or duodenal injury may induce free fluid and pneumoperitoneum as in the present case and should be suspected after abdominal trauma related to the bicycle handlebar.1 Yet, the CT scan excluded these lesions, and free fluid was finally identified as a hemoperitoneum due to a mesocolonic tear.Intraoperative view, with complete rectosigmoid junction rupture causing peritonitis and hemoperitoneum.Traumatic perforation of the colon and rectum (Figure 2) is mostly the result of penetrating injury and, after blunt trauma, is usually associated with other intra-abdominal organ injuries, most commonly the liver, pancreas, spleen, duodenum, and small intestine.1-3 Therefore, isolated colon injury after blunt trauma is rare, responsible for only 0.1% to 1.1% of all abdominal traumas,2,4,5 mainly after motor vehicle crashes and assaults. Three mechanisms have been described: crushing of the colonic segment between an object and vertebra or pelvis; rapid deceleration, with tears between the natural fixed points; and burst injury, which occurs by closure of the colonic segments during trauma.6 The part of the colon most frequently affected by injuries is the left colon (predominantly the sigmoid) followed by the transverse colon, right colon (mainly the cecum), and rectum.2,3Clinical assessment is not accurate for diagnosis: only 50% of gastrointestinal tract injuries resulting from blunt trauma have sufficient clinical findings to indicate the need for laparotomy (shock, tenderness, guarding).2 Also, among patients undergoing laparotomy based on clinical assessment after blunt abdominal trauma, exploration is negative in 40% of the cases, with an associated morbidity reaching 20%.7 This inaccurate preoperative clinical evaluation may lead to uncertain management and delayed diagnosis with high morbidity and up to 20% mortality.4,7,8Ultrasonography and CT have been proposed for diagnosis; however, use of CT is controversial. With reported sensitivity and specificity of 60% to 88% and 97% to 99%,9 respectively, CT is an appropriate imaging technique; yet, other authors reported that CT had less than 50% negative predictive value for hollow viscus injuries.4 Finally, free fluid may be related to various mechanisms (digestive fluid, blood, pus) and is mostly nonspecific for diagnosis. Consequently, the presence of free air in the abdomen or contrast extravasation and the surgeon’s index of suspicion are seemingly the determining factors.Treatment options include primary closure, resection with anastomosis, and colostomy. Primary closure can be performed for injuries involving less than 50% of the colonic wall and, when injuries exceed 50% of the colonic wall or when there is extensive mesenteric injury, resection with anastomosis should be preferred. Colostomy should be performed when there are more than 2 abdominal organ injuries, when the amount of intra-abdominal bleeding is more than 1000 mL, there is gross fecal contamination, and the time between injury and treatment exceeds 8 hours.7,10 The preferred treatment should be early primary repair, but in the presence of multiple risk factors, the best option remains unclear.

Surgery

A 48-year-old man was admitted to our emergency department 12 hours after a bicycle accident with abdominal pain, nausea, and vomiting. He described abdominal trauma caused by the bicycle handlebar. The patient reported undergoing an appendectomy at age 23 years and having ulcerative colitis since he was aged 30 years. He had received treatment (mesalazine and corticosteroids) for inflammatory bowel disease that had been discontinued.Physical examination revealed paraumbilical ecchymosis (Figure 1A), general abdominal tenderness, and distension. Body temperature, blood pressure, and heart and respiratory rates were normal. Laboratory test findings did not show abnormalities except for the leukocyte count (12 300 cells/μL [to convert to ×109/L, multiply by 0.001]); hemoglobin and hematocrit levels were within the reference ranges. An abdominal computed tomographic (CT) scan, performed immediately, revealed a pneumoperitoneum and free fluid in the lower quadrants of the abdomen (Figure 1B).Preoperative workup. A, Paraumbilical bruising. B, Abdominal computed tomography (CT) scan: coronal cut showing free fluid (white arrowhead) and pneumoperitoneum (red arrowheads).

what is your diagnosis?

What is your diagnosis?

Pancreas injury

Flaring ulcerative colitis

Rectosigmoid junction rupture

Duodenal injury

c

male

41-50

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2670732

A man in his early 30s with a 2-year history of chronic conjunctivitis and blurry vision in the left eye since his cornea was scratched by “a piece of wood” presented with progressive dull pain and decreased visual acuity in the left eye. Visual acuity was 20/400 in the left eye, improved to 20/100 with pinhole. Slitlamp examination revealed a small, nasal corneal scar, a small iris defect, iris heterochromia, and a cataract with overlying pigment (Figure 1A). Dilated funduscopic examination of the left eye demonstrated vitritis and a hazy view of the retina due to the opacity of the media. A color fundus photograph of the eye showed opacity of the media secondary to the cataract and vitritis and a slightly pale optic nerve. Fluorescein angiography (Figure 1B) demonstrated early hyperfluorescence of an inferotemporal chorioretinal lesion that increased slightly during the course of the study, consistent with possible leakage. There were multiple hypofluorescent dots throughout the retina and an appearance of segmentation of the vessels with slightly decreased venous filling and late staining. A computed tomography scan of the eye and orbit revealed a hyperdense foreign body located along the inferior aspect of the vitreous, approximately at the 5 o'clock position, abutting the retinal surface. Ultrasonography B scan revealed a highly reflective material causing posterior shadowing at the 5 o’clock position.A, Cataract with overlying pigment (yellow arrowhead). B, Fluorescein angiography of the left eye showed an early hyperfluorescent inferotemporal chorioretinal lesion (white arrowhead), diffuse hypofluorescent dots throughout the retina (double blue arrowheads), and segmentation of the vessels (yellow arrowhead). What Would You Do Next?

Surgery

Observation

Laboratory workup for uveitis

Topical and systemic corticosteroid treatment

Ocular siderosis secondary to retained iron-containing intraocular foreign body (IOFB)

A

Surgery

Ocular siderosis is caused by retention and oxidation of an iron-containing IOFB. Iron deposits can be found in the corneal endothelium, Descemet membrane, trabecular meshwork, pupillary muscles, nonpigmented ciliary epithelium, lens epithelium, retinal pigment epithelium, and internal-limiting membrane.1 Cataract and pigmentary retinopathy are the most common complications of retained iron IOFB, followed by iris heterochromia, mydriasis, secondary glaucoma, and optic nerve atrophy.1 Retinal arteriolar attenuation, full-thickness retinal degeneration and atrophy, as well as secondary rhegmatogenous retinal detachment have been reported as the sequelae of long-standing intraretinal iron-containing IOFB.1-3An electroretinogram is the most commonly performed study that is used not only to assess the degree of ocular injury from metallosis preoperatively, but also to monitor ocular recovery after surgical metallic foreign body removal.2 Decreased amplitudes of a- and b-wave waveforms are associated with ocular siderosis, and reversal of electroretinogram amplitude can be expected in early iron toxicity after removal of the IOFB.2,4 One of the most common causes of metallic IOFB is hammering on metal.1 Our patient did not report a clear history of trauma from a metallic source. In cases with an unclear history of metallic IOFB, ultrasonography, except in the case of suspected globe rupture, and computed tomography scan should be performed. Surgical removal of iron-containing IOFB is the treatment for ocular siderosis to reduce the ocular toxic effects and achieve the optimal visual outcome. Tetanus booster status should be updated for patients with metallic IOFB.Observation is not recommended in this patient with progressive and severe visual loss and signs and symptoms of ocular siderosis. Laboratory workup for uveitis should be considered, given the symptoms of photophobia and blurry vision. However, because an IOFB is evident on imaging, surgical treatment is the next step in management. Finally, starting with topical and systemic corticosteroid treatment is not advised before ruling out the possibility of infectious endophthalmitis, vitritis, or IOFB.The patient underwent cataract extraction with intraocular lens implantation, pars plana vitrectomy, vitreous biopsy, and removal of the metallic IOFB. The vitreous biopsy and cultures were negative for infection, ruling out chronic endophthalmitis. Postoperative color fundus photography (Figure 2) revealed a pale optic nerve, attenuated vessels, ghost white vessels, and multiple small, white retinal dot lesions distributed throughout the retina. In the inferotemporal arcade, there was a large round area of chorioretinal atrophy with central retinal pigment epithelium clumps corresponding to the area where the IOFB hit the retina. A full-field electroretinogram demonstrated marked attenuation of the a-wave and b-wave amplitudes from the combined rod and cone responses, using dark-adapted 3.0 and 10.0 electroretinogram.5 The electronegative waveforms, indicating b-wave/a-wave ratio deterioration, were consistent with ocular siderosis. The patient’s visual acuity was stable at 20/60 at a 2-year follow-up visit.Color fundus photography of the left eye demonstrated multiple white dots throughout the retina (yellow arrowhead), ghost white vessels (double blue arrowheads), and a large, atrophic chorioretinal lesion with central retinal pigment epithelial clumps (white arrowhead).

Ophthalmology

A man in his early 30s with a 2-year history of chronic conjunctivitis and blurry vision in the left eye since his cornea was scratched by “a piece of wood” presented with progressive dull pain and decreased visual acuity in the left eye. Visual acuity was 20/400 in the left eye, improved to 20/100 with pinhole. Slitlamp examination revealed a small, nasal corneal scar, a small iris defect, iris heterochromia, and a cataract with overlying pigment (Figure 1A). Dilated funduscopic examination of the left eye demonstrated vitritis and a hazy view of the retina due to the opacity of the media. A color fundus photograph of the eye showed opacity of the media secondary to the cataract and vitritis and a slightly pale optic nerve. Fluorescein angiography (Figure 1B) demonstrated early hyperfluorescence of an inferotemporal chorioretinal lesion that increased slightly during the course of the study, consistent with possible leakage. There were multiple hypofluorescent dots throughout the retina and an appearance of segmentation of the vessels with slightly decreased venous filling and late staining. A computed tomography scan of the eye and orbit revealed a hyperdense foreign body located along the inferior aspect of the vitreous, approximately at the 5 o'clock position, abutting the retinal surface. Ultrasonography B scan revealed a highly reflective material causing posterior shadowing at the 5 o’clock position.A, Cataract with overlying pigment (yellow arrowhead). B, Fluorescein angiography of the left eye showed an early hyperfluorescent inferotemporal chorioretinal lesion (white arrowhead), diffuse hypofluorescent dots throughout the retina (double blue arrowheads), and segmentation of the vessels (yellow arrowhead).

what would you do next?

What would you do next?

Laboratory workup for uveitis

Topical and systemic corticosteroid treatment

Observation

Surgery

d

male

0-10

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2671938

A 67-year-old African American man with a history of hypertension and type 2 diabetes status with kidney transplant presented with a 10-day history of sudden-onset, painless vision loss in the right eye. The kidney transplant was performed 4 years previously presumably secondary to diabetic nephropathy, and the patient was receiving daily 5 mg of oral prednisone and 1500 mg of mycophenolate mofetil hydrochloride. The patient denied significant ocular history before this episode of vision loss. On examination, his visual acuity was counting fingers OD at 2 ft and 20/20 OS. Intraocular pressures were measured at 15 mm Hg OD and 14 mm Hg OS, and normal pupillary and anterior segment examination findings were noted in each eye. The patient had several large pigment epithelial detachments (PEDs) with associated tears and scrolling of the retinal pigment epithelium (RPE) seen on enhanced-depth imaging optical coherence tomography in the right eye (Figure 1A). Intravenous fluorescein angiography demonstrated several large window defects with hyperfluorescence in the regions of the RPE tears in the late phase (Figure 1B). Indocyanine green angiography was also performed and did not reveal any hyperfluorescent regions.A, Enhanced-depth imaging optical coherence tomography (OCT) of a foveal cross-section at presentation shows a serous retinal detachment and a retinal pigment epithelium tear with scrolled edges seen along the Bruch membrane inferiorly in the image and the other edge of the tear seen attached to the retina at the top left. B, Late-phase intravenous fluorescein angiograph at presentation shows large window defects inferior and superior to the fovea and inferior to the inferior arcade with additional defects seen at nasal and inferotemporal edges of the photograph.Administer intravitreal anti–vascular endothelial growth factor treatment Refer the patient to the nephrologist for evaluation of kidney function What Would You Do Next?

Monitor the patient

Administer intravitreal anti–vascular endothelial growth factor treatment

Refer the patient to the nephrologist for evaluation of kidney function

Provide photodynamic therapy with verteporfin

Multiple myeloma with light chain deposition disease leading to serous retinal detachments, PEDs, and RPE tears

C

Refer the patient to the nephrologist for evaluation of kidney function

Hypertensive choroidopathy in the context of renovascular hypertension and kidney failure was postulated to result in this patient’s PEDs and RPE tears. The patient was referred to the nephrologist, who noted an elevated blood pressure and creatinine level. Because of concern about the patient’s transplant being rejected, he underwent a kidney biopsy. Congo red staining of the biopsy specimen revealed deposition of immunoglobulin κ chain without evidence of birefringence, and the patient was diagnosed with light chain deposition disease (LCDD). He was found to have more than 60% plasmacytosis with free κ levels of 2070 mg/dL and λ levels at 6.24 mg/L, and he was diagnosed with κ chain–only multiple myeloma with LCDD. The patient initiated chemotherapy with 3 cycles of carfilzomib, lenalidomide, and dexamethasone sodium phosphate and later underwent an autologous stem cell transplant. Administering intravitreal anti–vascular endothelial growth factor treatment (option B) may be an appropriate treatment option for PEDs secondary to age-related macular degeneration (AMD). The most common source of PEDs and RPE tears is choroidal neovascularization secondary to wet AMD.1 Sub-RPE choroidal neovascularization leads to fluid accumulation resulting in a PED. Significant hydrostatic pressure into the PED can result in tears, which are associated with scrolling of the RPE edges.2 Patients with RPE tears due to AMD have shown improvement with anti–vascular endothelial growth factor treatment possibly because of the antiangiogenic feature of the treatment and reduction of subretinal fluid aid in vision improvement.1 The patient, however, did not have evidence of AMD.Monitoring the patient, as may be done for central serous chorioretinopathy, or providing photodynamic therapy (PDT) for treatment of polypoidal choroidal vasculopathy would not be appropriate in this circumstance because PEDs have not classically been found in central serous chorioretinopathy and the patient did not have any hot spots on indocyanine green angiography. Red krypton laser therapy and PDT have been linked with the development of RPE tears. Gass3 described 3 cases of RPE tears secondary to the use of red krypton laser in patients with AMD. He hypothesized that the longer wavelength of the laser is preferentially absorbed by pigmented cells of the choroid with a sudden contraction of the RPE, resulting in a tear. Goldstein et al4 described 7 cases of RPE tears secondary to the use of PDT in patients with AMD, hypothesizing that PDT makes the RPE vulnerable with decreased intercellular adhesions owing to altered choroidal perfusion and sub-RPE exudation.There is scarce literature pertaining to LCDD-induced RPE tears. In a series of 3 patients, large RPE tears were found to be associated with biopsy-proven LCDD similar to that found in the patient in our report.5 These were similar findings to those in an autopsy specimen from a patient who died of LCDD with evidence of light chain deposits at the level of Bruch membrane seen on electron microscopy.6 Our hypothesis is similar to that proposed by Bird7 in 1991: Protein accumulation (instead of lipid) at the level of Bruch membrane may prevent RPE-dependent fluid transfer from the subretinal space into the choriocapillaris, thereby accumulating in the sub-RPE space.The patient was seen in the clinic 4 months following the initiation of chemotherapy and was found to have reattachment of the retina and RPE (Figure 2) and improved visual acuity of 20/40.Enhanced-depth imaging optical coherence tomography at 4-month follow-up visit shows resolution of serous and retinal pigment epithelial detachment.

Ophthalmology

A 67-year-old African American man with a history of hypertension and type 2 diabetes status with kidney transplant presented with a 10-day history of sudden-onset, painless vision loss in the right eye. The kidney transplant was performed 4 years previously presumably secondary to diabetic nephropathy, and the patient was receiving daily 5 mg of oral prednisone and 1500 mg of mycophenolate mofetil hydrochloride. The patient denied significant ocular history before this episode of vision loss. On examination, his visual acuity was counting fingers OD at 2 ft and 20/20 OS. Intraocular pressures were measured at 15 mm Hg OD and 14 mm Hg OS, and normal pupillary and anterior segment examination findings were noted in each eye. The patient had several large pigment epithelial detachments (PEDs) with associated tears and scrolling of the retinal pigment epithelium (RPE) seen on enhanced-depth imaging optical coherence tomography in the right eye (Figure 1A). Intravenous fluorescein angiography demonstrated several large window defects with hyperfluorescence in the regions of the RPE tears in the late phase (Figure 1B). Indocyanine green angiography was also performed and did not reveal any hyperfluorescent regions.A, Enhanced-depth imaging optical coherence tomography (OCT) of a foveal cross-section at presentation shows a serous retinal detachment and a retinal pigment epithelium tear with scrolled edges seen along the Bruch membrane inferiorly in the image and the other edge of the tear seen attached to the retina at the top left. B, Late-phase intravenous fluorescein angiograph at presentation shows large window defects inferior and superior to the fovea and inferior to the inferior arcade with additional defects seen at nasal and inferotemporal edges of the photograph.Administer intravitreal anti–vascular endothelial growth factor treatment Refer the patient to the nephrologist for evaluation of kidney function

what would you do next?

What would you do next?

Monitor the patient

Provide photodynamic therapy with verteporfin

Refer the patient to the nephrologist for evaluation of kidney function

Administer intravitreal anti–vascular endothelial growth factor treatment

c

male

61-70

African American

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2672737

A woman in her early 60s presented with bilateral progressive painless blurring of vision for 1 week, associated with metamorphopsia. She was otherwise well and had no history of tuberculosis or underlying immunocompromise. Her best-corrected visual acuity was 20/80 OD and 20/60 OS. Ophthalmoscopy revealed bilateral swollen, hyperemic optic discs with multifocal yellowish choroidal lesions located at the midperiphery and posterior pole of the retina. The lesions varied in size, ranging from one-fourth to twice the diameter of the optic disc. Punctate areas of choroiditis were also seen along the temporal arcades (Figure 1A). Results of fundus fluorescein angiography showed bilateral early hypofluorescence, with late staining and leakage from the optic discs. Results of systemic examination were normal, except for coarse crepitations of the right lung. The erythrocyte sedimentation rate was elevated, at 80 mm/h, as was the C-reactive protein level, at 20.2 mg/L (to convert to nanomoles per liter, multiply by 9.524). Chest radiograph showed consolidation in the right lower zone (Figure 1B). However, results of tuberculin skin test, sputum for acid-fast bacilli, and sputum culture were negative. Three days after initial presentation, the patient developed acute binocular horizontal diplopia and disorientation.A, Color fundus photograph revealed bilateral swollen, hyperemic optic discs with multifocal choroidal lesions. B, Chest radiograph showed consolidation in the right lower zone.Order urgent magnetic resonance imaging of the brain What Would You Do Next?

Perform a lumbar puncture

Order urgent magnetic resonance imaging of the brain

Repeat sputum culture and sensitivity testing

Start broad-spectrum intravenous antibiotics

Bilateral optic neuropathy and multifocal choroiditis with meningitis secondary to disseminated tuberculosis

B

Order urgent magnetic resonance imaging of the brain

In view of the patient’s neurologic symptoms and bilateral optic disc edema, radiographic imaging of the brain is required. Magnetic resonance imaging (MRI) of the brain showed multiple ring-enhancing lesions scattered throughout the cerebral hemispheres, characteristic of tuberculomas (Figure 2). All ventricles were dilated, suggestive of communicating hydrocephalus. Although cerebrospinal fluid analysis may give clues to the possible cause of meningitis,1 lumbar puncture is contraindicated prior to exclusion of high intracranial pressure, owing to the risk of conal herniation. Sputum culture may be repeated but is not the priority at this time and has no value in diagnosing tuberculous meningitis.1,2 Although empirical antibiotics may be initiated, they will not aid in the diagnostic workup and will not be effective in cases of tuberculous infection.1Magnetic resonance imaging of the brain showed multiple ring-enhancing lesions scattered throughout the cerebral hemispheres. H indicates head; L, left.Tuberculosis is commonly associated with depressed cell-mediated immunity,3 but even among healthy patients it can cause significant morbidity. Central nervous system tuberculosis in particular requires prompt initiation of antituberculosis therapy upon clinical suspicion, as the mortality rate is high, even with treatment.4 In adults, central nervous system tuberculosis usually takes the form of meningitis, often presenting with subacute, nonspecific prodromal features such as fever, headache, and confusion.5 This patient had no prodromal symptoms, but her sixth nerve palsy was a red flag for increased intracranial pressure, evidenced by dilated ventricles seen on the results of the brain MRI.6 Hydrocephalus in tuberculous meningitis has been attributed to high protein levels obstructing the flow of cerebrospinal fluid.7 The optic disc swelling in this patient may be owing to papilledema or papillitis occurring as part of the inflammatory response, both of which demonstrate late hyperfluorescence on fundus fluorescein angiography.8The diagnostic challenge in the presentation of this case was that, unlike the characteristic unilateral, focal choroiditis seen in tuberculosis, the patient presented with bilateral, diffuse choroiditis more typical of choroidal metastases.9 Furthermore, her chest radiograph showed lower zone consolidation instead of the more commonly reported apical foci, and results of conventional investigations for acid-fast bacilli infection were negative. Multifocal choroiditis and ring-enhancing lesions on the results of the brain MRI may mimic metastases,2 but investigations to exclude a systemic malignant neoplasm were negative, leaving tuberculosis as the most likely diagnosis.Tuberculosis can have a variable multisystemic presentation. Clinicians worldwide should maintain a high index of suspicion for the disease, especially in view of the migration-associated increase in cases of tuberculosis.10 Early diagnosis and treatment may prevent sight-threatening and potentially fatal complications.The patient was treated empirically with an oral antituberculosis regimen of isoniazid, 300 mg, rifampicin, 600 mg, pyrazinamide, 1500 mg, and ethambutol hydrochloride, 1000 mg. Her mental status improved and the diplopia resolved 2 weeks after initiation of treatment. However, the patient’s vision remained impaired, as the choroiditis resolved with scar formation. Results of MRI of the brain after 1 month of antituberculosis treatment showed a reduction in the size and numbers of ring-enhancing lesions.

Ophthalmology

A woman in her early 60s presented with bilateral progressive painless blurring of vision for 1 week, associated with metamorphopsia. She was otherwise well and had no history of tuberculosis or underlying immunocompromise. Her best-corrected visual acuity was 20/80 OD and 20/60 OS. Ophthalmoscopy revealed bilateral swollen, hyperemic optic discs with multifocal yellowish choroidal lesions located at the midperiphery and posterior pole of the retina. The lesions varied in size, ranging from one-fourth to twice the diameter of the optic disc. Punctate areas of choroiditis were also seen along the temporal arcades (Figure 1A). Results of fundus fluorescein angiography showed bilateral early hypofluorescence, with late staining and leakage from the optic discs. Results of systemic examination were normal, except for coarse crepitations of the right lung. The erythrocyte sedimentation rate was elevated, at 80 mm/h, as was the C-reactive protein level, at 20.2 mg/L (to convert to nanomoles per liter, multiply by 9.524). Chest radiograph showed consolidation in the right lower zone (Figure 1B). However, results of tuberculin skin test, sputum for acid-fast bacilli, and sputum culture were negative. Three days after initial presentation, the patient developed acute binocular horizontal diplopia and disorientation.A, Color fundus photograph revealed bilateral swollen, hyperemic optic discs with multifocal choroidal lesions. B, Chest radiograph showed consolidation in the right lower zone.Order urgent magnetic resonance imaging of the brain

what would you do next?

What would you do next?

Order urgent magnetic resonance imaging of the brain

Perform a lumbar puncture

Start broad-spectrum intravenous antibiotics

Repeat sputum culture and sensitivity testing

a

female

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2673281

A white woman in her mid-60s presented with progressive bilateral scleral pigmentation (Figure 1A). Her ocular history included narrow angles and ocular hypertension that were managed with laser peripheral iridotomy and topical antiglaucomatous medications in both eyes. On examination, her visual acuity was 20/25 OD and 20/20 OS, with intraocular pressure of 21 mm Hg OD and 21 mm Hg OS. Slitlamp examination demonstrated mild cataract with narrow angles, with patent laser peripheral iridotomy in each eye. Ophthalmoscopic examination demonstrated peripheral paving-stone degeneration in the right eye and peripheral retinal pigmentary abnormalities in both eyes. During subsequent visits to the clinic, pigmentation was also noted in the auricles of both ears (Figure 1B).External photographs taken at initial presentation. Arrowheads indicate pigmentation. What Would You Do Next?

Order a B-scan

Review medical history and systemic medications

Discontinue antiglaucomatous medications

Obtain a 24-hour urine sample

Minocycline-induced scleral and periocular pigmentation

B

Review medical history and systemic medications

Common causes of scleral pigmentation include racial melanosis, a benign pigmentation seen in a large number of patients of black race/ethnicity, and age-related ocular pigmentation. Other, less common causes include conjunctival nevi, conjunctival melanoma, oculodermal melanocytosis, disorders of collagen synthesis such as Ehlers-Danlos syndrome and osteogenesis imperfecta, and metabolic diseases such as alkaptonuria.1 In addition, a number of medications have been linked to ocular pigmentation, including phenothiazine drugs, antimalarial agents, amiodarone, topical epinephrine, and tetracycline antibiotics. With this in mind, the most appropriate next step in the workup of this otherwise healthy 64-year-old white woman would be to review her medical history and medications. Ordering a B-scan or 24-hour urine sample were not deemed to be top priorities, as concern for an ocular tumor or alkaptonuria, respectively, was low. Although prostaglandin analogues have been linked to eyelid and iris pigmentation, antiglaucomatous eyedrops have not been implicated in causing scleral or retinal pigmentation.2Minocycline, one of the tetracycline antibiotics, is often used to treat conditions such as acne vulgaris, rosacea, and some autoimmune disorders. The medication has long been known to cause pigmentation of various parts of the body, including the eyes, skin, brain, thyroid, and bone, owing to its high lipid permeability.3,4 Multiple mechanisms have been proposed for this effect, such as its ability to chelate with hemosiderin and form insoluble products within macrophages or to form complexes with melanin in the epidermis.5,6 With certain exceptions, patterns of minocycline-induced pigmentation typically develop after long periods of administration at cumulative doses greater than 100 g.6Although minocycline-induced dermal pigmentation has been reported extensively, ocular pigmentation is rare. The first case of conjunctival pigmentation was reported by Brothers and Hidayat7 in 1981, detailing dark brown-black pigmentary deposits found at the palpebral conjunctiva bilaterally. Multiple cases of scleral pigmentation have been described, often involving a characteristic blue-gray band of 3 to 5 mm extending from the limbus.8 To the best of our knowledge, there have been 2 reports of minocycline-induced retinal pigmentation, and it is unclear whether the retinal pigmentation seen in this patient is related to her use of the medication.9Although there have been no reported adverse effects from minocycline-induced pigmentation, it is recommended that minocycline be discontinued immediately on recognizing it as the cause. Unlike dermal and oral pigmentation, minocycline-induced ocular pigmentation is irreversible.5 Laser therapy has been successful in treating certain types of dermal pigmentation, although no effective treatment for ocular pigmentation currently exists.10 It is recommended that any patient taking minocycline for longer than 1 year should be screened regularly for pigmentation.5The patient was reassured that the pigmentation was a result of minocycline use, and the medication was discontinued. On subsequent visits, the patient stated that her dermatologist had noted some decrease in the skin pigmentation, although the scleral pigmentation remained stable (Figure 2).External photograph of the right eye and brow taken at a follow-up visit after discontinuation of minocycline therapy showing decreased pigmentation of the brow with stable pigmentation of the sclera.

Ophthalmology

A white woman in her mid-60s presented with progressive bilateral scleral pigmentation (Figure 1A). Her ocular history included narrow angles and ocular hypertension that were managed with laser peripheral iridotomy and topical antiglaucomatous medications in both eyes. On examination, her visual acuity was 20/25 OD and 20/20 OS, with intraocular pressure of 21 mm Hg OD and 21 mm Hg OS. Slitlamp examination demonstrated mild cataract with narrow angles, with patent laser peripheral iridotomy in each eye. Ophthalmoscopic examination demonstrated peripheral paving-stone degeneration in the right eye and peripheral retinal pigmentary abnormalities in both eyes. During subsequent visits to the clinic, pigmentation was also noted in the auricles of both ears (Figure 1B).External photographs taken at initial presentation. Arrowheads indicate pigmentation.

what would you do next?

What would you do next?

Obtain a 24-hour urine sample

Review medical history and systemic medications

Order a B-scan

Discontinue antiglaucomatous medications

b

female

61-70

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2673565

An 11-day-old girl presented with a worsening corneal opacity of the right eye. The patient had received a diagnosis of conjunctivitis at 6 days of life but failed to respond to treatment with topical erythromycin ophthalmic ointment, 0.5%. The baby was an otherwise healthy girl born at full term. Her perinatal history was significant only for a positive maternal test for group B Streptococcus agalactiae, which was treated prior to delivery.Results of the initial examination were significant for conjunctival hyperemia or vasodilation of the right eye, with a 3 × 4-mm central corneal ulcer. Results of B-scan ultrasonography showed no posterior chamber involvement. Corneal cultures for bacteria, fungi, and herpes simplex virus were obtained. Owing to concern for systemic involvement of group B S agalactiae, herpes simplex virus, and other infectious causes, the patient was admitted to the children’s hospital for a full sepsis workup. Treatment with topical polymyxin B sulfate-trimethoprim and intravenous ampicillin, cefepime hydrochloride, and acyclovir sodium was initiated. Results of spinal ultrasonography demonstrated spinal cord tethering at L4, preventing lumbar puncture and collection of cerebrospinal fluid for culture.Two days later, the patient’s right eye developed a hypopyon, and its intraocular pressure was elevated (Figure). Anterior chamber fluid was sent for culture. Results of another B-scan ultrasonography showed a normal posterior segment without inflammation. The topical antibiotic eyedrops were changed to fortified vancomycin hydrochloride, 50 mg/mL, and tobramycin sulfate, 14 mg/mL, and topical timolol maleate, 0.5%, and dorzolamide hydrochloride, 2.0%, were added. The following day, the hypopyon worsened.Photograph of the right eye demonstrating a central corneal infiltrate and large temporal layered hypopyon.Perform another anterior chamber paracentesis procedure and culture What Would You Do Next?

Perform another anterior chamber paracentesis procedure and culture

Perform corneal biopsy

Inject intravitreal antibiotics

Start prednisolone eyedrops

Fungal keratitis caused by Fusarium falciforme

B

Perform corneal biopsy

Infectious keratitis is a significant cause of ocular morbidity worldwide.1-3 In pediatric populations, ocular trauma is the most common predisposing factor to microbial keratitis.2,3 Neonates are a unique population for corneal infections because they do not present in a similar manner as older children and adults; a corneal defect is often the first symptom described by the parents, followed by discharge and tearing.1 Prior studies postulate that lower concentrations of immunoglobulin A and lysozyme in neonates increase their susceptibility to corneal infections.4 Keratitis typically responds to topical antibiotics or systemic antivirals; however, the development of a hypopyon and the lack of improvement after potent broad-spectrum antibiotics and antivirals should lead to a revised differential diagnosis to include fungal pathogens.Fusarium species are filamentous fungi that are well-described pathogens responsible for keratitis, with a reported prevalence ranging from 10% to 75% of all cases of fungal keratitis.5 Because Fusarium species are found in soil and on plants, the most common predisposing factor for keratitis is ocular trauma with vegetable matter.5 Patients living in a rural environment or who are engaged in an agricultural occupation are at higher risk for keratitis.6 Climate and geographical location play an important role in the prevalence of fungal species, and Fusarium is the prevailing isolate in tropical climates.5,6 In south Florida, a tropical climate, it was reported that extended use of contact lenses constituted ocular trauma and predisposed to Fusarium infection.7 Other factors associated with Fusarium infections are nasolacrimal duct obstruction, systemic disease such as diabetes, and corticosteroid use.5,8,9 Although exceptionally rare in neonates, potential risk factors for Fusarium keratitis in children include prematurity, prolonged stay in the neonatal intensive care unit, ocular malformations, and maternal infections.1Rapid diagnosis of Fusarium is paramount because the infection is often severe and penetrates into the anterior chamber.9 Fungal cultures may grow within 3 to 4 days; however, a corneal biopsy (choice B) is the best option after initial cultures return negative results because histopathologic studies and microbiological evaluation of the specimen may yield positive results.9 Biopsy should be performed prior to initiating prednisolone eyedrops (choice D) because corticosteroids are contraindicated for fungal pathogens.9 Performing another anterior chamber paracentesis procedure and culture (choice A) would likely be low yield because this test was previously performed and thus would be unlikely to yield new clinical information. Results of posterior segment ultrasonography that show a clear vitreous make endophthalmitis less likely; therefore, an injection of intravitreal antibiotics (choice C) would not be warranted.Natamycin is first-line treatment of filamentous fungal infections. Amphotericin B may also be considered. Fusarium species are notoriously difficult to treat owing to their relative resistance to most azole medications. However, voriconazole has been shown to be efficacious and may be used independently or in conjunction with natamycin in refractory cases or in cases of deep stromal and anterior chamber invasion. Surgical intervention may be necessary for cases involving the anterior chamber or when medical management fails.8The patient underwent corneal biopsy, yielding the diagnosis of F falciforme. She started treatment with natamycin, 5%, eyedrops and has continued to improve since hospital discharge. Owing to the central location of the corneal scar, she is undergoing amblyopia therapy with phenylephrine hydrochloride, 2.5%, eyedrops to dilate the pupil around the opacity in the affected eye and patching of the contralateral eye.

Ophthalmology

An 11-day-old girl presented with a worsening corneal opacity of the right eye. The patient had received a diagnosis of conjunctivitis at 6 days of life but failed to respond to treatment with topical erythromycin ophthalmic ointment, 0.5%. The baby was an otherwise healthy girl born at full term. Her perinatal history was significant only for a positive maternal test for group B Streptococcus agalactiae, which was treated prior to delivery.Results of the initial examination were significant for conjunctival hyperemia or vasodilation of the right eye, with a 3 × 4-mm central corneal ulcer. Results of B-scan ultrasonography showed no posterior chamber involvement. Corneal cultures for bacteria, fungi, and herpes simplex virus were obtained. Owing to concern for systemic involvement of group B S agalactiae, herpes simplex virus, and other infectious causes, the patient was admitted to the children’s hospital for a full sepsis workup. Treatment with topical polymyxin B sulfate-trimethoprim and intravenous ampicillin, cefepime hydrochloride, and acyclovir sodium was initiated. Results of spinal ultrasonography demonstrated spinal cord tethering at L4, preventing lumbar puncture and collection of cerebrospinal fluid for culture.Two days later, the patient’s right eye developed a hypopyon, and its intraocular pressure was elevated (Figure). Anterior chamber fluid was sent for culture. Results of another B-scan ultrasonography showed a normal posterior segment without inflammation. The topical antibiotic eyedrops were changed to fortified vancomycin hydrochloride, 50 mg/mL, and tobramycin sulfate, 14 mg/mL, and topical timolol maleate, 0.5%, and dorzolamide hydrochloride, 2.0%, were added. The following day, the hypopyon worsened.Photograph of the right eye demonstrating a central corneal infiltrate and large temporal layered hypopyon.Perform another anterior chamber paracentesis procedure and culture

what would you do next?

What would you do next?

Perform another anterior chamber paracentesis procedure and culture

Perform corneal biopsy

Inject intravitreal antibiotics

Start prednisolone eyedrops

b

female

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2673566

A man in his 30s presented with bilateral blurry vision a week after starting prednisone therapy for a presumed seronegative spondyloarthropathy. He had no other pertinent medical history and no relevant ocular history other than anisometropia, for which he wears a corrective contact lens in his right eye. At his initial ophthalmology visit, his best-corrected visual acuity was 20/40 OD and 20/20 OS. In both corneas, he had numerous multicolored, highly refractile crystals located primarily in the subepithelium and anterior stroma (Figure 1). No deposits were noted in the retina of either eye on funduscopic examination.External slitlamp examination of the left eye shows extensive subepithelial and anterior stromal crystals. Similar findings were seen in the right eye. What Would You Do Next?

Initiate topical prednisolone therapy

Superficial corneal biopsy

Begin topical fortified vancomycin therapy

Penetrating keratoplasty

Paraproteinemic keratopathy due to cryoglobulinemia

B

Superficial corneal biopsy

The patient presented with a crystalline keratopathy of the anterior stroma and epithelium. No stromal haze or cellular infiltrate consistent with an inflammatory response, which would potentially benefit from topical prednisolone therapy, was observed. Topical vancomycin is used for the management of infectious crystalline keratopathy, which presents with needlelike crystalline stromal deposits owing to the presence of bacterial colonies in the corneal stroma often after long-term use of topical corticosteroids.1 The deposits in our case are not consistent with those of an infectious crystalline keratopathy, and the patient had no sign of intraocular inflammation that might be seen in cases of infectious crystalline keratopathy. Biopsies can provide invaluable information in the management of a patient presenting with crystalline keratopathy, and moving right to a corneal transplant is not appropriate in a patient who has preserved visual acuity.Light microscopy revealed multiple subepithelial bullae associated with crystalloid material and breaks in the Bowman layer. Electron microscopic examination demonstrated intraepithelial, intracytoplasmic, electron-dense crystalline inclusions with rectangular and rhombohedral configurations. Focally, intracytoplasmic electron-dense deposits with striking microtubular substructures (Figure 2) were observed. Immunofluorescence showed several crystals within the corneal epithelium that stained brightly for IgG and λ immunoglobulin and negative for κ immunoglobulin, consistent with a diagnosis of cryocrystal globulinemia. Subsequently, the patient was diagnosed with type I cryoglobulinemia (monoclonal IgG λ).2Electron microscopic examination revealed intracytoplasmic electron-dense crystalline inclusion, rectangular and rhomboid in shape, with a linear array substructure (white arrowhead). A microtubular substructure was also seen intermixed with the crystalline inclusions (red arrowhead) (original magnification, ×11 000).Paraproteinemic keratopathy, characterized by corneal immunoglobulin deposits, is classically associated with multiple myeloma and monoclonal gammopathy of undetermined significance and less commonly with lymphoma, autoimmune disorders, and cryoglobulinemia.3 In a series of 47 patients with corneal deposits due to paraproteinemia described by Garibaldi et al,4 paraproteinemic keratopathy was attributable to cryoglobulinemia in a single patient. In all the other patients, the deposits were attributable to lymphoma, monoclonal gammopathy, and multiple myeloma.Oglesby5 likely described the first case of cryoglobulinemia crystalline keratopathy, and although the case had no histologic confirmation in regard to the corneal deposits, the patient underwent a biopsy of subcutaneous nodules, confirming cryoglobulin deposits. The opacities were located predominantly in the posterior stroma and also involved the Descemet membrane and corneal endothelium.5 Kremer et al6 described another patient with bilateral corneal deposits and serum cryoprecipates. Results of corneal biopsy revealed eosinophilic deposits between the Bowman layer and superficial stroma. Electron microscopy revealed that the deposits were composed of numerous rod-shaped bodies, confirming the cryoglobulinemia diagnosis.6 Kremer et al6 hypothesized that the presence of precipitates in the anterior cornea was attributable to the cold temperature in the cornea, because it has been reported to be one of the coldest regions of the human body.In this case, the patient’s underlying systemic disease was not identified until after his corneal biopsy. At this time, this patient has not received systemic chemotherapy because no other systemic symptoms related to his cryoglobulinemia and monoclonal gammopathy of undetermined significance have been observed. His best-corrected visual acuity has ranged from 20/20 to 20/30 OD and continues to be 20/20 OS after approximately 12 months of follow-up.

Ophthalmology

A man in his 30s presented with bilateral blurry vision a week after starting prednisone therapy for a presumed seronegative spondyloarthropathy. He had no other pertinent medical history and no relevant ocular history other than anisometropia, for which he wears a corrective contact lens in his right eye. At his initial ophthalmology visit, his best-corrected visual acuity was 20/40 OD and 20/20 OS. In both corneas, he had numerous multicolored, highly refractile crystals located primarily in the subepithelium and anterior stroma (Figure 1). No deposits were noted in the retina of either eye on funduscopic examination.External slitlamp examination of the left eye shows extensive subepithelial and anterior stromal crystals. Similar findings were seen in the right eye.

what would you do next?

What would you do next?

Penetrating keratoplasty

Superficial corneal biopsy

Initiate topical prednisolone therapy

Begin topical fortified vancomycin therapy

b

male

31-40

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2665172

A man in his 60s presented with a 1-year history of a mild, dry cough. He was otherwise asymptomatic and had no physical limitations. He had never smoked, and results of his physical examination were normal. Results of complete blood cell counts, basic metabolic panel, and liver function tests were all within normal limits. A chest radiograph revealed a 10 × 9-cm lobulated left lower lobe mass. Examination of a biopsy specimen showed a primary adenocarcinoma with an immunohistochemical profile of CDX2 positive, CK20 positive, TTF-1 negative, and napsin A negative. His EGFR (OMIM 131550), ALK (OMIM 105590), and ROS1 (OMIM 165020) genes were wild type, and results of testing for programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) were 0%. Results of upper gastrointestinal tract endoscopy and colonoscopy did not reveal any evidence of a primary malignant neoplasm. Positron emission tomography showed no evidence of mediastinal lymphadenopathy or extrathoracic disease. Given the patient’s excellent performance status, he underwent a mediastinoscopy with left lower lobe lobectomy. Results of postoperative pathologic testing showed a 13-cm adenocarcinoma with similar immunohistochemical markers as in the prior biopsy specimen. Surgical margins were negative for involvement, with no large vessel or perineural invasion seen. Five sampled lymph nodes were negative for involvement. Repeat pathologic interpretation was performed (Figure).Initial pathologic testing of a left lower lobe biopsy specimen (hematoxylin-eosin stain, original magnification ×100). What Is Your Diagnosis?

Metastatic colorectal cancer

Pulmonary enteric adenocarcinoma (PEA)

Adenocarcinoma of unknown primary

Lymphoma

B. Pulmonary enteric adenocarcinoma (PEA)

B

Pulmonary enteric adenocarcinoma (PEA)

This pathologic specimen revealed an adenocarcinoma with immunohistochemical staining identical to that of colorectal adenocarcinoma. Positron emission tomography and upper and lower endoscopy did not reveal any evidence of colorectal malignant neoplasm or pathologic lymphadenopathy. Thus, the diagnosis of PEA was made.Pulmonary enteric adenocarcinoma is a histopathologic diagnosis defined as a primary non–small cell lung adenocarcinoma (NSCLC) with intestinal differentiation. Patients present with pulmonary-predominant lesions without evidence of gastrointestinal malignant neoplasm at workup.1,2 There are approximately 50 cases of PEA described in the literature that immunohistochemically compared PEA, NSCLC, and metastatic colorectal cancer.1,3 Pulmonary enteric adenocarcinoma shares the same immunohistochemical markers used to distinguish metastatic colorectal cancer and NSCLC, including CDX2 and CK20, which are characteristic of metastatic colorectal cancer.3,4Management can pose a dilemma for the oncologist in deciding to treat PEA as a gastrointestinal tract or lung primary malignant neoplasm, because their treatments and prognoses differ. Although the presentation of PEA is well described, few reports describe treatment response. One case report showed a partial response and progression-free survival of 4 months with adjuvant docetaxel and cisplatin therapy.5 Despite the histologic similarity of PEA to metastatic colorectal cancer, PEA may not respond well to typical colorectal chemotherapy regimens such as fluorouracil plus oxaliplatin or gemcitabine.5To reduce the risk of recurrence, the patient was treated with adjuvant docetaxel and cisplatin for 4 cycles, which was well tolerated. Six months later, he developed a new 3.9 × 3.2-cm left adrenal gland mass and nodules in the right middle lobe (0.9 × 0.7 cm) and right lower lobe (1.5 × 1.4 cm). The patient remained asymptomatic at that time. Examination of biopsy specimens of the adrenal mass showed similar morphologic characteristics and immunohistochemical profile as the prior left lower lobe malignancy.Given the progression of the patient’s condition after adjuvant chemotherapy, nivolumab, an immune checkpoint inhibitor that is approved by the US Food and Drug Administration as second-line treatment for metastatic NSCLC irrespective of PD-1 staining percentage, was initiated. Stereotactic body radiotherapy was also initiated for the left adrenal mass. There is evidence that radiotherapy-associated tumor injury releases antigens that lead to a more aggressive immune response when using immune checkpoint inhibitors.6 Results of subsequent imaging 3 months later demonstrated a greater than 50% reduction in the right middle lobe and right lower lobe nodules. The patient’s adrenal mass had decreased significantly to 1.4 × 1.0 cm. Since initiation of nivolumab, the patient has demonstrated greater than 14 months of durable response.Pulmonary enteric adenocarcinoma represents a unique manifestation of treatment-refractory NSCLC that has had a remarkable durable response with immune checkpoint inhibition. For metastatic NSCLC in particular, PD-1 and PD-L1 inhibitors have become a center point of discussion. In approximately 20% of patients, these responses can last more than 12 months, as was noted in this patient.7 However, the strength of PD-1 and PD-L1 staining correlation does not adequately estimate response. In fact, up to 19% of individuals with negative PD-1 and PD-L1 staining respond to nivolumab.7,8 The current literature suggests that that the tumor microenvironment and mutational burden are important and may explain the efficacy of treatment in the patient. Biopsy specimens demonstrating high inflammatory white cell infiltration 1 to 2 months after nivolumab therapy have been shown to be associated with excellent response.9 Mutational burden and microsatellite instability may also explain immune response.9,10 Next-generation sequencing genomic testing performed on the PEA biopsy specimen did not show microsatellite instability, although results were remarkable for intermediate mutational burden with 8 significant mutations including TP53 (OMIM 191170) and CCND1 (OMIM 168461).This patient with PEA represents a unique NSCLC phenotype that continues to have durable response of greater than 14 months with nivolumab therapy despite a low PD-1 expression. We suggest that immunotherapy may have a significant efficacious role in the treatment of PEA owing to its mutational burden.

Oncology

A man in his 60s presented with a 1-year history of a mild, dry cough. He was otherwise asymptomatic and had no physical limitations. He had never smoked, and results of his physical examination were normal. Results of complete blood cell counts, basic metabolic panel, and liver function tests were all within normal limits. A chest radiograph revealed a 10 × 9-cm lobulated left lower lobe mass. Examination of a biopsy specimen showed a primary adenocarcinoma with an immunohistochemical profile of CDX2 positive, CK20 positive, TTF-1 negative, and napsin A negative. His EGFR (OMIM 131550), ALK (OMIM 105590), and ROS1 (OMIM 165020) genes were wild type, and results of testing for programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) were 0%. Results of upper gastrointestinal tract endoscopy and colonoscopy did not reveal any evidence of a primary malignant neoplasm. Positron emission tomography showed no evidence of mediastinal lymphadenopathy or extrathoracic disease. Given the patient’s excellent performance status, he underwent a mediastinoscopy with left lower lobe lobectomy. Results of postoperative pathologic testing showed a 13-cm adenocarcinoma with similar immunohistochemical markers as in the prior biopsy specimen. Surgical margins were negative for involvement, with no large vessel or perineural invasion seen. Five sampled lymph nodes were negative for involvement. Repeat pathologic interpretation was performed (Figure).Initial pathologic testing of a left lower lobe biopsy specimen (hematoxylin-eosin stain, original magnification ×100).

what is your diagnosis?

What is your diagnosis?

Adenocarcinoma of unknown primary

Pulmonary enteric adenocarcinoma (PEA)

Lymphoma

Metastatic colorectal cancer

b

male

0-10

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2672568

A 92-year-old woman with a history of long-term bronchiectasis and atrial flutter presented after a fall. She experienced severe pain over the left hip. Radiography of the hip showed a femoral neck fracture, and she was scheduled for emergent hip arthroplasty. She denied any head trauma or loss of consciousness but described occasional palpitations. Her medications included 125 mcg digoxin daily and 2.5 mg apixaban twice daily.On presentation, she was afebrile. Her blood pressure was 168/96 mm Hg, her heart rate was 88 beats per minute, and her respiratory rate was 18 breaths per minute. Physical examination showed no gross physical deformity. The trachea was midline and the neck was supple, without any engorged veins. Lung sounds were clear to auscultation bilaterally. Precordial palpation revealed a nonpalpable apex beat. Heart sounds were appreciated loudest over the right parasternal area. S1 and S2 were normal. No S3, murmur, rub, or gallop were present. A soft S4 was heard. The 12-lead electrocardiogram showed marked right axis deviation with poor R wave progression across the precordial leads V1-V6 (Figure 1).Standard 12-lead electrocardiogram shows upright R wave in avR and R wave regression across the precordial leads. What Would You Do Next?

Obtain high-sensitivity troponin I level

Obtain D-dimer level

Obtain electrocardiogram with right-sided precordial leads

Obtain ventilation/perfusion lung scan

Mirror-image dextrocardia

C

Obtain electrocardiogram with right-sided precordial leads

The patient’s electrocardiogram (ECG) findings were consistent with a rare condition called mirror-image dextrocardia. In this condition, the right and left orientation of the heart are interchanged; however, the anterior-posterior relationships of all anatomical aspects of the heart remain normal. In such patients, the ECG can be easily mistaken for limb lead reversal.The ECG characteristically shows marked right axis deviation of the P wave. Because the predominant vector of cardiac depolarization is directed toward the right, the QRS complex also shows right axis deviation. Inverted P and T waves are seen in lead I, along with a negatively oriented QRS complex. Because of a reversal of QRS complexes in leads avL and avR, the R wave in avR is upright. A 12-lead ECG typically shows an absence of precordial R wave progression. The R wave amplitude is remarkably low in lateral chest leads V4, V5, and V6. The R wave regression in precordial leads is particularly important to differentiate right and left limb lead reversal from true mirror-image dextrocardia. In the former, R wave progression from V1 to V6 remains intact.A right-sided ECG involves reverse placement of chest and limb leads. This gives the most accurate assessment of the heart’s electrical activity in mirror-image dextrocardia. A good R wave progression pattern on right-sided precordial leads confirms the diagnosis (Figure 2A).A, Right-sided electrocardiogram with reversed chest leads still shows an upright R wave in avR but a good R wave progression across the precordial leads. B, Chest radiography confirms dextrocardia.Chest radiography showed a rightward-directed cardiac apex and a cardiac silhouette in the right hemithorax. If situs inversus is present, a right-sided gastric bubble may be seen (Figure 2B). This confirms the ECG findings of mirror-image dextrocardia. This is the most common form of mirror-image dextrocardia, also termed situs inversus with dextrocardia or situs inversus totalis. The first published case of cardiac malposition was described by Baille in the 18th century.1Dextrocardia associated with situs inversus has a prevalence of 0.01%.2 It is clinically important to distinguish it from limb lead reversal to correctly diagnose more serious pathologies, such as anterior wall myocardial infarction. It can be associated with bronchiectasis and primary ciliary dyskinesia (likely in this patient). This form of dextrocardia has not been linked to increased risk of congenital heart disease.3 In contrast, dextrocardia with situs solitus (or dextroversion), which involves embryological ventricular rotation to the right, is associated with serious congenital heart diseases in up to 90% of cases (often with congenitally corrected transposition of the great arteries), with a high incidence of ventricular septal defect.4 Thus, differentiating the 2 forms of dextrocardia is clinically important. A 12-lead ECG with both chest and limb leads reversed along with radiography of the chest can reliably diagnose dextrocardia with situs inversus.5This patient underwent successful arthroplasty for the fracture. Her hospital course was uneventful.

Cardiology

A 92-year-old woman with a history of long-term bronchiectasis and atrial flutter presented after a fall. She experienced severe pain over the left hip. Radiography of the hip showed a femoral neck fracture, and she was scheduled for emergent hip arthroplasty. She denied any head trauma or loss of consciousness but described occasional palpitations. Her medications included 125 mcg digoxin daily and 2.5 mg apixaban twice daily.On presentation, she was afebrile. Her blood pressure was 168/96 mm Hg, her heart rate was 88 beats per minute, and her respiratory rate was 18 breaths per minute. Physical examination showed no gross physical deformity. The trachea was midline and the neck was supple, without any engorged veins. Lung sounds were clear to auscultation bilaterally. Precordial palpation revealed a nonpalpable apex beat. Heart sounds were appreciated loudest over the right parasternal area. S1 and S2 were normal. No S3, murmur, rub, or gallop were present. A soft S4 was heard. The 12-lead electrocardiogram showed marked right axis deviation with poor R wave progression across the precordial leads V1-V6 (Figure 1).Standard 12-lead electrocardiogram shows upright R wave in avR and R wave regression across the precordial leads.

what would you do next?

What would you do next?

Obtain electrocardiogram with right-sided precordial leads

Obtain high-sensitivity troponin I level

Obtain D-dimer level

Obtain ventilation/perfusion lung scan

a

female

91-100

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2675081

A woman in her 60s presented with a 3-month history of right-sided sinus pressure progressing to dental pain. She was prescribed antibiotics and steroids by her family physician, which initially provided intermittent, symptomatic improvement; however, she ultimately experienced a progressive decrease in tactile sensation on her face, anosmia, and changes in her right peripheral vision. She had a remote 2 pack-year smoking history. Sinus computed tomography (CT) and neck magnetic resonance imaging (MRI) revealed a large expansile mass arising from the right side of the skull base and nasopharynx with extension into the pterygopalatine fossa, masticator, parapharyngeal, retropharyngeal, and carotid spaces. In addition, imaging showed involvement of the right posterior orbit with erosion of the posterior maxillary sinus wall, anterior and middle cranial fossa with erosion through the cribriform plate, and cavernous sinus. Physical examination revealed slight right-sided facial fullness, grossly intact extraocular motion, decreased vision in the right lateral field, and palpable bilateral level 2 neck lymph nodes. Flexible laryngoscopy revealed a right-sided lobulated mass involving the medial middle turbinate, posterior septum, and nasal floor, as well as the posterior aspect of the maxillary sinus extending superiorly to the nasopharynx and skull base posteriorly. The mass extended into the left superior nasopharynx and superior septum. In-office biopsy specimens were obtained and revealed a primitive small round cell tumor with the following immunohistochemical (IHC) staining profile: diffusely positive for desmin, myogenin, and CD56; focally positive for low-molecular-weight kininogen (LMWCK), p63, and S-100; and negative for AE1/AE3, CK 5/6, CK7, CK20, p40, chromogranin, SOX10, HMB45, CD99, and CD20 (Figure 1).Histopathologic images. A, Nests of primitive small round blue cells surrounded by fibrovascular septa. Hematoxylin-eosin. B, Diffuse, nuclear positivity. Myogenin stain. What Is Your Diagnosis?

Esthesioneuroblastoma

Ewing sarcoma

Alveolar rhabdomyosarcoma

Non-Hodgkin lymphoma

C. Alveolar rhabdomyosarcoma

C

Alveolar rhabdomyosarcoma

These histologic and IHC findings are consistent with the alveolar subtype of rhabdomyosarcoma (RMS). Although it is the most common soft-tissue sarcoma in children, RMS represents only 2% to 5% of adult soft-tissue tumors.1 RMS is divided into 3 main histologic subtypes: embryonal, alveolar, and pleomorphic.1 The embryonal subtype is more common in children and frequently occurs in the genitourinary tract and the head and neck region. The alveolar and pleomorphic subtypes are more common in adults and often occur in the extremities, as well as in the head and neck region.2 Although alveolar RMS is more commonly seen in adults, this diagnosis is often unexpected in the older age group.3Histologically, alveolar RMS is characterized by small round cells arranged in clusters lined by fibrovascular septa with scattered rhabdomyoblasts. On IHC, alveolar RMS shows diffuse positivity for markers of muscular differentiation, including desmin, myogenin, and MyoD1; however, a number of other markers typically associated with neuroendocrine, squamous, and neural crest differentiation can also be positive and lead to a misdiagnosis. In this patient, focal positivity for LMWCK and diffuse positivity for CD56 could have easily have led to a completely different differential diagnosis that included neuroendocrine neoplasms and small cell carcinoma. However, acknowledging that CD56 is diffusely positive in nearly all alveolar RMSs and other neuroendocrine markers, such as chromogranin and synaptophysin, can be positive in up to a third of cases should prevent this pitfall.3,4 Furthermore, staining for p63 was focally positive but negative for p40. Staining for p63 is often used in the workup to rule out a poorly differentiated squamous cell carcinoma; however, p63 positivity is seen in about half of cases of alveolar RMS and lymphomas of the sinonasal tract and can be observed in a small subset of Ewing sarcomas and esthesioneuroblastomas.5 In these cases, though, p40 is a much more specific marker of squamous differentiation and staining is negative in all of the aforementioned diagnoses.5 Finally, S100 was focally positive and can be observed in many neoplasms, including those of neural crest differentiation, such as melanoma or schwannoma. Staining for S100, however, has been reported to be positive in about a quarter of cases of alveolar RMSs.3In summary, the lack of CD99, SOX10, and HMB45, and CD20 in the case described herein provided additional evidence to rule out Ewing sarcoma, melanoma, and a B-cell lymphoma, respectively. Although not required in this case, cytogenetic studies can aid in the diagnosis of alveolar RMS, which is characterized by the translocations t(2;13)(q35;q14) and t(1;13)(p36;q14) and their associated fusion transcripts PAX3-FOXO1 and PAX7-FOXO1.6Rhabdomyosarcoma prognosis varies by age, histologic subtype, and extent at presentation. Treatment for RMS involves chemotherapy, surgical resection when feasible, and radiation.7 In adults, RMS carries a worse prognosis, with survival rates ranging from 20% to 40%.8 However, it is unclear whether this difference may be related to the difference in prevalent histologic subtypes, more advanced disease at presentation, or inadequate treatment in adults. Alveolar RMS carries a worse prognosis than embryonal RMS, with higher rates of nodal metastases.9This patient’s imaging revealed extensive disease (Figure 2) and hypermetabolic foci in cervical, hilar, and periaortic lymph nodes, right rectus, and humerus. She was treated with chemoradiation therapy. She is currently 8 months from treatment with no evidence of disease. This case highlights the importance of including RMS in the differential diagnosis for sinonasal tumors, enabling early diagnosis and aggressive multimodality treatment in adults as well as children.Head and neck magnetic resonance imaging on presentation. A, Coronal view. B, Axial view.

General

A woman in her 60s presented with a 3-month history of right-sided sinus pressure progressing to dental pain. She was prescribed antibiotics and steroids by her family physician, which initially provided intermittent, symptomatic improvement; however, she ultimately experienced a progressive decrease in tactile sensation on her face, anosmia, and changes in her right peripheral vision. She had a remote 2 pack-year smoking history. Sinus computed tomography (CT) and neck magnetic resonance imaging (MRI) revealed a large expansile mass arising from the right side of the skull base and nasopharynx with extension into the pterygopalatine fossa, masticator, parapharyngeal, retropharyngeal, and carotid spaces. In addition, imaging showed involvement of the right posterior orbit with erosion of the posterior maxillary sinus wall, anterior and middle cranial fossa with erosion through the cribriform plate, and cavernous sinus. Physical examination revealed slight right-sided facial fullness, grossly intact extraocular motion, decreased vision in the right lateral field, and palpable bilateral level 2 neck lymph nodes. Flexible laryngoscopy revealed a right-sided lobulated mass involving the medial middle turbinate, posterior septum, and nasal floor, as well as the posterior aspect of the maxillary sinus extending superiorly to the nasopharynx and skull base posteriorly. The mass extended into the left superior nasopharynx and superior septum. In-office biopsy specimens were obtained and revealed a primitive small round cell tumor with the following immunohistochemical (IHC) staining profile: diffusely positive for desmin, myogenin, and CD56; focally positive for low-molecular-weight kininogen (LMWCK), p63, and S-100; and negative for AE1/AE3, CK 5/6, CK7, CK20, p40, chromogranin, SOX10, HMB45, CD99, and CD20 (Figure 1).Histopathologic images. A, Nests of primitive small round blue cells surrounded by fibrovascular septa. Hematoxylin-eosin. B, Diffuse, nuclear positivity. Myogenin stain.

what is your diagnosis?

What is your diagnosis?

Non-Hodgkin lymphoma

Alveolar rhabdomyosarcoma

Esthesioneuroblastoma

Ewing sarcoma

b

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2676012

A man in his 60s with a history of chronic obstructive pulmonary disease (COPD) and dyspnea presented with right lower quadrant abdominal pain. A noncontrast computed tomographic (CT) scan of the abdomen demonstrated splenomegaly, ascites, and a retroperitoneal mass posterior to the pancreatic head. Fine-needle aspiration from the retroperitoneal mass and ascitic fluid revealed no malignant cells. The patient subsequently developed a left-sided lateral chest wall hematoma, and, in retrospect, it was thought that the retroperitoneal mass was actually a hematoma because multiple follow-up studies demonstrated the mass steadily decreasing in size. Echocardiography showed right atrial and ventricular dilatation and increased thickness of the interventricular septum. Laboratory tests showed elevated results for serum-free λ light chain and proteinuria levels and altered liver function tests but a normal coagulation profile. Routine surveillance noncontrast CT imaging of the neck demonstrated a submucosal soft-tissue mass containing few punctate calcifications centered in the epiglottis with clinically significant narrowing of the oropharyngeal and supraglottic laryngeal airways by the enlarged epiglottis (Figure).Computed tomographic images show a soft-tissue mass containing punctate calcifications centered on the epiglottis. What Is Your Diagnosis?

Squamous cell carcinoma

Lymphoma

Amyloidosis

Rhabdomyosarcoma

C. Amyloidosis

C

Amyloidosis

A bone marrow biopsy specimen showed 5% λ-restricted plasma cells and amyloid deposition. The patient was started on a chemotherapeutic regimen of cyclophosphamide, bortezomib, and dexamethaxone followed by autologous stem cell transplant.Immunoglobulin light chain (AL) amyloidosis of the larynx is an uncommon diagnosis involving the deposition of insoluble amyloid fibrils in normal tissues of the larynx.1-3 The exact cause of AL amyloidosis has yet to be clarified, but the condition can be fatal if the depositions are large enough to obstruct respiratory tracts to the extent that breathing mechanics are interrupted.3,4 Amyloid deposits in tissue can be confirmed using microscopic staining techniques. The deposits take up Congo red stain and display apple green birefringence when exposed to polarized light.4 The major mechanism of bleeding in AL amyloidosis is due to amyloid deposit infiltration of the vasculature, which causes angiopathy, frailty, impaired vasoconstriction, and tears with hemorrhage. AL amyloidosis can also affect the heart, kidneys, skin, nerves, and liver. Other types of amyloidosis include AA amyloidosis, which occurs with chronic infectious or inflammatory diseases and mostly affects the kidneys, hereditary amyloidosis, and dialysis-related amyloidosis.Amyloidosis occurs twice as frequently in the larynx as other parts of the head and neck, forming tumorlike deposits and diffuse infiltration. Locations for deposits have been reported most commonly in the epiglottis, the ventricles, and vocal cords.5 Computed tomographic imaging demonstrates amyloid as a homogenous soft-tissue mass containing occasional punctate calcifications.5,6 Magnetic resonance imaging demonstrates lesions with intensity equal to surrounding muscles on T1 and slightly hyperintense on T2 weighted images. In a case series of 4 patients with localized amyloidosis in the head and neck regions, Gean-Marton et al6 reported a unique appearance in T2-weighted images, which they attributed to the change in the magnetic fields caused by the density of the beta sheets.Interestingly, this patient had few symptoms consistent with such a diagnosis. Commonly reported presenting symptoms of laryngeal AL amyloidosis are hoarseness and dysphagia,7 but dyspnea, pain, hemoptysis, and dysphonia have also been reported.1,2 At the time of diagnosis, this patient reported chronic nasal stuffiness and some dyspnea (likely from his COPD), but his oropharynx remained clear on visual examination. Given the possibility of fatality from airway obstruction specific to laryngeal amyloidosis, it is important to identify this diagnosis early. This patient was not experiencing any distress as a result of the amyloid deposits in this region; hence, removal of the deposits was not discussed with him. Surgical removal of amyloid masses in this area remains a common treatment, although other approaches involving radiotherapy are being explored.3,7This case provides a unique demonstration of the systemic effects of amyloidosis and the subsequent complications as a result of deposition in other tissues. The complications that occurred as a result of amyloid deposition, including the bleeding and cardiac abnormalities, highlight the seriousness of this diagnosis. Annual or biennial surveillance of patients with amyloidosis with iodine I 23-labeled serum amyloid P component scintigraphy is recommended to pick up visceral deposits. Even though this patient presented with few symptoms consistent with laryngeal deposits, he did have evidence of amyloid in the neck region, which has the potential for negative outcomes, highlighting the need for surveillance imaging to ensure early diagnosis.

General

A man in his 60s with a history of chronic obstructive pulmonary disease (COPD) and dyspnea presented with right lower quadrant abdominal pain. A noncontrast computed tomographic (CT) scan of the abdomen demonstrated splenomegaly, ascites, and a retroperitoneal mass posterior to the pancreatic head. Fine-needle aspiration from the retroperitoneal mass and ascitic fluid revealed no malignant cells. The patient subsequently developed a left-sided lateral chest wall hematoma, and, in retrospect, it was thought that the retroperitoneal mass was actually a hematoma because multiple follow-up studies demonstrated the mass steadily decreasing in size. Echocardiography showed right atrial and ventricular dilatation and increased thickness of the interventricular septum. Laboratory tests showed elevated results for serum-free λ light chain and proteinuria levels and altered liver function tests but a normal coagulation profile. Routine surveillance noncontrast CT imaging of the neck demonstrated a submucosal soft-tissue mass containing few punctate calcifications centered in the epiglottis with clinically significant narrowing of the oropharyngeal and supraglottic laryngeal airways by the enlarged epiglottis (Figure).Computed tomographic images show a soft-tissue mass containing punctate calcifications centered on the epiglottis.

what is your diagnosis?

What is your diagnosis?

Lymphoma

Squamous cell carcinoma

Rhabdomyosarcoma

Amyloidosis

d

male

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2676586

A woman in her 40s presented with right pulsatile tinnitus. She reported constant pulsatile tinnitus with a whooshing quality for 4 years. Factors exacerbating her symptoms included holding her breath and turning her head to the left. She reported that compression of her right neck and turning her head to the right decreased the loudness of the tinnitus. She had not experienced hypertension, vertigo, sleep apnea, hyperthyroidism, hearing loss, head trauma, history of ear infections, otorrhea, rhinorrhea, ear surgery, or family history of ear problems. The external auditory canals were clear bilaterally. Tympanic membranes were intact and mobile bilaterally. There was no evidence of any vascular masses in the middle ear space. Results from testing with tuning forks were normal. Toynbee stethoscope revealed a bruit in the right ear that could be stopped with gentle compression of the right side of the neck. An audiogram showed hearing within normal limits with slight air-bone gaps present at 250, 1000, and 3000 Hz on the right and within normal limits on the left. Speech reception threshold on the right was 10 dB with a word recognition score of 100% bilaterally. The tympanogram result revealed type A bilaterally, and acoustic reflexes were all present. A computed tomographic (CT) temporal bone scan was completed (Figure 1).Computed tomographic images of the right temporal bone. The arrowheads indicate the findings. What Is Your Diagnosis?

Carotid cochlear dehiscence

Semicircular canal dehiscence

Sigmoid sinus diverticulum

Aberrant internal carotid artery

C. Sigmoid sinus diverticulum

C

Sigmoid sinus diverticulum

Sigmoid sinus diverticulum (SSD) was demonstrated on imaging and was the cause of the patient’s pulsatile tinnitus. Two distinctive diverticula were demonstrated on high-resolution CT temporal bone scan: anterior (Figure 1, A) and superior (Figure 1, B). The other diagnoses listed in the quiz are not correct because gentle neck pressure would not resolve the tinnitus in these conditions. These other diagnoses were also ruled out given the lack CT imaging evidence and classic clinical signs and symptoms expressed by the patient.Sigmoid sinus diverticulum was first reported as a cause of pulsatile tinnitus and successfully treated with endovascular coiling in 2000 by Houdart et al.1 Tinnitus is the perception of sound or noise without external source. It can be divided into 2 categories: pulsatile and nonpulsatile. Pulsatile tinnitus has a distinct differential diagnosis, which includes the following: persistent stapedial artery, aberrant internal carotid artery, carotid cochlear dehiscence, intracranial and/or dural arteriovenous fistula, intracranial vascular stenosis, idiopathic intracranial hypertension, jugular diverticulum, and superior semicircular canal dehisence.2-4Studies have shown that approximately 12% to 14% of the US population endures chronic or persistent tinnitus.5 Pulsatile tinnitus occurs in only 4% of tinnitus cases.6 It has been suggested that SSD causes turbulent flow of blood within the abnormal venous structures and transmits this sound to the inner ear when flowing in a nonlaminar pattern. Although SSD was once thought to be rare, newer evidence has shown that it may be more common than thought. Schoeff et al7 studied the imaging prevalence of SSD in CT scans of temporal bones of patients with and without tinnitus. They found SSD in 2 of 164 asymptomatic patients (0.6%) and 7 of 30 symptomatic patients (23%).7 A study of 43 patients with pulsatile tinnitus showed that 22% had imaging results consistent with SSD.8 The etiology of SSD remains unknown. If the pulsatile tinnitus can be objectively heard in the ear or over the neck and/or skull, a vascular cause should be suspected and needs to be definitely identified. Several imaging modalities may be used to diagnose SSD; previous reports have used CT, CT angiogram, magnetic resonance imaging, or digital subtraction angiography to diagnose this condition.Sigmoid sinus diverticulum may be addressed in several ways, all with curative intent. In this case, SSD was surgically repaired with transmastoid approach, skeletonization of the diverticula (Figure 2), reduction, and reinforcement of the diverticula, as in other reports.9 There has been a report of SSD1 treated with retromastoid suboccipital craniectomy and clip application. One of the other treatment modalities is endovascular embolization of the diverticulum and stent placement. A recent systematic review of SSD repair showed that surgical repair is used more frequently than endovascular repair (in 91.4% vs 7.9% cases, respectively).10 In this series, 93 patients underwent surgical repair, with a 73% complete resolution, in comparison with 10 patients who underwent endovascular repair with 91% complete resolution. The resolution rate was not statistically significant between techniques.10 Regardless of technique, patients often report complete resolution of symptoms following these procedures, as was the case with this patient.Skeletonized anterior abnormality in transmastoid approach during repair marked with black arrowhead; unskeletonized abnormality marked with white arrowhead.In conclusion, the diagnosis of sigmoid sinus diverticulum should be considered when pulsatile tinnitus is a complaint. It is easily diagnosed with several imaging modalities and cured through several surgical and/or endovascular approaches.

General

A woman in her 40s presented with right pulsatile tinnitus. She reported constant pulsatile tinnitus with a whooshing quality for 4 years. Factors exacerbating her symptoms included holding her breath and turning her head to the left. She reported that compression of her right neck and turning her head to the right decreased the loudness of the tinnitus. She had not experienced hypertension, vertigo, sleep apnea, hyperthyroidism, hearing loss, head trauma, history of ear infections, otorrhea, rhinorrhea, ear surgery, or family history of ear problems. The external auditory canals were clear bilaterally. Tympanic membranes were intact and mobile bilaterally. There was no evidence of any vascular masses in the middle ear space. Results from testing with tuning forks were normal. Toynbee stethoscope revealed a bruit in the right ear that could be stopped with gentle compression of the right side of the neck. An audiogram showed hearing within normal limits with slight air-bone gaps present at 250, 1000, and 3000 Hz on the right and within normal limits on the left. Speech reception threshold on the right was 10 dB with a word recognition score of 100% bilaterally. The tympanogram result revealed type A bilaterally, and acoustic reflexes were all present. A computed tomographic (CT) temporal bone scan was completed (Figure 1).Computed tomographic images of the right temporal bone. The arrowheads indicate the findings.

what is your diagnosis?

What is your diagnosis?

Aberrant internal carotid artery

Carotid cochlear dehiscence

Semicircular canal dehiscence

Sigmoid sinus diverticulum

d

female

41-50

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2676587

A man in his 60s presented to a tertiary care center after several months of having right-sided lateral neck pain. He described the pain as “electric” and “stabbing.” He reported no numbness of the region and had not experienced any other symptoms, including new neck masses. His medical history was significant for obstructive sleep apnea, gastroesophageal reflux disease, a right ear skin cancer excised by a dermatologist, and coronary artery disease with angina on stress test. His physical examination revealed a well-healed excision site of the right ear without new skin lesions. His facial nerve was fully intact. He had full strength of the shoulder and no numbness of the right ear or cheek. Palpation of the lateral neck demonstrated a mass running along the lateral border of the sternocleidomastoid (SCM) muscle. Magnetic resonance imaging (MRI) showed an elongated enhancing tubular structure along the lateral surface of the right SCM muscle (Figure 1).A and B, Anterior to posterior coronal fat-saturated T1-weighted postcontrast magnetic resonance imaging (MRI) with an enhancing tubular mass of the right side of the neck (yellow arrowhead) that extends posterior and deep to sternocleidomastoid (SCM) (blue arrowheads). C, Axial T1-weighted postcontrast MRI with an enhancing tubular mass (blue arrowheads) that extends posterior and deep to the SCM (blue arrowheads) (white arrowhead indicates external jugular vein). What Is Your Diagnosis?

Primary nerve sheath tumor

Thrombophlebitis of external jugular vein

Traumatic neuroma from prior surgery

Perineural spread of cutaneous squamous cell carcinoma

D. Perineural spread of cutaneous squamous cell carcinoma

D

Perineural spread of cutaneous squamous cell carcinoma

Perineural spread (PNS) is a metastatic process in which cancer invades nearby nerve tissue and spreads along the nerve within the perineurium and endoneurium away from the primary tumor. This results in radiographic changes of the nerve as well as clinical signs and symptoms, including nerve dysfunction, pain, or mass. Spread of disease within nerves is usually quickly progressive owing to a relatively unimpeded path of invasion. PNS is distinct from incidental perineural invasion (PNI), which is the discovery of tumor invasion into nearby nerves during pathologic review.1-5 PNS has been linked to a worse overall prognosis and thus higher staging of tumors, with a 5-year overall survival rate ranging from 50% to 64%.5,6 Within the head and neck, PNS is commonly seen within the trigeminal nerve causing hypoesthesia, anesthesia, or pain and the facial nerve causing paresis or paralysis, hyperacusis, or taste dysfunction.1,5,7 It is associated with adenoid cystic carcinoma, basal cell carcinoma, squamous cell carcinoma (SCC), and melanoma.1,6The great auricular nerve (GAN) is a sensory nerve to the periauricular skin and superficial parotid gland that originates from the cervical plexus. It courses deep to the SCM in the inferior cervical neck, then passes posterior to the SCM at Erb’s point as it courses superiorly, becoming superficial to the SCM. At the superior aspect of the SCM, it has an anterior and posterior branch. It is not routinely seen on imaging except when pathologic abnormalities are present.8 On imaging for this patient, the GAN had enlargement and enhancement along its entire course, including the anterior and posterior branches superiorly on T1-weighted imaging (Figure 1, A and B). Primary nerve sheath tumors and traumatic neuromas have similar enhancement on T1-weighted imaging; however, their appearance is normally spindle or oval shaped, and they are bright on T2-weighted imaging.9 In addition, this patient had no scars in the area from prior surgery to cause a traumatic neuroma. The external jugular vein has a more medial position to the GAN and can be seen separate from the tubular mass making thrombophlebitis unlikely (Figure 1C, white arrowhead).The diagnosis of PNS of SCC in the GAN was confirmed in this patient with fine-needle biopsy performed in the clinic. Eight months prior to presentation, he had SCC of the right helical rim that was excised in a dermatology clinic. Final pathologic findings showed clear margins; however, there was no comment on PNI. He did not undergo any adjuvant treatment at that time. MRI showed extensive involvement of the GAN with nerve enhancement extending from the auricle and within the parotid gland down the lateral border of the SCM into the cervical plexus (Figure 1). He was taken to the operating room for a modified radical neck dissection (levels II-V), including excision of the external jugular vein and associated lymph nodes, superficial parotidectomy, and removal of the GAN extending from the dermal distributions of the pinna to the cervical plexus. Intraoperatively, the entire length of the GAN from the lobule to Erb’s point was grossly enlarged (Figure 2). Final pathologic tests revealed a SCC along the length of the GAN with extensive perineural and intraneural invasion. All resected lymph nodes were negative for disease. The patient recovered well from surgery. Owing to the extensive PNS, the patient was scheduled for adjuvant radiation therapy.Intraoperative image showing a grossly enlarged great auricular nerve (asterisks) along the lateral border of the right sternocleidomastoid (black arrowheads) extending to Erb’s point (blue arrowhead) (white arrowhead indicates external jugular vein).

General

A man in his 60s presented to a tertiary care center after several months of having right-sided lateral neck pain. He described the pain as “electric” and “stabbing.” He reported no numbness of the region and had not experienced any other symptoms, including new neck masses. His medical history was significant for obstructive sleep apnea, gastroesophageal reflux disease, a right ear skin cancer excised by a dermatologist, and coronary artery disease with angina on stress test. His physical examination revealed a well-healed excision site of the right ear without new skin lesions. His facial nerve was fully intact. He had full strength of the shoulder and no numbness of the right ear or cheek. Palpation of the lateral neck demonstrated a mass running along the lateral border of the sternocleidomastoid (SCM) muscle. Magnetic resonance imaging (MRI) showed an elongated enhancing tubular structure along the lateral surface of the right SCM muscle (Figure 1).A and B, Anterior to posterior coronal fat-saturated T1-weighted postcontrast magnetic resonance imaging (MRI) with an enhancing tubular mass of the right side of the neck (yellow arrowhead) that extends posterior and deep to sternocleidomastoid (SCM) (blue arrowheads). C, Axial T1-weighted postcontrast MRI with an enhancing tubular mass (blue arrowheads) that extends posterior and deep to the SCM (blue arrowheads) (white arrowhead indicates external jugular vein).

what is your diagnosis?

What is your diagnosis?

Perineural spread of cutaneous squamous cell carcinoma

Traumatic neuroma from prior surgery

Thrombophlebitis of external jugular vein

Primary nerve sheath tumor

a

male

61-70

White

original

https://jamanetwork.com/journals/jama/fullarticle/2677996

A 58-year-old overweight African American man presented with a 5-year history of a slightly pruritic and painful rash of the right lateral area of the neck and right axilla. It was worse during the summers, and blisters sometimes developed. Emollients were unhelpful. The patient was otherwise healthy. His sister had diabetes mellitus and a similar rash in her axillae. The patient performed indoor manual labor as a maintenance engineer and had no significant sun exposure. Physical examination revealed irregularly thickened skin of the right axilla (Figure 1, left) and right lateral area of the neck (Figure 1, right) containing hyperpigmentation, hypopigmentation, multiple acrochordons (skin tags), malodorous crust, and areas of maceration and erosion. Further examination of the skin revealed pseudofolliculitis barbae in the submental and mandibular regions bilaterally. The nails, oral cavity, and mucosal membranes appeared normal. A biopsy of right axillary skin was performed (Figure 2).Left, Rash of right axilla. Right, Rash of right lateral area of the neck with global view and close-up view (inset).Epidermal acantholysis causing separation of keratinocytes into dilapidated brick wall appearance (hematoxylin-eosin, original magnification ×10).Prescribe a topical corticosteroid and a topical antimicrobial What Would You Do Next?

Prescribe topical ketoconazole

Obtain glycated hemoglobin (HbA1C) level

Prescribe a topical corticosteroid and a topical antimicrobial

Consult for surgical excision

Hailey-Hailey disease (benign familial pemphigus)

C

Prescribe a topical corticosteroid and a topical antimicrobial

The key to the correct diagnosis is the presence of an intertriginous rash with report of blistering, summertime exacerbation, and family history of a similar rash. First-line treatment for Hailey-Hailey disease is topical and should include a topical corticosteroid with or without a topical antimicrobial.1,2 Hailey-Hailey disease can have an appearance similar to that of acanthosis nigricans in dark-skinned patients, but acanthosis nigricans is typically asymptomatic and unlikely to vary with season. A crusted rash with seasonal variation could suggest seborrheic dermatitis or candidal intertrigo, which can be treated with ketoconazole. Seborrheic dermatitis, however, usually involves the face or scalp and worsens during winter. Lack of satellite lesions makes candidal intertrigo unlikely.Hailey-Hailey disease is a rare autosomal dominant acantholytic disease with variable penetrance.3,4 The disease was first described in 1939 by brothers William and Hugh Hailey, who were both afflicted with the condition.3 Hailey-Hailey disease is often misdiagnosed and is part of a broad differential diagnosis that includes common diseases such as intertrigo, inverse psoriasis, seborrheic dermatitis, erythrasma, and acanthosis nigricans, as well as rare diseases such as Darier disease, Galli-Galli disease, and autoimmune pemphigus variants.3-5 Accurate diagnosis and proper treatment are essential, because Hailey-Hailey disease profoundly affects quality of life4 and increases risk of bacterial infection, fungal infection, and squamous cell carcinoma.2 The disease is caused by a mutation in the ATP2C1 gene, which encodes a Ca+2/Mn+2 ATPase, hSPCA1, in the Golgi apparatus.1,3,6 hSPCA1 is present throughout the body and is critical to keratinocyte function.3 Malfunction of hSPCA1 dysregulates calcium metabolism, which impairs keratinocyte intercellular adherence and results in acantholysis, which consists of epidermal cell separation.1,6,7Hailey-Hailey disease presents as a chronic painful and pruritic rash in flexural and intertriginous areas, with intermittent development of blisters. Erosions and a malodorous crust may result after blisters drain.1,3,4,6 The appearance of the rash is dependent on blister stage and can vary widely, which can alter the differential diagnosis. The disease typically has no mucous membrane involvement,8 but fingernails may develop longitudinal white bands.1,6 Heat, sweat, friction, and tight clothing often cause symptoms to worsen and the disease to progress, making summertime exacerbations common.1,6 The disease is often complicated by superimposed bacterial or fungal infections, which can potentiate acantholysis.1 Rarely, fatal eczema herpeticum can also occur if Hailey-Hailey disease becomes infected with herpes simplex virus. Clinicians should consider herpes simplex testing in patients with Hailey-Hailey disease and signs of systemic infection, vesiculopustular eruptions in the rash, or significant rash tenderness.9Diagnosis of Hailey-Hailey disease is made clinically and can be confirmed histologically.4 Histopathologic examination reveals acantholysis, which separates keratinocyte layers into a classic dilapidated brick wall appearance (Figure 2).4 An overlying neutrophilic crust is common.1 Dyskeratosis, or premature epithelial keratinization, is usually mild, as opposed to Darier disease, in which dyskeratosis predominates over acantholysis.8 The dermis may be normal or have mild lymphocytic perivascular inflammatory infiltrate.7 If there is clinical concern for autoimmune pemphigus, immunofluorescence can be performed.7First-line treatment options for Hailey-Hailey disease include topical corticosteroids to reduce inflammation and topical antimicrobials to treat infection.1,2 The disease occurs in intertriginous areas, which are particularly susceptible to topical corticosteroid–induced adverse effects such as skin atrophy, striae, telangiectasias, purpura, and hypertrichosis. Use of topical corticosteroids should therefore be limited to acute exacerbations, while topical calcineurin inhibitors such as tacrolimus or pimecrolimus can be used for long-term inflammation control.2 Topical antimicrobials should be used in combination with topical corticosteroids if the rash exhibits signs of infection such as a malodorous crust or if microbial colonization is seen on histologic examination. Antimicrobial selection can include antibiotics, antifungals, or both.1,2 Common options include topical clindamycin, mupirocin, gentamicin, and ketoconazole.1,2 Lifestyle modifications such as loose-fitting clothes, weight loss, periodic chlorohexidine gluconate baths, and avoidance of humidity are also helpful.2-4 Hailey-Hailey disease is often refractory to first-line treatments.4 Second-line treatments with the best supporting evidence are oral antibiotics, surgical excision with skin grafting, botulinum toxin injections, CO2 laser, and dermabrasion.2,4 Other options for refractory disease include intralesional corticosteroids, systemic antifungals, systemic corticosteroids, other systemic immunosuppressants, low-dose naltrexone, and oral retinoids.2,4,10Biopsy confirmed the diagnosis of Hailey-Hailey disease, and the patient was treated with topical clindamycin (1% lotion) and triamcinolone (0.1% cream). At 1-month follow-up, the patient was asymptomatic and the rash was nearly resolved. Postinflammatory hyperpigmentation remained.

General

A 58-year-old overweight African American man presented with a 5-year history of a slightly pruritic and painful rash of the right lateral area of the neck and right axilla. It was worse during the summers, and blisters sometimes developed. Emollients were unhelpful. The patient was otherwise healthy. His sister had diabetes mellitus and a similar rash in her axillae. The patient performed indoor manual labor as a maintenance engineer and had no significant sun exposure. Physical examination revealed irregularly thickened skin of the right axilla (Figure 1, left) and right lateral area of the neck (Figure 1, right) containing hyperpigmentation, hypopigmentation, multiple acrochordons (skin tags), malodorous crust, and areas of maceration and erosion. Further examination of the skin revealed pseudofolliculitis barbae in the submental and mandibular regions bilaterally. The nails, oral cavity, and mucosal membranes appeared normal. A biopsy of right axillary skin was performed (Figure 2).Left, Rash of right axilla. Right, Rash of right lateral area of the neck with global view and close-up view (inset).Epidermal acantholysis causing separation of keratinocytes into dilapidated brick wall appearance (hematoxylin-eosin, original magnification ×10).Prescribe a topical corticosteroid and a topical antimicrobial

what would you do next?

What would you do next?

Consult for surgical excision

Prescribe topical ketoconazole

Obtain glycated hemoglobin (HbA1C) level

Prescribe a topical corticosteroid and a topical antimicrobial

d

female

51-60

African American

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2672392

A neonate in her second week of life was brought to our hospital for evaluation of a scalp lesion initially thought to be an open abscess. She was born full term to a primigravid mother, who had an uncomplicated pregnancy. At parturition, the baby presented in occiput posterior position and remained partly crowned for more than 24 hours of maternal labor. Finally, due to failure to progress, the baby was delivered by urgent cesarean delivery. Birth weight was 3.13 kg (15th percentile), head circumference was 31 cm (<1 percentile), and Apgar score was 9 of 9. The baby’s head had a markedly elongate vertex, which the neonatal intensive care unit team diagnosed as cephalohematoma. On day 5 of life, her serum total bilirubin and conjugated bilirubin were 20.5 mg/dL (>95 percentile) and 0.3 mg/dL (to convert to micromoles per liter, multiply by 17.104), respectively. The girl was hospitalized for 1 day of phototherapy before being discharged home weighing 2.95 kg (−5.75%). She was exclusively breastfed.She was admitted to our hospital for evaluation of the scalp. Wound culture samples were sent for analysis, and she was given empirical intravenous clindamycin hydrochloride. Dermatology was consulted. On examination, the baby was alert and healthy appearing, although her sclerae were icteric. The vertex of her scalp was uniformly boggy, soft, and edematous, extending beyond suture lines, consistent with a diagnosis of caput succedaneum. On the right occiput, there was a mat of hair and thick serosanguineous crust adhering to the scalp (Figure 1A). Beneath the mat and extending laterally in both directions was a deep, 8 × 1-cm, trenchlike ulcer with no drainage (Figure 1B). It was nontender to palpation.A, Serosanguineous crust adhering to occipital scalp of a neonate. Prior to removing this crust it was being treated as an open ulcer. B, Trenchlike linear ulcer revealed after removal of the crust. It was 8 × 1 cm in size, was nontender to palpation, and did not appear to be infected.Cellulitis and abscess associated with neonatal group B streptococcal infection What Is Your Diagnosis?

Aplasia cutis congenita

Cellulitis and abscess associated with neonatal group B streptococcal infection

Epidermolysis bullosa

Halo scalp ring (pressure necrosis)

D. Halo scalp ring (pressure necrosis)

D

Halo scalp ring (pressure necrosis)

The baby had a halo scalp ring (HSR), which is caused by prolonged near-circumferential pressure of the primigravid cervix on the widest diameter of the head. Aplasia cutis congenita is characterized by noninflammatory, well-demarcated lesions with a predilection for the scalp, most commonly a shallow ulcer-like lesion at the vertex. Cellulitis and abscesses are often associated with fever, erythema, and warmth over sites of inflammation. Epidermolysis bullosa encompasses a group of disorders characterized by formation of fragile mechanobullous lesions at or adjacent to the dermal-epidermal junction. Epidermolysis bullosa does not produce deep dermal ulcers.Halo scalp ring is a benign, although often dramatic, cause of alopecia in the perinatal period. It occurs when there is prolonged pressure on the scalp, most often seen in babies of primigravid women, who experience failure to progress and prolonged labor. The tight cervical os forms a near-circumferential constricting band around the widest diameter of the head. This creates a caput succedaneum, a serosanguineous fluid collection between the scalp and periosteum due to a tourniquet-like effect of the cervix during labor. In caput succedaneum, the vertex of the baby’s scalp elongates as a result of marked edema that extends beyond the confines of suture lines.1,2Sequelae of caput succedaneum can include pressure necrosis from the cervical os leading to ringlike areas of tissue damage, also known as HSR.3 Not uncommonly, areas of pressure necrosis may become infected by normal skin flora, most notably staphylococcal and streptococcal species. In such cases, culture samples should be taken and antibiotic coverage provided. Routine wound care and dressing changes should be established, and the wound should be allowed to heal by secondary intention.1 Halo scalp ring generally resolves through reepithelialization and subsequent regrowth of hair if the follicles have not been destroyed. However, when the pressure is prolonged and sufficiently intense, the skin can undergo significant ischemia and necrosis, resulting in linear ulcers that may heal with scarring alopecia.4 It is important to note that HSR is not associated with cephalohematoma, which is characterized by subperiosteal hematoma formation that remains within the confines of the adjacent suture lines. In cephalohematoma, the insult is deep and does not damage the dermis, epidermis, or adnexal structures. This distinction is important because cephalohematoma is associated with numerous possible complications including skull fractures, subperiosteal calcification, infection, anemia due to blood extravasation, and severe hyperbilirubinemia proportional to the amount of extravascular blood. In contrast, caput succedaneum is a relatively benign condition and HSR is one of its few sequelae.2In our case, wound cultures had negative results and histopathologic examination of the eschar showed necrotic tissue with abscess formation (Figure 2). The dermatology service recommended cessation of antibiotic treatment and adoption of gentle debridement using cotton-tipped applicators moistened with normal saline. The plastic surgery service concurred with the plan to allow the lesions to heal by secondary intention. The baby’s hyperbilirubinemia and neonatal jaundice were presumably due to hemolysis of extravagated blood within the caput succedaneum.Histopathologic analysis of crust taken from occipital scalp of a neonate showing tissue necrosis and abscess formation (hematoxylin-eosin, original magnification ×10).On follow-up examination 5 weeks later, there was mild edema of the posterior occipital scalp consistent with resolving caput succedaneum. There was an overlying healing 3- to 4-cm linear, atrophic plaque with decreased hair density and the appearance of follicular dropout due to scarring.Halo scalp ring is likely a common condition that is underrecognized and overlooked. The observation of HSR and necrosis with the classic linear or curvilinear, partly circumferential ulceration should help distinguish this condition from others, such as aplasia cutis congenita, epidermolysis bullosa, or perinatal infections.

Dermatology

A neonate in her second week of life was brought to our hospital for evaluation of a scalp lesion initially thought to be an open abscess. She was born full term to a primigravid mother, who had an uncomplicated pregnancy. At parturition, the baby presented in occiput posterior position and remained partly crowned for more than 24 hours of maternal labor. Finally, due to failure to progress, the baby was delivered by urgent cesarean delivery. Birth weight was 3.13 kg (15th percentile), head circumference was 31 cm (<1 percentile), and Apgar score was 9 of 9. The baby’s head had a markedly elongate vertex, which the neonatal intensive care unit team diagnosed as cephalohematoma. On day 5 of life, her serum total bilirubin and conjugated bilirubin were 20.5 mg/dL (>95 percentile) and 0.3 mg/dL (to convert to micromoles per liter, multiply by 17.104), respectively. The girl was hospitalized for 1 day of phototherapy before being discharged home weighing 2.95 kg (−5.75%). She was exclusively breastfed.She was admitted to our hospital for evaluation of the scalp. Wound culture samples were sent for analysis, and she was given empirical intravenous clindamycin hydrochloride. Dermatology was consulted. On examination, the baby was alert and healthy appearing, although her sclerae were icteric. The vertex of her scalp was uniformly boggy, soft, and edematous, extending beyond suture lines, consistent with a diagnosis of caput succedaneum. On the right occiput, there was a mat of hair and thick serosanguineous crust adhering to the scalp (Figure 1A). Beneath the mat and extending laterally in both directions was a deep, 8 × 1-cm, trenchlike ulcer with no drainage (Figure 1B). It was nontender to palpation.A, Serosanguineous crust adhering to occipital scalp of a neonate. Prior to removing this crust it was being treated as an open ulcer. B, Trenchlike linear ulcer revealed after removal of the crust. It was 8 × 1 cm in size, was nontender to palpation, and did not appear to be infected.Cellulitis and abscess associated with neonatal group B streptococcal infection

what is your diagnosis?

What is your diagnosis?

Cellulitis and abscess associated with neonatal group B streptococcal infection

Aplasia cutis congenita

Halo scalp ring (pressure necrosis)

Epidermolysis bullosa

c

female

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2664341

A man in his 20s with panhypopituitarism, septo-optic dysplasia, developmental delay, duodenal stricture, and a history of pancreatitis presented with a painful eruption on his bilateral lower legs. The patient was well until 2 days prior to hospitalization when he developed bilateral lower extremity edema. The day prior to admission, he developed painful pink lesions on both legs. He had not applied any topical medications to his legs or had recent exposure to hot tubs or fish tanks at the home. He had a history of keratosis pilaris on the lower legs and was otherwise well with no fevers, recent upper respiratory infections, abdominal pain, vomiting, or diarrhea.Physical examination showed a man in no apparent distress. On the bilateral anterior legs were scattered tender, pink to purple nodules, and plaques (Figure, A). There was also a background of pinpoint folliculocentric papules on leg and thighs consistent with keratosis pilaris. There was 2+ pitting edema of the lower extremities. A punch biopsy specimen was obtained for histopathology and microbiology cultures (Figure, B-D). Routine complete blood cell count and complete metabolic panel had results within normal limits.A, Clinical photograph shows scattered pink to purple nodules and plaques on the bilateral lower extremities. B, C, and D, Histopathologic images of a biopsy specimen (hematoxylin-eosin). B, Subcutaneous tissue with superficial and deep, dermal and perivascular inflammation, fibrosis, and fat necrosis. C, Lobular panniculitis. D, Dense neutrophilic infiltration of subcutaneous fat associated with fat necrosis and deposition of granular basophilic material (arrowhead). What Is Your Diagnosis?

Erythema nodosum

Pancreatic panniculitis

Alpha-1-antitrypsin deficiency panniculitis

Polyarteritis nodosa

B. Pancreatic panniculitis

B

Pancreatic panniculitis

Skin biopsy revealed a superficial and deep, dermal inflammation with associated fibrosis (Figure, B), lobular panniculitis (Figure, C), and necrotic adipocytes with basophilic, granular material (Figure, D) most consistent with a diagnosis of pancreatic panniculitis. Fungal, bacterial, and mycobacterial cultures had negative results.Subsequent laboratory and imaging workup revealed elevated amylase (611 U/L; reference range, 30-110 U/L; to convert to microkatals per liter, multiply by 0.0167) and lipase (4041 U/L; reference range, 23-300 U/L; to convert to microkatals per liter, multiply by 0.0167) levels. Serum α-1-antitrypsin (A1AT) levels were normal. Abdominal ultrasonography demonstrated hypoechogenicity of the pancreatic body and tail most compatible with pancreatitis.Pancreatic panniculitis is rare, occurring in 2% of all patients with pancreatic disease including acute and chronic pancreatitis, pancreatic trauma, and rheumatologic diseases.1,2 The pathophysiologic mechanism is not completely understood, but it is thought that pancreatic inflammation leads to pancreatic enzyme (trypsin and lipase) release, which in turn leads to fat necrosis and development of subcutaneous nodules.3 Levels of amylase and lipase have not been found to be predictive of the development of pancreatic panniculitis.2Pancreatic panniculitis presents as tender red and purple nodules most commonly on the lower extremities, but they have also been reported to appear elsewhere. The nodules subsequently ulcerate and discharge an oily brown substance that is the result of liquefactive necrosis of adipocytes. Analysis of this fluid in 1 case revealed a high level of free fatty acids.4 Histopathological findings of pancreatic panniculitis include a lobular panniculitis with necrotic adipocytes with granular, basophilic material also known as “ghost cells.”5 The treatment of pancreatic panniculitis involves wound care and management of the underlying pancreatic disease. Some patients also experience sequelae of lipocyte degeneration in other organs including secondary acute arthritis. Arthritis has been reported in up to 88% of cases and most frequently involves the ankles and knees.4Up to 40% of patients with pancreatic panniculitis have other clinical symptoms of pancreatitis at the time of presentation.4 Our patient was atypical in that he did not present with nor did he ever develop any other symptoms of pancreatitis. Therefore, other potential mimickers were also considered. α-1-antitrypsin deficiency is a clinical and histopathologic mimicker of pancreatic panniculitis. Both present with painful nodules usually on the lower extremities, although patients with A1AT deficiency often have pulmonary and hepatic involvement, which our patient did not. Histopathologic findings are similar, demonstrating a predominantly lobular panniculitis with fat necrosis. However, a specific finding of A1AT panniculitis is the splaying of neutrophils between collagen bundles,1 which our patient did not have. Furthermore, his serum A1AT levels were normal during the hospitalization. Other panniculitides such as erythema nodosum can also mimic pancreatic panniculitis. However, the biopsy did not demonstrate a septal-predominant pattern as seen in erythema nodosum. Finally, vasculitides such as polyarteritis nodosa can present on the lower extremities as painful nodules and plaques with systemic involvement, most commonly the kidneys. In our patient, the biopsy did not demonstrate necrotizing vasculitis of medium-sized arteries in the subcutis.Taking together the histopathologic findings, ultrasonography, and serum pancreatic enzyme levels, a diagnosis of pancreatic panniculitis was made. Given our patient’s lack of nausea, abdominal pain, and vomiting, he was prescribed a regular diet with low-fat restriction. He was treated supportively with compression, elevation, and local wound care, and his lesions resolved slowly over a period of weeks. Our patient did not develop arthritis. At follow-up 10 days after discharge, his amylase and lipase levels were 288 and 1697 U/L, respectively.Pancreatitis panniculitis can be the first and rarely the only symptom of pancreatitis. Its presence should prompt the clinician to investigate pancreatic diseases in patients with panniculitis, especially those with a history of pancreatic disease or underlying risk factors.

Dermatology

A man in his 20s with panhypopituitarism, septo-optic dysplasia, developmental delay, duodenal stricture, and a history of pancreatitis presented with a painful eruption on his bilateral lower legs. The patient was well until 2 days prior to hospitalization when he developed bilateral lower extremity edema. The day prior to admission, he developed painful pink lesions on both legs. He had not applied any topical medications to his legs or had recent exposure to hot tubs or fish tanks at the home. He had a history of keratosis pilaris on the lower legs and was otherwise well with no fevers, recent upper respiratory infections, abdominal pain, vomiting, or diarrhea.Physical examination showed a man in no apparent distress. On the bilateral anterior legs were scattered tender, pink to purple nodules, and plaques (Figure, A). There was also a background of pinpoint folliculocentric papules on leg and thighs consistent with keratosis pilaris. There was 2+ pitting edema of the lower extremities. A punch biopsy specimen was obtained for histopathology and microbiology cultures (Figure, B-D). Routine complete blood cell count and complete metabolic panel had results within normal limits.A, Clinical photograph shows scattered pink to purple nodules and plaques on the bilateral lower extremities. B, C, and D, Histopathologic images of a biopsy specimen (hematoxylin-eosin). B, Subcutaneous tissue with superficial and deep, dermal and perivascular inflammation, fibrosis, and fat necrosis. C, Lobular panniculitis. D, Dense neutrophilic infiltration of subcutaneous fat associated with fat necrosis and deposition of granular basophilic material (arrowhead).

what is your diagnosis?

What is your diagnosis?

Erythema nodosum

Alpha-1-antitrypsin deficiency panniculitis

Pancreatic panniculitis

Polyarteritis nodosa

c

male

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2665394

A woman in her 60s presented with numerous whitish papules on the back of more than 10 years’ duration. The lesions previously resolved with topical corticosteroids but flared soon after treatment discontinuation. Some papules became pruritic and extended to the waist and anterior trunk in the past month. No family history of similar lesions was recorded. Physical examination revealed multiple hypopigmented, flat-topped papules on the back, waist, and inframammary area without genital involvement (Figure, A). Most lesions were folliculocentric under close inspection. Dermoscopy revealed central keratin plugs and some foci of structureless, whitish, and homogenous areas with surrounding erythema (Figure, B). The results of laboratory tests for antinuclear antibody and hyperglobulinemia were negative. A biopsy specimen was obtained from the back for histologic analysis (Figure, C).A, Multiple hypopigmented, atrophic, keratotic, and folliculocentric papules are seen on the trunk. B, Dermascopic findings included 2 foci of central keratin plugs and another ill-defined, whitish, and homogenous area with surrounding erythema. Scale bar corresponds to 1 mm. C, Histopathologic examination of a biopsy specimen (hematoxylin-eosin, original magnification ×100). What Is Your Diagnosis?

Lichen amyloidosis

Folliculocentric lichen sclerosus et atrophicus

Guttate vitiligo

Eruptive tumors of the follicular infundibulum

B. Folliculocentric lichen sclerosus et atrophicus

B

Folliculocentric lichen sclerosus et atrophicus

Histopathologic examination revealed a central follicular plug and epidermal atrophy covered by orthokeratotic stratum corneum. The papillary dermis was markedly thickened with homogenized collagens, areas of edema, and sparse bandlike lymphocytic infiltration (Figure, C). There were some eosinophils in infiltrate and red blood cell extravasation. Congo red and mucicarmine stains produced negative results for amyloid and mucin. After the biopsy, fluocinonide cream, 0.05%, was prescribed, and the itchy papules resolved but still recurred after intermittent treatment.Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory dermatosis first described by Hallopeau in 1887.1 The cause is unclear, but LSA is linked clinically to autoimmune diseases, such as vitiligo, autoimmune thyroiditis, alopecia areata, pernicious anemia, and scleroderma.2,3 The association with genetic factors, specific HLA types, estrogen deficiency, human papillomavirus and spirochete Borrelia burgdorferi infections, and trauma is also implicated.2,3 Classically, LSA manifests as porcelain white, polygonal papules that often coalesce into plaques over the anogenital area. Approximately 15% to 20% of LSA involves only extragenital regions, among which the most common locations affected are the trunk, proximal extremities, buttocks, breast, inframammary area, and neck.2 Typical histopathologic findings include hyperkeratotic, thinned, and effaced epidermis with a wide band of hyalinization in the upper dermis and a lichenoid infiltrate below.The folliculocentric variant of extragenital LSA has only been published in the literature twice. Mann et al4 described a woman in her 70s, and El Habr et al5 described a 10-year-old girl. Including the current study, all 3 patients were female from different ethnic groups and had bimodal age distributions, with 2 peaks occurring before puberty and after menopause.2 The affected areas were generalized over the trunk and/or extremities without genital or facial involvement.Dermoscopy may aid in the diagnosis of LSA with the homogenously whitish to yellowish areas and other minor features at various stages. Keratotic plugs and comedonelike openings correlate with histopathologic findings of follicular plug in the early phase.6,7 Different from typical extragenital form, folliculocentric LSA demonstrates the keratotic plug standing out at the center of the expected follicle in the present case. Surrounding erythematous halo is the vascular pattern found in some active lesions. In older lesions, chrysalis structures correspond to the increased homogenized collagen and fibrosis in the upper dermis.7The differential diagnosis of hypopigmented, atrophic, and keratotic eruption includes LSA, lichen amyloidosis, morphea, anetoderma, mycosis fungoides, eruptive tumors of the follicular infundibulum, guttate psoriasis, pityriasis versicolor, verruca plana, lichen planus, and pityriasis lichenoides chronica. Histologic findings were essential for the diagnosis. Special staining and laboratory tests exclude other causes. The folliculocentric feature is rare and specific for identification of the subtype.Potent topical corticosteroid is the mainstream treatment for LSA, and topical calcineurin inhibitors are also recommended for maintenance.2 Phototherapies, including psoralen plus UV-A, UV-A1, and narrow-band UV-B therapy, are the alternatives for extragenital LSA in the refractory condition.2 Topical corticosteroid was used as the first-line option in all 3 reported cases with variable results, and pimecrolimus cream, 1%, was given twice daily at the weekends to enhance the therapeutic effect in one of them.4,5The diagnosis of folliculocentric LSA is challenging and should be considered in the differential diagnoses of atrophic and folliculocentric lesions. The present case illustrates the clinical, dermoscopic, and histopathologic characteristics in the rare variant. A thorough evaluation helps to identify the folliculocentric component and leads to the final diagnosis.

Dermatology

A woman in her 60s presented with numerous whitish papules on the back of more than 10 years’ duration. The lesions previously resolved with topical corticosteroids but flared soon after treatment discontinuation. Some papules became pruritic and extended to the waist and anterior trunk in the past month. No family history of similar lesions was recorded. Physical examination revealed multiple hypopigmented, flat-topped papules on the back, waist, and inframammary area without genital involvement (Figure, A). Most lesions were folliculocentric under close inspection. Dermoscopy revealed central keratin plugs and some foci of structureless, whitish, and homogenous areas with surrounding erythema (Figure, B). The results of laboratory tests for antinuclear antibody and hyperglobulinemia were negative. A biopsy specimen was obtained from the back for histologic analysis (Figure, C).A, Multiple hypopigmented, atrophic, keratotic, and folliculocentric papules are seen on the trunk. B, Dermascopic findings included 2 foci of central keratin plugs and another ill-defined, whitish, and homogenous area with surrounding erythema. Scale bar corresponds to 1 mm. C, Histopathologic examination of a biopsy specimen (hematoxylin-eosin, original magnification ×100).

what is your diagnosis?

What is your diagnosis?

Folliculocentric lichen sclerosus et atrophicus

Eruptive tumors of the follicular infundibulum

Guttate vitiligo

Lichen amyloidosis

a

female

61-70

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2672039

An 8-month-old boy born full term presented to dermatology for evaluation of a bump on his neck that was present from birth (Figure). The parent noted that clear fluid drained from this bump when the patient ate. In addition, the parent reported that, at birth, the patient failed multiple hearing tests and that he had small kidneys. The patient was asymptomatic. Upon physical examination, the patient was noted to have a preauricular sinus and ear pit as well as a skin-colored papule on the antitragus of the right ear. He also had a pedunculated, skin-colored papule on the right lateral neck.Photograph of infant’s lateral neck depicting skin-colored papule with clear drainage. What Is Your Diagnosis?

Alport syndrome

Branchio-oto-renal syndrome

Goldenhar syndrome (oculoauriculovertebral spectrum)

Papillorenal syndrome

B. Branchio-oto-renal syndrome

B

Branchio-oto-renal syndrome

The skin-colored papule on the patient’s ear was consistent with an accessory tragus and the location and history of the lesion on the right lateral neck made it likely to be a branchial cleft cyst, fistula, or remnant. Based on the likely branchial cleft cyst, renal abnormalities, and ear findings, branchio-oto-renal (BOR) syndrome was suspected. The patient underwent ultrasonography of the neck, which revealed a cutaneous tract or fistula extending to the subcutaneous tissues of the neck and likely to the hypopharynx or esophagus. Results of abdominal ultrasonography revealed small kidneys with increased echogenicity. The kidneys measured 4.3 cm and 3.9 cm in length (normal for the patient’s age, 6.2 cm). Nephrology evaluation supported the diagnosis of BOR syndrome. Blood urea nitrogen and creatinine levels were normal and no additional renal testing was completed.Branchio-oto-renal syndrome is a clinically heterogeneous developmental disorder characterized by ear, renal, and branchial anomalies. It accounts for an estimated 2% of cases of congenital deafness, with an incidence of 1 in 40 000.1 The most common features of BOR syndrome include hearing impairment, auricular malformation, branchial fistulae or cysts, preauricular sinuses or ear pits, and renal abnormalities.2 Renal anomalies range from mild hypoplasia to aplasia and agenesis.3-5 Hearing loss in BOR syndrome is progressive and may be conductive, sensorineural, or mixed.3 Some branchial anomalies are asymptomatic, but symptomatic branchial cleft fistulae often present with recurrent infections.6Major diagnostic criteria for BOR syndrome include branchial abnormalities, hearing deficit, preauricular pits, and renal abnormalities. Minor criteria include external, middle, or internal ear abnormalities; preauricular tags; facial asymmetry; and palate abnormalities. For a diagnosis of BOR syndrome, an individual must have a minimum of either 3 major criteria or 2 major criteria and 2 minor criteria.7 The diagnosis may also be considered in an individual with any of these abnormalities and a family history of possible BOR syndrome.7 Other findings reported in BOR syndrome include lacrimal duct stenosis, retrognathia, facial nerve palsy, and pancreatic duplication cysts.3,4Most often, BOR syndrome results from mutations in the EYA1 gene (OMIM 601653), located on chromosome 8, and is transmitted in an autosomal dominant pattern.8 Mutations in the SIX5 gene (OMIM 600963) are also associated, although much less frequently.9 Proteins encoded by the EYA1 and SIX genes form a complex that activates DNA transcription, and mutations in these genes disrupt complex formation.9 Transcription activation by the EYA1 and SIX proteins is involved in the development of fetal tissues of the second branchial arch, from which the neck, eyes, ears, and kidneys are derived. In roughly 40% of individuals meeting the criteria for BOR syndrome, EYA1 mutations are present.7 Most of these mutations can be detected by gene sequence analysis, but approximately 20% are owing to chromosomal rearrangements of EYA1 and require more advanced testing.7There have been cases of misdiagnosis of BOR syndrome as Alport syndrome, owing to clinical similarities between the 2 conditions.4 Alport syndrome is caused by defective type 4 collagen and presents during the first decade of life with hematuria, hearing loss, and ophthalmologic abnormalities.10 Hearing loss in patients with Alport syndrome tends to present during mid-childhood to late childhood rather than in infancy.10Goldenhar syndrome and papillorenal syndrome were also included in the differential. Papillorenal syndrome is characterized by optic disc dysplasia and renal hypoplasia; this diagnosis would not explain our patient’s auricular findings. Goldenhar syndrome typically presents with auricular malformations, bony spinal deformities, hemifacial microsomia, and benign growths of the eye.Families may not seek medical attention immediately if a child is not experiencing significant functional deficits secondary to the condition, as was the case with this 8-month-old patient. Cutaneous findings such as a draining papule, preauricular ear pits, and/or an accessory tragus may be clues to investigate the possibility of BOR syndrome.

Pediatrics

An 8-month-old boy born full term presented to dermatology for evaluation of a bump on his neck that was present from birth (Figure). The parent noted that clear fluid drained from this bump when the patient ate. In addition, the parent reported that, at birth, the patient failed multiple hearing tests and that he had small kidneys. The patient was asymptomatic. Upon physical examination, the patient was noted to have a preauricular sinus and ear pit as well as a skin-colored papule on the antitragus of the right ear. He also had a pedunculated, skin-colored papule on the right lateral neck.Photograph of infant’s lateral neck depicting skin-colored papule with clear drainage.

what is your diagnosis?

What is your diagnosis?

Goldenhar syndrome (oculoauriculovertebral spectrum)

Branchio-oto-renal syndrome

Alport syndrome

Papillorenal syndrome

b

male

0-10

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2671388

A 78-year-old man with a history of deep vein thrombosis and pulmonary embolism who had been taking warfarin for the last 20 years presented with 1 day of severe abdominal pain, which began after eating dinner. The pain had no associated nausea, vomiting, or obstipation. On examination, he was afebrile and had a normal heart rate but was notably hypotensive. He was given 2 L of crystalloid, and his blood pressure responded appropriately. His physical examination showed an abdomen that was soft but diffusely tender without rebound or guarding. He had a well-healed appendectomy scar. Blood testing revealed an elevated creatinine level of 1.7 mg/dL (to convert to micromoles per liter, multiply by 88.4), an elevated lactate level of 29.7 mg/dL (to convert to micromoles per liter, multiply by 0.111), an international normalized ratio of 4.6, a lowered hemoglobin level of 10.7 g/dL (to convert to grams per liter, multiply by 10), and a lowered hematocrit level of 27.2%; all other results were unremarkable. Given his coagulopathy, low hematocrit level, and abdominal pain, a computed tomography angiogram was performed to rule out bleeding (Figure 1).A, Axial cross-section computed tomography without contrast of the abdomen and pelvis revealed gallstones in the neck of the gallbladder, high-density material within the lumen, and free intraperitoneal fluid. B, Axial cross-section computed tomography with intravenous contrast was significant for a blush of contrast within the lumen of the gallbladder and surrounding hyperemia of the liver at the gallbladder fossa.Hemorrhagic shock secondary to perforated hemorrhagic calculous cholecystitis What Is Your Diagnosis?

Anaphylactic shock secondary to ruptured echinococcal cyst

Hemorrhagic shock secondary to perforated hemorrhagic calculous cholecystitis

Hemorrhagic shock secondary to spontaneous intra-abdominal hemorrhage

Septic shock secondary to perforated cholecystitis

B. Hemorrhagic shock secondary to perforated hemorrhagic calculous cholecystitis

B

Hemorrhagic shock secondary to perforated hemorrhagic calculous cholecystitis

The computed tomographic scan demonstrated calculi within the gallbladder and surrounding hyperemia indicative of cholecystitis. Additionally, there was active extravasation into the distended gallbladder associated with hemorrhagic ascites. The constellation of findings on the scan, his presentation, and examination findings were most consistent with acute perforated hemorrhagic cholecystitis. This patient was promptly taken to the operating room for a laparoscopic cholecystectomy; Figure 2 clearly shows an inflamed gallbladder with a perforated wall.Laparoscopic cholecystectomy with grasper on cystic duct and instrument retracting liver. Perforation was noted in the gallbladder wall adjacent to the liver with hemorrhagic contents.Cholelithiasis is an extremely common diagnosis in Americans, affecting approximately 20% of the population, one-third of whom will go on to develop cholecystitis.1 However, both hemorrhagic cholecystitis and perforated cholecystitis are uncommon. Gallbladder perforation due to ischemia and gangrene occurs in only 10% of patients with acute cholecystitis and is associated with a mortality rate of up to 70%.2 Case reports of hemorrhagic cholecystitis are most consistently associated with malignancy or bleeding diathesis but can be related to obstructive cholecystitis, trauma, percutaneous interventions, or parasites. Diagnosis of hemorrhagic cholecystitis can be difficult because the presentation can range from a simple cholecystitis to acute abdomen pain. Prompt diagnosis is necessary to avoid significant morbidity and mortality.3-5Although there are, to our knowledge, no randomized studies or case series published on perforated hemorrhagic cholecystitis, most case reports recommend evaluating with ultrasonography or computed tomography if there is concern for this pathology. However, it should be noted that it can be difficult to see perforation on ultrasonography. There are several studies6,7 that emphasize the utility of computed tomography in the setting of complications of acute cholecystitis. Computed tomography also offers several distinct advantages over ultrasonography, including widespread availability, speed of imaging, lack of operator dependence, and increased anatomical coverage.5,6 Most reports agree that cholecystectomy is the appropriate treatment.After correction of coagulopathy and packed red blood cell transfusion, the patient was taken to the operating room to proceed with laparoscopic cholecystectomy. Intraoperatively, there was evidence of gallbladder perforation with active bleeding through the perforation, and greater than 1 L of blood clot was found intra-abdominally. Pathology revealed acute on chronic cholecystitis with cholelithiasis and a full-thickness gallbladder perforation. The patient did well postoperatively and was discharged home on postoperative day 3.

Surgery

A 78-year-old man with a history of deep vein thrombosis and pulmonary embolism who had been taking warfarin for the last 20 years presented with 1 day of severe abdominal pain, which began after eating dinner. The pain had no associated nausea, vomiting, or obstipation. On examination, he was afebrile and had a normal heart rate but was notably hypotensive. He was given 2 L of crystalloid, and his blood pressure responded appropriately. His physical examination showed an abdomen that was soft but diffusely tender without rebound or guarding. He had a well-healed appendectomy scar. Blood testing revealed an elevated creatinine level of 1.7 mg/dL (to convert to micromoles per liter, multiply by 88.4), an elevated lactate level of 29.7 mg/dL (to convert to micromoles per liter, multiply by 0.111), an international normalized ratio of 4.6, a lowered hemoglobin level of 10.7 g/dL (to convert to grams per liter, multiply by 10), and a lowered hematocrit level of 27.2%; all other results were unremarkable. Given his coagulopathy, low hematocrit level, and abdominal pain, a computed tomography angiogram was performed to rule out bleeding (Figure 1).A, Axial cross-section computed tomography without contrast of the abdomen and pelvis revealed gallstones in the neck of the gallbladder, high-density material within the lumen, and free intraperitoneal fluid. B, Axial cross-section computed tomography with intravenous contrast was significant for a blush of contrast within the lumen of the gallbladder and surrounding hyperemia of the liver at the gallbladder fossa.Hemorrhagic shock secondary to perforated hemorrhagic calculous cholecystitis

what is your diagnosis?

What is your diagnosis?

Hemorrhagic shock secondary to spontaneous intra-abdominal hemorrhage

Septic shock secondary to perforated cholecystitis

Anaphylactic shock secondary to ruptured echinococcal cyst

Hemorrhagic shock secondary to perforated hemorrhagic calculous cholecystitis

d

male

71-80

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2673184

A 71-year-old man with a history of coronary artery bypass graft using the left internal mammary artery (LIMA) to the left anterior descending (LAD) in 1997 presented with frequent ventricular tachycardia on routine pacemaker interrogation. He reported dyspnea on exertion and left leg claudication at 23 m. At rest, his blood pressure was 146/65 mm Hg measured on the right arm and 85/50 mm Hg on the left arm. Physical examination was notable for a diminished left radial pulse. In 2014, he experienced angina that resolved following placement of a drug-eluting stent in his LAD. Coronary angiography via the left femoral artery is displayed in the Figure. What Is Your Diagnosis?

Normal coronary angiography

Coronary steal syndrome

Subclavian steal syndrome

Subclavian stenosis

B. Coronary steal syndrome

B

Coronary steal syndrome

The coronary angiogram in the Figure demonstrates retrograde filling of the LIMA and left subclavian artery from the LAD as well as chronic total occlusion of the left subclavian artery proximal to the vertebral artery takeoff, defining coronary steal syndrome anatomy (Figure and Video). Antegrade vertebral artery flow was also seen on a separate series. Although subclavian stenosis is, by definition, present, this diagnosis elides the aberrant filling path through the LAD and LIMA seen in the associated video. Subclavian stenosis may also lead to subclavian steal syndrome; however, this syndrome presents as a constellation of vertebrobasilar symptoms, including dizziness or diplopia, with retrograde, not antegrade, flow through the ipsilateral vertebral artery.Antegrade and retrograde attempts to cross the subclavian artery occlusion were unsuccessful. Subsequently, this patient was referred to vascular surgery for a left carotid–subclavian bypass to prevent further ischemia-related arrhythmias. His procedure was uncomplicated, and at the 4-month postoperative follow-up, he reported no symptoms and demonstrated no further arrhythmias. Patients treated for central vascular disease often harbor or develop peripheral vascular disease.1,2 This case highlights an uncommon presentation: coronary steal syndrome developing after LAD stent placement. Subclavian stenosis is diagnosed after coronary artery bypass graft in 3.4% to 6.8% of patients.1,2 Symptoms may be as subtle as an increased frequency of arrhythmia, as in our patient, or more dramatic manifestations such as right heart failure and acute coronary syndrome.3 No guidelines exist regarding treatment of a stenotic subclavian artery before or after LIMA grafting. Case reports cite symptoms as the indication to revascularize, either by endovascular or open surgical means2; other small studies recommend preemptive intervention prior to LIMA grafting.1 A large series from a group in Beijing, China, found 94% vs 89% 10-year patency in coronary steal syndrome patients treated with extraanatomic bypass and endovascular intervention, respectively.3

Surgery

A 71-year-old man with a history of coronary artery bypass graft using the left internal mammary artery (LIMA) to the left anterior descending (LAD) in 1997 presented with frequent ventricular tachycardia on routine pacemaker interrogation. He reported dyspnea on exertion and left leg claudication at 23 m. At rest, his blood pressure was 146/65 mm Hg measured on the right arm and 85/50 mm Hg on the left arm. Physical examination was notable for a diminished left radial pulse. In 2014, he experienced angina that resolved following placement of a drug-eluting stent in his LAD. Coronary angiography via the left femoral artery is displayed in the Figure.

what is your diagnosis?

What is your diagnosis?

Subclavian stenosis

Coronary steal syndrome

Subclavian steal syndrome

Normal coronary angiography

b

male

71-80

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2666580

A man in his early 70s with 2 months of progressive dimming of his vision was referred for evaluation. He initially presented to his primary care physician reporting unintentional weight loss, fevers, and subacute visual decline. Subsequent ophthalmic examination revealed mild anterior and posterior inflammation, raising suspicion for panuveitis. Results of laboratory tests for sarcoidosis, Lyme disease, and syphilis were negative. However, a right upper lobe lung mass noted on the chest radiograph proved to be T2N2M0 stage III non–small-cell lung cancer on biopsy.On presentation to us, the patient’s visual acuity was 20/150 OD and 20/200 OS, but improved to 20/70 OU with pinhole. He was pseudophakic with bilateral mild anterior chamber inflammation, moderate vitreous haze, and inferior vitreous condensations. The posterior pole demonstrated bilateral diffuse retinal pigment epithelial alterations with a prominent leopard spot pattern and focal choroidal pigmented lesions. Macular subretinal fluid tracked to the inferior periphery in both eyes (Figure 1A). Optical coherence tomography confirmed bilateral subretinal fluid and retinal pigment epithelial irregularity (Figure 1B); nummular hypoautofluorescent lesions were interspersed within areas of hyperautofluorescence on autofluorescence imaging. The optic disc and peripheral vasculature leaked on fluorescein angiography. B-scan ultrasonography also showed diffuse choroidal thickening with focal choroidal thickening consistent with the pigmented choroidal lesions. Ultrasonographic biomicroscopy revealed ciliary cysts associated with anterior thickening of both ciliary bodies.A, Optos photograph of the left eye demonstrating diffuse retinal pigment epithelial alterations in a leopard spot pattern (white arrowhead) and focal choroidal pigmented lesions, as well as subretinal fluid that tracks to the inferior periphery. B, Optical coherence tomography (OCT) of the macula of the left eye demonstrating subretinal fluid (asterisk) with areas of retinal pigment epithelium loss (yellow arrowhead) and irregular thickening (white arrowhead).Pars plana vitrectomy with drainage of subretinal fluid What Would You Do Next?

Choroidal biopsy of the right eye lesion

Pars plana vitrectomy with drainage of subretinal fluid

Refer for serial plasmapheresis

Bilateral external-beam radiotherapy

Bilateral diffuse melanocytic uveal proliferation

C

Refer for serial plasmapheresis

The diagnosis in this patient was bilateral diffuse melanocytic uveal proliferation (BDUMP) syndrome and he was referred for plasmapheresis. Choroidal biopsy of the lesion and external-beam radiotherapy would not be appropriate management since the lesions are not malignant. Pars plana vitrectomy with subretinal fluid drainage is not required since the subretinal fluid may improve with appropriate treatment.BDUMP is a paraneoplastic ocular syndrome characterized by bilateral simultaneous vision loss due to rapid cataract formation and the development of multifocal pigmented and nonpigmented uveal masses with diffuse choroidal thickening, ciliary and iris cysts, and exudative retinal detachments.1,2 Patients may be referred for bilateral uveal melanomas. More than 50 cases of BDUMP have been reported to date, the majority of which were associated with lung cancer, followed by carcinomas of the gastrointestinal and genitourinary tracts.3 When the clinical presentation was first described by Machemer4 in 1966, the uveal masses were thought to represent diffuse bilateral malignant uveal melanoma. This finding prompted enucleation as the primary management for many years. It was not until 1990—more than 2 decades after the first case had been reported by Machemer—that Gass and colleagues5 proposed a potential paraneoplastic etiology for this rare condition. Their group postulated that the outer retinal damage observed on the histopathology examination of patients with BDUMP was not the direct result of the proliferative melanocytic infiltration observed throughout the uveal tract, but rather a byproduct of either hormonal or autoimmune interaction between the primary carcinoma and the retinal pigment epithelium and photoreceptors.This suggestion of a plausible immune interplay between a systemic, frequently occult, cancer and the eye led to a novel shift in paradigm toward the management of BDUMP. Plasma exchange was soon evaluated in 2 patients with BDUMP and was shown to be effective at halting what was previously thought to be an inevitable course of progressive vision loss.6 Miles et al7 have since shown that melanocytic growth-stimulating hormone is present in the immunoglobulin G fraction of the serum of patients with BDUMP. They have also demonstrated that this serum stimulates a statistically significant increase in the proliferation of normal human melanocytes in vitro, providing a strong rationale for clinical treatments that target circulating autoantibodies. Plasma exchange therapy has subsequently been replaced by plasmapheresis as the mainstay of treatment for BDUMP, with many patients demonstrating marked visual recovery.8-10 Plasmapheresis has limited efficacy when eyes have extensive exudative detachment. Prompt treatment is preferred to observation as delays in management could increase the risk of permanent blindness. Comanagement with an oncologist is also warranted, so that patients can receive simultaneous systemic chemotherapy or targeted radiotherapy for their underlying systemic cancer.8Improved characterization of this clinical entity using contemporary imaging techniques, such as optical coherence tomography, is also making it possible to detect BDUMP early, before patients suffer extensive loss of the retinal pigment epithelium or photoreceptors.9,10 With the advent of modern imaging technology and plasmapheresis, our ability to diagnose and manage BDUMP before irreversible vision loss is finally realizable.The patient underwent 9 cycles of plasmapheresis followed by chemotherapy for adenocarcinoma of the lung. His vision improved to 20/30 OU with complete resolution of subretinal fluid 6 months following his initial presentation (Figure 2).Optical coherence tomography of the macula of the left eye demonstrating resolution of the subretinal fluid (white arrowhead), irregular thickening of the retinal pigment epithelium (yellow arrowhead), and patchy loss of the ellipsoid zone (black arrowhead).

Ophthalmology

A man in his early 70s with 2 months of progressive dimming of his vision was referred for evaluation. He initially presented to his primary care physician reporting unintentional weight loss, fevers, and subacute visual decline. Subsequent ophthalmic examination revealed mild anterior and posterior inflammation, raising suspicion for panuveitis. Results of laboratory tests for sarcoidosis, Lyme disease, and syphilis were negative. However, a right upper lobe lung mass noted on the chest radiograph proved to be T2N2M0 stage III non–small-cell lung cancer on biopsy.On presentation to us, the patient’s visual acuity was 20/150 OD and 20/200 OS, but improved to 20/70 OU with pinhole. He was pseudophakic with bilateral mild anterior chamber inflammation, moderate vitreous haze, and inferior vitreous condensations. The posterior pole demonstrated bilateral diffuse retinal pigment epithelial alterations with a prominent leopard spot pattern and focal choroidal pigmented lesions. Macular subretinal fluid tracked to the inferior periphery in both eyes (Figure 1A). Optical coherence tomography confirmed bilateral subretinal fluid and retinal pigment epithelial irregularity (Figure 1B); nummular hypoautofluorescent lesions were interspersed within areas of hyperautofluorescence on autofluorescence imaging. The optic disc and peripheral vasculature leaked on fluorescein angiography. B-scan ultrasonography also showed diffuse choroidal thickening with focal choroidal thickening consistent with the pigmented choroidal lesions. Ultrasonographic biomicroscopy revealed ciliary cysts associated with anterior thickening of both ciliary bodies.A, Optos photograph of the left eye demonstrating diffuse retinal pigment epithelial alterations in a leopard spot pattern (white arrowhead) and focal choroidal pigmented lesions, as well as subretinal fluid that tracks to the inferior periphery. B, Optical coherence tomography (OCT) of the macula of the left eye demonstrating subretinal fluid (asterisk) with areas of retinal pigment epithelium loss (yellow arrowhead) and irregular thickening (white arrowhead).Pars plana vitrectomy with drainage of subretinal fluid

what would you do next?

What would you do next?

Refer for serial plasmapheresis

Pars plana vitrectomy with drainage of subretinal fluid

Choroidal biopsy of the right eye lesion

Bilateral external-beam radiotherapy

a

male

71-80

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2666805

A 25-year-old man with a history of rheumatoid arthritis currently taking oral methotrexate, 25 mg per week, presented with a lesion of the left bulbar conjunctiva of about 1 month’s duration. He had no other symptoms other than occasionally noticing a sensation of a foreign body in that eye and denied any changes in his vision. He had no history of contact lens use, ocular trauma, or ocular surgery. His only other medications were oral vitamin D and folic acid. He was initially treated with topical antibiotics followed by a course of oral sulindac, 200 mg twice daily, without any improvement. On examination, his visual acuity was 20/20 OD and 20/25 OS. Intraocular pressure was 16 mm Hg OD and 23 mm Hg OS. The lesion measured 6.5 × 2.5 mm and was firm, nonvascular, slightly mobile, and located on the superotemporal portion of the bulbar conjunctiva (Figure 1). It was purulent in appearance, but no material was expressed with attempted incision and drainage at the slitlamp. A culture was positive only for Propionibacterium acnes. Tests for herpes simplex, cytomegalovirus, and Epstein-Barr virus polymerase chain reactions were negative.External slitlamp photograph showing conjunctival lesion at presentation. What Would You Do Next?

Initiate oral colchicine therapy

Observe with serial examinations

Perform excisional biopsy

Perform intralesional dexamethasone injection

Rheumatoid nodule

C

Perform excisional biopsy

The patient underwent an excisional biopsy, which revealed necrotizing granulomatous inflammation with palisading histiocytes, consistent with a rheumatoid nodule (Figure 2). Gomori methanamine silver and acid-fast bacilli stains were negative for organisms. Prior to surgery, the patient had not responded to topical antibiotics or oral sulindac. This lack of response to therapy makes observation inappropriate, given the malignancy potential in this immunocompromised patient. An infectious etiology also needs to be excluded prior to considering more aggressive anti-inflammatory therapy, such as intralesional corticosteroids, which have previously been used for ocular rheumatoid nodules.1,2 The same applies for oral colchicine, which is used in the treatment of systemic rheumatoid nodulosis.3Histopathological specimen showing granulomatous inflammation with an area of necrosis and palisading histiocytes (arrowheads).Ocular manifestations of rheumatoid arthritis include episcleritis, scleritis, keratoconjunctivitis sicca, and ulcerative keratitis. However, there are several case reports1,2 of rheumatoid nodules occurring within ocular structures but only 3 reported cases4,5 occurring within the conjunctiva. In 2003, Frederickson et al5 published 2 cases of biopsy-proven rheumatoid nodules of the conjunctiva in patients being treated with methotrexate. Another case was described in a 49-year-old woman who had a 1.5 × 1.0-mm rheumatoid nodule in the bulbar conjunctiva.4 However, she had never been treated with methotrexate. This patient also presented with a prolonged course of conjunctival hyperemia and irritation before an excisional biopsy was performed.4Rheumatoid nodules are the most common dermatological finding in patients with rheumatoid arthritis.6 These nodules typically occur at sites of pressure on the skin, such as the olecranon process, metacarpophalangeal, and proximal interphalangeal joints. Histologically, the nodules have a necrotic center surrounded by palisades of histiocytes.7 These nodules, when occurring at pressure points in a patient with rheumatoid arthritis, do not require diagnostic biopsy or excision. Lesions that grow rapidly or occur in an atypical location, as in this patient, necessitate a biopsy.It is well known that other extra-articular manifestations of rheumatoid arthritis, such as pericarditis, glomerulonephritis, Felty syndrome, and vasculitis, as well as ophthalmologic findings, such as scleritis, episcleritis, and ulcerative keratitis, are associated with increased cardiovascular risks.8,9 However, these studies excluded rheumatoid nodules from their analyses when examining the extra-articular cardiovascular risk factors. A study by Kaushik et al10 specifically examined the relationship between the presence of rheumatoid nodules and cardiovascular events. These researchers found an increase in myocardial infarctions, strokes, and other cardiovascular events in patients with rheumatoid nodules, even when adjusting for age, sex, and other cardiovascular risk factors.10In conclusion, ocular rheumatoid nodules are a rare presentation of extra-articular rheumatoid arthritis and, as in this patient, can present as a presumed conjunctival abscess, thus warranting a diagnostic evaluation. The discovery of a rheumatoid nodule should alert the clinician to the associated systemic cardiovascular risks.The patient has had complete resolution of the nodule postoperatively. We alerted his primary care physician of the findings of the conjunctival rheumatoid nodule. At this time, no change to his methotrexate has been made, and he has not developed any other rheumatoid nodules.

Ophthalmology

A 25-year-old man with a history of rheumatoid arthritis currently taking oral methotrexate, 25 mg per week, presented with a lesion of the left bulbar conjunctiva of about 1 month’s duration. He had no other symptoms other than occasionally noticing a sensation of a foreign body in that eye and denied any changes in his vision. He had no history of contact lens use, ocular trauma, or ocular surgery. His only other medications were oral vitamin D and folic acid. He was initially treated with topical antibiotics followed by a course of oral sulindac, 200 mg twice daily, without any improvement. On examination, his visual acuity was 20/20 OD and 20/25 OS. Intraocular pressure was 16 mm Hg OD and 23 mm Hg OS. The lesion measured 6.5 × 2.5 mm and was firm, nonvascular, slightly mobile, and located on the superotemporal portion of the bulbar conjunctiva (Figure 1). It was purulent in appearance, but no material was expressed with attempted incision and drainage at the slitlamp. A culture was positive only for Propionibacterium acnes. Tests for herpes simplex, cytomegalovirus, and Epstein-Barr virus polymerase chain reactions were negative.External slitlamp photograph showing conjunctival lesion at presentation.

what would you do next?

What would you do next?

Observe with serial examinations

Initiate oral colchicine therapy

Perform excisional biopsy

Perform intralesional dexamethasone injection

c

male

21-30

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2666824

A female patient with a history of premature birth (24 weeks’ gestational age, 538 g) and zone I, stage 3 retinopathy of prematurity (ROP) with plus disease treated with a single injection of 0.625 mg of intravitreal bevacizumab in each eye presented for routine examination at 2 years of age. Examination with the patient under anesthesia with fluorescein angiography (Figure 1) revealed significant peripheral retinal avascularity, circumferential vascular loops at the border of vascular and avascular retina, and arteriovenous anastomoses in both eyes. There was no evidence of retinal neovascularization or recurrence of ROP.Fluorescein angiography 2 years after intravitreal bevacizumab treatment for retinopathy of prematurity (ROP) shows sparse retinal vasculature with peripheral retinal avascularity (white arrowheads) and arteriovenous anastomoses (yellow arrowhead) without evidence of neovascularization or recurrent ROP.Observe or perform laser photocoagulation to areas of peripheral retinal nonperfusionAdminister intravitreal anti–vascular endothelial growth factor therapy againAdminister combined intravitreal anti–vascular endothelial growth factor therapy and laser photocoagulation to areas of nonperfusion What Would You Do Next?

Observe or perform laser photocoagulation to areas of peripheral retinal nonperfusion

Administer intravitreal anti–vascular endothelial growth factor therapy again

Administer combined intravitreal anti–vascular endothelial growth factor therapy and laser photocoagulation to areas of nonperfusion

Perform pars plana vitrectomy

Persistent retinal vascular abnormalities after intravitreal anti–vascular endothelial growth factor therapy for ROP

A

Observe or perform laser photocoagulation to areas of peripheral retinal nonperfusion

Retinopathy of prematurity is a potentially blinding disease of premature and low-birth-weight infants characterized by incomplete and abnormal retinal vascularization, which can lead to retinal neovascularization and detachment. Consensus guidelines based on the Early Treatment of ROP study1 recommend laser photocoagulation for type 1 ROP. More recently, off-label intravitreal anti–vascular endothelial growth factor (VEGF) injection is increasingly being used for the treatment of posterior type 1 ROP. The Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity (BEAT-ROP) study2 provided support for this practice, although there were limitations to the study, and controversy exists regarding the efficacy, ocular and systemic safety, and optimal timing, choice of medication, and dosage of anti-VEGF for ROP. To this end, additional multicenter randomized clinical trials (eg, Ranibizumab Compared With Laser Therapy for the Treatment of Infants Born Prematurely With Retinopathy of Prematurity and Pediatric Eye Disease Investigator Group) are under way.Two major concerns after anti-VEGF therapy for ROP are ROP recurrence and persistent angiographic abnormalities. Although there is a better understanding of the frequency and length of follow-up after laser photocoagulation for ROP, there are no long-term results from prospective studies to guide ROP management after anti-VEGF therapy. Studies have reported ROP recurrence rates of up to 14% in bevacizumab-treated eyes2-4 and 0% to 83% in ranibizumab-treated eyes,4,5 with some cases reported as late as 2½ years after anti-VEGF.2-6 Another study7 likewise reported persistent fluorescein angiographic abnormalities in up to 90% of anti-VEGF–treated eyes, including extensive peripheral avascularity; abnormal vascular patterns, such as circumferential loops at the vascular-avascular border; and arteriovenous anastomoses, similar to findings in the case reported here. Perivascular leakage and absence of the foveal avascular zone have also been described.7The management of persistent retinal avascularity after anti-VEGF treatment for ROP is unclear, and potential management includes observation or laser photocoagulation to areas of retinal nonperfusion. The long-term implications of these angiographic abnormalities have not yet been evaluated. There is also no consensus agreement on what normal angiographic findings are in children. A previous study8 suggested that up to 1.5 disc diameters of avascular retina in the periphery may be a routine finding in children. Theoretically, persistent retinal ischemia may promote neovascularization and ROP recurrence. It may also be possible that patients with these large, avascular areas in regressed ROP are predisposed to developing lattice-like changes, retinal tears, and rhegmatogenous retinal detachments later in life.9 Thus, laser photocoagulation to reduce risk of recurrence or future rhegmatogenous complications may be considered.10 In the absence of definitive evidence regarding the efficacy and safety of laser in this context, observation, as elected in our case, may also be considered. Subsequent anti-VEGF therapy alone or in combination with laser is not indicated in the absence of active ROP recurrence. Because there were no surgical pathologic findings in this case, pars plana vitrectomy is not appropriate.The options of observation vs laser photocoagulation to the peripheral retinal nonperfusion were discussed with the parents, and the decision was made to continue close monitoring. Examination with the patient under anesthesia with fluorescein angiography 2 years later, 4 years after intravitreal bevacizumab therapy, revealed stable peripheral retinal avascularity in both eyes with no neovascularization, tears, detachment, or recurrent ROP (Figure 2). Visual acuity was 20/25 bilaterally.Fluorescein angiography 4 years after intravitreal bevacizumab treatment of retinopathy of prematurity (ROP) shows stable retinal avascularity and arteriovenous anastomoses without evidence of neovascularization or recurrent ROP in the right eye. Similar findings were noted in the left eye (not pictured).

Ophthalmology

A female patient with a history of premature birth (24 weeks’ gestational age, 538 g) and zone I, stage 3 retinopathy of prematurity (ROP) with plus disease treated with a single injection of 0.625 mg of intravitreal bevacizumab in each eye presented for routine examination at 2 years of age. Examination with the patient under anesthesia with fluorescein angiography (Figure 1) revealed significant peripheral retinal avascularity, circumferential vascular loops at the border of vascular and avascular retina, and arteriovenous anastomoses in both eyes. There was no evidence of retinal neovascularization or recurrence of ROP.Fluorescein angiography 2 years after intravitreal bevacizumab treatment for retinopathy of prematurity (ROP) shows sparse retinal vasculature with peripheral retinal avascularity (white arrowheads) and arteriovenous anastomoses (yellow arrowhead) without evidence of neovascularization or recurrent ROP.Observe or perform laser photocoagulation to areas of peripheral retinal nonperfusionAdminister intravitreal anti–vascular endothelial growth factor therapy againAdminister combined intravitreal anti–vascular endothelial growth factor therapy and laser photocoagulation to areas of nonperfusion

what would you do next?

What would you do next?

Administer intravitreal anti–vascular endothelial growth factor therapy again

Perform pars plana vitrectomy

Observe or perform laser photocoagulation to areas of peripheral retinal nonperfusion

Administer combined intravitreal anti–vascular endothelial growth factor therapy and laser photocoagulation to areas of nonperfusion

c

female

21-30

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2667546

A woman in her late 50s was referred to the neuro-ophthalmology clinic for evaluation of a 7-month history of recurrent, transient vision loss in the right eye. She reported 5 episodes, each lasting a few minutes and all occurring on awakening. Further inquiry revealed that symptoms always developed after using her electronic reader tablet in dim lighting while lying on her left side. Notably, the patient reported immediate resolution of vision loss on turning on the lights. She denied headaches, visual aura, or neurologic symptoms. Her other medical history was unremarkable.Six months prior to presentation, workup at her local hospital for the transient vision loss revealed an enhancing right orbital mass on magnetic resonance imaging (Figure, A). Carotid ultrasonography and head magnetic resonance angiography showed no abnormalities. Inflammatory marker levels were normal. Magnetic resonance imaging 3 months later showed a stable mass without change in size or appearance.A, T1-weighted magnetic resonance image (MRI) of the orbit with contrast shows a well-circumscribed, enhancing soft-tissue lesion in the right orbit superomedially (arrowhead). B, Computed tomographic (CT) scan of the orbit with contrast shows the mass (arrowhead); no change noted on Valsalva maneuver.On examination, visual acuity was 20/25 OD. Pupils, intraocular pressure, and motility were unremarkable. Anterior segment examination showed mild cataract and dry eye. Posterior pole examination revealed evidence of posterior vitreous detachment and normal optic nerves with 0.2 cup-to-disc ratio in each eye. The retina was flat without evidence of whitening or Hollenhorst plaques. Humphrey visual fields were full. Normal retinal nerve fiber and ganglion cell layer thickness were observed in each eye on optical coherence tomography. Computed tomography of the head revealed no change in orbital lesion size with Valsalva maneuver (Figure, B). What Would You Do Next?

Perform echocardiogram and Holter monitoring

Biopsy orbital mass

Observe

Perform hypercoagulability workup

Transient smartphone blindness (TSB)

C

Observe

The patient’s presentation of monocular vision loss and the finding of a right enhancing orbital lesion prompted 2 important differential diagnoses. The differential diagnosis for monocular, transient vision loss includes amaurosis fugax from emboli, retinal migraine, vasospasm, ocular ischemic syndrome, giant cell arteritis, and ocular causes, such as hyphema,1,2 whereas orbital lesions carry a wide differential of tumors and vascular lesions, such as cavernous hemangiomas. However, the patient’s monocular vision loss, occurring only on awakening after use of her electronic reader tablet that resolved with turning on lights, is consistent with a benign cause of vision loss: transient smartphone blindness (TSB).Transient smartphone blindness is a recently described phenomenon in a report of 2 cases occurring in young women with recurrent monocular vision loss thought to be related to on-awakening smartphone use.3 Both women experienced visual impairment after several minutes of viewing a smartphone screen in the dark, lying in bed on their side. The authors suggested the vision loss was due to differential bleaching of retinal photopigment causing light adaptation of the viewing eye and perception of “blindness.” Our patient’s history of monocular exposure to an electronic screen in a predisposing environment, recurrent episodes, immediate resolution on light exposure, and negative evaluation is similar.A recent study by Bouffard et al4 retrospectively reviewed 29 patients with transient monocular vision loss on awakening. The authors discovered that at least 8 of the 29 patients (28%) experienced rapid resolution on light exposure. They also noted that systemic evaluations and imaging were uniformly negative in all of the cases with follow-up and concluded that monocular vision loss on awakening was a benign phenomenon. Although the specific use of electronics was not evaluated in this study, it is possible that it played a role.Most other causes of transient monocular vision loss, such as amaurosis fugax, would not occur only in the morning or resolve immediately with turning on lights. Therefore, echocardiogram, Holter monitoring, and hypercoagulability workup are not indicated. There were also no abnormalities on carotid ultrasonography to suggest ocular ischemic syndrome.We also believe that the finding of the orbital lesion was incidental. An orbital mass can cause transient vision loss with eye movements (gaze-evoked amaurosis), but this potential cause did not match the clinical history. The lesion was small and not adjacent to or compressing the optic nerve. The mass also did not enlarge with Valsalva maneuver, which is another way that orbital masses can cause transient vision loss. This patient’s lesion is likely a benign cavernous hemangioma—a diagnosis supported by lack of growth noted over 6 months on serial imaging and would not warrant biopsy.The initial evaluation of transient vision loss should always begin with detailed history. Not recognizing TSB or misinterpreting its symptoms could lead to unnecessary investigations, medical expenses, and treatment.5 The natural history of TSB is benign and self-limited. As such, there is no role for medications or therapy; rather, the patient should be made aware of its physiologic cause.The patient now reads with lights on and has reported no recurrent events of transient vision loss.

Ophthalmology

A woman in her late 50s was referred to the neuro-ophthalmology clinic for evaluation of a 7-month history of recurrent, transient vision loss in the right eye. She reported 5 episodes, each lasting a few minutes and all occurring on awakening. Further inquiry revealed that symptoms always developed after using her electronic reader tablet in dim lighting while lying on her left side. Notably, the patient reported immediate resolution of vision loss on turning on the lights. She denied headaches, visual aura, or neurologic symptoms. Her other medical history was unremarkable.Six months prior to presentation, workup at her local hospital for the transient vision loss revealed an enhancing right orbital mass on magnetic resonance imaging (Figure, A). Carotid ultrasonography and head magnetic resonance angiography showed no abnormalities. Inflammatory marker levels were normal. Magnetic resonance imaging 3 months later showed a stable mass without change in size or appearance.A, T1-weighted magnetic resonance image (MRI) of the orbit with contrast shows a well-circumscribed, enhancing soft-tissue lesion in the right orbit superomedially (arrowhead). B, Computed tomographic (CT) scan of the orbit with contrast shows the mass (arrowhead); no change noted on Valsalva maneuver.On examination, visual acuity was 20/25 OD. Pupils, intraocular pressure, and motility were unremarkable. Anterior segment examination showed mild cataract and dry eye. Posterior pole examination revealed evidence of posterior vitreous detachment and normal optic nerves with 0.2 cup-to-disc ratio in each eye. The retina was flat without evidence of whitening or Hollenhorst plaques. Humphrey visual fields were full. Normal retinal nerve fiber and ganglion cell layer thickness were observed in each eye on optical coherence tomography. Computed tomography of the head revealed no change in orbital lesion size with Valsalva maneuver (Figure, B).

what would you do next?

What would you do next?

Observe

Perform echocardiogram and Holter monitoring

Perform hypercoagulability workup

Biopsy orbital mass

a

female

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2668282

A healthy 1-year-old boy had a history of restricted movements of the left eye since birth. He had been diagnosed as having an orbital capillary hemangioma at 3 months of age after orbital magnetic resonance imaging (MRI), which had reportedly revealed an orbital mass with enlarged extraocular muscles. He was treated with oral propranolol with no improvement.On examination, the patient had inferior displacement of the left globe with a severe limitation of supraduction and a mild limitation of horizontal movement in the left eye. He was unable to maintain fixation with the left eye. Results of modified Krimsky testing showed 6 prism diopters (PD) of exotropia and 16 PD of left hypotropia. Retinoscopy disclosed a cycloplegic refraction of +2.00 diopters (D) in the right eye and +6.00 D in the left eye. Thyrotropin, thyroxine, and thyroid-stimulating immunoglobulin levels were all within reference ranges. Repeated MRI with coronal images showed massive enlargement of the superior, inferior, and medial rectus muscles (Figure 1). The medial rectus mass extended nasally to produce bowing of the lamina papyrecea, with no extension into adjacent structures. The enlarged extraocular muscles were hypointense on T1- and T2-weighted sequences. An abnormal curvilinear signal in the intraconal fat was isointense with muscle (Figure 1).A, Coronal T1-weighted magnetic resonance imaging (MRI) of both orbits shows enlarged inferior, medial, and superior rectus muscles with an isointense curvilinear signal in the intraconal fat (arrowhead). B, Axial T1-weighted MRI of both orbits shows an orbital mass incorporating the medial rectus muscle.Genetic testing for congenital fibrosis of extraocular muscles What Would You Do Next?

Investigate for systemic involvement

Genetic testing for congenital fibrosis of extraocular muscles

Strabismus surgery

Orbital biopsy

Congenital orbital fibrosis

D

Orbital biopsy

Incisional biopsy of the medial orbital mass showed disarrayed skeletal muscle fibers with extensive hyaline fibrosis (Figure 2). The diagnosis congenital orbital fibrosis (COF) first appeared in the literature in 2009 when Mavrikakis and colleagues1 described 4 patients with unilateral congenital restrictive strabismus, all of whom had orbital masses incorporating 1 or more extraocular muscles. Patients for whom biopsy was performed demonstrated dense focal fibrosis with no inflammation. However, Hertle and colleagues2 were the first to report cases with similar features, which they grouped together as a unilateral subtype of congenital fibrosis of the extraocular muscles. Three years later, Dickson and colleagues3 reported a similar case of congenital unilateral extraocular muscle enlargement and suggested that this constellation of findings could represent a unique entity rather than a subtype of congenital fibrosis of the extraocular muscles. Numerous other cases have since been reported.4-7Histopathologic evaluation of the medial orbital mass shows disarrayed extraocular muscle fibers intermixed with fibrosis (delimited by arrowheads) (hematoxylin-eosin, original magnification ×200). Scale bar indicates 50 μm.Congenital orbital fibrosis is a unilateral condition that is nonhereditary and nonprogressive. It is characterized by enlargement of 1 or more extraocular muscles and, in most cases, an intraorbital mass incorporating 1 or more extraocular muscles. This results in restrictive strabismus with variable degrees of globe displacement, enophthalmos, and blepharoptosis.2 In this context, clinicians should exclude congenital fibrosis of the extraocular muscles type 3 (CFEOM), which can manifest with similar unilateral signs2 but shows hypoplastic ocular motor nerves and small, atrophic, bandlike extraocular muscles on MRI.8 In this patient, genetic testing for CFEOM was not appropriate because the muscles were more enlarged than atrophic. The unilaterality, variable intraorbital mass, paradoxical enophthalmos, lack of inflammatory signs, and normal results of thyroid function tests in COF help to distinguish it from thyroid eye disease in infancy.9 Magnetic resonance imaging is also helpful in distinguishing COF from intraorbital capillary hemangioma, in which the intraorbital mass shows mixed areas of hyperintensity and hypointensity with homogenous contrast enhancement.10 The absence of bony erosion, nonextension into adjacent structures, and lack of progression also distinguish COF from malignant neoplasms. Strabismus surgery was not appropriate before extraocular muscle biopsy, because malignant disease and inflammatory disorders can manifest similarly but may progress later and cause a change in alignment; therefore, they need to be definitively ruled out with a biopsy. Incisional biopsy in COF usually shows abundant fibrous tissue without inflammatory cells or malignant features.1,7 Investigations for systemic involvement were not appropriate because none of the previously reported cases showed systemic involvement.The pathogenesis of COF is unknown; however, the additional findings of ipsilateral facial hypoplasia and hypoglobus in some patients1 suggest that this condition represents a regional mesodermal dysgenesis. The final visual outcome depends on how early amblyopia treatment is instituted. Even when realignment of the eyes is possible with strabismus surgery, however, ocular rotations will remain limited in the involved eye.The patient was treated with occlusion therapy of the right eye in anticipation of a strabismus surgery. After his amblyopia has resolved (as judged by the ability to maintain fixation with the left eye) or failed to improve during 3 successive visits, we will proceed with a left inferior rectus muscle recession.

Ophthalmology

A healthy 1-year-old boy had a history of restricted movements of the left eye since birth. He had been diagnosed as having an orbital capillary hemangioma at 3 months of age after orbital magnetic resonance imaging (MRI), which had reportedly revealed an orbital mass with enlarged extraocular muscles. He was treated with oral propranolol with no improvement.On examination, the patient had inferior displacement of the left globe with a severe limitation of supraduction and a mild limitation of horizontal movement in the left eye. He was unable to maintain fixation with the left eye. Results of modified Krimsky testing showed 6 prism diopters (PD) of exotropia and 16 PD of left hypotropia. Retinoscopy disclosed a cycloplegic refraction of +2.00 diopters (D) in the right eye and +6.00 D in the left eye. Thyrotropin, thyroxine, and thyroid-stimulating immunoglobulin levels were all within reference ranges. Repeated MRI with coronal images showed massive enlargement of the superior, inferior, and medial rectus muscles (Figure 1). The medial rectus mass extended nasally to produce bowing of the lamina papyrecea, with no extension into adjacent structures. The enlarged extraocular muscles were hypointense on T1- and T2-weighted sequences. An abnormal curvilinear signal in the intraconal fat was isointense with muscle (Figure 1).A, Coronal T1-weighted magnetic resonance imaging (MRI) of both orbits shows enlarged inferior, medial, and superior rectus muscles with an isointense curvilinear signal in the intraconal fat (arrowhead). B, Axial T1-weighted MRI of both orbits shows an orbital mass incorporating the medial rectus muscle.Genetic testing for congenital fibrosis of extraocular muscles

what would you do next?

What would you do next?

Genetic testing for congenital fibrosis of extraocular muscles

Strabismus surgery

Investigate for systemic involvement

Orbital biopsy

d

male

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2668506

A 65-year-old man was referred for evaluation of uveitis in the left eye. Several days after YAG capsulotomy for posterior capsule opacification, his left eye had become red and painful and his visual acuity had declined to counting fingers. Inflammation improved but persisted after vitreous tap and injection of intravitreal vancomycin hydrochloride (1.0 mg) and ceftazidime (2.25 mg) followed by intravitreal triamcinolone acetonide. Vitreous cultures yielded no growth.Six months after the patient’s symptoms began, he presented to our clinic. His visual acuity was 20/20 OD and 20/160 OS improving to 20/120 OS with pinhole. His intraocular pressure was 32 mm Hg OD and 20 mm Hg OS. The results of ophthalmic examination of the left eye were notable for pigmented keratic precipitates, a rare anterior chamber cell, 2+ (ie, 16-25 cells per field) anterior vitreous cells, epiretinal membrane, and cystoid macular edema. Tuberculosis, sarcoidosis, syphilis, and HLA-B27 laboratory test results were negative. The macular edema improved with 4 times daily topical prednisolone acetate and ketorolac tromethamine.After 2 months, the patient reported recurrent pain, redness, and decreased visual acuity. At that time, the visual acuity in the left eye was 20/200E at 2 ft, and there were 4+ (ie, >50 cells per field) anterior chamber cells, a layered hypopyon and 2+ anterior vitreous cells. A subsequent vitreous tap and injection of intravitreal vancomycin hydrochloride (1.0 mg) and ceftazidime (2.25 mg) were performed. Cultures yielded 1+ Propionibacterium acnes.Prescribe topical moxifloxacin and consult an infectious diseases specialistPerform another vitreous tap and intravitreal vancomycin injectionPerform intraocular lens explantation, capsulectomy, and intravitreal vancomycin injectionInject intravitreal vancomycin and administer systemic vancomycin and prednisone What Would You Do Next?

Prescribe topical moxifloxacin and consult an infectious diseases specialist

Perform another vitreous tap and intravitreal vancomycin injection

Perform intraocular lens explantation, capsulectomy, and intravitreal vancomycin injection

Inject intravitreal vancomycin and administer systemic vancomycin and prednisone

Chronic postoperative endophthalmitis secondary to P acnes infection

C

Perform intraocular lens explantation, capsulectomy, and intravitreal vancomycin injection

This patient was referred to us with a delayed postoperative uveitis after YAG capsulotomy and prior cataract extraction in the left eye. His initial vitreous culture results were negative. However, his intraocular inflammation recurred despite intravitreal antibiotics and prolonged treatment with topical corticosteroids. The recurrent inflammation as manifested by decreased visual acuity, anterior chamber inflammation, and vitritis prompted a subsequent vitreous tap and antibiotic injection. The vitreous culture results from this tap were positive for P acnes. After a discussion of options with the patient that included observation vs surgery with capsulectomy alone or with capsulectomy and lens removal, the intraocular lens was explanted, the lens capsule was removed, a pars plana vitrectomy was performed, and vancomycin was given as an intravitreal injection for left eye chronic endophthalmitis secondary to P acnes infection. Intraoperatively, iris retractors were placed to mechanically dilate the pupil and revealed previously hidden subcapsular, fluffy white infiltrates behind the posterior chamber intraocular lens (Figure). Topical, intravitreal, or systemic antibiotics and corticosteroids without surgical removal of the intraocular lens and capsule would not adequately treat the infection because the lens and capsule serve as a nidus for chronic infection.Intraoperative view of the left eye shows (A) subcapsular, fluffy white infiltrates behind the posterior chamber intraocular lens (arrowhead) and (B) close-up of the white infiltrates (arrowhead).Chronic endophthalmitis after cataract surgery can be challenging to diagnose and treat. Patients traditionally present with indolent low-grade inflammation from 6 weeks to several years after cataract surgery; thus, it is difficult to distinguish from a mild case of rebound iritis or a new case of granulomatous uveitis.1-3 Clues to the diagnosis include the delayed presentation along with the presence of keratic precipitates, beaded fibrin strands in the anterior chamber, vitritis, an intracapsular white plaque, and/or a hypopyon. Development of acute pain and inflammation after YAG capsulotomy may be attributable to liberation of organisms from the capsular plaque.3 Raised intraocular pressure has also been reported.4The subtle presentation of chronic endophthalmitis frequently leads to delays in diagnosis. Patients may respond transiently to topical corticosteroids, and initial aqueous or vitreous culture results may be negative, precipitating a misdiagnosis of sterile inflammation. Intravitreal antibiotics alone are usually inadequate if there are microbial colonies sequestered in a subcapsular plaque. In a recent case series5 of patients with chronic pseudophakic endophthalmitis, electron microscopy demonstrated microorganisms within the intraocular lens and capsule. Low virulence organisms, such as coagulase-negative Staphylococcus and P acnes, are the most common chronic endophthalmitis culprits, although rarely fungal organisms, such as Candida albicans and Aspergillus, may be at fault.6P acnes, a gram-positive, anaerobic, pleomorphic bacterium present in periocular flora, may be particularly resilient to treatment because of its ability to inhibit suppressor T cells7 and to prevent phagocytosis by neutrophils or macrophages with its cell wall.8Surgical management is recommended to eradicate the infection.9 A more conservative approach would include a pars plana vitrectomy and limited posterior capsulectomy to remove the capsular plaque, followed by intravitreal antibiotic injections. More definitive management entails lens explantation and total lens capsulectomy, along with intravitreal antibiotic injections.4,9,10 In this particular case, poor dilation did not reveal subcapsular infiltrate until surgery and the YAG capsulotomy had removed any potentially visible posterior capsular plaque. With appropriate and timely management, visual prognosis for chronic endophthalmitis is better than that for acute endophthalmitis due to more virulent organisms.Six weeks after surgery, the patient’s best-corrected visual acuity had improved to 20/60, and he had 3+ (ie, 26-50 cells per field) pigmented cells in the anterior chamber with mild vitreous debris in the left eye. As his corticosteroids are tapered, he will be closely followed up for any evidence of recurrence.

Ophthalmology

A 65-year-old man was referred for evaluation of uveitis in the left eye. Several days after YAG capsulotomy for posterior capsule opacification, his left eye had become red and painful and his visual acuity had declined to counting fingers. Inflammation improved but persisted after vitreous tap and injection of intravitreal vancomycin hydrochloride (1.0 mg) and ceftazidime (2.25 mg) followed by intravitreal triamcinolone acetonide. Vitreous cultures yielded no growth.Six months after the patient’s symptoms began, he presented to our clinic. His visual acuity was 20/20 OD and 20/160 OS improving to 20/120 OS with pinhole. His intraocular pressure was 32 mm Hg OD and 20 mm Hg OS. The results of ophthalmic examination of the left eye were notable for pigmented keratic precipitates, a rare anterior chamber cell, 2+ (ie, 16-25 cells per field) anterior vitreous cells, epiretinal membrane, and cystoid macular edema. Tuberculosis, sarcoidosis, syphilis, and HLA-B27 laboratory test results were negative. The macular edema improved with 4 times daily topical prednisolone acetate and ketorolac tromethamine.After 2 months, the patient reported recurrent pain, redness, and decreased visual acuity. At that time, the visual acuity in the left eye was 20/200E at 2 ft, and there were 4+ (ie, >50 cells per field) anterior chamber cells, a layered hypopyon and 2+ anterior vitreous cells. A subsequent vitreous tap and injection of intravitreal vancomycin hydrochloride (1.0 mg) and ceftazidime (2.25 mg) were performed. Cultures yielded 1+ Propionibacterium acnes.Prescribe topical moxifloxacin and consult an infectious diseases specialistPerform another vitreous tap and intravitreal vancomycin injectionPerform intraocular lens explantation, capsulectomy, and intravitreal vancomycin injectionInject intravitreal vancomycin and administer systemic vancomycin and prednisone

what would you do next?

What would you do next?

Prescribe topical moxifloxacin and consult an infectious diseases specialist

Inject intravitreal vancomycin and administer systemic vancomycin and prednisone

Perform intraocular lens explantation, capsulectomy, and intravitreal vancomycin injection

Perform another vitreous tap and intravitreal vancomycin injection

c

male

61-70

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2663281

A woman in her 20s previously prescribed and currently taking valproic acid and phenytoin for epilepsy presented to the clinic with a 2-month history of gradually worsening pruritic plaques that initially involved the scalp, face, and neck, and later affected the anterior and posterior chest wall, abdomen, upper arms, and thighs; she also had nodules over the nose and cheeks (Figure 1A).Clinical photographs show (A) nodules on the head and neck on presentation and (B) nodules of of increasing thickness after 6 months.It was thought that she developed exfoliative dermatitis secondary to valproic acid and phenytoin. Medications were switched to levetiracetam, and a tapering dose of steroid was prescribed. Her skin lesions slightly improved.Two months later, she developed diffuse urticarial lesions of varying sizes over the old plaques. These lesions were well-defined with demarcated borders and were minimally pruritic at the time.Given that her condition worsened despite changing her medication, the lesions were biopsied and analyzed, and the results were inconclusive, demonstrating atypical lymphoid infiltrate. The T cell receptor γ gene (TRG) rearrangement analysis by polymerase chain reaction (PCR) was negative.The plaques and nodules worsened over a 6-month period, becoming more numerous and increasing in thickness, especially on the face, and early leonine facies developed (Figure 1B). The results from analysis of a second biopsy specimen showed dense band-like lymphoid infiltrate in the superficial dermis with mild epidermotropism. As her condition continued to worsen, a third biopsy specimen was obtained, and the result was consistent with the suspected diagnosis. What Is Your Diagnosis?

Lymphomatoid papulosis

Reactive lymphomatoid reaction secondary to drugs

Mycosis fungoides

Adult T-cell leukemia lymphoma

C. Mycosis fungoides

C

Mycosis fungoides

The papules in lymphomatoid papulosis are characterized by the presence of central necrosis and crusting. Lesions subside by discontinuing the causative drug in reactive lymphomatoid reaction where TRG gene rearrangement is always negative. In adult T cell leukemia lymphoma, the antibody against human T-lymphotropic virus 1 is found in the blood. Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma (CTCL) subtype and is considered extranodal indolent non-Hodgkin lymphoma with T-cell origin. Mycosis fungoides accounts for 54% of the CTCLs and almost 4% of cases of non-Hodgkin lymphoma in the United States. Its incidence is higher in men and black patients, with the incidence rate increasing with age.1 Clinically, MF presentation mimics other dermatological conditions, making the diagnosis challenging at early stages.2 Given the difficulty of MF diagnosis, a diagnostic algorithm was developed by the International Society for Cutaneous Lymphomas and the European Organization for Research and Treatment of Cancer to help in establishing the diagnosis. This point-based algorithm takes into account 4 aspects: clinical, histopathologic, molecular biological, and immunopathologic features. A total of 4 points is needed to establish the diagnosis of MF.3This patient’s skin lesions started as small patches and plaques, progressed to exfoliative lesions, then to nodules. Histopathologic findings were positive for upper dermal atypical lymphoid infiltrate. Molecular testing showed positive TRG gene rearrangement. Immunopathologic testing showed T cells from multiple nodular aggregates with expression of CD2, CD4, and CD5. Her stage was IIIB.The cause of MF is ill defined, though theories suggest underlying genetic predisposition with environmental triggers.4 Patients usually have similar symptoms to other inflammatory dermatological conditions such as psoriasis, chronic dermatitis, and vitiligo.4 Mycosis fungoides usually affects multiple areas simultaneously and generally affect body parts not exposed to the sun. The lesion of MF might present as patches, plaques, or tumors, which are the most common cutaneous manifestations, or generalized erythroderma. Poikiloderma is a more distinct but rare variant of MF. These lesions may increase in size and coalesce, affecting more surface areas. As in this patient, topical and/or oral steroids are effective in early-stage MF, which may confuse the diagnosis with other dermopathies, delaying diagnosis for a long time.5Diagnosis of early-stage MF is not only challenging clinically but also histopathologically. Several pathological features observed in MF can also be seen in other inflammatory diseases. Examples of those features include the following: haloed lymphocytes, Pautrier abscesses, disproportional exocytosis, and lymphocytes aligned within the basal layer. Haloed lymphocytes are considered the most suggestive of MF.6 The most substantial prognostic factors in the survival rate of MF are patient age at presentation; T, N, and B classifications; overall clinical stage; and the presence or absence of extracutaneous disease.7 The preferred method of treatment in early stage MF is skin-directed therapy, which includes topical corticosteroids, ultraviolet B, combination treatment consisting of Psoralens and then exposure of the skin to ultraviolet A, localized radiotherapy, and mechlorethamine. For more advanced stages, systemic therapy is indicated.8 This patient received multiple therapies in adjunct with radiotherapy, including bexarotene, which was discontinued because of allergic adverse effects; vorinostat, which resulted in worsening of the patient’s underlying epilepsy; and romidepsin, which resulted in resolved skin lesions (Figure 2).Clinical photograph of resolved skin lesions on the head and neck.Romidepsin is one of the histone deacetylase inhibitors that are approved for the treatment of MF, with an overall response rate of 34%.9 This case illustrates the importance of identifying indolent CTCLs, mainly MF, and offering patients new treatments if previous regimens fail. In such patients with refractory skin involvement or extracutaneous disease, enrollment in a clinical trial of novel agents is appropriate.

Oncology

A woman in her 20s previously prescribed and currently taking valproic acid and phenytoin for epilepsy presented to the clinic with a 2-month history of gradually worsening pruritic plaques that initially involved the scalp, face, and neck, and later affected the anterior and posterior chest wall, abdomen, upper arms, and thighs; she also had nodules over the nose and cheeks (Figure 1A).Clinical photographs show (A) nodules on the head and neck on presentation and (B) nodules of of increasing thickness after 6 months.It was thought that she developed exfoliative dermatitis secondary to valproic acid and phenytoin. Medications were switched to levetiracetam, and a tapering dose of steroid was prescribed. Her skin lesions slightly improved.Two months later, she developed diffuse urticarial lesions of varying sizes over the old plaques. These lesions were well-defined with demarcated borders and were minimally pruritic at the time.Given that her condition worsened despite changing her medication, the lesions were biopsied and analyzed, and the results were inconclusive, demonstrating atypical lymphoid infiltrate. The T cell receptor γ gene (TRG) rearrangement analysis by polymerase chain reaction (PCR) was negative.The plaques and nodules worsened over a 6-month period, becoming more numerous and increasing in thickness, especially on the face, and early leonine facies developed (Figure 1B). The results from analysis of a second biopsy specimen showed dense band-like lymphoid infiltrate in the superficial dermis with mild epidermotropism. As her condition continued to worsen, a third biopsy specimen was obtained, and the result was consistent with the suspected diagnosis.

what is your diagnosis?

What is your diagnosis?

Adult T-cell leukemia lymphoma

Mycosis fungoides

Reactive lymphomatoid reaction secondary to drugs

Lymphomatoid papulosis

b

female

21-30

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2669916

A 30-year-old man presented for evaluation of palpitations and exertional dyspnea when climbing stairs, mostly at night. Physical examination was unremarkable, except for sinus tachycardia. Laboratory test results were all within normal limits. The electrocardiogram showed sinus rhythm and early repolarization changes (Figure, A). Thirty-day event monitoring showed sinus tachycardia during episodes of palpitation. The transthoracic echocardiogram is shown in Figure, B, and Video 1. The left ventricular ejection fraction was between 56% and 60%. The estimated pulmonary artery systolic pressure was 24 mm Hg. A transesophageal echocardiogram was also performed (Video 2 and Video 3).A, Electrocardiography showing sinus rhythm and early repolarization changes. B, Four-chamber view of 2-dimensional transthoracic echocardiography.Manage the patient medically and perform repeated transthoracic echocardiography in 6 months What Would You Do Next?

Manage the patient medically and perform repeated transthoracic echocardiography in 6 months

Perform transcatheter balloon mitral valvuloplasty

Perform surgical mitral valve repair and annuloplasty

Perform surgical left atriotomy and membrane resection

Cor triatriatum

C

Perform surgical mitral valve repair and annuloplasty

D. Perform surgical left atriotomy and membrane resectionA rare congenital abnormality, cor triatriatum sinister is a surgically treatable heart defect. The first surgical procedure to correct the defect was performed in 1956, and ever since, corrective surgery has been the treatment of choice in symptomatic patients.1 The surgical procedure involves left or right atriotomy, fibrous membrane removal, and concomitant correction of associated intracardiac defects. Uncorrected cor triatriatum may lead to left atrial enlargement and development of arrhythmias. Cor triatriatum represents 0.1% of all congenital cardiac anomalies2 and can be diagnosed at any age, depending on the severity of the obstruction and concomitant presenting symptoms. The defect is slightly more predominant in men than women, with a ratio of 1.5:1.3Classically in this defect, the left atrium is divided into a posterior and an anterior chamber by a diaphragm. The diaphragm may have 1 or more restrictive ostia. Pulmonary veins enter the posterior proximal left atrial chamber, and the anterior distal left atrial chamber contains the mitral valve and the left atrial appendage. Cor triatriatum may be an isolated lesion or may occur in association with other congenital cardiac aberrations.Presenting symptoms simulate those of supravalvular mitral ring, mitral stenosis, or pulmonary venous stenosis. All of these conditions have a hemodynamic obstruction between the pulmonary venous system and left heart chambers. The usual symptoms are dyspnea, orthopnea, hemoptysis, and chest pain. In symptomatic patients, treatment consists of resection of the diaphragm and correction of the associated congenital heart defects. Echocardiography is the most commonly used noninvasive method to diagnose anatomical cardiac defects, especially those that are located within the intra-atrial area.4More often than not, the defect is a hemodynamically benign finding. The membrane of cor triatriatum looks like a linear shadow that divides the left atrium into an upper chamber (embryonic common pulmonary vein) and a lower chamber (embryonic left atrium). The lower chamber leads to the mitral inflow tract. On color flow mapping, mild increases in flow velocity are seen that signify minimal obstruction.In adults, cardiac magnetic resonance imaging may be useful. However, it is not a good choice for infants and children. Compared with echocardiography and angiography, magnetic resonance imaging has been shown to have a greater rate of detection.5After detailed discussion of the treatment options, the patient was recommended to undergo elective surgery. He declined surgery at this time and continues to be observed with medical management.

Cardiology

A 30-year-old man presented for evaluation of palpitations and exertional dyspnea when climbing stairs, mostly at night. Physical examination was unremarkable, except for sinus tachycardia. Laboratory test results were all within normal limits. The electrocardiogram showed sinus rhythm and early repolarization changes (Figure, A). Thirty-day event monitoring showed sinus tachycardia during episodes of palpitation. The transthoracic echocardiogram is shown in Figure, B, and Video 1. The left ventricular ejection fraction was between 56% and 60%. The estimated pulmonary artery systolic pressure was 24 mm Hg. A transesophageal echocardiogram was also performed (Video 2 and Video 3).A, Electrocardiography showing sinus rhythm and early repolarization changes. B, Four-chamber view of 2-dimensional transthoracic echocardiography.Manage the patient medically and perform repeated transthoracic echocardiography in 6 months

what would you do next?

What would you do next?

Perform transcatheter balloon mitral valvuloplasty

Perform surgical mitral valve repair and annuloplasty

Manage the patient medically and perform repeated transthoracic echocardiography in 6 months

Perform surgical left atriotomy and membrane resection

b

male

21-30

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2670737

An otherwise healthy 3-year-old boy presented with symptoms of sleep-disordered breathing. He had no reported respiratory issues at birth and no feeding difficulties. His symptoms included gasping and apneic episodes at night, as well as nighttime nasal congestion. He had been evaluated by an outside otolaryngologist, who had scheduled an adenoidectomy. Intraoperatively, he was found to have a nasopharyngeal mass, and thus surgery was aborted. Nasal endoscopy in clinic revealed a firm, mobile mass in the nasopharynx. Magnetic resonance imaging of the brain revealed a 21 × 14 × 18-mm irregular, but well-defined, heterogeneously enhancing mass in the left nasopharynx with increased perfusion (Figure, A). Given the vascularity of the tumor, the boy underwent preoperative embolization with interventional radiology. He was subsequently taken to the operating room, where endoscopic resection of the mass and division of the pedicle were performed without complication (Figure, B). Final pathologic results demonstrated keratinizing squamous cysts and collections of ductal structures set within a myxoid stroma, with small nests of primitive mesenchyme (Figure, C and D). What Is Your Diagnosis?

Dermoid

Salivary gland anlage tumor

Nasopharyngeal carcinoma

Hemangioma

B. Salivary gland anlage tumor

B

Salivary gland anlage tumor

Salivary gland anlage tumors (SGATs) are benign, congenital tumors that traditionally are diagnosed in the first week of life owing to nasal obstruction in neonates, who are obligate nasal breathers.1 These tumors are rare, with fewer than 50 reported in the literature. There is a male sex predilection, with males comprising more than 70% of reported cases.1,2 Smaller SGATs may not present with respiratory distress initially at birth and may present later in childhood. To date, no cases of SGAT have been reported to be associated with sleep-disordered breathing or obstructive sleep apnea. This report of SGAT presentation at a relatively older age with no perinatal respiratory distress demonstrates that these tumors may remain undiagnosed for years, particularly if causing primarily unilateral nasal obstruction.Salivary anlage tumors are thought to arise from minor salivary glands.3 Histopathologic reviews have suggested these lesions are actually hamartomas rather than neoplasms given their benign nature and congenital status.1,3 The tissues of the SGAT generally stain strongly positive for salivary amylase, suggesting a salivary gland origin.3 However, the exact histogenesis is still unknown because mature salivary gland structures are generally absent. In addition, the fact that these lesions appear only on the midline nasal septum, and not in other minor salivary gland locations, brings this proposed pathogenesis into question. Histologically, these appear as heterogeneous benign tumors with epithelial and mesenchymal components. The epithelium generally is nonkeratinizing squamous epithelium with tubular glandular components. The stromal component generally consists of benign-appearing spindle cells.3In general, these lesions are attached by a thin, vascular stalk along the posterior septum or midline nasopharynx, as in this patient. Thus, usually these lesions are easily treated with endoscopic resection. Because these are benign tumors, there are few descriptions of local invasion. Only 1 reported salivary anlage tumor case had intracranial extension, requiring a combined bicoronal and endoscopic approach to excision.4 Outcomes are almost universally good, with no reports of recurrence after complete excision.The differential diagnosis of midline nasal lesions in children can be broad, ranging from benign to aggressive malignant lesions. Included in the differential diagnoses of a midline posterior nasal mass are benign lesions (dermoid cysts, encephaloceles, gliomas, teratomas), malignant neoplasms (lymphoma, rhabdomyosarcoma, nasopharyngeal carcinoma), and vascular tumors. Salivary gland anlage tumors may be suspected clinically as opposed to these other lesions based on their pedunculated nature, overall benign behavior, and typical early age of presentation.

General

An otherwise healthy 3-year-old boy presented with symptoms of sleep-disordered breathing. He had no reported respiratory issues at birth and no feeding difficulties. His symptoms included gasping and apneic episodes at night, as well as nighttime nasal congestion. He had been evaluated by an outside otolaryngologist, who had scheduled an adenoidectomy. Intraoperatively, he was found to have a nasopharyngeal mass, and thus surgery was aborted. Nasal endoscopy in clinic revealed a firm, mobile mass in the nasopharynx. Magnetic resonance imaging of the brain revealed a 21 × 14 × 18-mm irregular, but well-defined, heterogeneously enhancing mass in the left nasopharynx with increased perfusion (Figure, A). Given the vascularity of the tumor, the boy underwent preoperative embolization with interventional radiology. He was subsequently taken to the operating room, where endoscopic resection of the mass and division of the pedicle were performed without complication (Figure, B). Final pathologic results demonstrated keratinizing squamous cysts and collections of ductal structures set within a myxoid stroma, with small nests of primitive mesenchyme (Figure, C and D).

what is your diagnosis?

What is your diagnosis?

Nasopharyngeal carcinoma

Salivary gland anlage tumor

Dermoid

Hemangioma

b

male

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2672746

A man in his 50s presented for an emergency examination with a hard swelling of the left inner cheek. He stated that he had recently bitten his cheek and had since experienced increasing spontaneous pain and swelling. There was no obvious swelling extraorally. Oral examination revealed an erythematous, 15 × 10-mm lesion of the buccal mucosa, adjacent to the maxillary first molar. The lesion was hard and produced a small amount of bleeding with palpation (Figure 1). What Is Your Diagnosis?

Mucoepidermoid carcinoma

Sialolith

Intraoral lipoma

Unusual mucocele

B. Sialolith

B

Sialolith

Sialoliths are calcified structures that form within the ducts of salivary glands, most of which develop in the submandibular gland. The longer length and tortuous nature of the submandibular duct with the thicker consistency of submandibular saliva likely contribute to this predilection. Although rarer in occurrence, sialoliths can also develop in ducts of minor salivary glands, the sublingual gland, and, as in this case, the parotid gland.1,2 The rarity of sialoliths in the parotid gland duct is likely due to the serous nature of parotid gland saliva. Formation of a sialolith involves the concentric deposition of calcified material around a central nidus. Symptoms are episodic pain and swelling, especially at mealtime, owing to salivary flow obstruction during stimulation.3 Longstanding sialoliths can become secondarily infected with pus formation.While treatment of small stones located near the surface can be removed with gentle massaging of mucosal tissue, larger stones may require surgical removal.3 Larger stones located distally in the duct can be removed through an intraoral approach or extraoral approach in combination with endoscopy for visualization of the sialolith; the addition of endoscopy to surgery can spare patients from excisional gland procedures and risk of nerve injury.3-5 Although often cost-prohibitive, extracorporeal shockwave lithotripsy and thulium-YAG laser are alternative methods to remove larger sialoliths through fragmentation.5 Clinically, an ulcerated mass in the buccal mucosa can be a diagnostic dilemma for the clinician. One cause for concern is that mucoepidermoid carcinoma is one of the most common malignant neoplasms of the parotid gland, and can present as a slow-growing indolent tumor. Yet mucoceles can present in locations other than the lower lip6 and become unusually large, especially when there is low resistance in surrounding connective tissues. But given that sialoliths are radiopaque, radiographic studies, such as computed tomography4 and even simple radiographs, can help to reliably diagnosis sialolithiasis. The presence of radiopaque stones would effectively rule out mucoepidermoid carcinoma, unusual mucocele, and intraoral lipoma. In this case, the lesion was located approximately where the parotid gland duct opens into the oral cavity, normally marked by a small papilla adjacent to the maxillary molars (Stensen duct).Suspecting a superficial sialolith, local anesthetic was directly applied to the lesion and a shallow incision was created. Pressure was applied to the lesion, and an 8 × 5-mm stone was removed through the incision line (Figure 2). The patient reported instant relief. The parotid duct was palpated, and salivary flow was restored from the duct.

General

A man in his 50s presented for an emergency examination with a hard swelling of the left inner cheek. He stated that he had recently bitten his cheek and had since experienced increasing spontaneous pain and swelling. There was no obvious swelling extraorally. Oral examination revealed an erythematous, 15 × 10-mm lesion of the buccal mucosa, adjacent to the maxillary first molar. The lesion was hard and produced a small amount of bleeding with palpation (Figure 1).

what is your diagnosis?

What is your diagnosis?

Sialolith

Intraoral lipoma

Mucoepidermoid carcinoma

Unusual mucocele

a

male

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2672752

A woman in her 30s with a history of bruxism and long-term use of a bite guard presented with pain centering on left submandibular area for 2 years. She was initially prescribed a muscle relaxant without notable improvement. Physical examination revealed a mild firmness in the left submandibular area. The mucosa of the oral cavity and floor of mouth was normal. Cranial nerve function, including tongue mobility and sensation, was also normal. Contrast-enhanced computed tomography (CT) demonstrated a 1.7 × 1.5 × 1.4-cm mass, adjacent to the left submandibular gland. Scattered, nonenlarged lymph nodes were observed (Figure, A). An ultrasonography-guided fine needle aspiration biopsy was nondiagnostic owing to an inability to obtain sufficient tissue. The patient underwent surgical exploration with left submandibular gland excision and resection of the left submandibular mass (Figure, B). Histopathologic findings showed spindle cell neoplasm with morphologic features and no malignant neoplasm identified (Figure, C). Results from immunohistochemical analysis were positive for S100 (Figure, D) and negative for smooth muscle actin, CD34, and pankeratin.A, Contrast-enhanced computed tomographic (CT) image. B, Submandibular mass after removing the left submandibular gland. C, Hematoxylin-eosin–stained frozen section of the mass. D, Positive S-100 immunohistochemical stain. What Is Your Diagnosis?

Submandibular gland pleomorphic adenoma

Chronic lymphadenitis

Hypoglossal nerve schwannoma

Chronic submandibular sialadenitis

C. Hypoglossal nerve schwannoma

C

Hypoglossal nerve schwannoma

Once the left submandibular gland was excised, intraoperative findings showed that the hypoglossal nerve ran both proximally and distally out of the mass. The histologic features of the excised mass were characteristic of a schwannoma. The initial frozen hematoxylin-eosin–stained sections showed a bland proliferation of spindle cells in early Antoni A pattern with poorly formed Verocay bodies (Figure, C). Immunohistochemical analysis was positive for S100 (Figure, D), negative for smooth muscle actin, CD34, and pankeratin. Based on these findings, the diagnosis of hypoglossal nerve schwannoma was confirmed.Nonvestibular schwannomas are rare, and schwannomas originating from a pure motor cranial nerve, such as the hypoglossal nerve, are even more scarce.1 Hypoglossal nerve schwannomas are benign and slow-growing tumors. Surgical resection has been considered the standard treatment for the treatment of nonvestibular schwannomas.2A grading scale is useful to guide surgical treatment for this rare type of tumor. Based on a review of previous studies of hypoglossal schwannomas,3,4 along with the different growth patterns of these tumors, Nonaka et al5 proposed a modified grading scale for hypoglossal nerve schwannomas. The classification of hypoglossal nerve schwannomas includes type A, intradural tumor; type B, dumbbell-shaped tumor; type C, extracranial cranial base tumor; and type D, peripheral tumor as a tumor without osseous involvement. According to the imaging results, this case belongs to type D, which allowed a high cervical approach without the need for bone removal. According to the modified classification, type A, B, C, and D tumors were seen in 31.7%, 38.6%, 6.2%, and 23.4%5 of cases, respectively.Nonvestibular head and neck schwannomas occur most frequently in the parapharyngeal space, and presenting signs and symptoms are usually related to mass effect or neural deficit.6 Patients presented most commonly with tongue atrophy on the side of the tumor, followed by headache, dysphagia, dizziness, hearing loss, and speech disturbance.7 Clinical presentation of the peripheral type (type D) of hypoglossal nerve schwannomas is varied. The most common is painless palpable and mass at neck (84.4%),5 which is not specific. Peripheral type D is also may present as tongue atrophy (28.0%), dysphagia (21.9%), or speech disturbance, or may be asymptomatic. More than 40% of nonsyndromic benign solitary schwannomas are located in the head and neck region.8

General

A woman in her 30s with a history of bruxism and long-term use of a bite guard presented with pain centering on left submandibular area for 2 years. She was initially prescribed a muscle relaxant without notable improvement. Physical examination revealed a mild firmness in the left submandibular area. The mucosa of the oral cavity and floor of mouth was normal. Cranial nerve function, including tongue mobility and sensation, was also normal. Contrast-enhanced computed tomography (CT) demonstrated a 1.7 × 1.5 × 1.4-cm mass, adjacent to the left submandibular gland. Scattered, nonenlarged lymph nodes were observed (Figure, A). An ultrasonography-guided fine needle aspiration biopsy was nondiagnostic owing to an inability to obtain sufficient tissue. The patient underwent surgical exploration with left submandibular gland excision and resection of the left submandibular mass (Figure, B). Histopathologic findings showed spindle cell neoplasm with morphologic features and no malignant neoplasm identified (Figure, C). Results from immunohistochemical analysis were positive for S100 (Figure, D) and negative for smooth muscle actin, CD34, and pankeratin.A, Contrast-enhanced computed tomographic (CT) image. B, Submandibular mass after removing the left submandibular gland. C, Hematoxylin-eosin–stained frozen section of the mass. D, Positive S-100 immunohistochemical stain.

what is your diagnosis?

What is your diagnosis?

Submandibular gland pleomorphic adenoma

Chronic submandibular sialadenitis

Chronic lymphadenitis

Hypoglossal nerve schwannoma

d

female

31-40

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2674043

A male smoker in his 60s presented to the dermatology department with a right supraclavicular cutaneous mass that had persisted for 2 years (Figure, A). This mass underwent progressive growth during the first year but subsequently stabilized. Despite causing occasional pruritus, the lesion was otherwise asymptomatic. A shave biopsy specimen revealed islands of large epithelioid cells with increased mitotic index surrounded by a dense lymphocytic infiltrate (Figure, B and C). The tumor cells expressed p16 (Figure, D) and epithelial membrane antigen (EMA), p63, and CK903, and were negative for prostate-specific antigen, CDX2, thyroid transcription factor 1, S-100, chromogranin, synaptophysin, and CD56. In situ hybridization for Epstein-Barr virus (EBV) was negative. Otolaryngology referral was sought to rule out a head or neck primary neoplasm. With the exception of the cutaneous neoplasm, the findings from the otolaryngologic examination were unremarkable. A screening chest computed tomographic (CT) image showed multiple right lung nodules, the largest of which measured 2.4 cm in diameter. A biopsy of this pulmonary nodule showed a well-differentiated adenocarcinoma with lepidic pattern, and further workup revealed an intestinal tumor as the primary source. Positron emission tomography and CT imaging demonstrated a mildly fludeoxyglucose F 18–avid superficial supraclavicular soft-tissue mass but no primary head or neck malignant neoplasm or local nodal metastases. A wide local excision of the cutaneous mass and a right level Vb neck dissection were performed. The final pathology report showed residual neoplasm with negative margins and 5 negative lymph nodes. Clinical observation was recommended.A, 6.5 × 2.5-cm erythematous, raised, nontender lesion localized to skin without underlying tethering. B, Carcinoma and rich lymphoplasmacytic infiltrate (original magnification ×200). C, Carcinoma showing anaplasia and atypical mitoses (arrowhead) (original magnification ×400). D, Immunohistochemical staining for p16 with strong and diffuse expression (original magnification ×200). What Is Your Diagnosis?

Metastatic nasopharyngeal carcinoma

Melanoma

Lymphoepithelioma-like carcinoma

Cutaneous lymphadenoma

C. Lymphoepithelioma-like carcinoma

C

Lymphoepithelioma-like carcinoma

Lymphoepithelioma-like carcinoma (LELC) is a rare malignant neoplasm that occurs outside of the nasopharynx and has histologic features that are indistinguishable from nonkeratinizing nasopharyngeal carcinoma. Sites of origin include the salivary glands, larynx, soft palate, lungs, and skin.1 The cutaneous variant was first described in the literature in 1988 by Swanson et al.2 Since then, fewer than 60 additional cases have been documented.3 LELC of the skin exhibits a male preponderance, with a propensity for middle-aged and elderly adults. It tends to occur on sun-exposed areas of the head and neck, and the typical presentation entails a slow-growing, firm, flesh-colored, or erythematous nodule, plaque, or papule.1,4The characteristic histomorphologic findings include nests, cords, or sheets of polygonal epithelioid cells interspersed with a dense, heterogeneous B- and T-cell infiltrate.4 The tumor cells are positive for keratins, EMA, and p63, and negative for S-100 and the neuroendocrine markers chromogranin, synaptophysin, and CD56. EMA expression may indicate an origin in sweat glands.5,6 In this patient, p16 was strongly and diffusely expressed. Expression of p16 has been reported in LELC of various sites but seems to be unrelated to human papillomavirus (HPV) infection. Results for HPV in situ hybridization in this patient were negative. However, this technique detects only HPV 16 and 18, and the presence of other HPV subtypes cannot be ruled out. Although an etiologic link between the EBV and primary LELC of other anatomic sites has been established, this is a very rare finding in the cutaneous variant.1,6Histologic features and immunohistochemical results are, therefore, essential to differentiate cutaneous LELC from other entities with similar histologic features, including melanoma, cutaneous lymphadenoma, lymphoma, and metastases from nasopharyngeal carcinoma and other sites. Primary nasopharyngeal carcinoma rarely metastasizes to the skin and is positive for EBV.4 Melanoma can be excluded on the basis of its positivity for S-100 and other melanoma markers, and negative staining for cytokeratins.7 Cutaneous lymphadenoma consists of lobules of cytologically bland basaloid cells with peripheral palisading in fibrous tissue.3 Lymphoma is negative for keratins and expresses a variety of lymphoid markers depending of the subtype.5Treatment of cutaneous LELC typically entails wide local excision with evaluation of surgical margins with subsequent close clinical observation.3 Mohs micrographic surgery has also been used given the tendency to recurrence after incomplete surgical excision.8 Radiation therapy has traditionally been reserved for tumor recurrences or patients with metastatic disease.3 Cutaneous LELC has low metastatic potential, and patients have a relatively good prognosis.1,3

General

A male smoker in his 60s presented to the dermatology department with a right supraclavicular cutaneous mass that had persisted for 2 years (Figure, A). This mass underwent progressive growth during the first year but subsequently stabilized. Despite causing occasional pruritus, the lesion was otherwise asymptomatic. A shave biopsy specimen revealed islands of large epithelioid cells with increased mitotic index surrounded by a dense lymphocytic infiltrate (Figure, B and C). The tumor cells expressed p16 (Figure, D) and epithelial membrane antigen (EMA), p63, and CK903, and were negative for prostate-specific antigen, CDX2, thyroid transcription factor 1, S-100, chromogranin, synaptophysin, and CD56. In situ hybridization for Epstein-Barr virus (EBV) was negative. Otolaryngology referral was sought to rule out a head or neck primary neoplasm. With the exception of the cutaneous neoplasm, the findings from the otolaryngologic examination were unremarkable. A screening chest computed tomographic (CT) image showed multiple right lung nodules, the largest of which measured 2.4 cm in diameter. A biopsy of this pulmonary nodule showed a well-differentiated adenocarcinoma with lepidic pattern, and further workup revealed an intestinal tumor as the primary source. Positron emission tomography and CT imaging demonstrated a mildly fludeoxyglucose F 18–avid superficial supraclavicular soft-tissue mass but no primary head or neck malignant neoplasm or local nodal metastases. A wide local excision of the cutaneous mass and a right level Vb neck dissection were performed. The final pathology report showed residual neoplasm with negative margins and 5 negative lymph nodes. Clinical observation was recommended.A, 6.5 × 2.5-cm erythematous, raised, nontender lesion localized to skin without underlying tethering. B, Carcinoma and rich lymphoplasmacytic infiltrate (original magnification ×200). C, Carcinoma showing anaplasia and atypical mitoses (arrowhead) (original magnification ×400). D, Immunohistochemical staining for p16 with strong and diffuse expression (original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Metastatic nasopharyngeal carcinoma

Cutaneous lymphadenoma

Melanoma

Lymphoepithelioma-like carcinoma

d

male

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2676086

A 56-year-old woman with no medical comorbidities presented to her primary care clinician with postprandial retrosternal burning that occurred multiple times daily for several years. She had no dysphagia, gastrointestinal bleeding, weight loss, anemia, or exertional chest pain. Over-the-counter antacids provided incomplete benefit. She was prescribed proton pump inhibitor (PPI) therapy with esomeprazole 40 mg, which she took daily, 30 minutes before breakfast. Her heartburn did not improve and continued to bother her daily despite adding famotidine at bedtime.Esophagogastroduodenoscopy (EGD) results, with esophageal mucosal biopsies, were normal. She was referred for esophageal physiologic testing for possible gastroesophageal reflux disease (GERD). Twenty-four-hour ambulatory reflux monitoring was performed after acid suppressive medications were discontinued for 1 week (Table). What Would You Do Next?

Increase esomeprazole to 40 mg twice daily.

Perform a barium esophagogram.

Refer to a surgeon for antireflux surgery.

Replace esomeprazole with nortriptyline.

D

Replace esomeprazole with nortriptyline.

When heartburn does not improve with empirical PPI therapy within 4 weeks, the next appropriate step is an EGD.2 Advanced erosive esophagitis (visible inflammation), Barrett esophagus, or peptic stricture on EGD are confirmatory evidence for GERD1; heartburn improves with antireflux therapy in more than 70% of patients in these settings.3For patients with persisting esophageal symptoms and unremarkable EGD results, ambulatory reflux monitoring quantifies esophageal acid exposure time (AET) and assesses relationships between reflux episodes and symptoms ( performed after stopping PPI therapy for 5-7 days in the absence of prior confirmatory evidence for GERD [as in this patient]).2 Testing can be performed with a transnasal esophageal catheter (24 hours of recording before catheter removal) or a wireless capsule attached to the esophageal mucosa at endoscopy (with the esophageal pH sensor positioned 5 cm above the lower esophageal sphincter). Esophageal AET indicates the duration of time when pH is less than 4 at this sensor, expressed as a percentage of the recording duration. When AET is greater than 4%, symptom improvement with antireflux therapy is seen in 73% to 76% of patients.3-5 In 2017, Medicare paid $152.46 for ambulatory reflux monitoring.Two parameters from ambulatory reflux monitoring are used for diagnosing GERD: AET and reflux-symptom association.6 During monitoring, symptoms occurring within 2 minutes following a reflux episode are considered associated with reflux, reported either as the ratio of associated symptoms to all symptoms (symptom index positive if >50%) or as a statistical association analyzing the presence or absence of reflux episodes and symptoms during each 2-minute period of the reflux study (symptom association probability positive if >95%).2 Evidence for GERD is strongest and symptom relief with antireflux therapy highest if AET and reflux-symptom association are both positive.6 In contrast, normal AET and negative reflux-symptom association fulfill criteria for functional heartburn, which is defined by Rome IV as more than 6 months of burning retrosternal discomfort at least twice weekly; no symptom relief with PPI therapy; and absence of evidence for GERD, eosinophilic esophagitis, or a major esophageal motor disorder.7This patient’s heartburn did not improve with PPI therapy, and EGD did not reveal evidence of GERD or eosinophilic esophagitis. Esophageal manometry results were normal, and ambulatory reflux monitoring demonstrated physiologic acid exposure without reflux-symptom association. Therefore, Rome IV diagnostic criteria for functional heartburn were met. Neuromodulators (such as tricyclic antidepressants or selective serotonin reuptake inhibitors) improve symptoms in functional esophageal disorders, with response rates of 37% to 66%.3,7 Esomeprazole was therefore discontinued, and a central neuromodulator (nortriptyline at bedtime) was initiated.Symptom relief with an empirical trial of PPI therapy has a sensitivity of 71% but a specificity of only 44%, compared with objective esophageal testing for the diagnosis of GERD.8 However, initial empirical treatment is associated with cost-savings compared with initial invasive testing, estimated at approximately $125 over 6 months in a Norwegian analysis.9 Thus, empirical PPI treatment is recommended by gastroenterology consensus guidelines,1 and invasive testing should only be performed if symptoms persist.2Erosive esophagitis is found in 30% of people with heartburn not previously treated with PPI and in less than 10% of people with heartburn who are receiving PPI therapy; therefore, the value of EGD is limited to evaluation for complications (Barrett esophagus, strictures) and exclusion of alternate diagnoses (eosinophilic esophagitis, infectious esophagitis, malignancy). Barium radiography can assess esophageal peristalsis, but spontaneous reflux on a barium study has a sensitivity of only 26% and specificity of 77% for GERD defined by a positive pH study.10At follow-up, this patient reported marked improvement in heartburn frequency and severity. She was weaned off nortriptyline after 3 months and remained symptom free over 1.5 years of follow-up.Patients with typical reflux symptoms (heartburn or regurgitation) without dysphagia, weight loss, gastrointestinal bleeding, or anemia should be empirically treated with proton pump inhibitor (PPI) therapy to assess symptomatic benefit.If symptoms do not resolve with PPI after 4 weeks, and esophagogastroduodenoscopy with esophageal biopsies is normal, ambulatory reflux monitoring can be used to diagnose gastroesophageal reflux disease (GERD). This is best performed off PPI therapy when there is no prior confirmation of GERD.When esophageal acid exposure times are normal and reflux-symptom association is absent on reflux monitoring performed off PPI therapy, symptoms are likely due to a non-GERD or functional (esophageal hypersensitivity) process.

Diagnostic

A 56-year-old woman with no medical comorbidities presented to her primary care clinician with postprandial retrosternal burning that occurred multiple times daily for several years. She had no dysphagia, gastrointestinal bleeding, weight loss, anemia, or exertional chest pain. Over-the-counter antacids provided incomplete benefit. She was prescribed proton pump inhibitor (PPI) therapy with esomeprazole 40 mg, which she took daily, 30 minutes before breakfast. Her heartburn did not improve and continued to bother her daily despite adding famotidine at bedtime.Esophagogastroduodenoscopy (EGD) results, with esophageal mucosal biopsies, were normal. She was referred for esophageal physiologic testing for possible gastroesophageal reflux disease (GERD). Twenty-four-hour ambulatory reflux monitoring was performed after acid suppressive medications were discontinued for 1 week (Table).

what would you do next?

What would you do next?

Replace esomeprazole with nortriptyline.

Increase esomeprazole to 40 mg twice daily.

Perform a barium esophagogram.

Refer to a surgeon for antireflux surgery.

a

female

51-60

original

https://jamanetwork.com/journals/jama/fullarticle/2675526

A 56-year-old woman with a history of ovarian cancer and surgical colostomy presented with a nontender nodule adjacent to her stoma. She was diagnosed 6 years ago with recurrent poorly differentiated serous ovarian carcinoma and underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, with multiple regimens of chemotherapy, most recently with ixabepilone and bevacizumab. Complications included a large bowel obstruction, for which she underwent a transverse loop colostomy 3 years ago.The nodule first appeared 1 year prior. It appeared to increase in size after contact with fecal matter and decrease in size after cleaning of the ostomy site, although it never resolved completely. She reported no pain at the site but described mild burning with fecal-induced irritation. She noted “pus-like” drainage from the nodule and received several courses of antibiotics.Examination revealed a 3-cm firm, pink to violaceous, irregularly shaped multilobulated nodule with a central 1-cm ulcer with undermined borders, overlying an erythematous base (Figure). The nodule was rock-hard, with a friable yellow-red plaque between the nodule and ostomy site. The stoma was red, moist, and well-perfused. What Would You Do Next?

Swab and send for cultures

Obtain a biopsy of the nodule

Consult wound care for barrier protection

Prescribe topical steroids

Cutaneous metastasis from primary serous adenocarcinoma of the ovary

B

Obtain a biopsy of the nodule

The keys to the correct diagnosis are the persistent nature of the nodule despite multiple rounds of antibiotics, as well as its rock-hard nature on palpation. Although the patient reported seeing changes in size associated with stoma hygiene, it is important to recognize that chemotherapy may have affected the size of the nodule as well. While an infection should be considered and may be a secondary component, an expanding or persistent skin nodule in a patient with a history of ovarian cancer should be biopsied, particularly when located within a surgical site. Additional diagnoses to consider include pyoderma gangrenosum, given the undermined ulcer and peristomal location, and granulomatous response secondary to chronic irritation. The possibility of a primary cutaneous carcinoma, such as squamous cell carcinoma or amelanotic melanoma, should also be considered.Cutaneous metastases, although rare, can occur in up to 10.4% of all solid-tumor malignancies.1 They most commonly appear as nodules and may vary in color, with relatively rapid and persistent growth. Metastases to the skin often indicate widespread, advanced disease. Less often, metastases to the skin can be the initial sign of an internal malignancy. Skin metastases are most commonly associated with metastases from melanoma and breast cancer.2 In women, ovarian cancer is the third most common malignancy to present with cutaneous spread.2 Among women with ovarian cancer, skin metastases occur in 3.3% to 3.5%.2,3 Cutaneous metastases have been linked to several different types of ovarian cancer, including serous papillary adenocarcinoma, endometrioid carcinoma, and mucinous carcinoma.3The most common site of cutaneous metastases is on the abdomen, but surgical-site metastases are a well-documented phenomenon in ovarian cancer. These can include port-site metastases, trocar site metastases, and intraperitoneal dissemination following intra-abdominal surgery or diagnostic procedures.2,4,5 The estimated incidence of surgical-site metastasis in patients with gynecologic disease is up to 2%.4 However, van Dam et al found trocar site metastasis in 58% of closed diagnostic laparoscopies and in only 2% of open laparoscopies.5 Several theories have emerged to explain surgical-site metastases, involving gas leak around port sites during use of pneumoperitoneum, spillage of tumor cells along a trocar, or implantation of tumor cells via contact from surgical instruments.4,6Because ovarian cancer–associated cutaneous metastases are rare, data on outcomes for cutaneous metastases are limited. However, making the diagnosis of cutaneous metastases informs prognosis and helps guide overall treatment goals for patients. Cutaneous metastases in ovarian cancer appear later in the course of disease, at a median of 23 months after diagnosis, and are associated with a poor prognosis.3,7 Reported median survival after diagnosis of cutaneous metastases is 4 months (range, 2-65 months).3 Treatment options include skin-directed therapies, such as surgical excisions, localized radiation therapy, and intralesional chemotherapies or immunotherapies; localized radiation therapy; and additional systemic therapies for ovarian cancer.1,7A biopsy of the nodule revealed metastatic adenocarcinoma. The patient was discharged and continued chemotherapy with the addition of pemetrexed. She subsequently declined further treatment and was transitioned to hospice care.

General

A 56-year-old woman with a history of ovarian cancer and surgical colostomy presented with a nontender nodule adjacent to her stoma. She was diagnosed 6 years ago with recurrent poorly differentiated serous ovarian carcinoma and underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, with multiple regimens of chemotherapy, most recently with ixabepilone and bevacizumab. Complications included a large bowel obstruction, for which she underwent a transverse loop colostomy 3 years ago.The nodule first appeared 1 year prior. It appeared to increase in size after contact with fecal matter and decrease in size after cleaning of the ostomy site, although it never resolved completely. She reported no pain at the site but described mild burning with fecal-induced irritation. She noted “pus-like” drainage from the nodule and received several courses of antibiotics.Examination revealed a 3-cm firm, pink to violaceous, irregularly shaped multilobulated nodule with a central 1-cm ulcer with undermined borders, overlying an erythematous base (Figure). The nodule was rock-hard, with a friable yellow-red plaque between the nodule and ostomy site. The stoma was red, moist, and well-perfused.

what would you do next?

What would you do next?

Prescribe topical steroids

Obtain a biopsy of the nodule

Swab and send for cultures

Consult wound care for barrier protection

b

female

51-60

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2658193

A man in his 20s presented with a 2-month history of itchy skin lesions on his trunk, arms, and groin. He was otherwise healthy, with no other underlying conditions, and he was taking no medications. He had no history of atopic dermatitis or other eczematous dermatoses. There were no associated extracutaneous symptoms. His family medical history was relevant only in that his mother had systemic lupus erythematosus.On physical examination, there were several erythematous annular patches on the abdomen (flanks and periumbilical region), lower back, groin, wrists, and legs (Figure, A). The lesions showed slightly raised red-brown borders and a clear center in some patches with no visible scaling, hypopigmentation, induration, or atrophy. Results of laboratory studies including complete blood cell count, biochemical analysis, complement levels, antinuclear antibodies, anti-Ro, anti-La, anti-ribonucleoprotein, anti-Smith, and anti-dsDNA antibodies, as well as serologic testing for syphilis and hepatitis B and C virus, were all normal or negative. A punch biopsy specimen was obtained for histopathologic evaluation (Figure, B and C).A, Clinical image shows several erythematous annular patches on the flanks and periumbilical region. B, Histopathologic analysis of a punch biopsy sample from the abdomen showing superficial lymphocytic infiltrates in the papillary and superficial reticular dermis. C, There are also prominent vacuolar changes at the dermoepidermal junction, and in some areas mild lymphocytic exocytosis. What Is Your Diagnosis?

Pigmented purpuric dermatosis

Mycosis fungoides

Annular lichenoid dermatitis of youth

Secondary syphilis

C. Annular lichenoid dermatitis of youth

C

Annular lichenoid dermatitis of youth

A biopsy specimen was taken from the margins of a lesion and showed a bandlike lymphocytic infiltrate in the papillary dermis with vacuolar changes at the dermoepidermal junction, and some areas of the specimen showed mild exocytosis. Dermal lymphocytes expressed CD3, CD4, and CD8 with slight predominance of CD4-positive over CD8-positive lymphocytes in the infiltrate with no immunophenotypic alterations. The clinicopathologic findings were highly suggestive of annular lichenoid dermatitis of youth (ALDY).The patient was treated with emollients, oral antihistamines for pruritus, topical corticosteroids for a week, and then pimecrolimus cream for maintenance. After 1 month of treatment, he had no pruritus, the lesions presented a marked clinical improvement, and most lesions had almost disappeared. Eleven months later he was still in complete remission.A rare clinicopathological entity, ALDY was first described in 2003 by Annessi et al.1 To date, 46 cases have been reported in the literature. It mainly affects children and young people but has also been described in adults.2 The etiopathogenesis of ALDY is currently unknown, and no relationship has been detected with drug use, autoimmune diseases, infections, or neoplasms.1-6Clinically, ALDY is characterized by erythematous annular patches with centrifugal growth, slightly raised borders, and a clear center.1,2,4 The lesions can be single or multiple and are primarily located on the trunk, abdomen, flanks, and groin. Lesions are usually asymptomatic, but pruritus is occasionally present.1,6Complementary tests such as blood tests (blood cell count, biochemistry, coagulation), as well as autoimmune studies, multiple infectious serologic analysis tests, and patch tests have had negative results in all cases. Annular lichenoid dermatitis of youth usually presents a chronic course with frequent recurrences.1,3-6 The treatments used have shown variable responses. In some cases, treatment with topical corticosteroids or topical tacrolimus monohydrate, 0.03%, has achieved a complete resolution with no recurrences.4-6 Spontaneous resolution has also been described in some cases.Histopathological findings in ALDY show a lymphocytic lichenoid infiltrate with basal vacuolization and the presence of occasional necrotic keratinocytes.1,3,5,6 These changes are characteristically seen at the tip of the epidermal rete ridges.1,4,5 Immunohistochemical studies have shown lymphocyte infiltrates with slight predominance of CD4-positive over CD8-positive lymphocytes, and molecular analysis shows a polyclonal T-cell rearrangement.1,5,6Annular lichenoid dermatitis of youth is probably underdiagnosed given its clinical and histological similarity to other dermatoses, especially early mycosis fungoides (MF).1,2,4-6 Differential diagnosis should be made with pigmented purpuric dermatoses, secondary syphilis, and especially with early-stage MF, to which it may present great clinical and histopathological similarity. Clinically, all cases present in a similar way, with asymptomatic erythematous macules on the trunk and extremities that can resolve by themselves or with topical corticosteroid therapy. Histologically, they share a lichenoid inflammatory infiltrate of CD4-positive T lymphocytes. Immunohistochemical analysis and molecular studies of T-cell receptor gene rearrangement are not conclusive because there is no monoclonality at the early stages of MF. Regarding secondary syphilis, negative serological results and negative immunohistochemical staining for Treponema pallidum, in addition to the absence of plasma cell infiltrates, rule this out. The most difficult differential diagnosis is with the early stages of MF because the initial forms of MF are indistinguishable from ALDY by clinical, histological, immunohistochemical, and molecular analysis. Clinical follow-up of these patients is essential to make a correct and definitive diagnosis.Annular lichenoid dermatitis of youth is a well-defined clinical and pathological entity with an excellent prognosis. However, because of its similarities with early MF, an accurate differential diagnosis and follow-up are essential to determine adequate treatment.

Dermatology

A man in his 20s presented with a 2-month history of itchy skin lesions on his trunk, arms, and groin. He was otherwise healthy, with no other underlying conditions, and he was taking no medications. He had no history of atopic dermatitis or other eczematous dermatoses. There were no associated extracutaneous symptoms. His family medical history was relevant only in that his mother had systemic lupus erythematosus.On physical examination, there were several erythematous annular patches on the abdomen (flanks and periumbilical region), lower back, groin, wrists, and legs (Figure, A). The lesions showed slightly raised red-brown borders and a clear center in some patches with no visible scaling, hypopigmentation, induration, or atrophy. Results of laboratory studies including complete blood cell count, biochemical analysis, complement levels, antinuclear antibodies, anti-Ro, anti-La, anti-ribonucleoprotein, anti-Smith, and anti-dsDNA antibodies, as well as serologic testing for syphilis and hepatitis B and C virus, were all normal or negative. A punch biopsy specimen was obtained for histopathologic evaluation (Figure, B and C).A, Clinical image shows several erythematous annular patches on the flanks and periumbilical region. B, Histopathologic analysis of a punch biopsy sample from the abdomen showing superficial lymphocytic infiltrates in the papillary and superficial reticular dermis. C, There are also prominent vacuolar changes at the dermoepidermal junction, and in some areas mild lymphocytic exocytosis.

what is your diagnosis?

What is your diagnosis?

Pigmented purpuric dermatosis

Secondary syphilis

Mycosis fungoides

Annular lichenoid dermatitis of youth

d

male

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2663275

An 82-year-old Chinese woman presented with a 6-month history of a nonhealing ulcer and multiple indurated plaques on the legs. The first lesion appeared as an erythematous papule, which grew and subsequently ulcerated. Within a few months, she developed other indurated plaques on her legs. The ulcer was painful on palpation, but the plaques were mostly asymptomatic. The patient did not have fevers, chills, weight loss, dyspnea, chest pain, cough, or hemoptysis. She had moved to Canada from China 30 years ago and was unsure about tuberculosis (TB) exposure and Bacillus Calmette–Guérin vaccine status. Her medical history included atrial fibrillation, type 2 diabetes mellitus, dyslipidemia, cerebrovascular disease, hypertension, and Parkinson disease. Physical examination showed a 5 × 4-cm, well-demarcated, oval ulcer with a violaceous, dusky border and central yellow fibrin mixed with granulation tissue on the left lateral aspect of the calf (Figure, A). There were numerous violaceous to dull red, indurated plaques on the posterior aspect of the legs (Figure, B). Wound cultures were negative for bacteria, mycobacteria, and fungi (Figure, C and D). What Is Your Diagnosis?

Infective panniculitides

Erythema nodosum

Erythema induratum

Pyoderma gangrenosum

C. Erythema induratum

C

Erythema induratum

Histopathological examination showed unremarkable epidermis and dermis overlying a mixed septal and lobular nonnecrotizing granulomatous panniculitis with occasional giant cells and small numbers of lymphocytes, plasma cells, and eosinophils (Figure, C). The medium-size subcutaneous vessels were involved by granulomatous inflammation, but no neutrophils were identified (Figure, D). Special stains for fungi and acid-fast bacilli were negative, and no foreign material was identified. The pathological differential diagnosis included erythema induratum, other infectious panniculitidies, erythema nodosum (EN), foreign-body reaction, granulomatosis with polyangiitis, and pyoderma gangrenosum (PG). Erythema induratum was favored owing to the presence of granulomatous vasculitis. The absence of neutrophils made PG and infectious panniculitis unlikely, and the mixed lobular and septal pattern did not favor EN.A tuberculin skin test was strongly positive with an induration of 25 × 30 mm. A chest radiograph showed linear opacities in the right and left mid lung zones, reported as scarring from a previous granulomatous infection. The patient received wound care for her ulcer and was referred to the infectious disease team. Induced sputum smears were negative for TB owing to inadequate sampling, and the decision was made to treat her empirically with anti-TB therapy consisting of isoniazid, pyrazinamide, ethambutol, moxifloxacin, and vitamin B6. She was given moxifloxacin instead of the standard agent rifampin owing to potential for interaction with her current medications. Her leg ulcer began to heal 1 month after initiating treatment.Erythema induratum is the most common form of predominately lobular panniculitis, although it can present with mixed lobular and septal inflammation.1 It is often associated with mycobacterium tuberculosis (MTB) infection, although associations with other infectious and noninfectious etiologies are also reported. The term erythema induratum (EI), coined by Bazin in 1855, is used interchangeably with nodular vasculitis, although the latter often denotes EI without MTB association.2 Erythema induratum presents as recurrent erythematous to violaceous nodules and plaques on the posterior lower legs, which may be tender and frequently ulcerate. It occurs most commonly in middle-aged women, and may be difficult to differentiate both clinically and histologically from other types of panniculitidies, such as EN and infective panniculitis.Although cultures of these lesions are often negative, 39% to 77% of cutaneous biopsy specimens of EI have demonstrated MTB DNA on polymerase chain reaction (PCR) testing.3,4 This supports the notion that MTB is involved in the pathogenesis of EI. Erythema induratum has been considered to be a hypersensitivity reaction mediated by either immune complexes (type 3) or T-lymphocytes (type 4).2 Evidence of T-lymphocyte hyperresponsiveness is evident in the highly positive tuberculin skin test results seen in patients with EI, as with this case.Histologically, EI is a predominantly lobar panniculitis, although it can involve both the septa and lobules. Classic findings include nonnecrotizing granulomas consisting of epithelioid histiocytes and a neutrophilic vasculitis with disruption of the vessel wall, which can lead to thrombosis. This vascular compromise leads to tissue necrosis and cutaneous ulceration. Vasculitis involving lobular veins, septal veins, or septal arteries has been shown to be present in 90% of EI cases, which is a classic distinguishing factor from other types of panniculitides.1 The presence of a predominantly lobar or mixed panniculitis with vessel involvement and ulceration can differentiate EI histopathologically from EN, which demonstrates a predominately septal pattern of inflammation with rare vessel involvement and rare ulceration. Because EI shows histopathologic features similar to those of other infective panniculitidies, special stains and cultures can be helpful in differentiating these entities.5Herein, we describe a case of EI, which presented with erythematous plaques and ulceration on the lower legs, and signs of MTB infection, including a positive result from a skin test and pulmonary scarring on radiography. These features, along with the supportive histologic findings, highlight a classic case of EI. Patients with strongly positive skin test results or MTB DNA on PCR should receive a full course of triple or quadruple therapy for MTB, as well as local wound care and medical therapy for cutaneous lesions.2,6 The causes of nonhealing leg ulcers are numerous; therefore, we suggest a low threshold to consider EI in the differential, especially in high-risk populations.

Dermatology

An 82-year-old Chinese woman presented with a 6-month history of a nonhealing ulcer and multiple indurated plaques on the legs. The first lesion appeared as an erythematous papule, which grew and subsequently ulcerated. Within a few months, she developed other indurated plaques on her legs. The ulcer was painful on palpation, but the plaques were mostly asymptomatic. The patient did not have fevers, chills, weight loss, dyspnea, chest pain, cough, or hemoptysis. She had moved to Canada from China 30 years ago and was unsure about tuberculosis (TB) exposure and Bacillus Calmette–Guérin vaccine status. Her medical history included atrial fibrillation, type 2 diabetes mellitus, dyslipidemia, cerebrovascular disease, hypertension, and Parkinson disease. Physical examination showed a 5 × 4-cm, well-demarcated, oval ulcer with a violaceous, dusky border and central yellow fibrin mixed with granulation tissue on the left lateral aspect of the calf (Figure, A). There were numerous violaceous to dull red, indurated plaques on the posterior aspect of the legs (Figure, B). Wound cultures were negative for bacteria, mycobacteria, and fungi (Figure, C and D).

what is your diagnosis?

What is your diagnosis?

Infective panniculitides

Erythema induratum

Erythema nodosum

Pyoderma gangrenosum

b

female

81-90

Chinese

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2663941

A woman in her 20s was seen with a 6-year history of recurrent, pruritic skin eruptions involving the middle and lower back. Before evaluation in our department, the patient had undergone a skin biopsy that showed spongiotic dermatitis, had patch testing that was reportedly negative, and received a diagnosis of atopic dermatitis. She was treated with potent topical corticosteroids and oral prednisone, with no improvement. She denied use of heating pads, space heaters, or other forms of external radiation. Physical examination showed several discrete, erythematous, scaly papules admixed with light brown reticulated macules and patches (Figure, A and B). Punch biopsy specimens were obtained for further evaluation (Figure, C and D).A, Light brown macules and patches on the back show a strikingly reticular pattern. B, Discrete erythematous and scaly papules and overlying hyperpigmented patches are shown. C, Histopathologic examination shows eosinophilic spongiosis with interface dermatitis, dyskeratosis, and neutrophilic exocytosis (hematoxylin-eosin, original magnification ×20). D, Prominent dermal melanophages are present (hematoxylin-eosin, original magnification ×20). What Is Your Diagnosis?

Erythema ab igne

Prurigo pigmentosa

Dowling-Degos disease

Confluent and reticulated papillomatosis

B. Prurigo pigmentosa

B

Prurigo pigmentosa

Histopathologic examination of an inflammatory papule showed vacuolar interface change with eosinophilic spongiosis, scattered keratinocyte apoptosis, and perivascular and intraepidermal neutrophils (Figure, C). A second biopsy specimen from a hyperpigmented macule showed prominent dermal pigment incontinence (Figure, D). Periodic acid–Schiff diastase and Congo red stains were negative. Direct immunofluorescence testing of perilesional skin was negative. The patient was treated with oral doxycycline monohydrate (100 mg twice daily) for 4 weeks and had complete resolution of the inflammatory papules.Since the original description of prurigo pigmentosa (PP) by Nagashima et al1 in 1971, more than 200 cases have been reported in the Japanese population.2 However, far fewer reports have described non-Japanese patients, and only 7 individuals with PP have been described to date in the United States.3-7Prurigo pigmentosa is clinically characterized by pruritic papules or papulovesicles distributed symmetrically over the neck, chest, and back. Inflammatory lesions typically resolve within 1 week, leaving hyperpigmented macules or patches in a distinctive reticulated pattern.2,8,9 The mean age at disease onset is 23.5 years, and patients generally have no family history of the condition.2 Girls and women are affected at least twice as frequently as boys and men, with a review article9 suggesting a female to male ratio of 7:1. As in this patient, PP is frequently misdiagnosed as eczema.8The pathogenesis of PP is unclear, although some reports describe exacerbating external factors, such as UV radiation, sweating, friction from clothing, and physical trauma.2,5 In addition, metabolic disorders have been implicated as potential causes, with numerous reports describing PP after ketotic states, particularly in the setting of diabetes, anorexia nervosa, or prolonged fasting.2,5,9 The condition was also observed in a patient shortly after bariatric surgery.10 Dietary modification generally leads to resolution of PP in these patients, without recurrences. This patient had no history of metabolic derangement.The histopathologic features of PP are distinct and classically evolve over 3 stages.2 The first stage shows a perivascular and interstitial neutrophilic infiltrate with slight epidermal spongiosis, often with epidermal microabscesses that resemble those seen in psoriasis. The second stage is characterized by increased epidermal spongiosis, a mixed eosinophilic and neutrophilic infiltrate, and vacuolar alteration with degenerating keratinocytes. Eosinophils frequently outnumber neutrophils in this intermediate stage. In the third (final) stage, a lymphocytic patchy lichenoid infiltrate predominates. Very late lesions are typified by focal parakeratosis and variable numbers of dermal melanophages.Collectively, the clinical and histopathologic features of PP distinguish it from other causes of reticulate hyperpigmentation. Confluent and reticulated papillomatosis may have a similar distribution on the trunk, but it lacks the preceding inflammatory papules of PP, and histopathology shows prominent papillomatosis. Erythema ab igne may also manifest with hyperpigmented patches, but it too lacks the transient inflammatory papules seen in PP. In addition, history of a heating source is usually easily elicited. Dowling-Degos disease is differentiated by its notable predilection for the flexures and histopathologically by its epidermal stranding with absence of inflammation.4The mainstay of treatment for PP includes tetracycline antibiotics and oral dapsone. The efficacy of these medications may be due to their ability to inhibit neutrophil chemotaxis and function, thereby aborting the early inflammatory stage of PP.2 Notably, the condition is refractory to topical and oral corticosteroids, which are commonly prescribed to patients with early-stage PP that is presumed to be intractable eczema; this course sometimes leads to considerable delays in diagnosis8 and was the experience of this patient. Diagnostic delays of PP are especially problematic because no effective therapies exist for the reticulated hyperpigmentation that invariably occurs in chronic cases.2This case highlights the unique histopathologic features of PP, which distinguish it from clinical mimickers characterized by reticulate hyperpigmentation. Early diagnosis and prompt treatment are critical to prevent extensive pigmentary changes.

Dermatology

A woman in her 20s was seen with a 6-year history of recurrent, pruritic skin eruptions involving the middle and lower back. Before evaluation in our department, the patient had undergone a skin biopsy that showed spongiotic dermatitis, had patch testing that was reportedly negative, and received a diagnosis of atopic dermatitis. She was treated with potent topical corticosteroids and oral prednisone, with no improvement. She denied use of heating pads, space heaters, or other forms of external radiation. Physical examination showed several discrete, erythematous, scaly papules admixed with light brown reticulated macules and patches (Figure, A and B). Punch biopsy specimens were obtained for further evaluation (Figure, C and D).A, Light brown macules and patches on the back show a strikingly reticular pattern. B, Discrete erythematous and scaly papules and overlying hyperpigmented patches are shown. C, Histopathologic examination shows eosinophilic spongiosis with interface dermatitis, dyskeratosis, and neutrophilic exocytosis (hematoxylin-eosin, original magnification ×20). D, Prominent dermal melanophages are present (hematoxylin-eosin, original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Prurigo pigmentosa

Erythema ab igne

Confluent and reticulated papillomatosis

Dowling-Degos disease

a

female

0-10

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2670429

An adolescent boy presented with cognitive and behavioral changes, headaches, and progressively worsening weakness of the left arm and leg. The patient was subsequently admitted to our hospital for further evaluation. Sixteen months earlier, the patient was admitted to a hospital for weakness of the left fingers and mild spasticity of the left lower extremity. Magnetic resonance imaging (MRI) at the time revealed a suspicious lesion in the right basal ganglia (Figure, A). In addition, carotid and intracranial angiography revealed no abnormalities (not shown). Slight weakness in the left lower extremity was detected 3 months later. Magnetic resonance imaging revealed nonhomogeneous hyperintensity on T2-weighted images in the right basal ganglia without mass effect (Figure, B). Atrophy of the right cerebral hemisphere and right cerebral peduncle was observed (not shown). A, T2-weighted axial brain magnetic resonance imaging (MRI) at the basal ganglia level performed 16 months before the current hospitalization showing slight hyperintensity at the right putamen and posterior limb of the internal capsule (arrowhead). B, T2-weighted axial MRI performed 13 months before the current hospitalization showing moderate hyperintensity at the right basal ganglia without mass effect (arrowhead). C, T2-weighted axial MRI at the basal ganglia level showing remarkable progression of the lesions in the right basal ganglia and thalamus with heterogeneous high signal intensity and multicystic change (arrowhead).There was no history of tumors elsewhere, and his family history was unremarkable. Neurological examination revealed distal left hemiparesis, left facial palsy, and decreased pinprick sensation in his left face and extremities. On MRI, the lesion appeared larger than before (Figure, C), with remarkable heterogeneous enhancement (not shown). Human chorionic gonadotropin (HCG) levels in both serum and cerebrospinal fluid (CSF) were normal. A hormone assay disclosed normal pituitary function. What Is Your Diagnosis?

Glioma

Infarction

Germinoma

Demyelination

C. Germinoma

C

Germinoma

Germinoma was diagnosed via stereotactic brain biopsy. Radiation therapy and subtotal resection were performed following the biopsy. Pathologically, the neoplastic infiltration was composed of large round cells with moderate amounts of clear cytoplasm and prominent vesicular nuclei with plump nucleoli resembling primordial germ cells. Immunohistochemical staining showed expression of proto-oncogene c-Kit (CD117a) by the neoplastic cells.Germinoma belongs to the class of germ cell tumors that comprise embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma (mature and immature). Approximately two-thirds of intracranial germ cell tumors are germinomas.1 Germinomas are commonly large and circumscribed lesions, typically in the pineal or suprasellar regions, that infiltrate and compress adjacent structures, causing various clinical symptoms. Intracranial ectopic germinomas (IEGs) are tumors arising in the basal ganglia and periventricular white matter in addition to the pineal and suprasellar regions.2 Intracranial ectopic germinomas are rare, although their incidence in East Asia is higher. They have a male predominance, and most patients are younger than 20 years.3Clinical manifestation corresponding to the site and dimension of the lesions varies among patients with IEGs. The most common symptoms and signs include hemiparesis, abnormal sensation, extrapyramidal signs, and cognitive and behavioral changes.4 Signs of intracranial hypertension usually do not occur until the late stages, and most IEGs progress slowly, as observed in this patient.Human chorionic gonadotropin is an extremely sensitive and specific marker for trophoblastic tumors of placental and germ cell origin. However, the blood-brain barrier may decrease the sensitivity of serum HCG levels to intracranial germinomas. Therefore, the cerebrospinal fluid HCG level that reflects intracranial HCG secretion is more sensitive to IEGs than serum HCG level.5 In our previous study,6 the sensitivity of cerebrospinal fluid HCG level for IEGs in 14 male patients was 100%, and only 1 false-positive result was detected among 201 male control patients with nonmalignant neurological diseases.Magnetic resonance imaging has played an important role in the diagnosis of IEGs, even when serum HCG levels are normal. Compared with germinomas in other regions, the typical MRI findings, including large tumor size with mild space-occupying effect, cystic formation, calcification, and/or intratumoral bleeding, are commonly observed in IEGs,7 and almost all IEGs demonstrate irregular circular gadolinium enhancement. In addition to these typical findings, there are 2 unique neuroimaging characteristics. One is the negative space-occupying effect of the tumor and cortical/brainstem atrophy ipsilateral to the initial lesion in the early stages; this sign strongly indicates the possibility of an IEG.8 The other characteristic is the evolution of IEGs on neuroimaging from the early to late stages. In the early stages, the tumor is typically associated with only subtle abnormal signal on MRI and is similar in appearance to dilated perivascular spaces, lacunar infarcts, or demyelinating lesions. Space-occupying effects and peritumoral edema, which are common characteristics of most intracranial malignant tumors, are unusual. Susceptibility-weighted imaging has improved the sensitivity for detecting early IEGs compared with conventional MRI sequences because of its ability to demonstrate intratumoral blood products and biological metal accumulation.9 However, if patients were misdiagnosed or left untreated, large, space-occupying, multicystic, and gadolinium-enhancing tumors would appear at the site of initial lesion and/or other sites distant or even contralateral to the initial lesion in the late stages. Such dynamic neuroimaging changes can be considered specific for IEGs. Detection of IEGs is important because it is highly radiosensitive and potentially curable by radiation therapy alone, if correctly diagnosed at an early stage. Children with early-stage IEGs usually display strokelike episodes and mimic subacute lacunar infarct lesions or demyelination on conventional MRI. Advanced MRI techniques, such as susceptibility-weighted imaging, have the potential to differentiate IEGs from other diseases and can help accurately diagnose IEGs at an early stage.

Neurology

An adolescent boy presented with cognitive and behavioral changes, headaches, and progressively worsening weakness of the left arm and leg. The patient was subsequently admitted to our hospital for further evaluation. Sixteen months earlier, the patient was admitted to a hospital for weakness of the left fingers and mild spasticity of the left lower extremity. Magnetic resonance imaging (MRI) at the time revealed a suspicious lesion in the right basal ganglia (Figure, A). In addition, carotid and intracranial angiography revealed no abnormalities (not shown). Slight weakness in the left lower extremity was detected 3 months later. Magnetic resonance imaging revealed nonhomogeneous hyperintensity on T2-weighted images in the right basal ganglia without mass effect (Figure, B). Atrophy of the right cerebral hemisphere and right cerebral peduncle was observed (not shown). A, T2-weighted axial brain magnetic resonance imaging (MRI) at the basal ganglia level performed 16 months before the current hospitalization showing slight hyperintensity at the right putamen and posterior limb of the internal capsule (arrowhead). B, T2-weighted axial MRI performed 13 months before the current hospitalization showing moderate hyperintensity at the right basal ganglia without mass effect (arrowhead). C, T2-weighted axial MRI at the basal ganglia level showing remarkable progression of the lesions in the right basal ganglia and thalamus with heterogeneous high signal intensity and multicystic change (arrowhead).There was no history of tumors elsewhere, and his family history was unremarkable. Neurological examination revealed distal left hemiparesis, left facial palsy, and decreased pinprick sensation in his left face and extremities. On MRI, the lesion appeared larger than before (Figure, C), with remarkable heterogeneous enhancement (not shown). Human chorionic gonadotropin (HCG) levels in both serum and cerebrospinal fluid (CSF) were normal. A hormone assay disclosed normal pituitary function.

what is your diagnosis?

What is your diagnosis?

Demyelination

Germinoma

Infarction

Glioma

b

male

11-20

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2668643

A young boy and his parents presented for consultation about the child’s risk for development of hearing loss, given a family history of deafness in both parents. Both parents were diagnosed with profound, nonprogressive sensorineural hearing loss within the first year of life. A homozygous mutation in the connexin 26 gene (GJB2 [OMIM 121011]) was found in the mother, whereas the father remained without a causative diagnosis. No other relatives had hearing impairment.The child was born full term without complications. Growth and language skills were appropriate for age. Hearing screening at birth and the repeated auditory evaluations at follow-up had normal findings. The physical examination was unremarkable except for some midfacial features consisting of a lateral displacement of the inner canthi of the eyes with a broad nasal root, small nostrils, and medial eyebrow flare (Figure, A). The same midfacial anomalies were observed in his father (Figure, B), in whom a hypopigmented patch on the left arm and bright blue eyes were also noticed. Visual acuity and kidney function were normal, and no skeletal deformities were appreciated in the child or his father.The child and his father demonstrate a lateral displacement of the inner canthi. What Is Your Diagnosis?

Stickler syndrome

Waardenburg syndrome type 1

X-linked Alport syndrome

Autosomal dominant GJB2 gene mutation

B. Waardenburg syndrome type 1

B

Waardenburg syndrome type 1

Waardenburg syndrome type 1 (WS-1) is an autosomal dominant auditory-pigmentary disorder caused by a heterozygous mutation in PAX3 gene (OMIM 606597) on chromosome 2q36. The diagnosis of WS-1 is established when 2 major clinical criteria or 1 major plus 2 minor criteria, as proposed by the Waardenburg Consortium,1 are present (Table). Genetic testing for the identification of the PAX3 pathogenic variant confirms the diagnosis. The WS-1 phenotype is extremely variable, even in the same family, owing to incomplete penetrance and variable expression of all clinical features.7 Lateral displacement of the inner canthi, termed dystopia canthorum, is observed in more than 90% of patients6,7; it manifests as fusion of the inner eyelids, leading to a reduction of the medial sclera, and can be identified using the W index, which combines the inner canthal, interpupillary, and outer canthal distances.6 Congenital sensorineural hearing loss affects 47% to 69% of patients with WS-1, which is prelingual, profound (>100 dB), and unilateral or bilateral.2-5 Owing to incomplete penetrance, hearing impairment can be present or absent even in families segregating the same mutation.8,9 Other WS-1 features are pigmentation abnormalities of the iris, hair, and skin, as reported in the Table.2-5 Differential diagnoses include other WS types and causes of syndromic hearing impairment.Three other forms of WS are known; WS-3 is allelic to WS-1, whereas WS-2 and WS-4 are genetically heterogeneous. Waardenburg syndrome type 3 differs from WS-1 for the presence of abnormalities of the upper limbs; WS-2, lack of dystopia canthorum; and WS-4, association with Hirschsprung disease.4Stickler syndrome is a connective tissue disorder with ocular, orofacial, and auditory anomalies. Myopia and vitreous abnormalities are prominent findings. Epicanthal folds can be observed, but no pigmentation anomalies are present. Hearing impairment is usually mild and progressive with age.Alport syndrome is caused by mutations of type IV collagen genes. Hearing loss due to cochlear dysfunction appears in late childhood, whereas microhematuria is always present from early childhood, evolving toward renal insufficiency with advancing age. Ocular anomalies include lenticonus and maculopathy. No facial dysmorphisms are present in the syndrome.Mutation of GJB2 is the most common cause of severe-to-profound autosomal recessive nonsyndromic hearing loss. Dominant negative mutations within the GJB2 gene cause autosomal dominant inherited forms of progressive sensorineural hearing impairment. In these forms, hearing loss can be postlingual; however, no associated dymorphisms or malformations are present. GJB2 gene mutations associated with autosomal dominant hearing impairment also differ from autosomal recessive forms.This patient had 1 major (dystopia canthorum) and 3 minor (broad nasal root, small nostrils, and medial eyebrow flare) criteria of WS-1, whereas his father had 2 major (dystopia canthorum and congenital deafness) and 5 minor (leukoderma, brilliant blue irises, broad nasal root, small nostrils, and medial eyebrow flare) criteria, allowing a clinical diagnosis of the syndrome. Genetic analysis revealed the same PAX3 pathogenic mutation in both patients.After the diagnosis, the parents were informed that the child was not at increased risk of developing hearing loss and did not require repeated audiogram evaluations.5,7 Genetic counseling was provided to the parents. Because the father had a PAX3 pathogenetic variant, there is a 50% chance of recurrence of WS-1 in future children; however, recurrence of the clinical phenotype and the risk of deafness cannot be estimated.This case reminds clinicians that the WS-1 phenotype is variable even in the same family carrying the same gene defect. Dystopia canthorum is present in virtually all cases and should suggest the diagnosis. Hearing impairment affects half of individuals with the syndrome; although its recurrence cannot be estimated, knowing its congenital nature rules out the possibility of late-onset hearing loss.

Pediatrics

A young boy and his parents presented for consultation about the child’s risk for development of hearing loss, given a family history of deafness in both parents. Both parents were diagnosed with profound, nonprogressive sensorineural hearing loss within the first year of life. A homozygous mutation in the connexin 26 gene (GJB2 [OMIM 121011]) was found in the mother, whereas the father remained without a causative diagnosis. No other relatives had hearing impairment.The child was born full term without complications. Growth and language skills were appropriate for age. Hearing screening at birth and the repeated auditory evaluations at follow-up had normal findings. The physical examination was unremarkable except for some midfacial features consisting of a lateral displacement of the inner canthi of the eyes with a broad nasal root, small nostrils, and medial eyebrow flare (Figure, A). The same midfacial anomalies were observed in his father (Figure, B), in whom a hypopigmented patch on the left arm and bright blue eyes were also noticed. Visual acuity and kidney function were normal, and no skeletal deformities were appreciated in the child or his father.The child and his father demonstrate a lateral displacement of the inner canthi.

what is your diagnosis?

What is your diagnosis?

X-linked Alport syndrome

Autosomal dominant GJB2 gene mutation

Waardenburg syndrome type 1

Stickler syndrome

c

male

11-20

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2666829

A 25-year-old woman with a history of ulcerative colitis (UC) presented to the emergency department with lower abdominal pain. She received a diagnosis of UC 6 years earlier and has taken mesalamine to control UC. She was discharged a week before this admission for a UC flare that was managed with prednisone. Review of systems was notable for diarrhea; however, she denied hematochezia, melena, emesis, fevers, or changes in urination.Her last colonoscopy was 3 years ago, and UC without evidence of dysplasia was confirmed. Otherwise, her medical history was unremarkable. Family history was negative for inflammatory bowel diseases and gastrointestinal malignancies. On examination, she was afebrile with normal vital signs. Her abdomen was tender to palpation in the left lower quadrant, which was soft and nondistended.The patient’s complete blood cell count and comprehensive metabolic panel results were unremarkable. Computed tomographic scan of the abdomen/pelvis demonstrated a thickened colon from the middescending colon to the rectosigmoid. There was also a 2.7-cm intramural abscess in the descending colon. She started receiving piperacillin/tazobactam but began to have increased abdominal pain, emesis, and inability to tolerate oral intake. A repeated computed tomographic scan performed 4 days after the original scan demonstrated that the intramural mass had increased to 3.5 cm and was partially obstructing the descending colon. She underwent a colonoscopy, which demonstrated multiple areas of inflammation in the rectum through the descending colon (Figure 1). Nothing proximal to the midtransverse colon was visualized because of a large fecal burden. What Is Your Diagnosis?

Ulcerative colitis flare

Conversion to Crohn disease

Adenocarcinoma

Lymphoma

C. Adenocarcinoma

C

Adenocarcinoma

Biopsy results from the colonoscopy were consistent with poorly differentiated adenocarcinoma and chronic active colitis. There were no DNA mismatch repair genes absent, nor was microsatellite instability appreciated. Staging studies demonstrated enhanced perirectal lymph nodes with no signs of distant metastasis. The patient underwent a total proctocolectomy with end ileostomy. The final pathology specimen (Figure 2) was consistent with multifocal, high-grade adenocarcinoma involving the rectum, sigmoid, and descending colon with negative margins and 43 of 150 lymph nodes positive for metastatic disease, staging the cancer as T4aN2bM0.The incidence of UC in young adults is rising. Ulcerative colitis increases the amount of exposure the colonic mucosa has to inflammatory cytokines.1 These inflammation flares are thought to increase the rate of colon cancer in patients with UC by activation of epithelial cell survival pathways such as proliferation and reactive oxygen species damage to DNA.1,2 A diagnosis of primary sclerosing cholangitis further increases the risk of colon cancer; however, the pathogenesis is not fully understood.1A patient’s risk for colon cancer increases in proportion to the amount of time elapsed since the diagnosis of UC. The risk is estimated to be approximately 2%, 8%, and 18% by year 10, 20, and 30 after diagnosis, respectively.3 Overall, the rate of colon cancer in patients with UC is on the decline, which is likely secondary to improvements in medical therapy for UC and screening for colon cancer in addition to early total colectomies.4 Screening guidelines differ among different international societies. The American Society for Gastrointestinal Endoscopy recommends annual colonoscopies with random biopsies beginning 8 years after the diagnosis of UC.5Patients with UC have a 2.4-fold increased rate of developing colon cancer compared with the general population.2 Ulcerative colitis–associated colon cancer (UCC) does not follow the typical adenoma to carcinoma course. Rather, UCC precursor lesions are usually nonadenomatous dysplastic epithelial cells.1,2 Many of the genetics insults seen in sporadic colon cancer, such as microsatellite instability, aneuploidy, and mutations in TP53, KRAS, and BCL2 genes, are also seen in UCC. However, these insults are usually found earlier in patients with UC, even before the development of colon cancer.2 These early insults are likely secondary from reactive oxygen species damage to DNA; hence, the risk of UCC increases with increased episodes and severity of inflammatory flares.Patients with UCC are usually younger and have multifocal disease compared with patients with sporadic colon cancer.2,6 One study demonstrated that the stage on final pathology after surgical resection was similar for both groups with similar 5-year survival rates for stage I, II, and IV.6 The patients with UCC had a worse prognosis with stage III disease, with a 5-year survival rate of 43.3% compared with 57.4% (P = .03).6

Surgery

A 25-year-old woman with a history of ulcerative colitis (UC) presented to the emergency department with lower abdominal pain. She received a diagnosis of UC 6 years earlier and has taken mesalamine to control UC. She was discharged a week before this admission for a UC flare that was managed with prednisone. Review of systems was notable for diarrhea; however, she denied hematochezia, melena, emesis, fevers, or changes in urination.Her last colonoscopy was 3 years ago, and UC without evidence of dysplasia was confirmed. Otherwise, her medical history was unremarkable. Family history was negative for inflammatory bowel diseases and gastrointestinal malignancies. On examination, she was afebrile with normal vital signs. Her abdomen was tender to palpation in the left lower quadrant, which was soft and nondistended.The patient’s complete blood cell count and comprehensive metabolic panel results were unremarkable. Computed tomographic scan of the abdomen/pelvis demonstrated a thickened colon from the middescending colon to the rectosigmoid. There was also a 2.7-cm intramural abscess in the descending colon. She started receiving piperacillin/tazobactam but began to have increased abdominal pain, emesis, and inability to tolerate oral intake. A repeated computed tomographic scan performed 4 days after the original scan demonstrated that the intramural mass had increased to 3.5 cm and was partially obstructing the descending colon. She underwent a colonoscopy, which demonstrated multiple areas of inflammation in the rectum through the descending colon (Figure 1). Nothing proximal to the midtransverse colon was visualized because of a large fecal burden.

what is your diagnosis?

What is your diagnosis?

Adenocarcinoma

Conversion to Crohn disease

Ulcerative colitis flare

Lymphoma

a

female

21-30

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2664075

A 25-year-old white man with acute lymphoblastic leukemia reported blurry vision in the left eye for 24 hours and gradually worsening floaters for 1 week. He was already admitted for induction chemotherapy after a relapse of his acute lymphoblastic leukemia. The findings of a previous inpatient eye examination performed 3 weeks earlier were unremarkable. During his hospitalization, he was noted to have persistent fevers of unclear origin and neutropenia. He was receiving prophylactic cefepime and amphotericin B prescribed by the infectious diseases service. Up to this point, the results of multiple systemic cultures were negative other than a skin biopsy specimen of a concerning papular rash that was noted to yield Candida tropicalis. Vision was 20/20 OD and 20/100 OS. He denied any pain or photophobia. Anterior segment examination findings were unremarkable. Dilated fundoscopy revealed multiple yellow-white subretinal lesions with associated hemorrhages and vitritis in the left eye (Figure 1).Left eye fundus photograph shows multiple creamy white subretinal lesions with associated hemorrhages and optic nerve head edema. Vitritis accounts for the hazy view. What Would You Do Next?

Vitreous tap and inject

Perform pars plana vitrectomy with subretinal biopsy

Change systemic antimicrobials

Perform lumbar puncture

Endophthalmitis secondary to disseminated C tropicalis

B

Perform pars plana vitrectomy with subretinal biopsy

Despite broad-spectrum intravenous antimicrobial therapy, this patient had persistent fevers and worsening ocular course. Computed tomography of the chest revealed scattered pulmonary nodules concerning for disseminated fungal infection. We made the decision to proceed with pars plana vitrectomy and subretinal biopsy to identify a causative organism.Vitrectomy with subretinal biopsy was performed. No abnormal cellular proliferation was noted. A Grocott methenamine silver stain of the biopsy specimen revealed thin-walled, budding ovoid forms; the culture yielded C tropicalis (Figure 2). Subretinal white lesions in this context of concomitant neutropenia should always raise concern for an endogenous infection. In our patient, the insidious onset of symptoms and gradual progression pointed toward a fungal cause. However, given the relapsed acute lymphoblastic leukemia, a compromised immune response to a bacterial pathogen was possible. An atypical pathogen (eg, Nocardia species) and leukemic infiltration were also discussed.Pars plana vitrectomy with subretinal biopsy was deemed to be the best course of action. Vitrectomy has a higher diagnostic yield than vitreous aspiration alone in endogenous endophthalmitis.1,2 Furthermore, vitrectomy allowed us to directly access lesions with subretinal forceps. This approach gave us the opportunity to debulk subretinal fungal infiltrates and send a generous sample to the pathology department for evaluation. Given the extensive subretinal infiltration, intravitreal biopsy and antimicrobial administration alone were judged not to be adequate. Because of the lack of significant vitritis, we estimated that the yield from vitreous biopsy alone would be limited. Although changing antimicrobial therapy was discussed with the infectious diseases service, our patient had already been receiving broad-spectrum systemic antibiotic and antifungal therapy throughout his hospital course. Despite this aggressive antimicrobial therapy, his ocular disease was progressive, warranting further evaluation to determine whether other interventions might be appropriate. In addition, as opposed to changing antimicrobials indiscriminately, vitrectomy was chosen to isolate a target organism. A lumbar puncture would be a reasonable diagnostic step if meningeal signs were present, although it would not have provided a therapeutic benefit.This case highlights important considerations in hospitalized immunocompromised patients. Endogenous mycotic endophthalmitis is seen almost exclusively in patients with suppressed immune systems or intravenous drug abusers.3Candida species are most often the causative organisms in these patients.1 Symptoms initially can be subtle and nonspecific, leading to delays in diagnosis.2-4 In this case, the patient had persistent fevers and intermittent altered mentation. He had negative eye examination findings earlier in his hospital course. A subsequent consultation was requested after he reported floaters. Treatment teams should have a high level of suspicion in this patient population, although ocular involvement from disseminated fungal infection remains rare, with positive findings in only 1% to 5% of all such consultations.5,6 Diagnostic vitrectomy and subretinal biopsy were only considered after the patient’s course continued to progress despite aggressive antifungal treatment.Amphotericin was switched to micafungin based on sensitivities, and fevers resolved. The subretinal lesions regressed, and the patient’s ocular examination findings stabilized; however, vision was counting fingers attributable to macular scarring.

Ophthalmology

A 25-year-old white man with acute lymphoblastic leukemia reported blurry vision in the left eye for 24 hours and gradually worsening floaters for 1 week. He was already admitted for induction chemotherapy after a relapse of his acute lymphoblastic leukemia. The findings of a previous inpatient eye examination performed 3 weeks earlier were unremarkable. During his hospitalization, he was noted to have persistent fevers of unclear origin and neutropenia. He was receiving prophylactic cefepime and amphotericin B prescribed by the infectious diseases service. Up to this point, the results of multiple systemic cultures were negative other than a skin biopsy specimen of a concerning papular rash that was noted to yield Candida tropicalis. Vision was 20/20 OD and 20/100 OS. He denied any pain or photophobia. Anterior segment examination findings were unremarkable. Dilated fundoscopy revealed multiple yellow-white subretinal lesions with associated hemorrhages and vitritis in the left eye (Figure 1).Left eye fundus photograph shows multiple creamy white subretinal lesions with associated hemorrhages and optic nerve head edema. Vitritis accounts for the hazy view.

what would you do next?

What would you do next?

Change systemic antimicrobials

Vitreous tap and inject

Perform lumbar puncture

Perform pars plana vitrectomy with subretinal biopsy

d

male

21-30

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2664083

A 45-year-old man presented to the emergency department after being shot with a .22-caliber pistol. The bullet passed through a wooden door before entering the patient’s right orbit. His ocular history included exotropia and amblyopia in the right eye. An examination revealed normal pupillary light reflexes, a visual acuity of 20/70 OD and 20/40 OS, and normal color vision OU.There was 3 mm of proptosis in the right eye, as well as right-sided periocular ecchymosis. An entry wound was visible inferior to the right medial canthus, and the right upper and lower eyelids had full-thickness lacerations involving the canaliculi. The patient had a large-angle alternating exotropia, as well as mild supraduction, infraduction, and adduction deficits in the right eye. Severe pain was noted with supraduction and infraduction of the right eye. A slitlamp examination of the right eye revealed a normal anterior segment, while a mild vitreous hemorrhage, extramacular retinal whitening, and a subretinal hemorrhage in the inferonasal periphery was noted on ophthalmoscopic examination. The left globe was within normal limits and intraocular pressure was 16 mm Hg OD and 8 mm Hg OS.A computed tomography scan showed a large extraconal inferonasal metallic foreign body (FB) within the right orbit that was abutting the inferior rectus muscle without fractures or intracranial intrusion (Figure 1).Computed tomography scan of the orbit demonstrates a large extraconal metallic foreign body of the right orbit abutting the inferior rectus muscle on coronal (A) and sagittal (B) images.Obtain a magnetic resonance imaging study to further delineate the soft tissue injuryRepair canalicular lacerations and leave the foreign body in placeRepair canalicular lacerations and perform an orbitotomy for FB removal What Would You Do Next?

Observe the patient

Obtain a magnetic resonance imaging study to further delineate the soft tissue injury

Repair canalicular lacerations and leave the foreign body in place

Repair canalicular lacerations and perform an orbitotomy for FB removal

Retained intraorbital metallic FB with canalicular lacerations

D

Repair canalicular lacerations and perform an orbitotomy for FB removal

Projectile injury to the orbit is a function of size, speed, and trajectory. Air and BB gun pellets are small with limited velocity and typically come to rest within the orbit, causing minimal soft tissue injury.1,2 Conversely, bullets are larger and travel at much higher speeds, often resulting in significant destruction to the orbit, adjacent sinuses, and brain.2 Although this patient was shot with a .22-caliber bullet, it passed through a barrier, reducing its velocity and limiting damage.In contrast to metallic intraocular FBs, retained metallic intraorbital (IOrb) FBs are usually well tolerated. In one large series of metallic IOrbFBs, only 5% of patients developed long-term complications when the globe was not penetrated.3 These complications included pain with eye movement, an optic neuropathy, restrictive strabismus, fistula formation, and infection.1-3 Although infection is often a feared complication, fewer than 10% of inorganic IOrbFBs result in cellulitis or abscesses.1,3 By contrast, 54% to 68% of patients with organic IOrbFBs develop infections.1,4Locating a small projectile within postseptal fat can be challenging, and associated morbidities include an orbital hemorrhage or optic neuropathy.1 The decision to perform an orbitotomy and remove an IOrbFB depends on the composition and location of the FB, as well as potential complications if left unaddressed. General recommendations are (1) remove all organic FBs that can be exposed without excessive orbital morbidity, (2) remove any inorganic FBs that are associated with complications, (3) observe inorganic, asymptomatic postseptal FBs, and (4) electively remove inorganic preseptal FBs.1-3Despite these broad recommendations, individual cases can have unique factors. If an inorganic FB is readily exposed and surgery is required for other reasons, including orbital fractures and periocular lacerations, then removal should be considered. Magnetic resonance imaging is contraindicated in patients with retained ferromagnetic material for concern of FB displacement or heat generation.5 Although the core of a bullet is typically made of lead or a lead alloy, ferromagnetic metal can be present.5-7 Therefore, if magnetic resonance imaging is needed, the bullet should first be extracted. Although lead toxicity is possible with an FB that is located within a synovial space,8 to our knowledge, no systemic lead toxicity has been documented with an IOrbFB. In addition, many surgeons will remove iron-containing or pure copper IOrbFBs that are contacting the sclera, especially if an electroretinography shows gradual retinal deterioration.1,3,9,10In this case, the patient had a large, accessible postseptal IOrbFB with severe pain and the need for canalicular repair, rendering repairing canalicular lacerations and performing an orbitotomy for FB removal the most appropriate choice. Repairing canalicular lacerations and leaving the FB in place is less appropriate because of the presence of significant pain with eye movements. Obtaining a magnetic resonance image study to further delineate the soft tissue injury is contraindicated because of the possibility of ferromagnetic material. Observing the patient is incorrect because of the high likelihood of posttraumatic epiphora and persistent orbital pain.An orbitotomy with exploration was performed. A .22-caliber bullet was identified and extracted (Figure 2). The canalicular lacerations were repaired using a bicanalicular stent. There were no surgical complications. Postoperatively, the patient’s pain rapidly resolved and his visual acuity remained unchanged.An orbitotomy with a .22-caliber bullet extraction (inset) and a bicanalicular repair of lacerations were performed.

Ophthalmology

A 45-year-old man presented to the emergency department after being shot with a .22-caliber pistol. The bullet passed through a wooden door before entering the patient’s right orbit. His ocular history included exotropia and amblyopia in the right eye. An examination revealed normal pupillary light reflexes, a visual acuity of 20/70 OD and 20/40 OS, and normal color vision OU.There was 3 mm of proptosis in the right eye, as well as right-sided periocular ecchymosis. An entry wound was visible inferior to the right medial canthus, and the right upper and lower eyelids had full-thickness lacerations involving the canaliculi. The patient had a large-angle alternating exotropia, as well as mild supraduction, infraduction, and adduction deficits in the right eye. Severe pain was noted with supraduction and infraduction of the right eye. A slitlamp examination of the right eye revealed a normal anterior segment, while a mild vitreous hemorrhage, extramacular retinal whitening, and a subretinal hemorrhage in the inferonasal periphery was noted on ophthalmoscopic examination. The left globe was within normal limits and intraocular pressure was 16 mm Hg OD and 8 mm Hg OS.A computed tomography scan showed a large extraconal inferonasal metallic foreign body (FB) within the right orbit that was abutting the inferior rectus muscle without fractures or intracranial intrusion (Figure 1).Computed tomography scan of the orbit demonstrates a large extraconal metallic foreign body of the right orbit abutting the inferior rectus muscle on coronal (A) and sagittal (B) images.Obtain a magnetic resonance imaging study to further delineate the soft tissue injuryRepair canalicular lacerations and leave the foreign body in placeRepair canalicular lacerations and perform an orbitotomy for FB removal

what would you do next?

What would you do next?

Obtain a magnetic resonance imaging study to further delineate the soft tissue injury

Repair canalicular lacerations and perform an orbitotomy for FB removal

Observe the patient

Repair canalicular lacerations and leave the foreign body in place

b

male

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2665185

A woman in her 20s was referred to our retina clinic for blurry vision in the left eye that she noticed on waking. Her medical history was negative for diabetes, hypertension, dyslipidemia, and smoking. Her only medication was oral contraception (OCP). The patient’s uncorrected visual acuity was 20/20 OU, and intraocular pressures were 14 mm Hg OD and 15 mm Hg OS. Confrontational visual fields and results of external eye examination were normal. She had full ocular motility and no afferent pupillary defect. Results of the right eye fundus examination were unremarkable (Figure, A). The left eye (Figure, B) had tortuosity and dilation of all branches of the retinal vein, disc edema, scattered intraretinal hemorrhages, and nasal macula nerve fiber layer infarcts. The vitreous was clear, macula flat, and there was no retinal neovascularization. Results of optical coherence tomography confirmed the absence of cystoid macular edema and demonstrated nerve fiber layer thickening and hyperreflectivity, consistent with a nerve fiber layer infarct.A, Right fundus photograph demonstrating absence of vessel tortuosity and dilation, disc edema, infarcts, and hemorrhages. B, Left fundus photograph demonstrating venous tortuosity and dilation, disc edema, scattered intraretinal hemorrhages, and nasal macula nerve fiber layer infarct (arrowheads).Review medical and family history for hypercoagulable or inflammatory systemic diseases What Would You Do Next?

Perform intravitreal corticosteroid injection

Perform intravitreal anti–vascular endothelial growth factor injection

Review medical and family history for hypercoagulable or inflammatory systemic diseases

Perform panretinal photocoagulation

Perfused central retinal vein occlusion

C

Review medical and family history for hypercoagulable or inflammatory systemic diseases

Results of the clinical examination were consistent with central retinal vein occlusion (CRVO). Young age and lack of common risk factors for CRVO, such as hypertension, diabetes, hyperlipidemia, and smoking, was concerning for underlying systemic disease. We inquired about the patient’s medical and family history of hypercoagulable and inflammatory states associated with CRVO in young patients (choice C).1 Treatment is reserved for sequelae of CRVO, such as macular edema or neovascularization, none of which were present in our patient. Macular edema causing vision loss typically is treated with intravitreous anti–vascular endothelial growth factor (anti-VEGF) therapy (choice B) and also may resolve with intravitreous corticosteroids (choice A) or, when due to a branch retinal vein occlusion, grid laser treatment. Neovascularization may be treated with scatter photocoagulation (choice D)2 or intravitreous anti-VEGF therapy. The patient’s primary care physician diagnosed her as having factor V Leiden mutation, a hypercoagulable state associated with CRVO. The patient reported that her father was previously diagnosed as having factor V Leiden mutation after a branch retinal vein occlusion was diagnosed at 48 years of age.Globally, the prevalence of CRVO is 0.8% and increases from 0.027% to 0.5% from the fourth to eighth decade of life.3 Individuals younger than 50 years of age make up less than 20% of cases.4Review of medical and family history may be necessary in young adults with CRVO and diagnostic testing may be performed to assess for systemic disease.2 Although not proof of causality, associated systemic disease was found in 40% to 67% of young adults with CRVO.4,5 Inquiry might include hereditary thrombophilias, blood dyscrasias, autoimmune disease, and HIV.4 Pregnancy, use of OCPs, hormone therapy, and diuretics also might be considered.1,4,6 Dehydration has been implicated in some reports of young patients with CRVO.7,8 Assessment also might include measurement of blood pressure, hemoglobin A1c, complete blood cell count, lipid profile, and erythrocyte sedimentation rate.9 Diagnostic studies, often performed by the primary care physician, may include HIV and pregnancy tests, coagulation panel, and autoimmune markers,4 although the risk to benefit ratio of these workups has not been elucidated.Thrombophilias, including resistance to activated protein C, antiphospholipid antibodies, factor XII deficiency, and anticoagulant protein deficiencies, have been associated with CRVO in young patients.6 These disorders, however, are not rare in the general population without CRVO, raising the possibility that CRVO is unrelated when reported in association with these abnormalities. Factor V Leiden mutation is found in 5% of the general population and 7.9% of those with retinal vein occlusion.10Oral contraception is also associated with CRVO. More than 20% of patients with perfused CRVO and younger than 45 years used OCPs,1 although it could be that a matched control group would have a similar percentage of OCP users. Thus, the risk to benefit ratio of recommending that individuals with CRVOs not commence OCPs remains unknown. Discontinuation of OCPs after CRVO probably should be decided on a case-by-case basis.9Our patient’s primary care physician was informed of the CRVO to consider with any management of factor V Leiden mutation. Anticoagulation and antiplatelet agents are not routinely prescribed after diagnosis of CRVO as a first thrombotic event in those with factor V Leiden mutation because of the unknown risk to benefit ratio. Our patient discontinued OCPs, after discussion about risks and benefits, and started aspirin, although the precise risk to benefit ratio of this management is not known. The patient returned to her home town for follow-up and developed decreased visual acuity due to cystoid macular edema, returning to 20/20 after anti-VEGF intravitreal injection.

Ophthalmology

A woman in her 20s was referred to our retina clinic for blurry vision in the left eye that she noticed on waking. Her medical history was negative for diabetes, hypertension, dyslipidemia, and smoking. Her only medication was oral contraception (OCP). The patient’s uncorrected visual acuity was 20/20 OU, and intraocular pressures were 14 mm Hg OD and 15 mm Hg OS. Confrontational visual fields and results of external eye examination were normal. She had full ocular motility and no afferent pupillary defect. Results of the right eye fundus examination were unremarkable (Figure, A). The left eye (Figure, B) had tortuosity and dilation of all branches of the retinal vein, disc edema, scattered intraretinal hemorrhages, and nasal macula nerve fiber layer infarcts. The vitreous was clear, macula flat, and there was no retinal neovascularization. Results of optical coherence tomography confirmed the absence of cystoid macular edema and demonstrated nerve fiber layer thickening and hyperreflectivity, consistent with a nerve fiber layer infarct.A, Right fundus photograph demonstrating absence of vessel tortuosity and dilation, disc edema, infarcts, and hemorrhages. B, Left fundus photograph demonstrating venous tortuosity and dilation, disc edema, scattered intraretinal hemorrhages, and nasal macula nerve fiber layer infarct (arrowheads).Review medical and family history for hypercoagulable or inflammatory systemic diseases

what would you do next?

What would you do next?

Perform intravitreal anti–vascular endothelial growth factor injection

Perform panretinal photocoagulation

Review medical and family history for hypercoagulable or inflammatory systemic diseases

Perform intravitreal corticosteroid injection

c

female

21-30

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2665829

A 63-year-old white man with a history of cigarette use (≥80 pack-years) and alcohol dependence presented to the ophthalmology clinic with several weeks of left eye pain and redness. A review of systems was remarkable for unintentional weight loss, night sweats, and cough with scant sputum. On presentation, best-corrected visual acuity was 20/20 OU. Intraocular pressure, pupillary reaction, and ocular motility were normal. The right eye had normal anterior and posterior segment examination findings. The left eye was notable for mostly superior conjunctival and scleral hyperemia with dilated scleral vessels and associated scleral thinning with a conjunctival epithelial defect (Figure 1). The results of posterior examination of the left eye were normal. Results of serologic tests, including Treponema pallidum particle agglutination assay, HIV, hepatitis B and C, Lyme antibody, rheumatoid factor, and anticyclic citrullinated peptide, were negative. Angiotensin-converting enzyme level, uric acid level, erythrocyte sedimentation rate, complete blood cell count, and basic metabolic panel results were within normal limits. The results of proteinase 3–antineutrophil cytoplasmic antibody (ANCA) testing and interferon γ release assay using QuantiFERON-TB gold (QFT) (Qiagen) were positive. Chest computed tomography revealed tiny, scattered solid pulmonary nodules that were too small to characterize according to the radiology department. The patient was referred to the infectious diseases clinic, where the results of sputum culture and polymerase chain reaction for Mycobacteria tuberculosis were negative. Pulmonology evaluation determined that the pulmonary nodules were too small for biopsy via bronchoscopy.Slitlamp photograph of the left eye shows diffuse hyperemia with dilated vessels and scleral thinning.Initiate rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy What Would You Do Next?

Perform an incisional biopsy

Prescribe oral prednisone

Initiate rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy

Inject sub-Tenon triamcinolone

Necrotizing anterior scleritis

C

Initiate rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy

Necrotizing scleritis can be vision-threatening and warrants investigation to determine the underlying cause and appropriate treatment. The cause could be idiopathic, infectious, or secondary to an underlying autoimmune disorder, such as rheumatoid arthritis or granulomatous polyangiitis.1 Positive serologic test results for proteinase 3–ANCA are present in approximately two-thirds of patients with granulomatous polyangiitis, and in the context of scleritis with positive ANCA results, the odds ratio of developing subsequent granulomatous polyangiitis is 22.91.2,3 This case was challenging because the patient also had positive QFT results and a history of positive tuberculin skin test results and exposure to a family member with active pulmonary tuberculosis. His QFT titer was high (>10 IU/mL; reference range, >1.09 IU/mL), but it still lacked the specificity to differentiate active vs latent tuberculosis.4Scleral biopsy could help to differentiate the cause. However, surgical trauma to an inflamed sclera could exacerbate scleral necrosis, particularly if the cause is autoimmune related.5 Oral prednisone would be the treatment option if the cause was secondary to an autoimmune disease. Although the patient tested positive for proteinase 3–ANCA, initiating corticosteroid treatment orally or locally with sub-Tenon injection without ruling out an infectious cause could accelerate disease progression.Although the patient had a negative sputum culture and polymerase chain reaction results, the combination of prior exposure, positive tuberculin skin test results, and a high QFT titer strongly suggests the diagnosis of tuberculosis scleritis.6 In a large cohort study of scleritis,7 9.4% of cases were infectious, and among these, 10% were related to tuberculosis. Ocular involvement secondary to systemic tuberculosis occurs in 1% to 2% of patients, and most have no history of pulmonary or systemic symptoms. Up to 50% can have normal chest radiography findings. Ocular manifestations may be secondary to direct invasion or a result of a hypersensitivity reaction to tuberculosis antigens. Tuberculosis scleritis typically presents as an anterior nodular scleritis but can be necrotizing and does not respond to topical corticosteroids.8 QuantiFERON-TB gold can be useful in guiding therapy because patients with higher titers respond better clinically to RIPE therapy.9The patient was counseled for alcohol cessation and prescribed 6 months of RIPE therapy with close observation for clinical improvement. If the patient failed to improve, the treatment would be changed to systemic immunosuppression with oral corticosteroids and concomitant prophylaxis with oral isoniazid only.After 2 days of RIPE therapy, the patient experienced acute worsening of symptoms and redness likely because of an ocular Jarisch-Herxheimer reaction secondary to lysis of the mycobacterium that exacerbated the inflammatory response.10 The patient was subsequently prescribed 40 mg of oral prednisone with a slow taper in conjunction with continuation of RIPE therapy. The patient noted an improvement of symptoms of redness on subsequent follow-up visits and at 4 months after initiation of RIPE therapy had complete resolution of the scleritis (Figure 2), which remained stable even after the discontinuation of oral prednisone therapy. The patient remained clinically stable without signs of inflammation after completing 6 months of RIPE therapy.Photograph from 4 months after initiation of rifampin, isoniazid, pyrazinamide, and ethambutol therapy shows the resolution of the scleritis.

Ophthalmology

A 63-year-old white man with a history of cigarette use (≥80 pack-years) and alcohol dependence presented to the ophthalmology clinic with several weeks of left eye pain and redness. A review of systems was remarkable for unintentional weight loss, night sweats, and cough with scant sputum. On presentation, best-corrected visual acuity was 20/20 OU. Intraocular pressure, pupillary reaction, and ocular motility were normal. The right eye had normal anterior and posterior segment examination findings. The left eye was notable for mostly superior conjunctival and scleral hyperemia with dilated scleral vessels and associated scleral thinning with a conjunctival epithelial defect (Figure 1). The results of posterior examination of the left eye were normal. Results of serologic tests, including Treponema pallidum particle agglutination assay, HIV, hepatitis B and C, Lyme antibody, rheumatoid factor, and anticyclic citrullinated peptide, were negative. Angiotensin-converting enzyme level, uric acid level, erythrocyte sedimentation rate, complete blood cell count, and basic metabolic panel results were within normal limits. The results of proteinase 3–antineutrophil cytoplasmic antibody (ANCA) testing and interferon γ release assay using QuantiFERON-TB gold (QFT) (Qiagen) were positive. Chest computed tomography revealed tiny, scattered solid pulmonary nodules that were too small to characterize according to the radiology department. The patient was referred to the infectious diseases clinic, where the results of sputum culture and polymerase chain reaction for Mycobacteria tuberculosis were negative. Pulmonology evaluation determined that the pulmonary nodules were too small for biopsy via bronchoscopy.Slitlamp photograph of the left eye shows diffuse hyperemia with dilated vessels and scleral thinning.Initiate rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy

what would you do next?

What would you do next?

Initiate rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) therapy

Prescribe oral prednisone

Inject sub-Tenon triamcinolone

Perform an incisional biopsy

a

male

61-70

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2661764

A man in his 20s presented with a 2-month history of vague, right upper-quadrant abdominal pain, with associated 5-kg weight loss, loss of appetite, and increasing abdominal distension. He reported a small mass in the right scrotum that was evaluated 5 years previously and was reassured to be a nonmalignant lesion. Physical examination was notable for a distended abdomen with a palpable left abdominal mass. Testicular examination revealed an approximately 1-cm firm right spermatic cord nodule. Laboratory tests showed lactate dehydrogenase levels of 818 U/L (to convert to μkat/L, multiply by 0.0167), with no significant β-human chorionic gonadotropin and α-fetoprotein levels. Computed tomography (CT) of the abdomen (Figure, A and B) revealed innumerable masses throughout the abdomen and pelvis, with the largest measuring 17.5 × 14 × 14 cm and a 3.9-cm enhancing lesion in the left hepatic lobe, and a small amount of ascites. Testicular sonogram disclosed a 1.5-cm right epididymal cyst. Percutaneous biopsy and histologic examination of the dominant left abdominal mass revealed neoplastic cells (Figure, C) that were positive for cytokeratin, desmin but negative for S100. Fluorescence in situ hybridization (FISH) was positive for EWS-WT1 rearrangement.A, Coronal view and B, sagittal view contrast-enhanced computed tomographic imaging revealed innumerable abdominopelvic masses. Blue arrowheads indicate the dominant mass and the red arrowhead indicates the liver mass. C, Hematoxylin-eosin stain (original magnification ×40). What Is Your Diagnosis?

Metastatic neuroendocrine carcinoma

Metastatic gastrointestinal stromal tumor

Metastatic testicular carcinoma

Advanced desmoplastic small round cell tumor

D. Advanced desmoplastic small round cell tumor

D

Advanced desmoplastic small round cell tumor

Histopathologic analysis revealed islands and nests of uniform small round cells with round hyperchromatic nuclei and minimal cytoplasm embedded in a prominent fibroblastic stroma characteristic of desmoplastic small round cell tumor (DSRCT). Immunoprofile showed varying degrees of epithelial, muscle, and neural marker expressions. Results of FISH yielded pathognomonic EWSR1-WT1 fusion oncogene that results from t(11;22)(p13;q12) translocation.1Desmoplastic small round cell tumor is a rare and highly fatal soft tissue sarcoma of mesenchymal origin that was first described by Gerald and Rosai in 1989.2 Etiology of DSRCT remains uncertain. The name DSRCT derives from its characteristic histologic findings of clusters of small round blue cells surrounded by abundant desmoplastic stroma. It is a disease of pediatric and young adult patients with peak incidence from 20 to 24 years and is more common in men.3 Patients usually present with nonspecific abdominal symptoms, such as distension, pain, discomfort, and constipation. Most patients have advanced disease at presentation evidenced by imaging findings of large abdominal masses and peritoneal implants with ascites.4Contrast-enhanced CT scan is the initial imaging study of choice. Magnetic resonance imaging (MRI) can be considered for detailed delineation of pelvic and hepatic lesions.4 Positron emission tomography scan can detect occult lesions, including pelvic and cervical lymph nodes perhaps missed by CT and MRI.5 Multiple disseminated abdominopelvic masses with a large dominant lesion is the common presenting finding, whereas solitary well-defined abdominal mass is rare.5,6 Ascites can be present in 35% of cases.6 More than half of patients have metastatic disease at presentation with liver, lungs, pleura, and mediastinum being the common locations,4,6 whereas cervical, lymph nodes, and bone are rare.6 Approximately 50% of patients have thoracoabdominal lymphadenopathies.6Biopsy is often performed for tissue diagnosis. However, for solitary intra-abdominal or retroperitoneal mass, particularly in suspected sarcoma, surgical resection should be performed without biopsy to prevent tumor seeding. Desmoplastic small round cell tumor frequently has diffuse abdominopelvic involvement; thus, conventional sarcoma staging may not be useful for prognosis and treatment decision. Therefore, a new staging system4 is being proposed, although it is not yet validated, as follows:Stage 1: tumor localized to 1 or 2 sites in the abdomen or 1 site elsewhere.Stage 2: presence of extensive peritoneal disease.Stage 3: involving peritoneal disease and liver metastasis.Stage 4: additional disease outside the abdominal cavity, including lymph nodes.Stage 1: tumor localized to 1 or 2 sites in the abdomen or 1 site elsewhere.Stage 3: involving peritoneal disease and liver metastasis.Stage 4: additional disease outside the abdominal cavity, including lymph nodes.Desmoplastic small round cell tumor is a highly aggressive neoplasm, which has poor prognosis despite multimodality treatments. It is extremely rare; thus, recommendations are based on level 2 and 3 clinical data, which may be debatable. Surgery is the preferred initial approach in patients with solitary lesion, however, most patients have advanced disease at presentation and are always treated with multiagent intensive chemotherapy. This is followed by maximal surgical debulking with or without hyperthermic intraperitoneal chemotherapy, then adjuvant radiotherapy and/or chemotherapy.4 Kushner et al7 developed a P6 chemotherapy regimen that includes cyclophosphamide, ifosfamide, vincristine, doxorubicin, and etoposide. Owing to its high toxicity, a more tolerable alternative regimen was used for this patient, which comprises neoadjuvant vincristine, ifosfamide, dexrazoxane, doxorubicin, and etoposide and adjuvant irinotecan plus temozolomide.4 Combined with surgical and radiation modalities, this regimen yielded disease-free interval of approximately 2 years.4 Addition of irinotecan, temozolomide, and bevacizumab to P6 chemotherapy regimen in newly diagnosed patients is proven to be effective without notable additional toxic effects.8Adjuvant total abdominal radiotherapy has considerable hematological and gastrointestinal toxic effects. Although intensity-modulated radiation therapy has reduced these toxic effects, it is associated with suboptimal disease-free survival.4 Myeloablative therapy with autologous stem cell rescue following debulking surgery is ineffective.9 Intraperitoneal radioimmunotherapy with 131I-8H9 has promising preliminary results.4 Additional newer approaches include poly ADP-ribose polymerase 1 and 2 inhibitors (PARPi), trabectedin, and agents targeting mTOR and androgen receptor pathways.4,10

Oncology

A man in his 20s presented with a 2-month history of vague, right upper-quadrant abdominal pain, with associated 5-kg weight loss, loss of appetite, and increasing abdominal distension. He reported a small mass in the right scrotum that was evaluated 5 years previously and was reassured to be a nonmalignant lesion. Physical examination was notable for a distended abdomen with a palpable left abdominal mass. Testicular examination revealed an approximately 1-cm firm right spermatic cord nodule. Laboratory tests showed lactate dehydrogenase levels of 818 U/L (to convert to μkat/L, multiply by 0.0167), with no significant β-human chorionic gonadotropin and α-fetoprotein levels. Computed tomography (CT) of the abdomen (Figure, A and B) revealed innumerable masses throughout the abdomen and pelvis, with the largest measuring 17.5 × 14 × 14 cm and a 3.9-cm enhancing lesion in the left hepatic lobe, and a small amount of ascites. Testicular sonogram disclosed a 1.5-cm right epididymal cyst. Percutaneous biopsy and histologic examination of the dominant left abdominal mass revealed neoplastic cells (Figure, C) that were positive for cytokeratin, desmin but negative for S100. Fluorescence in situ hybridization (FISH) was positive for EWS-WT1 rearrangement.A, Coronal view and B, sagittal view contrast-enhanced computed tomographic imaging revealed innumerable abdominopelvic masses. Blue arrowheads indicate the dominant mass and the red arrowhead indicates the liver mass. C, Hematoxylin-eosin stain (original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Metastatic gastrointestinal stromal tumor

Advanced desmoplastic small round cell tumor

Metastatic testicular carcinoma

Metastatic neuroendocrine carcinoma

b

male

21-30

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2666626

A white woman in her late 50s presented with palpitations, breathlessness, chest pain, and episodes of light-headedness. Her risk profile included a family history of sudden cardiac death: her cousin died unexpectedly in his mid-40s while playing football. A physical examination showed no remarkable findings. Her systolic blood pressure was 125 mm Hg, diastolic blood pressure was 70 mm Hg, and resting heart rate was 52 beats/min. Portions of her electrocardiogram (Figure 1A) and 24-hour Holter monitoring trace (Figure 1B) are shown. Echocardiographic findings included mildly impaired systolic function (left ventricular ejection fraction, 45%-50%) but were otherwise normal. Coronary angiography was performed and revealed normal coronary arteries.Patient electrocardiogram (A) and a portion of the 24-hour Holter monitor trace (B).Implant a device to determine frequency of ventricular tachycardia What Would You Do Next?

Conduct an invasive electrophysiological study

Implant a device to determine frequency of ventricular tachycardia

Order cardiac magnetic resonance imaging

Order cardiac positron emission tomography

Arrhythmogenic left ventricular cardiomyopathy

C

Order cardiac magnetic resonance imaging

This patient’s electrocardiogram indicated a normal sinus rhythm with evidence of an intraventricular conduction delay and widespread repolarization abnormality. The Holter monitor trace showed a short run of nonsustained ventricular tachycardia. Cardiac magnetic resonance imaging (MRI) findings revealed prominent epicardial fat and borderline dilatation of the left ventricle with a mildly reduced ejection fraction. Regional wall motion abnormalities were observed, including mild hypokinesis in the midanterolateral segment and severe hypokinesis in the apical inferior and lateral segments (Video 1 and Video 2). No abnormalities were detected in the right ventricular size, wall thickness, or regional or global function. Late gadolinium enhancement imaging demonstrated epicardial enhancement of the midanterolateral, basal and midinferior, and inferolateral segments (Figure 2).Late gadolinium enhancement cardiac magnetic resonance imaging. Epicardial and midwall enhancement of the anterior, anteroseptal, anterolateral, and inferior segments extending partially into the inferoseptal segment (arrowheads).We suspected that the patient had isolated arrhythmogenic left ventricular cardiomyopathy and thus referred her for genetic testing. A deletion was identified in the desmoplakin gene (DSP; GenBank NM_004415), with the cDNA variant c.4423del producing the protein change p.Thr1475fs, which to the best of our knowledge has not previously been reported. This mutation is predicted to cause a frameshift and premature termination of translation in the DSP gene, an action similar to that of other DSP variants that have been implicated in arrhythmogenic right ventricular cardiomyopathy.Arrhythmogenic cardiomyopathy affecting the left ventricle is increasingly being recognized as having pathophysiological features similar to those of arrhythmogenic right ventricular cardiomyopathy. Fibro-fatty changes and similar mutations in genes encoding desmosomal proteins are observed in both conditions, which also appear to share prognostic features.1Genetic screening has been used previously to detect arrhythmogenic left ventricular cardiomyopathy, with a reported case of a frameshift mutation and introduction of a premature stop codon in the DSP gene (S1015fsX1017) and MRI features of late gadolinium enhancement in the midmyocardial and epicardial regions.2 Another study reported a family with autosomal dominant, left-sided arrhythmogenic cardiomyopathy caused by a frameshift mutation in desmoplakin, which was identified following cardiac evaluation triggered by the sudden death of a young member of the family.3The patient underwent a reveal implantation procedure that identified complete heart block with ventricular standstill. An implantable cardioverter-defibrillator was fitted for cardiac pacing to ameliorate bradycardia and to provide primary prevention. Screening for this gene mutation was instigated for all other family members.This case highlights the importance of cardiac MRI in early detection of a rare cardiac abnormality, which led to a substantial difference in the management of the condition for this patient and her family. Although traditionally considered to be an indicator of previous myocarditis, isolated subepicardial enhancement observed with MRI may be a subtle feature of nonischemic cardiomyopathy. The MRIs, although not typical for ischemic cardiomyopathy, could have been interpreted as such.

Cardiology

A white woman in her late 50s presented with palpitations, breathlessness, chest pain, and episodes of light-headedness. Her risk profile included a family history of sudden cardiac death: her cousin died unexpectedly in his mid-40s while playing football. A physical examination showed no remarkable findings. Her systolic blood pressure was 125 mm Hg, diastolic blood pressure was 70 mm Hg, and resting heart rate was 52 beats/min. Portions of her electrocardiogram (Figure 1A) and 24-hour Holter monitoring trace (Figure 1B) are shown. Echocardiographic findings included mildly impaired systolic function (left ventricular ejection fraction, 45%-50%) but were otherwise normal. Coronary angiography was performed and revealed normal coronary arteries.Patient electrocardiogram (A) and a portion of the 24-hour Holter monitor trace (B).Implant a device to determine frequency of ventricular tachycardia

what would you do next?

What would you do next?

Conduct an invasive electrophysiological study

Implant a device to determine frequency of ventricular tachycardia

Order cardiac magnetic resonance imaging

Order cardiac positron emission tomography

c

female

51-60

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2666576

An otherwise healthy man in his 40s was referred to our ear, nose, and throat department for the evaluation of a giant, left-sided neck mass. He reported no antecedent neck trauma or neck infection, nor any history of swelling during childhood. He experienced dyspnea, limitation of neck movements, and neck tightness owing to the bulkiness of the lesion. The swelling had been present for approximately 12 months, and the growth was gradual and continuous. Contrast-enhanced T1- and T2-weighted magnetic resonance imaging (MRI) revealed a 15 × 7-cm homogenous ovoid bilobulated cystic mass in the left lateral region of the neck with displacement of the surrounding musculature and vascular structures but no sign of invasion. The imaging of the lesion revealed fibrous septae in the central and inferior parts, with extension to the supraclavicular region (Figure, A and B). After written informed consent was obtained, the patient underwent total excision of the cystic mass through an apron flap incision combined with T-incision for preservation of cranial nerve XI and sternocleoidomastoid muscle (Figure, C).A, T1-weighted magnetic resonance image (MRI) shows a homogenous ovoid bilobulated hypointense cystic mass in left parapharyngeal area and posterior cervical region, extending to the supraclavicular triangle. B, T2-weighted MRI demonstrates thin-walled, markedly hyperintense cystic mass indenting neighboring structures. No fluid-fluid level is observed. C, Cervical mass with preservation of the vital structures of the neck. What Is Your Diagnosis?

Branchial cleft cyst

Glomus tumor

Liposarcoma

Cervical lymphatic malformation

D. Cervical lymphatic malformation

D

Cervical lymphatic malformation

Histopathological evaluation showed dilated lymphatic spaces lined with flat, cuboidal endothelial cells, consistent with the diagnosis of macrocystic lymphatic malformation (LM). The healing was uneventful, and the patient was disease-free at his 12-month follow-up.Cervical macrocystic LM is well recognized in pediatric practice but seldom presents de novo in adulthood. There are 4 types of LMs on the cervical region: capillary, cavernous, cystic, and venolymphatic forms. The International Society for the Study of Vascular Anomalies (ISSVA) updated the classification of vascular anomalies in 2014, and simple vascular malformations were thenceforward classified by the principle type of vessel they are composed of as well as their ultrasonographic Doppler findings of low or high flow: capillary, venous, lymphatic, or arterial.1 Lymphatic malformations are accordingly classified as microcystic, macrocystic, and mixed type, as distinguished by ultrasonography and MRI findings. They usually present as a progressive and painless growth, although occasionally growth may be sudden. According to location and size of the mass, LMs can cause symptoms such as dysphagia, airway obstruction, dyspnea, and even drop attacks.2,3 Diagnosis in children is usually straightforward, but it can be problematic in adults because of the rarity.4 A limited number of idiopathic adult-onset LM cases in various sites, including head and neck region, have been reported in the literature.5 The etiology of macrocystic LMs is poorly understood, but the lines of investigation support the notion that failure to establish or maintain communication between the developing lymphatic channels and the venous system results in autonomous lymphatic structures and LM formation.6 This assumption is still doubtful in an adult patient, as in the case reported herein, because no triggering factor, such as trauma, infection, or hormonal change,7 was present in patient’s medical history. In this case, the cystic-appearing mass of the left cervical region has intermediate-hypointense signal on T1-weighted MRI and hyperintensity on T2-weighted images. Very high and homogenous signal intensity of T2-weighted sequences are the characteristics of a cystic lesion. Lack of contrast enhancement rules out solid masses as a general rule. Thin- and regular-walled appearance without invasion of neighboring structures are the indicators of a benign cystic mass.Referring to the current ISSVA classification,1 macrocystic LMs, composed of lesions greater than 2 cm3 in size, are less challenging to treat and respond well to both surgical resection and sclerotherapy. However, microcystic lesions less than 2 cm3 in size are often composed of microlymphatic channels that are integrated and infiltrate normal soft tissue. Poorly defined borders relative to adjacent tissue complicate treatment and limit surgical and sclerotherapy outcomes. Thus, multimodal and frequently staged therapy will be required.8 In conclusion, cervical macrocystic LM, although rather rare in adults, should be included in the differential diagnosis for a neck swelling in an adult.

General

An otherwise healthy man in his 40s was referred to our ear, nose, and throat department for the evaluation of a giant, left-sided neck mass. He reported no antecedent neck trauma or neck infection, nor any history of swelling during childhood. He experienced dyspnea, limitation of neck movements, and neck tightness owing to the bulkiness of the lesion. The swelling had been present for approximately 12 months, and the growth was gradual and continuous. Contrast-enhanced T1- and T2-weighted magnetic resonance imaging (MRI) revealed a 15 × 7-cm homogenous ovoid bilobulated cystic mass in the left lateral region of the neck with displacement of the surrounding musculature and vascular structures but no sign of invasion. The imaging of the lesion revealed fibrous septae in the central and inferior parts, with extension to the supraclavicular region (Figure, A and B). After written informed consent was obtained, the patient underwent total excision of the cystic mass through an apron flap incision combined with T-incision for preservation of cranial nerve XI and sternocleoidomastoid muscle (Figure, C).A, T1-weighted magnetic resonance image (MRI) shows a homogenous ovoid bilobulated hypointense cystic mass in left parapharyngeal area and posterior cervical region, extending to the supraclavicular triangle. B, T2-weighted MRI demonstrates thin-walled, markedly hyperintense cystic mass indenting neighboring structures. No fluid-fluid level is observed. C, Cervical mass with preservation of the vital structures of the neck.

what is your diagnosis?

What is your diagnosis?

Liposarcoma

Branchial cleft cyst

Glomus tumor

Cervical lymphatic malformation

d

male

41-50

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2666769

A woman in her 20s with a history of cystic fibrosis underwent bilateral endoscopic sinus surgery and medial maxillectomy 4 months after bilateral lung transplantation. She presented to her rhinologist for follow-up 6 weeks after surgery reporting improved nasal obstruction and olfaction, but complained of 2 weeks of throat pain and swelling. Physical examination revealed bilateral tonsillar erythema, exudate, tenderness, and peritonsillar edema. She was prescribed amoxicillin–clavulanic acid for presumed tonsillitis and began to improve. Two weeks later her symptoms returned, now accompanied by new-onset snoring and nasal obstruction. Nasal endoscopy revealed nasopharyngeal soft-tissue swelling with mucopurulent secretions on the left side. She was referred for a computed tomographic scan with contrast, which showed a rim-enhancing, multilocular hypodense collection extending from the left nasopharynx inferiorly to the level of the right palatine tonsil (Figure 1). On the basis of the radiographic findings, she was taken to the operating room urgently. Intraoperative endoscopy revealed ulceration and necrotic debris in the nasopharynx and oropharynx. Culture and biopsy specimens were obtained. What Is Your Diagnosis?

Mycobacterial abscess

Posttransplant lymphoproliferative disorder

Acute invasive fungal sinusitis

Nasopharyngeal carcinoma

B. Posttransplant lymphoproliferative disorder

B

Posttransplant lymphoproliferative disorder

Based on the imaging findings, the differential diagnosis includes lesions arising from the pharyngeal mucosal space with retropharyngeal extension and, less likely, a primary process of the retropharyngeal space. Pathologic conditions occurring in the pharyngeal mucosal space include malignant neoplasms arising from the mucosal and lymphoid tissues of the pharynx, inflammatory and infectious lesions, and neoplasms of musculoskeletal and salivary origin.1 Malignant neoplasms presenting in the nasopharynx include nasopharyngeal carcinoma, locally advanced squamous cell carcinoma from adjacent primary sites, rhabdomyosarcoma, and lymphoma. While retropharyngeal abscess in the setting of acute bacterial pharyngitis might represent a typical diagnosis in children and healthy adults, other infectious etiologies include tuberculosis and fungal infections.2 In this patient, the multifocal involvement of the Waldeyer ring and the history of posttransplant immunosuppression are key to understanding the ultimate diagnosis.Posttransplant lymphoproliferative disorder (PTLD) is a widely recognized complication of solid-organ transplantation, arising in the context of the immunosuppression necessary for long-term survival of transplanted organs. It is the most common malignant neoplasm after solid-organ transplantation in children and the second in adults behind nonmelanoma skin cancer, affecting roughly 10% to 15% of patients after transplantation.3 Posttransplant lymphoproliferative disorder comprises a continuum of lymphoproliferative disease, ranging from early hyperplastic lesions to classic Hodgkin lymphoma. Monomorphic PTLD is the most common subtype, the most common phenotype being diffuse large B cell lymphoma.3,4There is a strong association between PTLD and Epstein Barr virus (EBV) infection, with higher rates of PTLD observed in children and adults first infected with EBV after transplant. Epstein-Barr virus is a human herpesvirus that infects B cells and epithelial cells, particularly the lymphoid tissue in the oral cavity, oropharynx, and nasopharynx.4 Once it has entered a host, the virus can propagate a lytic phase, which classically presents as infectious mononucleosis, or reside in the host in a latent phase, expressing proteins that promote clonal cell proliferation. The latter is implicated in the malignant transformation of host cells that precedes PTLD.5 Excisional tissue biopsy is preferred for diagnosis, while laboratory tests, viral serologies, and positron emission tomography/computed tomography (PET/CT) imaging complete the initial workup.3,6Posttransplant lymphoproliferative disorder is more aggressive than classical lymphoma with greater likelihood of extranodal involvement, making early diagnosis paramount, especially because conventional therapies may be ineffective.7 The initial approach to therapy consists of a reduction in immunosuppression, often with the addition of rituximab, a chimeric antibody against B cells. Chemotherapy is used in patients whose disease does not respond to these measures or with a burden of disease necessitating a more rapid clinical response. Localized therapy consists of surgical debulking or radiation therapy. Antivirals are not currently recommended for prophylaxis or treatment. Novel therapies being researched include adoptive T cell therapy using EBV-specific cytotoxic lymphocytes and pharmacologic modulation of the mammalian target of rapamycin (mTOR) pathway, which is implicated in malignant transformation.3,5,6In this patient, pathologic analysis was consistent with EBV-positive, monomorphic PTLD, with a diffuse large B cell lymphoma phenotype (Figure 2). The patient underwent staging PET, which showed disease limited to the nasopharynx and oropharynx. She subsequently completed 5 cycles of chemotherapy and showed complete response on follow-up PET/CT.Histopathological images, original magnification ×10. A, Hematoxylin-eosin (H&E) staining of large atypical lymphoid cells. B, Positive stain for B-cell surface marker CD20. C, Positive stain for Epstein-Barr virus RNA using Epstein-Barr encoding region in situ hybridization (EBER-ISH).

General

A woman in her 20s with a history of cystic fibrosis underwent bilateral endoscopic sinus surgery and medial maxillectomy 4 months after bilateral lung transplantation. She presented to her rhinologist for follow-up 6 weeks after surgery reporting improved nasal obstruction and olfaction, but complained of 2 weeks of throat pain and swelling. Physical examination revealed bilateral tonsillar erythema, exudate, tenderness, and peritonsillar edema. She was prescribed amoxicillin–clavulanic acid for presumed tonsillitis and began to improve. Two weeks later her symptoms returned, now accompanied by new-onset snoring and nasal obstruction. Nasal endoscopy revealed nasopharyngeal soft-tissue swelling with mucopurulent secretions on the left side. She was referred for a computed tomographic scan with contrast, which showed a rim-enhancing, multilocular hypodense collection extending from the left nasopharynx inferiorly to the level of the right palatine tonsil (Figure 1). On the basis of the radiographic findings, she was taken to the operating room urgently. Intraoperative endoscopy revealed ulceration and necrotic debris in the nasopharynx and oropharynx. Culture and biopsy specimens were obtained.

what is your diagnosis?

What is your diagnosis?

Acute invasive fungal sinusitis

Mycobacterial abscess

Nasopharyngeal carcinoma

Posttransplant lymphoproliferative disorder

d

female

21-30

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2666814

An adolescent girl presented with a history of multiple, slowly growing masses of the face and head. The lesions were first reported when she was 5 years of age and gradually increased in size. However, her medical history was otherwise unremarkable. On clinical examination, the lesions were hard in consistency with normal overlying skin. There was significant bilateral exophthalmos (the left eye was more pronounced), with visual changes, and dental malocclusion. However, there were no clinical signs of endocrinopathy. A skeletal survey showed no involvement of other bones. The patient’s serum calcium, phosphate, alkaline phosphatase, thyroid, and parathyroid hormone levels were within normal limits. A computed tomographic (CT) examination of the craniofacial skeleton was performed (Figure).Noncontrast axial bone algorithm computed tomographic images of the facial bones. What Is Your Diagnosis?

Florid osseous dysplasia

Paget disease of bone

Fibrous dysplasia

Gardner syndrome

C. Fibrous dysplasia

C

Fibrous dysplasia

Fibrous dysplasia (FD) is a nonheritable, genetic disorder characterized by the replacement of normal bone by immature, haphazardly distributed bony and fibrous tissues. It is caused by a mutation in the GNAS1 gene on chromosome 20, resulting in abnormal osteoblast differentiation and irregular bone formation.1 Fibrous dysplasia may affect a single bone (monostotic form) or multiple bones (polyostotic form), and the latter may be divided into 3 subtypes: (1) craniofacial FD, in which only the bones of the craniofacial skeleton are affected; (2) Jaffe-Lichtenstein syndrome, characterized by polyostotic FD and skin pigmentation (café au lait spots); and (3) McCune-Albright syndrome, characterized by the triad of polyostotic FD, café au lait spots, and hyperfunctional endocrinopathic abnormalities, especially precocious puberty in girls.2The most common clinical feature of FD is painless, slowly progressive swelling of the involved bone. If extensive craniofacial lesions have impinged on skull foramina, neurologic deficits may develop.3 Monostotic FD accounts for approximately 80% of all cases, with the jaws being among the most commonly affected bones. However, the maxilla is involved almost twice as often as the mandible.4 The polyostotic disease typically has an onset in children younger than 10 years, whereas the monostotic form usually is discovered in a slightly older age group. Whereas both monostotic and polyostotic forms occur with equal frequency in males and females, McCune-Albright syndrome affects females almost exclusively.1The radiological features of FD can vary considerably depending on the maturity of the lesion. In the early stage, FD appears as a unilocular or multilocular radiolucency with ill-defined or well-defined borders. In the mixed stage, radiopaque tissue appears in the radiolucent structure. In the mature stage, the internal structure exhibits mottled radiopaque patterns often described as resembling ground glass, orange peel, or fingerprints, with ill-defined borders blending into the normal adjacent bone.5In the case described herein, axial computed tomographic (CT) images (Figure) demonstrate diffuse bilateral expansile lesions with ground-glass density involving the cranial vault, skull base, frontoethmoid region, and maxillofacial skeleton, with extensive involvement of the orbits and sinus cavities.There are several conditions that can alter the bone pattern in a similar fashion. Hyperparathyroidism may produce a similar internal pattern, but this disease, in contrast to FD, does not commonly cause bone expansion. Paget disease of bone and florid osseous dysplasia may cause expansion; however, they occur in an older age group. Fibrous dysplasia seems to be unique in its ability to displace the mandibular canal in a superior direction. This finding is extremely useful in distinguishing FD from ossifying fibroma. Osteomyelitis and osteosarcoma that invade the mandible at times may be difficult to differentiate from FD. However, periosteal reaction and sequestra formation aid in the identification of osteomyelitis. Osteosarcoma should show more aggressive or malignant radiologic features.6In most cases, the disease stabilizes after the child reaches skeletal maturity; thus, cosmetic surgery and orthodontic treatment may be postponed until this time. Medical treatment with intravenous bisphosphonates has shown some promising results.7 It has been estimated that 25% to 50% of patients show some regrowth after surgical reduction.8 Malignant transformation of FD has been reported, especially after therapeutic irradiation.9In conclusion, the imaging features of FD are characteristic, but not specific, and depend on the histopathologic analysis. Surgery remains the mainstay of therapy for FD. However, lesions without functional impairment or aesthetic deformity can be treated by close follow-up. Radiation is not a recommended treatment of FD.

General

An adolescent girl presented with a history of multiple, slowly growing masses of the face and head. The lesions were first reported when she was 5 years of age and gradually increased in size. However, her medical history was otherwise unremarkable. On clinical examination, the lesions were hard in consistency with normal overlying skin. There was significant bilateral exophthalmos (the left eye was more pronounced), with visual changes, and dental malocclusion. However, there were no clinical signs of endocrinopathy. A skeletal survey showed no involvement of other bones. The patient’s serum calcium, phosphate, alkaline phosphatase, thyroid, and parathyroid hormone levels were within normal limits. A computed tomographic (CT) examination of the craniofacial skeleton was performed (Figure).Noncontrast axial bone algorithm computed tomographic images of the facial bones.

what is your diagnosis?

What is your diagnosis?

Paget disease of bone

Florid osseous dysplasia

Gardner syndrome

Fibrous dysplasia

d

female

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2667845

A young boy presented to the emergency department with a 2-week history of left facial and eye pain with intermittent diplopia on upward and lateral gaze. He was otherwise healthy and exhibited no constitutional complaints. His remaining medical, surgical, family, and social history was noncontributory. Examination showed a healthy-appearing child with left abducens nerve palsy and an afferent pupillary defect. There was no chemosis, exophthalmos, or enophthalmos. Findings from nasal endoscopy were unremarkable. A computed tomographic scan of the sinuses without contrast showed a well-circumscribed posterior-medial extraconal mass extending into the orbital apex with smooth, nonaggressive bony remodeling and expansion of the left superior orbital fissure with further dorsal extension into the left cavernous sinus (Figure, A). Magnetic resonance imaging of the orbits showed that orbital component was inseparable from medial rectus muscle. Tumor also resulted in lateral displacement and compression of the left optic nerve (Figure, B). The patient underwent an image-guided left endoscopic orbital decompression with biopsy of the orbital mass. Representative hematoxylin-eosin–stained sections are shown in the Figure, C and D. The tumor was negative for FUS (FUsed in Sarcoma; also termed TLS, Translocated in LipoSarcoma)-CHOP (C/EBP HOmologous Protein; also termed DDIT3, DNA Damage-Inducible Transcript 3) fusion oncogene on fluorescent in situ hybridization (FISH).A, Axial cut of noncontrast computed tomographic (CT) scan of facial bones. B, Axial cut of T1-weighted magnetic resonance image (MRI). C and D, Representative hematoxylin-eosin–stained histologic sections of the lesion. What Is Your Diagnosis?

Lipoblastoma

Liposarcoma, conventional myxoid variant

Liposarcoma, pleomorphic myxoid variant

Teratoma

C. Liposarcoma, pleomorphic myxoid variant

C

Liposarcoma, pleomorphic myxoid variant

Traditionally, liposarcomas can be classified as typical myxoid or round cell, pleomorphic, or dedifferentiated subtypes.1 Since its first description by Alaggio et al2 in 2009, pleomorphic myxoid liposarcoma (PML) is now increasingly being recognized as a distinct subtype based on genomic analyses. Specifically, several reported cases of PML3,4 showed an absence of t(12;16) (q13;p11) translocation and the subsequent lack of fusion transcripts of the CHOP and FUS genes classically found in conventional myxoid liposarcomas.At low power, PML shows a rich myxoid matrix with a well-developed capillary pattern and bland round cells (Figure, C). In addition to areas displaying typical low-grade myxoid liposarcoma features, higher magnification reveals foci with a transition into an increasingly cellular and pleomorphic area with marked hyperchromatism, cellular atypia, bizarre mitotic forms, and giant pleomorphic lipoblasts (Figure, D). Liposarcoma is further differentiated from lipoblastoma, which is a disease occurring primarily in infancy to young childhood, with a relatively benign clinical course. Teratomas and dermoid cysts contain calcifications or cystic areas in addition to soft-tissue and fatty elements. When PML was first described in detail by Alaggio et al2 in a pediatric liposarcoma case series consisting of 82 patients (which remains the largest case series to date), only 12 cases had been reported, only 1 of which had originated in the head and neck region. A more recent, albeit smaller, multi-institutional review of pediatric liposarcomas by Huh et al5 with 33 patients revealed 3 patients with the PML subtype; however, there was no mention of corresponding location of primary site.Pleomorphic myxoid liposarcoma should be recognized as a high-grade sarcoma in the pediatric population because it is usually associated with aggressive tumor behavior and poor prognosis. Data from the case series reported by Alaggio et al2 showed that 7 of 10 children with PML were known to have died of their disease before 3 years of age. The 1 child with head and neck PML in the series had presented with unresectable disease, underwent 3 cycles of chemotherapy, followed by resection with adjuvant radiation. Her disease recurred within 1 year with retroperitoneal metastasis, and she died within 3 years.Similarly, primary liposarcoma in the orbit is rare, even in the adult population. Less than 50 cases of primary orbital liposarcomas have been reported in the literature to date, most of which were characterized as the myxoid variant. In our review of the literature, we encountered a few cases of orbital liposarcomas, an adult and a child, with descriptive features reminiscent of PML. Salam et al6 described a case of orbital liposarcoma in a 32-year-old man with Li-Fraumeni syndrome that morphologically resembled the myxoid variant but lacked the typical cytogenic translocation of CHOP or FUS. He underwent skin-sparing orbital exenteration and was recurrence-free at 18 months following the surgery. Similarly, Rudzinski et al7 reported a case of orbital pleomorphic liposarcoma in an 8-year-old boy with variably myxoid features that did not show the reciprocal translocation between chromosomes 12 and 16: t(12;16) (q13; p11) classically seen in myxoid and round cell variants. His disease followed an aggressive course, and he eventually died of metastatic sacral liposarcoma despite surgical debulking and chemoradiotherapy. It is possible that these examples represent unrecognized cases of PML.In conclusion, unlike adult sarcomas, pediatric liposarcomas are exceptionally rare. As its name implies, pleomorphic myxoid subtype is a variant encompassing histopathologic features of conventional myxoid and pleomorphic subtypes and is now becoming recognized as a distinct subtype based on its absence of FUS-CHOP and EWSR1-CHOP rearrangements on FISH. Emphasis should also be placed on thorough histopathologic examination because PMLs seem to exhibit distinct tumor biologic characteristics and carry a notably poorer prognosis than its conventional myxoid lookalike.

General

A young boy presented to the emergency department with a 2-week history of left facial and eye pain with intermittent diplopia on upward and lateral gaze. He was otherwise healthy and exhibited no constitutional complaints. His remaining medical, surgical, family, and social history was noncontributory. Examination showed a healthy-appearing child with left abducens nerve palsy and an afferent pupillary defect. There was no chemosis, exophthalmos, or enophthalmos. Findings from nasal endoscopy were unremarkable. A computed tomographic scan of the sinuses without contrast showed a well-circumscribed posterior-medial extraconal mass extending into the orbital apex with smooth, nonaggressive bony remodeling and expansion of the left superior orbital fissure with further dorsal extension into the left cavernous sinus (Figure, A). Magnetic resonance imaging of the orbits showed that orbital component was inseparable from medial rectus muscle. Tumor also resulted in lateral displacement and compression of the left optic nerve (Figure, B). The patient underwent an image-guided left endoscopic orbital decompression with biopsy of the orbital mass. Representative hematoxylin-eosin–stained sections are shown in the Figure, C and D. The tumor was negative for FUS (FUsed in Sarcoma; also termed TLS, Translocated in LipoSarcoma)-CHOP (C/EBP HOmologous Protein; also termed DDIT3, DNA Damage-Inducible Transcript 3) fusion oncogene on fluorescent in situ hybridization (FISH).A, Axial cut of noncontrast computed tomographic (CT) scan of facial bones. B, Axial cut of T1-weighted magnetic resonance image (MRI). C and D, Representative hematoxylin-eosin–stained histologic sections of the lesion.

what is your diagnosis?

What is your diagnosis?

Liposarcoma, conventional myxoid variant

Lipoblastoma

Teratoma

Liposarcoma, pleomorphic myxoid variant

d

male

11-20

original

https://jamanetwork.com/journals/jama/fullarticle/2672333

A woman in her 60s presented with a 2-year history of an abnormal left second fingernail. A previous biopsy showed a pyogenic granuloma, and she had been treated with curettage and electrodessication. In the few months before presentation, she experienced partial nail loss and her nail had become painful with intermittent drainage. Her medical history was significant for streptococcal glomerulonephritis and 2 prior kidney transplants. Her medications included prednisone, tacrolimus, and mycophenolate mofetil. Physical examination of the left second fingernail showed a tender ulcerated nodule encompassing the nail bed with near-complete nail loss and purulent drainage (Figure 1, left). A nail biopsy was repeated by performing a 4-mm punch through the nail bed. The specimen was analyzed by histopathology with hematoxylin-eosin staining and once again showed a pyogenic granuloma–like response characterized by proliferating blood vessels in a background of fibrosis and reactive plasmacytic infiltration (Figure 1, right). Careful inspection of the pyogenic granulomatous process at higher power demonstrated atypical epithelioid and spindled cells adjacent to blood vessels.Left, Physical examination of left second fingernail. Right, Histopathologic findings under low-power magnification (hematoxylin-eosin, original magnification ×20).Perform tissue culture for bacterial and fungal organisms What Would You Do Next?

Treat with cryotherapy