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kenza-ily

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JAMA_Chen2024

like 0

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2718841

A 64-year-old man presented to the emergency department with 2 months of progressively worsening vision in both eyes. The worsening vision was preceded by binocular diplopia, which was intermittent at first and then became constant. He had no relevant ocular or other medical history. A review of systems was notable for a 2-month history of progressively worsening shortness of breath. He denied any fevers, night sweats, or unintentional weight loss. Visual acuity was found to be 20/200 OD and 20/25 OS. His pupils were round and equally reactive, and there was no relative afferent pupillary defect. The intraocular pressure was normal in both eyes. On external examination, bilateral proptosis and increased resistance to retropulsion was observed. There was very limited extraocular motility in all directions of gaze on the right side and moderately limited extraocular motility on the left side. In addition, the patient had an esotropia and right hypertropia. Anterior segment examination revealed bilateral chemosis. The fundus examination (Figure 1) showed chorioretinal folds in both eyes and intraretinal hemorrhages in the right eye. The optic discs had normal color and sharp margins bilaterally.A, Fundus photograph of the right eye showing prominent chorioretinal folds throughout the macula and 2 intraretinal hemorrhages near the vascular arcades. B, Fundus photograph of the left eye, also demonstrating chorioretinal folds. Both photographs were taken in the emergency department using a smartphone-based camera system.Order a computed tomographic scan of the orbitsPerform emergency canthotomy and cantholysis to decompress the orbits What Would You Do Next?

Perform an orbital biopsy

Order a computed tomographic scan of the orbits

Obtain a consultation from the retina service

Perform emergency canthotomy and cantholysis to decompress the orbits

Bilateral chorioretinal folds owing to globe compression from bilateral orbital masses

B

Order a computed tomographic scan of the orbits

The differential diagnosis of chorioretinal folds includes hypotony maculopathy, a neovascular membrane, an ocular or orbital inflammatory process, or globe compression by tumor.1 In this case, the proptosis, chemosis, resistance to retropulsion, and bilateral presentation suggest an orbital cause. A computed tomographic scan of the orbits (choice B) is indicated for initial workup. Orbital biopsy (choice A) would not be appropriate before imaging to determine the underlying causative mechanism. Consulting the retina service (choice C) would not be the most appropriate next step because retinal causes (eg, neovascular membrane, hypotony maculopathy, posterior scleritis) are lower on the list of differential diagnoses. Canthotomy and cantholysis (choice D) would be appropriate management for acute orbital compartment syndrome caused by a retrobulbar hematoma.A computed tomographic scan (Figure 2) demonstrated bilateral extraconal soft-tissue hyperdensities exerting mass effect on both globes, measuring 4.9 × 2.1 cm on the right side and 3.2 × 1.3 cm on the left side. The Division of Hematology-Oncology recommended systemic workup. A positron emission tomography and computed tomography confirmed hypermetabolic orbital lesions and revealed widespread metastatic disease including lymph node and pleural space involvement. A decision was made to avoid orbital biopsy and instead proceed with biopsy of a supraclavicular lymph node, which revealed a dense, diffuse infiltrate of CD20-positive, BCL-1–positive cells. Three days after admission, the patient required thoracentesis for shortness of breath. Flow cytometry of pleural fluid showed a CD5-positive, kappa-restricted, mature B-cell neoplasm. The patient was diagnosed with stage IV mantle-cell lymphoma and began treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (the R-CHOP regimen).Computed tomographic images of the orbits reveal bilateral extraconal orbital hyperdensities (white arrowheads) measuring 4.9 × 2.1 cm on the right (A) and 3.2 × 1.3 cm on the left (B). Both hyperdensities exert mass effect on each globe, with the right more affected than the left.Mantle-cell lymphoma is an aggressive non-Hodgkin B-cell lymphoma caused by clonal proliferation of pregerminal B cells.2,3 In 95% of cases, the driving mutation is a chromosomal translocation (t(11;14)) causing overexpression of the cell cycle regulatory protein cyclin D1 (also known as BCL-1).4 Mantle-cell lymphoma makes up 9% of all lymphoma occurring in the ocular and periocular region and may simultaneously involve multiple sites including the orbit (in 90% of patients), eyelid (50%), lacrimal gland (50%), or nasolacrimal sac (20%).2 Affected patients are often elderly men. In 67% of cases, the ocular or periocular disease was the first presenting sign of lymphoma, and most patients have stage III or stage IV disease at presentation.2,5 Less than one-third of patients with mantle-cell lymphoma have B symptoms (eg, fever, night sweats, or unintentional weight loss).6 A workup of mantle-cell lymphoma in the orbital or adnexal region must include systemic imaging.On computed tomographic scans, lymphoma appears as a homogeneous mass isodense or hyperdense to extraocular muscles; it is weakly contrast enhancing.7 On magnetic resonance imaging, lymphoma shows homogeneous enhancement and exhibits restricted diffusion. Most lymphomas mold to the shape of the globe, but an aggressive lymphoma such as mantle-cell lymphoma may not.In this case, the patient’s decreased visual acuity was because of a mass effect that caused chorioretinal folds, and there were no signs of compressive optic neuropathy. He was treated medically with chemotherapy. Among patients with orbital or adnexal disease, those who had R-CHOP instead of CHOP therapy had significantly higher rates of overall survival at 5 years (83% vs 8%).5 On outpatient follow-up, the patient’s visual acuity had improved to 20/20 OU.

Ophthalmology

A 64-year-old man presented to the emergency department with 2 months of progressively worsening vision in both eyes. The worsening vision was preceded by binocular diplopia, which was intermittent at first and then became constant. He had no relevant ocular or other medical history. A review of systems was notable for a 2-month history of progressively worsening shortness of breath. He denied any fevers, night sweats, or unintentional weight loss. Visual acuity was found to be 20/200 OD and 20/25 OS. His pupils were round and equally reactive, and there was no relative afferent pupillary defect. The intraocular pressure was normal in both eyes. On external examination, bilateral proptosis and increased resistance to retropulsion was observed. There was very limited extraocular motility in all directions of gaze on the right side and moderately limited extraocular motility on the left side. In addition, the patient had an esotropia and right hypertropia. Anterior segment examination revealed bilateral chemosis. The fundus examination (Figure 1) showed chorioretinal folds in both eyes and intraretinal hemorrhages in the right eye. The optic discs had normal color and sharp margins bilaterally.A, Fundus photograph of the right eye showing prominent chorioretinal folds throughout the macula and 2 intraretinal hemorrhages near the vascular arcades. B, Fundus photograph of the left eye, also demonstrating chorioretinal folds. Both photographs were taken in the emergency department using a smartphone-based camera system.Order a computed tomographic scan of the orbitsPerform emergency canthotomy and cantholysis to decompress the orbits

what would you do next?

What would you do next?

Perform emergency canthotomy and cantholysis to decompress the orbits

Order a computed tomographic scan of the orbits

Obtain a consultation from the retina service

Perform an orbital biopsy

b

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2715814

A woman in her early 30s presented with acute onset of painful proptosis of the right eye and mild epistaxis with no inciting trauma. Her medical history was notable for hypertension, treated with clonidine hydrochloride, and opiate abuse, treated with methadone hydrochloride. Her blood pressure was 138/87 mm Hg. The patient was afebrile with no leukocytosis. Her visual acuity was 20/20 OU with no afferent pupillary defect and normal intraocular pressures. Examination revealed periorbital edema, proptosis, and limitation in supraduction, abduction, and adduction in the right eye. There was no periorbital soft-tissue erythema, warmth, or tenderness to palpation. Computed tomography showed hyperattenuating soft tissue in the superior, medial, and inferior right orbit (Figure 1A, arrowheads). Magnetic resonance imaging showed no internal flow voids to suggest vascular malformation. Results of a laboratory workup revealed mildly elevated erythrocyte sedimentation rate (49 mm/h; reference range, 0-20 mm/h) and antinuclear antibody titer (1:80; reference range, <1:40) as well as positive results for anti-Ro and anti-La antibodies. Results of further autoimmune and infectious workup were negative. Two weeks later, new proptosis and periocular edema of the left eye developed, with no inciting trauma. Her examination results were significant for proptosis, periorbital edema, and limitation in supraduction in the left eye. Computed tomography showed new hyperattenuating soft tissue in the left superior and lateral orbit (Figure 1B, arrowhead).A, Coronal contrast-enhanced computed tomographic scan shows hyperattenuating soft tissue in the superior, medial, and inferior subperiosteal space of the right orbit (arrowheads). B, Computed tomographic scan, not contrast enhanced, shows hyperattenuating orbital soft tissue in the left orbit (arrowhead). What Would You Do Next?

Empirical corticosteroid treatment

Orbitotomy with biopsy

External beam radiotherapy

Intravenous antibiotic therapy

Bilateral sequential, nontraumatic, subperiosteal hemorrhage in a patient with systemic lupus erythematosus

B

Orbitotomy with biopsy

This is a case of a patient presenting with bilateral sequential acute proptosis without a history of trauma. The differential diagnosis included infection, such as orbital cellulitis or subperiosteal abscess; orbital vascular abnormalities; nonvascular neoplastic processes; inflammatory processes, such as nonspecific orbital inflammatory syndrome; and spontaneous subperiosteal hemorrhage. Given the presentation and clinical examination findings, neoplastic and infectious processes were less likely. Imaging showed no evidence of vascular abnormalities. Therefore, orbital exploration with biopsy was indicated to establish a diagnosis. Corticosteroid treatment and radiotherapy may be helpful for certain inflammatory and neoplastic conditions, but tissue diagnosis is recommended before initiating treatment. Antibiotic treatment could be considered empirically if there is suspicion for infection but would not be the primary treatment in this case given the clinical picture.The patient underwent orbital exploration and biopsy, which revealed well-organized subperiosteal hematoma with no evidence of vasculitis. Results of further autoimmune and infectious disease workup were negative, including results for rheumatoid factor, anti-DNA, antinuclear antibody, perinuclear antineutrophil cytoplasmic antibody, cytoplasmic antineutrophil cytoplasmic antibody, HIV, varicella and cytomegalovirus IgM, tuberculosis (spot test), and hepatitis B virus surface antigen. Results of a coagulopathy workup were negative, including platelet count, prothrombin time, activated partial thromboplastin time, thrombin time, von Willebrand antigen, factors VIII and XIII, cardiolipin antibody, and peripheral blood smear. A bullous rash developed on the patient’s face, neck, and trunk; findings of a skin biopsy specimen indicated bullous systemic lupus erythematosus (SLE) (Figure 2). Renal insufficiency was discovered, and the patient underwent renal biopsy, the results of which were consistent with lupus nephritis class IV. Treatment with hydroxychloroquine sulfate, prednisone, and mycophenolate mofetil was started.Skin biopsy specimen shows subepidermal bullous dermatosis (arrowhead) with mild underlying perivascular chronic inflammation consistent with bullous systemic lupus erythematosus (hematoxylin-eosin, original magnification ×100).Ocular involvement in SLE occurs in approximately one-third of patients and can involve various ocular structures.1 Common manifestations of ocular involvement include keratoconjunctivitis sicca, episcleritis, scleritis, uveitis, and retinopathy.1 Orbital involvement is rare, but orbital inflammation, ischemia, and myositis have been reported.2-4 This patient presented with bilateral sequential subperiosteal hemorrhage without inciting trauma. Nontraumatic spontaneous subperiosteal hemorrhage is rare and may be idiopathic, but it has been reported to occur in patients without SLE after Valsalva events, such as vomiting, weight lifting, or bowel movements, or in association with general anesthesia, paranasal sinus infections, mucocele, and bleeding diatheses.5 Spontaneous soft-tissue, pulmonary, and intracranial hemorrhages have been reported in patients with SLE, although the mechanism remains elusive.6 In these cases, laboratory evaluation may reveal antiphospholipid antibodies, thrombocytopenia, or elevated prothrombin time, or results may be normal.6Other possible causes of hemorrhage in this patient must be considered. She had a history of hypertension; however, the elevation in her blood pressure was mild at both presentations. Methadone may cause bleeding due to thrombocytopenia, but this patient had platelet counts within the reference range. The patient had sinusitis on her first presentation; however, at the time of her second spontaneous hemorrhage, the sinuses were clear, making sinusitis less likely as the causative factor.Although rare, spontaneous subperiosteal hemorrhage should be considered in the differential diagnosis of acute proptosis. In patients with no history of an inciting event, a systemic workup to rule out hematologic and rheumatologic disorders should be considered.One month after starting treatment, the patient’s proptosis and rash had resolved. One year later, she had no further recurrences of subperiosteal hemorrhage.

Ophthalmology

A woman in her early 30s presented with acute onset of painful proptosis of the right eye and mild epistaxis with no inciting trauma. Her medical history was notable for hypertension, treated with clonidine hydrochloride, and opiate abuse, treated with methadone hydrochloride. Her blood pressure was 138/87 mm Hg. The patient was afebrile with no leukocytosis. Her visual acuity was 20/20 OU with no afferent pupillary defect and normal intraocular pressures. Examination revealed periorbital edema, proptosis, and limitation in supraduction, abduction, and adduction in the right eye. There was no periorbital soft-tissue erythema, warmth, or tenderness to palpation. Computed tomography showed hyperattenuating soft tissue in the superior, medial, and inferior right orbit (Figure 1A, arrowheads). Magnetic resonance imaging showed no internal flow voids to suggest vascular malformation. Results of a laboratory workup revealed mildly elevated erythrocyte sedimentation rate (49 mm/h; reference range, 0-20 mm/h) and antinuclear antibody titer (1:80; reference range, <1:40) as well as positive results for anti-Ro and anti-La antibodies. Results of further autoimmune and infectious workup were negative. Two weeks later, new proptosis and periocular edema of the left eye developed, with no inciting trauma. Her examination results were significant for proptosis, periorbital edema, and limitation in supraduction in the left eye. Computed tomography showed new hyperattenuating soft tissue in the left superior and lateral orbit (Figure 1B, arrowhead).A, Coronal contrast-enhanced computed tomographic scan shows hyperattenuating soft tissue in the superior, medial, and inferior subperiosteal space of the right orbit (arrowheads). B, Computed tomographic scan, not contrast enhanced, shows hyperattenuating orbital soft tissue in the left orbit (arrowhead).

what would you do next?

What would you do next?

Orbitotomy with biopsy

Empirical corticosteroid treatment

External beam radiotherapy

Intravenous antibiotic therapy

a

female

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2716469

A 52-year-old woman with a history of well-controlled type 2 diabetes mellitus, well-controlled hypertension, and breast cancer previously treated with tamoxifen presented with blurry vision in the right eye of 2 weeks’ duration. She reported no history of diabetic retinopathy. Visual acuity with correction was 20/80 OD and 20/30 OS. Dilated fundus examination results were notable for mild cataracts in both eyes and fine superficial retinal hemorrhages surrounded by a cluster of exudates in the right retina (Figure 1A). An examination of the left retina produced unremarkable results.Color fundus and optical coherence tomographic imaging of the right eye. A, A color fundus photograph of the right macula showing superficial retinal hemorrhages surrounded by a cluster of exudates; B, Optical coherence tomography of the right eye showing nasal intraretinal fluid and exudates as well as a distinct cystoid cavitary abnormality just temporal to the center of the macula.Optical coherence tomography of the right eye showed nasal intraretinal hyporeflective spaces that were likely consistent with intraretinal fluid and hyperreflective areas most likely consistent with transudates of lipid, as well as a distinct cystoid cavitary abnormality just temporal to the center of the macula (Figure 1B). A similar cystoid change was seen in the left eye (not shown). Fluorescein angiography showed an area of bright hyperfluorescence nasal to the fovea that progressively intensified with the leakage of dye, obscuring the borders of this area in the late phases, as well as mild leakage temporal to the fovea in both eyes (not shown).Recommend intravitreal anti–vascular endothelial growth factor (anti-VEGF) injection.Recommend continued blood glucose control and consider intravitreal anti–VEGF injection or focal laser treatment if the macular edema persists.Explain to the patient that these changes are medication-associated and recommend close observation.Recommend referral to the patient’s primary care physician for stricter blood pressure control. What Would You Do Next?

Recommend intravitreal anti–vascular endothelial growth factor (anti-VEGF) injection.

Recommend continued blood glucose control and consider intravitreal anti–VEGF injection or focal laser treatment if the macular edema persists.

Explain to the patient that these changes are medication-associated and recommend close observation.

Recommend referral to the patient’s primary care physician for stricter blood pressure control.

Subretinal neovascularization secondary to macular telangiectasia

A

Recommend intravitreal anti–vascular endothelial growth factor (anti-VEGF) injection.

Macular telangiectasia results in loss of central vision, typically in adulthood, owing to exudation or ischemia of retinal capillaries in the foveal or perifoveal region.1 It is classified into 3 types.Type 1 is unilateral and seen only in males. It typically has lipid-rich exudation in a ring configuration.Type 2 is bilateral and seen in both sexes equally. Fluorescein angiography shows late perifoveal leakage in the temporal fovea. Exudates and macular edema develop only in patients who develop subretinal neovascularization.2 The pathogenesis of type 2 macular telangiectasia is unknown. It has been hypothesized that venous stasis caused by obstruction of the retinal veins as they cross the retinal arteries on both sides of the horizontal raphe may be a contributing factor.3 Recently, steroidal sex hormones have been implicated in the pathogenesis of this disease.4Type 3 is bilateral. It is seen in association with systemic illness, including multiple myeloma, ulcerative colitis, polycythemia, and chronic lymphocytic leukemia.A telling sign in macular telangiectasia is the distinct cystoid cavitary abnormality seen on optical coherence tomography. These hyporeflective cavities within the inner retina are seen usually in the temporal fovea.5Diabetes mellitus is a common cause of macular edema; however, the patient did not have other fundus findings to suggest diabetic retinopathy, and the fluorescein angiogram findings are consistent with subretinal neovascularization, which does not occur in diabetic retinopathy. Thus, choice B is incorrect.Tamoxifen retinopathy can mimic type 2 macular telangiectasia, because the crystals seen on ophthalmoscopic examination can be mistaken for the exudates seen in type 2 macular telangiectasia, and a cystoid cavitary change is seen in both diseases. In cases in which a patient presents with ambiguous findings that can be attributed to either tamoxifen use or type 2 macular telangiectasia, fluorescein angiography is a useful test to determine the correct diagnosis, because tamoxifen retinopathy will not show the late leakage in the temporal fovea that is seen in type 2 macular telangiectasia.6 Thus, choice C is incorrect.Retinal arterial macroaneurysms are associated with hypertension in almost 80% of cases and can cause circinate exudation.7 In rare cases, subretinal neovascularization can be seen as well.8 Choice D is incorrect, however, because the leakage on fluorescein angiography does not show the ovoid pooling of dye that is seen in a retinal arterial macroaneurysm. Further, the bilateral leakage in the temporal fovea is much more characteristic of type 2 macular telangiectasia.The patient was diagnosed with subretinal neovascularization associated with type 2 macular telangiectasia. Intravitreal bevacizumab has been shown to improve visual acuity and induce involution of subretinal neovascularization in patients with type 2 macular telangiectasia.9 The patient received a series of 3 intravitreal bevacizumab injections monthly. Visual acuity with correction improved to 20/25 and optical coherence tomography showed almost complete resolution of the intraretinal fluid (Figure 2).Follow-up optical coherence tomography of the right eye. This image shows almost complete resolution of the nasal intraretinal fluid. The temporal distinct cystoid cavitary abnormality change remains present.

Ophthalmology

A 52-year-old woman with a history of well-controlled type 2 diabetes mellitus, well-controlled hypertension, and breast cancer previously treated with tamoxifen presented with blurry vision in the right eye of 2 weeks’ duration. She reported no history of diabetic retinopathy. Visual acuity with correction was 20/80 OD and 20/30 OS. Dilated fundus examination results were notable for mild cataracts in both eyes and fine superficial retinal hemorrhages surrounded by a cluster of exudates in the right retina (Figure 1A). An examination of the left retina produced unremarkable results.Color fundus and optical coherence tomographic imaging of the right eye. A, A color fundus photograph of the right macula showing superficial retinal hemorrhages surrounded by a cluster of exudates; B, Optical coherence tomography of the right eye showing nasal intraretinal fluid and exudates as well as a distinct cystoid cavitary abnormality just temporal to the center of the macula.Optical coherence tomography of the right eye showed nasal intraretinal hyporeflective spaces that were likely consistent with intraretinal fluid and hyperreflective areas most likely consistent with transudates of lipid, as well as a distinct cystoid cavitary abnormality just temporal to the center of the macula (Figure 1B). A similar cystoid change was seen in the left eye (not shown). Fluorescein angiography showed an area of bright hyperfluorescence nasal to the fovea that progressively intensified with the leakage of dye, obscuring the borders of this area in the late phases, as well as mild leakage temporal to the fovea in both eyes (not shown).Recommend intravitreal anti–vascular endothelial growth factor (anti-VEGF) injection.Recommend continued blood glucose control and consider intravitreal anti–VEGF injection or focal laser treatment if the macular edema persists.Explain to the patient that these changes are medication-associated and recommend close observation.Recommend referral to the patient’s primary care physician for stricter blood pressure control.

what would you do next?

What would you do next?

Explain to the patient that these changes are medication-associated and recommend close observation.

Recommend continued blood glucose control and consider intravitreal anti–VEGF injection or focal laser treatment if the macular edema persists.

Recommend intravitreal anti–vascular endothelial growth factor (anti-VEGF) injection.

Recommend referral to the patient’s primary care physician for stricter blood pressure control.

c

female

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2716822

A 63-year-old healthy woman presented with a 3-week history of fluctuating left eye swelling and redness. She also reported a 1-week history of left eye discomfort and left-sided tinnitus and a 1-day history of binocular horizontal diplopia. She denied any history of recent trauma. Ophthalmologic examination at the time revealed visual acuities of 20/30 OD and 20/40 OS. Intraocular pressures were 15 mm Hg OD and 21 mm Hg OS, with a widened pulse pressure of the left eye. Extraocular motility revealed a left eye abduction deficit. Pupils and confrontational visual fields were unremarkable. Hertel measured 16 mm and 17 mm, respectively. Slitlamp examination of the right eye was unremarkable, but examination of the left eye revealed a large subconjunctival hemorrhage and engorged episcleral veins (Figure 1). Fundus examination of both eyes was unremarkable.Clinical photographs taken 3 weeks apart. A, Dilated nasal episcleral vessels and conjunctival chemosis near the onset of the patient’s symptoms. B, Photograph taken 3 weeks later revealing increased dilated episcleral vessels and subconjunctival hemorrhage. Orbital ecchymosis is also evident. What Would You Do Next?

Reassurance and artificial tears

Computed tomography of head

Magnetic resonance imaging of brain and orbits

Urgently refer to neurosurgery

Dural cavernous fistula

C

Magnetic resonance imaging of brain and orbits

Carotid cavernous fistulas (CCF) are connections between the cavernous sinus and the internal carotid artery (ICA) or external carotid artery. Fistulas may involve intercavernous portions of the ICA (type A), ICA dural branches (type B), external carotid artery dural branches (type C), or ICA and external carotid artery dural branches (type D).1 Type D accounts for 71% of indirect fistulas.2Type A (direct fistulas) typically occurs after high-velocity head trauma from motor vehicle collisions, falls, or crush injuries,3 with high-flow rates presenting with acute orbital signs. Dural fistulas develop spontaneously, typically in postmenopausal women with atherosclerotic risk factors, during pregnancy, or associated with connective tissue disorders.4 With low-flow nature, clinical courses can be indolent, mortality rare, and spontaneous closure feasible.3 Mean time from symptom onset to correct diagnosis is approximately 1.5 months for a direct CCF and 3.7 months for an indirect CCF.4Reverse venous filling into the orbit may result in elevated intraocular pressure, chemosis, proptosis, extraocular movement restriction, or ocular ischemia. Reverse venous flow into the brain or optic nerve is associated with a higher risk of intracerebral hemorrhage or visual loss, respectively, when urgent intervention is recommended. In the absence of threatened visual loss or reverse cerebral venous drainage, intervention is less urgent but justifiable in cases with cranial nerve palsy, proptosis, or disfigurement.5Magnetic resonance imaging detection of a dilated superior ophthalmic vein supports diagnosis of a CCF.6 However, 27% of patients with confirmed indirect CCFs via cerebral angiography have negative noninvasive imaging results, making cerebral angiography the criterion standard for diagnosing a CCF.4 A 2017 study7 revealed a common association between indirect CCFs and hypercoagulable states and malignancies, highlighting the importance of recognizing and treating these associations in addition to treating the CCF.7Magnetic resonance angiogram demonstrated dural arterial engorgement along the left cavernous sinus. Fat-suppressed T1 magnetic resonance imaging demonstrated asymmetric lobular filling of the left cavernous sinus, engorgement of the left lacrimal gland, and dural enhancement along the left petrous bone. There was no superior ophthalmic vein enlargement. Cerebral angiography revealed a fistula of the left posterior cavernous sinus, with drainage into the inferior petrosal vein (Figure 2). The fistula was dominantly supplied by branches of the left foramen rotundum artery, with possible additional supply of the right ascending pharyngeal artery. Two microcoils were placed into the fistula site, accessed via the left inferior petrosal sinus. The fistula was subsequently occluded.Catheter angiography confirmed an indirect fistula of the left cavernous sinus. The arrowhead denotes the site of the fistula where branches of the left foramen rotundum artery can be seen feeding into the cavernous sinus with early filling of the left inferior petrosal sinus.After coiling, the patient’s orbital signs quickly improved. Bloodwork revealed a heterozygous factor V Leiden mutation, elevated factor VIII, and anticardiolipin IgM. She started receiving lifelong anticoagulation with rivaroxaban.

Ophthalmology

A 63-year-old healthy woman presented with a 3-week history of fluctuating left eye swelling and redness. She also reported a 1-week history of left eye discomfort and left-sided tinnitus and a 1-day history of binocular horizontal diplopia. She denied any history of recent trauma. Ophthalmologic examination at the time revealed visual acuities of 20/30 OD and 20/40 OS. Intraocular pressures were 15 mm Hg OD and 21 mm Hg OS, with a widened pulse pressure of the left eye. Extraocular motility revealed a left eye abduction deficit. Pupils and confrontational visual fields were unremarkable. Hertel measured 16 mm and 17 mm, respectively. Slitlamp examination of the right eye was unremarkable, but examination of the left eye revealed a large subconjunctival hemorrhage and engorged episcleral veins (Figure 1). Fundus examination of both eyes was unremarkable.Clinical photographs taken 3 weeks apart. A, Dilated nasal episcleral vessels and conjunctival chemosis near the onset of the patient’s symptoms. B, Photograph taken 3 weeks later revealing increased dilated episcleral vessels and subconjunctival hemorrhage. Orbital ecchymosis is also evident.

what would you do next?

What would you do next?

Urgently refer to neurosurgery

Reassurance and artificial tears

Computed tomography of head

Magnetic resonance imaging of brain and orbits

d

female

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2716823

A 38-year-old man with a history of refractive surgery in both eyes and well-controlled HIV receiving antiretroviral therapy (CD4+ lymphocyte count, 881) presented with worsening blurry vision and floaters in the left eye for 3 weeks in the setting of sinus congestion and left-sided jaw pain for 6 months. He denied flashing lights, visual field defects, trauma, pain, redness, discharge, or other systemic symptoms.On examination, the patient’s uncorrected visual acuity was 20/20 OD and 20/50 OS (no improvement on refraction), his pupils were equally round and reactive with no relative afferent pupillary defect, his intraocular pressures were normal, and extraocular motility and confrontational visual fields were full. Results from slitlamp and dilated fundus examinations of the right eye were normal. Anterior segment examination of the left eye showed mild fine keratic precipitates and pigmented cell; dilated fundus examination showed significant vitritis but no obvious vascular sheathing or chorioretinal lesions (Figure 1A). Optical coherence tomography of the macula confirmed there was no intraretinal or subretinal fluid (Figure 1B), and fluorescein angiography did not show any vascular leakage or areas of nonperfusion. Results of further workup showed normal complete blood cell count and comprehensive metabolic panel laboratory testing, undetectable HIV viral load, and unremarkable chest radiography; laboratory results for tuberculosis (T-SPOT.TB testing), syphilis (rapid plasma reagin with reflex treponemal testing), cytoplasmic and perinuclear antineutrophil cytoplasmic antibodies, and blood cultures were all negative as well.A, On color fundus photography, significant vitreous haze obscuring most of the retinal vessels was observed in the left eye, but no apparent chorioretinal lesions were seen. B, Optical coherence tomography imaging through the posterior pole of the left eye showed vitreous cell but no intraretinal or subretinal fluid or lesions.Perform head/maxillofacial computed tomography or magnetic resonance imaging What Would You Do Next?

Observe

Start topical or systemic steroids

Perform head/maxillofacial computed tomography or magnetic resonance imaging

Perform vitreous biopsy

Plasmablastic lymphoma

C

Perform head/maxillofacial computed tomography or magnetic resonance imaging

Given the sinus and jaw symptoms in an immunocompromised patient, further maxillofacial imaging is warranted to rule out occult infectious or neoplastic etiologies prior to starting empirical treatment. Observation is not appropriate given his progressive symptoms with evidence of panuveitis. Vitreous biopsy is fairly invasive, so noninvasive imaging is first indicated. In this case, both computed tomography and magnetic resonance imaging showed a large mass (5.1 × 4.7 × 4.6 cm) in the left maxillary sinus and nasal cavity with no intraorbital or intracranial extension. Otolaryngology was subsequently consulted, and surgical biopsy was consistent with plasmablastic lymphoma (PBL) (Figure 2).Surgical pathology specimen of sinonasal mass stained with hematoxylin-eosin (original magnification ×20) showed sheets of relatively discohesive, markedly pleomorphic cells with prominent nucleoli, eosinophilic cytoplasm, eccentric nuclei, and vesicular chromatin. Further special stains (not pictured) showed the neoplasm was positive for Epstein-Barr virus–encoded RNA in situ hybridization, λ light chain, and MYC gene translocation; the neoplasm was negative for κ light chain.Plasmablastic lymphoma is a rare, rapidly progressive subtype first described as distinct from diffuse large B-cell lymphoma in 1997 and is strongly associated with HIV and immunodeficiencies.1 It often involves extranodal sites (head/neck in 50% to 60% of cases) and accounts for 2.6% of all HIV-related non-Hodgkin lymphomas.2Its cell of origin is the plasmablast, an activated B cell transitioning to a plasma cell, often seen in reactive infectious processes (eg, HIV and Epstein-Barr virus). Pathologically, it expresses plasma cell markers (eg, CD138 and VS38c) with monoclonal light chain restriction (κ or λ) and often MYC oncogene rearrangement but lacks immunoblastic markers (ie, CD20).1Orbital and ocular involvement of PBL is exceedingly rare but primarily occurs in HIV-positive males (about 70% of cases).3 Orbital PBL presents similarly to diffuse large B-cell lymphoma but more frequently has painful proptosis and periocular sensory loss.4 To our knowledge, only 2 case reports of intraocular PBL have been published: one presenting as secondary choroidal lymphoma in a patient with known systemic PBL5 and the other incidentally noted on an enucleation specimen of an HIV-positive patient.6 This is the first report of PBL with an initial ophthalmic presentation of floaters and blurry vision.The prognosis for PBL is dismal, with an untreated median overall survival of 15 months in HIV-positive patients and a 3-year survival rate of 25%.1 There is no standard of care, and even the most aggressive lymphoma chemotherapy regimens remain inadequate; recent attempts to use adjunctive agents, allogenic stem cell transplant, and radiation are controversial but encouraging.1Since the diagnosis of PBL is often delayed secondary to variability in presentation and pathologic mimicry, it is critical to maintain a high threshold of suspicion for these rare neoplasms in immunocompromised individuals, even if the presenting symptoms appear relatively benign. As with this patient, comprehensive review of systems and workup is indicated to evaluate any occult etiologies in an HIV-positive patient with evidence of intraocular inflammation.The patient was treated with 6 cycles of systemic and intrathecal chemotherapy. His vitritis and uncorrected visual acuity improved immediately after the first cycle to 20/30 OS; after all cycles (6 months after initial presentation), his visual acuity was 20/20 OU with near resolution of vitritis and no new intraocular lesions. Repeated maxillofacial imaging showed stable size of maxillary lesion, with plan for adjunctive radiation.

Ophthalmology

A 38-year-old man with a history of refractive surgery in both eyes and well-controlled HIV receiving antiretroviral therapy (CD4+ lymphocyte count, 881) presented with worsening blurry vision and floaters in the left eye for 3 weeks in the setting of sinus congestion and left-sided jaw pain for 6 months. He denied flashing lights, visual field defects, trauma, pain, redness, discharge, or other systemic symptoms.On examination, the patient’s uncorrected visual acuity was 20/20 OD and 20/50 OS (no improvement on refraction), his pupils were equally round and reactive with no relative afferent pupillary defect, his intraocular pressures were normal, and extraocular motility and confrontational visual fields were full. Results from slitlamp and dilated fundus examinations of the right eye were normal. Anterior segment examination of the left eye showed mild fine keratic precipitates and pigmented cell; dilated fundus examination showed significant vitritis but no obvious vascular sheathing or chorioretinal lesions (Figure 1A). Optical coherence tomography of the macula confirmed there was no intraretinal or subretinal fluid (Figure 1B), and fluorescein angiography did not show any vascular leakage or areas of nonperfusion. Results of further workup showed normal complete blood cell count and comprehensive metabolic panel laboratory testing, undetectable HIV viral load, and unremarkable chest radiography; laboratory results for tuberculosis (T-SPOT.TB testing), syphilis (rapid plasma reagin with reflex treponemal testing), cytoplasmic and perinuclear antineutrophil cytoplasmic antibodies, and blood cultures were all negative as well.A, On color fundus photography, significant vitreous haze obscuring most of the retinal vessels was observed in the left eye, but no apparent chorioretinal lesions were seen. B, Optical coherence tomography imaging through the posterior pole of the left eye showed vitreous cell but no intraretinal or subretinal fluid or lesions.Perform head/maxillofacial computed tomography or magnetic resonance imaging

what would you do next?

What would you do next?

Observe

Perform head/maxillofacial computed tomography or magnetic resonance imaging

Start topical or systemic steroids

Perform vitreous biopsy

b

male

31-40

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2704206

A black man in his 30s presented for evaluation of papules and plaques on his bilateral lower extremities. Nine months before the current presentation, he was treated with intramuscular penicillin for syphilis. His medical history was also significant for HIV, for which he was receiving highly active antiretroviral therapy, and metastatic programmed cell death ligand 1–positive squamous non–small cell lung cancer. Four months before the current presentation, the patient had started pembrolizumab monotherapy as a first-line treatment for his cancer. One month before this presentation, multiple ulcers developed on his buccal mucosa, as well as a nonpainful shallow penile ulcer and pruritic, mildly painful, hyperpigmented papules and plaques on the bilateral soles of his feet in a pattern identical to previous syphilitic eruption. The patient denied fever, chills, and weight loss. Physical examination revealed multiple hyperpigmented papules and plaques with violaceous borders on his bilateral soles and lateral feet (Figure, A) and scattered, violaceous papules and nodules with overlying scale on his bilateral lower extremities. He was referred to the dermatology service, and a punch biopsy specimen was obtained from the right medial sole (Figure, B).A, Right foot with multiple hyperpigmented, lichenified papules, and plaques with violaceous borders. B, A punch biopsy specimen from the right medial sole. Lymphocytes, eosinophils, and plasma cells can be seen within the infiltrate (hematoxylin-eosin, original magnification ×40). What Is Your Diagnosis?

Secondary syphilis

Lichen planus

Lichenoid drug reaction

Janeway lesions secondary to endocarditis

C. Lichenoid drug reaction

C

Lichenoid drug reaction

Immunohistochemical staining of the biopsy specimen from the right medial sole showed a lichenoid interface dermatitis with vacuolar changes and necrotic keratinocytes at the dermal-epidermal junction. Lymphocytes, eosinophils, and plasma cells were identified within the infiltrate. The epidermis was hyperplastic and demonstrated hypergranulosis (Figure, B). Results of an immunostain for syphilis were negative, and a serum rapid plasma reagin screen was nonreactive, excluding secondary syphilis as the primary source of the skin findings.Taken together, this patient’s clinical and pathologic findings are consistent with a diagnosis of a lichenoid drug reaction secondary to pembrolizumab, one of the more common dermatologic immune-related adverse events seen with immune-checkpoint inhibition. Pembrolizumab is a monoclonal antibody directed against programmed cell death 1 (PD-1), a molecule normally found on the surface of T lymphocytes that maintains immune tolerance, which can be repurposed by tumor cells as an effective method of immune evasion.1 Programmed cell death 1 antagonists, such as pembrolizumab and nivolumab, are approved by the US Food and Drug Administration for the treatment of multiple malignant neoplasms, with immune-related adverse events similar across tumor types. Common dermatologic adverse effects of anti–PD-1 therapies include mucosal erosions, papular eruptions with overlying scale, and pruritus.2 The reported incidence of dermatologic immune-related adverse effects to anti–PD-1 monotherapy varies, but between 1.2% and 11% of patients receiving anti–PD-1 monotherapy experience a lichenoid cutaneous reaction, 12% to 25% experience pruritus, and 2.6% to 15% experience vitiligo.3-5 Regardless of tumor type, anti–PD-1–induced dermatitis typically presents as discrete papules or nodules limited to 1 region of the body or as larger plaques generally distributed over the trunk.2 Despite this variation in clinical presentation, histopathologic study of anti–PD-1 dermatitis almost always shows lichenoid infiltrates composed of CD4 lymphocytes within the dermis and CD8 lymphocytes within the epithelium.2The mechanism of lichenoid drug reactions has not been elucidated, nor has the mechanism of cutaneous reactions to anti–PD-1 therapy. The leading hypothesis is that antagonizing PD-1 leads to T-lymphocyte–mediated toxic effects directed against basal keratinocytes.6The time from initiation of anti–PD-1 therapy to cutaneous presentation varies, but cutaneous events have been reported from 3 days to 13 months after starting treatment and can also occur after discontinuation of treatment.2 Anti–PD-1–induced dermatitis is generally easy to manage with topical or intralesional glucocorticoid drugs and does not always require discontinuation of pembrolizumab or nivolumab therapy because they are typically not high grade per the National Cancer Institute Common Terminology of Criteria of Adverse Events, version 4.03.2 There is evidence to suggest that the development of cutaneous reactions after anti-PD1 therapy may be associated with improved tumor response and increased patient survival.6,7 Future research regarding the association between immune-related adverse events and outcomes after anti–PD-1 therapy is needed and currently ongoing.The patient was prescribed triamcinolone acetonide 0.1% ointment to be applied to the affected area twice daily and a series of intralesional corticosteroid injections, with improvement in the appearance of the papules and plaques over the course of several months. He used the triamcinolone ointment for a total of 6 months. Findings on interval imaging revealed improved antitumor response after the development of the eruption; at the time of publication, the patient had been receiving pembrolizumab for 11 months.

Oncology

A black man in his 30s presented for evaluation of papules and plaques on his bilateral lower extremities. Nine months before the current presentation, he was treated with intramuscular penicillin for syphilis. His medical history was also significant for HIV, for which he was receiving highly active antiretroviral therapy, and metastatic programmed cell death ligand 1–positive squamous non–small cell lung cancer. Four months before the current presentation, the patient had started pembrolizumab monotherapy as a first-line treatment for his cancer. One month before this presentation, multiple ulcers developed on his buccal mucosa, as well as a nonpainful shallow penile ulcer and pruritic, mildly painful, hyperpigmented papules and plaques on the bilateral soles of his feet in a pattern identical to previous syphilitic eruption. The patient denied fever, chills, and weight loss. Physical examination revealed multiple hyperpigmented papules and plaques with violaceous borders on his bilateral soles and lateral feet (Figure, A) and scattered, violaceous papules and nodules with overlying scale on his bilateral lower extremities. He was referred to the dermatology service, and a punch biopsy specimen was obtained from the right medial sole (Figure, B).A, Right foot with multiple hyperpigmented, lichenified papules, and plaques with violaceous borders. B, A punch biopsy specimen from the right medial sole. Lymphocytes, eosinophils, and plasma cells can be seen within the infiltrate (hematoxylin-eosin, original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Secondary syphilis

Janeway lesions secondary to endocarditis

Lichen planus

Lichenoid drug reaction

d

male

31-40

Black

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2704012

A 63-year-old woman with atrial fibrillation, who was receiving warfarin and had a history of atrial septal defect (ASD) and ventricular septal defect (VSD) repair in her 20s, presented with stupor and new facial droop. A computed tomographic examination of the brain showed a right frontal lobe abscess with vasogenic edema (Figure 1). She underwent burrhole aspiration of the abscess, which grew mixed oral flora. Treatment involved a prolonged course of intravenous antibiotics, steroids, and medications for seizure prophylaxis. What Would You Do Next?

Transesophageal echocardiogram

Computed tomographic imaging of the chest

Cardiac magnetic resonance imaging

Transthoracic echocardiogram with a bubble study

Persistent left superior vena cava

D

Transthoracic echocardiogram with a bubble study

The best first test in the workup for brain abscess in a patient with possible underlying cardiac shunt physiology is a transthoracic echocardiogram with a bubble study (choice D). It is the least invasive test and provides useful information on shunt direction and size, as well as general cardiac and valvular function.1 Transthoracic echocardiogram with a bubble study helps identify patent foramen ovale, which is more prevalent in patients with cryptogenic stroke, as well as evidence of ASD, VSD, or vegetations.1 Transthoracic echocardiography also allows for the examination of any masses or clots. Chest computed tomography (choice B), especially multislice computed tomography, and cardiac magnetic resonance imaging (choice C) can provide more information about any structural abnormalities, but they will not give further insight into the functional aspects of an intracardiac shunt.1 Computed tomography and magnetic resonance imaging are also generally more invasive and more expensive, and computed tomography exposes patients to radiation.Interestingly, a transthoracic echocardiogram revealed complete opacification of the left atrium with injection of agitated saline into a vein of the right arm, suggesting complete drainage of the right superior vena cava (SVC) into the left system (Video). Computed tomography and cardiac magnetic resonance imaging with velocity mapping, intended to further evaluate the venous anomalies, uncovered drainage of a persistent left SVC into an enlarged coronary sinus (Figure 2). Given venous blood flow directly into the left atrium, it is feasible that emboli can take this pathway to enter the brain.Persistent left SVC, while rare, is the most common abnormality of the venous circulation, with an incidence of 0.3% in the general population and 10% in patients with congenital heart disease.2 Typically, these venous anomalies are clinically asymptomatic and have seemingly normal physiologic drainage. However, anomalous venous vasculature should be carefully considered in the setting of rhythm aberrancies or invasive procedures and as a source of paradoxical emboli in patients with stroke and/or brain abscess.3Duplicate SVC usually present as incidental findings on imaging or with attempted insertion of central lines or during cardiac catheterizations. Implications are limited to awareness of anatomy prior to such insertions in these patients, as well as some suggestion of possible arrhythmogenicity of left SVC drainage into the coronary sinus. This is theorized to stem from the proximity of the coronary sinus to the sinoatrial node and from the turbulent flow through this venous anomaly, which increases the risk of coronary sinus thrombosis.4The risk of stroke and usefulness of anticoagulation for stroke prevention has yet to be studied in this population, and thus treatment is controversial. However, observational data have shown that right-to-left shunts increase morbidity associated with stroke complications, transient ischemic attacks, and cerebral abscess.1 Surgery may be indicated in cases of shunt closure; however, most cases of SVC duplication require no interventions, because there is no cross drainage between the atria.5In this case, it is also interesting to point out that the bubble study identified a pattern of flow dependent on which arm was injected with agitated saline. This demonstrates some usefulness in checking bilateral injections in patients with known congenital heart disease, especially in the setting of embolic strokes of undetermined source.After intensive physical therapy, the patient is back home and walking independently. She was successfully treated for her brain abscess, but experiences frequent bouts of dizziness. She was referred to an adult congenital clinic in June 2018 and is undergoing cardiac catheterization in the next month for anticipated surgical closure of her right-to-left shunt with a possible maze procedure for atrial fibrillation.

Cardiology

A 63-year-old woman with atrial fibrillation, who was receiving warfarin and had a history of atrial septal defect (ASD) and ventricular septal defect (VSD) repair in her 20s, presented with stupor and new facial droop. A computed tomographic examination of the brain showed a right frontal lobe abscess with vasogenic edema (Figure 1). She underwent burrhole aspiration of the abscess, which grew mixed oral flora. Treatment involved a prolonged course of intravenous antibiotics, steroids, and medications for seizure prophylaxis.

what would you do next?

What would you do next?

Cardiac magnetic resonance imaging

Transesophageal echocardiogram

Transthoracic echocardiogram with a bubble study

Computed tomographic imaging of the chest

c

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2715831

A man in his 50s with a history of chronic hepatitis C, hypothyroidism, and alcoholism presented to the outpatient clinic complaining of nasal congestion and epistaxis. Nonenhanced computed tomography of the paranasal sinuses revealed a soft-tissue mass extending from the nasopharynx into the left sphenoid sinus with erosion of the sphenoid sinus floor and the clivus (Figure 1A). The sella was apparently normal with no disruption of its floor. The intracranial and orbital soft tissues were grossly normal, as were the remaining soft tissues under the skull base.A, Sagittal nonenhanced computed tomography images of the paranasal sinus depicting a soft-tissue mass involving the sphenoid sinus, the nasopharynx, and the clivus. B, Postcontrast sagittal T1-weighted magnetic resonance shows avid enhancement of the mass; involvement of the clivus is also depicted.A magnetic resonance imaging study was also performed (Figure 1B). There was a lobulated mass centered to the nasopharynx, measuring about 2.8 × 2.6 × 4.5 cm (anteroposterior × transverse × craniocaudal planes, respectively) in maximal diameters. The mass demonstrated intermediate T2 hyperintense signal and avid postcontrast enhancement. It extended inferiorly down to the oropharynx and superiorly along the floor of the left sphenoid sinus with extension into the sinus itself; posteriorly, there were erosions involving the sphenoid bone and the clivus. The floor of sella was intact, and a normal enhancing pituitary gland and infundibulum were seen within the sella. No sellar or suprasellar mass was evident. Both Meckel caves were normal, and the cavernous sinuses were also normal and without evidence of asymmetric mass or abnormal enhancement. The patient underwent a total mass resection via endoscopic anterior cranial base approach, with extradural tumor resection, reconstruction of the skull base, and a nasoseptal flap. What Is Your Diagnosis?

Squamous cell carcinoma

Lymphoma

Ectopic pituitary adenoma

Granulomatous disease

C. Ectopic pituitary adenoma

C

Ectopic pituitary adenoma

Histopathology revealed pituitary adenoma tissue, favoring a null cell type (Figure 2). Pituitary adenomas are benign neoplasms accounting for 10% to 15% of all primary intracranial tumors.1 Most occur within the sella turcica; however, they can develop in other sites. Ectopic pituitary adenomas (EPAs) are defined by the World Health Organization as benign pituitary gland neoplasms occurring separate from the sella without connection to the normal anterior pituitary gland.2 They are rare and can occur in the sphenoid sinus, suprasellar cistern, cavernous sinus, clivus, nasal cavity, sphenoid wing, temporal bone, superior orbital fissure, and the third ventricle.3,4 Although exceedingly rare, they can also appear as a nasopharyngeal mass. We report a case of a patient with a nasopharyngeal mass that histopathology revealed as an EPA after resection.Pituitary adenoma shows a monomorphic tumor cell population with pale, granular cytoplasm and bland nuclear features (hematoxylin-eosin staining, original magnification ×200).The exact pathogenesis of EPA is not fully established. Some authors hypothesize that they originate from the embryological development of the anterior pituitary.5,6 The anterior pituitary primordium appears around the fourth week of embryogenesis. During the eighth week, the pituitary divides into sellar and pharyngeal components. At this point, there is a superior attachment to the pituitary stalk and an inferior invagination known as Rathke pouch, consisting of an infolding of the buccopharyngeal membrane. This Rathke pouch will eventually push upward through the developing sphenoid bone into the sella, giving rise to the adenohypophysis and meeting the neurohypophysis. Remnants of this pouch can remain along the course of the craniopharyngeal canal from the upper pharynx to the sella.4,5 Adenomatous transformations of these remnant cells are thought to be the origin of EPA. Pure EPA are rare lesions, and the most frequent site is the sphenoid sinus.4 However, they can also appear in different sites, such as the nasopharynx.7 This case illustrates a patient with a nasopharyngeal mass detected on a nonenhanced computed tomography of the paranasal sinus and further examined through magnetic resonance imaging. The differential diagnosis included, in addition to functioning or nonfunctioning EPA, squamous cell carcinoma, lymphoma, and granulomatous disease. Although uncommon, EPA needs to be considered in the differential diagnosis of a nasopharyngeal, sphenoid sinus, or clival mass so that there can be appropriate medical and surgical management.

General

A man in his 50s with a history of chronic hepatitis C, hypothyroidism, and alcoholism presented to the outpatient clinic complaining of nasal congestion and epistaxis. Nonenhanced computed tomography of the paranasal sinuses revealed a soft-tissue mass extending from the nasopharynx into the left sphenoid sinus with erosion of the sphenoid sinus floor and the clivus (Figure 1A). The sella was apparently normal with no disruption of its floor. The intracranial and orbital soft tissues were grossly normal, as were the remaining soft tissues under the skull base.A, Sagittal nonenhanced computed tomography images of the paranasal sinus depicting a soft-tissue mass involving the sphenoid sinus, the nasopharynx, and the clivus. B, Postcontrast sagittal T1-weighted magnetic resonance shows avid enhancement of the mass; involvement of the clivus is also depicted.A magnetic resonance imaging study was also performed (Figure 1B). There was a lobulated mass centered to the nasopharynx, measuring about 2.8 × 2.6 × 4.5 cm (anteroposterior × transverse × craniocaudal planes, respectively) in maximal diameters. The mass demonstrated intermediate T2 hyperintense signal and avid postcontrast enhancement. It extended inferiorly down to the oropharynx and superiorly along the floor of the left sphenoid sinus with extension into the sinus itself; posteriorly, there were erosions involving the sphenoid bone and the clivus. The floor of sella was intact, and a normal enhancing pituitary gland and infundibulum were seen within the sella. No sellar or suprasellar mass was evident. Both Meckel caves were normal, and the cavernous sinuses were also normal and without evidence of asymmetric mass or abnormal enhancement. The patient underwent a total mass resection via endoscopic anterior cranial base approach, with extradural tumor resection, reconstruction of the skull base, and a nasoseptal flap.

what is your diagnosis?

What is your diagnosis?

Squamous cell carcinoma

Ectopic pituitary adenoma

Granulomatous disease

Lymphoma

b

male

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2716815

A woman in her 30s presented with a 1-year history of left ear fullness. She reported diminished left-sided hearing that would temporarily improve with autoinsufflation. She denied facial numbness or weakness, and reported no dizziness or vertigo. Physical examination revealed a retrotympanic, nonpulsatile, tan-gray mass anterior to the malleus handle. A tuning fork examination revealed lateralization to the left ear and bone conduction louder than air conduction on the left side with a 512-Hz tuning fork. The remainder of the physical examination, including facial nerve function, was normal. An audiogram confirmed mild conductive hearing loss in the left ear. Computed tomography (CT) revealed a middle ear lesion lateral to the geniculate ganglion with possible extension into the peritubal space. Magnetic resonance imaging (MRI) demonstrated an enhancing lesion lateral to the geniculate ganglion (Figure, A-C). The patient was initially observed but then experienced progressive hearing loss that no longer improved with the Valsalva maneuver, persistent ear fullness, and rare facial twitching. The middle ear mass appeared enlarged on repeated MRI and began to obstruct the eustachian tube. Transcanal endoscopy demonstrated a gray middle ear mass occupying the anterior mesotympanum and epitympanum and extending into the eustachian tube (Figure, D). The tegmen was intact. The specimen revealed predominantly spindled stroma with a focus of tumor that was positive for antiepithelial membrane antigen and somatostatin receptor 2A.A, Noncontrast axial computed tomogram (CT) of the left temporal bone demonstrates an anterior mesotympanic mass lateral to the cochlea (yellow arrowhead) with blockage and extension into the supratubal recess (white arrowhead). A partial mastoid effusion (asterisk) is also visible. B, The coronal CT demonstrates an intact tegmen tympani with hyperostosis (arrowhead). C, Axial, fat-suppressed, postgadolinium, T1-weighted magnetic resonance image (MRI) reveals an enhancing mass of the left perigeniculate region (yellow arrowhead). The geniculate ganglion is marked (white arrowhead). D, Intraoperative transcanal photograph of a lobulated, gray, middle ear mass involving the left protympanum and epitympanum. What Is Your Diagnosis?

Facial nerve venous malformation

Jugulotympanic paraganglioma

Primary middle ear meningioma

Middle ear adenoma

C. Primary middle ear meningioma

C

Primary middle ear meningioma

Meningiomas are benign intracranial neoplasms that may occur wherever the meninges are found and most commonly along the parasagittal regions and large dural sinuses.1,2 These tumors typically arise between the third and sixth decades of life, have a strong female predilection, and are common, comprising 30% of all adult central nervous system tumors.1,2 About 2% of meningiomas appear extracranially with most appearing as an extension of an existing intracranial meningioma.3Middle ear meningiomas typically form as a result of migration of meningothelial cells through the tegmen tympani, jugular foramen, internal auditory meatus, posterior fossa plate, or grooves of the greater superficial and lesser superficial petrosal nerves.4 Primary middle ear meningiomas are exceedingly rare, with fewer than 150 cases reported as of 2014.4 The predominant theory behind the mechanism of primary tumor formation is entrapment of arachnoid cap cells during embryonic development.4 Other explanations include extension of meningothelial cells through skull base defects or development from ectopic neural crest cells in the middle ear.5Patients typically present with tinnitus, otalgia, otorrhea, headaches, hearing changes (either sensorineural or conductive), and eventually facial nerve weakness.1,4 Patients often endure symptoms for an average of 2 years before a diagnosis is made.4 Magnetic resonance imaging is considered the imaging modality of choice and is especially useful in identifying intracranial extension or concurrent intracranial meningioma.3 Meningiomas are characteristically isodense on T1-weighted MRI and have homogenous enhancement with gadolinium owing to local destruction of the blood-brain barrier.1,2 Computed tomography is often performed in conjunction with MRI to further characterize osseous involvement.1 Meningiomas appear isodense on non–contrast enhanced CT and uniformly enhance with contrast.Close observation is acceptable in relatively asymptomatic patients because meningiomas are often slow growing.1 If more persistent symptoms arise or significant tumor growth is observed, surgery is the treatment of choice.1 Aggressive surgical resection is advocated given the likelihood of local recurrence and difficulty distinguishing between normal and diseased tissue.1 In patients with a substantial adherent tumor, subtotal resection may be considered if no preoperative facial nerve deficit or sensorineural hearing loss is present.1Diagnosis of meningioma is confirmed with histopathologic findings and immunohistochemical staining. Cells appear uniform, are arranged in nests and whorls, and psammoma bodies are commonly identified. Immunohistochemically, meningiomas are positive for antiepithelial membrane antigen and somatostatin receptor 2A, with a reported diagnostic sensitivity and specificity of 100% and 94.8%, respectively, when found in combination.6 The presence of estrogen and progesterone hormone receptors, as well as S100, keratin, and SOX10, may also be indicative of meningioma.6,7Given the difficulty of complete resection, close follow-up with yearly CT is recommended postoperatively because the recurrence rate after total excision has been reported to be 28%.4 Stereotactic radiosurgery has been proposed for the treatment of residual middle ear meningiomas.8 Overall, primary middle ear meningiomas have an excellent prognosis, with a reported survival rate of 15.5 years.4In contrast to primary middle ear meningiomas, facial nerve venous malformations (answer choice A) typically have irregular expansion and broadening of the facial nerve canal on CT and evidence of vascular dilation and fibrosis on hematoxylin and eosin stain.9 Jugulotympanic paraganglioma (answer choice B), the most common tumor of the middle ear, has highly vascular stroma and characteristic nested chromaffin cells (ie, Zellballen appearance) on pathology.10 Middle ear adenomas (answer choice D), also known as carcinoid or adenomatous tumors of the middle ear, have sparse desmoplastic stroma and immunohistochemical positivity for pancytokeratin, chromogranin, and CD56.10Primary middle ear meningiomas pose a unique diagnostic and surgical challenge. This case demonstrates the need to include this benign neoplasm in the differential diagnosis in patients presenting with nonspecific otologic symptoms and a middle ear mass.

General

A woman in her 30s presented with a 1-year history of left ear fullness. She reported diminished left-sided hearing that would temporarily improve with autoinsufflation. She denied facial numbness or weakness, and reported no dizziness or vertigo. Physical examination revealed a retrotympanic, nonpulsatile, tan-gray mass anterior to the malleus handle. A tuning fork examination revealed lateralization to the left ear and bone conduction louder than air conduction on the left side with a 512-Hz tuning fork. The remainder of the physical examination, including facial nerve function, was normal. An audiogram confirmed mild conductive hearing loss in the left ear. Computed tomography (CT) revealed a middle ear lesion lateral to the geniculate ganglion with possible extension into the peritubal space. Magnetic resonance imaging (MRI) demonstrated an enhancing lesion lateral to the geniculate ganglion (Figure, A-C). The patient was initially observed but then experienced progressive hearing loss that no longer improved with the Valsalva maneuver, persistent ear fullness, and rare facial twitching. The middle ear mass appeared enlarged on repeated MRI and began to obstruct the eustachian tube. Transcanal endoscopy demonstrated a gray middle ear mass occupying the anterior mesotympanum and epitympanum and extending into the eustachian tube (Figure, D). The tegmen was intact. The specimen revealed predominantly spindled stroma with a focus of tumor that was positive for antiepithelial membrane antigen and somatostatin receptor 2A.A, Noncontrast axial computed tomogram (CT) of the left temporal bone demonstrates an anterior mesotympanic mass lateral to the cochlea (yellow arrowhead) with blockage and extension into the supratubal recess (white arrowhead). A partial mastoid effusion (asterisk) is also visible. B, The coronal CT demonstrates an intact tegmen tympani with hyperostosis (arrowhead). C, Axial, fat-suppressed, postgadolinium, T1-weighted magnetic resonance image (MRI) reveals an enhancing mass of the left perigeniculate region (yellow arrowhead). The geniculate ganglion is marked (white arrowhead). D, Intraoperative transcanal photograph of a lobulated, gray, middle ear mass involving the left protympanum and epitympanum.

what is your diagnosis?

What is your diagnosis?

Primary middle ear meningioma

Jugulotympanic paraganglioma

Facial nerve venous malformation

Middle ear adenoma

a

female

0-10

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2717900

A newborn twin girl was referred to the pediatric otolaryngology clinic at a tertiary pediatric hospital for evaluation of a left-sided nasal mass causing nasal obstruction and difficulty breathing, especially with feeding (Figure 1A). She was born at 36 weeks’ gestation and spent 10 days in the neonatal intensive care unit. Her parents noted that the lesion was present at birth and she always seemed congested on the left side. There was no report of clear drainage. Physical examination showed an approximately 1-cm, firm, pedunculated polypoid mass in the anterior nasal cavity at the vestibule. The base was located just anterior to the septum and encompassed nearly the entire left nasal cavity. There was no fluid in the mass, and there was a negative Furstenberg sign. Nasal endoscopy was performed in the clinic, and there were no additional masses or mucosal abnormalities. The choana was patent. The patient was also noted to have left eye ptosis and left preauricular branchial remnants but no other significant abnormalities on examination. Magnetic resonance imaging was performed (Figure 1B) and showed a 0.8 × 0.5–cm hyperintense mass on T1-weighted images, suggesting a fatty component and no intracranial tract.Photograph (A) and magnetic resonance imaging (MRI) (B) of the left anterior nasal cavity mass. What Is Your Diagnosis?

Dermoid cyst (mature teratoma)

Hairy polyp

Glioma

Encephalocele

B. Hairy polyp

B

Hairy polyp

Congenital midline nasal masses are rare and occur in only 1 of 20 000 to 40 000 births.1 The differential diagnosis includes nasal dermoids, encephaloceles, and gliomas, which represent the most common causes. All of the previously listed masses may have intracranial extension.1 Hairy polyps are epithelial-lined polypoid masses that usually arise from the oropharynx or the nasopharynx.2Hairy polyps have keratinizing squamous epithelium on the surface and surround underlying pilosebaceous units and a fibrofatty core (Figure 2A and B). Mature adipose tissue makes up the core (Figure 2C). Hairy polyps differ from mature teratomas (dermoids) histopathologically because they lack endodermal elements. Both hairy polyps and mature teratomas contain ectodermal and mesodermal contents. Hairy polyps may contain mesodermal elements, such as cartilage, bone, or muscle, but they lack endodermal elements and are not true teratomas. A hairy polyp is classified as a type of choristoma, which is a nonneoplastic mass composed of mature heterotopic tissue.3,4 Reported cases of hairy polyps have occurred mainly in the nasopharynx and oropharynx, including the soft palate, hard palate, tonsils, eustachian tube, middle ear cavity, and tongue.5,6 To our knowledge, there is only one other case report of a hairy polyp in the nasal cavity.1A, Histologic examination (hematoxylin-eosin stain) of the mass shows polypoid fibrofatty core surfaced by skin, a diagnostic feature of a hairy polyp (original magnification ×40). B, Close-up of the surface shows keratinizing epithelium with pilosebaceous units (original magnification ×100). C, Mature adipose in the core (original magnification ×100).Congenital midline nasal masses include a broad list of diseases to consider in the differential diagnosis. Up to 61% of these lesions are reported as dermoids or epidermoids.7 Meningoceles, encephaloceles, gliomas, and multiple other rare lesions are included in the differential diagnosis.1 Magnetic resonance imaging is the established imaging modality to ensure that there is no intracranial extension before any surgical intervention.8Hairy polyps in the nasopharynx and oropharynx are commonly associated with airway obstruction and feeding problems. For this reason and to prevent recurrence, surgical resection is the treatment of choice and has been described in multiple previous case reports.1,2,5,6 The patient described herein underwent surgical resection in the operating room without difficulty. Her postoperative visit showed a well-healed surgical site without signs of residual disease. This case emphasizes the importance of considering a broad list of diseases in the differential diagnosis when evaluating and treating congenital midline nasal masses.

General

A newborn twin girl was referred to the pediatric otolaryngology clinic at a tertiary pediatric hospital for evaluation of a left-sided nasal mass causing nasal obstruction and difficulty breathing, especially with feeding (Figure 1A). She was born at 36 weeks’ gestation and spent 10 days in the neonatal intensive care unit. Her parents noted that the lesion was present at birth and she always seemed congested on the left side. There was no report of clear drainage. Physical examination showed an approximately 1-cm, firm, pedunculated polypoid mass in the anterior nasal cavity at the vestibule. The base was located just anterior to the septum and encompassed nearly the entire left nasal cavity. There was no fluid in the mass, and there was a negative Furstenberg sign. Nasal endoscopy was performed in the clinic, and there were no additional masses or mucosal abnormalities. The choana was patent. The patient was also noted to have left eye ptosis and left preauricular branchial remnants but no other significant abnormalities on examination. Magnetic resonance imaging was performed (Figure 1B) and showed a 0.8 × 0.5–cm hyperintense mass on T1-weighted images, suggesting a fatty component and no intracranial tract.Photograph (A) and magnetic resonance imaging (MRI) (B) of the left anterior nasal cavity mass.

what is your diagnosis?

What is your diagnosis?

Glioma

Hairy polyp

Dermoid cyst (mature teratoma)

Encephalocele

b

female

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2718258

A 6-year-old boy presented with several tumoral lesions on sun-exposed skin. These lesions developed from local freckles beginning at 6 months of age and gradually spread with protruding growth. Over the past 2 years, tumors started to form and develop rapidly, becoming ulcerative and bleeding. The patient was intellectually standard and denied blurred vision, impaired hearing, or any other systemic symptoms. He lived in a remote area in China. His parents were first cousins, but no similar cutaneous presentation was reported by other relatives.The physical examination revealed scaly skin with diffuse warty lesions on sun-exposed areas. The patient’s face was severely disfigured, with numerous ulcerative, malodorous tumors (Figure 1A). The general examination findings, including neurological and ophthalmologic tests, were unremarkable. The lesional discharge culture revealed infection with Proteus vulgaris. Punch biopsy of a paranasal mass was performed (Figure 1B). Craniofacial computed tomography showed heterogenous soft tissue masses located superficially without bony invasion. No signs of cerebral atrophy were noticed. Genetic testing was advised but was declined.A, Preoperative clinical photography revealed a face severely disfigured by diffuse warty lesions and numerous tumors. B, Infiltrating basal cell carcinoma (original magnification ×40). What Is Your Diagnosis?

Trichothiodystrophy

Cockayne syndrome

Xeroderma pigmentosum

Actinic keratosis

C. Xeroderma pigmentosum

C

Xeroderma pigmentosum

The patient underwent palliative tumor excision and skin graft resurfacing. Intraoperative frozen sections showed clear margins. The histopathologic examination confirmed squamous cell carcinoma, basal cell carcinoma, and angiosarcoma. All grafts survived with acceptable cosmetic results at the 50-day follow-up (Figure 2). The patient showed improved self-esteem, absent malodor, and was reintegrated in social activities. The patient was referred to a specialized cancer center for further management and follow-up. The patient’s parents were recommended to pursue prenatal counseling when they intended to conceive another child.Xeroderma pigmentosum (XP), first described by Hebra and Kaposi in 1874, is a rare autosomal recessive genetic disorder.1 Mutations of the XPA through XPG genes and PolH gene disrupt the DNA repair machinery and result in characteristic diseases. Genetic sequencing and functional cellular tests are confirmative; however, XP can be diagnosed clinically based on photosensitivity, early onset of pigmented freckling, and skin cancer predisposition. Xeroderma pigmentosum affects 1 in 20 000 people in Japan and 1 in 250 000 people in the United States, and the prevalence is increased in areas where consanguinity is common.2 The patient described herein had such severe tumor burden at a young age and a simultaneous involvement of 3 kinds of tumors, especially angiosarcoma, that had rarely been reported.The genes XPA through XPG encode enzymes that are included in the repair of UV-induced DNA damage through the nucleotide excision repair pathway. Mutation of each of these 7 genes impedes normal correction of photoproducts. Subsequently, the accumulated photoproducts disturb the process of DNA replication and lead to cell death or mutagenesis.3 The eighth XP gene, PolH, or the so-called XP variant, is not involved in nucleotide excision repair. Rather, it encodes DNA polymerase η, which allows translesional DNA synthesis.3 To date, 8 complementation groups of XP have been identified, namely XPA through XPG and XP variant, with mutations in the corresponding XP genes.4Patients with XP show extreme sensitivity to sunlight and have characteristic skin changes, including pigmented freckling, poikiloderma, and premature aging of sun-exposed areas.5 Patients with XP also have a strong predisposition to malignant tumors on the skin, including an estimated 10 000-fold increased risk for nonmelanoma skin cancer and a 2000-fold increased risk for melanoma.4 The ocular system is frequently affected, resulting in photophobia, loss of vision, inflammatory lesions, and benign or cancerous growths.5 Approximately 20% to 30% of patients have progressive neurological degeneration that varies greatly in terms of onset and progress. Typical signs include hyporeflexia, progressive hearing loss, cognitive impairment, and dyskinesia.1 This young patient developed severe skin lesions and rapidly progressing neoplasms that may be attributed to delayed diagnosis and poor photoprotection.There is no cure for XP; therefore, early diagnosis and strict avoidance of UV exposure are crucial.1 All patients with XP should be under regular surveillance for malignant tumors as well as ocular and neurologic complications.2 Excisional surgery should be considered once an invasive tumor is detected, and aesthetic reconstruction with tissues from UV-protected body sites are thought to be rewarding.6 If regional lymph nodes are invaded, radical lymphadenectomy should be considered when feasible and well tolerated by the patient.6 Postoperative adjuvant therapy is recommended while the detailed therapeutic plan is largely empirical. Complete physical and radiographic examination should be planned as regular surveillance of possible recurrence and metastasis.6 Other supportive measures, such as vitamin D supplements and a psychosocial assistant, are necessary.2 Gene therapy has shown exciting results but has not yet arrived at clinical practice.5 The major concerns for this boy were life-threatening malignant tumors, a poor appearance, and an unpleasant smell, all of which disturbed social interactions. As a result, palliative tumor excision and skin grafting were performed to improve the disease course and enable social reintegration.Trichothiodystrophy and Cockayne syndrome are 2 other nucleotide excision repair defective disorders that should be distinguished from XP.7 Trichothiodystrophy results from mutations in 1 of 4 genes, namely XPB, XPD or p8/TTDA, and TTDN1. Patients with trichothiodystrophy are characterized by photosensitivity, brittle hair, short stature, ichthyosis, and intellectual impairment.8 The mutation of the CSA or CSB genes will cause Cockayne syndrome, which is featured by pigmentary retinopathy, cachectic dwarfism, microcephaly, cognitive deficits, and cataracts.9 However, neither trichothiodystrophy nor Cockayne syndrome shows lentiginous pigmentation and increased frequency of malignant tumors.7 Actinic keratosis can present as scaly, wartlike skin and cancerous lesions on sun-damaged areas that resembles XP; however, it progresses slowly and is more common in elderly patients with a history of frequent or intense UV exposure.10

General

A 6-year-old boy presented with several tumoral lesions on sun-exposed skin. These lesions developed from local freckles beginning at 6 months of age and gradually spread with protruding growth. Over the past 2 years, tumors started to form and develop rapidly, becoming ulcerative and bleeding. The patient was intellectually standard and denied blurred vision, impaired hearing, or any other systemic symptoms. He lived in a remote area in China. His parents were first cousins, but no similar cutaneous presentation was reported by other relatives.The physical examination revealed scaly skin with diffuse warty lesions on sun-exposed areas. The patient’s face was severely disfigured, with numerous ulcerative, malodorous tumors (Figure 1A). The general examination findings, including neurological and ophthalmologic tests, were unremarkable. The lesional discharge culture revealed infection with Proteus vulgaris. Punch biopsy of a paranasal mass was performed (Figure 1B). Craniofacial computed tomography showed heterogenous soft tissue masses located superficially without bony invasion. No signs of cerebral atrophy were noticed. Genetic testing was advised but was declined.A, Preoperative clinical photography revealed a face severely disfigured by diffuse warty lesions and numerous tumors. B, Infiltrating basal cell carcinoma (original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Trichothiodystrophy

Xeroderma pigmentosum

Cockayne syndrome

Actinic keratosis

b

male

0-10

original

https://jamanetwork.com/journals/jama/fullarticle/2720319

A 28-year-old nonsmoking woman was referred to the pulmonary clinic for further evaluation of shortness of breath with exertion. She had slowly progressing dyspnea over the past year and general fatigue. She did not report a history of xerostomia, keratoconjunctivitis sicca, pleural effusions, pneumothoraces, seizure, cognitive impairment, recurrent sinopulmonary infections, or previous autoimmune disease diagnosis and had no relevant family history of lung disease. Her physical examination findings were unremarkable and there was no evidence of cutaneous lesions. A high-resolution computed tomographic (CT) scan of her chest revealed diffuse thin-walled pulmonary cysts without nodules, parenchymal changes, or lymphadenopathy (Figure). Imaging of her abdomen did not show kidney lesions or abdominal masses. The patient’s serum vascular endothelial growth factor D (VEGF-D) level was elevated at 1300 pg/mL (reference range, <600 pg/mL).High-resolution computed tomography scan of the chest showing numerous, diffuse, thin-walled lung cysts surrounded by normal-appearing lung parenchyma. There is no mediastinal or hilar adenopathy.The VEGF-D level is nonspecific and the patient should undergo further evaluation with a lung biopsy.The VEGF-D level is supportive of a diagnosis of pulmonary Langerhans cell histiocytosis.The VEGF-D level is supportive of a diagnosis of lymphangioleiomyomatosis.The VEGF-D level indicates that the patient should undergo folliculin gene test for Birt-Hogg-Dubé syndrome. How Do You Interpret These Results?

The VEGF-D level is nonspecific and the patient should undergo further evaluation with a lung biopsy.

The VEGF-D level is supportive of a diagnosis of pulmonary Langerhans cell histiocytosis.

The VEGF-D level is supportive of a diagnosis of lymphangioleiomyomatosis.

The VEGF-D level indicates that the patient should undergo folliculin gene test for Birt-Hogg-Dubé syndrome.

C

The VEGF-D level is supportive of a diagnosis of lymphangioleiomyomatosis.

Pulmonary cysts are characteristic of different diseases that include, but are not limited to, Langerhans cell histiocytosis, lymphangioleiomyomatosis (LAM), and Birt-Hogg-Dubé syndrome. Pulmonary Langerhans cell histiocytosis is a rare lung disease characterized by accumulation of Langerhans cells in small airways and is usually seen in young adult smokers.1 High-resolution CT images commonly demonstrate nodules and upper and middle lobe cysts that may progress to a thick, irregular-walled, bizarre-shaped appearance.1 Birt-Hogg-Dubé is an autosomal dominant syndrome characterized by multiple irregular lung cysts commonly found in the peripheral lung zones at the lung bases and along the mediastinum, and it is associated with cutaneous fibrofolliculomas, spontaneous pneumothorax, and kidney cancer.1 LAM is a rare disease that predominantly affects women of childbearing age, with a prevalence of approximately 3 to 8 cases per million women.2 LAM may occur sporadically or in association with tuberous sclerosis complex.2 A diagnosis of LAM can be confidently made with characteristic high-resolution CT image findings of diffuse thin-walled pulmonary cysts surrounded by normal lung parenchyma and 1 of the following: renal angiomyolipomas, chylous effusions, lymphangioleiomyomas, or a diagnosis of tuberous sclerosis complex.3 In the absence of these other findings, a lung biopsy may be required to differentiate the symptoms from other cystic lung diseases. More recently, serum VEGF-D testing has emerged as a noninvasive means of confirming the diagnosis in a subset of patients with cystic lung disease in whom the level is documented to be elevated.4VEGF is an angiogenic growth factor that is usually produced by malignant cells. A member of the VEGF family is VEGF-D, a ligand for lymphatic growth factor VEGF receptors (VEGFR), specifically VEGFR-2 (fetal liver kinase 1) and VEGFR-3 (fms-like tyrosine kinase 4).5 Activation of VEGFR-3 can promote lymphatic formation and spread of malignant tumor cells through the lymphatic system to the lymph nodes.6The serum level of VEGF-D has been found to be elevated in patients with LAM compared with healthy controls as well as patients with other forms of cystic lung disease and emphysema.7 The VEGF-D levels also seem to inversely correlate with pulmonary function testing, which was demonstrated in the Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus (MILES) trial that showed that patients with elevated VEGF-D levels treated with US Food and Drug Administration–approved sirolimus had improvement in forced expiratory volume in the first second (FEV1) and decreased VEGF-D levels compared with the placebo group.8 In patients with high-resolution CT image findings indicative of cystic lung disease, a serum VEGF-D cutoff of greater than 800 pg/mL has a sensitivity of 73% and a specificity of 100% and a definite diagnosis of LAM can be made in the right clinical context without the need for a lung biopsy.7 However, a VEGF-D level less than or equal to 800 pg/mL does not rule out a diagnosis of LAM. Recent guidelines by the American Thoracic Society/Japanese Respiratory Society recommend that in patients with cystic lung disease suggestive of LAM but no other clinical or radiological confirmatory features besides lung cysts, a VEGF-D level should be obtained before proceeding with lung biopsy, with a threshold of greater than 800 pg/mL to be used to diagnose LAM.4 Among patients with LAM who are treated with sirolimus, there is sustained reduction in VEGF-D levels while undergoing therapy compared with before therapy.9In the United States, the only serum VEGF-D testing certified by the College of American Pathologists and Clinical Laboratory Improvement Amendments is conducted at the translational trial development and support laboratory at the Cincinnati Children’s Hospital Medical Center.The patient’s clinical presentation and high-resolution CT image findings of cystic lung disease are suggestive of LAM. However, in the absence of other clinical or radiographic features, the diagnosis cannot be definitively established. The elevated VEGF-D level in this setting can confidently confirm the diagnosis of LAM without the need for lung biopsy.LAM was diagnosed based on the patient’s serum VEGF-D level and pulmonary function testing results that showed a restrictive lung pattern with a reduced FEV1 at 65%; there was no bronchodilator response. The patient was prescribed sirolimus with improvement in her symptoms. Two years after her initial presentation, she continues to follow up in pulmonary clinic with serial pulmonary function testing that has shown stabilization of her lung function over time.Serum VEGF-D is a useful noninvasive, diagnostic test for patients presenting with cystic lung disease.Serum VEGF-D levels greater than 800 pg/mL are almost 100% specific for the diagnosis of LAM and can help avoid invasive diagnostic procedures, such as lung biopsy.Approximately 30% of patients with LAM can have normal serum VEGF-D levels, and a normal level does not exclude the diagnosis of LAM.Sirolimus is an effective, FDA-approved treatment for LAM that also leads to consistent reductions in serum VEGF-D levels.

Diagnostic

A 28-year-old nonsmoking woman was referred to the pulmonary clinic for further evaluation of shortness of breath with exertion. She had slowly progressing dyspnea over the past year and general fatigue. She did not report a history of xerostomia, keratoconjunctivitis sicca, pleural effusions, pneumothoraces, seizure, cognitive impairment, recurrent sinopulmonary infections, or previous autoimmune disease diagnosis and had no relevant family history of lung disease. Her physical examination findings were unremarkable and there was no evidence of cutaneous lesions. A high-resolution computed tomographic (CT) scan of her chest revealed diffuse thin-walled pulmonary cysts without nodules, parenchymal changes, or lymphadenopathy (Figure). Imaging of her abdomen did not show kidney lesions or abdominal masses. The patient’s serum vascular endothelial growth factor D (VEGF-D) level was elevated at 1300 pg/mL (reference range, <600 pg/mL).High-resolution computed tomography scan of the chest showing numerous, diffuse, thin-walled lung cysts surrounded by normal-appearing lung parenchyma. There is no mediastinal or hilar adenopathy.The VEGF-D level is nonspecific and the patient should undergo further evaluation with a lung biopsy.The VEGF-D level is supportive of a diagnosis of pulmonary Langerhans cell histiocytosis.The VEGF-D level is supportive of a diagnosis of lymphangioleiomyomatosis.The VEGF-D level indicates that the patient should undergo folliculin gene test for Birt-Hogg-Dubé syndrome.

how do you interpret these results?

How do you interpret these results?

The VEGF-D level is nonspecific and the patient should undergo further evaluation with a lung biopsy.

The VEGF-D level is supportive of a diagnosis of pulmonary Langerhans cell histiocytosis.

The VEGF-D level indicates that the patient should undergo folliculin gene test for Birt-Hogg-Dubé syndrome.

The VEGF-D level is supportive of a diagnosis of lymphangioleiomyomatosis.

d

female

21-30

original

https://jamanetwork.com/journals/jama/fullarticle/2719861

A 58-year-old woman with a history of cervical spondylosis and hypothyroidism presented with a 2-week history of joint pain. She noted pain and swelling in her right knee, which migrated to the right ankle and then affected the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of her fingers. About 2 weeks before her symptoms began, her 5-year-old grandson had a febrile illness characterized by headaches, body aches, malaise, and rash on the cheeks, trunk, and extremities but no arthritis. Ten days later, her 10-month-old granddaughter developed a similar febrile illness. Eight days ago, her 25-year-old daughter developed headaches, malaise, and significant arthralgias affecting her wrists and knees but no rash or fever. Manifestations in all of the family members resolved spontaneously within 1 week.On examination, the patient was afebrile with normal vital signs. A malar rash was present (Figure), but there was no rash on the trunk or extremities. She had swelling and tenderness of the MCP and PIP joints and had difficulty making a fist and fully extending her fingers. Laboratory studies revealed a mild normochromic normocytic anemia with a hemoglobin level of 11.5 g/dL, normal white blood cell and platelet counts, and normal results for a comprehensive metabolic panel. She had a positive antinuclear antibody (ANA) result (1:160 [homogeneous pattern; negative <1:80 serum dilution]). Testing for rheumatoid factor was negative; levels of inflammatory markers were normal.Order testing for anticyclic citrullinated peptide (CCP) antibody What Would You Do Next?

Check for anti–double-stranded DNA and anti-Smith antibodies

Schedule bilateral hand radiographs

Order serologic testing for parvovirus

Order testing for anticyclic citrullinated peptide (CCP) antibody

Parvovirus-associated arthritis

C

Order serologic testing for parvovirus

The key to the correct diagnosis in this patient is the history of recent exposure to children with a febrile illness associated with a facial rash (“slapped cheek”), suggestive of erythema infectiosum, also known as fifth disease. Diagnosis of recent parvovirus infection requires detection of parvovirus B19–specific IgM antibodies. Therefore, option C is the correct answer. Given the recent history of similar illnesses in other family members, evaluation for chronic autoimmune diseases, eg, systemic lupus erythematosus (option A) and rheumatoid arthritis (option D), would be premature. Furthermore, given that after onset of rheumatoid arthritis, characteristic radiographic changes can take 6 to 12 months to develop, and that no radiographic changes are seen in systemic lupus erythematosus or parvovirus arthropathy, hand radiographs (option B) would not help establish the diagnosis.Human parvovirus B19 belongs to the family Parvoviridae and genus Erythrovirus (because it preferentially replicates in human erythroid progenitor cells).1 Children are commonly infected first and then can infect healthy family members. The infectious phase begins 24 to 48 hours before the viral prodrome and lasts until the rash appears. Clinical presentation is variable, depending on age and immunologic status. The 5 well-established syndromes associated with parvovirus B19 include erythema infectiosum, arthropathy, transient aplastic crisis (TAC), transplacental fetal infection, and pure red blood cell aplasia.Erythema infectiosum (fifth disease) is commonly seen in children, presenting with a febrile influenza–like illness for 5 to 7 days, followed by a classic “slapped cheek” rash with relative circumoral pallor. An erythematous, maculopapular rash sometimes follows 1 to 2 days later, covering the rest of the body and fading to produce a lacy appearance. The classic slapped-cheek rash, although less common in adults, can still occur, as in this case.2,3 A rash in a “gloves-and-socks” distribution can also appear.4Joint symptoms attributable to arthropathy are rare in children but common in adults, and they occur more often in women than in men.5,6 Arthropathy is nonerosive and often symmetric, mainly affecting the small joints of the hands and feet.7,8 In children, however, arthropathy can be asymmetric, often involving the knees and ankles. Joint symptoms usually last for 1 to 3 weeks, although in some patients symptoms may persist for months.6Transient aplastic crisis is classically described in chronic hemolytic disorders (eg, sickle cell anemia [90% of cases]) and causes abrupt cessation of erythropoiesis and a consequent self-limiting (4-8 days) anemia, which can be potentially life-threatening.9 Patients need to be isolated because they are highly contagious.9Transplacental fetal infection occurs in about 30% of cases during pregnancy9 and is associated with a 2% to 6% risk of fetal loss.4,9 It can lead to nonimmune hydrops fetalis, intrauterine growth restriction, or isolated serositis.4Pure red blood cell aplasia causes prolonged anemia in patients with congenital and acquired immunodeficiencies. Giant proerythroblasts can be seen on bone marrow biopsy.The diagnosis of acute parvovirus infection is based on detection of circulating IgM antibodies to parvovirus B19.6 By the time the rash appears, 90% of cases are IgM antibody–positive.6 This antibody remains detectable for up to 3 months. The IgG antibody appears within 1 week of illness and remains detectable for life.6 Results of other laboratory tests, including tests for acute phase reactants, are usually normal. ANA and rheumatoid factor may be transiently detectable.6 Additional testing may include detection of viral nucleic acid (parvovirus B19 DNA) in blood by qualitative polymerase chain reaction. This test is critical in immunocompromised patients because they may not test positive for IgM and IgG antibodies.4,9,10Treatment for acute parvoviral arthritis is symptomatic with nonsteroidal anti-inflammatory drugs. Treatment for other manifestations include blood transfusions for aplastic crisis and temporary cessation of immunosuppression and intravenous immunoglobulins for patients with chronic infection (persistent viremia associated with prolonged polyarthritis or anemia). Intrauterine blood transfusions can be performed for cases of hydrops fetalis.Additional laboratory results showed significant titers of IgM (15.04 index value) and IgG (6.45 index value) antibodies to parvovirus B19 (interpretation for both IgM and IgG parvovirus B19 antibodies: positive >1.1 index value). Results of tests for antibodies to CCP, double-stranded DNA, and extractable nuclear antigens were negative. The patient was treated with prednisone starting at 35 mg daily and tapering over the course of 1 week, which resolved her joint symptoms. Six months later, results of repeat studies were negative for IgM antibodies to parvovirus B19 and for ANA.

General

A 58-year-old woman with a history of cervical spondylosis and hypothyroidism presented with a 2-week history of joint pain. She noted pain and swelling in her right knee, which migrated to the right ankle and then affected the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of her fingers. About 2 weeks before her symptoms began, her 5-year-old grandson had a febrile illness characterized by headaches, body aches, malaise, and rash on the cheeks, trunk, and extremities but no arthritis. Ten days later, her 10-month-old granddaughter developed a similar febrile illness. Eight days ago, her 25-year-old daughter developed headaches, malaise, and significant arthralgias affecting her wrists and knees but no rash or fever. Manifestations in all of the family members resolved spontaneously within 1 week.On examination, the patient was afebrile with normal vital signs. A malar rash was present (Figure), but there was no rash on the trunk or extremities. She had swelling and tenderness of the MCP and PIP joints and had difficulty making a fist and fully extending her fingers. Laboratory studies revealed a mild normochromic normocytic anemia with a hemoglobin level of 11.5 g/dL, normal white blood cell and platelet counts, and normal results for a comprehensive metabolic panel. She had a positive antinuclear antibody (ANA) result (1:160 [homogeneous pattern; negative <1:80 serum dilution]). Testing for rheumatoid factor was negative; levels of inflammatory markers were normal.Order testing for anticyclic citrullinated peptide (CCP) antibody

what would you do next?

What would you do next?

Order testing for anticyclic citrullinated peptide (CCP) antibody

Check for anti–double-stranded DNA and anti-Smith antibodies

Order serologic testing for parvovirus

Schedule bilateral hand radiographs

c

female

51-60

White

original

https://jamanetwork.com/journals/jama/fullarticle/2719582

A 67-year-old man with type 2 diabetes mellitus and hyperlipidemia was evaluated for unintentional weight loss of 28 lb (12.7 kg) and increasing fasting blood glucose values over the past 6 months. A computed tomography scan showed diffuse enlargement of the pancreas with peripheral hypoenhancement but no discrete mass. Soft tissue surrounded the infrarenal abdominal aorta, extended along the common iliac arteries, and obstructed the left ureter, causing hydronephrosis. He was referred for evaluation of possible malignancy. Laboratory studies including immunoglobulin G subgroup 4 (IgG4) levels are shown in the Table. Fine-needle aspiration of the pancreas showed no malignancy. Colonoscopy results 8 months ago were normal.Test results indicate pancreatic cancer but the patient is a carbohydrate antigen (CA) 19-9 nonsecretor. What Would You Do Next?

Test results indicate presence of IgG4-related disease.

Test results indicate locally invasive pancreatic lymphoma.

Test results indicate viral hepatitis.

Test results indicate pancreatic cancer but the patient is a carbohydrate antigen (CA) 19-9 nonsecretor.

A

Test results indicate presence of IgG4-related disease.

IgG4-related disease is a relapsing, immune-mediated, multiorgan, fibroinflammatory disease (characterized by intense inflammation and fibrosis) that presents similarly to a nonspecific malignant, infectious, and inflammatory condition. IgG4 is a subclass of IgG that accounts for less than 5% of the total IgG in healthy adults.1,2 The sensitivity of any elevation of IgG4 for diagnosing IgG4-related disease is approximately 70% and the specificity is 85%. Some criteria for diagnosing IgG4-related disease use a 2-fold elevation of IgG4 levels as the threshold for a positive test, in which case the sensitivity is approximately 60% and the specificity is 90%.1,3,4 Because the prevalence of IgG4-related disease is low (4.6 cases per 100 000),5 the positive predictive value of IgG4 elevation is only 36%.3 IgG4 may be elevated in conditions other than IgG4-related disease. For example, IgG4-related disease is elevated in 7% to 10% of patients with pancreatic cancer, cholangiocarcinoma, primary sclerosing cholangitis, acute pancreatitis, and healthy individuals.3 The precise role of IgG4 in the pathogenesis of IgG4-related disease remains unknown. Elevated IgG4 levels in IgG4-related disease may result from type 2 helper cell activation, in response to prolonged exposure to an unknown antigen.2,6 The 2018 Medicare reimbursement for the IgG4 assay is $9.90.Individual organ manifestations of IgG4-related disease were previously regarded as unrelated disease entities (eg, autoimmune pancreatitis, IgG4-associated cholangitis, Mikulicz disease, retroperitoneal fibrosis, orbital pseudolymphoma, interstitial lung disease, IgG4-related tubulointerstitial nephritis) but are now considered part of a single disease process that involves various organs. Multiple organs may be involved successively or at the same time. IgG4-related disease typically affects males in a 3:1 ratio.1,2 An isolated elevation of IgG4 levels is not diagnostic of IgG4-related disease, but a combination of elevated IgG4 levels and typical imaging features (diffuse/localized swelling of the pancreas with peripheral hypoenhancement) is diagnostic, as in this patient with autoimmune pancreatitis and retroperitoneal fibrosis.7 In such typical cases, a biopsy is not required for diagnosis.7 However, as manifestations of IgG4-related disease are often mass forming, a fine-needle aspiration should be performed to rule out malignancy.IgG4-related disease can also be diagnosed based on characteristic histology. However, samples from fine-needle aspiration are typically inadequate for histologic diagnosis of IgG4-related disease. Tissue diagnosis of IgG4-related disease requires preserved architecture, such as that obtained from a core or wedge biopsy or resection specimens. Histologic findings are similar across affected organs and are characterized by lymphoplasmacytic infiltration, storiform (cartwheel) fibrosis, and obliterative phlebitis. Staining the histopathology specimen facilitates calculation of the absolute number and relative proportion of IgG4+ cells from the total number of IgG+ plasma cells, which are components of the histologic criteria for IgG4-related disease.8Specific laboratory tests alone cannot diagnose IgG4-related disease. Approximately 60% of patients with IgG4-related disease have elevated serum IgE levels, approximately 25% have elevated inflammatory markers such as C-reactive protein, and approximately one-third have elevated levels of eosinophils and antinuclear antibody.4Levels of IgG4 are unreliable for assessing response to treatment and can rebound above normal in up to 70% patients after withdrawal of glucocorticoid treatment.9 Even patients with a false-positive elevation of IgG4 (ie, not related to underlying IgG4-related disease) can have improvement in IgG4 levels with steroids, presumably due to reduced inflammation.10 Therefore, IgG4 levels cannot be used to measure responsiveness to therapy. Repeat imaging, along with specific laboratory testing, depending on the organ involved (eg, liver biochemistries in cases with autoimmune pancreatitis or IgG4-associated cholangitis) are often the best indicators of response to treatment.The patient was prescribed prednisone, 40 mg/daily, for 1 month followed by a prednisone taper over 8 weeks. Repeat computed tomographic scan 2 weeks after starting treatment showed significant improvement in pancreatic inflammation. A ureteral stent was placed for ureteral stenosis due to retroperitoneal fibrosis and left hydronephrosis. At 3-month follow-up, liver biochemistry levels were normal. At 6-month follow-up, pancreatic changes and hydronephrosis had resolved, and the ureteral stent was removed. The patient had a relapse 3 years after presentation, which was treated again with corticosteroids. The patient was relapse free at his most recent follow-up (3 months ago).Immunoglobulin G subgroup 4 (IgG4)-related disease is a relapsing, immune-mediated, fibroinflammatory disease (characterized by intense inflammation and fibrosis) that resembles malignant, infectious, and inflammatory conditions in its presentation and can affect multiple organs.Elevated IgG4 levels are insufficient for diagnosing IgG4-related disease. In the case of pancreatic involvement from IgG4-related disease (ie, autoimmune pancreatitis), a combination of elevated IgG4 levels and characteristic imaging features can lead to a diagnosis without biopsy.Alternatively, a core or wedge biopsy can be obtained for a histologic diagnosis of IgG4-related disease. Histology is similar across all involved organs.Corticosteroids should be used for treating the initial episode and relapses.Levels of IgG4 commonly increase after treatment. An isolated elevation in IgG4 levels is insufficient evidence for relapse in the absence of other clinical data.

Diagnostic

A 67-year-old man with type 2 diabetes mellitus and hyperlipidemia was evaluated for unintentional weight loss of 28 lb (12.7 kg) and increasing fasting blood glucose values over the past 6 months. A computed tomography scan showed diffuse enlargement of the pancreas with peripheral hypoenhancement but no discrete mass. Soft tissue surrounded the infrarenal abdominal aorta, extended along the common iliac arteries, and obstructed the left ureter, causing hydronephrosis. He was referred for evaluation of possible malignancy. Laboratory studies including immunoglobulin G subgroup 4 (IgG4) levels are shown in the Table. Fine-needle aspiration of the pancreas showed no malignancy. Colonoscopy results 8 months ago were normal.Test results indicate pancreatic cancer but the patient is a carbohydrate antigen (CA) 19-9 nonsecretor.

what would you do next?

What would you do next?

Test results indicate pancreatic cancer but the patient is a carbohydrate antigen (CA) 19-9 nonsecretor.

Test results indicate viral hepatitis.

Test results indicate presence of IgG4-related disease.

Test results indicate locally invasive pancreatic lymphoma.

c

male

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2697215

A man in his 20s presented with rapidly growing, severely painful oral lesions on the left hard palate of 2 months’ duration. His medical history was significant for Philadelphia chromosome-negative B-cell acute lymphocytic leukemia refractory to multiple treatments, including chimeric antigen receptor T-cell therapy, with transformation to acute myeloid leukemia (AML) status posttreatment. At the time of evaluation, he had been hospitalized for 5 months with severe protein-calorie malnutrition, pancytopenia, and recurrent neutropenic fevers. The patient was febrile (38.3°C), with a white blood cell count of 0.5/μL (absolute neutrophil count 0.00; to convert to ×109/L, multiply by 0.001), hemoglobin levels of 7.6g/dL (to convert to g/L, multiply by 10.0), hematocrit 21%, and platelet count 9/μL (to convert to ×109/L, multiply by 1.0). He was not receiving active cancer treatment. He appeared cachectic and pale. Intraoral examination revealed poor oral hygiene. The left hard palate exhibited a large swelling with a 5×3-cm indurated area of ulceration, central necrosis, and desquamation (Figure, A). The patient was treated palliatively with dexamethasone solution and nystatin rinse. A biopsy was not recommended owing to medical instability. However, the patient retained a sloughed fragment of the affected tissue, which was submitted for histologic evaluation. A maxillofacial computed tomography (CT) scan completed the etiological investigation.A, The left hard palate shows enlargement with a large, focal, necrotic lesion. B, Hematoxylin-eosin stain of palatal tissue (original magnification ×1000). C, Grocott methenamine silver stain of palatal tissue (original magnification ×1000). D, Computed tomographic image of the maxillofacial complex shows tissue enlargement in the left hard palate and maxillary sinus. What Is Your Diagnosis?

Squamous cell carcinoma

Mucormycosis

Aspergillosis

Myeloid sarcoma

B. Mucormycosis

B

Mucormycosis

Histologic evaluation revealed fragments of fibrotic, necrotic tissue with large, branching, nonseptate hyphae, positive for periodic acid-Schiff (Figure, B) and Grocott methenamine silver stains (Figure, C). These findings are consistent with mucormycosis. In addition, CT imaging results showed enlarged left palatal tissue with left maxillary sinus cysts and scattered areas of high attenuation, also consistent with a fungal etiology (Figure, D).Mucormycosis is a deep fungal infection caused by Mucorales organisms, common thermotolerant fungi in soil and decaying foods.1 Inoculation occurs through ingestion or inhalation of spores. In immunocompetent hosts, spores are quickly phagocytosed whereas in immunocompromised individuals, they can lead to rapidly spreading, invasive infections with high mortality.2 This occurs most commonly in the setting of hematologic malignant diseases, estimated at 4.29 cases per 100 000 patients with a 60% mortality rate in these patients.3,4 Mucormycosis has also been reported in patients with poorly controlled diabetes, chronic corticosteroid use, solid organ transplant, and, as in this case, malnourishment.1,5 Although mucormycosis is less common than invasive candidiasis or aspergillosis,6 it is the most common fungal infection in neutropenic patients with acute leukemia and lymphoma.1 Thirty percent to 50% of these patients show orofacial involvement, most commonly rhinocerebral, as an early sign of this disease.1,3 Angioinvasion is a clinical hallmark of mucormycosis, resulting in vascular occlusion and thrombosis.7 Subsequent tissue necrosis frequently manifests in the hard palate.7Regardless of infection site, patients with mucormycosis present with fever in at least 80% of cases.4 Imaging studies show focal areas of consolidation with fungal infiltrates. Biopsy results tend to show broad aseptate hyphae, granuloma formation, and vascular invasion.7 Each of these features is consistent with this case.Mucormycosis is treated with surgical debridement and high-dose antifungal therapy (primarily intravenous amphotericin B). Control is closely linked to management of the precipitating condition.1,7 Posaconazole and others are considered if amphotericin treatment fails or if patients relapse.3-5,7 Successful treatment of mucormycosis requires early detection, diagnosis, and initiation of appropriate therapy.In this case, solid malignant abnormality and deep fungal infection comprised the differential diagnosis. Aspergillosis can present as an invasive, opportunistic fungal infection with similar systemic symptoms to mucormycosis.1 However, it less commonly presents in the hard palate and maxillary sinus.7 Squamous cell carcinoma represents 95% of malignant oral lesions, but more frequently involves the lips, tongue, or floor of the mouth as a red, white, or mixed lesion.8 Myeloid sarcoma is an extramedullary tumor of myeloid precursor cells associated with preexisting bone marrow malignant abnormality. It has rarely been reported in the hard palate, occurring as a nodular growth.9 Here, tissue sample was consistent with mucormycosis. However, given the patient’s poor overall prognosis, additional testing and definitive treatment were not recommended. Instead, the patient’s previous antifungal prophylaxis with posaconazole was continued until discharge to hospice care where the patient subsequently died.

Dermatology

A man in his 20s presented with rapidly growing, severely painful oral lesions on the left hard palate of 2 months’ duration. His medical history was significant for Philadelphia chromosome-negative B-cell acute lymphocytic leukemia refractory to multiple treatments, including chimeric antigen receptor T-cell therapy, with transformation to acute myeloid leukemia (AML) status posttreatment. At the time of evaluation, he had been hospitalized for 5 months with severe protein-calorie malnutrition, pancytopenia, and recurrent neutropenic fevers. The patient was febrile (38.3°C), with a white blood cell count of 0.5/μL (absolute neutrophil count 0.00; to convert to ×109/L, multiply by 0.001), hemoglobin levels of 7.6g/dL (to convert to g/L, multiply by 10.0), hematocrit 21%, and platelet count 9/μL (to convert to ×109/L, multiply by 1.0). He was not receiving active cancer treatment. He appeared cachectic and pale. Intraoral examination revealed poor oral hygiene. The left hard palate exhibited a large swelling with a 5×3-cm indurated area of ulceration, central necrosis, and desquamation (Figure, A). The patient was treated palliatively with dexamethasone solution and nystatin rinse. A biopsy was not recommended owing to medical instability. However, the patient retained a sloughed fragment of the affected tissue, which was submitted for histologic evaluation. A maxillofacial computed tomography (CT) scan completed the etiological investigation.A, The left hard palate shows enlargement with a large, focal, necrotic lesion. B, Hematoxylin-eosin stain of palatal tissue (original magnification ×1000). C, Grocott methenamine silver stain of palatal tissue (original magnification ×1000). D, Computed tomographic image of the maxillofacial complex shows tissue enlargement in the left hard palate and maxillary sinus.

what is your diagnosis?

What is your diagnosis?

Mucormycosis

Aspergillosis

Myeloid sarcoma

Squamous cell carcinoma

a

male

21-30

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2697564

A child presented with multiple, asymptomatic, scattered white macules on the lower abdomen and pubic area, which were present at birth and had gradually increased in size and number. Physical examination revealed multiple, well-demarcated, hypopigmented 1- to 5-mm macules on the lower abdomen and pubic area (Figure, A and B). There was no history of any systemic disorder and no family history of similar lesions. Direct microscopic examination of scales soaked in potassium hydroxide did not reveal hyphae. Wood light examination revealed no accentuation. A punch biopsy specimen was obtained for further evaluation (Figure, C and D).A, Multiple discrete hypopigmented macules on the lower abdomen and pubic area. B, Well-demarcated hypopigmented macules on the lower abdomen. C, Histopathological examination revealed mild hyperkeratosis, acanthosis, and scattered clear cells in the epidermis (hematoxylin-eosin). D, The clear cells are larger than the neighboring keratinocytes and contain abundant pale cytoplasm (hematoxylin-eosin). What Is Your Diagnosis?

Tinea versicolor

Vitiligo

Clear cell papulosis

Idiopathic guttate hypomelanosis

C. Clear cell papulosis

C

Clear cell papulosis

Histopathological examination revealed mild hyperkeratosis and acanthosis, and scattered clear cells in the epidermis. On histochemical and immunohistochemical evaluation, the Fontana-Masson stain did not indicate any reduction in melanin level, and the melan-A stain revealed that the melanocyte number was normal. The clear cells were positive for cytokeratin AE1/AE3 and 7, carcinoembryonic antigen (CEA), and epithelial membrane antigen (EMA). In contrast, the cells did not stain positively for the S-100 protein.Clear cell papulosis (CCP) is a rare skin condition first described by Kuo et al.1 The disease is characterized by multiple hypopigmented macules or flat-topped papules on the lower abdomen or along the milklines in children.2 An Asian predisposition is apparent. Histopathologically, clear cells are scattered among basal keratinocytes that exhibit mild hyperkeratosis and mild-to-moderate acanthosis. The diagnostic clear cells are larger than the neighboring keratinocytes and contain abundant pale cytoplasm. These cells stain immunohistochemically for cytokeratin AE1/AE3 and 7, CEA, EMA, and cell adhesion molecule 5.2.3It is necessary to perform a clinical differential diagnosis of hypopigmented lesions, including vitiligo, idiopathic guttate hypomelanosis, tinea versicolor, and postinflammatory hypopigmentation. Given the typical clinical appearance in young children, Wood light examination, direct microscopic examination of scales, and microscopic findings can be used to differentiate CCP from the other conditions. The histological differential diagnosis of scattered clear cells in the epidermis includes extramammary Paget disease, pagetoid squamous carcinoma, and clear cells of Toker. Extramammary Paget disease and pagetoid squamous cell carcinoma exhibit malignant features, including cytological atypia, nuclear pleomorphism, hyperchromasia, and abnormal mitoses. Paget cells immunostain positively for HER2/neu, but the clear cells of CCP do not. Toker cells, found in 10% of histologically normal nipples, are polygonal, with a clear cytoplasm and rounded nuclei, and are distributed in the basal or spinous layer. The clear cells of CCP immunostain positively for CEA, but Toker cells do not.3-5It is not necessary to treat CCP because the skin lesions are asymptomatic. Also, spontaneous regression was noted in approximately 12 of 14 patients during 11 years of follow-up, without any clinically apparent scarring or epidermal change at the site of the previous lesion.5Clear cell papulosis can be pathologically misconstrued as normal skin. Therefore, CCP should be included in the differential diagnosis of hypopigmented lesions, and physicians should be aware of the relevant microscopic findings.

Dermatology

A child presented with multiple, asymptomatic, scattered white macules on the lower abdomen and pubic area, which were present at birth and had gradually increased in size and number. Physical examination revealed multiple, well-demarcated, hypopigmented 1- to 5-mm macules on the lower abdomen and pubic area (Figure, A and B). There was no history of any systemic disorder and no family history of similar lesions. Direct microscopic examination of scales soaked in potassium hydroxide did not reveal hyphae. Wood light examination revealed no accentuation. A punch biopsy specimen was obtained for further evaluation (Figure, C and D).A, Multiple discrete hypopigmented macules on the lower abdomen and pubic area. B, Well-demarcated hypopigmented macules on the lower abdomen. C, Histopathological examination revealed mild hyperkeratosis, acanthosis, and scattered clear cells in the epidermis (hematoxylin-eosin). D, The clear cells are larger than the neighboring keratinocytes and contain abundant pale cytoplasm (hematoxylin-eosin).

what is your diagnosis?

What is your diagnosis?

Tinea versicolor

Clear cell papulosis

Idiopathic guttate hypomelanosis

Vitiligo

b

neutral

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2698664

A 33-year-old white man presented with a 5-month history of a progressively necrotic plaque on the nose and scattered nodules on the extremities. The plaque first appeared as a small inflammatory papule on the left nostril. Shortly thereafter, the patient was hospitalized at an outside facility for multifocal pneumonia. He was also treated for a methicillin-resistant Staphylococcus aureus infection of his nose. Despite antibiotic therapy, the papule continued to grow and ulcerate and eventually became necrotic (Figure, A). One month before presentation at our facility, the patient began developing erythematous papules on his arms and legs. The papules enlarged and ulcerated. Some of them healed spontaneously with poxlike scars. He had no recent history of travel. At admission, the patient was tachycardic and febrile to a temperature of 38.5°C. Routine laboratory testing revealed normocytic anemia (hemoglobin, 7.7 g/dL [to convert to grams per liter, multiply by 10]). Shave biopsies of necrotic nodules on the left arm and left cheek (Figure, B-D) and, later, an excisional biopsy of a cervical lymph node were performed. Head computed tomography demonstrated a soft-tissue mass that encased the nasal bone and extended into the right maxillary sinus and left nasal cavity. Chest computed tomography showed bilateral pulmonary nodules. Physical examination revealed a necrotic plaque with surrounding erythema on the distal nose (Figure, A). A 1 × 1-cm crateriform papule with central necrosis was present on the left malar cheek. Multiple nodules with central, dry necrosis and areas of poxlike scarring were scattered across the extremities. Slight contractures of his fingers were also noted.A, Clinical photograph. B-D, Analyses of a shave biopsy specimen of the necrotic papule on the patient’s left cheek (B, hematoxylin-eosin, original magnification ×400; C, original magnification ×400; D, original magnification ×200). What Is Your Diagnosis?

Extranodal natural killer/T-cell lymphoma, nasal type

Lymphomatoid granulomatosis

Granulomatosis with polyangiitis (Wegener granulomatosis)

Histoplasmosis

B. Lymphomatoid granulomatosis

B

Lymphomatoid granulomatosis

Biopsy revealed surface ulceration. An angiocentric and angiodestructive infiltrate was present (Figure, A), composed of an admixture of atypical lymphocytes with a marked increased number of mitotic figures. Immunohistochemical analysis showed that the neoplastic cells were positive for CD20 (Figure, C), PAX-5, and CD30 and had a marked increased proliferation index by Ki-67. Staining results for Epstein-Barr virus (EBV)–encoded messenger RNA (EBER) by in situ hybridization were positive, with areas showing more than 50 EBER-positive cells per high-power field (HPF) (Figure, D). The malignant cells tested negative for CD3 and CD56. Although the patient’s presentation was concerning for extranodal natural killer/T-cell lymphoma, nasal type (ENKTL-NT), the immunophenotypic findings were diagnostic of lymphomatoid granulomatosis (LG) grade III. The EBV load was 78 400 copies/mL. Culture results were negative for bacteria and fungi. Results of serologic screening for HIV and an autoantibody screen, including antinuclear and antineutrophil cytoplasmic antibodies, were negative. A genetics consultation was performed for concern of an underlying immunodeficiency syndrome. Testing for Fanconi anemia was recommended, but the results were negative. Bone marrow biopsy and positron emission tomography–computed tomography demonstrated involvement of the lymph nodes and spleen. The patient was prescribed chemoimmunotherapy with rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride, which he tolerated well, with improvement in his cutaneous lesions.Lymphomatoid granulomatosis is a rare, progressive, EBV-driven lymphoproliferative disease. The condition may affect multiple organs, including the skin, nervous system, kidneys, and, most commonly, the lungs. It typically presents in middle age, and there is a 2:1 male predilection.1 Because there is an association with immunodeficiency, diagnosis should prompt an investigation for underlying disorders.2,3 Although LG typically presents with fever and a cough, 10% to 15% of patients will initially exhibit cutaneous manifestations only.1,2,4 The appearance is variable and may include skin-colored to violaceous or erythematous macules, papules, nodules, or indurated plaques. The most common presentation involves erythematous papules or nodules that localize mainly to the trunk and extremities.2 If left untreated, the lesions may ulcerate and can become necrotic. Diagnosis is made by pathologic review of biopsy samples, typically from the lung and sometimes from skin samples.4 On histologic examination, LG is characterized by an angiocentric and angionecrotic infiltrate composed of EBV-positive B lymphocytes in a background of T lymphocytes, plasma cells, and histiocytes.2,5 Lesions are classified according to a 3-scale grading system, based on the number of EBV-positive B cells detected per HPF. Proper grading is essential because it carries therapeutic and prognostic implications.1 Grade I disease (<5 EBV-positive lymphocytes per HPF) is more indolent, and many cases resolve spontaneously.1 In contrast, grade III disease (>50 EBV-positive lymphocytes per HPF) requires a therapeutic approach similar to that of diffuse large B-cell lymphoma.1 Standard treatment consists of chemoimmunotherapy, and there is a high rate of relapse.1,6Lymphomatoid granulomatosis creates an interesting yet challenging diagnostic picture. As demonstrated in our case, LG has features similar to those of ENKTL-NT. Both conditions may result in destruction of midline facial structures and, on biopsy, show an angiocentric and angiodestructive lymphoma.3,7 For this reason, immunohistochemical and molecular studies are crucial for proper diagnosis: ENKTL-NT test results are positive for CD3, CD56, and cytotoxic markers and negative for CD20 and PAX-5.2,3 Careful histologic examination can also differentiate LG from granulomatosis with polyangiitis (GPA), a necrotizing vasculitis that also presents with fever and pulmonary nodules. However, on histologic analysis, only GPA demonstrates well-formed granulomas.3 Furthermore, patients with GPA typically test positive for cytoplasmic antineutrophil cytoplasmic antibodies. Infectious conditions, particularly tuberculosis and histoplasmosis, should also be included in the differential diagnosis. Travel history, special stains, and tissue cultures provide accurate distinction from these diagnoses.3 This case highlights the need for a high index of suspicion and meticulous histologic and immunophenotypic examination when considering a diagnosis of LG.

Dermatology

A 33-year-old white man presented with a 5-month history of a progressively necrotic plaque on the nose and scattered nodules on the extremities. The plaque first appeared as a small inflammatory papule on the left nostril. Shortly thereafter, the patient was hospitalized at an outside facility for multifocal pneumonia. He was also treated for a methicillin-resistant Staphylococcus aureus infection of his nose. Despite antibiotic therapy, the papule continued to grow and ulcerate and eventually became necrotic (Figure, A). One month before presentation at our facility, the patient began developing erythematous papules on his arms and legs. The papules enlarged and ulcerated. Some of them healed spontaneously with poxlike scars. He had no recent history of travel. At admission, the patient was tachycardic and febrile to a temperature of 38.5°C. Routine laboratory testing revealed normocytic anemia (hemoglobin, 7.7 g/dL [to convert to grams per liter, multiply by 10]). Shave biopsies of necrotic nodules on the left arm and left cheek (Figure, B-D) and, later, an excisional biopsy of a cervical lymph node were performed. Head computed tomography demonstrated a soft-tissue mass that encased the nasal bone and extended into the right maxillary sinus and left nasal cavity. Chest computed tomography showed bilateral pulmonary nodules. Physical examination revealed a necrotic plaque with surrounding erythema on the distal nose (Figure, A). A 1 × 1-cm crateriform papule with central necrosis was present on the left malar cheek. Multiple nodules with central, dry necrosis and areas of poxlike scarring were scattered across the extremities. Slight contractures of his fingers were also noted.A, Clinical photograph. B-D, Analyses of a shave biopsy specimen of the necrotic papule on the patient’s left cheek (B, hematoxylin-eosin, original magnification ×400; C, original magnification ×400; D, original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Histoplasmosis

Extranodal natural killer/T-cell lymphoma, nasal type

Lymphomatoid granulomatosis

Granulomatosis with polyangiitis (Wegener granulomatosis)

c

male

31-40

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2696618

A man in his 50s of West African descent with a history of prostate cancer treated with robotic prostatectomy 2 years ago presented with 1 year of progressively worsening postprandial nausea or vomiting, epigastric abdominal pain, anorexia, and weight loss of 27 kg. Four months earlier, he had presented to another hospital and received a diagnosis of adhesive small bowel obstruction, for which he underwent laparotomy and lysis of small adhesive bands that provided only temporary symptomatic improvement. At his current presentation, he was unable to tolerate any oral intake and entirely dependent on total parenteral nutrition. On examination, he was cachectic with a moderately distended, nontender abdomen. The result of a blood test (QuantiFERON-TB Gold; Qiagen) was positive for tuberculosis exposure. An abdominal computed tomography scan showed markedly dilated stomach and duodenum with decompressed, thickened distal small bowel without a clear transition point.Nonoperative management with persistently high nasogastric tube output failed, and the patient was subsequently taken to the operating room for exploratory laparotomy. Intraoperative findings are shown in Figure 1.Exploratory laparotomy showing the appearance of the small bowel. What Is Your Diagnosis?

Abdominal tuberculosis

Sclerosing encapsulating peritonitis

Adhesive small bowel obstruction

Peritoneal carcinomatosis

B. Sclerosing encapsulating peritonitis

B

Sclerosing encapsulating peritonitis

During surgery, this patient was found to have a thick fibrous sac encapsulating the small bowel along its entire length, from the ligament of Treitz to the ileocecal junction, consistent with sclerosing encapsulating peritonitis (SEP). Opening of the sac revealed the small bowel to be compressed and kinked longitudinally and transversely, resulting in mechanical obstruction (Figure 2).The dense fibrous capsule was opened longitudinally to reveal the small bowel compressed and kinked within.Also known as abdominal cocoon syndrome, SEP is a rare cause of intestinal obstruction in which part or all of the small bowel, and sometimes the colon, becomes encased and compressed in a fibrous sac.1 The condition can be primary (idiopathic), classically seen in adolescent girls in tropical latitudes,1,2 or secondary, most commonly caused by chronic peritoneal dialysis.1,3 Other known secondary causes include chronic inflammatory or infectious insults such as recurrent peritonitis, intraperitoneal chemotherapy, peritovenous or ventriculoperitoneal shunting, systemic lupus erythematosus, sarcoidosis, abdominal tuberculosis, and parasitic infections.1-4 Clinical presentation usually includes symptoms of progressive chronic or intermittent intestinal obstruction, such as nausea, vomiting, abdominal pain, weight loss, and abdominal mass.1,4,5Sometimes, SEP can be diagnosed on preoperative imaging, but often it is diagnosed only during operative intervention.1 Early cases with partial or intermittent obstruction may respond to nonoperative management, but the mainstay of treatment is the complete operative stripping and resection of the encasing rind. The available literature on SEP is dominated by single case reports, but several single-institution case series exist. These studies involve 18 to 65 patients with long-term recurrent obstruction rates, ranging from 0% to 28% after the full resection of the fibrous encapsulating sheath, and with at least 1 year of follow-up.4-7 The largest of these case series identified preoperative nutritional optimization and intraoperative intestinal stenting to be protective against early recurrent obstruction.4After the diagnosis of idiopathic SEP during the initial operation, the patient underwent the placement of a decompressive gastrostomy tube and then remained in the hospital for parenteral nutritional optimization. Later, he returned to the operating room for stripping and excision of the fibrous capsule from the entire involved bowel as well as lysis of thin adhesions between loops of bowel within the capsule. Despite a positive tuberculosis test result, no evidence of nodules or plaques was found to suggest abdominal tuberculosis, and biopsies did not show any evidence of mycobacterial infection or malignant neoplasm.This patient had a prolonged ileus, which slowly resolved. One month later, he was tolerating a regular diet and his gastrostomy tube was removed. He continues to be asymptomatic more than 2 years after treatment.

Surgery

A man in his 50s of West African descent with a history of prostate cancer treated with robotic prostatectomy 2 years ago presented with 1 year of progressively worsening postprandial nausea or vomiting, epigastric abdominal pain, anorexia, and weight loss of 27 kg. Four months earlier, he had presented to another hospital and received a diagnosis of adhesive small bowel obstruction, for which he underwent laparotomy and lysis of small adhesive bands that provided only temporary symptomatic improvement. At his current presentation, he was unable to tolerate any oral intake and entirely dependent on total parenteral nutrition. On examination, he was cachectic with a moderately distended, nontender abdomen. The result of a blood test (QuantiFERON-TB Gold; Qiagen) was positive for tuberculosis exposure. An abdominal computed tomography scan showed markedly dilated stomach and duodenum with decompressed, thickened distal small bowel without a clear transition point.Nonoperative management with persistently high nasogastric tube output failed, and the patient was subsequently taken to the operating room for exploratory laparotomy. Intraoperative findings are shown in Figure 1.Exploratory laparotomy showing the appearance of the small bowel.

what is your diagnosis?

What is your diagnosis?

Abdominal tuberculosis

Adhesive small bowel obstruction

Sclerosing encapsulating peritonitis

Peritoneal carcinomatosis

c

male

51-60

West African

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2698951

A 74-year-old man presented to the primary care physician with a 3-month history of weight loss, anorexia, and back pain. His medical history was significant for hypertension, hyperlipidemia, and kidney stones. His surgical history was significant for a bilateral staged carotid endarterectomy in 1999 and 2000 and an open repair of a 7.4-cm transverse diameter juxtarenal abdominal aortic aneurysm with a knitted Dacron tube graft (18 mm) in 2014. Ligation of the left renal vein adjacent to the inferior vena cava was performed to gain proximal control of the aorta. The patient underwent extraction of a tooth secondary to an abscess 4 months earlier. Physical examination revealed poor dental hygiene and findings in the lower extremity suggestive of postthrombotic syndrome. The patient was afebrile with a heart rate of 108 beats per minute and a leukocyte level of 11 600/cm (normal range, 4000-11 000/cm), with 84% polymorphic neutrophils (normal, <75%); erythrocyte sedimentation rate was 57 mm/h (normal range, 0-10 mm/h), and C-reactive protein level was 15.9 mg/dL (normal, <0.6 mg/dL [to convert to nmol/L, multiply by 9.524]). Computed tomography (CT) of the abdomen and pelvis was performed (Figure 1A and B).CT indicates computed tomography; WBC, white blood cell. What Is Your Diagnosis?

Carcinoma in the body of the pancreas

Advanced carcinoma of the duodenum

Posterior perforation of a duodenal ulcer

Infected aortic graft with aortoduodenal fistula

D. Infected aortic graft with aortoduodenal fistula

D

Infected aortic graft with aortoduodenal fistula

The CT scan demonstrated postsurgical changes of the abdominal aorta after the patient’s aneurysmal repair, with the presence of mural fluid and a small amount of gas. There was a sacular out-pouching of the abdominal aorta containing gas at the proximal anastomotic site, which appeared to be inseparable from the duodenum and associated fat stranding. An indium ln 111 altumomab pentetate–labeled white blood cell scan (Figure 1C) revealed abnormal uptake at the midline suggestive of an aortic graft infection, with increased uptake inferiorly consistent with a developing abscess. The patient developed bright red rectal bleeding and was emergently taken to the operating room. Proximal aortic control was obtained using a balloon catheter, which was placed near the celiac axis. Laparotomy revealed an inframesenteric mass near the third and fourth part of the duodenum that was adherent to the proximal aortic graft anastomosis. Further dissection revealed the site of perforation in the duodenum with the proximal anastomosis of unincorporated Dacron graft (aortoduodenal fistula). Culture of grayish-white purulent material obtained from around the graft was positive for Streptococcus constellatus. The opening in the duodenum was closed in 2 layers. The proximal aortic stump was closed with a 3-0 polypropylene suture (Ethicon), and an extra-anatomic bypass was performed after closure of the abdomen. The patient died during the postoperative period due to multisystem organ failure.The patient’s clinical presentation was suggestive of carcinoma of the body of the pancreas; however, CT did not reveal a pancreatic mass. Locally advanced carcinoma of the duodenum, which is relatively uncommon, was unlikely given the absence of a duodenal mass on CT imaging.1 Posterior perforation of a duodenal ulcer results in retroperitoneal abscesses but is usually located in the first and second parts of the duodenum.2Primary or secondary aortoduodenal fistula is one of the most challenging vascular pathologies. Primary aortoduodenal fistulas are rare and develop when there is communication between a large abdominal aortic aneurysm and the small bowel.Secondary aortoduodenal fistulas are associated with prior aortic reconstruction, occurring in 0.5% to 1.2% of all aortic reconstructions.3 Patients often present 2 to 4 years after aortic graft reconstruction.4 Manifestations of infection are present in approximately half of the patients and include weight loss, fever, and leukocytosis. Patients often present with a herald bleed followed by massive hemorrhage. After the diagnosis is highly suspected, 2 radically different approaches are selected: (1) sequential extra-anatomic bypass graft followed by excision of the infected aortic graft or (2) aortic graft excision with inline aortic graft replacement with a venous autograft (femoral vein), cryopreserved allograft, or a rifampin-impregnated new prosthetic graft.For an unstable patient, an emergent exploratory laparotomy is performed to gain proximal and distal control to excise the involved aorta. Ligation of the aorta is performed just below the renal arteries, and an omental pedicle is used to buttress the aortic closure. An extra-anatomic bypass (axillofemoral) is performed.

Surgery

A 74-year-old man presented to the primary care physician with a 3-month history of weight loss, anorexia, and back pain. His medical history was significant for hypertension, hyperlipidemia, and kidney stones. His surgical history was significant for a bilateral staged carotid endarterectomy in 1999 and 2000 and an open repair of a 7.4-cm transverse diameter juxtarenal abdominal aortic aneurysm with a knitted Dacron tube graft (18 mm) in 2014. Ligation of the left renal vein adjacent to the inferior vena cava was performed to gain proximal control of the aorta. The patient underwent extraction of a tooth secondary to an abscess 4 months earlier. Physical examination revealed poor dental hygiene and findings in the lower extremity suggestive of postthrombotic syndrome. The patient was afebrile with a heart rate of 108 beats per minute and a leukocyte level of 11 600/cm (normal range, 4000-11 000/cm), with 84% polymorphic neutrophils (normal, <75%); erythrocyte sedimentation rate was 57 mm/h (normal range, 0-10 mm/h), and C-reactive protein level was 15.9 mg/dL (normal, <0.6 mg/dL [to convert to nmol/L, multiply by 9.524]). Computed tomography (CT) of the abdomen and pelvis was performed (Figure 1A and B).CT indicates computed tomography; WBC, white blood cell.

what is your diagnosis?

What is your diagnosis?

Carcinoma in the body of the pancreas

Advanced carcinoma of the duodenum

Posterior perforation of a duodenal ulcer

Infected aortic graft with aortoduodenal fistula

d

male

71-80

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2706482

A 75-year-old woman of white race/ethnicity was referred for bilateral choroidal lesions. She described her vision as being blurred in the left eye, with areas of her vision being “blocked.” Her review of systems was unremarkable. Her medical and ocular histories were significant for pseudophakia of both eyes, obstructive sleep apnea, and hypertension treated with hydrochlorothiazide.On examination, visual acuity was 20/40 OD and 20/64 OS. Intraocular pressure, pupillary reaction, and ocular motility were normal. Confrontation visual fields revealed a deficit in the inferotemporal quadrant of the left eye. External and slitlamp examinations were unremarkable. Dilated fundus examination revealed an epiretinal membrane, as well as extramacular, elevated, hypopigmented, yellow lesions with retinal pigment epithelium changes in both eyes, along with overlying subretinal fluid, subretinal hemorrhage, and exudates in the left eye (Figure, A). Optical coherence tomography showed an epiretinal membrane with cystoid macular edema and drusen in both eyes, along with subretinal fluid extending into the left macula, explaining her decreased vision. B-scan ultrasonography demonstrated hyperechoic, plaquelike, solid lesions with posterior acoustic shadowing corresponding anatomically to the lesions seen on clinical examination (Figure, B). Fluorescein and indocyanine angiography demonstrated leakage in the area of subretinal hemorrhage in the left eye (Figure, C).A, A yellowish lesion is located in the superonasal quadrant with nasal subretinal hemorrhage (asterisk). B, B-scan ultrasonography (transverse at the 11-o’clock equator) reveals a hyperechoic, plaquelike, solid lesion with posterior acoustic shadowing, consistent with calcification corresponding to the clinically visible lesion. C, Superonasal leakage corresponding to the area of clinically visible subretinal hemorrhage.Check parathyroid hormone, vitamin D, and calcium levels What Would You Do Next?

Perform transvitreous biopsy

Begin oral corticosteroid therapy

Check parathyroid hormone, vitamin D, and calcium levels

Treat with plaque brachytherapy

Sclerochoroidal calcifications with secondary choroidal neovascularization

C

Check parathyroid hormone, vitamin D, and calcium levels

The clinical and imaging findings in this patient, including bilateral, extramacular, yellowish lesions with overlying retinal pigment epithelium changes and calcification (as evidenced by acoustic shadowing on B-scan ultrasonography), are consistent with sclerochoroidal calcifications (SCCs). The angiographic findings (Figure, C), subretinal fluid, and subretinal hemorrhage in the left eye are consistent with secondary choroidal neovascularization (CNV). Sclerochoroidal calcifications are deposits of calcium in the sclera, most commonly found in older patients of white race/ethnicity. Lesions may be unilateral or bilateral, unifocal or multifocal, yellow, white, or yellow-orange, and they are most commonly located in the superotemporal or superonasal quadrants near or anterior to the vascular arcades.1,2 The lesions may exhibit overlying choroidal or retinal pigment epithelium atrophy. Patients with SCCs are often referred for evaluation of choroidal nevus, melanoma, lymphoma, metastasis, and osteoma.1Optical coherence tomography will reveal lesions originating in the sclera, with variable topographic contours, overlying choroidal thinning, and abnormalities of the retinal pigment epithelium, ellipsoid zone, and external limiting membrane.2 Fundus autofluorescence imaging may show a mixture of isoautofluorescent, hypoautofluorescent, and hyperautofluorescent zones corresponding to optical coherence tomography findings. Areas with normal choriocapillaris architecture will be isoautofluorescent, areas with decreased choriocapillaris thickness may exhibit hyperautofluorescence, and areas with outpouching of the retinal pigment epithelium–choriocapillaris complex may demonstrate hypoautofluorscence.3Generally, SCCs are benign, asymptomatic, and often discovered incidentally during routine examinations.1,4 Sclerochoroidal calcifications are most commonly idiopathic but have been associated with several systemic calcium disorders, such as primary (eg, parathyroid adenoma), secondary (eg, chronic kidney disease and vitamin D deficiency), or tertiary hyperparathyroidism, as well as hypomagnesemia, diuretic use, Bartter syndrome, and Gitelman syndrome.1,4-8 Therefore, patients should undergo a systemic workup, including laboratory testing for parathyroid hormone, vitamin D, and calcium levels (choice C), as well as levels of calcitonin, phosphate, magnesium, potassium, alkaline phosphatase, and renal function, among others.One potential rare complication of SCCs, as seen in this patient, is CNV, which to our knowledge has previously been reported in only 4 other cases.4,7,9,10 If the exudation from the CNV extends into the macula, as in our patient, it can affect vision. Positive treatment responses of CNV associated with SCCs have been shown with intravitreous anti–vascular endothelial growth factor (VEGF) injections, photodynamic therapy, and argon laser photocoagulation.7,9,10 A biopsy is unnecessary to make the diagnosis (choice A) because the clinical presentation and shadowing on B-scan ultrasonography are typical for SCCs. Oral corticosteroids have not been shown to successfully treat SCCs or CNV (choice B). Plaque brachytherapy is unnecessary because SCCs are not associated with tumors (choice D).This patient was found to have idiopathic SCCs given a negative laboratory workup for renal or calcium metabolic disorders. The right eye has not required treatment. The CNV in her left eye has been treated with intravitreous anti-VEGF therapy, as well as a single posterior subtenon injection of triamcinolone acetonide, in an attempt to reduce the concomitant cystoid macular edema. The patient’s visual acuity has remained stable in both eyes, with reduction in the subretinal fluid and hemorrhage associated with CNV, as well as cystoid macular edema in the left eye, in response to treatment.

Ophthalmology

A 75-year-old woman of white race/ethnicity was referred for bilateral choroidal lesions. She described her vision as being blurred in the left eye, with areas of her vision being “blocked.” Her review of systems was unremarkable. Her medical and ocular histories were significant for pseudophakia of both eyes, obstructive sleep apnea, and hypertension treated with hydrochlorothiazide.On examination, visual acuity was 20/40 OD and 20/64 OS. Intraocular pressure, pupillary reaction, and ocular motility were normal. Confrontation visual fields revealed a deficit in the inferotemporal quadrant of the left eye. External and slitlamp examinations were unremarkable. Dilated fundus examination revealed an epiretinal membrane, as well as extramacular, elevated, hypopigmented, yellow lesions with retinal pigment epithelium changes in both eyes, along with overlying subretinal fluid, subretinal hemorrhage, and exudates in the left eye (Figure, A). Optical coherence tomography showed an epiretinal membrane with cystoid macular edema and drusen in both eyes, along with subretinal fluid extending into the left macula, explaining her decreased vision. B-scan ultrasonography demonstrated hyperechoic, plaquelike, solid lesions with posterior acoustic shadowing corresponding anatomically to the lesions seen on clinical examination (Figure, B). Fluorescein and indocyanine angiography demonstrated leakage in the area of subretinal hemorrhage in the left eye (Figure, C).A, A yellowish lesion is located in the superonasal quadrant with nasal subretinal hemorrhage (asterisk). B, B-scan ultrasonography (transverse at the 11-o’clock equator) reveals a hyperechoic, plaquelike, solid lesion with posterior acoustic shadowing, consistent with calcification corresponding to the clinically visible lesion. C, Superonasal leakage corresponding to the area of clinically visible subretinal hemorrhage.Check parathyroid hormone, vitamin D, and calcium levels

what would you do next?

What would you do next?

Treat with plaque brachytherapy

Begin oral corticosteroid therapy

Perform transvitreous biopsy

Check parathyroid hormone, vitamin D, and calcium levels

d

female

71-80

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2707246

A 60-year-old man presented with a 6-month history of progressive painless visual loss, photophobia, and color vision impairment in both eyes. The symptoms started in the right eye and progressed to the left eye 4 months later. His medical history included hypothyroidism and meningioma of the cervical spine. There was no history of trauma or surgery in the previous year. The patient had been evaluated elsewhere for suspected autoimmune retinopathy, with normal results for serum antibodies against recoverin and enolase, a complete blood cell count, antinuclear antibody, rheumatoid factor, anticitrullinated protein antibody, extractable nuclear antigens, and serologies for syphilis and Lyme disease. A previous neuro-ophthalmologic evaluation, including magnetic resonance imaging of the brain and orbits, had been unrevealing.His best-corrected visual acuity measured 20/400 OD and 20/100 OS. The results of a kinetic perimetry with a Goldmann perimeter demonstrated dense bilateral cecocentral scotomata. There was no afferent pupillary defect in either eye. A fundus examination showed trace temporal optic disc pallor in the right eye and a normal-appearing optic disc in the left eye (Figure 1A). Full-field electroretinography results were normal, but multifocal electroretinography (mfERG) showed reduced wave amplitudes nasal to the fovea in each eye (Figure 1B). Fundus autofluorescence and spectral-domain optical coherence tomography (SD-OCT) scans of the macula and optic nerve showed no abnormalities.A, Fundus photography shows a normal-appearing optic disc of the left eye. B, Multifocal electroretinography demonstrates reduced amplitudes of waveforms nasal to the fovea of the left eye. In the papillomacular region, the amplitudes are reduced by approximately 50% compared with the normal amplitudes in the temporal region.Analyze the thickness of retinal layers by SD-OCT segmentationAsk about antihypertensives taken in the evening, sleep apnea, and cardiovascular risk factors What Would You Do Next?

Analyze the thickness of retinal layers by SD-OCT segmentation

Ask about antihypertensives taken in the evening, sleep apnea, and cardiovascular risk factors

Order mitochondrial genetic testing

Ask about toxic agents and nutritional deficiencies

Leber hereditary optic neuropathy caused by homoplasmic variant in ND6 (m.14484T>C)

C

Order mitochondrial genetic testing

Leber hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by variants in the mitochondrial DNA. Most cases are caused by 1 of 3 variants: m.3460G>A, m.11778G>A, and m.14484T>C.1 Leber hereditary optic neuropathy mostly affects men from age 15 to 35 years.1 The vision loss is secondary to the degeneration of retinal ganglion cells (RGC), particularly of smaller axons in the papillomacular bundle.2 In asymptomatic carriers, peripapillary microangiopathy and the swelling of the retinal nerve fiber layer herald progression to the symptomatic stage, when vision loss occurs.3 The optic disc develops variable degrees of pallor. The segmentation of retinal layers on SD-OCT is helpful in pointing toward a diagnosis of LHON if thinning of the RGC is demonstrated (Figure 2); however, it does not establish the diagnosis.3,4 The thickening of the outer retina has also been described,4 although studies have not demonstrated damage to photoreceptors and the retinal pigment epithelium.5 To our knowledge, it is unknown whether the outer retinal thickening results from the abnormal mitochondrial metabolism in photoreceptors or as an anatomical response to RGC thinning.4Spectral-domain optical coherence tomography segmentation of the left eye demonstrates a thinning of the ganglion cell layer.Although the full-field electroretinography results were normal, the mfERG results may be abnormal. Reduced amplitudes in mfERG responses in first- and second-order kernels have been described, and it is unclear whether these changes reflect cone dysfunction or contributions from the inner retina.6 For patients like this one whose mfERG amplitudes are reduced, the differentiation of LHON from maculopathy is challenging and genetic testing is necessary to confirm the diagnosis. The presence of a variant in the mitochondrial DNA does not always lead to vision loss. The heteroplasmy levels influence the susceptibility to vision loss.1 In this case, mitochondrial gene testing results revealed homoplasmy and confirmed LHON as the cause of the vision loss.Because toxic and nutritional optic neuropathies may have similar presentations, patients should be asked about the use of methanol, ethambutol, linezolid, amiodarone, phosphodiesterase type 5 inhibitors, and alcohol and tobacco and should be tested for deficiencies of vitamin B12, B1, folate, and copper. This patient denied use of these substances and nutritional deficiencies. Nonarteritic anterior ischemic optic neuropathy should also be considered in patients older than 50 years.7 It is painless, may sequentially affect both eyes, and does not cause an afferent pupillary defect when both eyes are affected. Patients should be asked about cardiovascular disease and sleep apnea, risk factors that are associated with nonarteritic anterior ischemic optic neuropathy.7 This patient did not have these risk factors.The key clinical feature in this case is the abnormal mfERG in a neuropathy that is known to affect the RGC. Optic neuropathies and maculopathies may have overlapping presentations, but abnormal mfERG generally excludes optic neuropathies. Leber hereditary optic neuropathy can cause reduced mfERG amplitudes, and mitochondrial genetic testing is necessary to distinguish it from maculopathies. There is spontaneous visual improvement in some patients and gene therapy and drugs, such as idebenone, are being tested as a prevention against progressive visual loss.8 Clinical misdiagnosis of this constellation of signs and symptoms can lead to unwarranted treatments and patient harm.The patient’s visual acuity and other functional and structural test results have remained stable, and he has been periodically followed up.

Ophthalmology

A 60-year-old man presented with a 6-month history of progressive painless visual loss, photophobia, and color vision impairment in both eyes. The symptoms started in the right eye and progressed to the left eye 4 months later. His medical history included hypothyroidism and meningioma of the cervical spine. There was no history of trauma or surgery in the previous year. The patient had been evaluated elsewhere for suspected autoimmune retinopathy, with normal results for serum antibodies against recoverin and enolase, a complete blood cell count, antinuclear antibody, rheumatoid factor, anticitrullinated protein antibody, extractable nuclear antigens, and serologies for syphilis and Lyme disease. A previous neuro-ophthalmologic evaluation, including magnetic resonance imaging of the brain and orbits, had been unrevealing.His best-corrected visual acuity measured 20/400 OD and 20/100 OS. The results of a kinetic perimetry with a Goldmann perimeter demonstrated dense bilateral cecocentral scotomata. There was no afferent pupillary defect in either eye. A fundus examination showed trace temporal optic disc pallor in the right eye and a normal-appearing optic disc in the left eye (Figure 1A). Full-field electroretinography results were normal, but multifocal electroretinography (mfERG) showed reduced wave amplitudes nasal to the fovea in each eye (Figure 1B). Fundus autofluorescence and spectral-domain optical coherence tomography (SD-OCT) scans of the macula and optic nerve showed no abnormalities.A, Fundus photography shows a normal-appearing optic disc of the left eye. B, Multifocal electroretinography demonstrates reduced amplitudes of waveforms nasal to the fovea of the left eye. In the papillomacular region, the amplitudes are reduced by approximately 50% compared with the normal amplitudes in the temporal region.Analyze the thickness of retinal layers by SD-OCT segmentationAsk about antihypertensives taken in the evening, sleep apnea, and cardiovascular risk factors

what would you do next?

What would you do next?

Order mitochondrial genetic testing

Ask about toxic agents and nutritional deficiencies

Analyze the thickness of retinal layers by SD-OCT segmentation

Ask about antihypertensives taken in the evening, sleep apnea, and cardiovascular risk factors

a

male

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2708001

A boy in his late teens with short stature presented with gradual loss of vision in both eyes since 8 years of age. He received a diagnosis of type 1 diabetes at 10 years of age and has been taking insulin since the diagnosis. He had consulted several physicians for hearing loss during the past 2 years. He had received multiple courses of antibiotics for frequent urinary tract infections. The results of a systemic examination revealed hypochondroplasia, alopecia (Figure 1), and generalized hypotonia. His best-corrected visual acuity was 6/60 OU. Bjerrum tangent screen visual field analysis showed preservation of central 10 degrees of fields. His color vision was defective, and his pupils were slow reactive to light. The results of an optic nerve examination revealed bilateral pale optic discs with no evidence of edema and normal retinal vasculature. The results of the examination of the macula were normal in both eyes, with no diabetic retinopathy. A urine specific gravity test was performed, and the urine specific gravity was found to be low (sp g 1.001-1.003), consistent with diabetes insipidus.Physical presentation of the patient, an adolescent boy presenting with hypochondroplasia, alopecia, and short stature.Order a hormone profile (thyrotropin, adrenocorticotrophic hormone, growth hormone, and testosterone) and consult endocrinology What Would You Do Next?

Order magnetic resonance imaging of the brain

Order a hormone profile (thyrotropin, adrenocorticotrophic hormone, growth hormone, and testosterone) and consult endocrinology

Perform a peripheral blood smear examination

Order targeted genetic testing

Wolfram disease (DIDMOAD [diabetes insipidus, diabetes mellitus, optic atrophy, and deafness] syndrome)

B

Order a hormone profile (thyrotropin, adrenocorticotrophic hormone, growth hormone, and testosterone) and consult endocrinology

This is a case of an adolescent boy with bilateral optic atrophy (Figure 2). The differential diagnosis includes hereditary optic neuropathies such as Leber optic neuropathy, autosomal dominant optic atrophy, and Wolfram disease1; compressive tumors; and traumatic and toxic neuropathy. Systemic involvement including bilateral sensorineural deafness, diabetes mellitus, and diabetes insipidus led us to the diagnosis of DIDMOAD syndrome.Fundus image showing optic atrophy: pale disc with well-defined margins and normal retinal vasculature.Wolfram disease is also called DIDMOAD syndrome, an eponym for diabetes insipidus, diabetes mellitus, optic atrophy, and deafness. The initial manifestation is insulin-dependent diabetes mellitus around 6 years of age, followed by optic atrophy at 11 years of age.2 In the second decade, many patients develop diabetes insipidus and sensorineural deafness. Inheritance is autosomal recessive and is due to mutations in the WFS1 gene in the short arm of chromosome 4 that encodes transmembrane proteins in endoplasmic reticulum, thus resulting in a multi-organ system disorder.3Neuroimaging in the setting of primary optic atrophy is to rule out intracranial tumors. Magnetic resonance imaging of the brain (choice A) was not the preferred answer because progressive neurodegeneration manifesting as optic atrophy is common in Wolfram disease. In advanced stages of Wolfram disease, neuroimaging will detect cerebral and cerebellar atrophy, absence of hypophyseal signal, and brain stem atrophy, which causes respiratory failure and early death.4,5 Magnetic resonance imaging of the brain did not reveal a space-occupying lesion or atrophic changes in this patient.Although there is no cure for Wolfram disease, a thorough endocrinology evaluation (choice B) and necessary hormone supplementation will profoundly affect these patients.6 Degeneration of the hypothalamohypophyseal axis results in varying degrees of hormonal imbalances. As polyuria and polydipsia are seen in both diabetes mellitus and diabetes insipidus, the latter was overlooked by other physicians. The patient was much more comfortable after starting oral desmopressin acetate, 0.05 mg twice daily, to treat his diabetes insipidus.Reports suggest that megaloblastic anemia might be part of DIDMOAD syndrome owing to improper thiamine metabolism and that early treatment with thiamine supplementation might play a role in preventing the full-blown expression of the syndrome.7 However, this observation needs further research. Hence, a peripheral blood smear examination (choice C) was not the preferred answer.Although genetic analysis is confirmatory, targeted genetic testing (choice D) was not the preferred answer because DIDMOAD syndrome is a clinical diagnosis. Genetic testing for at-risk relatives and prenatal screening are possible if the disease-causing mutations are known.8This case emphasizes the importance of multidisciplinary care of patients with Wolfram disease. Ophthalmologists are among the first physicians these patients seek, owing to early vision loss. A high index of suspicion will identify the underlying systemic associations.The patient started hormone replacement (oral desmopressin acetate, testosterone, and thyroxine) by the endocrinologist. Aids for low vision were prescribed, including a handheld magnifier and spectacle-mounted telescope. He was advised to return for regular eye examinations to identify any diabetic retinopathy. Interested family members were screened and counselling was provided regarding the progressive nature of the disease, its complications, and reduced life expectancy.

Ophthalmology

A boy in his late teens with short stature presented with gradual loss of vision in both eyes since 8 years of age. He received a diagnosis of type 1 diabetes at 10 years of age and has been taking insulin since the diagnosis. He had consulted several physicians for hearing loss during the past 2 years. He had received multiple courses of antibiotics for frequent urinary tract infections. The results of a systemic examination revealed hypochondroplasia, alopecia (Figure 1), and generalized hypotonia. His best-corrected visual acuity was 6/60 OU. Bjerrum tangent screen visual field analysis showed preservation of central 10 degrees of fields. His color vision was defective, and his pupils were slow reactive to light. The results of an optic nerve examination revealed bilateral pale optic discs with no evidence of edema and normal retinal vasculature. The results of the examination of the macula were normal in both eyes, with no diabetic retinopathy. A urine specific gravity test was performed, and the urine specific gravity was found to be low (sp g 1.001-1.003), consistent with diabetes insipidus.Physical presentation of the patient, an adolescent boy presenting with hypochondroplasia, alopecia, and short stature.Order a hormone profile (thyrotropin, adrenocorticotrophic hormone, growth hormone, and testosterone) and consult endocrinology

what would you do next?

What would you do next?

Order targeted genetic testing

Perform a peripheral blood smear examination

Order a hormone profile (thyrotropin, adrenocorticotrophic hormone, growth hormone, and testosterone) and consult endocrinology

Order magnetic resonance imaging of the brain

c

male

11-20

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2714695

A woman in her 70s and of Korean descent reported difficulty seeing in dimly lit settings for the past 6 years and was referred for evaluation. Her medical history was remarkable for long-standing hypertension, diabetes, and mixed connective tissue disease. On examination, the best-corrected visual acuity was 20/40 OD and 20/25 OS. Slitlamp examination showed prominent nuclear sclerosis and a posterior subcapsular cataract in the right eye and a well-positioned intraocular lens in the left eye. Ophthalmoscopic examination revealed bilateral pigment mottling with extensive peripheral depigmentation of the retinal pigment epithelium, sparing the central fovea bilaterally. Spectral-domain optical coherence tomography showed complete loss of photoreceptors outside the fovea, with retinal pigment epithelial atrophy, irregular proliferation, and some remodeling (Figure, A). Fundus autofluorescence showed a ring of parafoveal hypofluorescence and hyperfluorescence, with speckled hypofluorescence peripherally (Figure, B). Goldmann perimetry of both eyes (Figure, C) revealed significant constriction of the V-4-e isopter with an extensive ring scotoma between approximately 10° and 30° eccentricity. Central vision with the I-4-e isopter was constricted to 5° to 7°. A multifocal electroretinogram (ERG) showed profound signal attenuation throughout the examined area. The full-field electroretinogram was nonrecordable under both scotopic and photopic conditions.A, Spectral-domain optical coherence tomography (SD-OCT) reveals extensive and diffuse retinal thinning (arrowhead) beyond the fovea, with loss of photoreceptors and pigment migration into the retina. B, Fundus autofluorescence of the left eye shows a perimacular ring of hypofluorescence (blue asterisk) and hyperfluorescence (black asterisk) in a bull’s-eye configuration with diffuse scattered granular areas. C, Goldmann visual field of the left eye shows an evolving ring scotoma (asterisk) and a small preserved central island of vision (arrowhead). What Would You Do Next?

Perform genetic testing

Order antiretinal antibodies

Perform systemic evaluation for malignancy

Review medications

Hydroxychloroquine retinopathy

D

Review medications

This patient presented with severely constricted peripheral fields and a flat ERG consistent with an end-stage retinal degenerative process. These findings would clinically be consistent with rod-cone dystrophy (retinitis pigmentosa) or severe autoimmune or cancer-associated retinopathy, and genetic (choice A) and antibody tests (choice B) are not unreasonable; however, the patient’s mixed connective tissue disease should have been a clue. A review of her medications (choice D) revealed that she had been taking hydroxychloroquine at an elevated dose (6 mg/kg daily) for the past 12 years. Advanced hydroxychloroquine retinopathy can mimic the appearance of retinitis pigmentosa, thus potentially explaining the findings.1The patient’s hydroxychloroquine dose is higher than the current guidelines of a maximum dose less than 5.0 mg/kg real weight, and 12 years of usage puts her at significant risk for toxicities.2 In addition, individuals of Asian ancestry often show initial signs of retinopathy outside the central macula. Therefore, if screening had focused only on the parafoveal region, it might have missed peripheral changes, leading to relatively severe disease by the time of eventual discovery.3,4In this case, the patient’s visual problems were initially ascribed to cataracts. While she did have visually significant cataracts contributing to her decreased acuity, a more comprehensive evaluation at this juncture would have revealed the concurrent retinal findings. As her visual symptoms and difficulties persisted following cataract extraction in the left eye, alternative causes were sought and she was subsequently referred for further evaluation that revealed underlying severe retinal degenerative changes. This chronology emphasizes the critical importance of annual screening for patients treated with hydroxychloroquine, especially in susceptible older patients for whom cataracts may merely be a contributing factor to their visual loss.Genetic testing (choice A) was not pursued because the patient had no family history of retinal degenerative disease. In addition, genetic testing may not have been an optimal choice given that the patient had reported poor night vision only in the past 6 years compared with the majority of her life as is typically reported in long-standing heredodegeneration. The recent development of severe retinal degeneration during her 70s is more compatible with a diagnosis of advanced hydroxychloroquine retinopathy.Identification of the presence of antiretinal antibodies (choice B) was not requested because visual loss in cancer-associated or nonspecific autoimmune retinopathy is usually fairly rapid and progressive and, with the exception of antirecoverin disease, much milder and cone dominated. Cancer-associated retinopathy due to antirecoverin is associated with the presence of malignancy (which may be subclinical) and with circulating autoantibodies, but the fundus changes are often unimpressive in early stages because of the rapid course. While the age of the patient and the pattern of visual loss in this case could be consistent with cancer-associated retinopathy, there was no history of cancer and the degenerative changes had a pattern consistent with hydroxychloroquine retinopathy, suggesting that systemic evaluation for malignancy (choice C) would not be recommended.Hydroxychloroquine treatment was discontinued. Unfortunately, no vision improvement has been noted during 2 years of follow-up. With severe disease, progression may continue for several years5 and threaten foveal vision over time despite discontinuation of therapy.

Ophthalmology

A woman in her 70s and of Korean descent reported difficulty seeing in dimly lit settings for the past 6 years and was referred for evaluation. Her medical history was remarkable for long-standing hypertension, diabetes, and mixed connective tissue disease. On examination, the best-corrected visual acuity was 20/40 OD and 20/25 OS. Slitlamp examination showed prominent nuclear sclerosis and a posterior subcapsular cataract in the right eye and a well-positioned intraocular lens in the left eye. Ophthalmoscopic examination revealed bilateral pigment mottling with extensive peripheral depigmentation of the retinal pigment epithelium, sparing the central fovea bilaterally. Spectral-domain optical coherence tomography showed complete loss of photoreceptors outside the fovea, with retinal pigment epithelial atrophy, irregular proliferation, and some remodeling (Figure, A). Fundus autofluorescence showed a ring of parafoveal hypofluorescence and hyperfluorescence, with speckled hypofluorescence peripherally (Figure, B). Goldmann perimetry of both eyes (Figure, C) revealed significant constriction of the V-4-e isopter with an extensive ring scotoma between approximately 10° and 30° eccentricity. Central vision with the I-4-e isopter was constricted to 5° to 7°. A multifocal electroretinogram (ERG) showed profound signal attenuation throughout the examined area. The full-field electroretinogram was nonrecordable under both scotopic and photopic conditions.A, Spectral-domain optical coherence tomography (SD-OCT) reveals extensive and diffuse retinal thinning (arrowhead) beyond the fovea, with loss of photoreceptors and pigment migration into the retina. B, Fundus autofluorescence of the left eye shows a perimacular ring of hypofluorescence (blue asterisk) and hyperfluorescence (black asterisk) in a bull’s-eye configuration with diffuse scattered granular areas. C, Goldmann visual field of the left eye shows an evolving ring scotoma (asterisk) and a small preserved central island of vision (arrowhead).

what would you do next?

What would you do next?

Perform systemic evaluation for malignancy

Perform genetic testing

Order antiretinal antibodies

Review medications

d

female

71-80

Black

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2712695

A right-handed man in his 50s with a medical history of hypertension was referred for optic disc edema in the right eye and double vision. He was initially seen locally for new-onset double vision in upgaze without other visual symptoms. The patient had a 3–prism diopter left hypertropia in upgaze with full motility and was incidentally found to have optic disc edema in the right eye. His best-corrected visual acuity was 20/15 OU. Automated visual fields were normal, and there was no relative afferent pupillary defect. Magnetic resonance imaging (MRI) revealed no apparent abnormalities (Figure 1A). During the subsequent 6 months, the patient experienced graying of vision on rightward gaze. Results of an evaluation again demonstrated normal visual acuity and visual fields. Results of a local workup were negative, including acetylcholine receptor antibody. The patient presented to our clinic 2 years after initial symptom onset with continued graying of vision on eccentric gaze. His best-corrected visual acuity on examination was 20/25 OD and 20/20 OS. Relative afferent pupillary defect was noted in the right eye. There was prominent chronic-appearing optic disc edema in the right eye without abnormalities in the left eye (Figure 1B). Results of visual field testing showed superior greater than inferior peripheral field loss in the right eye and normal visual field in the left eye.A, T1-weighted magnetic resonance imaging scan of the orbit with contrast reveals trace enhancement at the orbital apex 2 years prior to presentation (arrowhead). B, Fundus photograph of the right eye demonstrates prominent chronic-appearing optic disc edema. What Would You Do Next?

Risk factor modification

Perform a lumbar puncture

Another MRI scan of the orbit

Initiate corticosteroids

Optic nerve sheath meningioma

C

Another MRI scan of the orbit

The initial presentation of unilateral optic disc edema with intact vision raises an interesting differential diagnosis, including incipient nonarteritic anterior ischemic optic neuropathy (NAION), unilateral papilledema, compressive optic neuropathy, and optic perineuritis. Risk factor modification (choice A) would not be correct because it is the next step in the management of NAION, for which hypertension, hyperlipidemia, diabetes, and obstructive sleep apnea are commonly found modifiable vascular risk factors.1 Visual acuity can be normal in the setting of disc edema in incipient NAION; however, the duration of optic swelling would have been shorter, and NAION would not have caused gaze-evoked amaurosis.1,2 Nonarteritic anterior ischemic optic neuropathy most commonly causes an inferior altitudinal defect, whereas our patient had peripheral field loss in the right eye. A lumbar puncture (choice B) is not the next step, but it would be used to obtain the opening pressure to diagnose papilledema, which can also cause visually asymptomatic disc edema. However, papilledema causes transient visual obscurations and not gaze-evoked amaurosis.The prominent gaze-evoked amaurosis suggested an orbital mass as the cause of the disc edema. When the patient developed a slowly progressive optic neuropathy, the diagnosis of an orbital lesion was almost a certainty.3 In retrospect, the lesion was just barely appreciable on the MRI performed at initial presentation (Figure 1A). Optic nerve sheath meningioma (ONSM) is the most likely possible cause underlying progressively worsening vision loss and gaze-evoked amaurosis. Although the initial MRI scan did not show an obvious lesion 2 years ago, imaging often can miss ONSM, which can present subtly early in its development; repeat imaging is warranted here.Another MRI scan of the orbit (choice C) revealed thin circumferential enhancement around the right optic nerve in the optic canal and extending into the posterior right orbit and along the intracranial right optic nerve (Figure 2). Given the clinical course of slowly progressive worsening vision during a 2-year period, the circumferential enhancing lesion was determined to be an ONSM. Management is based on tumor size and the extent of vision loss. Treatment is radiotherapy to preserve vision loss and prevent progression.A T1-weighted magnetic resonance imaging scan of the orbit with contrast at presentation reveals thin circumferential enhancement of the right optic nerve sheath in the optic canal that extends into the posterior right orbit and along the intracranial right optic nerve (arrows), which is more obvious than in the scan performed 2 years prior to presentation.Corticosteroids (choice D) would not be the next step. Corticosteroids treat optic perineuritis, which may radiographically simulate ONSM, but patients present with subacute monocular visual loss and would have pain with eye movements and not gaze-evoked amaurosis.4,5 This case highlights the importance of recognizing gaze-evoked amaurosis as a sign of an orbital compressive lesion.The patient elected observation because his vision was mostly intact. Four months later, he developed significant worsening vision in the right eye with only temporal vision remaining. Visual acuity was 5/200 OD, and color vision was 0/13 OD. The disc appearance was unchanged.The patient underwent a 6-week course of radiotherapy with 28 fractions for a total dose of 50.40 Gy to the ONSM.6 One year after initial consultation in our clinic and 6 months after radiotherapy, his best-corrected visual acuity improved to 20/200 OD. The optic disc edema resolved, leaving 3+ generalized pallor. Another MRI scan of the orbit was stable.

Ophthalmology

A right-handed man in his 50s with a medical history of hypertension was referred for optic disc edema in the right eye and double vision. He was initially seen locally for new-onset double vision in upgaze without other visual symptoms. The patient had a 3–prism diopter left hypertropia in upgaze with full motility and was incidentally found to have optic disc edema in the right eye. His best-corrected visual acuity was 20/15 OU. Automated visual fields were normal, and there was no relative afferent pupillary defect. Magnetic resonance imaging (MRI) revealed no apparent abnormalities (Figure 1A). During the subsequent 6 months, the patient experienced graying of vision on rightward gaze. Results of an evaluation again demonstrated normal visual acuity and visual fields. Results of a local workup were negative, including acetylcholine receptor antibody. The patient presented to our clinic 2 years after initial symptom onset with continued graying of vision on eccentric gaze. His best-corrected visual acuity on examination was 20/25 OD and 20/20 OS. Relative afferent pupillary defect was noted in the right eye. There was prominent chronic-appearing optic disc edema in the right eye without abnormalities in the left eye (Figure 1B). Results of visual field testing showed superior greater than inferior peripheral field loss in the right eye and normal visual field in the left eye.A, T1-weighted magnetic resonance imaging scan of the orbit with contrast reveals trace enhancement at the orbital apex 2 years prior to presentation (arrowhead). B, Fundus photograph of the right eye demonstrates prominent chronic-appearing optic disc edema.

what would you do next?

What would you do next?

Perform a lumbar puncture

Risk factor modification

Another MRI scan of the orbit

Initiate corticosteroids

c

male

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2712994

A man in his mid-50s presented with painless blurry vision in the left eye. According to the patient’s report, he had experienced this vision abnormality in the left eye for 1 week. At presentation, visual acuity was 20/20 OD and 20/400 OS. Results of a dilated fundus examination were normal in the right eye and notable for a macular serous retinal detachment in the left eye (Figure 1A). Findings on optical coherence tomography (OCT) showed a dome-shaped collection of subretinal fluid in the macula (not shown). Late-phase fluorescein angiography revealed multifocal pinpoint areas of hyperfluorescence with mild leakage within the area of detachment (Figure 1B).Left eye. A, A color fundus photograph shows serous macular detachment. B, Late-phase fluorescein angiography shows multifocal pinpoint areas of hyperfluorescence with mild leakage.The patient was given a diagnosis of central serous chorioretinopathy (CSR) in the left eye. After 3 weeks of observation, visual acuity in the patient’s left eye improved to 20/40. Examination and OCT showed resolution of subretinal fluid. Two weeks later, he experienced acute worsening of visual acuity to 20/200 OU. Examination and OCT findings showed subretinal fluid in the macula bilaterally. Late-phase fluorescein angiography again revealed multifocal pinpoint areas of hyperfluorescence with mild leakage. No inflammatory cells were seen in either eye.Order tests for syphilis, tuberculosis, and sarcoidosis; if results are negative, start treatment with oral corticosteroidsOrder magnetic resonance imaging of the brain and orbitsObserve the patient; offer photodynamic therapy if the subretinal fluid persists for 3 months What Would You Do Next?

Order tests for syphilis, tuberculosis, and sarcoidosis; if results are negative, start treatment with oral corticosteroids

Order a complete blood cell count

Order magnetic resonance imaging of the brain and orbits

Observe the patient; offer photodynamic therapy if the subretinal fluid persists for 3 months

Acute myeloid leukemia

B

Order a complete blood cell count

The patient started treatment with oral prednisone, 60 mg/d. Test results for syphilis, tuberculosis, and sarcoidosis were negative. One week later, the patient presented with fatigue and shortness of breath. A complete blood cell count revealed a white blood cell count of 90 000 cells/μL (reference range, 4500-10 000 cells/μL) (to convert to ×109 per liter, multiply by 0.001). A bone marrow biopsy specimen showed immature myeloid cells, which prompted a diagnosis of acute myeloid leukemia (AML).Ocular involvement in AML is common, occurring in 73% to 89% of eyes according to a postmortem study.1 Involvement of the retina is found more frequently than other ocular tissues. Typical manifestations of ocular involvement include retinal hemorrhages and dilation as well as tortuosity of the venules.2A small number of cases in the literature have described serous retinal detachments alone as the initial manifestation of AML.3-7 The mechanism is unknown but may be related to choroidal infiltration, with subsequent ischemia and dysfunction of the retinal pigment epithelium.5 While such a presentation is seemingly rare, it is increasingly recognized as a possible manifestation of AML. Furthermore, a recent study found AML to be the most common primary medical diagnosis for which inpatient ophthalmology consultations are requested, stressing the importance of familiarity with the possible ocular manifestations of the disease.8 A complete blood cell count should thus be considered in cases of serous retinal detachments of unclear etiology.Obtaining tests for syphilis, tuberculosis, and sarcoidosis (choice A) is prudent in a patient with unexplained retinal findings; however, oral corticosteroid therapy should not be started prior to obtaining a complete blood cell count to consider acute leukemia as the underlying diagnosis. In this patient’s case, treatment with oral corticosteroids should not have been initiated. Magnetic resonance imaging (choice C) is not necessary at this time without evidence of optic neuropathy or central nervous system dysfunction. Photodynamic therapy is a reasonable treatment for persistent CSR (choice D) but not for serous retinal detachments due to leukemia.The patient’s fundus findings were initially misattributed to CSR and then to Vogt-Koyanagi-Harada–like inflammatory disease once the disease worsened. This misattribution led to the initiation of corticosteroid therapy. The presence of multifocal pinpoint areas of leakage on fluorescein angiography, however, is atypical of CSR. While this pattern may occur in patients with Vogt-Koyanagi-Harada disease, the absence of intraocular inflammation is atypical. Posterior scleritis can also present with serous retinal detachments; however, ultrasonography was not requested because there was no pain in either eye and posterior scleritis was not suspected.The patient began chemotherapy shortly after receiving a diagnosis of AML. Six weeks later, the patient reported marked vision improvement. Visual acuity was 20/20 OD and 20/25 OS. Examination and OCT findings revealed resolution of the serous retinal detachments. Fundus autofluorescence showed irregular and increased hyperautofluorescence likely due to reactive retinal pigment epithelial changes as well as a “gutter” showing where the subretinal fluid tracked inferiorly owing to gravity (Figure 2). Because results of the clinical examination and OCT had normalized by this time, fundus autofluorescence imaging was helpful for appreciating the extent of previous serous detachments.Fundus autofluorescence of the left eye shows irregular and increased hyperautofluorescence likely due to reactive retinal pigment epithelial changes as well as a “gutter” (arrowhead) where the subretinal fluid tracked inferiorly owing to gravity.

Ophthalmology

A man in his mid-50s presented with painless blurry vision in the left eye. According to the patient’s report, he had experienced this vision abnormality in the left eye for 1 week. At presentation, visual acuity was 20/20 OD and 20/400 OS. Results of a dilated fundus examination were normal in the right eye and notable for a macular serous retinal detachment in the left eye (Figure 1A). Findings on optical coherence tomography (OCT) showed a dome-shaped collection of subretinal fluid in the macula (not shown). Late-phase fluorescein angiography revealed multifocal pinpoint areas of hyperfluorescence with mild leakage within the area of detachment (Figure 1B).Left eye. A, A color fundus photograph shows serous macular detachment. B, Late-phase fluorescein angiography shows multifocal pinpoint areas of hyperfluorescence with mild leakage.The patient was given a diagnosis of central serous chorioretinopathy (CSR) in the left eye. After 3 weeks of observation, visual acuity in the patient’s left eye improved to 20/40. Examination and OCT showed resolution of subretinal fluid. Two weeks later, he experienced acute worsening of visual acuity to 20/200 OU. Examination and OCT findings showed subretinal fluid in the macula bilaterally. Late-phase fluorescein angiography again revealed multifocal pinpoint areas of hyperfluorescence with mild leakage. No inflammatory cells were seen in either eye.Order tests for syphilis, tuberculosis, and sarcoidosis; if results are negative, start treatment with oral corticosteroidsOrder magnetic resonance imaging of the brain and orbitsObserve the patient; offer photodynamic therapy if the subretinal fluid persists for 3 months

what would you do next?

What would you do next?

Order magnetic resonance imaging of the brain and orbits

Order a complete blood cell count

Observe the patient; offer photodynamic therapy if the subretinal fluid persists for 3 months

Order tests for syphilis, tuberculosis, and sarcoidosis; if results are negative, start treatment with oral corticosteroids

b

male

51-60

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2701716

A 67-year-old man presented with a rapidly enlarging scalp lesion (Figure 1A) first noticed 3 months earlier as a pimple. The lesion was itchy but without generalized pruritus. The patient reported a weight loss of 10 pounds over the preceding 3 months. In addition, he reported a longer history of vague, nonspecific, intermittent abdominal pain without nausea, vomiting, or fever starting about 3 years prior to presentation. Previous work-up had revealed minimal abdominal adenopathy, but the patient declined further workup. On examination, he had no other cutaneous lesions, but he did have cervical lymphadenopathy. All other physical findings were within normal limits. Laboratory findings were unremarkable, save for a mild normochromic normocytic anemia and a mildly elevated levels of lactate dehydrogenase. A biopsy specimen from the skin lesion is shown in Figure 1B.A, Clinical image of the patient at presentation. B, Biopsy specimen from the skin lesion is shown. What Is Your Diagnosis?

Mycosis fungoides

Follicular lymphoma

Lichen planus

Marginal zone lymphoma

B. Follicular lymphoma

B

Follicular lymphoma

Scalp lesion, lymph node, and bone marrow biopsy demonstrated involvement by CD10-positive, low-grade B-cell non-Hodgkin lymphoma (NHL), consistent with follicular lymphoma. A positron emission tomography (PET) scan revealed extensive hypermetabolic activity in the scalp soft tissue (standardized uptake value [SUV], 7.0) (Figure 2) and in the cervical (SUV, 9.1), axillary, upper thoracic, and abdominal lymph nodes (SUV, 3.9) compatible with lymphoma with a FLIPI score (Follicular Lymphoma International Prognostic Index) of 5. The patient underwent 6 cycles of R-CHOP chemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) and achieved a complete response verified by PET scan after cycle 4.Positron emission tomography reveals extensive hypermetabolic activity in the scalp soft tissue.Follicular lymphoma is one of the most common subtypes of NHL and is the most common of the clinically indolent NHLs. In the United States, follicular lymphoma accounts for approximately 35% of NHLs, the majority of which present with diffuse lymphadenopathy. In the present case, the patient had clear evidence of systemic disease, but the skin involvement was the most prominent presenting feature. Skin involvement is uncommon in follicular lymphoma, reported in fewer than 5% of the patients.Histopathologic examination of the skin lesion exhibited a predominant follicular pattern of small B cells that tested positive for CD20, CD10, Bcl2, and Bcl6 and negative for CD3, CD5, TdT, cyclin D1, and CD21, consistent with follicular lymphoma. The proportion of centroblasts was fewer than 15 per high-power field, and there were no morphologic areas of transformation to large B-cell lymphoma. However, the lymphoma exhibited some atypical features, demonstrating lymphoid cells with blastoid cytomorphologic characteristics rather than classic centrocytes. In addition, there were focal areas of increased mitotic activity. While overall Ki-67 nuclear proliferation rate was not substantially elevated, in some foci it was as high as 40%. Follicular lymphoma with blastoid features, or a “blastoid variant” of follicular lymphoma, is not a defined category owing to a lack of a reproducible definition of blastoid features in the literature.1-4At first glance the scalp lesion in the present case is suggestive of cutaneous T-cell lymphoma, especially mycosis fungoides. However, the predominant presence of monoclonal B cells in the scalp biopsy (Figure 1B), the lack of epidermotropism and Pautrier microabscesses, and the absence of immunophenotypic evidence of a T-cell neoplasm argue against this diagnosis.The location and size of the lesion would also be atypical for lichen planus, which, in addition, is an unlikely cause of diffuse lymphadenopathy. On histopathologic analysis, lichen planus usually demonstrates a bandlike infiltrate at the dermal-epidermal interface with extension of lymphocytes into basal and parabasal keratinocytes. The epidermis may demonstrate prominent acanthosis and hyperkeratosis.Marginal zone lymphoma B cells do not exhibit a germinal center profile, and they test negative for CD10 and Bcl6. They also characteristically exhibit small lymphoid cells with abundant pale cytoplasm and irregular nuclei with mature chromatin, thus showing “monocytoid appearance” of the lymphoid cells. In addition to this, the presence of centrocytes and centroblasts in the present case argue against a diagnosis of marginal zone B-cell lymphoma.

Oncology

A 67-year-old man presented with a rapidly enlarging scalp lesion (Figure 1A) first noticed 3 months earlier as a pimple. The lesion was itchy but without generalized pruritus. The patient reported a weight loss of 10 pounds over the preceding 3 months. In addition, he reported a longer history of vague, nonspecific, intermittent abdominal pain without nausea, vomiting, or fever starting about 3 years prior to presentation. Previous work-up had revealed minimal abdominal adenopathy, but the patient declined further workup. On examination, he had no other cutaneous lesions, but he did have cervical lymphadenopathy. All other physical findings were within normal limits. Laboratory findings were unremarkable, save for a mild normochromic normocytic anemia and a mildly elevated levels of lactate dehydrogenase. A biopsy specimen from the skin lesion is shown in Figure 1B.A, Clinical image of the patient at presentation. B, Biopsy specimen from the skin lesion is shown.

what is your diagnosis?

What is your diagnosis?

Lichen planus

Follicular lymphoma

Marginal zone lymphoma

Mycosis fungoides

b

male

61-70

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2701747

A 71-year-old man presented with a 3-hour history of central chest pain associated with breathlessness. His medical history was significant for remote percutaneous coronary intervention 19 years ago, with no available details at the time of the patient’s presentation. On arrival, the patient was hemodynamically unstable, with a blood pressure of 85/55 mm Hg. He was tachycardiac, with a heart rate of 105 beats per minute, and his oxygen saturation level was 91% on room air. The patient was afebrile. Physical examination showed no jugular vein distension or peripheral edema, the presence of bibasilar rales, and no cardiac murmurs. A 12-lead electrocardiogram showed inferior ST-segment elevation in leads II, III, and aVF. The patient was transferred urgently to the cardiac catheter laboratory. Coronary angiography was undertaken via the right radial artery, and both left and right coronary arteries were selectively engaged (Figure 1 and Videos 1 and 2).Selective left (A) and right (B) coronary angiography.Perform coronary intervention with stenting of the left anterior descending arteryDetermine severity of the left anterior descending artery plaque by measuring fractional flow reservePursue the culprit coronary artery as yet not identified What Would You Do Next?

Perform coronary intervention with stenting of the left anterior descending artery

Determine severity of the left anterior descending artery plaque by measuring fractional flow reserve

Pursue the culprit coronary artery as yet not identified

Order urgent computed tomography angiography

Occluded anomalous origin of the left circumflex coronary artery

C

Pursue the culprit coronary artery as yet not identified

C. Pursue the culprit coronary artery as yet not identifiedThe key feature in this clinical case is that the full coronary tree was not well defined on selective coronary angiography. While severe in-stent restenosis was identified in the left anterior descending artery, this did not reflect the current pattern of injury on electrocardiogram, suggesting ischemia of the inferior left ventricle.Coronary artery anomalies are rare findings, with an incidence of 1.0% to 1.5% of all coronary angiograms, although studies using computed tomography angiography reported higher incidence.1,2 Based on their clinical and hemodynamic consequences, congenital abnormalities are divided into benign and malignant anomalies reflecting their risk of sudden cardiac death.1 Further classification relies on the anatomical variations of coronary anomalies and is proposed based on the origin, route, and coronary termination.1,3Anomalous origin of right coronary artery from the left coronary sinus and the origin of left circumflex artery from the right coronary sinus are the most common coronary anomalies.1 Nonetheless, a few patients present with atherosclerotic-related disease, and they may be asymptomatic.4,5 In a study of more than 126 000 individuals,5 anomalous origin of a coronary artery was identified in less than 1%, and none of these patients presented with an acute coronary syndrome. Anomalous coronary arteries may trigger intermittent ischemia to which the mechanism is complex and not fully understood.1 Acute angles and anatomical adjacencies related to the aorta and pulmonary trunk are the most plausible explanations, and obstructive atheromatous plaque is considered very unlikely.1 More importantly, it is rare for an anomalous coronary artery to present as the culprit artery in the setting of ST-segment elevation myocardial infarction. Failure to recognize the culprit artery or to suboptimally achieve flow has previously been reported, highlighting the technical challenges in recognizing and treating this condition.5-7 In this case, the anomalous left circumflex artery was occluded at the ostium, making the diagnosis and treatment even more challenging and mandating a stepwise approach to tackle this presentation in an emergent setting.A flush occlusion of an anatomically correct left circumflex artery was excluded by intravascular ultrasonography and separate origin from the left coronary sinus by nonselective angiography. Contrast injection of the right coronary sinus showed abnormal contrast hangup, indicating a flush occlusion of an anomalous origin of the left circumflex artery from the right sinus. Flow was reestablished using balloon angioplasty, and the artery was then stented with 2 overlapping drug eluting stents (Figure 2 and Video 3), with restoration of normal flow. The patient made an uneventful recovery and was discharged from the hospital to be followed up by the cardiac rehabilitation team.Restoration of flow of the occluded anomalous left circumflex coronary artery.

Cardiology

A 71-year-old man presented with a 3-hour history of central chest pain associated with breathlessness. His medical history was significant for remote percutaneous coronary intervention 19 years ago, with no available details at the time of the patient’s presentation. On arrival, the patient was hemodynamically unstable, with a blood pressure of 85/55 mm Hg. He was tachycardiac, with a heart rate of 105 beats per minute, and his oxygen saturation level was 91% on room air. The patient was afebrile. Physical examination showed no jugular vein distension or peripheral edema, the presence of bibasilar rales, and no cardiac murmurs. A 12-lead electrocardiogram showed inferior ST-segment elevation in leads II, III, and aVF. The patient was transferred urgently to the cardiac catheter laboratory. Coronary angiography was undertaken via the right radial artery, and both left and right coronary arteries were selectively engaged (Figure 1 and Videos 1 and 2).Selective left (A) and right (B) coronary angiography.Perform coronary intervention with stenting of the left anterior descending arteryDetermine severity of the left anterior descending artery plaque by measuring fractional flow reservePursue the culprit coronary artery as yet not identified

what would you do next?

What would you do next?

Determine severity of the left anterior descending artery plaque by measuring fractional flow reserve

Pursue the culprit coronary artery as yet not identified

Order urgent computed tomography angiography

Perform coronary intervention with stenting of the left anterior descending artery

b

male

71-80

original

https://jamanetwork.com/journals/jama/fullarticle/2719033

A 55-year-old man with no significant medical history presented with several weeks of malaise and a 6.8-kg weight loss associated with poor appetite. He reported no fevers, night sweats, abdominal pain, emesis, and diarrhea. Physical examination revealed a thin habitus; no palmar erythema, spider angiomas, or gynecomastia were observed. Laboratory tests showed normal complete blood cell count and chemistry panel findings. Hepatic panel showed an elevated alkaline phosphatase level (209 U/L; upper limit of normal [ULN], 150 U/L [3.49 μkat/L; ULN, 2.5 μkat/L]), normal total bilirubin level (0.4 mg/dL [6.84 μmol/L]), elevated alanine aminotransferase level (41 U/L; ULN, 35 U/L [0.68 μkat/L; ULN, 0.58 μkat/L]), and normal aspartate aminotransferase level (27 U/L [0.45 μkat/L]). A single-phase computed tomography (CT) scan of the abdomen revealed multiple hypoattenuating masses with rim enhancement throughout the liver, intussusception of the small bowel, and normal liver contour with no signs of portal hypertension (Figure 1, left). α-Fetoprotein (AFP) level was elevated (1252 ng/mL; ULN, 9 ng/mL); levels of carbohydrate antigen 19-9 (<2 U/mL) and carcinoembryonic antigen (2.8 ng/mL) were normal. A triple-phase CT scan was obtained to further evaluate the small bowel, which revealed no small bowel abnormalities but instead demonstrated a 3.3 × 2.8-cm heterogeneously enhancing pancreatic tail mass not seen on the previous single-phase CT (Figure 1, right).Left, Axial view from single-phase computed tomography (CT) scan of the abdomen revealing bilobar liver masses. Right, Coronal view from venous phase of triple-phase CT scan revealing a pancreatic tail mass (arrowhead) in addition to the bilobar liver masses.Begin FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) chemotherapyPerform a fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET) scanPerform an endoscopic ultrasound of the pancreas with fine-needle aspiration What Would You Do Next?

Begin FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) chemotherapy

Begin sorafenib

Perform a fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET) scan

Perform an endoscopic ultrasound of the pancreas with fine-needle aspiration

Pancreatic neuroendocrine tumor

D

Perform an endoscopic ultrasound of the pancreas with fine-needle aspiration

The key to the correct diagnosis is recognizing that the presence of multifocal liver masses in the background of normal liver parenchyma is unlikely to represent hepatocellular carcinoma (HCC), despite the significant elevation in serum AFP level,1 which was misleading in this case. Given the pancreatic tail mass subsequently discovered, a primary pancreatic malignancy metastasizing to the liver was the likely diagnosis. Thus, endoscopic ultrasound with fine-needle aspiration of the pancreatic mass would be the appropriate next step.2 FOLFIRINOX would be indicated for metastatic pancreatic adenocarcinoma and sorafenib would be indicated for unresectable or metastatic HCC, but a histologic diagnosis should be obtained before starting either of these agents. An 18F-FDG PET scan would not be useful in identifying the histologic type of mass.Pancreatic neuroendocrine tumors (PNETs) account for only 1% to 3% of all pancreatic neoplasms. Functional PNETs can secrete a variety of peptide hormones, including gastrin, insulin, glucagon, somatostatin, and vasoactive intestinal peptide, that should be measured if there is concern for an associated clinical syndrome, such as refractory peptic ulcer disease, episodic hypoglycemia, necrolytic migratory erythema and diabetes mellitus, or persistent diarrhea.3 The majority of PNETs are nonfunctioning but still produce measurable levels of substances, including chromogranin A (which diagnostically has a high sensitivity but poor specificity) and AFP, as with this patient.4 The absence of readily identifiable hormonal syndromes means that patients often present with metastatic disease.5The production of AFP by HCC is a widely recognized association.6 In fact, an AFP level of 200 ng/mL is considered diagnostic for HCC with appropriate imaging.1 However, this threshold only applies to patients with chronic liver disease. Failure to recognize this distinction can lead to premature diagnostic closure favoring HCC in a patient without cirrhosis. As evidenced by this case, a significant increase in AFP level in the absence of cirrhosis should prompt consideration of other sources. In this patient, cytology from endoscopic ultrasound with fine-needle aspiration revealed tumor cells positive for chromogranin and synaptophysin with less than 3% positive for Ki67, consistent with a well-differentiated neuroendocrine tumor (Figure 2). The AFP immunostain was also positive, demonstrating the ability of the tumor to generate AFP.Hypercellular Papanicolaou stain composed of loosely cohesive, monotonous cells with stippled ("salt and pepper") chromatin (original magnification ×200).The challenge of diagnosing PNETs can often be overcome with triple-phase CT imaging, which diagnostically outperforms single-phase imaging (sensitivity, 63%-94.4% vs 28.6%, respectively).7,8 Furthermore, a gallium Ga 68 DOTATATE (68Ga-DOTATATE) PET/CT scan, which uses a positron-emitter somatostatin analogue that binds to the large number of somatostatin receptors seen on PNETs, is diagnostically superior to an 18F-FDG PET scan in localizing well-differentiated neuroendocrine tumors that have low metabolic rates (sensitivity, 82% vs 66%, respectively).9 These somatostatin receptors are also the main therapeutic target of metastatic PNETs. Somatostatin analogues (eg, octreotide) are considered first-line therapy. Radiolabeled somatostatin analogues (eg, lutetium Lu 177 DOTATATE) can be used when there is disease progression with use of somatostatin analogues.10 Surgical resection can also be considered for localized hepatic metastases, but the recurrence rate is high.A subsequent 68Ga-DOTATATE PET scan confirmed tumor burden in both the pancreas and liver. Because of the clinical absence of a hormonal syndrome, hormone levels were not checked. He was subsequently started on lanreotide (120-mg monthly depot injection) without disease progression on imaging 6 months later.

General

A 55-year-old man with no significant medical history presented with several weeks of malaise and a 6.8-kg weight loss associated with poor appetite. He reported no fevers, night sweats, abdominal pain, emesis, and diarrhea. Physical examination revealed a thin habitus; no palmar erythema, spider angiomas, or gynecomastia were observed. Laboratory tests showed normal complete blood cell count and chemistry panel findings. Hepatic panel showed an elevated alkaline phosphatase level (209 U/L; upper limit of normal [ULN], 150 U/L [3.49 μkat/L; ULN, 2.5 μkat/L]), normal total bilirubin level (0.4 mg/dL [6.84 μmol/L]), elevated alanine aminotransferase level (41 U/L; ULN, 35 U/L [0.68 μkat/L; ULN, 0.58 μkat/L]), and normal aspartate aminotransferase level (27 U/L [0.45 μkat/L]). A single-phase computed tomography (CT) scan of the abdomen revealed multiple hypoattenuating masses with rim enhancement throughout the liver, intussusception of the small bowel, and normal liver contour with no signs of portal hypertension (Figure 1, left). α-Fetoprotein (AFP) level was elevated (1252 ng/mL; ULN, 9 ng/mL); levels of carbohydrate antigen 19-9 (<2 U/mL) and carcinoembryonic antigen (2.8 ng/mL) were normal. A triple-phase CT scan was obtained to further evaluate the small bowel, which revealed no small bowel abnormalities but instead demonstrated a 3.3 × 2.8-cm heterogeneously enhancing pancreatic tail mass not seen on the previous single-phase CT (Figure 1, right).Left, Axial view from single-phase computed tomography (CT) scan of the abdomen revealing bilobar liver masses. Right, Coronal view from venous phase of triple-phase CT scan revealing a pancreatic tail mass (arrowhead) in addition to the bilobar liver masses.Begin FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) chemotherapyPerform a fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET) scanPerform an endoscopic ultrasound of the pancreas with fine-needle aspiration

what would you do next?

What would you do next?

Perform a fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET) scan

Perform an endoscopic ultrasound of the pancreas with fine-needle aspiration

Begin sorafenib

Begin FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) chemotherapy

b

male

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2705983

A woman in her early 70s presented to her local emergency department with the recent onset of wheezing and dyspnea. Noncontrast computed tomography of her chest showed a 1.1-cm nodular lesion in the upper trachea that appeared to be originating from the right lobe of the thyroid (Figure 1A). She was referred to our center for evaluation and management of what appeared to be an aggressive thyroid malignant neoplasm. She presented with obvious biphasic stridor and a report of dyspnea on mild exertion. A CT of the chest showed a soft-tissue mass protruding into the trachea in the posterolateral aspect of the right side of the tracheal region that appeared to be contiguous with the thyroid gland. Ultrasound-guided fine-needle aspiration of the thyroid was performed; however, there was no nodule in the right thyroid lobe that correlated with the CT findings. The left thyroid lobe contained an 8-mm nodule. Examination of a biopsy specimen from this nodule showed medullary thyroid cancer (MTC). The patient’s serum calcitonin level was 23 pg/mL. Magnetic resonance imaging (MRI) of the neck revealed a hyperintense tracheal mass on T2-weighted imaging (Figure 1B) that showed enhancement on administration of contrast medium (not shown). In addition, a 0.3-cm nonenhancing nodule at the lower pole of the right thyroid lobe, separate from the tracheal mass, was identified. Vocal cord mobility was normal on fiberoptic laryngoscopy, and the patient verbally denied having dysphagia. Both ultrasonography and CT/magnetic resonance imaging failed to identify any suspicious adenopathy.A, Axial computed tomogram (CT) of the chest without contrast medium shows a 1.1-cm hypodense, exophytic right posterolateral intratracheal mass with apparent continuity with the right thyroid lobe. B, Axial, T2-weighted magnetic resonance image (MRI) with contrast medium revealed a hyperintense soft-tissue mass within the tracheal lumen. A T1-weighted image before the addition of contrast medium (not shown) showed a slightly hyperintense mass to the thyroid gland. That lesion showed enhancement on administration of contrast medium. What Is Your Diagnosis?

Aggressive invasive thyroid cancer

Amyloidosis

Benign thyroid rest

Mucoid pseudotumor

C. Benign thyroid rest

C

Benign thyroid rest

Direct laryngoscopy and biopsy of the intratracheal mass was performed. On imaging, the mass had a smooth appearance and was arising posterolaterally, inseparable from the right thyroid lobe. Biopsy and debulking of the lesion were performed. The lesion was found to be a benign thyroid rest on the basis of final pathological review (Figure 2). This patient returned to the operating room after preoperative counseling. She underwent further laser debulking of the intratracheal mass followed by a total thyroidectomy and central compartment lymph node dissection. Final pathological analysis showed a 0.35-cm pT1aN0 unifocal MTC in the left lobe. In addition, there were 2 foci of papillary microcarcinoma (largest focus, 0.05 cm) in the right lobe with no adverse histologic features, such as angioinvasion, lymphatic invasion, and extrathyroidal extension. Pathological analysis of the additional tissue from the intratracheal mass was again interpreted as benign intratracheal thyroid tissue. Seven central compartment lymph nodes were examined, and none were positive for metastatic thyroid cancer. At 1 year following surgery, she had no evidence of recurrence but did have a stable yet small, nonobstructing intratracheal mass.Biopsy specimen obtained from the intratracheal mass shows benign thyroid tissue (hematoxylin-eosin, digitalized image, low-power magnification).Ectopic thyroid tissue is a rare mass that is typically found at any location along the thyroglossal duct or at the base of the tongue.1 Although thyroid ectopia in the intratracheal region is less common,2 its occurrence has been reported in the literature, with patients most often presenting with dyspnea or signs of upper airway obstruction.2-6 Concomitant medullary and papillary thyroid carcinoma (PTC) is similarly rare.Mucoid pseudotumors are one of the most common entities encountered in the airway. While they generally present with low attenuation on CT, as was true in this case, mucoid pseudotumors often contain mixed bubbles. However, when mucous is thick and adherent to a nondependent wall of the airway, it may be difficult to differentiate it from a mass.7 Amyloidosis of the airway is less common. These lesions are generally nodular with irregular luminal narrowing and may calcify. In this patient, the tracheal lesion was smooth and not calcified.8 Complete preoperative evaluation successfully ruled out both of these differential diagnoses.The presentation of intratracheal thyroid ectopia in the setting of thyroid carcinoma is of particular interest to this case. Brandwein et al9 described a case of intratracheal thyroid ectopia in the setting of PTC. The preoperative assessment for that patient mistakenly identified aggressive PTC with tracheal invasion and resulted in aggressive surgical resection. The authors noted that the treatment options differ greatly when the diagnosis of benign intratracheal thyroid tissue is established prior to surgery. Similarly, Scherl et al6 described a series of 9 cases initially presenting as potential invasive thyroid cancer but later diagnosed as different histopathologic entities, including tracheal thyroid rest, tracheal stenosis, and a recurrent laryngeal nerve schwannoma. The authors concluded that it is important for clinicians and pathologists to consider the possibility of the presence of benign intratracheal thyroid ectopia.6,9As shown in these case reports, an intratracheal mass can be managed in a conservative fashion despite the presence of both MTC and PTC. Complete examination of a patient with this presentation includes endoscopic evaluation of the intratracheal process with tissue sampling. Verification of the diagnosis of a benign intratracheal rest allows for initial consideration of nonsurgical options, such as radioactive iodine ablation of the intratracheal component.9 Tracheal resection is the most common treatment option as reported in the literature; however, endoscopic laser excision or debulking in addition to suppression of thyrotropin is also recommended.9

General

A woman in her early 70s presented to her local emergency department with the recent onset of wheezing and dyspnea. Noncontrast computed tomography of her chest showed a 1.1-cm nodular lesion in the upper trachea that appeared to be originating from the right lobe of the thyroid (Figure 1A). She was referred to our center for evaluation and management of what appeared to be an aggressive thyroid malignant neoplasm. She presented with obvious biphasic stridor and a report of dyspnea on mild exertion. A CT of the chest showed a soft-tissue mass protruding into the trachea in the posterolateral aspect of the right side of the tracheal region that appeared to be contiguous with the thyroid gland. Ultrasound-guided fine-needle aspiration of the thyroid was performed; however, there was no nodule in the right thyroid lobe that correlated with the CT findings. The left thyroid lobe contained an 8-mm nodule. Examination of a biopsy specimen from this nodule showed medullary thyroid cancer (MTC). The patient’s serum calcitonin level was 23 pg/mL. Magnetic resonance imaging (MRI) of the neck revealed a hyperintense tracheal mass on T2-weighted imaging (Figure 1B) that showed enhancement on administration of contrast medium (not shown). In addition, a 0.3-cm nonenhancing nodule at the lower pole of the right thyroid lobe, separate from the tracheal mass, was identified. Vocal cord mobility was normal on fiberoptic laryngoscopy, and the patient verbally denied having dysphagia. Both ultrasonography and CT/magnetic resonance imaging failed to identify any suspicious adenopathy.A, Axial computed tomogram (CT) of the chest without contrast medium shows a 1.1-cm hypodense, exophytic right posterolateral intratracheal mass with apparent continuity with the right thyroid lobe. B, Axial, T2-weighted magnetic resonance image (MRI) with contrast medium revealed a hyperintense soft-tissue mass within the tracheal lumen. A T1-weighted image before the addition of contrast medium (not shown) showed a slightly hyperintense mass to the thyroid gland. That lesion showed enhancement on administration of contrast medium.

what is your diagnosis?

What is your diagnosis?

Benign thyroid rest

Amyloidosis

Aggressive invasive thyroid cancer

Mucoid pseudotumor

a

female

71-80

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2712314

A woman in her 70s with a history of pulmonary embolism presented to the emergency department with acute right eye vision loss. She described a 2-week medical history of diplopia and blurry vision as well as 4 months of nasal congestion and progressive headaches despite multiple antibiotic courses. She denied a medical history of sinonasal issues, immunodeficiency, autoimmune disease, malignant disease, or diabetes.On examination, she was afebrile with stable vital signs. Ophthalmologic evaluation revealed a right afferent pupillary defect and cranial sixth-nerve palsy. Computed tomographic and magnetic resonance imaging of the sinuses revealed abnormal soft tissue throughout her sinuses with destruction of the sinus walls and skull base as well as extension of abnormal appearing tissue into the right orbital apex and posterior nasal septum. Laboratory evaluation demonstrated a normal white blood cell count and an elevated erythrocyte sedimentation rate and C-reactive protein level. Nasal endoscopy showed bloody mucus and crusting around the right middle turbinate and sphenoethmoidal recess.The acute nature of her vision loss amid concern for a destructive sinonasal process warranted operative intervention. Abnormal soft tissue with associated destruction throughout her sinonasal cavities and right orbital apex was identified. Frozen sections revealed negative results for fungal elements and cellular dysplasia but demonstrated widespread inflammation with giant cells. A representative final pathology slide is shown in the Figure.Sinonasal mucosal biopsy results demonstrate numerous multinucleated giant cells (black arrowheads), necrosis (white arrowhead), and inflammatory cells invading vessel walls (blue arrowheads). Hematoxylin-eosin stain (original magnification ×10). What Is Your Diagnosis?

Lymphoma

Acute invasive fungal sinusitis

Granulomatosis with polyangiitis

Sinonasal undifferentiated carcinoma

C. Granulomatosis with polyangiitis

C

Granulomatosis with polyangiitis

Widespread inflammation with giant cells suggested vasculitis or acute invasive fungal sinusitis (AIFS). Frozen section analysis for fungal elements in AIFS has a reported sensitivity as low as 72.7%, therefore stat pathologic analysis was requested.1 This was available within 24 hours and revealed giant cells, noncaseating granulomas, destruction of vessel walls, and vasculitic changes with concentric accumulation of plasma cells and lymphocytes (Figure). Stains for CD20 (B cells), CD3 (T cells), acid fast bacilli, fungal elements, and Epstein-Barr virus had negative results. The patient’s serological analysis revealed positive test results for antinuclear antibody (ANA) and autoantibody to proteinase-3 (PR3) but negative results for cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA). Her clinical, radiographic, and pathologic findings were consistent with granulomatosis with polyangiitis (GPA) despite the negative c-ANCA results.Intraoperatively, abnormal soft tissue with associated destruction was found throughout her sinonasal cavity, including the ethmoids, sphenoids/sphenoid face, and posterior septum. There was dehiscence bilaterally along the lamina papyracea and thinning of the ethmoid skull base. The abnormal soft tissue invaded the right orbital apex, causing compression on the optic nerve and resultant vision loss. Although GPA can present in the orbit, it is unusual for the ocular findings to result from extension through the sinonasal cavity.2,3 Indeed this case represents a rare presentation of GPA with diffuse sinonasal erosion and sudden blindness.This patient highlights another important manifestation of GPA: localized sinonasal GPA. Although GPA is frequently a systemic phenomenon with nasal, renal and pulmonary manifestations, up to one-third of patients present with disease limited to the sinonasal region.4 Early detection of GPA, especially localized sinonasal GPA, is difficult. First, sinonasal limited GPA is often negative for autoantibodies to PR3/ANCA. Antineutrophil cytoplasmic antibody autoantibodies are found in more than 90% of patients with systemic GPA, compared with only 50% to 80% of sinonasal specific cases.5 Furthermore, pathologic diagnosis can be challenging. In a pathologic review of 126 patients with GPA, the classic triad of vasculitis, necrosis, and granulomatous changes was only present in 16% of the biopsies.6 The high false-negative rate of serologic testing and nonspecific clinical features in focal disease necessitates a high degree of clinical suspicion along with a careful evaluation of all clinical, radiographic, and histologic data to achieve an accurate diagnosis for these patients.Treatment of sinonasal GPA involves debridement for large disease burden or involvement of critical structures, followed by immunosuppression with corticosteroids and chemotherapy.7 This leads to 5-year survival rates greater than 80%.5 The patient in this case experienced considerable improvement in her sinonasal symptoms following debridement. Unfortunately, her visual prognosis remained poor in the right eye. After surgery, she received high-dose intravenous methylprednisolone followed by prednisone at the discretion of the rheumatology team. Overall, this case highlights a rare presentation of GPA and outlines the importance of considering GPA in the differential diagnosis of progressive, destructive sinusitis unresponsive to medical treatment.

General

A woman in her 70s with a history of pulmonary embolism presented to the emergency department with acute right eye vision loss. She described a 2-week medical history of diplopia and blurry vision as well as 4 months of nasal congestion and progressive headaches despite multiple antibiotic courses. She denied a medical history of sinonasal issues, immunodeficiency, autoimmune disease, malignant disease, or diabetes.On examination, she was afebrile with stable vital signs. Ophthalmologic evaluation revealed a right afferent pupillary defect and cranial sixth-nerve palsy. Computed tomographic and magnetic resonance imaging of the sinuses revealed abnormal soft tissue throughout her sinuses with destruction of the sinus walls and skull base as well as extension of abnormal appearing tissue into the right orbital apex and posterior nasal septum. Laboratory evaluation demonstrated a normal white blood cell count and an elevated erythrocyte sedimentation rate and C-reactive protein level. Nasal endoscopy showed bloody mucus and crusting around the right middle turbinate and sphenoethmoidal recess.The acute nature of her vision loss amid concern for a destructive sinonasal process warranted operative intervention. Abnormal soft tissue with associated destruction throughout her sinonasal cavities and right orbital apex was identified. Frozen sections revealed negative results for fungal elements and cellular dysplasia but demonstrated widespread inflammation with giant cells. A representative final pathology slide is shown in the Figure.Sinonasal mucosal biopsy results demonstrate numerous multinucleated giant cells (black arrowheads), necrosis (white arrowhead), and inflammatory cells invading vessel walls (blue arrowheads). Hematoxylin-eosin stain (original magnification ×10).

what is your diagnosis?

What is your diagnosis?

Granulomatosis with polyangiitis

Sinonasal undifferentiated carcinoma

Acute invasive fungal sinusitis

Lymphoma

a

female

71-80

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2714045

A 32-year-old Hispanic man without significant medical history presented with nasal pain and swelling, progressive for 6 weeks. He had been hospitalized for this problem at an outside hospital and treated with antibiotics, without improvement. The swelling worsened and extended to his upper lip. He developed difficulty swallowing, headache, and nasal drainage. On presentation, he was afebrile without leukocytosis. Physical examination demonstrated diffuse swelling and tenderness of the nose with honey-colored crusting that extended to above his upper lip.Axial and sagittal contrast-enhanced computed tomography (CT) (Figure, A and B) demonstrated marked soft tissue swelling and fullness with abnormal enhancement along the nasal cavity, including bilateral nasal ala, with areas of necrosis and emphysema. No significant bony erosion or associated calcification on bone windows was noted. After bedside debridement of the nasal soft tissue region, axial postcontrast T1-weighted fat-suppressed and sagittal T2-weighted fat-suppressed magnetic resonance imaging through the nasal cavity (Figure, C and D) demonstrated soft tissue fullness isointense to muscle on T1-weighted images, hyperintense on T2-weighted images, and with homogenous enhancement of the solid component on postcontrast T1-weighted images. No intracranial or intraorbital disease extension was noted.Contrast-enhanced computed tomography (CT) demonstrates marked soft tissue swelling and fullness with abnormal enhancement along the nasal cavity, including bilateral nasal ala, with areas of necrosis and emphysema. Fat-suppressed magnetic resonance imaging (MRI) demonstrates soft tissue fullness isointense to muscle on T1-weighted images, hyperintense on T2-weighted images, and with homogenous enhancement of the solid component on postcontrast T1-weighted images.Granulomatosis with polyangiitis (Wegner granulomatosis) and relapsing polychondritis What Is Your Diagnosis?

Extranodal T-cell lymphoma

Granulomatosis with polyangiitis (Wegner granulomatosis) and relapsing polychondritis

Squamous cell carcinoma

Necrotizing fasciitis

A. Extranodal T-cell lymphoma

A

Extranodal T-cell lymphoma

With a presumed diagnosis of nasal vestibular abscess refractory to conservative management, the patient underwent incision and drainage, without purulence noted. He was taken to surgery, where nasal cavities were filled with necrotic debris, and a perforation was noted along the cartilaginous segment of the nasal septum. Biopsy demonstrated atypical angiocentric and angiodestructive natural killer and T (NK/T)–cell proliferation, positive for cytoplasmic CD3, CD2, CD7, CD30, CD56, granzyme B, and TIA1 and negative for surface CD3, CD4, CD5, CD8, and CD57. In situ hybridization for Epstein-Barr virus–encoded RNA was diffusely positive, supporting the diagnosis of extranodal NK/T-cell lymphoma, nasal type. Results of a bone marrow biopsy were normal. Staging fludeoxyglucose F 18–labeled positron emission tomography and CT demonstrated multiple bilateral fludeoxyglucose F 18–avid cervical lymph nodes. The patient began treatment with dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC regimen) with concurrent radiotherapy.Nasal type NK/T-cell lymphoma is rare in the United States and Europe and more common in Asia, South and Central America, and Mexico.1 The disease is highly associated with Epstein-Barr virus infection, spans a wide age range, and peaks in the sixth decade of life, with male predominance.2 Despite its typical confinement to the nasal cavity, NK/T-cell lymphoma has a worse prognosis than B-cell lymphoma. Nodal and distant metastases are rare. Invasion of vascular walls causes vascular occlusion, resulting in ischemic necrosis of tumor and normal tissue, as in this case. Nodal lymphoma is characterized by nonnecrotic nodal mass isointense on T1- and iso- to hyperintense on T2-weighted images, restricted diffusion, and homogeneous enhancement. Rather than a discernible mass or node, findings of NK/T-cell lymphoma include sheetlike infiltration of mucosal and submucosal layers involving the entire nasal chamber.3 Little bony destruction is present, especially when diagnosed early, as in this case. At present, no consensus exists regarding treatment, which includes radiotherapy and/or chemotherapy.4Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is a necrotizing granulomatous disease with multiple head and neck manifestations. More common in the fourth and fifth decades of life, GPA may present at any age. Most cases involve the head and neck, with osseous erosion and destruction usually affecting the nasal septum and turbinates, mucosal thickening, most common in the maxillary sinuses, and neo-osteogenesis on imaging. The absence of bony erosion and neo-osteogenesis in our case makes GPA less likely. Granulomatosis with polyangiitis can mimic cocaine necrosis on imaging; the clinical history is important to diagnosis.5Squamous cell carcinoma, the most common sinonasal malignant neoplasm, is frequently associated with occupational exposure.6 Squamous cell carcinoma typically originates from the maxillary sinuses, followed by the ethmoid sinuses, nasal vestibule, and cavity. Computed tomographic imaging typically demonstrates a sinonasal soft tissue mass with prominent bone destruction, not seen in our case. Intermediate T1- and hypointense T2-weighted signal intensity, with variable enhancement on contrast-enhanced T1-weighted images (less than the sinus mucosa), are typical magnetic resonance imaging features. Smaller lesions are typically homogeneous in signal intensity; larger tumors are usually more heterogeneous, with areas of necrosis and hemorrhage.7Most cases of necrotizing fasciitis occur in patients with underlying conditions such as diabetes, immunosuppression, and malignant neoplasm, which were absent in our patient. Necrotizing fasciitis in the head and neck is rare; most cases are odontogenic, and presenting signs and symptoms are relatively benign compared with other sites. Distinguishing features from simple cellulitis include rapid clinical progression, systemic toxic effects, and presence of subdermal gas, best seen on CT imaging. Progressive liquefaction of subcutaneous fat and connective tissue spares overlying skin, characterized on CT by bizarre-shaped hypodense areas, irrespective of cervical fascia or compartment, without rim enhancement.8 The imaging appearance differs from abscess, which demonstrates circumscribed fluid attenuation with peripheral rim enhancement. The presented case could have suggested an imaging diagnosis of necrotizing fasciitis, emphasizing the importance of close clinical observation.

General

A 32-year-old Hispanic man without significant medical history presented with nasal pain and swelling, progressive for 6 weeks. He had been hospitalized for this problem at an outside hospital and treated with antibiotics, without improvement. The swelling worsened and extended to his upper lip. He developed difficulty swallowing, headache, and nasal drainage. On presentation, he was afebrile without leukocytosis. Physical examination demonstrated diffuse swelling and tenderness of the nose with honey-colored crusting that extended to above his upper lip.Axial and sagittal contrast-enhanced computed tomography (CT) (Figure, A and B) demonstrated marked soft tissue swelling and fullness with abnormal enhancement along the nasal cavity, including bilateral nasal ala, with areas of necrosis and emphysema. No significant bony erosion or associated calcification on bone windows was noted. After bedside debridement of the nasal soft tissue region, axial postcontrast T1-weighted fat-suppressed and sagittal T2-weighted fat-suppressed magnetic resonance imaging through the nasal cavity (Figure, C and D) demonstrated soft tissue fullness isointense to muscle on T1-weighted images, hyperintense on T2-weighted images, and with homogenous enhancement of the solid component on postcontrast T1-weighted images. No intracranial or intraorbital disease extension was noted.Contrast-enhanced computed tomography (CT) demonstrates marked soft tissue swelling and fullness with abnormal enhancement along the nasal cavity, including bilateral nasal ala, with areas of necrosis and emphysema. Fat-suppressed magnetic resonance imaging (MRI) demonstrates soft tissue fullness isointense to muscle on T1-weighted images, hyperintense on T2-weighted images, and with homogenous enhancement of the solid component on postcontrast T1-weighted images.Granulomatosis with polyangiitis (Wegner granulomatosis) and relapsing polychondritis

what is your diagnosis?

What is your diagnosis?

Granulomatosis with polyangiitis (Wegner granulomatosis) and relapsing polychondritis

Extranodal T-cell lymphoma

Squamous cell carcinoma

Necrotizing fasciitis

b

male

31-40

Hispanic

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2714283

A girl presented with a left posterior triangle neck mass that had progressed for 3 years following a motor vehicle accident. On physical examination, the mass was firm, mobile, tender to palpation, and caused restricted range of motion. Ultrasound imaging of the soft tissue of the neck was obtained, which demonstrated a neck mass with dense acoustic shadowing (Figure 1A). Further evaluation with contrasted computed tomography (CT) imaging showed a 3.3×2.9×2.6-cm ossified lesion in the left posterior-lateral cervical soft tissue near the atlanto-axial junction. The lesion was well circumscribed and separate from the underlying bone (Figure 1B). The patient underwent excision of the mass without complication. The gross pathology specimen showed a firm, irregular, encapsulated mass.A, Ultrasonography of the neck soft tissue demonstrating a neck mass with dense acoustic shadowing in the left posterior triangle. B, Axial computed tomographic imaging of the neck with contrast depicting a 3.3-cm well-circumscribed ossified mass that is separated from the C2 vertebral body. No aggressive-appearing periosteal reaction is present (arrowhead indicates calcified neck mass). What Is Your Diagnosis?

Osteochondroma

Osteoid osteoma

Osteosarcoma

Myositis ossificans

D. Myositis ossificans

D

Myositis ossificans

Myositis ossificans (MO) is a reactive pseudotumor of skeletal muscle characterized by intramuscular proliferation of fibroblasts causing heterotrophic bone formation.1-3 There are rare cases in pediatric populations, but MO typically affects young adults. Approximately 80% of lesions arise in the large muscles of the extremities.4 Myositis ossificans rarely occurs in the head and neck. Most instances of MO in the head and neck occur in muscles of mastication, with the sternocleidomastoid muscle accounting for only 8% of instances.5 Most cases (60%-75%) occur secondary to trauma, which leads to a local inflammatory cascade, with vascular endothelial cell transition into fibroblasts, chondrocytes, and osteoblasts.2,6 This patient presented with a progressive neck mass following a motor vehicle accident, which may have been the inciting traumatic event although she denied specific trauma to that region. Less commonly, MO occurs as part of an autosomal dominant genetic disorder called myositis ossificans progressiva. Myositis ossificans can also occur following spinal cord injury or severe thermal injury.3 Clinical examination reveals a palpable firm mass with pain and local edema.2,3 Surgical excision is an option for treatment and diagnosis; however, up to 35% of lesions spontaneously regress after several months of clinical monitoring.7 Once the possibility of malignant disease is eliminated, treatment with conservative measures, including ice and immobilization, is a viable option.2Myositis ossificans has distinct radiographic characteristics that differentiate it from similar lesions. Myositis ossificans progresses through 3 distinct phases of development: an initial acute phase characterized by central fibroblastic proliferation; a subacute phase characterized by osteoblastic differentiation and peripheral deposition of an osteoid matrix; and a late phase, characterized by development of calcified bone at the periphery of the lesion.1 Early biopsy, taken when acute fibroplastic proliferation is dominant, may mistake MO for osteosarcoma. As the lesion matures, a “zone phenomenon” of layered central fibroblasts, intermediate osteoblasts, and peripheral calcified bone develops. In early stages of development, ultrasound may be the most sensitive diagnostic modality because it may detect this zone phenomenon before ossification is apparent. Computed tomographic imaging is more sensitive than standard radiographic imaging for detecting early ossification and central fibroproliferation.1 In the subacute phase, CT imaging shows peripheral calcification and a central zone isodense to muscle. The mature lesion demonstrates dense calcification on CT.3 Computed tomographic imaging is useful for differentiation of MO from other entities, such as osteosarcoma. Osteosarcoma demonstrates an inner layer of ossification and diminished ossification at the periphery. Myositis ossificans displays the opposite pattern with an outer layer of ossification.3 Magnetic resonance imaging (MRI) characteristics also evolve as the lesion matures. Early features include peripheral enhancement on gadolinium contrasted T1 images and central heterogeneity on T2. Late features include diminished peripheral signal intensity indicative of mature bone and increase central signal intensity indicative of bone marrow.8On hematoxylin-eosin staining, the mature MO lesion displays an outer layer of benign trabecular bone with mature trilinear hematopoietic bone marrow and focal cartilage (Figure 2). The maturity of the hematopoietic bone marrow suggests an osteochondroma. However, on CT imaging, osteochondroma demonstrates a marrow cavity continuous with the marrow cavity of the associated bone, which is not present in this example.9 Osteoid osteoma, also considered in our differential diagnosis, is found to be an intracortical, intramedullary, or subperiosteal lesion on CT.10 Osteoma has neither cartilaginous nor bone marrow components histologically. Osteosarcoma demonstrates an opposite pattern of MO with dense ossification in the center of the lesion and diminished ossification at the periphery, thus differentiating malignant disease from MO.3Hematoxylin-eosin staining of surgical specimen at (original magnification ×100) showing an encapsulated lesion with trabecular bone (black arrowhead) and mature hematopoietic bone marrow (blue arrowhead).

General

A girl presented with a left posterior triangle neck mass that had progressed for 3 years following a motor vehicle accident. On physical examination, the mass was firm, mobile, tender to palpation, and caused restricted range of motion. Ultrasound imaging of the soft tissue of the neck was obtained, which demonstrated a neck mass with dense acoustic shadowing (Figure 1A). Further evaluation with contrasted computed tomography (CT) imaging showed a 3.3×2.9×2.6-cm ossified lesion in the left posterior-lateral cervical soft tissue near the atlanto-axial junction. The lesion was well circumscribed and separate from the underlying bone (Figure 1B). The patient underwent excision of the mass without complication. The gross pathology specimen showed a firm, irregular, encapsulated mass.A, Ultrasonography of the neck soft tissue demonstrating a neck mass with dense acoustic shadowing in the left posterior triangle. B, Axial computed tomographic imaging of the neck with contrast depicting a 3.3-cm well-circumscribed ossified mass that is separated from the C2 vertebral body. No aggressive-appearing periosteal reaction is present (arrowhead indicates calcified neck mass).

what is your diagnosis?

What is your diagnosis?

Osteoid osteoma

Osteochondroma

Osteosarcoma

Myositis ossificans

d

female

original

https://jamanetwork.com/journals/jama/fullarticle/2717584

A previously healthy man in his 30s presented with a 5-day history of fever, anorexia, and rash. Five days before arrival, he developed throat pain, rhinorrhea, nonproductive cough, and fever. Two days later he noticed a maculopapular rash on his neck and trunk, which later involved his upper and lower extremities. He did not smoke and only drank alcohol occasionally. He was living in Japan and recently visited a neighboring island but denied any international travel.On examination, his blood pressure was 142/84 mm Hg; temperature, 38.3°C; pulse, 91/min; respiratory rate, 24/min; and oxygen saturation, 97% on ambient air. He was alert and oriented. There were no mucosal lesions or conjunctival injection. A maculopapular rash was noted on the trunk and extremities (Figure) as well as the palms and soles. The face was not involved. The lungs were clear to auscultation. No hepatosplenomegaly was noted. Neurologic examination, including results of motor, sensory, and reflex testing, was unremarkable. There was no neck stiffness or lymphadenopathy. Laboratory testing showed a white blood cell count of 2900/μL (80% neutrophils, 13% lymphocytes, 6% monocytes, 0% eosinophils, and 0% basophils); hemoglobin level, 15.2 g/dL; and platelet count, 187 ×103/μL. Serum electrolyte levels were normal. Aspartate aminotransferase level was 635 U/L (10.6 μkat/L); alanine aminotransferase (ALT), 491 U/L (8.2 μkat/L); lactate dehydrogenase, 807 U/L (13.48 μkat/L); γ-glutamyltransferase, 329 U/L (5.49 μkat/L); and bilirubin, 1.3 mg/dL (22.24 μmol/L). What Would You Do Next?

Administer an intravenous steroid

Obtain an HIV immunoassay

Perform liver biopsy

Initiate negative-pressure isolation

Measles

D

Initiate negative-pressure isolation

The key to the correct diagnosis is the presence of fever, maculopapular rash, and cough, coryza, or conjunctivitis.1 People with measles may develop complications such as pneumonia, encephalitis,2 and hepatitis,3 as in this case. A high index of suspicion is warranted from both medical and public health perspectives, because the basic reproduction number (the number of secondary cases generated by 1 patient) of measles ranges from 14 to 18.2 This number is significantly higher than that for other airborne infectious diseases (approximately 5 to 7). The contagious period extends from 4 days before to 4 days after the appearance of the rash.2 Both standard and airborne precautions should be implemented,4 including isolating patients to negative-pressure rooms.Glucocorticoids should be avoided in this setting because they may increase the risk of developing sepsis. Hepatitis associated with acute HIV infection is rare, and isolation should be prioritized when measles is suspected. Histopathologic evaluation is invasive and therefore not the best next step for making a diagnosis of measles.Measles remains a highly contagious viral infection worldwide. In 2017, there were 149 142 cases reported worldwide.5 Measles can be a diagnostic challenge during the prodromal phase because the maculopapular rash may not be visible until 4 to 7 days after disease onset.2 Additionally, patients with preexisting immunity may develop modified measles with a prolonged incubation period and mild symptoms.6 This patient did not recall any vaccination history, nor could we obtain his vaccination records; however, the severity of his presentation suggested no prior vaccination.Complications occur in approximately 30% of adults and children with measles.6 In a retrospective analysis, an elevated ALT level was observed in 67.5% of 147 consecutive adult patients. Liver involvement was more common in men than women, and 23% presented with an ALT level more than 5 times the upper normal limit (185 U/L [3.09 μkat/L]).3 Levels of ALT and aspartate aminotransferase were reported to be higher in young adults than in children.7Serology test results, such as a positive antimeasles virus IgM result or a 4-fold increase in level of antimeasles virus IgG, are commonly used in making the diagnosis.6 Alternatively, the detection of the measles virus RNA by polymerase chain reaction is useful because it allows genotype identification and helps distinguish wild-type measles from vaccine-associated measles during outbreaks.1No specific antiviral therapy is currently available for measles. Case reports have suggested the effectiveness of ribavirin in severe cases.8 In acute pediatric cases, the World Health Organization recommends the administration of vitamin A because its deficiency is associated with delayed recovery and an increased complication rate.9 Specific antiviral agents are currently at various stages of development, including intranasally delivered fusion-inhibitory peptides.10For prevention, 2 doses of vaccine after 1 year of age are recommended. One dose of the measles, mumps, and rubella (MMR) vaccine ensures that 95% of children develop immunity; this number increases to 99% with 2 doses.6 Vaccine-associated complications are rare.2Additional history revealed that this patient had visited an area with a measles outbreak on a neighboring island. The detection of measles virus RNA by polymerase chain reaction confirmed the diagnosis. Serology test results for other viral infectious diseases, including Epstein-Barr virus, cytomegalovirus, HIV, and hepatitis A, B, and E virus, were negative. Conservative treatment was provided and symptoms resolved after 9 days. Complete resolution of liver function test results was confirmed 2 months later.

General

A previously healthy man in his 30s presented with a 5-day history of fever, anorexia, and rash. Five days before arrival, he developed throat pain, rhinorrhea, nonproductive cough, and fever. Two days later he noticed a maculopapular rash on his neck and trunk, which later involved his upper and lower extremities. He did not smoke and only drank alcohol occasionally. He was living in Japan and recently visited a neighboring island but denied any international travel.On examination, his blood pressure was 142/84 mm Hg; temperature, 38.3°C; pulse, 91/min; respiratory rate, 24/min; and oxygen saturation, 97% on ambient air. He was alert and oriented. There were no mucosal lesions or conjunctival injection. A maculopapular rash was noted on the trunk and extremities (Figure) as well as the palms and soles. The face was not involved. The lungs were clear to auscultation. No hepatosplenomegaly was noted. Neurologic examination, including results of motor, sensory, and reflex testing, was unremarkable. There was no neck stiffness or lymphadenopathy. Laboratory testing showed a white blood cell count of 2900/μL (80% neutrophils, 13% lymphocytes, 6% monocytes, 0% eosinophils, and 0% basophils); hemoglobin level, 15.2 g/dL; and platelet count, 187 ×103/μL. Serum electrolyte levels were normal. Aspartate aminotransferase level was 635 U/L (10.6 μkat/L); alanine aminotransferase (ALT), 491 U/L (8.2 μkat/L); lactate dehydrogenase, 807 U/L (13.48 μkat/L); γ-glutamyltransferase, 329 U/L (5.49 μkat/L); and bilirubin, 1.3 mg/dL (22.24 μmol/L).

what would you do next?

What would you do next?

Initiate negative-pressure isolation

Perform liver biopsy

Administer an intravenous steroid

Obtain an HIV immunoassay

a

male

31-40

White

original

https://jamanetwork.com/journals/jama/fullarticle/2717815

A 68-year-old woman with Rai stage 0 chronic lymphocytic leukemia (CLL) presented with a 2-day history of dyspnea on exertion. She reported no cough, chest pain, orthopnea, leg swelling, or viral-like symptoms. Her temperature was 36.8°C, heart rate 102/min, respiratory rate 22/min, and blood pressure 124/76 mm Hg. She had conjunctival pallor and scleral icterus, but no lymphadenopathy, hepatosplenomegaly, or ecchymosis. Results of initial laboratory testing are presented in the Table. How Do You Interpret These Results?

The patient has cold agglutinin disease.

The patient has pure red cell aplasia.

The patient has undergone Richter transformation.

The patient has warm autoimmune hemolytic anemia.

D

The patient has warm autoimmune hemolytic anemia.

Autoimmune hemolytic anemia (AIHA) develops due to autoantibody production against surface antigens expressed on a patient’s red blood cells (RBCs). AIHA is subdivided based on immunoglobulin temperature reactivity—warm or cold. Warm IgG antibodies predominantly bind to RBC surface antigens at body temperature and cause warm AIHA, whereas cold IgM agglutinins bound to RBCs fix complement at temperatures below 37°C and can cause cold agglutinin hemolysis. These anti-RBC autoantibodies can be detected using the direct antiglobulin test (DAT), also called the Coombs test.1To detect cold and warm autoantibodies through the conventional test tube method, the patient’s RBCs are first washed with saline to remove immunoglobulins and complement that are not bound to RBCs, leaving behind immunoglobulins and complement bound to RBCs.1 These RBCs are mixed with an antihuman globulin reagent, containing polyspecific rabbit anti-IgG and monoclonal murine anticomplement antibodies.2 In the presence of bound immunoglobulins and complement on the RBC surface, the antihuman globulins produce crosslinks between the patient’s RBCs, resulting in agglutination. The assay is semiquantitative, and results are generally reported on a scale of 0 to 4+ (0, no agglutination; 4+, solid agglutination). If the DAT is positive, it is repeated using monospecific antibodies to explicitly measure anti-IgG or anticomplement, usually C3d, reactivity.1In a single-institution series of 100 patients with a positive DAT, only 29 patients had serologic evidence of hemolytic anemia, defined as hemoglobin lower than 12.3 g/dL, hematocrit lower than 37.4%, total bilirubin above 1.5 mg/dL, lactate dehydrogenase above 220 U/L, and haptoglobin lower than 6 mg/dL.3 Of note, the DAT is positive but not clinically significant in 7% to 8% of all hospitalized patients, even in those without evidence of hemolysis.1 False-positive results can occur due to spontaneous RBC agglutination or technical issues such as insufficient washing, overcentrifugation, or clotted specimens.1 The test tube method for the DAT is 43% sensitive and 87% specific for AIHA.4During their lifetime, 7% to 10% of patients with CLL develop AIHA (warm, 90%; cold, 10%).5 The purported mechanism is polyclonal T-cell–dependent production of pathogenic antibodies, largely by nonmalignant B cells.6 A positive DAT can develop over the course of CLL, but actual AIHA is less common; in a prospective study of 777 CLL patients, the DAT had a positive predictive value of 28% and negative predictive value of 93% for AIHA.7 The 2018 Medicare midpoint reimbursement for a DAT is $6.65.8This patient has evidence of hemolysis (low haptoglobin, high lactate dehydrogenase, and reticulocytosis) and a positive IgG DAT, indicating warm AIHA. Warm AIHA can be primary or associated with lymphoproliferative disorders such as CLL, autoimmune diseases, viral infections, and drugs.3,9Cold agglutinin disease occurs due to IgM autoantibodies. The presence of IgM autoantibodies is indicated by anti-C3d activity due to the complement-fixing property of IgM.1 This patient had a negative C3d DAT, indicating the absence of IgM autoantibodies. Pure RBC aplasia, characterized by severe anemia, normal white blood cell and platelet count, with decreased erythroid precursors in the bone marrow, occurs in less than 1% of CLL patients and is associated with reticulocytopenia.5 Richter transformation is the development of a more aggressive lymphoma and occurs in 3% of patients with CLL. Patients often develop lymphadenopathy and systemic symptoms rather than hemolytic anemia.10DAT remains the primary test for determining whether an autoimmune hemolysis is present. Specialized testing, flow cytometry for RBC IgG and enzyme-linked anti-IgG assay, can detect IgG that is not measured by DAT, but it is rarely available in standard clinical laboratories. Thus, a definitive diagnosis of DAT-negative AIHA can often not be made.9 If DAT-negative AIHA is suspected, hematology consultation is recommended to guide further testing (if available) and empirical treatment.The patient was diagnosed with CLL–associated warm AIHA and treated with oral prednisone (1 mg/kg per day). Because she was hemodynamically stable, no blood products were transfused. The patient received weekly follow-up with complete blood cell counts and markers of hemolysis. After 2 weeks, hemoglobin began improving (8.8 g/dL), and at 4 weeks, her hemoglobin level was 10.2 g/dL. Prednisone was tapered to 10 mg/d and discontinued after 5 months. At that time, her hemoglobin was 12.3 g/dL and hemolysis markers were negative. The patient remains in remission at her most recent follow-up, 9 months after completing therapy. Rituximab is a reasonable alternative therapy for patients with CLL-associated warm AIHA.The direct antiglobulin test (DAT) is a semiquantitative assay that detects the presence of bound anti–red blood cell (RBC) antibodies through RBC agglutination.Warm autoimmune hemolytic anemia (AIHA) is primarily caused by IgG agglutinins that are active at body temperature and develops in 7% to 10% of patients with chronic lymphocytic leukemia (CLL).The DAT has a low positive predictive value (28%) for warm AIHA in patients with CLL.

Diagnostic

A 68-year-old woman with Rai stage 0 chronic lymphocytic leukemia (CLL) presented with a 2-day history of dyspnea on exertion. She reported no cough, chest pain, orthopnea, leg swelling, or viral-like symptoms. Her temperature was 36.8°C, heart rate 102/min, respiratory rate 22/min, and blood pressure 124/76 mm Hg. She had conjunctival pallor and scleral icterus, but no lymphadenopathy, hepatosplenomegaly, or ecchymosis. Results of initial laboratory testing are presented in the Table.

how do you interpret these results?

How do you interpret these results?

The patient has pure red cell aplasia.

The patient has warm autoimmune hemolytic anemia.

The patient has cold agglutinin disease.

The patient has undergone Richter transformation.

b

female

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2716410

A 36-year-old healthy gravida 3, para 3 woman with a history of asthma and elective cesarean delivery 11 days prior presented to the emergency department with 3 days of exertional chest pain. The pain was described as crushing and substernal, but she denied radiation or associated dyspnea, nausea, vomiting, or diaphoresis. On physical examination, her blood pressure was 167/105 mm Hg bilaterally, heart rate was 71/min, respiratory rate 18/min, and oxygen saturation 98% on room air. Initial laboratory evaluation revealed a troponin I level of 0.12 ng/mL (reference range, 0.00-0.04 ng/mL). An electrocardiogram showed normal sinus rhythm with diffuse ST-segment depressions but without q waves or ST-segment elevation (Figure, left). Computed tomography angiography did not show pulmonary embolism or aortic dissection. Echocardiography demonstrated a left ventricular ejection fraction of 53%, with apical akinesis and no valvular disease.Clinical findings from 12-lead electrocardiography (left) and right anterior oblique cranial angiography of the left anterior descending artery during diastole (right).The patient was started on aspirin and ticagrelor, heparin infusion, and metoprolol tartrate for treatment of non–ST-segment elevation myocardial infarction. She underwent coronary angiography (Figure, right; Video).Continue medical therapy alone, with a β-blocker and antiplatelet therapyRefer for coronary artery bypass graft (CABG) surgery What to Do Next

Administer thrombolytic therapy

Continue medical therapy alone, with a β-blocker and antiplatelet therapy

Perform percutaneous coronary intervention (PCI)

Refer for coronary artery bypass graft (CABG) surgery

Spontaneous coronary artery dissection (SCAD)

B

Continue medical therapy alone, with a β-blocker and antiplatelet therapy

The keys to the correct diagnosis are the epidemiology and unique angiographic characteristics of SCAD. Expert consensus recommends medical therapy for this condition. Thrombolysis carries risk of propagation, as does mechanical revascularization with PCI or CABG surgery; these interventions are thus reserved for select patients.SCAD is increasingly recognized as an etiology of acute coronary syndrome (ACS). The prevalence of SCAD in ACS is estimated to be between 1% and 4% but may be underrecognized and underdiagnosed.1 Women account for more than 90% of cases,2 and the prevalence has been reported to be as high as 35% in women younger than 50 years with ACS.1 Conditions that adversely affect vessel wall integrity or increase shear stress are thought to increase the risk of dissection.3 Fibromuscular dysplasia is present in 25% to 86% of patients in cohort studies.1 Pregnancy, including multiparity, is another important risk factor, with most cases occurring within 4 weeks of delivery.1In atherosclerotic coronary artery disease, plaque rupture or erosion initiates the intravascular thrombotic cascade, causing ischemia. The pathophysiology of SCAD is less well defined. One hypothesis is that hematoma within the coronary artery wall initiates the dissection.4 Intramural hematoma may form through a tear in the intima or by spontaneous bleeding from the vasa vasorum.5 The true coronary lumen is compressed, and thrombus formation may also occur. Ultimately, this leads to myocardial ischemia or infarction.1The clinical presentation of SCAD is often indistinguishable from that of atherosclerotic ACS. Patients report chest pain and may have ischemic electrocardiographic abnormalities or elevated levels of cardiac biomarkers. Rarely, patients with SCAD present with ventricular arrhythmias or sudden cardiac death.6 ACS, whether atherosclerotic or due to SCAD, often warrants coronary angiography. SCAD can have 1 of 3 angiographic appearances. Type 1 indicates multiple visible lumens, with contrast staining of the arterial wall; type 2, diffuse stenosis and an abrupt change in artery caliber at either end of that stenosis; and type 3, focal or tubular stenosis that mimics artherosclerosis.7 Type 1 is pathognomonic for SCAD, type 2 most common, and type 3 most deceiving. The lesion in this case is most consistent with type 2 SCAD. A high index of suspicion is necessary to distinguish SCAD from atherosclerotic coronary artery disease or vasospasm.Treatment recommendations for SCAD are primarily based on expert consensus. β-blockers are widely recommended for acute and long-term management of SCAD, because they decrease coronary artery wall stress and myocardial oxygen demand.1 A prospective cohort study demonstrated a significant decrease in recurrence of SCAD in patients treated with β-blockers.6 Antiplatelet therapy, whether single- or dual-agent, is reasonable given the known benefits of aspirin in other forms of ACS.8 Statin therapy is appropriate for patients when indicated for primary prevention of atherosclerotic cardiovascular disease.1Revascularization can be technically difficult or hazardous and should be reserved for patients for whom intensive medical therapy has failed or for those who have high-risk clinical features (eg, left main coronary artery involvement, persistent ischemia, ventricular arrhythmias, or shock). PCI is technically difficult because of the potential of entering the false lumen with the guidewire and carries risk of extending the dissection proximally or distally.8 CABG surgery has been performed successfully, but data are limited to case reports and small series. There may be a high incidence of graft failure, and CABG surgery is not protective for recurrent SCAD. Thus, CABG surgery should be reserved for patients with multiple or proximal dissections, those with left main coronary artery disease not amenable to PCI, or those for whom PCI has failed.1 Thrombolytic therapy should be avoided because of the risk of worsening coronary artery intramural hematoma.9In a recent study of 310 patients, the rate of de novo SCAD recurrence was 11%, with a median time to recurrence of 4 years.10 Vessel tortuosity is the only risk factor identified for recurrence.1 Follow-up is generally clinically driven; repeat imaging may be useful if patients have recurrent symptoms or other evidence of recurrent ischemia.The patient was prescribed metoprolol succinate, aspirin, and clopidogrel. Her chest pain resolved, and her troponin I level peaked at 1.25 ng/mL. At 4-month follow-up, an echocardiogram showed resolution of the apical wall motion abnormality. She remained active and asymptomatic at 9-month follow-up.

General

A 36-year-old healthy gravida 3, para 3 woman with a history of asthma and elective cesarean delivery 11 days prior presented to the emergency department with 3 days of exertional chest pain. The pain was described as crushing and substernal, but she denied radiation or associated dyspnea, nausea, vomiting, or diaphoresis. On physical examination, her blood pressure was 167/105 mm Hg bilaterally, heart rate was 71/min, respiratory rate 18/min, and oxygen saturation 98% on room air. Initial laboratory evaluation revealed a troponin I level of 0.12 ng/mL (reference range, 0.00-0.04 ng/mL). An electrocardiogram showed normal sinus rhythm with diffuse ST-segment depressions but without q waves or ST-segment elevation (Figure, left). Computed tomography angiography did not show pulmonary embolism or aortic dissection. Echocardiography demonstrated a left ventricular ejection fraction of 53%, with apical akinesis and no valvular disease.Clinical findings from 12-lead electrocardiography (left) and right anterior oblique cranial angiography of the left anterior descending artery during diastole (right).The patient was started on aspirin and ticagrelor, heparin infusion, and metoprolol tartrate for treatment of non–ST-segment elevation myocardial infarction. She underwent coronary angiography (Figure, right; Video).Continue medical therapy alone, with a β-blocker and antiplatelet therapyRefer for coronary artery bypass graft (CABG) surgery

what to do next

What would you do next?

Refer for coronary artery bypass graft (CABG) surgery

Perform percutaneous coronary intervention (PCI)

Administer thrombolytic therapy

Continue medical therapy alone, with a β-blocker and antiplatelet therapy

d

female

31-40

original

https://jamanetwork.com/journals/jama/fullarticle/2716329

A 73-year-old man underwent esophageal resection for cancer. He had a history of hypertension that was treated with an angiotensin receptor blocker. Preoperative estimated glomerular filtration rate (GFR) was 98 mL/min/1.73 m2. On the second postoperative day, body temperature was 38.6°C. Chest x-ray revealed bilateral lung consolidations consistent with pneumonia. Blood pressure decreased from 145/72 mm Hg to 96/53 mm Hg with a heart rate of 105/min. The patient was admitted to the intensive care unit (ICU) with acute respiratory failure and was placed on mechanical ventilation. In the ICU, urine output was 50 mL over 3 hours. On day 3, he received 4.5 L of Ringer lactate over 12 hours. Laboratory values are shown in the Table.The change in serum creatinine is within the coefficient of variation.The patient has acute kidney injury most likely related to sepsis.There are insufficient data to conclude that a decrease in glomerular filtration rate has occurred. How Do You Interpret the Test Results From Day 3 Postoperatively at 3 am?

The change in serum creatinine is within the coefficient of variation.

The patient has acute kidney injury most likely related to sepsis.

The patient has prerenal azotemia.

There are insufficient data to conclude that a decrease in glomerular filtration rate has occurred.

B

The patient has acute kidney injury most likely related to sepsis.

Serum creatinine is a marker of GFR. Serum creatinine level depends on creatinine production and elimination. Elimination mostly depends on GFR but tubular secretion is also important, especially in patients with markedly reduced kidney function. While muscle injury (ie, rhabdomyolysis) might increase creatine release, sepsis may decrease creatinine production such that serum creatinine may not increase despite a decrease in GFR. Serum creatinine increases slowly after acute kidney injury (AKI). Creatinine distributes in a large volume, approximating 60% to 70% of total body weight. The increase in serum creatinine is further delayed by administration of large amounts of fluid and positive fluid balance.1 For example, when patients with sepsis receive a large amount of fluids, AKI might be underrecognized.2 Reaching a steady state of serum creatinine level requires that all compartments in which creatinine distributes are at equilibrium between production and elimination. Current international consensus criteria for AKI include a relative increase in serum creatinine (≥50% from baseline within 7 days) or an absolute increase in serum creatinine (≥0.3 mg/dL within a 48-hour period).3 Mean Medicare reimbursement for serum creatinine testing is $5 to $6.Application of the Test Results for This PatientOn postoperative day 3 at 3am, serum creatinine was only marginally increased despite AKI. Increased volume of distribution would be expected to lead to a decrease in serum creatinine level if the GFR was stable. The slight increase in serum creatinine, in this specific clinical context, led to early identification of AKI. Low urine output is also characteristic in AKI diagnosis (<0.5 mL/kg/h for more than 6 hours) and may precede the increase of serum creatinine. However, AKI can develop without oliguria, and 6-hour urine output monitoring is not always available, as in this case. The patient later met criteria for AKI stage 3 (ie, 3-fold increase in serum creatinine above baseline or ≥4 mg/dL). Early identification of AKI, however, allows for rapid identification of sepsis severity,4 which may facilitate earlier initiation of optimal care and avoidance of nephrotoxins (ie, vancomycin).5 It is important to recognize that AKI can develop in patients with sepsis, despite absence of arterial hypotension or shock.6Cystatin C may be less affected by muscle mass and metabolism than creatinine, but it is not more sensitive to detect AKI than serum creatinine. Alternative biomarkers (eg, neutrophil gelatinase–associated lipocalin, insulin-like growth factor binding protein 7, and tissue inhibitor of metalloproteinases-2) can detect kidney damage and indicate impending AKI but do not directly measure GFR7 and should not replace serum creatinine. Urine analysis is important for some forms of AKI (eg, glomerular nephritis) but lacks sensitivity and specificity. Measuring creatinine clearance estimates GFR but requires a steady-state serum creatinine, urine creatinine, and precise urine volume measurement. Formulas have been proposed for correcting serum creatinine for fluid overload.8 In this case, correcting serum creatinine based on a positive fluid balance of 4.5 L and an estimated volume of distribution of 45 L (ie, 60% of 75 kg) indicated a corrected serum creatinine of 1.22 mg/dL at 3 am on day 3.The patient was diagnosed with postoperative pneumonia complicated by sepsis and AKI. The patient’s condition improved and he was discharged 23 days after admission to the ICU. At discharge, his serum creatinine was 0.7 mg/dL. Recovery can be overestimated because of muscle mass loss during an ICU stay and persistent positive fluid balance.9 Measured creatinine clearance was 72 mL/min/1.73 m2 over a 24-hour urine volume collection, reflecting partial recovery from AKI because the GFR had not reverted to baseline levels.10

Diagnostic

A 73-year-old man underwent esophageal resection for cancer. He had a history of hypertension that was treated with an angiotensin receptor blocker. Preoperative estimated glomerular filtration rate (GFR) was 98 mL/min/1.73 m2. On the second postoperative day, body temperature was 38.6°C. Chest x-ray revealed bilateral lung consolidations consistent with pneumonia. Blood pressure decreased from 145/72 mm Hg to 96/53 mm Hg with a heart rate of 105/min. The patient was admitted to the intensive care unit (ICU) with acute respiratory failure and was placed on mechanical ventilation. In the ICU, urine output was 50 mL over 3 hours. On day 3, he received 4.5 L of Ringer lactate over 12 hours. Laboratory values are shown in the Table.The change in serum creatinine is within the coefficient of variation.The patient has acute kidney injury most likely related to sepsis.There are insufficient data to conclude that a decrease in glomerular filtration rate has occurred.

how do you interpret the test results from day 3 postoperatively at 3 am?

How do you interpret these results?

The patient has acute kidney injury most likely related to sepsis.

There are insufficient data to conclude that a decrease in glomerular filtration rate has occurred.

The patient has prerenal azotemia.

The change in serum creatinine is within the coefficient of variation.

a

male

71-80

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2687976

A man in his 40s presented with a 3-month history of discrete, dark red, circular lesions in his right axilla. He endorsed severe pruritus at these sites that would wake him up at night. He denied any recent trauma or history of similar lesions. He denied associated pain, blisters, or systemic symptoms (eg, fever, chills). His medical history was unremarkable, and he noted no environmental triggers or new medications. Treatment with over-the-counter hydrocortisone cream, ketoconazole cream, and discontinuation of underarm deodorant yielded no improvement. Physical examination revealed 3 well-circumscribed, violaceous, annular patches without scale or erosion that are limited to his right axilla (Figure, A). No other lesions were noted on his skin or mucous membranes. A Wood lamp examination was negative. A punch biopsy specimen from a lesion was obtained (Figure, B and C).A, Clinical photograph shows oval and annular thin violaceous patches in the right axilla. B, Hematoxylin-eosin stain (original magnification ×40) demonstrates lymphocytes obscuring the dermal-epidermal junction. C, Hematoxylin-eosin stain (original magnification ×200). What Is Your Diagnosis?

Familial benign pemphigus (Hailey-Hailey disease)

Inverse lichen planus

Fixed drug eruption

Erythrasma

B. Inverse lichen planus

B

Inverse lichen planus

Histopathologic examination showed a lichenoid infiltrate of lymphocytes obscuring the dermal-epidermal junction. The lymphocytes are associated with saw-toothed epidermal hyperplasia, hypergranulosis, hyperorthokeratosis, and the presence of necrotic keratinocytes, all of which are features consistent with lichen planus. With the distribution occurring in an intertriginous area, the diagnosis of inverse lichen planus was made. On the basis of these findings, triamcinolone acetonide cream, 0.1%, twice daily for 3 weeks was prescribed. The patient returned 5 months later with resolution of his right-axilla lesions but with new onset of similar lesions in his left axilla and bilateral inguinal folds. Laboratory workup for hepatitis C was negative.Lichen planus is typically described as violaceous, polygonal, flat-topped papules and plaques with a reticulated network of fine white scale, known as Wickham striae, presenting on the flexor surfaces of the forearms, wrists, ankles, mucous membranes, and genitalia.1,2 However, more than a dozen clinical variants2-4 of lichen planus have been described. Inverse lichen planus is a rare and unusual morphological variant characterized by involvement of the axillae as well as the inframammary and inguinal regions.5 These lesions can present with poorly defined borders and absent scale because of the occlusive nature of their location.2,4 Like other cutaneous lichen planus variants, the inverse variant tends to be pruritic without other associated symptoms.1 A definitive diagnosis of inverse lichen planus is made by histopathologic analysis.Similar to typical lichen planus, the exact cause of the inverse variant is unknown. However, the pathogenesis is likely mediated by cytotoxic T-lymphocytes targeting basal keratinocytes.5 Hepatitis B immunization and hepatitis C infection are known to be associated with lichen planus.6,7 In addition, a number of medications (eg, nonsteroidal anti-inflammatory drugs, β-blockers, antimalarials) can produce lichen planus–like eruptions.8Evidence on treatment of inverse lichen planus is scarce, but topical corticosteroids appear to be an effective first-line regimen, as observed in this patient. Tacrolimus ointment has also shown efficacy in 1 patient presenting with inverse lichen planus.9

Dermatology

A man in his 40s presented with a 3-month history of discrete, dark red, circular lesions in his right axilla. He endorsed severe pruritus at these sites that would wake him up at night. He denied any recent trauma or history of similar lesions. He denied associated pain, blisters, or systemic symptoms (eg, fever, chills). His medical history was unremarkable, and he noted no environmental triggers or new medications. Treatment with over-the-counter hydrocortisone cream, ketoconazole cream, and discontinuation of underarm deodorant yielded no improvement. Physical examination revealed 3 well-circumscribed, violaceous, annular patches without scale or erosion that are limited to his right axilla (Figure, A). No other lesions were noted on his skin or mucous membranes. A Wood lamp examination was negative. A punch biopsy specimen from a lesion was obtained (Figure, B and C).A, Clinical photograph shows oval and annular thin violaceous patches in the right axilla. B, Hematoxylin-eosin stain (original magnification ×40) demonstrates lymphocytes obscuring the dermal-epidermal junction. C, Hematoxylin-eosin stain (original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Familial benign pemphigus (Hailey-Hailey disease)

Fixed drug eruption

Inverse lichen planus

Erythrasma

c

male

41-50

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2695082

An 80-year-old white woman presented with an asymptomatic white patch affecting the tongue of 1 month’s duration. She had a 15-year history of oral lichen planus (OLP) managed with betamethasone dipropionate, 0.05%, gel twice daily and clotrimazole troches, 10 mg, 3 times daily as needed for symptomatic OLP flares. Medical history revealed stage 1A mycosis fungoides/cutaneous T-cell lymphoma affecting the right calf and left thigh managed primarily with halobetasol, 0.05%, cream owing to intolerance of narrowband UV-B therapy and mechlorethamine, 0.016%, gel. Immunosuppression or history of infectious diseases, including human immunodeficiency virus (HIV), was not reported. A 1.5 × 1.0-cm nonremovable white, plaquelike lesion was observed on the left lateral tongue (Figure 1A). Biopsy specimens were obtained with a 3-mm punch instrument at 3 different sites, which demonstrated similar microscopic findings (Figure 1B and C).A, A corrugated, nonremovable white lesion on left lateral tongue. B, Histologic image showing hyperkeratotic, acanthotic stratified squamous epithelium exhibiting cells with lightly stained cytoplasm (balloon cells) throughout the stratum spinosum and superficial layer (hematoxylin-eosin). C, Histologic image showing several epithelial nuclei with peripheral chromatin margination also described as chromatin beading (arrowheads) (hematoxylin-eosin). What Is Your Diagnosis?

Oral frictional keratosis

Oral lichen planus

Oral hairy leukoplakia

Oral squamous cell carcinoma

C. Oral hairy leukoplakia

C

Oral hairy leukoplakia

Microscopic analysis of all specimens demonstrated hyperkeratosis and acanthosis with a band of cells characterized by lightly stained cytoplasm (balloon cells). The superficial cells contained nuclei with peripheral chromatin margination or nuclear beading typical of Epstein-Barr virus–infected oral keratinocytes and consistent with oral hairy leukoplakia (OHL). The patient was prescribed valacyclovir 1 g 3 times daily, which she discontinued taking after 3 days owing to medication adverse effects. On reexamination, the tongue lesion had completely resolved (Figure 2).Physicians would consider a clinical diagnosis of oral leukoplakia when they find a white plaque of questionable risk and have excluded other known diseases or disorders that carry no increased risk for cancer.1,2 Oral hairy leukoplakia was first described in 1984 during the AIDS epidemic and named for its white color and corrugated appearance.3 Historically, it has been associated with HIV infection and as a sign of disease progression.3 Recently, several reports describe OHL in non–HIV infected individuals in association with inhaled or topical corticosteroids.4-6 Epstein-Barr virus is a DNA B-lymphotropic human herpesvirus that infects more than 90% of the world’s population and is associated with the etiopathogenesis of OHL.4,5 Typically, OHLs appear on the lateral borders of the tongue and are asymptomatic. Microscopic analysis of OHLs may demonstrate several histopathologic features: (1) hyperkeratosis and acanthosis, (2) ballooning degeneration of keratinocytes, and (3) little to no inflammatory infiltrate in the lamina propria.5 However, peripheral chromatin margination or nuclear beading is the only essential diagnostic criteria, and in situ hybridization for Epstein-Barr virus detection is often used to confirm the diagnosis.5 Although treatment of OHL is not typically warranted, lesions have responded to antiviral agents such as acyclovir and valacyclovir.3 In the present case, development of OHL may have occurred due to long-term use of topical corticosteroids for OLP management in the absence of any known systemic immunosuppressive conditions. The patient was recommended for further evaluation of possible immunosuppression. It was indeterminate if OHL resolution was attributed to use of valacyclovir or spontaneous resolution.Oral frictional keratosis, OLP, and oral squamous cell carcinoma (OSCC) were included in the differential diagnosis owing to clinical similarities. Oral frictional keratosis is considered a benign lesion caused by chronic rubbing between 2 surfaces, occurring at higher frequency in areas prone to mechanical trauma.7 The characteristic white appearance of oral frictional keratosis is due to generation of keratin filaments from chronic irritation.8 These lesions have been observed on multiple surfaces, including the tongue, buccal mucosa, gingiva, and alveolar ridges.7 Oral frictional keratosis lesions typically reduce or resolve within 3 weeks if the causative agent is identified.7Oral lichen planus is a chronic, immune-mediated disorder with prevalence ranging from 0.1% to 2% and predominantly affecting middle-aged women.8 Oral lichen planus lesions have a wide range of clinical presentations, from mild inflammation with striae to plaquelike lesions to severely painful ulcerations, which can affect multiple areas of the oral cavity.8 Treatment of OLP may involve topical and/or systemic immunomodulators to manage signs and symptoms of the condition.8Routine monitoring of OLP is recommended due to risk of dysplasia and/or malignant transformation to OSCC, which is estimated at approximately 1%.8Oral and oropharyngeal cancer are typically considered collectively, with greater than 48 000 diagnosed cases in the United States annually.9 Squamous cell carcinoma comprises over 90% of malignancies in this region, and OSCC is thought to be a complex, multistep progressive disorder with an accumulation of both genetic and epigenetic alterations.9 Oral squamous cell carcinoma often presents as a nonhealing ulcer but can also present as a white plaque and/or red patch.8 High-risk sites for development of OSCC include the lateral or ventral tongue and floor of mouth, but it may affect any intraoral surface.8,9 Suspected OSCC lesions must undergo microscopic analysis to confirm the diagnosis, and subsequent therapy may include surgery, radiation therapy, and/or chemotherapy. Overall 5-year survival rate for OSCC is 60%, with poorer prognosis for cancers detected in later stages of disease.9

Dermatology

An 80-year-old white woman presented with an asymptomatic white patch affecting the tongue of 1 month’s duration. She had a 15-year history of oral lichen planus (OLP) managed with betamethasone dipropionate, 0.05%, gel twice daily and clotrimazole troches, 10 mg, 3 times daily as needed for symptomatic OLP flares. Medical history revealed stage 1A mycosis fungoides/cutaneous T-cell lymphoma affecting the right calf and left thigh managed primarily with halobetasol, 0.05%, cream owing to intolerance of narrowband UV-B therapy and mechlorethamine, 0.016%, gel. Immunosuppression or history of infectious diseases, including human immunodeficiency virus (HIV), was not reported. A 1.5 × 1.0-cm nonremovable white, plaquelike lesion was observed on the left lateral tongue (Figure 1A). Biopsy specimens were obtained with a 3-mm punch instrument at 3 different sites, which demonstrated similar microscopic findings (Figure 1B and C).A, A corrugated, nonremovable white lesion on left lateral tongue. B, Histologic image showing hyperkeratotic, acanthotic stratified squamous epithelium exhibiting cells with lightly stained cytoplasm (balloon cells) throughout the stratum spinosum and superficial layer (hematoxylin-eosin). C, Histologic image showing several epithelial nuclei with peripheral chromatin margination also described as chromatin beading (arrowheads) (hematoxylin-eosin).

what is your diagnosis?

What is your diagnosis?

Oral squamous cell carcinoma

Oral hairy leukoplakia

Oral lichen planus

Oral frictional keratosis

b

female

71-80

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2696637

A man in his 40s presented to the dermatology clinic for evaluation of a new pigmented lesion on his left second toenail. The lesion first appeared 12 months before presentation and was progressively growing. This was his first time presenting to a physician for this problem, and no prior treatments had been attempted. The lesion was asymptomatic. He was otherwise well and denied any fevers or weight loss.Clinical examination revealed a dark brown longitudinal pigment band covering the full length of the toenail of the left second digit with corresponding nail thickening over the pigmented band. The pigment was the same width throughout the band and extended to the proximal nail fold (Figure, A). No other nail or skin lesions were found at the time of examination. A biopsy specimen was obtained from the nail plate and nail matrix and stained with hematoxylin-eosin (Figure, B-D).A dark brown longitudinal pigment band on the second toenail with pigment extends to the proximal nail fold (A). Histopathologic examination of the specimen with hematoxylin-eosin stain is seen at original magnification of ×40 (B), ×100 (C), and ×200 (D). What Is Your Diagnosis?

Pigmented onychomatricoma

Subungual melanoma

Pigmented squamous cell carcinoma in situ

Pigmented onychopapilloma

A. Pigmented onychomatricoma

A

Pigmented onychomatricoma

Histologic examination of the nail plate and nail matrix showed bland spindle cell proliferation within the nail matrix with invaginations of the epithelium. No melanocytic lesions were observed, and immunostaining was negative for S100 and CD34. Intracorneal hemorrhage and adjacent verrucous hyperkeratosis were present.Based on the histologic findings of villous fibroepithelial projections into the nail plate without melanocytic proliferation or keratinocyte atypia, a diagnosis of pigmented onychomatricoma was made. The nail was surgically removed to fully excise the lesion after the original biopsy. At approximately 3 months of follow-up, the patient was doing well and without evidence of recurrence of the lesion.Onychomatricoma is a rare benign nail matrix tumor, with fewer than 80 cases reported since it was first described in 1992 by Baran and Kint.1,2 The classic findings include a longitudinal yellow and thickened nail plate segment with transversal curvature of the discolored segment, with filamentous projections of the nail matrix creating visible cavities at the free end of the nail plate.3 Diagnosis of onychomatricoma involves a combination of gross appearance, dermoscopy, and histopathologic findings.2 Under dermoscopy, honeycomblike cavities are seen at the free end of the nail plate.4 Histopathologic findings include 2 distinct regions of tumor. The proximal zone, involving the nail matrix beneath the proximal nail fold, is characterized by an epithelial proliferation that appears to invaginate into the dermis, where bland spindle cell proliferation is also found. The distal zone, defined by the borders of the lunula, has the appearance of fibroepithelial projections consisting of matrix epithelium overlaying a loose spindle cell stroma.5Pigmented onychomatricomas represent a rare variant of this rare disease, with only 8 cases previously reported total in the literature.6,7 They present as a single-digit longitudinal melanonychia with a broad differential diagnosis, including subungual melanoma, pigmented squamous cell carcinoma in situ, pigmented onychopapilloma, and subungual hematoma.6,7 Review of 8 published cases of pigmented onychomatricomas6-8 notes that 3 cases were associated with prior trauma to the affected nail, and 3 cases had a history of treatment of the affected nail for onychomycosis; however, the cause of this lesion is unknown. Biopsy of pigmented onychomatricomas demonstrates epithelial extensions into the dermis and proliferation of dermal spindle cells, the latter of which can stain positive for CD34 immunoperoxidase. Importantly, no evidence of melanocyte proliferation is found, which helps to distinguish this entity from subungual melanoma.7 Staining with cytokeratin immunoperoxidase can aid in identifying the epithelial component of the tumor.7 Pigmentation of the nail is thought to be secondary to activation of the melanocytes in the nail matrix.8This case presented with high suspicion for subungual melanoma, and consultation was sought from a nail specialist to obtain an appropriate biopsy. Proper orientation of the specimen for longitudinal sectioning is important to facilitate the correct diagnosis of pigmented onychomatricomas by the dermatopathologist.7 Long-term follow-up of onychomatricoma in the literature shows that the tumor responds well to complete surgical excision.9 Long-term prognosis for pigmented onychomatricomas is unknown owing to the small number of case reports and limited follow-up.

Dermatology

A man in his 40s presented to the dermatology clinic for evaluation of a new pigmented lesion on his left second toenail. The lesion first appeared 12 months before presentation and was progressively growing. This was his first time presenting to a physician for this problem, and no prior treatments had been attempted. The lesion was asymptomatic. He was otherwise well and denied any fevers or weight loss.Clinical examination revealed a dark brown longitudinal pigment band covering the full length of the toenail of the left second digit with corresponding nail thickening over the pigmented band. The pigment was the same width throughout the band and extended to the proximal nail fold (Figure, A). No other nail or skin lesions were found at the time of examination. A biopsy specimen was obtained from the nail plate and nail matrix and stained with hematoxylin-eosin (Figure, B-D).A dark brown longitudinal pigment band on the second toenail with pigment extends to the proximal nail fold (A). Histopathologic examination of the specimen with hematoxylin-eosin stain is seen at original magnification of ×40 (B), ×100 (C), and ×200 (D).

what is your diagnosis?

What is your diagnosis?

Pigmented squamous cell carcinoma in situ

Pigmented onychopapilloma

Subungual melanoma

Pigmented onychomatricoma

d

male

41-50

original

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2707239

A 17-year-old boy was referred from the general practitioner to the local psychosis early-detection clinic owing to a drop in functioning and social withdrawal during the previous 6 months. He began college 6 months prior but had found the workload difficult and failed his examinations. He had no family history of mental disorders, denied any current or past use of drugs, and reported no significant medical history. He was well kempt, was quiet during his interview, and provided short answers. He reported that he no longer enjoyed his former interests and could not relate to people at college or to friends, but there were no clear signs of depressive disorders. No formal thought disorders were elicited. He was 80% convinced that random people looked and talked about him when he was out in public but was able to question it. He stated that these people were probably commenting on the way he looked, but he did not believe these individuals meant him harm. He never acted on these thoughts. He also reported a vague feeling of perplexity and derealization. These experiences began when he started college and continued to occur every day for up to an hour at a time, causing significant distress. The Structured Clinical Interview for DSM did not reveal any mental disorder.Discharge to general practitioner with no clinical recommendationsClinical follow-up for at least 3 years and indicated primary prevention What Would You Do Next?

Discharge to general practitioner with no clinical recommendations

Pharmacotherapy with low-dose atypical antipsychotics

Clinical follow-up for at least 3 years and indicated primary prevention

Treatment with ω-3 fish oil dietary supplementation

The designation (not properly a diagnosis) is Clinical High Risk for Psychosis (CHR-P),1 attenuated psychotic symptoms subgroup, determined using the Comprehensive Assessment of At-risk Mental States (CAARMS).2 Prognosis: The increased risk of developing psychosis is 26% at 3 years (95% CI, 23%-30%).3

C

Clinical follow-up for at least 3 years and indicated primary prevention

Children, adolescents, and young adults (aged 8-40 years) who seek help at specialized early-detection clinics have an enhanced risk of developing mental disorders, such as psychosis, compared with the local age-matched general population (15%4 vs 0.43%5 at 3 years, respectively) (Figure). Fully addressing their presenting problems requires a prognosis, which is forecasting their risk (ie, probability) of developing future outcomes. The development of semistructured psychometric interviews (prognostic tools) to assess CHR-P criteria has allowed formulating a prognosis of being at risk or not at risk for psychosis.3 The original prognostic tool in this field (CAARMS2) was developed on the basis of accumulating knowledge of the specific symptoms that may predate the onset of psychosis (defined as binary outcome). The CAARMS is transdiagnostic, allowing the presence of several comorbid mental disorders at baseline, which are frequent in these patients.6 Specific training is needed to use it, and its administration usually requires 2 hours in the context of a clinical assessment.7 Extensive international validation has confirmed that in people referred to psychosis early-detection services, the CAARMS has an adequate prognostic performance, comparable with other prognostic instruments used in medicine.3 Vice versa, it does not work well outside these samples.3 Its potentials include a good ability to rule out a state of risk for psychosis, while its limitations include only a moderate ability to rule in a state of risk for psychosis (Figure).4 This prognostic tool has allowed one of the first preventive approaches to psychotic disorders to be implemented in psychiatry.8 Several other variants of the CAARMS have been developed with almost comparable prognostic performance.3 The use of these prognostic tools in individuals seeking help at psychosis early-detection clinics can impact their clinical management by (1) informing patients about their risk of developing psychosis, (2) establishing whether clinical monitoring is required, and (3) deciding whether to initiate preventive treatments or not.Individuals seeking help at specialized psychosis early-detection clinics have a higher risk of developing psychosis (15% at 3 years4) than the general population (0.43% at 3 years).5 Those who will meet the clinical high risk for psychosis (CHR-P) criteria at the prognostic interview (Comprehensive Assessment of At-risk Mental States [CAARMS]) will have only a modest increase in their level of risk for psychosis (1.8-fold, from 15% to 26%). Those not meeting the CHR-P criteria3 will have a substantial decrease of their risk (9-fold, from 15% to 1.56%).This patient was meeting the CHR-P criteria and therefore was predicted to have an enhanced risk (26% at 3 years3) (Figure) of developing emerging psychotic disorders over time, compared with help-seeking individuals not meeting CHR-P criteria (who have only 1.56% risk of developing psychosis at 3 years3) (Figure). First, we shared with this patient the result of the prognostic test in the context of psychoeducational support offered by psychosis early-detection clinics. Informing patients about their risks is an essential component of preventive approaches in all branches of medicine. For example, individuals who meet CHR-P criteria accumulate several risk factors for psychosis, some of which may be potentially modifiable.9 The second clinical impact of our prognostic assessment was to recommend close clinical monitoring for adverse clinical outcomes during the ensuing 3 years because this is the peak of risk.3 Finally, this patient was offered specific preventive interventions (indicated primary prevention) that were based on psychological therapies (cognitive behavioral therapy). These treatments aim to improve the presenting symptoms and disability10 and to stop the progression to psychosis. Although psychological therapies are currently recommended (while antipsychotics are not recommended),8 their effectiveness is not fully established and other experimental therapeutics have been investigated. Over the past years, ω-3 interventions have received high levels of interest because of their benign profile, but they were recently found not to be effective. The first ever pharmaceutical-funded randomized clinical trial in these patients (testing a phosphodiesterase-9 inhibitor) has just started and other first-in-class treatments are under testing.At 3-year follow-up, the patient had not developed psychosis. He fully recovered from his initial problems, completed his college examinations, and was able to enjoy his social life.

Psychiatry

A 17-year-old boy was referred from the general practitioner to the local psychosis early-detection clinic owing to a drop in functioning and social withdrawal during the previous 6 months. He began college 6 months prior but had found the workload difficult and failed his examinations. He had no family history of mental disorders, denied any current or past use of drugs, and reported no significant medical history. He was well kempt, was quiet during his interview, and provided short answers. He reported that he no longer enjoyed his former interests and could not relate to people at college or to friends, but there were no clear signs of depressive disorders. No formal thought disorders were elicited. He was 80% convinced that random people looked and talked about him when he was out in public but was able to question it. He stated that these people were probably commenting on the way he looked, but he did not believe these individuals meant him harm. He never acted on these thoughts. He also reported a vague feeling of perplexity and derealization. These experiences began when he started college and continued to occur every day for up to an hour at a time, causing significant distress. The Structured Clinical Interview for DSM did not reveal any mental disorder.Discharge to general practitioner with no clinical recommendationsClinical follow-up for at least 3 years and indicated primary prevention

what would you do next?

What would you do next?

Treatment with ω-3 fish oil dietary supplementation

Discharge to general practitioner with no clinical recommendations

Pharmacotherapy with low-dose atypical antipsychotics

Clinical follow-up for at least 3 years and indicated primary prevention

d

male

11-20

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2707476

A 16-year-old girl presented to our ataxia unit with a report of a peculiar finding in fundoscopy. Her parents were nonconsanguineous, and her family history was unremarkable. She had unsteadiness and frequent falls at gait initiation since age 16 months. There was a progressive worsening of her gait difficulties, and she complained of loss of balance.On examination, she had saccadic pursuit, subtle appendicular ataxia, and a spastic gait with a wide base. She could not stand or walk with her feet in the tandem position. Her muscle strength was normal. Achilles tendon reflexes and plantar responses were absent, and vibration sense was decreased in her toes and ankles.Visual acuity, color vision, and visual fields were normal. Fundoscopy revealed increased visibility of retinal nerve fibers, hiding the contours of retinal vessels bilaterally. Optical coherence tomography (OCT) showed increased thickness in the retinal nerve fiber layer (RNFL) (Figure 1).Ophthalmological findings include color fundus photograph of the right eye (A) with increased visibility of the retinal nerve fiber layer, which hides retinal vessel contour; an optical coherence tomographic vertical B-scan revealing a markedly thickened retinal nerve fiber layer (asterisks) (B), captured along the green line seen on a red-free image of fundus (C). What Is Your Diagnosis?

Leber hereditary optic neuropathy

Friedreich ataxia

Autosomal recessive spastic ataxia of Charlevoix-Saguenay

Complicated hereditary spastic paraplegia

C. Autosomal recessive spastic ataxia of Charlevoix-Saguenay

C

Autosomal recessive spastic ataxia of Charlevoix-Saguenay

Brain magnetic resonance imaging (MRI) showed upper cerebellar vermis atrophy, linear pontine T2 hypointensities, lateral pontine T2 hyperintensities, a posterior fossa arachnoid cyst, and thinning of the corpus callosum and cervical spinal cord (Figure 2). Per the clinical features, fundoscopy findings, and abnormalities on MRI, autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was suspected. Genetic testing identified biallelic pathogenic SACS mutations.Magnetic resonance imaging of the skull, including axial T2-weighted scan (A) revealing linear pontine hypointensities (black arrowhead) and lateral pontine hyperintensities (yellow arrowhead); sagittal T1-weighted scan (B) demonstrating atrophy of upper cerebellar vermis (yellow arrowhead), posterior fossa arachnoid cyst (asterisk), thinning of the corpus callosum (black arrowhead), and cervical spinal cord atrophy (white arrowhead).The first description of ARSACS derives from families of the Charlevoix and Saguenay regions of Quebec, Canada. The patients had unsteadiness and falls at gait initiation, followed by slowly progressive spastic ataxia and axonal-demyelinating peripheral neuropathy. Every affected individual presented with slurred speech, saccadic pursuit, and nystagmus, accompanied by a distinctive fundus appearance involving an increased visibility of the retinal nerve fibers hiding parts of the retinal vessels.1 Identification of the causative gene, SACS, and its product, the protein sacsin, occurred in 2000. Outside of Canada, most patients have disease onset in the first decade of life and display progressive spastic ataxia and peripheral neuropathy. However, retinal abnormalities are less frequent in non-Canadian individuals, and divergent presentations may exhibit adult onset, hearing loss, and supranuclear vertical gaze palsy.2 Moreover, the ataxia, spasticity, and peripheral neuropathy of the classic ARSACS triad might each be missing in patients with SACS mutations.3 Findings on MRI include upper cerebellar vermis atrophy, linear pontine T2 hypointensities, lateral pontine T2 hyperintensities, thickening of middle cerebellar peduncles, posterior fossa arachnoid cyst, corpus callosum thinning, and parietal atrophy.3 Optical coherence tomography reveals thickening of the RNFL, which is unknown in any other progressive neurodegenerative condition. Also, OCT is more sensitive in detecting retinal abnormalities in ARSACS compared with fundoscopy.4The authors of the original series considered the fundus seen in ARSACS similar to that in the acute phase of Leber hereditary optic neuropathy (LHON).1 Patients with LHON occasionally exhibit variable degrees of ataxia, spasticity, and peripheral neuropathy,5,6 and OCT may show increased RNFL thickness.7 However, retinal changes are asymptomatic and visual function is usually preserved in ARSACS, while in LHON, considerable visual loss occurs, accompanied by optic atrophy in late stages.Friedreich ataxia is the most common hereditary ataxia worldwide. Patients typically have childhood-onset ataxia, peripheral neuropathy, and a positive Babinski sign.8 This phenotype may resemble ARSACS, with mild or no spasticity. Nonetheless, OCT results are distinguishing; they demonstrate RNFL atrophy in most individuals with Friedreich ataxia.9Complicated cases of hereditary spastic paraplegia usually have autosomal recessive inheritance, and ataxia occurs in several types.10 One should differentiate patients with ataxia and corpus callosum atrophy, such as autosomal recessive spastic paraplegia-11 and spastic paraplegia-15, from ARSACS.3 Thickening of the RNFL is not a feature of hereditary spastic paraplegia, which may guide molecular investigation.In conclusion, fundoscopy and OCT findings were important diagnostic clues in a patient with mild spasticity; OCT can be diagnostic in ARSACS4 and is useful to refine genetic testing in recessive ataxias and spastic paraplegia. ARSACS is not curable, has no specific treatment, and progresses slowly, so diagnosis bears important prognostic implications. This patient received physiotherapy and is stable.

Neurology

A 16-year-old girl presented to our ataxia unit with a report of a peculiar finding in fundoscopy. Her parents were nonconsanguineous, and her family history was unremarkable. She had unsteadiness and frequent falls at gait initiation since age 16 months. There was a progressive worsening of her gait difficulties, and she complained of loss of balance.On examination, she had saccadic pursuit, subtle appendicular ataxia, and a spastic gait with a wide base. She could not stand or walk with her feet in the tandem position. Her muscle strength was normal. Achilles tendon reflexes and plantar responses were absent, and vibration sense was decreased in her toes and ankles.Visual acuity, color vision, and visual fields were normal. Fundoscopy revealed increased visibility of retinal nerve fibers, hiding the contours of retinal vessels bilaterally. Optical coherence tomography (OCT) showed increased thickness in the retinal nerve fiber layer (RNFL) (Figure 1).Ophthalmological findings include color fundus photograph of the right eye (A) with increased visibility of the retinal nerve fiber layer, which hides retinal vessel contour; an optical coherence tomographic vertical B-scan revealing a markedly thickened retinal nerve fiber layer (asterisks) (B), captured along the green line seen on a red-free image of fundus (C).

what is your diagnosis?

What is your diagnosis?

Leber hereditary optic neuropathy

Autosomal recessive spastic ataxia of Charlevoix-Saguenay

Complicated hereditary spastic paraplegia

Friedreich ataxia

b

female

11-20

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2689025

A 65-year-old woman was seen at the surgical clinic with reports of chronic back pain and a bulge in her back. History revealed multilevel cervical and lumbar fusion surgical procedures using anterior, left lateral, and posterior approaches over a 10-year period. The patient subsequently noted a new, slowly enlarging bulge in her left midback that was bothersome with activities of daily living (Figure, A). She denied pain directly overlying the area and was otherwise tolerating a regular diet and having usual bowel function. Physical examination revealed a soft bulge in the lateral left midback. There were no apparent associated skin changes, and the palpable mass appeared fixed and nonreducible. The mass was most apparent with upright posture and was accentuated with a cough impulse, but it was less distinct when examined in the prone position. Computed tomography of the abdomen and pelvis was obtained (Figure, B).Patient presentation (A) and computed tomography of the abdomen and pelvis (B). What Is Your Diagnosis?

Left lateral lumbar lipoma

Posterior lateral muscular atrophy with pseudohernia

Superior lumbar hernia (Grynfeltt-Lesshaft hernia)

Postoperative infected seroma

C. Superior lumbar hernia (Grynfeltt-Lesshaft hernia)

C

Superior lumbar hernia (Grynfeltt-Lesshaft hernia)

First described more than 4 centuries ago, lumbar hernias are rare defects of the posterior abdominal wall, with only 300 cases reported in the literature.1 Bounded by the 12th rib, iliac crest, erector spinae muscle, and external oblique muscle, the lumbar region can be further divided into the superior Grynfeltt-Lesshaft triangle and the inferior Petit triangle. The larger, more common area for lumbar hernia is within the Grynfeltt-Lesshaft triangle, defined by the 12th rib superiorly, quadratus lumborum medially, and internal oblique laterally.2 Lumbar hernias can be congenital or acquired in nature, and acquired hernias can be primary (spontaneous) or secondary (traumatic or incisional) in etiology.2 Incisional lumbar hernias have historically been most associated with nephrectomy, abdominal aortic aneurysm repair, resection of abdominal wall tumors, iliac bone donations, and latissimus dorsi flaps in plastic surgery.1 Because of the rarity of lumbar hernias, diagnosis is often challenging and requires clinical suspicion to avoid misdiagnosis and the potential complications of such hernias. Patient presentation is often variable and nonspecific, ranging from an asymptomatic bulge, to a lumbago with a palpable mass that increases with strenuous activity, to vague abdominal discomfort with changes in bowel or bladder function. Contents of the hernia sac may include colon, omentum, small bowel, kidney, spleen, or stomach, with a potential risk for incarceration or strangulation and the resulting sequelae.1 Thorough physical examination and a high index of suspicion are critical to guiding the selection of supporting imaging studies for lumbar hernias. Extraperitoneal fat herniated through a wall defect may mimic a lipoma, which may be incorrectly confirmed if ultrasound is performed and interpreted by an inexperienced technologist.3 However, computed tomography is more likely to make a definitive diagnosis and add information on parietal defect size, hernia content, and muscular atrophy.4Given this patient’s extensive lumbar surgical history, clinical suspicion of a lumbar hernia had to be considered in the differential diagnosis. Although the physical characteristics of the patient’s mass may have been suggestive of other pathologies that manifest as a superficial flank mass more commonly, such as a lipoma, the reducibility of the mass on prone positioning and prominence with cough impulse was more suggestive of lumbar hernia.5 The addition of computed tomography to the preoperative workup was essential for distinguishing a true lumbar hernia from posterior lateral wall muscular atrophy with pseudohernia. Flank incisions, as may be encountered with this patient’s surgical history, can result in denervation injury to intercostal nerves and laxity of the oblique abdominal wall musculature, without true fascial defect.6 There was nothing to suggest local or systemic infection in the patient’s history or physical examination. No skin changes or pain overlying the palpable mass was observed on physical examination, and computed tomography did not demonstrate a fluid collection but rather a Grynfeltt-Lesshaft lumbar hernia containing a portion of incarcerated colon. After the correct diagnosis was made, the patient underwent a successful laparoscopic repair with mesh.

Surgery

A 65-year-old woman was seen at the surgical clinic with reports of chronic back pain and a bulge in her back. History revealed multilevel cervical and lumbar fusion surgical procedures using anterior, left lateral, and posterior approaches over a 10-year period. The patient subsequently noted a new, slowly enlarging bulge in her left midback that was bothersome with activities of daily living (Figure, A). She denied pain directly overlying the area and was otherwise tolerating a regular diet and having usual bowel function. Physical examination revealed a soft bulge in the lateral left midback. There were no apparent associated skin changes, and the palpable mass appeared fixed and nonreducible. The mass was most apparent with upright posture and was accentuated with a cough impulse, but it was less distinct when examined in the prone position. Computed tomography of the abdomen and pelvis was obtained (Figure, B).Patient presentation (A) and computed tomography of the abdomen and pelvis (B).

what is your diagnosis?

What is your diagnosis?

Left lateral lumbar lipoma

Postoperative infected seroma

Superior lumbar hernia (Grynfeltt-Lesshaft hernia)

Posterior lateral muscular atrophy with pseudohernia

c

female

61-70

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2695514

A 56-year-old man presented to the emergency department with a 3-week history of worsening neck and shoulder pain. He had been seen in his primary care physician’s office about 2 weeks prior to emergency department presentation and had been treated for musculoskeletal symptoms. He had no history of recent trauma. He admitted to paresthesia and pain radiating down his right arm but denied any weakness. He had no difficulty with speech or swallowing. He had no medical comorbidities or prior surgery. On examination, he was noted to have some cervical midline spine tenderness. No weakness or sensory deficits were identified. No palpable lymphadenopathy, swelling, or mass was noted. A plain radiograph of the neck demonstrated tracheal deviation, and he then underwent computed tomography of the chest (Figure 1A) and magnetic resonance imaging of the cervical and thoracic spine (Figure 1B).Computed tomography scan and magnetic resonance image. A, Coronal computed tomography image of the chest; B, sagittal magnetic resonance image of the cervical and thoracic spine. What Is Your Diagnosis?

Metastatic lung cancer

Traumatic vertebral body fracture

Thyroid goiter with compressive symptoms

A pathological vertebral body fracture

D. A pathological vertebral body fracture, in this case from metastatic thyroid cancer

D

A pathological vertebral body fracture

In the absence of trauma or injury, there was a high index of suspicion that the fracture of the first thoracic vertebral body noted on imaging was pathological. The thyroid goiter was primarily mediastinal and not associated with any symptoms of dysphagia or airway obstruction. A fine-needle aspiration of the left thyroid lobe was performed. The cervical spine fracture was felt to be unstable. The patient underwent a posterior spinal fusion and concurrent bone biopsy. The tissue samples from the thyroid gland and the first thoracic vertebral body were suggestive of papillary thyroid cancer. Four weeks later, he underwent a total thyroidectomy and central compartment lymph node dissection (Figure 2).Thyroid cancer is the fastest-growing cancer in the United States. A small proportion of differentiated thyroid cancers present with bone metastases (2%-13%).1 The prognosis in localized differentiated thyroid cancer is good, with 97% of patients surviving to 10 years. Ten-year survival is reduced by at least 14% in the presence of osseous metastases.1 The frequency of skeletal metastases is highest to the spine and pelvis.1 Most of these patients have follicular thyroid cancer.1 Although cervical cord compression from the direct extension of papillary thyroid cancer to the cervical spine has been reported, metastases to the spine from localized papillary thyroid cancer are uncommon.2,3 Multiple bone metastases have been noted as more common than single bone lesions.3 Distant metastases in the setting of well-differentiated thyroid cancer without neck swelling are extremely rare4; when they occur, osseous and pulmonary metastases are the most frequent sites.4Therapeutic options for patients with spinal metastases from well-differentiated thyroid cancer include radioiodine therapy, pharmacological treatment with bisphosphonates, surgical resection of the primary cancer, and standard or minimally invasive spine surgery.5,6 A multidisciplinary approach is required to achieve goals of care, which are primarily to control pain, stabilize neurological function, and achieve local disease control.6In this case, the initial priority was to stabilize the cervical spine, after which the primary cancer was resected. A sternotomy was required for optimal exposure. The final pathology on the resected specimen showed a tumor with papillary features; however, this was noted to be poorly differentiated and classified as an insular thyroid cancer. This is a rare thyroid malignant subtype, often characterized by an advanced stage at initial presentation and an aggressive course.7The patient recovered from surgery and underwent radioiodine ablative therapy. In addition to the spinal disease, he was noted to have multiple subcentimeter pulmonary nodules that raised concerns about metastases. The presence of both pulmonary and skeletal metastases significantly reduces long-term survival in patients with well-differentiated thyroid cancer.8 Pulmonary metastases in young patients have been associated with a 10-year survival rate of 50%; in contrast, no patients with skeletal metastases survived this long.8 The principal determinants of long-term survival in patients with metastatic thyroid cancer are age, the site of distant metastases, and whether the metastatic lesions take up radioactive iodine.8Thyroid cancer and neck pain are common clinical problems. However, this case uniquely describes a presentation of spinal metastases with neck pain in the setting of a large mediastinal malignant thyroid mass, with the unusual feature of no visible or palpable neck swelling.

Surgery

A 56-year-old man presented to the emergency department with a 3-week history of worsening neck and shoulder pain. He had been seen in his primary care physician’s office about 2 weeks prior to emergency department presentation and had been treated for musculoskeletal symptoms. He had no history of recent trauma. He admitted to paresthesia and pain radiating down his right arm but denied any weakness. He had no difficulty with speech or swallowing. He had no medical comorbidities or prior surgery. On examination, he was noted to have some cervical midline spine tenderness. No weakness or sensory deficits were identified. No palpable lymphadenopathy, swelling, or mass was noted. A plain radiograph of the neck demonstrated tracheal deviation, and he then underwent computed tomography of the chest (Figure 1A) and magnetic resonance imaging of the cervical and thoracic spine (Figure 1B).Computed tomography scan and magnetic resonance image. A, Coronal computed tomography image of the chest; B, sagittal magnetic resonance image of the cervical and thoracic spine.

what is your diagnosis?

What is your diagnosis?

Thyroid goiter with compressive symptoms

Traumatic vertebral body fracture

A pathological vertebral body fracture

Metastatic lung cancer

c

male

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2702289

An otherwise healthy woman in her 30s presented to an outside health care professional with a 2-day history of floaters in her left eye. She denied additional ocular symptoms and reported no relevant medical, ocular, or family history; medication use; or allergies. The findings of a review of systems were unremarkable. A workup for posterior uveitis was initiated, and the patient began therapy with oral antiviral and oral corticosteroid medications. One week later, her symptoms had worsened, and she was referred for consultation.Best-corrected visual acuity was 20/15 OD and 20/60 OS. Intraocular pressures, extraocular movements, visual fields by confrontation, and pupil responses were normal. Anterior segment examination and dilated fundus examination of the right eye had normal findings. However, the left eye had 3+ anterior chamber cell and 1+ flare, nongranulomatous keratic precipitates, and a clear lens. The dilated fundus examination revealed 2+ vitritis, a hyperemic disc with blurred margins, macular striae with a blunted foveal reflex, and vascular sheathing with segmental periarteriolar inflammatory plaques in multiple quadrants. The peripheral retina had well-demarcated peripheral retinal whitening with scalloped margins and intraretinal hemorrhages in all quadrants (Figure 1A and B). Four days later, repeat fundus photography showed that the peripheral lesions had coalesced into larger circumferential necrotic regions (Figure 1C).A, Color fundus photography montage of the left eye shows hyperemic disc with blurred margins, vascular sheathing, and peripheral retinal whitening. B, Magnified image of the temporal retina shows well-demarcated infiltrates with scalloped margins and adjacent intraretinal hemorrhages. C, Montage from 4 days later shows convergence of necrotic lesions in a circumferential pattern around the equator with confluence in the anterior periphery. Fresh laser barricade spots are seen at the posterior margin of the areas of necrosis.Order a hypercoagulable workup and start a regimen of aspirin, 325 mg dailyObtain an aqueous fluid sample for polymerase chain reaction and treat with antiviral agentsObtain a vitreous sample for culture and inject vancomycin and ceftazidime What Would You Do Next?

Inject an antivascular endothelial growth factor agent

Order a hypercoagulable workup and start a regimen of aspirin, 325 mg daily

Obtain an aqueous fluid sample for polymerase chain reaction and treat with antiviral agents

Obtain a vitreous sample for culture and inject vancomycin and ceftazidime

Acute retinal necrosis

C

Obtain an aqueous fluid sample for polymerase chain reaction and treat with antiviral agents

The patient received a diagnosis of acute retinal necrosis (ARN) on the basis of clinical findings, with aqueous fluid polymerase chain reaction confirming varicella zoster virus DNA. Multifocal, full-thickness peripheral retinal whitening with scalloped borders and vitritis in a healthy adult is a classic presentation. Treatment with an antivascular endothelial growth factor agent (choice A) or possibly a hypercoagulable workup (choice B) would be indicated for a healthy young patient who developed a central retinal vein occlusion with macular edema. Collection of a vitreous sample and culture with injection of intravitreal antibiotics (choice D) is indicated in cases of suspected bacterial endophthalmitis.Acute retinal necrosis was first reported in a case series by Urayama et al1 in 1971. It is characterized by the triad of peripheral necrotizing retinitis, vitritis, and vasculitis with a high risk of rhegmatogenous retinal detachment. The peripheral necrotizing retinitis is multifocal and full thickness in well-demarcated patches with scant hemorrhage. These lesions coalesce circumferentially and progress rapidly toward the posterior pole (Figure 1C).2-4Acute retinal necrosis is rare, with a British study reporting an annual incidence of 1 case per 2 million people, and can occur in healthy or immunocompromised patients of any sex or age, with bimodal peaks at 20 and 50 years of age.5 Members of the human herpes virus family are the causative agents, most commonly varicella zoster virus followed by herpes simplex virus.6 Although ARN is primarily a clinical diagnosis, laboratory studies, including polymerase chain reaction testing, can be useful.Management focuses on halting the spread of disease and preventing late-onset sequelae, especially rhegmatogenous retinal detachment. Classic treatment includes hospitalization and treatment with intravenous acyclovir at a dosage of 10 mg/kg 3 times daily for 7 to 10 days followed by long-term maintenance therapy with oral valacyclovir at a dosage of 1 g daily for 6 months or more.6 A 2017 report from the American Academy of Ophthalmology recommended initial induction with oral valacyclovir at a dosage of 2 g administered 4 times daily for cases without central nervous system involvement. Intravitreal injections of foscarnet at a dosage of 2.4 mg/0.1 mL or ganciclovir 4 mg/0.1 mL can supplement systemic therapy.Without treatment, two-thirds of patients with ARN will develop bilateral ARN and/or rhegmatogenous retinal detachment.7 Prognosis is poor, with a study reporting final visual acuity worse than 20/200 in 50% of all patients 3 months after diagnosis, increasing to 75% after 5 years.8Improved outcomes are associated with the absence of optic neuropathy, sparing of the posterior pole, prompt initiation of antiviral therapy, prophylactic vitrectomy, and prophylactic laser barricade to regions with peripheral necrosis.7,9The patient was treated with systemic and intravitreal antiviral medications and was provided long-term oral antiviral prophylaxis. Confluent 360 prophylactic laser barricade was performed. Subsequent complications included vitreomacular traction syndrome and rhegmatogenous retinal detachment requiring separate pars plana vitrectomy operations. The patient’s vision has remained stable for 6 years with best-corrected visual acuity 20/40 in the affected eye.

Ophthalmology

An otherwise healthy woman in her 30s presented to an outside health care professional with a 2-day history of floaters in her left eye. She denied additional ocular symptoms and reported no relevant medical, ocular, or family history; medication use; or allergies. The findings of a review of systems were unremarkable. A workup for posterior uveitis was initiated, and the patient began therapy with oral antiviral and oral corticosteroid medications. One week later, her symptoms had worsened, and she was referred for consultation.Best-corrected visual acuity was 20/15 OD and 20/60 OS. Intraocular pressures, extraocular movements, visual fields by confrontation, and pupil responses were normal. Anterior segment examination and dilated fundus examination of the right eye had normal findings. However, the left eye had 3+ anterior chamber cell and 1+ flare, nongranulomatous keratic precipitates, and a clear lens. The dilated fundus examination revealed 2+ vitritis, a hyperemic disc with blurred margins, macular striae with a blunted foveal reflex, and vascular sheathing with segmental periarteriolar inflammatory plaques in multiple quadrants. The peripheral retina had well-demarcated peripheral retinal whitening with scalloped margins and intraretinal hemorrhages in all quadrants (Figure 1A and B). Four days later, repeat fundus photography showed that the peripheral lesions had coalesced into larger circumferential necrotic regions (Figure 1C).A, Color fundus photography montage of the left eye shows hyperemic disc with blurred margins, vascular sheathing, and peripheral retinal whitening. B, Magnified image of the temporal retina shows well-demarcated infiltrates with scalloped margins and adjacent intraretinal hemorrhages. C, Montage from 4 days later shows convergence of necrotic lesions in a circumferential pattern around the equator with confluence in the anterior periphery. Fresh laser barricade spots are seen at the posterior margin of the areas of necrosis.Order a hypercoagulable workup and start a regimen of aspirin, 325 mg dailyObtain an aqueous fluid sample for polymerase chain reaction and treat with antiviral agentsObtain a vitreous sample for culture and inject vancomycin and ceftazidime

what would you do next?

What would you do next?

Obtain a vitreous sample for culture and inject vancomycin and ceftazidime

Order a hypercoagulable workup and start a regimen of aspirin, 325 mg daily

Inject an antivascular endothelial growth factor agent

Obtain an aqueous fluid sample for polymerase chain reaction and treat with antiviral agents

d

female

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2702290

A 47-year old woman with a history of adult-onset asthma and waxing and waning bilateral swelling of the upper eyelids presented with greater swelling of the left than right upper eyelids with yellow lesions (Figure 1A). Previous episodes had been treated successfully with oral prednisone, and the patient had numerous recurrences within the past 10 years. According to the patient’s report, a biopsy was performed several years ago at an outside institution, and the diagnosis was xanthelasma. She denied visual changes.A, External photograph demonstrating bilateral periorbital swelling greater in the left than right eyelids, with associated yellow lesions. B, Axial computed tomographic scan with contrast demonstrating enlargement and homogeneous enhancement of the left lacrimal gland and left lateral rectus muscle and bilateral preseptal soft tissues.Visual acuity was 20/40 OU and improved to 20/25 OU with pinhole testing. Intraocular pressures were normal, extraocular motility was full, and the pupils were round and reactive without an afferent pupillary defect. Results of the examination revealed yellow lesions on both eyelids, palpebral swelling greater in the left than the right eye, erythema, ptosis, an S-shaped deformity of the left upper eyelid, and a palpable mass of the left superolateral orbit (Figure 1A). Hertel exophthalmometry showed 2 mm of relative proptosis in the left eye. Results of slitlamp and dilated fundus examinations were unremarkable. A computed tomographic scan showed preseptal soft tissue swelling in both eyes and an extraconal left lacrimal gland mass extending behind the globe (Figure 1B). We contacted the outside institution, and no reports of histopathologic examination of the biopsy specimen were found. What Would You Do Next?

Oral antibiotic treatment

Surgical debulking

Oral corticosteroid treatment and biopsy

Corticosteroid-sparing immunosuppressive therapy

Adult-onset asthma and periocular xanthogranuloma

C

Oral corticosteroid treatment and biopsy

The patient started prednisone therapy with rapid improvement of symptoms. Biopsy with surgical debulking was performed in both eyes, and histopathologic evaluation revealed an inflammatory infiltration of foamy histiocytes and Touton giant cells consistent with xanthogranuloma (Figure 2). The mass noted on examination and imaging is not a common manifestation of an infection, making oral antibiotics (choice A) a less preferred answer. Surgical debulking (choice B) could be considered; however, most cases treated with debulking require additional therapy for resolution.1 Starting immunosuppressive therapy (choice D) could be considered; however, these agents elicit a variable response and often are used in conjunction with other modalities.1Histopathologic sample of the left upper eyelid mass revealing mononucleated foamy histiocytes (xanthoma cells) with lymphocytes, plasma cells, and Touton giant cells (hematoxylin-eosin stain, original magnification ×10).Adult orbital xanthogranulomatous disease consists of 4 syndromes defined as class II non–Langerhans cell histiocytic disorders. The syndromes are distinguished by the degree of systemic involvement, with adult-onset xanthogranuloma and adult-onset asthma and periocular xanthogranuloma (AAPOX) typically being localized to the orbit with a good prognosis, and necrobiotic xanthogranuloma and Erdheim Chester disease having more extensive systemic features and a poor prognosis. Their histopathologic findings have a similar appearance, although necrosis is seen only in necrobiotic xanthogranuloma.1 Given the patient’s histopathologic findings, history of adult-onset asthma, and lack of other systemic findings, she was diagnosed with AAPOX. A complete blood cell count and serum immunofixation were evaluated to rule out lymphoproliferative disorders and paraproteinemia, which can occasionally be associated with AAPOX and commonly with necrobiotic xanthogranuloma.Patients with adult-onset xanthogranulomatous disease frequently present with palpebral swelling, a yellow-orange elevated eyelid, and/or orbital masses.1,2 Although the yellowish patches are described as xanthelasmalike, true xanthelasmas are rarely associated with xanthogranulomatous disease of the orbit.3 Although this presentation was suggestive of xanthogranulomatous disease, the diagnosis is histopathologic, and a biopsy is required for confirmation. Sheets of mononucleated, foamy histiocytes and the presence of Touton giant cells are diagnostic.At present, no randomized clinical trials have evaluated therapies for periocular xanthogranuloma. Systemic and intralesional corticosteroids, surgical debulking, radiotherapy, and various immunosuppressive chemotherapeutic agents have shown variable success.4-6 Systemic corticosteroids are the most commonly used treatment at a dose of 1 mg/kg, and recurrence with tapering of corticosteroid therapy is common.1 Surgical debulking is reported to have been successful in 75% of patients with AAPOX,6 although Jakobiec et al7 report recurrence of disease within 6 to 12 months when surgical debulking is performed without any other concurrent therapy. Although their recommended therapy consists of corticosteroids plus radiotherapy, other investigators8 have shown exacerbation of signs and symptoms in 75% of patients receiving orbital radiation therapy. Immunosuppressive therapies that have shown success include methotrexate sodium, rituximab, cyclosporine, and etanercept.4-6 Chemotherapeutic agents, including chlorambucil, cyclophosphamide, melphalan hydrochloride, etoposide, vincristine sulfate, vinblastine sulfate, and doxorubicin hydrochloride, are generally reserved for necrobiotic xanthogranuloma and Erdheim Chester disease, for which prognosis is considerably worse and mortality can be high.6After a course of oral prednisone and surgical debulking, the patient’s signs and symptoms resolved. However, owing to her recurrent disease, she is currently considering starting systemic immunosuppressive therapy.

Ophthalmology

A 47-year old woman with a history of adult-onset asthma and waxing and waning bilateral swelling of the upper eyelids presented with greater swelling of the left than right upper eyelids with yellow lesions (Figure 1A). Previous episodes had been treated successfully with oral prednisone, and the patient had numerous recurrences within the past 10 years. According to the patient’s report, a biopsy was performed several years ago at an outside institution, and the diagnosis was xanthelasma. She denied visual changes.A, External photograph demonstrating bilateral periorbital swelling greater in the left than right eyelids, with associated yellow lesions. B, Axial computed tomographic scan with contrast demonstrating enlargement and homogeneous enhancement of the left lacrimal gland and left lateral rectus muscle and bilateral preseptal soft tissues.Visual acuity was 20/40 OU and improved to 20/25 OU with pinhole testing. Intraocular pressures were normal, extraocular motility was full, and the pupils were round and reactive without an afferent pupillary defect. Results of the examination revealed yellow lesions on both eyelids, palpebral swelling greater in the left than the right eye, erythema, ptosis, an S-shaped deformity of the left upper eyelid, and a palpable mass of the left superolateral orbit (Figure 1A). Hertel exophthalmometry showed 2 mm of relative proptosis in the left eye. Results of slitlamp and dilated fundus examinations were unremarkable. A computed tomographic scan showed preseptal soft tissue swelling in both eyes and an extraconal left lacrimal gland mass extending behind the globe (Figure 1B). We contacted the outside institution, and no reports of histopathologic examination of the biopsy specimen were found.

what would you do next?

What would you do next?

Surgical debulking

Oral antibiotic treatment

Corticosteroid-sparing immunosuppressive therapy

Oral corticosteroid treatment and biopsy

d

female

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2703142

A 29-year-old white woman presented for a second opinion of left eye pain, blurred vision, and photophobia. Six weeks before, she received eyebrow laser epilation with an 800-nm diode laser (LightSheer; Lumenis). During the session, the physician assistant removed the metal eye shield for better exposure, immediately after which the patient developed eye pain and blurred vision. She was initially treated for acute iritis with difluprednate, 4 times daily, which was tapered to once daily, with minimal improvement in her symptoms. The patient reported a negative review of systems and denied recent travel, trauma, use of antibiotics, or pregnancy. Her examination was notable for best-corrected visual acuity of 20/20 OU, anterior chamber (AC) pigment and flare in the left eye, and iris irregularities, including decreased iris reactivity, peripupillary transillumination defects (Figure, A), and posterior synechiae. She had mild intraocular pressure (IOP) asymmetry of 12 mm Hg OD and 17 mm Hg OS.A, An irregular pupil, iris atrophy, and peripupillary transillumination defects are observed. B, After discontinuation of the cycloplegic agent, posterior concavity of the iris and iris-lens touch consistent with reverse pupillary block are observed.Gonioscopy revealed increased trabecular meshwork pigmentation in the left eye. Ultrasonographic biomicroscopy and anterior segment optical coherence tomography demonstrated a normal anterior segment in the right eye and posterior bowing of the iris and lens-iris touch (Figure, B) with a normal AC depth in the left eye. Optical biometry (Lenstar LS 900; Haag-Streit) was unremarkable bilaterally, with normal axial length, AC depth, and lens thickness.Further taper her corticosteroid dosage and start a cycloplegic agent to break posterior synechiaePerform AC paracentesis and send fluid for viral polymerase chain reaction analysis What Would You Do Next?

Increase her topical corticosteroid dosage

Further taper her corticosteroid dosage and start a cycloplegic agent to break posterior synechiae

Perform AC paracentesis and send fluid for viral polymerase chain reaction analysis

Perform urgent peripheral iridotomy given IOP asymmetry

Pigment dispersion syndrome secondary to diode laser eyebrow epilation

B

Further taper her corticosteroid dosage and start a cycloplegic agent to break posterior synechiae

Laser-assisted hair removal has become increasingly popular since lasers were approved for hair removal in 1996. Epilation is achieved via thermal photothermolysis.1 Laser light is selectively absorbed by melanin and does not affect the surrounding dermal or epidermal tissue. The most commonly used lasers are ruby (694 nm), alexandrite (755 nm), diode (800-810 nm), Nd:YAG (1064 nm), and intense pulsed-light source (550-1200 nm). Serious ocular complications have been reported, leading guidelines to advise the use of special eye protection.2,3Of the prior reported cases of laser ocular complications, alexandrite laser was the most commonly used, followed by the diode laser.4-10 These complications can occur even when proper eye protection was used,9 although in most cases patients were not wearing eye shields. Damage occurs because the laser is selectively absorbed by melanin of the iris.Initial visual acuity in reported cases ranged from 20/20 to 20/40 in the affected eyes.4-10 The most common complaints were eye redness, photophobia, and pain. The most common examination findings included pupil irregularities, decreased pupil reactivity, AC inflammation, and posterior synechiae. All patients were treated with topical corticosteroid and cycloplegic agents.This patient was treated for 6 weeks with potent topical corticosteroids with incomplete resolution of AC cell and pigment changes. We concluded that the AC reaction was associated with pigment dispersion rather than acute inflammation, given the iris transillumination, atrophy, and increased meshwork pigmentation, making an increase in corticosteroid therapy (choice A) less favorable. The history and course point to a clear causative agent of AC changes; therefore, AC paracentesis for herpes simplex virus, varicella-zoster virus, and Epstein-Barr virus polymerase chain reaction analysis (choice C) was not performed. If she experienced a flare during the corticosteroid taper, AC viral polymerase chain reaction for further workup would be a reasonable choice.Ultrasonographic biomicroscopy and anterior segment optical coherence tomography demonstrated posterior bowing of the iris and lens-iris touch. Given the lack of acute pupillary block, peripheral iridotomy was not performed (choice D). Based on the evidence of persistent reverse pupillary block and IOP asymmetry, we recommended that she undergo routine follow-up for suspected glaucoma. If she develops further IOP elevation or measurable glaucoma damage, laser peripheral iridotomy could be considered as a low-risk intervention to prevent glaucomatous vision loss. Of course, selective laser trabeculoplasty or treatment with ocular hypotensives could be considered in this situation as well.The patient started a topical corticosteroid taper and cycloplegic drops to break posterior synechiae. At 4 weeks after presentation, she had completed the prescription for eyedrops. By 5 months, she was improved, but continued to have photophobia, despite the resolution of AC inflammation. Her iris function normalized, but she continued to have diffuse peripupillary transillumination defects and posterior synechiae. For light sensitivity, she was fitted with opaque contact lenses. She reports that the persistent photophobia and nighttime glare continue to have a substantial effect on her quality of life.

Ophthalmology

A 29-year-old white woman presented for a second opinion of left eye pain, blurred vision, and photophobia. Six weeks before, she received eyebrow laser epilation with an 800-nm diode laser (LightSheer; Lumenis). During the session, the physician assistant removed the metal eye shield for better exposure, immediately after which the patient developed eye pain and blurred vision. She was initially treated for acute iritis with difluprednate, 4 times daily, which was tapered to once daily, with minimal improvement in her symptoms. The patient reported a negative review of systems and denied recent travel, trauma, use of antibiotics, or pregnancy. Her examination was notable for best-corrected visual acuity of 20/20 OU, anterior chamber (AC) pigment and flare in the left eye, and iris irregularities, including decreased iris reactivity, peripupillary transillumination defects (Figure, A), and posterior synechiae. She had mild intraocular pressure (IOP) asymmetry of 12 mm Hg OD and 17 mm Hg OS.A, An irregular pupil, iris atrophy, and peripupillary transillumination defects are observed. B, After discontinuation of the cycloplegic agent, posterior concavity of the iris and iris-lens touch consistent with reverse pupillary block are observed.Gonioscopy revealed increased trabecular meshwork pigmentation in the left eye. Ultrasonographic biomicroscopy and anterior segment optical coherence tomography demonstrated a normal anterior segment in the right eye and posterior bowing of the iris and lens-iris touch (Figure, B) with a normal AC depth in the left eye. Optical biometry (Lenstar LS 900; Haag-Streit) was unremarkable bilaterally, with normal axial length, AC depth, and lens thickness.Further taper her corticosteroid dosage and start a cycloplegic agent to break posterior synechiaePerform AC paracentesis and send fluid for viral polymerase chain reaction analysis

what would you do next?

What would you do next?

Perform AC paracentesis and send fluid for viral polymerase chain reaction analysis

Perform urgent peripheral iridotomy given IOP asymmetry

Increase her topical corticosteroid dosage

Further taper her corticosteroid dosage and start a cycloplegic agent to break posterior synechiae

d

female

21-30

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2705357

A healthy 10-year-old girl with a recent history of blunt trauma to the left eye presented to the emergency department with acute-onset blurry vision and pain. On her initial ophthalmic examination 3 weeks earlier, she was diagnosed with commotio retinae and traumatic iritis in the left eye after being struck with the brim of a hat. She was treated with a topical corticosteroid, with rapid resolution of iritis and commotio. However, she developed ipsilateral, asymptomatic grade 2 optic disc edema. Best-corrected visual acuity was 20/20 OU with a 2-diopter myopic shift in the left eye. There was no afferent pupillary defect, color vision was normal, and intraocular pressure (IOP) was 10 mm Hg OD and 8 mm Hg OS. Visual field testing revealed an enlarged blind spot in the left eye, and optical coherence tomography of the left eye revealed thickening of the retinal nerve fiber layer in all quadrants. The results of examination and testing of the right eye were unremarkable. The results of workup with a complete blood cell count, basic metabolic panel, angiotensin-converting enzyme measurement, Lyme disease testing, and antinuclear antibody measurement were unremarkable.Ophthalmic examination in the emergency department revealed diminished visual acuity to counting fingers, an IOP of 59 mm Hg, and a relative afferent pupillary defect in the left eye. Additional findings included corneal microcystic edema, formed anterior chamber without hyphema, and stable grade 2 optic disc edema.Order magnetic resonance imaging of the brain with venography What Would You Do Next?

Order magnetic resonance imaging of the brain with venography

Perform gonioscopy

Instill a miotic agent

Perform peripheral iridotomy

Closure of traumatic cyclodialysis cleft

C

Instill a miotic agent

Given the high suspicion for traumatic cyclodialysis cleft (CDC) closure, attempted gonioscopy is indicated. Magnetic resonance imaging of the brain with venography can be considered if the cause of optic disc edema remains unclear. A miotic agent can result in enlargement of cleft and is contraindicated. Peripheral iridotomy has no role in cleft treatment.Historically, iatrogenic CDCs were offered in the treatment of glaucoma.1,2 Today, CDCs mostly occur after blunt ocular trauma and less commonly after intraocular surgery.3 Cyclodialysis clefts cause hypotony secondary to separation of the ciliary body’s longitudinal muscle from the scleral spur, resulting in increased uveoscleral outflow.4 Most occur in males because of increased prevalence of trauma.5 Suspicion for cleft should increase if hyphema or iris sphincter tear is present.4 If hypotony is severe (IOP <5 mm Hg), patients may develop ocular hypotony syndrome, which can manifest with shallowed anterior chamber, optic disc edema, and/or chorioretinal folds.4In the past, gonioscopy was the criterion standard for diagnosis; however, the addition of ultrasound biomicroscopy is now recommended.6 Ultrasound biomicroscopy allows visualization of the cleft’s extent and associated suprachoroidal fluid, even if the angle cannot be visualized through gonioscopy. In cases of severely shallow anterior chamber, instillation of viscoelastic and direct gonioscopy in the operating room may be necessary.7A well-known complication of CDC is IOP spike after cleft closure, secondary to restoration of ciliary body function with aqueous humor production and underperformance of the trabecular meshwork.6 Ocular hypertension typically responds well to topical IOP-lowering medications, the use of which can be discontinued as the trabecular meshwork regains its function. Progression to glaucoma is rare.5,8A recent review by González-Martín-Moro et al6 provided an up-to-date summary of treatment options. A mydriatic agent, such as atropine, is recommended initially to relax the ciliary body and reoppose the muscle to sclera. If a topical corticosteroid is initially indicated, rapid corticosteroid taper is recommended to promote cleft closure. Because visual acuity outcomes are most dependent on the presence of retinal pathologic findings, González-Martín-Moro et al6 conclude that surgical intervention is indicated in cases of symptomatic hypotony that last longer than 8 weeks. If a cataract is present, lens extraction with sulcus intraocular lens or sulcus capsular tension rings should be considered first. Otherwise, the following interventions are recommended: argon laser for clefts smaller than 3 clock hours in size, direct cyclopexy for clefts 3 to 6 clock hours in size, and vitrectomy with endotamponade for clefts larger than 6 clock hours in size.The patient presented with spontaneous cleft closure and a resultant spike in IOP. Gonioscopy revealed a cleft that spanned 2 clock hours (Figure, A). Immediate treatment with topical antihypertensives and 1 dose of 500 mg of intravenous acetazolamide resulted in reduction of IOP to 30 mm Hg within 3 hours. The next day, visual acuity returned to 20/20, IOP was 14 mm Hg, and corneal edema resolved. Topical therapy was tapered, and the myopia resolved. Cleft closure was further confirmed by ultrasound biomicroscopy (Figure, B). Three months after cleft closure, the optic disc edema resolved.A, Gonioscopy showing a cyclodialysis cleft that spans approximately 2 clock hours. B, Ultrasound biomicroscopy showing angle recession (yellow arrowhead) and residual suprachoroidal fluid (red arrowhead) after cleft closure.

Ophthalmology

A healthy 10-year-old girl with a recent history of blunt trauma to the left eye presented to the emergency department with acute-onset blurry vision and pain. On her initial ophthalmic examination 3 weeks earlier, she was diagnosed with commotio retinae and traumatic iritis in the left eye after being struck with the brim of a hat. She was treated with a topical corticosteroid, with rapid resolution of iritis and commotio. However, she developed ipsilateral, asymptomatic grade 2 optic disc edema. Best-corrected visual acuity was 20/20 OU with a 2-diopter myopic shift in the left eye. There was no afferent pupillary defect, color vision was normal, and intraocular pressure (IOP) was 10 mm Hg OD and 8 mm Hg OS. Visual field testing revealed an enlarged blind spot in the left eye, and optical coherence tomography of the left eye revealed thickening of the retinal nerve fiber layer in all quadrants. The results of examination and testing of the right eye were unremarkable. The results of workup with a complete blood cell count, basic metabolic panel, angiotensin-converting enzyme measurement, Lyme disease testing, and antinuclear antibody measurement were unremarkable.Ophthalmic examination in the emergency department revealed diminished visual acuity to counting fingers, an IOP of 59 mm Hg, and a relative afferent pupillary defect in the left eye. Additional findings included corneal microcystic edema, formed anterior chamber without hyphema, and stable grade 2 optic disc edema.Order magnetic resonance imaging of the brain with venography

what would you do next?

What would you do next?

Instill a miotic agent

Order magnetic resonance imaging of the brain with venography

Perform gonioscopy

Perform peripheral iridotomy

a

female

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2704055

A man in his 70s presented for a routine follow-up appointment. He denied any visual or systemic symptoms, and his medical history was significant for hypertension and atrial fibrillation treated with cardiac catheterization and ablation. Medications included amlodipine besylate, 5 mg daily, and aspirin, 81 mg daily. His family and social history were unremarkable. On examination, his visual acuity was 20/20 OU. The intraocular pressure in both eyes was normal, and there was no relative afferent pupillary defect. Extraocular motility and confrontational visual fields were also normal. On physical examination, facial plethora was evident (Figure 1A). Retinal examination of the left eye revealed 2 blot hemorrhages and dilatation of the retinal veins (Figure 1B). Retinal examination of the right eye also revealed dilatation of the retinal veins. These abnormal findings were not present 1 year earlier. Fluorescein angiography revealed a prolonged arm-to-retina transit time of 22.6 seconds (normal, 10-16 seconds). Optical coherence tomography scans of the macula in both eyes were normal. In addition, an area of bruising was noted on the right shoulder in the absence of any history of trauma to the shoulder.A, Facial plethora. B, Ultra widefield retinal imaging of the left eye showing peripheral retinal hemorrhages (black arrowheads) and retinal vein dilatation (white arrowhead).Order a computed tomography scan of the abdomen What Would You Do Next?

Order a computed tomography scan of the abdomen

Perform ocular massage

Obtain a complete blood cell count

Perform genetic testing for the VHL gene

Retinal hyperviscosity syndrome secondary to polycythemia vera

C

Obtain a complete blood cell count

Early recognition of ocular and systemic signs of hyperviscosity syndrome, even in asymptomatic patients, can prevent serious complications such as central retinal vein occlusion, myocardial infarction, and stroke. Findings of retinal vein dilatation and tortuosity, retinal hemorrhages, facial plethora, and bruising in the absence of trauma should prompt a search for a systemic cause of hyperviscosity. The recommended initial workup is to obtain a complete blood cell count. Computed tomography of the abdomen (choice A) would not be recommended unless the results of an initial laboratory workup were suspicious for neoplastic causes of hyperviscosity syndrome, such as renal cell carcinoma. Ocular massage (choice B) is a controversial treatment for central retinal artery occlusion, not hyperviscosity syndrome. Genetic testing for the VHL gene (choice D) would be indicated if there were retinal findings such as a hemangioblastoma.The complete blood cell count revealed a hemoglobin level of 21.7 g/dL (reference range, 13.5-17.0 g/dL) (to convert hemoglobin to grams per liter, multiply by 10.0), a hematocrit level of 66% (reference range, 40%-50%) (to convert to proportion of 1.0, multiply by 0.01), and a red blood cell count of 8.1 × 106/μL (reference range, 4.4-5.7 × 106/μL) (to convert to ×1012/L, multiply by 1.0). White blood cell and platelet counts were within normal limits. On referral to the division of hematology, the serum erythropoietin level was found to be 2 mU/mL (reference range, 2-29 mU/mL); the JAK2 V617F mutation was identified, consistent with polycythemia vera (PV).Polycythemia vera is a chronic proliferative neoplasm characterized by clonal expansion of myeloid lineage cells, leading to elevated red blood cell mass and hyperviscosity.1 Elevated hemoglobin and hematocrit levels, low erythropoietin levels, and the presence of the JAK2 V617F mutation are diagnostic of PV. A low erythropoietin level distinguishes PV from secondary causes of polycythemia, including chronic hypoxia, physiologic high-altitude polycythemia, or erythropoietin-secreting tumors. The JAK2 V617F mutation increases the sensitivity of myeloid progenitors to erythropoietin and is present in 95% of patients with PV.1In the eye, the earliest manifestations of hyperviscosity from PV are retinal vein dilatation and tortuosity, which occur when hematocrit levels exceed 50%.2 Retinal hemorrhages may also be present. Systemic manifestations of PV include facial plethora, bruising, aquagenic pruritus, and erythromelalgia.3,4 Patients may experience transient monocular blindness and scintillating scotomas due to delayed choroidal and retinal perfusion.5 Hyperviscosity syndrome can cause central retinal vein occlusion, central retinal artery occlusion, anterior ischemic optic neuropathy, papilledema, and serous macular detachment.2,6-8 Patients with PV are at increased risk of systemic thrombosis and hemorrhage, including myocardial infarction, stroke, and deep venous thrombosis.9Early treatment of PV can prevent complications with high morbidity and mortality. Treatment aims to decrease the hematocrit level below 45% to minimize symptoms and extend life expectancy.10 Patients at low risk of complications may be treated with therapeutic phlebotomy alone, whereas patients at high risk of complications require both a phlebotomy and a cytoreductive agent such as hydroxyurea. For patients with transient monocular blindness who demonstrated a delayed arm-to-retina fluorescein angiography transit time, treatment with hydroxyurea resolved symptoms and decreased the transit time.5 Biologic therapy using JAK inhibitors can be used in hydroxyurea-resistant patients.1The patient’s hematologist treated his PV with a phlebotomy and hydroxyurea. Three months after initiating treatment, the patient’s complete blood count improved, with a hemoglobin level of 15.2 g/dL, a hematocrit level of 45.8%, and a red blood cell count of 5.26 × 106/μL, and there was improvement in the facial plethora (Figure 2). One year later, the patient’s vision remained stable, and results of a fundus examination showed resolution of retinal hemorrhages and persistence of venular dilatation; he did not experience any further systemic complications.Improved facial plethora after initiating therapeutic phlebotomy and hydroxyurea.

Ophthalmology

A man in his 70s presented for a routine follow-up appointment. He denied any visual or systemic symptoms, and his medical history was significant for hypertension and atrial fibrillation treated with cardiac catheterization and ablation. Medications included amlodipine besylate, 5 mg daily, and aspirin, 81 mg daily. His family and social history were unremarkable. On examination, his visual acuity was 20/20 OU. The intraocular pressure in both eyes was normal, and there was no relative afferent pupillary defect. Extraocular motility and confrontational visual fields were also normal. On physical examination, facial plethora was evident (Figure 1A). Retinal examination of the left eye revealed 2 blot hemorrhages and dilatation of the retinal veins (Figure 1B). Retinal examination of the right eye also revealed dilatation of the retinal veins. These abnormal findings were not present 1 year earlier. Fluorescein angiography revealed a prolonged arm-to-retina transit time of 22.6 seconds (normal, 10-16 seconds). Optical coherence tomography scans of the macula in both eyes were normal. In addition, an area of bruising was noted on the right shoulder in the absence of any history of trauma to the shoulder.A, Facial plethora. B, Ultra widefield retinal imaging of the left eye showing peripheral retinal hemorrhages (black arrowheads) and retinal vein dilatation (white arrowhead).Order a computed tomography scan of the abdomen

what would you do next?

What would you do next?

Obtain a complete blood cell count

Perform ocular massage

Order a computed tomography scan of the abdomen

Perform genetic testing for the VHL gene

a

male

71-80

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2705356

A white man in his mid-80s with an ocular history of remote left cataract extraction and a medical history of well-controlled hypertension, ankylosing spondylitis, ulcerative colitis, and osteoporosis was referred by an outside optometrist for possible birdshot chorioretinopathy. He denied any vision changes, eye pain, or light sensitivity. A comprehensive review of symptoms was negative, including no fatigue, weight loss, or night sweats. Best-corrected visual acuity was 20/40 OD and 20/30 OS. Anterior segment examination revealed ocular surface dryness and a nuclear sclerotic cataract in the right eye. On dilated fundoscopy, multiple yellow-white subretinal deposits were scattered throughout the left posterior pole, with parafoveal coalescence but sparing the far periphery. There was no concomitant vitritis (Figure, A). Optical coherence tomography showed choroidal thickening and irregularity of the overlying retinal pigment epithelium (Figure, B). The right eye was unremarkable.A, Fundus photograph of the left eye shows scattered hypopigmented subretinal deposits with parafoveal coalescence. B, Optical coherece tomographic findings show patchy choroidal thickening with irregularity of the overlying retinal pigment epithelium (arrowhead). The neurosensory retina maintained its regular architecture. N indicates nasal; T, temporal.Initiation of treatment with systemic corticosteroids and immunosuppression after HLA-A29 laboratory analysis What Would You Do Next?

Observation

Initiation of treatment with systemic corticosteroids and immunosuppression after HLA-A29 laboratory analysis

Hematologic workup

Vitreous biopsy

Waldenström macroglobulinemia

C

Hematologic workup

The initial differential diagnosis included infectious (tuberculosis, syphilis), inflammatory (Vogt-Koyanagi-Harada, birdshot, and sarcoidosis), and masquerade (primary central nervous system lymphoma, oncologic metastases) syndromes. Given his age as well as the lack of vitritis and local symptoms, infectious and inflammatory conditions were less likely. Observation was insufficient (choice A), and systemic treatment with corticosteroids and immunomodulatory therapy was not indicated before further evaluation (choice B). Vitreous biopsy (choice D) was deferred in lieu of less invasive testing.A hematologic workup was initiated (choice C). A complete blood cell count revealed normocytic anemia, with a hemoglobin level of 11.7 g/dL (12.5-16.3 g/dL) and hematocrit of 34.8% (36.7%-47.1%). (To convert the hemoglobin level to grams per liter, multiply by 10; hematocrit to a proportion of 1.0, multiply by 0.01.) The serum level of prostate-specific antigen and results of a colonoscopy were normal. Peripheral blood flow cytometry showed a CD20+ B-cell clonal population co-expressing CD5, CD23, and a κ light chain comprising 29% of lymphocytes and 10% of all white blood cells. These results prompted referral for hematologic analysis. A thorough systemic workup included syphilis and tuberculosis serology, lysozyme and angiotensin-converting enzyme levels, and HLA-A29 detection, which were all normal.Findings of full-body positron-emission tomography–computed tomography were unremarkable. Urine protein electrophoresis and serum protein electrophoresis showed a spike in the γ-globulin concentration of 1.8 g/dL (0.7-1.6 g/dL), with markedly elevated IgM and β2-microglobulin levels of 1458 mg/dL (48-271 mg/dL) and 4.18 mg/L (0-2.51mg/L), respectively. (To convert the γ-globulin concentration to grams per liter and the IgM level to milligrams per liter, multiply by 10.) Examination of a bone marrow biopsy specimen showed abnormal trisomy 12 karyotype in 35% of cells, consistent with a lymphoproliferative disorder. Polymerase chain reaction–based pyrosequencing detected MYD88 L265P, confirming a diagnosis of Waldenström macroglobulinemia (WM).Waldenström macroglobulinemia is a lymphoproliferative B-cell disorder causing an IgM-producing monoclonal population. It typically presents in white men aged 60 to 70 years as an indolent disease. Hyperviscosity symptoms develop in only 15% to 17% of patients; these may include “B symptoms,” neurologic disturbances, and vascular abnormalities, including vertigo, epistaxis, gastrointestinal hemorrhage, and congestive heart failure.1-3 Asymptomatic patients with WM can be monitored without treatment given its slow progression.3Ocular findings occur at varying levels of IgM.4 Vision may be normal.5 Classic hyperviscosity retinopathy causes venous dilation, retinal hemorrhages, exudates, and vein occlusions. Arterial involvement, serous macular detachment, and optic disc edema are less common.1,5,6 Intraretinal and subretinal IgM deposits have also been detected, although definitive identification of IgM would require biopsy. In light of the entire clinical and laboratory picture, subretinal deposits are presumed to be IgM collections as was true for this patient.3,6-8 Others have reported a paraneoplastic retinopathy resulting in photoreceptor dysfunction detectable on electroretinogram.1 Waldenström macroglobulinemia can rarely manifest as secondary orbital cellulitis from increased susceptibility to infection due to relative agammaglobulinemia.5 Ocular findings are most often bilateral given that WM is a systemic disease, but some ocular findings may be asymmetric or unilateral as was true in this patient.1,7,9Waldenström macroglobulinemia can masquerade as birdshot chorioretinopathy, idiopathic central serous retinopathy, or more common ocular diseases, such as diabetic or hypertensive retinopathy.2 This case highlights the importance of also considering malignancy when faced with a case of atypical chorioretinal lesions in an older patient.In the absence of systemic or ocular symptoms, this patient did not qualify for immediate systemic or local treatment. The patient’s condition is monitored regularly in retina and hematology clinics, and he has exhibited stable disease to date.

Ophthalmology

A white man in his mid-80s with an ocular history of remote left cataract extraction and a medical history of well-controlled hypertension, ankylosing spondylitis, ulcerative colitis, and osteoporosis was referred by an outside optometrist for possible birdshot chorioretinopathy. He denied any vision changes, eye pain, or light sensitivity. A comprehensive review of symptoms was negative, including no fatigue, weight loss, or night sweats. Best-corrected visual acuity was 20/40 OD and 20/30 OS. Anterior segment examination revealed ocular surface dryness and a nuclear sclerotic cataract in the right eye. On dilated fundoscopy, multiple yellow-white subretinal deposits were scattered throughout the left posterior pole, with parafoveal coalescence but sparing the far periphery. There was no concomitant vitritis (Figure, A). Optical coherence tomography showed choroidal thickening and irregularity of the overlying retinal pigment epithelium (Figure, B). The right eye was unremarkable.A, Fundus photograph of the left eye shows scattered hypopigmented subretinal deposits with parafoveal coalescence. B, Optical coherece tomographic findings show patchy choroidal thickening with irregularity of the overlying retinal pigment epithelium (arrowhead). The neurosensory retina maintained its regular architecture. N indicates nasal; T, temporal.Initiation of treatment with systemic corticosteroids and immunosuppression after HLA-A29 laboratory analysis

what would you do next?

What would you do next?

Vitreous biopsy

Hematologic workup

Initiation of treatment with systemic corticosteroids and immunosuppression after HLA-A29 laboratory analysis

Observation

b

male

81-90

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2696333

A young man in his early 20s presented with a 1-day history of pleuritic chest pain and shortness of breath, with no fever or cough. He smoked approximately 10 cigarettes per day for 4 years. Results of the physical examination were unremarkable. Radiography of the chest revealed an ill-defined consolidation in the right lower lung field. Laboratory investigations were significant for elevated levels of lactate dehydrogenase (273 U/L; reference range, 135-225 U/L [to convert to microkatals per liter, multiply by 0.0167]), C-reactive protein (125.3 mg/L; reference range, 0.0-4.9 mg/L [to convert to nanomoles per liter, multiply by 9.524]), and alkaline phosphatase (217 U/L; reference range, 40-129 U/L [to convert to microkatals per liter, multiply by 0.0167]). Computed tomography of the chest confirmed the presence of a dense consolidation involving most of the right middle lobe with right hilar and subcarinal lymphadenopathy (Figure, A). He underwent endobronchial ultrasonography-guided transbronchial needle aspiration of a fleshy, whitish endobronchial lesion obstructing both uptakes to the medial and lateral segments. Histologic analysis revealed a poorly differentiated malignant neoplasm (Figure, B). Most of the cells were relatively monotonous, with enlarged vesicular nuclei, prominent nucleoli, and a high ratio of nucleus to cytoplasm. Foci of abrupt squamous differentiation, including keratinization and intercellular bridges, were identified. Immunohistochemical staining showed tumor cells to be strongly and diffusely positive for keratin AE1/AE3, cytokeratin 5/6, and p63. However, findings were negative for S-100, melan A, placental alkaline phosphatase, CD56, thyroid transcription factor-1, terminal deoxynucleotidyl transferase, CD45, and cytokeratin 7. A positron emission tomography–computed tomography scan showed a fludeoxyglucose-enhanced avid right middle lobe mass, a large right-sided pleural effusion, and fludeoxyglucose-enhanced avid mediastinal and right hilar lymph nodes, with extensive skeletal metastases to both proximal humeri and scapulae, the sacrum, spine, iliac bones, and both hips.A, Computed tomography of the chest revealed a dense consolidation in the middle lobe of the right lung with right hilar and subcarinal lymphadenopathy. B, Histologic analysis of the mass revealed a poorly differentiated malignant neoplasm. Most cells showed enlarged vesicular nuclei, prominent nucleoli, and a high ratio of nucleus to cytoplasm (hematoxylin-eosin; original magnification ×200). What Is Your Diagnosis?

Squamous cell carcinoma of the lung

Carcinoid tumor

Primary malignant mediastinal germ cell tumor

Nuclear protein in testis midline carcinoma

D. Nuclear protein in testis midline carcinoma

D

Nuclear protein in testis midline carcinoma

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive human cancer that presents as a poorly differentiated carcinoma originating from midline locations and does not arise from any specific tissue type or organ.1 NUT midline carcinoma is driven by a rearrangement of the NUT gene (OMIM 608963) located on chromosome 15. This rearrangement commonly occurs between the NUT gene and a member of the BET genes family, most commonly BRD4 (OMIM 608749), resulting in the formation of the fusion oncogene BRD4-NUT.2,3 NUT midline carcinoma is extremely aggressive, with most cases presenting at an advanced stage as widely metastatic and unresectable disease when diagnosed,3,4 and has a highly lethal course.5The tumor arises in many sites, although large series suggest predilection for the head and neck and mediastinum.4 Existing literature suggests that primary pulmonary NMC is exceptionally rare and has shorter median survival when compared with the median survival reported for NMC arising at all sites (2.2 vs 6.7 months). This difference has been hypothesized to be partly owing to a relatively delayed onset of clinical symptoms for primary tumors of the lung compared with the other more common sites, for instance, the head and neck. The estimated 2-year progression-free survival is 9% based on studies incorporating all sites of disease.4From a histopathologic perspective, the appearance is commonly that of a poorly differentiated carcinoma with focal, abrupt squamous differentiation. The NMC cells are usually medium sized and round and often monomorphic in appearance in contrast to many other poorly differentiated carcinomas, which consist of highly pleomorphic large cells. These features are characteristic although not diagnostic.6 Reactivity of CD34 is occasionally seen.5The patient’s age was very unusual for conventional pulmonary squamous cell carcinoma, which is typically a disease of older patients who smoke. This characteristic, along with the characteristic histologic findings, raised the possibility of NMC. Interphase fluorescent in situ hybridization performed at Brigham and Women’s Hospital in Boston, Massachusetts, demonstrated BRD4-NUT rearrangement in 66% of cells, consistent with NMC. NUT midline carcinoma is more common among young patients, with a median age of 30 years at the time of diagnosis.4By the time the diagnosis was established, the patient had developed significant right shoulder pain. He started chemotherapy with cisplatin and docetaxel (75 mg/m2 every 3 weeks for each). He experienced meaningful improvement in symptoms and was pain free without use of narcotics 24 hours after cycle 1. However, during the following weeks, he slowly developed worsening skeletal pain and recurrent pleural effusions requiring placement of a pleural catheter (PleurX; Becton, Dickinson and Company). Palliative radiotherapy of 2500 cGy to the right humerus in 5 fractions provided modest pain relief. He then received cycle 2 of chemotherapy delayed by 2 weeks with no clinical evidence of response, continued skeletal pain, and recurrent effusions. Radiotherapy of 800 cGy delivered in a single fraction to the right hemithorax 3 weeks later was of limited benefit. Recurrent pleural effusions repeatedly delayed treatment with multiple hospital admissions, and eventually required thoracoscopy and talc pleurodesis. He opted to transition to hospice care and died less than 4 months after his diagnosis.The patient experienced a brief and rapid clinical response to treatment initially but rapid progression afterwards, which appears to be a commonly observed theme with NMCs.2 Involvement of BRD4 and possibly NUT in chromatin regulation suggests that BRD4-NUT might somehow modify chromatin to prevent the expression of genes needed for epithelial differentiation, and this is an area of ongoing research.1,3 Because no standard treatment exists and given the refractory nature of NMC to conventional chemotherapy and radiotherapy, early recognition and consideration is important. Enrollment in clinical trials is suggested.

Oncology

A young man in his early 20s presented with a 1-day history of pleuritic chest pain and shortness of breath, with no fever or cough. He smoked approximately 10 cigarettes per day for 4 years. Results of the physical examination were unremarkable. Radiography of the chest revealed an ill-defined consolidation in the right lower lung field. Laboratory investigations were significant for elevated levels of lactate dehydrogenase (273 U/L; reference range, 135-225 U/L [to convert to microkatals per liter, multiply by 0.0167]), C-reactive protein (125.3 mg/L; reference range, 0.0-4.9 mg/L [to convert to nanomoles per liter, multiply by 9.524]), and alkaline phosphatase (217 U/L; reference range, 40-129 U/L [to convert to microkatals per liter, multiply by 0.0167]). Computed tomography of the chest confirmed the presence of a dense consolidation involving most of the right middle lobe with right hilar and subcarinal lymphadenopathy (Figure, A). He underwent endobronchial ultrasonography-guided transbronchial needle aspiration of a fleshy, whitish endobronchial lesion obstructing both uptakes to the medial and lateral segments. Histologic analysis revealed a poorly differentiated malignant neoplasm (Figure, B). Most of the cells were relatively monotonous, with enlarged vesicular nuclei, prominent nucleoli, and a high ratio of nucleus to cytoplasm. Foci of abrupt squamous differentiation, including keratinization and intercellular bridges, were identified. Immunohistochemical staining showed tumor cells to be strongly and diffusely positive for keratin AE1/AE3, cytokeratin 5/6, and p63. However, findings were negative for S-100, melan A, placental alkaline phosphatase, CD56, thyroid transcription factor-1, terminal deoxynucleotidyl transferase, CD45, and cytokeratin 7. A positron emission tomography–computed tomography scan showed a fludeoxyglucose-enhanced avid right middle lobe mass, a large right-sided pleural effusion, and fludeoxyglucose-enhanced avid mediastinal and right hilar lymph nodes, with extensive skeletal metastases to both proximal humeri and scapulae, the sacrum, spine, iliac bones, and both hips.A, Computed tomography of the chest revealed a dense consolidation in the middle lobe of the right lung with right hilar and subcarinal lymphadenopathy. B, Histologic analysis of the mass revealed a poorly differentiated malignant neoplasm. Most cells showed enlarged vesicular nuclei, prominent nucleoli, and a high ratio of nucleus to cytoplasm (hematoxylin-eosin; original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Primary malignant mediastinal germ cell tumor

Squamous cell carcinoma of the lung

Carcinoid tumor

Nuclear protein in testis midline carcinoma

d

male

21-30

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2698086

A 62-year-old woman was brought to the emergency department after she was found unresponsive on the ground with a presumed cardiac arrest. She had pulseless electrical activity. After resuscitation, the return of spontaneous circulation was achieved. She remained comatose and was intubated for airway protection. She had a history of deep vein thrombosis 3 years prior but was not receiving long-term anticoagulation. A physical examination revealed a rapid irregular pulse, no jugular venous distension, clear lung fields, and no cardiac murmurs. There was no peripheral edema. Laboratory findings were notable only for a troponin T level of 2.41 ng/mL (to convert to micrograms per liter, multiply by 1). An electrocardiogram (ECG) and a point-of-care transthoracic echocardiogram (TTE) were obtained (Figure 1; Video). What Would You Do Next?

Cardiac catheterization

Computed tomography of the head

Pulmonary computed tomography angiography

Transesophageal echocardiography

Neurogenic stress cardiomyopathy

B

Computed tomography of the head

Elevated cardiac enzyme levels, ST-segment depression in the precordial leads on the ECG (Figure 1A), and regional wall motion abnormalities on TTE (Figure 1B; Video) were all concerning for an acute myocardial infarction (AMI) and cardiac arrest. A cardiac catheterization with coronary angiography could be considered after the return of spontaneous circulation. Nevertheless, there were also important discriminating imaging features in the TTE that could suggest another diagnosis; the wall motion abnormality only involved the midventricular wall, without involvement of the basal or apical segments of the left ventricle. The midventricular (hypokinetic) and apical/basal (hyperkinetic) segments exhibited a discrepant contractile pattern. This “spindle-shaped” ventricular contractile dysfunction was not consistent with the myocardial territory of a single coronary artery. Taking her manifestation and unique imaging findings into account, we gave priority to a computed tomography of the head, which showed a diffuse subarachnoid hemorrhage (SAH) with an intraventricular extension (Figure 2). Therefore, neurogenic stress cardiomyopathy (NSC) was diagnosed. Given her history of deep vein thrombosis, a pulmonary embolism could possibly cause pulseless electrical activity and new-onset atrial fibrillation. However, the characteristic TTE findings prompted us to seek a different diagnosis, and performing pulmonary computed tomography angiography was not the first choice. A transesophageal echocardiography might improve the visualization of intracardiac anatomic structures, but it is unlikely that it would offer further diagnostic help.Computed tomography image of the head showing a diffuse subarachnoid hemorrhage (asterisks) with intraventricular extension.Intracranial hemorrhage, particularly SAH, is the leading cause of NSC. Left ventricular (LV) dysfunction can occur acutely and improve spontaneously over days to weeks. Neurogenic stress cardiomyopathy is thought to be caused by hemorrhage, ischemia, or edema of the hypothalamus, which stimulates the release of endogenous catecholamine and results in an extensive spasm of the systemic arteries, including the coronary arteries.1 In contrast to classical stress-induced cardiomyopathy, or Takotsubo syndrome, which is often associated with an LV “apical ballooning” pattern, NSC more commonly causes an “inverse” contractile dysfunction, which involves basal and middle, but not apical, LV segments.2 The cause of this difference is unclear, but neither ventricular contractile pattern is consistent with the myocardial territory of a single coronary artery, helping distinguish NSC and Takotsubo syndrome from AMI.The clinical manifestation and ECG changes of NSC can resemble those of AMI, including ST-segment elevation myocardial infarction. Current guidelines advocate using coronary angiography to direct the diagnosis and therapy.3 However, if SAH-induced NSC is misdiagnosed as AMI, anticoagulation and antiplatelet treatment can exacerbate bleeding. Even more catastrophic would be the use of fibrinolytic therapy in those hospitals that lack a catheterization laboratory. Characteristic noninvasive cardiac imaging findings can help appropriately triage patients with NSC and avoid harmful procedures/treatments and adverse events. Surveillance echocardiography can help assess the recovery of LV function during follow-up. The timely diagnosis of NSC also has important implications in management. In patients with hemodynamic instability, catecholamine inotropic and pressor agents should be avoided. α-adrenergic agonists are useful in maintaining peripheral vascular pressure and supporting cerebral perfusion. While the actual effect of intra-aortic balloon pumps is uncertain in patients with LV outflow tract obstruction, hemodynamic support from baroreflex activation therapy3 and percutaneously inserted ventricular assist devices4 are targets of current and future research. Because of limited donor organ availability, only about 10% of patients in the United States who may benefit from a heart transplant undergo this procedure annually. Meanwhile, many of the patients who experience brain death from neurological insults are deemed unsuitable donors for cardiac transplantation because of NSC. The LV dysfunction during stress-induced cardiomyopathy is usually reversible. In the largest analysis of donor hearts with transient LV dysfunction, such hearts have been successfully transplanted without increasing recipient mortality rates.5 Further investigation is warranted to better understand the underlying pathophysiology and reversibility of NSC, which may increase the number of donor hearts that would otherwise be rejected primarily because of poor LV function.Because of the anoxic brain injury and irreversible neurological dysfunction, the goals of care were transitioned to comfort measures. As a candidate for organ donation, she underwent serial echocardiography that documented a complete resolution of LV systolic dysfunction within 48 hours. Cardiac catheterization results confirmed a healthy coronary anatomy. However, she did not become a heart donor eventually because of controversies on accepting donor hearts with transient LV dysfunction.

Cardiology

A 62-year-old woman was brought to the emergency department after she was found unresponsive on the ground with a presumed cardiac arrest. She had pulseless electrical activity. After resuscitation, the return of spontaneous circulation was achieved. She remained comatose and was intubated for airway protection. She had a history of deep vein thrombosis 3 years prior but was not receiving long-term anticoagulation. A physical examination revealed a rapid irregular pulse, no jugular venous distension, clear lung fields, and no cardiac murmurs. There was no peripheral edema. Laboratory findings were notable only for a troponin T level of 2.41 ng/mL (to convert to micrograms per liter, multiply by 1). An electrocardiogram (ECG) and a point-of-care transthoracic echocardiogram (TTE) were obtained (Figure 1; Video).

what would you do next?

What would you do next?

Computed tomography of the head

Transesophageal echocardiography

Cardiac catheterization

Pulmonary computed tomography angiography

a

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2702302

A cigarette smoker in his 50s with a history of hypertension, chronic kidney disease, colon adenocarcinoma, and hyperuricemia presented with a right vocal fold mass that had been an incidental finding during esophagogastroduodenoscopy. He denied any symptoms related to the lesion, including dysphonia or dysphagia, and reported no fevers or weight loss. Rigid stroboscopy revealed normal vocal fold mobility and a nodular cystic-appearing lesion on the posterior inferior border of the right vocal process (Figure, A). There was no overlying ulceration, and vocal fold mucosal wave was intact in the adjacent membranous vocal fold.Suspension microlaryngoscopy incisional biopsy of the right infraglottic lesion was performed in the operating room. The endotracheal tube was displaced anteriorly with the laryngoscope. Intraoperatively, there was submucosal white caseous debris in the substance of the lesion. The surgical specimen was sent for histopathologic analysis (Figure, B). Cultures were analyzed for the presence of fungus, bacteria, and mycobacteria. Postoperatively, the patient was doing well and continued to have no symptoms of dysphagia or dysphonia. What Is Your Diagnosis?

Laryngeal tuberculosis

Laryngeal gout

Vocal fold granuloma

Laryngeal amyloidosis

B. Laryngeal gout

B

Laryngeal gout

Histopathologic analysis was consistent with gouty tophus, revealing amorphous gray-pink material representing monosodium urate crystal deposition, surrounded by mild chronic inflammation. At follow-up, flexible laryngoscopy revealed a healing biopsy site. Given that the patient was asymptomatic and the benign diagnosis, no additional treatment was pursued. He had previously been prescribed allopurinol for gouty arthritis, which he continued to receive postoperatively.Gout is a heterogenous disease state caused by hyperuricemia in the setting of imbalanced uric acid formation and elimination. When the plasma urate concentration has exceeded maximal solubility product, urate crystalizes and a significant inflammatory cascade ensues.1 The prevalence of asymptomatic hyperuricemia, defined as plasma urate level greater than 7 mg/dL (to convert to micromoles per liter, multiply by 59.485), is estimated to be 10% to 20% in all adults. The prevalence of clinically manifested gout is estimated to be 1% to 2% in developed countries, increasing to more than 8% in men older than 65 years.2 Classically, gout presents as an acute inflammatory arthritis due to monosodium urate crystal deposition in joints that may progress to chronic joint damage. More chronic manifestations include tophi formation in various tissues and associated metabolic syndrome.2Laryngeal gout is not widely present in the literature and was previously thought to be extremely uncommon. Recent literature has suggested that laryngeal manifestations of gout are not as rare as previously thought and that the small number of reported cases may be due to nonspecific symptoms.3-5 The pathophysiologic mechanism of laryngeal disease corresponds with that in other parts of the body.6 The cricoarytenoid joint is an arthrodial joint with a synovial capsule, allowing arthritic processes. The deposition of urate leads to acute inflammation, and over the long term to articular cartilage destruction and subsequent fibrous ankylosis.7 There is evidence to suggest that gouty cricoarytenoid arthritis leads to denervation atrophy, further impairing joint function.8Of the 20 reported cases in which subsite was identified, laryngeal gout was localized to the true vocal fold (7),3,5,6,9,10 laryngeal ventricle (1),3,6 subglottis (2),3,4,6 thyroid cartilage (3),6,11 arytenoid (1),3,6 and cricoarytenoid joint (6).3,6,12 Involvement of the true vocal fold typically presents with mild symptoms such as hoarseness or sore throat.5,6,9 Cricoarytenoid joint involvement is often associated with pain and, if severe, can cause airway compromise.6,12 When the vocal folds are uninvolved, symptoms may be less specific or absent.4,5 Gouty involvement should be considered in patients with systemic gout and unexplained laryngeal symptoms, and laryngoscopy should be performed.3,6-8,12There is a broad differential diagnosis for arytenoid lesions with or without impaired vocal fold mobility. In the case presented herein with a raised erythematous and white lesion, there must be consideration of carcinoma. After this is ruled out, one must consider the broad differential including atypical infectious etiologies such as laryngeal tuberculosis, and histoplasmosis, as well as inflammatory disease including autoimmune disease and granulomas.6Given the nonspecific presentation of laryngeal gout, diagnosis depends on biopsy and histopathologic analysis.4,6 Management of laryngeal gout is largely based on systemic measures. Lifestyle interventions are first line, including weight reduction and dietary avoidance of alcohol and purines. Acute inflammation may be treated with nonsteroidal anti-inflammatory drugs, steroids, or colchicine. In more severe cases, maintenance urate-lowering therapy with allopurinol or febuxostat should be considered.2,3 However, involvement of the larynx may also necessitate surgical intervention such as endoscopic tophus removal.3 Acute airway compromise due to vocal fold immobility may necessitate tracheotomy.6,12This case illustrates the importance of considering laryngeal gout as a diagnosis in patients who present with dysphagia, dysphonia, or laryngeal lesions, particularly in those with a history of gout. Because the prevalence of laryngeal gout may be higher than previously recognized, clinical awareness of the disease may result in increased rates of diagnosis.

General

A cigarette smoker in his 50s with a history of hypertension, chronic kidney disease, colon adenocarcinoma, and hyperuricemia presented with a right vocal fold mass that had been an incidental finding during esophagogastroduodenoscopy. He denied any symptoms related to the lesion, including dysphonia or dysphagia, and reported no fevers or weight loss. Rigid stroboscopy revealed normal vocal fold mobility and a nodular cystic-appearing lesion on the posterior inferior border of the right vocal process (Figure, A). There was no overlying ulceration, and vocal fold mucosal wave was intact in the adjacent membranous vocal fold.Suspension microlaryngoscopy incisional biopsy of the right infraglottic lesion was performed in the operating room. The endotracheal tube was displaced anteriorly with the laryngoscope. Intraoperatively, there was submucosal white caseous debris in the substance of the lesion. The surgical specimen was sent for histopathologic analysis (Figure, B). Cultures were analyzed for the presence of fungus, bacteria, and mycobacteria. Postoperatively, the patient was doing well and continued to have no symptoms of dysphagia or dysphonia.

what is your diagnosis?

What is your diagnosis?

Laryngeal tuberculosis

Laryngeal gout

Laryngeal amyloidosis

Vocal fold granuloma

b

male

51-60

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2703154

A farmer in his 50s presented with bilateral periauricular swelling that began 6 months prior (Figure 1). The swelling was mild at onset and gradually progressive. There was no history of associated pain, but he reported occasional pruritus over the swelling. There was no history of fever, weight loss, or loss of appetite. He denied any history of similar swelling elsewhere in his body. General physical and systemic examination had normal results. On examination of the swelling on the right side, there was a diffuse swelling around the pinna measuring approximately 6 cm over the preauricular, postauricular, and infra-auricular region. It was a nontender, soft swelling without fluctuation and abnormal pulsations. There were similar findings in the left side. Mouth opening was adequate, secretions from both parotid ducts were normal, and facial nerve function was intact on both sides. He had undergone fine-needle aspiration cytology and incisional biopsy. The results of both were consistent with reactive lymphadenitis. He was prescribed oral antibiotics for 1 week but showed no improvement. A contrast-enhanced computed tomographic scan of the head and neck showed bilateral multiple enhancing lymph nodes in the postauricular region, the largest measuring 16 × 11 mm2 on the right side and 15.4 × 10.6 mm2 on the left, along with bilateral intraparotid nodes, the largest measuring 16.4 × 10.2 mm2 on the right and 15.3 × 10.7 mm2 on the left side. His serum eosinophil count was slightly elevated, and his erythrocyte sedimentation rate was 15 mm/h. However, the IgE level was not measured. He was then scheduled for excisional biopsy at our center. The biopsy specimen included skin and subcutaneous tissue along with 2 underlying lymph nodes.Clinical photographs showing diffuse swelling of the preauricular, infra-auricular, and postauricular region. What Is Your Diagnosis?

Hodgkin lymphoma

Tubercular lymphadenitis

Kimura disease

Angiolymphoid hyperplasia with eosinophilia

C. Kimura disease

C

Kimura disease

The final histopathological reports of the skin specimen revealed inflammatory infiltrates consisting of predominant eosinophils, lymphocytes, and plasma cells with some areas of eosinophilic microabscess, while analysis of the lymph node specimen revealed hyperplastic lymphoid follicles with mantle zone along with mixed inflammatory cells and absence of neoplastic cells (Figure 2). These features were consistent with Kimura disease. He was thus given intralesional steroid injection. After 3 doses of intralesional triamcinolone acetonide, he showed significant improvement.Histologic analysis. A, Skin biopsy showing inflammatory infiltrates consisting of predominant eosinophils, lymphocytes, and plasma cells with some areas of eosinophilic microabscess. B, Lymph node biopsy showing hyperplastic lymphoid follicles with mantle zone along with mixed inflammatory cells. H&E indicates hematoxylin-eosin.First described by Kim and Szeto in 1937 as “eosinophilic hyperplastic lymphogranuloma” and named Kimura disease after a detailed description by Kimura et al1 in 1948, Kimura disease is a rare immune-mediated inflammatory disorder that is benign in nature. It most often occurs in Asians; few cases have been reported in the western world. Patients are usually 20 to 40 years old, with male preponderance.2 Kimura disease presents predominantly as unilateral lymphadenopathy, unlike in the present case, which presented as bilateral lymphadenopathy.3 The blood and tissue picture shows eosinophilia and elevated serum IgE level. Iwai et al4 have described blood eosinophilia at a mean count of 35.2% with elevated IgE levels in all Kimura disease cases, while our patient had an eosinophil count of 15%. According to a report published in 1997,5 less than 120 cases had been reported so far; however, the exact prevalence is not known. The etiopathogenesis of Kimura disease is still a mystery; hypotheses include immune regulation dysfunction, atopic reaction to a persistent antigenic stimulus by arthropod bites, viral origin, and neoplasm. The most interesting hypothesis suggests that Candida species act as a source of persistent antigen, although neither hyphae nor spores have been isolated.2The main differential diagnosis for Kimura disease includes Hodgkin lymphoma, tubercular lymphadenopathy, acute myelogenous leukemia with eosinophilia, angioimmunoblastic lymphadenopathy, and angiolymphoid hyperplasia with eosinophilia (ALHE).6 Among these, ALHE is the most important candidate. Both diseases have some common histological features, such as eosinophilia and vascular proliferation, but ALHE is usually seen in older patients, manifesting as multiple small dermal eruptions and only rarely with lymphadenopathy, salivary gland involvement, and elevated serum IgE.7 Similarly, another important differential diagnosis is Hodgkin lymphoma, which presents with constitutional symptoms along with histological features such as Reed-Sternberg cells presenting as classical binucleated cells along with neoplastic cells surrounded by nonneoplastic lymphocytes, eosinophils, plasma cells, and sometimes neutrophils unlike in this patient. Tubercular lymphadenopathy was another possibility because the patient resides in a developing country. However, his sputum smear was negative for tuberculosis and lymph node biopsy did not show features of tubercular lymphadenitis. Acute or chronic leukemia could be suspected, but blood cell count was normal except for the eosinophilia and the lymphadenopathy was more localized in the parotid region.Kimura disease is prone to recurrence. Given its immune-related nature and local infiltrative behavior, it is difficult to find a complete cure. Treatment options include surgical excision, radiotherapy, and regional and systemic steroids, as well as cytotoxic therapy.8,9 Good results with treatment with steroids and antihistamines have been reported.10 Likewise, in the present case, the patient has been treated with intralesional triamcinolone, which has resulted in significant reduction in the size of the mass.

General

A farmer in his 50s presented with bilateral periauricular swelling that began 6 months prior (Figure 1). The swelling was mild at onset and gradually progressive. There was no history of associated pain, but he reported occasional pruritus over the swelling. There was no history of fever, weight loss, or loss of appetite. He denied any history of similar swelling elsewhere in his body. General physical and systemic examination had normal results. On examination of the swelling on the right side, there was a diffuse swelling around the pinna measuring approximately 6 cm over the preauricular, postauricular, and infra-auricular region. It was a nontender, soft swelling without fluctuation and abnormal pulsations. There were similar findings in the left side. Mouth opening was adequate, secretions from both parotid ducts were normal, and facial nerve function was intact on both sides. He had undergone fine-needle aspiration cytology and incisional biopsy. The results of both were consistent with reactive lymphadenitis. He was prescribed oral antibiotics for 1 week but showed no improvement. A contrast-enhanced computed tomographic scan of the head and neck showed bilateral multiple enhancing lymph nodes in the postauricular region, the largest measuring 16 × 11 mm2 on the right side and 15.4 × 10.6 mm2 on the left, along with bilateral intraparotid nodes, the largest measuring 16.4 × 10.2 mm2 on the right and 15.3 × 10.7 mm2 on the left side. His serum eosinophil count was slightly elevated, and his erythrocyte sedimentation rate was 15 mm/h. However, the IgE level was not measured. He was then scheduled for excisional biopsy at our center. The biopsy specimen included skin and subcutaneous tissue along with 2 underlying lymph nodes.Clinical photographs showing diffuse swelling of the preauricular, infra-auricular, and postauricular region.

what is your diagnosis?

What is your diagnosis?

Angiolymphoid hyperplasia with eosinophilia

Hodgkin lymphoma

Kimura disease

Tubercular lymphadenitis

c

male

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2704026

A man in his 40s with Poland syndrome presented with a 6-month history of left throat pain and enlarging oropharyngeal mass. The patient had been seen repeatedly for odynophagia that persisted despite multiple courses of antibiotics, reflux medications, and steroids prescribed at clinics and emergency departments. Over the course of 5 months, he underwent a tonsillectomy and 3 separate biopsies at multiple institutions. All showed inconclusive results, and the mass progressively enlarged. At presentation for the present report, physical examination showed a 2-cm, well-mucosalized, left oropharyngeal mass not extending to the hard palate (Figure, A). Computed tomography (CT) revealed a 58-mm parapharyngeal mass lateralizing and narrowing the left carotid artery against the styloid process (Figure, B). A CT-guided fine-needle aspiration biopsy was performed but again was nondiagnostic. Further confounding the clinical picture, a pacemaker was required for multiple episodes of sinus asystole due to mass effect on the carotid body. To obtain the diagnosis of the parapharyngeal mass, the patient had a transcervical resection with transoral partial glossectomy, palatectomy, and pharyngectomy with reconstruction. Results of immunohistochemical analysis of the removed tissue were positive for CD4 (weak), CD21, CD23, and vimentin with a low proliferation rate (Figure, C and D).A, A 2-cm well-mucosalized left oropharyngeal soft-palate mass anterior to the tonsillar bed with surrounding erythema. B, Left parapharyngeal mass measuring 4.3 × 2.7 × 5.8 cm and lateralizing the left carotid artery. C, Fascicular, storiformed architecture with spindly, polygonal-shaped cells with eosinophilic cytoplasm and indistinct borders (original magnification ×10). D, Positive findings for CD21 (left; original magnification ×10) and CD23 (right; original magnification ×20). What Is Your Diagnosis?

Poorly undifferentiated carcinoma

Ectopic thymoma

Follicular dendritic cell sarcoma

Peripheral nerve sheath tumor

C. Follicular dendritic cell sarcoma

C

Follicular dendritic cell sarcoma

Follicular dendritic cells (FDCs), also known as dendritic reticulum cells, are nonlymphoid nonphagocytic cells in the dendritic reticulum of lymph nodes regulating the humoral immune response.1,2 The existence of FDC tumors was postulated by Lennert in 1978,3 but the first cases were not reported until 1986 by Monda et al.4 Follicular dendritic cell sarcoma (FDCS) is typically seen in the lymph nodes of the neck, axilla, and mediastinum.1 Chan et al5 described the first extranodal cases in 1994. While extranodal cases are rare, the most common sites include the head and neck (tonsil, nasopharynx, parapharyngeal space, hard and soft palates) and abdomen. To our knowledge, fewer than 150 cases of this neoplasm have been reported worldwide, and although there are case series and review articles, FDCS remains underrecognized, with up to 58% of extranodal cases being initially misdiagnosed.6Mean age at diagnosis is 44 years, with no female or male predilection. The only association reported is that 10% to 20% of cases have preceding or concurrent Castleman disease.1,6,7Diagnosis of FDCS is frequently delayed owing to initial misdiagnosis or biopsy specimens containing necrotic and reactive lymphoid tissue. Differential diagnosis is wide because this tumor has several microscopic appearances and shares ultrastructural features with other tumors. They include ectopic thymoma, malignant melanoma, extracranial meningioma, undifferentiated carcinoma, lymphoepithelial carcinoma, spindle cell carcinoma, peripheral nerve sheath tumor, sarcomas, and gastrointestinal stromal tumor.7 Histologically, FDCS appears spindlelike, with a prominent, whorled, storiform pattern and interdigitating processes. Nuclei are oval or rounded and may be irregular in contour with pleomorphism.1,7 The tumor can be misdiagnosed as vascular owing to a prominent pseudovascular pattern. These sarcomas can only be confirmed by immunohistochemical analysis . The cells of FDCS share the immunophenotype of nonneoplastic FDCs, with CD21, CD35, and CD23 being the most specific markers. Other markers include vimentin and desmoplakin. Some are variably positive for epithelial membrane antigen, S-100, and mannitol salt agar, presenting diagnostic pitfalls.1 They are negative for CD45, CD20, CD1a, and HMB-45.Likelihood of recurrence, metastasis, and mortality is based on size greater than 6 cm, presence of coagulative necrosis, high mitotic count (>5 per 10 high-power fields), nuclear pleomorphism, intra-abdominal location, and lack of adjuvant therapy.7 The lung, liver, and lymph nodes are the most common sites of metastasis, and the tumor may be highly aggressive and fatal within 2 years of diagnosis. One review7 showed an overall recurrence rate of 43%, a metastatic rate of 24%, and a mortality rate of 17%. For extranodal FDCS, 2- and 5-year recurrence-free survival rates were 62.3% and 27.4%, respectively.Owing to the variable clinical course of FDCS, there is no standardized treatment regimen. It is often treated with wide local resection with or without radiotherapy and/or chemotherapy (CHOP [cyclophosphamide, hydroxydaunorubicin, vincristine (Oncovin) (vincristine), and prednisone or prednisolone] or CHOP-like regimens).2,7 In the present case, final pathologic findings revealed FDCS with disease involving the margins. Given residual disease, the plan was for postoperative chemotherapy and irradiation. However, on postoperative week 6, clinical examination revealed recurrent oropharyngeal mass, and repeat magnetic resonance imaging was performed for surgical planning. Mandibulotomy with wide re-resection of pharyngeal mass and left modified radical neck dissection with reconstruction was performed. Final pathologic findings showed negative margins. After the second surgery, the patient received 3 cycles of CHOP followed by 54-Gy radiation therapy. Thirteen-month follow-up imaging and physical examination revealed no signs of recurrence.Early diagnosis and prompt treatment of FDCS requires a high index of suspicion for this commonly misdiagnosed cancer that has a high recurrence and metastatic rate.

General

A man in his 40s with Poland syndrome presented with a 6-month history of left throat pain and enlarging oropharyngeal mass. The patient had been seen repeatedly for odynophagia that persisted despite multiple courses of antibiotics, reflux medications, and steroids prescribed at clinics and emergency departments. Over the course of 5 months, he underwent a tonsillectomy and 3 separate biopsies at multiple institutions. All showed inconclusive results, and the mass progressively enlarged. At presentation for the present report, physical examination showed a 2-cm, well-mucosalized, left oropharyngeal mass not extending to the hard palate (Figure, A). Computed tomography (CT) revealed a 58-mm parapharyngeal mass lateralizing and narrowing the left carotid artery against the styloid process (Figure, B). A CT-guided fine-needle aspiration biopsy was performed but again was nondiagnostic. Further confounding the clinical picture, a pacemaker was required for multiple episodes of sinus asystole due to mass effect on the carotid body. To obtain the diagnosis of the parapharyngeal mass, the patient had a transcervical resection with transoral partial glossectomy, palatectomy, and pharyngectomy with reconstruction. Results of immunohistochemical analysis of the removed tissue were positive for CD4 (weak), CD21, CD23, and vimentin with a low proliferation rate (Figure, C and D).A, A 2-cm well-mucosalized left oropharyngeal soft-palate mass anterior to the tonsillar bed with surrounding erythema. B, Left parapharyngeal mass measuring 4.3 × 2.7 × 5.8 cm and lateralizing the left carotid artery. C, Fascicular, storiformed architecture with spindly, polygonal-shaped cells with eosinophilic cytoplasm and indistinct borders (original magnification ×10). D, Positive findings for CD21 (left; original magnification ×10) and CD23 (right; original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Ectopic thymoma

Follicular dendritic cell sarcoma

Poorly undifferentiated carcinoma

Peripheral nerve sheath tumor

b

male

41-50

original

https://jamanetwork.com/journals/jama/fullarticle/2708612

A 38-year-old woman presented with acute abdominal pain. Her history included bariatric gastric bypass surgery (3 years prior), hysterectomy for uterine leiomyomas (5 years prior), and pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (7 years prior). She had recently undergone ovarian stimulation for in-vitro fertilization.The patient’s physical examination showed a tender abdomen without rigidity. Auscultation revealed no abnormal findings. Results of routine blood testing were unremarkable. Imaging studies suggested intussusception at the jejunojejunal anastomosis and a right adnexal mass; the intussusception was successfully reduced laparoscopically. Multiple ruptured follicles were seen on the surface of the right ovary. A preoperative chest computed tomography scan revealed multiple lung nodules of variable sizes, predominantly in the lower lobes (Figure 1).Perform cardiac echocardiography to rule out right-sided endocarditis What Would You Do Next?

Observe only

Perform cardiac echocardiography to rule out right-sided endocarditis

Refer the patient to oncology for chemotherapy

Start treatment with sirolimus

Pulmonary benign metastasizing leiomyoma (PBML)

A

Observe only

The key to the correct diagnosis is the lung biopsy showing a proliferation of fascicles of spindle cells with entrapped benign alveolar tissue without necrosis, atypia, or mitotic activity (Figure 2). The cells were positive for smooth muscle actin, desmin, estrogen, and progesterone receptors. The findings are consistent with PBML. Despite its ability to metastasize, this tumor is not locally invasive and requires no treatment with chemotherapy. The biopsy showed no evidence of infection in the nodule, which excludes the diagnosis of septic pulmonary emboli from right-sided endocarditis. Sirolimus can stabilize lung function and reduce symptoms in lymphangioleiomyomatosis, which is a slow, progressive, and diffuse growth of smooth muscle cells infiltrating the lung parenchyma. Lymphangioleiomyomatosis manifests radiologically as a diffuse cystic disease as opposed to circumscribed nodules, which are characteristically seen in PBML.Biopsy of lung lesion showing spindle-shaped cells (hematoxylin-eosin, original magnification ×200). Inset, Cells stain positive for progesterone receptors.Whereas multiple small nodules smaller than 5 mm are often benign (granulomata, scars), multiple lung nodules larger than 1 cm are often attributable to metastatic disease. The workup of multiple nodules larger than 1 cm includes a physical examination and imaging, with emphasis on identifying a primary solid malignancy. Metastatic nodules tend to be of various sizes and predominantly affect the lower lobes in subpleural locations. In the workup of multiple lung nodules, abdominal and pelvic imaging should be considered to evaluate for an underlying malignancy. Endoscopic examination of the upper and lower gastrointestinal tract should be performed in the presence of symptoms and findings consistent with gastrointestinal malignancy such as iron-deficiency anemia, abdominal pain, and unexplained weight loss. If a primary malignancy is not identified, lung nodule biopsy is necessary.PBML was first described in the 1880s1; since then, more than 100 cases have been reported. PBML is characterized by metastatic spread and growth of uterine spindle-shaped smooth muscle cells. The lungs, heart, bones, vasculature, and retroperitoneum can be affected. PBML is usually considered to be clinically benign, although some pathologists believe that the tumors are extremely well-differentiated leiomyosarcomas.2,3PBML is typically diagnosed in women of late reproductive age but also has been described in other age groups. Most patients are asymptomatic, and the abnormal lesions are incidentally discovered. Occasionally, hemoptysis, chest pain, dyspnea, and, rarely, pneumothorax4 are the presenting symptoms. Characteristically, solitary or multiple pulmonary lesions with smooth borders and ranging in size from a few millimeters to several centimeters are present in the lower lobes. Rarely, the nodules can cavitate.5Several mechanisms have been suggested in the pathogenesis of PBML. The most popular theory posits iatrogenic lymphatic or vascular spread of uterine smooth muscle cells during surgical debulking or curettage of uterine leiomyoma (“transportation theory”). The median “latency” period between the procedure and the diagnosis of PBML is longer than 10 years.2,6 Spontaneous hematogenous spread and in situ growth of multiple fibroleiomyomatous hamartomas are other hypothesized mechanisms that may explain the unusual cases in which patients have no history of previous uterine surgery.3The diagnostic evaluation of PBML requires biopsy and histopathologic evaluation, as the radiographic manifestations are not specific. The characteristic microscopic findings include spindle-shaped cells resembling uterine leiomyoma, a low mitotic index, lack of local invasion, and no nuclear atypia. Immunohistochemical stains for smooth muscle markers such as actin, desmin, and caldesmon, as well as estrogen and progesterone receptors, can help establish the diagnosis.Conservative management with no intervention is generally recommended in asymptomatic patients. The lesions will often regress after menopause and during pregnancy.7,8 In younger, symptomatic patients, antiestrogen therapy, such as oophorectomy, gonadotropin-releasing hormone agonists, selective estrogen receptor modulators, and aromatase inhibitors can be considered.9,10 Surgical resection can be contemplated, especially if compression symptoms occur. Fatalities from PBML have been reported.1This patient had no respiratory symptoms, and a decision was made to monitor her. Ovarian stimulation for in-vitro fertilization was considered likely to have caused the growth of already existing microscopic leiomyomatous lesions. Some regression in size was seen in the following months, and the patient remained asymptomatic.

General

A 38-year-old woman presented with acute abdominal pain. Her history included bariatric gastric bypass surgery (3 years prior), hysterectomy for uterine leiomyomas (5 years prior), and pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension (7 years prior). She had recently undergone ovarian stimulation for in-vitro fertilization.The patient’s physical examination showed a tender abdomen without rigidity. Auscultation revealed no abnormal findings. Results of routine blood testing were unremarkable. Imaging studies suggested intussusception at the jejunojejunal anastomosis and a right adnexal mass; the intussusception was successfully reduced laparoscopically. Multiple ruptured follicles were seen on the surface of the right ovary. A preoperative chest computed tomography scan revealed multiple lung nodules of variable sizes, predominantly in the lower lobes (Figure 1).Perform cardiac echocardiography to rule out right-sided endocarditis

what would you do next?

What would you do next?

Observe only

Perform cardiac echocardiography to rule out right-sided endocarditis

Start treatment with sirolimus

Refer the patient to oncology for chemotherapy

a

female

31-40

original

https://jamanetwork.com/journals/jama/fullarticle/2706536

A previously healthy, 25-year-old woman presented with a hyperpigmented macule on the medial side of her right palm. She reported hypoesthesia over the lesion. Two years ago, she immigrated to the United States from Bangladesh. Five months ago, she visited Bangladesh to get married. A biopsy of the lesion obtained there showed multiple perineural granulomas with inflammatory cells. Gram stain and acid-fast bacillary and fungal stains of the biopsy specimen were negative. The patient was prescribed 1 dose each of doxycycline, ofloxacin, and rifampin and experienced no improvement.On physical examination there was a mildly erythematous macule located over the medial aspect of the right palm, with loss of touch and temperature sensation over the involved area (Figure). A thickened, nontender ulnar nerve was palpated on the ipsilateral side in the olecranon fossa.Perform a diagnostic biopsy of the hyperpigmented area and right ulnar nervePrescribe a 6-month course of isoniazid, rifampin, ethambutol, and pyrazinamidePrescribe a 12-month course of dapsone combined with rifampin What Would You Do Next?

No further treatment is indicated

Perform a diagnostic biopsy of the hyperpigmented area and right ulnar nerve

Prescribe a 6-month course of isoniazid, rifampin, ethambutol, and pyrazinamide

Prescribe a 12-month course of dapsone combined with rifampin

Tuberculoid leprosy with a single lesion and ulnar nerve involvement

D

Prescribe a 12-month course of dapsone combined with rifampin

The key to the correct diagnosis is the presence of a hypoesthetic macule and peripheral nerve enlargement in a patient from a region where tuberculoid leprosy is endemic. The diagnosis of tuberculoid leprosy is often based on clinical presentation, because skin biopsies, nerve biopsies, or both frequently do not reveal the pathogen. Single-dose therapy is inappropriate for patients with paucibacillary leprosy and peripheral nerve enlargement. A repeat biopsy is unlikely to be of benefit because of the low number of organisms in the tuberculoid form of leprosy. The presentation of a hypoesthetic macular patch with nerve enlargement is not consistent with a diagnosis of tuberculosis, so antituberculosis therapy would not be appropriate.Leprosy is a chronic infection caused by Mycobacterium leprae, which leads to permanent damage of the skin, nerves, eyes, and limbs, resulting in physically and socially disabling disease.1 Human-to-human aerosol spread of nasal secretions or prolonged direct contact with a person with skin lesions is considered the most likely mode of transmission. More than 200 000 new cases of leprosy are reported to the World Health Organization (WHO) each year.2 In 2014, the US Department of Health and Human Services reported 175 new cases of leprosy in the United States; most of these cases are identified in immigrants, although the infection may be endemic in parts of Louisiana, Florida, and Texas along the Gulf of Mexico. Leprosy may be a zoonosis (an infection acquired from animals) in the Southern United States, since armadillos serve as major reservoirs for M leprae.3,4 Because of the declaration of “elimination”—defined as a reduction of patients with leprosy requiring multidrug therapy to fewer than 1 per 10 000 population—by the WHO in 2000, there has been less funding allotted for the national control program in many countries.Lepromatous leprosy, commonly referred to as multibacillary, is characterized by multiple skin lesions (nodules, plaques) with high bacillary abundance. For the purpose of treatment, the WHO recently proposed a simple clinical classification, based on the number of skin lesions and nerve trunk involvement. Patients with 5 or fewer skin lesions, with or without nerve trunk involvement, are categorized as having paucibacillary leprosy; the remainder are categorized as having the multibacillary form.5,6Multidrug therapy including dapsone, clofazimine, and rifampin is the mainstay of treatment for leprosy because of emerging drug resistance to dapsone.3 According to the WHO, a single dose of combination therapy including rifampin (600 mg), ofloxacin (400 mg), and minocycline (100 mg) is adequate for paucibacillary leprosy with a single skin lesion and without nerve involvement (Table).7,8 Treatment regimens for 2 or more lesions include dapsone combined with rifampin for paucibacillary leprosy and dapsone combined with rifampin and clofazimine for multibacillary leprosy. In the United States, patients with leprosy are treated in consultation with the National Hansen’s Disease Program (a service of the Bureau of Primary Health Care of the US Department of Health and Human Services, primarily responsible for patient care of leprosy); the duration of treatment, as per US guidelines, is longer than the WHO recommendations, with a goal to prevent emergence of resistance and to enhance cure.7,9 In 1998, the WHO shortened the duration of therapy, likely owing to limited resources in endemic countries.During 3 months of follow-up, the patient experienced improved sensation over the palm. No family members were identified with similar skin lesions. The National Hansen’s Disease Program provided the patient with a 12-month supply of dapsone and rifampin.

General

A previously healthy, 25-year-old woman presented with a hyperpigmented macule on the medial side of her right palm. She reported hypoesthesia over the lesion. Two years ago, she immigrated to the United States from Bangladesh. Five months ago, she visited Bangladesh to get married. A biopsy of the lesion obtained there showed multiple perineural granulomas with inflammatory cells. Gram stain and acid-fast bacillary and fungal stains of the biopsy specimen were negative. The patient was prescribed 1 dose each of doxycycline, ofloxacin, and rifampin and experienced no improvement.On physical examination there was a mildly erythematous macule located over the medial aspect of the right palm, with loss of touch and temperature sensation over the involved area (Figure). A thickened, nontender ulnar nerve was palpated on the ipsilateral side in the olecranon fossa.Perform a diagnostic biopsy of the hyperpigmented area and right ulnar nervePrescribe a 6-month course of isoniazid, rifampin, ethambutol, and pyrazinamidePrescribe a 12-month course of dapsone combined with rifampin

what would you do next?

What would you do next?

No further treatment is indicated

Prescribe a 12-month course of dapsone combined with rifampin

Perform a diagnostic biopsy of the hyperpigmented area and right ulnar nerve

Prescribe a 6-month course of isoniazid, rifampin, ethambutol, and pyrazinamide

b

female

21-30

original

https://jamanetwork.com/journals/jama/fullarticle/2712744

A 68-year-old man was diagnosed with chronic hepatitis C genotype 1b 5 years ago. He had no evidence of advanced liver disease (eg, thrombocytopenia). Liver ultrasound showed no signs of cirrhosis, such as nodularity. Vibration-controlled transient elastography (VCTE) performed prior to treatment was negative for signficant fibrosis at 6.7 kPa. Hepatitis C was cured, based on viral load, with simeprevir and sofosbuvir for 12 weeks. He presents for follow-up. Laboratory studies and VCTE were performed (Table 1).The patient requires a liver biopsy to confirm fibrosis stage. How Do You Interpret These Results?

The patient has cirrhosis.

The patient has a healthy liver.

The patient has minimal fibrosis.

The patient requires a liver biopsy to confirm fibrosis stage.

A

The patient has cirrhosis.

Cirrhosis is the end result of chronic liver injury and progressive fibrosis.1 In the United States, the most common causes of cirrhosis and end-stage liver disease among adults awaiting liver transplantation are chronic hepatitis C (35%), alcoholic liver disease (18%), and nonalcoholic fatty liver disease (16%).2VCTE measures liver fibrosis (stiffness) noninvasively (Medicare national reimbursement, $41.04).3 VCTE measurements correlate with METAVIR, a histopathological 5-stage scoring system of fibrosis (stage 0 [no fibrosis] to stage 4 [cirrhosis]).4 VCTE was first validated against biopsy for detecting hepatitis C cirrhosis.5 The VCTE ultrasound transducer probe generates both an elastic shear wave that traverses the liver and a pulse echo that measures wave velocity through the liver. More fibrotic tissue is stiffer and resistant to deformation from the shear wave. Thus, higher wave velocities indicate greater liver fibrosis. Results are expressed as liver stiffness measurement (LSM; 1.5 kPa [no stiffness] to 75 kPa [greatest stiffness]).4,6 VCTE is more accurate for diagnosing cirrhosis than for staging fibrosis but is often considered a method of staging fibrosis.VCTE has limitations. First, postprandial increases in portal blood flow increase velocity. Therefore, patients should fast at least 3 hours prior to VCTE.5 Second, VCTE should not be performed in patients with ascites, alanine aminotransferase greater than 100 U/L, or acute liver injury (eg, acute hepatitis or ischemia) because poor wave transmission and inflammation cause falsely elevated results. Third, alcohol consumption, cholestasis, heart failure, and tumor infiltration increase hepatic venous pressure and wave attenuation, which leads to increased velocity and subsequent misdiagnosis of advanced fibrosis stage or cirrhosis.4,6 Fourth, VCTE may be uninterpretable due to poor transmission quality caused by small intercostal spaces or large body habitus. Fifth, VCTE cannot reliably distinguish between fibrosis stages (ie, stage 1 vs stage 2). Approximately 1% to 5% of adults undergoing VCTE have unreliable or inaccurate results, subsequently requiring liver biopsy.Despite limitations, LSM is highly accurate compared with the reference standard of liver biopsy for diagnosing cirrhosis. Diagnostic thresholds, sensitivity, and specificity for cirrhosis vary by underlying liver disease due to differences in hepatic venous pressure, cholestasis, inflammation, and fibrosis pattern (Table 2).4,5 Area under the receiver operating characteristic curves for cirrhosis ranges from 0.93 to 0.99 (Table 2).5The patient’s LSM of 20.0 kPa is consistent with cirrhosis because it is greater than the diagnostic threshold for cirrhosis (12.5 kPa). Liver biopsy is not required. Liver biopsy could confirm cirrhosis when uncertainty about the validity of VCTE exists or when histologic features are important for diagnosis. VCTE reliably detects cirrhosis in chronic hepatitis B, alcoholic liver disease, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, and nonalcoholic fatty liver disease.5 VCTE is approved for use in adults and children by the US Food and Drug Administration.4,5Although liver biopsy is the reference standard, biopsy size (sampling error) and interobserver variation among pathologists affect fibrosis staging.5 One noninvasive test alternative is magnetic resonance elastography, which uses magnetic resonance imaging rather than ultrasound to measure stiffness and has superior sensitivity and specificity for fibrosis staging. However, magnetic resonance elastography is more expensive, labor intensive, and has limited availability. Other noninvasive tests include blood tests, such as the aspartate aminotransferase-to-platelet ratio index and other serologic fibrosis markers, which are readily available but diagnose cirrhosis less accurately than VCTE.5VCTE diagnosed cirrhosis, thus the patient underwent testing for cirrhosis complications such as portal hypertension and liver cancer. Subsequently, upper endoscopy revealed large esophageal varices and the patient began taking a nonselective β-blocker to prevent variceal bleeding. Because of cirrhosis, he undergoes liver ultrasound every 6 months to evaluate for hepatocellular carcinoma. His liver function remains stable 2 years after cirrhosis diagnosis.Vibration-controlled transient elastography (VCTE) accurately confirms the presence or absence of cirrhosis in many etiologies of chronic liver disease.Liver stiffness measurement (LSM) should be interpreted within the clinical context for each patient, and results should be corroborated with other noninvasive tests or liver biopsy if questions persist regarding LSM accuracy.Clinicians must be aware of the limitations of VCTE in order to use and interpret results correctly.

Diagnostic

A 68-year-old man was diagnosed with chronic hepatitis C genotype 1b 5 years ago. He had no evidence of advanced liver disease (eg, thrombocytopenia). Liver ultrasound showed no signs of cirrhosis, such as nodularity. Vibration-controlled transient elastography (VCTE) performed prior to treatment was negative for signficant fibrosis at 6.7 kPa. Hepatitis C was cured, based on viral load, with simeprevir and sofosbuvir for 12 weeks. He presents for follow-up. Laboratory studies and VCTE were performed (Table 1).The patient requires a liver biopsy to confirm fibrosis stage.

how do you interpret these results?

How do you interpret these results?

The patient requires a liver biopsy to confirm fibrosis stage.

The patient has a healthy liver.

The patient has cirrhosis.

The patient has minimal fibrosis.

c

male

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2712522

A 65-year-old woman presented to her primary care physician with concerns about large fluctuations in her blood pressure (BP). The patient’s home BP measurements were often lower than 120/80 mm Hg but sometimes reached 200/100 mm Hg. She had a non–ST-segment elevation myocardial infarction 1 year ago and was treated with a drug-eluting stent in her right coronary artery. Her antihypertensive medications included carvedilol (12.5 mg, twice daily), lisinopril (40 mg daily), and chlorthalidone (12.5 mg daily). Additionally, the patient had generalized anxiety and panic disorders (treated with paroxetine, 30 mg), and she smoked for 90 pack-years but quit 2 months ago. The patient’s office BP measurement was 127/74 mm Hg. Her physical examination was unremarkable.Twenty-four-hour ambulatory BP monitoring was performed to evaluate patterns of elevated BP and potential etiologies. The patient kept a log of her diet, sleep pattern, and symptoms. Mean BP levels were 133/86 mm Hg overall (normal, <130/80 mm Hg); daytime, 135/88 mm Hg (normal, <135/85 mm Hg); and sleeping, 124/78 mm Hg (normal, <120/70 mm Hg).1 During the first sudden increase in BP (04:00-06:00; Figure), she awoke from sleep with a panic attack. The second sudden increase (07:00-10:00) occurred after eating a high-sodium breakfast.The patient has normal BP since the office BP was normal. How Do You Interpret These Results?

The patient has normal BP since the office BP was normal.

The patient has masked uncontrolled hypertension.

The patient has white coat hypertension.

The patient’s BP dips appropriately during sleep.

B

The patient has masked uncontrolled hypertension.

Twenty-four-hour ambulatory BP monitoring measures BP over 24 hours, every 15 to 30 minutes during the day, and every 30 to 60 minutes during sleep (eTable in the Supplement). Observational studies consistently demonstrated that ambulatory BP monitoring is more predictive of clinical outcomes than office BP measurement.1-4 Testing is indicated when clinicians suspect that office BP does not reflect ambulatory BP levels. White coat hypertension may be suspected in patients with office BP levels of 140/90 mm Hg to 169/99 mm Hg, who are nonsmokers, and who report anxiety at clinic visits; however, if patients with these characteristics are smokers, it is less likely that a clinician would suspect white coat hypertension because sustained hypertension is more common. Patients with normal office BP but hypertension-related end-organ damage, such as left ventricular hypertrophy, may have elevated ambulatory BP levels. A normal office BP without antihypertensive medication in a patient with elevated ambulatory BP is defined as having masked hypertension. Patients who meet criteria for masked hypertension and who are taking antihypertensive medication are classified as having masked uncontrolled hypertension.The Centers for Medicare & Medicaid Services covers ambulatory BP monitoring to evaluate white coat hypertension. The prevalence of white coat hypertension is 10% to 35% among patients evaluated for hypertension.2,4,5 Medicare reimbursement is $50 to $70.6 Some private insurers cover ambulatory BP monitors to evaluate additional phenotypes (see eTable in the Supplement), such as masked hypertension.1,2 Over a 10-year period, more than 40% of adults with white coat or masked hypertension may develop sustained hypertension.7The patient’s hypertension was associated with episodes of anxiety and high-sodium diet. Common causes of ambulatory hypertension include sleep disorders, medication nonadherence, tobacco use, and psychosocial stressors.8 Adults with masked hypertension or masked uncontrolled hypertension are more than twice as likely to develop cardiovascular disease as normotensive adults.4,9 Treatment should be based on potential etiologies (for this patient, anxiety and a high-sodium diet) and does not always require antihypertensive drugs.Normally, nocturnal BP decreases between 10% and 19%. Decreases of 10% or less are considered as inadequate (known as nondipping). Elevated morning BP levels, as read on home BP monitors, can suggest inadequate dipping. In a registry of 17 312 adults with hypertension, nondipping was associated with a 27% higher risk of cardiovascular events.10 Proposed explanations include increased sympathetic tone, arterial stiffness, or salt sensitivity. Strategies to treat nondipping include administering medication at night and treating sleep disorders. However, no randomized trials have evaluated whether restoring dipping with therapeutic interventions improves outcomes.Ambulatory BP monitoring could be repeated to confirm BP control in high-risk patients. Home BP monitoring, if performed correctly, provides similar information as daytime ambulatory BP monitors.2 Patients with white coat hypertension may benefit from repeat testing every 1 to 2 years to screen for sustained hypertension.1Home BP monitors are a reasonable alternative for patients without access to ambulatory BP monitoring. Results of home BP monitors are independently associated with cardiovascular risk, after adjusting for office BP.2,3 Advantages of ambulatory BP monitoring are that it includes nocturnal measurements, facilitates measurement outside of the home, does not rely on patient technique, and may be better tolerated by patients who experience anxiety with BP measurement. In contrast, home BP monitoring allows for BP measurement over more than 1 day and can also help improve BP control.2The patient was encouraged to follow a low-sodium diet. She began a regimen of amlodipine (5 mg) in the evening to restore nocturnal dipping. Because some of her hypertensive episodes were associated with anxiety or mental stress, paroxetine was increased to 40 mg, and she was referred for counseling. Her daytime BP control improved, based on home BP monitoring. Her anxiety remained difficult to manage. The large increases in BP level during panic attacks continued, although her systolic BP rarely reached 160 mm Hg. A repeat ambulatory BP monitoring would have been reasonable, but was not performed.Ambulatory BP monitoring is most often used to evaluate white coat hypertension.Progression from white coat hypertension to sustained hypertension is common.Additional hypertension phenotypes detected with ambulatory BP monitors include masked hypertension and nocturnal nondipping.Causes of masked hypertension or nondipping should be evaluated and treated accordingly (eg, high-sodium diet, sleep disorders, and psychosocial stress).

Diagnostic

A 65-year-old woman presented to her primary care physician with concerns about large fluctuations in her blood pressure (BP). The patient’s home BP measurements were often lower than 120/80 mm Hg but sometimes reached 200/100 mm Hg. She had a non–ST-segment elevation myocardial infarction 1 year ago and was treated with a drug-eluting stent in her right coronary artery. Her antihypertensive medications included carvedilol (12.5 mg, twice daily), lisinopril (40 mg daily), and chlorthalidone (12.5 mg daily). Additionally, the patient had generalized anxiety and panic disorders (treated with paroxetine, 30 mg), and she smoked for 90 pack-years but quit 2 months ago. The patient’s office BP measurement was 127/74 mm Hg. Her physical examination was unremarkable.Twenty-four-hour ambulatory BP monitoring was performed to evaluate patterns of elevated BP and potential etiologies. The patient kept a log of her diet, sleep pattern, and symptoms. Mean BP levels were 133/86 mm Hg overall (normal, <130/80 mm Hg); daytime, 135/88 mm Hg (normal, <135/85 mm Hg); and sleeping, 124/78 mm Hg (normal, <120/70 mm Hg).1 During the first sudden increase in BP (04:00-06:00; Figure), she awoke from sleep with a panic attack. The second sudden increase (07:00-10:00) occurred after eating a high-sodium breakfast.The patient has normal BP since the office BP was normal.

how do you interpret these results?

How do you interpret these results?

The patient has masked uncontrolled hypertension.

The patient has normal BP since the office BP was normal.

The patient has white coat hypertension.

The patient’s BP dips appropriately during sleep.

a

female

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2687002

A woman in her 60s presented for initial dermatologic evaluation of a 2-year history of a pruritic and sometimes burning hyperpigmented eruption on the bilateral palms. The eruption had gradually spread from the left palm to the right palm and then focally onto the bilateral volar aspect of the wrists in recent months (Figure, A and B). She had not experienced involvement of the plantar surfaces. No additional concerns were reported, and there was no family history of similar lesions. There was no known history of travel in relation to onset of the lesions. Limited clinical examination revealed well-marginated brown atrophic patches on the bilateral palms extending focally onto the volar aspect of the wrist and centrally surmounted by spiny keratotic pits in the palmar creases. Two punch biopsy specimens were obtained for diagnostic clarification (Figure, C and D).A, An atrophic hyperpigmented plaque with spiny papules in the palmar creases. B, Similar features extending onto the volar wrist. C and D, Histopathologic images (hematoxylin-eosin, original magnification ×100). What Is Your Diagnosis?

Lichen sclerosus et atrophicus

Acrodermatitis chronica atrophicans

Acquired palmoplantar keratoderma

Sclerotylosis (Huriez syndrome)

A. Lichen sclerosus et atrophicus

A

Lichen sclerosus et atrophicus

The first specimen demonstrated compact orthohyperkeratosis overlying an attenuated epidermis with a central dell and preserved granular layer. These features, in isolation, raised a histopathologic differential diagnosis of punctate palmoplantar keratoderma. The second specimen revealed similar orthohyperkeratosis and an effaced and atrophic epidermis; however, in the dermis, hyalinization of the papillary dermis above a thin band of lymphocytic inflammation was present. Close inspection and deeper levels of the first specimen revealed subtle interface changes and superficial dermal hyalinization. These features were diagnostic of lichen sclerosus of the palms.The patient returned to the clinic for discussion of biopsy results. When asked specifically, she reported significant vulvar pruritus, which had previously been treated unsuccessfully by her primary care physician and gynecologist; she realized in retrospect that this pruritus had developed around the same time as the palmar eruption. Examination of the external genitalia revealed a pearly white patch involving the anterior aspect of the labia minora and clitoral hood; no advanced scarring or fusion of anatomical structures was present. Treatment with an ultrapotent topical steroid and a calcineurin inhibitor was initiated at both sites of involvement.Lichen sclerosus involving the palms has been reported 3 times in the English-language literature. It was first described in 1971 by Purres and Krull in the setting of disseminated disease, both genital and extragenital.1 This report mentions small keratotic plugs on one of the palms, perceived to be located at the orifices of the sweat ducts. The presented histopathologic findings did not demonstrate the keratotic pits. Previously, the existence of palmar lichen sclerosus was the subject of debate; while Hallopeau’s original report mentions a lesion on the volar aspect of the left forearm, it is unclear whether the palmar surface proper was involved.2A second case was described in 1979 by Petrozzi et al.3 This patient had small whitish papules on the palms and soles in the absence of genital involvement. The histopathologic findings were reported to include hyperkeratotic plugs at adnexal orifices, but were not depicted. In 1984, Tudino and Wong described a patient with bullous and hemorrhagic lesions of the palms and wrists.4 Additional reports have appeared in non–English-language sources.5-7Lichen sclerosus is an inflammatory sclerosing condition that most commonly affects the external genitalia. Recognition of this entity is crucial because of the risk of squamous cell carcinoma that may develop in untreated or undertreated cases. A recent study revealed a significant decrease in the risk of carcinoma with proper treatment.8 Involvement of extragenital sites is not uncommon, but in general occurs on the trunk and proximal extremities. Involvement of the palms and soles is rare; less than one dozen cases have been reported, although this condition may be both underrecognized and underreported.The features of extragenital lichen sclerosus have been well documented in other sources.9 The histopathologic findings are similar to those found in the genital area but also include prominent follicular plugging at hair-bearing sites. The keratotic palmar pits, which may clinically simulate punctate keratoderma, may represent a recapitulation or forme fruste of this process at a glabrous site. While disease isolated to the palms and soles has been reported, most cases have presented with concomitant vulvar disease. Identification of palmar disease may lead to diagnosis of vulvar disease (as in this case), which may in turn reduce the patient’s risk of malignant neoplasm with proper treatment. While malignant transformation of extragenital lichen sclerosus has been reported, none of the patients with volar acral involvement have developed squamous cell carcinoma.10Acrodermatitis chronica atrophicans is a manifestation of chronic infection with Borrelial species, most commonly observed in persons who have visited or live in Europe. Nonvolar skin is more prominently affected clinically, and a prominent plasmacellular infiltrate is often seen histologically. Acquired palmoplantar keratoderma was considered in the initial differential diagnosis, and orthokeratotic epidermal dells with preserved granular layer typify the microscopic appearance of punctate keratoderma; however, the dermal infiltrate and sclerosis are not seen. Sclerotylosis is a rare variant of hereditary keratoderma characterized by diffuse inflammatory keratoderma of the palms and soles and scleroatrophic changes of the digits.

Dermatology

A woman in her 60s presented for initial dermatologic evaluation of a 2-year history of a pruritic and sometimes burning hyperpigmented eruption on the bilateral palms. The eruption had gradually spread from the left palm to the right palm and then focally onto the bilateral volar aspect of the wrists in recent months (Figure, A and B). She had not experienced involvement of the plantar surfaces. No additional concerns were reported, and there was no family history of similar lesions. There was no known history of travel in relation to onset of the lesions. Limited clinical examination revealed well-marginated brown atrophic patches on the bilateral palms extending focally onto the volar aspect of the wrist and centrally surmounted by spiny keratotic pits in the palmar creases. Two punch biopsy specimens were obtained for diagnostic clarification (Figure, C and D).A, An atrophic hyperpigmented plaque with spiny papules in the palmar creases. B, Similar features extending onto the volar wrist. C and D, Histopathologic images (hematoxylin-eosin, original magnification ×100).

what is your diagnosis?

What is your diagnosis?

Acquired palmoplantar keratoderma

Lichen sclerosus et atrophicus

Sclerotylosis (Huriez syndrome)

Acrodermatitis chronica atrophicans

b

female

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2687547

A woman in her 70s presented with a 1-year history of a facial cutaneous eruption initially affecting malar cheeks and eyebrows. Subsequently it spread to involve nose, chin, upper trunk, and extremities. The lesions were mildly pruritic. Her medical history included a cadaveric renal transplant 2 years earlier for end-stage renal failure. Immunosuppressant medications included mycophenolate mofetil, 200 mg, twice daily and tacrolimus, 8 mg, twice daily. Tacrolimus levels were therapeutic. Physical examination revealed multiple 1-mm flesh-colored follicular papules and keratin spines against a diffuse erythematous background affecting the face (Figure, A and B) and upper trunk. Her scalp and eyebrow hairs were unremarkable. Serology results were unremarkable. Results of skin biopsy from the right ear demonstrated dilatation and keratotic plugging of the hair infundibula with marked dystrophy and expansion of the inner root sheath. The inner root sheath cells were enlarged with irregular trichohyaline granules and apoptotic cells with abrupt cornification without formation of a granular layer (Figure, C). Immunohistochemical analysis for SV40 polyomavirus was positive (Figure, D).Photographs of (A) forehead and (B) nose depicting multiple follicular papules and keratin spines against a diffuse erythematous background. C, Hematoxylin-eosin staining (original magnification ×40). D, SV40 polyomavirus stain (original magnification ×40). What Is Your Diagnosis?

Trichodysplasia spinulosa

Lichen spinulosus

Demodecosis

Disseminated keratosis pilaris

A. Trichodysplasia spinulosa

A

Trichodysplasia spinulosa

Taking the clinical and histopathological findings together, the diagnosis is consistent with trichodysplasia spinulosa. Treatment options included reduction in tacrolimus dose; however, owing to the risk of transplant rejection this was not deemed to be a safe option. To date, the rash persists and has further spread to involve most of the trunk and extremities.Trichodysplasia spinulosa is a rare viral infection reported in immunosuppressed patients with a medical history of organ transplantation or patients who are immunosuppressed from hematologic malignant abnormalities treated with chemotherapy. Trichodysplasia spinulosa-associated polyomavirus (TSPγV) was first identified in 2010.1 The causal mechanism by which this TSPγV human polyomavirus causes trichodysplasia spinulosa remains unknown. Despite this, on a molecular level, TSPγV has been shown to activate factors implicated in the mitogen-activated protein kinase (MAPK) pathway leading to cellular proliferation characteristics of trichodysplasia spinulosus.2In addition to the skin, TSPγV virus has been identified in saliva, blood, and midturbinate nasal swabs supporting other possible transmission routes.1,3 Previous authors have detected high viral loads of TSPγV in the upper respiratory tract, suggesting this is an important transmission mode.3 It has been associated with a nonscarring alopecia and has previously been reported to affect not just scalp but also severely affecting both eyelashes and eyebrows.4Cases of trichodysplasia spinulosa in the literature are represented by renal and renal-pancreas transplant patients, cardiac transplant patients, lung and liver transplantation, B or T cell acute lymphoblastic leukemias, chronic lymphocytic leukemia, or lupus erythematosus.5Long-term consequences of TSPγV are unknown. In renal transplant patients, the other well-recognized human polyomaviruses such as the JC and BK are the causative agents for transplant-related kidney disease that are usually associated with disease following reactivation from latent infection.6 However, the oncogenic potential of TSPγV warrants continued close monitoring of patients affected with this disease.To date fewer than 36 cases of trichodysplasia spinulosa have been reported in the literature, with no specific treatment recommended. The disease appears to be clinically restricted to the skin. Treatment options reported include topical cidofovir, 1% to 3%, or tazarotene, 0.5% gel, oral valganciclovir, leflunomide, or a reduction in immunosuppression.7-10Patients with solid organ transplant are susceptible to viral-mediated cutaneous infections as a result of immunosuppression, and trichodysplasia spinulosa is 1 example. This case highlights the importance of recognizing TSPγV-associated distinctive folliculocentric spiky rash known as trichodysplasia spinulosa in the immunosuppressed population. Increased awareness of this condition occurring among the organ transplant population may prevent unnecessary investigations and support reduction of severe iatrogenic immunosuppression.

Dermatology

A woman in her 70s presented with a 1-year history of a facial cutaneous eruption initially affecting malar cheeks and eyebrows. Subsequently it spread to involve nose, chin, upper trunk, and extremities. The lesions were mildly pruritic. Her medical history included a cadaveric renal transplant 2 years earlier for end-stage renal failure. Immunosuppressant medications included mycophenolate mofetil, 200 mg, twice daily and tacrolimus, 8 mg, twice daily. Tacrolimus levels were therapeutic. Physical examination revealed multiple 1-mm flesh-colored follicular papules and keratin spines against a diffuse erythematous background affecting the face (Figure, A and B) and upper trunk. Her scalp and eyebrow hairs were unremarkable. Serology results were unremarkable. Results of skin biopsy from the right ear demonstrated dilatation and keratotic plugging of the hair infundibula with marked dystrophy and expansion of the inner root sheath. The inner root sheath cells were enlarged with irregular trichohyaline granules and apoptotic cells with abrupt cornification without formation of a granular layer (Figure, C). Immunohistochemical analysis for SV40 polyomavirus was positive (Figure, D).Photographs of (A) forehead and (B) nose depicting multiple follicular papules and keratin spines against a diffuse erythematous background. C, Hematoxylin-eosin staining (original magnification ×40). D, SV40 polyomavirus stain (original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Trichodysplasia spinulosa

Demodecosis

Lichen spinulosus

Disseminated keratosis pilaris

a

female

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2688583

A healthy woman in her 50s presented with a large annular erythematous plaque on her lower back that had appeared in June (1 month previously) and had centrifugally expanded. She complained about mild pruritus that had not responded to conventional antihistamine therapy or topical steroids. She could not recall an arthropod bite prior to the skin eruption and denied having traveled outside Spain in the past few years. She reported a 20-year history of the same annular plaques recurring on the trunk every single year by the beginning of summer and spontaneously resolving by the beginning of autumn. Such lesions had never appeared on the face, hands, or feet. She did not relate these lesions to any particular hobby or application of any skin care product. Physical examination revealed a large, 35-cm semicircular erythematous plaque on her lower back with central clearing and a distinctive, well-demarcated papular border (Figure, A and B). After obtaining informed consent, 2 biopsy specimens were taken from the papular border of the plaque for both hematoxylin-eosin stain and direct immunofluorescence (Figure, C).A, Large erythematous semicircular plaque with central postinflammatory hyperpigmentation on the lower back. B, Absence of epidermal changes, mild edema of the papillary dermis, and a superficial sparse perivascular inflammatory infiltrate. C, Inflammatory infiltrate composed mainly by lymphocytes and few neutrophils. D, Follow-up visit showing clinical resolution in October. What Is Your Diagnosis?

Granuloma annulare

Erythema papulosa semicircularis recidivans

Deep erythema annulare centrifugum

Erythema chronicum migrans

B. Erythema papulosa semicircularis recidivans

B

Erythema papulosa semicircularis recidivans

Histopathologic examination revealed no epidermal changes, mild edema of the papillary dermis, and a superficial sparse perivascular inflammatory infiltrate composed mainly of lymphocytes and few neutrophils (Figure, C). Periodic acid–Schiff staining was performed and did not show fungal microorganisms in the skin surface. Direct immunofluorescence studies were negative for IgG, IgM, IgA, complement, and fibrin deposition.Complete blood cell count and biochemical studies did not show any significant finding. Results for all serological analyses, including Borrelia burgdorferi antibodies, proved to be negative.Treatment with topical steroids and antihistamines was maintained daily during the first weeks of summer without an apparent clinical response. However, a subsequent follow-up visit in October confirmed that the lesion had spontaneously resolved without any further treatment a few weeks before evaluation (Figure, D).Erythema papulosa semicircularis recidivans (EPSR) represents a novel cutaneous disorder that manifests as centrifugally spreading semicircular erythematous plaques that typically relapse every year during the warm seasons and resolve in autumn.1 First described by Song et al2 in 2012, their case series of 9 middle-aged Chinese men ages 24 to 39 years from the Chongqing or Sichuan provinces presented with similar large figurate erythemas in the trunk that recurred yearly every summer. Since then, a few more cases have been also reported with the same seasonal pattern in young women from other countries.3 While the disease course of this disorder might share some similarities with annually recurring erythema annulare centrifugum,4 for some authors its clinical presentation differs slightly enough to consider it an independent entity.1,2Differential diagnosis in figurate erythemas can be challenging. A good clinical history and clinicopathological correlation in this setting is of utmost importance.5 Other annular erythemas similar to our case must be considered, such as erythema annulare centrifugum, erythema chronicum migrans, granuloma annulare, erythema marginatum, and dermatophytosis.Erythema annulare centrifugum can present as a superficial or deep variant. Both presentations begin as small papules that slowly expand centrifugally and develop central clearing.5,6 In the superficial form, a trailing scale is commonly observed at the advancing edge. The size of the plaques is much smaller than in EPSR, and it does not usually relapse in a seasonal pattern, although in some cases this has been described.4 A biopsy specimen from the peripheral border will commonly show a superficial and deep perivascular infiltrate of lymphocytes surrounding the vessels with a “coat-sleeve” arrangement. Superficial forms may present focal parakeratosis and spongiosis in the overlying epidermis. Such a pattern was not observed in this case.Erythema chronicum migrans is associated with the first stages of Lyme disease and usually presents as an expanding annular plaque that develops at the site of the bite of a Borrelia-infected tick.7 Histopathologic analysis usually shows a superficial and deep perivascular and interstitial infiltrate of lymphocytes, plasma cells, and eosinophils. Spirochetes can be identified with the Warthin-Starry silver stain in approximately half of the specimens. Anti–Borrelia burgdorferi IgM antibodies can be detected from 3 to 6 weeks into the acute infection, which in this case resulted repeatedly in negative results.Granuloma annulare is a self-limited dermatosis that can present in many different forms, ranging from localized, generalized, perforating, to subcutaneous variants.8 Histopathologic analysis commonly reveals collagenolytic granulomas, with areas of necrobiosis in the superficial and mid dermis surrounded by a peripheral rim of palisaded histiocytes and lymphocytes.According to the initial description by Song et al,2 the prognosis of their patients with EPSR is marked by a spontaneous resolution after 2 to 5 years of annual recurrences. However, in the patient described herein, the disease period has been even longer, as she has been experiencing seasonal relapses for the past 20 years.

Dermatology

A healthy woman in her 50s presented with a large annular erythematous plaque on her lower back that had appeared in June (1 month previously) and had centrifugally expanded. She complained about mild pruritus that had not responded to conventional antihistamine therapy or topical steroids. She could not recall an arthropod bite prior to the skin eruption and denied having traveled outside Spain in the past few years. She reported a 20-year history of the same annular plaques recurring on the trunk every single year by the beginning of summer and spontaneously resolving by the beginning of autumn. Such lesions had never appeared on the face, hands, or feet. She did not relate these lesions to any particular hobby or application of any skin care product. Physical examination revealed a large, 35-cm semicircular erythematous plaque on her lower back with central clearing and a distinctive, well-demarcated papular border (Figure, A and B). After obtaining informed consent, 2 biopsy specimens were taken from the papular border of the plaque for both hematoxylin-eosin stain and direct immunofluorescence (Figure, C).A, Large erythematous semicircular plaque with central postinflammatory hyperpigmentation on the lower back. B, Absence of epidermal changes, mild edema of the papillary dermis, and a superficial sparse perivascular inflammatory infiltrate. C, Inflammatory infiltrate composed mainly by lymphocytes and few neutrophils. D, Follow-up visit showing clinical resolution in October.

what is your diagnosis?

What is your diagnosis?

Granuloma annulare

Deep erythema annulare centrifugum

Erythema papulosa semicircularis recidivans

Erythema chronicum migrans

c

female

11-20

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2688299

A 63-year-old man with a history of well-controlled hypertension, lumbar stenosis, and hip arthroplasty with revisions presented with bilateral loss of vision and hearing for several weeks. He also reported a history of painful paresthesias at his feet beginning about 1 year prior.On examination, his visual acuity was initially 20/80 OD and 20/200 OS; it deteriorated over the next 2 months to finger counting bilaterally. The Weber test gave a nonlateralizing result, and bone conduction hearing was absent bilaterally. There was length-dependent loss of vibratory sensation and absent reflexes at both lower extremities. Magnetic resonance imaging demonstrated abnormal enhancement of bilateral optic nerves (Figure, A). Optical coherence tomography and fluorescein angiogram were normal. Nerve conduction studies showed mild sensory axonal polyneuropathy. Laboratory tests were notable for elevated thyrotropin (63 mlU/ml), low levels of free thyroxine (T4) (0.2 ng/dL), and elevated levels of cerebrospinal fluid protein (94 mg/dL). Cerebrospinal fluid IgG index, oligoclonal bands, aquaporin 4 antibody, paraneoplastic panel, and protein electrophoresis test results were all normal. He was treated empirically with high-dose steroids and plasmapheresis, with no improvement in symptoms.A, Axial postgadolinium, fat-suppressed, T-1–weighted magnetic resonance image of the orbits, demonstrating left greater than right enhancement of the optic nerves (arrowheads). The enhancement is centrally located within the optic nerves on coronal sections (not shown). No other lesions were seen in the brain. B, Axial T-2–weighted magnetic resonance image of the right hip, demonstrating susceptibility artifact of orthopedic hardware, as well as soft tissue heterotopic ossification (corroborated by plain-film radiographs), consistent with pseudotumor of metallosis with decompression into the right hip joint space (blue asterisk), the subiliac bursa (red asterisk), greater trochanter bursa (yellow asterisk) extending into the gluteus maximus muscle (arrowheads), and into a potential space between the tensor fascia lata and the rectus femoris (black asterisk).Four months after initial presentation, the patient reported new symptoms of chest tightness and dyspnea on exertion. An echocardiogram showed a left ventricle ejection fraction of 20% to 25%, which had been 55% to 60% at the last test 2 years prior. At 5 months after initial presentation, the patient developed acute worsening of dyspnea and was admitted for respiratory distress. He was found to have nonischemic cardiomyopathy and died on hospital day 13. What Is Your Diagnosis?

Neuromyelitis optica (Devic disease)

Amyloidosis

Susac syndrome

Cobalt toxicity

D. Cobalt toxicity

D

Cobalt toxicity

The patient’s prior hip replacement surgeries raised the possibility of cobalt toxicity as a cause of his constellation of symptoms. The patient had his first hip replacement surgery 7 years prior to presentation with a ceramic-on-ceramic implant and had required 2 revision surgeries. During the revisions, which occurred 2 years prior to presentation, extensive soft-tissue metallosis was noted. Given this history of failed hip replacement, serum cobalt levels were checked and were consistently elevated, ranging between 280 to 779 ng/mL (a normal level is less than 1.5 ng/mL). A plain-film radiographic image of the hip showed that the hardware was intact, and there was heterotopic ossification in the surrounding soft tissue (not shown). Magnetic resonance imaging demonstrated a pseudotumor of metallosis (Figure, B). The patient was referred to orthopedic surgery for revision but died before surgical intervention.The toxic effects of cobalt have been known since the 1960s, when the treatment of anemia with cobalt and the addition of cobalt to beer led to adverse effects.1,2 In more recent years, joint replacements have become an increasingly recognized cause of systemic cobalt toxicity. Potential neurotoxic effects of cobalt include sensorineural hearing loss, optic neuropathy, and sensorimotor peripheral neuropathy.3,4 Cognitive impairment has also been reported.5 Other systemic effects of cobalt include cardiomyopathy and thyroid dysfunction.6In this patient, bilateral vision loss with long segments of optic nerve enhancement immediately call to mind a demyelinating process, particularly neuromyelitis optica. The patient’s male sex and the lack of oligoclonal bands could be consistent with a seronegative case of neuromyelitis optica; however, the concurrent hearing loss is atypical. Furthermore, many nondemyelinating disease processes can disrupt the blood-nerve barrier and lead to abnormal optic nerve enhancement. Amyloidosis can cause peripheral neuropathy and cardiomyopathy but do not explain the patient’s presenting complaints of vision and hearing loss. Vision loss in Susac syndrome is because of occlusion of retinal arteries, and the syndrome is often associated with lesions in the corpus callosum. These findings were absent on fluorescein angiogram and magnetic resonance imaging. Cobalt toxicity is the unifying diagnosis that accounts for the patient’s neurological decline, as well as his endocrine and cardiac dysfunction. Metallic debris from prior failed implants may have contributed to the metallosis.7While cobalt toxicity is rare among the many patients who have benefited from joint replacement, there are an increasing number of people undergoing these procedures,8 making cobalt toxicity a growing area of concern. Neurologists may be the first clinicians to evaluate a patient suffering from cobalt toxicity, given the frequency of neurologic symptoms.4,5 The patient in this report had symptoms of peripheral neuropathy 1.5 years prior to his death from cardiomyopathy. If a patient with a history of a metal-containing implant develops symptoms that lead to concern of cobalt toxicity, serum cobalt levels and imaging of the joint should be obtained. If elevated cobalt levels and metallosis are discovered, surgical revision for source control should be considered urgently because it is considered the definitive treatment. Many of the effects of cobalt toxicity can be reversed with surgery. Conversely, failure to diagnose or treat expediently can have fatal consequences.7,9,10

Neurology

A 63-year-old man with a history of well-controlled hypertension, lumbar stenosis, and hip arthroplasty with revisions presented with bilateral loss of vision and hearing for several weeks. He also reported a history of painful paresthesias at his feet beginning about 1 year prior.On examination, his visual acuity was initially 20/80 OD and 20/200 OS; it deteriorated over the next 2 months to finger counting bilaterally. The Weber test gave a nonlateralizing result, and bone conduction hearing was absent bilaterally. There was length-dependent loss of vibratory sensation and absent reflexes at both lower extremities. Magnetic resonance imaging demonstrated abnormal enhancement of bilateral optic nerves (Figure, A). Optical coherence tomography and fluorescein angiogram were normal. Nerve conduction studies showed mild sensory axonal polyneuropathy. Laboratory tests were notable for elevated thyrotropin (63 mlU/ml), low levels of free thyroxine (T4) (0.2 ng/dL), and elevated levels of cerebrospinal fluid protein (94 mg/dL). Cerebrospinal fluid IgG index, oligoclonal bands, aquaporin 4 antibody, paraneoplastic panel, and protein electrophoresis test results were all normal. He was treated empirically with high-dose steroids and plasmapheresis, with no improvement in symptoms.A, Axial postgadolinium, fat-suppressed, T-1–weighted magnetic resonance image of the orbits, demonstrating left greater than right enhancement of the optic nerves (arrowheads). The enhancement is centrally located within the optic nerves on coronal sections (not shown). No other lesions were seen in the brain. B, Axial T-2–weighted magnetic resonance image of the right hip, demonstrating susceptibility artifact of orthopedic hardware, as well as soft tissue heterotopic ossification (corroborated by plain-film radiographs), consistent with pseudotumor of metallosis with decompression into the right hip joint space (blue asterisk), the subiliac bursa (red asterisk), greater trochanter bursa (yellow asterisk) extending into the gluteus maximus muscle (arrowheads), and into a potential space between the tensor fascia lata and the rectus femoris (black asterisk).Four months after initial presentation, the patient reported new symptoms of chest tightness and dyspnea on exertion. An echocardiogram showed a left ventricle ejection fraction of 20% to 25%, which had been 55% to 60% at the last test 2 years prior. At 5 months after initial presentation, the patient developed acute worsening of dyspnea and was admitted for respiratory distress. He was found to have nonischemic cardiomyopathy and died on hospital day 13.

what is your diagnosis?

What is your diagnosis?

Cobalt toxicity

Susac syndrome

Neuromyelitis optica (Devic disease)

Amyloidosis

a

male

61-70

Black

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2685871

A woman in her early 50s with a history of polycystic ovarian syndrome, diabetes, stroke, and coronary artery disease that required coronary artery bypass graft 6 years earlier presented to the emergency department with 12 hours of sudden-onset, constant, right lower quadrant abdominal pain associated with vomiting and melena. She denied any hematochezia or history of peptic ulcer disease. She had no other surgical history and denied alcohol use or smoking. On examination, she was hypertensive (blood pressure, 185/85 mm Hg) although not tachycardic and was afebrile. She was locally tender to palpation in the right lower quadrant with rebound and voluntary guarding. Her abdomen was not tympanitic. The patient had no abdominal scars, hernias, or palpable masses. Laboratory results were significant for the following: leukocyte count, 23 600/µL (to convert to ×109/L, multiply by 0.001) with neutrophilia (94%); blood urea nitrogen level, 28 mg/dL (to convert to millimoles per liter, multiply by 0.357); creatinine concentration, 0.01 mg/dL (to convert to micromoles per liter, multiply by 88.4); lipase concentration, 195 U/L (to convert to microkatals per liter, multiply by 0.0167); and lactate concentration, 2.02 mg/dL (to convert to millimoles per liter, multiply by 0.111). Electrolyte levels and liver function test results were within normal limits. An electrocardiogram showed normal sinus rhythm. Computed tomography of the abdomen and pelvis with oral and intravenous contrast enhancement was performed (Figure).Axial cross-sectional computed tomograms of the patient’s abdomen and pelvis with oral and intravenous contrast enhancement show segmental mural thickening of the anterior cecum with wall hypoenhancement and pneumatosis, adjacent fat stranding, and a lucency medial to the cecum (A) and bilateral renal hypodensities (B). What Is Your Diagnosis?

Acute appendicitis

Colonic ischemia

Diverticulitis with perforation

Infectious colitis

B. Colonic ischemia

B

Colonic ischemia

Computed tomography revealed cecal wall hypoenhancement with pneumatosis, sparing of the remaining colon and appendix, and bilateral renal infarcts. Given the patient’s abdominal pain, imaging findings, and history of early-onset stroke and cardiovascular disease, she was diagnosed with isolated cecal ischemia, an extremely rare presentation of acute colonic ischemia.Although the exact cause remains unclear, most cases are of nonocclusive origin,1,2 a variant of nonocclusive mesenteric ischemia, in which a low-flow state results in splanchnic vasoconstriction as blood flow is preferentially diverted to essential organs. It is associated with critical illness and cardiovascular disease. Occlusive causes are rarer and predominantly attributable to large arterial atherosclerotic disease with distal thromboembolism (spontaneous or after vascular procedures), cardiac arrhythmias with embolism of atrial thrombus, small arterial disease in patients with diabetes, or venous outflow obstruction from hypercoagulable states.3 Resultant segmental ischemia often occurs at watershed areas. The cecum may also represent a watershed area4 owing to its end arterial supply from the anterior and posterior cecal arteries. In most patients, there is dual arterial inflow from a vascular arcade that bridges the ileal and colic branches of the ileocolic artery5; however, the rare anatomical variant of a singular inflow off the colic branch may predispose these patients to ischemia.6 The appendix, terminal ileum, and ascending colon have multiple arterial sources, which may explain why these are at lesser risk of ischemia.Isolated cecal ischemia most commonly manifests as acute right lower quadrant abdominal pain with nausea and vomiting, leukocytosis, and nonspecific imaging findings of cecal wall thickening with adjacent fat stranding. It is frequently misdiagnosed as appendicitis, diverticulitis, or infectious colitis.7 A high index of suspicion is warranted, especially in elderly patients, those who are critically ill, or patients with atrial dysrhythmias or atherosclerotic disease. In addition, prompt imaging with intravenous contrast enhancement is important to evaluate for colonic ischemia. Caution is advised with colonoscopy because of the risk of perforation of a thin-walled ischemic cecum from increased intraluminal pressure.8 Mortality rates are high, and timely diagnosis is key to prevent rapid patient death.After the diagnosis is established, prompt surgical resection of the ischemic segment is crucial, although the role of primary anastomosis vs end ileostomy remains in debate.9,10 Schuler and Hudlin10 described 5 patients with isolated cecal necrosis: 4 had mucosal necrosis and underwent primary anastomosis, and 1 had transmural necrosis with perforation and underwent end ileostomy. Only the patients undergoing primary anastomosis survived. Çakar et al2 described 6 patients with transmural necrosis; half underwent primary anastomosis and the other half end ileostomy. Five patients underwent a second-look operation within 48 hours; all patients who had an initial anastomosis had evidence of staple-line ischemia and required another resection with end ileostomy. We advocate for end ileostomy in transmural necrosis; however, primary anastomosis may be considered if necrosis is limited to the mucosa when close examination of the patient is performed postoperatively.After initiation of fluid resuscitation, intravenous broad-spectrum antibiotic therapy, and a heparin drip, the patient underwent an emergency exploratory laparotomy. A 10 × 10–cm area of full-thickness cecal necrosis was identified with a normal appendix, terminal ileum, and ascending colon. An ileocecectomy was performed. Her renal function normalized postoperatively. The results of laboratory studies and findings of transesophageal echography were negative for a hypercoagulable cause or embolic source. Despite transition to dual antiplatelet therapy, 4 weeks postoperatively, the patient developed recurrent abdominal pain and melena with midtransverse colonic ischemia seen on imaging. She underwent another exploration with complete extended right hemicolectomy and end ileostomy. Pathologic analysis revealed transverse and ileocolic staple-line ischemia. She was transitioned to triple antithrombotic therapy and has had no embolic recurrences 1 year postoperatively.

Surgery

A woman in her early 50s with a history of polycystic ovarian syndrome, diabetes, stroke, and coronary artery disease that required coronary artery bypass graft 6 years earlier presented to the emergency department with 12 hours of sudden-onset, constant, right lower quadrant abdominal pain associated with vomiting and melena. She denied any hematochezia or history of peptic ulcer disease. She had no other surgical history and denied alcohol use or smoking. On examination, she was hypertensive (blood pressure, 185/85 mm Hg) although not tachycardic and was afebrile. She was locally tender to palpation in the right lower quadrant with rebound and voluntary guarding. Her abdomen was not tympanitic. The patient had no abdominal scars, hernias, or palpable masses. Laboratory results were significant for the following: leukocyte count, 23 600/µL (to convert to ×109/L, multiply by 0.001) with neutrophilia (94%); blood urea nitrogen level, 28 mg/dL (to convert to millimoles per liter, multiply by 0.357); creatinine concentration, 0.01 mg/dL (to convert to micromoles per liter, multiply by 88.4); lipase concentration, 195 U/L (to convert to microkatals per liter, multiply by 0.0167); and lactate concentration, 2.02 mg/dL (to convert to millimoles per liter, multiply by 0.111). Electrolyte levels and liver function test results were within normal limits. An electrocardiogram showed normal sinus rhythm. Computed tomography of the abdomen and pelvis with oral and intravenous contrast enhancement was performed (Figure).Axial cross-sectional computed tomograms of the patient’s abdomen and pelvis with oral and intravenous contrast enhancement show segmental mural thickening of the anterior cecum with wall hypoenhancement and pneumatosis, adjacent fat stranding, and a lucency medial to the cecum (A) and bilateral renal hypodensities (B).

what is your diagnosis?

What is your diagnosis?

Diverticulitis with perforation

Acute appendicitis

Infectious colitis

Colonic ischemia

d

female

51-60

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2687230

A postmenopausal woman in her mid-50s (gravida 2, aborta 2) with a known history of endometriosis and adenomyosis presented to the emergency department with severe abdominal pain that she rated 10 of 10 in intensity and which had developed suddenly 5 days before presentation. The abdominal pain was associated with diarrhea, nausea, and abdominal bloating. On examination, the patient was afebrile and her abdomen was soft and nondistended without guarding or rebound but tender in the left lower quadrant. The patient had a palpable nodule in the posterior vaginal fornix and fullness in the left lower quadrant of the abdomen on bimanual examination.Laboratory investigations had normal findings with the exception of an elevated cancer antigen 125 level of 158 U/mL (to convert to kilounits per liter, multiply by 1.0). Contrast-enhanced computed tomography (CT) revealed multiple abnormal findings that included a bulky uterus with a thickened myometrium, endometriomas, right pleural effusion, pelvic peritonitis and ascites, enlarged lymph nodes, and solid extracolonic implants in the omentum caudal to the transverse colon (Figure, A) and in the cul-de-sac adjacent to the upper rectum (Figure, B). Subsequent magnetic resonance imaging (MRI) showed 2 areas of focus corresponding with the extracolonic implants. What Is Your Diagnosis?

Rupture of an infected endometriotic implant

Inflamed diverticulum

Perforation by foreign bodies

Malignant growth with unknown primary tumor

C. Perforation by foreign bodies

C

Perforation by foreign bodies

In the Figure, arrowheads indicate the presence of metal brush filaments in the omentum caudal to the transverse colon and in the cul-de-sac adjacent to the upper rectum. There is the potential that metal bristles of barbeque brushes may be dislodged, adhere to food on the grill, and be ingested. If ingested, the metal bristles may cause injury to and/or perforate the gastrointestinal tract, which can lead to severe complications.1-5 Health Canada, the Centers for Disease Control and Prevention, and the media have made an effort to report cases of injury and inform the public of this problem.3,6,7 However, it is also important that physicians are aware of the clinical presentation, radiologic findings, and management options associated with injuries related to ingested metal barbeque brush bristles to ensure that patients with such injuries receive efficient diagnosis and treatment, especially in the summer months during barbeque season.Patients with injury to the gastrointestinal tract caused by ingested metal bristles typically present with severe, acute-onset abdominal pain or odynophagia, depending on the location of the injury.2-4 Although this pain may begin immediately at the time of eating, the onset of pain may also be delayed and has been shown to develop up to 14 days after ingestion of the foreign bodies.1 Patients with delayed onset of pain, such as the patient described here, may have greater difficulty associating their pain with having eaten grilled meat, and such cases may be more difficult to diagnose at initial presentation.Although metal foreign bodies can be detected with both CT and abdominal radiography, CT without oral contrast enhancement is recommended for identification of metal barbeque brush bristles in patients who present with abdominal pain.4 Oral contrast should be avoided because it may have a density similar to that of small metal objects and may reduce the sensitivity of CT. Intravenous contrast enhancement of the bowel may also reduce the sensitivity of CT in some cases. Flexible endoscopy is recommended for patients with odynophagia suspected to be related to ingested metal bristles.2,5 If endoscopic examination has negative findings, CT of the neck will allow accurate identification and localization of metal foreign bodies in the head and neck region.2,4,5In this patient, the metal bristles were not initially identified with contrast-enhanced CT because of the significant inflammatory changes and small nodular peritoneal abscesses, which were interpreted as signs of severe peritonitis or carcinomatosis. The uterus was enlarged, which limited our evaluation on CT. Therefore, MRI was performed for additional assessment of the pelvic organs. Small linear filaments of metal surrounded by highly conspicuous magnetic susceptibility artifacts were seen on MRI.8 The CT scan was reviewed again and demonstrated faint, thin wire filaments that corresponded to the artifacts detected on MRI. Magnetic resonance imaging is not typically indicated for visualization of metallic foreign bodies; however, it was performed in this case because of concern regarding a possible malignant tumor.Both conservative and surgical management options have been shown to be effective in treating patients who have ingested metal bristles.1,3,5 The patient’s overall clinical picture, the site of the injury and/or perforation, and associated complications should guide management decisions. Surgical intervention for removal of the metal fragments was considered for the patient. However, the decision was made for conservative management with a course of antibiotic therapy. Computed tomography performed 3 weeks later showed the formation of a multifocal abscess surrounding the omental metallic foreign body, and the patient received an additional 2 weeks of antibiotic therapy. At follow-up, the patient’s symptoms had improved, her cancer antigen 125 level was within reference limits, and omental inflammation and fluid collection had almost completely resolved. Conservative management of this case has been effective, and the patient has since remained largely asymptomatic and has experienced no complications.This case reveals the importance of increasing physicians’ knowledge of the presentation, diagnostic evaluation, and management of patients who may have ingested metal brush bristles, which may enable physicians to provide optimal care to these patients.

Surgery

A postmenopausal woman in her mid-50s (gravida 2, aborta 2) with a known history of endometriosis and adenomyosis presented to the emergency department with severe abdominal pain that she rated 10 of 10 in intensity and which had developed suddenly 5 days before presentation. The abdominal pain was associated with diarrhea, nausea, and abdominal bloating. On examination, the patient was afebrile and her abdomen was soft and nondistended without guarding or rebound but tender in the left lower quadrant. The patient had a palpable nodule in the posterior vaginal fornix and fullness in the left lower quadrant of the abdomen on bimanual examination.Laboratory investigations had normal findings with the exception of an elevated cancer antigen 125 level of 158 U/mL (to convert to kilounits per liter, multiply by 1.0). Contrast-enhanced computed tomography (CT) revealed multiple abnormal findings that included a bulky uterus with a thickened myometrium, endometriomas, right pleural effusion, pelvic peritonitis and ascites, enlarged lymph nodes, and solid extracolonic implants in the omentum caudal to the transverse colon (Figure, A) and in the cul-de-sac adjacent to the upper rectum (Figure, B). Subsequent magnetic resonance imaging (MRI) showed 2 areas of focus corresponding with the extracolonic implants.

what is your diagnosis?

What is your diagnosis?

Malignant growth with unknown primary tumor

Inflamed diverticulum

Perforation by foreign bodies

Rupture of an infected endometriotic implant

c

female

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2695497

A woman in her early 50s with hypothyroidism and a 10-month history of painless lumps in her neck presented with achiness and decreased visual acuity in her right eye for 2 months. Associated symptoms included dysphagia and fever and chills. A previous otolaryngology evaluation revealed an intranasal mass with enlargement of multiple submandibular lymph nodes. A needle aspiration biopsy of 1 of the submandibular lymph nodes revealed atypical cells with mature lymphocytes. Computed tomography of the sinus confirmed a nasal polyp and a soft tissue mass in the right lacrimal gland region. The excised nasal polyp was benign. Incisional biopsy of the lacrimal gland lesion revealed chronic inflammatory infiltrate composed of predominantly T cells with scattered B cells and mature plasma cells, but no evidence of a lymphoproliferative process. The patient was referred for evaluation in our clinic.Ocular history was noncontributory. On examination, visual acuity was 20/40 OD and 20/25 OS. Intraocular pressure was unremarkable and ocular motility was intact in both eyes. Clinical evaluation revealed a firm mass of 5 × 4 × 3 cm fixed to the superotemporal orbital rim in the right lacrimal gland region (Figure 1) with intact overlying skin. Slitlamp examination was unremarkable in both eyes without evidence of conjunctival inflammatory signs. Ophthalmoscopic examination was unremarkable in both eyes without compression of the optic nerve or disc edema.Color photograph depicting swelling over the right lacrimal gland region with intact epidermis and absence of inflammatory signs. What Would You Do Next?

Treat with oral corticosteroids

Treat with methotrexate sodium

Perform external beam radiotherapy to the orbit

Perform a second lacrimal gland biopsy

Rosai-Dorfman disease

D

Perform a second lacrimal gland biopsy

In this case, a second lacrimal gland excisional biopsy revealed unsuspected Rosai-Dorfman disease (RDD), despite the initial negative biopsy. Rosai-Dorfman disease is a rare, nonhereditary, histiocytic proliferative disorder that typically manifests in childhood or early adulthood. Rosai and Dorfman1 originally described the benign pseudolymphomatous disease in 1969, reporting that patients typically manifest bilateral, massive, painless, cervical lymphadenopathy, often mimicking lymphoma. Orbital involvement in RDD occurs in 10% of the cases and commonly manifests as a painless soft tissue mass with proptosis.2 Compressive optic neuropathy or serous retinal detachment can also be found.The cause of this condition is unknown; both autoimmunity and viral infection, such as Epstein-Barr virus and parvovirus, have been implicated.3 Although somatic mutations in BRAF proto-oncogene signaling are associated with other histiocytic disorders, such as Langerhans cell histiocytosis and Erdheim-Chester disease, BRAF mutation is absent in RDD.4The differential diagnosis for this case also includes idiopathic orbital inflammation (pseudotumor) and lymphoma. Orbital pseudotumor, which presents more commonly in middle-aged women, is a nongranulomatous disease of the orbit that has no distinct cause.5 In a series of 1264 orbital masses described by Shields et al,6 pseudotumor (n = 98) accounted for 74% of orbital inflammatory diseases. Patients typically present with proptosis or ptosis and either diffuse or focal inflammation involving the lacrimal gland, extraocular muscles, and orbital fat. Diagnosis of pseudotumor can be confirmed via orbital computed tomography, where a poorly demarcated mass becomes contrast enhanced.7In contrast, orbital lymphoma, the most common lymphoproliferative lesion, typically presents as a diffuse, solid, enhancing mass on imaging studies. It is usually a relatively low-grade malignant tumor. In 1 series of orbital lymphoid tumors without initial systemic involvement, eventual systemic involvement was found in 8% of patients at 1 year and 33% at 10 years.8 Complete systemic workup should be performed to determine whether there is remote involvement.In this case, excisional biopsy was the best next step to confirm the diagnosis. The pathologic hallmark of RDD, as depicted in this specimen (Figure 2), is emperipolesis, which is histiocytes containing differentiated lymphocytes, plasma cells, and erythrocytes within their cytoplasm.1 Immunohistochemical studies revealed positive staining for CD68, CD163, and S100 protein, and no CD1a expression.3 Some reports of patients with presumed RDD have shown IgG4–positive plasma cells on immunohistochemical analysis, but these specimens failed to exhibit emperipolesis, favoring IgG4–related sclerosing disease over RDD.3 Treatment of RDD is reserved primarily for symptomatic patients showing vital organ involvement. Systemic corticosteroids and second-line treatment, such as methotrexate, can reduce lymph node size and improve symptoms. Surgery and external beam radiotherapy can effectively manage RDD with persistent orbital, central nervous system, and airway involvement.9Histopathologic section revealing emperipolesis, which is the hallmark of Rosai-Dorfman disease (arrowheads), showing proliferative histiocytes containing mature lymphocytes and plasma cells (hematoxylin-eosin, original magnification x400).In this case, if biopsy had revealed pseudotumor, oral corticosteroids would have been the standard treatment. Methotrexate may be used in cases refractory to corticosteroids. As for lymphoma, management includes surgical resection, local radiotherapy, systemic chemotherapy, or immunotherapy, depending on the findings.10At 4-month follow-up, no complications or recurrence were observed. Rheumatologic evaluation was advised.

Ophthalmology

A woman in her early 50s with hypothyroidism and a 10-month history of painless lumps in her neck presented with achiness and decreased visual acuity in her right eye for 2 months. Associated symptoms included dysphagia and fever and chills. A previous otolaryngology evaluation revealed an intranasal mass with enlargement of multiple submandibular lymph nodes. A needle aspiration biopsy of 1 of the submandibular lymph nodes revealed atypical cells with mature lymphocytes. Computed tomography of the sinus confirmed a nasal polyp and a soft tissue mass in the right lacrimal gland region. The excised nasal polyp was benign. Incisional biopsy of the lacrimal gland lesion revealed chronic inflammatory infiltrate composed of predominantly T cells with scattered B cells and mature plasma cells, but no evidence of a lymphoproliferative process. The patient was referred for evaluation in our clinic.Ocular history was noncontributory. On examination, visual acuity was 20/40 OD and 20/25 OS. Intraocular pressure was unremarkable and ocular motility was intact in both eyes. Clinical evaluation revealed a firm mass of 5 × 4 × 3 cm fixed to the superotemporal orbital rim in the right lacrimal gland region (Figure 1) with intact overlying skin. Slitlamp examination was unremarkable in both eyes without evidence of conjunctival inflammatory signs. Ophthalmoscopic examination was unremarkable in both eyes without compression of the optic nerve or disc edema.Color photograph depicting swelling over the right lacrimal gland region with intact epidermis and absence of inflammatory signs.

what would you do next?

What would you do next?

Treat with oral corticosteroids

Treat with methotrexate sodium

Perform external beam radiotherapy to the orbit

Perform a second lacrimal gland biopsy

d

female

51-60

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2696737

A healthy 7-month-old boy presented for oculoplastic evaluation with an enlarging right periorbital mass. He was born full term with no complications during pregnancy or delivery. The parents noticed asymmetry between the child’s eyes since birth and progressive right lower eyelid fullness. He was seen by his pediatrician, a general ophthalmologist, and a pediatric ophthalmologist before presenting to our institution. On examination, the boy fussed when his left eye was covered, and his left eye was able to fixate and follow. The right globe could not be visualized within the palpebral fissure because of a large compressible mass that transilluminated (Figure, A). The remainder of the left eye examination findings were noncontributory. Orbital magnetic resonance imaging was ordered (Figure, B).A, Clinical photograph of child at presentation displaying a right orbital cyst. B, Coronal T2-weighted magnetic resonance image showing a large inferior right orbital cyst displacing the microphthalmic globe superiorly. What Would You Do Next?

Perform aspiration

Perform orbitotomy with excision

Administer radiotherapy

Administer intralesional corticosteroids

Microphthalmos with orbital cyst

B

Perform orbitotomy with excision

Microphthalmia with orbital cyst is a rare congenital anomaly that affects 1 per 10 000 births.1 It results from incomplete closure of the posterior embryonic fissure during 6 to 7 weeks’ gestation.2 The cyst develops through the congenital defect, communicates with the globe, and is lined with gliotic neuroretinal tissue.3 The abnormality is usually unilateral, has no sex preference, and, if bilateral, can be associated with systemic abnormalities that involve the cardiovascular, central nervous, or renal systems.2,3 Some genetic mutations and syndromes have been linked to this condition, such as partial trisomy 22, trisomy 18, chromosome 13q deletion syndrome, translocation of chromosomes 3 and 5, Lenz microphthalmia syndrome, and Aicardi and oculocerebrocutaneous syndromes.3-6Diagnosis is typically clinical, with children presenting at birth with globe asymmetry and dystopia, poor vision, and sometimes lower eyelid fullness from a large transilluminating orbital cyst.2 Other ocular abnormalities include microcornea, corneal edema, flat anterior chamber, dense cataract, optic nerve hypoplasia, and estoropia.2 Ultrasonography, computed tomography, and/or magnetic resonance imaging are important to confirm the size and location of the orbital cyst and its association with the microphthalmic globe.2 Imaging also aids in excluding other entities, including meningocele or meningoencephalocele, dermoid cyst, and teratoma.7There are different treatment options, depending on the cyst size, degree of microphthalmos, orbital bone growth, overall cosmesis, and general condition of the patient.3 Observation is generally the approach when the orbit has yet to reach maximal bony growth.1,3 If the cyst is disfiguring, surgical excision is preferred.3 McLean et al1 stressed the importance of keeping the cyst to ensure adequate bony growth. Because of evidence that excision in childhood can compromise bone growth, which develops better with cysts than orbital implants, excision is recommended at approximately 5 years of age to allow 90% of orbital bone maturation.1 During excision, alloplastic implants or dermis fat grafts can be used to restore orbital volume and aid in cosmesis. Dermis fat grafts have the advantage of being autogenous and able to enlarge as the child grows.1 If the cyst is small and orbital volume is adequate, an ocular prosthesis can be used for cosmesis without invasive intervention.3Aspiration is sometimes performed to aid in complete surgical removal or if the child cannot undergo general anesthesia.3 However, because of the high risk of recurrence and local complications, such as bleeding and infection, aspiration (choice A) should typically be avoided.1,3Recent studies8-10 have proposed using sclerotherapy as an uncomplicated definitive therapy. Naik et al9 determined that injection of ethanolamine oleate was 4 times more effective with fewer complications than aspiration alone. Cadet et al10 successfully used doxycycline as a sclerosing agent on a 4-year-old boy with bilateral microphthalmos and unilateral orbital cyst, suggesting that its fibrotic effect triggers an inflammatory response similar to bleomycin and ethanol responses. Radiotherapy (choice C) and corticosteroids (choice D) are not indicated because this condition is neither a malignant nor an inflammatory diagnosis.Magnetic resonance imaging confirmed a microphthalmic globe connected to and superiorly displaced by a large orbital cyst that measured 3.2 × 2.5 × 2.6 cm. Because of radiographic evidence of adequate orbital volume and the degree of disfigurement, a lateral orbitotomy was used to remove the globe and cyst. The orbital volume was restored with a dermis fat graft. Gross pathologic analysis revealed a microphthalmic globe with a coloboma in the posterior sclera communicating with the large cyst. The patient has had excellent cosmesis with no need for additional surgery after 7 years of follow-up.

Ophthalmology

A healthy 7-month-old boy presented for oculoplastic evaluation with an enlarging right periorbital mass. He was born full term with no complications during pregnancy or delivery. The parents noticed asymmetry between the child’s eyes since birth and progressive right lower eyelid fullness. He was seen by his pediatrician, a general ophthalmologist, and a pediatric ophthalmologist before presenting to our institution. On examination, the boy fussed when his left eye was covered, and his left eye was able to fixate and follow. The right globe could not be visualized within the palpebral fissure because of a large compressible mass that transilluminated (Figure, A). The remainder of the left eye examination findings were noncontributory. Orbital magnetic resonance imaging was ordered (Figure, B).A, Clinical photograph of child at presentation displaying a right orbital cyst. B, Coronal T2-weighted magnetic resonance image showing a large inferior right orbital cyst displacing the microphthalmic globe superiorly.

what would you do next?

What would you do next?

Administer radiotherapy

Perform aspiration

Perform orbitotomy with excision

Administer intralesional corticosteroids

c

male

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2697397

A previously healthy 12-year-old boy presented to an outside hospital for fever, headache, and unilateral red eye with periorbital edema. He received oral trimethoprim-sulfamethoxazole and 2 days of intravenous clindamycin phosphate and ceftriaxone sodium. On transfer to our institution for failure to improve and concern for orbital cellulitis, results of examination by the ophthalmology service revealed a unilateral hemorrhagic conjunctivitis without orbital signs, and computed tomography showed mild preseptal edema. The patient was discharged with a tentative diagnosis of viral conjunctivitis.Three days later, the patient returned with fever, prominent submandibular lymphadenopathy, and ipsilateral granulomatous conjunctivitis (Figure). Results of the remainder of the anterior segment and dilated examination were unremarkable. Results of laboratory tests revealed elevated inflammatory markers (C-reactive protein level, 9.47 mg/dL [to convert to nanomoles per liter, multiply by 9.524], and erythrocyte sedimentation rate, 48 mm/h), neutrophilic leukocytosis, and normocytic anemia. Additional history revealed that the boy had handled a bloody raccoon carcass without gloves several days before initial presentation. The pediatrics service planned to restart antibiotic therapy.External photograph of the left eye demonstrating periorbital edema, lash crusting, and follicular conjunctivitis with a granuloma in the inferolateral fornix.Perform conjunctival cultures on blood, chocolate, Löwenstein-Jensen, Sabouraud, and thioglycolate media before restarting antibiotic therapyProvide reassurance that the diagnosis is typically self-limitedPerform serologic testing for Bartonella henselae and Francisella tularensis What Would You Do Next?

Perform conjunctival cultures on blood, chocolate, Löwenstein-Jensen, Sabouraud, and thioglycolate media before restarting antibiotic therapy

Repeated computed tomography of orbits with contrast

Provide reassurance that the diagnosis is typically self-limited

Perform serologic testing for Bartonella henselae and Francisella tularensis

Oculoglandular tularemia

D

Perform serologic testing for Bartonella henselae and Francisella tularensis

The patient presented with hallmark features of Parinaud oculoglandular syndrome. Cat-scratch disease is the most classic cause of this syndrome. The differential diagnosis is broad, however, and includes infections, such as tuberculosis, syphilis, listeriosis, mumps, Epstein-Barr virus, sporotrichosis, and tularemia, along with noninfectious causes, such as sarcoidosis, leukemia, and lymphoma. Of the above infections, tularemia typically manifests with the most severe systemic findings.1 The patient’s significantly elevated inflammatory markers, neutrophilic leukocytosis, and history of exposure to a wild animal suggested tularemia.The diagnosis of tularemia is typically made by serologic testing. A 4-fold increase in titer between acute and convalescent serum samples is diagnostic, and a presumptive diagnosis can be made from elevated titers in the acute phase. In this patient, serologic tests for Bartonella species had negative results, and serologic tests for tularemia had equivocal results (1:80).A series examining the role of polymerase chain reaction in the diagnosis of oculoglandular tularemia reported that F tularensis has never been isolated directly from culture of conjunctival samples.2 However, several series have demonstrated growth of F tularensis on special media.3,4 The organism can grow on any cysteine-containing medium, and many formulations of chocolate agar are supplemented with cysteine. Therefore, conjunctival cultures could be considered in the diagnosis of oculoglandular tularemia. However, performing a conjunctival culture (choice A) is not the best course of action because F tularensis is a tier 1 select agent and category A bioterrorism agent; the pathogen is highly infectious and can aerosolize from culture plates, putting laboratory personnel at risk for life-threatening infection.5 If diagnosis is suspected, clinicians may elect to make the diagnosis by serologic testing alone. If cultures are performed, it is paramount to communicate the possibility of the diagnosis with the clinical laboratory to ensure that safety protocols are implemented when handling specimens.Conjunctival cultures were performed in this case and at 72 hours were positive for growth that resembled Haemophilus species, staining as gram-negative bacilli. A reference laboratory (University of Pittsburgh Medical Center Presbyterian Clinical Microbiology) was consulted for identification. A matrix-assisted laser desorption ionization biotyper (Bruker) did not provide identification because the select agent database was not used. Sanger sequencing of the 16S ribosome indicated a match for F tularensis. The Pennsylvania Department of Health confirmed the diagnosis by polymerase chain reaction and fluorescent antibody testing. Because tularemia is rare in western Pennsylvania, the laboratories were not alerted to the possibility of the diagnosis, and 6 exposed laboratory personnel were placed on watch for development of a fever. One laboratory professional chose to receive postexposure prophylaxis with doxycycline hyclate. None experienced illness.Although oculoglandular tularemia may be self-limiting, reassurance (choice B) would not be the preferred answer because untreated cases can lead to dacryocystitis, keratitis, keratouveitis, optic neuritis, and even death. Performing repeated computed tomography of the orbits (choice C) would not be the next recommended step because radiographic imaging is not necessary for the diagnosis.The patient initiated empirical doxcycyline hyclate, 100 mg twice daily, with prompt symptomatic improvement. After identification of F tularensis, the patient’s treatment was transitioned to ciprofloxacin hydrochloride, 500 mg twice daily, with complete resolution noted at the 1-month follow-up.

Ophthalmology

A previously healthy 12-year-old boy presented to an outside hospital for fever, headache, and unilateral red eye with periorbital edema. He received oral trimethoprim-sulfamethoxazole and 2 days of intravenous clindamycin phosphate and ceftriaxone sodium. On transfer to our institution for failure to improve and concern for orbital cellulitis, results of examination by the ophthalmology service revealed a unilateral hemorrhagic conjunctivitis without orbital signs, and computed tomography showed mild preseptal edema. The patient was discharged with a tentative diagnosis of viral conjunctivitis.Three days later, the patient returned with fever, prominent submandibular lymphadenopathy, and ipsilateral granulomatous conjunctivitis (Figure). Results of the remainder of the anterior segment and dilated examination were unremarkable. Results of laboratory tests revealed elevated inflammatory markers (C-reactive protein level, 9.47 mg/dL [to convert to nanomoles per liter, multiply by 9.524], and erythrocyte sedimentation rate, 48 mm/h), neutrophilic leukocytosis, and normocytic anemia. Additional history revealed that the boy had handled a bloody raccoon carcass without gloves several days before initial presentation. The pediatrics service planned to restart antibiotic therapy.External photograph of the left eye demonstrating periorbital edema, lash crusting, and follicular conjunctivitis with a granuloma in the inferolateral fornix.Perform conjunctival cultures on blood, chocolate, Löwenstein-Jensen, Sabouraud, and thioglycolate media before restarting antibiotic therapyProvide reassurance that the diagnosis is typically self-limitedPerform serologic testing for Bartonella henselae and Francisella tularensis

what would you do next?

What would you do next?

Perform serologic testing for Bartonella henselae and Francisella tularensis

Perform conjunctival cultures on blood, chocolate, Löwenstein-Jensen, Sabouraud, and thioglycolate media before restarting antibiotic therapy

Repeated computed tomography of orbits with contrast

Provide reassurance that the diagnosis is typically self-limited

a

male

11-20

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2698089

A white man in his early 50s presented to the emergency department of Massachusetts Eye and Ear with a 1-day history of sudden decreased visual acuity in the right eye. He denied any recent trauma, flashes, floaters, pain, or any prior similar episodes. His medical history was remarkable for asthma and prostate cancer, and review of systems was negative except for his visual loss.On examination, his best-corrected visual acuity was 20/400 OD and 20/20 OS. Pupils were reactive with no relative afferent pupillary defect, and intraocular pressure measurements were unremarkable, as were results of the external and slitlamp examinations. Dilated fundus examination of the right eye showed submacular hemorrhage with pigment epithelial detachment (Figure 1A). Results of a dilated fundus examination of the left eye were unremarkable. Optical coherence tomography (OCT) of the right eye (Figure 1B) revealed subretinal and sub–retinal pigment epithelium (RPE) hemorrhage; results were unremarkable in the left eye.A, Fundus photograph of the right eye shows macular hemorrhage. B, Optical coherence tomography (OCT) scan of the right eye. Green line indicates the position of the OCT scan. What Would You Do Next?

Computed tomography of the brain

Indocyanine green angiography, fluorescein angiography, or both

B-scan ultrasonography

Autofluorescence

Polypoidal choroidal vasculopathy

B

Indocyanine green angiography, fluorescein angiography, or both

The differential diagnosis for combined submacular and sub-RPE hemorrhage is broad and encompasses age-related macular degeneration, polypoidal choroidal vasculopathy (PCV), ruptured retinal macroaneurysm, and less likely Terson syndrome or hemorrhagic choroidal melanoma. In this patient, suspicion for PCV was high given the clinical appearance and OCT findings. Indocyanine green angiography (ICGA) demonstrated polypoidal vascular lesions, confirming the diagnosis of PCV (Figure 2). The fellow eye was normal.Indocyanine green angiography late-phase frame demonstrates focal areas of hyperfluorescence consistent with polypoidal choroidal vascular lesions.Computed tomography of the brain (choice A) is not recommended when suspicion of an intracranial process is low. B-scan ultrasonography (choice B) is not helpful because the clinical examination did not detect a choroidal mass. Autofluorescence (choice D) is not usually helpful in retinal hemorrhage workup.Polypoidal choroidal vasculopathy has been described as polypoidal subretinal vascular lesions associated with serous and hemorrhagic detachments of the RPE and is thought to be a variant of age-related macular degeneration.1 Polypoidal choroidal vasculopathy is more common in patients of East Asian and African origin and usually presents from 50 to 70 years of age.2On fundus examination, PCV is characterized by orange-red elevated lesions that correspond to the polypoidal vessels.3 These lesions are often associated with serous exudation and hemorrhage that may lead to detachment of the RPE or retina.1,2,4 Unlike typical age-related macular degeneration, the fellow eye often shows no signs of disease such as drusen or pigment changes. Optical coherence tomography may show pigment epithelial detachments with another reflective layer beneath that corresponds to the Bruch membrane (double-layer sign) (Figure 1B). The space between these reflective lines is thought to represent the branching vascular network of choroidal neovascularization.4 Indocyanine green angiography remains the criterion standard test to diagnose PCV because the long wavelength can penetrate through pigment or hemorrhage, as in this case, and image the choroidal vasculature. In the early phase, ICGA typically shows a distinct branching network of inner choroidal vessels terminating in aneurysmal dilatations.1 Late-phase ICGA frames demonstrate reversal of the fluorescence pattern: the area surrounding the lesion becomes hyperfluorescent, and the center of the lesion becomes hypofluorescent. Finally, in the very late phase, the dye disappears from the nonleaking lesions (washout phase); however, the leaking polypoidal lesions remain hyperfluorescent.3 Noninvasive OCT angiography may have potential in the detection and surveillance of PCV.5 However, in our clinical experience, current technology can be inconsistent in detection of polypoidal lesions secondary to issues with penetration of the deeper layers, especially with optical barriers such as hemorrhage.The mainstay of treatment for PCV is anti–vascular endothelial growth factor therapy with or without verteporfin photodynamic therapy. Recently, the EVEREST II (Efficacy and Safety of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy) trial6 showed that combination therapy of ranibizumab plus verteporfin photodynamic therapy achieved superior visual outcome and regression of polypoidal lesions compared with ranibizumab alone. Furthermore, results evaluating monotherapy with aflibercept are being evaluated in the PLANET (Aflibercept in Polypoidal Choroidal Vasculopathy) study.7Intravitreal injection of monthly anti–vascular endothelial growth factor was initiated in this patient. With the role of verteporfin photodynamic therapy in the current management of PCV being less clear, we will reserve it for a suboptimal anatomical response.

Ophthalmology

A white man in his early 50s presented to the emergency department of Massachusetts Eye and Ear with a 1-day history of sudden decreased visual acuity in the right eye. He denied any recent trauma, flashes, floaters, pain, or any prior similar episodes. His medical history was remarkable for asthma and prostate cancer, and review of systems was negative except for his visual loss.On examination, his best-corrected visual acuity was 20/400 OD and 20/20 OS. Pupils were reactive with no relative afferent pupillary defect, and intraocular pressure measurements were unremarkable, as were results of the external and slitlamp examinations. Dilated fundus examination of the right eye showed submacular hemorrhage with pigment epithelial detachment (Figure 1A). Results of a dilated fundus examination of the left eye were unremarkable. Optical coherence tomography (OCT) of the right eye (Figure 1B) revealed subretinal and sub–retinal pigment epithelium (RPE) hemorrhage; results were unremarkable in the left eye.A, Fundus photograph of the right eye shows macular hemorrhage. B, Optical coherence tomography (OCT) scan of the right eye. Green line indicates the position of the OCT scan.

what would you do next?

What would you do next?

Indocyanine green angiography, fluorescein angiography, or both

Computed tomography of the brain

Autofluorescence

B-scan ultrasonography

a

male

51-60

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2698942

A previously healthy man in his 50s presented with a 1-day history of sudden painful decreased vision in the right eye. On examination, his visual acuity was counting fingers at 3 ft OD and 20/20 OS. A slitlamp examination of the right eye revealed conjunctival hyperemia, nongranulomatous keratic precipitates in the inferior half of the corneal endothelium, and 3+ cells in the anterior chamber, while results of a dilated fundus examination showed 1+ vitritis, 360° of optic nerve swelling, intraretinal hemorrhages predominantly along the distribution of the retinal arteries and arterioles, and perivascular sheathing, as well as macula involving retinal whitening, thickening, and subretinal fluid (Figure, A). Fluorescein angiography revealed late vascular leakage with both arterial and venous involvement (Figure, B) and peripheral ischemia. Examination of the left eye revealed no abnormalities.A, Wide-field photograph of the right eye demonstrates optic nerve edema (white arrowhead), scattered intraretinal hemorrhages (red arrowheads), perivascular sheathing (yellow arrowheads), and retinal whitening and thickening with subretinal fluid in the macula extending inferiorly (blue arrowheads). B, Fluorescein angiograph shows arterial and venous vasculitis and peripheral ischemia. The black arrowhead points to leakage from the cilioretinal artery.Initiate uveitis workup and start topical corticosteroid therapyObtain aqueous sample through needle aspirate for viral polymerase chain reaction, and start intravitreal and systemic antiviral therapy What Would You Do Next?

Initiate uveitis workup and start topical corticosteroid therapy

Obtain aqueous sample through needle aspirate for viral polymerase chain reaction, and start intravitreal and systemic antiviral therapy

Perform a lumbar puncture

Perform pars plana vitrectomy

Acute retinal necrosis, posterior pole variant, from herpes simplex virus 1

B

Obtain aqueous sample through needle aspirate for viral polymerase chain reaction, and start intravitreal and systemic antiviral therapy

The differential diagnosis for panuveitis and occlusive vasculopathy with arterial involvement includes acute retinal necrosis (ARN); syphilis; idiopathic retinal vasculitis, aneurysm, and neuroretinitis; systemic lupus erythematosus; and polyarteritis nodosa. Of these conditions, ARN presents most commonly with both panuveitis and occlusive arteritis, and typically progresses rapidly without antiviral therapy. Therefore, obtaining an aqueous sample for viral polymerase chain reaction (PCR) with simultaneous initiation of intravitreal and systemic antiviral therapy (choice B) is the most appropriate first step. Initiating a uveitis workup and starting topical corticosteroid therapy (choice A) would not be the first step given the concern for a possible infectious cause. A lumbar puncture (choice C) or pars plana vitrectomy (choice D) is unnecessary and invasive.For this patient, results of aqueous PCR testing were positive for herpes simplex virus 1 (HSV-1) and negative for HSV-2, varicella zoster virus, and cytomegalovirus. While awaiting PCR results, the patient was admitted and started receiving intravenous acyclovir sodium, 10 mg/kg every 8 hours, for 2 weeks. Two doses of intravitreal foscarnet sodium, 2.4 mg/0.1 mL, were administered 3 days apart. The patient concurrently received a full systemic workup for other possible infectious and inflammatory causes, with negative results. Following hospital discharge, he received maintenance therapy with 1000 mg of oral valacyclovir hydrochloride 3 times daily.One month after presentation, the patient developed a total rhegmatogenous retinal detachment with reduction of visual acuity to light perception. He underwent a retinal detachment repair with pars plana vitrectomy, perfluorocarbon, laser retinopexy, and silicone oil. Intravitreal foscarnet sodium, 2.4 mg/0.1 mL, was given intraoperatively, and a vitreous sample was again positive for HSV-1.Although the clinical findings of panuveitis with occlusive arteritis and prominent intraocular inflammation in an immunocompetent patient are suggestive of ARN, involvement of the posterior pole early in the disease course is not typical for ARN.1 The other pattern of herpetic retinitis, progressive outer retinal necrosis, is characterized by multifocal, discrete, opacified lesions that can begin in the posterior pole.2 However, progressive outer retinal necrosis has been described almost exclusively in immunocompromised patients with HIV and lacks inflammatory cells in the anterior chamber and vitreous, and there is no occlusive vasculitis.2 Therefore, this patient’s clinical features are most consistent with a previously described variant of ARN affecting the posterior pole.3-5Acute retinal necrosis is caused most commonly by varicella zoster virus, followed by HSV-1 and HSV-2.4 A total of 48% of affected patients report vision worse than 20/200 six months after presentation.6 Vision loss occurs owing to retinal detachment, chronic vitritis, epiretinal membrane, macular ischemia, macular edema, and optic neuropathy.7 Rhegmatogenous retinal detachment occurs as a sequela of retinal atrophy from retinal necrosis.7 Bilateral disease affects up to 70% of untreated patients.8All patients with ARN should be treated with intravenous or oral antiviral therapy. A recent report by the American Academy of Ophthalmology found level 2 and 3 evidence supporting the similar therapeutic effectiveness of oral valacyclovir hydrochloride, 2000 mg 4 times daily, compared with intravenous acyclovir sodium, 10 mg/kg 3 times daily for 7 to 10 days, for the initial treatment of ARN.4 Early injection of intravitreal foscarnet sodium, 2.4 mg, was also recommended if available but should not be given in the absence of systemic therapy because it does not prevent the involvement of the fellow eye.4 Meanwhile, there was insufficient evidence to support the use of early pars plana vitrectomy or prophylactic laser retinopexy.4 After induction therapy, patients should continue with maintenance therapy (1000 mg of valacyclovir hydrochloride daily) for 6 months or more.4 Both aqueous and vitreous PCR testing were sensitive and specific, but aqueous sampling may be a safer technique.4 Owing to the rapid progression of ARN, the initiation of therapy in suspected cases should not be delayed while awaiting the results of diagnostic testing.Four years after presentation, the patient continued to receive maintenance therapy with oral valacyclovir sodium, tapered down to 1000 mg twice daily. His right eye remained quiet, with light perception visual acuity. The left eye remained uninvolved, with 20/20 visual acuity. The patient’s infectious disease specialist plans to taper the oral valacyclovir sodium dose to 1000 mg daily the following year if he remains stable receiving his current dose.

Ophthalmology

A previously healthy man in his 50s presented with a 1-day history of sudden painful decreased vision in the right eye. On examination, his visual acuity was counting fingers at 3 ft OD and 20/20 OS. A slitlamp examination of the right eye revealed conjunctival hyperemia, nongranulomatous keratic precipitates in the inferior half of the corneal endothelium, and 3+ cells in the anterior chamber, while results of a dilated fundus examination showed 1+ vitritis, 360° of optic nerve swelling, intraretinal hemorrhages predominantly along the distribution of the retinal arteries and arterioles, and perivascular sheathing, as well as macula involving retinal whitening, thickening, and subretinal fluid (Figure, A). Fluorescein angiography revealed late vascular leakage with both arterial and venous involvement (Figure, B) and peripheral ischemia. Examination of the left eye revealed no abnormalities.A, Wide-field photograph of the right eye demonstrates optic nerve edema (white arrowhead), scattered intraretinal hemorrhages (red arrowheads), perivascular sheathing (yellow arrowheads), and retinal whitening and thickening with subretinal fluid in the macula extending inferiorly (blue arrowheads). B, Fluorescein angiograph shows arterial and venous vasculitis and peripheral ischemia. The black arrowhead points to leakage from the cilioretinal artery.Initiate uveitis workup and start topical corticosteroid therapyObtain aqueous sample through needle aspirate for viral polymerase chain reaction, and start intravitreal and systemic antiviral therapy

what would you do next?

What would you do next?

Perform pars plana vitrectomy

Perform a lumbar puncture

Obtain aqueous sample through needle aspirate for viral polymerase chain reaction, and start intravitreal and systemic antiviral therapy

Initiate uveitis workup and start topical corticosteroid therapy

c

male

51-60

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2698943

A 41-year-old woman with a history of ocular hypertension (and using brimonidine tartrate and timolol maleate) was referred by her ophthalmologist for a second opinion regarding yellowish subfoveal precipitates in her left eye. Three months earlier, she had undergone pneumatic retinopexy for macula-on retinal detachment (RD) with a superotemporal tear, followed by vitrectomy with gas injection for macula-on inferonasal detachment 1 month later. She had persistent postoperative subretinal fluid inferonasally, and she was concerned about a central scotoma. An examination within 2 months of the vitrectomy revealed yellowish subfoveal precipitates. Her best-corrected visual acuity was 20/20 OD and 20/200 OS. Extraocular motility was full, but she displayed left exotropia. Confrontational visual fields were full for the right eye but showed a decreased field inferiorly for the left eye. Intraocular pressures as determined using Tonopen tonometry were 13 mm Hg OD and 12 mm Hg OS. A slitlamp examination revealed trace nuclear sclerosis and pigmented cells in the anterior vitreous of the left eye. An ophthalmoscopic examination indicated laser and cryotherapy scars 360° around a horseshoe tear superotemporally in the left eye, whereas the right eye appeared normal. In addition, pre-equatorial subretinal fluid in the left eye between the 6-o’clock and 8:30 position was associated with 2 tiny holes at the 7:30 position and with a small area of fibrotic tissue contraction consistent with early proliferative vitreoretinopathy. The macula had yellow-white, flat, vitelliform-like lesions with a surrounding high watermark (Figure). No cyst, exudate, or hemorrhage was detected in the macula.Color fundus photograph of the left eye demonstrating yellow-white vitelliform-like deposits in the fovea surrounded by a high watermark. What Would You Do Next?

Observe the patient

Administer intravitreal corticosteroid injection

Perform laser photocoagulation

Perform pars plana vitrectomy with endolaser

Subretinal precipitates secondary to chronic RD

D

Perform pars plana vitrectomy with endolaser

Vitelliform-like subretinal precipitates observed in chronic RD have been hypothesized to be caused by macrophage phagocytosis of degenerated outer photoreceptor segments and are associated with delayed subretinal fluid resorption.1 More recently, Rashaed2 reported a case of fovea-sparing RD manifesting as postoperative subfoveal deposits associated with residual subretinal fluid. In this case, the high watermark in the macula was suggestive of old fluid associated with resorbed subretinal fluid, and there was chronic pre-equatorial subretinal fluid. Subretinal precipitates and cystoid macular edema can develop owing to inflammation secondary to chronic RD, postoperative inflammation, or both. Cystoid macular edema is a relatively common complication after pars plana vitrectomy for macula-on or macula-off rhegmatogenous RD, occurring in approximately 15% of eyes.3,4 Cystoid macular edema is thought to be secondary to an inflammatory reaction and may be associated with proliferative vitreoretinopathy, as was the case for the present patient.5,6Patient observation (choice A) would not have been appropriate in the present case because chronic RD was likely to have been causing inflammatory changes and therefore the vision-limiting subfoveal precipitates. Thus, an intervention to repair chronic RD was necessary to recover the patient’s vision. Administering an intravitreal corticosteroid injection (choice B) would be a good option for cystoid macular edema secondary to postoperative inflammation alone but similarly would not have addressed the underlying chronic RD in the present case. Further laser photocoagulation (choice C) would have been unlikely to benefit the present patient given the large area of persistent subretinal fluid surrounding the 2 holes and the presence of laser scars already across 360°. Furthermore, laser photocoagulation would not have resolved the chronic RD and therefore would not have contributed to subfoveal precipitate regression. Scleral buckle surgery is a reasonable option to repair chronic RD even in early proliferative vitreoretinopathy, as suggested by a 2006 study by Yao et al.7 However, in the present case, pars plana vitrectomy with endolaser (choice D) was preferable because it might reduce inflammatory mediators in the vitreous cavity.8,9 Thus, pars plana vitrectomy was judged to be the best treatment option because it addressed both the chronic RD and postoperative inflammation.The patient underwent pars plana vitrectomy with membrane peel, gas-fluid exchange, perfluorooctane, endolaser, and cryotherapy. The subfoveal precipitates regressed postoperatively with concurrent resolution of the central scotoma during the next few months. Her best-corrected visual acuity at a 1-year follow-up examination was 20/60 OS, and cataract surgery was performed at that time. At the most recent examination in November 2017, the best-corrected visual acuity was 20/30 OS.

Ophthalmology

A 41-year-old woman with a history of ocular hypertension (and using brimonidine tartrate and timolol maleate) was referred by her ophthalmologist for a second opinion regarding yellowish subfoveal precipitates in her left eye. Three months earlier, she had undergone pneumatic retinopexy for macula-on retinal detachment (RD) with a superotemporal tear, followed by vitrectomy with gas injection for macula-on inferonasal detachment 1 month later. She had persistent postoperative subretinal fluid inferonasally, and she was concerned about a central scotoma. An examination within 2 months of the vitrectomy revealed yellowish subfoveal precipitates. Her best-corrected visual acuity was 20/20 OD and 20/200 OS. Extraocular motility was full, but she displayed left exotropia. Confrontational visual fields were full for the right eye but showed a decreased field inferiorly for the left eye. Intraocular pressures as determined using Tonopen tonometry were 13 mm Hg OD and 12 mm Hg OS. A slitlamp examination revealed trace nuclear sclerosis and pigmented cells in the anterior vitreous of the left eye. An ophthalmoscopic examination indicated laser and cryotherapy scars 360° around a horseshoe tear superotemporally in the left eye, whereas the right eye appeared normal. In addition, pre-equatorial subretinal fluid in the left eye between the 6-o’clock and 8:30 position was associated with 2 tiny holes at the 7:30 position and with a small area of fibrotic tissue contraction consistent with early proliferative vitreoretinopathy. The macula had yellow-white, flat, vitelliform-like lesions with a surrounding high watermark (Figure). No cyst, exudate, or hemorrhage was detected in the macula.Color fundus photograph of the left eye demonstrating yellow-white vitelliform-like deposits in the fovea surrounded by a high watermark.

what would you do next?

What would you do next?

Administer intravitreal corticosteroid injection

Perform laser photocoagulation

Perform pars plana vitrectomy with endolaser

Observe the patient

c

female

41-50

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2687963