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kenza-ily

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JAMA_Chen2024

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https://jamanetwork.com/journals/jamadermatology/fullarticle/2737326

A man in his 80s presented with an 18-month history of an irregularly linear, rusty-brown, atrophic, streaklike plaque extending from the tip of his right shoulder to the right biceps, where it ended in arborizing purple plaque with scattered, slightly indurated, irregular papules within it (Figure, A and B). There was no warmth, thrills, or pulsations across the affected area. The patient complained about a mild tingling sensation within the lesion. The patient could not think of any triggers or causes for his condition and denied any aggravating or alleviating factors as well as any treatment attempts. Complete review of systems yielded negative results except for easy bruising. He was taking finasteride, montelukast, enalapril, and metoprolol. His medical history was significant for right total reverse shoulder replacement 5 years prior. Apart from the previously described lesion, his physical examination was unremarkable, and he had full range of motion of his right shoulder. A punch biopsy of the slightly indurated papule from the involved area on the right biceps was completed (Figure, C and D).A and B, An irregularly linear, rusty-brown, atrophic, streaklike plaque extends from the tip of the right shoulder to the right biceps, where it ends in arborizing purple plaque with scattered, slightly indurated, irregular papules within it. C, Hematoxylin-eosin staining demonstrates a dermal infiltrate arranged in nodules with clefting between nodules; some inflammatory aggregates are also seen within dilated vessels. D, Immunohistochemical staining for CD68 antigen reveals that the infiltrate is composed mostly of histiocytes. What Is Your Diagnosis?

Linear morphea

Serpentine supravenous hyperpigmentation

Intraoperative cutaneous electrical injury (Lichtenberg figure)

Intralymphatic histiocytosis

D. Intralymphatic histiocytosis

D

Intralymphatic histiocytosis

Microscopic findings from the punch biopsy showed a dense, nodular infiltrate of lymphocytes and histiocytes (highlighted by immunohistochemical stain for CD68 antigen) throughout the dermis and within thin-walled lymphatic vessels (highlighted by immunohistochemical stain for D2-40 antigen). These are diagnostic findings of intralymphatic histiocytosis.Intralymphatic histiocytosis is a rare condition first described in 1994 as intravascular histiocytosis.1 It usually presents on limbs as ill-defined erythematous or reticulated plaques resembling livedo reticularis, and it may be associated with rheumatoid arthritis, malignant tumors (Merkel cell carcinoma, incidental finding at the periphery of the excision specimen2; breast carcinoma, in the mastectomy scar2; and lung adenocarcinoma, in the dermis overlying the soft tissue metastasis3), and orthopedic metal implants (such as in the present case).2-5 However, it may also occur without any other associated conditions.2 The pathogenesis is unclear, but it is hypothesized to be a nonspecific reaction to an injury such as trauma, including surgery; inflammation; or infiltrative cancers, all of which may cause impaired lymphatic flow.6 There is an attempt to include intralymphatic histiocytosis with other peculiar histiocytic proliferations occurring in various body sites under a unifying diagnosis of histiocytosis with raisinoid nuclei. All of these proliferations are benign and, except for the skin lesions, asymptomatic conditions.6 Mazloom and colleagues7 make a case that intralymphatic histiocytosis is a distinct entity from intravascular histiocytosis, which they include in the group of reactive angiomatoses.Linear morphea would not have arborizing appearance and would have entirely different histopathologic findings with dense collagen in the dermis, decreased adnexal structures, and sparse inflammation in the lower dermis and upper subcutaneous fat. Serpentine supravenous hyperpigmentation is a cutaneous adverse effect of chemotherapy infusion with fluorouracil, vinorelbine, fotemustine, and docetaxel.8 Histopathologic findings of the condition are very different from intralymphatic histiocytosis and may show interface dermatitis with isolated necrotic keratinocytes, papillary dermal edema, and superficial perivascular inflammatory infiltrates.9 Clinically, serpentine supravenous hyperpigmentation may look very similar to intralymphatic histiocytosis; however, it is self-limiting and resolves within several months. Intraoperative cutaneous electrical injury (Lichtenberg figure) could look similar to intralymphatic histiocytosis, but history of such injury is lacking in the present case, and histologic results were different in that one would expect to see necrosis of the epidermis and dermis, with epidermal and dermal cell nuclear elongation and homogenization of dermal collagen with vascular dilatation, congestion, hemorrhage, and thrombosis.A skin biopsy is needed to establish the diagnosis of intralymphatic histiocytosis with a characteristic histologic picture, as described in this case. In cases without clear association with rheumatoid arthritis or joint replacement, an underlying malignant tumor should be considered.2,3 Reported treatment options include topical and systemic steroids, intralesional triamcinolone acetonide and pressure bandaging,10 radiotherapy, pentoxifylline, cyclophosphamide, and arthrocentesis, all with variable success.2The patient in the present case declined any treatment, and his condition at last follow-up remained unchanged. The condition, though chronic and usually resistant to treatments, is deemed harmless.2

Dermatology

A man in his 80s presented with an 18-month history of an irregularly linear, rusty-brown, atrophic, streaklike plaque extending from the tip of his right shoulder to the right biceps, where it ended in arborizing purple plaque with scattered, slightly indurated, irregular papules within it (Figure, A and B). There was no warmth, thrills, or pulsations across the affected area. The patient complained about a mild tingling sensation within the lesion. The patient could not think of any triggers or causes for his condition and denied any aggravating or alleviating factors as well as any treatment attempts. Complete review of systems yielded negative results except for easy bruising. He was taking finasteride, montelukast, enalapril, and metoprolol. His medical history was significant for right total reverse shoulder replacement 5 years prior. Apart from the previously described lesion, his physical examination was unremarkable, and he had full range of motion of his right shoulder. A punch biopsy of the slightly indurated papule from the involved area on the right biceps was completed (Figure, C and D).A and B, An irregularly linear, rusty-brown, atrophic, streaklike plaque extends from the tip of the right shoulder to the right biceps, where it ends in arborizing purple plaque with scattered, slightly indurated, irregular papules within it. C, Hematoxylin-eosin staining demonstrates a dermal infiltrate arranged in nodules with clefting between nodules; some inflammatory aggregates are also seen within dilated vessels. D, Immunohistochemical staining for CD68 antigen reveals that the infiltrate is composed mostly of histiocytes.

what is your diagnosis?

What is your diagnosis?

Linear morphea

Intralymphatic histiocytosis

Intraoperative cutaneous electrical injury (Lichtenberg figure)

Serpentine supravenous hyperpigmentation

b

male

81-90

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2734253

A white man in his early 40s with a medical history of chronic lymphocytic leukemia (Rai stage 0) reported a 6-month history of a growing mass in his right axilla and weight loss. Physical examination revealed palpable right axillary lymphadenopathy. The patient was an active smoker (1 pack per day) with an unremarkable family history. A positron emission tomography scan showed a hypermetabolic right axillary lymph node that measured 5 × 5 cm as well as multiple liver lesions, the largest of which measured 8 cm. The results of a core needle biopsy specimen from the right axillary lymph node were consistent with malignant neoplasm, with immunohistochemistry staining positive for S100, HMB-45, and MART-1. He began pembrolizumab therapy.After starting treatment, the patient began to notice slowly worsening painless, nonpruritic, diffuse dark gray skin, nail beds, and eye discoloration (Figure). The results of laboratory studies revealed normal electrolytes, normal kidney function, mild elevation of liver function, and mild anemia with a hemoglobin level of 12 g/dL (for SI unit conversion, multiply by 10.0 to convert to liters). Computed tomography of the chest, abdomen, and pelvis showed worsening hepatic metastases and right axillary adenopathy. What Is Your Diagnosis?

Hemochromatosis

Diffuse melanosis cutis

Addison disease

Hyperpigmentation due to sun exposure

B. Diffuse melanosis cutis

B

Diffuse melanosis cutis

Diffuse melanosis cutis (DMC) is a rare condition characterized by the hyperpigmentation of skin and mucous membranes caused by increased melanin deposition in patients with malignant melanoma. According to a systematic review,1 fewer than 100 cases have been reported. Diffuse melanosis cutis presents more commonly in males (60% of cases) and white patients (95% of cases), with a median age at the time of diagnosis of about 50 years.1 This condition is also associated with melanuria in about 77% of cases.1 Usually, DMC is seen 12 months after an initial diagnosis of metastatic melanoma. Patients present with progressive and diffuse blue-gray hyperpigmentation of the skin and mucous membranes, leading to darkening of the skin, hair, peritoneal fluid, sputum, urine, and sometimes the internal organs.2Histopathologic findings include deposition of perivascular histiocytes filled with melanin and free pigment in the dermal connective tissue. The underlying pathogenesis for this condition is not fully understood. According to one hypothesis, when metastatic melanoma undergoes lysis by ischemia, immunological responses, or oncologic treatments, cells release melanin precursors into the bloodstream that undergo auto-oxidation, become ingested by histiocytes, and are then deposited in the dermis.3 Another hypothesis suggests that tumor cells release melanocyte peptide growth factors such as α melanocyte-stimulating hormone, which might be responsible for DMC. The role immunotherapy played in the manifestation of DMC in this case is unclear. One case series of patients who developed DMC after immunotherapy initiation concluded that DMC may be a negative predictor of response to anti–PD-1 (programmed cell death 1) treatment.4 In particular, it remains unclear whether immunotherapy promotes DMC development or just cannot control DMC that would inevitably develop.The discoloration of DMC is most prominently noted in sun-exposed areas, progressing in a cephalocaudal direction.2 Diffuse melanosis cutis is an ominous sign that is associated with a worse prognosis, with a median survival of 4 to 6 months after diagnosis.1,5 According to case reports,5,6 novel therapies that target a BRAF mutation and immunotherapies have shown a considerable survival benefit.Based on the results of the biopsy specimen, the patient was diagnosed with metastatic melanoma. Metastatic melanoma should be one of the differential diagnoses in patients presenting with unusual skin discoloration and/or dark-colored bodily secretions. Given this patient’s short survival after his initial presentation, prognosis should be discussed at the time of diagnosis. Other differential diagnoses include hemochromatosis, most notably the hereditary form, which demonstrates skin hyperpigmentation in most cases. Elevated liver function levels are more likely related to worsening hepatic metastases. In this case, hemochromatosis is less likely given the patient’s unremarkable family history and the absence of other clinical features of hemochromatosis, including arthropathy or diabetes. Addison disease, also known as primary adrenal insufficiency, can cause generalized brown hyperpigmentation. However, the absence of other features of adrenal insufficiency such as hypotension, hypoglycemia, and electrolyte abnormalities makes this diagnosis less likely. Hyperpigmentation due to sun exposure would be limited to sun-exposed areas and would not cause hyperpigmentation of nail beds and eyes, as is seen in this case.This patient’s treatment was changed to the combination of pembrolizumab and talimogene laherparepvec injection. However, the disease progressed and the patient declined further treatment. He was transitioned to hospice care and died 6 months after DMC onset.

Oncology

A white man in his early 40s with a medical history of chronic lymphocytic leukemia (Rai stage 0) reported a 6-month history of a growing mass in his right axilla and weight loss. Physical examination revealed palpable right axillary lymphadenopathy. The patient was an active smoker (1 pack per day) with an unremarkable family history. A positron emission tomography scan showed a hypermetabolic right axillary lymph node that measured 5 × 5 cm as well as multiple liver lesions, the largest of which measured 8 cm. The results of a core needle biopsy specimen from the right axillary lymph node were consistent with malignant neoplasm, with immunohistochemistry staining positive for S100, HMB-45, and MART-1. He began pembrolizumab therapy.After starting treatment, the patient began to notice slowly worsening painless, nonpruritic, diffuse dark gray skin, nail beds, and eye discoloration (Figure). The results of laboratory studies revealed normal electrolytes, normal kidney function, mild elevation of liver function, and mild anemia with a hemoglobin level of 12 g/dL (for SI unit conversion, multiply by 10.0 to convert to liters). Computed tomography of the chest, abdomen, and pelvis showed worsening hepatic metastases and right axillary adenopathy.

what is your diagnosis?

What is your diagnosis?

Diffuse melanosis cutis

Hemochromatosis

Hyperpigmentation due to sun exposure

Addison disease

a

male

41-50

White

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2738099

A 44-year-old woman with dilated cardiomyopathy while receiving maximally tolerated guideline-directed medical therapy presented after ventricular fibrillation arrest and subsequently underwent an uneventful implant of a subcutaneous cardioverter defibrillator (S-ICD; EMBLEM, version A219; Boston Scientific) for secondary prevention. The device was programmed with a conditional shock zone of 200 beats per minute and a shock zone of 230 beats per minute. Postprocedure chest radiography results showed appropriate device placement. Postimplant interrogation results showed appropriate device function. The patient was discharged the day after implant. Two weeks later, she presented to the emergency department (ED) after receiving several shocks from the device during the early morning, waking her up from sleeping. There were no reported symptoms associated with shortness of breath, chest pain, or syncope. Physical examination results revealed no signs of decompensated heart failure. Device interrogation results showed shock therapies delivered postimplant on days 3, 5, 6, and 10. The surface electrogram from the events, recorded at a paper speed of 25 millimeters per second and an amplitude of 2.5 mm/mvV) is shown in Figure 1. Repeated chest radiography at the ED showed appropriate device location, lead pin, and an absence of subcutaneous air trapping at the proximal and distal sense electrodes.Surface electrogram recorded by subcutaneous implantable cardioverter defibrillator from one of the events. Recorded at a paper speed of 25 millimeters per second and an amplitude of 25 mm/mV. The shock impedance was 57 ohms and the final shock polarity was standard.Administer anticoagulation and increase the dose of the β-blocker What Would You Do Next?

Administer anticoagulation and increase the dose of the β-blocker

Subcutaneous ICD reprogramming and observation

Administer a loading dose of amiodarone

Refer the patient for catheter ablation

Inappropriate S-ICD shock from the oversensing of the electrical noise

B

Subcutaneous ICD reprogramming and observation

The surface electrogram results from all the events shared similar characteristics and revealed an inappropriate ICD shock due to an oversensing of the electrical noise. The noise has the appearance of “flutter waves,” which terminated after the shock therapies. Initially, this noise could be interpreted as ventricular or atrial arrhythmia. There are few points used to accurately differentiate between appropriate and inappropriate therapy in this case. First, the marching intrinsic QRS complexes through tracing can be identified within this electrical rhythm with varying degrees of superimposition of the flutterlike wave on the R wave. Second, the morphology and amplitude of the flutter waves are irregular and variable in cycle length, suggesting that the flutter waves are unlikely to be caused by reentry mechanism. Third, the intrinsic ventricular rate in the range of 90 to 100 beats per minute remained the same before and after the shocks were administered.The S-ICD system uses 3 sensing electrodes for detection: (1) distal sensing, (2) proximal sensing, and (3) a pulse generator. These electrodes represent 3 vector projections of cardiac conduction: primary, secondary, and alternate (Figure 2). Based on the optimal QRS:T wave ratio, one of the vectors is selected by an automatic setup algorithm for use as a configuration for sensing and to avoid inappropriate therapy because of myopotentials, multiple counting (eg, double QRS and T-wave oversensing), or noise. However, inappropriate shocks remain a substantial problem in S-ICD.1 In this case, the secondary vector was automatically selected. The inappropriate shock event occurred during sleep within 1 to 2 weeks after the device implant. There were no identified sources of electromagnetic interference and no oversensing was detected at the time of presentation to the ED. Electrical noise occurring in the early postprocedural period can be seen with incomplete electrode insertion, subcutaneous air trapping in the midline or xiphoid incision, or fluid/air trapping within the device header1-3; however, subcutaneous air trapping commonly presents within 48 hours after the procedure. Reviewing all episodes, the noise decreased or was eliminated after the shocks. The shock or a sudden change in patient posture may result in a redistribution of fluid or escaped trapped air from the header. A damaged seal plug or a slightly loosened setscrew may be associated with the characteristic of the air and fluid transition. Over several days, the redistribution of fluid and air results in repeated episodes. However, this redistribution of fluid and air escape over time eventually replaces the air in the device header and the intermittent episodic electrical noise may subside.2 Therefore, observation can be a reasonable management of this condition. Additional mitigations at time of device implant include removing the torque wrench before the electrode header tug test and a gentle insertion and removal of the torque wrench with the seal plug. In the meantime, the patient’s device is reprogrammed to switch to the primary vector, thereby disabling the circuit involving the distal sensing electrode.Subcutaneous implantable cardioverter defibrillator sensing vectors superimposed to the chest radiography. A, An electrode superior to the sternal coil (distal sense electrode). B, An electrode inferior to the sternal defibrillation coil (proximal sense electrode). C, Pulse generator. These electrodes represent 3 vector projections of cardiac electrical conduction: primary, secondary, and alternate electrocardiogram (ECG) vectors. The device image at the left corner shows the terminal connectors of sensing electrode and coil.The primary vector could be used for this patient, as the R wave amplitude was suitable. The patient had no further episodes during follow-up.

Cardiology

A 44-year-old woman with dilated cardiomyopathy while receiving maximally tolerated guideline-directed medical therapy presented after ventricular fibrillation arrest and subsequently underwent an uneventful implant of a subcutaneous cardioverter defibrillator (S-ICD; EMBLEM, version A219; Boston Scientific) for secondary prevention. The device was programmed with a conditional shock zone of 200 beats per minute and a shock zone of 230 beats per minute. Postprocedure chest radiography results showed appropriate device placement. Postimplant interrogation results showed appropriate device function. The patient was discharged the day after implant. Two weeks later, she presented to the emergency department (ED) after receiving several shocks from the device during the early morning, waking her up from sleeping. There were no reported symptoms associated with shortness of breath, chest pain, or syncope. Physical examination results revealed no signs of decompensated heart failure. Device interrogation results showed shock therapies delivered postimplant on days 3, 5, 6, and 10. The surface electrogram from the events, recorded at a paper speed of 25 millimeters per second and an amplitude of 2.5 mm/mvV) is shown in Figure 1. Repeated chest radiography at the ED showed appropriate device location, lead pin, and an absence of subcutaneous air trapping at the proximal and distal sense electrodes.Surface electrogram recorded by subcutaneous implantable cardioverter defibrillator from one of the events. Recorded at a paper speed of 25 millimeters per second and an amplitude of 25 mm/mV. The shock impedance was 57 ohms and the final shock polarity was standard.Administer anticoagulation and increase the dose of the β-blocker

what would you do next?

What would you do next?

Administer anticoagulation and increase the dose of the β-blocker

Refer the patient for catheter ablation

Administer a loading dose of amiodarone

Subcutaneous ICD reprogramming and observation

d

female

41-50

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2734341

A young woman presented with a 1-year history of a right tongue mass that developed after initial bite trauma. The lesion waxed and waned but never completely healed; however, it greatly increased in size over 3 weeks before presentation. She reported constant, severe stabbing pain, right otalgia, and occasional swelling that caused oral dysphagia. She reported no constitutional symptoms or any history of tobacco or alcohol use. On examination, the mass was a 3 × 2-cm, exophytic and raised, plateaulike lesion on the right dorsolateral tongue with approximately 1 to 2 cm of surrounding induration (Figure, A).A, Right lateral tongue lesion at presentation. B, Spindled-cell proliferation with palisaded areas (Verocay bodies) and an associated inflammatory infiltrate with abundant eosinophils (hematoxylin-eosin, original magnification ×20).A biopsy was obtained that demonstrated ulceration, pseudoepitheliomatous hyperplasia, and abundant acute and chronic inflammation replete with eosinophils. The differential based on the biopsy included traumatic ulcerative granuloma with stromal eosinophilia and ulceration due to drug- or infection-related sources. In addition, the possibility of an unsampled submucosal mass with overlying ulceration was suggested by the pathologist who interpreted the biopsy findings. Given our clinical concern for an unsampled neoplasm, the patient subsequently underwent resection of the mass; histologic sections of the specimen are demonstrated in Figure, B. Immunohistochemistry studies for SOX-10 revealed positive staining in the proliferating spindle-shaped cells.Schwannoma with a traumatic ulcerative granuloma with stromal eosinophilialike reaction What Is Your Diagnosis?

Human papillomavirus–related squamous cell carcinoma

Schwannoma with a traumatic ulcerative granuloma with stromal eosinophilialike reaction

Ulcerated plexiform neurofibroma

Ulcerated granular cell tumor

B. Schwannoma with a traumatic ulcerative granuloma with stromal eosinophilialike reaction

B

Schwannoma with a traumatic ulcerative granuloma with stromal eosinophilialike reaction

This case demonstrates a unique example of a lateral tongue schwannoma with an associated traumatic ulcerative granuloma with stromal eosinophilia (TUGSE)–like reaction that produced a large, exophytic mass mimicking more clinically concerning lesions, such as squamous cell carcinoma.Schwannoma is a benign, peripheral nerve sheath tumor that can occur throughout the body, but most commonly develops in the head and neck.1 An oral tongue location has been a well-documented site for this tumor. The histologic features of schwannomas in an oral tongue location parallel those at other sites and consist of a spindled cell proliferation with hypercellular and hypocellular areas that refer to specific patterns known as Antoni A and Antoni B.1 In the hypercellular areas, there are foci with nuclear palisading known as Verocay bodies. Immunohistochemistry demonstrates that the spindled cells are strongly and diffusely positive for S-100 and SOX-10 and typically negative for markers of epithelial differentiation, such as cytokeratins.1 To our knowledge, a brisk inflammatory infiltrate, such as the kind seen with TUGSE, has not been reported to occur with schwannoma.Traumatic ulcerative granuloma with stromal eosinophilia is a rare, benign condition with a strong etiologic association with repetitive trauma.2,3 In addition, most lesions develop on the dorsal or lateral, mobile tongue, which readily contacts teeth or dentures.2 Also referred to as traumatic eosinophilic granuloma, TUGSE is a self-limiting ulcer. Its duration varies from weeks to months and, rarely up to a year before it resolves.2 Its gross appearance can be alarming and often mimics that of squamous cell carcinoma. Histologically, TUGSE is characterized by a diffuse, polymorphous cellular infiltrate with abundant eosinophils that infiltrate into the deep skeletal muscle fibers.4,5 Occasional large, atypical mononuclear cells that are CD30 positive and express T-cell antigens have been identified in TUGSE.2,6 Some cases also demonstrate T-cell clonality, leading some authors to suggest that a subset of lesions diagnosed as TUGSE may be within the spectrum of CD30-positive lymphoproliferative disease.6 Others consider TUGSE a benign entity that is most likely trauma related.2-5 If a trauma-related hypothesis for TUGSE is accepted, then it is conceivable that a traumatized neoplasm could develop secondary to TUGSE-like changes. We believe that this case illustrates this concept, as this patient’s history of biting the mass likely accounts for the TUGSE-like inflammatory changes associated with the schwannoma.Although the clinical presentation and young patient age are concerning for a human papillomavirus–related squamous cell carcinoma, these tumors occur most commonly in the oropharynx rather than the oral tongue.7 Although the patient described herein did not have an alcohol or tobacco use disorder, her presentation also raised the possibility of a non–HPV-related squamous cell carcinoma of the oral cavity; in our current era and patient population, there has been an increase in the incidence of these cancers.8Plexiform neurofibromas typically have a haphazard arrangement of spindled cells with buckled-shaped nuclei.9 The stroma of neurofibromas can vary from myxoid to hyalinized. While this tumor is also positive for S-100 and SOX-10, it is typically not as diffuse as seen in schwannoma.9 In addition, the Antoni A and Antoni B patterns and Verocay bodies are characteristic of schwannoma and not a typical feature of plexiform neurofibroma. Granular cell tumors are also S-100 and SOX-10 positive but are composed of plump, polygonal cells with abundant granular cytoplasm.10 Because plexiform neurofibromas and granular cell tumors cannot be distinguished clinically, histologic assessment is required for their distinction.Two years after presentation, there has been no recurrence of the lesion after en bloc resection and primary closure. Confirmed TUGSE with underlying schwannoma was found on final pathologic examination. This case reminds us that superficial biopsy samples of ulcerated elevated lesions may not adequately sample the underlying mass. The initial biopsy in this patient only contained the ulcer, inflammation, and squamous epithelium; the submucosa was not well represented, leading to a sampling pitfall. Given the elevated nature of the lesion, superficial initial sample, and both clinical and pathologic concern for an underlying neoplasm, surgical resection was undertaken and warranted in this particular case.

General

A young woman presented with a 1-year history of a right tongue mass that developed after initial bite trauma. The lesion waxed and waned but never completely healed; however, it greatly increased in size over 3 weeks before presentation. She reported constant, severe stabbing pain, right otalgia, and occasional swelling that caused oral dysphagia. She reported no constitutional symptoms or any history of tobacco or alcohol use. On examination, the mass was a 3 × 2-cm, exophytic and raised, plateaulike lesion on the right dorsolateral tongue with approximately 1 to 2 cm of surrounding induration (Figure, A).A, Right lateral tongue lesion at presentation. B, Spindled-cell proliferation with palisaded areas (Verocay bodies) and an associated inflammatory infiltrate with abundant eosinophils (hematoxylin-eosin, original magnification ×20).A biopsy was obtained that demonstrated ulceration, pseudoepitheliomatous hyperplasia, and abundant acute and chronic inflammation replete with eosinophils. The differential based on the biopsy included traumatic ulcerative granuloma with stromal eosinophilia and ulceration due to drug- or infection-related sources. In addition, the possibility of an unsampled submucosal mass with overlying ulceration was suggested by the pathologist who interpreted the biopsy findings. Given our clinical concern for an unsampled neoplasm, the patient subsequently underwent resection of the mass; histologic sections of the specimen are demonstrated in Figure, B. Immunohistochemistry studies for SOX-10 revealed positive staining in the proliferating spindle-shaped cells.Schwannoma with a traumatic ulcerative granuloma with stromal eosinophilialike reaction

what is your diagnosis?

What is your diagnosis?

Ulcerated plexiform neurofibroma

Ulcerated granular cell tumor

Schwannoma with a traumatic ulcerative granuloma with stromal eosinophilialike reaction

Human papillomavirus–related squamous cell carcinoma

c

female

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2734871

A 45-year-old man was admitted to the hospital following 3 weeks of dysphagia; 1 week of nasal regurgitation, nonproductive cough, and breathy voice; and a 25-pound weight loss over the preceding 2 months. He had been diagnosed a year earlier with HIV infection and hepatic tuberculosis. Baseline CD4 count was 7 cells/μL, and following treatment with HAART (highly active antiretroviral therapy) consisting of dolutegravir, emtricitabine, and tenofovir-disoproxil-fumarate, he achieved full virological suppression; however, CD4 counts remained low at 31 cells/μL. He had completed 12 months of directly observed therapy with ethambutol, moxifloxacin, and rifabutin—a liver-sparing regimen—owing to toxic effects from the first-line regimen 1 month prior to admission. Physical examination revealed evidence of perforation of the hard palate (Figure, A). A computed tomographic scan of the chest revealed necrotic lymph nodes, and a palatine biopsy was performed (Figure, B and C).A, Clinical view of the perforation of the hard palate. B, Low-power microscopic view of a biopsy specimen from the hard palate (hematoxylin-eosin). C, Oil immersion image of the same tissue shown panel B stained with Grocott methenamine silver. What Is Your Diagnosis?

Tuberculosis of the palate

Tertiary syphilis

Histoplasmosis

Sarcoidosis

C. Histoplasmosis

C

Histoplasmosis

Histoplasmosis, caused by a soil-based fungus,1 is the most common endemic mycosis in the United States, with a reported in-hospital crude mortality rate of 5% for children and 8% for adults.2 Clinical manifestations of histoplasmosis range from asymptomatic infection to rapidly progressive fatal illness.3 Oral histoplasmosis is an important entity to recognize because it is often a manifestation of disseminated disease.4 Moreover, the appearance may mimic other local or systemically manifested oral disease resulting in misdiagnosis.5Disruption of soil by activities such as spelunking, excavation, outdoor construction, and remodeling of old buildings inhabited by birds or bats1 results in aerosolization of Histoplasma spores, which are then inhaled by human hosts causing infection. The vast majority of these primary infections are either asymptomatic or result in self-limited influenzalike illness, depending on the intensity of exposure.6 Cellular immunity develops approximately 2 weeks after infection in immunocompetent hosts, producing granulomas3 that either resolve spontaneously or persist as calcifications most commonly seen in mediastinal lymph nodes, liver, and spleen.4 In approximately 8% cases of histoplasmosis, the fungus disseminates.1 Risk of dissemination is greatest in individuals with a compromised immune system, especially those with AIDS and hematological malignant conditions, and in individuals using immunosuppressive medications.7 Dissemination can cause an acute, rapidly fatal sepsis syndrome with low blood pressure and multiorgan failure7 or a more subacute to chronically progressive disease with presence of focal lesions in various organs including the oropharynx.1Oral manifestations of histoplasmosis range from nodular, papular lesions to plaques, deep ulcers, and perforation.8 In the oral cavity, the most common locations for these lesions are the tongue, palate, buccal mucosa, gingiva, and pharynx.9 Patients can present with a wide variety of symptoms, including hoarseness, loss of weight, pain at the site of the lesion, and malaise.4 Approximately 30% to 50% of patients with disseminated histoplasmosis have these oral lesions, and sometimes these could be the initial local presentation of disseminated disease.10Oral lesions caused by Histoplasma species mimic several other disease entities such as squamous cell carcinoma, tuberculosis, syphilis, and other fungal infections like cryptococcosis, leading to morbid consequences of misdiagnosis.1 Definitive diagnosis is dependent on tissue biopsy and culture of organisms from lesions. Since culture results may take up to a month, pathological evaluation with fungal stains of biopsy material demonstrating oval to round yeast cells measuring 2 to 4 μm can be helpful in rapid identification of Histoplasma.3 Detection of Histoplasma antigen in body fluids has very high sensitivity in patients with progressive disseminated histoplasmosis and is the mainstay of diagnosis.1 Treatment is primarily dependent on the severity of infection as well as the underlying immune status of the patient. Lipid-based formulations of amphotericin B are used for severe cases, while itraconazole could be an option in less severe cases with intact immune system.1The repeatedly low CD4 cell count of the patient in the present case, even after appropriate HAART treatment, was the biggest risk factor for disseminated histoplasmosis. Despite 2 weeks of aggressive antifungal therapy with amphotericin B, he died. The granulomatous response typically present in immunocompetent patients with histoplasmosis was absent in this patient given profound immunosuppression from CD4 T-cell deficiency. Therefore, performing histochemical stains for microorganisms and ideally fungal culture in biopsied material is critically important in these patients, so as not to miss the etiologic agent of infection.

General

A 45-year-old man was admitted to the hospital following 3 weeks of dysphagia; 1 week of nasal regurgitation, nonproductive cough, and breathy voice; and a 25-pound weight loss over the preceding 2 months. He had been diagnosed a year earlier with HIV infection and hepatic tuberculosis. Baseline CD4 count was 7 cells/μL, and following treatment with HAART (highly active antiretroviral therapy) consisting of dolutegravir, emtricitabine, and tenofovir-disoproxil-fumarate, he achieved full virological suppression; however, CD4 counts remained low at 31 cells/μL. He had completed 12 months of directly observed therapy with ethambutol, moxifloxacin, and rifabutin—a liver-sparing regimen—owing to toxic effects from the first-line regimen 1 month prior to admission. Physical examination revealed evidence of perforation of the hard palate (Figure, A). A computed tomographic scan of the chest revealed necrotic lymph nodes, and a palatine biopsy was performed (Figure, B and C).A, Clinical view of the perforation of the hard palate. B, Low-power microscopic view of a biopsy specimen from the hard palate (hematoxylin-eosin). C, Oil immersion image of the same tissue shown panel B stained with Grocott methenamine silver.

what is your diagnosis?

What is your diagnosis?

Histoplasmosis

Tertiary syphilis

Sarcoidosis

Tuberculosis of the palate

a

male

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2734819

A man in his late 30s with a history of proliferative diabetic retinopathy presented for evaluation of sudden-onset painless blurry vision of the right eye. His ocular history included nonclearing vitreous hemorrhage in the right eye requiring pars plana vitrectomy, panretinal photocoagulation, multiple treatments with intravitreous bevacizumab, and cataract extraction with placement of an intraocular lens (IOL) into the capsular bag approximately 4 years ago. At his routine follow-up visit 2 weeks prior, the proliferative diabetic retinopathy was quiescent, and his Snellen visual acuity was 20/20 OD with manifest refraction of −1.50 + 0.25 × 180. Examination of the anterior segment at that time was unremarkable.At his current visit, visual acuity with the previous correction had been reduced to 20/150. Repeated manifest refraction of the right eye was −4.00 + 1.50 × 166, resulting in a visual acuity of 20/25. Intraocular pressure of the right eye was 10 mm Hg by Goldmann applanation tonometry. Evaluation of the posterior segment, including dilated fundus examination and optical coherence tomography (OCT) of the macula, showed stability compared with previous results. Imaging of the anterior segment with OCT is shown in Figure 1. The anterior chamber did not appear shallow, and there was no cell or flare.Slitlamp photograph of the anterior segment (A) and optical coherence tomographic imaging of the lens–capsular bag complex (B) obtained at initial presentation (arrowheads show hyperdistention of the capsular bag with turbid fluid).Perform posterior capsulotomy as part of pars plana vitrectomy What Would You Do Next?

Perform posterior capsulotomy as part of pars plana vitrectomy

Perform posterior capsulotomy with Nd:YAG laser

Exchange the IOL

Observe the patient

Capsular bag distention syndrome

B

Perform posterior capsulotomy with Nd:YAG laser

The key to diagnosis is recognizing hyperdistention of the capsular bag with a turbid milieu posterior to the IOL (Figure 1) along with a myopic shift. Anterior segment OCT confirmed the diagnosis. Performing a posterior capsulotomy would allow egress of the turbid material into the vitreous cavity and provide immediate resolution of the refractive change with minimal risk. If this was not successful, we would then perform a posterior capsulotomy during pars plana vitrectomy (choice A). Exchanging the IOL (choice C) is not preferred because decreasing the new lens power to compensate for the myopic shift would result in a hyperopic surprise, as the procedure itself would resolve the capsular bag distention syndrome (CBDS). Observation (choice D) is preferable when the patient does not want intervention; however, the myopic shift needs to be corrected with an updated manifest refraction.Capsular bag distention syndrome, also known as capsular block syndrome, is a rare complication after phacoemulsification and placement of an IOL into the capsular bag.1,2 It is characterized by the accumulation of opaque fluid within the potential space between the posterior aspect of the IOL and the intact posterior capsule. Capsular bag distention syndrome is classified as intraoperative, early-onset, or late-onset on the basis of time of onset.3 Intraoperative CBDS occurs with lens luxation following hydrodissection. Early-onset CBDS is associated with retained viscoelastic materials. Late-onset CBDS is caused by residual cortical cells secreting alpha-crystallin proteins, which creates a turbid milieu that slowly accumulates and distends the posterior capsule.4 Patients with diabetes are not at increased risk for this syndrome. Although intraoperative and early-onset forms of CBDS are often associated with high intraocular pressure and shallowing of the anterior chamber, these features may be absent in the late-onset form.5 This patient presented with late-onset CBDS, demonstrating symptomatic visual acuity decline approximately 4 years after cataract surgery.Although CBDS can be diagnosed clinically, the value of using anterior segment OCT has been previously reported.6 The combination of increased refractive index of the turbid milieu along with convex configuration of the hyperdistended capsular bag forms a plus lens effect that causes a myopic shift, as experienced by this patient.Capsular bag distention syndrome can often be treated with Nd:YAG laser–assisted posterior capsulotomy, as this quick in-office procedure evacuates the turbid milieu from the capsular bag and resolves symptoms almost immediately.5,7 When an infectious etiology, in particular Propionibacterium acnes, is suspected, use of pars plana vitrectomy is necessary to surgically remove the contents of the bag, along with possible IOL exchange and/or injection of intraocular antibiotics.8,9 In this patient, there were no clinical findings of intraocular inflammation or capsular plaques to suggest infection.This patient underwent uneventful Nd:YAG laser–assisted posterior capsulotomy of the right eye; 1 hour after the procedure, the intraocular pressure was 11 mm Hg by applanation. Within 10 minutes after the procedure, the patient reported noticeably improved distance vision in the right eye. Repeated manifest refraction showed resolution of the myopic shift. Clinical examination revealed absence of the hyperdistended capsular bag or turbid fluid, which was confirmed on repeated anterior segment OCT (Figure 2).Anterior segment optical coherence tomography image showing the lens capsule complex after Nd:YAG laser capsulotomy.

Ophthalmology

A man in his late 30s with a history of proliferative diabetic retinopathy presented for evaluation of sudden-onset painless blurry vision of the right eye. His ocular history included nonclearing vitreous hemorrhage in the right eye requiring pars plana vitrectomy, panretinal photocoagulation, multiple treatments with intravitreous bevacizumab, and cataract extraction with placement of an intraocular lens (IOL) into the capsular bag approximately 4 years ago. At his routine follow-up visit 2 weeks prior, the proliferative diabetic retinopathy was quiescent, and his Snellen visual acuity was 20/20 OD with manifest refraction of −1.50 + 0.25 × 180. Examination of the anterior segment at that time was unremarkable.At his current visit, visual acuity with the previous correction had been reduced to 20/150. Repeated manifest refraction of the right eye was −4.00 + 1.50 × 166, resulting in a visual acuity of 20/25. Intraocular pressure of the right eye was 10 mm Hg by Goldmann applanation tonometry. Evaluation of the posterior segment, including dilated fundus examination and optical coherence tomography (OCT) of the macula, showed stability compared with previous results. Imaging of the anterior segment with OCT is shown in Figure 1. The anterior chamber did not appear shallow, and there was no cell or flare.Slitlamp photograph of the anterior segment (A) and optical coherence tomographic imaging of the lens–capsular bag complex (B) obtained at initial presentation (arrowheads show hyperdistention of the capsular bag with turbid fluid).Perform posterior capsulotomy as part of pars plana vitrectomy

what would you do next?

What would you do next?

Perform posterior capsulotomy as part of pars plana vitrectomy

Observe the patient

Exchange the IOL

Perform posterior capsulotomy with Nd:YAG laser

d

male

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2734988

A woman in her late 60s presented with progressive, painless blurring of vision in both eyes over the past 6 months. Medical history was significant for Sjögren syndrome, for which she was taking hydroxychloroquine sulfate. Ocular history was notable for neovascular age-related macular degeneration under good control with intravitreal injections in the right eye and intermediate dry age-related macular degeneration in the left eye. Family history was negative for corneal disease.On initial presentation to the clinic, the best-corrected visual acuity of the patient was 20/150 OD and 20/40 OS. She was found to have bilateral, gray-white, irregular, poorly circumscribed, linear and nummular central and peripheral corneal opacities, confined primarily to the subepithelium and focally to the underlying anterior stroma (Figure 1A). The epithelium itself and deeper corneal stroma were spared, and the remainder of her anterior segment and fundus examination results were within normal limits. Anterior segment optical coherence tomography documented deposition of hyperreflective material in the subepithelium with trace deposition in the anterior stroma (Figure 1B). Evaluation of the patient's children showed no evidence of corneal disease.A, Right eye gray-white, irregular, linear and nummular central and peripheral corneal opacities. The left eye had similar findings. B, Hyperreflective deposits in the subepithelium (black arrowhead) with trace deposit in the anterior stroma (white arrowhead). What Would You Do Next?

Begin oral acyclovir sodium

Perform penetrating keratoplasty

Initiate topical cyclosporine

Perform superficial corneal biopsy

Paraproteinemic keratopathy from smoldering myeloma

D

Perform superficial corneal biopsy

The patient presented with bilateral subepithelial and anterior stromal corneal opacification. Antiviral agents, such as acyclovir (choice A), would not be preferred because bilaterality of the process and the lack of inflammatory response are not typical of an infectious origin. Topical cyclosporine (choice C) was not recommended because the absence of appreciable epithelial involvement suggests that keratopathy is unlikely related to Sjögren syndrome.1The subacute, noninflammatory, and bilateral nature of corneal opacification suggests corneal deposits that are either dystrophic or nondystrophic. Noninvasive genetic testing on peripheral blood for corneal epithelial-stromal dystrophies may be informative. However, although corneal dystrophies can occasionally manifest at an older age without documented familial inheritance, this type of presentation is uncommon.2 Immunoglobulin corneal deposition is an important diagnostic consideration that should prompt systemic evaluation for paraproteinemia, obviating the need for diagnostic corneal biopsy.3,4In cases in which paraproteinemic keratopathy eludes clinical diagnosis, pathological evaluation of corneal tissue is of diagnostic value.4 Penetrating keratoplasty (choice B), although it provides adequate diagnostic tissue, is an unnecessarily aggressive option for the apparently superficial corneal process. In contrast, superficial corneal biopsy (choice D) can provide valuable pathological information with minimal trauma. Lamellar keratectomy may have the advantage of therapeutic clearing of visual axis while providing the diagnostic tissue. Femto-assisted lamellar keratectomy, a relatively new corneal biopsy technique, may yield excellent optical quality with minimal refractive change, making it a viable option, if available, for patients with anterior corneal dystrophies.5Light microscopy revealed eosinophilic subepithelial and anterior stromal corneal deposits, without appreciable disruption of the Bowman membrane. The deposits did stain with Masson trichrome stain and periodic acid-Schiff stain and did not stain with Congo red stain. Immunohistochemical studies revealed immunoreactivity of deposits for IgG heavy chains and κ light chains (Figure 2). The findings were interpreted as paraproteinemic keratopathy, prompting a systemic workup. Oncologic workup demonstrated IgG κ monoclonal protein in the patient’s serum and urine and 10% κ-restricted plasma cells in the patient’s bone marrow, leading to the diagnosis of smoldering plasma cell myeloma.The immunohistochemical evaluation of superficial keratectomy demonstrates subepithelial and anterior stromal corneal deposits that immunoreact with antibodies for κ light chains (arrowheads). There is no staining for κ light chains in the intact Bowman membrane (asterisk) and in the overlying epithelium (antibody κ; original magnification ×100).Paraproteinemic keratopathy has a diverse clinical presentation, often mimicking crystalline keratopathy, corneal dystrophies, interstitial keratitis, and corneal degenerations.3,4 Systemic paraproteinemia occurs in 98% of patients with immunoglobulin corneal deposits, and it is secondary to the underlying plasma cell myeloma in 43% of patients.3,4 Clinicians should have a high index of suspicion for paraproteinemic keratopathy in older patients with bilateral, noninflammatory, progressive corneal deposits. If diagnosis is suspected, systemic workup for paraproteinemia should be considered.3,4,6In this case, superficial lamellar keratectomy was integral to establishing the diagnosis of paraproteinemic keratopathy and the patient’s underlying smoldering plasma cell myeloma. The patient is currently under the care of an oncologist, with a plan of initiation of systemic chemotherapy. She will be clinically followed up by serum protein electrophoresis and her disease will be considered quiescent once her IgG monoclonal spike is absent. She will be considered for a corneal graft if her symptoms or visual acuity worsen and when her disease is in remission. However, keratopathy may recur despite good systemic control.6

Ophthalmology

A woman in her late 60s presented with progressive, painless blurring of vision in both eyes over the past 6 months. Medical history was significant for Sjögren syndrome, for which she was taking hydroxychloroquine sulfate. Ocular history was notable for neovascular age-related macular degeneration under good control with intravitreal injections in the right eye and intermediate dry age-related macular degeneration in the left eye. Family history was negative for corneal disease.On initial presentation to the clinic, the best-corrected visual acuity of the patient was 20/150 OD and 20/40 OS. She was found to have bilateral, gray-white, irregular, poorly circumscribed, linear and nummular central and peripheral corneal opacities, confined primarily to the subepithelium and focally to the underlying anterior stroma (Figure 1A). The epithelium itself and deeper corneal stroma were spared, and the remainder of her anterior segment and fundus examination results were within normal limits. Anterior segment optical coherence tomography documented deposition of hyperreflective material in the subepithelium with trace deposition in the anterior stroma (Figure 1B). Evaluation of the patient's children showed no evidence of corneal disease.A, Right eye gray-white, irregular, linear and nummular central and peripheral corneal opacities. The left eye had similar findings. B, Hyperreflective deposits in the subepithelium (black arrowhead) with trace deposit in the anterior stroma (white arrowhead).

what would you do next?

What would you do next?

Perform superficial corneal biopsy

Initiate topical cyclosporine

Perform penetrating keratoplasty

Begin oral acyclovir sodium

a

female

61-70

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2735628

A boy in his teens with no significant medical history, ocular history, or recent trauma was referred by an ophthalmologist for mild photophobia and an iris lesion. The referring clinician initially suspected traumatic iridodialysis and vitreous prolapse. On ophthalmic evaluation, visual acuity was 20/20 OS, intraocular pressure was 13 mm Hg OS, and slitlamp examination of the left eye demonstrated a clear, intrinsically vascularized, cystic lesion extending into the anterior chamber from the peripheral superonasal iris (Figure 1A). The base of the lesion was surrounded by iris atrophy and corectopia was noted. The remainder of the ocular examination was unremarkable. Examination of the right eye was also unremarkable. Ultrasonographic biomicroscopy of the anterior segment demonstrated a large, cystic lesion incorporated in the iris of the left eye with a thickness of 2.2 mm and a maximum radial extent of 6.1 mm (Figure 1B).A, Slitlamp photograph of the iris cyst in the superonasal periphery of the left eye. B, Ultrasonographic biomicroscopy of the anterior segment in the left eye with longitudinal orientation at the 10-o’clock position.Given the patient’s excellent visual acuity and no documented evidence of growth, the lesion was initially monitored closely. One month after presentation, the patient developed worsening photophobia, and his visual acuity declined to 20/50 OS. The iris lesion was noted to have grown, with maximum thickness measuring 3.5 mm and with radial extension now involving the visual axis. What Would You Do Next?

Aspiration with absolute alcohol injection

Surgical resection

Continued monitoring

Laser cystotomy

Iris stromal cyst

A

Aspiration with absolute alcohol injection

Pigmented cysts arising from the iris pigment epithelium are the most common type of primary iris cyst.1 They are often of no visual consequence and typically do not require intervention.1 However, iris stromal cysts are likely to enlarge with distortion of surrounding structures and potential consequences of compromised vision, amblyopia, recurrent iridocyclitis, and glaucoma.2,3 Stromal cysts represent approximately 3% of iris tumors, and approximately 40% of iris stromal cysts are congenital.4 Congenital cysts are typically diagnosed in patients younger than 20 years.4In this case, continued observation was not ideal given the extension into the visual axis and the significant growth over the course of 1 month. Aspiration,3 alcohol sclerosis,5,6 resection,7 and laser treatment8 have all been described; however, we believe aspiration with alcohol sclerosis is the preferred initial approach given that it is less invasive than surgical resection and potentially less inflammatory and less likely to yield recurrence than laser cystotomy.Complete resection with sector iridectomy was advocated for congenital iris cysts by Capó and colleagues7 after comparison with injection of trichloroacetic acid and xenon photocoagulation. However, owing to its adverse effect profile, surgical resection is often regarded as a treatment of last resort after failure of more conservative interventions.3 Gupta and colleagues8 reported 2 cases of laser cystotomy using Nd:YAG laser to puncture the cyst wall and allow the cyst’s contents to drain into the anterior chamber. One of the 2 cases demonstrated a recurrence, which was treated successfully with Nd:YAG laser. Allowing cyst material to drain into the anterior chamber may result in inflammatory sequelae, such as peripheral anterior synechiae and epithelial downgrowth from the cyst lining.9Of the treatments mentioned above, aspiration with absolute alcohol injection to allow damage to the epithelial cell lining of the cyst, as initially described by Behrouzi and Khodadoust,6 has substantial support in the literature.5 Shields and colleagues5 described a case series of 16 iris stromal cysts treated with aspiration and absolute alcohol sclerosis. All cysts in their series had recurred after prior simple aspiration. In 15 patients with adequate follow-up, 13 cysts involuted and 1 stabilized in size. Visual acuity was stable or improved in 14 patients. Treatment failed in only 1 patient in the series, later requiring surgical resection of the cyst.5 The most common complications included transient corneal edema and anterior chamber inflammation, which resolved in association with topical corticosteroid therapy.The patient underwent aspiration and absolute alcohol injection with improvement in the size of the cyst (Figure 2).10 Initial treatment was followed by a second aspiration 2 months later with improved visual acuity to 20/20. There were no treatment complications. The cyst remained small with visual acuity 20/20 and normal intraocular pressure in the left eye after 8 months.Slitlamp photograph of the iris cyst 2 weeks after aspiration and absolute alcohol injection.

Ophthalmology

A boy in his teens with no significant medical history, ocular history, or recent trauma was referred by an ophthalmologist for mild photophobia and an iris lesion. The referring clinician initially suspected traumatic iridodialysis and vitreous prolapse. On ophthalmic evaluation, visual acuity was 20/20 OS, intraocular pressure was 13 mm Hg OS, and slitlamp examination of the left eye demonstrated a clear, intrinsically vascularized, cystic lesion extending into the anterior chamber from the peripheral superonasal iris (Figure 1A). The base of the lesion was surrounded by iris atrophy and corectopia was noted. The remainder of the ocular examination was unremarkable. Examination of the right eye was also unremarkable. Ultrasonographic biomicroscopy of the anterior segment demonstrated a large, cystic lesion incorporated in the iris of the left eye with a thickness of 2.2 mm and a maximum radial extent of 6.1 mm (Figure 1B).A, Slitlamp photograph of the iris cyst in the superonasal periphery of the left eye. B, Ultrasonographic biomicroscopy of the anterior segment in the left eye with longitudinal orientation at the 10-o’clock position.Given the patient’s excellent visual acuity and no documented evidence of growth, the lesion was initially monitored closely. One month after presentation, the patient developed worsening photophobia, and his visual acuity declined to 20/50 OS. The iris lesion was noted to have grown, with maximum thickness measuring 3.5 mm and with radial extension now involving the visual axis.

what would you do next?

What would you do next?

Aspiration with absolute alcohol injection

Laser cystotomy

Continued monitoring

Surgical resection

a

male

11-20

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2736416

A 72-year-old woman was referred for evaluation of a choroidal mass and subluxed crystalline lens in the right eye. The patient had a history of congestive heart failure, cleft lip surgery as an infant, and right eye amblyopia. She reported occasional floaters and flashes in the right eye but denied any ocular complaints in the left eye. On examination, her visual acuity measured 3/200 OD and 20/30 OS, stable compared with her baseline. Her intraocular pressure was 18 mm Hg OD and 14 mm Hg OS. Right eye slitlamp biomicroscopy showed an irregular pupil, aphakia, and a pigmented mass behind the temporal iris (Figure 1A). Ophthalmoscopic examination results revealed a subluxed white cataractous lens in the inferior vitreous base (Figure 1B). An evaluation of the left eye yielded normal results aside for a moderate cataract. B-scan ultrasonography results showed the 2 masses described previously; both were moderately reflective, oval, and separate from the wall of the eye. Ultrasonography biomicroscopy (UBM) confirmed that the temporal mass and the inferiorly subluxed lens were separate from the iris and ciliary body and were similar to each other in size, shape, and density.A, Anterior fundus photograph of the right eye shows a dark mass behind the pupil temporally. B, Fundoscopy of the same eye shows a white cataractous lens subluxed into the inferior vitreous base.Pars plana lensectomy to remove the subluxed lensMagnetic resonance imaging of the brain and orbits What Would You Do Next?

Plaque radiotherapy

Pars plana lensectomy to remove the subluxed lens

Magnetic resonance imaging of the brain and orbits

Biopsy of the choroidal mass

Congenital biphakia with double subluxed crystalline lenses

C

Magnetic resonance imaging of the brain and orbits

This is a case of a patient who was referred for evaluation of a likely choroidal mass. However, B-scan ultrasonography and UBM results show that the mass was adjacent to, but separate from, the ciliary body temporally, and the presence of a subluxed lens in the inferior vitreous further complicates the diagnosis.Because of the uncertainty of the etiology of the mass as to whether it is benign or malignant or even from which tissue it arose, treatment with plaque radiotherapy would not be appropriate. With the patient’s ocular history of amblyopia and poor visual prognosis, there was no visual benefit to removing the subluxed lens. Further imaging of the right eye with magnetic resonance imaging (MRI) was obtained and reaffirmed that the mass was similar in shape and density to the inferior subluxed lens (Figure 2). The MRI, along with autofluorescence, B-scan ultrasonography, and UBM, led us to diagnose congenital biphakia with 2 subluxed lenses1 and we elected observation as opposed to a biopsy.T2-weighted axial magnetic resonance imaging results of the brain and orbits with fat-saturation confirm 2 crystalline lenses (biphakia) that are subluxed in the right eye (yellow arrowheads) and a crystalline lens in normal position in the left eye (blue arrowhead).Congenital biphakia (2 crystalline lenses in the same eye) was first published in a case report by Von Graefe in 18542 and is an extremely rare condition, having only been reported in a few cases since. These cases discuss the presence of biphakia with and without other ocular abnormalities,3 such as hourglass cornea,1 uveal coloboma,4 iris coloboma,2 cleft anterior segment,5 and diplophthalmos,6 as well as its appearance alongside congenital nasal and craniocervical deformities.4,6 Notably, in our review of the literature on congenital biphakia, all cases presented unilaterally rather than bilaterally. In the aforementioned report of biphakia with congenital nasal abnormality, the patient also had a bifid eyelid and developmental delay4; by contrast, this patient’s developmental abnormalities were limited to right eye biphakia and an orofacial cleft.Although, to our knowledge, there is no known link, we question whether this patient’s biphakia and orofacial cleft may be associated because both are congenital physical anomalies that occur during early gestation. It is believed that a sporadic event, such as the duplication of the lens placode during fetal development, can result in congenital biphakia.5Unlike previously reported cases of congenital biphakia, this patient presented with double subluxed crystalline lenses, 1 brunescent and 1 white in color. The brunescent lens was confused for a choroidal neoplasm because of its dark color and location adjacent to the ciliary body. The differential diagnosis of a mass behind the iris includes uveal tumor or metastasis, iris or ciliary body cyst, inflammatory nodule, and subluxed lens. We initially dismissed the possibility of subluxed lens for this patient because of the presence of an additional, more obvious subluxed lens until further diagnostic imaging results confirmed the similarities between the mass and the subluxed lens. Although rare, this case is a good reminder that congenital defects can masquerade as other ocular abnormalities, including choroidal tumor.Comparison photographs and ultrasonography over 8 years demonstrated minimal migration of the subluxed lenses and no change in size or shape for this patient.

Ophthalmology

A 72-year-old woman was referred for evaluation of a choroidal mass and subluxed crystalline lens in the right eye. The patient had a history of congestive heart failure, cleft lip surgery as an infant, and right eye amblyopia. She reported occasional floaters and flashes in the right eye but denied any ocular complaints in the left eye. On examination, her visual acuity measured 3/200 OD and 20/30 OS, stable compared with her baseline. Her intraocular pressure was 18 mm Hg OD and 14 mm Hg OS. Right eye slitlamp biomicroscopy showed an irregular pupil, aphakia, and a pigmented mass behind the temporal iris (Figure 1A). Ophthalmoscopic examination results revealed a subluxed white cataractous lens in the inferior vitreous base (Figure 1B). An evaluation of the left eye yielded normal results aside for a moderate cataract. B-scan ultrasonography results showed the 2 masses described previously; both were moderately reflective, oval, and separate from the wall of the eye. Ultrasonography biomicroscopy (UBM) confirmed that the temporal mass and the inferiorly subluxed lens were separate from the iris and ciliary body and were similar to each other in size, shape, and density.A, Anterior fundus photograph of the right eye shows a dark mass behind the pupil temporally. B, Fundoscopy of the same eye shows a white cataractous lens subluxed into the inferior vitreous base.Pars plana lensectomy to remove the subluxed lensMagnetic resonance imaging of the brain and orbits

what would you do next?

What would you do next?

Plaque radiotherapy

Magnetic resonance imaging of the brain and orbits

Biopsy of the choroidal mass

Pars plana lensectomy to remove the subluxed lens

b

female

71-80

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2737084

A woman in her 30s presented with frequent falls, right-sided lower-extremity weakness, and intermittent confusion. She had a medical history significant for a renal transplant performed 4 years prior. She received induction with alemtuzumab and maintenance immunosuppression with tacrolimus and mycophenolate. She was not on any antiviral therapies prior to presentation. On admission, the patient developed left eye pain and slurred speech. Physical examination revealed expressive aphasia, partial left abducens nerve palsy, decreased motor strength in her right upper and lower extremities, and right-sided pronator drift. Laboratory evaluation showed a white blood cell count of 9.6 K/μL (reference range, 4.5-11.0 K/μL), and a lactic acid dehydrogenase level of 547 U/L (reference range, 160-450 U/L). Cerebrospinal fluid analysis revealed a white blood cell count of 51 cells/μL (reference range, 0-5 cells/μL) with 92% lymphocytes, a glucose level of 76 mg/dL (reference range, 40-70 mg/dL), and a protein level of 136 mg/dL (reference range, 12-60 mg/dL). A computed tomography (CT) scan of the brain showed multifocal vasogenic edema around the left lentiform nuclei, left temporal occipital white matter, and right parietal white matter, with mass effect causing near complete effacement of the third ventricle and subsequent rightward midline shift. Magnetic resonance imaging of the brain revealed multiple ring-enhancing lesions (Figure, A). A fluorine 18 fluorodeoxyglucose positron emission tomography/CT demonstrated increased focal fluorodeoxyglucose activity throughout the brain only. The patient underwent a biopsy of the right posterior temporal lobe (Figure, B and C).A, Ring-enhancing lesions are visible. B, A lesional biopsy specimen of the brain was obtained (hematoxylin-eosin, original magnification ×400). C, Immunohistochemical stain of CD20 (original magnification ×400). What Is Your Diagnosis?

Toxoplasmosis

Primary central nervous system posttransplant lymphoproliferative disorder

Glioblastoma

Metastatic disease from unknown primary neoplasm

B. Primary central nervous system posttransplant lymphoproliferative disorder

B

Primary central nervous system posttransplant lymphoproliferative disorder

Histologic results of the biopsy revealed abundant perivascular infiltrates of small lymphocytes with admixed large cells and occasional plasma cells (Figure, B). Immunohistochemical staining showed large cells positive for CD20 (Figure, C), BCL6, and CD30, and negative for CD10, consistent with a diagnosis of polymorphic primary central nervous system posttransplant lymphoproliferative disorder (PCNS-PTLD).Initially described in 1968,1 PTLD is a potentially fatal complication of both solid organ and hematopoietic stem cell transplant. The incidence of PTLD varies based on type of transplanted organ, immunosuppressive regimen, and patient characteristics. Posttransplant lymphoproliferative disorder manifesting after solid organ transplant (SOT) occurs in approximately 2% to 3% of cases, with highest incidence in intestinal and multiple organ transplant recipients (5%-20%), followed by lung and heart transplant (2%-10%), and then pancreatic, renal, and liver transplant (1%-5%).2,3The World Health Organization divides PTLD into 3 pathologic categories: early lesions, polymorphic, and monomorphic, with monomorphic PTLD fulfilling the criteria for one of the B-cell or natural killer/T-cell neoplasms recognized in immunocompetent individuals.4 About 50% of PTLD cases are driven by Epstein-Barr virus (EBV) infection in the setting of immunosuppression and subsequent T-cell inhibition.5 This patient’s pathology was positive for EBV, confirmed by in situ hybridization for EBV-encoded RNA; however, circulating EBV DNA was not detected in the serum.Primary central nervous system posttransplant lymphoproliferative disorder comprises 5% to 15% of all PTLD cases.6 Neuroradiographic findings of PCNS-PTLD are nonspecific and tend to have overlapping features with CNS infections and primary CNS lymphoma in immunocompromised individuals. Several case series7,8 report multicentric, contrast-enhancing, intra-axial lesions with extensive edema and marked expansion of the perivascular spaces. These lesions tend to be deeper in supratentorial structures and periventricular regions, and occur less often in the cerebellum and brainstem.6 Manifestations in the spinal cord and leptomeninges are rare.7,8 Given that isolated CNS involvement of PTLD is uncommon, clinical evaluation should include complete staging with positron emission tomography/CT to exclude systemic involvement. Diagnosis of PCNS-PTLD is established by immunohistopathologic analysis of a tissue biopsy specimen.Primary central nervous system posttransplant lymphoproliferative disorder appears to embody a distinct clinicopathologic entity within the PTLD spectrum. Although the highest incidence of PTLD occurs within the first year after transplant, the median time from solid organ transplant to PCNS-PTLD diagnosis is 3 to 5 years.7-9 Compared with non-CNS PTLD, PCNS-PTLD is more frequently associated with higher rates of EBV infection, prior renal transplant, and monomorphic as opposed to polymorphic subtype.8,9Given the rarity of PCNS-PTLD, no standardized treatment has been established. Treatment options for PCNS-PTLD are dictated by the underlying morphologic subtype and include reduction of immunosuppression for all lesions, with inclusion of rituximab therapy for polymorphic lesions.8,9 Chemotherapy should be used to treat the functionally able patient with monomorphic PCNS-PTLD. Agents with proven efficacy in the treatment of PCNS lymphoma, including high-dose methotrexate, are often used to treat PCNS-PTLD.10 Whole-brain radiotherapy remains an option for relapsed or refractory disease.Prognosis remains suboptimal for PCNS-PTLD, with a multicenter study of 84 patients demonstrating a 3-year progression-free survival rate of 32% and an overall survival rate of 43%.9 Response to first-line therapy, rather than choice of treatment, was the most important predictor of progression-free survival and Overall survival among patients with PCNS-PTLD.9The patient was diagnosed with polymorphic, EBV-positive PCNS-PTLD 4 years after renal transplant. After diagnosis, mycophenolate was discontinued and the tacrolimus trough goal was reduced. The patient also received 4 weekly doses of rituximab. She subsequently had improvement in neurologic function. This case highlights the importance of maintaining clinical suspicion for delayed and rare presentations of PTLD in transplant recipients. Multicenter analyses of treatment and outcome data are warranted given the uncertainties regarding optimal initial therapy in this patient population.

Oncology

A woman in her 30s presented with frequent falls, right-sided lower-extremity weakness, and intermittent confusion. She had a medical history significant for a renal transplant performed 4 years prior. She received induction with alemtuzumab and maintenance immunosuppression with tacrolimus and mycophenolate. She was not on any antiviral therapies prior to presentation. On admission, the patient developed left eye pain and slurred speech. Physical examination revealed expressive aphasia, partial left abducens nerve palsy, decreased motor strength in her right upper and lower extremities, and right-sided pronator drift. Laboratory evaluation showed a white blood cell count of 9.6 K/μL (reference range, 4.5-11.0 K/μL), and a lactic acid dehydrogenase level of 547 U/L (reference range, 160-450 U/L). Cerebrospinal fluid analysis revealed a white blood cell count of 51 cells/μL (reference range, 0-5 cells/μL) with 92% lymphocytes, a glucose level of 76 mg/dL (reference range, 40-70 mg/dL), and a protein level of 136 mg/dL (reference range, 12-60 mg/dL). A computed tomography (CT) scan of the brain showed multifocal vasogenic edema around the left lentiform nuclei, left temporal occipital white matter, and right parietal white matter, with mass effect causing near complete effacement of the third ventricle and subsequent rightward midline shift. Magnetic resonance imaging of the brain revealed multiple ring-enhancing lesions (Figure, A). A fluorine 18 fluorodeoxyglucose positron emission tomography/CT demonstrated increased focal fluorodeoxyglucose activity throughout the brain only. The patient underwent a biopsy of the right posterior temporal lobe (Figure, B and C).A, Ring-enhancing lesions are visible. B, A lesional biopsy specimen of the brain was obtained (hematoxylin-eosin, original magnification ×400). C, Immunohistochemical stain of CD20 (original magnification ×400).

what is your diagnosis?

What is your diagnosis?

Metastatic disease from unknown primary neoplasm

Glioblastoma

Primary central nervous system posttransplant lymphoproliferative disorder

Toxoplasmosis

c

female

31-40

White

original

https://jamanetwork.com/journals/jama/fullarticle/2737057

A 28-year-old man presented to the emergency department with diffuse oral lesions, fever, and nonproductive cough for 1 week. He was diagnosed with herpes simplex virus (HSV) and discharged home with acyclovir. Two days later, he returned with worsening oral lesions, painful phonation, poor oral intake, odynophagia, and new painful penile lesions. He denied any abdominal pain, diarrhea, rectal bleeding, weight loss, arthralgia, fatigue, vision changes, or skin rashes. He reported a similar episode of widespread oral lesions 18 months earlier that was less severe and self-resolving. He had no other medical conditions, took no medications, and was sexually monogamous with his wife, who was asymptomatic.The patient was hemodynamically stable and had a normal respiratory examination. He had a fever (39.4°C) on presentation, but his temperature abated overnight and he remained afebrile for the rest of the admission. His superior and inferior lips had extensive well-circumscribed erosions and ulcerations with erythematous edges, crusting, and a gray-white base (Figure, left). Lesions extended into the buccal mucosa and soft palate. His tongue was enlarged with fissures. A genital examination showed similar lesions on the penis, with scalloped borders (Figure, right). There were no skin lesions, lymphadenopathy, or hepatosplenomegaly.Left, Extensive well-circumscribed oral lesions limited to the mucosa in a 28-year-old man. Right, Similar lesions with scalloped borders on the distal shaft and glans of the penis in the same patient.Results of laboratory tests from the emergency department were normal, and a chest radiograph showed no evidence of pneumonia. Results of further testing for antinuclear antibodies, erythrocyte sedimentation rate, C-reactive protein level, HIV, HSV serology, syphilis, chlamydia, and gonorrhea were negative. Bacterial and viral cultures of the oral and penile lesions were also negative. Serum enzyme immunoassay for Mycoplasma pneumoniae IgM was positive at 1280 U/mL. The patient did not consent to a punch biopsy of the oral lesions. What Would You Do Next?

Perform upper endoscopy and colonoscopy

Test for anti–double-stranded DNA antibodies

Prescribe oral azithromycin

Prescribe oral suspension nystatin

M pneumoniae–induced rash and mucositis (MIRM)

C

Prescribe oral azithromycin

The key to the correct diagnosis is the elevated M pneumoniae IgM titers in a patient with a nonproductive cough and 2 sites of mucosal lesions. Although Crohn disease and systemic lupus erythematosus can present with oral lesions, the patient’s lack of associated gastrointestinal or musculoskeletal symptoms make these diagnoses unlikely. Since the patient is HIV-negative and immunocompetent, oral candidiasis is unlikely.M pneumoniae infections are often asymptomatic but can also present as upper respiratory tract infections, bronchitis, or pneumonia. Less commonly, patients with M pneumoniae infection can have mucocutaneous manifestations. MIRM is an extremely rare complication of M pneumoniae infection (exact incidence unknown) and often is mistaken for Stevens-Johnson syndrome or HSV-associated erythema multiforme. Typically, MIRM occurs in older children or adolescents and involves the oral, ocular, and genitourinary mucosal surfaces in 94%, 82%, and 63% of cases, respectively. Skin involvement is typically sparse and occurs in an acral distribution.1In 2015, Caravan et al proposed a diagnostic criterion for MIRM that included 10% or less body surface area detachment, 2 or more mucosal sites involved, few vesiculobullous skin lesions or atypical targets, and clinical or laboratory evidence of atypical pneumonia.1 The gold standard for diagnosis is M pneumoniae nucleic acid amplification testing (NAAT) because of its superior sensitivity and specificity in an acute infection.2 However, NAAT is costly and often time-inefficient to run (eg, if it needs to be sent to an outside laboratory).3 Serum enzyme immunoassay IgM testing is an alternative that is more widely available, faster, and less costly2,3; however, recent studies have demonstrated both significant heterogeneity in sensitivity and specificity and inconsistent diagnostic accuracy.3 This is in part because IgM antibodies begin to appear 7 to 9 days after initial infection, with a peak at 3 to 6 weeks, and therefore may be missed when testing during acute infection or reinfection in adults.3-6 A systematic review concluded that during the acute phase of infection, the use of IgM in combination with polymerase chain reaction allows for a more precise and reliable M pneumoniae diagnosis.3There are no evidence-based guidelines for the treatment of MIRM. In a systematic review of 202 cases of MIRM, 80% of patients received antibiotics, 35% received systemic corticosteroids, and 8% received intravenous immunoglobulin.1M pneumoniae is very susceptible to antibiotics that interfere with protein and DNA synthesis, which includes macrolides, tetracyclines, and quinolones.7,8 Nevertheless, the full clinical benefits of antimicrobial therapy are unclear, and further studies are required. The efficacy and clinical benefit of systemic corticosteroid and intravenous immunoglobulin therapy in the treatment of MIRM are not definitive.1Based on the same systematic review, MIRM had a good prognosis in 81% of patients; however, 4% required admission to a medical intensive care unit.1 Mortality was 3%; however, these instances were all from the 1940s (preantibiotic era). Pulmonary complications and lack of treatment with antibiotics were associated with poorer outcomes.1 Other complications included permanent ocular, oral, genital, or cutaneous lesions or B-cell lymphopenia.1,9NAAT was not performed in this instance because it was unavailable in-house; the diagnosis of MIRM was based on physical examination and positive IgM titers. The patient was treated with 5 days of oral azithromycin and had full resolution of cough and mucosal symptoms 1 week later, which supported the diagnosis. Follow-up IgM convalescent titers completed 7 months after treatment had a more than 4-fold decrease from the acute titers, further supporting the diagnosis.4

General

A 28-year-old man presented to the emergency department with diffuse oral lesions, fever, and nonproductive cough for 1 week. He was diagnosed with herpes simplex virus (HSV) and discharged home with acyclovir. Two days later, he returned with worsening oral lesions, painful phonation, poor oral intake, odynophagia, and new painful penile lesions. He denied any abdominal pain, diarrhea, rectal bleeding, weight loss, arthralgia, fatigue, vision changes, or skin rashes. He reported a similar episode of widespread oral lesions 18 months earlier that was less severe and self-resolving. He had no other medical conditions, took no medications, and was sexually monogamous with his wife, who was asymptomatic.The patient was hemodynamically stable and had a normal respiratory examination. He had a fever (39.4°C) on presentation, but his temperature abated overnight and he remained afebrile for the rest of the admission. His superior and inferior lips had extensive well-circumscribed erosions and ulcerations with erythematous edges, crusting, and a gray-white base (Figure, left). Lesions extended into the buccal mucosa and soft palate. His tongue was enlarged with fissures. A genital examination showed similar lesions on the penis, with scalloped borders (Figure, right). There were no skin lesions, lymphadenopathy, or hepatosplenomegaly.Left, Extensive well-circumscribed oral lesions limited to the mucosa in a 28-year-old man. Right, Similar lesions with scalloped borders on the distal shaft and glans of the penis in the same patient.Results of laboratory tests from the emergency department were normal, and a chest radiograph showed no evidence of pneumonia. Results of further testing for antinuclear antibodies, erythrocyte sedimentation rate, C-reactive protein level, HIV, HSV serology, syphilis, chlamydia, and gonorrhea were negative. Bacterial and viral cultures of the oral and penile lesions were also negative. Serum enzyme immunoassay for Mycoplasma pneumoniae IgM was positive at 1280 U/mL. The patient did not consent to a punch biopsy of the oral lesions.

what would you do next?

What would you do next?

Prescribe oral azithromycin

Perform upper endoscopy and colonoscopy

Prescribe oral suspension nystatin

Test for anti–double-stranded DNA antibodies

a

male

21-30

White

original

https://jamanetwork.com/journals/jama/fullarticle/2736971

A 39-year-old woman presented to the emergency department after she noticed that her left pupil was dilated when looking in the mirror earlier in the day. She had a medical history of hypertension and palmar and axillary hyperhidrosis. She denied double vision, ptosis, headache, and weakness. On examination, she appeared well and her blood pressure was 128/78 mm Hg; heart rate, 76/min; and respiratory rate, 13/min. Visual acuity was 20/20 in both eyes, there was no ptosis, and extraocular movements were full. Pupillary examination revealed anisocoria that was more pronounced in bright lighting conditions (Figure). The right pupil measured 6 mm in the dark and 3 mm in the light, whereas the left pupil measured 9 mm in the dark and 8 mm in the light. The left pupil was poorly reactive to light and to a near target. Slitlamp examination revealed normal-appearing anterior chambers without any signs of intraocular inflammation. Cranial nerve function was otherwise normal. The remainder of the neurologic examination revealed normal muscle tone, strength, reflexes, and gait.Patient’s pupil sizes shown in dim and bright lighting conditions.Order computed tomography angiography of the head to rule out aneurysmal compression of the left third cranial nerveOrder magnetic resonance imaging of the brain to rule out a brainstem strokePerform detailed review of systemic and topical medicationsPerform pharmacologic testing with apraclonidine to confirm Horner syndrome What Would You Do Next?

Order computed tomography angiography of the head to rule out aneurysmal compression of the left third cranial nerve

Order magnetic resonance imaging of the brain to rule out a brainstem stroke

Perform detailed review of systemic and topical medications

Perform pharmacologic testing with apraclonidine to confirm Horner syndrome

Pharmacologic mydriasis from topical glycopyrronium bromide (glycopyrrolate) for hyperhidrosis

C

Perform detailed review of systemic and topical medications

The key to the correct diagnosis in this case is the presence of an isolated dilated pupil in a well-appearing patient with an otherwise normal neurologic examination. In an alert and oriented patient with a palsy of the third cranial nerve, there is almost always associated ptosis or limitation of extraocular eye movements in addition to pupillary symptoms.1 Since these symptoms were not present in this case, further investigations for a third-nerve palsy, such as computed tomography angiography or magnetic resonance imaging, were not required. Horner syndrome is a rare condition that occurs when there is disruption of the sympathetic pathway and results in ipsilateral ptosis and miosis. A carotid dissection should be ruled out in acute cases, especially when there is associated neck pain or headache. Since there was no ptosis and the anisocoria was worse in the light, not the dark, Horner syndrome was not considered in the differential diagnosis. Given this information, a detailed review of the patient’s medications was performed and it was discovered that she was using glycopyrronium bromide (glycopyrrolate), an anticholinergic medication.Anisocoria refers to unequal pupil sizes and may be the sign of a serious underlying neurologic condition. It requires careful attention, particularly when there are associated neurologic symptoms such as ptosis or diplopia, which may indicate dysfunction of the third cranial nerve, which is vulnerable to compression from aneurysmal and other lesions.When evaluating a patient with anisocoria, it is important to first establish which pupil is abnormal—this can be achieved by assessing the anisocoria in dim and bright lighting conditions.2 If the anisocoria is greater in dim lighting conditions, the abnormal pupil is the smaller pupil since it is unable to fully dilate, implying a problem with the sympathetic pathway, which innervates the iris dilator muscle. If the anisocoria is greater in bright lighting conditions, as in this case, the abnormal pupil is the larger pupil. Another indicator that the left pupil was abnormal was the poor reaction to light. The differential diagnosis for a large pupil that is poorly reactive to light mainly includes a palsy of the third cranial nerve, pharmacologic mydriasis, and a tonic pupil.3 A tonic pupil denotes a pupil with parasympathetic denervation and results in a pupil that is poorly reactive to light but strongly reactive to a near target. This may be seen in the context of infection (eg, herpes zoster), orbital surgery, or systemic autonomic neuropathies but may also be idiopathic (so-called Adie tonic pupil).3A detailed review of the patient’s medications revealed that she was using topical glycopyrronium bromide (glycopyrrolate) for palmar and axillary hyperhidrosis. Glycopyrronium bromide is a synthetically derived anticholinergic medication with primarily antimuscarinic effects.4 It decreases sweat production and has been found to result in a reduction in perspiration after oral or topical administration.5 It has also been used as a preoperative medication to inhibit salivary gland and respiratory secretions.4 Other commonly used anticholinergic medications include scopolamine and atropine. Parasympathetic cholinergic input to the iris results in activation of the smooth muscle cells in the iris sphincter muscle and constriction of the pupil.6 Inhibiting this pathway via topical or oral medications will therefore result in mydriasis. This patient likely inadvertently touched her left eye or periocular tissues, resulting in absorption of the medication and dilation of her left pupil. This emphasizes the importance of asking patients in this setting if they have put any eye drops in their eyes or someone else’s eyes, or touched any topical medications or unfamiliar plants. To confirm the diagnosis of pharmacologic mydriasis, pilocarpine eye drops (1%), a muscarinic agonist, can be administered to both eyes. This will constrict the normal pupil but not the pharmacologically dilated pupil.The patient was informed that the dilated pupil was likely a result of the glycopyrronium bromide used for her hyperhidrosis. She temporarily discontinued the medication and her pupil returned to normal size after 5 days, confirming the diagnosis. At a follow-up appointment 2 weeks later, her pupils were both normal-sized and symmetric, and she continued to have no ptosis or extraocular dysmotility.

General

A 39-year-old woman presented to the emergency department after she noticed that her left pupil was dilated when looking in the mirror earlier in the day. She had a medical history of hypertension and palmar and axillary hyperhidrosis. She denied double vision, ptosis, headache, and weakness. On examination, she appeared well and her blood pressure was 128/78 mm Hg; heart rate, 76/min; and respiratory rate, 13/min. Visual acuity was 20/20 in both eyes, there was no ptosis, and extraocular movements were full. Pupillary examination revealed anisocoria that was more pronounced in bright lighting conditions (Figure). The right pupil measured 6 mm in the dark and 3 mm in the light, whereas the left pupil measured 9 mm in the dark and 8 mm in the light. The left pupil was poorly reactive to light and to a near target. Slitlamp examination revealed normal-appearing anterior chambers without any signs of intraocular inflammation. Cranial nerve function was otherwise normal. The remainder of the neurologic examination revealed normal muscle tone, strength, reflexes, and gait.Patient’s pupil sizes shown in dim and bright lighting conditions.Order computed tomography angiography of the head to rule out aneurysmal compression of the left third cranial nerveOrder magnetic resonance imaging of the brain to rule out a brainstem strokePerform detailed review of systemic and topical medicationsPerform pharmacologic testing with apraclonidine to confirm Horner syndrome

what would you do next?

What would you do next?

Perform pharmacologic testing with apraclonidine to confirm Horner syndrome

Order magnetic resonance imaging of the brain to rule out a brainstem stroke

Order computed tomography angiography of the head to rule out aneurysmal compression of the left third cranial nerve

Perform detailed review of systemic and topical medications

d

female

31-40

original

https://jamanetwork.com/journals/jama/fullarticle/2736434

A 65-year-old Vietnamese man with hypertension, type 2 diabetes mellitus, and chronic hepatitis B with cirrhosis presented with a 2-week history of shortness of breath at rest, orthopnea, and lower extremity edema. He reported a 4-month history of nonproductive cough, 5-kg weight loss, and fatigue. He immigrated to the United States as an adult more than 20 years before presentation. His temperature was 37°C, heart rate was 78/min, respiratory rate was 17/min, and blood pressure was 158/95 mm Hg. A chest radiographic image suggested cardiomegaly and a computed tomographic scan demonstrated a moderate to large pericardial effusion. A pericardial drain was placed and pericardial fluid was sent to the laboratory for evaluation. Initial pericardial fluid study results are presented in the Table. Empirical treatment for tuberculosis was initiated. Three days later, an adenosine deaminase (ADA) level of 118.1 U/L (normal range, 0.0-11.3 U/L) from pericardial fluid was reported from the laboratory.Perform additional pericardial effusion cytology and culture testingStop further nontubercular diagnostic testing and continue antitubercular therapyInitiate oral colchicine, nonsteroidal anti-inflammatory drugs, and steroids for systemic inflammation What Would You Do Next?

Perform additional pericardial effusion cytology and culture testing

Stop further nontubercular diagnostic testing and continue antitubercular therapy

Initiate oral colchicine, nonsteroidal anti-inflammatory drugs, and steroids for systemic inflammation

Perform an interferon-γ release assay (IGRA)

B

Stop further nontubercular diagnostic testing and continue antitubercular therapy

ADA is an enzyme in lymphocytes and myeloid cells that recycles toxic purine pathway metabolites, which are essential for DNA metabolism and cell viability.1,2 ADA levels are elevated in inflammatory effusions, including pleural, pericardial, and joint effusion, caused by bacterial infections, granulomatous inflammation (eg, tuberculosis, sarcoidosis), malignancy, and autoimmune diseases (eg, lupus, vasculitis).1,2 ADA is normally elevated in neutrophil-predominant effusions and is not a useful diagnostic test in the setting of neutrophil-predominant effusions.3 However, among lymphocyte-predominant effusions, levels of ADA are typically higher in those caused by tuberculosis (TB) than those caused by other conditions.1,2In lymphocyte-predominant effusions, the most common threshold for an ADA test result indicating TB is an ADA level greater than 40 U/L. An ADA level greater than 40 U/L has a sensitivity of 87% to 93% and specificity of 89% to 97% for TB.2,4 At a threshold of greater than 35 U/L, sensitivity is higher (93%-95%) but specificity is lower (74%-90%).3,5,6 Given a pretest probability of 70% for TB in a lymphocyte-predominant pericardial effusion in a patient from an endemic country,7 an ADA level greater than 40 U/L results in a posttest probability of 96%, while a level less than or equal to 40 U/L results in a posttest probability of 19%. The Centers for Medicare & Medicaid Services reimbursement rate for ADA testing is $8.10 (Current Procedural Terminology code 84311).In the current patient, the ADA test was ordered from pericardial fluid to confirm the presumptive diagnosis of pericardial TB, for which antitubercular therapy was initiated. RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) therapy was started because of the high pretest probability of TB in a patient from a country with endemic TB with chronic cough, weight loss, and lymphocyte-predominant pericardial effusion. The patient’s ADA level of 118.1 U/L confirmed the diagnosis, enabling cessation of further evaluation and supporting continuation of antitubercular therapy.An alternative approach is to await a culture positive for TB before starting therapy. However, cultures positive for TB can take weeks to grow, which can allow infection to progress while awaiting confirmation. An ADA level greater than 40 U/L in a patient with a high pretest probability of disease results in a sufficiently high posttest probability to justify a full course of TB therapy. Furthermore, even with an ADA level less than or equal to 40 U/L in a patient with a high pretest probability, the posttest probability of approximately 20% is sufficiently high to warrant empirical therapy. However, the low ADA level would necessitate further diagnostic testing, including invasive pericardial biopsy and serologies, to rule out other causes (eg, sarcoid, malignancy, vasculitis) while treating the patient for TB. In that situation, empirical TB therapy could have been stopped if an alternative diagnosis was established.Elevated interferon-γ concentrations in effusions have high sensitivity (95.7%) and specificity (96.3%) for active TB, but their use is limited by cost and availability.1,4 Interferon-γ can also be measured from whole blood via IGRAs. However, IGRAs and the similar purified protein derivative skin test are only useful to diagnose latent TB. Laboratory test results indicating ADA values greater than 40 U/L cannot distinguish between latent and active TB (nonspecific), and IGRAs/purified protein derivatives are associated with false-negative results in up to 30% of patients with pulmonary TB and 50% of patients with disseminated TB,8,9 because active TB causes antigen-specific anergy of T cells.The patient’s sputum was negative for acid-fast bacilli smears and TB polymerase chain reaction. Pericardial fluid cytology demonstrated inflammatory cells, but was negative for malignant cells, acid-fast bacilli stain, and TB polymerase chain reaction. However, the pericardial fluid cultures grew TB at 3 weeks and the sputa cultures grew TB at 5 weeks. Seven months after the start of treatment, the patient was hospitalized and died of complications of pneumonia and septic shock unrelated to TB.ADA levels are typically elevated, and not diagnostically helpful, in neutrophil-predominant effusions.In lymphocyte-predominant effusions, ADA levels are elevated in effusions caused by tuberculosis, but typically not in effusions due to other diseases.In a patient with a low pretest probability of TB, an ADA level less than or equal to 40 U/L in a lymphocyte-predominant effusion essentially rules out TB.In a patient with a high pretest probability of pericardial TB, an ADA level greater than 40 U/L in a lymphocyte-predominant effusion is highly suggestive of TB, precluding the need for further diagnostic testing.

Diagnostic

A 65-year-old Vietnamese man with hypertension, type 2 diabetes mellitus, and chronic hepatitis B with cirrhosis presented with a 2-week history of shortness of breath at rest, orthopnea, and lower extremity edema. He reported a 4-month history of nonproductive cough, 5-kg weight loss, and fatigue. He immigrated to the United States as an adult more than 20 years before presentation. His temperature was 37°C, heart rate was 78/min, respiratory rate was 17/min, and blood pressure was 158/95 mm Hg. A chest radiographic image suggested cardiomegaly and a computed tomographic scan demonstrated a moderate to large pericardial effusion. A pericardial drain was placed and pericardial fluid was sent to the laboratory for evaluation. Initial pericardial fluid study results are presented in the Table. Empirical treatment for tuberculosis was initiated. Three days later, an adenosine deaminase (ADA) level of 118.1 U/L (normal range, 0.0-11.3 U/L) from pericardial fluid was reported from the laboratory.Perform additional pericardial effusion cytology and culture testingStop further nontubercular diagnostic testing and continue antitubercular therapyInitiate oral colchicine, nonsteroidal anti-inflammatory drugs, and steroids for systemic inflammation

what would you do next?

What would you do next?

Perform additional pericardial effusion cytology and culture testing

Stop further nontubercular diagnostic testing and continue antitubercular therapy

Perform an interferon-γ release assay (IGRA)

Initiate oral colchicine, nonsteroidal anti-inflammatory drugs, and steroids for systemic inflammation

b

male

61-70

Vietnamese

original

https://jamanetwork.com/journals/jama/fullarticle/2735973

A 51-year-old man with a history of hypertension, hypercholesterolemia, and nephrolithiasis presented to the emergency department with left flank and left upper quadrant abdominal pain. He stated that “I think I have a kidney stone blocking my kidney” but denied nausea, vomiting, fever, dysuria, hematuria, or weight loss. He had no history of chronic abdominal pain. Past surgical history was noteworthy for emergency exploratory laparotomy and splenectomy for blunt trauma 14 years prior. Physical examination revealed a comfortable-appearing patient in no acute distress. His temperature was 36.8°C; pulse, 77/min; and blood pressure, 125/86 mm Hg. Abdominal palpation elicited only mild epigastric tenderness without masses or rebound. There was no costovertebral angle tenderness.Laboratory data revealed normal levels of serum urea nitrogen and creatinine and normal liver function. A complete blood cell count showed leukocytosis (15 300/μL with 54% neutrophils, 38% lymphocytes, 8% monocytes); hemoglobin level, 15.5 g/dL; and hematocrit, 45.2%. Urinalysis revealed no red or white blood cells and was negative for leukocyte esterase and nitrate. A contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis revealed a well-circumscribed mass with a small focus of central high density resulting in surrounding streak artifact (Figure 1).Axial image from an unenhanced computed tomogram of the patient’s abdomen.Perform an exploratory laparotomy and excision of the massPerform an interventional radiology–guided biopsy of the mass What Would You Do Next?

Perform esophagogastroduodenoscopy (EGD)

Perform diagnostic laparoscopy with peritoneal washings

Perform an exploratory laparotomy and excision of the mass

Perform an interventional radiology–guided biopsy of the mass

Gossypiboma (retained surgical sponge)

C

Perform an exploratory laparotomy and excision of the mass

The key to the correct diagnosis is the remote history of a trauma laparotomy and the CT scan scout image that shows the characteristic finding of a radiopaque marker associated with a retained surgical sponge (Figure 2). All surgical sponges are equipped with such a marker, which manifests radiographically as a convoluted hyperdensity. These abdominal lesions may be confused with a gastrointestinal stromal tumor or other gastrointestinal malignancies. Since the lesion appears radiographically to be outside the lumen of the gastrointestinal tract, EGD has no role. Without a confirmed diagnosis of malignancy, laparoscopy with peritoneal washings to identify occult metastases would be premature. An interventional radiology–guided biopsy is unnecessary, given the early recognition of the radiopaque marker associated with gossypiboma.A sponge or laparotomy pad is the item most commonly retained after surgical procedures and when left behind in a body cavity is known as a gossypiboma. The abdominal cavity is the most frequent location of retained surgical items (56%). Recent reviews list the incidence of retained surgical items as between 1 in 8800 and 1 in 18 760 operations.1A retained surgical item should always be considered in the differential diagnosis of a patient with a history of prior emergency abdominal surgery who presents with pain, infection, or a palpable mass. Typically, retained laparotomy pads are detected early after the procedure but may be discovered days, months, or even decades later, as in this unusual instance. The clinical manifestations of a gossypiboma depend on the time elapsed from the index operation to detection. Many patients are asymptomatic, although abdominal pain is the most common symptom. Other manifestations can include bleeding, fever, intestinal obstruction, perforation, or fistula formation into adjacent organs.2 Approximately 10% to 15% of cases of retained sponges are complicated by acute intra-abdominal sepsis and can lead to peritonitis and, rarely, death. Alternatively, the object may become encapsulated by a giant-cell foreign body reaction and form a “mass,” which can mimic malignancy.3The diagnosis is usually made with plain radiography if the characteristic radiopaque marker is identified. However, the marker can degrade over time, making the diagnosis more challenging. CT imaging can reveal a thick-walled mass with or without gas, a cystic lesion with an internal spongiform appearance, concentric layering, or mottled mural calcification.4Removal of gossypibomas requires repeat surgical intervention; therefore, prevention is key. The biggest risk factors for a retained surgical item are emergency operation, unplanned change in the operation, and a high body mass index.1,5 In 80% to 90% of instances in which a surgical sponge is retained, the sponge count is erroneously documented as “correct.”6 However, additional factors contributing to retained surgical items include distraction of operating room personnel, poor operative team communication, and lack of surgeon participation in the final sponge and instrument count.7 The Joint Commission recommends use of intraoperative radiographs whenever the surgical sponge count is incorrect or routinely in high-risk cases, such as lengthy operations extending through more than 1 nursing shift, a change in the planned operation, and operations involving 2 or more surgical teams.8 Even when intraoperative radiographs are performed, retained items can still be missed, eg, when the film does not include the area in question, in patients with high body mass index, if inadequate history is provided to the interpreting radiologist, or when a junior member of the team reads the film. Furthermore, radiopaque markers can be misidentified as clips, intestinal contrast, drains, calcifications, or wires. Newer technologies that augment manual system include computerized detection systems with bar code–embedded sponges or radiofrequency-tagged sponges that can be detected with a special handheld wand.9Given imaging findings suggesting that the mass was extraluminal, the patient underwent excision of the gossypiboma, which was mildly adherent to the greater curvature of the stomach and transverse colon but easily removed. The resection was initially uncomplicated, without compromise to surrounding viscera or vascular structures. The specimen appeared as a tan, heavily encapsulated mass that contained the retained surgical sponge. On the seventh postoperative day the patient developed peritonitis and was taken back to the operating room and discovered to have an ischemic transverse colon; the etiology for this was unclear. An extended right hemicolectomy and ileostomy were performed. Six months later his ileostomy was reversed and he has subsequently done well.

General

A 51-year-old man with a history of hypertension, hypercholesterolemia, and nephrolithiasis presented to the emergency department with left flank and left upper quadrant abdominal pain. He stated that “I think I have a kidney stone blocking my kidney” but denied nausea, vomiting, fever, dysuria, hematuria, or weight loss. He had no history of chronic abdominal pain. Past surgical history was noteworthy for emergency exploratory laparotomy and splenectomy for blunt trauma 14 years prior. Physical examination revealed a comfortable-appearing patient in no acute distress. His temperature was 36.8°C; pulse, 77/min; and blood pressure, 125/86 mm Hg. Abdominal palpation elicited only mild epigastric tenderness without masses or rebound. There was no costovertebral angle tenderness.Laboratory data revealed normal levels of serum urea nitrogen and creatinine and normal liver function. A complete blood cell count showed leukocytosis (15 300/μL with 54% neutrophils, 38% lymphocytes, 8% monocytes); hemoglobin level, 15.5 g/dL; and hematocrit, 45.2%. Urinalysis revealed no red or white blood cells and was negative for leukocyte esterase and nitrate. A contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis revealed a well-circumscribed mass with a small focus of central high density resulting in surrounding streak artifact (Figure 1).Axial image from an unenhanced computed tomogram of the patient’s abdomen.Perform an exploratory laparotomy and excision of the massPerform an interventional radiology–guided biopsy of the mass

what would you do next?

What would you do next?

Perform esophagogastroduodenoscopy (EGD)

Perform an interventional radiology–guided biopsy of the mass

Perform an exploratory laparotomy and excision of the mass

Perform diagnostic laparoscopy with peritoneal washings

c

male

51-60

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2732678

A woman in her 50s with relapsed refractory acute myeloid leukemia and a remote history of breast cancer was admitted for treatment of presumed fungal pneumonia based on new pulmonary nodules on imaging and elevated serum β-D-glucan levels. She subsequently developed multiple asymptomatic pink papules on the trunk and extremities. The patient was afebrile and was receiving broad-spectrum antibiotic, antifungal, and antiviral treatment for a prior episode of neutropenic fever. Clinical examination revealed scattered pink papules with a white firm center and dark brown core scattered throughout the chest, abdomen (Figure, A and B), back, groin, and upper and lower extremities. Laboratory workup was significant for leukopenia with neutropenia, anemia, and thrombocytopenia. Creatinine and transaminase levels were within normal limits. Blood cultures were negative. A punch biopsy from the left flank was obtained for hematoxylin-eosin staining, and a punch biopsy from the left leg was sent for tissue and fungal culture. Histopathological analysis was subsequently performed (Figure, C and D).A, Multiple papules on the abdomen. B, Closer view of a single papule. C and D, Hematoxylin-eosin–stained lesional specimens. What Is Your Diagnosis?

Disseminated candidiasis with transepidermal elimination

Reactive perforating collagenosis

Disseminated cryptococcosis

Malassezia (formerly Pityrosporum) folliculitis

A. Disseminated candidiasis with transepidermal elimination

A

Disseminated candidiasis with transepidermal elimination

The analysis of the skin biopsy specimen revealed a large cluster of fungal organisms in the upper dermis extruding through a cuplike invagination of the epidermis into the stratum corneum (Figure, C and D). Periodic acid–Schiff (PAS) staining highlighted these fungal elements. Wound and fungal cultures subsequently grew Candida albicans. Histologic and laboratory findings supported a diagnosis of disseminated cutaneous candidiasis with transepidermal elimination, correlating clinically with the central core seen on examination. Ophthalmologic evaluation revealed chorioretinitis secondary to Candida infection, and otolaryngology assessment revealed thrush in the oropharynx. Blood cultures, however, remained negative. The patient’s antifungal regimen included amphotericin B and micafungin. The patient was transferred to the intensive care unit for septic shock 2 weeks after presentation and died shortly thereafter.Candida albicans is a dimorphic fungus that colonizes skin, genital, and oral mucosa in up to 70% of healthy individuals.1 The present patient displayed many of the known risk factors for invasive candidiasis, including prolonged hospital stays, neutropenia, and corticosteroid and broad-spectrum antibiotic treatment.2 Although her blood cultures were negative, she exhibited evidence of C albicans in the skin, oropharynx, and eyes. Blood cultures are negative in 30% to 50% of patients with disseminated candidiasis, and that number increases with use of systemic antifungal therapy.3,4While C albicans has traditionally been the predominant species in invasive Candida infections, there has been an increase in the incidence of non–C albicans Candida infections since the 1980s.2 A recent review of disseminated candidiasis in patients with neutropenia and skin lesions found that Candida tropicalis was the most commonly identified species, followed by Candida krusei and C albicans.5 It has been theorized that increased use of empirical fluconazole may contribute to infections with non-albicans species, specifically Candida glabrata and Candida krusei.6Candida albicans naturally exists in a spore form in the epidermis and invades as filamentous pseudohyphae in the dermis. The presence of C albicans at various levels of skin directs differentiated immune responses. Cutaneous host defenses against C albicans involve innate immunity via sensory cutaneous nerves, dermal dendritic cells, and melanocytes and adaptive immunity via helper T cell type 17 lineage.1 The present case reveals a clinicopathologic correlation between the punctumlike cores noted in the patient’s cutaneous papules and the transepidermal elimination of Candida spores. To our knowledge, this presentation of disseminated Candida in the skin has not yet been reported.Reactive perforating collagenosis may also present with papules with central keratotic plugs; however, biopsy would reveal collagen fibers rather than Candida organisms extruding through the dermal-epidermal junction. Disseminated cryptococcosis is a common opportunistic infection often associated with HIV infection and clinically presents as umbilicated papules; pathologic analysis reveals grouped pleomorphic yeasts and a gelatinous capsule, which stains red with mucicarmine. Malassezia folliculitis is a pruritic eruption caused by Malassezia furfur that presents as folliculocentric papules and pustules on the trunk, with histopathologic analysis revealing suppurative folliculitis with PAS stain highlighting fungal organisms in the follicle and surrounding dermis. The present patient had an increased risk for Malassezia folliculitis given immunosuppression and recent antibiotic courses, but the lesions were not folliculocentric.

Dermatology

A woman in her 50s with relapsed refractory acute myeloid leukemia and a remote history of breast cancer was admitted for treatment of presumed fungal pneumonia based on new pulmonary nodules on imaging and elevated serum β-D-glucan levels. She subsequently developed multiple asymptomatic pink papules on the trunk and extremities. The patient was afebrile and was receiving broad-spectrum antibiotic, antifungal, and antiviral treatment for a prior episode of neutropenic fever. Clinical examination revealed scattered pink papules with a white firm center and dark brown core scattered throughout the chest, abdomen (Figure, A and B), back, groin, and upper and lower extremities. Laboratory workup was significant for leukopenia with neutropenia, anemia, and thrombocytopenia. Creatinine and transaminase levels were within normal limits. Blood cultures were negative. A punch biopsy from the left flank was obtained for hematoxylin-eosin staining, and a punch biopsy from the left leg was sent for tissue and fungal culture. Histopathological analysis was subsequently performed (Figure, C and D).A, Multiple papules on the abdomen. B, Closer view of a single papule. C and D, Hematoxylin-eosin–stained lesional specimens.

what is your diagnosis?

What is your diagnosis?

Disseminated cryptococcosis

Malassezia (formerly Pityrosporum) folliculitis

Disseminated candidiasis with transepidermal elimination

Reactive perforating collagenosis

c

female

51-60

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2728242

A 30-year-old woman presented with a 4-month history of widespread thickened, verrucous, hyperpigmented plaques distributed symmetrically on her body, especially on the axillae (Figure 1A), anogenital region, inguinal skin, and both palms, with slight itching. The verrucous plaques also involved the conjunctiva, lips, and gingiva (Figure 1B). The patient had experienced a weight loss of 6 kg during the last 3 months. Within the last month, the patient’s thyroid became enlarged, and she developed anorexia and abdominal discomfort. Laboratory test results revealed remarkably elevated levels of carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, tissue polypeptide antigen and carbohydrate antigen 242. Biopsy specimens of lesions on the axillae and lips both revealed a papillary structure with hyperkeratosis. An endoscopic examination and computed tomographic scan of the abdomen were performed.Axilla with velvety, hyperpigmented skin (A) and verrucous plaques on the lips and gingiva (B). What Is Your Diagnosis?

Benign acanthosis nigricans

Cutaneous T-cell lymphoma

Malignant acanthosis nigricans

Malignant Addison disease

C. Malignant acanthosis nigricans

C

Malignant acanthosis nigricans

The keys to the correct diagnosis are the verrucous, hyperpigmented plaques in atypical sites (mucous membranes, palms and anogenital region), the additional paraneoplastic findings (tripe palms), and recent obvious weight loss. Most cases of acanthosis nigricans (AN) are benign and are associated with obesity and insulin resistance in which blood glucose and insulin levels are important for diagnosis. The disease is less commonly associated with a malignant neoplasm. Malignant AN is predominantly associated with gastrointestinal tract tumors, especially carcinoma of the stomach.1The gastroscopy findings revealed esophageal papillomatous polyposis and a submucosal mass involving the gastric angle. Biopsy results revealed that the mass was a mix of adenocarcinoma and signet-ring cell carcinoma (Figure 2). A computed tomographic scan of the abdomen showed a thickening of the gastric wall and multiple organ metastases. The results of biopsies of the thyroid and pancreas suggested metastases of gastric cancer. The patient was then transferred for further chemotherapy without any dermatological treatment and died 4 months later due to cancer progression.Histologic specimen of the gastric mass showed various types of cancer. Poorly differentiated adenocarcinoma and signet-ring cell carcinoma had developed in the lamina propria of the gastric angle (hematoxylin-eosin stain, original magnification ×100).Acanthosis nigricans is a reactive skin pattern that presents as velvety to verrucous hyperpigmented plaques in body folds such as the axilla, neck, groin, and umbilicus. Malignant AN has a more striking clinical presentation involving unusual locations such as the oral cavity, conjunctiva, and palms, in accordance with the severity of the disease.2-4 It can occur with other cutaneous markers of internal malignant neoplasm, such as tripe palms and the Leser-Trélat sign.2,3 It is mostly associated with gastric adenocarcinoma, followed by pulmonary carcinoma, hepatic carcinoma, esophageal carcinoma, and ovarian cancer,2,3 arising either before or after detection of the tumor. The onset for most patients is between age 41 and 70 years.1 Patients with malignant AN are generally not obese but have experienced a recent weight loss. Histologically, malignant and benign AN cannot be distinguished from each other. Their major features are hyperkeratosis and epidermal papillomatosis with increased melanin in the basal layer of the epidermis. A thorough endoscopic and radiological screening for cancer is much more important than serological testing.Pathogenically, elevated levels of transforming growth factor α participate in tumor progression through autosecretion and paracrine secretion, stimulating keratinocyte growth via epidermal growth factor receptors. Insulinlike growth factor 1, fibroblast growth factor, and melanocyte-stimulating hormone α regulate melanocyte pigmentation and stimulate the growth of keratocytes, which also play roles in the pathogenesis of hyperplasia and hyperpigmentation.5The management of malignant AN should be focused on the underlying neoplasm. The efficacy of therapies intended to directly improve the skin lesions of AN, such as using topical retinoids or vitamin D analogs, is limited. Improvement or resolution of AN has been reported in patients successfully treated for the associated cancer.6 Nevertheless, the prognosis for malignant AN is poor since the cancer is frequently diagnosed at an advanced stage. Patients may be misdiagnosed with eczema or other skin disorders during the early stages of the disease. Timely recognition of malignant AN could lead to earlier detection of the carcinoma and may improve the prognosis of these patients.

Oncology

A 30-year-old woman presented with a 4-month history of widespread thickened, verrucous, hyperpigmented plaques distributed symmetrically on her body, especially on the axillae (Figure 1A), anogenital region, inguinal skin, and both palms, with slight itching. The verrucous plaques also involved the conjunctiva, lips, and gingiva (Figure 1B). The patient had experienced a weight loss of 6 kg during the last 3 months. Within the last month, the patient’s thyroid became enlarged, and she developed anorexia and abdominal discomfort. Laboratory test results revealed remarkably elevated levels of carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, tissue polypeptide antigen and carbohydrate antigen 242. Biopsy specimens of lesions on the axillae and lips both revealed a papillary structure with hyperkeratosis. An endoscopic examination and computed tomographic scan of the abdomen were performed.Axilla with velvety, hyperpigmented skin (A) and verrucous plaques on the lips and gingiva (B).

what is your diagnosis?

What is your diagnosis?

Malignant Addison disease

Malignant acanthosis nigricans

Cutaneous T-cell lymphoma

Benign acanthosis nigricans

b

female

21-30

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2729678

A 70-year-old Indian woman presented with a generalized rash over the lower extremity associated with pedal edema extending up to the shins. The onset was gradual and started on the lower extremities and gradually extended to involve the lower trunk. The rash was associated with mild discomfort. The patient denied itching, weeping, or bleeding from the rash. She denied any constitutional symptoms (weight loss, fever, night sweats), joint pains, history of blood in urine, periorbital edema, and recent intake of medications or herbal medications. Social history was significant for 25 pack-years of smoking. Physical examination revealed multiple well-defined, coalescent, erythematous, palpable, purpuralike lesions that were predominantly present over the trunk and lower extremities (Figure, A and B). Laboratory test results at presentation included a hemoglobin level of 11.2 g/dL (to convert to g/L, multiply by 10), mean corpuscular volume of 84 fL, erythrocyte sedimentation rate of 72 mm/h, and a lactate dehydrogenase level of 412 IU/L. Hepatic and renal function levels were within normal limits. Complement levels were normal. Hepatitis B and C and HIV profiles were negative. A chest radiograph showed a 2-cm lesion in the upper lobe of the left lung. A computed tomographic scan of the chest showed a spiculated mass in the same region along with mediastinal lymphadenopathy. An ultrasound of the abdomen showed bilateral adrenal masses. A lesional skin biopsy specimen was obtained (Figure, C).Coalescent, erythematous, palpable lesions on the lower extremity (A) and trunk (B). C, Lesional skin biopsy sample. What Is Your Diagnosis?

Acrokeratosis paraneoplastica

Cutaneous leukocytoclastic vasculitis

Purpura fulminans

Henoch-Schönlein purpura

B. Cutaneous leukocytoclastic vasculitis

B

Cutaneous leukocytoclastic vasculitis

The histopathologic findings from a lesional skin biopsy specimen revealed neutrophilic infiltration of the small blood vessels in the skin along with necrosis and extravasation of the red blood cells (Figure, C). The findings from a biopsy specimen of a lung lesion revealed small cell carcinoma. The patient was diagnosed with extensive-stage small cell lung cancer and began systemic chemotherapy with cisplatin and etoposide. Unfortunately, the patient died soon after the first dose of chemotherapy due to neutropenic sepsis.Cutaneous manifestation of an internal malignant neoplasm may present as direct infiltration into the skin or may present indirectly as a paraneoplastic syndrome (PNS).1 The Curth postulates are the cornerstone for defining the association between internal malignant neoplasms and cutaneous disorders.1 Leukocytoclastic vasculitis is a histopathologic term denoting vasculitis of the small vessels with predominantly neutrophilic infiltrate.2 After degranulation, the neutrophils undergo apoptosis, a process known as leukocytoclasis, releasing nuclear debris, which is also called nuclear dust.2 According to the consensus statement developed at the Chapel Hill Conference on Nomenclature of Systemic Vasculitis in 1994, cutaneous leukocytoclastic vasculitis (CLV) is defined as an“[i]solated cutaneous leukocytoclastic angiitis without systemic vasculitis or glomerulonephritis.”2,3 As a PNS, CLV is the most commonly diagnosed vasculitis (45%) followed by polyarteritis nodosa (36.7%).4 Cutaneous leukocytoclastic vasculitis occurs most frequently with hematologic cancers followed by lung, gastrointestinal, or urinary tract tumors.5,6 Approximately 20% to 26% of patients with paraneoplastic CLV have lung cancer.4,6 Among lung cancers, adenocarcinoma and squamous cell are most commonly associated with CLV.4,6,7Cutaneous leukocytoclastic vasculitis presents as a palpable purpuric lesion that usually involves the dependent areas (mostly feet and lower extremities) and rarely involves the upper extremities and trunk.2 The lesions are usually chronic and persistent when associated with a malignant neoplasm.2 In contrast to the chronic pattern of CLV, Henoch-Schönlein purpura (HSP) is a recurring form of CLV that presents with symptom-free intervals.3,8 Deposits of IgA in the blood vessels are a defining feature of HSP. Henoch-Schönlein purpura usually affects children and has been reported as a PNS associated with solid organ malignant neoplasms, including small cell lung cancer.2,9 The diagnostic workup includes a skin biopsy to differentiate other cutaneous lesions from underlying vasculitis. Preferably, an immunofluorescence stain should be done in addition to a hematoxylin and eosin stain.2 However, the diagnostic yield of this test is considerably reduced after 48 hours owing to the destruction and removal of immunoglobulins deposited in the vessel wall.2 Judicious use of immunofluorescence for selected cases has been advocated recently, but the test is not readily available in settings with constrained resources, such as ours.10 In patients with chronic CLV, other causes not related to malignant neoplasms should be excluded, including hepatitis B and/or C virus, HIV, cryoglobulinemia, and systemic small-vessel vasculitis.The pathogenesis of CLV remains anecdotal. Leukocytoclastic vasculitis is a common response to circulating aggressors, be it microorganisms or immune complexes, and is likely influenced by the heterogeneity of the endothelium of postcapillary venules.2 The endothelial cells in these venules play a role in antigen presentation, and express Toll-like receptor family members, CD32 molecules, and histamine H1 receptors.2 Cutaneous leukocytoclastic vasculitis usually begins with deposition of immune complex in the vessel walls, leading to activation of the complement cascade (complement components C3a and C5a), which attracts neutrophils and eventually leads to degranulation and vessel wall destruction.2 The treatment of CLV associated with systemic malignant neoplasms is directed toward the primary cause, whereby improvement or worsening of the rash is seen in concordance with the treatment response of the underlying cancer.1,4 This case illustrates the importance of recognizing cutaneous manifestations of paraneoplastic syndromes, which can prompt an early diagnosis of an occult malignant neoplasm.

Oncology

A 70-year-old Indian woman presented with a generalized rash over the lower extremity associated with pedal edema extending up to the shins. The onset was gradual and started on the lower extremities and gradually extended to involve the lower trunk. The rash was associated with mild discomfort. The patient denied itching, weeping, or bleeding from the rash. She denied any constitutional symptoms (weight loss, fever, night sweats), joint pains, history of blood in urine, periorbital edema, and recent intake of medications or herbal medications. Social history was significant for 25 pack-years of smoking. Physical examination revealed multiple well-defined, coalescent, erythematous, palpable, purpuralike lesions that were predominantly present over the trunk and lower extremities (Figure, A and B). Laboratory test results at presentation included a hemoglobin level of 11.2 g/dL (to convert to g/L, multiply by 10), mean corpuscular volume of 84 fL, erythrocyte sedimentation rate of 72 mm/h, and a lactate dehydrogenase level of 412 IU/L. Hepatic and renal function levels were within normal limits. Complement levels were normal. Hepatitis B and C and HIV profiles were negative. A chest radiograph showed a 2-cm lesion in the upper lobe of the left lung. A computed tomographic scan of the chest showed a spiculated mass in the same region along with mediastinal lymphadenopathy. An ultrasound of the abdomen showed bilateral adrenal masses. A lesional skin biopsy specimen was obtained (Figure, C).Coalescent, erythematous, palpable lesions on the lower extremity (A) and trunk (B). C, Lesional skin biopsy sample.

what is your diagnosis?

What is your diagnosis?

Acrokeratosis paraneoplastica

Henoch-Schönlein purpura

Purpura fulminans

Cutaneous leukocytoclastic vasculitis

d

female

61-70

Indian

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2735318

A woman in her early 60s with a medical history of chest pain requiring a coronary angiogram (which demonstrated only mild luminal irregularities) approximately 1 year prior to presentation, hypertension, long-standing dyslipidemia, and multiparity presented to the emergency department with a sudden onset of dull, pressurelike chest pain radiating to the left arm. The pain started at rest, was 10 of 10 in severity, and was not alleviated by changing position. She also experienced concomitant nausea and diaphoresis. Her family history was notable for hypertension, and no other systemic diseases were reported. On physical examination, her blood pressure was 115/76 mm Hg, heart rate was regular at 72 beats per minute, respiratory rate was 20 breaths per minute, and oxygen saturation level was 98% on room air. The patient was afebrile. Physical examination also revealed mild bibasilar crackles and jugular venous distention, and no murmurs or lower extremity edema. Laboratory test results demonstrated an elevated troponin, and the 12-lead electrocardiogram showed marked ST-segment elevations in leads V2 to V5 (Figure, A). The ST-segment elevation myocardial infarction (STEMI) pager was activated, and the patient was transferred urgently to the catheterization laboratory. Coronary angiography of the patient’s left anterior descending coronary artery was performed, and the findings are depicted in the Figure, B.A, Twelve-lead electrocardiogram. B, Left anterior descending coronary artery angiogram.Treat medically with aspirin, β-blocker, clopidogrel, and a statinRevascularize with percutaneous coronary intervention and start medical therapy What Would You Do Next?

Treat medically with aspirin alone

Treat medically with aspirin, β-blocker, and clopidogrel

Treat medically with aspirin, β-blocker, clopidogrel, and a statin

Revascularize with percutaneous coronary intervention and start medical therapy

Spontaneous coronary artery dissection

C

Treat medically with aspirin, β-blocker, clopidogrel, and a statin

C. Treat medically with aspirin, β-blocker, clopidogrel, and a statinSpontaneous coronary artery dissection (SCAD) is a nontraumatic and noniatrogenic separation of the coronary arterial wall, typically leading to the formation of a false lumen, in the presence or absence of significant obstructive coronary artery disease.1 While the precise pathophysiological mechanism remains unclear, a tear in the intima of a coronary vessel or the development of an intramural hematoma due to bleeding from the rupture of the vasa vasorum have been suggested as possibilities.2,3 The disease process tends to affect women, particularly young women, with underlying fibromuscular dysplasia or other connective tissue disease (such as Marfan syndrome, Loeys-Dietz syndrome, and Ehlers-Danlos syndrome type 4).4 Hormonal therapy and postpartum or multiparous state are also known risk factors. Without early detection and treatment, SCAD can be life-threatening.3,5,6SCAD remains an underdiagnosed entity primarily owing to a low index of clinical suspicion and nonfamiliarity of clinicians with the angiographic variants of SCAD. Moreover, its presentation often mimics other more common acute coronary syndromes, including STEMI or non-STEMI, and therefore further confounds the diagnosis.7 Many patients with SCAD present with classic, dull, pressurelike chest pain at rest and have electrocardiographic changes (ie, ST-segment elevations or depressions).6Coronary angiography is the primary imaging modality used to diagnose SCAD.8 The following 3 specific angiographic findings outlined by Saw et al1 are often observed:Type 1: pathognomonic angiographic appearance of SCAD with contrast dye staining of the arterial wall with multiple radiolucent lumens;Type 2: diffuse (>20 mm), smooth stenosis of varying severity;Type 3: focal areas of stenosis that mirror atherosclerosis but are usually limited to 1 coronary vessel and are long (11-20 mm) and linear.Type 1: pathognomonic angiographic appearance of SCAD with contrast dye staining of the arterial wall with multiple radiolucent lumens;Type 2: diffuse (>20 mm), smooth stenosis of varying severity;Type 3: focal areas of stenosis that mirror atherosclerosis but are usually limited to 1 coronary vessel and are long (11-20 mm) and linear.The angiographic image of the patient’s left anterior descending coronary artery (Figure, B) depicts type 2 SCAD given the diffuse, smooth luminal narrowing observed (arrowheads). However, coronary angiography is imperfect for diagnosing SCAD because of limited visualization of the intra-arterial wall.8 Optical coherence tomography and intravascular ultrasonography have emerged as criterion standard diagnostic methods as they allow for direct visualization of vascular intima and media. However, these methods are not used frequently given the risk of propagating the dissection both mechanically, with the imaging catheter or guidewire, and hydraulically, with contrast injection required for optical coherence tomography.1In patients without persistent ischemia, a conservative treatment with aspirin, β-blocker, and clopidogrel is preferred.1 If a patient has concomitant long-standing dyslipidemia (as in this patient), the addition of a statin is suggested.1,9 In hemodynamically stable patients, percutaneous coronary intervention is relatively contraindicated given the risk of iatrogenic propagation of the dissection and exacerbation of an already ischemic myocardium.1The patient was treated conservatively with aspirin, β-blocker, clopidogrel, and a statin, and an initial improvement was observed in her symptoms. However, her symptoms became complicated thereafter by recurrent ischemia and infarction from the dissection, leading to left ventricular dysfunction (ejection fraction, 30%-35%), cardiogenic shock, and the eventual placement of a left ventricular assist device. While uncommon, left ventricular failure is a consequence of SCAD and results in extensive infarction.1 It usually occurs in patients with ongoing or recurrent ischemia, especially involving the left main coronary artery, and necessitates revascularization with either percutaneous coronary intervention or coronary artery bypass graft.1 The patient in this case died of a stroke considered to be a complication of her left ventricular assist device. However, her case raises the importance of physician awareness of SCAD and depicts that such patients must be regularly monitored for ongoing or recurrent ischemia despite being provided with optimal medical therapy.

Cardiology

A woman in her early 60s with a medical history of chest pain requiring a coronary angiogram (which demonstrated only mild luminal irregularities) approximately 1 year prior to presentation, hypertension, long-standing dyslipidemia, and multiparity presented to the emergency department with a sudden onset of dull, pressurelike chest pain radiating to the left arm. The pain started at rest, was 10 of 10 in severity, and was not alleviated by changing position. She also experienced concomitant nausea and diaphoresis. Her family history was notable for hypertension, and no other systemic diseases were reported. On physical examination, her blood pressure was 115/76 mm Hg, heart rate was regular at 72 beats per minute, respiratory rate was 20 breaths per minute, and oxygen saturation level was 98% on room air. The patient was afebrile. Physical examination also revealed mild bibasilar crackles and jugular venous distention, and no murmurs or lower extremity edema. Laboratory test results demonstrated an elevated troponin, and the 12-lead electrocardiogram showed marked ST-segment elevations in leads V2 to V5 (Figure, A). The ST-segment elevation myocardial infarction (STEMI) pager was activated, and the patient was transferred urgently to the catheterization laboratory. Coronary angiography of the patient’s left anterior descending coronary artery was performed, and the findings are depicted in the Figure, B.A, Twelve-lead electrocardiogram. B, Left anterior descending coronary artery angiogram.Treat medically with aspirin, β-blocker, clopidogrel, and a statinRevascularize with percutaneous coronary intervention and start medical therapy

what would you do next?

What would you do next?

Revascularize with percutaneous coronary intervention and start medical therapy

Treat medically with aspirin alone

Treat medically with aspirin, β-blocker, and clopidogrel

Treat medically with aspirin, β-blocker, clopidogrel, and a statin

d

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2731889

A 59-year-old Hispanic woman presented with a 6-month history of intermittent pain in the right posterior mandibular gingiva. Her local dentist had prescribed an antibiotic and performed a tooth extraction in the area 6 months prior with no improvement in symptoms. Ultimately, her pain became persistent and radiated to the right lower lip. She had a history of stage IV endometrial serous adenocarcinoma (ESA) 4 years prior that was treated with total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and peritoneal lavage. She had developed a recurrence for which she had just completed 3 cycles of treatment with carboplatin. She also had a history of anxiety, hypertension, and pterygium, and she was taking gabapentin, lorazepam, prochlorperazine, metoprolol succinate, bromfenac and ketorolac ophthalmic solution, and aprepitant. Intraoral examination revealed a 1.5 × 1.0-cm firm, erythematous gingival mass in the area of missing right mandibular second bicuspid and first molar with buccal and lingual expansion (Figure 1A). The right mandibular first bicuspid was grade 3 mobile. A periapical radiograph was obtained, and results showed a diffuse, poorly demarcated radiolucency measuring approximately 1.2 × 0.8 cm (Figure 1B). Findings from an incisional biopsy of the mass showed an infiltrative tumor (Figure 1C). Tumor cells were positive for CK7, PAX8, and WT-1, and negative for CK20 and TTF-1 (Figure 1C, inset).A, A 1.5 × 1-cm gingival mass is distal to the right mandibular first bicuspid. B, Diffuse, poorly demarcated radiolucency is seen in the area of the missing right mandibular second bicuspid and first molar (arrowheads). C, Multiple nests of round to ovoid epithelial cells form ducts (hematoxylin-eosin stain, original magnification ×100). Diffuse nuclear positivity for PAX8 (immunohistochemistry, original magnification ×200) (inset). What Is Your Diagnosis?

Pyogenic granuloma

Gingival/periodontal abscess

Oral metastasis

Squamous cell carcinoma

C. Oral metastasis

C

Oral metastasis

The histopathological and immunohistochemical findings were consistent with the patient’s preexisting ESA. Oral metastases in the jaws and soft tissues are uncommon and account for only 1% to 8% of all malignancies in the oral cavity. Bony metastases, particularly in the mandible, are twice as common as those in the oral soft tissues of the gingiva and tongue.1,2 The most common cancer that metastasizes in the oral cavity in female patients is carcinoma of the breast (25.4%-36.6%), while metastatic cancers of the female genital tract in the oral cavity are rare and have a frequency of 3% to 9%.2,3 The clinical presentation of metastatic disease in the oral cavity may be nonspecific. Patients may have pain, swelling, and/or bleeding. These signs may lead a clinician to first consider odontogenic infection or inflammatory gingival nodules such as pyogenic granuloma.3,4 Because odontogenic infections often present in a similar fashion and metastatic tumors are rare, lesions are often treated with antibiotics, which leads to diagnostic delay like with this case.3 It is likely the metastatic ESA in this case had originated in the bone (as it does in approximately two-thirds of cases) with extension into the soft tissues that presented as a gingival mass.Endometrial carcinoma is the most common gynecological cancer in the United States.5 There are 2 major categories of endometrial carcinoma: type 1 (endometrioid adenocarcinoma) and type 2 (ESA and clear cell carcinoma).6 Endometrial serous adenocarcinoma is an aggressive tumor and a histopathologically distinct subtype of type 2 endometrial carcinoma, which accounts for 5% to 10% of all endometrial cancers.7,8 It typically occurs in postmenopausal women with a median age at presentation of 68 years (range, 44-93 years).5 Unlike endometrioid adenocarcinoma, ESA is estrogen independent and arises from atrophic endometrium.9 Patients with ESA have a 5-fold increased risk of tumor recurrence compared with patients with endometrioid adenocarcinoma.6 In this case, despite previous total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and peritoneal lavage, the patient developed recurrence after 4 years. Results of a computed tomography scan revealed widespread recurrent disease despite the patient having been recently treated with carboplatin. Direct extension of the tumor into the fallopian tube was seen, and metastatic foci were identified in the mandible (Figure 2), lung, right common iliac, and mediastinal lymph nodes.Computed tomography scan of poorly demarcated radiolucency with soft tissue extension in the area of the right mandibular first bicuspid and missing second bicuspid and first molar (arrowheads).Distant metastasis of ESA is a common finding at the time of initial presentation.5 In a study of 129 cases, extrauterine metastasis was found in 72% of the cases.10 Endometrial serous adenocarcinoma is associated with poor prognosis and accounts for 40% of endometrial cancer–related deaths. The 5-year overall survival rate is 62.9% and 19.9% for stage I and IV disease, respectively.5,6 The patient was treated with a course of palliative radiotherapy of 3 Gy in 10 fractions. However, her disease worsened with progression of the mandibular mass and the lung nodules and, as such, she was started on pemetrexed therapy. At time of report, the patient was alive, 4 years and 10 months after the initial diagnosis of her tumor and 10 months after the diagnosis of her oral metastasis. Metastatic disease should always be considered in the broad differential diagnosis of a gingival nodule.

General

A 59-year-old Hispanic woman presented with a 6-month history of intermittent pain in the right posterior mandibular gingiva. Her local dentist had prescribed an antibiotic and performed a tooth extraction in the area 6 months prior with no improvement in symptoms. Ultimately, her pain became persistent and radiated to the right lower lip. She had a history of stage IV endometrial serous adenocarcinoma (ESA) 4 years prior that was treated with total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and peritoneal lavage. She had developed a recurrence for which she had just completed 3 cycles of treatment with carboplatin. She also had a history of anxiety, hypertension, and pterygium, and she was taking gabapentin, lorazepam, prochlorperazine, metoprolol succinate, bromfenac and ketorolac ophthalmic solution, and aprepitant. Intraoral examination revealed a 1.5 × 1.0-cm firm, erythematous gingival mass in the area of missing right mandibular second bicuspid and first molar with buccal and lingual expansion (Figure 1A). The right mandibular first bicuspid was grade 3 mobile. A periapical radiograph was obtained, and results showed a diffuse, poorly demarcated radiolucency measuring approximately 1.2 × 0.8 cm (Figure 1B). Findings from an incisional biopsy of the mass showed an infiltrative tumor (Figure 1C). Tumor cells were positive for CK7, PAX8, and WT-1, and negative for CK20 and TTF-1 (Figure 1C, inset).A, A 1.5 × 1-cm gingival mass is distal to the right mandibular first bicuspid. B, Diffuse, poorly demarcated radiolucency is seen in the area of the missing right mandibular second bicuspid and first molar (arrowheads). C, Multiple nests of round to ovoid epithelial cells form ducts (hematoxylin-eosin stain, original magnification ×100). Diffuse nuclear positivity for PAX8 (immunohistochemistry, original magnification ×200) (inset).

what is your diagnosis?

What is your diagnosis?

Oral metastasis

Gingival/periodontal abscess

Squamous cell carcinoma

Pyogenic granuloma

a

female

51-60

Hispanic

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2732495

A 27-year-old man with a history of pharyngeal gonorrhea presented with a 7-day history of severe sore throat and odynophagia, worse when swallowing solids than liquids. Owing to the odynophagia, he had presented to the emergency department for dehydration. At that time, he was febrile to 101°F and denied any dysphonia or dyspnea. The results of a rapid Streptococcus test, recent HIV screen, and a rapid plasma reagin test were all negative. He denied any genital lesions or symptoms at that time. He had been taking prophylactic emtricitabine-tenofovir daily and had received his last diphtheria booster 2 years prior to presentation. Treatment with amoxicillin clavulanate over several days had not prevented a worsening of his symptoms. On physical examination, there was no cervical lymphadenopathy, and there were no genital lesions. Flexible fiber-optic nasopharyngoscopy showed ulcerative lesions with exudate and erythema extending diffusely along the base of tongue, oropharynx, nasopharynx, hypopharynx, and epiglottis (Figure 1). What Is Your Diagnosis?

Diphtheria

Mononucleosis

Type 2 herpes simplex virus (HSV-2) pharyngitis

Pharyngeal gonorrhea

C. HSV-2 pharyngitis

C

Type 2 herpes simplex virus (HSV-2) pharyngitis

The patient underwent HIV, rapid plasma reagin, monospot, HSV-1, an HSV-2 blood tests. Oropharyngeal cultures were taken for bacteria, fungus, and gonorrhea/chlamydia. Results of a qualitative polymerase chain reaction assay performed on a tissue swab were positive for HSV-2 and negative for HSV-1. Screening detected HSV-1/HSV-2 IgM serum antibody, and IgG serum antibody findings were indeterminate, suggesting current or recent infection. All other laboratory and culture findings were negative; therefore, a diagnosis of HSV-2 pharyngitis was made. He subsequently began treatment with valacyclovir, 3 g/d. No exudates or lesions were noted on physical examination nor on flexible fiber-optic nasopharyngoscopy at his 2-week follow-up visit (Figure 2). At that time, he was no longer complaining of odynophagia.Type 2 HSV has seldom been associated with isolated oropharyngeal lesions, and only a handful of cases have been reported in the literature in immune-competent adults from oral genital transmission.1-3 Transmission of HSV is dependent on viral contact with mucosal surfaces or abraded skin in a susceptible seronegative individual. Although HSV-1 is highly prevalent in humans, oropharyngeal infections are rare.3,4 Type 2 HSV more commonly presents as a genital infection, and to our knowledge has only been reported to affect the oropharynx in neonates through vertical transmission, or by reactivation of latent virus in the immunocompromised state.1,5 On clinical presentation, patients with HSV pharyngitis often have ulcerative lesions with exudate. These lesions are thought to have originated with vesicular lesions and to have quickly progressed to the ulcerative state with exudate. In a study of 209 cases of clinically symptomatic primary HSV genital infections, Corey et al6 found that pharyngitis symptoms of ulcerative and exudative lesions of the posterior pharynx ranged from mild to severe. However, in the present case and in several previously reported cases, there has been no evidence of HSV-2 genital lesions, and HSV-2 remains an uncommonly recognized cause of oral lesions and isolated pharyngitis.1Diagnosis of HSV pharyngitis is made more challenging by the wide variation of findings on examination. Because white/gray exudate, with or without ulceration, is commonly seen in HSV pharyngitis, this may be difficult to distinguish from diphtheria. Diphtheria often presents with a similarly gradual onset of odynophagia, malaise, cervical lymphadenopathy, and a low-grade fever. In at least one-third of cases, a tightly adherent pseudomembrane can be observed, and may affect any portion of the respiratory tract extending from the nasal passages to the tracheobronchial tree.7 Patients with mononucleosis commonly present with tonsillar exudates, fever, and diffuse cervical lymphadenopathy.8 Oropharyngeal infections with Neisseria gonorrhoeae are most commonly asymptomatic, although sore throat and pharyngeal exudates with or without cervical lymphadenitis are present in some cases.9,10 Diphtheria, mononucleosis, HSV pharyngitis, and pharyngeal gonorrhea may all present in a similar manner, and only cultures or serologic testing can confirm one over the others. Thus, it is important to consider broad differential diagnoses in a patient for whom antibiotic therapy has failed.Given the rather broad range of differential diagnoses for pharyngeal exudates, a high index of suspicion is required for diagnosis of HSV pharyngitis. The patient in this case initially presented with odynophagia without any lesions, and he was treated for tonsillitis before returning for further workup and care. His history of pharyngeal gonorrhea and high-risk sexual behavior were concerning for infectious causes; however, HSV was not originally a primary consideration.This case illustrates the importance of considering HSV-2 as a diagnosis for patients presenting with new exudative or ulcerative pharyngeal lesions. Although it remains a rare cause of pharyngitis, we recommend including an HSV-1/HSV-2 assay as part of the workup in complicated exudative pharyngitis that does not respond to antibiotic treatment.

General

A 27-year-old man with a history of pharyngeal gonorrhea presented with a 7-day history of severe sore throat and odynophagia, worse when swallowing solids than liquids. Owing to the odynophagia, he had presented to the emergency department for dehydration. At that time, he was febrile to 101°F and denied any dysphonia or dyspnea. The results of a rapid Streptococcus test, recent HIV screen, and a rapid plasma reagin test were all negative. He denied any genital lesions or symptoms at that time. He had been taking prophylactic emtricitabine-tenofovir daily and had received his last diphtheria booster 2 years prior to presentation. Treatment with amoxicillin clavulanate over several days had not prevented a worsening of his symptoms. On physical examination, there was no cervical lymphadenopathy, and there were no genital lesions. Flexible fiber-optic nasopharyngoscopy showed ulcerative lesions with exudate and erythema extending diffusely along the base of tongue, oropharynx, nasopharynx, hypopharynx, and epiglottis (Figure 1).

what is your diagnosis?

What is your diagnosis?

Type 2 herpes simplex virus (HSV-2) pharyngitis

Diphtheria

Mononucleosis

Pharyngeal gonorrhea

a

male

21-30

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2733030

A woman in her 60s with a history of end-stage renal disease who had a kidney transplant 9 months previously presented with progressive cough, dyspnea, and hoarseness. Her history also included chronic gastroesophageal reflux disease and a 14-pack-year smoking history. She initially presented 3 months prior with upper respiratory symptoms, which continued to worsen despite oral antibiotic therapy. Her cough became productive with white, frothy phlegm that was accompanied by fever, wheezing, hoarseness, and fatigue. Her dyspnea worsened in the supine position.Flexible laryngotracheoscopy results revealed diffuse, white-to-yellow pseudomembranous changes involving the glottis and supraglottis (Figure, A), posterior tracheal wall, and left mainstem bronchus with skip lesions in the subglottis and distal 1 cm of the trachea (Figure, B). Glottic mobility was limited in both abduction and adduction with substantial airway obstruction. Computed tomographic findings revealed posterior tracheal wall thickening with the loss of the fat plane between the trachea and esophagus, and a moderate to severe obstruction within the distal left mainstem bronchus. Biopsy results are shown in Figure, C.Laryngoscopic images demonstrate pseudomembranous plaques lining supraglottis and glottis (A) and posterior wall of the trachea (B). Supraglottic biopsy demonstrates branching organisms superficial to squamous epithelium (original magnification ×400) (C). What Is Your Diagnosis?

Posttransplant lymphoproliferative disorder

Squamous cell carcinoma

Nocardiosis

Aspergillosis

D. Aspergillosis

D

Aspergillosis

Pathology results from supraglottic biopsy revealed branching, fungal microorganisms among superficial fragments of squamous epithelium. Culture and bronchoalveolar lavage results confirmed the diagnosis of Aspergillosis laryngotracheobronchitis.Aspergillus tracheobronchitis (ATB) is an unusual form of pulmonary aspergillosis that is seen in fewer than 10% of aspergillosis-related cases.1 Patients with neutropenia and/or who are immunocompromised are at particular risk for ATB.2 Patients usually present with dyspnea, cough, and wheezing. Diagnosis of this rare entity is often delayed because of its nonspecific clinical presentation and lack of radiographic findings at early stages.3 Radiologic findings may include thickening of airways, patchy infiltrates, or no findings at all.1 Definitive diagnosis requires visualization with laryngoscopy or bronchoscopy and both pathological and microbiological biopsies.4In 1995, Denning5 proposed a classification of 3 forms of ATB:Obstructive ATB: characterized by thick mucus plugs filled with aspergillus hyphae with little mucosal inflammation or invasionPseudomembranous ATB: characterized by extensive inflammation of the tracheobronchial tree with a membrane overlying the mucosa containing Aspergillus speciesUlcerative ATB: characterized by focal invasion of the tracheobronchial mucosa and/or cartilage by fungal hyphae (typically found around the suture line in patients who have had a lung transplant)Obstructive ATB: characterized by thick mucus plugs filled with aspergillus hyphae with little mucosal inflammation or invasionPseudomembranous ATB: characterized by extensive inflammation of the tracheobronchial tree with a membrane overlying the mucosa containing Aspergillus speciesUlcerative ATB: characterized by focal invasion of the tracheobronchial mucosa and/or cartilage by fungal hyphae (typically found around the suture line in patients who have had a lung transplant)The preferred agents for treatment and prevention of ATB are triazoles, with voriconazole recommended as the primary agent. Amphotericin B is an appropriate option for initial and salvage therapy. Echinocandins are effective in salvage therapy but are not recommended as monotherapy for primary treatment. Some evidence exists to suggest an additive or synergistic effect of treatment with polyenes and/or azoles with echinocandins; however, variable test designs and conflicting results have led to uncertainty as to how to interpret these findings. Early initiation of treatment is warranted while diagnostic evaluation is conducted. When feasible, eliminating or reducing the dose of immunosuppressive agents is advisable. Surgery for aspergillosis should be considered for local disease that is easily accessible to debridement.4In the present case, the patient developed acute, increased respiratory distress 9 days after admission secondary to profound plaque and debris nearly completely obstructing the glottis. After surgical debridement, a tracheostomy was placed for pulmonary hygiene. The patient was discharged 1 month after admission and treated with antifungal therapy for a total of 3 months. Results of repeat flexible laryngoscopy at 10 weeks from initial presentation revealed complete resolution of plaque and debris, and she was decannulated.This case demonstrates pseudomembranous and obstructive aspergillus tracheobronchitis in a solid organ transplant recipient. As the number of immunocompromised patients continues to rise, it is vital that the otolaryngology community remains attuned to opportunistic infections affecting the upper aerodigestive tract.

General

A woman in her 60s with a history of end-stage renal disease who had a kidney transplant 9 months previously presented with progressive cough, dyspnea, and hoarseness. Her history also included chronic gastroesophageal reflux disease and a 14-pack-year smoking history. She initially presented 3 months prior with upper respiratory symptoms, which continued to worsen despite oral antibiotic therapy. Her cough became productive with white, frothy phlegm that was accompanied by fever, wheezing, hoarseness, and fatigue. Her dyspnea worsened in the supine position.Flexible laryngotracheoscopy results revealed diffuse, white-to-yellow pseudomembranous changes involving the glottis and supraglottis (Figure, A), posterior tracheal wall, and left mainstem bronchus with skip lesions in the subglottis and distal 1 cm of the trachea (Figure, B). Glottic mobility was limited in both abduction and adduction with substantial airway obstruction. Computed tomographic findings revealed posterior tracheal wall thickening with the loss of the fat plane between the trachea and esophagus, and a moderate to severe obstruction within the distal left mainstem bronchus. Biopsy results are shown in Figure, C.Laryngoscopic images demonstrate pseudomembranous plaques lining supraglottis and glottis (A) and posterior wall of the trachea (B). Supraglottic biopsy demonstrates branching organisms superficial to squamous epithelium (original magnification ×400) (C).

what is your diagnosis?

What is your diagnosis?

Nocardiosis

Squamous cell carcinoma

Posttransplant lymphoproliferative disorder

Aspergillosis

d

female

61-70

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2733785

An 80-year-old man with acromegaly due to a hypoenhancing pituitary microadenoma opted for transsphenoidal resection. Preoperative magnetic resonance imaging examination of the sella revealed a left-sided pituitary microadenoma (Figure, A) and lobulated polypoid soft tissue masses in the superior nasal cavities arising from the olfactory clefts. These lesions demonstrated avid post–contrast enhancement with small areas of cystic change and heterogeneously hyperintense T2 signal. There was mild widening of the olfactory clefts, particularly on the left side (Figure, B). The intervening nasal septum was intact, and there was no intracranial extension. The patient did not have any noteworthy rhinological symptoms on review. He later underwent nasal endoscopy, and results showed tan-colored polypoid lesions emanating from the olfactory clefts of both nasal cavities (Figure, C). Biopsy findings revealed submucosal proliferation of seromucinous and respiratory epithelial glands (Figure, D).A, An incidental polypoid-enhancing mass in the nasal cavity demonstrating avid post–contrast enhancement (yellow arrowheads) was observed on the magnetic resonance imaging examination. The white arrowhead points to the pituitary adenoma. B, Widening and remodeling of the olfactory clefts (yellow arrowheads) was also observed on the magnetic resonance imaging examination. C, The incidental polypoid-enhancing mass in the nasal cavity (yellow arrowheads) as seen on nasal endoscopic analysis. D, Results of the nasal cavity mass biopsy (original magnification ×100) revealed submucosal proliferation of bland-appearing seromucinous and respiratory epithelial glands. What Is Your Diagnosis?

Low-grade sinonasal adenocarcinoma

Inflammatory nasal polyps

Inverted papilloma

Nasal cavity hamartoma

D. Nasal cavity hamartoma

D

Nasal cavity hamartoma

There are 2 types of sinonasal hamartomas identified on histopathologic analysis: respiratory epithelial adenomatoid hamartoma (REAH) and seromucinous hamartoma. The latter of these is included as a new entity in the fourth edition of WHO Classification of Head and Neck Tumours.1 These lesions are described as respiratory epithelial lesions in the current classification. It is difficult to differentiate the 2 types using histopathologic, endoscopic, or imaging analysis, and they are believed to represent a spectrum. Recently, a possible new subtype containing olfactory neuroepithelial cells was also described.2 It is still unclear whether these sinonasal lesions represent nonneoplastic lesions (hamartomas) or true benign neoplasms. Ozolek and colleagues3 demonstrated significant allelic loss in REAH, which raises the possibility of these being true neoplasms.On microscopic examination, the hamartomas are covered with ciliated respiratory epithelium, which shows invagination and submucosal glandular proliferation.4,5 The submucosal proliferating glands are predominantly multilayered ciliated respiratory epithelium in REAH or a single layer of cuboidal epithelium in seromucinous hamartoma, though a mixed picture is not uncommon, as seen in the present patient. A myxoid to fibrous stroma is often infiltrated with lymphocytes and plasma cells. Eosinophilic infiltration is absent in contrast with inflammatory polyps. Hyalinization of the basement membrane of the invaginated proliferating glands is common in REAH. In cases where there is coexistent osseous or cartilaginous metaplasia present, the term chondroosseous respiratory epithelial hamartoma may be applied. Chondroosseous respiratory epithelial hamartoma is a distinct entity from the nasal chondromesenchymal hamartoma, which occurs primarily in infants and may be characterized by locally aggressive involvement of the paranasal sinuses, nasal cavity, and orbits.1 Differentiating REAH from low-grade adenocarcinomas is very important and can be a challenge to the pathologist in a limited biopsy. Immunohistochemical stains also offer limited help.6Seromucinous hamartoma is rare and less common than REAH, and only a handful of cases exist in literature.5 Both can coexist with inflammatory sinonasal polyps. This frequently leads to their underrecognition. Typically, they are found in the middle-to-elderly age group. Nasal or sinus obstruction, rhinorrhea, dysosmia, or epistaxis can be the presenting symptoms, but they can be asymptomatic and picked up incidentally, as in the present case. They can occur anywhere in the nasal cavities or nasopharynx, but the posterior nasal septum and olfactory clefts are characteristic locations.5,7 On computed tomographic analysis, widening of the olfactory cleft and absence of aggressive features such as bony erosions or destruction are considered typical.8 REAH can be either unilateral or bilateral; as in this and previous cases, the bilaterality of a benign-appearing lesion may be a clue to the diagnosis.9 Magnetic resonance imaging provides better tissue characterization of the hamartomas, which are typically T2 hyperintense, polypoid lesions showing post–contrast enhancement. It is important to remember that the presence of post–contrast enhancement in particular can lead to a misdiagnosis of carcinoma.Sinonasal hamartomas are managed by endoscopic resection. These lesions rarely recur, and malignant transformation has not been reported.5 This necessitates a correct diagnosis for appropriate management. From an imaging point of view, the characteristic location, olfactory cleft widening, lack of aggressive features, intact cribriform plate, T2 brightness, and bilaterality are potential clues, but these lesions can still pose a challenge to the untrained eye.In the present case, additional and longer-term testing is needed to determine the endocrine status and outcome regarding the patient’s pituitary adenoma resection. The nasal cavity REAH was subtotally resected and stable at a 3-month postoperative magnetic resonance imaging examination.

General

An 80-year-old man with acromegaly due to a hypoenhancing pituitary microadenoma opted for transsphenoidal resection. Preoperative magnetic resonance imaging examination of the sella revealed a left-sided pituitary microadenoma (Figure, A) and lobulated polypoid soft tissue masses in the superior nasal cavities arising from the olfactory clefts. These lesions demonstrated avid post–contrast enhancement with small areas of cystic change and heterogeneously hyperintense T2 signal. There was mild widening of the olfactory clefts, particularly on the left side (Figure, B). The intervening nasal septum was intact, and there was no intracranial extension. The patient did not have any noteworthy rhinological symptoms on review. He later underwent nasal endoscopy, and results showed tan-colored polypoid lesions emanating from the olfactory clefts of both nasal cavities (Figure, C). Biopsy findings revealed submucosal proliferation of seromucinous and respiratory epithelial glands (Figure, D).A, An incidental polypoid-enhancing mass in the nasal cavity demonstrating avid post–contrast enhancement (yellow arrowheads) was observed on the magnetic resonance imaging examination. The white arrowhead points to the pituitary adenoma. B, Widening and remodeling of the olfactory clefts (yellow arrowheads) was also observed on the magnetic resonance imaging examination. C, The incidental polypoid-enhancing mass in the nasal cavity (yellow arrowheads) as seen on nasal endoscopic analysis. D, Results of the nasal cavity mass biopsy (original magnification ×100) revealed submucosal proliferation of bland-appearing seromucinous and respiratory epithelial glands.

what is your diagnosis?

What is your diagnosis?

Low-grade sinonasal adenocarcinoma

Nasal cavity hamartoma

Inverted papilloma

Inflammatory nasal polyps

b

male

71-80

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2732284

A 25-year-old woman was referred to the neuro-ophthalmology clinic because of a 6-month history of intermittent diplopia. The double vision occurred every day, multiple times throughout the day, and was provoked after looking to the right. There was no eye pain, headache, ptosis, difficulties swallowing, change in voice, or any other ocular or neurological symptoms.She had no history of strabismus, eye patching, or ocular surgery. Her medical history was notable for a growth hormone–producing pituitary macroadenoma for which she underwent surgical resection 2.5 years prior to presentation, followed by γ-knife radiosurgery (50 Gy) 6 months after the initial surgical procedure. She also had a history of congenital hip dysplasia. Medications included cabergoline, levothyroxine, ethinyl estradiol/drospirenone, and pasireotide.Her visual acuity was 20/20 OU. Her pupils were equal in size with no relative afferent pupillary defect. Automated perimetry was full in both eyes. The anterior and posterior segments were normal in both eyes. There was no proptosis or ptosis. On initial examination, the eye movements were full, with no ocular deviation in primary, right, or lateral gazes. However, on returning to a primary gaze from a sustained right-gaze position, a large angle exotropia was present, and on attempted left gaze, there was a limitation of adduction of the right eye (Figure). After 10 to 15 seconds, the exotropia resolved, and eye movements returned to normal.A, Eye positions in right gaze, and B, eye positions in primary gaze. After sustaining a right gaze position for 10 to 15 seconds (A) and then returning to primary gaze (B), there is a large-angle right exotropia. Note that the pupils are pharmacologically dilated. What Would You Do Next?

Initiate a trial of carbamazepine

Perform bilateral lateral rectus recessions

Order cranial magnetic resonance imaging

Obtain anti-acetylcholine receptor binding antibodies

Right sixth-nerve ocular neuromyotonia

A

Initiate a trial of carbamazepine

The differential diagnosis of intermittent double vision owing to an exodeviation is limited and includes third-nerve palsy, internuclear ophthalmoplegia, myasthenia gravis, orbital disease (such as myositis, tumor, or trauma), intermittent exotropia, and ocular neuromyotonia.1 In this patient, the findings on voluntary eye movements provided valuable information and narrowed the diagnosis to only 1 entity, a right sixth-nerve ocular neuromyotonia. Intermittent exotropia alone can occur from any of the entities mentioned, but only in a case of ocular neuromyotonia will there be an intermittent ocular misalignment after prolonged activity of the extraocular muscle innervated by the affected ocular motor cranial nerve. Symptomatic ocular neuromyotonia is treated medically, with the first-line treatment being carbamazepine (choice A), a voltage-gated sodium-channel blocker.2,3 Bilateral lateral rectus recessions (choice B) is not indicated for ocular neuromyotonia. Although most cases of acquired diplopia in a young person warrant neuroimaging, the history of γ-knife radiosurgery and eye movement findings consistent with ocular neuromyotonia obviated the need for a magnetic resonance imaging study (choice C). Checking anti-acetylcholine receptor binding antibodies (choice D) is not necessary, because myasthenia gravis does not cause an ocular deviation and limitation of eye movements after prolonged activity of a particular extraocular muscle.Ocular neuromyotonia was first described by E. Clark, MD, in 1966 in a patient with spasm of the superior oblique muscle, but it was K. Ricker and H. G. Mertens who coined the term in 1970.1,4 It is believed to be neurogenic in origin and specifically owing to ephaptic neural transmission (ie, lateral contact between nerve fibers allowing action potentials to travel between cell membranes instead of crossing synapses).1,2 Diplopic episodes are triggered by activation of the affected ocular motor cranial nerve, resulting in continued contraction of the innervated extraocular muscle with disruption of the Sherrington law of reciprocal innervation, leading to ocular misalignment and eye movement limitation opposite to the direction of the contracted extraocular muscle.Ocular neuromyotonia is a rare condition and has been most frequently associated with prior radiation therapy.4 However, γ-knife radiosurgery, which this patient received, has been previously documented in only 6 cases, to our knowledge.3,5 Giardina et al6 reviewed 66 cases published in the literature and found a female predominance (61.1%), with a mean age of 43.9 (range, 7-74) years. Fifty-seven percent of the cases involved the third cranial nerve, 39% the sixth cranial nerve, and 9.1% the fourth cranial nerve. The most common underlying pathologic mechanism was a suprasellar mass (60%), followed by an idiopathic origin (19.7%) and an association with thyroid dysfunction (4.5%). Of the suprasellar mass cases, 76.9% had therapeutic radiation exposure. Other less common conditions reported with ocular neuromyotonia included cranial trauma, thorium toxicity, Paget disease, nasopharyngeal carcinoma, central nervous system demyelination, botulinum neurotoxin injection, vitamin D deficiency, stroke, and cataract surgery.6,7The initial evaluation of any patient suspected of ocular neuromyotonia should begin with a detailed history specifically of prior radiation therapy. Misinterpreting the clinical findings can lead to unnecessary investigations, avoidable medical expenses, and inappropriate surgical intervention.The patient was prescribed 200 mg of carbamazepine twice a day, with the option to increase the dosage by 200 mg each week, going no higher than 1200 mg per day depending on the frequency of the double vision. Since starting the medication, she reported a decrease in the number of double-vision episodes.

Ophthalmology

A 25-year-old woman was referred to the neuro-ophthalmology clinic because of a 6-month history of intermittent diplopia. The double vision occurred every day, multiple times throughout the day, and was provoked after looking to the right. There was no eye pain, headache, ptosis, difficulties swallowing, change in voice, or any other ocular or neurological symptoms.She had no history of strabismus, eye patching, or ocular surgery. Her medical history was notable for a growth hormone–producing pituitary macroadenoma for which she underwent surgical resection 2.5 years prior to presentation, followed by γ-knife radiosurgery (50 Gy) 6 months after the initial surgical procedure. She also had a history of congenital hip dysplasia. Medications included cabergoline, levothyroxine, ethinyl estradiol/drospirenone, and pasireotide.Her visual acuity was 20/20 OU. Her pupils were equal in size with no relative afferent pupillary defect. Automated perimetry was full in both eyes. The anterior and posterior segments were normal in both eyes. There was no proptosis or ptosis. On initial examination, the eye movements were full, with no ocular deviation in primary, right, or lateral gazes. However, on returning to a primary gaze from a sustained right-gaze position, a large angle exotropia was present, and on attempted left gaze, there was a limitation of adduction of the right eye (Figure). After 10 to 15 seconds, the exotropia resolved, and eye movements returned to normal.A, Eye positions in right gaze, and B, eye positions in primary gaze. After sustaining a right gaze position for 10 to 15 seconds (A) and then returning to primary gaze (B), there is a large-angle right exotropia. Note that the pupils are pharmacologically dilated.

what would you do next?

What would you do next?

Obtain anti-acetylcholine receptor binding antibodies

Initiate a trial of carbamazepine

Perform bilateral lateral rectus recessions

Order cranial magnetic resonance imaging

b

female

21-30

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2732694

A 27-year-old man presented to the clinic for evaluation of a mass in his right eye. He had an unremarkable medical and ocular history and had not sustained any ocular trauma. He described a painless, reddish mass in his lateral conjunctiva, which had been present since birth. He was asymptomatic aside from rare episodes of pink tears in his right eye, and the lesion did not bother him cosmetically. He noted no blurry vision, diplopia, or pain with eye movements. His visual acuity was 20/20 OU, and there was no proptosis, ptosis, or afferent pupillary defect. Extraocular muscle movements were intact, and his intraocular pressure was 15 mm Hg OU. There was no change in lesion size observed with the Valsalva maneuver. A slitlamp examination revealed an 8-mm, round, fluctuant, vascular, multifocal mass involving the bulbar and palpebral conjunctiva near the lateral canthus (Figure). The results of the rest of the examinations, including cornea, anterior chamber, and dilated fundus examinations, were normal in both eyes.A vascular, multifocal mass (8 mm) involving the bulbar and palpebral conjunctiva near the lateral canthus, as shown by slitlamp examination.Obtain magnetic resonance imaging of the brain and orbits What Would You Do Next?

Obtain magnetic resonance imaging of the brain and orbits

Complete an excisional biopsy of the lesion

Complete needle drainage of the lesion

Initiate systemic propranolol

Superficial conjunctival lymphatic venous malformation

A

Obtain magnetic resonance imaging of the brain and orbits

The patient underwent magnetic resonance imaging of the brain and orbits (choice A), which demonstrated a nonenhancing lobular lesion in the right anterolateral periorbit without any posterior extension. The patient was clinically diagnosed with a superficial conjunctival lymphatic venous malformation, and he elected for observation.An excisional biopsy of the lesion (choice B) would not be the preferred next step because it is important to define the extent of the lesion prior to surgical intervention. While the patient lacked orbital symptoms and the lesion appeared superficial, lymphatic venous malformations are commonly multifocal and have deep components that must be assessed. Needle drainage of the lesion (choice C) would similarly not be the most appropriate next step without defining the lesion’s extent, and it is associated with a high likelihood of recurrence.1 Systemic propranolol (choice D) would not be the preferred choice because, while propranolol is commonly used to treat capillary hemangiomas in young children and infants, its use in older children and adults with vascular and lymphatic malformations is not well described and may not be as efficacious.2Lymphatic venous malformations (LVMs), or lymphangiomas, are benign, hamartomatous, vascular lesions that may present in the orbit or adnexa. They represent no-flow or low-flow system of cystlike channels lined by endothelial cells of lymphatic or venous origin. The distinction between lymphatic and venous malformations may not be clinically relevant because many lesions demonstrate a mixture of both cell types.3 The cystic spaces may be filled with blood, as in this case. They are typically present from birth and may remain stable or gradually enlarge, but orbital lesions may present with sudden proptosis owing to spontaneous hemorrhage.4 In classic cases, these lesions tend to swell when respiratory infections occur.Lymphatic venous malformations can be divided into superficial, deep, and combined, based on location. Superficial LVMs involving only the eyelid and/or conjunctiva, as in this patient, are the least common subtype.4 Superficial LVMs tend to be of cosmetic importance only and are commonly asymptomatic. Deep and combined LVMs demonstrate orbital involvement and represent most cases. Therefore, orbital imaging is important for evaluation and management. Magnetic resonance and computed tomographic imaging demonstrate multiloculated, heterogeneous masses with cystic spaces.5 Lymphatic venous malformations may be similar in appearance to other benign lesions, such as orbital varices, capillary hemangiomas, and cavernous hemangiomas. Variation of lesion size with the Valsalva maneuver and head positioning may be useful in distinguishing LVMs from orbital varices. Capillary hemangiomas may be present from birth but would be expected to regress over time. Diagnosis of LVM can be confirmed with histopathologic analysis, but a biopsy has the potential to cause excessive bleeding6 and would not likely change the patient’s management.Asymptomatic LVMs may be observed for growth or symptoms. Symptoms depend on lesion location and may include poor cosmesis, proptosis, pain, diplopia, and headache. In case of symptoms, the most commonly described treatment for orbital and adnexal LVMs is surgical resection. However, total resection often proves difficult because the lesions are prone to bleeding,5 and there is a high rate of recurrence with surgical excision.7 Furthermore, it is often not possible to fully resect the lesion.7 Therefore, if the patient is asymptomatic, it is generally recommended to choose observation.The patient has been observed without intervention. He has remained asymptomatic and without lesion growth at the time of latest follow-up.

Ophthalmology

A 27-year-old man presented to the clinic for evaluation of a mass in his right eye. He had an unremarkable medical and ocular history and had not sustained any ocular trauma. He described a painless, reddish mass in his lateral conjunctiva, which had been present since birth. He was asymptomatic aside from rare episodes of pink tears in his right eye, and the lesion did not bother him cosmetically. He noted no blurry vision, diplopia, or pain with eye movements. His visual acuity was 20/20 OU, and there was no proptosis, ptosis, or afferent pupillary defect. Extraocular muscle movements were intact, and his intraocular pressure was 15 mm Hg OU. There was no change in lesion size observed with the Valsalva maneuver. A slitlamp examination revealed an 8-mm, round, fluctuant, vascular, multifocal mass involving the bulbar and palpebral conjunctiva near the lateral canthus (Figure). The results of the rest of the examinations, including cornea, anterior chamber, and dilated fundus examinations, were normal in both eyes.A vascular, multifocal mass (8 mm) involving the bulbar and palpebral conjunctiva near the lateral canthus, as shown by slitlamp examination.Obtain magnetic resonance imaging of the brain and orbits

what would you do next?

What would you do next?

Obtain magnetic resonance imaging of the brain and orbits

Initiate systemic propranolol

Complete needle drainage of the lesion

Complete an excisional biopsy of the lesion

a

male

21-30

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2733447

A boy aged 13 years was referred for choroidal mass of the right eye. Visual acutiy was 20/60 OD and 20/20 OS. Intraocular pressures and anterior segment examination findings were normal. Fundus examination revealed orange, subretinal mass with associated subretinal fluid in the posterior pole. The lesion was followed closely and throughout a series of visits, the lesion and fluid continued to progress, the visual acuity worsened to 20/200, and the tumor mass extended closer to the fovea (Figure 1). The mass measured 15 mm in basal diameter with a thickness of 6.4 mm on B-scan ultrasonography.Large choroidal vascular mass of inferotemporal right choroid. Note large choroidal mass on B-scan ultrasonography. What Would You Do Next?

Photodynamic therapy

Iodine 125 plaque brachytherapy

Anti–vascular endothelial growth factor therapy injections

External beam radiotherapy

Circumscribed choroidal hemangioma

B

Iodine 125 plaque brachytherapy

Circumscribed choroidal hemangioma (CCH) is a benign, vascular tumor considered to be congenital in nature. It is classically described as an orange-red tumor, usually in the posterior pole.1 Circumscribed choroidal hemangioma is usually diagnosed when it is causing visual disturbance from exudative retinal detachment. Circumscribed choroidal hemangioma can be treated by a variety of methods including photodynamic therapy (PDT), laser photocoagulation, cryotherapy, external beam radiotherapy, stereotactic radiotherapy, proton beam radiotherapy, episcleral plaque radiotherapy, and transpupillary thermotherapy PDT.2The results of PDT for CCH are very favorable; however, the exact treatment regimen of PDT for CCH varies depending on lesion size and location. In 2 studies of PDT in CCH, tumor thickness ranged from 1.9 mm to 5.9 mm (smaller than in this patient) and thicker lesions are less responsive to PDT or require more sessions.2,3 Diffuse choroidal hemangiomas and those associated with Sturge-Weber syndrome can achieve similar thicknesses, but it is unusual for true circumscribed lesions to be this thick. Additionally, placement of an intravenous catheter, infusion of verteporfin, and multiple sessions of laser with a slitlamp delivery system would be challenging for a 13-year-old patient (choice A).Bevacizumab has been recently reported as an option for CCH treatment.4,5 Tumor thickness was not reported, but laser photocoagulation was used as adjunctive therapy for each patient. Sagong et al5 reported a case series of 3 patients receiving intravitreal bevacizumab injections as primary treatment for CCH. The tumor thickness of these patients ranged from 1.6 mm to 2.6 mm. Of note, each of these patients were also given adjunctive PDT. Bevacizumab injections were not an option in our case owing to the need for adjunctive therapy with either PDT or thermal laser, which as described above would have proved infeasible. Additionally, a tumor thickness of 6.5 mm has not been studied with bevacizumab, to our knowledge (choice C).Schilling et al6 published a case series of 36 eyes treated with external beam radiation for the treatment of CCH. The age of the patients ranged from 22 to 66 years. Of the tumors that received external beam radiotherapy without laser photocoagulation, none showed tumor regression on ultrasonography. In addition, Harbron et al7 published a series of 7257 children receiving external beam radiotherapy, of which 42 secondary malignant neoplasms were diagnosed. Although external beam radiotherapy may have been effective in this case, the risk of secondary malignant neoplasm outweighed benefit (choice D).Iodine 125 plaque brachytherapy is successfully used to treat many tumors of the retina and choroid. A case study of 8 patients with CCH who underwent episcleral plaque brachytherapy was reported by López-Caballero et al.8 The tumor thickness of the patients ranged from 2.8 mm to 6.5 mm, and all tumors were successfully treated with episcleral plaque brachytherapy targeting 29 Gy to the apex. With the ability to control our surroundings with anesthesia and need for a definitive, we elected plaque brachytherapy (choice B).This patient was treated with iodine 125 episcleral brachytherapy with apex dose of 35 Gy. At 6 months after plaque radiotherapy, his visual acuity improved to 20/100. His tumor apex decreased from 6.5 mm to 4.2 mm. His vision is stable, and he has no early signs of cataract or radiation retinopathy (Figure 2). We will continue to monitor as in our experience, radiation changes occur around 18 months after plaque radiotherapy.Regressed choroidal mass after iodine 125 plaque brachytherapy. Note reattachment of fovea and resolution of subretinal fluid.

Ophthalmology

A boy aged 13 years was referred for choroidal mass of the right eye. Visual acutiy was 20/60 OD and 20/20 OS. Intraocular pressures and anterior segment examination findings were normal. Fundus examination revealed orange, subretinal mass with associated subretinal fluid in the posterior pole. The lesion was followed closely and throughout a series of visits, the lesion and fluid continued to progress, the visual acuity worsened to 20/200, and the tumor mass extended closer to the fovea (Figure 1). The mass measured 15 mm in basal diameter with a thickness of 6.4 mm on B-scan ultrasonography.Large choroidal vascular mass of inferotemporal right choroid. Note large choroidal mass on B-scan ultrasonography.

what would you do next?

What would you do next?

Iodine 125 plaque brachytherapy

External beam radiotherapy

Photodynamic therapy

Anti–vascular endothelial growth factor therapy injections

a

male

11-20

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2734132

A 52-year-old man was referred to the neuro-ophthalmology clinic for evaluation of visual field loss. He had exotropia and amblyopia of the left eye. He was diagnosed as having glaucoma 6 months prior to presentation owing to optic nerve cupping and visual field deficits on automated perimetry and was taking latanoprost. His medical history was significant for pyruvate dehydrogenase deficiency, and his family history was notable for glaucoma in his grandmother. He was being treated by the neurology department for his pyruvate dehydrogenase deficiency with thiamine, vitamin C, and oxaloacetate. His systemic symptoms included hyperhidrosis and episodes of hand tremors, ataxia, and dysarthria that occur every 2 to 3 years.Best-corrected visual acuity was 20/40 −2 OD and 20/100 +2 OS, with a relative afferent pupillary defect in the left eye. Intraocular pressure (IOP) was 16 mm Hg OU, and pachymetry was 611 μM OD and 592 μM OS (normal mean [SD], 542.4 [33.5] μM). He identified 8/8 OD and 3/8 OS Ishihara color plates. He had an exotropia with full range of motion in both eyes. His nuclear sclerotic cataracts were not consistent with visual acuity in both eyes; his anterior segment examination was otherwise within normal limits. His dilated examination was normal except for cupping and pallor in both eyes with a supratemporal optic nerve pit in the right eye. The optic discs and automated perimetry are shown in the Figure. Optical coherence tomography (OCT) of the retinal nerve fiber layer showed a mean thickness of 64 μM OD and 47 μM OS (normal mean [SD], 97.3 [9.6] μM), and OCT of the macula showed perifoveal thinning with normal foveal thickness in both eyes.A and B, Fundus photographs show cupping with optic nerve pallor in both eyes and a supratemporal optic nerve pit in the right eye (arrowhead). C and D, Automated perimetry demonstrating temporal hemianopia respecting the vertical midline in the left eye with cecocentral scotoma in the right eye, consistent with a junctional scotoma.Repeated visual fields with IOP check in 1 month What Would You Do Next?

Observation

Magnetic resonance imaging of the brain/orbits

Referral to endocrinology

Repeated visual fields with IOP check in 1 month

Chiasmal syndrome secondary to pyruvate dehydrogenase deficiency

B

Magnetic resonance imaging of the brain/orbits

Junctional scotomas are visual field defects affecting the central or cecocentral visual field in 1 eye with a contralateral temporal deficit that respects the vertical midline. These scotomas localize to the junction of the optic nerve and chiasm and are not compatible with the diagnosis of glaucoma. The most frequent cause of junctional syndrome is pituitary adenoma,1 but it has also been reported in trauma, substance abuse, infection, inflammatory disease such as sarcoidosis or multiple sclerosis, meningioma, or aneurysm.2-4 Any patient with a junctional scotoma should undergo magnetic resonance imaging of the optic chiasm.Observation and repeating visual fields in 1 month (options A and D) are not appropriate because mass lesions, including pituitary apoplexy and aneurysm, frequently cause chiasmal syndrome and would require urgent treatment. Referral to endocrinology (option B) would not be appropriate at this time. Although the most common cause of chiasmal syndrome is a pituitary adenoma that would benefit from endocrinology consult, it would be inappropriate to make this referral without further evidence of a pituitary lesion.The pyruvate dehydrogenase complex is found in the mitochondria and is responsible for converting pyruvate to acetyl coenzyme A, thus producing the substrate for the tricarboxylic acid cycle and aerobic respiration. Deficits in pyruvate dehydrogenase lead to a decrease in aerobic respiration causing lactic acidosis and an increase in plasma concentrations of pyruvate. Owing to the high metabolic demand of the central nervous system tissue, neurologic manifestations of pyruvate dehydrogenase deficiency include peripheral neuropathy, ataxia, and seizures.5 Pyruvate dehydrogenase deficiency is a rare cause of optic neuropathy, and to our knowledge, there have only been 2 cases of optic neuropathy reported owing to pyruvate dehydrogenase deficiency.6,7 Similar to our case, both of these patients had ocular motility deficits with stable vision for many years before their acute visual loss owing to optic neuropathy. Owing to the rarity of patients surviving with pyruvate dehydrogenase deficiency to adulthood, there are no treatments that have been proven in prospective trials, but case reports have suggested that there are a subset of patients who respond to thiamine supplementation,8 activators of pyruvate dehydrogenase such as dichloroacetate,9 or a ketogenic diet.10Magnetic resonance imaging of the brain did not reveal abnormalities of the optic nerves or chiasm but did demonstrate atrophy of the cerebellum. Repeated serologic testing demonstrated increased levels of lactate and pyruvate. After 5 years of follow-up, his visual acuity remained stable at 20/30 OD and 20/70 OS. Ishihara color plates were 7/8 OD and 3/8 OS. His maximum IOP during this period was 17 mm Hg OU while receiving latanoprost. His fundus examination remained unchanged, and his mean deviation on visual fields remained stable in both eyes between his initial visit to his last follow-up (−10.00 dB to −9.34 dB OD and −16.23 dB to −16.69 dB OS).

Ophthalmology

A 52-year-old man was referred to the neuro-ophthalmology clinic for evaluation of visual field loss. He had exotropia and amblyopia of the left eye. He was diagnosed as having glaucoma 6 months prior to presentation owing to optic nerve cupping and visual field deficits on automated perimetry and was taking latanoprost. His medical history was significant for pyruvate dehydrogenase deficiency, and his family history was notable for glaucoma in his grandmother. He was being treated by the neurology department for his pyruvate dehydrogenase deficiency with thiamine, vitamin C, and oxaloacetate. His systemic symptoms included hyperhidrosis and episodes of hand tremors, ataxia, and dysarthria that occur every 2 to 3 years.Best-corrected visual acuity was 20/40 −2 OD and 20/100 +2 OS, with a relative afferent pupillary defect in the left eye. Intraocular pressure (IOP) was 16 mm Hg OU, and pachymetry was 611 μM OD and 592 μM OS (normal mean [SD], 542.4 [33.5] μM). He identified 8/8 OD and 3/8 OS Ishihara color plates. He had an exotropia with full range of motion in both eyes. His nuclear sclerotic cataracts were not consistent with visual acuity in both eyes; his anterior segment examination was otherwise within normal limits. His dilated examination was normal except for cupping and pallor in both eyes with a supratemporal optic nerve pit in the right eye. The optic discs and automated perimetry are shown in the Figure. Optical coherence tomography (OCT) of the retinal nerve fiber layer showed a mean thickness of 64 μM OD and 47 μM OS (normal mean [SD], 97.3 [9.6] μM), and OCT of the macula showed perifoveal thinning with normal foveal thickness in both eyes.A and B, Fundus photographs show cupping with optic nerve pallor in both eyes and a supratemporal optic nerve pit in the right eye (arrowhead). C and D, Automated perimetry demonstrating temporal hemianopia respecting the vertical midline in the left eye with cecocentral scotoma in the right eye, consistent with a junctional scotoma.Repeated visual fields with IOP check in 1 month

what would you do next?

What would you do next?

Observation

Magnetic resonance imaging of the brain/orbits

Repeated visual fields with IOP check in 1 month

Referral to endocrinology

b

male

51-60

original

https://jamanetwork.com/journals/jama/fullarticle/2734579

A 61-year-old man with a history of hypertension presented to the emergency department with a 1-day history of fever, dyspnea, and generalized weakness. His vital signs were temperature, 38.4°C (101.1°F); blood pressure, 94/40 mm Hg; heart rate, 116/min; and respiratory rate, 26/min. He was diaphoretic and had poor dentition. A soft S1 was present on cardiac examination, and crackles were auscultated in basilar lung fields bilaterally. Three sets of blood cultures from different sites were obtained. Cardiology, cardiac surgery, and infectious disease physicians were consulted. A bedside transthoracic echocardiogram was performed, the patient was transferred to the intensive care unit, and a transesophageal echocardiogram was obtained (Figure 1).Transesophageal echocardiogram obtained from the patient in diastole on the midesophageal long-axis view. What Would You Do Next?

Order diuresis with furosemide and serial echocardiograms

Perform emergency surgery for aortic valve repair

Place an intra-aortic balloon pump

Start broad-spectrum antibiotics and observe

Severe acute aortic regurgitation secondary to infective endocarditis

B

Perform emergency surgery for aortic valve repair

The key to the correct diagnosis is the presence of fever and hemodynamic instability with physical examination findings consistent with pulmonary edema and aortic regurgitation. Imaging demonstrated acute regurgitation, consistent with acute aortic valve insufficiency. Emergency intervention is indicated because of his symptoms of heart failure.Acute aortic regurgitation causes a sudden reflux of blood from the aorta into the left ventricle during diastole. Decreased cardiac output results in compensatory tachycardia and increased myocardial oxygen demand. The incompetent aortic valve reduces coronary arterial flow, impairing myocardial perfusion. Increased left atrial pressure causes flash pulmonary edema, leading to cardiopulmonary failure.1 Symptoms of acute aortic regurgitation include diaphoresis, fatigue, and dyspnea. Examination may reveal a widened pulse pressure from decreased diastolic pressure or a soft S1 murmur caused by increased left ventricular diastolic pressure and early mitral valve closure. A faint systolic murmur may be present if aortic regurgitation is severe. Bilateral crackles from pulmonary edema may be auscultated.1Acute native-valve aortic regurgitation is most commonly caused by infective endocarditis. As many as 54% of patients presenting with acute aortic regurgitation have infective endocarditis of the aortic valve.2 Risk factors include bicuspid aortic valve, previous infective endocarditis, and poor dentition.1,3 While 80% to 90% of acute native-valve aortic regurgitation is caused by staphylococci, streptococci, and enterococci, other organisms should be considered depending on risk factors for infective endocarditis, such as Candida in intravenous drug users. When infective endocarditis is suspected, 3 sets of blood cultures from different venipuncture sites should be collected and empirical antibiotics, such as vancomycin and cefepime, should be initiated.1,3 Early consultation with infectious disease specialists is important to ensure appropriate antibiotic selection. Using the modified Duke Criteria,1,4 a diagnosis of infective endocarditis can be established.4 The initial diagnostic test is a transthoracic echocardiogram because of its accessibility. A transesophageal echocardiogram is more sensitive than a transthoracic echocardiogram, with similar specificity in assessing hemodynamics and valvular damage in infective endocarditis (sensitivity, 70% vs 96%; specificity, 90% vs 90%),1 but the transesophageal echocardiogram is more invasive.Echocardiographic features associated with a complicated hospital course include ventricular dysfunction or perivalvular abscess. Severity of aortic regurgitation is based on pressure half-time (PHT; time for regurgitation to reach half of peak velocity), vena contracta (width of the regurgitant jet), and jet to left ventricular outflow tract (LVOT) ratio (ratio of regurgitant jet width to LVOT). Severe aortic regurgitation, defined as PHT of 300 m/s, jet:LVOT ratio greater than 0.65, or vena contracta wider than 6 mm, necessitates surgery, while regurgitation not meeting these criteria may be treated with antibiotics alone.5 Other indications for surgery include heart failure, endocarditis from organisms highly resistant to antibiotics, persistent fever and positive blood cultures despite appropriate antibiotics, mobile vegetations larger than 10 mm, septic emboli, and relapsing infection.5In severe aortic regurgitation, early intervention is associated with improved in-hospital and long-term mortality, and urgent surgical consultation is required.6 Initially, afterload reduction with nitroprusside and positive inotropy with dobutamine can improve hemodynamic function. β-Blockers should be avoided because of negative inotropic and chronotropic effects.1,3,7 Intra-aortic balloon pump is contraindicated in this setting because augmenting diastolic pressure worsens regurgitation.4Considerations for valve repair vs replacement include assessment of whether repair is likely to reestablish normal valve function and the increased thromboembolic risk associated with valve replacement. Compared with valve replacement, surgical repair is associated with better 5-year patient survival (88%-65%), comparable recurrence of infective endocarditis (6%-9%), but a lower 5-year rate of freedom from reoperation (65%-90%).7,8 There are no apparent advantages between replacement valve types in terms of reinfection (mechanical, bioprosthetic, homograft), but recent studies suggest better long-term patient survival with mechanical valves.9 Considerations include the need for lifelong anticoagulation with mechanical valves and the risk of structural deterioration of bioprosthetic valves.This patient’s transesophageal echocardiogram demonstrated central jet width of 67% of the LVOT, consistent with severe acute aortic regurgitation. Vegetations were identified between the left and right coronary cusps (Figure 2). The patient was started on intravenous dobutamine and taken to the operating room for emergency aortic valve replacement with a bioprosthetic valve. Intraoperative cultures isolated methicillin-sensitive Staphylococcus aureus. Postoperatively, the patient was treated for 6 weeks with intravenous nafcillin. Three weeks postoperatively he had normal ventricular function and no evidence of aortic regurgitation. He followed up with his dentist for treatment of his poor dentition.

General

A 61-year-old man with a history of hypertension presented to the emergency department with a 1-day history of fever, dyspnea, and generalized weakness. His vital signs were temperature, 38.4°C (101.1°F); blood pressure, 94/40 mm Hg; heart rate, 116/min; and respiratory rate, 26/min. He was diaphoretic and had poor dentition. A soft S1 was present on cardiac examination, and crackles were auscultated in basilar lung fields bilaterally. Three sets of blood cultures from different sites were obtained. Cardiology, cardiac surgery, and infectious disease physicians were consulted. A bedside transthoracic echocardiogram was performed, the patient was transferred to the intensive care unit, and a transesophageal echocardiogram was obtained (Figure 1).Transesophageal echocardiogram obtained from the patient in diastole on the midesophageal long-axis view.

what would you do next?

What would you do next?

Perform emergency surgery for aortic valve repair

Order diuresis with furosemide and serial echocardiograms

Place an intra-aortic balloon pump

Start broad-spectrum antibiotics and observe

a

male

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2729747

A man in his 50s presented with dysphagia, arthritis, joint contractures, carpal tunnel syndrome, and infiltrated and redundant skin with sheets of 1- to 2-mm-wide waxy, firm, skin-colored papules. The patient first noticed papules on his forehead 1 year prior to presentation that spread to his face, trunk, and extremities. He had mild dysphagia and severe joint pain in his hands and wrists, with carpal tunnel of his right wrist. Additionally, his daily activities were impaired owing to decreased mobility. During clinical evaluation, he denied cough, shortness of breath, chest pain, Raynaud phenomenon, fevers, night sweats, weight loss, seizures, or confusion.Physical examination revealed diffuse skin-colored to pink papules coalescing into plaques on the entire face, with exaggerated skin folds of the forehead (Figure, A), glabella, periocular regions, and superior cutaneous lip. This was accompanied by swelling and erythema of both ears. On his extremities and trunk, he had diffuse infiltration of the skin, with exaggerated skin folds (Figure, B), decreased finger flexion, and four-fifths grip strength. His nailfold capillaries were normal. Skin sensation was intact.A, Clinical image of the exaggerated skin folds of the forehead and glabella. B, Clinical image of the wrist and hand depicting the exaggerated skin folds and decreased finger flexion. C, Hematoxylin-eosin stain image from the punch biopsy featuring fibroblastic proliferation from the papillary to the reticular dermis (original magnification ×40). D, Hematoxylin-eosin and Alcian blue stain image featuring mucin deposition in the reticular dermis.Notable laboratory results included a normal level of thyroid-stimulating hormone, macrocytic anemia, normal creatinine and calcium levels, and a monoclonal spike on a serum protein electrophoresis test. Serum free light chains revealed normal κ free light chains, λ free light chains, and a normal κ/λ ratio. Immunofixation results revealed IgG λ monoclonal gammopathy. A punch biopsy was obtained for diagnostic clarification (Figure, C and D). What Is Your Diagnosis?

Cutaneous T-cell lymphoma (mycosis fungoides [MF])

Scleromyxedema

Lepromatous leprosy

Scleroderma

B. Scleromyxedema

B

Scleromyxedema

Histologic results of the biopsy showed a fibroblastic proliferation from the papillary to the reticular dermis, with admixed lymphocytes (Figure, C). There was a notable increase in dermal mucin, highlighted with Alcian blue (Figure, D). The biopsy results were consistent with scleromyxedema. Scleromyxedema is a rare, chronic, and progressive disease that can result in death.1 It usually occurs in middle-aged individuals in association with paraproteinemia.1 Immunoglobulin G λ light chain monoclonal gammopathy is associated in almost 80% of cases, with an average 1% per-year risk of progression to multiple myeloma.2,3Typical cutaneous findings in scleromyxedema include a generalized eruption of 1- to 3-mm-wide, firm, skin-colored to pink, flat-topped or dome-shaped papules coalescing into infiltrated plaques.1-3 The coalescing plaques and surrounding skin are often indurated and may have a shiny appearance. Additional distinguishing features include deep furrows on the trunk or extremities, producing the characteristic “shar-pei sign.” As the skin becomes infiltrated, patients may develop decreased oral aperture and decreased motility of smaller joints. The “donut sign” is a classic finding referring to a central depression surrounded by an elevated rim of thickened skin in the proximal interphalangeal joints. Finally, patients with scleromyxedema often develop deep facial furrows producing the characteristic leonine facies. Histopathological findings include an increased number of fibroblasts and stromal cells, thickened collagen bundles with variable amounts of mucin deposition in the mid and deep dermis, and sparing of the papillary dermis.3,4Systemic sclerosis (scleroderma) typically begins with edematous hands in combination with Raynaud phenomenon and nailfold capillary dilation and hemorrhage—findings not seen in scleromyxedema. The edema then progresses to sclerodactyly (tight, bound-down skin with tapering of the fingers), in contrast to the mobile and redundant skin seen in scleromyxedema. Patients with systemic sclerosis develop “pinched noses” and appear younger owing to loss of facial wrinkling from sclerosis. Patients with systemic sclerosis do not develop leonine facies. Histopathologic examination of systemic sclerosis reveals increased collagen deposition without an associated increase in fibroblasts or mucin, in contrast to the increase in fibroblasts and mucin typically seen in scleromyxedema.4-6Lepromatous leprosy and MF can also present with leonine facies and should be part of the differential diagnosis.7 As with scleromyxedema, lepromatous leprosy can also present with earlobe infiltration. Distinguishing clinical findings in lepromatous leprosy include saddle nose deformity, madarosis, rhinitis, oral and nasal nonhealing ulcers, and acquired ichthyosis. Lesions of lepromatous leprosy are often accompanied by anesthesia, hypoesthesia, and paresthesia. Eye findings include lagophthalmos, corneal anesthesia, episcleritis, and/or keratitis. Left untreated, patients with lepromatous leprosy will develop characteristic red or copper-colored papules or nodules called lepromas. The histopathological findings of lepromatous leprosy include a normal epidermis, a band of normal-appearing dermis (Grenz zone), and a nodular infiltrate of foamy histiocytes (Virchow cells), plasma cells, and lymphocytes with abundant bacilli and globi (clumps of bacilli). Typically, MF presents with well-defined, erythematous, pruritic patches in UV-protected areas.8 Leonine facies is a rare presentation of MF that has been associated with folliculotropic involvement, stage IV disease, and blood involvement.9 Histopathological findings of MF include superficial perivascular and perifollicular infiltrate with folliculotropism.8 There is a variable amount of mucinous degeneration of the follicular epithelium that is more evident with special stains, including Alcian blue or colloidal iron. There is no increase in fibroblasts.The diagnosis of scleromyxedema requires the combination of characteristic clinical and histopathological findings without thyroid disease.1-3 Our patient presented with typical cutaneous and extracutaneous findings of scleromyxedema with corroborative biopsy results. Once the patient completed 6 months of intravenous immunoglobulin therapy in combination with systemic glucocorticoids, his systemic symptoms resolved, and his skin findings dramatically improved. He remained in remission 1.5-years later without further therapy.

Dermatology

A man in his 50s presented with dysphagia, arthritis, joint contractures, carpal tunnel syndrome, and infiltrated and redundant skin with sheets of 1- to 2-mm-wide waxy, firm, skin-colored papules. The patient first noticed papules on his forehead 1 year prior to presentation that spread to his face, trunk, and extremities. He had mild dysphagia and severe joint pain in his hands and wrists, with carpal tunnel of his right wrist. Additionally, his daily activities were impaired owing to decreased mobility. During clinical evaluation, he denied cough, shortness of breath, chest pain, Raynaud phenomenon, fevers, night sweats, weight loss, seizures, or confusion.Physical examination revealed diffuse skin-colored to pink papules coalescing into plaques on the entire face, with exaggerated skin folds of the forehead (Figure, A), glabella, periocular regions, and superior cutaneous lip. This was accompanied by swelling and erythema of both ears. On his extremities and trunk, he had diffuse infiltration of the skin, with exaggerated skin folds (Figure, B), decreased finger flexion, and four-fifths grip strength. His nailfold capillaries were normal. Skin sensation was intact.A, Clinical image of the exaggerated skin folds of the forehead and glabella. B, Clinical image of the wrist and hand depicting the exaggerated skin folds and decreased finger flexion. C, Hematoxylin-eosin stain image from the punch biopsy featuring fibroblastic proliferation from the papillary to the reticular dermis (original magnification ×40). D, Hematoxylin-eosin and Alcian blue stain image featuring mucin deposition in the reticular dermis.Notable laboratory results included a normal level of thyroid-stimulating hormone, macrocytic anemia, normal creatinine and calcium levels, and a monoclonal spike on a serum protein electrophoresis test. Serum free light chains revealed normal κ free light chains, λ free light chains, and a normal κ/λ ratio. Immunofixation results revealed IgG λ monoclonal gammopathy. A punch biopsy was obtained for diagnostic clarification (Figure, C and D).

what is your diagnosis?

What is your diagnosis?

Scleroderma

Scleromyxedema

Lepromatous leprosy

Cutaneous T-cell lymphoma (mycosis fungoides [MF])

b

male

51-60

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2730770

A man in his 60s presented with a 10-year history of a slowly progressive, asymptomatic cutaneous eruption on his left leg (Figure 1A). He had a 16-year history of diabetes mellitus that was being treated with metformin. Hematological and biochemical test results were unremarkable. There was no history of another endocrine disorder or malignant neoplasm. There was no family history of similar cutaneous findings. Physical examination revealed reddish brown hyperkeratotic papules 1 to 10 mm wide on the front and back of the left leg from knee to ankle. The rest of the physical examination findings were unremarkable. Removal of the scales caused slight bleeding. A lesional skin biopsy was performed (Figure 1B and C).A, Clinical image of the reddish brown hyperkeratotic papules on the front of the left leg. B and C, Hematoxylin-eosin–stained lesional skin biopsy specimens revealing compact hyperkeratosis, epidermal atrophy, and bandlike lymphocyte infiltrate in the superficial dermis. What Is Your Diagnosis?

Stucco keratoses

Hyperkeratosis lenticularis perstans

Disseminated superficial actinic porokeratosis

Kyrle disease

B. Hyperkeratosis lenticularis perstans

B

Hyperkeratosis lenticularis perstans

Histopathologic examination revealed focal epidermal atrophy, orthokeratotic hyperkeratosis, and a bandlike infiltrate of lymphocytes in the superficial dermis compatible with unilateral hyperkeratosis lenticularis perstans (HLP) (Figure 1B and C). He was treated with acitretin and topical tacalcitol with substantial improvement of his cutaneous lesions (Figure 2).The clinical image after treatment with systemic retinoids and vitamin D derivates demonstrates improvement of hyperkeratotic papules.Described by Flegel1 in 1958, HLP is a disease of uncertain origin, though it has been shown to have an autosomal dominant inheritance pattern with late onset.2 This rare disorder is characterized by numerous symmetric hyperkeratotic papules. Lesions are most common on the distal portion of the legs and dorsal surface of the feet. Arms, palms, and soles can be affected. Other parts of the body, including the oral mucosa, are rarely affected, and the trunk is usually spared.3 The patient has localized unilateral HLP, which is a rarely seen form of the disease4,5 The lesions are usually hyperkeratotic papules 1 to 5 mm in diameter, with an initial erythematous coloration that with time acquires brownish coloration. When the papules are dislodged, they give rise to a depression with punctate bleeding. It runs a chronic course, and lesions persist indefinitely.Histologically, there is compact hyperkeratosis with focal parakeratosis on an atrophic epidermis, with a thinned or absent stratum granulosum. In the papillary dermis, there is a band of lymphocytic infiltrate with dilatation and proliferation of superficial vessels.6 Given the rarity of cases, no standard modality exists for treatment. Reported treatments include topical tretinoin, fluorouracil cream, and vitamin D derivates.7,8 Systemic retinoids have been used with good results.9,10Differential diagnosis of HLP includes causes of acral keratosis, particularly stucco keratoses, disseminated superficial actinic porokeratosis, and Kyrle disease. Stucco keratoses are usually located on the distal portion of the extremities and clinically manifest as small, scaly white or greyish hyperkeratotic papules, but they do not bleed when scraped off, and histopathologic evaluation reveals hyperkeratosis with epidermal hyperplasia instead of atrophy of the epidermis. Disseminated superficial actinic porokeratosis is characterized by brownish hyperkeratotic papules predominantly found on the arms and legs, and symptoms appear later in adult life. The papules have a hyperkeratotic ridge at the periphery, and histologic results show the presence of cornoid lamellae. Acquired reactive perforating dermatosis (Kyrle disease) presents with keratotic papules up to 1 cm in diameter that are seen primarily on the legs and arms. It is most often seen in conjunction with diabetes or renal failure. Kyrle disease has more prominent keratotic plugs, and there is transepidermal elimination of connective tissue.This patient had an uncommon presentation of HLP given the rarity of unilateral presentation. It is important for clinicians to recognize HLP because it may mimic other more common dermatoses such as porokeratosis or stucco keratoses.

Dermatology

A man in his 60s presented with a 10-year history of a slowly progressive, asymptomatic cutaneous eruption on his left leg (Figure 1A). He had a 16-year history of diabetes mellitus that was being treated with metformin. Hematological and biochemical test results were unremarkable. There was no history of another endocrine disorder or malignant neoplasm. There was no family history of similar cutaneous findings. Physical examination revealed reddish brown hyperkeratotic papules 1 to 10 mm wide on the front and back of the left leg from knee to ankle. The rest of the physical examination findings were unremarkable. Removal of the scales caused slight bleeding. A lesional skin biopsy was performed (Figure 1B and C).A, Clinical image of the reddish brown hyperkeratotic papules on the front of the left leg. B and C, Hematoxylin-eosin–stained lesional skin biopsy specimens revealing compact hyperkeratosis, epidermal atrophy, and bandlike lymphocyte infiltrate in the superficial dermis.

what is your diagnosis?

What is your diagnosis?

Disseminated superficial actinic porokeratosis

Stucco keratoses

Hyperkeratosis lenticularis perstans

Kyrle disease

c

male

0-10

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2729008

A man in his 60s was evaluated in the epilepsy monitoring unit for various spells he had been having up to 5 times a day over the previous 8 months. He described transient episodes of expressive speech difficulties, paroxysmal dizziness, and involuntary nonsuppressible jerks of the right arm, which occurred without warning and were associated with mild disorientation. Video electroencephalography (EEG) captured the movements (Figure, A). They consisted of involuntary, synchronous contractions of the right face, arm, and leg that were sustained for a few seconds before muscle relaxation occurred (Figure, B and C; Video). The movements were not elicited by action or exertion. There was no epileptic abnormality that correlated with the movements on EEG, and head magnetic resonance imaging was unremarkable.A, Electroencephalogram (EEG) during the event (bipolar montage, 60-Hz filter, 7-uV/mm sensitivity). B, Patient position prior to the event. C, Patient position while experiencing an involuntary, sustained contraction of the right lower face, arm, and leg lasting almost 2 seconds before spontaneous resolution. The event took place during the time span marked with red vertical lines on the EEG and did not show a clear change from baseline rhythm. Muscle artifacts are seen prior to and during the event. What Is Your Diagnosis?

Myoclonus

Paroxysmal dyskinesia

Faciobrachial dystonic seizures

Tic disorder

C. Faciobrachial dystonic seizures

C

Faciobrachial dystonic seizures

Paroxysmal dyskinesia (choice B) is unlikely, because the phenomena are not triggered by movement or exertion, which would suggest kinesigenic or exercise-induced dyskinesia, respectively. Paroxysmal nonkinesigenic dyskinesia may occur, but the attacks would last minutes to hours rather than seconds. Furthermore, his age at onset is late for this group of genetic disorders. A tic disorder (choice D) is also unlikely, because there is no premonitory urge that is relieved by performing the tic, and the movement is not even briefly suppressible. The movement is jerky, but contractions are sustained for a few seconds, which is too prolonged for myoclonus (choice A) and more reminiscent of dystonic posturing.The phenomenology of the patient’s abnormal movement was most closely in keeping with faciobrachial dystonic seizures (FBDS), and serum testing was positive for anti–leucine-rich glioma-inactivated 1 (LGI-1) antibodies by a cell-based assay. These tonic muscle contractions classically affect the lower face and ipsilateral arm, but involvement of the leg, alternating episodes, or bilateral episodes may occur.1 They are typically brief (<3 seconds) and can occur up to hundreds of times a day.2 These movements are nearly pathognomonic for anti–LGI-1 autoimmunity and can be seen in about half of patients with this trait.3 Although EEG is frequently obscured by muscle artifact, preceding rhythmic δ activity and EEG attenuation after FBDS may be seen.4 Associated ictal features may occur with FBDS, including fear, oral automatism, and/or loss of awareness.4The LGI-1 protein is secreted by neurons in the central nervous system and forms a transsynaptic complex involved in synaptic transmission of neuronal excitability.5 The association between LGI-1 protein dysfunction and altered neuronal excitability is seen in autosomal-dominant lateral temporal–lobe epilepsy, also known as autosomal-dominant partial epilepsy with auditory features, in which an LGI-1 gene mutation is identified in one-third to half of affected individuals.6 This disorder is usually characterized by a family history of focal seizures, often involving auditory auras (humming, buzzing, ringing, or [less frequently] complex sounds or distortions) or ictal aphasia in the absence of structural abnormalities or other substantial neurological deficits.6Anti–LGI-1 IgG4 antibodies are thought to be causative of LGI-1 encephalitis, which is the second most common cause of autoimmune encephalitis after anti–N-methyl-d-aspartate receptor encephalitis and has an incidence of about 1 case per million population.5 Anti–LGI-1 autoimmunity often begins with subtle focal seizures or FBDS, which precede the onset of cognitive decline, personality changes, psychiatric symptoms, and tonic-clonic seizures typical of autoimmune limbic encephalitis.3 Other clinical manifestations include sleep disturbances, paroxysmal dizzy spells, parkinsonism, and myoclonus.7 Hyponatremia may be found in up to half of affected patients and can be a clue to the diagnosis. A malignant condition is identified in about 10% of patients and may occur in the thymus, lung, breasts, prostate, ovaries, kidneys, or alimentary tract.5 On magnetic resonance imaging, T2 hyperintensity of the medial temporal lobes is commonly found in patients with anti–LGI-1 limbic encephalitis, and T1 hyperintensity of the basal ganglia may be seen in patients with FBDS.7Recognition of FBDS is crucial to arrange for appropriate testing of anti–LGI-1 antibodies. Serum should be tested, because it may have a higher sensitivity than cerebrospinal fluid.3,7 Expedited immunotherapy in patients with FBDS is more effective than antiseizure medications to control the movements and is associated with reduced long-term disability.8 Early treatment may also prevent the evolution from FBDS to limbic encephalitis in patients with preserved cognition, further emphasizing the need to accurately diagnose these movements promptly.1 Even with immunotherapy, however, relapses can occur in one-third of patients,3 and close clinical monitoring is required so that treatment can be intensified if necessary.The patient was treated with 1-g doses of intravenous methylprednisolone for 5 days, with an oral prednisone taper that consisted of 50 mg daily for a month, followed by further decreases of 10 mg monthly. After 1 day of treatment, he had full resolution of FBDS and no further spells of any kind. On 4-month follow-up, he continued to be symptom-free.

Neurology

A man in his 60s was evaluated in the epilepsy monitoring unit for various spells he had been having up to 5 times a day over the previous 8 months. He described transient episodes of expressive speech difficulties, paroxysmal dizziness, and involuntary nonsuppressible jerks of the right arm, which occurred without warning and were associated with mild disorientation. Video electroencephalography (EEG) captured the movements (Figure, A). They consisted of involuntary, synchronous contractions of the right face, arm, and leg that were sustained for a few seconds before muscle relaxation occurred (Figure, B and C; Video). The movements were not elicited by action or exertion. There was no epileptic abnormality that correlated with the movements on EEG, and head magnetic resonance imaging was unremarkable.A, Electroencephalogram (EEG) during the event (bipolar montage, 60-Hz filter, 7-uV/mm sensitivity). B, Patient position prior to the event. C, Patient position while experiencing an involuntary, sustained contraction of the right lower face, arm, and leg lasting almost 2 seconds before spontaneous resolution. The event took place during the time span marked with red vertical lines on the EEG and did not show a clear change from baseline rhythm. Muscle artifacts are seen prior to and during the event.

what is your diagnosis?

What is your diagnosis?

Faciobrachial dystonic seizures

Paroxysmal dyskinesia

Myoclonus

Tic disorder

a

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2728251

A woman in her early 70s with a history of hypertension, Cushing disease status post–pituitary radiotherapy (1973), left sphenoid wing meningioma involving the left optic nerve and cavernous sinus status postsurgical debulking (2009), radiotherapy with concurrent temozolomide followed by intravenous bevacizumab, and a single prior episode of deep venous thrombosis presented with 2 months of eye redness and decreased vision in her right eye. She previously received a diagnosis of viral conjunctivitis at an outside institution and was treated with topical prednisolone acetate without improvement before presenting to our institution. On examination, visual acuity was 20/25 OD and hand motions OS. A relative afferent pupillary defect was present on the left in the setting of left optic atrophy from the patient’s locally invasive meningioma. Confrontational visual fields were otherwise full in the right eye. Intraocular pressures were within normal limits in both eyes. Hertel exophthalmometry was notable for 3 mm of proptosis on the right. Slitlamp examination demonstrated 3 to 4+ meibomian gland dysfunction in both eyes, but with prominent conjunctival injection in the right eye only. Dilated funduscopy revealed scattered intraretinal hemorrhages (IRHs) and cystoid macular edema (CME) in the right eye, which was also seen on optical coherence tomography (Figure 1). Vital signs, complete blood cell count, and the results of thyroid function tests were within reference ranges. Magnetic resonance imaging and magnetic resonance angiography of the brain and orbits with and without contrast showed a stable size of the meningioma and were otherwise normal.A, Color fundus photograph of the right eye showing scattered intraretinal hemorrhages and a blunted foveal light reflex. B, Optical coherence tomography of the right eye showing cystoid macular edema manifesting as foveal-involving cystoid intraretinal spaces and a small pocket of subfoveal subretinal fluid.Perform an intravitreal injection of an antivascular endothelial growth factor agent What Would You Do Next?

Perform an intravitreal injection of an antivascular endothelial growth factor agent

Start systemic corticosteroids

Obtain laboratory workup for uveitis

Order cerebral angiography

Venous stasis retinopathy in the right eye associated with a right carotid-cavernous sinus fistula

D

Order cerebral angiography

The differential diagnosis for CME with IRHs includes retinal vein occlusion, microvascular disease (eg, diabetic retinopathy, radiation retinopathy), hyperviscosity syndrome (eg, plasma cell dyscrasias), and orbital diseases resulting in impaired venous outflow. This patient initially presented elsewhere with eye redness and decreased vision in the right eye, but by the time she presented to our institution, there was greater evidence of inadequate venous outflow (ie, unilateral proptosis, corkscrew vessels extending to the limbus, blood in Schlemm canal, IRHs, and CME). These findings can classically result from venous congestion (eg, thyroid eye disease, retrobulbar mass), arteriovenous fistulization (eg, carotid cavernous sinus fistula [CCF], Sturge-Weber syndrome), or an idiopathic disease (eg, Radius-Maumenee syndrome).1 The patient’s neuroimaging was unrevealing, but given the strong clinical suspicion for CCF, a cerebral angiogram was obtained, which revealed an indirect CCF supplied by dural branches of the right cavernous internal carotid artery. Cerebral angiography is considered to be the diagnostic standard and can detect a CCF missed by less-invasive neuroimaging methods (eg, magnetic resonance angiography). In this case, use of an antivascular endothelial growth factor agent would be inappropriate because doing so would delay the diagnosis and timely treatment of the underlying CCF. Systemic therapy with corticosteroids and a laboratory workup for uveitis are also unwarranted because there was no evidence of concurrent intraocular or orbital inflammation.A CCF is an abnormal vascular communication between the internal and/or external carotid artery and cavernous sinus and may present with any combination of unilateral proptosis, engorged episcleral vessels, chemosis, diplopia, decreased vision, and even stroke.2 It may present with a bruit or pulsatile proptosis, neither of which was present in the patient described herein. The Barrow classification system categorizes CCFs as direct (type A) and indirect (types B-D).3 Direct CCFs are high-flow fistulas that typically occur following head trauma, progress rapidly, and require urgent treatment. Indirect CCFs, however, are low-flow fistulas classically seen in elderly women that tend to present more insidiously, with conjunctival injection and chemosis being the most common presenting signs.4Carotid-cavernous sinus fistulas can also present with decreased vision owing to CME and IRHs. Venous stasis retinopathy is more frequently associated with indirect CCFs and may not manifest until the venous system posterior to the cavernous sinus becomes obstructed and arterial blood flow is redirected anteriorly to the orbit, resulting in chemosis, proptosis, IRHs, CME, retinal ischemia, optic neuropathy, and/or secondary glaucoma from elevated episcleral venous pressure.5,6 When IRHs are observed, fluorescein angiography may help to determine the state of retinal perfusion and, thus, visual prognosis.Whereas direct CCFs should be treated urgently, indirect CCFs may spontaneously close and can be observed.2-4 However, indirect CCFs that fail to self-thrombose or are vision threatening (eg, severe exposure keratopathy, venous stasis retinopathy, optic neuropathy, secondary glaucoma) should be promptly treated. Endovascular embolization is considered to be the treatment of choice, with good long-term outcomes and low complication rates.7 Return of baseline visual acuity after successful CCF closure has been previously reported.8,9The patient’s CCF was embolized by neurosurgery. One week later, her vision returned to baseline, with marked improvement of her CME (Figure 2).Optical coherence tomography of the right eye showing marked improvement in cystoid macular edema within 1 week of endovascular embolization.

Ophthalmology

A woman in her early 70s with a history of hypertension, Cushing disease status post–pituitary radiotherapy (1973), left sphenoid wing meningioma involving the left optic nerve and cavernous sinus status postsurgical debulking (2009), radiotherapy with concurrent temozolomide followed by intravenous bevacizumab, and a single prior episode of deep venous thrombosis presented with 2 months of eye redness and decreased vision in her right eye. She previously received a diagnosis of viral conjunctivitis at an outside institution and was treated with topical prednisolone acetate without improvement before presenting to our institution. On examination, visual acuity was 20/25 OD and hand motions OS. A relative afferent pupillary defect was present on the left in the setting of left optic atrophy from the patient’s locally invasive meningioma. Confrontational visual fields were otherwise full in the right eye. Intraocular pressures were within normal limits in both eyes. Hertel exophthalmometry was notable for 3 mm of proptosis on the right. Slitlamp examination demonstrated 3 to 4+ meibomian gland dysfunction in both eyes, but with prominent conjunctival injection in the right eye only. Dilated funduscopy revealed scattered intraretinal hemorrhages (IRHs) and cystoid macular edema (CME) in the right eye, which was also seen on optical coherence tomography (Figure 1). Vital signs, complete blood cell count, and the results of thyroid function tests were within reference ranges. Magnetic resonance imaging and magnetic resonance angiography of the brain and orbits with and without contrast showed a stable size of the meningioma and were otherwise normal.A, Color fundus photograph of the right eye showing scattered intraretinal hemorrhages and a blunted foveal light reflex. B, Optical coherence tomography of the right eye showing cystoid macular edema manifesting as foveal-involving cystoid intraretinal spaces and a small pocket of subfoveal subretinal fluid.Perform an intravitreal injection of an antivascular endothelial growth factor agent

what would you do next?

What would you do next?

Order cerebral angiography

Obtain laboratory workup for uveitis

Start systemic corticosteroids

Perform an intravitreal injection of an antivascular endothelial growth factor agent

a

female

71-80

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2728252

A 75-year-old woman was referred to the ophthalmology clinic for evaluation of double vision and a droopy left upper eyelid. Over the previous 5 months, the patient had experienced gradual onset of binocular, horizontal diplopia and ptosis of the left upper eyelid. There were no neurological deficits and no pain. Her symptoms were constant, without fluctuation during the day. There was no history of trauma or prior surgery of the eye. Her medical history was notable for hypertension and type 2 diabetes. Family history was positive for hypertension in her mother, prostate cancer in her father, and ductal carcinoma in situ in her daughter. She was a current daily smoker at presentation. An ophthalmologic examination revealed a visual acuity of 20/25 OD and 20/30 OS. Pupillary, intraocular pressure, and dilated fundus examinations were unremarkable. Abduction was severely restricted in the left eye, but it did not elicit pain, and extraocular muscle movements were otherwise full. There was substantial resistance to retropulsion of the left eye. Bilateral blepharoptosis, with more severity on the left side, was noted. The margin-to-reflex distance 1 was 2 mm on the right and 0 mm on the left. A 3.5-mm left enophthalmos was noted compared with the right side, and there was hollowing of the left superior sulcus. Testing of cranial nerves V and VII were unremarkable.Computed tomographic scan of the orbits with contrast What Would You Do Next?

Computed tomographic scan of the orbits with contrast

Myasthenia gravis testing

Referral for strabismus surgery

Thyroid function testing

Infiltrating lobular breast carcinoma

A

Computed tomographic scan of the orbits with contrast

While the differential diagnosis of strabismus is broad, the findings of enophthalmos and resistance to retropulsion of the globe, in the context of the patient’s age, sex, and family history of cancer, should raise concern for a malignant orbital causative mechanism. Myasthenia gravis testing (choice B) would not be preferred because the patient lacks the characteristic fluctuating symptoms. Thyroid function testing (choice D) would not be preferred because thyroid dysfunction would be expected to have presented earlier in life. Strabismus surgery (choice C) would not address the underlying cause of strabismus. Furthermore, pursuing laboratory testing or strabismus surgery may delay the diagnosis of a malignant and potentially fatal condition.Orbital computed tomography and magnetic resonance imaging with contrast (choice A) were performed and demonstrated a diffuse infiltrative lesion within the left orbit, including the extraocular muscles (Figure). The patient underwent a left orbitotomy with exploration and biopsy of the mass, which produced pathological findings consistent with infiltrating lobular breast carcinoma. Although a breast examination revealed fullness of the left breast near the areola, a diagnostic mammogram, breast ultrasonography, and magnetic resonance imaging of the breast were unremarkable. Despite negative imaging, she underwent a core-needle biopsy of the left breast in the area of fullness, which confirmed the diagnosis of an infiltrating, well-differentiated breast carcinoma with lobular features.Fat-suppressed, T1-weighted, post-contrast magnetic resonance image of the orbits demonstrating a diffuse infiltration of the left intraconal and extraconal orbital contents, not easily distinguished from and isointense to the extraocular muscles (arrowheads). There is gross enophthalmos of the left globe compared with the right.Breast carcinoma is the most common primary tumor to metastasize to the orbits.1 Orbital breast carcinoma metastases characteristically involve infiltration of the extraocular muscles and orbital fat. While this tumor classically involves cicatrization that results in enophthalmos, as in this case, some patients may present with exophthalmos.2 Typically, orbital metastasis will occur late in the course of breast cancer, with a mean latency between the diagnosis of primary and metastatic orbital disease of 5 years,3 with a maximum latency of as many as 25 years.4 Therefore, it is quite rare for an orbital metastasis to be the presenting finding. In such cases, breast examination or imaging will typically be revealing of the primary tumor.4-6 The presented case was unique in the absence of radiographic evidence of a primary malignant condition.In most cases of orbital breast carcinoma metastasis, personal medical history will be revealing of the primary tumor, and biopsy of the orbital lesion may be deferred.7 However, absence of established diagnosis of a primary malignant condition does not rule out the possibility of metastasis, and imaging is essential in such cases. Imaging may provide diagnostic clues,8 and a biopsy will provide definitive diagnosis and guide further testing or treatment.Treatment of orbital breast carcinoma typically involves systemic chemotherapy. External-beam radiotherapy is a generally safe and effective adjunctive treatment option,2,9 but it must be weighed against the risks of radiation to the orbit. Surgical excision is generally contraindicated, because this would not cure the underlying disease and can cause considerable morbidity, depending on the extent of involvement. However, it may be considered in case of severe symptoms refractory to other palliative efforts.2This case demonstrates the possibility that an ophthalmologist may be the first to diagnose a metastatic malignant condition such as breast carcinoma. The ophthalmologist should be aware of this possibility, and metastasis should remain on the differential in the appropriate clinical context, even in the absence of a personal cancer history in the patient. Imaging with thin-cut orbital sections should be considered in patients with strabismus but also those with enophthalmos and resistance to retropulsion.The patient is currently undergoing chemotherapy. Radiotherapy to the orbit is deferred unless she develops worsening visual symptoms or progression.

Ophthalmology

A 75-year-old woman was referred to the ophthalmology clinic for evaluation of double vision and a droopy left upper eyelid. Over the previous 5 months, the patient had experienced gradual onset of binocular, horizontal diplopia and ptosis of the left upper eyelid. There were no neurological deficits and no pain. Her symptoms were constant, without fluctuation during the day. There was no history of trauma or prior surgery of the eye. Her medical history was notable for hypertension and type 2 diabetes. Family history was positive for hypertension in her mother, prostate cancer in her father, and ductal carcinoma in situ in her daughter. She was a current daily smoker at presentation. An ophthalmologic examination revealed a visual acuity of 20/25 OD and 20/30 OS. Pupillary, intraocular pressure, and dilated fundus examinations were unremarkable. Abduction was severely restricted in the left eye, but it did not elicit pain, and extraocular muscle movements were otherwise full. There was substantial resistance to retropulsion of the left eye. Bilateral blepharoptosis, with more severity on the left side, was noted. The margin-to-reflex distance 1 was 2 mm on the right and 0 mm on the left. A 3.5-mm left enophthalmos was noted compared with the right side, and there was hollowing of the left superior sulcus. Testing of cranial nerves V and VII were unremarkable.Computed tomographic scan of the orbits with contrast

what would you do next?

What would you do next?

Referral for strabismus surgery

Myasthenia gravis testing

Computed tomographic scan of the orbits with contrast

Thyroid function testing

c

female

71-80

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2729895

A 74-year-old man was referred to the ocular oncology clinic for a right eye corneal mass. He had a history of herpetic keratitis and cataract surgery 2 years prior, both in the right eye, complicated by postoperative bullous keratopathy without treatment. The patient noted a corneal scar after the cataract surgery that gradually thickened over the ensuing 6 months. In our office, his examination in the right eye was notable for hand motion visual acuity and a pearly white, raised, 10 × 10-mm, gelatinous, corneal lesion with both intrinsic and feeder vessels (Figure 1A). There was no view of the anterior segment. Ultrasound biomicroscopy showed a hyperechoic opacity on the surface of the cornea, with maximal thickness of 1.5 mm. A cleft was noted between the lesion and the cornea (Figure 1B). There was no extension posteriorly into the anterior chamber, iris, or ciliary body.A, Slitlamp external photograph of right-eye corneal lesion showing prominent elevation and both intrinsic and feeder vessels. B, Ultrasound biomicroscopy showing hyperechoic anterior corneal lesion with hypoechoic cleft labeled centrally. The lesion did not involve any other adjacent structures. What Would You Do Next?

Local therapy with 5-fluorouracil

Incisional biopsy

Excisional biopsy

Observe

Corneal keloid

C

Excisional biopsy

Given the cleft seen on biomicroscopy (Figure 1B), a #57 ultrasharp blade was used to gently but completely excise the lesion. Pathology results were positive for corneal keloid (hyperplastic corneal pannus),1 a rare corneal lesion usually occurring during the first 3 decades of life.2 No link has been found with cutaneous keloids, nor is this lesion more common among African American or Asian individuals. While bilateral cases are typically associated with systemic disorders such as Lowe syndrome and Rubenstein-Taybi syndrome, isolated unilateral cases are usually secondary to corneal trauma, surgery, keratouveitis, or infection.3-8Ultrasound biomicroscopy is helpful in defining the extent of these hyperechoic lesions and involvement of adjacent ocular structures, which is uncommon (Figure 1B). The differential diagnosis of corneal keloid includes (in order of relevance in this case) squamous cell carcinoma, limbal dermoid, corneal myxoma, Salzmann nodular degeneration, fibrous histiocytoma, anterior staphyloma, metabolic disease, and others. While diagnosis can be made based on clinical presentation, the gold standard is histopathologic examination. In contrast to true cutaneous keloids, the corneal variant is marked by less prominent hyalinized collagen bundles, disruption of the Bowman membrane, and increased relative cellularity and vascularity (Figure 2).9 This histologic distinction supports abandoning the term keloid for hyperplastic pannus.1 Pathogenesis is still debatable, but evidence suggests that corneal stromal keratocytes undergo transformation into fibroblasts and myofibroblasts.10 Treatment for corneal keloids (excision) is generally reserved for those causing significant visual dysfunction.The excisional biopsy showed irregular and vascularized connective tissue with a few bands of hyalinized collagen at the arrowheads. As previously stated, this case requires excisional biopsy (choice C) and histopathologic examination. The 5-fluorouracil choice (choice A) would not be a reasonable next step in this unusual case in the absence of histopathologic confirmation of ocular surface squamous neoplasia. Incisional biopsy (choice B) would not address the patient’s severely limited vision, and incomplete excision is associated with keloid recurrence.7 Observation (choice D) alone does not address the patient’s poor vision and would not be appropriate given the possibility of neoplasia.At postoperative week 2, the patient still had counting fingers visual acuity that persisted at week 12. His examination was notable for a 360° pannus and central corneal haze. At postoperative week 16, he had hand motion visual acuity at 3 ft, an irregular corneal surface without epithelial defect, superficial neovascularization across the corneal surface, and diffuse stromal haze and edema. He is subjectively doing well but will be followed up for the development of recurrence.

Ophthalmology

A 74-year-old man was referred to the ocular oncology clinic for a right eye corneal mass. He had a history of herpetic keratitis and cataract surgery 2 years prior, both in the right eye, complicated by postoperative bullous keratopathy without treatment. The patient noted a corneal scar after the cataract surgery that gradually thickened over the ensuing 6 months. In our office, his examination in the right eye was notable for hand motion visual acuity and a pearly white, raised, 10 × 10-mm, gelatinous, corneal lesion with both intrinsic and feeder vessels (Figure 1A). There was no view of the anterior segment. Ultrasound biomicroscopy showed a hyperechoic opacity on the surface of the cornea, with maximal thickness of 1.5 mm. A cleft was noted between the lesion and the cornea (Figure 1B). There was no extension posteriorly into the anterior chamber, iris, or ciliary body.A, Slitlamp external photograph of right-eye corneal lesion showing prominent elevation and both intrinsic and feeder vessels. B, Ultrasound biomicroscopy showing hyperechoic anterior corneal lesion with hypoechoic cleft labeled centrally. The lesion did not involve any other adjacent structures.

what would you do next?

What would you do next?

Excisional biopsy

Incisional biopsy

Local therapy with 5-fluorouracil

Observe

a

male

71-80

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2723577

A 31-year-old gravida 1, para 1 woman with a history of Wolff-Parkinson-White disease and recently diagnosed stage II Hodgkin lymphoma presented with a pruritic rash. She was diagnosed with Hodgkin lymphoma at 35 weeks’ gestation, and 1 week later she underwent cesarean delivery. At 3 weeks’ postpartum, she began chemotherapy (cycle 1, day 1) with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). On day 15 of cycle 1, she presented with linear, hyperpigmented streaks and welts on her arms, back, and legs. Intense, diffuse pruritus had developed within 24 hours of the patient’s first day of treatment, and her symptoms were poorly responsive to antihistamines and topical steroids. Pruritus was followed by the appearance of dark scratch marks as demonstrated in the Figure. Laboratory test results revealed a white blood cell count of 1.6 ×103 cells/mm3, with an absolute neutrophil count of 500 cells/mm3 and a total bilirubin of 0.3 mg/dL (to convert to μmol/L, multiply by 17.104), which was unchanged from the baseline total bilirubin.Clinical photograph of the patient’s back shows scratch marks that appeared after diffuse pruritus.Prior to the diagnosis of Hodgkin lymphoma, she was receiving routine prenatal care, and the only complication was pruritus without a rash that developed during the first trimester. She was evaluated for right supraclavicular adenopathy that was unresponsive to antibiotics during the third trimester. Findings from a lymph node biopsy were consistent with classic Hodgkin lymphoma, nodular sclerosis subtype. Staging imaging revealed bilateral supraclavicular jugular chain, paratracheal and mediastinal lymphadenopathy, and the erythrocyte sedimentation rate was 67 mm/h. She was diagnosed with stage II, unfavorable-risk Hodgkin lymphoma. What Is Your Diagnosis?

Bleomycin toxic effects

Paraneoplastic skin disease

Polymorphic eruption of pregnancy

Vinblastine toxic effects

A. Bleomycin toxic effects

A

Bleomycin toxic effects

This patient developed bleomycin flagellate dermatitis, a cutaneous reaction to bleomycin characterized by the appearance of pruritic, whiplike streaks of hyperpigmentation, predominantly affecting the trunk and extremities. Bleomycin is a sulfur-containing, antineoplastic agent that blocks the G2 phase of the cell cycle through inhibition of thymidine integration into replicating DNA, degradation of single- and double-stranded DNA, and cleavage of cellular RNA.1 Bleomycin distributes widely throughout the body and is inactivated in every organ except the skin and lungs owing to the absence of the hydrolase enzyme responsible for the drug’s metabolism.2 Absence of this enzyme permits drug accumulation, which can lead to pulmonary fibrosis and various adverse cutaneous manifestations associated with bleomycin.1Flagellate dermatitis is primarily a clinical diagnosis because there are no pathognomonic histologic features. Early histologic findings are consistent with a fixed-drug reaction, and in later stages, reflect a postinflammatory reaction.3 Time of onset varies, occurring within hours or up to 9 weeks following exposure, and the reported incidence of bleomycin flagellate dermatitis is between 8% and 22%.4 Symptoms are generally well controlled with antihistamines, corticosteroids, and withdrawal of bleomycin. Early descriptions of bleomycin flagellate dermatitis documented an apparent dose-dependent occurrence in 8% to 66% of patients; however, the flagellate exanthem has since been reported with bleomycin doses as low as 5 mg with no predictable patient demographic.2-4 Nonetheless, Ziemer et al4 observed in a meta-analysis that women receiving bleomycin specifically for lymphoproliferative disorders might be most susceptible to developing acute-onset flagellate dermatitis at lower doses of exposure.This patient initially discontinued bleomycin for 1 cycle, but she tolerated successful reintroduction of bleomycin with an adjuvant steroid regimen. She remained in remission more than 2 years after chemotherapy completion and had no evidence of bleomycin pulmonary toxic effects. Until recently, there have been no definitive guidelines regarding whether to withdraw bleomycin or rechallenge following an eruption of flagellate dermatitis. The Response Adapted Therapy for Advanced Hodgkin Lymphoma (RATHL) trial randomized patients with negative findings on positron-emission tomography after 2 cycles of ABVD to continue ABVD or deescalate treatment to adriamycin, vinblastine, and dacarbazine (AVD).5 The absolute difference in the 3-year progression-free survival rate between the 2 groups was 1.6% (95% CI, −3.2% to 5.3%) and there was a lower incidence of pulmonary toxic effects when bleomycin was omitted.5 Another important phase 3 clinical trial (ECHELON-1)6 compared brentuximab vedotin plus AVD (A+AVD) with standard ABVD in previously untreated patients with stage III or IV Hodgkin lymphoma. Brentuximab vedotin plus AVD was superior, with a 4.9% lower combined risk of disease progression, death, or incomplete disease response at 2 years, and pulmonary toxic effects were documented in less than 1% of patients receiving A+AVD compared with 3% in those receiving ABVD.6 Although these studies do not specifically address flagellate dermatitis, the data suggest an impending transition in the standard of care favoring withdrawal of bleomycin treatment in patients with complications associated with the toxic effects of the drug, especially if they demonstrate favorable initial clinical response to treatment.Cutaneous toxic effects are a common reaction among chemotherapies in general, and bleomycin is associated with a variety of cutaneous manifestations, including inflammatory nodules, plaques, blistering, nail changes, and alopecia.3 Flagellate dermatitis, however, is considered a classic presentation for the toxic effects of bleomycin.4 Paraneoplastic skin involvement related to Hodgkin disease is well documented but typically encompasses nonspecific occurrence of severe pruritus with or without prurigo, acquired ichthyosis, alopecia or other eruptions that do not reflect tumor invasion. Rarely, cutaneous dissemination of malignant cells can cause more skin changes, which classically develop as painless papules, nodules, plaques, and ulcerations, that are histologically comparable to their affected lymph node counterparts and generally portend a poor prognosis.7,8 Polymorphic eruption of pregnancy could be considered as a differential diagnosis because it occurs in the immediate postpartum period; however, variable pruritic papules and plaques are the defining features of polymorphic eruption of pregnancy.9

Oncology

A 31-year-old gravida 1, para 1 woman with a history of Wolff-Parkinson-White disease and recently diagnosed stage II Hodgkin lymphoma presented with a pruritic rash. She was diagnosed with Hodgkin lymphoma at 35 weeks’ gestation, and 1 week later she underwent cesarean delivery. At 3 weeks’ postpartum, she began chemotherapy (cycle 1, day 1) with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). On day 15 of cycle 1, she presented with linear, hyperpigmented streaks and welts on her arms, back, and legs. Intense, diffuse pruritus had developed within 24 hours of the patient’s first day of treatment, and her symptoms were poorly responsive to antihistamines and topical steroids. Pruritus was followed by the appearance of dark scratch marks as demonstrated in the Figure. Laboratory test results revealed a white blood cell count of 1.6 ×103 cells/mm3, with an absolute neutrophil count of 500 cells/mm3 and a total bilirubin of 0.3 mg/dL (to convert to μmol/L, multiply by 17.104), which was unchanged from the baseline total bilirubin.Clinical photograph of the patient’s back shows scratch marks that appeared after diffuse pruritus.Prior to the diagnosis of Hodgkin lymphoma, she was receiving routine prenatal care, and the only complication was pruritus without a rash that developed during the first trimester. She was evaluated for right supraclavicular adenopathy that was unresponsive to antibiotics during the third trimester. Findings from a lymph node biopsy were consistent with classic Hodgkin lymphoma, nodular sclerosis subtype. Staging imaging revealed bilateral supraclavicular jugular chain, paratracheal and mediastinal lymphadenopathy, and the erythrocyte sedimentation rate was 67 mm/h. She was diagnosed with stage II, unfavorable-risk Hodgkin lymphoma.

what is your diagnosis?

What is your diagnosis?

Polymorphic eruption of pregnancy

Vinblastine toxic effects

Bleomycin toxic effects

Paraneoplastic skin disease

c

female

31-40

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2725399

A man in his 30s presented with painless swelling of the left upper limb and nodules on the left side of the chest and abdomen. The lesions had started a month previously as red nodules on the left axilla, ipsilateral chest, and back. Twenty days later, he developed edema in the left upper limb. While being evaluated for the cutaneous lesions, the patient was diagnosed with AIDS and began antiretroviral therapy.On examination, 6 erythematous, firm, subcutaneous nodules were present on the left side of the chest, abdomen, and left upper limb, varying in size from 2 × 2 cm to 4 × 4 cm (Figure, A). There was diffuse erythema and edema on the left upper limb, leading to difficulty in limb movement (Figure, A). Multiple dilated superficial vessels were present on the posterior aspect of the left arm and ipsilateral chest wall. Left axillary lymph nodes were grossly enlarged, firm, nontender, and nonmatted, with the largest lymph node measuring 6 × 4 cm. The patient’s CD4 cell count was 141/μL (to convert to ×109/L, multiply by 0.001), and his HIV load was 504 473 copies/mL. A skin biopsy sample was obtained from the plaque and sent for histopathologic examination (Figure, B and C).A, Multiple erythematous indurated plaques and nodules confined to the left side of the chest and abdomen with axillary lymphadenopathy and upper limb edema. B, Skin biopsy sample showing infiltration with lymphoid cells and few histiocytes in the subcutaneous tissue (hematoxylin-eosin, original magnification ×400). C, On immunohistochemical analysis, these cells showed nuclear positivity for c-Myc (c-Myc, original magnification ×400). What Is Your Diagnosis?

Kaposi sarcoma

Diffuse large B-cell lymphoma

Burkitt lymphoma

Leukemia cutis

C. Burkitt lymphoma

C

Burkitt lymphoma

Skin biopsy findings revealed large atypical lymphocytes with coarse chromatin, prominent nucleoli, and a scant amount of deeply basophilic cytoplasm in the lower dermis and subcutaneous tissue. Brisk mitosis and many atypical mitotic figures were observed. The classic starry-sky pattern, an effect of benign histiocytes engulfing apoptotic tumor cells, could be seen focally in the dermis. On immunohistochemical analysis, these atypical lymphoid cells were strongly positive for CD10 and CD20 and showed nuclear positivity for c-Myc (>40%) (Figure, C), with a Ki-67 index of more than 95%. These cells were negative for CD3, CD30, terminal deoxynucleotidyl transferase (TdT), and Bcl2. The results of immunohistochemical detection of latent membrane protein 2 expression and Epstein-Barr virus (EBV) encoded RNA in situ hybridization procedures were positive. Cytogenetic analysis revealed translocation (8;14), consistent with Burkitt lymphoma (BL).There was a rapid increase in the size and number of lesions in the patient within 3 weeks. Computed tomography of the chest and abdomen showed discrete to conglomerate, multiple enlarged lymph nodes in the left axilla. The left subclavian artery was compressed by the rapidly growing axillary lymphadenopathy, leading to upper limb edema. Complete blood cell count and renal and liver function test results were normal at baseline. The patient was scheduled for chemotherapy; however, he was subsequently unavailable for follow-up.Burkitt lymphoma is a rapidly proliferating, aggressive B-cell neoplasm with a doubling time as short as 25 hours.1,2 It is classified into endemic, sporadic, and immunodeficiency-associated types. The endemic type is mostly associated with EBV and frequently affects jaw and other facial bones of African children aged 4 to 7 years.3 The sporadic and immunodeficiency-associated subtypes are more common in adults and frequently present with extranodal (particularly gastrointestinal tract) involvement.2 Sporadic types often do not show the rearrangement of the c-Myc and immunoglobulin genes, and EBV positivity is seen in less than 15% to 30% patients. Immunodeficiency type is observed in patients with HIV infection, allograft recipients, and patients with primary immunodeficiency. It is more frequent in patients with CD4 cell counts of 200/μL or higher, and EBV positivity is observed in 40% of patients or more.4 Burkitt lymphoma is composed of monomorphic, intermediate-sized, mature B cells, which are positive for CD19, CD20, CD22, CD79a, CD10, and Bcl6 but negative for CD5 and Bcl2, with abundant mitotic figures and a typical starry-sky appearance on histologic analysis.2 The genetic hallmark of BL is overexpression of c-Myc, which drives its pathogenesis.5Cutaneous presentation of BL is rare and mostly attributed to hematogenous spread, local invasion, or iatrogenic seeding of malignant cells through surgical procedures.6 This case showed evidence of regional metastases on the same side of the chest, back, and abdomen, not directly communicating with the main tumor. These, in our opinion, represent extensions of tumor via lymphatics as evidenced by predominant subcutaneous tissue involvement in the patient.1,7The main differential diagnoses of BL include other high-grade B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). Immunohistochemical features that favor BL over DLBCL are CD10+, Bcl6+, Bcl2−, and TdT−, with a Ki-67 index close to 100%.8 Dysregulation of c-Myc can occur as a primary event in BL or as a secondary event in 5% to 15% of patients with DLBCL and 30% to 50% of patients with aggressive B-cell lymphomas unclassified with features intermediate between DLBCL and BL. Secondary c-Myc changes occur often against a background of complex karyotype and often confer aggressive clinical behavior, including poor survival rate and increased risk of relapse in the central nervous system. The adverse prognosis arises because of concurrent BCL2 (OMIM 151430) or BCL6 (OMIM 109565) gene rearrangements, which are subsequently termed double- or triple-hit lymphomas.8Leukemia cutis can be easily ruled out based on characteristic histologic and immunohistochemical findings.9 AIDS-associated Kaposi sarcoma appears more erythematous-violaceous and has characteristic histopathologic features with vascular proliferation, slitlike spaces, and solid cords and fascicles of spindle cells interspersed between vascular channels.10In conclusion, cutaneous BL is rare, and the diagnosis is mainly confirmed by histopathologic analysis; however, the rapid increase in the size of lesions in this patient was an important clinical clue.

Oncology

A man in his 30s presented with painless swelling of the left upper limb and nodules on the left side of the chest and abdomen. The lesions had started a month previously as red nodules on the left axilla, ipsilateral chest, and back. Twenty days later, he developed edema in the left upper limb. While being evaluated for the cutaneous lesions, the patient was diagnosed with AIDS and began antiretroviral therapy.On examination, 6 erythematous, firm, subcutaneous nodules were present on the left side of the chest, abdomen, and left upper limb, varying in size from 2 × 2 cm to 4 × 4 cm (Figure, A). There was diffuse erythema and edema on the left upper limb, leading to difficulty in limb movement (Figure, A). Multiple dilated superficial vessels were present on the posterior aspect of the left arm and ipsilateral chest wall. Left axillary lymph nodes were grossly enlarged, firm, nontender, and nonmatted, with the largest lymph node measuring 6 × 4 cm. The patient’s CD4 cell count was 141/μL (to convert to ×109/L, multiply by 0.001), and his HIV load was 504 473 copies/mL. A skin biopsy sample was obtained from the plaque and sent for histopathologic examination (Figure, B and C).A, Multiple erythematous indurated plaques and nodules confined to the left side of the chest and abdomen with axillary lymphadenopathy and upper limb edema. B, Skin biopsy sample showing infiltration with lymphoid cells and few histiocytes in the subcutaneous tissue (hematoxylin-eosin, original magnification ×400). C, On immunohistochemical analysis, these cells showed nuclear positivity for c-Myc (c-Myc, original magnification ×400).

what is your diagnosis?

What is your diagnosis?

Kaposi sarcoma

Leukemia cutis

Burkitt lymphoma

Diffuse large B-cell lymphoma

c

male

31-40

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2727334

An adult with a history of alcohol abuse was admitted to the cardiac unit with progressive shortness of breath, lower extremity edema, and tachycardia, which had developed during several days. He had no history of drug use or cardiac events. On physical examination, he had warm extremities. His body temperature was 36.8°C. His blood pressure was 100/60 mm Hg, heart rate was 130 beats/min, respiratory rate was 24 breaths/min, and pulse oximetry was 98% on ambient air. There were bibasilar rales on lung auscultation. The heart sounds were normal, and bilateral ankle edema was present. Laboratory tests revealed hyponatremia (sodium, 124 mEq/L [to convert to millimoles per liter, multiply by 1]), a compensated metabolic acidosis with a bicarbonate concentration of 14 mEq/L (to convert to millimoles per liter, multiply by 1), and a lactate concentration of 82.0 mg/dL (to convert to millimoles per liter, multiply by 0.111). The D-dimer level was 0.0003 μg/mL (to convert to nanomoles per liter, multiply by 5.476), and the pro–brain-type natriuretic peptide level was 6062 pg/mL (to convert to nanograms per liter, multiply by 1). The electrocardiogram on presentation is shown in the Figure. Echocardiography (Video 1 and Video 2) revealed a left ventricular ejection fraction of 50%. What Would You Do Next?

Start extracorporeal membrane oxygenation therapy

Administer intravenous β-blocker therapy

Administer intravenous bicarbonate therapy

Administer intravenous thiamine therapy

Shoshin (wet) beriberi

D

Administer intravenous thiamine therapy

At first glance, this case might be interpreted as an ordinary case of severe heart failure due to alcoholic cardiomyopathy. However, echocardiography revealed only a mild reduced left ventricular function, which does not fully explain all the clinical features. In particular, the metabolic acidosis with high lactate levels should trigger an explanation for an alternative diagnosis.Thiamine deficiency (vitamin B1), also known as beriberi, is a rare condition in developed countries. However, individuals prone to malnourishment, such as individuals with alcoholism, patients receiving total parenteral nutrition without adequate vitamin supplements, or individuals on a diet or after weight loss surgery, are more likely to develop thiamine deficiency.1 Thiamine plays a fundamental role in cellular metabolism, has a half-life of 18 days, and is quickly depleted. Acidosis and the inability to use the Krebs cycle are the major pathophysiologic mechanisms of the clinical manifestations of thiamine deficiency.Beriberi may present in 2 forms: a dry form with neurologic features and a wet form with the clinical features of high-output heart failure (shortness of breath, tachycardia, and edema).2,3 In rare cases, a fulminant variant termed Shoshin beriberi (translated from Japanese sho, meaning acute damage, and shin, meaning heart) may occur, which is characterized with features of cardiovascular collapse and multiorgan failure. Inappropriate management may prove fatal, and the only definitive treatment of beriberi is thiamine supplementation. Intravenous administration of thiamine markedly improves the hemodynamic parameters.4 In critically ill patients suspected of having a malnourished diet who have unexplained heart failure, lactic acidosis, or multiorgan failure, thiamine administration should be considered without delay.After excluding pulmonary embolism with computed tomography and other causes of unexplained lactate acidosis, intravenous administration of 200 mg of thiamine led to swift recovery of the patient, with normalization of hemodynamic parameters and metabolic acidosis within hours. Laboratory tests later confirmed vitamin B1 deficiency. After a few days, the patient was discharged with a prescription for oral thiamine and advised to monitor his alcohol and dietary intake.

Cardiology

An adult with a history of alcohol abuse was admitted to the cardiac unit with progressive shortness of breath, lower extremity edema, and tachycardia, which had developed during several days. He had no history of drug use or cardiac events. On physical examination, he had warm extremities. His body temperature was 36.8°C. His blood pressure was 100/60 mm Hg, heart rate was 130 beats/min, respiratory rate was 24 breaths/min, and pulse oximetry was 98% on ambient air. There were bibasilar rales on lung auscultation. The heart sounds were normal, and bilateral ankle edema was present. Laboratory tests revealed hyponatremia (sodium, 124 mEq/L [to convert to millimoles per liter, multiply by 1]), a compensated metabolic acidosis with a bicarbonate concentration of 14 mEq/L (to convert to millimoles per liter, multiply by 1), and a lactate concentration of 82.0 mg/dL (to convert to millimoles per liter, multiply by 0.111). The D-dimer level was 0.0003 μg/mL (to convert to nanomoles per liter, multiply by 5.476), and the pro–brain-type natriuretic peptide level was 6062 pg/mL (to convert to nanograms per liter, multiply by 1). The electrocardiogram on presentation is shown in the Figure. Echocardiography (Video 1 and Video 2) revealed a left ventricular ejection fraction of 50%.

what would you do next?

What would you do next?

Administer intravenous thiamine therapy

Administer intravenous bicarbonate therapy

Administer intravenous β-blocker therapy

Start extracorporeal membrane oxygenation therapy

a

male

31-40

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2730376

A woman in her 30s presented with a 1-year medical history of a painless, slowly enlarging, midline neck mass without associated dysphagia, odynophagia, weight loss, or history of infection. The mass was soft, mobile, and compressible in midline level IA, measuring 7 cm and posterior-superiorly displacing the tongue. The mass was visible as a clear blue lesion in the floor of the mouth and was nontender. Computed tomographic (CT) scan of the neck with IV contrast was performed (Figure). The patient was taken to the operating room for a successful combined intraoral and transcervical approach to excision.Computed tomographic images. A, Coronal view of midline neck mass. B, Sagittal view of midline neck mass. What Is Your Diagnosis?

Simple ranula

Epidermoid cyst

Vascular malformation

Odontogenic abscess

B. Epidermoid cyst

B

Epidermoid cyst

Epidermoid cysts (ECs) are classically small, benign, cystic masses with 32% of lesions occurring in the head and neck.1 They usually arise because of failure of primitive epithelial cells to separate from underlying deep tissue during branchial arch formation.2 True ECs are fluid-filled lesions lined by simple squamous epithelium and a layer of keratin. They have been referred to by other terms such as epidermal cysts, epidermal inclusion cysts, sebaceous cysts, and seborrheic cysts. However, the terms “seborrheic cysts” and “sebaceous cysts” are misnomers, not synonymous with epidermoid cysts. Epidermoid cysts are normally close to the skin and can be located anywhere on the face, scalp, and neck. However, in the deep tissue planes, ECs in the head and neck make up only 1.6% to 6.9% of cases in the entire body.3The typical presentation of an EC is a soft, slow-growing, nontender mass without fixation to underlying tissues. Epidermoid cysts frequently do not cause symptoms and go unnoticed until they reach a large size or become infected.4 Obstructive symptoms like dysphagia, odynophagia, dysphonia, and dyspnea are more typical for lesions above the mylohyoid because this results in superior displacement of the tongue. In contrast, masses below the mylohyoid cause protrusion into the chin in the front of the neck, giving rise to the characteristic double chin appearance.5,6 In this case, the cyst was quite large, measuring over 8 cm in greatest dimension, but it produced no obstructive symptoms.Both benign and malignant neoplasms may present as cystic lesions in the floor of mouth.7 However, malignant disease is generally limited to necrotic squamous cell carcinoma lymphadenopathy. These lesions generally are thick-walled and found in the submandibular space, which is inconsistent with the sublingual lesion described herein. Venous malformations may also present as cystic masses in the neck with the presence of phleboliths as the characteristic imaging finding.8 Arteriovenous malformations may be visualized as high-flow lesions with multiple tortuous channels.8 The absence of characteristic imaging findings excludes vascular malformation as a viable consideration in this case.On CT scan, ECs are described as unilocular masses, and ranulas appear as well-circumscribed, lobulated cystic lesions with central homogeneous low CT attenuation.8 However, not all lesions present with these characteristic radiologic signs. Indeed, Coit et al7 note that ECs cannot be absolutely distinguished from ranulas by radiographic means alone. In this case, initial imaging and physical examination findings were more consistent with a ranula than an EC. The mass had a bluish coloration on examination, which is a common feature of ranulas. Findings of the CT scan showed a cystic, homogenous mass without hypoattenuating fat nodules, calcifications, or septations contained in the floor of the mouth and sublingual space, increasing our suspicion of a ranula. We initially planned for intraoral marsupialization with sublingual gland excision. However, working diagnosis was intraoperatively changed to dermoid cyst vs EC owing to thick cyst wall. The decision was made to completely excise the mass leaving the sublingual gland. Final pathologic diagnosis confirmed EC.Although inflamed ECs without infection may be treated with intralesional steroids alone, complete surgical excision or enucleation is regarded as the definitive treatment of choice.4 Recurrence after total excision is rare.9 Giant ECs greater than 5 cm are uncommon, and few cases in the head and neck have been reported.10 Herein we present a case of a giant deep tissue EC mimicking a simple ranula, serving as a reminder to include EC in the differential for cystic masses of the floor of mouth or midline of the neck.

General

A woman in her 30s presented with a 1-year medical history of a painless, slowly enlarging, midline neck mass without associated dysphagia, odynophagia, weight loss, or history of infection. The mass was soft, mobile, and compressible in midline level IA, measuring 7 cm and posterior-superiorly displacing the tongue. The mass was visible as a clear blue lesion in the floor of the mouth and was nontender. Computed tomographic (CT) scan of the neck with IV contrast was performed (Figure). The patient was taken to the operating room for a successful combined intraoral and transcervical approach to excision.Computed tomographic images. A, Coronal view of midline neck mass. B, Sagittal view of midline neck mass.

what is your diagnosis?

What is your diagnosis?

Vascular malformation

Epidermoid cyst

Odontogenic abscess

Simple ranula

b

female

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2731469

A 36-year-old otherwise healthy white woman with a history of chronic sinusitis presented with progressive left facial pain and swelling of 5 months’ duration. Associated symptoms included epistaxis and left-sided epiphora. Prior to presentation, she had been treated as an outpatient with multiple rounds of oral antibiotics and steroids for presumed sinusitis without improvement. Social history included routine cocaine use 10 years ago. Physical examination demonstrated substantial erythema and edema of the left infraorbital region and left nasal sidewall and purulent nasal secretions (Figure 1A). Endoscopic nasal examination revealed substantial swelling of the left nasal vestibule completely obstructing the left naris, swelling of the left nasolacrimal duct orifice, nearly total septal perforation with areas of necrotic bone, and no identifiable intranasal landmarks except for a remnant of the left middle turbinate (Figure 1B). There was no cervical lymphadenopathy. Laboratory evaluation revealed a white blood cell count of 12 300/μL with normal neutrophil count; erythrocyte sedimentation rate of 83 mm/h; and a C-reactive protein level of 134 mg/L. (To convert white blood cells to ×109/L, multiply by 0.001; C-reactive protein to nanomoles per liter, multiply by 9.524.) A maxillofacial computed tomographic (CT) scan demonstrated cartilaginous and anterior osseous nasal septal perforation and left nasal and preseptal soft-tissue thickening with associated periosteal reaction of the nasal process of the maxilla.A, Periorbital and nasal cellulitis. B, Nasal endoscopic examination demonstrating significant soft-tissue necrosis. What Is Your Diagnosis?

Granulomatosis with polyangiitis

Cocaine-induced midline destructive lesion

Extranodal natural killer/T-cell lymphoma, nasal type

Chronic invasive fungal sinusitis

B. Cocaine-induced midline destructive lesion

B

Cocaine-induced midline destructive lesion

The patient began treatment with broad-spectrum intravenous antibiotics, which was deescalated to oral trimethoprim-sulfamethoxazole and rifampin treatment for 6 weeks after nasal swab culture grew methicillin-sensitive Staphylococcus aureus. A repeated nasal culture at follow-up grew Pseudomonas aeruginosa, so she was then treated with a 6-week regimen of levofloxacin and rifampin. After completion of the antibiotics regimen, her condition showed only mild improvement, so she underwent biopsy and surgical debridement of necrotic tissue, which exposed an underlying nasocutaneous fistula over the left nasal sidewall (Figure 2). Biopsy specimens demonstrated necroinflammatory debris and acute and chronic osteomyelitis, which together with her history were suggestive of cocaine-induced midline destructive lesion (CIMDL). No pathognomonic lesions suggestive of granulomatosis with polyangiitis (GPA) were seen.Axial noncontrast computed tomographic maxillofacial scan after antibiotic treatment demonstrates destruction of the left frontal process of the maxilla and cartilaginous and osseous nasal septum.Cocaine acts as a local anesthetic, vasoconstrictive, and euphoric agent. It blocks sodium channels and thereby halts electrical propagation of neurons to cause local anesthesia.1 It also inhibits the reuptake of norepinephrine and dopamine at the presynaptic nerve endings, leading to an accumulation of these neurotransmitters at nerve synapses.2 In the peripheral nervous system, norepinephrine primarily accumulates, causing an increase in sympathetic tone.3 In the central nervous system, dopamine accumulation is responsible for cocaine’s euphoric and addictive properties.3,4 It is reported that close to 30 million people in the United States have used cocaine and that 6 million of them are compulsive users; however, CIMDL is only seen in 4.8% of users.5,6Nasal septal perforation, nasal cavity wall erosion, pharyngeal wall ulceration, and hard palate perforation are all manifestations of CIMDL. The damage to the nasal architecture is multifactorial, primarily the result of intense vasoconstriction with repeated cocaine use, leading to local tissue necrosis. However, the chemical irritation from adulterants, such as lactose and inositol, and mechanical irritation from self-instrumentation and high-velocity cocaine crystal inhalation have also been implicated in mucosal and perichondrial erosion.7The clinical presentation of CIMDL also mimics certain systemic diseases, most notably GPA. Clinical differentiation can be made based on more severe destruction of nasal architecture, such as loss of inferior and middle turbinates, and lack of systemic manifestations in CIMDL.8 Histopathological findings are very similar in CIMDL and GPA unless discriminatory findings of GPA are seen, such as necrotizing granulomas and multinucleated giant cells.8 Finally, positive findings for antineutrophil cytoplasmic antibodies (ANCAs) are common in both patient populations, but reaction against human neutrophil elastase (HNE) in CIMDL is its most distinguishing feature.9 The presence of HNE-ANCA is what is believed to predispose select cocaine users to CIMDL because it enhances the local inflammatory response to injury—highlighting a possible autoimmune component to the disease.9 It is also reported that there is a time and cocaine-dose dependence to developing the disease, suggesting a chronicity, rather than fulminant stage, to the disease entity.6It is important to remember that patients tend to understate cocaine use, as did this patient, who only reported recent use after her pain progressed. Treatment includes complete abstinence from cocaine, debridement of necrotic tissue, and treatment of any superinfection. The most common surgical procedures are closure of septal and palatal perforation, with most surgeons requiring 6 to 12 months of cocaine abstinence prior to intervention.9 Of note, immunosuppression is not indicated; therefore, correct identification of the underlying disease process is critical.6 The present case demonstrates an uncommonly severe presentation of CIMDL and illustrates the importance of correct and timely diagnosis to guide subsequent treatment.

General

A 36-year-old otherwise healthy white woman with a history of chronic sinusitis presented with progressive left facial pain and swelling of 5 months’ duration. Associated symptoms included epistaxis and left-sided epiphora. Prior to presentation, she had been treated as an outpatient with multiple rounds of oral antibiotics and steroids for presumed sinusitis without improvement. Social history included routine cocaine use 10 years ago. Physical examination demonstrated substantial erythema and edema of the left infraorbital region and left nasal sidewall and purulent nasal secretions (Figure 1A). Endoscopic nasal examination revealed substantial swelling of the left nasal vestibule completely obstructing the left naris, swelling of the left nasolacrimal duct orifice, nearly total septal perforation with areas of necrotic bone, and no identifiable intranasal landmarks except for a remnant of the left middle turbinate (Figure 1B). There was no cervical lymphadenopathy. Laboratory evaluation revealed a white blood cell count of 12 300/μL with normal neutrophil count; erythrocyte sedimentation rate of 83 mm/h; and a C-reactive protein level of 134 mg/L. (To convert white blood cells to ×109/L, multiply by 0.001; C-reactive protein to nanomoles per liter, multiply by 9.524.) A maxillofacial computed tomographic (CT) scan demonstrated cartilaginous and anterior osseous nasal septal perforation and left nasal and preseptal soft-tissue thickening with associated periosteal reaction of the nasal process of the maxilla.A, Periorbital and nasal cellulitis. B, Nasal endoscopic examination demonstrating significant soft-tissue necrosis.

what is your diagnosis?

What is your diagnosis?

Granulomatosis with polyangiitis

Cocaine-induced midline destructive lesion

Extranodal natural killer/T-cell lymphoma, nasal type

Chronic invasive fungal sinusitis

b

female

31-40

White

original

https://jamanetwork.com/journals/jama/fullarticle/2731736

A 24-year-old woman who worked on a farm in Connecticut developed fever, chills, vomiting, and a truncal maculopapular rash 3 weeks before presentation. One week after symptom onset, she remained febrile (maximum temperature, 39.6°C [103.2°F]) and the rash spread to her palms and soles, with some progression to pustules (Figure, left panel). She developed right knee pain, followed by pain in other joints. Two weeks after symptom onset, she presented to a local emergency department, reporting inability to stand due to severe joint pain. Results of tests for sexually transmitted infections and respiratory viruses were negative. She was presumptively diagnosed with a viral illness and discharged home with supportive care. Approximately 3 weeks after symptom onset, she presented to the emergency department again with persistent fever, worsening arthralgia, back pain, and progressive purpuric and pustular rash. Her vital signs were unremarkable. White blood cell count was 12 100/μL (reference range, 4000/μL-10 000/μL), with 84% neutrophils. Urinalysis results and levels of serum electrolytes and liver enzymes were within normal limits. Gram stain of blood culture is shown in the Figure (right panel).Obtain joint fluid for bacterial analysis and cultures What Would You Do Next?

Inquire about rodent and other animal exposures

Obtain joint fluid for bacterial analysis and cultures

Test for Borrelia burgdorferi

Test vesicular fluid for enterovirus

Rat bite fever

A

Inquire about rodent and other animal exposures

The key to the correct diagnosis was symptoms of persistent fever, migratory polyarthralgias, and purpuric rash extending to the palms and soles. When questioned, the patient recalled a rat bite 3 days before symptom onset. Based on this history, pustule fluid and blood were submitted for culture. Blood cultures became positive, and Gram stain revealed filamentous gram-negative bacilli in “nests,” with occasional bulbous swellings. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed to identify the organism, but 16S rDNA sequencing identified Streptobacillus moniliformis, the causative agent of rat bite fever. No growth occurred from pustule fluid cultures.Because of the nonspecific presentation of rat bite fever, patients with a high index of clinical suspicion should be carefully questioned for rodent exposure.1 Even without a known exposure, rat bite fever should be considered in patients with an unexplained febrile illness and rash, arthritis, or risk factors such as occupational or recreational exposure to rodents.2 The duration of the patient’s symptoms and absence of oral symptoms made the diagnosis of hand, foot, and mouth disease due to enterovirus unlikely. Although testing for tick-transmitted diseases or joint fluid analysis may eventually be warranted, the next best step is obtaining a thorough history regarding exposure to rodents. This approach improves pretest probability and avoids premature conclusions by developing a focused differential diagnosis based on history and examination.3Rat bite fever is caused by S moniliformis in the United States or Spirillum minus in Asia. S moniliformis is a fastidious, facultatively anaerobic, filamentous gram-negative bacteria that colonizes the oral and nasopharyngeal tracts of rats, mice, squirrels, gerbils, and other rodents. Rat bite fever is not a notifiable disease in the United States, and, while incidence appears low, its precise incidence is unknown.1 However, infections are increasing, especially in children, because of the popularity of rodents as pets.4 Transmission also occurs by ingesting food contaminated by urine of colonized rats, causing a syndrome known as “Haverhill fever.”5Rat bite fever is characterized by fever, chills, headache, and vomiting 3 to 10 days after exposure. Without treatment, fever typically follows a relapsing-remitting pattern. Most patients develop a maculopapular, petechial, or purpuric rash, especially on the extensor surfaces of the extremities and extending to the hands and feet. Lesions can evolve into pustules and hemorrhagic vesicles. Most patients develop migratory polyarthralgias involving both small and large joints.1Rodent bite wounds should be thoroughly cleansed, and antibiotic prophylaxis and tetanus immunization may be warranted if not up to date. Rabies prophylaxis is almost never indicated for small rodent bites.6 Symptoms of rat bite fever can present early, but diagnosis is usually delayed or missed because of poor memory of rodent exposure. Additionally, the nonspecific presentation may mimic viral infections, sexually transmitted infections, drug reactions, and vasculitis.1,7S moniliformis is fastidious, and its growth is inhibited by an anticoagulant used in blood cultures. In this patient, growth occurred in the aerobic blood culture bottle but only on anaerobic solid media. No special incubation or plating strategies were used for the blood cultures, but supplemented culture methods have historically been recommended to identify S moniliformis.1 There should be communication with the microbiology laboratory to optimize the diagnostic approach for patients with suspected rat bite fever. Identification of cultured S moniliformis is challenging, as it may not be present in commercial identification databases. Definitive identification may require specialized biochemical analysis,1 sequencing, or both.Infectious diseases consultation can assist with risk assessment, laboratory communication to optimize testing, and choice of empirical antimicrobial therapy. Penicillin is the treatment of choice when diagnosis is confirmed; cephalosporins and tetracyclines may also be effective. Rat bite fever can be associated with serious complications including endocarditis, hepatitis, nephritis, septic arthritis, osteomyelitis, meningitis, and sepsis. When diagnosed, rat bite fever can be successfully treated; however, mortality can reach 13% without treatment.7-10,The patient was initially treated with penicillin and doxycycline empirically. After the diagnosis of rat bite fever, treatment was changed to intravenous penicillin G monotherapy. Transthoracic echocardiography did not reveal valvular vegetations. Persistent back pain prompted magnetic resonance imaging of the spine, which revealed changes consistent with lumbar osteomyelitis. Treatment was extended to 6 weeks, and the patient’s symptoms resolved without need for repeat imaging.

General

A 24-year-old woman who worked on a farm in Connecticut developed fever, chills, vomiting, and a truncal maculopapular rash 3 weeks before presentation. One week after symptom onset, she remained febrile (maximum temperature, 39.6°C [103.2°F]) and the rash spread to her palms and soles, with some progression to pustules (Figure, left panel). She developed right knee pain, followed by pain in other joints. Two weeks after symptom onset, she presented to a local emergency department, reporting inability to stand due to severe joint pain. Results of tests for sexually transmitted infections and respiratory viruses were negative. She was presumptively diagnosed with a viral illness and discharged home with supportive care. Approximately 3 weeks after symptom onset, she presented to the emergency department again with persistent fever, worsening arthralgia, back pain, and progressive purpuric and pustular rash. Her vital signs were unremarkable. White blood cell count was 12 100/μL (reference range, 4000/μL-10 000/μL), with 84% neutrophils. Urinalysis results and levels of serum electrolytes and liver enzymes were within normal limits. Gram stain of blood culture is shown in the Figure (right panel).Obtain joint fluid for bacterial analysis and cultures

what would you do next?

What would you do next?

Obtain joint fluid for bacterial analysis and cultures

Test for Borrelia burgdorferi

Inquire about rodent and other animal exposures

Test vesicular fluid for enterovirus

c

female

21-30

White

original

https://jamanetwork.com/journals/jama/fullarticle/2730536

A 71-year-old otherwise healthy woman presented with an enlarging, immobile, painless mass in her right gluteal area. She had no other associated symptoms. On examination, she had a large, palpable, nontender right gluteal mass. She had no neurovascular deficits. Results of laboratory studies were within normal limits. Computed tomography (CT) revealed an 11-cm heterogeneous lipomatous tumor involving the right gluteal musculature (Figure).Axial (left) and coronal (right) computed tomography images of patient’s right gluteal mass. What Would You Do Next?

Incisional biopsy of the lesion

Core needle biopsy of the lesion

Simple excision of the lesion

Repeat imaging in 6 months

Well-differentiated/dedifferentiated liposarcoma

B

Core needle biopsy of the lesion

Core needle biopsy should be performed to obtain tissue diagnosis. Incisional biopsy should be avoided and can complicate surgical and oncologic management.1 Surgical management should be deferred until a tissue diagnosis is made and preoperative workup is complete. Because this tumor is enlarging, larger than 5 cm, deep (subfascial), and heterogeneous, it should be considered malignant until proven otherwise. Repeat imaging is unnecessary and likely would be inadequate.Liposarcomas are rare, often aggressive, malignancies that require surgical resection and multidisciplinary management. There are approximately 2400 new cases of liposarcoma diagnosed in the United States per year.2,3 Subtypes of liposarcoma include well-differentiated, dedifferentiated, myxoid, and pleomorphic. A well-differentiated liposarcoma of the extremity may also be referred to as an atypical lipomatous tumor.As with all soft tissue sarcomas, liposarcomas are most frequently found on the extremities or in the retroperitoneum. Lipomatous tumors are relatively asymptomatic. A lipomatous tumor arising in the extremity typically presents as a painless mass and in the retroperitoneum occasionally presents with vague abdominal symptoms.Cross-sectional imaging, either CT or magnetic resonance imaging (MRI), should be obtained for all patients. Extremity tumors that are large (>5 cm), subfascial, or enlarging and any retroperitoneal mass should be considered malignant until proven otherwise. In most cases, core needle biopsy should be obtained for tissue diagnosis. Incisional biopsy should be avoided and can complicate surgical and oncologic management.1MDM2 amplification, detected by fluorescence in situ hybridization, can provide additional information. This is particularly useful in distinguishing a well-differentiated liposarcoma (MDM2 amplification) from a benign lipoma (no MDM2 amplification), as this is often a difficult histologic distinction, radiologic distinction, or both.4 Dedifferentiated (MDM2 amplification), myxoid (no MDM2 amplification), and pleomorphic (no MDM2 amplification) liposarcomas have more characteristic appearances on histology and imaging, so MDM2 amplification may be less useful in these cases.All patients diagnosed with liposarcoma should undergo CT of the chest to complete preoperative staging, as sarcomas spread hematogenously, most frequently to the lung. A chest radiograph may be an appropriate substitute for CT of the chest for patients diagnosed with a well-differentiated liposarcoma/atypical lipomatous tumor in an extremity. Patients diagnosed with myxoid liposarcoma should additionally undergo CT of the abdomen/pelvis and be considered for MRI of the spine, as this liposarcoma subtype can metastasize to other anatomical locations.Surgery remains the mainstay of treatment for liposarcoma, and oncologic margin–negative resection is associated with improved disease-free survival. Amputation is rarely, if ever, required for primary extremity disease. Identifying malignant tumors preoperatively is critical for surgical planning and avoiding unnecessarily aggressive operations to obtain local control. A patient who undergoes a simple excision for a presumed lipoma that is found to be a liposarcoma should undergo repeat imaging and often a wide reresection of the surgical site, as there is a 50% to 80% rate of gross residual disease in this setting.5Radiation therapy has been shown to improve local control for patients with primary high-grade extremity soft tissue sarcomas, including liposarcomas. However, the exceptions of the use of radiation are small, low-grade liposarcomas or well-differentiated liposarcomas/atypical lipomatous tumors, given their low risk of recurrence and the potential long-term complications from radiation.6 Although the benefit is less clear for retroperitoneal disease, radiation may be used in highly selected cases for the treatment of aggressive histologic subtypes by centers with expertise in treating sarcoma in this location. For both the extremity and retroperitoneum, preoperative (neoadjuvant) radiation is preferred because of its favorable late toxicity profile, shorter course, and potential operative benefits of downsizing the tumor.7 The benefit of systemic therapy (chemotherapy, molecularly targeted therapy, or immunotherapy) for high-risk liposarcomas is less clear and is only considered for specific histologic subtypes or for patients with metastatic or locally advanced disease.8Risk of local recurrence (5%-15%) and distant metastasis (5%-70%) of extremity liposarcomas ranges widely and is dependent on the histologic subtype, grade, and size. In comparison to extremity liposarcomas, the risk of local recurrence for retroperitoneal liposarcomas is significantly higher (40%-50%). Widely validated prognostic models or nomograms more accurately determine oncologic prognosis than existing TNM staging systems. Websites, such as the Memorial Sloan Kettering Cancer Center nomogram, and applications, such as Sarculator (which uses validated nomogram data), give patient-specific prognosis data and are used by both sarcoma oncologists and patients.9A patient diagnosed with liposarcoma should be referred to a sarcoma specialty center whenever possible, as multidisciplinary treatment and surveillance by physicians specializing in sarcoma has been shown to improve patient outcomes.10Core needle biopsy revealed a spindle and pleomorphic sarcoma, most consistent with a well-differentiated/dedifferentiated liposarcoma with MDM2 amplification present. CT of the chest showed no systemic disease. After a multidisciplinary discussion, the patient underwent neoadjuvant radiation followed by resection. She has undergone surveillance imaging every 6 months since her surgery and remains disease-free 2 years postoperatively.

General

A 71-year-old otherwise healthy woman presented with an enlarging, immobile, painless mass in her right gluteal area. She had no other associated symptoms. On examination, she had a large, palpable, nontender right gluteal mass. She had no neurovascular deficits. Results of laboratory studies were within normal limits. Computed tomography (CT) revealed an 11-cm heterogeneous lipomatous tumor involving the right gluteal musculature (Figure).Axial (left) and coronal (right) computed tomography images of patient’s right gluteal mass.

what would you do next?

What would you do next?

Repeat imaging in 6 months

Core needle biopsy of the lesion

Simple excision of the lesion

Incisional biopsy of the lesion

b

female

71-80

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2728813

A man in his 40s was admitted to the hospital with a 10-day history of edema and presented with vesicles and bullae on his right cheek, neck, back, both eyelids, and the dorsal surface of his hands (Figure 1A). Prior to presentation, he had been treated for herpes zoster with famciclovir for 1 week, during which the lesions kept developing and were accompanied with irregular fever (maximum temperature, 39°C). Physical examination revealed edema on both eyelids; multiple papules, blisters, and crusted erosions with thin exudation on his right cheek and neck; and erythematous plaques and tense blisters and bullae on his back and on the dorsal surface of both hands (Figure 1B). A full laboratory workup was performed for autoantibodies for systemic lupus erythematosus (SLE), pemphigus, and bullous pemphigoid; skin and bone-marrow biopsies and direct immunofluorescence were performed; and immunohistochemichal analysis, a swab of exudation, and bacterial, fungal, and atypical mycobacterial cultures from blood and tissue were also examined.A, Edema on both eyelids; multiple papules, blisters, and crusted erosions with thin exudation on right cheek and neck. B, Erythematous plaques, tense blisters, and bullae on both hands (right hand depicted). What Is Your Diagnosis?

Famciclovir-resistant disseminated herpes zoster

Bullous Sweet syndrome

Bullous Wells syndrome

Bullous pemphigoid

C. Bullous Wells syndrome

C

Bullous Wells syndrome

The complete blood cell count showed an elevated eosinophil count (1.36 × 109/L). No additional anomalies were found besides a mild increase in eosinophil levels in the bone marrow biopsy. Enterococcus faecalis was isolated from the exudation swab. Blood and tissue cultures and autoantibody profiles of SLE, pemphigus (Dsg-1 and Dsg-3), and bullous pemphigoid (BP-180 and BP-230) were all negative. Histopathologic examination indicated irregular hyperplasia and spongiosis of the epidermis with hyperkeratosis and localized necrosis (Figure 2A). Additionally, extensive edema of dermal papillary and mixed infiltrate of marked diffuse eosinophils and lymphocytes were found in the dermis, accompanied by scattered neutrophils (Figure 2B). Direct immunoflourescence results for IgA, IgG, IgM, and C3 were negative. Initially, the patient was given levofloxacin for 5 days owing to a concern of bacterial infection but did not respond. Following the histopathologic results, the diagnosis of bullous Wells syndrome was made. Intravenous methylprednisolone at 1.5mg/kg/d was given for 1 week, followed by rapid relief of fever and lesions. The lesions completely cleared, and the patient showed no sign of relapse at 12-month follow-up.Hematoxylin-eosin stained sections. A, Irregular hyperplasia and spongiosis of the epidermis, extensive edema of dermal papillary and massive inflammatory cell infiltration. B, Extensive edema of dermal papillary and mixed infiltrate of marked diffuse eosinophils and lymphocytes in the dermis, accompanied by scattered neutrophils.Wells syndrome, also known as eosinophilic cellulitis, was first described in 1971.1 The main clinical variants include plaque type, annular granulomalike, urticarialike, papulovesicular, bullous, papulonodular, and fixed drug eruptionlike, among which the bullous type is quite rare and more likely to affect adults.2The low prevalence of Wells syndrome, along with its variability of manifestation, often delays its diagnosis until a patient does not respond to an initial antimicrobial regimen.3 Although the onset of Wells syndrome is acute, the systemic symptoms are generally mild. The irregular fever presented in this case is not a common complication. Besides bacterial cellulitis, differential diagnoses of Wells syndrome include, but are not limited to, necrotizing fasciitis, parasitoses, urticaria, Churg-Strauss syndrome, granuloma annulare, and hypereosinophilic syndrome.4 In patients presenting blisters or bullae, the diagnoses of herpes virus infection, bullous pemphigoid, acute contact dermatitis, bullous SLE, and bullous Sweet syndrome should also be considered. Notably, bullous Sweet syndrome can present symptoms very similar to the present case. However, the histologic traits of Sweet syndrome feature dense neutrophils and nuclear dust in the mid-dermis, with occasional eosinophils or lymphocytes.A variety of triggers are reported to be associated with Wells syndrome, including drugs, infections, insect bites, cancer, and vaccinations.5 However, in this case, no obvious triggers could be found. The history, physical examination, and regular laboratory workup excluded systemic diseases. Furthermore, the blood tests and bone-marrow biopsy provided no evidence to indicate either hematological or myeloproliferative diseases. Therefore, this case was diagnosed as idiopathic Wells syndrome.A gold standard for Wells syndrome diagnostic criteria is currently nonexistent. Heelan et al6 have proposed a set of diagnostic criteria for Wells syndrome, which include 4 major characteristics (2 of which need to be present) and 4 minor ones (at least 1 of which needs to be present). However, larger patient cohorts are needed for its validation. In a recent review, Räßler et al5 suggested that the correlation of clinical features, the course of skin lesions, and histopathological examination of a skin biopsy are necessary for a definitive diagnosis of Wells syndrome.Owing to the benign course and generally good prognosis, local therapy is the main strategy for treating Wells syndrome, whereas systemic treatment is used in cases with widespread lesions or systemic involvement. Topical and systemic glucocorticosteroids are the most common treatments for Wells syndrome and to our knowledge are the only clearly beneficial therapies reported so far.5 Other treatment options include cyclosporine, dapsone, oral or topical tacrolimus, antihistamines, interferon-α, interferon-γ, tumor necrosis factor inhibitors, sulphone or sulfasalazine, psoralen and UV-A therapy, colchicines, antimalarial drugs, azathioprine, minocycline, and griseofulvin.5

Dermatology

A man in his 40s was admitted to the hospital with a 10-day history of edema and presented with vesicles and bullae on his right cheek, neck, back, both eyelids, and the dorsal surface of his hands (Figure 1A). Prior to presentation, he had been treated for herpes zoster with famciclovir for 1 week, during which the lesions kept developing and were accompanied with irregular fever (maximum temperature, 39°C). Physical examination revealed edema on both eyelids; multiple papules, blisters, and crusted erosions with thin exudation on his right cheek and neck; and erythematous plaques and tense blisters and bullae on his back and on the dorsal surface of both hands (Figure 1B). A full laboratory workup was performed for autoantibodies for systemic lupus erythematosus (SLE), pemphigus, and bullous pemphigoid; skin and bone-marrow biopsies and direct immunofluorescence were performed; and immunohistochemichal analysis, a swab of exudation, and bacterial, fungal, and atypical mycobacterial cultures from blood and tissue were also examined.A, Edema on both eyelids; multiple papules, blisters, and crusted erosions with thin exudation on right cheek and neck. B, Erythematous plaques, tense blisters, and bullae on both hands (right hand depicted).

what is your diagnosis?

What is your diagnosis?

Bullous Wells syndrome

Bullous pemphigoid

Famciclovir-resistant disseminated herpes zoster

Bullous Sweet syndrome

a

male

41-50

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2729070

A woman in her 60s presented to the clinic with a 3-month history of pain, swelling, and erythema on her face. Eleven years earlier, she had been diagnosed with left breast carcinoma and had undergone a mastectomy with subsequent radiotherapy and chemotherapy. Seven years later, she had been found to have left supraclavicular lymph nodes metastasis and had undergone a surgical excision. On presentation for the current problem, the patient experienced pain on palpation, but denied fever, chills, or other symptoms. A physical examination revealed violaceous swelling with telangiectasia and necrosis on the forehead, eyelids, nose, and cheek, predominantly involving the left side of the face (Figure 1). A biopsy of the lesion was performed for histopathological analysis (Figure 2).A, A full image and B, a three-quarters image of the face, showing telangiectatic, swelling erythema mainly involving the left side of the forehead, eyelids, nose, and cheek. What Is Your Diagnosis?

Cutaneous angiosarcoma

Radiation dermatitis

Wolf isotopic response

Telangiectatic metastatic breast carcinoma

D. Telangiectatic metastatic breast carcinoma

D

Telangiectatic metastatic breast carcinoma

Histopathological examination revealed hyperkeratosis, epidermal atrophy, and dilated vessels in the dermis. One vessel had nests of highly atypical cells (Figure 2A). On immunohistochemical examination, epithelial cells in the dilated vessels were positive for CD31, and the atypical cells were strongly positive for GATA3 (Figure 2B). A diagnosis of telangiectatic metastatic breast carcinoma (TMBC) was made.A, Highly atypical cells in a dilated vessel in the dermis (hematoxylin-eosin stain; original magnification, ×10). B, Atypical cells in dilated vessels (streptavidin-peroxidase stain; original magnification, ×20).Breast carcinoma is the most prevalent cancer and the second most common cause of cancer death in women.1 Metastatic breast carcinoma most frequently involves the lymph nodes, lung, liver, and bone marrow; cutaneous metastases are relatively uncommon, with an incidence of 2.42%.2 Clinical manifestations can include nodules (47%-80%), alopecia neoplastica (2%-12%), telangiectatic carcinoma (8%-11%), carcinoma erysipeloides (3%-6%), and melanoma-like metastases (6%).1,3 Common sites of cutaneous metastases are the chest and abdomen; the face is rarely affected.4,5 To our knowledge, 2 cases of metastatic breast carcinoma involving the face have been reported, simulating cutaneous angiosarcoma: one with facial telangiectasia and erythema4 and the other with a large red-purplish plaque and stony, hard nodules.5Cases of TMBC have variable clinical appearances and usually present as fleshy to erythematous nodules on the chest; they rarely involve the face. Cutaneous angiosarcoma usually begins as bruise-like patches on the skin, as well as erythematous or violaceous macules, patches, papules, and nodules on the face and scalp of elderly people.6 Lesions may be solitary or multiple; facial swelling may occur. The clinical difference might be the lesion spreading pattern. Cutaneous angiosarcoma usually spreads centrifugally and involves both sides of the face, whereas metastases from a left breast carcinoma mainly affect the left side of the face, as in this case. Histopathologically, cutaneous angiosarcoma is lined by atypical endothelial cells that exhibit apparent nuclear pleomorphism and high mitotic activity, as opposed to those in TMBC, which typically displays tumor cells within dilated vessels in the superficial dermis that can be seen in cutaneous metastases of other carcinomas. Panels of immunohistochemical markers can help determine primary sites of metastasis, including estrogen, progesterone, cytokeratin 7, GATA binding protein 3, and gross cystic disease fluid protein–15.Other differential diagnoses include radiation dermatitis, Wolf isotopic response, and herpes zoster. Radiation dermatitis usually exhibits poikilodermatous changes on the skin surface, including erythema, telangiectasia, hyperpigmentation, and hypopigmentation. Since the patient underwent radiotherapy 11 years earlier, this lesion may be confused with chronic radiation dermatitis, which also presents as painful erythema with telangiectasia and necrosis and displays vascular dilation histopathologically.7 However, other histopathological features of chronic radiation dermatitis did not exist, including pigmentary alteration in the epidermis, dermal fibrosis, irregular shaped fibroblasts, and loss of adnexal structures. It is also important to suspect herpes zoster when a painful, edematous erythema with unilateral dermatomal distribution occurs in an elderly woman who had received immunosuppressive therapy. Histopathologically, herpes zoster is characterized by intraepidermal vesicles, ballooning degeneration of enlarged keratinocytes, and eosinophilic intranuclear inclusion bodies in multinucleated giant cells.8 Also, Wolf isotopic response is the subsequent occurrence of a new skin condition at the site of another unassociated, previously healed disease. The most common primary disease is herpes zoster, which has been reported to be followed by a variety of conditions.9 Thus, the cutaneous angiosarcoma–like lesion in zosteriform distribution raised the possibility of Wolf isotopic response. However, the patient did not recall a varicella-zoster infection or any skin condition on her face. The presence of atypical cells in dilated vessels excluded these diagnoses.The 5-year survival rate is reported10 to be 38% in patients with cutaneous metastases vs 99% in those with localized breast cancer. Recognition is crucial for early diagnosis and management, and suspicion for metastatic spread should be raised in patients with breast cancer who have telangiectatic facial swelling. Unfortunately, the patient was in poor health and could not undergo or afford further treatment. She was still alive at 5-month follow-up.

Dermatology

A woman in her 60s presented to the clinic with a 3-month history of pain, swelling, and erythema on her face. Eleven years earlier, she had been diagnosed with left breast carcinoma and had undergone a mastectomy with subsequent radiotherapy and chemotherapy. Seven years later, she had been found to have left supraclavicular lymph nodes metastasis and had undergone a surgical excision. On presentation for the current problem, the patient experienced pain on palpation, but denied fever, chills, or other symptoms. A physical examination revealed violaceous swelling with telangiectasia and necrosis on the forehead, eyelids, nose, and cheek, predominantly involving the left side of the face (Figure 1). A biopsy of the lesion was performed for histopathological analysis (Figure 2).A, A full image and B, a three-quarters image of the face, showing telangiectatic, swelling erythema mainly involving the left side of the forehead, eyelids, nose, and cheek.

what is your diagnosis?

What is your diagnosis?

Cutaneous angiosarcoma

Telangiectatic metastatic breast carcinoma

Radiation dermatitis

Wolf isotopic response

b

female

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2729591

A man in his 50s presented with an abdominal skin eruption of 2 days’ duration. His medical history included hepatitis C, cirrhosis, and an orthotopic liver transplant (OLT) 3 years prior that was subsequently treated with tacrolimus, 5 mg, and mycophenolate, 750 mg, twice daily. Approximately 2½ years after the transplant, the patient developed gastric outlet obstruction secondary to an infiltrative gastric wall mass. The gastric wall mass was found to be associated with plasmablastic posttransplantation lymphoproliferative disorder (pPTLD). He was subsequently instructed to stop use of mycophenolate and decrease use of tacrolimus to 0.25 mg daily, then treated with 1 cycle of CHOP chemotherapy (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) and lenalidomide, resulting in symptomatic and radiologic improvement. Five weeks after treatment with CHOP chemotherapy, the patient presented with an acute-onset abdominal skin eruption without fever or pain. A computed tomographic scan of the abdomen and pelvis showed possible abdominal wall cellulitis, so treatment with piperacillin-tazobactam and vancomycin was empirically started. Physical examination revealed confluent indurated violaceous papules and plaques coalescing into an annular pattern encircling the healed OLT incisional scar with central sparing (Figure 1A). A 4-mm punch biopsy specimen was obtained for histopathological evaluation (Figure 1B and C) and bacterial and fungal cultures.A, Confluent, indurated, violaceous papules and plaques coalescing into an annular pattern encircling the well-healed orthotopic liver transplant incisional scar. B, Hematoxylin-eosin staining of the punch biopsy shows an atypical, hyperchromatic infiltrate present throughout the superficial and deep dermis. C, High magnification reveals crushed but markedly atypical-appearing lymphoid cells with nuclear hyperchromasia and scant amounts of cytoplasm. Multiple mitotic and apoptotic figures are easily identified. What Is Your Diagnosis?

Reactive granulomatous disorder

Posttransplantation lymphoproliferative disorder

Deep fungal infection

Cutaneous T-cell lymphoma

B. Posttransplantation lymphoproliferative disorder

B

Posttransplantation lymphoproliferative disorder

Histopathologic analysis showed diffuse, atypical lymphoid proliferation infiltrating throughout the superficial and deep dermis with epidermal sparing (Figure 1B). High-powered examination revealed enlarged, markedly atypical-appearing crushed hyperchromatic cells with irregular nuclei and scant amounts of pale eosinophilic and amphophilic cytoplasm (Figure 1C). Numerous apoptotic and mitotic figures were identified. Plasmacytic features were seen. The histologic differential included cutaneous involvement by the known pPTLD vs high-grade lymphoma or leukemia cutis (acute B-cell or T-cell lymphoblastic lymphoma or leukemia), diffuse large B-cell lymphoma, mantle cell lymphoma, acute myeloid leukemia, and small round blue cell tumors (Merkel cell carcinoma and metastatic small cell carcinoma). In situ hybridization and kappa light chain immunohistochemical staining were negative for CD3, CD20, BCL2, BCL6, and Epstein-Barr virus (EBV). CD138 (Figure 2) and lambda chain staining were strongly and diffusely positive. The histology and presence of plasmacytic features in the setting of similar immunohistochemical findings to the patient’s gastric pPTLD made the diagnosis most likely multiorgan pPTLD.Immunohistochemical stain shows that the lesional cells are strongly and diffusely positive for the plasma cell marker CD138.Owing to liver rejection concern, treatment with tacrolimus was initially continued. The patient was treated with 1 cycle of CHOP chemotherapy with resolution of cutaneous findings. However, his internal posttransplantation lymphoproliferative disorder (PTLD) progressed. Cessation of tacrolimus treatment, and additional treatment with CHOP chemotherapy, lenalidomide, bortezomib, and daratumumab were trialed without response, and the patient was referred to hospice care for refractory, rapidly progressive disease.The malignancy PTLD is a complication of immunosuppression for solid organ and hematopoietic stem cell transplants. The incidence of PTLD following OLT in adults is 2% to 3%.1 Usual sites of involvement include the lymph nodes and gastrointestinal tract, whereas cutaneous involvement is very rare.2 Multiorgan involvement occurs in 41% of cases.1The broader PTLD encompass a heterogeneous group of lymphoproliferative diseases categorized histologically. A pPTLD diagnosis is very rare. Only 21 cases of cutaneous pPTLD have been reported, and 8 of those cases involve multiorgan disease.2,3 Cutaneous pPTLD presents as red to purple papules, plaques, and nodules often involving lower extremities, head, and trunk. Interestingly, we report pPTLD in a unique annular configuration encircling an OLT scar. Only 1 report of cutaneous diffuse large B-cell lymphoma presenting with an annular configuration has been reported.4 Histologically, pPTLD presents as a diffuse infiltrate of atypical lymphoid cells with plasmablastic features of eccentric nuclei, clumpy chromatin, prominent central nucleoli, and abundant basophilic cytoplasm. The CD20 stain is negative to weak, CD138 staining is positive, and monoclonality is seen with kappa or lambda light chain restriction.Most cases of B-cell PTLD are associated with primary infection or reactivation of EBV. It is unclear if the present patient’s pathology was related to EBV. In-situ hybridization stains of skin and stomach biopsies were negative, but the patient had a history of EBV infection (positive immunoglobulin G serology), which cannot be used to definitively determine EBV cause.5Initial treatment of PTLD is immune suppression reduction, but further steps are unclear. One study suggests that immune suppression reduction combined with local therapy is insufficient to prevent disease progression, but immune suppression reduction combined with systemic chemotherapy can result in durable, complete remissions.6Cases of pPTLD are particularly aggressive with poor prognosis.7 Progression and survival statistics for pPTLD are unavailable, but data can be extrapolated from plasmablastic lymphoma arising in patients with immunosuppression because of HIV, thought to be a similar disease differentiated by immunosuppression type.6,8 In these patients, 53% reported disease progression with an average survival of 15 months.9 A negative test for EBV, gene translocations, and multisite disease further increase the risk for partial or no remission. Multisite disease is associated with increased rates of mortality compared with single-site disease.1,7A case of pPTLD is a rare and serious complication of solid organ transplant that rarely involves the skin and is associated with high recurrence and mortality. We recommend early decrease and cessation, when possible, of intensive immunosuppression and initiation of intensive treatment owing to the disorder’s highly aggressive nature.

Dermatology

A man in his 50s presented with an abdominal skin eruption of 2 days’ duration. His medical history included hepatitis C, cirrhosis, and an orthotopic liver transplant (OLT) 3 years prior that was subsequently treated with tacrolimus, 5 mg, and mycophenolate, 750 mg, twice daily. Approximately 2½ years after the transplant, the patient developed gastric outlet obstruction secondary to an infiltrative gastric wall mass. The gastric wall mass was found to be associated with plasmablastic posttransplantation lymphoproliferative disorder (pPTLD). He was subsequently instructed to stop use of mycophenolate and decrease use of tacrolimus to 0.25 mg daily, then treated with 1 cycle of CHOP chemotherapy (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) and lenalidomide, resulting in symptomatic and radiologic improvement. Five weeks after treatment with CHOP chemotherapy, the patient presented with an acute-onset abdominal skin eruption without fever or pain. A computed tomographic scan of the abdomen and pelvis showed possible abdominal wall cellulitis, so treatment with piperacillin-tazobactam and vancomycin was empirically started. Physical examination revealed confluent indurated violaceous papules and plaques coalescing into an annular pattern encircling the healed OLT incisional scar with central sparing (Figure 1A). A 4-mm punch biopsy specimen was obtained for histopathological evaluation (Figure 1B and C) and bacterial and fungal cultures.A, Confluent, indurated, violaceous papules and plaques coalescing into an annular pattern encircling the well-healed orthotopic liver transplant incisional scar. B, Hematoxylin-eosin staining of the punch biopsy shows an atypical, hyperchromatic infiltrate present throughout the superficial and deep dermis. C, High magnification reveals crushed but markedly atypical-appearing lymphoid cells with nuclear hyperchromasia and scant amounts of cytoplasm. Multiple mitotic and apoptotic figures are easily identified.

what is your diagnosis?

What is your diagnosis?

Posttransplantation lymphoproliferative disorder

Deep fungal infection

Reactive granulomatous disorder

Cutaneous T-cell lymphoma

a

male

51-60

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2725382

A 13-year-old boy with a longstanding history of gait imbalance presented with 2 episodes of acute-onset left hemibody weakness and dysarthria without changes in sensorium in a 24-hour period. Symptoms lasted approximately 60 minutes each before completely resolving; prior to the day of the events, he had never experienced similar phenomena. Initial examination following the second event revealed mild-to-moderate dysarthria, pes planovalgus and tight achilles tendons bilaterally, and decreased vibratory and fine touch sensation from the great toe up to the mid shin bilaterally. Reflexes were absent at the patella and achilles bilaterally. Bilateral dorsiflexion weakness was present (4 of 5). There were otherwise no motor deficits, muscle atrophy, or lateralizing neurologic abnormalities.On arrival, the patient underwent a stroke/transient ischemic attack workup. Results of a comprehensive metabolic panel, complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, and a coagulation panel were within normal limits. Computed tomography angiogram demonstrated no evidence of extra or intracranial dissection. Magnetic resonance imaging of the brain with and without contrast (Figure) demonstrated symmetric, bilateral, restricted diffusion, with T2 hyperintensities in the supratentorial white matter and corpus callosum. Lumbar puncture was obtained and revealed normal cell counts and no oligoclonal bands or evidence of infection.A, Diffusion-weighted imaging sequence demonstrating bilateral, symmetric, restricted diffusion of the supratentorial white matter (corresponding hypointensity noted on apparent diffusion coefficient sequences). B, T2 sequence demonstrating bilateral and symmetric increased signal in the supratenorial white matter–sparing U-fibers. The patient had reportedly always walked on the outside of his feet and had been considered clumsy when compared with other children but had no history of motor delays. Family history revealed a mother with diminished reflexes, hand tremor, and balance issues with a prior inconclusive electromyogram and nerve conduction study. A younger brother with attention-deficit/hyperactivity disorder also had similar gait abnormalities. What Is Your Diagnosis?

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes

Metachromatic leukodystrophy

X-linked Charcot-Marie-Tooth disease

Pediatric-onset multiple sclerosis

C. X-linked Charcot-Marie-Tooth disease

C

X-linked Charcot-Marie-Tooth disease

The patient had no further events following his admission and neurodiagnostic workup. His examination was consistent with peripheral nerve pathology (diminished reflexes and decrements in sensorium), which appeared to be longstanding as demonstrated by pes planovalgus and tight Achilles tendons. The patient’s superimposed acute events were felt to be reflective of a strokelike phenomenon, given the duration and pattern of neurologic symptoms.In reviewing the patient’s case, examination, and neuroimaging, it was determined that the patient’s clinical findings fit most closely with a diagnosis of Charcot-Marie-Tooth disease (CMTX). The imaging findings, particularly with prominent bilateral and symmetric restricted diffusion in the supratentorial white matter, were thought to be more characteristic of CMTX-related strokelike episode and would not be typical for leukodystrophies (specifically, metachromatic leukodystrophy, X-linked adrenoleukodystrophy, and Alexander disease). Given the symmetric pattern of involvement, mitochondrial disorders were considered although were thought to be less likely given the patient’s normal growth and development and lack of lactic acidosis and other laboratory abnormalities. Acute disseminated encephalomyelitis was considered, but the large-scale confluent lesions involving only the white matter were considered unusual as would be the symmetry of this pattern. Multiple sclerosis and neuromyelitis optica typically do not exhibit these patterns and were thought to be very low on the differential. Myelin oligodendrocyte antibody spectrum disorders can present with large T2-hyperintense lesions but are rarely symmetric or isolated to the white matter only. Although a classic mimic in nearly all central demyelinating disorders, central nervous system lymphoma was lower on the differential based on symmetry, age of patient, and lack of other findings.Ultimately, the patient was discharged at full neurologic capacity. He had an outpatient neurogenetics workup that identified a hemizygous mutation in gap junction β-1 (GJB1) c.227 t > G. Loss-of-function variants in the GJB1 gene are associated with type 1 CMTX (CMTX1) and thus presumed to be a pathogenic variant.As noted previously, CMTX1 is an inherited neuropathy caused by mutation of the GJB1 gene. This gene encodes for connexin 32, which is a gap junction protein that is expressed by Schwann cells in the peripheral nervous system.1 Owing to X-linked inheritance, this disorder mostly affects male patients, although female carries may also be symptomatic, as is possible in this case. Transient neurologic events, also described as strokelike episodes, have been reported in the literature and are often associated with symmetric white matter abnormalities.1-7 The pathophysiology underlying these events and white matter changes is unknown, although it is presumed to be associated with connexin 32 expression in oligodendrocytes in the central nervous system.8 Because most patients with CMTX1 do not have long-term central neurologic phenomenon, there is great debate regarding whether other connexin subtypes may provide compensatory support at gap junctions in patients.9,10Clinically, the strokelike episodes observed in CMTX1 are heterogenous and include transient generalized weakness resembling periodic paralysis, ataxia, dysarthria, or combinations of these deficits.1,6,7 The fluctuation in these neurologic disturbances and magnetic resonance imaging findings should prompt suspicion of the diagnosis. The central nervous system phenotype of CMTX1 disease has a favorable prognosis with respect to central nervous system function, and recognition will avoid unnecessary investigations and potentially harmful therapeutic intervention. There is no clear evidence for steroids or other immunomodulatory therapy in CMTX1-associated transient neurologic phenomenon, with clinical and imaging findings usually being self-limited.6,7This case highlights one of the rarer strokelike presentations in a patient with a neuromuscular disorder. The presence of long-standing peripheral nerve pathology should prompt interrogation of other etiologies to strokelike presentations in children and young adults.

Neurology

A 13-year-old boy with a longstanding history of gait imbalance presented with 2 episodes of acute-onset left hemibody weakness and dysarthria without changes in sensorium in a 24-hour period. Symptoms lasted approximately 60 minutes each before completely resolving; prior to the day of the events, he had never experienced similar phenomena. Initial examination following the second event revealed mild-to-moderate dysarthria, pes planovalgus and tight achilles tendons bilaterally, and decreased vibratory and fine touch sensation from the great toe up to the mid shin bilaterally. Reflexes were absent at the patella and achilles bilaterally. Bilateral dorsiflexion weakness was present (4 of 5). There were otherwise no motor deficits, muscle atrophy, or lateralizing neurologic abnormalities.On arrival, the patient underwent a stroke/transient ischemic attack workup. Results of a comprehensive metabolic panel, complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, and a coagulation panel were within normal limits. Computed tomography angiogram demonstrated no evidence of extra or intracranial dissection. Magnetic resonance imaging of the brain with and without contrast (Figure) demonstrated symmetric, bilateral, restricted diffusion, with T2 hyperintensities in the supratentorial white matter and corpus callosum. Lumbar puncture was obtained and revealed normal cell counts and no oligoclonal bands or evidence of infection.A, Diffusion-weighted imaging sequence demonstrating bilateral, symmetric, restricted diffusion of the supratentorial white matter (corresponding hypointensity noted on apparent diffusion coefficient sequences). B, T2 sequence demonstrating bilateral and symmetric increased signal in the supratenorial white matter–sparing U-fibers. The patient had reportedly always walked on the outside of his feet and had been considered clumsy when compared with other children but had no history of motor delays. Family history revealed a mother with diminished reflexes, hand tremor, and balance issues with a prior inconclusive electromyogram and nerve conduction study. A younger brother with attention-deficit/hyperactivity disorder also had similar gait abnormalities.

what is your diagnosis?

What is your diagnosis?

Metachromatic leukodystrophy

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes

X-linked Charcot-Marie-Tooth disease

Pediatric-onset multiple sclerosis

c

male

11-20

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2726035

A 43-year-old healthy human leukocyte antigen (HLA) B27–positive man was referred to the retina clinic with progressively worsening blurry vision in both of his eyes. His right eye had experienced an episode of blurry vision 4 months previously that had spontaneously improved over a few weeks. Two weeks before presentation, he experienced blurry vision in his left eye and received a diagnosis of vasculitis based on fluorescein angiography (FA) findings. He was referred to a rheumatologist and received high-dose oral prednisone therapy for presumed autoimmune vasculitis. Over the next 2 weeks, he experienced a rapid worsening of vision in both eyes and presented to the Illinois Eye and Ear Infirmary. During an interview, he noted that the laboratory workup results had recently come back as notable for a mildly reactive fluorescent treponemal antibody absorption test. In the absence of other signs or symptoms of syphilis, he was scheduled to undergo a lumbar puncture later that day.On presentation, his visual acuity was counting fingers OD and 20/300 OS, with manifest refraction to 20/60 OS only. He had no afferent pupillary defect and his intraocular pressures were healthy. The anterior segment examination yielded normal results without evidence of anterior chamber inflammation. A dilated fundus examination was notable for mild vitritis of both eyes, mild hyperemia of the right optic nerve, and a large white lesion that encompassed the nerve and macula of both eyes. Fluorescein angiography results revealed multiple hyperfluorescent lesions in late frames (Figure 1).A, Color fundus photograph of the left eye shows a large placoid lesion in the macula. B, Late fluorescein angiography. showing multiple areas of hyperfluorescence in the macula and periphery with peripheral vascular leakage. What Would You Do Next?

Perform bilateral posterior sub-Tenon triamcinolone injections

Increase the dose of oral prednisone

Initiate antiviral therapy

Initiate intravenous penicillin therapy

Acute syphilitic posterior placoid chorioretinitis

D

Initiate intravenous penicillin therapy

The patient presented with vasculitis in the setting of HLA-B27 positivity and had been presumed to have autoimmune vasculitis. Although patients with HLA-B27 may present with isolated ocular findings, they typically have acute-onset unilateral anterior uveitis.1 Posterior uveitis may develop with concurrent anterior or panuveitis and commonly results in extensive phlebitis that is associated with optic disc leakage and cystoid macular edema.2 Isolated retinal vasculitis is rare but has been reported in patients with inflammatory bowel disease.1 Therefore, this patient’s presentation is atypical for HLA-B27-associated uveitis and should have prompted further investigation for infectious etiologies before treatment with systemic steroids. A local steroid injection, such as posterior sub-Tenon triamcinolone, is likewise contraindicated when infection has not yet been ruled out.Viral retinopathy due to herpes simplex virus, varicella-zoster virus, and cytomegalovirus may present with vitreous inflammation. However, the patient lacked retinitis, which typically begins as multifocal areas of retinal whitening in the periphery, and retinal hemorrhages, which are characteristic of cytomegalovirus retinitis.3 Therefore, antiviral therapy would not treat his symptoms.Ocular syphilis can manifest with almost any symptom and ocular finding, including retinal vasculitis.4 Centers for Disease Control and Prevention guidelines define ocular syphilis as affecting any person with clinical symptoms or signs consistent with ocular disease, including uveitis and diminished vision with any stage of syphilis.5 In this patient, a reactive fluorescent treponemal antibody absorption in the setting of decreased vision qualifies as ocular syphilis. This patient’s fundus findings and FA on presentation are typical for acute syphilitic posterior placoid chorioretinitis with the large, yellowish, placoid outer retinal lesion in the macula.6 Fluorescein angiography results show progressive hyperfluorescence in the lesion area, often accompanied by scattered focal hypofluorescence known as leopard spotting.6 Optical coherence tomography may show disruption of the ellipsoid zone, hyperreflective thickening of the retinal pigment epithelium, and subretinal fluid (Figure 2).7 The lesion areas may appear hypofluorescent on indocyanine green angiography and hyperautofluorescent on fundus autofluorescence.6Optical coherence tomography of the left eye shows a loss of the ellipsoid zone and retinal pigment epithelium stippling.Ocular syphilis should be managed according to treatment recommendations for neurosyphilis, which consist of intravenous aqueous crystalline penicillin G or intramuscular procaine penicillin with probenecid for 10 to 14 days.5 In patients who are allergic to penicillin, intravenous or intramuscular ceftriaxone for 10 to 14 days can be used, although some clinicians advocate penicillin desensitization prior to treatment with penicillin.5 Oral or topical steroids may be used concurrently with penicillin treatment as an adjunct to reduce infection-induced inflammation, but oral prednisone alone is not recommended.7 Reports from small case series suggest that intravitreal injection of triamcinolone should be avoided.6 Testing for the human immunodeficiency virus (HIV) often is recommended for patients because of the risk of concurrent infection.5The patient completed a 14-day course of intravenous penicillin therapy and noted immediate visual improvement. His rapid plasma reagin test results showed an elevated titer of 1:64, but his lumbar puncture study results were healthy. He had a negative result for HIV. At 2 months after presentation, his visual acuity was 20/40 OD and 20/20 OS with resolution of the placoid lesions on examination and reconstitution of the ellipsoid zone on optical coherence tomography.

Ophthalmology

A 43-year-old healthy human leukocyte antigen (HLA) B27–positive man was referred to the retina clinic with progressively worsening blurry vision in both of his eyes. His right eye had experienced an episode of blurry vision 4 months previously that had spontaneously improved over a few weeks. Two weeks before presentation, he experienced blurry vision in his left eye and received a diagnosis of vasculitis based on fluorescein angiography (FA) findings. He was referred to a rheumatologist and received high-dose oral prednisone therapy for presumed autoimmune vasculitis. Over the next 2 weeks, he experienced a rapid worsening of vision in both eyes and presented to the Illinois Eye and Ear Infirmary. During an interview, he noted that the laboratory workup results had recently come back as notable for a mildly reactive fluorescent treponemal antibody absorption test. In the absence of other signs or symptoms of syphilis, he was scheduled to undergo a lumbar puncture later that day.On presentation, his visual acuity was counting fingers OD and 20/300 OS, with manifest refraction to 20/60 OS only. He had no afferent pupillary defect and his intraocular pressures were healthy. The anterior segment examination yielded normal results without evidence of anterior chamber inflammation. A dilated fundus examination was notable for mild vitritis of both eyes, mild hyperemia of the right optic nerve, and a large white lesion that encompassed the nerve and macula of both eyes. Fluorescein angiography results revealed multiple hyperfluorescent lesions in late frames (Figure 1).A, Color fundus photograph of the left eye shows a large placoid lesion in the macula. B, Late fluorescein angiography. showing multiple areas of hyperfluorescence in the macula and periphery with peripheral vascular leakage.

what would you do next?

What would you do next?

Perform bilateral posterior sub-Tenon triamcinolone injections

Initiate antiviral therapy

Initiate intravenous penicillin therapy

Increase the dose of oral prednisone

c

male

41-50

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2726036

A woman in her 30s was referred for evaluation of bilateral papilledema and progressive visual loss in the right eye, which deteriorated to blindness in 3 months. She denied any other neurologic symptoms, such as headache, nausea, vomiting, seizures, and paresis. She had a 4-year history of Behçet disease (BD), and her condition had been stabilized with thalidomide. Her optic neuropathy of BD had been treated with high-dose intravenous methylprednisolone for 4 days followed by oral prednisone for a month without improvement.Her best-corrected visual acuity was no light perception OD and 20/20 OS. Intraocular pressure was 21 mm Hg OD and 19 mm Hg OS. Fundus examination revealed papilledema in both eyes (Figure 1A). No obvious sign of optic disc ischemia or active uveitis was observed by fundus fluorescein angiography bilaterally. Humphrey visual fields showed complete visual field loss in the right eye and peripheral visual field defects in the left eye. Her anterior segment was normal in both eyes except for relative afferent pupillary defect in the right eye. Cranial nerve examination was otherwise unremarkable. Magnetic resonance imaging of the brain showed no remarkable abnormalities except for partially empty sella (Figure 1B). She had normal blood pressure levels. Results of laboratory testing regarding systemic infection were negative, and her serum D-dimer level was normal.A, Fundus photograph of the right eye indicated papilledema, disc congestion, venous distension, and macular exudates. B, Sagittal T1-weighted magnetic resonance imaging showed partially empty sella (arrowhead).Obtain cerebral magnetic resonance venography or computed tomographic venography What Would You Do Next?

Add immunosuppressant to corticosteroid therapy

Increase the prednisone dose

Obtain cerebral magnetic resonance venography or computed tomographic venography

Perform catheter cerebral angiography

Cerebral venous thrombosis

C

Obtain cerebral magnetic resonance venography or computed tomographic venography

Optic neuropathy of BD usually occurs with systemic flare-up and responds well to steroids.1 This patient showed no signs of relapse of BD, and her vision continued to deteriorate despite the use of corticosteroids. Therefore, it is not proper to use immunosuppressants and corticosteroids (choices A and B) before a definite diagnosis. Although the patient lacked neurological symptoms other than visual loss, the bilateral papilledema and partially empty sella indicated intracranial hypertension, the possible causes of which include arteriovenous malformations, intracranial mass lesions, obstruction to venous drainage, decreased flow through arachnoid granulations, and idiopathic intracranial hypertension.2 Moreover, a negative magnetic resonance imaging result cannot fully rule out cerebral vascular abnormalities, among which cerebral venous thrombosis (CVT) accounts for 9.4% of the presumed idiopathic intracranial hypertension.3 In suspected CVT, magnetic resonance venography or computed tomographic venography (choice C) is recommended when the magnetic resonance imaging result is negative.4 Therefore, a cerebral magnetic resonance venography of the patient was performed, showing thromboses of the superior sagittal sinus and the right transverse and sigmoid sinus (Figure 2). Draining cerebrospinal fluid is suggested when intracranial hypertension results in vision-threatening papilledema.5 Therefore, a lumber puncture was performed to confirm intracranial hypertension (showing opening pressure of 30.5 cm H2O) and to remove cerebrospinal fluid. Acetazolamide was also initiated to lower the intracranial pressure. Anticoagulation therapy of heparin was started to facilitate recanalization and to prevent recurrent CVT and other venous thrombosis. Endovascular thrombolysis was performed to prevent visual loss of the left eye. The catheter cerebral angiography (choice D), which is invasive, is only considered when magnetic resonance venography or computed tomography venography results are inconclusive or an endovascular procedure is performed.4 Therefore, it was performed along with endovascular thrombolysis to visualize thrombosed veins.Cerebral magnetic resonance venography showed thromboses of the superior sagittal sinus, the right transverse sinus and the right sigmoid sinus (white arrowheads), and stenosis of the left sigmoid sinus (yellow arrowhead).Cerebral venous thrombosis is a rare cerebrovascular disease, with an annual incidence of 3 to 4 cases per million.6 Headache is the most common symptom, presenting in 90% of patients, while focal seizures, paresis, impaired consciousness, and visual disturbance are less common.6 Cerebral venous thrombosis only presenting visual loss is extremely rare.7 The lack of headaches and other neurological symptoms in this case might be caused by the gradually raised intracranial pressure and compensatory anatomical adjustments. Empty sella might be caused by the persistent intracranial hypertension, which pressed the subarachnoid space through the incomplete sellar diaphragm. The normal D-dimer level might be attributed to the prolonged duration of symptoms (more than 1 week).8 Risk factors of CVT were miscellaneous, including prothrombotic conditions, infections, trauma, cancer, and systemic diseases such as BD.6 This patient had BD and had taken thalidomide, both of which are predisposing factors of CVT.6,9One month following thrombolysis, the patient’s bilateral papilledema resolved. Three months later, the visual field of her left eye became normal, while the blindness of her right eye was irreversible. This case reminded us that when empty sella meets bilateral papilledema, intracranial hypertension should be considered even in the absence of neurologic symptoms, and CVT can be one of the possible diagnoses.

Ophthalmology

A woman in her 30s was referred for evaluation of bilateral papilledema and progressive visual loss in the right eye, which deteriorated to blindness in 3 months. She denied any other neurologic symptoms, such as headache, nausea, vomiting, seizures, and paresis. She had a 4-year history of Behçet disease (BD), and her condition had been stabilized with thalidomide. Her optic neuropathy of BD had been treated with high-dose intravenous methylprednisolone for 4 days followed by oral prednisone for a month without improvement.Her best-corrected visual acuity was no light perception OD and 20/20 OS. Intraocular pressure was 21 mm Hg OD and 19 mm Hg OS. Fundus examination revealed papilledema in both eyes (Figure 1A). No obvious sign of optic disc ischemia or active uveitis was observed by fundus fluorescein angiography bilaterally. Humphrey visual fields showed complete visual field loss in the right eye and peripheral visual field defects in the left eye. Her anterior segment was normal in both eyes except for relative afferent pupillary defect in the right eye. Cranial nerve examination was otherwise unremarkable. Magnetic resonance imaging of the brain showed no remarkable abnormalities except for partially empty sella (Figure 1B). She had normal blood pressure levels. Results of laboratory testing regarding systemic infection were negative, and her serum D-dimer level was normal.A, Fundus photograph of the right eye indicated papilledema, disc congestion, venous distension, and macular exudates. B, Sagittal T1-weighted magnetic resonance imaging showed partially empty sella (arrowhead).Obtain cerebral magnetic resonance venography or computed tomographic venography

what would you do next?

What would you do next?

Add immunosuppressant to corticosteroid therapy

Increase the prednisone dose

Perform catheter cerebral angiography

Obtain cerebral magnetic resonance venography or computed tomographic venography

d

female

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2726698

An 8-year-old girl was referred to the vitreoretinal service for evaluation of bilateral macular lesions noted by her pediatric ophthalmologist. Bilateral lateral rectus muscle recession for exotropia was performed 4 years before this presentation. Medical history was otherwise unremarkable. The patient was born full term after a normal pregnancy and delivery, with normal growth assessments. The patient was performing well in school.On examination, her best-corrected visual acuity was 20/40 OD and 20/40 OS, which was stable from previous visits. Her pupils were round and reactive. There was a residual intermittent exotropia of 4 prism diopters bilaterally. Findings on slitlamp examination of the anterior segment were unremarkable. A single, 1-cm, oval, lightly pigmented macule with irregular borders was noted on her right upper arm. Dilated fundus examination revealed eccentric, yellow-clear, preretinal lesions in the maculas of both eyes. Optical coherence tomography revealed hyperreflective areas on the surface of the macula with a spiculated appearance, projecting anteriorly into the vitreous. There was an increase in retinal thickness and loss of the foveal contour in both eyes (Figure).Optical coherence tomography of the right eye (A) showing an atypical epiretinal membrane with anterior projection into the vitreous and hazy borders and the left eye (B) showing a similar epiretinal membrane with mild anterior projection and hazy borders.Obtain a family medical history and genetic testingRecommend pars plana vitrectomy with epiretinal membrane peel What Would You Do Next?

Obtain a family medical history and genetic testing

Recommend pars plana vitrectomy with epiretinal membrane peel

Observe the lesions

Give an intravitreal ocriplasmin injection

Neurofibromatosis 2–related epiretinal membranes

A

Obtain a family medical history and genetic testing

After further questioning, the patient’s father had a history of neurofibromatosis type 2 (NF2) and died in his early 40s. Her younger brother was previously diagnosed with bilateral parasellar masses that extended into the right orbital apex, causing a neurogenic ptosis of the right upper eyelid. The brother subsequently tested positive for NF2 gene with deletion of exons 1 through 7. Genetic testing results obtained for the patient were positive for an abnormality in the NF2 gene with deletion of the NF2 exons 1 through 7. Observation (choice C) and surgical intervention (choice B) are both potential management options for patients with epiretinal membranes. However, an epiretinal membrane in a child should prompt further medical history, family medical history, and potential genetic testing (choice A) for systemic disorders. Ocriplasmin injection (choice D) would not be the correct treatment for removal of epiretinal membranes.An autosomal dominant inherited disorder, neurofibromatosis type 2, is caused by mutations in the NF2 gene located on chromosome 22.1 Abnormalities in the NF2 gene, which produces the tumor suppressor merlin protein, lead to the disease. Individuals with the disease are predisposed to tumors of the nervous system, including bilateral vestibular schwannomas, meningiomas, and spinal tumors. Although thought to be rare, the incidence of NF2 may be as high as 1 in 25 000 persons.2 Skin lesions are an important diagnostic criterion for neurofibromatosis type 1; however, skin lesions can also be found in patients with NF2.3 Ophthalmic manifestations can be seen including cataracts, epiretinal membranes, retinal hamartomas, and optic nerve meningiomas.Epiretinal membranes are a common finding in NF2 and are usually solitary within each eye and located in the macula. They have been described in children as young as 4 years and are likely to be congenital.4 Many epiretinal membranes in NF2 have a spiculated appearance with curled edges, projecting anteriorly into the vitreous and best visualized using optical coherence tomography.5There has been controversy about whether these epiretinal membranes could represent a mild form of combined hamartomas of the retinal and retina pigment epithelium. Although both are similar congenital macular lesions, there are certain optical coherence tomographic characteristics that can differentiate them. Combined hamartomas of the retinal and retina pigment epithelium lesions show greater retinal disorganization, photoreceptor attenuation, and loss of the foveal depression compared with NF2 epiretinal membranes.5Although observation of NF2-related epiretinal membranes is an option if the vision loss is mild, recent studies have shown gains in vision with early pars plana vitrectomy and epiretinal membrane peel.6,7 Bonnin et al7 reported operating on 13 patients with epiretinal membranes who were 12 years or younger. Of the 13 patients, 12 had improvement in visual acuity and the corrected visual acuity improved from an average of 20/160 to 20/40.The patient has continued to follow up with a pediatric neurologist, who has recommended magnetic resonance imaging of the brain to rule out central nervous system lesions. The family reported that they prefer observation of the retinal lesions and will consider surgery if the patient’s vision worsens.

Ophthalmology

An 8-year-old girl was referred to the vitreoretinal service for evaluation of bilateral macular lesions noted by her pediatric ophthalmologist. Bilateral lateral rectus muscle recession for exotropia was performed 4 years before this presentation. Medical history was otherwise unremarkable. The patient was born full term after a normal pregnancy and delivery, with normal growth assessments. The patient was performing well in school.On examination, her best-corrected visual acuity was 20/40 OD and 20/40 OS, which was stable from previous visits. Her pupils were round and reactive. There was a residual intermittent exotropia of 4 prism diopters bilaterally. Findings on slitlamp examination of the anterior segment were unremarkable. A single, 1-cm, oval, lightly pigmented macule with irregular borders was noted on her right upper arm. Dilated fundus examination revealed eccentric, yellow-clear, preretinal lesions in the maculas of both eyes. Optical coherence tomography revealed hyperreflective areas on the surface of the macula with a spiculated appearance, projecting anteriorly into the vitreous. There was an increase in retinal thickness and loss of the foveal contour in both eyes (Figure).Optical coherence tomography of the right eye (A) showing an atypical epiretinal membrane with anterior projection into the vitreous and hazy borders and the left eye (B) showing a similar epiretinal membrane with mild anterior projection and hazy borders.Obtain a family medical history and genetic testingRecommend pars plana vitrectomy with epiretinal membrane peel

what would you do next?

What would you do next?

Give an intravitreal ocriplasmin injection

Obtain a family medical history and genetic testing

Observe the lesions

Recommend pars plana vitrectomy with epiretinal membrane peel

b

female

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2726699

A woman in her mid-80s presented with ptosis and blurred vision in the right eye. The ptosis was first noticed 3 weeks prior to presentation and had gradually worsened. She denied any acute changes in her health and review of her systems was unremarkable. The patient had an ocular history of bilateral cataract surgery in 2016, a medical history of thyroid cancer with thyroidectomy in 1990, and stage IIIc lobular carcinoma of the right breast with mastectomy of the right breast in 2008.On examination, her visual acuity was 20/80 OD and 20/30 OS. Pupils were equal in size and reactive without an afferent pupillary defect. Intraocular pressures were 21 mm Hg OD and 16 mm Hg OS. Assessment of the extraocular motility demonstrated moderate limitation to up gaze of the right eye and full ductions of the left eye. External examination confirmed right upper eyelid ptosis without substantial proptosis. On slitlamp examination, eversion of the right upper eyelid revealed a solid, superior bulbar conjunctival mass measuring 10 mm in diameter (Figure 1A). B-scan ultrasonography demonstrated an extraconal, noncompressible lesion of orbital tissue (Figure 1B). A computed tomographic scan showed nonspecific, increased soft-tissue density in the superior and anterior orbit.A, External photograph of the right eye demonstrating an elevated conjunctival lesion. B, Ultrasonographic image of the conjunctival lesion; the arrowhead indicates the tumor location.Complete blood cell count, basic metabolic panel, and liver function tests What Would You Do Next?

Topical corticosteroid eyedrops

Conjunctival biopsy

Complete blood cell count, basic metabolic panel, and liver function tests

Serum and urine electrophoresis

Breast cancer metastasis to the conjunctiva

B

Conjunctival biopsy

The differential diagnosis for an acquired conjunctival lesion is broad.1,2 The lesion can be classified as epithelial, subepithelial, pigmented, or inflammatory. Acquired epithelial lesions include squamous cell carcinoma and papilloma. Subepithelial lesions range from benign causes, such as lacrimal gland duct cysts and myxomas, to infiltrative conditions, such as metastatic carcinoma. Pigmented lesions typically consist of nevi or malignant melanoma, and inflammatory lesions can stem from conditions such as sarcoidosis.2When a patient presents with a conjunctival lesion, diagnostic imaging is important. Given the concern for an orbital mass in this case, orbital imaging was the initial step of evaluation. Findings of the computed tomographic scan that was performed were nonspecific, as was B-scan ultrasonography. Given the lack of diagnostic information from imaging, a conjunctival biopsy was performed to evaluate the lesion, which is important given the patient’s history of both thyroid and breast cancer.3 Although a systemic workup, including complete blood cell count and basic metabolic panel as well as serum and urine electrophoresis, are important in the evaluation for lymphoma or amyloidosis, the conjunctival biopsy was the next step given its ability to provide a more specific diagnosis.4,5 Histopathologic testing results revealed tumor cells with estrogen-receptor positive, progesterone-receptor positive, and ERBB2-negative, confirming the diagnosis of metastatic breast carcinoma (Figure 2). Topical corticosteroids are useful in inflammatory conditions, but would not be indicated in this patient.Histopathologic examination of a conjunctival lesion revealing tumor cells (hematoxylin-eosin, original magnification ×400).The most common primary tumor to give rise to ocular metastasis in the female population is breast carcinoma.6 The incidence of ocular metastasis among patients with breast cancer is approximately 8% to 10%, typically occurring 2 to 5 years after initial diagnosis of the primary tumor.7 Metastatic lesions to the conjunctiva are uncommon and indicate poor prognosis.3 Symptoms include pain, chemosis, and foreign body sensation.3,6-9 In this case, the patient noticed ptosis, but was not aware of the conjunctival lesion as the lesion was not visible until the upper eyelid was everted.Most metastatic conjunctival lesions regress with external-beam radiotherapy, excisional biopsy, and/or chemotherapy.3,7 Because ocular disease presents when the systemic malignant lesion is advanced, the prognosis tends to be poor.2 The mean reported survival time after diagnosis of a conjunctival mass varies, ranging from 3 weeks to 26 months.3,6 Therefore, it is important to recognize conjunctival metastasis upon examination to provide timely and adequate therapeutic intervention.6,8 In addition, our case highlights the importance of obtaining a thorough history, because distant metastases can present many years after the initial diagnosis of nonocular malignant diseases.The patient underwent an excisional conjunctival biopsy on the same day as presentation, confirming the diagnosis of metastatic breast carcinoma. Further systemic evaluation revealed additional metastases to the cervical, lumbar, and thoracic spine; sacrum and bilateral iliac bones; adrenal glands; and lymph nodes. She underwent antiestrogen therapy with an adjuvant cyclin-kinase inhibitor. Five months after presentation of the ocular symptoms, positron emission tomographic scan showed full remission of the malignant lesion.

Ophthalmology

A woman in her mid-80s presented with ptosis and blurred vision in the right eye. The ptosis was first noticed 3 weeks prior to presentation and had gradually worsened. She denied any acute changes in her health and review of her systems was unremarkable. The patient had an ocular history of bilateral cataract surgery in 2016, a medical history of thyroid cancer with thyroidectomy in 1990, and stage IIIc lobular carcinoma of the right breast with mastectomy of the right breast in 2008.On examination, her visual acuity was 20/80 OD and 20/30 OS. Pupils were equal in size and reactive without an afferent pupillary defect. Intraocular pressures were 21 mm Hg OD and 16 mm Hg OS. Assessment of the extraocular motility demonstrated moderate limitation to up gaze of the right eye and full ductions of the left eye. External examination confirmed right upper eyelid ptosis without substantial proptosis. On slitlamp examination, eversion of the right upper eyelid revealed a solid, superior bulbar conjunctival mass measuring 10 mm in diameter (Figure 1A). B-scan ultrasonography demonstrated an extraconal, noncompressible lesion of orbital tissue (Figure 1B). A computed tomographic scan showed nonspecific, increased soft-tissue density in the superior and anterior orbit.A, External photograph of the right eye demonstrating an elevated conjunctival lesion. B, Ultrasonographic image of the conjunctival lesion; the arrowhead indicates the tumor location.Complete blood cell count, basic metabolic panel, and liver function tests

what would you do next?

What would you do next?

Topical corticosteroid eyedrops

Conjunctival biopsy

Serum and urine electrophoresis

Complete blood cell count, basic metabolic panel, and liver function tests

b

female

81-90

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2727508

A 53-year-old male was referred for evaluation of a nonhealing corneal ulcer. He had not received medical care in 20 years and had no known medical diagnoses, but his social history was notable for consumption of approximately 12 alcoholic beverages per day. His ocular history was notable for left-eye enucleation from recent trauma. He initially presented to his local ophthalmologist with right eye redness, pain, and photophobia for 1 week. He was diagnosed with a corneal ulcer. Bacterial (aerobic and anaerobic) and fungal cultures were obtained, and the patient started receiving topical moxifloxacin. The cultures were negative after 1 week, but the patient did not demonstrate signs of clinical improvement. A complete blood cell count, metabolic panel, and serum test results (for antinuclear antibodies, peripheral antineutrophil cytoplasmic antibodies, cytoplasmic antineutrophil cytoplasmic antibodies, rheumatoid factor, and anti–cyclic citrullinated peptide) were unremarkable. On referral, his visual acuity was 20/100 OD, and his intraocular pressure was 16 mm Hg. Anterior examination revealed a diffusely hazy cornea with a blunted light reflex. A large, well-demarcated epithelial defect with substantial underlying stromal loss was seen in the inferonasal periphery (Figure). The stroma was 40% thinned without infiltrate. The epithelium was heaped up along the lesion borders. Corneal sensation was diminished. The conjunctiva demonstrated hyperemia, which was more prominent around the corneal lesion, although there was no discharge. A dilated ophthalmoscopic examination was unremarkable. Repeated bacterial and fungal cultures were obtained.An external photograph showing a large, well-demarcated epithelial defect with underlying stromal loss.Obtain herpes simplex virus tissue culture and antigen detection testsBroaden antibiotic coverage to include vancomycin and tobramycin What Would You Do Next?

Use confocal microscopy to evaluate for cysts

Obtain herpes simplex virus tissue culture and antigen detection tests

Broaden antibiotic coverage to include vancomycin and tobramycin

Obtain serum vitamin A levels

Keratomalacia

D

Obtain serum vitamin A levels

The patient was sent to the emergency department for serum vitamin A testing (choice D), which revealed undetectable vitamin A levels (normal range, 30-80 μg/dL; to convert to micromoles per liter, multiply by 0.0349). The differential diagnosis for a nonhealing corneal ulcer may include inadequate antibiotic coverage, a nonbacterial infectious source, systemic autoimmune conditions, and epithelial wound-healing deficits.The patient’s history and presentation is consistent with vitamin A deficiency–associated keratomalacia. Patients with alcoholism may have protein and vitamin deficiencies, including vitamin A,1 because of both low dietary intake and decreased absorption. Nyctalopia is often the initial finding in vitamin A deficiency,2 although it was not present in this case. Vitamin A deficiency may also lead to ocular surface disease, such as conjunctival and corneal xerosis, and diffuse or focal keratin accumulation with a foamy appearance (Bitôt spots). There is a lack of mucin because goblet cells in the mucosal surface are greatly reduced.3 In advanced stages, keratomalacia may develop, with severe corneal ulceration and thinning, and this may ultimately result in diffuse corneal necrosis.Confocal microscopy to evaluate for cysts (choice A) to diagnose Acanthamoeba keratitis would not be the preferred answer. An infectious causative mechanism that is inadequately treated by a fourth-generation fluoroquinolone, such as Acanthamoeba keratitis, typically presents as a nonhealing corneal ulcer in a patient who wears contact lenses, often associated with radial keratoneuritis and/or a ring ulcer.Similarly, a herpes simplex virus tissue culture and antigen detection test (choice B) would not be the preferred choice. While herpes simplex virus epithelial keratitis may be considered in cases of nonhealing corneal ulcers, it is primarily a clinical diagnosis, and this patient lacked the dendritic ulcerations, subepithelial or deep stromal infiltrates, and corneal edema characteristic of this clinical entity. Decreased corneal sensation may suggest a neurotrophic causative mechanism, owing to diabetes, chemical burns, contact lens use, and chronic topical medications. However, this patient’s metabolic profile, including his glucose level, was unremarkable, and the history and examination did not reveal burns, contact lens use, or topical medications.Broadening antibiotic coverage (choice C) would not be the preferred answer. There is a low suspicion of infection, given the lack of injection, infiltrate, and discharge on examination. In addition, bacterial and fungal cultures were negative. While it is reasonable to repeat cultures, vancomycin and tobramycin may induce corneal epithelial toxicity, which may exacerbate the problem.The urgency of identifying vitamin A deficiency is associated with both systemic and ocular manifestations. Children with keratomalacia owing to vitamin A deficiency have a high mortality rate, with estimates up to 30% to 80%.4,5 Keratomalacia may progress to corneal perforation in a matter of days if left untreated.6 Furthermore, stromal loss is irreversible, resulting in permanent structural damage.7This patient started receiving high-dose oral vitamin A supplementation at 200 000 IU for the first 2 consecutive days, followed by another dose 1 week later.8 He also started receiving aggressive lubricating ointment, while decreasing topical moxifloxacin use. He had marked improvement in his right eye pain, vision, and corneal thinning. His conjunctival and corneal keratinization also improved dramatically within several days. He was referred to a primary care physician for further nutritional evaluation.

Ophthalmology

A 53-year-old male was referred for evaluation of a nonhealing corneal ulcer. He had not received medical care in 20 years and had no known medical diagnoses, but his social history was notable for consumption of approximately 12 alcoholic beverages per day. His ocular history was notable for left-eye enucleation from recent trauma. He initially presented to his local ophthalmologist with right eye redness, pain, and photophobia for 1 week. He was diagnosed with a corneal ulcer. Bacterial (aerobic and anaerobic) and fungal cultures were obtained, and the patient started receiving topical moxifloxacin. The cultures were negative after 1 week, but the patient did not demonstrate signs of clinical improvement. A complete blood cell count, metabolic panel, and serum test results (for antinuclear antibodies, peripheral antineutrophil cytoplasmic antibodies, cytoplasmic antineutrophil cytoplasmic antibodies, rheumatoid factor, and anti–cyclic citrullinated peptide) were unremarkable. On referral, his visual acuity was 20/100 OD, and his intraocular pressure was 16 mm Hg. Anterior examination revealed a diffusely hazy cornea with a blunted light reflex. A large, well-demarcated epithelial defect with substantial underlying stromal loss was seen in the inferonasal periphery (Figure). The stroma was 40% thinned without infiltrate. The epithelium was heaped up along the lesion borders. Corneal sensation was diminished. The conjunctiva demonstrated hyperemia, which was more prominent around the corneal lesion, although there was no discharge. A dilated ophthalmoscopic examination was unremarkable. Repeated bacterial and fungal cultures were obtained.An external photograph showing a large, well-demarcated epithelial defect with underlying stromal loss.Obtain herpes simplex virus tissue culture and antigen detection testsBroaden antibiotic coverage to include vancomycin and tobramycin

what would you do next?

What would you do next?

Broaden antibiotic coverage to include vancomycin and tobramycin

Obtain serum vitamin A levels

Obtain herpes simplex virus tissue culture and antigen detection tests

Use confocal microscopy to evaluate for cysts

b

male

51-60

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2721232

A white man in his 20s presented with numerous pink and brown papules and plaques, some with ulceration, on the head and along the midline of the neck and spine (Figure). Medical history included medulloblastoma treated with irradiation of the brain and spine at age 2 years. He also received radiation therapy for a meningioma of the posterior fossa in adulthood. He was also treated for several seemingly similar lesions on the face and scalp and had a family history of similar cutaneous lesions reported in 2 brothers and 1 niece.Figures show crusted erythematous papules and plaques adjacent to the surgical excision scar within a prior irradiation field on the head and neck (A) and erythematous and hyperpigmented papules and plaques overlying diffuse postsurgical scarring within a prior irradiation field on the back (B). What Is Your Diagnosis?

Angiosarcoma

Leukemia cutis

Squamous cell carcinoma

Basal cell carcinoma

D. Basal cell carcinoma

D

Basal cell carcinoma

Basal cell carcinoma (BCC) is the most common cutaneous cancer in the United States and has an indolent growth pattern, though the lesions may become crusted and ulcerated. Although metastasis is rare, local invasion and destruction may occur with aggressive or chronic lesions. Thus, early identification and treatment is prudent. Risk factors include fair complexion; a history of intense, intermittent sun exposure; immunosuppression; and a positive family history. Radiation exposure may be especially carcinogenic in inducing BCC, and BCC is more likely than squamous cell carcinoma to develop following radiation exposure, with the greatest risk seen in patients who were younger than 10 years when exposed.1 Furthermore, several genetic syndromes are associated with an increased risk of multiple BCCs, including basal cell nevus syndrome (BCNS).Basal cell nevus syndrome is an autosomal dominant condition caused by mutations of genes involved in the Sonic Hedgehog signaling pathway, most often mutations of PTCH1, a tumor suppressor.2,3 In addition to multiple BCCs, which typically develop during late adolescence to early adulthood, other classic manifestations include odontogenic keratocysts of the jaw, palmoplantar pits, calcification of the falx cerebri, and skeletal anomalies.4-6 Other neoplasms, specifically, medulloblastoma, meningioma, and cardiac and bilateral ovarian fibromas, are also associated with BCNS. Although diagnosed at an earlier age and in multiplicity, BCCs associated with BCNS usually have a similar natural history and predilection for sun-exposed areas as seen in patients without the syndrome. Of note, exposure to ionizing radiation is especially detrimental to individuals with BCNS, with a high tumor burden occurring in irradiated sites.2,4,7Prior to the present patient’s initial visit, therapy with 150 mg/d of vismodegib, a systemic inhibitor of the Sonic Hedgehog signaling pathway, had been discontinued owing to adverse effects of headache and muscle spasms. Given the burden of disease at presentation, therapy with vismodegib was restarted with an amended dosing schedule. One month of 150-mg/d vismodegib was alternated with 1 month off of treatment, which the patient tolerated well. Dosing frequency was eventually increased to 150 mg/d for 5 days per week. In addition, curettage of larger lesions was performed with topical application of imiquimod at home. Despite this treatment regimen, several lesions continued to enlarge, leading to painful ulceration and bleeding. At the last follow-up visit, a plan was made for the patient to participate in an immunotherapy trial for refractory disease.

Oncology

A white man in his 20s presented with numerous pink and brown papules and plaques, some with ulceration, on the head and along the midline of the neck and spine (Figure). Medical history included medulloblastoma treated with irradiation of the brain and spine at age 2 years. He also received radiation therapy for a meningioma of the posterior fossa in adulthood. He was also treated for several seemingly similar lesions on the face and scalp and had a family history of similar cutaneous lesions reported in 2 brothers and 1 niece.Figures show crusted erythematous papules and plaques adjacent to the surgical excision scar within a prior irradiation field on the head and neck (A) and erythematous and hyperpigmented papules and plaques overlying diffuse postsurgical scarring within a prior irradiation field on the back (B).

what is your diagnosis?

What is your diagnosis?

Angiosarcoma

Leukemia cutis

Squamous cell carcinoma

Basal cell carcinoma

d

male

21-30

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2722615

A 41-year-old woman with a history of Hodgkin disease in her adolescence was diagnosed with melanoma of the left upper thigh that was classified as American Joint Committee on Cancer (AJCC) stage IIA with (pT3aN0 [sn0/1] M0) BRAF mutation. One year later she underwent inguinal lymphadenectomy for macrometastasis followed by adjuvant immunotherapy with ipilimumab, a monoclonal antibody that targets cytotoxic T-lymphocyte antigen 4. Owing to local disease progression, treatment escalation with combined immunotherapy (ipilimumab and nivolumab, an anti–PD-1 [programmed cell death 1]) antibody was initiated. Apart from immunotherapy-induced thyroiditis, the treatment was well tolerated. However, after 11 cycles of nivolumab, the patient presented with progressive painful reddening and swelling of the left thigh. There was no deterioration of the general condition, no fever, no change in current medication, and no recent cold exposure. Clinical examination revealed diffuse erythematous induration of the upper thigh expanding to the lower left abdominal area, as well as multiple small palpable subcutaneous nonindurated nodules on the ipsilateral gluteal region and leg (Figure, A). Fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) detected multiple FDG-active lesions in both lower extremities and the lumbar region; a previously described left iliac lymphadenopathy was partially regressed (Figure, B). A diagnostic biopsy specimen of the left thigh revealed a lobular lymphocytic panniculitis with dense infiltrate of mainly lymphocytes and plasma cells with no signs of vasculitis (Figure, C and D). Direct immunofluorescence and blood analysis showed an absence of specific autoimmune antigens (test results for α-1 antitrypsin, antinuclear antibody, anti-Sjögren syndrome–related antigen, and anti-Sjögren syndrome–related antigen B were all unremarkable).A, Localized erythematous brownish induration seen on the upper thigh. Arrowheads correlate with the most prominent clinical findings. B, Radioactive fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) reveals multiple subcutaneous lesions in both lower extremities, the lumbar region, and on the ipsilateral lower leg with high FDG uptake highly suggestive of (in transit) metastasis. C and D, Lesional skin biopsy samples obtained from the proximal left thigh show normal epidermis and dermis with patchy infiltrate of the deep subcutaneous fat (hematoxylin-eosin stain). Green arrows indicate the plasma cells, and blue arrows indicate the lymphocytes. What Is Your Diagnosis?

Disease progression

Nivolumab-induced extensive panniculitis

Cold panniculitis

Erythema nodosum under nivolumab

B. Nivolumab-induced extensive panniculitis

B

Nivolumab-induced extensive panniculitis

Immunologic checkpoint blockade has changed the treatment landscape for advanced melanoma with impressive response and survival rates,1 but it is associated with a large spectrum of immune-related toxic effects owing to an increase of the baseline T-cell–specific immune response.2,3 Skin toxic effects represent the most common adverse effects associated with immune checkpoint inhibitors, including pruritus, rash, vitiligolike depigmentation, and lichenoid, cytotoxic, and autoimmune bullous reactions.4 Interestingly, appearance of these adverse effects, especially vitiligo, is associated with a superior outcome and treatment response.5Panniculitis is a group of inflammatory disorders of the subcutaneous fat tissue. Diagnosis can be challenging because different forms of panniculitis may present with overlapping clinical findings. Panniculitis can either be classified clinically based on the cause (eg, infection, inflammation, trauma, enzymatic destruction, deposition, or cancer) or histologically as lobular or septal panniculitis with or without concomitant vasculitis. As for drug-induced panniculitis, clinical and histopathological features of drug-induced panniculitis are indistinguishable from those associated with other agents, and only the history of previous drug intake or clinical improvement after drug treatment interruption may prove a causative relationship.6Erythema nodosum (EN) is the most common type of panniculitis located on the anterior surface of the lower extremities. Mostly idiopathic in origin, EN may indicate an underlying systematic disease such as tuberculosis, deep bacterial and/or fungal infection, inflammatory bowel disease, or cancer. Erythema nodosum represents the cutaneous manifestation of sarcoidosis. Histologically, septal panniculitis can present without vasculitis and with radial granulomas. Erythema nodosum is also reported to be the most common drug-induced panniculitis.7In the setting of immune checkpoint inhibitors used for cell-mediated immunity, few reports in the literature have described a sarcoidlike granulomatous panniculitis.7-9 The typical histological pattern includes partly granulomatous reactions with mixed septal and lobular inflammatory infiltrate with lymphocytes and epithelioid histiocytes.Herein, we report a case of lobular panniculitis without vasculitis. Lobular panniculitis is usually considered in connective tissue diseases, such as systemic lupus erythematosus, pancreatic diseases or α-1 antitrypsin deficiency. Other histopathologic differential diagnoses include infection, trauma, or subcutaneous T-cell lymphoma.10 All of these differential diagnoses were ruled out through diagnostic workup in the present case. The absence of tumor cells in the biopsy specimen ruled out disease progression.The treatment with nivolumab was continued unchanged, and the patient achieved a complete metabolic response seen in the routine follow-up 18F-FDG PET-CTs. As for the panniculitis, the lesion regressed slowly without the need for systemic steroid or treatment cessation.With regard to the treatment approach for immunotherapy-induced panniculitis, the lesions usually regress spontaneously or after treatment with nonsteroidal anti-inflammatory drugs or oral or topical steroids. Cessation of immunotherapy is not generally necessary.To our knowledge, this is the first case of an extensive lobular panniculitis in a patient treated with an anti–PD-1 antibody. Until recently, panniculitides associated with immunotherapeutic agents have not been extensively described. Because inconclusive FDG-avid lesions may simulate disease progression, recognition of these adverse effects is important, and histopathological workup is mandatory to ensure adequate treatment and prevent unnecessary treatment discontinuation.

Oncology

A 41-year-old woman with a history of Hodgkin disease in her adolescence was diagnosed with melanoma of the left upper thigh that was classified as American Joint Committee on Cancer (AJCC) stage IIA with (pT3aN0 [sn0/1] M0) BRAF mutation. One year later she underwent inguinal lymphadenectomy for macrometastasis followed by adjuvant immunotherapy with ipilimumab, a monoclonal antibody that targets cytotoxic T-lymphocyte antigen 4. Owing to local disease progression, treatment escalation with combined immunotherapy (ipilimumab and nivolumab, an anti–PD-1 [programmed cell death 1]) antibody was initiated. Apart from immunotherapy-induced thyroiditis, the treatment was well tolerated. However, after 11 cycles of nivolumab, the patient presented with progressive painful reddening and swelling of the left thigh. There was no deterioration of the general condition, no fever, no change in current medication, and no recent cold exposure. Clinical examination revealed diffuse erythematous induration of the upper thigh expanding to the lower left abdominal area, as well as multiple small palpable subcutaneous nonindurated nodules on the ipsilateral gluteal region and leg (Figure, A). Fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) detected multiple FDG-active lesions in both lower extremities and the lumbar region; a previously described left iliac lymphadenopathy was partially regressed (Figure, B). A diagnostic biopsy specimen of the left thigh revealed a lobular lymphocytic panniculitis with dense infiltrate of mainly lymphocytes and plasma cells with no signs of vasculitis (Figure, C and D). Direct immunofluorescence and blood analysis showed an absence of specific autoimmune antigens (test results for α-1 antitrypsin, antinuclear antibody, anti-Sjögren syndrome–related antigen, and anti-Sjögren syndrome–related antigen B were all unremarkable).A, Localized erythematous brownish induration seen on the upper thigh. Arrowheads correlate with the most prominent clinical findings. B, Radioactive fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) reveals multiple subcutaneous lesions in both lower extremities, the lumbar region, and on the ipsilateral lower leg with high FDG uptake highly suggestive of (in transit) metastasis. C and D, Lesional skin biopsy samples obtained from the proximal left thigh show normal epidermis and dermis with patchy infiltrate of the deep subcutaneous fat (hematoxylin-eosin stain). Green arrows indicate the plasma cells, and blue arrows indicate the lymphocytes.

what is your diagnosis?

What is your diagnosis?

Cold panniculitis

Disease progression

Nivolumab-induced extensive panniculitis

Erythema nodosum under nivolumab

c

female

41-50

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2722743

A woman in her mid-50s presented to the hospital with acute, worsening dyspnea, with shortness of breath at rest and with minimum exertion. She had undergone mechanical mitral valve replacement and aortic dissection repair 2 months prior to presentation. On physical examination, she was found to have elevated jugular venous pressure, bilateral rales in her lungs, and reduced intensity of the mitral valve closure sound, and her international normalized ratio was subtherapeutic (1.5). An echocardiographic image showed a mean gradient of 12 mm Hg across the mitral valve, suggesting valve stenosis. Fluoroscopy showed restricted mobility of the leaflets (Video 1). Transesophageal echocardiography showed a large thrombus on the mechanical mitral valve, along with a small new dissection flap in the aortic root (Figure and Video 2). A chronic dissection flap was evident in the aortic arch and descending aorta, which was unchanged from the previous aortic dissection repair.Refer the patient for aortic root dissection repairAdminister a full dose of emergency tissue plasminogen activator What Would You Do Next?

Refer the patient for aortic root dissection repair

Start intravenous heparin

Administer a full dose of emergency tissue plasminogen activator

Perform emergency percutaneous clot removal

Acute mechanical mitral valve thrombosis

B

Start intravenous heparin

The decision was made to start the patient on intravenous heparin. Repeat surgery (choice A) was considered high risk in this patient because she had New York Heart Association functional class IV symptoms, pulmonary edema, and a history of surgery 2 months ago. The new dissection flap was small, with a small leak of blood into the false lumen. The patient presented with decompensated heart failure symptoms but had no chest pain. Tissue plasminogen activator (choice C) was not given because of the small stable dissection flap seen in the aortic root. Performing an emergency percutaneous clot removal procedure (choice D) is not correct because, for practical purposes, there is no device that can perform percutaneous removal of clots formed on mechanical valves.Mechanical valve thrombosis is a relatively uncommon complication that has an annual occurrence of 1% to 2%, even with appropriate antithrombotic therapy. It can occur despite international normalized ratio in a therapeutic range at testing intervals.1 The highest risk of thrombosis is in the immediate 3 to 6 months after valve replacement, particularly in the first 10 to 30 days, regardless of location of the valve. Mitral prostheses carry an approximately 2-fold to 3-fold greater risk for thrombosis than aortic protheses do.2The clinical manifestations of mechanical valve thrombosis vary depending on whether the valvular dysfunction is obstructive or nonobstructive. In the short-term setting, obstructive valve dysfunction can present with acute decompensated heart failure signs and symptoms (as with this patient), syncope (or presyncope), pulmonary embolism, stroke, or even myocardial infarction from thromboembolism, and (rarely) sudden cardiac death.3 When the valve is nonobstructive in nature, patients may even be asymptomatic, and thrombosis becomes evident through a change in closing clicks, abnormality or restriction in valve movement, or increased gradients on echocardiograms done incidentally for other causes.Echocardiographic evidence of more than a 50% increase in the mean transvalvular gradient should prompt further imaging regardless of prosthetic location. Further imaging depends on the location of the prosthetic valve of interest. When thrombosis is suspected, transesophageal echocardiography is often the initial modality for evaluation and can be useful in detecting severe obstruction.4 Transesophageal echocardiography is often the modality of choice for mitral or tricuspid prosthetic valves, while multidetector-row computed tomography has better visualization of mechanical aortic or pulmonic valves.5 Transesophageal echocardiography and/or multidetector-row computed tomography are often done in conjunction with fluoroscopy, which allows evaluation of mechanical valve leaflet motion without the interference of soft tissue.Immediate management options depend on the degree of symptoms, valve location (right vs left), and thrombus size. Patients with left-sided mechanical valve obstruction have high rates of mortality and morbidity, and immediate management with either fibrinolytics or surgical intervention should be initiated when this is considered feasible and safe. Presence of New York Heart Association functional class IV symptoms, a large thrombus size (>5 mm), and left-sided mechanical-valve thrombi are considered high-risk features and mandate emergency interventions, such as surgery. Based on the patient’s condition, risks and benefits of a surgical vs conservative approach and fibrinolytic vs anticoagulation therapy, along with heart failure management, should be considered. Low-dose fibrinolytic therapy is recommended for poor surgical candidates and patients with New York Heart Association functional class I, II, or III symptoms, small clot sizes (≤0.8 cm2), and no or mild coronary artery disease with no other concomitant valve disease or contraindication to fibrinolytic medications, based on patient’s choice.6This patient presented with a large thrombus burden on a left-sided valve in decompensated heart failure. A usual recommendation would be to send her for valve-replacement surgery. However, a repeat open-heart operation within 2 months is considered to involve a high risk of mortality. In this patient, the presence of a concomitant dissection flap in the aortic root also increased the risk for bleeding with use of fibrinolytic therapy. After thorough discussion with the patient, we pursued a conservative approach with intravenous heparin for 3 days. Her symptoms improved, and she remained well compensated.The patient’s symptoms improved in a few days, and her mean gradient across the mechanical mitral prosthesis was reduced to 5 mm Hg. She was discharged with a planned reevaluation and repeat imaging of the aortic root dissection flap in a few months.

Cardiology

A woman in her mid-50s presented to the hospital with acute, worsening dyspnea, with shortness of breath at rest and with minimum exertion. She had undergone mechanical mitral valve replacement and aortic dissection repair 2 months prior to presentation. On physical examination, she was found to have elevated jugular venous pressure, bilateral rales in her lungs, and reduced intensity of the mitral valve closure sound, and her international normalized ratio was subtherapeutic (1.5). An echocardiographic image showed a mean gradient of 12 mm Hg across the mitral valve, suggesting valve stenosis. Fluoroscopy showed restricted mobility of the leaflets (Video 1). Transesophageal echocardiography showed a large thrombus on the mechanical mitral valve, along with a small new dissection flap in the aortic root (Figure and Video 2). A chronic dissection flap was evident in the aortic arch and descending aorta, which was unchanged from the previous aortic dissection repair.Refer the patient for aortic root dissection repairAdminister a full dose of emergency tissue plasminogen activator

what would you do next?

What would you do next?

Administer a full dose of emergency tissue plasminogen activator

Perform emergency percutaneous clot removal

Refer the patient for aortic root dissection repair

Start intravenous heparin

d

female

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2726813

A white man in his 70s presented with a gradually enlarging right supraorbital mass that had been neglected for 4 years. His comorbidities included congestive heart failure, atrial fibrillation, coronary artery disease, chronic obstructive pulmonary disease, hypertension, and a 50-pack-year history of tobacco abuse. Physical examination revealed a firm, nonmobile, nontender, bulging mass situated over the right frontal sinus, which expanded to the upper right eyelid. The mass covered the globe completely, resulting in total vision obstruction (Figure, A). However, the patient’s vision remained intact when the mass was elevated off the eye with great effort. His right pupil was round and reactive to light without afferent pupillary defect. No palpable lymphadenopathy was noted. A non–contrast-enhanced computed tomography (CT) scan demonstrated a large, right supraorbital mass with bony destruction of the anterior table of the right frontal sinus (Figure, B). It extended into the superior aspect of the orbit, displacing the right globe inferiorly. Air was seen within the mass (Figure, C). A fine-needle aspiration biopsy yielded inconclusive results. After medical clearance, the patient was taken to the operating room for a wedge excisional biopsy with decompression of the right supraorbital mass under monitored anesthesia care. Histopathological investigation revealed large nests of neoplastic epithelioid cells surrounded by fibrotic tissue and necroinflammatory debris. The neoplastic cells contained round nuclei with single prominent nucleoli and abundant clear to vacuolated cytoplasm (Figure, D).A, Enlarged right supraorbital mass. B, Computed tomography (CT) scan of destruction of the anterior table of right frontal sinus. C, Air pocket within the mass. D, Neoplastic epithelioid cells of the mass (original magnification ×40). What Is Your Diagnosis?

Pott puffy tumor

Mucocele

Basal cell carcinoma

Sebaceous carcinoma

D. Sebaceous carcinoma

D

Sebaceous carcinoma

Sebaceous carcinoma (SC) is an aggressive, malignant epithelial tumor with a variable presentation and occasional multicentric origin due to the widespread distribution of sebaceous glands in the skin.1-3 Sebaceous carcinoma encompasses 0.67% of all tumors of the eyelid, and is the third most common cancer of the eyelid (3%) behind basal cell carcinoma (86%) and squamous cell carcinoma (7%).2,4-6 The majority of sebaceous carcinomas occur in the intratarsal Meibomian and Zeis glands (38.7%), with other locations noted in the literature including the trunk, scalp, neck, upper limbs, lower limbs, and genitalia.5-8 An SC typically presents as a painless, firm, and rounded mass with a yellow hue due to its lipid content.2 It can also present as treatment unresponsive unilateral blepharitis or as a pedunculated lesion with keratinization and ulceration similar to a cutaneous horn or basal cell carcinoma.7 One clinical feature that would suggest SC over its benign mimics is a diffuse loss of cilia, which is typically seen in malignant lesions.1,7 Other lesions to add to the differential diagnosis include basal cell carcinoma, cutaneous horn, blepharitis, squamous cell carcinoma, Pott puffy tumor, chalazion, hordeolum, and sebaceous adenoma. Sebaceous carcinoma tends to be locally aggressive and has been known to invade the orbit and cause orbital displacement.1 Invasion of the paranasal sinuses has been noted only once to our knowledge, involving the maxillary sinus and ethmoids.2 To the our knowledge, there have been no reports of an aggressive SC that has invaded the frontal sinus alone, as seen in this case. As seen in the Figure, B, this SC invaded the anterior wall of the frontal sinus with noted air pockets, and because of its location, appeared initially similar to a Pott puffy tumor. To distinguish SC from Pott puffy tumor, a biopsy with corresponding histological analysis was required (Figure, D). Final pathological findings revealed large pleomorphic cells with brisk mitotic activity, vacuolated cytoplasm, and zones of necrosis, which are consistent with SC.1,2 Extensive necrotic areas were noted without normal epithelial or stromal tissues, suggesting that the tumor’s rapid growth outpaced its vascular supply. Oil-red-O staining can be adjunctively used to demonstrate the large lipid components of these cells.1,2It has been widely reported that advanced age is the main risk factor for developing SC.1,5,7,8 Historically, Asian descent was noted as a risk factor for the development of SC, but recent studies have suggested otherwise.1,7 Multiple systematic reviews have shown that older, white men have the highest risk of developing SC.1,5,7Traditionally, wide local excision with 5-to 6-mm surgical margins was the standard treatment for SC, along with either frozen or permanent sections.1,7,9 The noted 5-year recurrence rate with wide local excision varies between 9% and 36%.10 If there is orbital involvement, either on presentation or with recurrence, exenteration of the eye is typically performed.1 Recently, emphasis has been placed with Mohs micrographic surgery as a curative treatment for SC because of its inherent tissue conservation. One study by Snow et al10 of 49 patients noted a local cure rate of 87.8% for SC with Mohs micrographic surgery.1 As for nonsurgical treatment options, both irradiation and cryotherapy have been used in poor surgical candidates and patients unwilling to undergo surgery. Callahan et al1 noted that 2 patients were treated with radiation and had no evidence of SC recurrence at 28 and 37 months. Doxanas and Green2 question the value of radiation therapy after reviewing 40 prior cases in the literature. In the present case, the patient elected against treatment for his SC and shortly after died of cardiovascular disease.

General

A white man in his 70s presented with a gradually enlarging right supraorbital mass that had been neglected for 4 years. His comorbidities included congestive heart failure, atrial fibrillation, coronary artery disease, chronic obstructive pulmonary disease, hypertension, and a 50-pack-year history of tobacco abuse. Physical examination revealed a firm, nonmobile, nontender, bulging mass situated over the right frontal sinus, which expanded to the upper right eyelid. The mass covered the globe completely, resulting in total vision obstruction (Figure, A). However, the patient’s vision remained intact when the mass was elevated off the eye with great effort. His right pupil was round and reactive to light without afferent pupillary defect. No palpable lymphadenopathy was noted. A non–contrast-enhanced computed tomography (CT) scan demonstrated a large, right supraorbital mass with bony destruction of the anterior table of the right frontal sinus (Figure, B). It extended into the superior aspect of the orbit, displacing the right globe inferiorly. Air was seen within the mass (Figure, C). A fine-needle aspiration biopsy yielded inconclusive results. After medical clearance, the patient was taken to the operating room for a wedge excisional biopsy with decompression of the right supraorbital mass under monitored anesthesia care. Histopathological investigation revealed large nests of neoplastic epithelioid cells surrounded by fibrotic tissue and necroinflammatory debris. The neoplastic cells contained round nuclei with single prominent nucleoli and abundant clear to vacuolated cytoplasm (Figure, D).A, Enlarged right supraorbital mass. B, Computed tomography (CT) scan of destruction of the anterior table of right frontal sinus. C, Air pocket within the mass. D, Neoplastic epithelioid cells of the mass (original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Pott puffy tumor

Basal cell carcinoma

Sebaceous carcinoma

Mucocele

c

male

71-80

White

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2727328

A 46-year-old African swimmer presented with a 1-month history of progressive left hearing loss and vertigo. He also reported asthenia, sleep disorders, and urinary frequency. The urinary frequency has been treated for 2 years with many drugs (tamsulosin, desmopressin, and solifenacin) without improvement. The patient had spent his childhood in eastern Africa, where he swam in Lake Tanganyika. His history did not reveal trauma, infection, or any other associated conditions at the onset of the complaints. The ear, nose, and throat examination revealed a right horizontal nystagmus and a poorly delineated hypoesthesia of the left pinna. He could not walk properly owing to his vertigo. The rest of the clinical examination findings were unremarkable. Additional examinations (ie, pure-tone audiometry, video nystagmography, tympanometry) revealed left profound hearing loss with an air-bone gap of 40 dB and central vertigo. Otoacoustic emissions were absent on the left side. There was no left acoustic reflex. Auditory brainstem responses showed asymmetric interpeak latencies of waves I through V and III through V, suggesting slower conduction on the left side. Computed tomography and cerebral magnetic resonance imaging (MRI) revealed a 24 × 20-mm hemorrhagic lesion in the left middle cerebellar peduncle associated with a thickening of the cochleovestibular nerve (Figure). The patient was referred to urology, where a 13 × 8-mm mass was discovered in the lateral wall of the prostate gland. Biopsies of prostate and brain lesions, blood tests, and urinalysis were performed.Computed tomography (CT) scan and magnetic resonance images (MRIs) of the left middle cerebellopontine angle and prostate gland. A, Axial CT scan showed a hyperdense lesion suggesting hemorrhage in the left middle cerebellar peduncle. B, The lesion extended to the base of the vestibulocochlear nerve that was thickened (arrowheads) on the Fast Imaging Employing Steady-State Acquisition (FIESTA) MRI (axial plane). C, Coronal postcontrast MRI demonstrated a T1 hyperintense lesion that was consistent with hemorrhagic lesion with no true enhancement. D, Axial pelvic MRI showed a prostatic lesion (13 × 4 mm) located in the left posterior and lateral wall (arrowhead); the prostatic volume and size were substantially increased (132 mL, 59 × 60 × 70 mm). What Is Your Diagnosis?

Prostate cancer with brain metastasis

Tuberculosis

Toxoplasmosis

Schistosomiasis

D. Schistosomiasis

D

Schistosomiasis

The cerebrospinal fluid analysis was unremarkable, but our additional examinations identified the presence of Schistosoma hematobium (schistosomiasis). The patient was treated with praziquantel and benefited from prostatectomy owing to the increased prostatic size (Figure). The vertigo progressively disappeared throughout the months of therapy.Trematode infections are transmitted when larval forms released by freshwater snails penetrate human skin during contact with infested water. The patient was probably infected during his training sessions in Lake Tanganyika. Six months after the end of the treatment, brain MRI revealed a disappearance of the lesion. Urogenital schistosomiasis is characterized by asthenia, fever, abdominal pain, and urogenital disorders.1 Neuroschistosomiasis is a rare form of the disease, affecting 3% to 5% of individuals infected with Schistosoma japonicum.1 The incidence of cerebral schistosomiasis caused by other Schistosoma species (including S hematobium, Schistosoma mansoni, Schistosoma intercalatum, and Schistosoma mekongi) is still unknown. Neurological manifestations are the result of the inflammatory response of the host to egg deposition in the brain and, depending on the location, may lead to headache, ataxia, transient flaccid paraplegia, sphincter dysfunction, sensory disturbance, and other dysfunctions.1The present case is exceptional in 2 respects. First, the clinical presentation of the disease characterized by vertigo and hearing loss developed many years after disease transmission, which is unusual. Indeed, the mean delay of the disease manifestation is approximately 1 month after the initial infection, and dormant forms of the disease are rare.2 Egg deposition on the cochleovestibular nerve explains the atypical presentation of the disease. To our knowledge, no similar case has been reported.Second, urogenital schistosomiasis (due to S hematobium infection) is rarely associated with an impairment of the central nervous system. When the disease spreads to the central nervous system, the eggs usually deposit in the spine rather than the brain.1 Moreover, as described in postmortem studies, the deposition of trematode eggs in the brain is usually asymptomatic.3 The definitive diagnosis is made with an identification of eggs in urine, while the diagnosis can be indirectly suspected by blood analyses.1 As found in the present case, physicians should take into consideration that the cerebrospinal fluid can be normal in this setting or can show nonspecific findings.3In the present case, main differential diagnoses included prostatic cancer with cerebral metastasis, tuberculosis, and toxoplasmosis. The MRI findings of cancer and metastasis are usually characterized by T1 hyposignal, T2 hypersignal, and diffusion-weighted hypersignal. In the present case, the absence of diffusion hypersignal put into question the cancer/metastasis diagnosis. Toxoplasmosis may occur with similar neurological presentation, and the MRI findings of toxoplasmosis granuloma under treatment may be characterized by T1 and Fast Imaging Employing Steady-State Acquisition (FIESTA) hypersignal with hemorrhagic presentation.4 Furthermore, the spread of the disease into the prostate gland is only anecdotally reported and mainly in immunosuppressed patients.Tuberculosis may display numerous clinical presentations, but the imaging studies commonly find small tubercles with T1 hyposignal. Although tubercles can be characterized by an annular enhanced signal on the MRI, there is no hemorrhagic finding, such as was found in the present case. In addition, we did not identify Mycobacterium tuberculosis in either urine or cerebrospinal fluid.Although schistosomiasis is rarely associated with ear, nose, and throat disorders,5 physicians should consider the diagnosis in patients who visited endemic areas and who present with head and neck neurological deficits. The disease may manifest several years after the contamination, making the diagnosis difficult and the patient history crucial.

General

A 46-year-old African swimmer presented with a 1-month history of progressive left hearing loss and vertigo. He also reported asthenia, sleep disorders, and urinary frequency. The urinary frequency has been treated for 2 years with many drugs (tamsulosin, desmopressin, and solifenacin) without improvement. The patient had spent his childhood in eastern Africa, where he swam in Lake Tanganyika. His history did not reveal trauma, infection, or any other associated conditions at the onset of the complaints. The ear, nose, and throat examination revealed a right horizontal nystagmus and a poorly delineated hypoesthesia of the left pinna. He could not walk properly owing to his vertigo. The rest of the clinical examination findings were unremarkable. Additional examinations (ie, pure-tone audiometry, video nystagmography, tympanometry) revealed left profound hearing loss with an air-bone gap of 40 dB and central vertigo. Otoacoustic emissions were absent on the left side. There was no left acoustic reflex. Auditory brainstem responses showed asymmetric interpeak latencies of waves I through V and III through V, suggesting slower conduction on the left side. Computed tomography and cerebral magnetic resonance imaging (MRI) revealed a 24 × 20-mm hemorrhagic lesion in the left middle cerebellar peduncle associated with a thickening of the cochleovestibular nerve (Figure). The patient was referred to urology, where a 13 × 8-mm mass was discovered in the lateral wall of the prostate gland. Biopsies of prostate and brain lesions, blood tests, and urinalysis were performed.Computed tomography (CT) scan and magnetic resonance images (MRIs) of the left middle cerebellopontine angle and prostate gland. A, Axial CT scan showed a hyperdense lesion suggesting hemorrhage in the left middle cerebellar peduncle. B, The lesion extended to the base of the vestibulocochlear nerve that was thickened (arrowheads) on the Fast Imaging Employing Steady-State Acquisition (FIESTA) MRI (axial plane). C, Coronal postcontrast MRI demonstrated a T1 hyperintense lesion that was consistent with hemorrhagic lesion with no true enhancement. D, Axial pelvic MRI showed a prostatic lesion (13 × 4 mm) located in the left posterior and lateral wall (arrowhead); the prostatic volume and size were substantially increased (132 mL, 59 × 60 × 70 mm).

what is your diagnosis?

What is your diagnosis?

Prostate cancer with brain metastasis

Toxoplasmosis

Schistosomiasis

Tuberculosis

c

male

41-50

African

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2729841

A preschool boy presented with asymptomatic, reddish, raised lesions over his right ear, noticed 3 months earlier, associated with multiple painless swellings on the ipsilateral side of the neck for the past 3 weeks. On examination, there were multiple, erythematous papules coalescing to form a plaque with areas of scarring over the posterior aspect of right ear, along with firm, nontender posterior cervical lymphadenopathy (Figure, A). There was no history of trauma or intervention prior to the onset of lesions. His medical history was unremarkable, as were the rest of the mucocutaneous and systemic examination findings. A skin biopsy from the plaque was submitted for histopathological examination (Figure, C and D).A, Erythematous papules coalescing to form a plaque with areas of scarring, along with ipsilateral posterior cervical lymphadenopathy. B, The lesions have healed with atrophic scarring after 6 weeks of treatment. C, Microphotograph showing unremarkable epidermis with evidence of granulomatous inflammation and central caseous necrosis in the dermis (original magnification ×100). D, Ziehl-Neelsen stain shows acid-fast bacilli (oil immersion; original magnification ×1000). What Is Your Diagnosis?

Fixed cutaneous sporotrichosis

Lupus vulgaris

Atypical mycobacterial infection

Cutaneous leishmaniasis

B. Lupus vulgaris

B

Lupus vulgaris

Histopathological examination revealed multiple foci of caseating epithelioid cell granulomas with occasional Langerhans type giant cells and moderate lymphomononuclear infiltrate (Figure, C). Ziehl-Neelsen staining for acid-fast bacilli was positive (Figure, D), while stainings for fungus (periodic acid–Schiff and Grocott stains) were negative. Fine-needle aspirate from 1 of the enlarged lymph nodes revealed loose epithelioid cell granulomas in a necrotic background. Chest radiography was normal. Intradermal testing with purified protein derivative produced an induration of 15 × 15 mm. Culture studies for leishmaniasis, fungus, and mycobacteria yielded no growth. Overall features were consistent with a diagnosis of cutaneous tuberculosis, lupus vulgaris type. Therapy was begun with antitubercular treatment (ATT) consisting of 6-month regimen of 4 drugs, known as 2 HRZE/4 HR (2 months of isoniazid [H], 10-15 mg/kg/; rifampicin [R], 10-15 mg/kg/d; pyrazinamide [Z], 20-30 mg/kg/d; and ethambutol [E], 15 mg/kg/d followed by 4 months of isoniazid [H] and rifampicin [R] for 4 months at the same doses). At 6-week follow-up, there was remarkable improvement in the lesions (Figure, B).Childhood tuberculosis is a major health problem, especially in developing countries. Though pulmonary tuberculosis is the most common form, extrapulmonary forms have steadily been on the rise. Cutaneous tuberculosis is a rare form of extrapulmonary tuberculosis with myriad of clinical presentations accounting for approximately 1% to 2% of cases.1 Though the spectrum of cutaneous tuberculosis in children is similar to that in adults, widespread disease, unusual variants, and systemic involvement are more common. The 2 most common forms of childhood cutaneous tuberculosis are lupus vulgaris and scrofuloderma.1Lupus vulgaris is a gradually progressive form of cutaneous tuberculosis, usually seen in patients with fairly good immunity. Lesions most commonly occur on the lower extremities and buttocks, and are usually solitary, though multiple lesions can occur in children. It begins as asymptomatic papules that coalesce to form soft, reddish-brown plaques, which are seen as “apple jelly” nodules on diascopy. The gradually progressive plaque generally shows an actively spreading margin at one end, with involution and scarring at the other end of the lesion, often resulting in a geographic shape. Several variants of lupus vulgaris have been described, namely, plaque form, ulcerative and mutilating forms, vegetating, tumorlike, and papulonodular forms.2 Though systemic manifestations are rare, lymph node involvement can occur, as seen in the present case. Biopsy from the active margin of the plaque showed marked epithelial hyperplasia with tuberculoid granulomas showing caseous necrosis and Langerhans giant cells in the dermis, features typical of cutaneous tuberculosis.1 The foci of cutaneous tuberculosis and tubercular involvement of concomitant draining lymph nodes represents the cutaneous equivalent of pulmonary Ghon complex. Rapid clinical response to antituberculous treatment within 6 weeks further strengthened our diagnosis. At last follow-up, continued ATT was planned for a full course of 6 months, as mandated by revised national tuberculosis control program.3Lymphocutaneous sporotrichosis was a close differential diagnosis in the present case owing to the linear arrangement of the enlarged lymph nodes and the cutaneous lesion. Although sporotrichosis in children occurs on the face more often in children than in adults,4 and can arise without trauma, presence of scarring at one end in the lesion, absence of suppurative granulomas in the biopsy, negative tissue culture, and the favorable response to ATT helped to exclude this differential diagnosis.Nontuberculous mycobacterial infections have a diverse clinical presentation. It was a differential diagnosis in the present case owing to the lymphocutaneous nature of the lesion. However, its relative rarity in the pediatric age group, well-formed granulomas seen on histopathologic analysis, and a favorable response to ATT pointed to a diagnosis of lupus vulgaris.Cutaneous leishmaniasis usually involves exposed areas, and the nose and ears are among the common sites involved. Lesions commonly begin as a solitary, small, well-circumscribed papule at the site of inoculation and slowly enlarge over several weeks into a nodule or plaque, eventually becoming ulcerated orverrucous.5 Lesions may be solitary or multiple, with presence of satellite lesions or lymphatic spread. Absence of plasma cell infiltrate in the skin biopsy specimens in the present case along with presence of caseous granuloma steered the diagnosis toward cutaneous tuberculosis.In conclusion, this patient had an uncommon presentation of lupus vulgaris at an unusual site that mimicked other common cutaneous diseases such as lymphocutaneous sporotrichosis and cutaneous leishmaniasis. Diagnosis was confirmed histopathologically. The lesions responded well to antituberculous treatment.

General

A preschool boy presented with asymptomatic, reddish, raised lesions over his right ear, noticed 3 months earlier, associated with multiple painless swellings on the ipsilateral side of the neck for the past 3 weeks. On examination, there were multiple, erythematous papules coalescing to form a plaque with areas of scarring over the posterior aspect of right ear, along with firm, nontender posterior cervical lymphadenopathy (Figure, A). There was no history of trauma or intervention prior to the onset of lesions. His medical history was unremarkable, as were the rest of the mucocutaneous and systemic examination findings. A skin biopsy from the plaque was submitted for histopathological examination (Figure, C and D).A, Erythematous papules coalescing to form a plaque with areas of scarring, along with ipsilateral posterior cervical lymphadenopathy. B, The lesions have healed with atrophic scarring after 6 weeks of treatment. C, Microphotograph showing unremarkable epidermis with evidence of granulomatous inflammation and central caseous necrosis in the dermis (original magnification ×100). D, Ziehl-Neelsen stain shows acid-fast bacilli (oil immersion; original magnification ×1000).

what is your diagnosis?

What is your diagnosis?

Fixed cutaneous sporotrichosis

Lupus vulgaris

Cutaneous leishmaniasis

Atypical mycobacterial infection

b

male

original

https://jamanetwork.com/journals/jama/fullarticle/2730013

A 53-year-old man presented with 2 weeks of back pain, stiff neck, headache, and fevers. He also reported 3 days of right knee pain and swelling. He had a history of pseudogout and kidney transplant 13 years ago. He was taking sirolimus and prednisone, with excellent graft function. His temperature on presentation was 102°F (38.9°C). He had nuchal rigidity and positive Kernig sign. There were no focal neurologic deficits and no spinal tenderness. He had a right knee effusion without erythema and with full range of motion. Laboratory workup of serum showed a white blood cell (WBC) count of 10 200/μL (neutrophils, 63.8%; lymphocytes, 19.6%; monocytes, 15.1%) and erythrocyte sedimentation rate, 63 mm/h; workup of cerebrospinal fluid showed a WBC count of 0/μL; red blood cell count, 32/μL; total protein level, 109 mg/dL; and glucose level, 59 mg/dL (3.3 mmol/L). Magnetic resonance imaging (MRI) of the spine showed cervical degenerative changes with reactive marrow (Figure 1). He was prescribed intravenous vancomycin and cefepime. Blood and cerebrospinal fluid (CSF) cultures were negative. What Would You Do Next?

Continue intravenous antibiotics

Obtain additional imaging with computed tomography (CT)

Start gabapentin

Start high-dose ibuprofen

Crowned dens syndrome

B

Obtain additional imaging with computed tomography (CT)

The key to the correct diagnosis is the presence on a CT scan of synovial crown- or halo-like calcific densities of the atlantoaxial (C1/C2) joint, surrounding the odontoid process, in a patient with history of peripheral acute calcium pyrophosphate (CPP) crystal arthritis (“pseudogout”) (Figure 2). This patient had crowned dens syndrome (CDS), ie, deposition of CPP or, less frequently, basic calcium phosphate (BCP) crystals in the atlantoaxial joint, causing symptoms and signs of cervical spine inflammation. Continuation of antibiotics was not indicated, since CSF and MRI findings were not consistent with infection. Gabapentin is effective against neuropathic but not acute inflammatory pain. Like other forms of crystal deposition disease, CDS can be treated with corticosteroids or colchicine when there is a relative contraindication to use of nonsteroidal anti-inflammatory drugs (NSAIDs, eg, ibuprofen), such as renal transplant in this patient.Axial (A), coronal (B), and sagittal (C) computed tomography scan of C1/C2 showing periodontoid calcifications.CDS was first described in 19801 and is defined as otherwise unexplained neck pain in the presence of radiographic atlantoaxial (C1/C2) calcifications. Fever, headache, meningismus, and elevated levels of inflammatory markers are common.2-6The prevalence of CDS is not clearly established. In 1 US series of 513 consecutive CT scans obtained for acute trauma,7 the prevalence of atlantoaxial calcific depositions was 12.9% overall and was 34% after age 60 years. In 2 other recent reports, 12.5%8 to 36%9 of patients with atlantoaxial calcifications had neck pain.CDS is most commonly associated with osteoarthritis but can also be observed in patients with rheumatoid arthritis and metabolic disorders such as hyperparathyroidism or hemochromatosis, which are linked to acute CPP crystal arthritis.3,6,9,10 Synovial fluid analysis from a peripheral joint aspirate can show CPP crystals, with negative or weakly positive birefringence under polarized light microscopy. The absence of crystals does not rule out CPP crystal disease, since the sensitivity of microscopic examination for CPP crystal detection ranges from 12% to 83%.6 Radiographic imaging of the knees and wrists at the time of presentation is a noninvasive way to infer diagnosis of CDS, by visualizing peripheral chondrocalcinosis.3,5The gold standard for diagnosis is CT scan of the cervical spine, focusing on C1/2 (Figure 2). CT has greater sensitivity than MRI in demonstrating the characteristic calcifications surrounding the odontoid process3-6,9 and should be performed first when CDS is likely (eg, in patients with history of acute CPP crystal arthritis). MRI can also show signs of inflammatory arthropathy suggestive of CDS in the appropriate clinical context (degenerative changes with reactive marrow) (Figure 1). However, MRI is usually ordered when there is clinical suspicion of cord compression, osteomyelitis, or malignancy.6The differential diagnosis of CDS includes infectious meningitis, retropharyngeal abscess, and diskitis-osteomyelitis of the cervical spine.3-5 Importantly, CPP calcifications, including the C1/C2 joint, are often observed in asymptomatic individuals.5,7-10 Thus, radiographic findings suggestive of CDS can coexist with infectious causes of neck pain. Therefore, even when CDS is suspected, some patients should still undergo evaluation for infection (lumbar puncture, MRI) and receive antibiotics until infection is ruled out. Unremarkable CSF studies and MRI results favor noninfectious etiologies, prompting discontinuation of antibiotics. Other considerations are tension headache, occipital neuralgia, cervicobrachial syndrome, BCP calcific longus colli tendinitis,6 polymyalgia rheumatica/giant cell arteritis when neck stiffness is associated with shoulder pain or jaw claudication,3-6 and vertebral metastases in patients with cancer.3Treatment of CDS is similar to that of peripheral acute crystal arthritis and typically consists of a short course of high-dose NSAIDs.10 Colchicine and oral corticosteroids are effective alternatives.10 Anti-inflammatory treatment results in rapid resolution of symptoms, within days to weeks.1,4,5,10Before obtaining CT of the cervical spine, knee arthrocentesis was performed to rule out septic arthritis. Synovial fluid was consistent with aseptic inflammatory arthritis, although crystals were not seen. Three-view radiographs of the hands showed bilateral chondrocalcinosis. All antibiotics were stopped. On discharge, the patient was prescribed prednisone (40 mg daily) for 5 days with rapid clinical improvement and then resumed low-dose prednisone (5 mg daily). He has not had recurrence of his symptoms after 12 months.

General

A 53-year-old man presented with 2 weeks of back pain, stiff neck, headache, and fevers. He also reported 3 days of right knee pain and swelling. He had a history of pseudogout and kidney transplant 13 years ago. He was taking sirolimus and prednisone, with excellent graft function. His temperature on presentation was 102°F (38.9°C). He had nuchal rigidity and positive Kernig sign. There were no focal neurologic deficits and no spinal tenderness. He had a right knee effusion without erythema and with full range of motion. Laboratory workup of serum showed a white blood cell (WBC) count of 10 200/μL (neutrophils, 63.8%; lymphocytes, 19.6%; monocytes, 15.1%) and erythrocyte sedimentation rate, 63 mm/h; workup of cerebrospinal fluid showed a WBC count of 0/μL; red blood cell count, 32/μL; total protein level, 109 mg/dL; and glucose level, 59 mg/dL (3.3 mmol/L). Magnetic resonance imaging (MRI) of the spine showed cervical degenerative changes with reactive marrow (Figure 1). He was prescribed intravenous vancomycin and cefepime. Blood and cerebrospinal fluid (CSF) cultures were negative.

what would you do next?

What would you do next?

Start high-dose ibuprofen

Continue intravenous antibiotics

Obtain additional imaging with computed tomography (CT)

Start gabapentin

c

male

51-60

White

original

https://jamanetwork.com/journals/jama/fullarticle/2729031

A healthy 65-year-old woman presented with 2 days of sustained throbbing, bilateral temporal headache and bilateral blurred vision. Laboratory results are shown in the Table. Given her erythrocyte sedimentation rate (ESR) of 110 mm/h and symptoms concerning for giant cell arteritis (GCA), a temporal artery biopsy was obtained. Results showed a normal caliber lumen without infiltrating inflammatory cells. What Would You Do Next?

Brain magnetic resonance imaging

Empirical methotrexate prescription

Empirical sumatriptan prescription

Serum protein electrophoresis (SPEP)

D

Serum protein electrophoresis (SPEP)

While the patient had a nearly 50% pretest probability of GCA,1 the negative predictive value of temporal artery biopsy is approximately 83%.2,3 The negative biopsy results required consideration of an alternative diagnosis, such as brain abscess, cerebral venous sinus thrombosis, or hypergammaglobulinemia with hyperviscosity. The high ESR, low anion gap (2 mEq/mL), and elevated globulin gap (6.6 g/dL) support a diagnosis of hypergammaglobulinemia. Empirical steroids are recommended when GCA is strongly suspected, even before temporal artery biopsy, but were not prescribed because of high suspicion for the alternative diagnosis of hypergammaglobulinemia.The ESR measures the rate at which red blood cells (RBCs) settle in the plasma of anticoagulated blood in a standardized Westergren tube (Figure). Although the ESR is considered a measure of inflammation from infection, malignancy, or rheumatologic disease, multiple noninflammatory factors affect RBC sedimentation. These factors alter the ESR via distinct mechanisms: spatial interference, electrical charge, and viscosity (Supplement).4 Increased spatial interference, defined as physical factors interfering with the ability of RBCs to settle in the Westergren tube, slows the packing of erythrocytes at the tube bottom, thereby decreasing the ESR. With extreme leukocytosis, RBC downward flow is impeded by leukocytes, which decreases the ESR.5 Conversely, decreased spatial interference, such as with cases of anemia and consequently fewer RBCs, causes an increase in the ESR because RBCs can sediment with less obstruction.4 Electrical charge refers to the slight negative surface charge that RBCs have, which causes them to repel each other, impeding erythrocyte packing and sedimentation.5,6 However, if plasma is enriched with positively charged proteins, such as immunoglobulins or fibrinogen, this electrical repulsion is blunted and RBC agglutination occurs, speeding sedimentation.4 Fibrinogen is a large, positively charged protein and the most abundant acute-phase reactant. Elevated fibrinogen is the predominant reason for high ESR in inflammatory states.4,5,7 Increased plasma viscosity, such as in cases of hypergammaglobulinemia, can slow erythrocyte sedimentation through the plasma and decrease the ESR.4,8The erythrocyte sedimentation rate (ESR) is the distance (mm) that anticoagulated blood settles into the red blood cell and plasma components over 1 hour. The middle tube demonstrates an ESR of 20 mm/h.Because noninflammatory factors influence the ESR, its specificity for establishing a diagnosis of inflammatory conditions is modest. In an analysis of 1106 patients who underwent 1174 temporal artery biopsies, an ESR value greater than 22 mm/h in men and 29 mm/h in women had sensitivity of 84.2%, specificity of 29.5%, positive predictive value of 26.4%, and negative predictive value of 86.1% for a diagnosis of GCA.9 In another study,10 using a higher ESR cutoff improved specificity, but sensitivity markedly decreased; an ESR cutoff of greater than 107 mm/h had a sensitivity of 23%, specificity of 90.1%, positive predictive value of 30%, and negative predictive value of 86.5% for a diagnosis of GCA (positive and negative predictive values calculated by the authors from data provided by Walvick)10. In a study of 1006 patients, ESR greater than 100 mm/h had poor sensitivity for infection (36%), malignancy (25%), and inflammatory disorders (21%). However, it had high specificity (99%) for elevated sickness index, defined as the presence of a significant underlying disease.6 These results suggest an ESR greater than 100 mm/h deserves diagnostic attention but is nonspecific and cannot by itself establish a diagnosis. Common causes of ESR greater than 100 mm/h include deep-seated infection, such as endocarditis or osteomyelitis; connective tissue disorders, such as GCA; and malignancies, such as multiple myeloma and Waldenström macroglobulinemia.4 The ESR cost to Medicare is $3.33.The patient’s high ESR was related to noninflammatory factors. The low anion gap and elevated globulin gap suggested elevated paraproteins. SPEP results showed a monoclonal IgM concentration of 1260 mg/dL (reference range, 48-271 mg/dL). Because γ-globulins are positively charged plasma proteins, the repelling force of the negative surface charge of RBCs is blunted in hypergammaglobulinemia, which facilitates agglutination of RBCs and rapid sedimentation. The patient’s blood viscosity relative to water was 4.1 (reference range, 1.4-1.8). Although hyperviscosity decreases the ESR, the electrical charge effect of hypergammaglobulinemia is stronger, hence the patient’s ESR of 110 mm/h.4 Bone marrow biopsy results showed 10% Κ-restricted lymphoplasmacytic cells, confirming Waldenström macroglobulinemia. The patient’s presenting symptoms of headache and blurry vision are common presentations of this disease.In scenarios with high suspicion for GCA but negative temporal artery biopsy results, a second, contralateral biopsy can be considered. Approximately 5% of these contralateral biopsies will be positive when the first was negative.2,3 C-reactive protein (CRP) is an acute-phase reactant synthesized by the liver. CRP is elevated with most inflammatory conditions but is unaffected by noninflammatory factors.7 The patient had a normal CRP level, highlighting the noninflammatory cause of her elevated ESR. Obtaining concurrent ESR and CRP levels is less cost-effective than obtaining one before the other, but may provide benefit in select cases.The patient was treated with rituximab and has been in remission for 3 years. Her IgM concentration decreased to 261 mg/dL and her ESR decreased to 32 mm/h.Although commonly used to measure inflammation, the ESR is affected by noninflammatory factors, including anemia, polycythemia, hypofibrinogenemia or hyperfibrinogenemia, and hypergammaglobulinemia.Patients with ESR greater than 100 mm/h are likely to have a clinically relevant underlying condition, but the ESR test is nonspecific.Understanding the physiologic principles of erythrocyte sedimentation can facilitate the diagnosis of underlying etiologies.

Diagnostic

A healthy 65-year-old woman presented with 2 days of sustained throbbing, bilateral temporal headache and bilateral blurred vision. Laboratory results are shown in the Table. Given her erythrocyte sedimentation rate (ESR) of 110 mm/h and symptoms concerning for giant cell arteritis (GCA), a temporal artery biopsy was obtained. Results showed a normal caliber lumen without infiltrating inflammatory cells.

what would you do next?

What would you do next?

Empirical sumatriptan prescription

Empirical methotrexate prescription

Serum protein electrophoresis (SPEP)

Brain magnetic resonance imaging

c

female

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2727364

A man in his 60s presented with an approximately 4-month medical history of lip enlargement with nodular growths. Skin examination was significant for multiple erythematous and flesh-colored papules and nodules symmetrically affecting the upper and lower lips with extension onto the vermilion border (Figure 1A). There were no intraoral lesions, and all other findings of his examination were within normal limits. The patient denied fevers, chills, weight loss, night sweats, cough, lymphadenopathy, abdominal pain, change in bowel habits, or other systemic symptoms. A biopsy was obtained of the vermilion lip (Figure 1B).A, Symmetric lip enlargement with infiltrative erythematous and skin-colored papules and nodules extending onto the vermilion border. B, Hematoxylin-eosin stain (original magnification ×40). What Is Your Diagnosis?

Granulomatous cheilitis

Leukemia labialis

Lip licker’s dermatitis

Pyostomatitis vegetans

B. Leukemia labialis

B

Leukemia labialis

Histopathologic examination demonstrated a nodular and diffuse dermal lymphoid infiltrate composed of small, mature lymphocytes with hyperchromatic and slightly convoluted nuclei (Figure 2A). Findings from CD20, CD79a, and LEF-1 immunostaining highlighted a neoplastic B-cell population occurring in sheets and clusters with aberrant coexpression of CD5 and CD23 (Figure 2B).A, Lip biopsy demonstrating monotonous small lymphoid cells with hyperchromatic, slightly irregular and angulated nuclei with clumped chromatin (hematoxylin-eosin, original magnification ×400). B, immunostain diffusely highlighting the lymphoid infiltrate (CD20, original magnification ×600).A subsequent complete blood cell count showed a white blood cell count of 10 600/µL with an absolute lymphocytosis of 4378 cells/µL. Flow cytometry on the peripheral blood demonstrated a monoclonal B-cell population with dim to moderate CD20 expression and aberrant expression of CD5 and CD23. The clinical, histologic, and flow cytometry findings were consistent with a diagnosis of chronic lymphocytic leukemia (CLL) presenting initially with only lip involvement.Leukemia labialis is a rare subtype of leukemia cutis that presents as multiple plaques, papules, nodules, and (rarely) ulcerative lesions confined to the lips.1 Leukemia labialis as an initial manifestation of CLL is rare.2Approximately 25% of patients with CLL present with cutaneous manifestations of their disease.3 More common presentations include purpura, pruritus, urticaria, erythroderma, vasculitis, pyoderma gangrenosum, and Sweet syndrome.4 Leukemia cutis, however, is far less frequent in CLL than in T-cell leukemias or lymphomas.5 Leukemia cutis as the initial presenting sign of CLL is even more exceptional. Cerroni et al3 examined a cohort of 42 CLL patients with leukemia cutis and found that only 7 patients (16.7%) presented with skin lesions as the first sign of systemic disease. Importantly, 6 patients presented with leukemia cutis at sites of previous herpes zoster and herpes simplex eruptions.2,3 This finding suggests that an exaggerated herpes-induced inflammatory response may play a role in the pathogenesis of this presentation.Microscopically, cutaneous CLL is characterized by a periadnexal and perivascular, nodular and/or diffuse or band-like infiltration of CD20-positive neoplastic B cells that aberrantly express CD5 and CD23. Lymphoid enhancer binding factor 1, which was positive in the case, is a recently described highly specific marker for CLL.6 Cytologically, CLL is characterized by uniform, small lymphocytes with mature clumped and hyperchromatic chromatin. Scattered prolymphocytes with vesicular chromatin and prominent nucleoli may also be seen. A marked increase in prolymphocytes portends Richter transformation and a worse prognosis. In patients without Richter transformation, leukemia cutis in CLL likely does not significantly affect overall prognosis.3,7The differential diagnoses of multiple acquired labial papules are broad and may include infiltrative disorders (eg, granulomatous, systemic amyloidosis), infections (eg, verrucae, herpes labialis), and benign neoplasms (eg, Fordyce spots). Of the listed choices, granulomatous cheilitis (GC) typically presents in younger adults and may be associated with sarcoidosis, Crohn disease, and Melkersson-Rosenthal syndrome (MRS).8 Clinically it manifests as asymptomatic labial swelling that may have a nodular texture and may be accompanied by facial palsy and plicated tongue in MRS. Histologically, GC is distinguished from leukemia cutis by the presence of nonnecrotizing granulomas. Lip licker’s dermatitis is a form of chronic irritant contact dermatitis to saliva and repeated minor trauma secondary to habitual lip licking. Examination classically demonstrates perioral erythema, scale, crusting, or fissures. Histologic changes in irritant contact dermatitis include spongiosis, a superficial perivascular chronic inflammatory infiltrate, and scattered apoptotic keratinocytes. Pyostomatitis vegetans is strongly correlated with inflammatory bowel disease and typically presents with multiple white or yellow pustules on an erythematous base involving the oral mucosa, particularly the gingiva and lip.9 The absence of gastrointestinal symptoms and pustular lesions on examination excludes this diagnosis. In addition, biopsy will demonstrate acanthosis, exocytosis of neutrophils, and scattered neutrophilic and eosinophilic microabscesses.10This case highlights a rare presentation of leukemia labialis as the initial manifestation of CLL. It is important for clinicians to recognize both common and rare presentations of leukemia cutis to avoid delay in diagnosis and treatment.

Dermatology

A man in his 60s presented with an approximately 4-month medical history of lip enlargement with nodular growths. Skin examination was significant for multiple erythematous and flesh-colored papules and nodules symmetrically affecting the upper and lower lips with extension onto the vermilion border (Figure 1A). There were no intraoral lesions, and all other findings of his examination were within normal limits. The patient denied fevers, chills, weight loss, night sweats, cough, lymphadenopathy, abdominal pain, change in bowel habits, or other systemic symptoms. A biopsy was obtained of the vermilion lip (Figure 1B).A, Symmetric lip enlargement with infiltrative erythematous and skin-colored papules and nodules extending onto the vermilion border. B, Hematoxylin-eosin stain (original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Granulomatous cheilitis

Pyostomatitis vegetans

Leukemia labialis

Lip licker’s dermatitis

c

male

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2724217

A woman in her 50s with a right lower-eyelid yellow plaque presented with unremitting abdominal and back pain. Computed tomographic (CT) scan of the chest, abdomen, and pelvis demonstrated extensive infiltrative stranding from the thorax through the retroperitoneal space. Sclerotic changes in multiple osseous structures were noted. Idiopathic retroperitoneal fibrosis was diagnosed following biopsies. Prednisone and azathioprine were started. Biopsy of the lower-eyelid yellow plaque returned xanthelasma (Figure, A). Ureteral obstruction, chronic kidney disease, and lymphedema complicated her course. Azathioprine was stopped after 1 year. Prednisone was slowly tapered but she relapsed 3 years later. A second retroperitoneal biopsy exhibited fibroadipose tissue, foamy macrophages, and chronic inflammation with fibrosis. Azathioprine and prednisone were restarted. She required multiple surgeries for spinal stenosis and ureteral obstruction. Her kidney function continued declining. Then, owing to knee pain, a plain radiograph was obtained which demonstrated osteosclerosis of the distal femur. Consequently, the previous eyelid and retroperitoneal biopsies were reviewed. The clinicopathologic presentation was confirmed with a molecular test.A, Clinical image of a soft, nonscaly yellow-tan plaque on the medial canthus. B, Hematoxylin-eosin stain image demonstrating foamy histiocytes with Touton giant cells (original magnification ×100). C, CD68 immunohistochemical stain diffusely positive in the histiocytic infiltrate (original magnification ×100). D, Computed tomographic image with contrast demonstrating retroperitoneal stranding and fibrosis with hydronephrosis (arrowheads indicate hairy kidney appearance of fibrosis). What Is Your Diagnosis?

Necrobiotic xanthogranuloma

Xanthelasma palpebrum

Erdheim-Chester disease

Langerhans cell histiocytosis

C. Erdheim-Chester disease

C

Erdheim-Chester disease

The eyelid biopsy demonstrated expanded papillary and reticular dermis filled with foamy histiocytes in a background of lymphocytic infiltrate and scattered Touton giant cells (Figure, B). Histiocytes had positive results for CD68 (Figure, C) and factor XIIIa, and negative results for S100, CD1a. The CT findings showed extensive retroperitoneal fibrosis and a hairy kidney appearance (Figure, D). The DNA extracted from formalin-fixed, paraffin-embedded skin and retroperitoneal biopsies was amplified using allele-specific fluorescent PCR. Via capillary electrophoresis BRAF V600E mutation was detected. The retroperitoneal biopsy was similar to the eyelid demonstrating sheets of foamy histiocytes, scattered lymphocytic infiltrate, and fibrosis.Vemurafenib, 480 mg, twice daily was started following Erdheim-Chester disease (ECD) confirmation. BRAF inhibitor (BRAFi) therapy was initially tolerated for months, but despite intermittent prednisone fatigue and inflammatory arthropathy eventually prompted a drug holiday. Two dose reductions, first to 240 mg twice daily, then 240 mg daily failed to relieve her arthritis. Vemurafenib was discontinued and methotrexate initiated. Repeated CT scans showed stable disease. Her cutaneous lesion resolved.Erdheim-Chester disease was first described in 1930 by Austrian pathologist Jakob Erdheim and his student William Chester.1 Hundreds of cases highlight profound clinical variability in this L group of diseases, non–Langerhans cell histiocytosis, from bone limited disease to multisystem involvement with a poor prognosis.1-3Erdheim-Chester disease is more common in men, and most often presents in the sixth decade of life.1,2 The pathophysiology is characterized as a clonal neoplasia of histiocytes, which generate a robust Th1 cytokine profile.1 Histologically, cutaneous biopsy findings show dermal infiltration with foamy histiocytes and scattered Touton giant cells.4 In contrast, Langerhans cell histiocytosis shows positive eosinophilic histiocytes displaying kidney-bean shaped nuclei in a background of eosinophilic infiltrate. The ECD histiocytes are immunoreactive for CD68, CD163, and Factor XIIIa, and are negative for S100, CD1a, and Langerin. BRAF V600E driver mutations lend evidence for the neoplastic theory.1,5,6Patients diagnosed with necrobiotic xanthogranuloma (NXG) most commonly have an underlying monoclonal gammopathy and histologically show layered necrobiosis and peripheral multinucleated giant cells with haphazardly arranged nuclei. Clinically, both histiocytoses have a periorbital predilection for cutaneous involvement.Cutaneous involvement is present in 32% of ECD cases.4 In patients with skin involvement, it is the first sign of disease in 30%. The Xanthelasma-like lesion (XLL) is specific, as seen in this patient, and present in approximately 25%, most commonly on the inner canthus.4 The XLL can be difficult to distinguish from xanthelasma palpebrum, and was subtle in this case. Both display CD68+, CD163+, and Cd1a− histiocytes. The infiltrate in ECD involves the reticular dermis and has a higher density of multinucleated and Touton giant cells, less dermal fibrosis, and is less likely associated with dyslipidemia.4 Other cutaneous manifestations include erythematous-brownish localized or disseminated patches, papulonodules, and rarely erythroderma.4 Pediatric cases are described, some with cutaneous involvement.7 Several reports of concomitant LCH and ECD exist, and classic lesions of LCH may be present and should be sought for biopsy in any patient with ECD with cutaneous involvement.4,5BRAF V600E mutations are present in 54% to 60% of patients with ECD,6 and seen in considerably larger percentages of patients with XLL.4 Mutations are less common in other cutaneous lesions.4 An XLL biopsy can be easily undertaken, vs biopsy of bone, retroperitoneum, or other internal manifestation.Interferon-α (IFN-α) was the first-line treatment since the early 2000s, and the first agent to show increased survival.1,2 Other treatments include high-dose steroids, cladribine, imatanib, anakinra, tofacitinib, cobimetinib, methotrexate, and cyclophosphamide.1,2,8,9 Efficacy is difficult to ascertain given the relatively small numbers studied. However, since 2012 with discovery of BRAF mutations in most patients with ECD,6BRAF inhibitors have become a promising first-line modality. In the largest study to date, the LOVE study,10 vemurafanib and dabrafenib showed a high response rate of 91% in patients with BRAF-mutations. This included 76% partial response and 15% complete response.10 In addition, cobimetinib, an MEK inhibitor, had suggested benefit in patients with wild-type mutations, in combination with BRAF inhibitors in BRAF-mutants, and in those who had no improvement with BRAF-inhibition therapy.10 Relapse after interruption of BRAF inhibition is standard; however, all patients in the LOVE study subsequently responded again after reintroduction of therapy. Adverse events to BRAF inhibition were similar to prior studies of melanoma.10Dermatologists can recognize cutaneous manifestations of ECD, confirm BRAF mutations via skin biopsy, and aid in diagnosis and treatment of cutaneous adverse reactions associated with BRAF inhibition.

Dermatology

A woman in her 50s with a right lower-eyelid yellow plaque presented with unremitting abdominal and back pain. Computed tomographic (CT) scan of the chest, abdomen, and pelvis demonstrated extensive infiltrative stranding from the thorax through the retroperitoneal space. Sclerotic changes in multiple osseous structures were noted. Idiopathic retroperitoneal fibrosis was diagnosed following biopsies. Prednisone and azathioprine were started. Biopsy of the lower-eyelid yellow plaque returned xanthelasma (Figure, A). Ureteral obstruction, chronic kidney disease, and lymphedema complicated her course. Azathioprine was stopped after 1 year. Prednisone was slowly tapered but she relapsed 3 years later. A second retroperitoneal biopsy exhibited fibroadipose tissue, foamy macrophages, and chronic inflammation with fibrosis. Azathioprine and prednisone were restarted. She required multiple surgeries for spinal stenosis and ureteral obstruction. Her kidney function continued declining. Then, owing to knee pain, a plain radiograph was obtained which demonstrated osteosclerosis of the distal femur. Consequently, the previous eyelid and retroperitoneal biopsies were reviewed. The clinicopathologic presentation was confirmed with a molecular test.A, Clinical image of a soft, nonscaly yellow-tan plaque on the medial canthus. B, Hematoxylin-eosin stain image demonstrating foamy histiocytes with Touton giant cells (original magnification ×100). C, CD68 immunohistochemical stain diffusely positive in the histiocytic infiltrate (original magnification ×100). D, Computed tomographic image with contrast demonstrating retroperitoneal stranding and fibrosis with hydronephrosis (arrowheads indicate hairy kidney appearance of fibrosis).

what is your diagnosis?

What is your diagnosis?

Erdheim-Chester disease

Langerhans cell histiocytosis

Xanthelasma palpebrum

Necrobiotic xanthogranuloma

a

female

51-60

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2723492

A Japanese man in his 50s presented with a 6-month history of worsening pruritic hand dermatitis that progressed to involve his face, trunk, upper extremities, and feet. He had emigrated from Japan more than 10 years earlier but had no history of recent travel. He took no medications, had no significant medical or surgical history, and denied personal and family history of atopy. While he worked as a biomedical researcher, he denied any caustic exposures. On physical examination, his face, trunk, upper extremities, palms, and soles were marked by 1- to 2-mm erythematous papules and pustules coalescing into large, partially indurated and polycyclic plaques with centrifugal extension and occasional central clearing (Figure, A and B). Treatment with potent topical corticosteroids was ineffective. Punch biopsies of lesions on the shoulder (Figure, C) and foot (Figure, D) were performed.A, Annular erythematous plaque studded with papules and pustules on the cheek and temple. B, Erythematous plaques studded with papules and pustules on the shoulder. C and D, Lesional specimens under hematoxylin-eosin stain taken from the shoulder (C, original magnification ×400) and plantar foot (D, original magnification ×40). What Is Your Diagnosis?

Folliculotropic mycosis fungoides

Papulopustular rosacea

Eosinophilic pustular folliculitis

Majocchi granuloma

C. Eosinophilic pustular folliculitis (EPF)

C

Eosinophilic pustular folliculitis

Histopathologic analysis of a follicular papule on the shoulder demonstrated a perivascular and periadnexal eosinophilic and lymphocytic infiltrate concentrated at the follicular isthmus and sebaceous glands (Figure, C). A plaque on the glabrous plantar foot showed eosinophilic spongiosis and subcorneal and intraepidermal pustules (Figure, D). Tissue stains and cultures were negative for bacterial, mycobacterial, and fungal organisms. Neither lesional tissue nor blood demonstrated a monoclonal T-cell population on T-cell receptor (TCR) gene rearrangement studies. Flow cytometry did not detect an atypical B- or T-cell population in the blood. Laboratory workup was notable for an elevated absolute eosinophil count of 1100/μL (1.1 × 109/L). Complete blood cell counts, results of a comprehensive metabolic panel, and lactate dehydrogenase levels were otherwise unremarkable. Findings of human immunodeficiency virus (HIV) testing were negative. Collectively, these findings were compatible with a diagnosis of classic EPF, or Ofuji disease.After diagnosis, the patient began treatment with indomethacin, 50 mg/d. Within 1 month, he had demonstrated nearly complete resolution of all lesions with improvement in pruritus and resolution of eosinophilia. The condition was similarly well controlled by 6-month follow-up.Eosinophilic pustular folliculitis is a noninfectious inflammatory dermatosis first characterized in Japan in 1970 by Ofuji et al.1 Over 300 cases of EPF have been reported, with more than 100 cases in Japanese patients.2 Eosinophilic pustular folliculitis is classified into 3 variants: (1) classic EPF (Ofuji disease), which typically affects healthy Japanese adults; (2) immunosuppression-associated EPF, which is often associated with HIV; and (3) infancy-associated EPF.3 Classic EPF peaks in incidence during the third and fourth decades of life.4 Among Japanese patients, the male-to-female ratio approximates 5 to 1.5Clinically, classic EPF appears as recurrent papules and pustules on an erythematous base, which gradually become confluent to form indurated, annular plaques.6 Eruptions most commonly occur on the face (>80%), with frequent involvement of the trunk and extremities.2 Palmoplantar pustules occur in approximately one-fifth of patients despite the lack of follicles in these areas.2,5 There is no systemic involvement.5 Individual plaques typically last for 7 to 10 days, recur every 3 to 4 weeks, and are often pruritic.5Laboratory findings in classic EPF include leukocytosis with eosinophilia in up to 35% of patients, which normalize as skin lesions improve.2,4,6 Histologically, there is a periadnexal infiltrate of eosinophils and lymphocytes primarily involving the follicular isthmus, infundibulum, and sebaceous glands.3,5 On follicle-bearing areas, this infiltrate may form eosinophilic microabscesses, invade the pilosebaceous unit, and lead to destruction of the follicles in advanced cases.3,6 On follicle-free palmoplantar surfaces, histologic findings include eosinophilic spongiosis and subcorneal and intraepidermal pustules with eosinophils and neutrophils.7Differential diagnoses include fungal and bacterial folliculitides, parasitic infestations, drug eruption, rosacea, folliculotropic mycosis fungoides, and follicular mucinosis.3 General diagnostic workup includes complete blood cell count with differential, HIV testing, and skin punch biopsy.3Follicular mycosis fungoides can present clinically with pink indurated plaques with follicular involvement, demonstrating eosinophilic folliculitis and pustular changes on histologic analysis. However, the T-cell infiltrate often shows atypia and epidermotropism, and TCR gene rearrangement studies demonstrate a clonal T-cell population.8 Histopathologic analysis of papulopustular rosacea typically demonstrates a dense follicular and perivascular infiltrate composed of lymphocytes, plasma cells, and neutrophils without eosinophils.9 Majocchi granuloma is a clinical mimicker, but histologically, it demonstrates perifollicular granulomatous inflammation with numerous fungal organisms.10While the cause of EPF is uncertain, it has been proposed to be the result of immune dysregulation surrounding sebocytes, with excess prostaglandin D2 stimulating sebocyte release of the eosinophil chemoattractant, eotaxin-3.2 Indomethacin inhibits cyclooxygenase and arachidonic acid metabolites, including prostaglandin D2, thus disrupting this process.4,6 Oral indomethacin (25-75 mg/d) is suggested as first-line treatment for classic EPF,2-4,6 demonstrating clinical efficacy in numerous cases.2,3 The time to initial response to oral indomethacin is estimated from several days6 to 2 to 6 weeks.4 In patients with kidney failure or peptic ulcers, topical indomethacin can be considered as an alternative first-line treatment.3Eosinophilic pustular folliculitis should be considered as a diagnosis for recurrent pruritic plaques studded with papules and pustules, particularly in Japanese patients. Biopsy is necessary to make the diagnosis, and testing for HIV is required to differentiate classic EPF from immunosuppression-associated EPF in adult patients. In this case, the patient’s history, presentation, histopathologic findings, and clinical course with response to indomethacin were all characteristic of EPF. It is important to consider EPF in cases with palmoplantar involvement with eosinophilic pustulosis rather than folliculitis in these locations.

Dermatology

A Japanese man in his 50s presented with a 6-month history of worsening pruritic hand dermatitis that progressed to involve his face, trunk, upper extremities, and feet. He had emigrated from Japan more than 10 years earlier but had no history of recent travel. He took no medications, had no significant medical or surgical history, and denied personal and family history of atopy. While he worked as a biomedical researcher, he denied any caustic exposures. On physical examination, his face, trunk, upper extremities, palms, and soles were marked by 1- to 2-mm erythematous papules and pustules coalescing into large, partially indurated and polycyclic plaques with centrifugal extension and occasional central clearing (Figure, A and B). Treatment with potent topical corticosteroids was ineffective. Punch biopsies of lesions on the shoulder (Figure, C) and foot (Figure, D) were performed.A, Annular erythematous plaque studded with papules and pustules on the cheek and temple. B, Erythematous plaques studded with papules and pustules on the shoulder. C and D, Lesional specimens under hematoxylin-eosin stain taken from the shoulder (C, original magnification ×400) and plantar foot (D, original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Papulopustular rosacea

Folliculotropic mycosis fungoides

Majocchi granuloma

Eosinophilic pustular folliculitis

d

male

51-60

Japanese

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2727297

A 42-year-old white woman with a history of episodic migraine with visual aura presented for evaluation of transient right upper extremity weakness and word-finding difficulty associated with headache. She admitted to having developed new intermittent vertigo and more frequent and severe throbbing migraine with transient blurry vision and nonpulsatile tinnitus several months prior. She had recently developed hearing loss with a robotic quality of auditory perception. She denied mouth or genital ulcers. A neurologic examination revealed diminished hearing to a finger rub on the right side. Fundoscopy showed several segmental retinal arterial plaques, with the right side worse than the left. A brain magnetic resonance image (MRI) with gadolinium revealed multiple white-matter lesions that were hyperintense on diffusion-weighted imaging (DWI), including some with enhancement, as well as a small DWI-negative lesion in the left thalamus and corpus callosum that was hyperintense on T2/fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR; Figure 1). An MRI of the spine with gadolinium did not reveal a signal abnormality in the spinal cord. Infectious, rheumatologic, and hypercoaguable test results were negative. A lumbar puncture revealed a white blood cell count of 8 cells/μL (normal range, 0-5 cells/μL; to convert to cells × 109/L, multiply by 0.001) with 78% lymphocytes and 22% monocytes (to calculate these as proportions of 1.0, multiply by 0.01), and a protein level of 0.067 g/dL (normal range, 0.015-0.045 g/dL; to convert to grams per liter, multiply by 10). Cerebrospinal fluid (CSF) glucose and IgG index test results were normal, with culture and oligoclonal bands negative. An audiogram revealed bilateral sensorineural hearing loss, with the right side worse than the left. Retinal fluorescein angiography was obtained.A, Pink arrowheads indicate hyperintensities in the right centrum semiovale. B, The yellow arrowhead indicates a hyperintensity in the corpus callosum.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) What Is Your Diagnosis?

Multiple sclerosis

Behçet disease

Susac syndrome

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

C. Susac syndrome

C

Susac syndrome

Susac syndrome is a rare disorder caused by occlusions of microvessels in the brain, retina, and inner ear, with an autoimmune causative mechanism presumed based on signs of inflammation in biopsies of the brain and CSF testing, as well as contrast enhancement on retinal and brain imaging and case reports of good response to immunosuppressive and immunomodulatory therapies.1 John O. Susac, MD, described the initial case in the mid-1970s after he encountered a young woman with a previously unreported triad of encephalopathy, branch retinal artery occlusions, and deafness.2 Since then, more than 300 cases of Susac syndrome have been reported in the literature worldwide with female individuals (aged 20-40 years) affected more frequently than male individuals.1 The prevalence of this disease may not be as rare as once thought, given that the full clinical triad rarely exists at time of initial presentation and many cases are often being misdiagnosed as multiple sclerosis.3-6At clinical onset, the most common manifestation is central nervous system symptoms, followed by visual and hearing or vestibular disturbances. Headaches are present at disease onset in more than 80% of patients and often resemble migraine. Central nervous system symptoms can include focal neurological deficits owing to transient ischemic attack or stroke; later in the disease, patients can develop global deficits (eg, encephalopathy, dementia).1,7,8 Magnetic resonance imaging of the brain typically shows punctate hyperintense deep white and gray matter lesions consistent with microinfarctions on T2/FLAIR, some of which may have restricted diffusion suggestive of acute ischemia and contrast enhancement. Involvement of the central portion of the corpus callosum, rather than the periphery (as in multiple sclerosis), as evidenced by presence of so-called snowball lesions (Figure 1), is considered a characteristic sign of Susac syndrome.1 Echocardiography is usually low yield, because the deep location of the microinfarctions, including the corpus callosum, makes cardioembolism less likely. Cerebrospinal fluid studies may show pleocytosis and elevated protein, typically without oligoclonal bands. Catheter-based cerebral angiography results are usually normal. An audiogram usually shows bilateral sensorineural hearing loss. Retinal fluorescein angiography reveals unilateral or bilateral branched retinal artery occlusions and/or arterial wall hyperfluorescence (Figure 2) owing to microvasculitis, even in patients who are visually asymptomatic.1 Fundoscopy typically shows branched retinal artery occlusions as well as retinal arterial atheromatous plaques, ischemic fluffy white patches, and/or tiny hemorrhages.8Retinal fluorescein angiogram of the right eye with leakage of fluorescein dye through the wall of a branch retinal artery (pink arrowhead) and branch retinal artery occlusive disease inferiorly and temporally (yellow arrowheads).Susac syndrome is frequently misdiagnosed as multiple sclerosis owing to the presence of white matter lesions, corpus callosum involvement, and CSF pleocytosis; however, based on current multiple sclerosis diagnostic criteria,9 the absence of oligoclonal bands, involvement of deep gray matter, and presence of retinal and auditory pathology argue against this diagnosis. Recurrent oral and genital aphthous ulcers, uveitis or retinal vasculitis, pathergy, and skin or vascular lesions, characterize Behçet disease.10 The lack of ulcers and presence of corpus callosum pathology makes the diagnosis of Behçet disease unlikely. The imaging phenotype and involvement of hearing do not support the diagnosis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Genetic testing for CADASIL may be considered in patients with cryptogenic stroke with appropriate MRI findings; in this case, CADASIL genetic testing was not ordered based on clinical phenotype favoring Susac syndrome.There is no consensus on the treatment of Susac syndrome because of the lack of large well-designed studies addressing this rare, underreported disease. Based on the idea that Susac syndrome may have an inflammatory causative mechanism, some authors have reported variable benefit with immunosuppressive agents.5,8The patient has had improvement in auditory symptoms. She has remained clinically stable while receiving therapy with mycophenolate mofetil and a tapering dosage of oral prednisone.

Neurology

A 42-year-old white woman with a history of episodic migraine with visual aura presented for evaluation of transient right upper extremity weakness and word-finding difficulty associated with headache. She admitted to having developed new intermittent vertigo and more frequent and severe throbbing migraine with transient blurry vision and nonpulsatile tinnitus several months prior. She had recently developed hearing loss with a robotic quality of auditory perception. She denied mouth or genital ulcers. A neurologic examination revealed diminished hearing to a finger rub on the right side. Fundoscopy showed several segmental retinal arterial plaques, with the right side worse than the left. A brain magnetic resonance image (MRI) with gadolinium revealed multiple white-matter lesions that were hyperintense on diffusion-weighted imaging (DWI), including some with enhancement, as well as a small DWI-negative lesion in the left thalamus and corpus callosum that was hyperintense on T2/fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR; Figure 1). An MRI of the spine with gadolinium did not reveal a signal abnormality in the spinal cord. Infectious, rheumatologic, and hypercoaguable test results were negative. A lumbar puncture revealed a white blood cell count of 8 cells/μL (normal range, 0-5 cells/μL; to convert to cells × 109/L, multiply by 0.001) with 78% lymphocytes and 22% monocytes (to calculate these as proportions of 1.0, multiply by 0.01), and a protein level of 0.067 g/dL (normal range, 0.015-0.045 g/dL; to convert to grams per liter, multiply by 10). Cerebrospinal fluid (CSF) glucose and IgG index test results were normal, with culture and oligoclonal bands negative. An audiogram revealed bilateral sensorineural hearing loss, with the right side worse than the left. Retinal fluorescein angiography was obtained.A, Pink arrowheads indicate hyperintensities in the right centrum semiovale. B, The yellow arrowhead indicates a hyperintensity in the corpus callosum.Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

what is your diagnosis?

What is your diagnosis?

Behçet disease

Susac syndrome

Multiple sclerosis

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

b

female

41-50

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2723593

A woman in her 20s was referred by the optician to our acute and emergency department for suspected optic neuritis in the right eye. She reported a sudden onset of photopsia and visual disturbances described as “fixed swirl circles” in the central vision of both eyes noticed on awakening 5 days prior and persisting since that time. Her medical history included migraine and polycystic ovaries. She had a flulike episode 1 week prior to the onset of symptoms. The patient was taking oral contraceptives and denied the use of recreational drugs. Ocular movements were full but the patient reported pain and discomfort during movements of the right eye. Pupils were equal and reactive to light and there was no afferent pupillary defect. Best-corrected visual acuity was 20/20 OU; color vision was 17/17 OU on Ishishara plates. The anterior segment was unremarkable and intraocular pressure was 14 mm Hg in both eyes. Dilated fundus examination revealed a healthy optic disc and no obvious abnormalities at the macula of both eyes. Near-infrared reflectance imaging and spectral-domain optical coherence tomography (OCT) scans of the right eye are shown in the Figure.A, Near-infrared reflectance imaging of acute macular neuroretinopathy in the right eye at presentation reveals hyporeflective teardrop-shaped lesions (black arrowheads). B, Simultaneous spectral-domain optical coherence tomography scan passing through the acute macular neuroretinopathy lesions in the right eye reveals increased reflectivity of the outer plexiform layer (yellow arrowheads) and attenuation of the ellipsoid zone (white arrowheads). What Would You Do Next?

Perform fluorescein angiography

Observe the patient

Perform magnetic resonance imaging of the brain

Start a course of oral corticosteroids

Acute macular neuroretinopathy (AMN)

B

Observe the patient

Sudden-onset paracentral scotoma, good visual acuity, and the presence of wedge-shaped paracentral hyporeflective lesions on infrared reflectance imaging associated with hyperreflectivity of the junction of the outer plexiform layer and the outer nuclear layer on OCT were consistent with AMN. Observation (choice B) was the appropriate next step for this case. Fluorescein angiography (choice A) would not be the preferred answer as the next step because AMN is typically not detected on fluorescein angiography. Magnetic resonance imaging of the brain (choice C) was not recommended as the next step because diagnosis of AMN per se does not require brain imaging unless there are symptoms and/or signs suggestive of central nervous system involvement. There is no proven treatment for AMN; thus, treatment with oral corticosteroids (choice D) was not indicated.First described by Bos and Deutman in 1975,1 AMN is a rare condition that typically affects young women. The clinical presentation is with flat, reddish, wedge-shaped or teardrop-shaped intraretinal lesions usually pointing toward the fovea and best seen using near-infrared reflectance imaging.2 These lesions may be very subtle, and fundus examination may be unremarkable,3 as in the present patient.The patient was referred to us with a provisional diagnosis of optic neuritis in the right eye because of pain during ocular movements and sudden-onset scotoma. However, the patient’s clinical presentation was not consistent with optic neuritis in the right eye; the patient’s visual acuity and color vision were unaffected and there was no relative afferent pupillary defect. Moreover, pain during ocular movements has been reported in association with AMN at presentation,4 although it is uncommon.The clinical course of AMN is characterized by persistence of paracentral scotoma but patients typically retain good visual acuity. Optical coherence tomography is useful to monitor the natural course of the condition. In the acute phase of the disease, AMN typically presents on OCT with hyperreflective bands at the level of the junction of the outer plexiform layer and the outer nuclear layer. Subsequent attenuation of the outer nuclear layer and ellipsoid zone are the hallmark of this condition in the postacute phase of the disease.5The pathogenesis of AMN is still a matter of debate. Several risk factors, including use of oral contraceptives, preceding flulike illness, exposure to either epinephrine or ephedrine, intake of lisdexamphetamine, use of cocaine, antecedent trauma, systemic shock, and preeclampsia, have been associated with AMN.6Fawzi et al5 first described longitudinal features of AMN seen on results of OCT and showed that the earliest finding in AMN occurs at the level of the outer plexiform layer in the context of a completely normal outer retina and before the appearance of lesions on results of near-infrared reflectance imaging. Given the early involvement of the outer plexiform layer, a local impairment of the deep retinal circulation had been suggested as the possible cause of these lesions.5 However, recent reports using OCT angiography found that flow abnormalities in the choriocapillaris colocalize with the alterations of the AMN lesions seen on results of OCT and suggested a vascular insult in the choriocapillaris as the pathogenic mechanism of the AMN lesions.7-9Acute macular neuroretinopathy should be suspected in young healthy women with a sudden onset of paracentral scotoma and unremarkable clinical examination. Recognition of AMN in these patients may avoid unnecessary investigations. Identification of risk factors for AMN and its characteristic features on near-infrared reflectance imaging and OCT are critical for the recognition of this uncommon condition.The patient was reexamined after 4 weeks. Her best-corrected visual acuity was 20/20 OU. She denied ocular pain during ocular movements and reported the persistence of paracentral scotoma.

Ophthalmology

A woman in her 20s was referred by the optician to our acute and emergency department for suspected optic neuritis in the right eye. She reported a sudden onset of photopsia and visual disturbances described as “fixed swirl circles” in the central vision of both eyes noticed on awakening 5 days prior and persisting since that time. Her medical history included migraine and polycystic ovaries. She had a flulike episode 1 week prior to the onset of symptoms. The patient was taking oral contraceptives and denied the use of recreational drugs. Ocular movements were full but the patient reported pain and discomfort during movements of the right eye. Pupils were equal and reactive to light and there was no afferent pupillary defect. Best-corrected visual acuity was 20/20 OU; color vision was 17/17 OU on Ishishara plates. The anterior segment was unremarkable and intraocular pressure was 14 mm Hg in both eyes. Dilated fundus examination revealed a healthy optic disc and no obvious abnormalities at the macula of both eyes. Near-infrared reflectance imaging and spectral-domain optical coherence tomography (OCT) scans of the right eye are shown in the Figure.A, Near-infrared reflectance imaging of acute macular neuroretinopathy in the right eye at presentation reveals hyporeflective teardrop-shaped lesions (black arrowheads). B, Simultaneous spectral-domain optical coherence tomography scan passing through the acute macular neuroretinopathy lesions in the right eye reveals increased reflectivity of the outer plexiform layer (yellow arrowheads) and attenuation of the ellipsoid zone (white arrowheads).

what would you do next?

What would you do next?

Start a course of oral corticosteroids

Perform magnetic resonance imaging of the brain

Perform fluorescein angiography

Observe the patient

d

female

21-30

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2723990

A 44-year-old man with a 2-week history of fevers, night sweats, chills, and petechiae presented with painless, blurry vision in the left eye. His ocular symptoms began 2 days prior when he noticed dark scotomas in his central field and decreased visual acuity. There was no recent trauma or strenuous physical activity. He had no relevant medical, ocular, or family history, and he denied use of illicit drugs or anticoagulants.Uncorrected visual acuity was 20/30 OD and 20/400 OS. Extraocular motility and intraocular pressures were normal. Results of an anterior examination was unremarkable. Dilated funduscopic examination of the left eye revealed a pink optic nerve with sharp margins, diffuse intraretinal hemorrhages and Roth spots extending from the posterior pole to the far periphery, and preretinal hemorrhage overlying the central macula (Figure, A). Spectral-domain optical coherence tomography through the preretinal macular hemorrhage demonstrated layered blood in the sub–internal limiting membrane space (Figure, B). The right fundus exhibited a similar appearance aside from the preretinal hemorrhage.A, Bedside indirect ophthalmoscopy (slightly out of focus) of the left eye with a 20-diopter lens reveals diffuse retinal hemorrhages; the white arrowhead indicates hemorrhage corresponding to Figure, B and the blue arrowheads, Roth spots in the posterior pole with a normal-appearing optic nerve. Findings extended to the far periphery. B, Spectral-domain optical coherence tomography through macular hemorrhage reveals layering of blood in the sub–internal limiting membrane space of the left retina.Obtain a fluorescein angiogram to evaluate degree of ischemia and confirm a diagnosis of central retinal vein occlusionProvide the patient with stool softeners to prevent recurrence of Valsalva retinopathyImmediately begin intravenous antibiotics before any blood draws and consult cardiology for likely bacterial endocarditisDraw a complete blood cell count with differential to evaluate for leukemic retinopathy or blood dyscrasia What Would You Do Next?

Obtain a fluorescein angiogram to evaluate degree of ischemia and confirm a diagnosis of central retinal vein occlusion

Provide the patient with stool softeners to prevent recurrence of Valsalva retinopathy

Immediately begin intravenous antibiotics before any blood draws and consult cardiology for likely bacterial endocarditis

Draw a complete blood cell count with differential to evaluate for leukemic retinopathy or blood dyscrasia

Acute myeloid leukemia

D

Draw a complete blood cell count with differential to evaluate for leukemic retinopathy or blood dyscrasia

This patient had leukocytosis (white blood cells, 61 700/μL [to convert to cells × 109/L, multiply by 0.001]; normal limits, 4500-12 000/μL) with anemia (red blood cells, 2.71 × 106/μL [to convert to cell × 1012/L, multiply by 1.0]; normal limits, 3.9-5.5 × 106/μL; hemoglobin, 8.9 g/dL [to convert to g/L, multiply by 10.0]; normal limits, 14-18 g/dL; hematocrit, 26.8% [to convert to a proportion of 1.0, convert to 0.01]; normal limits, 40%-54%) and thrombocytopenia (platelet, 3.1 × 103/μL [to convert to cells × 109/L, multiply by 1.0]; normal limits, 150-400 × 103/μL). There were increases in the absolute number of neutrophils (7400/μL [to convert to cells × 109/L,multiply by 0.001]; normal limits, 17 800-53 600/μL), monocytes (18 040/μL [to convert to cells × 109/L, multiply by 0.001]; normal limits, 300-820/μL), basophils (620/μL [to convert to cells × 109/L, multiply by 0.001]; normal limits, 10-80/μL), and eosinophils (3700/μL [to convert to cells × 109/L, multiply by 0.001]; normal limits, 40-540/μL), with a normal lymphocyte count (2470/μL [to convert to  × 109/L, multiply by 0.001]; normal limits, 1320-3570/μL). Peripheral blood smear showed 35% blasts, while bone marrow flow cytometry revealed 50% abnormal monocytes and 23% myeloblasts. All findings were consistent with a diagnosis of acute myeloid leukemia with monocytic features; cytogenetic analysis revealed an inversion on chromosome 16, which has been associated with favorable prognostic outcomes.1Ocular involvement (often asymptomatic) is present in up to 50% of patients with leukemia at time of diagnosis, with retinal lesions the most common ocular manifestation.2 Leukemic retinopathy is characterized by retinal hemorrhages in the posterior pole secondary to anemia and thrombocytopenia. These hemorrhages are most commonly intraretinal but can also be subretinal, sub–internal limiting membrane, or subhyaloid.3 Other signs of leukemic retinopathy include Roth spots (retinal hemorrhages with central white spots), cotton wool spots, retinal vein tortuosity, microaneurysms, and neovascularization.4 Infiltration of the optic nerve is rare but a poor prognostic sign if observed.Other diagnoses that can manifest similar features include central retinal vein occlusion, Valsalva retinopathy, bacterial endocarditis, hypertensive retinopathy, and diabetic retinopathy. However, the presence of Roth spots with described systemic symptoms are atypical for any of these besides bacterial endocarditis, so fluorescein angiogram for evaluation of central retinal vein occlusion (choice A) and stool softeners for Valsalva retinopathy (choice B) would not be recommended next steps. While bacterial endocarditis should have been considered for this patient, initiation of antibiotics without first obtaining blood tests to rule out another causative mechanism (choice C) would be inappropriate. If leukemic retinopathy is suspected, the patient should obtain a complete blood cell count with differential and peripheral blood smear, followed by bone marrow aspiration for confirmation. Flow cytometry immunophenotyping helps distinguish between different types of leukemia, while cytogenetic analysis can provide valuable prognostic information.Treatment for leukemic retinopathy is directed toward the underlying leukemic disease rather than the ocular manifestations. Systemic chemotherapy (often with daunorubicin, cytarabine, and thioguanine) is the mainstay treatment, sometimes combined with adjunctive targeted drug therapy.5 This may be followed by stem cell transplant. Radiation has a limited role in the treatment of acute myeloid leukemia, but external beam radiation therapy may be used if the brain and spinal fluid are involved. The ophthalmic findings and decreased vision almost always resolve with induction of chemotherapy.6In this case report, we describe a patient with an unremarkable medical or ocular history presenting with leukemic retinopathy as the initial finding of acute myeloid leukemia. This case highlights the importance of considering leukemia as a diagnosis in an otherwise healthy patient presenting with retinopathy.Standard 7 + 3 induction chemotherapy was initiated with an intravenous continuous infusion of cytarabine, 100mg/m2, administered on days 1 through 7 and an intravenous bolus of idarubicin, 12mg/m2, concurrently administered on days 1 through 3. At day 43 of induction, the patient underwent a second ophthalmic examination, which showed complete resolution of leukemic retinopathy and restored baseline visual acuity. Ophthalmic return precautions were discussed with the patient and his cancer specialist team as he continues treatment for leukemia.

Ophthalmology

A 44-year-old man with a 2-week history of fevers, night sweats, chills, and petechiae presented with painless, blurry vision in the left eye. His ocular symptoms began 2 days prior when he noticed dark scotomas in his central field and decreased visual acuity. There was no recent trauma or strenuous physical activity. He had no relevant medical, ocular, or family history, and he denied use of illicit drugs or anticoagulants.Uncorrected visual acuity was 20/30 OD and 20/400 OS. Extraocular motility and intraocular pressures were normal. Results of an anterior examination was unremarkable. Dilated funduscopic examination of the left eye revealed a pink optic nerve with sharp margins, diffuse intraretinal hemorrhages and Roth spots extending from the posterior pole to the far periphery, and preretinal hemorrhage overlying the central macula (Figure, A). Spectral-domain optical coherence tomography through the preretinal macular hemorrhage demonstrated layered blood in the sub–internal limiting membrane space (Figure, B). The right fundus exhibited a similar appearance aside from the preretinal hemorrhage.A, Bedside indirect ophthalmoscopy (slightly out of focus) of the left eye with a 20-diopter lens reveals diffuse retinal hemorrhages; the white arrowhead indicates hemorrhage corresponding to Figure, B and the blue arrowheads, Roth spots in the posterior pole with a normal-appearing optic nerve. Findings extended to the far periphery. B, Spectral-domain optical coherence tomography through macular hemorrhage reveals layering of blood in the sub–internal limiting membrane space of the left retina.Obtain a fluorescein angiogram to evaluate degree of ischemia and confirm a diagnosis of central retinal vein occlusionProvide the patient with stool softeners to prevent recurrence of Valsalva retinopathyImmediately begin intravenous antibiotics before any blood draws and consult cardiology for likely bacterial endocarditisDraw a complete blood cell count with differential to evaluate for leukemic retinopathy or blood dyscrasia

what would you do next?

What would you do next?

Obtain a fluorescein angiogram to evaluate degree of ischemia and confirm a diagnosis of central retinal vein occlusion

Draw a complete blood cell count with differential to evaluate for leukemic retinopathy or blood dyscrasia

Immediately begin intravenous antibiotics before any blood draws and consult cardiology for likely bacterial endocarditis

Provide the patient with stool softeners to prevent recurrence of Valsalva retinopathy

b

male

41-50

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2723991

A 65-year-old white man was referred to the clinic with a pigmented conjunctival lesion in the left eye. The referring physician suspected primary acquired melanosis (PAM). His ocular history was notable for occupational exposure to sunlight and occasional smoking. There was no personal or family history of cancer, and he denied ocular surgery or trauma. On examination, his best-corrected visual acuity was 20/20 OD/OS, and intraocular pressures were 15 mm Hg OD and 18 mm Hg OS. A slitlamp examination of the right eye showed no conjunctival pigmentation. Examination of the left eye revealed a pigmented lesion at the temporal limbus from 3 to 4 o’clock with a 2-mm extension into the cornea (Figure 1A). Some opalescence underlied the pigment on the cornea. In addition, there was an adjacent small area of flat, superficial, mobile bulbar conjunctival pigmentation. The anterior segment high-resolution optical coherence tomography (HR-OCT) of the 4-o’clock corneolimbal lesion of the left eye demonstrated thickened hyperreflective corneal epithelium with an abrupt transition from normal to abnormal (Figure 1B).A, Slitlamp photography of the left eye shows a pigmented limbal lesion at 3 to 4 o’clock; another small area of bulbar conjunctival pigmentation is noted (arrowhead). B, High-resolution optical coherence tomography of the left eye through the area of the pigmented conjunctival lesion (inset with red line in area of scan), showing epithelial hyperreflectivity and thickening with an abrupt change from normal to mildly thickened epithelium (arrowhead). What Would You Do Next?

Refer to an oncologist for metastatic workup

Biopsy the conjunctival and corneal lesion

Perform cryotherapy over the lesion

Start oral doxycycline

Ocular surface squamous neoplasia in the left eye and PAM in the left eye

B

Biopsy the conjunctival and corneal lesion

This patient was referred with a diagnosis of primary acquired melanosis. PAM is an acquired flat, noncystic pigmented lesion of the conjunctiva, cornea, or caruncle. About 96% of cases occur in fair-skinned individuals with a mean age of 56 years.1,2 PAM without atypia does not progress to melanoma, whereas PAM with severe atypia has a 13% to 46% risk of progression.3 In this case, after referral for PAM, the subtle opalescence on clinical examination indicated a possible diagnosis of concurrent ocular surface squamous neoplasia (OSSN).Ocular surface squamous neoplasia includes a spectrum of dysplasia, ranging from mild to invasive carcinoma of conjunctiva, limbus, and cornea.4 It typically presents as a unilateral limbal lesion, which can appear papillomatous, gelatinous, or leukoplakic. When on the cornea, it may have an opalescent appearance. In the United States, OSSN is commonly found in white men older than 60 years and is infrequently associated with pigment. In Africa, the disease is seen in black individuals, and OSSN often has accompanying pigment.5 The lesions rarely ever metastasize, and as such, a metastatic workup for this lesion is not indicated (choice A).While this disease is typically diagnosed clinically, HR-OCT can assist in arriving at the correct diagnosis, especially in atypical cases. With this imaging, we could detect that this patient’s lesion was in fact OSSN coexisting with and, in a manner of speaking, hiding in PAM. The results of the patient’s HR-OCT imaging showed epithelial hyperreflectivity with thickening and an abrupt transition from normal to abnormal epithelium, which are classic for OSSN.6 PAM on HR-OCT appears very different, with only a linear basal epithelial hyperreflective band and normal epithelium with no thickening.7The HR-OCT suggested that this was not simply a small area of PAM; thus, a biopsy was performed to confirm these findings (choice B). The biopsy confirmed the HR-OCT findings of corneal OSSN and PAM. The corneal epithelium disclosed faulty maturational sequencing with pleomorphic nuclei that extended to near-full thickness with overlying superficial maturation. Morphologically benign melanin deposition was present within these cells (Figure 2). This case demonstrates how HR-OCT imaging can assist in the diagnosis of conjunctival lesions in complex ocular surface conditions, and gave an ad hoc optical biopsy of the ocular surface.Examination of fragmented, tangentially sectioned corneal epithelium shows faulty maturational sequencing with pleomorphic nuclei that extends to near-full thickness with overlying superficial maturation (asterisk). Morphologically benign melanin deposition is present in these cells (arrowhead); hematoxylin-eosin, original magnification ×600.Ocular surface squamous neoplasia is generally a slow-growing and treatable tumor. Surgery and chemotherapy are the main treatments. Surgery is approached using a no-touch technique with wide margins and adjuvant cryotherapy. Cryotherapy (choice C) alone is not ideal for the treatment of OSSN. Doxycycline (choice D), while helpful for meibomian gland disease, is not a treatment for OSSN or PAM. Topical chemotherapy is now often used as primary therapy.8 Both surgical excision and topical therapy have similar outcomes in terms of recurrence rates.9 The most commonly used agents are interferon–alfa 2b, 5-fluorouracil, and mitomycin C.10After the biopsy confirmed the HR-OCT findings of a corneal OSSN, the patient was treated with a cycle of topical 5-fluorouracil, 1%, 4 times daily for 1 week with 3 weeks off. After 2 cycles, the lesion resolved clinically and by HR-OCT, in that the epithelial thickening and hyperreflectivity were resolved. A total of 4 cycles were given. The patient will be followed up carefully for recurrence of the OSSN clinically and with HR-OCT.

Ophthalmology

A 65-year-old white man was referred to the clinic with a pigmented conjunctival lesion in the left eye. The referring physician suspected primary acquired melanosis (PAM). His ocular history was notable for occupational exposure to sunlight and occasional smoking. There was no personal or family history of cancer, and he denied ocular surgery or trauma. On examination, his best-corrected visual acuity was 20/20 OD/OS, and intraocular pressures were 15 mm Hg OD and 18 mm Hg OS. A slitlamp examination of the right eye showed no conjunctival pigmentation. Examination of the left eye revealed a pigmented lesion at the temporal limbus from 3 to 4 o’clock with a 2-mm extension into the cornea (Figure 1A). Some opalescence underlied the pigment on the cornea. In addition, there was an adjacent small area of flat, superficial, mobile bulbar conjunctival pigmentation. The anterior segment high-resolution optical coherence tomography (HR-OCT) of the 4-o’clock corneolimbal lesion of the left eye demonstrated thickened hyperreflective corneal epithelium with an abrupt transition from normal to abnormal (Figure 1B).A, Slitlamp photography of the left eye shows a pigmented limbal lesion at 3 to 4 o’clock; another small area of bulbar conjunctival pigmentation is noted (arrowhead). B, High-resolution optical coherence tomography of the left eye through the area of the pigmented conjunctival lesion (inset with red line in area of scan), showing epithelial hyperreflectivity and thickening with an abrupt change from normal to mildly thickened epithelium (arrowhead).

what would you do next?

What would you do next?

Start oral doxycycline

Refer to an oncologist for metastatic workup

Perform cryotherapy over the lesion

Biopsy the conjunctival and corneal lesion

d

male

61-70

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2721041

A 70-year old man with a history of soft contact lens wear presented for a general eye examination. Visual acuity was 20/20 OU with normal intraocular pressure. Several giant follicles were noted on the right inferior palpebral conjunctiva, and a few smaller follicles were noted in the left inferior fornix. Papillae were also noted bilaterally on the superior palpebral conjunctiva. He did not report any redness or discharge but did note mildly increased irritation mainly from soft contact lens wear. He had endorsed proper contact lens care and hygiene. He also noted an upper respiratory tract illness 4 weeks before presentation. Initially, he received a giant papillary conjunctivitis diagnosis because of soft contact lens intolerance and a recommendation to take a contact lens break. Because of the papillary reaction, prednisolone acetate, 1%, twice a day for 2 weeks was prescribed.After 3 months, the symptoms had improved in the left eye, but conjunctival follicles were still present in the right inferior palpebral conjunctiva (Figure 1). The patient subsequently underwent testing for chlamydia and gonorrhea, and the result was negative. At the 1-year follow-up, the examination findings were unchanged. During this follow-up, Lyme disease and Epstein-Barr virus serologic tests were performed in addition to repeated chlamydia testing. The results were negative, except for a positive Epstein-Barr virus IgG.Slitlamp photograph showing prominent large follicles (arrowhead) in the right inferior palpebral conjunctiva.Start a longer trial of topical steroid with topical antihistamineOrder chest radiography and an angiotensin-converting enzyme serum level test What Would You Do Next?

Start an empirical trial of oral azithromycin

Start a longer trial of topical steroid with topical antihistamine

Proceed with conjunctival biopsy

Order chest radiography and an angiotensin-converting enzyme serum level test

Conjunctival follicular lymphoma

C

Proceed with conjunctival biopsy

An empirical trial of oral azithromycin (choice A) would be less preferred because of the 2 negative chlamydia testing results. A longer trial of topical steroid with topical antihistamine (choice B) would be less favorable because symptoms and follicle appearance were not consistent with allergic conjunctivitis. Chest radiography and angiotensin-converting enzyme level test (choice D) would not be recommended as the patient’s more translucent follicles did not have the typical appearance of the yellow or tan conjunctival nodules found in ocular sarcoidosis. Because of the chronic nature and abnormal, large nodular appearance of the follicles, conjunctival biopsy was pursued for definitive diagnosis after a negative infectious serologic testing result. This biopsy showed centrocytes consistent with follicular lymphoma (Figure 2). Flow cytometry demonstrated a CD 10–positive monotypic B cell population. Fluorescence in situ hybridization testing detected a t(14;18) translocation. He was subsequently referred to the hematology-oncology service for systemic workup, including hepatitis B and C serologic tests, antinuclear antibody panel test, serum protein electrophoresis, Chlamydophila psittaci serologic test, serum κ or λ light chains, whole-body positron emission tomography–computed tomography, and magnetic resonance imaging of the brain and orbits. The systemic workup results were negative, except for mild cervical lymphadenopathy on the positron emission tomography–computed tomography. After discussion with the patient and because of the lymphoma’s localized indolent course, he elected to undergo observation with follow-up every 3 months.Hematoxylin-eosin stain showing nodular aggregates of centrocytes, with small, slightly rounded lymphoid cells (asterisks) (original magnification ×10).Follicular lymphomas are described pathologically as follicles with cellular pleomorphism and the absence of sharply demarcated germinal centers.1 Ocular adnexal lymphoproliferative lesions range from benign hyperplasia to malignant lymphomas that affect the orbit, eyelid, or conjunctiva. Most of these lesions are found unilaterally in the orbit, and most neoplastic lesions are of monoclonal B cell origin.2 Conjunctival lymphoid lesions are described as mobile salmon-pink or flesh-colored patches in the fornix or bulbar conjunctiva.2-5 Symptoms include irritation, blurred vision, and epiphora and can present as a mass, ptosis, or diplopia.3A greater concern is systemic involvement, with bilateral presentation of ocular adnexal lymphomas. In large institutional case reviews, the incidence of systemic lymphoma findings at the time of local ocular diagnosis or up to 5 years afterward was between 20% to 30%.3,6 Extraocular sites included lymph nodes, bone marrow, abdomen, brain, and lungs. A predictive factor in systemic involvement was the location in the conjunctival fornix or midbulbar conjunctiva.3 With or without treatment, the mortality rate from systemic lymphoma in the long term was less than 5%. With radiation treatment, recurrence of disease was low (0%-20%) in the first 1 to 5 years after the biopsy.6-8The differential diagnosis for chronic conjunctivitis is extensive, including allergic reaction, adverse effect from ophthalmic medications or contact lenses and their cleaning solutions, viral and bacterial etiologies, and blepharoconjunctivitis.9,10 Infectious etiologies include herpesviruses, adenoviruses, cytomegalovirus, Epstein-Barr virus, molluscum contagiosum virus, coxsackieviruses, Chlamydia trachomatis, Moraxella species, and Bartonella henselae. Important elements of medical history and system review include duration, laterality, recent illness, history of allergies, and pet exposure.10 An uncertain diagnosis supports the performance of tissue biopsy for a definitive identification.Ophthalmic and oncologic follow-up for this patient has continued. His examination findings 1 year after the biopsy have been unchanged. To date, no extraocular involvement of follicular lymphoma has been found.

Ophthalmology

A 70-year old man with a history of soft contact lens wear presented for a general eye examination. Visual acuity was 20/20 OU with normal intraocular pressure. Several giant follicles were noted on the right inferior palpebral conjunctiva, and a few smaller follicles were noted in the left inferior fornix. Papillae were also noted bilaterally on the superior palpebral conjunctiva. He did not report any redness or discharge but did note mildly increased irritation mainly from soft contact lens wear. He had endorsed proper contact lens care and hygiene. He also noted an upper respiratory tract illness 4 weeks before presentation. Initially, he received a giant papillary conjunctivitis diagnosis because of soft contact lens intolerance and a recommendation to take a contact lens break. Because of the papillary reaction, prednisolone acetate, 1%, twice a day for 2 weeks was prescribed.After 3 months, the symptoms had improved in the left eye, but conjunctival follicles were still present in the right inferior palpebral conjunctiva (Figure 1). The patient subsequently underwent testing for chlamydia and gonorrhea, and the result was negative. At the 1-year follow-up, the examination findings were unchanged. During this follow-up, Lyme disease and Epstein-Barr virus serologic tests were performed in addition to repeated chlamydia testing. The results were negative, except for a positive Epstein-Barr virus IgG.Slitlamp photograph showing prominent large follicles (arrowhead) in the right inferior palpebral conjunctiva.Start a longer trial of topical steroid with topical antihistamineOrder chest radiography and an angiotensin-converting enzyme serum level test

what would you do next?

What would you do next?

Proceed with conjunctival biopsy

Order chest radiography and an angiotensin-converting enzyme serum level test

Start a longer trial of topical steroid with topical antihistamine

Start an empirical trial of oral azithromycin

a

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2722669

A white man in his 30s employed as a metal worker presented with a 2-month history of slightly blurry vision in his right eye. He denied photopsia or floaters and did not note any visual field defects. His best-corrected visual acuity was 20/25 OD and 20/20 OS. He had no history of ocular trauma, drug use, or familial ocular diseases.The anterior segment of both eyes was normal on slitlamp examination, but the fundus examination of the right eye showed multiple refractile small crystals scattered on the posterior pole (Figure 1A). Isolated crystals were also present in the vitreous core. Optical coherence tomography of the macula revealed the crystals to be located preretinally on the surface of the inner limiting membrane with sporadic crystals within the cortical vitreous (Figure 1B).A, Fundus photography at presentation shows multiple refractile crystals at the posterior pole (black arrowheads). B, The corresponding optic coherence tomography at presentation shows these crystals adhering to the internal limiting membrane and floating in the vitreous (white arrowheads).Apart from this, biomicroscopy, fluorescein angiography, and optical coherence tomography of the posterior pole showed no abnormalities. The left eye was unremarkable, and an radiographic image of the right eye socket revealed no foreign bodies.Screen for intravenous abuse of opioids and other substances What Would You Do Next?

Request a genetic workup

Examine the retinal periphery

Measure oxalate levels in blood and urine

Screen for intravenous abuse of opioids and other substances

Crystalline retinopathy associated with a chronic retinal detachment

B

Examine the retinal periphery

Preretinal crystals are a rare sign of a chronic retinal detachment. In 1998, Ahmed et al1 published a series of 11 cases. All deposits were found no deeper than the inner limiting membrane, and the crystals themselves did not seem to cause any loss of visual acuity. More recently, Habib et al2 analyzed subretinal fluid from a patient with preretinal crystals secondary to a chronic retinal detachment. Owing to the small sample in the study by Habib et al,2 a biochemical assay was not possible, but a microscopic analysis with polarized light showed a visual resemblance of the crystals to calcium oxalate. The current hypothesis is that the crystals originate from the subretinal space, migrate into the vitreous, and then settle at the vitreoretinal interface, predominantly at the macula because of gravitation. There is no evidence that crystalline deposits lower the visual prognosis; however, the retinal detachment might progress.1-4In this case, the examination of the retinal periphery revealed an inferotemporal chronic retinal detachment with pigmented borders. Figure 2 shows the lesion 1 month after subsequent laser photocoagulation.Fundus photography of the periphery; 1 month after laser coagulation (black arrowheads), the inferotemporal chronic retinal detachment was stable.Other causes of refractile crystalline deposits include a variety of differential diagnoses, ranging from systemic disorders to primary ocular disorders. A genetic workup (choice A) for conditions like Sjögren-Larsson syndrome, cystinosis, or Bietti crystalline dystrophy is most likely futile, because these diseases usually present themselves in both eyes. Measuring oxalate levels (choice C) would not be recommended, because oxalosis similarly presents itself bilaterally, and oxalosis crystals are typically located along the retinal arterioles,3 where no crystals were detected in this case. A screening for intravenous abuse of opioids and other substances (choice D) would not yield relevant results, because drug-induced crystalline retinopathies, such as talc retinopathy, present with intraretinal instead of preretinal crystals. The preretinal crystal distribution likewise excludes other possible ocular causes of retinal crystals, such as calcified macular drusen and calcium or cholesterol emboli.3Possible treatments were discussed with the patient, and a barrier laser procedure was performed to wall off the retinal detachment. The detachment remained stable, and the patient’s visual acuity had improved spontaneously to 20/20 OD by a 1-month follow-up visit.

Ophthalmology

A white man in his 30s employed as a metal worker presented with a 2-month history of slightly blurry vision in his right eye. He denied photopsia or floaters and did not note any visual field defects. His best-corrected visual acuity was 20/25 OD and 20/20 OS. He had no history of ocular trauma, drug use, or familial ocular diseases.The anterior segment of both eyes was normal on slitlamp examination, but the fundus examination of the right eye showed multiple refractile small crystals scattered on the posterior pole (Figure 1A). Isolated crystals were also present in the vitreous core. Optical coherence tomography of the macula revealed the crystals to be located preretinally on the surface of the inner limiting membrane with sporadic crystals within the cortical vitreous (Figure 1B).A, Fundus photography at presentation shows multiple refractile crystals at the posterior pole (black arrowheads). B, The corresponding optic coherence tomography at presentation shows these crystals adhering to the internal limiting membrane and floating in the vitreous (white arrowheads).Apart from this, biomicroscopy, fluorescein angiography, and optical coherence tomography of the posterior pole showed no abnormalities. The left eye was unremarkable, and an radiographic image of the right eye socket revealed no foreign bodies.Screen for intravenous abuse of opioids and other substances

what would you do next?

What would you do next?

Request a genetic workup

Examine the retinal periphery

Measure oxalate levels in blood and urine

Screen for intravenous abuse of opioids and other substances

b

male

31-40

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2723092

A previously healthy African American man in his 20s presented to the emergency department after referral by an optometrist for “bleeding in the back of the eye.” The patient noted that 2 months prior he began experiencing throbbing headaches in the back of his head that were more painful and associated with lightheadedness when laying down. Two weeks prior to presentation, he started noticing black spots in his peripheral vision and progressive blurring of vision in both eyes. The patient denied recent travel, cough, gastrointestinal or genitourinary tract symptoms, ulcers, aching joints, tinnitus, or transient visual obscurations. He reported owning cats.On presentation, the patient’s blood pressure was 210/150 mm Hg, and he had a history of acute kidney failure and non–ST-elevation myocardial infarction. On ophthalmic examination, his uncorrected near visual acuity was 20/25 OD and 20/30 OS. Extraocular motility, Ishihara color plates, intraocular pressure, pupils, and results of slitlamp examination were within normal limits. Ophthalmoscopy showed Frisen grade 5 optic nerve head swelling in both eyes with extensive flame hemorrhages and nerve fiber layer infarcts surrounding both nerves and retinal exudates extending from the nerves temporally into both fovea’s (Figure 1). The vessels were of normal course and caliber. There were scattered peripheral dot-and-blot hemorrhages. Results of Humphrey visual field testing were reliable and showed bilateral concentric constriction and enlarged blind spots.Grade 5 optic nerve head edema. A, Fundus photograph of the right eye shows Frisen grade 5 optic disc edema, flame hemorrhages, and peripapillary exudation into the macula. B, Fluorescein angiogram of the right eye in the early venous phase shows blockage from flame hemorrhages, peripapillary microaneurysms, leakage from optic disc capillaries, and absence of vascular leakage at arcades.Control the systemic blood pressure and workup underlying possible cause of the hypertensionPerform magnetic resonance imaging and magnetic resonance venogram of the brain and orbits, then perform lumbar puncture What Would You Do Next?

Control the systemic blood pressure and workup underlying possible cause of the hypertension

Perform blood tests for neuroretinitis

Perform magnetic resonance imaging and magnetic resonance venogram of the brain and orbits, then perform lumbar puncture

All of the above

Papilledema secondary to intracranial venous sinus stenosis, exacerbated by hypertensive emergency

D

All of the above

Optic nerve edema can result from several causes. In this patient, hypertensive papillitis, neuroretinitis, and papilledema from intracranial hypertension were all in the differential diagnosis. Therefore, all of the above testing (choice D) was warranted to ensure a timely and accurate diagnosis. In the setting of hypertensive emergency, the patient was admitted for control of blood pressure and treatment of systemic sequelae. Hypertensive papillitis can present with macular exudation and optic nerve head edema.1 However, concluding that systemic hypertension was the sole underlying cause of the optic nerve head swelling would be inadequate management (choice A). No further update is available for suspected renal artery stenosis as an underlying cause for his malignant hypertension, as the patient is lost to follow-up.Although macular exudation can occur with severe papillitis or papilledema, given the patient’s demographics, cats, and fundoscopic appearance, blood tests were warranted to rule out neuroretinitis (choice B).2 Results of fluorescein angiography demonstrated angiographic leakage of the optic nerve head capillaries with absence of macular leakage characteristic of neuroretinitis (Figure 1). However, results of testing were negative for tuberculosis, syphilis, Bartonella quintana, Bartonella henselae, Lyme disease, sarcoidosis, and toxoplasmosis.The position-dependent headaches and constricted fields were concerning for intracranial hypertension, warranting imaging of the brain and orbits (choice C). Results of magnetic resonance imaging showed no intracranial pathologic findings; results of magnetic resonance venography revealed stenosis at the junction of the right transverse and sigmoid sinuses (Figure 2). Results of lumbar puncture demonstrated an opening pressure of 50 cm H2O. Acetazolamide sodium, 1 g twice daily, was started in the interim prior to urgent cerebral angiography and stenting of the venous sinus stenosis.Magnetic resonance venogram revealing stenosis at the junction of the right transverse and sigmoid sinuses (arrowhead).Given the severity of the optic nerve head edema, we postulated that the patient’s intracranial hypertension may have been exacerbated by the systemic hypertension. Elevated intracranial pressure with papilledema and concomitant hypertensive emergency is a rare clinical scenario, described only once previously to our knowledge,3 and the nerve edema from either is not readily distinguishable from the other.4 An incomplete workup can easily result in treatment of only 1 of the conditions, leading to continued visual deterioration and possible permanent damage from delay in appropriate treatment, showing again that choice D is necessary. A series studying risk factors for severe vision loss in patients with idiopathic intracranial hypertension showed that, while most patients had good long-term visual outcomes, 62% of patients with hypertension became significantly visually impaired, suggesting that systemic hypertension is a significant risk factor.5 Systemic hypertension may be underdiagnosed in patients with elevated intracranial pressure, compromising their visual potential. It is vital to obtain a complete workup (choice D) in patients with optic nerve head edema to ensure timely and accurate diagnosis.Three and a half months after the patient underwent venous sinus stenting, his vision was restored, with formal perimetry showing full visual fields. On fundus examination, the papilledema had decreased significantly bilaterally to Frisen grade 2 with resolved flame hemorrhages, no nerve fiber layer infarcts, absence of dot-and-blot hemorrhages, and decreased exudation into the macula.

Ophthalmology

A previously healthy African American man in his 20s presented to the emergency department after referral by an optometrist for “bleeding in the back of the eye.” The patient noted that 2 months prior he began experiencing throbbing headaches in the back of his head that were more painful and associated with lightheadedness when laying down. Two weeks prior to presentation, he started noticing black spots in his peripheral vision and progressive blurring of vision in both eyes. The patient denied recent travel, cough, gastrointestinal or genitourinary tract symptoms, ulcers, aching joints, tinnitus, or transient visual obscurations. He reported owning cats.On presentation, the patient’s blood pressure was 210/150 mm Hg, and he had a history of acute kidney failure and non–ST-elevation myocardial infarction. On ophthalmic examination, his uncorrected near visual acuity was 20/25 OD and 20/30 OS. Extraocular motility, Ishihara color plates, intraocular pressure, pupils, and results of slitlamp examination were within normal limits. Ophthalmoscopy showed Frisen grade 5 optic nerve head swelling in both eyes with extensive flame hemorrhages and nerve fiber layer infarcts surrounding both nerves and retinal exudates extending from the nerves temporally into both fovea’s (Figure 1). The vessels were of normal course and caliber. There were scattered peripheral dot-and-blot hemorrhages. Results of Humphrey visual field testing were reliable and showed bilateral concentric constriction and enlarged blind spots.Grade 5 optic nerve head edema. A, Fundus photograph of the right eye shows Frisen grade 5 optic disc edema, flame hemorrhages, and peripapillary exudation into the macula. B, Fluorescein angiogram of the right eye in the early venous phase shows blockage from flame hemorrhages, peripapillary microaneurysms, leakage from optic disc capillaries, and absence of vascular leakage at arcades.Control the systemic blood pressure and workup underlying possible cause of the hypertensionPerform magnetic resonance imaging and magnetic resonance venogram of the brain and orbits, then perform lumbar puncture

what would you do next?

What would you do next?

Perform blood tests for neuroretinitis

Control the systemic blood pressure and workup underlying possible cause of the hypertension

All of the above

Perform magnetic resonance imaging and magnetic resonance venogram of the brain and orbits, then perform lumbar puncture

c

male

21-30

African American

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2717998

A white woman in her 70s with advanced Alzheimer disease was referred to the hematology clinic for evaluation of a high hemoglobin level (169 g/L; normal range, 120-160 g/L) and red blood cell count (5.67 × 1012/L; normal range, 3.8-4.8 × 1012/L) as well as a generalized itch that was worse after a bath. On examination, she had a florid, erythematous macular eruption over the trunk and limbs (Figure, A) but no hepatosplenomegaly or lymphadenopathy. In addition to the high hemoglobin level, mild lymphocytosis (absolute lymphocyte count, 6.2 × 109/L, range 1.5-4.0 × 109/L) was noted with the lymphocyte morphology, suggesting reactive changes. Skin biopsy specimen (Figure, B) showed a normal epidermis with a pericapillary infiltrate of small lymphocytes restricted to the dermis and no leukocytoclastic vasculitis, fungal organisms, or dermal mucin. The absence of cellular atypia and epidermal involvement suggested a diagnosis of lupus, or gyrate or annular erythema, and the need for clinicopathological correlation.A, Photograph shows erythroderma. B, Skin biopsy specimen shows a pericapillary infiltrate of small lymphoid cells restricted to the dermis (hematoxylin-eosin, original magnification ×200). C, Blood smear shows a typical lymphocyte (May-Grünwald Giemsa stain, original magnification ×400).Treatment began with a topical emollient, steroid creams, and oral antihistamines. Skin biopsy was repeated 2 months after the original procedure owing to a suboptimal clinical response, but the histological appearances were unchanged. The hemoglobin level remained high, and the lymphocyte count had increased to 9.0 × 109/L (Figure, C). What Is Your Diagnosis?

T-cell prolymphocytic leukemia

Advanced cutaneous T-cell lymphoma/Sézary syndrome

Polycythemia rubra vera

Cutaneous lupus erythematosus

A. T-cell prolymphocytic leukemia

A

T-cell prolymphocytic leukemia

The blood smear test showed an excess of medium-sized lymphocytes, each with a round to oval nucleus, basophilic cytoplasm, and prominent nucleolus (Figure, C), which typify prolymphocytes. Immunophenotyping identified the expression of CD4 on lymphocytes along with the pan–T-cell antigens CD2, CD3, CD5, and CD7, but no CD8, B-cell, or natural killer cell markers, supporting a diagnosis of T-cell prolymphocytic leukemia (T-PLL).T-cell prolymphocytic leukemia, a rare lymphoid malignancy affecting older people (median age, 61 years) can be misdiagnosed as an alternative mature T-cell neoplasm or even a benign disorder, particularly in patients with an atypical presentation.1 Common features of T-PLL include a high white blood cell count, bone marrow failure, and splenomegaly or lymphadenopathy, but the presence of pseudopolycythemia, mild lymphocytosis, erythroderma, and pruritus made advanced cutaneous T-cell lymphoma (CTCL)/Sézary syndrome a diagnostic consideration.1-3 However, the malignant cells characteristic of CTCL have a hyperconvulated, cerebriform nucleus, which distinguishes these cells from prolymphocytes. Moreover, the absence of epidermotropism and cellular atypia in the skin biopsy results are characteristic of T-PLL. The preservation of CD7 expression on circulating and dermal prolymphocytes further supports a diagnosis of T-PLL over CTCL or adult T-cell lymphocytic leukemia/lymphoma,2,3 an alternative possibility. The patient’s race, low expression intensity of CD25 on neoplastic cells, and the absence of eosinophilia also argue against adult T-cell lymphocytic leukemia/lymphoma.The important learning point here is that with no unique antigen expression profile (except in a quarter of cases that coexpress CD4 and CD8), the morphological recognition of circulating prolymphocytes is key to diagnosing T-PLL.1 Thus, a failure to integrate the skin biopsy findings with blood cytomorphology could have easily become a diagnostic pitfall, particularly because the cytogenetic analysis was normal and noncontributory to the diagnosis. Fluorescence in situ hybridization probes failed to detect inversion in chromosome 14 (q11.2q32.1), the most frequent chromosomal abnormality in T-PLL that is associated with TCL1 overexpression.1-4 Nevertheless, TCRB and TCRG gene rearrangements confirmed the T-cell population to be clonal. Additional learning points relate to the original reason for referral to hematology: the patient was suspected to have polycythemia rubra vera (PRV) owing to a high hemoglobin level and itch, but patients with PRV generally do not have a rash.5 It is likely that fluid loss due to erythroderma caused pseudopolycythemia in the patient; indeed, the Janus kinase (JAK) 2 analysis was negative for mutations frequently found in PRV.6,7 Cutaneous lupus erythematosus was unlikely because parts of the body exposed to the sun were spared, and typical histological features (lymphoid involvement of the dermoepidermal junction, epithelial layer degeneration, or dermal mucin deposits) were absent,8 as were serum autoantibodies commonly associated with connective tissue disorders.Most patients with T-PLL require antileukemic therapy at presentation. Conventional chemotherapy and steroids have limited efficacy, but the anti-CD52 monoclonal antibody alemtuzumab can achieve responses rates of 70% to 90% when administered intravenously.1,2 The disease response to alemtuzumab is of prognostic significance and supersedes the use of pretreatment variables, including total white blood cell count, lymphocyte doubling time, and TCL1 expression intensity, as an important determinant of survival.1 However, responses are frequently not durable, and to optimize outcomes in eligible patients, consolidative treatment with an autologous or allogeneic stem cell transplant requires consideration.1,2 Recent reports have indicated the effectiveness of the B–cell lymphoma 2 antagonist venetoclax9 and JAK3 inhibitors10 (following identification of JAK/signal transducer and activator of transcription [STAT] pathway mutations) in T-PLL, but the optimal positioning of newer drugs in the treatment algorithms requires investigation.2The patient’s advanced cognitive impairment precluded a trial of alemtuzumab therapy, and management focused exclusively on symptom palliation. Eight months after the initial clinic visit, she presented with right-sided periorbital swelling owing to abnormal growth of soft tissue in the temporal and zygomatic region that was compressing the eyeball and worsening lymphocytosis (absolute lymphocyte count, 13 × 109/L). Disease progression was rapid, and she died.

Oncology

A white woman in her 70s with advanced Alzheimer disease was referred to the hematology clinic for evaluation of a high hemoglobin level (169 g/L; normal range, 120-160 g/L) and red blood cell count (5.67 × 1012/L; normal range, 3.8-4.8 × 1012/L) as well as a generalized itch that was worse after a bath. On examination, she had a florid, erythematous macular eruption over the trunk and limbs (Figure, A) but no hepatosplenomegaly or lymphadenopathy. In addition to the high hemoglobin level, mild lymphocytosis (absolute lymphocyte count, 6.2 × 109/L, range 1.5-4.0 × 109/L) was noted with the lymphocyte morphology, suggesting reactive changes. Skin biopsy specimen (Figure, B) showed a normal epidermis with a pericapillary infiltrate of small lymphocytes restricted to the dermis and no leukocytoclastic vasculitis, fungal organisms, or dermal mucin. The absence of cellular atypia and epidermal involvement suggested a diagnosis of lupus, or gyrate or annular erythema, and the need for clinicopathological correlation.A, Photograph shows erythroderma. B, Skin biopsy specimen shows a pericapillary infiltrate of small lymphoid cells restricted to the dermis (hematoxylin-eosin, original magnification ×200). C, Blood smear shows a typical lymphocyte (May-Grünwald Giemsa stain, original magnification ×400).Treatment began with a topical emollient, steroid creams, and oral antihistamines. Skin biopsy was repeated 2 months after the original procedure owing to a suboptimal clinical response, but the histological appearances were unchanged. The hemoglobin level remained high, and the lymphocyte count had increased to 9.0 × 109/L (Figure, C).

what is your diagnosis?

What is your diagnosis?

Cutaneous lupus erythematosus

Advanced cutaneous T-cell lymphoma/Sézary syndrome

T-cell prolymphocytic leukemia

Polycythemia rubra vera

c

female

71-80

White

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2718495

A man in his early 40s was admitted to the hospital because of acute chest pain. Laboratory test results were notable for high serum concentrations of IgG4 (5650 mg/dL; to convert to grams per liter, multiply by 0.01) and C-reactive protein (78.1 mg/L; to convert to nanomoles per liter, multiply by 9.524). Coronary computed tomographic angiography was performed (Figure, A and B). It revealed a large aneurysm (90 mm × 48 mm) with a thrombosis in the left anterior descending artery (LAD) and a perivascular soft-tissue mass involving the patent proximal right coronary artery (RCA) and left circumflex artery, which showed homogeneous moderate enhancement on contrast-enhanced images. Coronary computed tomographic angiography with cinematic rendering (Figure, C) showed multiple mass lesions around the RCA and LAD. Invasive coronary angiography results were unable to visualize the LAD but did identify a hypervascular mass in the proximal RCA.A, Contrast-enhanced axial computed tomographic image revealing perivascular soft-tissue masses involving the left circumflex and right coronary arteries (arrowheads). B, Maximum intensity projection reformatted image of coronary computed tomographic angiography revealing perivascular soft-tissue masses involving the left circumflex and right coronary arteries (arrowheads) and a large aneurysm with a thrombus involving the left anterior descending artery (asterisk). C, A 3-dimensional rendering demonstrated mass lesions involving the left anterior descending and right coronary arteries (arrowheads). What Would You Do Next?

High-dose corticosteroid therapy

High-dose immunosuppressant therapy

Percutaneous coronary intervention

Coronary artery bypass graft surgery

IgG4-associated coronary artery aneurysms

D

Coronary artery bypass graft surgery

A unique immune-mediated fibroinflammatory disorder, IgG4-related disease is characterized by elevated serum IgG4 levels and tumefied lesions that may concurrently or consecutively affect a wide variety of organs.1-3 It is most common in middle-aged or elderly men. Diagnosis of IgG4-related disease is based on histological findings that show IgG4-positive plasma cell and lymphocytic infiltration, fibrosis with storiform features, and obliterative phlebitis. Elevated serum IgG4 levels also indicate IgG4-related disease.Cases of IgG4-associated coronary artery involvement have rarely been reported. They can result in ischemic heart disease, as in this case, or sudden cardiac death. Because IgG4-associated coronary inflammation occurs in the adventitia, it can result in inflammatory pseudotumor, perivascular fibrosclerotic thickening, luminal stenosis, and aneurysmal dilatation. The typical mistletoe sign in coronary computed tomographic angiography is indicative of the diagnosis of IgG4-associated coronary artery disease,4 as this case shows. Positron emission tomography and computed tomography are also useful in evaluation and follow-up of IgG4-related disease with coronary artery involvement; these can show hypermetabolic coronary artery masses and identify alternative biopsy sites.5The optimal therapeutic approach for IgG4-related disease with coronary artery involvement is unclear. Steroid therapy is regarded as a first-line treatment that can prevent the further development of active inflammatory disease by suppressing lymphocyte activation to reduce inflammation.1-3 However, already existing lesions usually do not recover completely.1-3 Thus, surgical intervention is needed in some patients.The patient underwent coronary artery bypass graft surgery. Intraoperative findings included multiple coronary pseudoaneurysms with thrombosis. Pathological examinations of the mass resected from the LAD confirmed the diagnosis of IgG4-related disease. The patient was discharged with full symptomatic relief. A second coronary computed tomographic angiography 1 year later showed that 3 coronary bypass grafts were patent and the proximal native RCA was completely obstructed. No major adverse cardiac events were reported during the 1-year follow-up examination.

Cardiology

A man in his early 40s was admitted to the hospital because of acute chest pain. Laboratory test results were notable for high serum concentrations of IgG4 (5650 mg/dL; to convert to grams per liter, multiply by 0.01) and C-reactive protein (78.1 mg/L; to convert to nanomoles per liter, multiply by 9.524). Coronary computed tomographic angiography was performed (Figure, A and B). It revealed a large aneurysm (90 mm × 48 mm) with a thrombosis in the left anterior descending artery (LAD) and a perivascular soft-tissue mass involving the patent proximal right coronary artery (RCA) and left circumflex artery, which showed homogeneous moderate enhancement on contrast-enhanced images. Coronary computed tomographic angiography with cinematic rendering (Figure, C) showed multiple mass lesions around the RCA and LAD. Invasive coronary angiography results were unable to visualize the LAD but did identify a hypervascular mass in the proximal RCA.A, Contrast-enhanced axial computed tomographic image revealing perivascular soft-tissue masses involving the left circumflex and right coronary arteries (arrowheads). B, Maximum intensity projection reformatted image of coronary computed tomographic angiography revealing perivascular soft-tissue masses involving the left circumflex and right coronary arteries (arrowheads) and a large aneurysm with a thrombus involving the left anterior descending artery (asterisk). C, A 3-dimensional rendering demonstrated mass lesions involving the left anterior descending and right coronary arteries (arrowheads).

what would you do next?

What would you do next?

High-dose corticosteroid therapy

High-dose immunosuppressant therapy

Percutaneous coronary intervention

Coronary artery bypass graft surgery

d

male

41-50

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2724226

A 53-year-old African American man with a history of bipolar disorder presented to the emergency department with an enlarging right-sided tongue mass that had caused mild discomfort and halitosis over the course of 1 week. He denied recent injury, fever, chills, odynophagia, or difficulty breathing. Laboratory examination was significant for leukocytosis (white blood cell count, 15 700/μL) and hypercalcemia (total calcium level, 13.1 mg/dL) (to convert white blood cells to ×109 per liter, multiply by 0.001; to convert calcium to millimoles per liter, multiply by 0.25). Physical examination was notable for a 4- to 5-cm pedunculated, ulcerative mass on the dorsal oral aspect of the tongue near midline, anterior to the foramen cecum, without palpable cervical lymphadenopathy. Contrast-enhanced computed tomography (CT) demonstrated a rim-enhancing, centrally hypodense lesion in the right dorsal tongue abutting the lingual septum with a somewhat ill-defined border (Figure 1); there was no associated osseous erosion of the mandible or hard palate, no tongue prolapse to suggest hypoglossal nerve palsy, no involvement of the soft palate, and no cervical lymphadenopathy by radiological size criteria. An excisional biopsy of the anterior aspect of the mass was performed at bedside, and the patient was discharged home with instructions to follow up in the otolaryngology clinic.A, Sagittal contrast-enhanced computed tomography (CT) demonstrates an exophytic mass on the dorsal aspect of the tongue. B, Axial contrast-enhanced CT demonstrates a peripherally enhancing mass of the oral tongue, to the right of midline. What Is Your Diagnosis?

Squamous cell carcinoma

Oral eosinophilic ulcer

Abscess

Pleomorphic rhabdomyosarcoma

D. Pleomorphic rhabdomyosarcoma

D

Pleomorphic rhabdomyosarcoma

Fluorodeoxyglucose F18–labeled positron-emission tomography demonstrated the lesion to be intensely avid (standardized uptake value, 16.4) (Figure 2).A, Axial attenuation-corrected fluorodeoxyglucose F18 (FDG)-labeled positron-emission tomography single-photon emission computed tomography image after the administration of 12.1 mCi of FDG demonstrates an intensely avid oral tongue mass (standardized uptake value, 16.4); heterogeneity of activity suggests areas of necrosis. B, Fused image illustrates anatomical overlap between the region of uptake and rim-enhancing lesion seen on computed tomography.Rhabdomyosarcoma (RMS) is an aggressive cancer of mesenchymal origin, most common in the pediatric population, with 35% occurring in the head and neck region1; the tongue is an uncommon site of involvement. World Health Organization classification of RMS is based on histologic findings and includes 4 groups: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing.2 Pleomorphic RMS is rare and is seen almost exclusively in adults.3 Wide surgical resection is the mainstay of treatment for localized pleomorphic RMS, followed by postoperative radiotherapy because this RMS subtype is sometimes regarded as chemoresistant.2,4 In patients with metastatic disease, palliative radiation therapy and chemotherapy may be attempted.2 Pleomorphic RMS heralds poor prognosis by virtue of its histologic characteristics as well as the affected age group.4 Overall survival rates in the adult population with RMS of all sites and all histologic traits range from 40% to 54% at 5 years.5In the present case, a partial glossectomy was performed, and the mass was excised with 1.5-cm circumferential margins, followed by bilateral selective neck dissection of cervical chain nodal levels I through IV. The tongue was reconstructed using local tissue rearrangement rather than flap reconstruction, given the size of the defect and the intact tongue base. The definitive diagnosis of pleomorphic RMS (negative for FOX01 rearrangement) was rendered on pathologic examination, with a pathologic stage classification of pT3N0. Although the hypercalcemia was initially attributed to the RMS, the patient was subsequently found to have an atypical parathyroid adenoma, which was also excised.The imaging-based differential diagnosis of pleomorphic RMS of the tongue includes squamous cell carcinoma (SCC), traumatic ulcerative granuloma with stromal eosinophilia, and infectious ulcer, in addition to infected dermoid (if the lesion is midline) or venous malformation (if there are phleboliths). Squamous cell carcinoma represents more than 90% of oral cavity cancers and arises from squamous epithelial cells of the oral tongue. When centrally necrotic, SCC presents as a peripherally enhancing lesion with central hypoattenuation. However, given the thickness of the lesion in the present case, one would expect that there would be metastatic cervical lymphadenopathy.6 Moreover, the patient had none of the risk factors commonly associated with the development of SCC, such as tobacco or alcohol use; infection with human immunodeficiency virus, Epstein-Barr virus, or human papilloma virus; familial history; or occupational exposure.7Traumatic ulcerative granuloma with stromal eosinophilia is a differential consideration, given the development of a solitary, ulcerated lesion on the dorsal tongue surface over a short period of time. The pathophysiology of this benign, self-limiting condition is poorly understood, but it is thought to be related to aberrant wound-healing and is of clinical importance because it can mimic malignant entities such as SCC or mucoepidermoid carcinoma.8 This entity is usually seen in individuals with a history of trauma or iatrogenic tongue injury and demonstrates rapid healing after incisional biopsy, presumably due to induction of normal healing pathways,9 features not present in the present case.Infectious ulcers of the oral tongue may be due to cytomegalovirus, tuberculosis, or fungal agents, and are suggested by details in the clinical history, such as immune status, travel history, or the presence of multisystem disease.10 The pedunculated and masslike appearance of the present lesion make infectious ulcer less likely.

General

A 53-year-old African American man with a history of bipolar disorder presented to the emergency department with an enlarging right-sided tongue mass that had caused mild discomfort and halitosis over the course of 1 week. He denied recent injury, fever, chills, odynophagia, or difficulty breathing. Laboratory examination was significant for leukocytosis (white blood cell count, 15 700/μL) and hypercalcemia (total calcium level, 13.1 mg/dL) (to convert white blood cells to ×109 per liter, multiply by 0.001; to convert calcium to millimoles per liter, multiply by 0.25). Physical examination was notable for a 4- to 5-cm pedunculated, ulcerative mass on the dorsal oral aspect of the tongue near midline, anterior to the foramen cecum, without palpable cervical lymphadenopathy. Contrast-enhanced computed tomography (CT) demonstrated a rim-enhancing, centrally hypodense lesion in the right dorsal tongue abutting the lingual septum with a somewhat ill-defined border (Figure 1); there was no associated osseous erosion of the mandible or hard palate, no tongue prolapse to suggest hypoglossal nerve palsy, no involvement of the soft palate, and no cervical lymphadenopathy by radiological size criteria. An excisional biopsy of the anterior aspect of the mass was performed at bedside, and the patient was discharged home with instructions to follow up in the otolaryngology clinic.A, Sagittal contrast-enhanced computed tomography (CT) demonstrates an exophytic mass on the dorsal aspect of the tongue. B, Axial contrast-enhanced CT demonstrates a peripherally enhancing mass of the oral tongue, to the right of midline.

what is your diagnosis?

What is your diagnosis?

Pleomorphic rhabdomyosarcoma

Squamous cell carcinoma

Oral eosinophilic ulcer

Abscess

a

male

51-60

African American

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2725435

A 17-year-old girl with a history of chronic sinusitis presented with left-sided epiphora, purulent drainage, and pain and right-sided jaw pain. She had previously been treated with antibiotics and mupirocin nasal irrigation, with temporary improvement. The patient and her identical twin sister had required multiple surgical procedures in the past for osseous lesions in the upper and lower jaws, including an aggressive resection via bilateral Caldwell-Luc approach 2 years previously; a computed tomographic scan from that initial presentation is shown in the Figure, A. At the current presentation, examination using flexible nasal endoscopy revealed bulging of the left lateral nasal wall; imaging revealed a 14-mm, dense, expansile, sclerotic mass with moderate calcifications obstructing the left nasolacrimal duct; a similar 2.3 × 1.8–cm lesion of the right mandibular body; and evidence of previous sinus surgery (Figure, B). Because of these findings, left-sided endoscopic dacryocystorhinostomy and sinus surgery was performed. Histologic findings are shown in the Figure, C and D.A, Contrast-enhanced computed tomographic image at initial presentation. B, Non–contrast-enhanced computed tomographic image at 2 years after bilateral Caldwell-Luc resection showing mass in left nasolacrimal duct. C, Photomicrograph depicting a proliferation of highly cellular, fibrous connective tissue (arrow) and cementum-like hard tissue (arrowhead) (hematoxylin-eosin, original magnification ×100). D, Photomicrograph showing whorls of spindle cells (arrow) with relatively acellular calcified masses of cemento-osseous material (arrowhead) (hematoxylin-eosin, original magnification ×200). What Is Your Diagnosis?

Albers-Schönberg disease

Gigantiform cementoma

Fibrous dysplasia

Polyostotic ossifying fibroma