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JAMA_Chen2024

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https://jamanetwork.com/journals/jama/fullarticle/2320293

A 44-year-old man with a history of gastroesophageal reflux disease and anxiety presents for evaluation of mouth ulcers recurring for the past 2 years. The painful ulcers resolve within 2 weeks but recur on different mucosal surfaces. He denies new medications, foods, or oral hygiene products and involvement of cutaneous or other mucosal surfaces. He is uncertain whether he has a family history of oral ulcers. He was previously prescribed anesthetic rinses and fluconazole, without benefit. His current medications include omeprazole and lorazepam. Intraoral examination demonstrates an ulcer with a pseudomembrane and erythematous halo on the left lateral surface of the tongue (Figure). Physical examination results are otherwise normal.Round, symmetric ulcer, measuring approximately 8 mm × 8 mm, with pseudomembrane and erythematous halo on the left lateral surface of the tongue.Prescribe valacyclovir (1000 mg) 3 times daily for the next 7 daysOrder a complete blood cell count with differential to rule out a hematologic disorderPrescribe amoxicillin (500 mg) 3 times daily for the next 7 days What Would You Do Next?

Obtain a biopsy of the ulcer

Prescribe valacyclovir (1000 mg) 3 times daily for the next 7 days

Order a complete blood cell count with differential to rule out a hematologic disorder

Prescribe amoxicillin (500 mg) 3 times daily for the next 7 days

Aphthous stomatitis

C

Order a complete blood cell count with differential to rule out a hematologic disorder

The key to the correct diagnosis of aphthous stomatitis is the appearance of round, symmetric ulcers with an erythematous halo and pseudomembrane, healing within 2 weeks, and the recurrent nature of the ulcers.Recurrent aphthous stomatitis (RAS) is a common oral disease with onset typically in early adolescence and an estimated prevalence of 1.5% in children and adolescents and 0.85% in adults in the United States.1 Family history is the most consistent factor associated with RAS.2 Additional factors associated with the disease include nutritional deficiencies, stress, and systemic diseases.3,4For this case presentation, a biopsy is not indicated because of the appearance of the ulcer and the clinical history. Viral infections, bacterial infections, or both are typically not etiologic factors for RAS; therefore, antiviral and antibiotic therapies are not appropriate. Because of the patient’s age and frequency of ulcers, testing should be considered to rule out an underlying hematologic or nutritional disorder.5,6Classification of RAS is based on ulcer size, location, and healing pattern. Minor RAS (>85% of cases) is characterized by symmetric lesions less than 1 cm in diameter on nonkeratinized mucosa and healing within 2 weeks without scarring.3,7 Ulcers associated with RAS typically have an erythematous halo with a pseudomembrane (thin, adherent gray-white exudative layer primarily composed of necrotic epithelium, fibrin, and neutrophils). Major RAS is characterized by ulcers larger than 1 cm on nonkeratinized or keratinized mucosa, healing requiring more than 2 weeks with scarring, and ulcers that may appear asymmetric.3,7 Herpetiform RAS, which appears as clusters of mucosal ulcers, is rare and may be confused with recurrent intraoral herpes.3,7Diagnosis of RAS is usually based on clinical history and presentation.3,7 Family history of RAS is an important clue to the diagnosis. Positive responses in a review of systems may identify underlying systemic disease, including Behçet disease, inflammatory bowel disease, and celiac disease, as the potential etiology.3,7 Most cases are idiopathic, with disease activity diminishing after the teenage years. Suspicion for an underlying medical disorder increases when frequency and severity of RAS escalate with advancing age.3,7 Prior studies demonstrate an association of RAS with anemia and with iron, folate, and vitamin B12 deficiencies. In some patients, an evaluation for these disorders may be appropriate.5,6Management of RAS is determined by symptoms and by frequency, location, and duration of ulcers.3,7 Lifestyle counseling may be appropriate if RAS is associated with stress or nutritional deficiencies. Amlexanox (5%) is a topical anti-inflammatory paste approved by the US Food and Drug Administration (FDA) for treatment of RAS and is applied 4 times daily for up to 10 days.7 Topical corticosteroids are commonly used to treat RAS, but their use is based primarily on empirical evidence.8 Triamcinolone acetonide paste (0.1%) applied 2 to 3 times daily is FDA approved for treatment of RAS, whereas higher-potency corticosteroids commonly used for treatment, such as fluocinonide gel (0.05%), clobetasol gel (0.05%), and dexamethasone solution (0.5 mg/5 mL) applied 2 to 3 times daily, are not FDA approved.7 Topical corticosteroids are often coadministered with a topical antifungal agent, such as nystatin rinses (100 000 U/mL, 5 mL, 3 times daily) or clotrimazole troches (10 mg, 3 times daily) to prevent secondary candidiasis.3,7 Limited evidence suggests that over-the-counter antimicrobial rinses may reduce duration and severity of aphthous ulcers.9 For severe RAS, systemic therapies may be considered, such as a tapering dose of corticosteroids for acute episodes and off-label use of pentoxifylline, colchicine, or thalidomide.3,7,10 Individuals using systemic medications should be appropriately monitored.Complete blood cell count with differential, iron, folate, and vitamin B12 assays were obtained, with normal results. The patient uses dexamethasone rinse (0.5 mg/5 mL, 10 mL, 3 times daily), fluocinonide gel (0.05%, twice daily), and clotrimazole troches (10 mg, 3 times daily) concurrently for symptomatic episodes of RAS, with substantial benefit.

General

A 44-year-old man with a history of gastroesophageal reflux disease and anxiety presents for evaluation of mouth ulcers recurring for the past 2 years. The painful ulcers resolve within 2 weeks but recur on different mucosal surfaces. He denies new medications, foods, or oral hygiene products and involvement of cutaneous or other mucosal surfaces. He is uncertain whether he has a family history of oral ulcers. He was previously prescribed anesthetic rinses and fluconazole, without benefit. His current medications include omeprazole and lorazepam. Intraoral examination demonstrates an ulcer with a pseudomembrane and erythematous halo on the left lateral surface of the tongue (Figure). Physical examination results are otherwise normal.Round, symmetric ulcer, measuring approximately 8 mm × 8 mm, with pseudomembrane and erythematous halo on the left lateral surface of the tongue.Prescribe valacyclovir (1000 mg) 3 times daily for the next 7 daysOrder a complete blood cell count with differential to rule out a hematologic disorderPrescribe amoxicillin (500 mg) 3 times daily for the next 7 days

what would you do next?

What would you do next?

Prescribe valacyclovir (1000 mg) 3 times daily for the next 7 days

Obtain a biopsy of the ulcer

Order a complete blood cell count with differential to rule out a hematologic disorder

Prescribe amoxicillin (500 mg) 3 times daily for the next 7 days

c

male

41-50

original

https://jamanetwork.com/journals/jama/fullarticle/2319148

A 67-year-old man with a 45-pack-year smoking history presented with worsening dyspnea. His resting oxygen saturation was 94%, declining to 86% after walking for 60 meters. A pulmonary examination revealed inspiratory crackles at the bases and diminished breath sounds at the apices. A cardiovascular examination showed normal results, without peripheral edema. A chest x-ray showed hyperinflation and increased interstitial markings. Pulmonary function tests were obtained (Table; Figure).Spirometry cannot be used to evaluate for obstruction in the setting of a restrictive abnormality How Do You Interpret These Test Results?

Primarily restrictive abnormality

Obstructive abnormality with pseudorestriction

Mixed obstructive and restrictive abnormality

Spirometry cannot be used to evaluate for obstruction in the setting of a restrictive abnormality

C

Mixed obstructive and restrictive abnormality

Pulmonary function tests are essential for diagnosing and assessing severity of many pulmonary disorders (eTable in the Supplement). Spirometry measures forced vital capacity (FVC; the total exhaled volume) and the forced expiratory volume in the first second of expiration (FEV1) during a rapid and complete exhalation after maximal inspiration.1A reduced FEV1/FVC ratio indicates airflow obstruction, while a normal ratio suggests normal spirometry or restrictive impairment. Mild airflow obstruction may exist with a normal FEV1/FVC ratio and is suggested by diminished forced expiratory flow (FEF25%-75%) in the middle half of the FVC and concave shape of the expiratory limb of the flow-volume loop (FVL).2 Restriction is suggested by reduced FVC and FEV1 with a normal or elevated FEV1/FVC ratio, but must be confirmed by measuring lung volumes. Bronchodilator testing compares spirometry before and after an inhaled short-acting bronchodilator. Complete reversibility of airflow obstruction after bronchodilator inhalation suggests asthma rather than chronic obstructive pulmonary disease, although a lack of response does not exclude asthma or exclude benefit from bronchodilator therapy.2 An FVL is a graphical representation of flow rate vs volume during a maximal exhalation and inhalation. FVL patterns can suggest poor-quality spirometry, restriction, diffuse airflow obstruction, or a central airway–obstructing lesion (see examples2).Lung volume measurements, ideally obtained by plethysmography, estimate the volume of the lungs at maximal inhalation (total lung capacity [TLC]), relaxed exhalation (functional residual capacity [FRC]), and maximal exhalation (residual volume [RV]).3 A low TLC indicates restriction, while elevation of TLC and RV suggest hyperinflation and air trapping respectively, indicating obstruction. Pseudorestriction is defined as an elevated RV due to prominent air trapping with a normal or slightly increased TLC, thereby reducing the FVC.The carbon monoxide diffusing capacity (DLCO), measured using a test gas with a small amount of carbon monoxide, reflects the ability of the lungs to exchange gas into the bloodstream; it is diminished in emphysema, interstitial lung disease, pulmonary vascular disease, and anemia.4 Dividing the DLCO by the alveolar volume (VA) attempts to distinguish between a low DLCO due to abnormal gas exchange and a low DLCO due to reduced lung volume, although this is not a perfect correction.5 Medicare reimbursement ranges from $36.18 for spirometry to $168.73 for complete pulmonary function testing (eTable in the Supplement).6Pulmonary function test results depend on patient effort. Normal ranges are related to the patient’s sex, age, race, and body size. Interpretation requires patient-appropriate reference equations that allow calculation of individualized predicted values and lower limits of normal.2 Although an FEV1/FVC ratio (<0.70) has been used to define airflow limitation,7 the ratio declines with age and current recommendations favor defining a low ratio as below the lower limit of normal.2The FVL demonstrates a smooth expiratory flow, which suggests good patient effort. The concave upward expiratory limb suggests obstructive lung disease but does not exclude coexisting restriction. The patient’s FEV1/FVC ratio is below the lower limit of normal. When airflow obstruction is present, severity is graded by FEV1 as a percentage of the predicted value. This patient’s FEV1 of 62% indicates moderate airflow obstruction.2Along with a reduced FEV1/FVC ratio, the patient has a FVC below the lower limit of normal, suggesting either a mixed obstructive and restrictive deficit or pseudorestriction. The patient described in this article has a TLC below the lower limit of normal, indicating true restriction.The cause of a reduced DLCO is best determined together with spirometry and lung volume measurement. This patient’s severely reduced DLCO, and DLCO/VA, accompanied by airflow obstruction (suggesting emphysema) and restriction (suggesting interstitial lung disease), suggests a combination of these processes.Pulmonary function testing is the criterion standard for diagnosing obstructive and restrictive abnormalities. Gas exchange can be investigated with oximetry testing and arterial blood gas analysis; however, diffusing capacity detects more subtle changes.Computed tomographic imaging confirmed emphysema and interstitial fibrosis, consistent with the pulmonary function tests. Ultimately, idiopathic pulmonary fibrosis was diagnosed. Catheterization of the right heart showed pulmonary hypertension, a likely contributor to the reduced DLCO. The patient was offered evaluation for lung transplantation.Pulmonary function tests are interpreted using published reference formulas based on a patient’s age, sex, race, and anthropomorphic characteristics.Spirometry may demonstrate airflow obstruction and may suggest restrictive ventilatory impairment. Lung volumes confirm and quantify physiologic abnormalities.Reduced gas exchange (DLCO) is nonspecific and may indicate parenchymal lung disease, pulmonary vascular disease, or anemia.

Diagnostic

A 67-year-old man with a 45-pack-year smoking history presented with worsening dyspnea. His resting oxygen saturation was 94%, declining to 86% after walking for 60 meters. A pulmonary examination revealed inspiratory crackles at the bases and diminished breath sounds at the apices. A cardiovascular examination showed normal results, without peripheral edema. A chest x-ray showed hyperinflation and increased interstitial markings. Pulmonary function tests were obtained (Table; Figure).Spirometry cannot be used to evaluate for obstruction in the setting of a restrictive abnormality

how do you interpret these test results?

How do you interpret these results?

Primarily restrictive abnormality

Obstructive abnormality with pseudorestriction

Mixed obstructive and restrictive abnormality

Spirometry cannot be used to evaluate for obstruction in the setting of a restrictive abnormality

c

male

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2300573

A 36-year-old woman reported experiencing shortness of breath for 1 month. She reported a 6.3-kg weight loss, tremor, diaphoresis, and palpitations over the course of 2 months. She denied eye symptoms or muscle weakness. Physical examination revealed tachycardia, tongue and hand tremors, no exophthalmos, a 2-fold diffusely enlarged thyroid gland, and brisk reflexes.Laboratory results showed a thyroid-stimulating hormone (TSH) level of 0.005 mIU/L (normal, 0.45-4.50 mIU/L), free thyroxine level greater than 7.77 ng/dL (100.01 pmol/L) (normal, 0.82-1.77 ng/dL [10.55-22.78 pmol/L]), free triiodothyronine level of 30.6 pg/mL (47.1 pmol/L) (normal, 2.0-3.9 pg/mL [3.08-6.01 pmol/L]), and thyroid-stimulating immunoglobulin index of 5.5 (normal, <1.3). The patient began treatment with methimazole, 20 mg twice daily.A noncontrast computed tomography (CT) scan of the chest (Figure, left) and an 18F-fludeoxyglucose–positron emission tomography (FDG-PET)/CT scan (Figure, right) were completed to evaluate her dyspnea.Left, Noncontrast computed tomography (CT) scan of the upper chest shown in cross section. Right, 18F-fludeoxyglucose-positron emission tomography/CT scan of the whole body. Note the increased uptake in the thymus indicating increased metabolic activity. Refer to surgery for removal of the thymusDo nothing now but repeat CT scan in 3 to 6 months What Would You Do Next?

Refer to medical oncology

Perform biopsy of the thymus

Refer to surgery for removal of the thymus

Do nothing now but repeat CT scan in 3 to 6 months

Thymic hyperplasia complicating Graves disease

D

Do nothing now but repeat CT scan in 3 to 6 months

D. Do nothing now but repeat CT scan in 3 to 6 monthsThis patient presented with symptoms, signs, and laboratory test results typical of Graves disease. A CT scan showed a diffusely enlarged thymus, and FDG-PET/CT imaging revealed hypermetabolic thymic enlargement.Thymic enlargement has a broad differential diagnosis that includes thymoma, thymic carcinoma, lymphoma, thymolipoma, carcinoid, thymic hyperplasia, ectopic thyroid tissue, and germ cell tumors. The most common cause of thymic enlargement in Graves disease is thymic hyperplasia. This phenomenon was first described more than 100 years ago.1 In most cases, the thymic lesion is an incidental finding during the evaluation of other symptoms, eg, dyspnea. Therefore, the true prevalence of thymic lesions in patients with Graves disease remains unknown.Pathologically, 2 distinct features are seen in the thymus in Graves disease: lymphoid hyperplasia and true thymic hyperplasia.2 With lymphoid hyperplasia, there is an increased number of medullary lymphoid follicles, which can lead to disorganized thymic structure. In true thymic hyperplasia, the thymic structure is preserved. In both conditions, the thymus gland appears diffusely enlarged. Previous studies have suggested that there may be different mechanisms underlying these 2 distinct pathologies, such that thymic cortical hyperplasia is associated with the hyperthyroid state while lymphoid hyperplasia is likely related to immune abnormalities.2 Recently, angiogenesis has been implicated in the pathogenesis of thymic hyperplasia in patients with Graves disease.3In rats, administration of thyroid hormone causes thymic enlargement, and thyroidectomy induces a decrease in thymus size.4,5 However, thyroid-stimulating immunoglobulin from patients with Graves disease directly binds to thymocytes and stimulates thymocyte proliferation.6 This information, along with the fact that TSH receptors (to which the thyroid-stimulating immunoglobulin binds) are present in human thymus,7 is compatible with an autoimmune-mediated mechanism for thymic hyperplasia.On cross-sectional CT images, normal thymus glands in adults are of low intensity compared with muscle. Thymic hyperplasia, on the other hand, is usually isointense with smooth borders on precontrast scans and enhances homogeneously after administration of intravenous contrast.5 Lobulated thymic enlargement and invasion of adjacent tissues indicate malignancy. However, absence of these features does not rule out malignancy. Thymoma, an epithelial neoplasm of the thymus, is often associated with myasthenia gravis. People with Graves disease have an increased prevalence of myasthenia gravis.8 Therefore, it is important to inquire about muscle symptoms. Muscle symptoms related to myasthenia gravis should be distinguished from thyrotoxic periodic paralysis. On PET/CT scans of patients with Graves disease, hypermetabolism can be seen in multiple tissues, including the thymus gland, psoas muscles, and thyroid gland.9Treatment of Graves disease with antithyroid medications or thyroidectomy usually leads to involution of thymic hyperplasia.3,5,7,10 With improvement of Graves disease, there is a decrease in signal density of thymus on CT scan. The time to involution varies from 8 weeks (after thyroidectomy) to 4 to 25 months (after antithyroid medication).5,10 In a recent report, 4 cases of malignancy were confirmed among 107 cases of thymic enlargement in Graves disease, including 3 cases of thymoma and 1 case of T lymphoblastic leukemia/lymphoma. Therefore, it is reasonable to ensure involution of the thymus by repeat imaging once hyperthyroidism has been treated.3The patient developed severe neutropenia while receiving methimazole. Methimazole was discontinued and radioactive iodine ablation was performed. Three months later, most of the patient’s symptoms resolved, her thyroid function had normalized, and a repeat CT scan showed at least 25% reduction in the thymus size, from 4.9 cm × 2.4 cm to 3.9 cm × 2.4 cm.Because of the overwhelming likelihood that the diagnosis in this patient with Graves disease is thymic hyperplasia, this noninvasive management strategy, without biopsy, removal of the thymus, or referral to an oncologist, is appropriate. However, since the thymus is still enlarged, follow-up imaging is warranted.

General

A 36-year-old woman reported experiencing shortness of breath for 1 month. She reported a 6.3-kg weight loss, tremor, diaphoresis, and palpitations over the course of 2 months. She denied eye symptoms or muscle weakness. Physical examination revealed tachycardia, tongue and hand tremors, no exophthalmos, a 2-fold diffusely enlarged thyroid gland, and brisk reflexes.Laboratory results showed a thyroid-stimulating hormone (TSH) level of 0.005 mIU/L (normal, 0.45-4.50 mIU/L), free thyroxine level greater than 7.77 ng/dL (100.01 pmol/L) (normal, 0.82-1.77 ng/dL [10.55-22.78 pmol/L]), free triiodothyronine level of 30.6 pg/mL (47.1 pmol/L) (normal, 2.0-3.9 pg/mL [3.08-6.01 pmol/L]), and thyroid-stimulating immunoglobulin index of 5.5 (normal, <1.3). The patient began treatment with methimazole, 20 mg twice daily.A noncontrast computed tomography (CT) scan of the chest (Figure, left) and an 18F-fludeoxyglucose–positron emission tomography (FDG-PET)/CT scan (Figure, right) were completed to evaluate her dyspnea.Left, Noncontrast computed tomography (CT) scan of the upper chest shown in cross section. Right, 18F-fludeoxyglucose-positron emission tomography/CT scan of the whole body. Note the increased uptake in the thymus indicating increased metabolic activity. Refer to surgery for removal of the thymusDo nothing now but repeat CT scan in 3 to 6 months

what would you do next?

What would you do next?

Refer to surgery for removal of the thymus

Do nothing now but repeat CT scan in 3 to 6 months

Refer to medical oncology

Perform biopsy of the thymus

b

female

31-40

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2119343

A newborn girl with a nodular lesion on the scalp present since birth was seen at the dermatology clinic. The parents reported occasional erosions and crusting that resolved with topical mupirocin, 2%, cream, but with no continued growth. The mother had had a normal pregnancy. Physical examination revealed a firm, exophytic, and flat-topped nodule, with superficial erosion and crust on the right parietal side of the scalp measuring 3 cm in diameter and 1 cm thick (Figure, A). No other skin lesions were found. A 4-mm punch skin biopsy was performed, and tissue was sent for pathologic analysis (Figure, B and C). Cerebral and abdominal ultrasonography revealed no evidence of visceral involvement. The lesion regressed without treatment over a period of 8 months. Close follow-up every 3 months was scheduled, and complete involution of the tumor was noted at 10 months of age (Figure, D).A, Nodular lesion on the right parietal scalp at initial presentation. B, Histopathologic image of a biopsy specimen (hematoxylin-eosin, original magnification ×200). C, Immunohistochemical image of a biopsy specimen (actin stain, original magnification ×100). D, Complete regression of tumor at 10 months of age. What Is Your Diagnosis?

Giant cell fibroblastoma

Infantile myofibromatosis

Dermoid cyst

Keratoacanthoma

B. Infantile myofibromatosis

B

Infantile myofibromatosis

A biopsy specimen of the lesion showed an unencapsulated neoplastic proliferation of mesenchymal cells with peripheral myofibroblastic differentiation, fascicles of spindle cells, and central pericyte-like vascular areas consisting of less differentiated, rounder cells (Figure, B). Immunohistochemical analysis was positive for smooth muscle actin (Figure, C), particularly in areas of better differentiation, as well as CD-34 (strongest in less differentiated areas) and vimentin. Stain results for β-catenin and S-100 were negative. No visceral or intracranial involvement was found, and the lesion involuted without therapy by the age of 10 months.Williams and Schrum1 first described myofibromas in 1951, but the infantile form was further characterized later by Chung and Enzinger2 and called infantile myofibromatosis (IM). Infantile myofibromatosis, although rare, is the most common fibrous tumor of infancy.3 It may present as a solitary lesion of the skin, subcutaneous tissue, or muscle, or as a multicentric lesion in soft tissues and bone. The solitary form accounts for almost 75% of cases,4 and 37% of multicentric cases have visceral involvement, which can affect any organ, such as the lung and heart, but most frequently the gastrointestinal tract.4 Sporadic and familial cases have been reported.3 Genetic sequencing of familial cases suggest an autosomal dominant (AD) inheritance pattern and platelet-derived growth factor receptor-β (PDGFRB) mutations as common features; however, IM is a genetically heterogeneous disease with incomplete penetrance and variable expressivity.5 The same authors5 also identified a single family with an AD form of IM with a germline NOTCH3 mutation.Infantile myofibromatosis typically presents in early infancy or childhood as a solitary, well-circumscribed, fibrous, and skin-colored to purple nodule, sometimes with superficial telangiectasias or erosions. There is a male predominance in the solitary form, and it affects the head and neck region more frequently.4 In more than 50% of patients with solitary lesions and more than 90% with multiple lesions, the lesions are present at birth or soon after. In most of the remaining cases, lesions appear before the age of 2 years.2 The differential diagnosis includes other fibrous tumors, as well as xanthogranulomas, nasal gliomas, vascular or lymphatic tumors, dermoid cysts, neurofibromas, sarcomas, encephaloceles, meningiomas, lipomas, and teratomas.The diagnosis of myofibromatosis is confirmed on finding characteristic biphasic histopathologic findings consisting of bland-appearing fascicles of plump corkscrew myofibroblasts with abundant eosinophilic cytoplasm within a collagenous stroma merging with more cellular areas of less differentiated, rounded cells arranged around a central pericyte-like vasculature. Necrosis, calcification, and intravascular extension may occur.3 Immunohistochemical analysis shows smooth muscle differentiation with antibodies to muscle actins (always positive) and vimentin (not always positive). Myofibroblasts and their corresponding lesions rarely express desmin and are almost universally negative for S-100.3 Zelger et al6 suggested that myofibromas change histopathologically over time. Initially, the lesions have a monophasic pattern, but later a biphasic pattern develops, in which lesions first become myoid, then fibrotic, and finally hyalinized and/or sclerotic. A correlation between the histopathologic pattern and the lesional age has also been reported. Specifically, a vascular pattern suggests an early lesion, a nodular or multinodular pattern suggests a fully developed lesion, and a leiomyoma or fascicular pattern suggests a late lesion.7Imaging is useful in demonstrating the extent and progression of the tumor; however, it is not required in uncomplicated solitary cases.4 Solitary and multicentric forms without visceral involvement have an excellent prognosis and often exhibit spontaneous regression. Symptomatic visceral involvement is associated with a mortality rate of 73%, mainly from cardiopulmonary or gastrointestinal tract complications.8 Surgical excision is therefore typically reserved only for symptomatic patients or if vital organs are compromised. The recurrence rate after surgery is 7% to 10%, although reexcision of recurrent lesions is usually curative.3 Nonsurgical options include radiotherapy, chemotherapy, and local corticosteroids injections.8 Periodic clinical reevaluation is recommended until the lesion is stable. Our case exemplifies “watch and wait” as a valid option for biopsy-proven IM owing to the high likelihood of spontaneous regression.

Dermatology

A newborn girl with a nodular lesion on the scalp present since birth was seen at the dermatology clinic. The parents reported occasional erosions and crusting that resolved with topical mupirocin, 2%, cream, but with no continued growth. The mother had had a normal pregnancy. Physical examination revealed a firm, exophytic, and flat-topped nodule, with superficial erosion and crust on the right parietal side of the scalp measuring 3 cm in diameter and 1 cm thick (Figure, A). No other skin lesions were found. A 4-mm punch skin biopsy was performed, and tissue was sent for pathologic analysis (Figure, B and C). Cerebral and abdominal ultrasonography revealed no evidence of visceral involvement. The lesion regressed without treatment over a period of 8 months. Close follow-up every 3 months was scheduled, and complete involution of the tumor was noted at 10 months of age (Figure, D).A, Nodular lesion on the right parietal scalp at initial presentation. B, Histopathologic image of a biopsy specimen (hematoxylin-eosin, original magnification ×200). C, Immunohistochemical image of a biopsy specimen (actin stain, original magnification ×100). D, Complete regression of tumor at 10 months of age.

what is your diagnosis?

What is your diagnosis?

Giant cell fibroblastoma

Dermoid cyst

Keratoacanthoma

Infantile myofibromatosis

d

female

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2168934

A man in his 60s presented with a painless rapidly enlarging ulcer on his left leg 1 week after the onset of diverticulitis, a neutropenic fever, and severe sepsis due to multidrug-resistant Pseudomonas aeruginosa infection that necessitated admission to the intensive care unit. His medical history included a heart transplant for ischemic cardiomyopathy in his early 50s, and he was receiving long-term immunosuppressive therapy with cyclosporine, mycophenolate mofetil, and deflazacort. He had received a diagnosis of plasmablastic lymphoma 6 months earlier and was being treated with polychemotherapy (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone [CHOP] regimen).Physical examination revealed a well-demarcated 5 × 5-cm round ulcer with raised border, surrounding erythema, and a base with purulent debris (Figure 1A). A superficial swab culture sample grew P aeruginosa. A punch biopsy specimen from the edge of the ulcer was obtained and sent for histopathologic evaluation (Figure 1B).A, Cutaneous ulcer on the patient’s left leg with a raised erythematous border and a base with purulent debris. B, Diagnostic biopsy shows enlarged endothelial cells with intranuclear inclusions surrounded by a clear halo, and some cytoplasmic inclusions. Similar findings are detected in some macrophages (hematoxylin-eosin, original magnification ×400). What Is Your Diagnosis?

Ecthyma gangrenosum

Cytomegalovirus ulcer

Mucormycosis ulcer

Pyoderma gangrenosum

B. Cytomegalovirus ulcer

B

Cytomegalovirus ulcer

Pathologic findings revealed a superficial dermal edema with a perivascular diffuse lymphocytic inflammatory cell infiltrate. Among normal endothelial cells, there were many enlarged endothelial cells with large intranuclear and intracytoplasmic inclusions. In some cells, the intranuclear inclusions were surrounded by clear halos. These findings were also detected in some macrophages. In addition, mild polymorphonuclear leukocyte infiltration was observed in some small dermal vessels. These inclusions tested positive for cytomegalovirus antigen on immunohistochemical analysis (Figure 2).Ulcer biopsy shows positive immunohistochemical staining for cytomegalovirus in cytomegalic endothelial cells (original magnification, ×400).The patient was treated with oral valganciclovir for 3 weeks (900 mg every 12 hours) on an outpatient basis, with complete resolution of the lesion. No new cutaneous lesions were found; neither were other signs of disseminated infection during follow-up. A colonoscopy was performed, which had normal results.Cytomegalovirus (CMV) is a common opportunistic agent in immunocompromised patients with AIDS, hematological malignant neoplasms, and solid-organ or hematopoietic stem cell transplantation. It usually causes oligosymptomatic infections in childhood or adolescence and may reactivate many years later.1 Current evidence points to the hypothesis that CMV may target CD34+ hematopoietic cells, monocyte-derived macrophages, and dendritic cells as latency hosts.2Cytomegalovirus causes a variety of conditions, such as pneumonia, encephalitis, hepatitis, gastrointestinal ulcers, retinitis, and eventually disseminated disease.3 Cutaneous disease is a rare finding, and it may present as maculopapular rashes, scarlatiniform and urticarial eruptions, cutaneous and oral ulcers, or nodular and verrucous lesions, among others. It usually represents the first sign of disseminated CMV infection and is therefore associated with a high morbidity and mortality.4Most of the cutaneous lesions caused by CMV are ulcers localized on the perianal and perigenital areas, particularly in patients with human immunodeficiency virus infection. It has been postulated that the latent virus resides in the gastrointestinal tract and may infect the perineal skin via fecal shedding.5The differential diagnosis for cutaneous ulcers in immunocompromised patients is broad and should include malignant neoplasm; pyoderma gangrenosum; bacterial (ecthyma, septic emboli, anaerobic, mycobacteria, treponema), viral (gangrenous herpes simplex), or fungal infections (Mucor, Fusarium, Aspergillus,Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis); and parasites (free-living amebas), among others. Ecthyma gangrenosum is a characteristic cutaneous manifestation of Pseudomonas sepsis, particularly in severely neutropenic patients. In fact, it was our diagnostic impression when we first evaluated the patient.The histopathologic features are vascular dilation with cytomegalic endothelial cells, intranuclear and intracytoplasmic inclusion bodies (with a halo surrounding the intranuclear inclusions) forming an “owl’s eye” appearance, and variable perivascular inflammatory infiltrate. Cytomegalovirus immunostaining is specific and does not cross-react with other herpes viruses. The role that CMV plays in some cutaneous lesions is still controversial because it has been detected in coinfections with herpes simplex, and even unexpectedly in healthy skin.6 Nevertheless, its pathogenic role in this case has been demonstrated by the noticeable cytopathic changes in both endothelial cells and macrophages and by the clinical resolution of the lesion with specific treatment with valganciclovir. We believe that the growth of P aeruginosa in the superficial swab culture was due to a contamination of the ulcer.In summary, CMV is a common opportunistic agent in immunocompromised patients, but the clinical presentation of CMV infection as cutaneous ulcer is infrequent, often heralding disseminated infection, and is associated with a bad prognosis.

Dermatology

A man in his 60s presented with a painless rapidly enlarging ulcer on his left leg 1 week after the onset of diverticulitis, a neutropenic fever, and severe sepsis due to multidrug-resistant Pseudomonas aeruginosa infection that necessitated admission to the intensive care unit. His medical history included a heart transplant for ischemic cardiomyopathy in his early 50s, and he was receiving long-term immunosuppressive therapy with cyclosporine, mycophenolate mofetil, and deflazacort. He had received a diagnosis of plasmablastic lymphoma 6 months earlier and was being treated with polychemotherapy (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone [CHOP] regimen).Physical examination revealed a well-demarcated 5 × 5-cm round ulcer with raised border, surrounding erythema, and a base with purulent debris (Figure 1A). A superficial swab culture sample grew P aeruginosa. A punch biopsy specimen from the edge of the ulcer was obtained and sent for histopathologic evaluation (Figure 1B).A, Cutaneous ulcer on the patient’s left leg with a raised erythematous border and a base with purulent debris. B, Diagnostic biopsy shows enlarged endothelial cells with intranuclear inclusions surrounded by a clear halo, and some cytoplasmic inclusions. Similar findings are detected in some macrophages (hematoxylin-eosin, original magnification ×400).

what is your diagnosis?

What is your diagnosis?

Mucormycosis ulcer

Ecthyma gangrenosum

Cytomegalovirus ulcer

Pyoderma gangrenosum

c

male

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2169317

A woman in her 80s with a history of nonischemic cardiomyopathy and chronic kidney disease presented with purpuric lesions on her face, elbows, knees, and feet. She was initially admitted for altered mental status in the setting of an unwitnessed fall and was noted to have “bruises” on her lower extremities. Dermatology was consulted after the development of new lesions on her nose, ear, and the extensor surfaces of her arms bilaterally. Admission laboratory test results showed hypercalcemia (calcium level, 11.5 mg/dL) and acute kidney injury (creatinine level, 5.6 mg/dL).On physical examination, the patient’s nose, bilateral cheeks, forehead, and left ear (helical rim and antihelix [Figure, A]) were found to have dusky purpuric macules and patches. Her knees, feet, and the extensor surfaces of her arms had reticulated purpuric macules and patches. There was skin sloughing off the lesions on her elbows (Figure, B) and knees. Four-millimeter punch biopsy specimens were taken from the left ear, right arm, and forehead (Figure, C and D).Clinical and histopathologic images from a case of acral retiform purpura. A, Dusky purpuric macules on the helical rim and antihelix of the ear. B, Reticulated purpuric patches with focal areas of necrosis on the extensor surfaces of the arms. C and D, In specimens from the forehead, multifocal intravascular fibrinoid material consisting of a mix of cryoglobulins and fibrin thrombi with relatively little vessel wall inflammation was seen (hematoxylin-eosin, original magnification ×4 [C] and ×10 [D]). What is your diagnosis?

Leukocytoclastic vasculitis

Antiphospholipid syndrome

Type I cryoglobulinemia associated with multiple myeloma

Purpura fulminans

C. Type I cryoglobulinemia associated with multiple myeloma

C

Type I cryoglobulinemia associated with multiple myeloma

All biopsy specimens demonstrated multifocal intravascular fibrinoid material consisting of a mix of cryoglobulins and fibrin thrombi, with relatively little vessel wall inflammation (Figure, C and D). Further laboratory workup revealed rouleaux and cryoprotein precipitate on peripheral blood smear, abnormal paraprotein band on serum and urine protein electrophoreses, and a monoclonal IgG-κ protein on immunofixation electrophoresis (IFE). Results of blood tests for hepatitis, antinuclear antibodies, rheumatoid factor, heparin-induced thrombocytopenia antibodies, and antineutrophil cytoplasmic antibodies were all negative. A diagnosis of type I cryoglobulinemia was confirmed serologically with elevated serum cryoglobulin levels (cryocrit, 16%) in combination with the monoclonal IgG-κ protein on IFE. A computed tomographic scan of the pelvis revealed lytic bony lesions. A bone-marrow biopsy demonstrated hypercellular marrow consisting of 80% plasma cells with atypical morphology and κ-light-chain restriction, consistent with the diagnosis of multiple myeloma.Cryoglobulinemia is a disease characterized by serum cryoglobulins, which are immunoglobulins that undergo reversible precipitation on cooling. These immunoglobulins were first described by Wintrobe and Buell1 in 1933 in a patient with multiple myeloma, and in 1947, Lerner and colleagues2 coined the term cryoglobulin. Cryoglobulinemia may be classified into 3 subtypes depending on the associated immunoglobulin. Type I involves a single monoclonal immunoglobulin (typically IgM or IgG), whereas types II and III (mixed) involve monoclonal (type II) or polyclonal (type III) IgM, typically with rheumatoid factor activity against the corresponding antigen (usually polyclonal IgG).3Type I cryoglobulinemia is caused by the precipitation of a monoclonal immunoglobulin, usually IgM or IgG, leading to vascular occlusion with minimal vascular inflammation. Clinically, patients manifest with purpuric or necrotic lesions that are often retiform in cold-exposed acral sites. Other skin findings may include acral cyanosis, Raynaud phenomenon, and livedo reticularis.3,4 In contrast, types II and III cryoglobulinemias result in immune complex deposition and small-vessel vasculitis, clinically manifesting as palpable purpura in addition to possible multiple-organ involvement (neuropathy, arthralgias, and renal disease).4 While mixed cryoglobulinemias often occur in the setting of hepatitis C infection, type I cryoglobulinemia is predominantly associated with B-cell lymphoproliferative diseases, particularly Waldenstrom macroglobulinemia and multiple myeloma.4 A case series of 7 patients with type I cryoglobulinemia in the setting of multiple myeloma revealed that IgG was the most common immunoglobulin found in 6 of 7 patients.5The differential diagnosis for retiform purpura is extensive but in the case of type 1 cryoglobulinemia can be narrowed based on the acral distribution. The differential diagnosis for disorders of cryogelling and cryoagglutination (cryoglobulinemia, cryofibrinogenemia, cold agglutins) includes infections (eg, Lucio phenomenon of leprosy), purpura fulminans, antiphospholipid syndrome, distal occlusion syndromes (eg, cholesterol emboli), levamisole-associated vasculitis (commonly involving the earlobe), and perniosis (less acute and rarely present with purpura or necrosis). As seen in the present case, the diagnosis of type I cryoglobulinemia is made in the clinical context of a lymphoproliferative disease in conjunction with characteristic cutaneous and histopathologic findings with a positive laboratory test result for cryoglobulins. Because cryoglobulins are unstable molecules, it is imperative that blood samples be collected, transported, and clotted at 37°C to prevent false-negative interpretation due to precipitation at room temperature.6 On rewarming of the cryoprecipitate to 37°C, further analysis by immunofixation may be performed to characterize the type of cryoglobulin.Mainstay therapy for type 1 cryoglobulinemia is treatment of the underlying hematologic condition. Corticosteroids and plasmapheresis may be used in the setting of severe complications to decrease the quantity of circulating immunoglobulins.4 Aggressive therapy with chemotherapeutic agents was not pursued in our patient owing to her advanced disease and poor prognosis, and her family elected for comfort care.

Dermatology

A woman in her 80s with a history of nonischemic cardiomyopathy and chronic kidney disease presented with purpuric lesions on her face, elbows, knees, and feet. She was initially admitted for altered mental status in the setting of an unwitnessed fall and was noted to have “bruises” on her lower extremities. Dermatology was consulted after the development of new lesions on her nose, ear, and the extensor surfaces of her arms bilaterally. Admission laboratory test results showed hypercalcemia (calcium level, 11.5 mg/dL) and acute kidney injury (creatinine level, 5.6 mg/dL).On physical examination, the patient’s nose, bilateral cheeks, forehead, and left ear (helical rim and antihelix [Figure, A]) were found to have dusky purpuric macules and patches. Her knees, feet, and the extensor surfaces of her arms had reticulated purpuric macules and patches. There was skin sloughing off the lesions on her elbows (Figure, B) and knees. Four-millimeter punch biopsy specimens were taken from the left ear, right arm, and forehead (Figure, C and D).Clinical and histopathologic images from a case of acral retiform purpura. A, Dusky purpuric macules on the helical rim and antihelix of the ear. B, Reticulated purpuric patches with focal areas of necrosis on the extensor surfaces of the arms. C and D, In specimens from the forehead, multifocal intravascular fibrinoid material consisting of a mix of cryoglobulins and fibrin thrombi with relatively little vessel wall inflammation was seen (hematoxylin-eosin, original magnification ×4 [C] and ×10 [D]).

what is your diagnosis?

What is your diagnosis?

Antiphospholipid syndrome

Purpura fulminans

Type I cryoglobulinemia associated with multiple myeloma

Leukocytoclastic vasculitis

c

female

81-90

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2319756

A woman in her 60s presented with a 1-month history of painless, blurred vision in the left eye. Her medical history was significant for Waldenström macroglobulinemia (WM), and recent laboratory test results showed active WM with bone marrow involvement. Results of the eye examination showed best-corrected visual acuity of 20/20 OD and 20/40 OS. Anterior segment examination results showed a relatively shallow anterior chamber in the left eye. Results of a dilated fundus examination showed a choroidal detachment in the left eye extending circumferentially from the 2-o’clock to the 5-o’clock position and extending posteriorly up to 3 to 4 disc diameters temporal to the macula (Figure, A). There was vitreous hemorrhage with a poor view of the posterior pole (Figure, A).A, Ultra-widefield fundus photograph of the left eye showing posterior vitreous hemorrhage (white arrowhead) and a choroidal detachment temporally (yellow arrowheads). B, Anterior segment spectral domain optical coherence tomography of the left eye showing the narrow angle from suprachoroidal effusion.Results of fundus fluorescein angiography of the left eye showed hypofluorescence corresponding to vitreous hemorrhage. Tortuosity of the temporal vessels was prominent, with diffuse peripheral vascular leakage temporally. Choroidal folds were observed 3 disc diameters temporal to the macula, extending to the periphery. Peripheral capillary nonperfusion, vascular reorganization, neovascularization, and choroidal detachment were noted.Anterior segment spectral domain optical coherence tomographic results showed a shallow anterior chamber and 360° narrow angles in the left eye (Figure, B). Results of B-scan ultrasonography confirmed choroidal detachment in the left eye and revealed a small area of suprachoroidal effusion in the right eye in the superotemporal periphery.Treat with combined systemic chemotherapy and pars plana vitrectomy What Would You Do Next?

Observe the patient

Perform pars plana vitrectomy

Treat with systemic chemotherapy

Treat with combined systemic chemotherapy and pars plana vitrectomy

Waldenström macroglobulinemia with bilateral choroidal detachment

D

Treat with combined systemic chemotherapy and pars plana vitrectomy

Waldenström macroglobulinemia is a rare lymphoplasmacytic malignant lymphoma characterized by the overproduction of monoclonal IgM.1 The clinical manifestations of WM are classified according to those related to the following 3 causes: direct tumor infiltration, the amount and specific properties of circulating IgM, and the deposition of IgM in various tissues. Because IgM is a large pentamer compound that easily forms aggregates, elevated serum IgM levels in WM can cause hyperviscosity syndrome, leading to ocular manifestations. Most known ophthalmic manifestations, including retinal hemorrhages, peripheral retinal capillary nonperfusion, macular detachment, and central retinal vein occlusion, have been linked to hyperviscosity syndrome because of WM.2 Other characteristic retinal findings caused by high viscosity in patients with WM are microaneurysms, vascular dilation and tortuosity, venous beading, and optic disc edema. Approximately 30% of all patients with WM develop chorioretinal complications.2 Patients may experience visual disturbance (8%) and may exhibit some degree of hyperviscosity-related retinopathy (37%),3 which can lead to central retinal vein occlusion, peripheral nonperfusion, retinal hemorrhage,3,4 and central serous macular detachment.5 We describe a patient with WM who developed bilateral choroidal detachment, which, to our knowledge, has not been previously reported. The precise mechanism underlying the choroidal alterations in WM remains poorly understood. The microvasculature of the retina and choroid are particularly susceptible to the effects of serum hyperviscosity.6 It is possible that increased IgM in choroidal vessels spills and leaks into the suprachoroidal space. The high molecular weight of IgM may have increased the fluid oncotic pressure within the suprachoroidal space and hence resulted in fluid transudation and choroidal detachment in this patient with WM.This report also describes wide-field fundus photography and fluorescein angiography for visualization of peripheral fundus findings, including peripheral vascular leakage, capillary nonperfusion, vascular remodeling, and neovascularization. The patient did not have diabetes mellitus or sickle cell disease, thereby ruling out some other known causes of peripheral vascular ischemia or leakage. B-scan ultrasonography was helpful in delineating the extent and height of detachment in the left eye and detecting the small choroidal detachment in the right eye, which was not readily seen on clinical examination.For our patient, chemotherapy was initiated for the reactivated WM. She underwent pars plana vitrectomy with endolaser in the left eye and vision in that eye improved to 20/20, with resolution of the choroidal detachment at the 1-month follow-up.

Ophthalmology

A woman in her 60s presented with a 1-month history of painless, blurred vision in the left eye. Her medical history was significant for Waldenström macroglobulinemia (WM), and recent laboratory test results showed active WM with bone marrow involvement. Results of the eye examination showed best-corrected visual acuity of 20/20 OD and 20/40 OS. Anterior segment examination results showed a relatively shallow anterior chamber in the left eye. Results of a dilated fundus examination showed a choroidal detachment in the left eye extending circumferentially from the 2-o’clock to the 5-o’clock position and extending posteriorly up to 3 to 4 disc diameters temporal to the macula (Figure, A). There was vitreous hemorrhage with a poor view of the posterior pole (Figure, A).A, Ultra-widefield fundus photograph of the left eye showing posterior vitreous hemorrhage (white arrowhead) and a choroidal detachment temporally (yellow arrowheads). B, Anterior segment spectral domain optical coherence tomography of the left eye showing the narrow angle from suprachoroidal effusion.Results of fundus fluorescein angiography of the left eye showed hypofluorescence corresponding to vitreous hemorrhage. Tortuosity of the temporal vessels was prominent, with diffuse peripheral vascular leakage temporally. Choroidal folds were observed 3 disc diameters temporal to the macula, extending to the periphery. Peripheral capillary nonperfusion, vascular reorganization, neovascularization, and choroidal detachment were noted.Anterior segment spectral domain optical coherence tomographic results showed a shallow anterior chamber and 360° narrow angles in the left eye (Figure, B). Results of B-scan ultrasonography confirmed choroidal detachment in the left eye and revealed a small area of suprachoroidal effusion in the right eye in the superotemporal periphery.Treat with combined systemic chemotherapy and pars plana vitrectomy

what would you do next?

What would you do next?

Perform pars plana vitrectomy

Treat with combined systemic chemotherapy and pars plana vitrectomy

Observe the patient

Treat with systemic chemotherapy

b

female

61-70

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2319757

A white man in his 30s with a remote history of right eye enucleation following globe trauma presented to our clinic in July 2014 with decreased visual acuity in the left eye. He described a history of initially intermittent (lasting hours to days) then constant (for the past 6-8 weeks) central and peripheral blurred vision in the left eye. He reported no headaches, numbness, weakness, eye pain, hearing loss, or other neurologic issues. Eight years earlier, he had sustained a fireworks injury to his right eye followed by globe repair and enucleation within 3 days. He had no other significant medical or ocular history.His right eye’s external appearance was normal, and the prosthesis fit well. Uncorrected visual acuity was Snellen 20/70−1 OS (no improvement with pinhole); intraocular pressure was 13 mm Hg. Slitlamp examination results of the anterior segment were normal. Ophthalmoscopy demonstrated 1+ cells in the anterior vitreous and a serous retinal detachment involving the macula and extending from the 2-o’clock to the 10-o’clock position with pigmentary and atrophic changes in the macula. No breaks were noted on scleral depressed examination. Fluorescein angiography showed multifocal areas of early hyperfluorescence with late leakage and diffuse retinal vascular leakage predominantly in the inferior retina (Figure 1A). Optical coherence tomography (OCT) showed a thickened choroid and subretinal fluid throughout the macula (Figure 1B). Enhanced depth imaging showed an enlarged choroid throughout the posterior pole, and ultrasonography confirmed extensive inferior retinal detachment (not shown).A, Fluorescein late-phase angiogram shows multifocal areas of posterior choroidal leakage and diffuse retinal vascular leakage in the inferior (detached) retina. B, Optical coherence tomographic en face infrared image (left) and vertical line scan (right) through the fovea show subretinal fluid extending inferiorly with hyperreflective subretinal deposits. What Would You Do Next?

Systemic corticosteroid therapy

Observation

Photodynamic therapy

Antivascular endothelial growth factor therapy (anti-VEGF)

Central serous chorioretinopathy

C

Photodynamic therapy

The 2 leading diagnoses under consideration were chronic central serous chorioretinopathy (CSR) and sympathetic ophthalmia (SO). There was an extensive serous retinal detachment with vitreous cell and diffuse vascular leakage in our patient with a history of eye trauma, which raised the possibility of SO. Many of the patient’s nonspecific visual symptoms could have been consistent with the early loss of accommodation that can be observed with mild SO. However, the pace of the disease, lack of anterior chamber inflammation, and overall angiographic features were more consistent with chronic CSR (the classic “starry sky” appearance of the choroiditis associated with SO was not present).In terms of the available therapeutic options, observation did not seem appropriate, and the role of anti-VEGF therapy, in the absence of clear evidence of choroidal neovascularization, is not clear. Thus, the decision was based on our ability to definitively differentiate SO from CSR. The classic clinical and angiographic presentations of each condition are different; however, the present case had features of both and was classic for neither. On imaging, both SO and CSR can present with exudative detachments, choroidal thickening on enhanced depth imaging OCT, elongated photoreceptor segments in detached retina, and multifocal hyperfluorescent angiographic lesions with late leakage.1-4Considering the large serous detachment, widespread angiographic retinal vascular leakage, vitreous cell, and poor prognosis of untreated SO, we opted for a diagnostic (and possibly therapeutic) trial of high-dose corticosteroid therapy (intravenous methylprednisolone sodium succinate and oral prednisone). During the first 2 weeks of therapy, there were no appreciable clinical or angiographic changes. At the 3-week follow-up examination, careful review of macular OCT topography revealed gradually increased overall macular volume and subretinal fluid as well as a clinically worsening inferior serous retinal detachment. We believed that this finding confirmed an underlying diagnosis of CSR slowly worsening during corticosteroid therapy. Multiple-spot photodynamic therapy was then performed, targeting the areas of leakage on fluorescein and indocyanine green angiography, and corticosteroid therapy was tapered to discontinuation across a few weeks. One month after photodynamic therapy, the patient’s macular OCT was markedly improved and his inferior serous retinal detachment had nearly resolved (Figure 2). At 3 months, there was complete resolution of the subretinal fluid and his visual acuity returned to 20/50 on Snellen examination, with mild intraretinal fluid.Optical coherence tomographic en face infrared image (left) and vertical line scan (right) through the fovea 1 month after photodynamic therapy show improvement in the subretinal fluid.This atypical and dramatic presentation of chronic CSR was confounded by the patient’s history of traumatic injury and enucleation and by the evident intraocular “inflammation,” which made the diagnosis of SO higher on the differential than it might have been based solely on the imaging findings. Although the remoteness of the patient’s trauma and the early enucleation overall made SO less likely, both late onset and onset of SO after early enucleation have been reported,5-7 with as many as 10% of cases of SO occurring more than 1 year after the trauma. The clinical presentation of SO is variable, ranging from mild anterior-segment inflammation to severe granulomatous panuveitis with variable degrees of retinal involvement, and onset can be insidious or acute.5-7 In retrospect, we infer that the “vitritis” and diffuse vascular leakage were secondary to the chronic retinal detachment with subsequent breakdown of the blood-retinal barrier and were not a priori evidence of inflammatory disease (neither condition responded to prednisone therapy). We encourage continued advancement of multimodal imaging modalities to improve our ability to differentiate these pathophysiologically different diseases.

Ophthalmology

A white man in his 30s with a remote history of right eye enucleation following globe trauma presented to our clinic in July 2014 with decreased visual acuity in the left eye. He described a history of initially intermittent (lasting hours to days) then constant (for the past 6-8 weeks) central and peripheral blurred vision in the left eye. He reported no headaches, numbness, weakness, eye pain, hearing loss, or other neurologic issues. Eight years earlier, he had sustained a fireworks injury to his right eye followed by globe repair and enucleation within 3 days. He had no other significant medical or ocular history.His right eye’s external appearance was normal, and the prosthesis fit well. Uncorrected visual acuity was Snellen 20/70−1 OS (no improvement with pinhole); intraocular pressure was 13 mm Hg. Slitlamp examination results of the anterior segment were normal. Ophthalmoscopy demonstrated 1+ cells in the anterior vitreous and a serous retinal detachment involving the macula and extending from the 2-o’clock to the 10-o’clock position with pigmentary and atrophic changes in the macula. No breaks were noted on scleral depressed examination. Fluorescein angiography showed multifocal areas of early hyperfluorescence with late leakage and diffuse retinal vascular leakage predominantly in the inferior retina (Figure 1A). Optical coherence tomography (OCT) showed a thickened choroid and subretinal fluid throughout the macula (Figure 1B). Enhanced depth imaging showed an enlarged choroid throughout the posterior pole, and ultrasonography confirmed extensive inferior retinal detachment (not shown).A, Fluorescein late-phase angiogram shows multifocal areas of posterior choroidal leakage and diffuse retinal vascular leakage in the inferior (detached) retina. B, Optical coherence tomographic en face infrared image (left) and vertical line scan (right) through the fovea show subretinal fluid extending inferiorly with hyperreflective subretinal deposits.

what would you do next?

What would you do next?

Systemic corticosteroid therapy

Observation

Antivascular endothelial growth factor therapy (anti-VEGF)

Photodynamic therapy

d

male

31-40

White

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2299689

An adolescent girl presented to her pediatrician reporting abdominal distention. She first became aware of her increased abdominal girth when friends at school asked whether she was pregnant. She had noticed her clothing becoming tighter over recent weeks. She had not experienced abdominal pain or other symptoms, and there was no history of trauma. Physical examination revealed a firm, distended abdomen without bowel sounds. Pregnancy test results were negative. Results of laboratory studies, including a complete blood cell count, basic metabolic panel, and liver function tests, were within normal limits. An abdominal radiograph showed a paucity of bowel gas markings (Figure 1A). A subsequent computed tomographic scan of the abdomen and pelvis revealed a 30-cm retroperitoneal cystic structure causing significant mass effect on the abdominal viscera, displacing the right kidney superiorly under the liver causing moderate hydronephrosis (Figure 1B).A, Abdominal radiograph showing a paucity of bowel gas markings. B, Abdominal computed tomographic scan showing a massive retroperitoneal cystic lesion with displacement of abdominal organs and right moderate hydronephrosis. What Is Your Diagnosis?

Retroperitoneal abscess

Lymphatic malformation

Urinoma

Pancreatic pseudocyst

B. Lymphatic malformation

B

Lymphatic malformation

The patient had a lymphatic malformation (LM). Most LMs are congenital, but there have been a few reports1 of development after trauma or infection. There are no known risk factors. Lymphatic malformations are a type of congenital vascular malformation caused by a development abnormality resulting in formation of vascular channels without cellular proliferation.2 Vascular malformations are subtyped as high-flow (arterial) vs low-flow (venous or lymphatic) lesions, with low-flow lesions being the most common.2 Approximately 25% of these low-flow lesions are completely or partially lymphatic in origin. Only 1% of LMs occur in the retroperitoneum; they most frequently develop in the neck and axilla.3 Lymphatic malformations of the retroperitoneum may be asymptomatic and thus undiagnosed until adolescence or early adulthood. Lymphatic malformations of the head or neck are quickly identified by the caregiver or physician owing to their external location; however, a retroperitoneal mass must grow to a substantial size before exhibiting any symptoms or physical findings. In some situations, a retroperitoneal LM is discovered as an incidental finding on radiographic imaging obtained for another reason, such as trauma. In addition, there have been reports4 of trauma causing hemorrhage in a previously undiagnosed LM.Radiographic imaging, such as ultrasonography, magnetic resonance imaging, and computed tomographic scanning, is necessary to diagnose a retroperitoneal mass and is useful in evaluation of vascular malformations. Intravenous contrast may distinguish low-flow lesions from hemangioma or high-flow lesions. The differential diagnosis for a large, multilobulated, cystic retroperitoneal mass in a child includes LM, pancreatic pseudocyst, choledochal cyst, urinoma, and teratoma.2-4 There are no clinical features that can conclusively differentiate a retroperitoneal LM from other retroperitoneal masses; thus, surgery is required to make a definitive diagnosis. However, the other possibilities have components of the patient’s history, physical examination, laboratory work, or imaging that may be more suggestive of other causes including pancreatic pseudocyst (usually follows an episode of pancreatitis or blunt trauma), choledochal cyst (frequently presents with cholestasis), urinoma (often related to a blunt traumatic injury), and teratoma (frequently appears heterogeneous with calcifications, although a large cystic component may mimic an LM).The mainstay of therapy for an LM is surgical resection, although sclerotherapy with OK-432 or ethanol has been done with success.2,3 Sclerotherapy is considered for diffuse or large LMs in which a complete surgical resection cannot be performed owing to involvement of vital structures. In such a case, a combined approach of partial resection for volume reduction followed by sclerotherapy to completely fibrose the remaining lymphovenous tissue could be used. Surgical excision may have a 10% recurrence rate in head and neck LMs; there are limited data regarding the rate in retroperitoneal LMs.5 For this reason, long-term surveillance with ultrasonography or magnetic resonance imaging should be performed to monitor for recurrence.This patient underwent successful resection after placement of bilateral ureteral stents. The retroperitoneal location was confirmed when the right ureter was identified intraoperatively on the anterior aspect of the mass (Figure 2). She made an uneventful postoperative recovery. Magnetic resonance imaging obtained 5 months postoperatively showed no evidence of recurrence.Intraoperative image of a massive retroperitoneal mass with displacement of the ureter.

Pediatrics

An adolescent girl presented to her pediatrician reporting abdominal distention. She first became aware of her increased abdominal girth when friends at school asked whether she was pregnant. She had noticed her clothing becoming tighter over recent weeks. She had not experienced abdominal pain or other symptoms, and there was no history of trauma. Physical examination revealed a firm, distended abdomen without bowel sounds. Pregnancy test results were negative. Results of laboratory studies, including a complete blood cell count, basic metabolic panel, and liver function tests, were within normal limits. An abdominal radiograph showed a paucity of bowel gas markings (Figure 1A). A subsequent computed tomographic scan of the abdomen and pelvis revealed a 30-cm retroperitoneal cystic structure causing significant mass effect on the abdominal viscera, displacing the right kidney superiorly under the liver causing moderate hydronephrosis (Figure 1B).A, Abdominal radiograph showing a paucity of bowel gas markings. B, Abdominal computed tomographic scan showing a massive retroperitoneal cystic lesion with displacement of abdominal organs and right moderate hydronephrosis.

what is your diagnosis?

What is your diagnosis?

Retroperitoneal abscess

Lymphatic malformation

Urinoma

Pancreatic pseudocyst

b

female

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2210370

A man in his 60s had an 8-month history of right-sided nasal congestion and rhinorrhea. He had no clinically significant improvement in symptoms despite multiple courses of oral antibiotics. Over the previous 2 months, he had developed progressive right-sided facial swelling, pain, blurred vision, and a 6.8-kg weight loss. There was no history of immunocompromise or foreign travel. A computed tomographic (CT) scan at an outside hospital showed complete opacification and an invasive process centered in the right maxillary sinus. An endoscopic maxillary antrostomy and biopsy showed inflammatory changes and numerous fungal organisms consistent with Aspergillus species. The patient was started on treatment with intravenous antifungal and broad-spectrum antibiotics, and he was transferred for further evaluation and management. The patient’s examination was notable for right-sided facial and periorbital swelling, severe pain, and limitation of lateral gaze of the right eye. A repeated CT scan was completed (Figure).A-C, Computed tomographic images. A, Coronal view of the paranasal sinuses in bone windows showing near-complete opacification of the right maxillary sinus with soft-tissue thickening, a calcific focus, and associated erosion of the bony walls. B, Coronal view of the paranasal sinuses in soft-tissue windows. C, Axial view of the paranasal sinuses in bone windows. What Is Your Diagnosis?

Fungal ball

Chronic invasive fungal sinusitis

Invasive squamous cell carcinoma

Fungal ball and invasive squamous cell carcinoma

D. Fungal ball and invasive squamous cell carcinoma

D

Fungal ball and invasive squamous cell carcinoma

Despite the initial intervention of endoscopic surgery and systemic antifungal therapy, our patient exhibited signs and symptoms of a progressive, locally aggressive disease.Because of the severe symptoms, we performed a right Caldwell Luc procedure to remove the fungal disease completely and to obtain tissue at the site of bone erosion for definitive diagnosis. On gross inspection of the maxillary sinus, extensive fungal debris was found. In addition, abnormal tissue was noted to be invading through several bones of the maxillary sinus. The histologic appearance of the tissue biopsied was consistent with concurrent sinus fungus ball and invasive squamous cell carcinoma (SCC) of the right maxillary sinus.Unilateral sinonasal symptoms with associated unilateral maxillary sinus opacification are relatively common and suggest a broad differential diagnosis: chronic rhinosinusitis with or without nasal polyposis; fungal sinus disease, including fungus ball, allergic fungal sinusitis, chronic invasive fungal sinusitis, and acute invasive fungal sinusitis; mucocele; inverted papilloma; and malignant neoplasm. Prior reviews1,2 suggest that certain presenting symptoms, such as unilateral pain, swelling, numbness, epistaxis, diplopia, and decreased vision, are more common in patients with sinonasal malignant neoplasm. Certain findings on CT scans may also be suggestive of etiology. Inflammatory diseases are typically associated with small, thick-walled paranasal sinuses without evidence of bony erosion. Malignant neoplasms are typically associated with enlarged sinuses with thin, eroded bony walls.3 Magnetic resonance imaging scans detail soft-tissue and fungal disease better than CT scans. In this case, our approach was to clear the fungal ball and establish a diagnosis and possibly debulk invasive fungal disease. After the diagnosis of SCC, the patient subsequently had an MRISinonasal cancers are rare, comprising 5% of head and neck cancers and less than 1% of malignant neoplasms overall. Squamous cell carcinoma is the most common, representing 50% to 80% of all sinonasal cancers.4 These tumors most frequently originate in the maxillary sinus.5 Initial symptoms of unilateral pain, obstruction, and epistaxis are nonspecific. Late presenting symptoms of anosmia, diplopia, and cranial neuropathy occur as the tumor invades beyond the boundaries of the sinus into adjacent structures. In most series, more than 50% of patients presented with advanced-stage disease. These locally aggressive malignant neoplasms are associated with poor overall survival rates, reported as 50% or less at 5 years.4,5As with other diseases of the paranasal sinuses, CT is the initial imaging modality of choice for evaluation of sinonasal tumors. It allows for characterization of cortical bone erosion and destruction of surrounding structures.5Paranasal sinus fungus balls are common in individuals who have normal immunologic function. Most fungus balls occur in the maxillary sinus. Common causative organisms include Aspergillus species, Alternaria, and Mucor. Treatment with endoscopic surgical removal is recommended.6Typical findings for fungus balls on CT include variable mucosal thickening and foci of metallic or calcific hyperdensities within an opacified sinus. The characteristic gross appearance is a friable, darkened mass with associated clay-like inspissated mucus. Histopathologic findings include dense accumulations of hyphae in concentric layers that form the fungus ball. Computed tomographic findings have a positive predictive value of 60%, whereas the gross appearance has a positive predictive value of nearly 100% for the histologic appearance of a fungus ball.7Unilateral sinus opacification may be related to a broad spectrum of diseases; however, coexisting disease processes within a single affected sinus are uncommon. Case reports have been published detailing presentations of a fungus ball within a mucocele of the sphenoid sinus8 and simultaneous appearance of an inverted papilloma and a fungus ball in the maxillary sinus.9 To our knowledge, this is the first reported case of concurrent invasive SCC and fungus ball of a unilateral maxillary sinus.

General

A man in his 60s had an 8-month history of right-sided nasal congestion and rhinorrhea. He had no clinically significant improvement in symptoms despite multiple courses of oral antibiotics. Over the previous 2 months, he had developed progressive right-sided facial swelling, pain, blurred vision, and a 6.8-kg weight loss. There was no history of immunocompromise or foreign travel. A computed tomographic (CT) scan at an outside hospital showed complete opacification and an invasive process centered in the right maxillary sinus. An endoscopic maxillary antrostomy and biopsy showed inflammatory changes and numerous fungal organisms consistent with Aspergillus species. The patient was started on treatment with intravenous antifungal and broad-spectrum antibiotics, and he was transferred for further evaluation and management. The patient’s examination was notable for right-sided facial and periorbital swelling, severe pain, and limitation of lateral gaze of the right eye. A repeated CT scan was completed (Figure).A-C, Computed tomographic images. A, Coronal view of the paranasal sinuses in bone windows showing near-complete opacification of the right maxillary sinus with soft-tissue thickening, a calcific focus, and associated erosion of the bony walls. B, Coronal view of the paranasal sinuses in soft-tissue windows. C, Axial view of the paranasal sinuses in bone windows.

what is your diagnosis?

What is your diagnosis?

Fungal ball and invasive squamous cell carcinoma

Chronic invasive fungal sinusitis

Invasive squamous cell carcinoma

Fungal ball

a

male

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2210371

A man in his 40s with a 10-year history of smoking 180 packs of cigarettes per year choked easily and had experienced a foreign body sensation in his throat for 6 months. He was a tour guide, a profession that requires speech. Because he experienced voice fatigue frequently, he visited a hospital for professional assistance. Fibroscopy showed a well-circumscribed mass of approximately 3 × 3 × 2 cm, with a smooth surface, located at the laryngeal side of the left aryepiglottic fold and covering nearby structures, such as the bilateral vocal cords and left pyriform sinus (Figure 1, A). A biopsy was performed, and the patient visited our institution (Taipei Veterans General Hospital) for further intervention. The laryngeal mass was removed through transoral laser microsurgery. The tumor was at the submucosa with focally ulcerated overlying epithelium. It was composed of adipocytes of various sizes in a fibromyxoid background. In the fibromyxoid areas, atypical spindle cells with hyperchromatic and enlarged nuclei were present, as well as scattered lipoblasts without areas of dedifferentiation (Figure 1, B). Immunohistochemically, the tumor exhibited substantial nuclear staining for both CDK4 and MDM2 and stains (Figure 1, C). What Is Your Diagnosis?

Hemangioma of the larynx

Well-differentiated liposarcoma of the larynx

Schwannoma of the larynx

Laryngocele of the larynx

B. Well-differentiated liposarcoma of the larynx

B

Well-differentiated liposarcoma of the larynx

Laryngeal cancers are the second most common type of head and neck cancer; however, they are mostly squamous cell carcinomas (SCCs). Sarcoma, unlike epithelial neoplasms, such as SCCs, is derived from mesenchymal tissue, and constitutes less than 1% of all human malignant neoplasms annually.1-3Liposarcoma constitutes 9% to 30% of all soft-tissue sarcomas in the human body. It is less common in the head and neck region (2%-9%).1-4 Only 2.2% of lesions are located in the larynx.1 The mean ages of patients with liposarcoma are 40 to 60 years, and there is a male predominance.4,5Liposarcomas are classified into 4 categories: atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS), dedifferentiated liposarcoma, myxoid liposarcoma, and pleomorphic liposarcoma. The most common type is the well-differentiated subtype, followed by myxoid type.1 ALT/WDLPS has a ring and giant marker chromosome, with amplification of the 12q13-15 region, including the MDM2 gene. Dedifferentiated liposarcoma, similar to ALT/WDLPS, often has a ring or giant marker chromosome with amplification of MDM2. The myxoid liposarcoma harbors t(12;16)(q13;p11) gene rearrangement in more than 90% of cases, leading to fusion of the DDIT3 and FUS genes. In addition, less than 5% of cases carry t(12;22)(q13;q12) gene rearrangement, which fuses DDIT3 with EWSR1 genes. Pleomorphic liposarcoma has not been found to carry specific genetic changes. It has a more complex cytogenetic profile that is more akin to that of other pleomorphic sarcomas. Generally, a well-differentiated subtype grows slowly and does not metastasize; patients with this condition have a favorable chance of survival if the tumor can be excised thoroughly. When the tumor grows in a location that does not allow it to be removed entirely, it can recur easily and may become a dedifferentiated subtype that metastasizes. These subtypes have a relatively poor outscome.3,6Well-differentiated liposarcoma is diagnosed according to the presence of a lipomatous tumor or a tumor with nonlipomatous part with septa or nodules, as revealed by computed tomography or magnetic resonance imaging. Generally, it is slow-growing, painless, and difficult to distinguish from benign lipoma. Therefore, numerous cases were diagnosed after surgery.The mainstay of the treatments for liposarcoma is surgical excision with proper margins. For liposarcoma in lymph nodes with a relatively low metastasis rate, routine neck dissection is not recommended.2,3,5 Achieving adequate margins in the head and neck region is sometimes difficult because of the abundance of complex and vital neurovascular structures and functional upper aerodigestive organs. Some authors2-5 have reported that postoperative adjuvant radiotherapy reduced the local recurrence rate from 60% to 40% without improving the overall survival and metastasis rates. However, the review from M. D. Anderson Cancer Center showed no difference in the local recurrence rate with or without adjuvant therapies.The 5-year disease survival rate for liposarcoma of the head and neck region was reported to be 72.8%, and that for well-differentiated liposarcoma was 85% to 100%.2,3 In the present case, the patient’s liposarcoma was treated through transoral laser microsurgery with negative margins. His wound had healed well 1 month after surgery (Figure 2), and he regained normal swallowing ability within 2 weeks. He did not receive adjuvant therapy.

General

A man in his 40s with a 10-year history of smoking 180 packs of cigarettes per year choked easily and had experienced a foreign body sensation in his throat for 6 months. He was a tour guide, a profession that requires speech. Because he experienced voice fatigue frequently, he visited a hospital for professional assistance. Fibroscopy showed a well-circumscribed mass of approximately 3 × 3 × 2 cm, with a smooth surface, located at the laryngeal side of the left aryepiglottic fold and covering nearby structures, such as the bilateral vocal cords and left pyriform sinus (Figure 1, A). A biopsy was performed, and the patient visited our institution (Taipei Veterans General Hospital) for further intervention. The laryngeal mass was removed through transoral laser microsurgery. The tumor was at the submucosa with focally ulcerated overlying epithelium. It was composed of adipocytes of various sizes in a fibromyxoid background. In the fibromyxoid areas, atypical spindle cells with hyperchromatic and enlarged nuclei were present, as well as scattered lipoblasts without areas of dedifferentiation (Figure 1, B). Immunohistochemically, the tumor exhibited substantial nuclear staining for both CDK4 and MDM2 and stains (Figure 1, C).

what is your diagnosis?

What is your diagnosis?

Well-differentiated liposarcoma of the larynx

Laryngocele of the larynx

Hemangioma of the larynx

Schwannoma of the larynx

a

male

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2210440

A teenage girl presented with new onset of bilateral upper extremity numbness and paresthesias. The rest of the clinical history and neurological examination was unremarkable. A magnetic resonance imaging (MRI) study of the brain and cervical spine obtained to evaluate for demyelinating disease demonstrated a normal brain and cervical cord, but an incidental T2 hyperintense lesion within the right pterygoid muscles was noted. On further consultation with the otolaryngology department, the patient stated that she had not experienced any sensation of a mass, and results from a focused otolaryngologic examination were also normal. A dedicated fifth cranial nerve MRI examination performed to better characterize the lesion revealed a well-defined, lobulated T2 hyperintense lesion within the right pterygoid muscles without mass effect, adjacent edema, or other invasive features (Figure, A). There was a small focus of signal void on the T2-weighted images, suspicious for tiny calcification. On gadolinium administration, there was sequential increased enhancement on the postcontrast T1-weighted axial images (Figure, B and C). Further imaging workup with single-proton emission computed tomography-CT (SPECT-CT) using technetium Tc 99m–labeled red blood cells (RBCs) demonstrated increased tracer pooling within the lesion (Figure, D).A-C, Magnetic resonance imaging studies (axial views) of a teenager with an incidental masticator space lesion. D, Single-proton emission computed tomographic image (axial view) using technetium Tc 99m–labeled red blood cells demonstrating increased tracer pooling within the lesion. What Is the Diagnosis?

Rhabdomyosarcoma

Venous malformation

Masticator space abscess

Chronic hematoma

B. Venous malformation

B

Venous malformation

A venous malformation is defined as a low-flow vascular malformation in the International Society for the Study of Vascular Anomalies Classification system.1 Approximately 40% of venous malformations occur in the head and neck region.2 These are present at birth and are generally discovered later in life, with location and depth affecting symptoms and presentation. The lesion in our patient was located within the pterygoid musculature of the masticator space and was asymptomatic. Other common locations of venous malformation in the head and neck include the periorbital space and the subcutaneous tissues.3 Venous malformations can be identified reliably using a combination of clinical presentation and imaging features and are considered “do not touch” lesions not needing a biopsy to establish the diagnosis.To identify a lesion as a venous malformation on cross-sectional imaging, it is imperative to know its characteristic imaging features. These include the presence of homogeneous regions of T2 hyperintensity (venous lakes), phleboliths (seen as signal voids on MRI and calcifications on CT), sequential contrast enhancement, often in a centripetal manner, and the absence of any invasive features, which were all were present in our patient, strongly supporting a diagnosis of venous malformation.2-4 Furthermore, increased blood pool activity as evidenced by focal increased activity on the technetium Tc 99m–labeled RBC SPECT study confirmed the diagnosis.Differential diagnosis of masticator space lesions can be broad and include vascular malformations, inflammatory, infectious, and neoplastic processes. The absence of any symptoms related to the lesion and the incidental nature of its detection were an important clue in our patient, because vascular malformations are most often asymptomatic. While inflammatory abnormalities related to dental infection are more common in the masticator space, these typically result in fever, pain, and/or trismus. Primary masticator space neoplasms, such as sarcoma, are rare and would also be expected to produce similar clinical symptoms. The lack of invasive features, such as edema or infiltration surrounding the mass and periostitis in the adjacent mandible, were also evidence against an inflammatory or neoplastic process. The imaging features in this case also exclude other vascular malformations. For example, the absence of vascular flow voids on T1- and T2-weighted sequences, as well as the presence of a discrete mass, differentiated the lesion from a high-flow arteriovenous malformation. In addition, the presence of diffuse enhancement precludes consideration of a lymphatic malformation, in which there should be no such internal enhancement. Another important differential consideration for an asymptomatic enhancing lesion in this particular location is an asymmetrically prominent pterygoid venous plexus, which is a normal anatomic variant that might be mistaken for an enhancing mass.5While the constellation of MRI findings were quite supportive of venous malformation in our patient, when in doubt, confirmation of the diagnosis can also be obtained using the uptake pattern of labeled RBCs on a tagged RBC scan (performed at the request of the patient in this instance). The technetium Tc 99m–labeled RBC scintigraphy using SPECT-CT has been established as a relatively accurate test for identifying hepatic venous malformations, often called “cavernous hemangiomas.”6,7 This imaging modality has also been shown to be highly accurate in the diagnosis of extracranial venous malformations.8Because the patient in this case had been completely asymptomatic, no treatment was offered. In symptomatic venous malformations in the head and neck, there are several treatment options that include a multidisciplinary approach based on lesion size and extent, such as laser therapy, embolization, percutaneous sclerotherapy, or surgical resection.4,9

General

A teenage girl presented with new onset of bilateral upper extremity numbness and paresthesias. The rest of the clinical history and neurological examination was unremarkable. A magnetic resonance imaging (MRI) study of the brain and cervical spine obtained to evaluate for demyelinating disease demonstrated a normal brain and cervical cord, but an incidental T2 hyperintense lesion within the right pterygoid muscles was noted. On further consultation with the otolaryngology department, the patient stated that she had not experienced any sensation of a mass, and results from a focused otolaryngologic examination were also normal. A dedicated fifth cranial nerve MRI examination performed to better characterize the lesion revealed a well-defined, lobulated T2 hyperintense lesion within the right pterygoid muscles without mass effect, adjacent edema, or other invasive features (Figure, A). There was a small focus of signal void on the T2-weighted images, suspicious for tiny calcification. On gadolinium administration, there was sequential increased enhancement on the postcontrast T1-weighted axial images (Figure, B and C). Further imaging workup with single-proton emission computed tomography-CT (SPECT-CT) using technetium Tc 99m–labeled red blood cells (RBCs) demonstrated increased tracer pooling within the lesion (Figure, D).A-C, Magnetic resonance imaging studies (axial views) of a teenager with an incidental masticator space lesion. D, Single-proton emission computed tomographic image (axial view) using technetium Tc 99m–labeled red blood cells demonstrating increased tracer pooling within the lesion.

what is the diagnosis?

What is your diagnosis?

Venous malformation

Masticator space abscess

Rhabdomyosarcoma

Chronic hematoma

a

female

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2213734

A woman in her 50s presented with dysphagia and frequent throat clearing. A right pyriform sinus mass was seen on fiber-optic laryngoscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the finding of a hypopharyngeal mass. The patient underwent an endoscopic laser excision. Immunohistochemical stains revealed tumor cells that were focally positive for myogenin and diffusely positive for desmin and myoglobin. An MRI scan obtained 1 month postoperatively demonstrated a persistent mass or swelling. The patient continued to experience dysphagia, globus, and a choking sensation when coughing. On fiber-optic examination, right pyriform sinus fullness was visualized. During operative laryngoscopy, no mass was identified. An interval MRI demonstrated a 2-cm soft-tissue mass in the cervical esophagus (Figure, A). Using rigid suspension laryngoscopy, we identified a large, smooth-walled ovoid mass herniating from the cervical esophageal opening. A mucosal stalk anchored the mass to the lateral pyriform sinus wall. Endoscopic snare cautery was used to excise the mass. The tumor was well-defined, solitary, tan-red, and composed of sheets of large, round-to-polygonal cells with marked eosinophilic, granular cytoplasm (Figure, B). Most tumor cells exhibited peripherally or centrally located vesicular nuclei with prominent nucleoli. Peripheral intracellular vacuoles indenting the cytoplasm were seen, which represent a processing artifact due to intracellular glycogen loss (Figure, C).A, Axial contrast-enhanced spoiled gradient magnetic resonance image. B and C, Histopathological images. B, Hematoxylin-eosin, original magnification ×20. C, Hematoxylin-eosin, original magnification ×40. What Is Your Diagnosis?

Paraganglioma

Adult rhabdomyoma

Squamous cell carcinoma

Sarcoidosis

B. Adult rhabdomyoma

B

Adult rhabdomyoma

Rhabdomyomas are benign tumors of striated muscle. Rhabdomyomas occur less frequently than rhabdomyosarcomas and account for less than 2% of all striated muscle tumors.1 Rhabdomyomas are classified by location as cardiac and extracardiac. Cardiac rhabdomyomas are more common than extracardiac rhabdomyomas and are the most common cardiac tumor in infants. Cardiac rhabdomyomas are commonly associated with tuberous sclerosis.2 Extracardiac forms can further be divided into 3 morphological subtypes: adult, fetal, and genital.Adult rhabdomyoma (ARM) is the most common and typically presents as a solitary mass in the head and neck region of adults.1,3 Patients are usually older than 40 years (median age, 60 years), and men are affected 3 to 4 times more commonly than women. The tumor is thought to arise from the third and fourth branchial arches, accounting for the head and neck prevalence of this tumor.1 They have been reported to occur in the oral cavity, pharynx, and larynx.3 Symptoms are often related to location and can include airway obstruction, dysphagia, hoarseness, odynophagia, eustachian tube dysfunction, and aspiration. There are no reported instances of rhabdomyoma giving rise to rhabdomyosarcoma; therefore, the treatment of choice for this benign lesion is complete surgical extirpation.4-6Approximately 7% of ARMs are multifocal at diagnosis.4 Since 1948, 26 cases of multifocal ARM have been reported. Occasionally, the second site becomes evident only years after the initial diagnosis.7 After excision, the local recurrence rate is estimated to be 42% and is presumed to be due to incomplete excision.4To our knowledge, only 4 cases of esophageal ARM can be found in the literature. The first occurred in an 8-year-old boy and was located in the cervical esophagus.8 The second occurred in a 21-year-old woman and was located in the middle third of the esophagus. Both underwent excision via an open neck exploration. The third case occurred in a 30-year-old man and was located in the distal esophagus. The mass required a lateral thoracotomy for excision.9 The fourth case occurred in a 72-year-old woman who had a symptomatic left aryepiglottic fold rhabdomyoma and an asymptomatic cervical esophageal rhabdomyoma. She underwent an endoscopic laser resection of the laryngeal lesion and later underwent a microsurgical excision of the esophageal lesion via an external approach.5Macroscopically, these tumors are soft, well-circumscribed, lobulated, and tan-gray lesions.4,5,7 Histologically, they are composed of well-demarcated, unencapsulated lobules with closely packed, large polygonal cells and scant stroma. The tumor cells have a small, round, centrally or peripherally located nucleus with prominent nucleoli and abundant, eosinophilic, granular, or vacuolated cytoplasm. Most tumor cells stain for myoglobin, muscle-specific actin, and desmin, which aids in the differentiation from other tumors with similar appearance (eg, granular cell tumor, hibernoma, oncocytoma, paraganglioma).4This is the fifth case of esophageal ARM reported. It is unclear if this was persistent disease, recurrence, or a truly separate focus. Nonetheless, to our knowledge, this is the first case of a purely endoluminal esophageal ARM and is the first case treated endoscopically. In all previous cases, patients underwent excision using an external approach. In this case, the tumor was located just inferior to the cricopharyngeus. We felt that complete excision via an external approach would likely result in a functional deficit of swallow and could be complicated by a salivary leak or esophageal stricture. Because this is a benign lesion, we felt it appropriate to consider a minimally invasive, endoscopic resection. While microscopic disease remained, we were able to avoid the morbidity associated with an open surgical resection. Though the recurrence rate may be increased, a recurrence likely will be amenable to another minimally invasive, endoscopic excision.

General

A woman in her 50s presented with dysphagia and frequent throat clearing. A right pyriform sinus mass was seen on fiber-optic laryngoscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the finding of a hypopharyngeal mass. The patient underwent an endoscopic laser excision. Immunohistochemical stains revealed tumor cells that were focally positive for myogenin and diffusely positive for desmin and myoglobin. An MRI scan obtained 1 month postoperatively demonstrated a persistent mass or swelling. The patient continued to experience dysphagia, globus, and a choking sensation when coughing. On fiber-optic examination, right pyriform sinus fullness was visualized. During operative laryngoscopy, no mass was identified. An interval MRI demonstrated a 2-cm soft-tissue mass in the cervical esophagus (Figure, A). Using rigid suspension laryngoscopy, we identified a large, smooth-walled ovoid mass herniating from the cervical esophageal opening. A mucosal stalk anchored the mass to the lateral pyriform sinus wall. Endoscopic snare cautery was used to excise the mass. The tumor was well-defined, solitary, tan-red, and composed of sheets of large, round-to-polygonal cells with marked eosinophilic, granular cytoplasm (Figure, B). Most tumor cells exhibited peripherally or centrally located vesicular nuclei with prominent nucleoli. Peripheral intracellular vacuoles indenting the cytoplasm were seen, which represent a processing artifact due to intracellular glycogen loss (Figure, C).A, Axial contrast-enhanced spoiled gradient magnetic resonance image. B and C, Histopathological images. B, Hematoxylin-eosin, original magnification ×20. C, Hematoxylin-eosin, original magnification ×40.

what is your diagnosis?

What is your diagnosis?

Adult rhabdomyoma

Paraganglioma

Squamous cell carcinoma

Sarcoidosis

a

female

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2250428

A man in his 50s presented with a facial mass growing over 1 year, with 28.5-kg weight loss due to poor oral intake. He reported a 44–pack-year smoking history and remote alcohol abuse. On physical examination he had a 10-cm right-sided facial mass extending under the auricle from the mastoid to the zygoma and inferiorly to the angle of the mandible. The mass was firm, mildly tender, but without overlying skin changes or cervical lymphadenopathy. Computed tomographic (CT) and magnetic resonance imaging (MRI) scans showed maxillary sinus compression with partial destruction of the zygomatic arch, mandible, and orbital floor (Figure, A and B). The mass extended into the right pterygopalatine fossa, disrupting the floor of the middle cranial fossa and widening the foramen ovale. A core biopsy specimen revealed spindle cell proliferation with abundant collagen that stained focally with CD34, smooth muscle actin, and Bcl-2. The Figure, C, shows a gross pathologic image after excision of the mass.Histopathologic findings demonstrated spindle cells arranged in long fascicles with abundant interstitial collagen (Figure, D). Tumor cells exhibited central, oval nuclei, and moderate amounts of pale-pink cytoplasm with indistinct borders. There was no increased or atypical mitosis, necrosis, or vascular invasion. Immunostaining demonstrated strong nuclear staining for β-catenin antibody and was positive for smooth muscle actin antibody, while stains for desmin, pan-keratin, S-100, CD34, and Bcl-2 antibodies were negative. The Ki67 index was less than 1%.A, Coronal computed tomographic scan of the mass. B, Postcontrast axial T1-weighted magnetic resonance image. C, Gross pathologic image of the mass. D, Histopathologic image of excised tissue (hematoxylin-eosin, original magnification ×40). What Is Your Diagnosis?

Pleomorphic adenoma

Desmoid tumor

Fibrosarcoma

Rhabdomyosarcoma

B. Desmoid tumor

B

Desmoid tumor

Desmoid tumors, also called aggressive fibromatoses, are rare, locally aggressive soft-tissue tumors that occur in 2 to 4 cases per million per year. They are categorized as benign neoplasms owing to their lack of mitotic activity or metastatic potential. However, some authors1 consider them malignant tumors owing to their aggressive behavior. The median age of affected patients is 37 years.2 Presentation is largely due to mass effect and local destruction of organs. Most present in the abdomen and abdominal wall. Only 12% of desmoid tumors presents in the head and neck.3 Of these, most present at the base of the neck and perivertebral space.4The etiology of desmoid tumors remains controversial. Some postulate that estrogen may be involved. Estrogen and progesterone receptors can be found in 30% of tumors. Some series demonstrate increased incidence in pregnant women, and case reports have also demonstrated women developing desmoid tumors after starting oral contraceptives.5 More recent series suggest there is no association with pregnancy and that this association is even less relevant for desmoid tumors of the head and neck. Traumatic history can be elicited in 25% of cases. However, this association is questionable because these are clonal disorders rather than reactive inflammatory proliferations.6Desmoid tumors are associated with syndromes involving inactivating mutations in the APC gene, a tumor suppressor that negatively regulates the Wnt signaling pathway. These syndromes include familial adenomatous polyposis, hereditary desmoid disease, and familial infiltrative fibromatosis.7 However, most patients have sporadic tumors, which are associated with activating mutations in β-catenin, a positive regulator of the Wnt pathway.8Imaging helps to determine the true size of these tumors and to evaluate local invasion into surrounding structures such as bone and the skull base in order to plan the resection.5 On CT scans they are isodense to hyperdense relative to muscle, and they do not enhance significantly with contrast.4 Although MRI has little value in determining margins, it is helpful in delineating relationships with neurovascular structures, particularly at the skull base.4 These lesions demonstrate wide variability in signal intensity on MRI, although most demonstrate marked enhancement on contrast-MRI along with nonenhancing bands, the latter of which are correlated with hypocellular areas with dense collagen stroma on histopathologic examination.4 These tumors cannot be distinguished from other soft-tissue tumors on imaging alone.The differential diagnosis of desmoid tumors of the head and neck includes solitary fibrous tumor, fibrosarcomas, leiomyomas, low-grade fibromyxoid sarcoma, neurofibroma, and schwannomas. Grossly, they are firm, fibrous, and often infiltrative into adjacent tissue. Although they may appear encapsulated, microscopic invasion often extends beyond the apparent capsule.5 Microscopically, they are characterized by spindle cells representing mesenchymal fibroblastic and myofibroblastic cells in a dense collagenous stroma. Desmoid tumors have less mitotic activity, smaller nucleus to cytoplasm ratio, and less vascularity than fibrosarcomas.5 Extra-abdominal desmoid tumors demonstrate nuclear translocation of β-catenin and stain positively for cathepsin D, actin, desmin, and vimentin.9,10 A minority stains positively for somatostatin, androgen receptor, estrogen receptor β, and Ki-67.10The behavior of these tumors can vary from multiple local recurrences with local destruction, stability after a period of growth, and regression.2 Up to 40% to 60% of desmoids recur, mostly within 2 years of resection. However, rates of recurrence have decreased in the setting of postoperative radiation and systemic therapy.2 Potential medical therapies have limited benefits, but chemotherapy, antiestrogen medications, nonsteroidal anti-inflammatory drugs, and imatinib are options to consider. Younger age at presentation, larger tumor size, and extra-abdominal tumors are associated with poorer survival rates.2

General

A man in his 50s presented with a facial mass growing over 1 year, with 28.5-kg weight loss due to poor oral intake. He reported a 44–pack-year smoking history and remote alcohol abuse. On physical examination he had a 10-cm right-sided facial mass extending under the auricle from the mastoid to the zygoma and inferiorly to the angle of the mandible. The mass was firm, mildly tender, but without overlying skin changes or cervical lymphadenopathy. Computed tomographic (CT) and magnetic resonance imaging (MRI) scans showed maxillary sinus compression with partial destruction of the zygomatic arch, mandible, and orbital floor (Figure, A and B). The mass extended into the right pterygopalatine fossa, disrupting the floor of the middle cranial fossa and widening the foramen ovale. A core biopsy specimen revealed spindle cell proliferation with abundant collagen that stained focally with CD34, smooth muscle actin, and Bcl-2. The Figure, C, shows a gross pathologic image after excision of the mass.Histopathologic findings demonstrated spindle cells arranged in long fascicles with abundant interstitial collagen (Figure, D). Tumor cells exhibited central, oval nuclei, and moderate amounts of pale-pink cytoplasm with indistinct borders. There was no increased or atypical mitosis, necrosis, or vascular invasion. Immunostaining demonstrated strong nuclear staining for β-catenin antibody and was positive for smooth muscle actin antibody, while stains for desmin, pan-keratin, S-100, CD34, and Bcl-2 antibodies were negative. The Ki67 index was less than 1%.A, Coronal computed tomographic scan of the mass. B, Postcontrast axial T1-weighted magnetic resonance image. C, Gross pathologic image of the mass. D, Histopathologic image of excised tissue (hematoxylin-eosin, original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Fibrosarcoma

Rhabdomyosarcoma

Desmoid tumor

Pleomorphic adenoma

c

male

51-60

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2246278

A man in his 40s presented with sudden left-sided abdominal pain that was sharp, severe, and associated with emesis. He denied fevers, dizziness, or recent trauma. He had no notable medical or surgical history. He was afebrile with normal vital signs. He was well nourished, alert, and in no acute distress. Results of an abdominal examination revealed normoactive bowel sounds, no distention, but tenderness on the left side. Computed tomography (CT) of the abdomen and pelvis with intravenous contrast revealed a 12 × 13 × 11-cm left-sided adrenal mass (Figure 1). Results of laboratory examination revealed plasma levels of metanephrines, normetanephrines, cortisol, renin, and aldosterone within reference limits. What Is Your Diagnosis?

Adrenal liposarcoma

Renal hamartoma

Adrenal myelolipoma

Nonfunctional paraganglioma

C. Adrenal myelolipoma

C

Adrenal myelolipoma

Given the hemorrhage and the severe symptoms, the patient underwent resection, although CT findings of bulk fat within a circumscribed adrenal mass suggested a benign adrenal myelolipoma (AML). Intraoperative findings included discrete borders without invasion of surrounding structures, except for the posterior aspect, where approximately 600 to 700 mL of clot was found (Figure 2), consistent with a ruptured AML. The diagnosis was confirmed by final results of a pathologic examination.Adrenal myelolipomas are uncommon, benign tumors composed of mature adipose tissue and hematopoietic elements. They are not generally associated with endocrinopathies or with malignant potential. Incidence ranges from 0.06% to 0.20%, and they account for 2.6% to 7.0% of all primary adrenal tumors without convincing sex predilection.1,2 In an Armed Forces Institute of Pathology series (1981-1997) of 86 AMLs in 74 patients with a mean age of approximately 55 (range, 28-77) years, AMLs were more than 3-fold more likely to be right than left sided.2,3Although the most common symptoms are abdominal and flank pain, AMLs can present as an acute abdomen after tumor hemorrhage, which appears to be more likely in lesions larger than 10 cm and 9-fold more likely in right- than in left-sided lesions.2 Diagnosis may be made by CT showing a round, well-demarcated, encapsulated adrenal mass containing adipose tissue similar in attenuation to retroperitoneal fat. Magnetic resonance imaging (MRI) typically shows a circumscribed, solitary adrenal mass with areas of T1-weighted hyperintensity (fat) demonstrating signal dropout on fat-saturated T1-weighted sequences. The myelogenous portion of the lesion varies in density on CT (usually >20 Hounsfield units) and signal intensity (usually hyperintense on T2-weighted MRI). Despite the ability to diagnose this benign lesion on CT and MRI, resection may be warranted for symptomatic lesions or for those of diagnostic uncertainty.4

Surgery

A man in his 40s presented with sudden left-sided abdominal pain that was sharp, severe, and associated with emesis. He denied fevers, dizziness, or recent trauma. He had no notable medical or surgical history. He was afebrile with normal vital signs. He was well nourished, alert, and in no acute distress. Results of an abdominal examination revealed normoactive bowel sounds, no distention, but tenderness on the left side. Computed tomography (CT) of the abdomen and pelvis with intravenous contrast revealed a 12 × 13 × 11-cm left-sided adrenal mass (Figure 1). Results of laboratory examination revealed plasma levels of metanephrines, normetanephrines, cortisol, renin, and aldosterone within reference limits.

what is your diagnosis?

What is your diagnosis?

Adrenal myelolipoma

Adrenal liposarcoma

Nonfunctional paraganglioma

Renal hamartoma

a

male

41-50

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2280710

A man in his mid-20s with a history of alcohol abuse presented with abdominal pain after 3 days of drinking. He described the pain as a sharp, left upper-quadrant pain migrating to the epigastric region for 24 hours. The patient had a history of multiple episodes of hematemesis attributed to alcoholic gastritis; however, at this admission, he indicated he had not experienced vomiting. He admitted to early satiety over the past few months. Physical examination revealed a soft nondistended abdomen, but it was very tender in the epigastric region without rebound or guarding. There was no palpable mass. Elevated results of liver function tests, as well as amylase and lipase levels consistent with alcoholic pancreatitis, were noted. Magnetic resonance imaging, computed tomographic imaging, and upper endoscopy findings are shown in Figure 1. Biopsy results of the mass were reported as normal gastric mucosa.Diagnostic imaging. A, Computed tomographic scan and magnetic resonance imaging (inset) demonstrating a heterogeneous mass lesion in the fundus and body of the stomach. B, Upper endoscopic image directly visualizing the mass intruding into the lumen of the stomach. What Is Your Diagnosis?

Leiomyosarcoma

Gastrointestinal stromal tumor

Gastric duplication

Pancreatic pseudocyst

C. Gastric duplication

C

Gastric duplication

Initial abdominal and pelvic computed tomographic and magnetic resonance imaging studies demonstrated a large (9.8 × 7.4 × 7.6-cm) heterogeneous mass located in the fundus and body of the stomach with areas of enhancement, suspicious for a possible gastrointestinal stromal tumor. On upper endoscopy, the mass occupied the upper half of the stomach, including the gastroesophageal junction, but did not extend proximally into the esophagus. Specimens obtained during progressively deeper biopsies on 2 successive occasions revealed no pathologic diagnosis.Preoperatively, endoscopic ultrasonography with fine-needle aspiration biopsy was considered.1,2 Social issues prevented the patient from undergoing this test. The mass was surgically resected for diagnostic and therapeutic purposes. The patient recovered well postoperatively and was discharged home on hospital day 8. Final pathology examination revealed this lesion to be composed of stomach duplication tissue, confirming a diagnosis of gastric duplication cyst (Figure 2).Gross pathologic examination of the specimen demonstrates a noncommunicating gastric duplication cyst. The inset demonstrates gastric mucosal lining on either side of the gastric duplication wall (hematoxylin-eosin; original magnification ×20).Gastrointestinal duplication cysts are a rare congenital anomaly, accounting for approximately 4% of all intestinal duplications. 3,4 In 1959, Rowling5 proposed 3 morphologic criteria for the correct diagnosis of gastric duplication cysts: first, the cyst must be contiguous with the stomach wall; second, the cyst must be surrounded by at least 1 coat of smooth muscle, fusing with muscularis propria of the stomach; and third, the cyst must be lined with typical gastric mucosa. Figure 2 depicts normal gastric mucosa, a common muscularis, and attenuated gastric mucosa of the duplication on the right. The clinical presentation generally includes bowel obstruction or gastrointestinal bleeding early in life; torsion, hemorrhage, pancreatitis, and fistula formation may also occur.3,5-8 Rarely does gastric duplication present in adulthood.9 Malignant transformation has been identified in patients with gastric duplication; thus, complete resection is recommended at the time of diagnosis.10There was an associated small, noncommunicating esophageal duplication as noted. Findings at surgery included a large proximal gastric mass fibrotically adherent to the diaphragm in a desmoplastic and presumed neoplastic fashion. Total gastrectomy with removal of adherent diaphragm was undertaken with Roux-en-Y esophagojejunostomy. We believe the chronic, unopposed acid production within the excluded gastric remnant led to full-thickness ulceration, perforation, and adherence of the stomach to the diaphragm and retroperitoneum.

Surgery

A man in his mid-20s with a history of alcohol abuse presented with abdominal pain after 3 days of drinking. He described the pain as a sharp, left upper-quadrant pain migrating to the epigastric region for 24 hours. The patient had a history of multiple episodes of hematemesis attributed to alcoholic gastritis; however, at this admission, he indicated he had not experienced vomiting. He admitted to early satiety over the past few months. Physical examination revealed a soft nondistended abdomen, but it was very tender in the epigastric region without rebound or guarding. There was no palpable mass. Elevated results of liver function tests, as well as amylase and lipase levels consistent with alcoholic pancreatitis, were noted. Magnetic resonance imaging, computed tomographic imaging, and upper endoscopy findings are shown in Figure 1. Biopsy results of the mass were reported as normal gastric mucosa.Diagnostic imaging. A, Computed tomographic scan and magnetic resonance imaging (inset) demonstrating a heterogeneous mass lesion in the fundus and body of the stomach. B, Upper endoscopic image directly visualizing the mass intruding into the lumen of the stomach.

what is your diagnosis?

What is your diagnosis?

Gastrointestinal stromal tumor

Gastric duplication

Pancreatic pseudocyst

Leiomyosarcoma

b

male

21-30

original

https://jamanetwork.com/journals/jama/fullarticle/2293273

An 87-year-old woman with a history of open-angle glaucoma in her right eye presented with longer, thicker eyelashes on the right side compared with the left. Her irises were also different colors: the right iris was brown, and the left was hazel (green-brown) (Figure 1). The patient had noticed a gradual darkening of her right iris and lengthening of her eyelashes during the last year but denied visual changes or foreign-body sensation. Her medical history included a cerebrovascular accident, hypercholesterolemia, and hypertension and a remote history of breast cancer treated with lumpectomy and radiation therapy. Her medications included bimatoprost, atenolol, atorvastatin, and clopidogrel.A, Upper facial profile showed iris heterochromia and eyelash hypertrichosis. B, Right eyelid and eye showed thick, long eyelashes with brown iris. C, Left eyelid and eye showed thin, shorter eyelashes with hazel (green-brown) iris.Order serologic studies including erythrocyte sedimentation rate, antinuclear antibody titers, complete blood cell count, and basic chemistry panelRefer to an ophthalmologist urgently for slit-lamp and dilated examination What Would You Do Next?

Perform eye and orbit computed tomography

Order serologic studies including erythrocyte sedimentation rate, antinuclear antibody titers, complete blood cell count, and basic chemistry panel

Reassure the patient

Refer to an ophthalmologist urgently for slit-lamp and dilated examination

Iris hyperpigmentation and eyelash hypertrichosis secondary to topical use of a prostaglandin analogue (PGA)

C

Reassure the patient

Iris hyperpigmentation and eyelash hypertrichosis are adverse effects of bimatoprost, a PGA used for open-angle glaucoma.Because this patient had glaucoma in only 1 eye, a history and review of medications revealed the cause to be unilateral use of the PGA bimatoprost. Approaches such as serologic workup and imaging could be indicated if the history or review of systems or medications suggest other etiologies, but these approaches should not be the first step in workup. Should such causes be suspected, prompt referral to an ophthalmologist would be warranted.Prostaglandin analogues are commonly used for treatment of open-angle glaucoma, a leading cause of irreversible blindness worldwide.1 Benign effects associated with bimatoprost include eye pruritus, conjunctival hyperemia, periorbital lipodystrophy, and darkening of the iris, eyelashes, and periocular skin.2,3 Changes related to lipodystrophy include periorbital fat atrophy, deepening of the upper eyelid sulcus, relative enophthalmos (posterior displacement of the globe into the orbit), and loss of lower eyelid fullness. Darkening of iris pigmentation and eyelash hypertrichosis are classic findings associated with use of PGAs (occuring in 1.5%-1.9% and 42.6%-53.6% of patients using bimatoprost, respectively).2 With the exception of permanent changes in iris color, the other effects may be reversible following discontinuation of the agent. Similar effects have been noted to occur with other PGAs, including latanoprost and travoprost, but are more severe in bimatoprost users.4Topical bimatoprost is approved by the FDA for cosmetic eyelash growth. However, outside the ophthalmology and dermatology communities, it is not widely known that bimatoprost and other PGAs can cause not only eyelash growth but also irreversible changes in iris color, skin hyperpigmentation, and lipodystrophy. As these features can also be associated with inflammation, infection, hemorrhage, and malignancies, a familiarity with medication-associated changes of the eye and surrounding structures remains important for the general practitioner.The pigmentation changes associated with use of PGAs are a result of increased melanin content in melanocytes present in the iris, eyelash hair follicle, and skin.5,6 Hypertrichosis is attributable to stimulated transition of hair follicles from telogen (resting phase of growth) to anagen (growing phase).7The differential diagnosis of iris heterochromia includes sympathetic dysfunction (eg, congenital Horner syndrome or neuroblastoma in children), retained intraocular metals (eg, iron, copper) secondary to trauma, intraocular hemorrhage (eg, traumatic hyphema, neovascular glaucoma), local and systemic inflammation (eg, Fuch heterochromatic iridocyclitis, sarcoidosis), and neoplasms (eg, metastases, iris nevus, uveal melanoma, lymphoma, leukemia, retinoblastoma).8 Iris heterochromia can also been seen in hereditary conditions such as Waardenberg syndrome, a group of genetic conditions associated with hearing loss and pigmentation changes of the hair, skin, and eyes.9Eyelash hypertrichosis has a broad differential diagnosis, including congenital disorders (eg, Oliver-McFarlane syndrome involving long eyelashes and pigmentary degeneration of the retina; oculocutaneous albinism type 1, characterized by hypopigmentation and reduced iris pigment); acquired inflammatory, infectious causes (eg, dermatomyositis, systemic lupus erythematosus, HIV, paraneoplastic syndrome); and findings associated with use of interferons, anticonvulsants (topiramate), immunosuppressives (cyclosporine, tacrolimus), and antiepidermal growth factor agents (cetuximab, erlotinib, gefitinib).10The patient was reassured that the condition was related to use of a PGA, since the unilateral changes occurred after initiation of medication. Because these changes are generally benign, the patient continues PGA use, and her glaucoma remains stable.

General

An 87-year-old woman with a history of open-angle glaucoma in her right eye presented with longer, thicker eyelashes on the right side compared with the left. Her irises were also different colors: the right iris was brown, and the left was hazel (green-brown) (Figure 1). The patient had noticed a gradual darkening of her right iris and lengthening of her eyelashes during the last year but denied visual changes or foreign-body sensation. Her medical history included a cerebrovascular accident, hypercholesterolemia, and hypertension and a remote history of breast cancer treated with lumpectomy and radiation therapy. Her medications included bimatoprost, atenolol, atorvastatin, and clopidogrel.A, Upper facial profile showed iris heterochromia and eyelash hypertrichosis. B, Right eyelid and eye showed thick, long eyelashes with brown iris. C, Left eyelid and eye showed thin, shorter eyelashes with hazel (green-brown) iris.Order serologic studies including erythrocyte sedimentation rate, antinuclear antibody titers, complete blood cell count, and basic chemistry panelRefer to an ophthalmologist urgently for slit-lamp and dilated examination

what would you do next?

What would you do next?

Order serologic studies including erythrocyte sedimentation rate, antinuclear antibody titers, complete blood cell count, and basic chemistry panel

Reassure the patient

Refer to an ophthalmologist urgently for slit-lamp and dilated examination

Perform eye and orbit computed tomography

b

female

81-90

original

https://jamanetwork.com/journals/jama/fullarticle/2281674

A previously healthy 32-year-old man presented with 27-kg weight loss over the course of 1 year, dyspnea, nonproductive cough, subjective fevers, night sweats, and painful hematuria. He had tattoos placed 3 years before presentation and noticed skin lesions confined to his tattoos 1 year ago. His medical history includes a 5-pack-year smoking history but no illicit drug or alcohol use, promiscuous sexual activity, or recent travel outside of the United States. He works with Mexican immigrants. Vital signs revealed temperature, 36.7°C; heart rate, 76/min; respiratory rate, 17/min; blood pressure, 128/82 mm Hg; and oxygen saturation, 99% on room air. Examination revealed a well-appearing patient with clear lungs bilaterally and numerous scattered red to violaceous macules and papules along his tattoos (Figure 1, left). Complete blood cell count showed hemoglobin level, 11.3 g/dL; white blood cell count, 4.5 ×103/mm3; and platelet count, 189 ×103/mm3. Results of a complete metabolic panel were normal except for elevated levels of blood urea nitrogen (33 mg/dL), creatinine (3.0 mg/dL), and ionized calcium (6.7 mg/dL). Urinalysis showed gross hematuria, with 10 to 20 red blood cells per high-power field and 0 to 5 white blood cells per high-power field. Chest radiography showed bilateral hilar lymphadenopathy without consolidations, nodules, or cavitary lesions (Figure 1, right). Computed tomography of the abdomen showed right-sided hydronephrosis with an obstructive stone.Left, Numerous scattered red to violaceous macules and papules along patient’s tattoos. Right, Chest radiograph showing bilateral hilar lymphadenopathy. What Would You Do Next?

Prescribe topical corticosteroids

Obtain a biopsy of the skin lesion

Prescribe oral antibiotics

Order respiratory isolation and rule out tuberculosis

Sarcoidosis

B

Obtain a biopsy of the skin lesion

B. Obtain a biopsy of the skin lesionThe key features of this patient’s clinical presentation that are concerning for sarcoidosis include hypercalcemia, bilateral hilar lymphadenopathy, and skin lesions along his tattoos. The best way to diagnose sarcoidosis is to biopsy affected tissue. Topical corticosteroids and antibiotics are not used for systemic sarcoidosis. The patient’s chest radiograph is not suggestive of tuberculosis.Sarcoidosis, a noninfectious process, commonly involves the lungs, eyes, and skin but can affect any organ. Sarcoidosis is diagnosed by clinical, radiological, and histological findings. A biopsy is usually obtained from the lymph nodes, lacrimal glands, or skin, and histology shows noncaseating granulomas (Figure 2). Löfgren syndrome is a triad of erythema nodosum, bilateral hilar lymphadenopathy, and migratory polyarthralgia occurring in 9% to 34% of patients with sarcoidosis.1 Presence of all features of Löfgren syndrome has a 95% specificity for sarcoidosis, allowing clinical diagnosis without biopsy.2Biopsy of skin from left shoulder. The nodularity of the skin is caused by large superficial noncaseating (“naked”) granulomas within the dermis, consisting of epithelioid histiocytes with few surrounding lymphocytes (hematoxylin-eosin, original magnification ×110).The pathogenesis of granuloma formation in sarcoidosis is thought to occur from a genetically dysregulated TH1 response to an extrinsic antigen causing inflammation.3 Granulomas are compact, centrally organized collections of macrophages and epithelioid cells encircled by lymphocytes.4 Granulomas form to confine pathogens, restrict inflammation, and protect surrounding tissue. Sarcoid granulomas produce angiotensin-converting enzyme (ACE), but measurement of ACE levels in 1 study5 lacked both sensitivity (58.1%) and specificity (83.8%) in diagnosing sarcoidosis. Activation of T cells within granulomas produces 1, 25-dihydroxyvitamin D3, leading to hypercalcemia, which can then lead to calcium oxalate nephrolithiasis. Abnormal calcium metabolism is also seen in other granulomatous diseases such as tuberculosis.Skin manifestations account for 25% to 30% of cases.6 Sarcoid lesions can present as macules, papules, plaques, nodules, infiltrated scars, and lupus pernio (erythematous-violaceous nodules or plaques on the cheeks, ears, forehead, or nose).7 Rarely, sarcoid granulomas develop in old tattoos or scars, resulting in papules that are firm, raised, and edematous. These lesions can present months to decades after tattoo placement and are likely caused by retention of an exogenous antigen or foreign body or an overactive immune response in a previously injured region.8 Many patients are asymptomatic, with lymphadenopathy detected incidentally on routine chest radiography leading to the diagnosis of sarcoidosis. Differential diagnosis of the skin lesions includes drug eruptions, T-cell lymphoma, and tuberculosis.Initial therapy is guided by organ system and clinical status. An international expert panel suggested initiating treatment for systemic sarcoidosis with oral prednisone at 20 to 40 mg/d, with reevaluation after 1 to 3 months.9 Lack of response after 3 months suggests the presence of irreversible fibrotic disease, nonadherence to therapy, or an inadequate dose of prednisone.9 In most people, sarcoidosis improves with treatment, but in about one-third of individuals, it becomes chronic or progressive.10 Less than 5% of affected individuals die of sarcoidosis, and death is usually attributable to pulmonary fibrosis with respiratory failure, cardiomyopathy, or cognitive dysfunction.4The patient underwent perihilar lymph node and skin biopsy, both of which revealed noncaseating granulomas. He had an elevated ACE level of 299 U/L, testing for HIV was negative, and quantiferon gold testing was negative for tuberculosis. Initial pulmonary function tests revealed a restrictive lung pattern. The patient was treated with 3 months of oral prednisone, after which his skin lesions reduced in size by 50% and pulmonary function tests showed improvement of lung function. The patient had a ureteral stent placed for his calcium oxalate stone, with improvement in creatinine level and no stone recurrence.

General

A previously healthy 32-year-old man presented with 27-kg weight loss over the course of 1 year, dyspnea, nonproductive cough, subjective fevers, night sweats, and painful hematuria. He had tattoos placed 3 years before presentation and noticed skin lesions confined to his tattoos 1 year ago. His medical history includes a 5-pack-year smoking history but no illicit drug or alcohol use, promiscuous sexual activity, or recent travel outside of the United States. He works with Mexican immigrants. Vital signs revealed temperature, 36.7°C; heart rate, 76/min; respiratory rate, 17/min; blood pressure, 128/82 mm Hg; and oxygen saturation, 99% on room air. Examination revealed a well-appearing patient with clear lungs bilaterally and numerous scattered red to violaceous macules and papules along his tattoos (Figure 1, left). Complete blood cell count showed hemoglobin level, 11.3 g/dL; white blood cell count, 4.5 ×103/mm3; and platelet count, 189 ×103/mm3. Results of a complete metabolic panel were normal except for elevated levels of blood urea nitrogen (33 mg/dL), creatinine (3.0 mg/dL), and ionized calcium (6.7 mg/dL). Urinalysis showed gross hematuria, with 10 to 20 red blood cells per high-power field and 0 to 5 white blood cells per high-power field. Chest radiography showed bilateral hilar lymphadenopathy without consolidations, nodules, or cavitary lesions (Figure 1, right). Computed tomography of the abdomen showed right-sided hydronephrosis with an obstructive stone.Left, Numerous scattered red to violaceous macules and papules along patient’s tattoos. Right, Chest radiograph showing bilateral hilar lymphadenopathy.

what would you do next?

What would you do next?

Prescribe oral antibiotics

Prescribe topical corticosteroids

Order respiratory isolation and rule out tuberculosis

Obtain a biopsy of the skin lesion

d

male

31-40

Mexican

original

https://jamanetwork.com/journals/jama/fullarticle/2281677

A 54-year-old man with hypertension and diabetes presented to the endocrinology clinic with a 5-month history of fatigue, weight gain, interrupted sleep, and daytime somnolence. He has normal libido but experiences occasional erectile dysfunction, which is being successfully managed with a phosphodiesterase-5 inhibitor. His other medications include metformin and amlodipine. He is married, has 3 children, and reports a sedentary lifestyle. He recently heard on the radio that his symptoms might be due to “low T.” One month ago, he saw his primary care physician and requested measurement of his testosterone level. His morning total testosterone level (measured by mass spectrometry) was 279 ng/dL (normal reference range for this laboratory, 300-900 ng/dL), prompting his referral. On physical examination, his body mass index was 34.7 (calculated as weight in kilograms divided by height in meters squared).He was not cushingoid and his visual fields were normal. Acanthosis nigricans was noticed on the neck. There was no gynecomastia. His testes were normal in size. His muscle strength was normal. Relevant laboratory tests, including repeat morning total testosterone assessed in an endocrinology clinic, are reported in Table.Further evaluation is required; repeat total testosterone measurement using an immunoassay.The patient has androgen deficiency; no further evaluation is required. How Do You Interpret These Test Results?

The patient has androgen deficiency; measure gonadotropins.

Further evaluation is required; repeat total testosterone measurement using an immunoassay.

Further evaluation is required; measure free testosterone.

The patient has androgen deficiency; no further evaluation is required.

C

Further evaluation is required; measure free testosterone.

Testosterone, a steroid hormone, circulates in plasma mostly bound to plasma proteins, mainly albumin and sex hormone–binding globulin (SHBG). Approximately 1% to 2% of testosterone circulates in free form, which is the fraction that is considered biologically active.The initial test for diagnosing androgen deficiency is serum total testosterone, which should be measured in patients who experience specific (and consistent) signs and symptoms of testosterone deficiency.1,2 These signs and symptoms can be categorized as specific (reduced libido, decreased spontaneous erections, gynecomastia, loss of body hair, testicular atrophy, infertility, and hot flushes), or nonspecific (decreased energy, decreased motivation, depressed mood, sleepiness, reduced muscle bulk, increased body fat, increased body mass index, and diminished physical performance).2 Testosterone is secreted in a circadian fashion with peak levels occurring early in the morning; therefore, serum testosterone levels should be measured during the morning hours.2 Mass spectrometry is considered the gold standard for measuring total testosterone and is now offered by some commercial laboratories in the United States. If clinicians lack access to a laboratory that offers mass spectrometry, measurement of total testosterone by immunoassays that have been validated against mass spectrometry is appropriate. A single low total testosterone value should always be confirmed by a second measurement because a substantial number of men have normal values on repeat testing.3Although measurement of serum total testosterone is the first step in the diagnosis of androgen deficiency, total testosterone concentrations may not be reliable in patients with conditions that result in alterations in serum SHBG levels. Conditions associated with an increase in SHBG level include aging, hyperthyroidism, hyperestrogenemia, liver disease, HIV disease, and anticonvulsant use. Conditions associated with a decrease in SHBG level include obesity, insulin resistance and diabetes, hypothyroidism, growth hormone excess, glucocorticoids, androgens, progestins, and nephrotic syndrome.2 In these cases, measurement of free testosterone is helpful.In 2014, the Medicare midpoint reimbursements were $47.60 for total testosterone, $46.95 for free testosterone, and $40.07 for SHBG.4The patient described in this case is obese and has insulin resistance, conditions that are associated with reduced serum SHBG levels, thereby leading to decreased total testosterone levels (while levels of free testosterone are generally preserved).2,5-7 The low SHBG levels lead to low serum total testosterone levels in the absence of hypothalamic, pituitary, or testicular disease. Measurement of free testosterone levels in obese patients aids in making an accurate diagnosis of androgen deficiency. This patient’s 2 serum total testosterone levels were measured using mass spectrometry, the standard method2; therefore, repeat measurement with an immunoassay is unlikely to be helpful. Serum gonadotropins are measured to distinguish primary from secondary hypogonadism. However, gonadotropins should be measured once the diagnosis of androgen deficiency is confirmed, which is not the case in this patient.The next step in this patient's evaluation is measurement of free testosterone. Although equilibrium dialysis is considered the gold standard for measuring free testosterone,2 it is not widely available to clinicians. Calculation of free testosterone by mass action equation using values of SHBG, albumin, and total testosterone (measured by a reliable assay) provides a reasonable alternative.8,9 Algorithms for calculating free testosterone concentrations are available on the Internet (http://www.issam.ch/freetesto.htm). The tracer analog displacement assays for free testosterone that are offered by many hospital and private laboratories are inaccurate and their use is not recommended.In this patient, total testosterone level is only moderately reduced, which in the presence of obesity and insulin resistance and absence of specific symptoms of androgen deficiency, is likely because of low SHBG levels.6,7 The patient’s SHBG level was measured and free testosterone level was calculated. His SHBG level was low at 7.0 nmol/L (normal reference range for this laboratory, 17-56 nmol/L) and his calculated free testosterone was normal at 12 ng/dL (normal reference range for this laboratory, 9-30 ng/dL).Measurement of bioavailable testosterone (free testosterone + albumin-bound testosterone) could be considered; however, it is not widely available. The algorithms that calculate free testosterone also provide concentrations for bioavailable testosterone. The Endocrine Society guidelines recommend against population-level screening for androgen deficiency because its cost-effectiveness and effect on public health remains unclear.This patient’s symptoms of interrupted sleep and daytime somnolence suggested underlying sleep apnea, commonly encountered in obesity, which was likely contributing to his fatigue. The patient was counseled regarding weight loss10 and was referred for a sleep study, which confirmed sleep apnea. Treatment with continuous positive airway pressure significantly improved his symptoms.The diagnosis of androgen deficiency should be based on at least 2 morning testosterone measurements (collected on separate days; using a reliable assay) in a symptomatic patient.Obesity is associated with reduced levels of SHBG, which results in low total testosterone levels. Therefore, free testosterone should be measured in the evaluation of androgen deficiency in obese men.In obese men presenting with nonspecific symptoms of androgen deficiency, underlying conditions responsible for such symptoms should be excluded.

Diagnostic

A 54-year-old man with hypertension and diabetes presented to the endocrinology clinic with a 5-month history of fatigue, weight gain, interrupted sleep, and daytime somnolence. He has normal libido but experiences occasional erectile dysfunction, which is being successfully managed with a phosphodiesterase-5 inhibitor. His other medications include metformin and amlodipine. He is married, has 3 children, and reports a sedentary lifestyle. He recently heard on the radio that his symptoms might be due to “low T.” One month ago, he saw his primary care physician and requested measurement of his testosterone level. His morning total testosterone level (measured by mass spectrometry) was 279 ng/dL (normal reference range for this laboratory, 300-900 ng/dL), prompting his referral. On physical examination, his body mass index was 34.7 (calculated as weight in kilograms divided by height in meters squared).He was not cushingoid and his visual fields were normal. Acanthosis nigricans was noticed on the neck. There was no gynecomastia. His testes were normal in size. His muscle strength was normal. Relevant laboratory tests, including repeat morning total testosterone assessed in an endocrinology clinic, are reported in Table.Further evaluation is required; repeat total testosterone measurement using an immunoassay.The patient has androgen deficiency; no further evaluation is required.

how do you interpret these test results?

How do you interpret these results?

The patient has androgen deficiency; measure gonadotropins.

Further evaluation is required; repeat total testosterone measurement using an immunoassay.

The patient has androgen deficiency; no further evaluation is required.

Further evaluation is required; measure free testosterone.

d

male

51-60

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2039084

A woman in her 70s with a medical history of hyperthyroidism, hypertension, and neuropathy was admitted to the hospital with a 6-day history of painful lesions involving both ears. Initially, the left ear developed very painful lesions that resembled bruises. Subsequently, her right ear became involved and developed similar lesions, but she denied any other areas being affected. She had recently been treated for a urinary tract infection with trimethoprim-sulfamethoxazole and levofloxacin. The lesions appeared while she was taking levofloxacin; however, on admission the antibiotic therapy was continued. Her other medications included propylthiouracil, amlodipine besylate, pravastatin sodium, solifenacin succinate, and gabapentin. On physical examination, the patient had localized retiform purpura on the right earlobe and bilateral helices that were tender to palpation (Figure, A). Findings from laboratory tests, including a hypercoagulability workup, complete blood cell count, comprehensive metabolic panel, urinalysis, cryoglobulins, cytoplasmic antineutrophil cytoplasmic antibodies, and complement levels were all unremarkable. However, the test result for perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) was positive. A punch biopsy for histopathologic examination was performed (Figure, B and C).A, Retiform purpura on the right helix. B, Abundant red blood cell extravasation and fibrin thrombi (hematoxylin-eosin, original magnification ×10). C, Leukocytoclastic vasculitis and fibrin thrombi (hematoxylin-eosin, original magnification ×40). What Is Your Diagnosis?

Levamisole-induced vasculopathy

Mixed cryoglobulinemia

Propylthiouracil-induced hypersensitivity vasculitis

Septic vasculitis

C. Propylthiouracil-induced hypersensitivity vasculitis

C

Propylthiouracil-induced hypersensitivity vasculitis

The biopsy specimen showed leukocytoclastic vasculitis with extensive fibrin thrombi and red blood cell extravasation consistent with propylthiouracil-induced hypersensitivity vasculitis. A Gram stain of the lesion was negative for any organisms. Treatment with propylthiouracil was discontinued in the patient, and she was started on a prednisone taper with complete resolution of her lesions.The first case of propylthiouracil-induced ANCA–associated vasculitis (AAV) was reported by Stankus et al1 in 1992. This condition is seen more commonly in younger female patients, likely attributable to the greater prevalence of thyroid disease in young women. The risk of propylthiouracil-induced AAV increases with increased exposure to propylthiouracil.2 Symptoms and severity of propylthiouracil-induced AAV can differ widely among patients, ranging from nonspecific constitutional symptoms (eg, fever, fatigue, weight loss, arthralgia) to life-threatening disease including renal failure and severe pulmonary hemorrhage.3 The most frequent symptoms at onset include cutaneous eruption, fever, arthralgia, and myalgias. The skin is most commonly involved at onset, and cutaneous vasculitis is a common manifestation.4,5 The skin lesions are usually described as maculopapular or purpuric and are most commonly found on the face, helices, chest, and distal extremities.6 Although the patient lacked any systemic symptoms, she presented with the characteristic cutaneous lesions to the bilateral helices.The pathogenesis for the diverse clinical manifestations is not clearly understood. Current evidence suggests that the interaction between propylthiouracil and myeloperoxidase, the target antigen for ANCAs, contributes to the development of propylthiouracil-induced AAV.7 Propylthiouracil may also modify the configuration of myeloperoxidase found within neutrophils resulting in an autoimmune response.8,9 Other theories suggest that the metabolites of propylthiouracil are immunogenic for T cells leading to activation of B cells, resulting in the production of ANCAs.7 Because of the proposed pathogenesis, evaluation for ANCAs should be performed routinely on anyone treated with propylthiouracil. Most patients with propylthiouracil-induced AAV will have p-ANCA positivity. The presence of p-ANCAs, with the temporal relationship between clinically evident vasculitis and administration of propylthiouracil, is suggestive of propylthiouracil-induced hypersensitivity vasculitis. A tissue biopsy is necessary for diagnosing vasculitis and to determine disease severity. Skin biopsy findings typically show cutaneous leukocytoclastic vasculitis, characterized by fibrinoid necrosis of the blood vessels, as was present in the patient described herein.10 The histologic differential of a mixed vasculitis and vasculopathy pattern includes levamisole-induced hypersensitivity vasculitis, septic vasculitis, secondary vasculitis due to an overlying ulcer, and propylthiouracil-induced vasculitis. Abnormalities including anemia, leukocytosis, and thrombocytopenia may also be present.7 It is also important to rule out other medical conditions that can mimic vasculitis, including, but not limited to, infection and malignant conditions. Once propylthiouracil-induced AAV is suspected, immediate cessation of the drug therapy is recommended. For patients with mild systemic disease (fever, malaise, arthralgias, without organ involvement), cessation of propylthiouracil use may be sufficient to induce disease remission. However, if more severe disease is present, patients should receive corticosteroids in addition to cessation of propylthiouracil use.7 Evidence in the literature suggests that once propylthiouracil therapy is withdrawn and remission of vasculitis is achieved, propylthiouracil-induced AAV is not prone to reocurr.2 However, patients should be switched to an alternative medication for the treatment of hyperthyroidism.Propylthiouracil-induced AAV should be a diagnostic consideration in patients who present with cutaneous lesions and are receiving propylthiouracil. The temporal relationship between starting propylthiouracil therapy and the development of lesions can help guide diagnosis. The present case illustrates the importance of considering propylthiouracil-induced AAV in the differential of a patient presenting with purpuric lesions while receiving propylthiouracil. Early diagnosis is important to prevent the multiorgan dysfunction associated with the condition. Discontinuation of propylthiouracil use with a steroid taper can lead to remission, as was seen in the patient described herein.

Dermatology

A woman in her 70s with a medical history of hyperthyroidism, hypertension, and neuropathy was admitted to the hospital with a 6-day history of painful lesions involving both ears. Initially, the left ear developed very painful lesions that resembled bruises. Subsequently, her right ear became involved and developed similar lesions, but she denied any other areas being affected. She had recently been treated for a urinary tract infection with trimethoprim-sulfamethoxazole and levofloxacin. The lesions appeared while she was taking levofloxacin; however, on admission the antibiotic therapy was continued. Her other medications included propylthiouracil, amlodipine besylate, pravastatin sodium, solifenacin succinate, and gabapentin. On physical examination, the patient had localized retiform purpura on the right earlobe and bilateral helices that were tender to palpation (Figure, A). Findings from laboratory tests, including a hypercoagulability workup, complete blood cell count, comprehensive metabolic panel, urinalysis, cryoglobulins, cytoplasmic antineutrophil cytoplasmic antibodies, and complement levels were all unremarkable. However, the test result for perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) was positive. A punch biopsy for histopathologic examination was performed (Figure, B and C).A, Retiform purpura on the right helix. B, Abundant red blood cell extravasation and fibrin thrombi (hematoxylin-eosin, original magnification ×10). C, Leukocytoclastic vasculitis and fibrin thrombi (hematoxylin-eosin, original magnification ×40).

what is your diagnosis?

What is your diagnosis?

Mixed cryoglobulinemia

Septic vasculitis

Levamisole-induced vasculopathy

Propylthiouracil-induced hypersensitivity vasculitis

d

female

71-80

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2108470

A woman in her 40s with a history of atopy presented with a 1-year history of asymptomatic red-brown patches on the distal extensor extremities. The lesions began on the bilateral lower legs and spread to the thighs, buttocks, hands, forearms, and proximal arms. Physical examination revealed numerous stellate red-brown patches without induration, scale, or ulceration (Figure, A). Review of systems was notable for episodic muscle cramping and numbness involving the lower extremities. The patient had no notable recent medical illnesses, illicit drug use, or new medications. An incisional wedge biopsy was performed on a lesion from the lower extremity, and the specimen was stained with hematoxylin-eosin (Figure, B and C).A, Stellate red-brown patches on the patient's right lower extremity. B, Specimen from a lower-extremity lesion (original magnification ×10). C, Same specimen as shown in panel B but at higher magnification (×20). What is Your Diagnosis?

Granulomatosis with polyangiitis

Microscopic polyangiitis

Leukocytoclastic vasculitis

Polyarteritis nodosa

D. Polyarteritis nodosa

D

Polyarteritis nodosa

The biopsy revealed a medium-sized artery at the junction of the deep reticular dermis and the subcutaneous tissue. The vessel was hyalinized, thrombosed, and showed numerous mononuclear cells infiltrating the vessel wall. The remaining dermis showed a mild predominantly perivascular lymphohistiocytic infiltrate.Initial laboratory workup was significant for an elevated erythrocyte sedimentation rate of 30 mm/h and C-reactive protein level of 1.1 mg/dL. Antinuclear antibody level was 8 IU/mL with a titer of 1:40 to 1:80. Double-stranded DNA levels were indeterminate. A complete blood count with differential, complete metabolic panel, serum protein electrophoresis, urine protein electrophoresis, and antineutrophil cytoplasmic antibody values were all within normal limits.The patient underwent electromyography, the results of which suggested multiple mononeuropathies. A left sural nerve biopsy was performed and illustrated a profound large- and small-fiber axonal neuropathy accompanied by perivascular inflammation. A magnetic resonance arteriogram of the abdomen and lower extremities was normal.The patient began treatment with prednisone, 60 mg/d, and azathioprine titrated to 250 mg/d. Her prednisone dose was gradually tapered to 10 mg/d; she did not develop additional cutaneous lesions, and the existing lesions began to resolve. Her neurologic symptoms stabilized. She did not develop additional systemic manifestations.Polyarteritis nodosa (PAN) is a rare necrotizing vasculitis affecting medium-sized arteries that may present with systemic symptoms, internal organ involvement, or localized lesions. Cutaneous findings are seen in 25% to 60% of patients1 and are due to involvement of vessels in the dermis or subcutaneous tissue. Cutaneous PAN (c-PAN) is considered a distinct entity limited to the skin seen in 10% of all cases of PAN and is the most common form of PAN seen in children.2 Cutaneous PAN often presents with fevers, myalgias, arthralgias, and peripheral neuropathy.2 Peripheral neuropathy is reported in 20% of patients and presents as mononeuritis multiplex,2 which is clinically notable for asymmetric sensorimotor deficits over the extremities.3In patients with c-PAN, lesions first affect the legs (97%), followed by the arms (33%) and the trunk (8%).4 The condition may present as subcutaneous nodules, livedo reticularis, ulcers, or gangrene.2,4 Less common presentations include inflammatory plaques with peripheral nodules on the trunk and the extremities,5 maculopapular eruption, vesiculobullous lesions, and pupura.6Because there is no specific serologic test for c-PAN, the diagnosis relies on clinicopathologic correlation. Biopsy reveals a necrotizing vasculitis involving medium-sized arteries in the deep dermis or subcutaneous tissue. Studies of c-PAN report fibrinoid necrosis of the vessel wall and infiltration of lymphocytes and monocytes in the vessel lumen and wall.7,8 Direct immunofluorescence findings are variable and do not distinguish between c-PAN and systemic PAN.4,9While the cause of c-PAN is unknown, it has been associated with group A β-hemolytic Streptococcus, parvovirus B19, human immunodeficiency virus, and hepatitis B infections.2,4 Screening for these conditions should be considered. Exclusion of systemic PAN is critical. All patients require a thorough physical examination and laboratory evaluation for underlying systemic involvement.4Controversy exists as to whether c-PAN represents a variant of systemic PAN confined to the skin or an early limited form of PAN.2,9 In general, c-PAN has a favorable prognosis characterized by a chronic course with relapse and remission common.2,9 There are, however, rare cases of progression of c-PAN to systemic PAN.7 For patients with mild disease, nonsteroidal anti-inflammatory drugs or colchicine may be used.2,4 Patients with refractory disease, severe cutaneous disease, or extracutaneous involvement require more aggressive treatment. Prednisone is often first-line treatment at doses of up to 1 mg/kg/d followed by the initiation of a steroid-sparing regimen with slow taper of corticosteroid dose. Additional options include hydroxychloroquine, dapsone, pentoxifylline, azathioprine, cyclophosphamide, methotrexate, and intravenous immunoglobulin.2,4 For acral necrosis, prostaglandins and nifedipine may be used.2

Dermatology

A woman in her 40s with a history of atopy presented with a 1-year history of asymptomatic red-brown patches on the distal extensor extremities. The lesions began on the bilateral lower legs and spread to the thighs, buttocks, hands, forearms, and proximal arms. Physical examination revealed numerous stellate red-brown patches without induration, scale, or ulceration (Figure, A). Review of systems was notable for episodic muscle cramping and numbness involving the lower extremities. The patient had no notable recent medical illnesses, illicit drug use, or new medications. An incisional wedge biopsy was performed on a lesion from the lower extremity, and the specimen was stained with hematoxylin-eosin (Figure, B and C).A, Stellate red-brown patches on the patient's right lower extremity. B, Specimen from a lower-extremity lesion (original magnification ×10). C, Same specimen as shown in panel B but at higher magnification (×20).

what is your diagnosis?

What is your diagnosis?

Granulomatosis with polyangiitis

Microscopic polyangiitis

Leukocytoclastic vasculitis

Polyarteritis nodosa

d

female

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2110019

A man in his 30s with no medical history of illness presented with a lesion of concern on his left scalp. The patient noted that the lesion had slowly enlarged over the preceding 5 years from when he first noticed it as a small bump. He denied a history of trauma prior to its development. The patient denied any spontaneous bleeding, crusting, or itching, and he was primarily concerned about its growth. There was no personal or family history of malignancy. On physical examination, the patient’s left frontal scalp revealed a mobile 1.2-cm mammillated, soft, brown plaque with protruding terminal hairs (Figure, A). The remainder of the patient’s skin examination revealed no other concerning lesions. There was no lymphadenopathy present. Dermoscopically, the lesion was characterized by irregular pigment globules, milialike cysts, and focal arborizing vessels (Figure, B). A shave biopsy was performed for histopathologic examination (Figure, C and D). What Is Your Diagnosis?

Basal cell carcinoma

Apocrine poroma

Congenital nevus

Seborrheic keratosis

B. Apocrine poroma

B

Apocrine poroma

Histopathologic examination revealed epidermal projections composed of monotonous basaloid and squamous epithelial cells. Some tumor islands contained mature sebocytes and ductal structures with an eosinophilic cuticle. Areas of pigmented poroid cells and cystic structures correlated with dermoscopic brown globules and milialike cysts, respectively (Figure, C and D).The patient was informed of his diagnosis and presented with options for treatment. Because of the possibility of lesion recurrence and sensitive cosmetic location, he elected surgical excision of the tumor.Poromas are rare, benign neoplasms composed of ductal cells generally believed to be of eccrine derivation. However, the apocrine poroma, a variant with apocrine, sebaceous, and follicular differentiation has been described.1 Also known as sebocrine adenoma, it typically presents as a slow-growing papule or plaque that shows no sex predilection and has been described in individuals from early to late adulthood. Frequently, it is confused with seborrheic keratosis, basal cell carcinoma, angiofibroma, or irritated nevus.2 Unlike eccrine poromas, which have been most commonly reported on acral skin in sites of highest eccrine gland density, apocrine poromas prefer the head, neck, trunk, and proximal extremities.3Histologically, apocrine poromas closely mimic their eccrine counterpart: this is characterized by interconnected trabeculae of monomorphous cells with multiple foci of epidermal attachment, ductal differentiation with eosinophilic lining, and occasional necrosis.3 Apocrine poromas differ in that they may have proliferations of sebocytes forming sebaceous lobules, ductal structures lined by brightly eosinophilic apocrine cells, and occasional follicular differentiation, reflecting the common embryologic origin of the folliculosebaceous-apocrine unit.4 Because it is not possible to distinguish between apocrine and eccrine ductal cells, the diagnosis of apocrine poroma rests on recognizing foci of sebaceous, apocrine, or follicular development within the tumor. A diagnostic pitfall may be entrapment of normal adnexal structures by an expanding eccrine poroma, generating the illusion of folliculosebaceous or apocrine differentiation.3The dermoscopic findings in poroma have been described,1 and the classic features may help distinguish it from the more common entities that it mimics. Vascular patterns consisting of leaf and flowerlike vessels may be seen, although a polymorphous vessel pattern is most commonly encountered. A gridlike pattern of interconnecting white lines has also been described, but is not specific for poromas.1 Notably, arborizing vessels have been previously reported in a pigmented variant.5 The “out-of-focus” appearance of these vessels suggests they are deeper within the poroid tumor than the classic arborizing vessels of basal cell carcinoma. The irregular pigmented globules may simulate melanoma or basal cell carcinoma.Poromas are considered benign lesions that can be treated with simple shave removal, electrosurgical destruction, or excision.6 Although histologic features differentiate between benign poromas and porocarcinomas, a case of malignant eccrine poroma manifesting as in-transit and nodal metastasis after an initial diagnosis of benign poroma has been reported.7 As such, establishing good clinicopathologic correlation and maintaining an open dialogue with the dermatopathologist is paramount in determining appropriate management of apocrine poroma and other rare adnexal neoplasms.

Dermatology

A man in his 30s with no medical history of illness presented with a lesion of concern on his left scalp. The patient noted that the lesion had slowly enlarged over the preceding 5 years from when he first noticed it as a small bump. He denied a history of trauma prior to its development. The patient denied any spontaneous bleeding, crusting, or itching, and he was primarily concerned about its growth. There was no personal or family history of malignancy. On physical examination, the patient’s left frontal scalp revealed a mobile 1.2-cm mammillated, soft, brown plaque with protruding terminal hairs (Figure, A). The remainder of the patient’s skin examination revealed no other concerning lesions. There was no lymphadenopathy present. Dermoscopically, the lesion was characterized by irregular pigment globules, milialike cysts, and focal arborizing vessels (Figure, B). A shave biopsy was performed for histopathologic examination (Figure, C and D).

what is your diagnosis?

What is your diagnosis?

Seborrheic keratosis

Basal cell carcinoma

Apocrine poroma

Congenital nevus

c

male

31-40

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2212145

A woman in her 50s was referred to a neurologist for a history of gait, balance, personality, and judgment changes over 4 years. Her family noted that her first symptoms appeared at age 55, with subtle gait dysfunction and then evident imbalance. By age 57, there was concern over progressive withdrawal from social interchange, personality changes, and impairment of judgment. By age 59, she was experiencing bouts of inappropriate out-of-context laughter and tears, inattention, daytime fatigue, and frank memory impairment. She developed visuoperceptive changes and difficulties using the television remote control device. She developed obsessive checking behaviors. She started having swallowing difficulties but nonetheless had unexpected weight gain. She developed progressively worse motoric problems, with stiffness, abnormal posturing, a left toe pointing upward, and falls. Her medical history was significant only for restless legs syndrome, hypertension, hyperlipidemia, myopia, and a deviated nasal septum. Her family history revealed that her father was alive and well at approximately age 90 years, and her mother had died at approximately age 80 years with a history of neuropsychiatric disease and gait change. There was no history of tobacco, excess alcohol, or recreational drug use. General examination findings were noncontributory. Neurological examination revealed abnormal mental status, with full orientation and good registration, concentration, digit span, and language function but with poor calculations and constructions (Figure 1A) and decreased short-term memory. Nonetheless, her Mini-Mental State Examination score was 28 of 30. Cranial nerve examination revealed some decreased upgaze and mild facial masking. Motor examination revealed rigidity and dystonic posturing in the left arm and leg, imbalance on gait, decreased arm swing, and retropulsion but no significant tremor. Sensory examination findings were normal. Reflex examination showed mild left hyperreflexia with an upgoing left toe. Blood and urine laboratory study results were within normal limits. Cerebrospinal fluid was unremarkable except for biomarkers that showed a mid-range β-amyloid 42 level of 530 pg/mL and normal total tau and phosphotau levels of 182 and 25 pg/mL, respectively. Magnetic resonance imaging of the brain was reported as unremarkable (Figure 1B). Positron emission tomography (PET) imaging of the brain revealed right frontotemporoparietal hypometabolism with some sensorimotor sparing (Figure 1C), which was neither typical nor atypical of Alzheimer disease. Electroencephalography showed left frontotemporal sharp waves and slowing. She had continued progressive decline in cognition and motor function and died almost mute and bedridden in her early 60s after a 9-year course of illness.A, Patient testing. Constructional apraxia is seen in her copying of the top row template figures, with preserved writing in script. B, Brain magnetic resonance imaging at the time of presentation. The top panel shows selected sagittal T1-weighted images, and the bottom panel shows selected axial T1-weighted images. C, Brain positron emission tomography using fluorodeoxyglucose F 18 tracer in the axial plane. Frontal and temporal hypometabolism is seen, more marked on the right, with some apparent sensorimotor sparing bilaterally. What is your diagnosis?

Alzheimer disease, frontal variant

Frontotemporal dementia

Progressive supranuclear palsy

Corticobasal degeneration

Progressive supranuclear palsy

C

Progressive supranuclear palsy

During her life, the patient’s diagnoses included frontotemporal dementia (because of her behavioral changes, with relative preservation of cognition early on), progressive supranuclear palsy (because of her motor changes, including falls), and corticobasal syndrome (because of her markedly asymmetric dystonia). However, progressive supranuclear palsy was the most likely diagnosis because of the early features of imbalance and falls, parkinsonism without tremor, and marked midbrain atrophy visible on magnetic resonance (MR) imaging (hummingbird sign is seen in the sagittal midline slice [top right of Figure 2]).1-5 Alzheimer disease was unlikely because of the lack of early memory change, the MR imaging and PET results, and the normal tau and phosphotau levels in cerebrospinal fluid. While there was considerable imbalance and cerebellar atrophy, the asymmetric examination findings, prominent brainstem atrophy, cognitive changes,3 and lack of dysmetria, nystagmus, or other classic cerebellar signs all militated against spinocerebellar degeneration. Although the asymmetric motor examination results could be indicative of corticobasal ganglionic degeneration (corticobasal degeneration), these findings can also be seen in progressive supranuclear palsy. The lack of a classic pattern of bicentral hypometabolism on PET, the presence of marked midbrain tectal atrophy2 and dysphagia, and the absence of alien limb or dysgraphesthesia all make corticobasal syndrome less likely. Finally, while several features were suggestive of behavioral variant frontotemporal degeneration, the presence of such prominent motor signs and symptoms early in the disease course, as well as the MR imaging and PET results, makes such a diagnosis less likely. The diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) was confirmed at autopsy.1,5 Throughout the cortex and subcortical gray nuclei, a diffuse and severe burden of glial phosphorylated tau pathology was observed, evidenced through immunohistochemical staining with antibody AT8. There were frequent tufted astrocytes, scattered neuronal and glial tangles, marked gliosis, and glial cytoplasmic inclusions in the white matter. Neuronal losses in the substantia nigra, pars compacta, and pars reticulata were severe. There were few neuronal tangles and no evident plaques using immunohistochemical stains for β-amyloid. Finally, there was no evidence of α-synuclein aggregates (as seen in Lewy body disease) or transactive response DNA-binding protein 32 (TDP-43) abnormalities (as seen in some frontotemporal dementia disorders).Brain magnetic resonance imaging (same as Figure 1B) was interpreted as “normal” but in fact shows marked midbrain atrophy, most prominent in the tectum (yellow arrowhead), and also evident in the “hummingbird” sign seen on sagittal image (white arrowhead).

Neurology

A woman in her 50s was referred to a neurologist for a history of gait, balance, personality, and judgment changes over 4 years. Her family noted that her first symptoms appeared at age 55, with subtle gait dysfunction and then evident imbalance. By age 57, there was concern over progressive withdrawal from social interchange, personality changes, and impairment of judgment. By age 59, she was experiencing bouts of inappropriate out-of-context laughter and tears, inattention, daytime fatigue, and frank memory impairment. She developed visuoperceptive changes and difficulties using the television remote control device. She developed obsessive checking behaviors. She started having swallowing difficulties but nonetheless had unexpected weight gain. She developed progressively worse motoric problems, with stiffness, abnormal posturing, a left toe pointing upward, and falls. Her medical history was significant only for restless legs syndrome, hypertension, hyperlipidemia, myopia, and a deviated nasal septum. Her family history revealed that her father was alive and well at approximately age 90 years, and her mother had died at approximately age 80 years with a history of neuropsychiatric disease and gait change. There was no history of tobacco, excess alcohol, or recreational drug use. General examination findings were noncontributory. Neurological examination revealed abnormal mental status, with full orientation and good registration, concentration, digit span, and language function but with poor calculations and constructions (Figure 1A) and decreased short-term memory. Nonetheless, her Mini-Mental State Examination score was 28 of 30. Cranial nerve examination revealed some decreased upgaze and mild facial masking. Motor examination revealed rigidity and dystonic posturing in the left arm and leg, imbalance on gait, decreased arm swing, and retropulsion but no significant tremor. Sensory examination findings were normal. Reflex examination showed mild left hyperreflexia with an upgoing left toe. Blood and urine laboratory study results were within normal limits. Cerebrospinal fluid was unremarkable except for biomarkers that showed a mid-range β-amyloid 42 level of 530 pg/mL and normal total tau and phosphotau levels of 182 and 25 pg/mL, respectively. Magnetic resonance imaging of the brain was reported as unremarkable (Figure 1B). Positron emission tomography (PET) imaging of the brain revealed right frontotemporoparietal hypometabolism with some sensorimotor sparing (Figure 1C), which was neither typical nor atypical of Alzheimer disease. Electroencephalography showed left frontotemporal sharp waves and slowing. She had continued progressive decline in cognition and motor function and died almost mute and bedridden in her early 60s after a 9-year course of illness.A, Patient testing. Constructional apraxia is seen in her copying of the top row template figures, with preserved writing in script. B, Brain magnetic resonance imaging at the time of presentation. The top panel shows selected sagittal T1-weighted images, and the bottom panel shows selected axial T1-weighted images. C, Brain positron emission tomography using fluorodeoxyglucose F 18 tracer in the axial plane. Frontal and temporal hypometabolism is seen, more marked on the right, with some apparent sensorimotor sparing bilaterally.

what is your diagnosis?

What is your diagnosis?

Frontotemporal dementia

Corticobasal degeneration

Alzheimer disease, frontal variant

Progressive supranuclear palsy

d

female

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2292600

A woman in her 70s was referred for treatment of a choroidal melanoma of the left eye approximately 4 years ago. At presentation, she reported occasional photopsias, floaters, and blurred vision but no pain. Visual acuity was 20/25−2 OD and 20/40 OS. Her choroidal melanoma was located at the 11- to 1-o’clock position, anterior to the equator but posterior to the ciliary body. Low internal reflectivity and a mass measuring 8.4 mm in height by 12.9 mm across the base (Figure, A and B) were revealed on B-scan ultrasonography. A complete blood cell count and results of liver function tests were within reference limits; a computed tomographic scan of the abdomen, chest, brain, and orbits showed no evidence of metastasis.A and B, B-scan ultrasonography of the left eye. A, Original scan shows a mass with a height of 8.4 mm and a base dimension of 12.9 mm. B, Follow-up scan shows the mass in a transverse 12-o’clock position with a decrease in tumor height to 1.4 mm 4½ years after iodine 125 plaque brachytherapy. C, An external slitlamp photograph of the left eye shows a bluish black pigmented lesion on the sclera measures 4.5 × 3.0 mm (anterior-posterior by horizontal orientation). This lesion corresponds to the site of the choroidal melanoma and plaque placement.A radioactive episcleral iodine 125 (125I) plaque was surgically placed over the lesion and removed 1 week later. The tumor decreased in height, and visual acuity remained stable at 20/30 OS. The tumor height decreased to 2.3 mm by 1 year and remained at less than 2 mm in years 2 through 4½ on B-scan ultrasonography (Figure, B).At her last follow-up, the patient had a 4.5 × 3.0-mm bluish black flat lesion on the sclera (Figure, C). Results of a dilated fundus examination showed a grayish black, minimally elevated choroidal lesion with surrounding retinal pigment epithelial atrophy but without subretinal fluid, hemorrhage, or hard exudates. What Would You Do Next?

Repeat iodine 125 plaque brachytherapy

External beam radiotherapy

Enucleation

Observation

Scleral melting after plaque brachytherapy (125I)

D

Observation

Scleral necrosis is a well-documented but rare complication after plaque radiotherapy for uveal melanomas.1,2 Scleral thinning after radiotherapy is asymptomatic and found at the treatment site. Because scleral necrosis is a rare complication, it is often mistaken for extrascleral extension of the original melanoma.Kaliki et al1 noted several differences between these conditions. For example, blue discoloration of the Tenon fascia and an overall decrease in the size of intraocular melanoma suggest scleral thinning. In recurrence, the tumor often spreads through the emissarial canals and forms a blue nodule under the Tenon fascia with intact sclera above (almost always with associated growth of the intraocular tumor). Scleral necrosis with regressed tumor will be associated with increased transillumination compared with shadowing in tumor recurrence.1 Shields et al3 found that local recurrence of intraocular melanoma after combined plaque brachytherapy and transpupillary thermotherapy was rare and found in 3% of cases at 5 years.Kaliki et al1 examined more than 5000 patients who underwent plaque radiotherapy for uveal melanoma and found that approximately 1% developed radiotherapy-induced scleral necrosis. The incidence of scleral necrosis increased in patients with larger tumor thickness (<1% in tumors <3 mm thick; 1% in tumors 3-8 mm thick; and 5% in tumors >8 mm thick). Location of the melanoma was also important, with melanoma of the ciliary body having a significantly higher rate of scleral melting (29%) compared with choroidal (<1%) and iridial (0%) melanomas. The mean time from plaque therapy to scleral necrosis was 32 months. A higher dose of radiotherapy (>400 Gy [to convert to rad, multiply by 100]) was found to result in an increased risk for scleral necrosis.1 The scleral necrosis remained stable in most patients, with only 4% developing perforation during a follow-up of 79 months. Observation constituted effective treatment in more than 80% of their patients.Radin et al2 reported 23 cases (0.63%) of scleral necrosis after plaque radiotherapy (with 125I or cobalt 60) or proton beam radiotherapy for uveal melanomas. They found that the mean time of scleral necrosis onset after radiotherapy was 70.4 months. Scleral necrosis remained stable in almost three-quarters of these cases; necrosis progressed and led to preperforation status in only 2 cases.2 Radin et al2 also found that melanomas of the ciliary body were much more likely to develop scleral necrosis after treatment compared with choroidal melanomas. Kaliki et al1 and Radin et al2predicted that this outcome may be related to difficulty with visualization of the sclera posterior to the equator and the difficulty of diagnoses on B-scan ultrasonography. Also, melanomas of the ciliary body tend to be thicker and thus require a higher dose of radiation.1This patient developed an area of concerning scleral pigmentation after treatment with 125I plaque brachytherapy. The differential diagnoses include scleral melting and tumor extension. At 53 months after 125I plaque brachytherapy, she remained clinically cancer free with stability of the lesion during the past 4.5 years. Thus, external extension of the tumor is unlikely; the pigmentation probably represents asymptomatic scleral necrosis.Owing to the height of the original lesion, we postulate that it required a higher dose of radiotherapy, which increased her risk for scleral melting. In addition, the anterior location of the lesion contributed to the detection of this rare complication after radioactive plaque placement.Observation is the correct choice because most of these lesions remain stable over time, and no treatment is needed in most patients. Patients should be warned about wearing protective eyewear because minimal trauma can lead to full-thickness perforation in this weakened area.

Ophthalmology

A woman in her 70s was referred for treatment of a choroidal melanoma of the left eye approximately 4 years ago. At presentation, she reported occasional photopsias, floaters, and blurred vision but no pain. Visual acuity was 20/25−2 OD and 20/40 OS. Her choroidal melanoma was located at the 11- to 1-o’clock position, anterior to the equator but posterior to the ciliary body. Low internal reflectivity and a mass measuring 8.4 mm in height by 12.9 mm across the base (Figure, A and B) were revealed on B-scan ultrasonography. A complete blood cell count and results of liver function tests were within reference limits; a computed tomographic scan of the abdomen, chest, brain, and orbits showed no evidence of metastasis.A and B, B-scan ultrasonography of the left eye. A, Original scan shows a mass with a height of 8.4 mm and a base dimension of 12.9 mm. B, Follow-up scan shows the mass in a transverse 12-o’clock position with a decrease in tumor height to 1.4 mm 4½ years after iodine 125 plaque brachytherapy. C, An external slitlamp photograph of the left eye shows a bluish black pigmented lesion on the sclera measures 4.5 × 3.0 mm (anterior-posterior by horizontal orientation). This lesion corresponds to the site of the choroidal melanoma and plaque placement.A radioactive episcleral iodine 125 (125I) plaque was surgically placed over the lesion and removed 1 week later. The tumor decreased in height, and visual acuity remained stable at 20/30 OS. The tumor height decreased to 2.3 mm by 1 year and remained at less than 2 mm in years 2 through 4½ on B-scan ultrasonography (Figure, B).At her last follow-up, the patient had a 4.5 × 3.0-mm bluish black flat lesion on the sclera (Figure, C). Results of a dilated fundus examination showed a grayish black, minimally elevated choroidal lesion with surrounding retinal pigment epithelial atrophy but without subretinal fluid, hemorrhage, or hard exudates.

what would you do next?

What would you do next?

Repeat iodine 125 plaque brachytherapy

Observation

External beam radiotherapy

Enucleation

b

female

71-80

Black

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2292601

A 56-year-old man with systemic lupus erythematosus was taking chloroquine for 7 years (2.6 mg/kg daily; cumulative dose, 332 g). He was diagnosed as having nephropathy 5 years ago. He presented with a history of bilateral, painless, progressive visual diminution for 2 years. On examination, his best-corrected visual acuity was 20/200 in both eyes. He had bilateral posterior subcapsular cataracts. Both the corneas were clear. Intraocular pressures were 14 and 16 mm Hg in the right and left eyes, respectively, by Goldmann applanation tonometry. Dilated ophthalmoscopy revealed a hypopigmented zone in the parafoveal macula (Figure). Color vision testing revealed red-green deficiencies in both eyes.Advanced chloroquine retinopathy. Fundus photographs of the right (A) and left (B) eyes showing hypopigmented zones concentric to the fovea consistent with chloroquine retinopathy. What Would You Do Next?

Discontinue treatment with chloroquine

Reassure and observe

Treat with intravitreous corticosteroids

Examine family members for macular dystrophy

Chloroquine toxicity

A

Discontinue treatment with chloroquine

Chloroquine and its analogue hydroxychloroquine are used as disease-modifying antirheumatic drugs in autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Ocular manifestations of toxicity include whorl-pattern epithelial keratopathy, subcapsular cataracts, retinopathy, optic atrophy, paralysis of accommodation, and extraocular muscle palsy.1The risk of retinal toxic effects from chloroquine is approximately 1% after 5 to 7 years of use.2 Hydroxychloroquine is less toxic than chloroquine. The drug binds to melanin in the retinal pigment epithelium, which prolongs its toxic effects. The earliest changes of retinopathy might be picked up by automated central visual field charting, multifocal electroretinography, spectral-domain optical coherence tomography, or fundus autofluorescence.3 Fundus changes progress from the loss of foveal reflex and subtle parafoveal depigmentation to bull’s-eye maculopathy. Once fundus changes appear, the disease may be irreversible and progressive.4 Patients with renal dysfunction are at an increased risk of toxic effects because of decreased clearance of the drug. There is no medical therapy for the treatment of the toxic effects other than cessation of use of the drug. Hence, periodic screening is absolutely essential.The American Academy of Ophthalmology recommends annual screening from the initiation of therapy in patients with nephropathy. The recommended screening procedures at each visit should include a thorough ocular examination, automated visual fields (acquired bilateral paracentral scotomas), and one or more of the following objective tests: multifocal electroretinography (localized paracentral electroretinographic depression), spectral-domain optical coherence tomography (ellipsoid parafoveal loss), and fundus autofluorescence (reduced autofluorescence that indicates subtle retinal pigment epithelial defects and increased autofluorescence that indicates areas of early photoreceptor damage and accumulation of outer segment debris in the parafoveal macula).3Chloroquine was substituted with methotrexate. However, vision continued to worsen and ultimately resulted in optic atrophy.

Ophthalmology

A 56-year-old man with systemic lupus erythematosus was taking chloroquine for 7 years (2.6 mg/kg daily; cumulative dose, 332 g). He was diagnosed as having nephropathy 5 years ago. He presented with a history of bilateral, painless, progressive visual diminution for 2 years. On examination, his best-corrected visual acuity was 20/200 in both eyes. He had bilateral posterior subcapsular cataracts. Both the corneas were clear. Intraocular pressures were 14 and 16 mm Hg in the right and left eyes, respectively, by Goldmann applanation tonometry. Dilated ophthalmoscopy revealed a hypopigmented zone in the parafoveal macula (Figure). Color vision testing revealed red-green deficiencies in both eyes.Advanced chloroquine retinopathy. Fundus photographs of the right (A) and left (B) eyes showing hypopigmented zones concentric to the fovea consistent with chloroquine retinopathy.

what would you do next?

What would you do next?

Discontinue treatment with chloroquine

Treat with intravitreous corticosteroids

Reassure and observe

Examine family members for macular dystrophy

a

male

51-60

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2281580

A healthy 7-year-old girl presented with a 2-month history of an itchy rash on her elbows, knees, hands, and feet. The patient was otherwise healthy with normal development and growth. She had no other medical problems and was not taking any medications. The rash started as small pink bumps on her knees and elbows, spreading to her hands and feet and progressively thickening. The patient’s history was otherwise unremarkable; she had no pets, had no recent travel outside the United States, and her vaccinations were up to date.On physical examination, the patient had well-defined, follicular, pink, scaly papules coalescing into thin plaques on her knees (Figure 1A), elbows, and dorsal hands and feet, as well as diffuse, marked orange-red hyperkeratosis and hyperlinearity of her palms with clear demarcation at the wrists (Figure 1B).A, Well-defined follicular, pink, scaly papules coalescing into plaques on the patient’s knees. B, Marked orange-red hyperkeratosis of the patient’s palms.Initial treatment with hydrocortisone valerate cream, 0.2%, provided minimal improvement. A 4-mm skin punch biopsy was performed. What Is Your Diagnosis?

Psoriasis

Ichthyosis

Circumscribed juvenile pityriasis rubra pilaris

Atopic dermatitis

C. Circumscribed juvenile pityriasis rubra pilaris (PRP)

C

Circumscribed juvenile pityriasis rubra pilaris

A biopsy was performed to support our clinical suspicion. Results of histologic examination of the rash demonstrated alternating vertical and horizontal orthokeratosis and parakeratosis in a checkerboard pattern (Figure 2). Sparse lymphohistiocytic infiltrate was seen in the papillary dermis. While not pathognomonic, these characteristic histologic findings, correlated with the clinical presentation, are most consistent with a diagnosis of PRP.1,2 The patient applied triamcinolone acetonide cream, 0.1%, daily to the thick areas, with moderate improvement. Hydrocortisone valerate cream, 0.2%, which the patient had previously used, was not strong enough for these thick lesions.Results of histologic examination revealed alternating vertical and horizontal orthokeratosis (white arrowheads) and parakeratosis (blue arrowheads) in a checkerboard pattern (hematoxylin-eosin, original magnification x40).Pityriasis rubra pilaris is a chronic disorder of cornification with onset in early childhood. No clear etiology has been established, although there has been suggestion of vitamin A deficiency and viral infections playing a role in the pathogenesis of PRP.3 Case reports have implicated varicella-zoster virus, β-hemolytic streptococcal infection, and even Kawasaki disease, suggesting that PRP may be a reactive exanthema related to a superantigen.4 Human immunodeficiency virus–related PRP cases have been reported, suggesting an abnormal immunologic response to particular antigens.5Pityriasis rubra pilaris has been divided into 5 subtypes, although types III and IV are the forms most commonly seen in children.3,6 The classic adult subtype, type I, accounts for half of the cases of PRP and is typically seen in adults in the sixth decade of life. This form of PRP usually begins in the head and neck region and progressively advances caudally. Type II, the atypical adult form seen in 5% of patients, differs from type I in that it includes a palmoplantar keratoderma with a coarse lamellated scale and occasional alopecia. Types III to V are seen in children and young adults. Type III is the classic juvenile form, seen in 10% of cases. Patients with this form of PRP present similarly to patients with type I; however, they are younger at disease onset. Type IV, circumscribed juvenile PRP, is the most common juvenile form seen in 25% of cases and is characterized by hyperkeratotic plaques on the knees and elbows. Type V, the atypical juvenile form, presents most commonly in early childhood, with thickening of the palms and soles.The differential diagnosis for our patient with type IV (circumscribed juvenile) PRP includes psoriasis, keratosis pilaris, erythrokeratodermia variabilis, drug eruption, atopic dermatitis, contact dermatitis, and Sézary syndrome. Psoriasis has a similar distribution and similar spectrum of severity, including erythroderma; therefore, it is the most likely clinical differential diagnosis. Psoriasis tends to have more adherent scale without the areas of sparing seen in patients with erythroderma. A lack of family history of psoriasis and the presence of follicular papules that have a nutmeg grater texture also help distinguish PRP from psoriasis.Treatment for PRP varies based on the clinical scenario. Standard initial therapy for patients with limited disease is a class 1 or 2 topical corticosteroid ointment or oil with or without keratolytics. Our patient gained relief and improvement with the application of a potent topical corticosteroid alternating with a solution of lactic acid, 12%, under occlusion. Patients with more severe manifestations of disease may require systemic corticosteroids necessitating tapering, systemic retinoids, methotrexate, azathioprine, or cyclosporine.3 Phototherapy can exacerbate PRP or induce remission7; success has been reported with narrow-band UV-B in combination with acitretin for more widespread disease.8 Although the prognosis is variable, with some patients’ symptoms resolving within 6 months and others’ symptoms persisting for many years, type IV PRP typically persists for 1 to 2 years and fades with no scarring, as was the case in our patient.3,6

Pediatrics

A healthy 7-year-old girl presented with a 2-month history of an itchy rash on her elbows, knees, hands, and feet. The patient was otherwise healthy with normal development and growth. She had no other medical problems and was not taking any medications. The rash started as small pink bumps on her knees and elbows, spreading to her hands and feet and progressively thickening. The patient’s history was otherwise unremarkable; she had no pets, had no recent travel outside the United States, and her vaccinations were up to date.On physical examination, the patient had well-defined, follicular, pink, scaly papules coalescing into thin plaques on her knees (Figure 1A), elbows, and dorsal hands and feet, as well as diffuse, marked orange-red hyperkeratosis and hyperlinearity of her palms with clear demarcation at the wrists (Figure 1B).A, Well-defined follicular, pink, scaly papules coalescing into plaques on the patient’s knees. B, Marked orange-red hyperkeratosis of the patient’s palms.Initial treatment with hydrocortisone valerate cream, 0.2%, provided minimal improvement. A 4-mm skin punch biopsy was performed.

what is your diagnosis?

What is your diagnosis?

Psoriasis

Ichthyosis

Atopic dermatitis

Circumscribed juvenile pityriasis rubra pilaris

d

female

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2173808

A preteen boy presented with a 1-year history of right-sided nasal obstruction and a 4-day history of intermittent right-sided epistaxis following blunt trauma to the nose. The epistaxis occurred 3 to 4 times a day and resolved with pressure. He did not have facial pain, facial paresthesia, or visual changes. There was no family or personal history of bleeding disorders. Nasal endoscopy revealed a large, well-vascularized, polypoid mass filling the right anterior nasal cavity. A computed tomographic scan showed a right nasal cavity mass (4.5 × 1.7 cm) extending to the posterior choana with opacification and bony remodeling of the right maxillary sinus. The mass had heterogeneous intermediate signal intensity on T2-weighted magnetic resonance imaging (Figure, A). The patient was taken to the operating room for biopsy and possible excision of the nasal mass. As the lesion was biopsied, there was brisk bleeding. However, the lesion was found to have a narrow pedicle of attachment and was resected in its entirety. The mass was based on the superior aspect of the nasal septum and cribriform plate. Hematoxylin-eosin stain showed a sheet-like proliferation of epithelioid and polygonal cells with pale eosinophilic granular cytoplasm and relatively uniform vesicular nuclei (Figure, B). The cells were arranged in nests. Branching, staghorn-like blood vessels were scattered throughout the tumor. The tumor cells stained positive for smooth muscle actin (Figure, C), muscle specific actin, Bcl-2, INI-1, and transcription factor E3 (Figure, D). A, T2-weighted magnetic resonance imaging (MRI) scan of a right nasal cavity mass extending to the posterior choana with heterogeneous intermediate signal intensity. B and C, Histopathologic images. B, A sheetlike proliferation of epithelioid and polygonal cells with pale eosinophilic granular cytoplasm and relatively uniform vesicular nuclei (hematoxylin-eosin, original magnification ×40). C, The tumor cells stained positive for smooth muscle actin (original magnification ×20). D, The tumor cells stained positive for transcription factor E3 (original magnification ×20). What Is Your Diagnosis?

Alveolar rhabdomyosarcoma

Nasal alveolar soft part sarcoma

Malignant melanoma

Juvenile nasopharyngeal angiofibroma

B. Nasal alveolar soft part sarcoma

B

Nasal alveolar soft part sarcoma

These findings were consistent with alveolar soft part sarcoma (ASPS), an extremely rare malignant tumor representing 0.4% to 1.0% of all soft-tissue sarcomas.1 These tumors usually present in the lower extremities of adolescents or young adults.1 Approximately 25% of ASPS tumors present in the head and neck, with a predilection for the tongue and orbit.1,2 Alveolar soft part sarcoma of the nasal and paranasal region is even more rare, with only 4 cases reported in the English literature.1,3-5 They are more common in women than men by a 2:1 ratio.1 The etiology of ASPS is unknown.6This tumor was first described by Christopherson et al6 based on a unique histological appearance and clinical behavior. Alveolar soft part sarcoma is usually a slow-growing and well-vascularized mass with no clinical features to suggest malignant disease.1 When ASPS presents in the nasal cavity, nasal obstruction may be the only symptom. The patient in this case had nonspecific nasal obstruction for 1 year but denied facial pain or clinical symptoms consistent with neural or orbital invasion. Magnetic resonance imaging was negative for intracranial extension.Grossly, ASPS tends to be friable and hemorrhagic with a yellow-red surface.6 The light microscopic characteristics are distinctive and nearly pathognomonic. Alveolar soft part sarcoma cells are large, oval to polyhedral, usually with distinct cell boundaries.6 Typically, cells are arranged in nests with central sloughing creating a pseudo-alveolar shape.7 These tumor cell nests are separated by vascular channels and fibrous septa.2 Of note, head and neck ASPA in children will more commonly have a solid pattern of growth without nesting.7 The nuclei are round with vesicular chromatin and single prominent eccentric nucleoli.6,8 The cytoplasm is finely granular with occasional vacuoles, lightly eosinophilic on hematoxylin-eosin stain, and contains rhomboid-shaped, periodic acid–Schiff–positive crystalline structures.8Alveolar soft part sarcoma has uncertain histogenesis. This tumor stains negatively for myoglobin.6 Only a subset of ASPS cases express desmin as well as neuron-specific enolase.2 Nuclear expression of transcription factor E3 (TFE3) is a sensitive and specific marker for ASPS that represents the fusion of the novel alveolar soft part sarcoma gene (ASPL) on chromosome 17q25 to the TFE3 gene on chromosome Xp11.9Histologically, the differential diagnosis includes paraganglioma, adrenal cortical carcinoma, hepatocellular carcinoma, alveolar rhabdomyosarcoma, malignant melanoma, granular cell tumor, and metastatic renal cell carcinoma.8 The pseudoalveolar arrangement of cells is similar to that found in paragangliomas.6 Vascular invasion and, more rarely, mitotic features seen in ASPS may also be seen in melanoma. Clear-cell changes in ASPS may closely resemble those in metastatic renal cell carcinoma.8 This differential diagnosis was narrowed based on age, physical examination, immunohistochemical staining, and radiographic workup.Despite the slow growth of the tumor, overall prognosis is poor, with a high tendency for early metastatic spread. In a study by Cho et al,8 48% of patients with ASPS presented with metastatic disease. Lieberman et al10 reported a 19% incidence of local recurrence over 27 years. The overall survival rates reported are 77% at 2 years, 60% at 5 years, 38% at 10 years, and 15% at 20 years.10 No specific survival data exist in the literature on ASPS in the sinonasal region.Radical surgical excision with tumor-free margins is the preferred treatment for ASPS.8 Radiation and/or chemotherapy is used as adjuvant treatment. Nasal and paranasal sinus tumors can be difficult to excise with tumor-free margins, and therefore, postoperative radiation is common. In this patient, we performed complete surgical resection of the tumor. He recovered well and is currently receiving adjuvant chemotherapy.

General

A preteen boy presented with a 1-year history of right-sided nasal obstruction and a 4-day history of intermittent right-sided epistaxis following blunt trauma to the nose. The epistaxis occurred 3 to 4 times a day and resolved with pressure. He did not have facial pain, facial paresthesia, or visual changes. There was no family or personal history of bleeding disorders. Nasal endoscopy revealed a large, well-vascularized, polypoid mass filling the right anterior nasal cavity. A computed tomographic scan showed a right nasal cavity mass (4.5 × 1.7 cm) extending to the posterior choana with opacification and bony remodeling of the right maxillary sinus. The mass had heterogeneous intermediate signal intensity on T2-weighted magnetic resonance imaging (Figure, A). The patient was taken to the operating room for biopsy and possible excision of the nasal mass. As the lesion was biopsied, there was brisk bleeding. However, the lesion was found to have a narrow pedicle of attachment and was resected in its entirety. The mass was based on the superior aspect of the nasal septum and cribriform plate. Hematoxylin-eosin stain showed a sheet-like proliferation of epithelioid and polygonal cells with pale eosinophilic granular cytoplasm and relatively uniform vesicular nuclei (Figure, B). The cells were arranged in nests. Branching, staghorn-like blood vessels were scattered throughout the tumor. The tumor cells stained positive for smooth muscle actin (Figure, C), muscle specific actin, Bcl-2, INI-1, and transcription factor E3 (Figure, D). A, T2-weighted magnetic resonance imaging (MRI) scan of a right nasal cavity mass extending to the posterior choana with heterogeneous intermediate signal intensity. B and C, Histopathologic images. B, A sheetlike proliferation of epithelioid and polygonal cells with pale eosinophilic granular cytoplasm and relatively uniform vesicular nuclei (hematoxylin-eosin, original magnification ×40). C, The tumor cells stained positive for smooth muscle actin (original magnification ×20). D, The tumor cells stained positive for transcription factor E3 (original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Alveolar rhabdomyosarcoma

Juvenile nasopharyngeal angiofibroma

Nasal alveolar soft part sarcoma

Malignant melanoma

c

male

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2195884

A young boy with mild developmental delay and autism presented with a 1-week history of progressive left periorbital swelling. His parents reported that he complained of left orbital pain just before they noticed the swelling, and he was treated with cold compresses with only slight improvement. He had never experienced these symptoms before. The patient had not experienced diplopia, change in visual acuity, nasal obstruction, change in oral intake, weight loss, recent upper respiratory infection, sick contacts, fevers, or chills. At the time of presentation, the patient was breathing comfortably and was afebrile. Findings from his head and neck examination were significant for a firm mass over the left zygoma and lateral infraorbital rim, 2 × 3 cm in diameter. The mass was nontender, nonerythematous, and fixed to the underlying zygoma and lateral infraorbital rim. There was no cervical lymphadenopathy. Ophthalmology examination revealed intact extraocular movements, bilateral visual acuity of 20/50, and no evidence of afferent papillary defect. Computed tomographic (CT) images showed a round, soft-tissue mass with osseous destruction and erosion into the zygoma, infratemporal fossa, inferolateral orbit, and maxillary sinus (Figure, A and B). Concern for orbital involvement prompted magnetic resonance imaging (MRI) of the maxillofacial region (Figure, C and D). He was taken to the operating room the following day for open biopsy. A and B, Computed tomographic images of the maxillofacial region showing a round, soft-tissue mass. A, Coronal view. B, Axial view. C and D, Magnetic resonance imaging (MRI) scans of the maxillofacial region; C, T2-weighted MRI scan, axial view. D, Postcontrast T1-weighted MRI scan, coronal view. What Is Your Diagnosis?

Metastatic neuroblastoma

Rhabdomyosarcoma

Lymphoma

Lipoma

B. Rhabdomyosarcoma

B

Rhabdomyosarcoma

Rhabdomyosarcomas are rapidly growing, aggressive neoplasms in children, representing 4% to 8% of all malignant neoplasms in children younger than 15 years. Rhabdomyosarcomas are more common in white males, with a peak incidence at ages 2 to 6 years.1,2 Rhabdomyosarcomas originate from the embryonic mesenchymal precursor of striated muscle, and the diagnosis is largely based on immunohistochemical staining.3 Histologically, rhabdomyosarcomas are divided into 5 groups: embryonic (58%), alveolar (31%), botryoid (6%), pleomorphic (4%), and undifferentiated (1%).4In our patient, computed tomographic images showed a 2.7 × 2.1 × 2.2-cm round, soft-tissue mass with bony erosion of the left zygoma and orbit. The exact site of origin was unclear. It was difficult to determine if the lesion was a bony metastatic lesion or a soft-tissue lesion with surrounding bony erosion. The mass displaced the globe medially, but there was an intact soft-tissue plane between the mass and the globe (Figure, A and B). Owing to the extensive destruction of the inferior and lateral orbit, the patient also underwent MRI. On T2-weighted axial MRI, the mass showed intermediate signal intensity (Figure, C). On postcontrast T1-weighted coronal MRI, the mass was hypointense with irregular enhancement (Figure, D).Rhabdomyosarcoma has variable reported imaging findings. Owing to the rarity of head and neck rhabdomyosarcoma, most CT and MRI findings are derived from small case series. Furthermore, different subtypes may have different radiographic findings.5 They are commonly isodense or slightly hypodense on precontrast CT images with homogeneous enhancement on postcontrast CT images. They are isointense or variably hyperintense on T1-weighted MRI. On T2-weighted MRI, they are moderate to markedly hyperintense with homogeneous and heterogeneous enhancement.5The differential diagnosis also included metastatic neuroblastoma, Langerhans cell histiocytosis, Ewing sarcoma, lymphoma, and osteosarcoma. Neuroblastoma is the third most common pediatric malignant neoplasm, with 25% of patients presenting with metastases to the orbit with bony destruction.6 Both Langerhans cell histiocytosis and metastatic neuroblastoma characteristically involve the posterolateral part of the orbit.6 This patient’s tumor was not in this characteristic location, although neuroblastoma metastases to the maxilla have been reported.7 Ewing sarcoma of the orbit is rare.8 On CT, Ewing sarcoma appears as a diffuse, unevenly enhancing mass associated with mottled bone destruction, making the exact site of origin difficult to determine.5 Lymphoma of the orbit is hyperdense on CT, hypointense on T1-weighted MRI, and hypointense to hyperintense on T2-weighted MRI with homogeneous enhancement. Typically, lymphoma molds to rather than destroys the orbital rim.9 Any portion of the orbit may be affected.9Among these differential diagnoses, there are no pathognomonic imaging findings. Further imaging with ultrasound or positron emission tomography/CT has not proven to significantly contribute to diagnosing these tumors. Biopsy is necessary for diagnosis. This patient underwent a sublabial approach for open biopsy. The frozen specimen revealed a small round blue cell tumor. The tumor stained strongly for muscle markers desmin, myogenin, and myoD1. Myogenin and MyoD1 identify nuclear proteins and are sensitive and specific for rhabdomyosarcoma.4 It was negative for NB84 and chromogranin, markers for neuroblastoma. The final pathologic diagnosis was embryonal rhabdomyosarcoma.Treatment of rhabdomyosarcoma has evolved over the past 25 years to multidisciplinary protocols consisting of surgery, radiation, and various chemotherapy regimens. In this case, extensive orbital erosion prevented primary surgical resection owing to concern for significant functional morbidity and incomplete resection. The use of risk-adapted multidrug chemotherapy combined with radiotherapy and surgical excision when possible has improved the overall 5-year survival rate for pediatric head and neck rhabdomyosarcoma from 25% in 1970 to 74% in 1997.10 The patient was referred for chemotherapy and proton beam radiation.

General

A young boy with mild developmental delay and autism presented with a 1-week history of progressive left periorbital swelling. His parents reported that he complained of left orbital pain just before they noticed the swelling, and he was treated with cold compresses with only slight improvement. He had never experienced these symptoms before. The patient had not experienced diplopia, change in visual acuity, nasal obstruction, change in oral intake, weight loss, recent upper respiratory infection, sick contacts, fevers, or chills. At the time of presentation, the patient was breathing comfortably and was afebrile. Findings from his head and neck examination were significant for a firm mass over the left zygoma and lateral infraorbital rim, 2 × 3 cm in diameter. The mass was nontender, nonerythematous, and fixed to the underlying zygoma and lateral infraorbital rim. There was no cervical lymphadenopathy. Ophthalmology examination revealed intact extraocular movements, bilateral visual acuity of 20/50, and no evidence of afferent papillary defect. Computed tomographic (CT) images showed a round, soft-tissue mass with osseous destruction and erosion into the zygoma, infratemporal fossa, inferolateral orbit, and maxillary sinus (Figure, A and B). Concern for orbital involvement prompted magnetic resonance imaging (MRI) of the maxillofacial region (Figure, C and D). He was taken to the operating room the following day for open biopsy. A and B, Computed tomographic images of the maxillofacial region showing a round, soft-tissue mass. A, Coronal view. B, Axial view. C and D, Magnetic resonance imaging (MRI) scans of the maxillofacial region; C, T2-weighted MRI scan, axial view. D, Postcontrast T1-weighted MRI scan, coronal view.

what is your diagnosis?

What is your diagnosis?

Rhabdomyosarcoma

Lymphoma

Metastatic neuroblastoma

Lipoma

a

male

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2204928

A man in his 40s presented with a 2-year history of a few small painful nodules on both ears. The nodules were painful on touch, especially while the patient was sleeping in a lateral position. There was no history of trauma. However, he used to wear a cap, which created pressure and friction on the upper part of both ears. On examination, the free border of the helix of both the ears showed a few dull red, dome-shaped, firm nodules 2 to 3 mm in size with central crusting (Figure, A). They were tender on palpation. No cervical lymphadenopathy was observed. One of the nodules on the right ear was excised; histopathologic features of the nodule are shown in the Figure, B. It showed a sharply defined, centrally depressed ulcer covered by a hyperkeratotic parakeratotic scale, occasional bacterial colonies, and plasma. The adjacent epidermis showed hyperplasia. The base of ulcer showed eosinophilic degeneration of collagen and solar elastosis. In addition, there were a few proliferating blood vessels and mild lymphomononuclear infiltrate. Underlying cartilage was not seen in the section. On serial sectioning, cartilage was seen and found to be normal.A, An ear with dull red, dome-shaped, firm nodules 2 to 3 mm in size with central crusting (arrowheads). B, Histopathologic image (hematoxylin-eosin, original magnification ×100). What Is Your Diagnosis?

Keratoacanthoma

Chondrodermatitis nodularis chronica helicis

Glomus tumor

Rheumatoid nodule

B. Chondrodermatitis nodularis chronica helicis

B

Chondrodermatitis nodularis chronica helicis

Chondrodermatitis nodularis chronica helicis (CNCH) was first described by Winkler in 1915 and later on, in 1918, by Foerste.1 It is an uncommon disorder of middle-aged and elderly individuals, with a preponderance toward males.2 It has rarely been reported in children.3 It usually involves helical rim in men and the antihelix in women. The right auricle is affected most commonly, but in some cases it may be bilateral, as was seen in this case.CNCH usually presents as a solitary, firm, dome-shaped, immobile nodule that is less than 1 cm in size and is exquisitely tender. On closer inspection, an erythematous nodule having central ulceration with overlying crust can be appreciated.CNCH results from ischemic damage to the cartilage and collagen.4-6 The anatomy of the auricle (ie, lack of a thick cushioning subcutaneous layer and the presence of the small dermal blood vessels) predisposes it to ischemia. The degeneration of collagen and cartilage results from vascular compromise caused by mechanical pressure during sleep, prolonged cell phone use, or pressure caused by a tight-fitting cap, as was seen in this case. Frost bite, actinic damage, and sometimes autoimmune etiology have also been implicated. The transepidermal elimination of the damaged collagen and cartilage may be considered as a reparative process.Biopsy is necessary to confirm the diagnosis. The characteristic histopathologic features are epidermal ulceration or a wedge-shaped epidermal defect, epithelial hyperplasia, collagen degeneration, focal fibrinoid necrosis, and inflammatory components.5 Cartilage may be altered, but it may frequently be normal. Peripheral solar elastosis and the presence of glomus cell aggregates are common. The histopathologic features of this case were very characteristic.The clinical differential diagnosis includes a number of other benign and malignant conditions, such as cutaneous horns, warts, clavus, tophus, rheumatoid, or rheumatic nodules, pseudocysts and discoid lupus erythematosus, senile keratosis, keratoacanthoma, basal cell carcinoma, and squamous cell carcinomas.4,7First-line therapy includes using protective padding placed around the external ear while sleeping.8 The standard treatment is deep shave or excision of the lesion with the underlying cartilage.9,10 Other treatment modalities are topical and intralesional glucocorticoid, curettage, electrocauterization, cryotherapy, intralesional collagen injection, pentoxifylline, and carbon-dioxide or argon laser.

General

A man in his 40s presented with a 2-year history of a few small painful nodules on both ears. The nodules were painful on touch, especially while the patient was sleeping in a lateral position. There was no history of trauma. However, he used to wear a cap, which created pressure and friction on the upper part of both ears. On examination, the free border of the helix of both the ears showed a few dull red, dome-shaped, firm nodules 2 to 3 mm in size with central crusting (Figure, A). They were tender on palpation. No cervical lymphadenopathy was observed. One of the nodules on the right ear was excised; histopathologic features of the nodule are shown in the Figure, B. It showed a sharply defined, centrally depressed ulcer covered by a hyperkeratotic parakeratotic scale, occasional bacterial colonies, and plasma. The adjacent epidermis showed hyperplasia. The base of ulcer showed eosinophilic degeneration of collagen and solar elastosis. In addition, there were a few proliferating blood vessels and mild lymphomononuclear infiltrate. Underlying cartilage was not seen in the section. On serial sectioning, cartilage was seen and found to be normal.A, An ear with dull red, dome-shaped, firm nodules 2 to 3 mm in size with central crusting (arrowheads). B, Histopathologic image (hematoxylin-eosin, original magnification ×100).

what is your diagnosis?

What is your diagnosis?

Keratoacanthoma

Rheumatoid nodule

Chondrodermatitis nodularis chronica helicis

Glomus tumor

c

male

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2204930

A healthy nonsmoking woman in her 30s presented with a 6-year history of a nontender mass on the right side of the inferior face, overlying the mandible. She first noticed the mass following an uncomplicated dental procedure. It grew slowly for a few years but then stabilized. She stated that it was sensitive to cold liquids but was otherwise asymptomatic. Results from routine laboratory tests and hematologic markers were normal. Examination revealed a roughly 4 × 2.5-cm, nontender, firm mass anterior to the right mandibular parasymphysis. The mass was fully mobile relative to the underlying mandible and could be seen bulging into the gingivolabial sulcus. There were no overlying skin or mucosal changes, and the skin and mucosa moved freely over the mass. Computed tomographic (CT) imaging demonstrated a well-defined, hyperdense, mildly heterogeneous mass with few focal areas of fat attenuation along the inferior aspect of the lesion (Figure, A-C). The mass was separate from the right mandibular parasymphysis without evidence of periosteal reaction or erosion into the underlying bone. The surrounding soft tissues appeared unremarkable. No additional lesions were noted. The patient was taken to the operating theater, where a firm, multilobulated, yellow mass was excised through a gingivolabial incision (Figure, D). The mass was not fixed to any adjacent structures.A-C, Computed tomographic images. Axial views of soft tissue (A) and bony windows (B) demonstrating an ossified hyperdense mass within the right gingivobuccal space with well-defined margins. D, The intraoperative photograph shows the well-defined mass, just prior to removal, arising in the right gingivobuccal space, separate from the underlying mandible. What Is Your Diagnosis?

Osteolipoma

Myositis ossificans

Liposarcoma

Calcified teratoma/dermoid

A. Osteolipoma

A

Osteolipoma

Lipomas are the most common soft-tissue tumor of adulthood. A rare variant is the osteolipoma, which has been reported in the literature under various interchangeable names, including ossifying lipoma, osseous lipoma, lipoma with osseous metaplasia, and osteolipomatous hamartoma. There are fewer than 20 reported cases of extracranial osteolipoma in the head and neck.An osteolipoma is classified as a lesion with adipose tissue and randomly distributed trabeculae of laminated bone.1 Osteolipomas are predominately located within long bones (intraosseous) or attached to the trunk bones (parosteal). The parosteal subtype is situated directly overlying the bony cortex, beneath the periosteum, and demonstrates hyperostosis and/or pathological changes of the adjacent bone.2 Sun et al3 reported a case of ossifying parosteal lipoma of the mandible with the CT appearance of a “broad-based, well-demarcated hypodense mass with an exophytic osseous protuberance and branch-like periosteal thickening from the underlying symphysis of the mandible.” Intraoperatively, it was necessary to chisel through bone to free the osteolipoma from the mandible. That case differs considerably from the case described herein, in which, radiographically and clinically, the mass was completely separate from the mandible. This represents the least common subtype of osteolipoma, which interestingly has been reported with highest frequency in the head and neck region.4The pathogenesis of an osteolipoma is unclear. The proposed mechanisms include5 (1) adipose and osseous proliferation from pluripotent mesenchymal stem cells; (2) metaplasia of fibroblasts within a lipoma; (3) osteo-inducing factors released in a lipoma by blood-borne monocytes; and (4) microtrauma and/or mechanical stress in a long-standing lipoma, resulting in ischemia and subsequent calcification.The differential diagnosis for a well-defined, extraosseous soft-tissue mass containing both adipose and osseous components is limited and includes both benign and, rarely, malignant processes. While it depends on the location, the differential diagnosis should include fat-containing lesions with calcification, such as teratoma, dermoid cyst, and myositis ossificans, and more ominous diagnoses, such as liposarcoma. Given the imaging appearance in this case of a benign, well-defined, predominantly ossified solid lesion with minimal fat, the differential diagnosis included myositis ossificans vs a calcified lipoma or osteolipoma. Although dermoids and teratomas can contain both fat and calcification, they are usually more heterogenous and cystic in imaging appearance. Liposarcomas, and other bone-forming malignant soft-tissue tumors, have a more aggressive appearance on imaging, with infiltrative margins, abnormal periosteal reaction, and enhancing soft-tissue components. Myositis ossificans (MO) is a process of bone metaplasia within muscle tissue. The most common type is circumscribed or traumatic MO, with a typical appearance on CT of an intramuscular lesion with a well-circumscribed lesion with a distinct zoning pattern in which lesional maturation (ossification) progresses from an immature, central, nonossified cellular focus, to osteoid, and then to a peripheral rim of mature bone over days to weeks. On delayed imaging (≥5-6 months), these appear as sharply circumscribed ossified masses, usually separate from the underlying bone by a radiolucent zone. There is some associated pain and tenderness in the early stages. In the head and neck, MO is often found in the pterygoid muscles but can be seen in the masseter, temporalis, buccinators, sternocleidomastoid, and platysma.6,7 The ossification in MO is presumed to result from repeated microtrauma or inflammatory disease. In contrast with the case described herein, the fat component of the osteolipomas typically predominates the calcified and/or ossified component.In conclusion, osteolipoma represents a rare lesion in the head and neck, which may present a diagnostic challenge owing to variations in location, presentation, and imaging appearance. These lesions should be in the differential for a well-defined soft-tissue mass containing both fat and osseous component. Fortunately, the prognosis is good and surgical excision is curative, with no reported cases of recurrence in the literature.

General

A healthy nonsmoking woman in her 30s presented with a 6-year history of a nontender mass on the right side of the inferior face, overlying the mandible. She first noticed the mass following an uncomplicated dental procedure. It grew slowly for a few years but then stabilized. She stated that it was sensitive to cold liquids but was otherwise asymptomatic. Results from routine laboratory tests and hematologic markers were normal. Examination revealed a roughly 4 × 2.5-cm, nontender, firm mass anterior to the right mandibular parasymphysis. The mass was fully mobile relative to the underlying mandible and could be seen bulging into the gingivolabial sulcus. There were no overlying skin or mucosal changes, and the skin and mucosa moved freely over the mass. Computed tomographic (CT) imaging demonstrated a well-defined, hyperdense, mildly heterogeneous mass with few focal areas of fat attenuation along the inferior aspect of the lesion (Figure, A-C). The mass was separate from the right mandibular parasymphysis without evidence of periosteal reaction or erosion into the underlying bone. The surrounding soft tissues appeared unremarkable. No additional lesions were noted. The patient was taken to the operating theater, where a firm, multilobulated, yellow mass was excised through a gingivolabial incision (Figure, D). The mass was not fixed to any adjacent structures.A-C, Computed tomographic images. Axial views of soft tissue (A) and bony windows (B) demonstrating an ossified hyperdense mass within the right gingivobuccal space with well-defined margins. D, The intraoperative photograph shows the well-defined mass, just prior to removal, arising in the right gingivobuccal space, separate from the underlying mandible.

what is your diagnosis?

What is your diagnosis?

Liposarcoma

Calcified teratoma/dermoid

Osteolipoma

Myositis ossificans

c

female

0-10

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2203827

A previously healthy woman in her 50s presented with complaints of increasing forgetfulness, fatigue, and depressed mood after dealing with the deaths of several close relatives. She was diagnosed with depression and began treatment with antidepressant medication.After 8 months, she had worsening complaints. At that time, a family member reported that her memory problems had progressed. She was no longer able to find misplaced objects, remember appointments, or handle financial affairs. She was often subdued, her mood depressed, and her sleeping time increased. Clinical examination at that time revealed a flattened affect and a 22 of 30 Mini-Mental State Examination score. Findings were otherwise normal, and there were no focal neurologic deficits. Basic laboratory workup results were unremarkable. She was referred to a neurologist, who ordered contrast-enhanced magnetic resonance imaging (MRI) of the brain.The MRI (Figure) revealed extensive ill-defined areas of FLAIR (fluid-attenuated inversion recovery) and T2 signal abnormalities with additional enhancing nodular foci located within deep white matter structures, the basal ganglia, the caudate, the pons, and the midbrain. Also identified was enhancement of the interpeduncular cistern and cerebral peduncles, suggestive of leptomeningeal involvement.Magnetic resonance images (MRIs) of the head obtained 8 months after patient’s first clinical visit. A, Axial T2-weighted MRI of the head at the level of the lateral ventricles demonstrates extensive ill-defined areas of increasing signal with only minimal associated mass effect involving the frontal lobe white matter, greater on the left than on the right. B, Contrast-enhanced T1-weighted MRI at the same level demonstrates abnormal patchy enhancement of the head of the left caudate nucleus and the deep anterior left frontal lobe white matter.Neoplasms such as multicentric glioma, glioblastoma multiforme, and metastases What Is Your Diagnosis?

Inflammatory demyelinating processes such as multiple sclerosis

Neoplasms such as multicentric glioma, glioblastoma multiforme, and metastases

Infectious causes including tuberculosis, neurosyphilis, and toxoplasmosis

Primary central nervous system lymphoma

D. Primary central nervous system lymphoma

D

Primary central nervous system lymphoma

Following imaging, the patient underwent stereotactic brain biopsy, which revealed diffuse large B-cell lymphoma. Further workup revealed no other sites of disease, and Primary central nervous system lymphoma (PCNSL) was diagnosed.Contrast-enhanced MRI is the preferred imaging technique for evaluating PCNSL because it is useful for staging and biopsy planning (ability to identify spinal and/or leptomeningeal involvement). Histologically, PCNSL demonstrates dense cellular lesions that have the classic appearance of isodense to hyperdense areas on computed tomography scans and isointense to hypointense regions on T1-weighted MRI scans, which are hyperintense to white matter on T2-weighted MRI images. Unlike metastatic lesions, which often have a distinct border with contiguous brain parenchyma, PCNSL often demonstrates an infiltrative pattern within brain parenchyma. These lesions typically exhibit intense, homogeneous enhancement after contrast administration. In a study that looked at MRI features in 100 patients with PCNSL,1 only 1 patient had lesions that did not have strong or moderately strong contrast enhancement. Ring enhancement of the lesions can be seen in cases of PCNSL in immunocompromised individuals, such as those with human immunodeficiency virus (HIV), but such enhancement is considered a rare finding in immunocompetent patients.2In the same study,1 90 of a subpopulation of 96 patients with PCNSL had significant edema on MRI imaging. Along with contrast enhancement, surrounding edema is another classic finding with PCNSL, which often results in local mass effect.In immunocompetent patients, PCNSL most frequently presents as a single lesion. In some cases, however, it can present as multiple lesions, which is a typical imaging finding in patients with HIV lymphoma. In the review of 100 patients with PCNSL,1 it was found that 65% of patients presented with only 1 lesion.Most frequently involving the cerebral hemispheres, PCNSL can also involve all areas of the craniospinal axis, including brain parenchyma, leptomeninges, spinal cord, and eyes. Within the brain itself, PCNSL can involve the cortex, deep structures such as basal ganglia, corpus callosum, and periventricular regions.3 Of 100 patients with PCNSL,1 cerebral hemispheric involvement was present in 38% (most commonly in the frontal lobes). The basal ganglia were involved in 16% of cases, corpus callosum in 14%, and periventricular regions in 14%. Leptomeningeal and cerebellar involvement was found to be the least likely location.1Primary central nervous system lymphoma can also present with ocular involvement, estimated to be present in 10% to 20% of patients with PCNSL. Such ocular involvement often presents as uveitis or optic nerve infiltration on imaging.4Histologic verification of PCNSL with biopsy is necessary prior to initiation of treatment. Many patients with PCNSL who are symptomatic at presentation have lesions of considerable size with associated edema and mass effect and are consequently treated with corticosteroids to relieve the associated symptoms. The corticosteroids can rapidly “melt away” lymphomatous tumors, making stereotactic biopsy and resection difficult. Suspicion of PCNSL from imaging is crucial in the workup of these central nervous system lesions so that clinicians can refrain from prescribing corticosteroids prior to biopsy. An imaging-based suggestion of a diagnosis of PCNSL may allow for a diagnostic biopsy to be completed prior to initiation of corticosteroid administration. Quick implementation of treatment regimens can improve prognosis and quality of life for these patients.Our case highlights the notion that the characteristic features of PCNSL may be changing. Imaging of PCNSL in immunocompetent patients most commonly reveals a solitary infiltrative mass in the cerebral hemispheres, basal ganglia, or periventricular white matter.1,3 Recently, there have been increasing numbers of immunocompetent individuals presenting with multifocal intracranial lesions that involve both the supratentorial and infratentorial regions,2 as in our patient. Given the increasing incidence and insidious nature of PCNSL, it is essential to recognize this disease clinically and with imaging. It is imperative for radiologists and clinicians to be aware of the characteristic imaging findings of PCNSL in immunocompetent patients as well as the apparently evolving imaging findings of these lesions.

Oncology

A previously healthy woman in her 50s presented with complaints of increasing forgetfulness, fatigue, and depressed mood after dealing with the deaths of several close relatives. She was diagnosed with depression and began treatment with antidepressant medication.After 8 months, she had worsening complaints. At that time, a family member reported that her memory problems had progressed. She was no longer able to find misplaced objects, remember appointments, or handle financial affairs. She was often subdued, her mood depressed, and her sleeping time increased. Clinical examination at that time revealed a flattened affect and a 22 of 30 Mini-Mental State Examination score. Findings were otherwise normal, and there were no focal neurologic deficits. Basic laboratory workup results were unremarkable. She was referred to a neurologist, who ordered contrast-enhanced magnetic resonance imaging (MRI) of the brain.The MRI (Figure) revealed extensive ill-defined areas of FLAIR (fluid-attenuated inversion recovery) and T2 signal abnormalities with additional enhancing nodular foci located within deep white matter structures, the basal ganglia, the caudate, the pons, and the midbrain. Also identified was enhancement of the interpeduncular cistern and cerebral peduncles, suggestive of leptomeningeal involvement.Magnetic resonance images (MRIs) of the head obtained 8 months after patient’s first clinical visit. A, Axial T2-weighted MRI of the head at the level of the lateral ventricles demonstrates extensive ill-defined areas of increasing signal with only minimal associated mass effect involving the frontal lobe white matter, greater on the left than on the right. B, Contrast-enhanced T1-weighted MRI at the same level demonstrates abnormal patchy enhancement of the head of the left caudate nucleus and the deep anterior left frontal lobe white matter.Neoplasms such as multicentric glioma, glioblastoma multiforme, and metastases

what is your diagnosis?

What is your diagnosis?

Primary central nervous system lymphoma

Neoplasms such as multicentric glioma, glioblastoma multiforme, and metastases

Inflammatory demyelinating processes such as multiple sclerosis

Infectious causes including tuberculosis, neurosyphilis, and toxoplasmosis

a

female

51-60

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2173308

A 36-year-old man presented with 2 weeks of episodic numbness and paresthesias in both feet, with symptom-free intervals between episodes. Episodes progressed in frequency and duration, occurring several times daily and lasting for hours. His symptoms were prominent after activity and reliably triggered by straining with urination and terminated by lying supine. The patient also reported a 1-week history of urinary retention requiring intermittent self-catheterization. Neurological examinations both during and between episodes revealed symmetric patellar and Achilles hyperreflexia with bilateral crossed adductor response, but otherwise the results were normal. A thoracic spine magnetic resonance imaging scan with fast imaging employing steady-state acquisition (FIESTA) sequences was obtained (Figure). A dynamic computed tomographic myelogram demonstrated a lesion compressing the dorsal spinal cord at the T7 level (Video).Magnetic resonance imaging (MRI) of the thoracic spine using fast imaging employing steady-state acquisition (FIESTA) sequences. The MRI scan with FIESTA sequences revealed a blurry spinal cord signal alteration at the T7-T8 level with deformation of the cord posteriorly (arrowhead). What Is Your Diagnosis?

Anterior thoracolumbar spinal cord herniation

Malignant neoplasm of the spinal cord

Spinal dural arteriovenous fistula

Spinal extradural arachnoid cyst

D. Spinal extradural arachnoid cyst

D

Spinal extradural arachnoid cyst

The differential diagnosis for acute urinary retention, lower extremity hyperreflexia, and intermittent sensory or motor deficits dependent on activity and position includes spinal dural arteriovenous fistula, anterior thoracolumbar spinal cord herniation, and symptomatic thoracic arachnoid cysts. Our initial concern that it was a spinal dural arteriovenous fistula led us to perform magnetic resonance imaging of the thoracic spine using FIESTA sequences in hopes of visualizing dilated serpentine spinal veins that may be seen in this entity. The findings were not consistent with a spinal dural arteriovenous fistula but rather demonstrated a flattened spinal cord with edema at the T7-T8 vertebral level (Figure), which is thought to be most compatible with anterior spinal cord herniation or a symptomatic arachnoid cyst. A subsequent computed tomographic myelogram confirmed the presence of a 14.0 × 8.4-mm posterior extradural arachnoid cyst obstructing the free flow of the contrast agent and causing intermittent deformity of the spinal cord at the T7 level with cerebrospinal fluid pulsation (Video).Spinal arachnoid cysts are uncommon protrusions of the spinal cord that rarely cause symptomatic compression of the cord. Although their pathogenesis is poorly understood, they are thought to arise from congenital deformities or dural trauma.1-3 Although magnetic resonance imaging is useful for identifying a soft tissue mass, computed tomographic myelography is the diagnostic study of choice for spinal dural arachnoid cysts because it can reveal a cyst’s access to the subarachnoid space.2,4-6 Furthermore, the dynamic nature of computed tomographic myelography enables real-time visualization of cerebrospinal fluid pulsations accounting for intermittent cord compression by the cyst and the resultant episodic symptoms. The origin of these pulsations has been suggested to be primarily related to the cardia, arising from intracranial pulsations in the cerebrovascular bed and choroid plexus, along with local pulsations in the spinovascular beds.7,8 Respiration has also been shown to variably influence the magnitude and duration of cerebrospinal fluid pulsations.9The definitive treatment of spinal arachnoid cysts is complete surgical excision of the cyst with repair of the communicating dural defect.2 The prognosis is favorable, often with complete resolution of neurological symptoms following operative resection. Those presenting with a shorter duration of symptoms tend to have better outcomes than those with a more prolonged duration.10 Urinary retention may be reversible or irreversible depending on the duration and extent of cord compression.The patient underwent T7-T8 laminectomy with resection of the cyst and experienced immediate resolution of sensory symptoms. Urinary retention resolved 1 week after surgery. He remains asymptomatic more than 1 year later.

Surgery

A 36-year-old man presented with 2 weeks of episodic numbness and paresthesias in both feet, with symptom-free intervals between episodes. Episodes progressed in frequency and duration, occurring several times daily and lasting for hours. His symptoms were prominent after activity and reliably triggered by straining with urination and terminated by lying supine. The patient also reported a 1-week history of urinary retention requiring intermittent self-catheterization. Neurological examinations both during and between episodes revealed symmetric patellar and Achilles hyperreflexia with bilateral crossed adductor response, but otherwise the results were normal. A thoracic spine magnetic resonance imaging scan with fast imaging employing steady-state acquisition (FIESTA) sequences was obtained (Figure). A dynamic computed tomographic myelogram demonstrated a lesion compressing the dorsal spinal cord at the T7 level (Video).Magnetic resonance imaging (MRI) of the thoracic spine using fast imaging employing steady-state acquisition (FIESTA) sequences. The MRI scan with FIESTA sequences revealed a blurry spinal cord signal alteration at the T7-T8 level with deformation of the cord posteriorly (arrowhead).

what is your diagnosis?

What is your diagnosis?

Malignant neoplasm of the spinal cord

Spinal dural arteriovenous fistula

Spinal extradural arachnoid cyst

Anterior thoracolumbar spinal cord herniation

c

male

31-40

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2205900

A woman in her 60s presented to the emergency department with a 1-day history of abdominal pain. She reported acute onset of pain that woke her up from sleep, was crampy in nature, and was localized to the right upper quadrant. She denied any nausea or vomiting and there was no association with eating. She reported similar pain over the previous month but not to the current severity. There was no history of fevers/chills, diarrhea, melena, or hematochezia. She had never had a colonoscopy. Her medical history included hypertension and gastroesophageal reflux. She had no smoking or alcohol history. Her only operations in the past were nononcologic, nongastrointestinal procedures.On examination, her heart and lungs were normal. Her abdomen was soft but tender in the right upper quadrant. Laboratory evaluation revealed a normal compete blood cell count, including a white blood cell count of 8900/µL (to convert to ×109 per liter, multiply by 0.001). Results from a complete metabolic panel, including lipase, and from carcinoembryonic antigen and carbohydrate antigen 19-9 testing were normal. Ultrasonography revealed asymmetric thickening of the gallbladder wall without pericholecystic fluid. Computed tomographic scans of the abdomen with oral and intravenous contrast were obtained (Figure 1).Computed tomographic scan with coronal (A) and sagittal (B) views showing a soft-tissue mass associated with the fundus of the gallbladder. What Is Your Diagnosis?

Acute cholecystitis

Xanthogranulomatous cholecystitis

Gallbladder cancer

Adenomyomatosis of the gallbladder

B. Xanthogranulomatous cholecystitis

B

Xanthogranulomatous cholecystitis

Given the 5-cm mass associated with the gallbladder fundus seen on computed tomographic scan, there was concern for gallbladder cancer. Intraoperative ultrasonography revealed no deep liver masses but an inflamed gallbladder wall containing stones and a soft-tissue mass. She underwent open cholecystectomy with en bloc hepatectomy (1-cm margin of segments 4B and 5). The fundus of the gallbladder was rock hard and grossly concerning for cancer. Two areas of the transverse colon and a portion of the greater omentum appeared inseparably adhered to the gallbladder fundus. The colon dissected away but the omentum was removed en bloc. The infundibulum and cystic duct were free of inflammation but contained a 2-cm stone. Results from testing of all frozen sections, including a wedge biopsy of a whitish nodule in segment 5, returned benign. Final pathological evaluation of the gallbladder specimen revealed pericholecystic bile extravasation with chronic xanthomatous inflammation, confirming diagnosis of xanthogranulomatous cholecystitis (XGC) (Figure 2).Photomicrograph of the resected specimen (hematoxylin-eosin; original magnification ×200).Xanthogranulomatous cholecystitis is a rare form of chronic cholecystitis marked by intense inflammation with asymmetrical thickening of the gallbladder wall, often without pericholecystic fluid, a constellation of findings associated with incidental gallbladder cancer.1 The chronic inflammatory process tends to result in adhesions of the gallbladder with neighboring organs and potential for formation of fistulae and strictures.2 Although a benign disease, XGC is often confused with gallbladder cancer. Studies have reported incidence of 0.7% to 13.2% of all cases of inflammatory disease of the gallbladder.3Computed tomographic findings of XGC include gallbladder wall thickening, hypodense intramural nodule, gallstones, and pericholecystic infiltration.4 Cholecystectomy is the treatment of choice. Given that XGC is a benign disease, frozen section may be helpful in avoiding liver resection but the risk for cancer dissemination associated with tumor violation5-8 must be weighed against the risk of an extended cholecystectomy. A study on distinguishing XGC from gallbladder cancer found that tumor marker carbohydrate antigen 19-9 is significantly higher in XGC, whereas signs and symptoms, such as pain, jaundice, fever, and anorexia, are significantly more common in XGC than early gallbladder cancer.4

Surgery

A woman in her 60s presented to the emergency department with a 1-day history of abdominal pain. She reported acute onset of pain that woke her up from sleep, was crampy in nature, and was localized to the right upper quadrant. She denied any nausea or vomiting and there was no association with eating. She reported similar pain over the previous month but not to the current severity. There was no history of fevers/chills, diarrhea, melena, or hematochezia. She had never had a colonoscopy. Her medical history included hypertension and gastroesophageal reflux. She had no smoking or alcohol history. Her only operations in the past were nononcologic, nongastrointestinal procedures.On examination, her heart and lungs were normal. Her abdomen was soft but tender in the right upper quadrant. Laboratory evaluation revealed a normal compete blood cell count, including a white blood cell count of 8900/µL (to convert to ×109 per liter, multiply by 0.001). Results from a complete metabolic panel, including lipase, and from carcinoembryonic antigen and carbohydrate antigen 19-9 testing were normal. Ultrasonography revealed asymmetric thickening of the gallbladder wall without pericholecystic fluid. Computed tomographic scans of the abdomen with oral and intravenous contrast were obtained (Figure 1).Computed tomographic scan with coronal (A) and sagittal (B) views showing a soft-tissue mass associated with the fundus of the gallbladder.

what is your diagnosis?

What is your diagnosis?

Adenomyomatosis of the gallbladder

Gallbladder cancer

Xanthogranulomatous cholecystitis

Acute cholecystitis

c

female

61-70

White

original

https://jamanetwork.com/journals/jama/fullarticle/2279691

An 82-year-old woman with bladder cancer and treated hypertension was referred by her family physician after she reported experiencing a few days’ history of mild fever, cough, limited deep inspiration, and left-sided pleuritic chest pain. She had no personal or family history of venous thrombosis and did not have any recent surgery, trauma, or admission to hospital. Her long-term medications included fluoxetine, vitamin D, and hydrochlorothiazide.On examination, temperature was 38.3°C (101°F), blood pressure was 157/78 mm Hg, pulse rate was 82 beats per minute, and respiratory rate was 20 breaths per minute. Oxygen saturation was 97% in room air. She had a regular heart rate with a mild systolic murmur; her jugular venous pressure was normal; and lung auscultation revealed reduced air entry at the left base. She had no leg swelling and no pain on calf palpation. Laboratory testing results are reported in Table 1. The attending physician raised the diagnosis of a pulmonary embolism (PE) among the differentials. The clinical probability of PE was unlikely (Wells score).D-dimer test result is positive. Imaging test is required.D-dimer test result is positive. The diagnosis of PE is confirmed.D-dimer test result is positive but below her age-adjusted cutoff. PE is ruled out.D-dimer test result is positive due to active malignancy. PE is ruled out. How Do You Interpret These Test Results?

D-dimer test result is positive. Imaging test is required.

D-dimer test result is positive. The diagnosis of PE is confirmed.

D-dimer test result is positive but below her age-adjusted cutoff. PE is ruled out.

D-dimer test result is positive due to active malignancy. PE is ruled out.

C

D-dimer test result is positive but below her age-adjusted cutoff. PE is ruled out.

D-dimers result from the fibrinolysis of acute thrombi. Enzyme-linked immunosorbent assay (ELISA) and immunoturbidimetric D-dimer assays are highly sensitive for the diagnosis of PE. The D-dimer test should be used in combination with a pretest clinical probability assessment (Table 2). The D-dimer is useful only in patients with a low-intermediate or unlikely pretest clinical probability of PE, as assessed by a validated clinical decision rule.1,2 It should not be used in patients with a high/likely pretest clinical probability. Systematic reviews report a sensitivity of greater than 95% and negative likelihood ratios of 0.10 for ELISA or immuneturbidimetric assays, with a specificity of 40% and a positive likelihood ratio of 1.64.3 Using a cutoff value of 500 ng/mL, a negative D-dimer assay safely rules out the diagnosis of PE in patients with a low-intermediate or unlikely clinical probability. This was demonstrated in several outcome studies in which patients with a low-intermediate or unlikely pretest probability and a negative D-dimer test result were left untreated and followed up for 3 months (ie, the 3-month risk of venous thromboembolism was 0.14% [95% CI, 0.05%-0.41%], lower than the risk observed after a negative pulmonary angiography).4Conversely, because D-dimers increase in many other clinical situations (eg, infection, inflammation, malignancy, postsurgical status, pregnancy), the specificity of the test is low (approximately 50%) and as a result, a positive D-dimer test is not diagnostic for PE.The Medicare midpoint reimbursement is $18.77 for a quantitative D-dimer test.5The D-dimer test result for this patient was 68 ng/mL. This result indicates a positive D-dimer test as per most commercial assays (conventional cutoff value 500 ng/mL). Given the low specificity of the test, a high D-dimer level never rules in the diagnosis of PE. Patients with positive D-dimer results should undergo an imaging test, such as a computed tomography pulmonary angiography (CTPA) or a ventilation-perfusion lung scan.6 However, D-dimer levels increase with age, and as a result, the proportion of patients in whom the diagnosis may be ruled out on the basis of a negative D-dimer test decreases with age—only 5% of patients older than 80 years have a negative D-dimer, as compared with more than 50% of patients aged 40 years or younger.7 An age-adjusted D-dimer cutoff value was recently derived and validated in several retrospective analyses and one prospective management outcome study.8,9 D-dimer results are typically reported without providing the age-adjusted upper limit of normal. However, the age-adjusted cutoff value is easy to compute: in patients aged 50 years or more, a D-dimer level below the product of their age multiplied by 10 (eg, 820 ng/mL in this 82-year-old patient) appears to safely rule out PE without any imaging test.In some centers, most patients with suspected PE are directly referred for a CTPA without prior use of pretest probability assessment and D-dimer. The combination of a D-dimer test with a clinical probability assessment allows ruling out PE without undergoing an imaging test in approximately one-third of outpatients.4 The cost effectiveness of this approach has been demonstrated.7 Moreover, there is an increasing concern about the risk of cancer in patients exposed to radiation from medical imaging.10 The D-dimer test represents a safe and reliable option to avoid the use of CTPA in an important proportion of patients with clinically suspected PE.A chest x-ray film revealed a left inferior lobar consolidation. The patient was treated with antibiotics, discharged home on the same day, and asked to follow up with her general practitioner. She had a good and uneventful recovery.In combination with a validated clinical decision rule, a negative D-dimer assay allows the physician to safely rule out the diagnosis of PE in approximately one-third of outpatients.A positive D-dimer is not diagnostic for PE. Patients with clinically suspected PE and positive D-dimer should undergo imaging tests for PE.According to recent studies, PE might be ruled out in patients with a low-intermediate or unlikely pretest probability and D-dimer level that is less than their age-adjusted cutoff (ie, patient’s age × 10 in patients aged 50 years or older).In combination with a validated clinical decision rule, a negative D-dimer assay allows the physician to safely rule out the diagnosis of PE in approximately one-third of outpatients.A positive D-dimer is not diagnostic for PE. Patients with clinically suspected PE and positive D-dimer should undergo imaging tests for PE.According to recent studies, PE might be ruled out in patients with a low-intermediate or unlikely pretest probability and D-dimer level that is less than their age-adjusted cutoff (ie, patient’s age × 10 in patients aged 50 years or older).

Diagnostic

An 82-year-old woman with bladder cancer and treated hypertension was referred by her family physician after she reported experiencing a few days’ history of mild fever, cough, limited deep inspiration, and left-sided pleuritic chest pain. She had no personal or family history of venous thrombosis and did not have any recent surgery, trauma, or admission to hospital. Her long-term medications included fluoxetine, vitamin D, and hydrochlorothiazide.On examination, temperature was 38.3°C (101°F), blood pressure was 157/78 mm Hg, pulse rate was 82 beats per minute, and respiratory rate was 20 breaths per minute. Oxygen saturation was 97% in room air. She had a regular heart rate with a mild systolic murmur; her jugular venous pressure was normal; and lung auscultation revealed reduced air entry at the left base. She had no leg swelling and no pain on calf palpation. Laboratory testing results are reported in Table 1. The attending physician raised the diagnosis of a pulmonary embolism (PE) among the differentials. The clinical probability of PE was unlikely (Wells score).D-dimer test result is positive. Imaging test is required.D-dimer test result is positive. The diagnosis of PE is confirmed.D-dimer test result is positive but below her age-adjusted cutoff. PE is ruled out.D-dimer test result is positive due to active malignancy. PE is ruled out.

how do you interpret these test results?

How do you interpret these results?

D-dimer test result is positive. The diagnosis of PE is confirmed.

D-dimer test result is positive but below her age-adjusted cutoff. PE is ruled out.

D-dimer test result is positive. Imaging test is required.

D-dimer test result is positive due to active malignancy. PE is ruled out.

b

female

81-90

original

https://jamanetwork.com/journals/jama/fullarticle/2275423

A 15-year-old obese girl presented to clinic with increasing right shin pain of 4 weeks’ duration. The pain began after the patient began to play competitive basketball and was localized to her mid shin. Dietary and menstrual histories revealed no abnormalities. Examination demonstrated focal tenderness along the distal mid shaft of the tibia anteriorly. The single-leg hop test elicited severe localized pain. Radiographs were obtained for further evaluation (Figure).Radiography of the right lower leg. Left, Anteroposterior view. Right, Lateral view.Obtain laboratory work to assess for nutritional or hormonal abnormalitiesOrder observation and pain management with nonsteroidal anti-inflammatory drugs (NSAIDS) What Would You Do Next?

Obtain laboratory work to assess for nutritional or hormonal abnormalities

Refer for immediate surgery

Order immobilization with non–weight-bearing activity

Order observation and pain management with nonsteroidal anti-inflammatory drugs (NSAIDS)

Stress fracture of the anterior tibia

C

Order immobilization with non–weight-bearing activity

The key finding is abnormal radiographs demonstrating a lucency along the distal mid-shaft of the tibia anteriorly, along with anterior cortical thickening, best seen on the lateral view. These findings are consistent with a stress fracture, preceded by a recent increase in activity. The location of the stress fracture on the anterior tibial cortex increases the risk for complete fracture, thereby classifying it as high risk.1 Immobilization with non–weight-bearing activity is the most appropriate first-line management for stress fractures.2Stress fractures are common in sports involving prolonged walking, running, or jumping. They account for 0.7% to 20% of injuries encountered by athletes, involving multiple regions of the body.3 The most frequently reported sites include the tibia, metatarsals, and fibula. Multiple intrinsic and extrinsic factors increase risk for stress fracture. Extrinsic risk factors include the environment, type of activity, and equipment used. These factors influence the amount of mechanical stress introduced. Mechanical stress makes the bone susceptible to microfractures, which can subsequently develop into stress fractures through repetitive stresses. Repetitive tensile or compressive forces and activities that increase the magnitude or rate of bone loading can contribute to damage formation. Mechanical stresses to the bone may individually be below the threshold for fracture but with repetition may increase above that threshold, overcoming the structural properties of the bone.4Intrinsic factors refer to physiologic characteristics such as sex, anatomy, hormone balance, obesity, bone health, and nutrition. These factors influence how the body responds to mechanical stressors. There is an increased risk for musculoskeletal injury in females with disordered eating, menstrual dysfunction, and low bone mineral density, also referred to as the female athletic triad.5 On the other hand, obesity, as in this patient, increases the magnitude of bone loading during activity, which can also increase the risk of stress fracture.4Although performing laboratory studies is useful for determining the presence of any underlying risk factors in the development of stress fractures, a thorough history including dietary and menstrual history is more efficient and cost-effective as the initial method for determining the need for further studies.Plain film radiographs are the preferred initial imaging modality due to their availability and low cost; however, they lack sensitivity. This is because radiographs typically remain normal for the first 2 to 3 weeks after symptom onset.6 If the clinical presentation suggests a stress fracture and initial plain films are negative, magnetic resonance imaging is the preferred subsequent modality. Radiographs in this patient demonstrated a fracture line consistent with a stress fracture of the tibia; therefore, no further imaging was necessary.Because this is a “high risk” fracture because of its location, consultation with an orthopedic surgeon may be beneficial; however, immediate surgery is not necessary, given the acute onset of symptoms and the lack of prior attempts at conservative management. If radiographs demonstrate nonunion or lack of progressive healing after conservative treatment, surgical intervention may be necessary.7Observation and pain management with NSAIDs is not recommended because healing of the fracture requires the removal of the extrinsic mechanical stressor. In this case, the stressor is repetitive jumping and movements associated with basketball. Some literature suggests that use of NSAIDs may be associated with delayed bone formation following fracture; however, a causal relationship has yet to be established.8,9 Nevertheless, NSAIDs are relatively contraindicated because of potential negative effects on bone consolidation.10Immobilization with non–weight-bearing activity is the ideal choice for managing the care of this patient. A boot, splint, or short leg cast decreases the extrinsic load and creates an environment that improves healing.2 The resting period can be as long as 4 to 6 months, with a minimum of 12 weeks to allow for recovery.1 Reimaging and evaluation should typically be performed at the midpoint of treatment. As healing is noted radiographically, activity is advanced slowly and by alternating the types of activities performed. Rehabilitation includes a focus on proper training technique, attire, and nutrition.Four months after immobilization, radiographs demonstrated good bone consolidation. The boot was removed, and the patient was able to ambulate without pain. She gradually returned to full activity after 4 weeks of pain-free ambulation.

General

A 15-year-old obese girl presented to clinic with increasing right shin pain of 4 weeks’ duration. The pain began after the patient began to play competitive basketball and was localized to her mid shin. Dietary and menstrual histories revealed no abnormalities. Examination demonstrated focal tenderness along the distal mid shaft of the tibia anteriorly. The single-leg hop test elicited severe localized pain. Radiographs were obtained for further evaluation (Figure).Radiography of the right lower leg. Left, Anteroposterior view. Right, Lateral view.Obtain laboratory work to assess for nutritional or hormonal abnormalitiesOrder observation and pain management with nonsteroidal anti-inflammatory drugs (NSAIDS)

what would you do next?

What would you do next?

Order immobilization with non–weight-bearing activity

Order observation and pain management with nonsteroidal anti-inflammatory drugs (NSAIDS)

Obtain laboratory work to assess for nutritional or hormonal abnormalities

Refer for immediate surgery

a

female

11-20

original

https://jamanetwork.com/journals/jama/fullarticle/2214057

A 71-year-old man with a history of bronchiectasis presents with a painful rash and swelling of his right foot for 1 day. He has had no fevers, joint pain, recent trauma, or new exposures to the area. He was diagnosed with bronchiectasis of unknown etiology 6 years ago and notes a worsening of his cough and dyspnea over the past few months. A recent computed tomography scan of the chest revealed mild bronchiectasis and ground glass inflammation (Figure, left), and recent pulmonary function tests showed combined obstructive and restrictive defects. His medications include albuterol inhaler, fluticasone-salmeterol inhaler, guaifenesin, and loratadine.Left, Axial computed tomography scan of the chest revealing mild bronchiectasis and ground glass inflammation. Right, Purpuric plaque on the right medial ankle and dorsal foot, with central vesicles.On examination, the patient’s vital signs are normal. He has a purpuric plaque on the right medial ankle and dorsal foot, with central vesicles (Figure, right). The rash is tender to palpation, and there is associated nonpitting edema of the right foot and ankle. Laboratory values are notable for a leukocyte count of 15 700 cells/µL, with 38% eosinophils (absolute count, 5950 cells/µL; normal, <350). His platelet count was 272 000, and his hemoglobin level was 14.7 g/dL. A skin punch biopsy of the rash on the right ankle was performed and results are pending.Obtain blood cultures and empirically treat with intravenous vancomycinPerform a herpes simplex virus/varicella zoster virus direct fluorescent antibody test and empirically treat with valacyclovir What Would You Do Next?

Obtain blood cultures and empirically treat with intravenous vancomycin

Perform a herpes simplex virus/varicella zoster virus direct fluorescent antibody test and empirically treat with valacyclovir

Obtain antineutrophilic cytoplasmic antibodies (ANCA) titers

Start a high-potency topical steroid

Eosinophilic granulomatosis with polyangiitis (EGPA), previously known as Churg-Strauss syndrome

C

Obtain antineutrophilic cytoplasmic antibodies (ANCA) titers

EGPA is a small- and medium-vessel vasculitis classically characterized by asthma, rhinosinusitis, nasal polyposis, and peripheral blood eosinophilia.1 ANCA titers are useful in the diagnosis of EGPA while results of skin biopsy are pending.The patient’s rash presented as a purpuric plaque rather than tender, spreading erythema, as would be expected with cellulitis. It is reasonable to obtain blood cultures to evaluate for infective endocarditis as a cause of a vasculitis-like presentation; however, empirical treatment with systemic antibiotics is not warranted. It is also reasonable to perform a herpes simplex virus/varicella zoster virus direct fluorescent antibody test, given the presence of vesicles and pain; however, empirical treatment with valacyclovir is also not warranted. It is not appropriate to start a high-potency topical steroid until the diagnosis of vasculitis is established.EGPA is a multisystem disorder that most commonly involves the lung and skin but can also present with ear, nose, and throat (ENT) involvement as well as involvement of the cardiovascular, renal, gastrointestinal, and central nervous systems.2 Of the 6 American College of Rheumatology criteria—asthma, more than 10% peripheral blood eosinophilia, mononeuropathy or polyneuropathy, pulmonary opacities, paranasal sinus abnormality, and extravascular eosinophils on tissue biopsy—4 are needed for the diagnosis of EGPA.2 More than 90% of patients with EGPA have a history of asthma, and it is unusual that this patient developed bronchiectasis without a history of asthma.3 The Five-Factors Score (FFS) was developed to assess disease severity and guide therapy in patients with EGPA.4 The 5 scoring criteria, each of which is associated with worse prognosis, are as follows: older than 65 years, cardiac insufficiency, renal insufficiency, gastrointestinal tract involvement, and the absence of ENT manifestations. A score of 0 is assigned when no factors are present: 1 for 1 factor, and 2 for 2 or more factors.Skin involvement affects up to two-thirds of patients with EGPA. Tender subcutaneous nodules on the extensor surface of the arms and legs,2 palpable purpura, hemorrhagic lesions ranging from petechiae to ecchymosis, and macular or papular erythematous rash may be seen.5 Vesicles arising within purpuric plaques of vasculitis, as seen in this patient, occur when the epidermis separates from ischemic dermis as a result of superficial blood vessel occlusion. Biopsy of skin lesions can aid in diagnosis and often reveals a leukocytoclastic vasculitis with eosinophil infiltration.5Antineutrophilic cytoplasmic antibodies are found in 30% to 40% of patients with EGPA, mainly with a perinuclear immunofluorescence pattern (perinuclear ANCA [p-ANCA]); these antibodies, directed against myeloperoxidase, are thus also referred to as antimyeloperoxidase antibodies.3,6 ANCA-positive patients are more likely to have renal involvement and peripheral neuropathy; ANCA-negative patients more commonly have cardiac disease.3,6Systemic glucocorticoid therapy is the mainstay of treatment for EGPA, and most patients achieve remission with this therapy alone.7 However, patients with more severe disease may require the addition of cyclophosphamide to help achieve remission. It is recommended that patients with an FFS of 2 and some patients with an FFS of 1 be treated with cyclophosphamide, which has been shown to significantly prolong survival among patients with severe EGPA.8,9The patient’s skin biopsy revealed small and medium-sized vessel vasculitis with eosinophil-rich vascular and interstitial infiltrates, supporting the diagnosis of EGPA. The p-ANCA (antimyeloperoxidase) titers were positive, and further workup revealed microscopic hematuria with dysmorphic red blood cells and red blood cell casts along with an elevated creatinine level. Renal biopsy was not performed, because glomerulonephritis was suggested by the elevated creatinine level and the results from the urine studies. An ENT examination revealed nasal polyps. With peripheral eosinophilia identified by leukocyte count, pulmonary infiltrates, extravascular eosinophilia on biopsy, and nasal polyposis, the patient met 4 of 6 criteria for diagnosis of EGPA, with an FFS of 2 (age >65 years and renal insufficiency). The patient began oral prednisone (60 mg daily) and cyclophosphamide (2 mg/kg [125 mg] daily). Within 3 days both his painful rash and pulmonary symptoms substantially improved. He continues to do well as the prednisone dose is slowly tapered down.

General

A 71-year-old man with a history of bronchiectasis presents with a painful rash and swelling of his right foot for 1 day. He has had no fevers, joint pain, recent trauma, or new exposures to the area. He was diagnosed with bronchiectasis of unknown etiology 6 years ago and notes a worsening of his cough and dyspnea over the past few months. A recent computed tomography scan of the chest revealed mild bronchiectasis and ground glass inflammation (Figure, left), and recent pulmonary function tests showed combined obstructive and restrictive defects. His medications include albuterol inhaler, fluticasone-salmeterol inhaler, guaifenesin, and loratadine.Left, Axial computed tomography scan of the chest revealing mild bronchiectasis and ground glass inflammation. Right, Purpuric plaque on the right medial ankle and dorsal foot, with central vesicles.On examination, the patient’s vital signs are normal. He has a purpuric plaque on the right medial ankle and dorsal foot, with central vesicles (Figure, right). The rash is tender to palpation, and there is associated nonpitting edema of the right foot and ankle. Laboratory values are notable for a leukocyte count of 15 700 cells/µL, with 38% eosinophils (absolute count, 5950 cells/µL; normal, <350). His platelet count was 272 000, and his hemoglobin level was 14.7 g/dL. A skin punch biopsy of the rash on the right ankle was performed and results are pending.Obtain blood cultures and empirically treat with intravenous vancomycinPerform a herpes simplex virus/varicella zoster virus direct fluorescent antibody test and empirically treat with valacyclovir

what would you do next?

What would you do next?

Perform a herpes simplex virus/varicella zoster virus direct fluorescent antibody test and empirically treat with valacyclovir

Start a high-potency topical steroid

Obtain blood cultures and empirically treat with intravenous vancomycin

Obtain antineutrophilic cytoplasmic antibodies (ANCA) titers

d

male

71-80

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2089058

An elderly woman of Bahamian heritage with Fitzpatrick VI skin type presented with a 1-week history of indolent papules all over her body. She was otherwise asymptomatic. Findings from physical examination were notable for discrete skin-colored to pink papules coalescing into plaques on her face, trunk (Figure, A and B), and all 4 extremities. There was no scale or other epidermal change. A punch biopsy for hematoxylin-eosin staining was performed (Figure, C). The patient returned 1 week later with worsening cutaneous eruptions and new complaints of fever, weakness, and malaise. Repeat physical examination revealed splenomegaly and axillary lymphadenopathy. A peripheral blood smear (Figure, D) and other diagnostic tests were performed.A, Discrete skin-colored to pink papules on the abdomen. B, Discrete papules coalescing into plaques on superior gluteal cleft. C, Punch biopsy specimen (hematoxylin-eosin). D, Peripheral blood smear (hematoxylin-eosin, original magnification ×100). What Is the Diagnosis?

Sarcoidosis

Syphilis

Indeterminate cell histiocytosis

Adult T-cell leukemia/lymphoma

D. Adult T-cell leukemia/lymphoma

D

Adult T-cell leukemia/lymphoma

Hematoxylin-eosin staining of the initial biopsy revealed atypical hyperchromatic lymphocytes with pronounced nuclear irregularity infiltrating into the upper dermis with epidermotropism (Figure, C). Results from laboratory studies were noteworthy for a white blood cell count of 102 × 103/μL and a lactate dehydrogenase level of 5712 U/L. Findings from peripheral blood smear showed markedly atypical lymphocytes with a flower petal appearance (Figure, D). A bone marrow biopsy specimen showed hypercellular marrow with infiltration by atypical lymphocytes in an interstitial distribution. Immunophenotyping revealed an abnormal population of CD2+, CD3+, CD4+, CD7+ cells with partial loss of CD5 expression and partial CD25 coexpression. The result from a serological test for type 1 human T-lymphotropic virus (HTLV-1) was positive and the patient was diagnosed as having acute adult T-cell leukemia/lymphoma (ATLL).The patient was initially treated with high-dose zidovudine and interferon alfa with no response. She was transitioned to therapy with cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone (CHOP). Two weeks after initiating treatment with CHOP, her white blood cell count normalized and her skin lesions began to improve. Within 3 weeks the cutaneous papules continued to progress and she was next treated with brentuximab vedotin. While this initially resulted in significant flattening of the papules, her disease progressed. Etoposide and bortezomib were added to her CHOP regimen. However, her white blood cell count, lactate dehydrogenase level, and burden of cutaneous lesions continued to increase. She died 9 months after presenting to our clinic.Adult T-cell leukemia/lymphoma is a peripheral T-cell neoplasm caused by HTLV-1. Four clinical subtypes of ATLL have been described: acute, smoldering, chronic, and lymphomatous. This discussion focuses on the acute subtype; other subtypes are reviewed elsewhere.1 HTLV-1 is endemic to Japan, the Caribbean basin, Brazil, Peru, West Africa, and parts of the Middle East. HTLV-1 is also associated with tropical spastic paraparesis; however, it rarely occurs coincident with ATLL.The pathogenesis of ATLL is complex. First, the viral tax protein transactivates many genes involved in T-cell proliferation, including the interleukin (IL)-2 receptor α chain (CD25) and IL-2.2 Tax and the HTLV-1 basic leucine zipper factor further contribute to this polyclonal proliferation via modulation of mitotic pathways and cell-cycle regulatory genes.3,4 The low incidence of ATLL (4%-5%) among HTLV-1–infected individuals and extended period of latency suggest that HTLV-1 infection alone is not sufficient for malignant transformation to occur; additional unknown events are likely required.2,5The acute subtype represents 60% of cases and has the worst prognosis.6 The diagnostic criteria include histological or cytological evidence of a lymphoid malignancy (CD2+, CD3+, mostly CD4+, CD5+, strongly CD25+); the presence of circulating malignant T lymphocytes with multiple nuclear convolutions and lobules (flower cells); and a serologic test result positive for HTLV-1.2 Approximately half of patients with ATLL have cutaneous manifestations at presentation.7 Of these, 38.7% presented with nodules or tumors, 26.9% with plaques, 19.3% with multiple papules, 6.7% with patches, 4.2% with purpura, and 4.2% with erythroderma. When the cutaneous T-cell lymphoma TNM staging system was applied to the Japanese population, the cutaneous presentation correlated with prognosis.7 Median survival times ranged from 114.9 months for plaque-type disease to 3 months for erythroderma.7Management of acute ATLL is challenging given the aggressive nature of the disease, inherent multidrug resistance, and underlying immunodeficiency associated with HTLV-1 infection. While a retrospective meta-analysis has shown that first-line treatment with zidovudine plus interferon alfa results in highest overall 5-year survival (28%),8 multiagent chemotherapy remains an important corner stone of therapy. Combined treatment with vincristine, cyclophosphamide, doxorubicin, prednisone, ranimustine, vindesine, etoposide, and carboplatin affords the longest median survival time (12.7 months) in prospective trials.9 Hematopoietic stem cell transplant provides sustained survival for select patients, although morbidity is significant with a median survival time of 7 months.10

Dermatology

An elderly woman of Bahamian heritage with Fitzpatrick VI skin type presented with a 1-week history of indolent papules all over her body. She was otherwise asymptomatic. Findings from physical examination were notable for discrete skin-colored to pink papules coalescing into plaques on her face, trunk (Figure, A and B), and all 4 extremities. There was no scale or other epidermal change. A punch biopsy for hematoxylin-eosin staining was performed (Figure, C). The patient returned 1 week later with worsening cutaneous eruptions and new complaints of fever, weakness, and malaise. Repeat physical examination revealed splenomegaly and axillary lymphadenopathy. A peripheral blood smear (Figure, D) and other diagnostic tests were performed.A, Discrete skin-colored to pink papules on the abdomen. B, Discrete papules coalescing into plaques on superior gluteal cleft. C, Punch biopsy specimen (hematoxylin-eosin). D, Peripheral blood smear (hematoxylin-eosin, original magnification ×100).

what is the diagnosis?

What is your diagnosis?

Syphilis

Adult T-cell leukemia/lymphoma

Sarcoidosis

Indeterminate cell histiocytosis

b

female

71-80

Bahamian

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2091534

A man in his 70s with a history of T2N2 melanoma, locally metastatic squamous cell carcinoma, and non-Hodgkin follicular lymphoma presented with weakness, a blistering erythematous eruption, and painful oral lesions of 1 month’s duration. On physical examination, the patient was in severe discomfort with limited movement owing to cutaneous pain. He was cachectic and had widespread erosions and tense and flaccid bullae with overlying crust affecting his trunk and extremities (including the palms and soles) but sparing his scalp (Figure, A). He had severe stomatitis with localized hemorrhagic lesions, shaggy erosions on the buccal and gingival mucosa, and erythematous macules on his hard and soft palates (Figure, B). Findings from laboratory tests, including a complete blood cell count and a comprehensive metabolic panel, were unremarkable except for mild anemia. Results from a computed tomographic scan of the chest and neck showed adenopathy suspicious for lymphoproliferative disorder or potentially metastatic disease. A punch biopsy for histopathologic examination (Figure, C) and direct immunofluorescence (DIF) was performed, and serum was tested for indirect immunofluorescence (IIF) on rodent epithelium (Figure, D).A, Erosions, tense and flaccid bullae, and overlying crust over the dorsal side of the foot. B, Severe stomatitis and hemorrhagic crust. C, Histopathologic image of a biopsy specimen showing suprabasal acantholysis and a dermal infiltrate of lymphocytes, histiocytes, and scattered eosinophils (hematoxylin-eosin, original magnification ×20). D, Positive indirect immunofluorescence test of rat urinary bladder epithelium. What Is the Diagnosis?

Bullous pemphigoid

Stevens-Johnson syndrome

Paraneoplastic pemphigus

Pemphigus vulgaris

C. Paraneoplastic pemphigus

C

Paraneoplastic pemphigus

Results from the biopsy showed suprabasal acantholysis with separation of the superficial epidermis and a dermal infiltrate consisting of lymphocytes, histiocytes, and scattered eosinophils. Direct immunofluorescence revealed intercellular deposits of IgG and C3. Based on these results, a presumptive diagnosis of pemphigus vulgaris (PV) was made; however, the severe stomatitis and palmar and plantar involvement raised the possibility of paraneoplastic pemphigus (PNP). To confirm, IIF assay using rodent epithelium was performed. Therapy was initiated with intravenous methylprednisolone sodium succinate (1 g/d for 10 days) and rituximab (650 mg/wk for 4 weeks), then intravenous immunoglobulin (IVIg) (1 g/kg for 5 days). He still had progression of his skin disease, so he elected comfort care and died shortly thereafter.Paraneoplastic pemphigus was first described in 1990 by Anhalt et al1 as a severe autoimmune blistering disease. It is life threatening and is almost exclusively diagnosed in patients with an underlying hematologic malignant disease, the most common being non-Hodgkin lymphoma, chronic lymphocytic leukemia, and Castleman disease.2 The prognosis is poor, with a mortality rate as high as 90%, commonly owing to sepsis and complications from the underlying neoplasm.3 Bronchiolitis obliterans is another feared complication, characterized by sloughing of the respiratory epithelium resulting in dyspnea and respiratory failure. Owing to PNP’s etiology and associated systemic involvement, the alternative term paraneoplatic autoimmune multiorgan syndrome has been proposed.4Patients commonly present with painful mucosal erosions and a polymorphous skin eruption.5 The earliest findings are severe stomatitis with erosions and crusting involving the tongue and lips; however, any mucosal area can be affected.6 Cutaneous lesions appear shortly thereafter and are characterized by lesions of varying morphologic characteristics, including flaccid bullae, tense bullae, targetoid lesions, and papules on the upper body more than on the lower. With numerous cutaneous morphologic characteristics, PNP is often misdiagnosed as several other skin conditions, namely PV, pemphigus foliaceus, bullous pemphigoid, and erythema multiforme or Stevens-Johnson syndrome. The presence of flaccid bullae over acral regions can help distinguish PNP from PV, tense bullae can distinguish PNP from pemphigus foliaceus, and the widespread nature differentiates it from erythema multiforme.The clinical manifestations described herein result from autoantibodies against desmogleins (Dsg) and plakin proteins, leading to loss of epithelial cell adhesion.4 The specific antigens targeted include Dsg 3 (130 kd), Dsg 1 (160 kd), envoplakin (210 kd), periplakin (190 kd), desmoplakin 1 (250 kd), desmoplakin II (210 kd), bullous pemphigoid antigen 1 (230 kd), and alpha-2-macroglobulin–like-1 (170 kd). Diagnosis of PNP is based on the presence of these autoantibodies and can be confirmed using immunoprecipitation, DIF, and/or IIF. Immunoprecipitation is a serum-based test that demonstrates the presence of multiple autoantibodies quickly with high sensitivity and specificity.7 It is a favorable technique to confirm the diagnosis of PNP in patients with severe stomatitis when performing a skin biopsy may be difficult.6 Classically, DIF reveals IgG and C3 deposits in an intercellular and linear basement membrane zone pattern, differentiating PNP from other types of pemphigus. The linear deposits were not observed in this case and are not uncommonly missed.4 Indirect immunofluorescence is performed on rat bladder epithelium because plakins are strongly expressed in rodent epithelium and autoantibodies to plakins are most specific to PNP.7The histological findings of PNP are variable, ranging from suprabasal acantholysis to lichenoid dermatitis depending on the clinical morphologic characteristics of the lesions. For this reason, a combination of clinical and histopathological criteria are used for diagnosis.6 Treatment for PNP is initially aimed at treating the underlying malignant disease in attempt to slow the autoantibody response. Systemic corticosteroids are used most frequently, often in combination with rituximab, azathioprine, cyclosporine, methotrexate, mycophenolate mofetil hydrochloride, cyclophosphamide, or IVIg.5Paraneoplastic pemphigus should be a diagnostic consideration in patients with widespread mucosal erosions and should prompt evaluation for possible underlying malignant disease. Multiple clinical morphologic variants may occur simultaneously, which may serve as a clinical clue to the correct diagnosis. Our patient’s follicular lymphoma was thought to be quiescent; however, the skin findings raised suspicion that his lymphoma may have been advancing, increasing the urgency for a positron-emission tomographic scan and reinforcing the need for ongoing chemotherapy.

Dermatology

A man in his 70s with a history of T2N2 melanoma, locally metastatic squamous cell carcinoma, and non-Hodgkin follicular lymphoma presented with weakness, a blistering erythematous eruption, and painful oral lesions of 1 month’s duration. On physical examination, the patient was in severe discomfort with limited movement owing to cutaneous pain. He was cachectic and had widespread erosions and tense and flaccid bullae with overlying crust affecting his trunk and extremities (including the palms and soles) but sparing his scalp (Figure, A). He had severe stomatitis with localized hemorrhagic lesions, shaggy erosions on the buccal and gingival mucosa, and erythematous macules on his hard and soft palates (Figure, B). Findings from laboratory tests, including a complete blood cell count and a comprehensive metabolic panel, were unremarkable except for mild anemia. Results from a computed tomographic scan of the chest and neck showed adenopathy suspicious for lymphoproliferative disorder or potentially metastatic disease. A punch biopsy for histopathologic examination (Figure, C) and direct immunofluorescence (DIF) was performed, and serum was tested for indirect immunofluorescence (IIF) on rodent epithelium (Figure, D).A, Erosions, tense and flaccid bullae, and overlying crust over the dorsal side of the foot. B, Severe stomatitis and hemorrhagic crust. C, Histopathologic image of a biopsy specimen showing suprabasal acantholysis and a dermal infiltrate of lymphocytes, histiocytes, and scattered eosinophils (hematoxylin-eosin, original magnification ×20). D, Positive indirect immunofluorescence test of rat urinary bladder epithelium.

what is the diagnosis?

What is your diagnosis?

Paraneoplastic pemphigus

Stevens-Johnson syndrome

Pemphigus vulgaris

Bullous pemphigoid

a

male

71-80

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2091957

A woman in her 20s with a medical history significant for systemic lupus erythematosus (SLE) presented with tender erythematous nodules after undergoing right knee arthroscopy (Figure, A). SLE had been diagnosed ten years previously after she presented with a positive antinuclear antibody titer (most recent titer, 1:1280), arthralgias, leukopenia, oral ulcers, and a malar erythematous eruption. There was no history of discoid or tumid lupus lesions. Initially, the lesions were thought secondary to soft-tissue infection and were treated with courses of clindamycin, vancomycin, and doxycycline. Physical examination revealed poorly demarcated erythematous plaques and nodules, tender to palpation, ranging from the distal thigh to the lower leg, adjacent to arthroscopy sites. Lesions around the suture sites appeared more violaceous. A punch biopsy of the lesion was performed (Figure, B and C).A, Clinical photograph of right knee demonstrating ill-defined erythematous plaques and nodules adjacent to 2 small incisional scars from previous arthroscopy. B and C, Photomicrographs of punch biopsy specimen. B, Hematoxylin-eosin, original magnification ×4. C, Hematoxylin-eosin, original magnification ×10. What Is the Diagnosis?

Cellulitis

Tumid lupus erythematosus

Gyrate erythema

Erythema nodosum

B. Tumid lupus erythematosus

B

Tumid lupus erythematosus

The biopsy specimen showed dense, superficial and deep, perivascular and periadnexal lymphocytic infiltrate (Figure, B). Higher-power magnification (Figure, C) demonstrated deep periadnexal lymphocytic infiltrate. The patient had been taking hydroxychloroquine for her well-controlled SLE prior to presentation. The patient was treated with prednisone taper, which improved the lesions, but flares occurred with tapering. Clobetasol ointment improved the redness, but the lesions were still sore and edematous. Quinacrine treatment was subsequently added to the hydroxychloroquine, and worst areas were treated with intralesional kenalog. The patient noted the most significant improvement with the intralesional kenalog, and the lesions improved substantially over the next several months. Of note, the patient developed a deep venous thrombosis in the same extremity and a subsequent pulmonary embolus. Lupus anticoagulant antibody titer was negative, and the patient was treated with rivaroxaban.Tumid lupus erythematosus (TLE) is an uncommon distinct subset of chronic cutaneous lupus erythematosus. First described in 1930, TLE is an infrequent topic in the literature. Characteristic descriptions of TLE include nonscarring erythematous plaques or papules, symmetrically distributed on sun-exposed areas of the face, neck, arms, and back. The histologic differential diagnosis includes polymorphous light eruption, Jessner lymphocytic infiltration of the skin, reticular erythematous mucinosis, and pseudolymphoma. It is rare for TLE lesions to present unilaterally,1,2 below the waistline,1,2 and concomitantly with SLE.1,3 To our knowledge, only 2 other cases of TLE occurring at a site of trauma haven been reported.4 In both cases, the patients presented with asymptomatic plaques appearing weeks after the trauma, in contrast to our patient who presented with symptomatic lesions within days. In addition, neither of these cases carried a diagnosis of SLE. The Koebner phenomenon with chronic cutaneous lupus at the sites of scratches or scars has been reported in patients with SLE.5 However, discoid lesions are more often noted, and the scars are generally mature, whereas our patient’s scar was new. The Koebner phenomenon frequently correlates to the activity of the associated disease,5 but the patient’s SLE was well-controlled at the time she developed TLE. Topical corticosteroids or sunscreens alone may lead to complete resolution of TLE, and systemic antimalarial agents are effective in treating approximately ninety percent of cases.1 Systemic corticosteroids or immunosuppressants may be effective in persistent cases.1

Dermatology

A woman in her 20s with a medical history significant for systemic lupus erythematosus (SLE) presented with tender erythematous nodules after undergoing right knee arthroscopy (Figure, A). SLE had been diagnosed ten years previously after she presented with a positive antinuclear antibody titer (most recent titer, 1:1280), arthralgias, leukopenia, oral ulcers, and a malar erythematous eruption. There was no history of discoid or tumid lupus lesions. Initially, the lesions were thought secondary to soft-tissue infection and were treated with courses of clindamycin, vancomycin, and doxycycline. Physical examination revealed poorly demarcated erythematous plaques and nodules, tender to palpation, ranging from the distal thigh to the lower leg, adjacent to arthroscopy sites. Lesions around the suture sites appeared more violaceous. A punch biopsy of the lesion was performed (Figure, B and C).A, Clinical photograph of right knee demonstrating ill-defined erythematous plaques and nodules adjacent to 2 small incisional scars from previous arthroscopy. B and C, Photomicrographs of punch biopsy specimen. B, Hematoxylin-eosin, original magnification ×4. C, Hematoxylin-eosin, original magnification ×10.

what is the diagnosis?

What is your diagnosis?

Gyrate erythema

Erythema nodosum

Cellulitis

Tumid lupus erythematosus

d

female

21-30

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2211142

A man in his late 30s presented to the emergency department for a left eye mass impairing his vision. He reported that he first noticed a small lesion on the nasal conjunctiva of his left eye 6 months earlier; there was rapid growth during the last 2 months. The mass became painful 4 weeks earlier and started to affect his vision 2 weeks earlier. His ocular history included enucleation of his right eye secondary to a traumatic ruptured globe 6 years previously. He denied any systemic medical problems and was not taking any medications. On examination, his visual acuity was no light perception OD (prosthesis) and light perception OS. External examination revealed a well-fitting prosthesis in the right eye with a healthy upper and lower eyelid fornix. The left eye is shown in Figure 1. An incisional biopsy was performed.Clinical photograph at presentation demonstrating a large, hemorrhagic, necrotic mass obscuring the entire globe and eyelids of the left eye. What Would You Do Next?

Exenteration

Computed tomographic scan of the orbit

Enucleation

Testing for human immunodeficiency virus (HIV)

Conjunctival squamous cell carcinoma (SCC)

B

Computed tomographic scan of the orbit

The patient presented with a large exophytic mass obscuring the globe, originating from the conjunctiva. The differential diagnosis of a large, rapidly growing conjunctival lesion includes SCC, lymphoma, melanoma, and, because the lesion may have originated from the eyelid skin, eyelid SCC, basal cell carcinoma, and keratoacanthoma. Incisional biopsy was performed to make the diagnosis. The next best step is to determine the extent of disease by orbital imaging (either computed tomography or magnetic resonance imaging). Computed tomography of the orbit demonstrated intraorbital extension (Figure 2). Testing for HIV should be performed on younger patients who develop skin or conjunctival cancers.Axial computed tomographic scan of the orbit at presentation demonstrating a large, infiltrating, heterogeneous mass encapsulating the left globe with extension into the retrobulbar postseptal space without evidence of intracranial or bony involvement.The biopsy demonstrated conjunctival SCC. Conjunctival SCC has an incidence of 0.2 to 3.5 cases per 100 000 persons.1 Incidence varies based on risk factors, including age older than 60 years, European descent, light eye and skin pigment, UV light exposure, smoking, and comorbidities such as xeroderma pigmentosa, human papilloma virus 16 and 18, and HIV.2 Patients with HIV are younger and develop more aggressive lesions.3 Local extension can be intraocular (4%-11%), involve the cornea and/or sclera (30%-38%), or invade the orbit (8%-15%).4,5 Metastasis, while rare, occurs most commonly to regional lymph nodes. Computed tomography or magnetic resonance imaging of the head and neck is recommended for invasive or recurrent cases to identify occult lymphadenopathy and metastases.Treatment options include topical chemotherapy, surgery, or radiation. Small lesions (typically <4 clock hours) with limited extension can undergo excision using a no-touch technique (with or without lamellar sclerectomy) and cryotherapy to the wound bed and adjacent conjunctiva. Patients with tumors that are extensive or involve a large corneal area should receive topical chemotherapy after resection.6 Chemotherapeutic agents commonly used are mitomycin C, 5-fluorouracil, or interferon alfa-2b, which have comparable rates of resolution and recurrence.7 Patients with advanced disease, intraocular extension, or multiple recurrences require enucleation, while those with intraorbital extension require exenteration. Radiation is reserved for positive or close surgical margins, therapy failure, and diffuse or spreading disease.2,5Follow-up is extremely important as recurrence within the first 2 years after treatment ranges from 15% to 52%. Recurrence is most related to incomplete resection; other risk factors include increased age, large lesion diameter, and high proliferation index of the tumor.4,5,8 Excision plus cryotherapy can reduce recurrence to 5.3%.9 Patients should also be monitored for treatment-related complications such as ocular surface toxic effects, limbal stem cell deficiency, and radiation-induced keratopathy, retinopathy, and neuropathy.The patient’s young age and aggressive presentation prompted HIV testing and he was found to be positive. He was referred to the infectious disease service for HIV management. Whole-body positron emission tomography was negative for metastases. Globe salvage was not possible owing to the intraorbital involvement and the patient underwent exenteration with referral to blind services.

Ophthalmology

A man in his late 30s presented to the emergency department for a left eye mass impairing his vision. He reported that he first noticed a small lesion on the nasal conjunctiva of his left eye 6 months earlier; there was rapid growth during the last 2 months. The mass became painful 4 weeks earlier and started to affect his vision 2 weeks earlier. His ocular history included enucleation of his right eye secondary to a traumatic ruptured globe 6 years previously. He denied any systemic medical problems and was not taking any medications. On examination, his visual acuity was no light perception OD (prosthesis) and light perception OS. External examination revealed a well-fitting prosthesis in the right eye with a healthy upper and lower eyelid fornix. The left eye is shown in Figure 1. An incisional biopsy was performed.Clinical photograph at presentation demonstrating a large, hemorrhagic, necrotic mass obscuring the entire globe and eyelids of the left eye.

what would you do next?

What would you do next?

Testing for human immunodeficiency virus (HIV)

Exenteration

Computed tomographic scan of the orbit

Enucleation

c

male

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2211143

A 38-year-old woman developed acute painless blurred vision in her right eye 3 weeks after receiving a single injection of corticosteroid in her deltoid for stenosing tenosynovitis. Her medical history was significant for stage II breast carcinoma with positive lymph nodes, which was diagnosed and treated 5 years prior. Subsequent annual metastatic surveillance test results had been negative for recurrence. Visual acuity was 20/60 OD and 20/20 OS. Ophthalmoscopy of the right eye revealed a 6 × 6-mm circumscribed serous macular detachment with turbid subretinal fluid. Similar lesions were present in the nasal and inferior midperiphery (Figure, A and B). The left eye was unremarkable. Fluorescein angiography (FA) showed hyperfluorescent pinpoint hot spots with interspersed hypofluorescent patches in the areas of the lesions (Figure, C-F). Notably absent on FA were retinal pigment epithelium (RPE) leakage, a smokestack pattern of subretinal leakage, or RPE gutter defects. B-scan ultrasonography demonstrated choroidal thickening nasal to the optic disc (Figure, G); vascularity could not be assessed. Optical coherence tomography (OCT) showed a localized serous macular detachment with a focal area of choriocapillaris infiltration and thickening near the nasal edge of the detachment (Figure, H).Fundus photograph (A-B) of the right eye demonstrates a serous macular detachment with yellowish choroidal discoloration. A, Similar yellowish choroidal lesions (arrowheads) were present in the nasal and inferior midperiphery. B, The enlarged image demonstrates the extent of serous macular detachment (arrowheads). C, Wide-angle fluorescein angiography in the late venous phase of the right eye shows an area between the disc and fovea with scattered hyperfluorescent hotspots. Magnified views of the macular lesion (D), nasal lesion (E), and inferior lesion (F). G, B-scan ultrasonography of the right eye shows a subtle nonspecific choroidal thickening with medium internal reflectivity. The arrowhead points to the choroidal infiltration by the metastatic tumor. H, Spectral-domain optical coherence tomography of the right eye demonstrates serous macular detachment with localized subtle choroidal vascular attenuation, infiltration, and thickening (arrowheads).Blood tests to consider diagnosis of syphilitic chorioretinitis What Would You Do Next?

Consider managing as multifocal central serous chorioretinopathy

Consider a diagnosis of choroidal metastasis

Obtain workup for Vogt-Koyanagi-Harada syndrome

Blood tests to consider diagnosis of syphilitic chorioretinitis

A diagnosis of metastatic breast cancer was suspected and a systemic workup was obtained. A bone scan revealed multiple active foci within the ribs and brain magnetic resonance imaging revealed an 8 × 4-mm dural-based enhancing lesion at the superior falx, consistent with metastasis.

B

Consider a diagnosis of choroidal metastasis

Breast cancer is the most common primary site of choroidal metastasis in women.1 Choroidal metastasis from breast cancer typically presents as a creamy yellow choroidal mass with overlying serous retinal detachment most commonly occurring in the posterior pole.2 The lesions are often multiple and bilateral. Ultrasonography typically shows an elevated choroidal mass with medium-high irregular internal reflectivity and minimal vascularity. Fluorescein angiography often shows patchy late hyperfluorescence with pinpoint leakage.In contrast, the FA appearance of central serous chorioretinopathy (CSCR) typically reveals 1 or more pinpoint areas of leakage at the level of the RPE (often in a smokestack or expansile dot pattern of dye leakage in the subretinal space) and geographic areas of chronic RPE mottling. These findings are occasionally accompanied by linear tracks or gutters of RPE alteration at sites of previous subretinal fluid.3In both choroidal metastasis and CSCR, the OCT may show serous retinal detachment but these entities differ in the appearance of the choroid. Central serous chorioretinopathy is often associated with marked thickening of the choroid due to enlargement of choroidal vessels.4 In contrast, here choroidal metastasis appeared on the OCT as a thickening of the choroid owing to infiltration and attenuation of choroidal vessels by solid tissue. Optical coherence tomography was very helpful in this patient by showing the subtle choroidal mass that was not detectable on clinical examination and nondiagnostic on ultrasonography.Patients with suspected choroidal metastasis should undergo metastatic workup, which may include magnetic resonance imaging of the brain, computed tomography of the chest/abdomen/pelvis, a bone scan, a positron emission tomographic scan, and serum cancer markers. If the metastatic workup result is negative and there remains a strong suspicion for choroidal metastasis, a fine-needle aspiration biopsy can often establish the diagnosis. Treatment options for choroidal metastasis include systemic chemotherapy, external beam radiation therapy, laser photocoagulation, photodynamic therapy, transpupillary thermotherapy, and observation. Systemic chemotherapy was used in this patient owing to systemic involvement and external beam radiation therapy was recommended owing to macular involvement and visual impairment.5Metastasis of systemic cancer to the choroid can present with a wide range of clinical findings. Features of this case that initially suggested a diagnosis of CSCR included the serous retinal detachments, lack of obvious choroidal mass, history of corticosteroid use, and geographic areas of RPE mottling on FA. The features that favored a choroidal metastasis diagnosis included the yellowish color, choroidal infiltration on OCT, lack of FA findings typical of CSCR, and history of breast cancer. This case highlights the value of OCT in such cases and emphasizes the importance of obtaining a detailed history in patients with suspected CSCR in whom the clinical features are atypical.Systemic therapy was instituted with intravenous bevacizumab, paclitaxel, and denosumab along with 12 fractions (25 Gy) of external beam radiotherapy to the right eye. At 14 weeks after completion of external beam radiation therapy, visual acuity returned to 20/25 OD and has remained stable through 1 year of follow-up with no radiation retinopathy or cataract.

Ophthalmology

A 38-year-old woman developed acute painless blurred vision in her right eye 3 weeks after receiving a single injection of corticosteroid in her deltoid for stenosing tenosynovitis. Her medical history was significant for stage II breast carcinoma with positive lymph nodes, which was diagnosed and treated 5 years prior. Subsequent annual metastatic surveillance test results had been negative for recurrence. Visual acuity was 20/60 OD and 20/20 OS. Ophthalmoscopy of the right eye revealed a 6 × 6-mm circumscribed serous macular detachment with turbid subretinal fluid. Similar lesions were present in the nasal and inferior midperiphery (Figure, A and B). The left eye was unremarkable. Fluorescein angiography (FA) showed hyperfluorescent pinpoint hot spots with interspersed hypofluorescent patches in the areas of the lesions (Figure, C-F). Notably absent on FA were retinal pigment epithelium (RPE) leakage, a smokestack pattern of subretinal leakage, or RPE gutter defects. B-scan ultrasonography demonstrated choroidal thickening nasal to the optic disc (Figure, G); vascularity could not be assessed. Optical coherence tomography (OCT) showed a localized serous macular detachment with a focal area of choriocapillaris infiltration and thickening near the nasal edge of the detachment (Figure, H).Fundus photograph (A-B) of the right eye demonstrates a serous macular detachment with yellowish choroidal discoloration. A, Similar yellowish choroidal lesions (arrowheads) were present in the nasal and inferior midperiphery. B, The enlarged image demonstrates the extent of serous macular detachment (arrowheads). C, Wide-angle fluorescein angiography in the late venous phase of the right eye shows an area between the disc and fovea with scattered hyperfluorescent hotspots. Magnified views of the macular lesion (D), nasal lesion (E), and inferior lesion (F). G, B-scan ultrasonography of the right eye shows a subtle nonspecific choroidal thickening with medium internal reflectivity. The arrowhead points to the choroidal infiltration by the metastatic tumor. H, Spectral-domain optical coherence tomography of the right eye demonstrates serous macular detachment with localized subtle choroidal vascular attenuation, infiltration, and thickening (arrowheads).Blood tests to consider diagnosis of syphilitic chorioretinitis

what would you do next?

What would you do next?

Consider managing as multifocal central serous chorioretinopathy

Blood tests to consider diagnosis of syphilitic chorioretinitis

Consider a diagnosis of choroidal metastasis

Obtain workup for Vogt-Koyanagi-Harada syndrome

c

female

31-40

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2214030

A 7-year-old girl presented to the dermatology clinic with a 4-week history of progressive nail changes. Her mother reported a sudden onset of brittle nails with cracks followed by painless sloughing of nails. Initially only the fingernails had been affected, but the toenails soon showed the same pathology. The family was concerned and suspected an internal disease or vitamin deficiency. The child was otherwise well and no previous skin or nail conditions were known. On clinical examination, most fingernails showed semilunar whitish grooves in the middle of the nail plate (Figure, A). The toenails had transverse partial cracks of the proximal nail plate with distal onycholysis but normal proximal nail growth (Figure, B).Findings on clinical examination. A, Fingernails showed semilunar whitish grooves in the middle of the nail plate. B, Toenails had transverse partial cracks of the proximal nail plate with distal onycholysis. What Is Your Diagnosis?

Drug intake

Kawasaki syndrome

Vaccination reaction

Hand-foot-and-mouth disease

D. Hand-foot-and-mouth disease (HFMD)

D

Hand-foot-and-mouth disease

Onychomadesis describes the complete shedding of the nail plate from the nail bed, occurring after a sudden growth arrest of the nail matrix (Figure, B). As a milder variant, Beau lines may be seen presenting as semilunar transverse grooves of the nail plate (Figure, A). While nail changes can be an important marker of genetic conditions or internal disease in pediatric patients, they are usually associated with additional changes of the skin, mucous membranes, or hair. Although often suspected by parents, onychomycosis is rare overall in young children.1 Nail dystrophy in childhood is often due to eczema or paronychia affecting the nail matrix. Onycholysis and hyperkeratosis of the nail may be the result of subungual warts.2 Acute onychomadesis is often considered to be idiopathic, but various infectious triggers have been described.The history of our patient revealed HFMD 7 weeks before the onset of the nail changes. It is a rather common infection in children caused by coxsackievirus, a member of the family of enteroviruses. Small epidemic outbreaks are usually reported in autumn or spring. The condition is characterized by low-grade fever and an acute vesicular eruption of the hands, feet, buttocks, oral cavity, lips, and perioral area. The blisters are usually small, oval shaped, and grayish with an erythematous border in combination with a vesicular and erosive stomatitis. However, the clinical presentation is very variable, with some children presenting with only a few blisters and others with generalized exanthema (eczema coxsackium).3Since the first 5 cases reported in 2000,4 HFMD has come to be associated with nail matrix arrest and onychomadesis. Several local epidemics of HFMD with up to 220 patients affected by onychomadesis have been reported.5 Several strains were identified, most commonly coxsackievirus B1 as in Spain6 and coxsackievirus A6 as in Japan.7 The mechanism for post-HFMD nail matrix arrest remains unclear. No relationship seems to exist between the severity of HFMD, location of blisters, and fever. One group was able to detect coxsackievirus A6 DNA extracted from nail fragments in children with onychomadesis, supporting the idea of direct nail matrix damage due to virus replication.8 Others have discussed secondary appearance due to inflammation of the nail matrix.9 Nail changes typically appear 3 to 10 weeks after the onset of infection. During the North American HFMD epidemic in 2011-2012, secondary nail changes were noted in approximately one-quarter of cases.3 Others report higher incidences of up to 70% when coxsackievirus is involved.6 To our knowledge, no reports of onychomadesis have been reported when other enteroviruses such as enterovirus 71 were the cause of HFMD. Other causes for acute onychomadesis include infections involving high fever (norovirus infection, swine flu, scarlet fever), Kawasaki syndrome, drug intake (anticonvulsants, antibiotics, chemotherapy agents, and retinoids), acute paronychia, Stevens-Johnson syndrome, systemic lupus erythematosus, pemphigus vulgaris, and epidermolysis bullosa.2Onychomadesis following HFMD is a self-limiting condition with subsequent normal nail regrowth within weeks. No specific treatment is indicated. Affected patients and their parents should be reassured about the benign nature of this appearance.

Pediatrics

A 7-year-old girl presented to the dermatology clinic with a 4-week history of progressive nail changes. Her mother reported a sudden onset of brittle nails with cracks followed by painless sloughing of nails. Initially only the fingernails had been affected, but the toenails soon showed the same pathology. The family was concerned and suspected an internal disease or vitamin deficiency. The child was otherwise well and no previous skin or nail conditions were known. On clinical examination, most fingernails showed semilunar whitish grooves in the middle of the nail plate (Figure, A). The toenails had transverse partial cracks of the proximal nail plate with distal onycholysis but normal proximal nail growth (Figure, B).Findings on clinical examination. A, Fingernails showed semilunar whitish grooves in the middle of the nail plate. B, Toenails had transverse partial cracks of the proximal nail plate with distal onycholysis.

what is your diagnosis?

What is your diagnosis?

Drug intake

Kawasaki syndrome

Vaccination reaction

Hand-foot-and-mouth disease

d

female

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2119039

A man in his 50s presented with a 7-month history of worsening, primarily left-sided, sinus obstruction and congestion with associated hyposmia, facial pressure, and headaches. He had no history of sinus disease or surgery and had no epistaxis, weight loss, or visual symptoms. Computed tomography showed a 3.1-cm mass in the left ethmoid sinus and nasal cavity (Figure, A). Positron emission tomographic scanning showed no evidence of metastasis. Nasal endoscopy revealed a friable, polypoid mass in the ethmoid sinus with extension into the nasal cavity and superiorly to the skull base. A biopsy specimen showed a heterogeneous tumor with small, angulated, blue cells with hyperchromatic nuclei, apoptosis, and mitosis, malignant glands lined by cuboidal cells with round nuclei, prominent nucleoli, and eosinophilic cytoplasm. The glands had luminal mucin production (Figure, B). Focally, there were also scattered round cells with abundant eosinophilic, refractile cytoplasm, features of rhabdomyoblasts (Figure, C). These latter cells were strongly positive for desmin (Figure, D) and myogenin. Ethmoid sinus mass. A, Computed tomographic scan. The arrowhead indicates the mass. B, Blastema as indicated by the asterisk and malignant glands as indicated by the arrowhead. C, Rhabdomyoblasts as indicated by the arrowheads (hematoxylin-eosin, original magnification ×40). D, Desmin immunohistochemistry with strong positive staining in the rhabdomyoblasts (original magnification ×20). What Is Your Diagnosis?

Olfactory neuroblastoma

Sinonasal teratocarcinosarcoma

Small cell carcinoma

Alveolar rhabdomyosarcoma

B. Sinonasal teratocarcinosarcoma

B

Sinonasal teratocarcinosarcoma

Sinonasal teratocarcinosarcoma (SNTCS) is a rare and aggressive malignant neoplasm with fewer than 100 reported cases. It most commonly involves the nasal cavity and paranasal sinuses, particularly the ethmoid and maxillary sinuses, although cases have been reported in the oral cavity, nasopharynx, and orbit.1 It occurs primarily in men at a mean age of 55 to 60 years.1,2 The clinical differential diagnosis for an upper nasal cavity mass includes nonneoplastic, benign, and malignant lesions. The latter includes olfactory neuroblastoma, squamous cell carcinoma, lymphoma, melanoma, neuroendocrine carcinoma, rhabdomyosarcoma, sinonasal undifferentiated carcinoma, and many other rarer entities. SNTCS is so rare as to be very low on this list.SNTCS most commonly presents with nasal obstruction (in 76% of cases) and epistaxis (in 63%). Frontal headaches are relatively common (in 20%), but other symptoms, such as visual changes, proptosis, anosmia or hyposmia, airway obstruction, and frontal lobe-related neurologic changes, occur in less than 10% of cases.1 Tumors are large at presentation, averaging 5.3 cm.1Histologically, SNTCS has a highly complex and variable mixture of immature neural or blastemal-appearing components and various benign, atypical, or overtly malignant epithelial and mesenchymal elements without features of specific germ cell tumors, such as seminoma, embryonal carcinoma, choriocarcinoma, or yolk sac tumor.1,3-5 The epithelial component is typically immature and comprises “fetal appearing” squamous cells in 50% to 75% of cases.3 Ciliated columnar and mucin-producing cells with glandular and duct formation are also common.5 Mesenchymal elements possible in SNTCS include fibroblasts, cartilage, and smooth or striated muscle.1 Rhabdomyoblasts (primitive skeletal muscle cells) are sometimes seen and consist of polygonal or spindle-shaped cells with refractile, eosinophilic cytoplasm.5 Primitive neuroectodermal or blastemal components are characterized by small, hyperchromatic cells that may be organized in nests, sheets, or rosettes, and stain positively for neuroendocrine markers, such as synaptophysin, chromogranin A, and CD99.2 Staining of the epithelial and mesenchymal elements depends on the particular components of a given tumor. Given their histologic heterogeneity and rarity, SNTCS is commonly misdiagnosed, especially when inadequately sampled during biopsy, with an initial identification rate of roughly 50%.1SNTCS histogenesis is speculative, with most authors agreeing that it likely arises either from immature pluripotent cells sequestered in the sinonasal tract or from totipotent olfactory epithelial cells that can differentiate into the neuroectodermal, mesenchymal, and epithelial components characteristic of SNTCS.3,6 It is unlikely a germ cell tumor given that it lacks true germ cell tumor elements. This is further evidenced by the lack of chromosome 12p amplification in SNTCS, an alteration which is commonly associated with true germ cell tumors.7 Furthermore, these tumors almost always occur in adult men, a pattern inconsistent with germ cell tumors.Treatment of SNTCS is challenging given its aggressive clinical behavior and is centered on surgical resection. In a literature review by Misra et al1 involving 86 cases (the largest and most complete to date), 87.2% of patients with SNTCS underwent surgery. The most common treatment regimen was surgery with adjuvant radiation therapy, the treatment used in 59.5% of all cases. Chemotherapy with or without surgery or radiation was used in only 18.6% of all cases, although some evidence suggests that the use of chemotherapy in addition to surgery and radiation may improve survival and decrease rates of recurrence and metastasis.1 The patient described herein underwent surgery to negative margins, received postoperative radiation, and is currently without evidence of recurrence 6 months postdiagnosis.The prognosis of SNTCS is poor. Survival rates are reported to be 30% to 54% at 3 years and 20% at 5 years,2,8 with a mean survival of 1.7 to 1.9 years.3,6 Recurrence and metastasis rates are high, occurring in 67% of patients treated with surgery alone2 and 45.7% of patients treated with surgery and radiation.1

General

A man in his 50s presented with a 7-month history of worsening, primarily left-sided, sinus obstruction and congestion with associated hyposmia, facial pressure, and headaches. He had no history of sinus disease or surgery and had no epistaxis, weight loss, or visual symptoms. Computed tomography showed a 3.1-cm mass in the left ethmoid sinus and nasal cavity (Figure, A). Positron emission tomographic scanning showed no evidence of metastasis. Nasal endoscopy revealed a friable, polypoid mass in the ethmoid sinus with extension into the nasal cavity and superiorly to the skull base. A biopsy specimen showed a heterogeneous tumor with small, angulated, blue cells with hyperchromatic nuclei, apoptosis, and mitosis, malignant glands lined by cuboidal cells with round nuclei, prominent nucleoli, and eosinophilic cytoplasm. The glands had luminal mucin production (Figure, B). Focally, there were also scattered round cells with abundant eosinophilic, refractile cytoplasm, features of rhabdomyoblasts (Figure, C). These latter cells were strongly positive for desmin (Figure, D) and myogenin. Ethmoid sinus mass. A, Computed tomographic scan. The arrowhead indicates the mass. B, Blastema as indicated by the asterisk and malignant glands as indicated by the arrowhead. C, Rhabdomyoblasts as indicated by the arrowheads (hematoxylin-eosin, original magnification ×40). D, Desmin immunohistochemistry with strong positive staining in the rhabdomyoblasts (original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Olfactory neuroblastoma

Small cell carcinoma

Alveolar rhabdomyosarcoma

Sinonasal teratocarcinosarcoma

d

male

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2089807

A woman in her 50s presented with an 8-week history of increasing headache, hyposmia, hypogeusia, and nasal congestion. Endoscopic nasopharyngoscopy revealed a large polypoid nasal mass occupying the left nasal roof and completely obstructing the nasal passage. Contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed a 1.7 × 3.5 × 2.6-cm soft-tissue mass within the left ethmoid cavity, eroding through the cribriform plate with adjacent dural enhancement (Figure, A). Intraoperative pathologic examination showed polypoid spindle cell proliferation. Histopathologic findings showed respiratory epithelium with submucosal vascular proliferation with no atypia among the lining endothelial cells. The Figure, B, shows a central vessel surrounded by lobules of endothelial lined capillaries. The Figure, C, highlights the endothelial cells of the numerous capillaries and the central vessel.A, Contrast-enhanced T1-weighted magnetic resonance imaging of a soft-tissue mass within the left ethmoid cavity. B, Central vessel surrounded by lobules of endothelial-lined capillaries (hematoxylin-eosin, original magnification ×20). C, Endothelial cells of the numerous capillaries and the central vessel on CD34 staining (original magnification ×20). What Is Your Diagnosis?

Juvenile nasopharyngeal angiofibroma

Lobular capillary hemangioma

Inverting papilloma

Respiratory epithelial adenomatoid hamartoma

B. Lobular capillary hemangioma

B

Lobular capillary hemangioma

Nasal lobular capillary hemangiomas, also known as pyogenic granulomas, are benign skin and mucosal lesions of unclear etiology, associated with trauma, pregnancy, and oral contraceptive use. Because they are neither infectious nor granulomatous, the later term has fallen out of favor. Most lobular capillary hemangiomas are found in the oral cavity, with rare occurrence in the nasal cavity. While the exact cause in unknown, pregnant women and individuals with a history of trauma comprise 15% and 12% of reported cases, respectively, suggesting a relationship between these lesions and elevated hormone states and inflammatory changes.1 One study2 suggests that up to 5% of pregnant women may be found to have these lesions. Furthermore, cytogenetic analysis of one individual identified a deletion on the long arm of chromosome 21 as the sole clonal cytogenic abnormality among cells of the lesion, suggesting a neoplastic basis.3On histologic examination, lesions typically appear grossly as 0.2- to 2.5-cm polypoid masses that may have areas of ulceration, although lesions as large as 5 cm have been described.2 Superficial stratified squamous epithelium may contain sites of atrophy of ulceration.4 The lamina propria is filled with lobular proliferations of capillaries lined by thickened endothelial cells and filled with blood.5 Lobules are separated by fibrous septa containing scattered inflammatory cells and thin vessels feeding into larger “feeder vessels” that surround the lobules circumferentially.6 While a surrounding infiltrate of inflammatory cells may be observed, lobules are usually present to make the diagnosis. Endothelial cells stain positive for typical endothelial markers, including CD31, CD34, and factor VIII.4 Other differential diagnoses include angiofibromas, angiomatous polyp, and malignant neoplasms, such as nasopharyngeal carcinoma or nasopharyngeal teratoma.6Individuals typically present with some combination of epistaxis, congestion, and pain. Visualization reveals a unilateral mobile, nonpulsatile polypoid mass. Lesions affect individuals of all ages and have no preference with regard sex.6 Sixty-seven percent of lesions involve the septum; 18%, the vestibule; 12%, the turbinate; and 3%, the ethmoid sinus.1Imaging shows a soft-tissue enhancing mass. Bony destruction is rare.7 Contrast-enhanced computed tomography shows an enhancing mass with a surrounding border of isoattenuation or hypoattenuation. Magnetic resonance imaging shows hypointensity on T1-weighted imaging, hyperintensity on T2-weighted imaging, and enhancement with gadolinium. Imaging has been found to be useful in assessing the vascular nature of these lesions and in assessing the extent of involvement, although often unnecessary for well-localized lesions of small size.8Treatment typically involves embolization and excision. Paranasal endoscopic techniques are most common and are often accompanied by further treatment, such as electrocautery, silver nitrate, or absorbable hemostatic agents.1 While small lesions are amenable to endoscopic removal, larger lesions have typically necessitated open craniofacial techniques, with bleeding being the main deterrent.7 This case demonstrates that even large lesions with intradural extension can be completely resected via endoscopic techniques.While a review4 performed in 2006 found no recurrence among the 40 cases included, a 2013 review1 of 34 cases found recurrence in up to 42% of individuals with nasal lobular capillary hemangioma. This review found that lesions recur an average of 5.7 months later. Whether this represents a failure to excise the lesion completely or an increase in spontaneous cellular changes among susceptible hosts is unclear. In addition, within adolescents and gravid women, lesions may be observed to gradually regress over a period of weeks without intervention.5Lobular capillary hemangiomas of the nasal cavity are rare and may be detected later than those of the oral cavity. They should be considered in the presence of any enlarging vascular lesion within the nasal cavities.

General

A woman in her 50s presented with an 8-week history of increasing headache, hyposmia, hypogeusia, and nasal congestion. Endoscopic nasopharyngoscopy revealed a large polypoid nasal mass occupying the left nasal roof and completely obstructing the nasal passage. Contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed a 1.7 × 3.5 × 2.6-cm soft-tissue mass within the left ethmoid cavity, eroding through the cribriform plate with adjacent dural enhancement (Figure, A). Intraoperative pathologic examination showed polypoid spindle cell proliferation. Histopathologic findings showed respiratory epithelium with submucosal vascular proliferation with no atypia among the lining endothelial cells. The Figure, B, shows a central vessel surrounded by lobules of endothelial lined capillaries. The Figure, C, highlights the endothelial cells of the numerous capillaries and the central vessel.A, Contrast-enhanced T1-weighted magnetic resonance imaging of a soft-tissue mass within the left ethmoid cavity. B, Central vessel surrounded by lobules of endothelial-lined capillaries (hematoxylin-eosin, original magnification ×20). C, Endothelial cells of the numerous capillaries and the central vessel on CD34 staining (original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Respiratory epithelial adenomatoid hamartoma

Inverting papilloma

Lobular capillary hemangioma

Juvenile nasopharyngeal angiofibroma

c

female

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2108339

A woman in her 60s presented with a 10-year history of oropharyngeal discomfort and recent episodes of snoring and obstructive sleep disturbance. Although she had been experiencing a gradually increasing lumpy feeling on swallowing for at least 6 months, she did not experience of dysphagia, dyspnea, or pain. Physical examination revealed a mass measuring approximately 4 × 3 cm and covered with normal mucosa on the posterior oropharyngeal wall. This tumor was firm, nontender, and firmly adherent (Figure, A). Computed tomography (CT) showed a segmented bony lesion located at the odontoid process and the body of the C2 vertebra (Figure, B). This mass showed high signal intensity with a hypointense rim in both T1- and T2-weighted magnetic resonance images (MRI) (Figure, C and D, respectively). Polysomnography was performed and showed an apnea-hypopnea index of 58.7/h and a minimal oxygen saturation of 76%, which led to a diagnosis of obstructive sleep apnea. The mass was considered causative of obstructive sleep apnea. Hence, we performed total excision of the mass using a per-oral approach.A, Photograph of an oropharyngeal mass. B, Computed tomographic image showing a segmented bony lesion located at the odontoid process and the body of the C2 vertebra. C, T1-weighted magnetic resonance image (MRI) of an oropharyngeal mass. D, T2-weighted MRI of an oropharyngeal mass. What Is Your Diagnosis?

Exuberant osteophytes

Diffuse idiopathic skeletal hyperostosis

Osteochondroma

Osteoid osteoma

C. Osteochondroma

C

Osteochondroma

Osteochondroma is the most common benign bone tumor that generally affects long bones. However, osteochondroma rarely show spinal involvement, and this finding is reported in less than 5% of solitary osteochondromas.1 When osteochondromas present as multiple lesions, a diagnosis of hereditary multiple exostoses, an autosomal dominant hereditary disease, can be made.2The C2 vertebra is the most common site of spinal osteochondroma, and approximately half of the spinal osteochondromas occur in the cervical spine.3 Although most spinal osteochondromas are located in the posterior element of the spine, involvement of the anterior element may occurs, as observed in this patient. Osteochondromas are usually asymptomatic in the early phase, and symptoms slowly progress along with an increase in the size of the tumor. Osteochondromas that occur in the posterior spine can cause cord or nerve compression, giving rise to myelopathy or radiculopathy. On contrast, osteochondromas arising from the anterior elements of the cervical spine can present with symptoms such as dysphagia, throat discomfort, or obstructive sleep apnea.4Both CT and MRI are used to confirm the diagnosis of osteochondroma. Computed tomography can reveal the appearance of the marrow and cortical continuity with its relationship to the vertebra.1 On CT images, spinal osteochondromas generally present as round, sharply outlined masses with scattered calcification and density similar to that of the bones.2 Osteosclerotic changes may also be seen in neighboring bones.2 This type of tumor does not show contrast enhancement.2 Magnetic resonance imaging is much more valuable than CT in evaluating the relationship between the tumor and soft tissue and generally demonstrates a peripheral rim of low signal intensity corresponding to the cortical bone, and a signal for fatty marrow in the central area of the tumor.1 A cartilaginous cap, which may be observed with osteochondroma, appears as isointense to hyperintense on T1-weighted MRI, and hyperintense on T2-weighted MRI.2 However, cartilaginous caps become thinner and disappear with age. Therefore, malignant neoplasm should be considered in adults with a cartilaginous cap more than 1 cm in thickness.1Exuberant osteophytes, diffuse idiopathic skeletal hyperostosis (DISH), and osteoid osteoma have been reported as bony masses causing oropharyngeal symptoms.3-5 However, osteophytes and DISH, which do not show the marrow and cartilaginous cap, could be distinguished from osteochondroma.1 Osteoid osteoma usually shows a nidus (a radiolucent center surrounded by sclerotic bone).1,3 Also, solitary malignant tumors rarely occur in the cervical spine. However, metastatic malignant diseases, compared with primary malignant neoplasms, develop more commonly in patients older than 30 years.1Complete removal of tumors, including the cartilaginous cap, is the recommended treatment approach for osteochondroma.6 Incomplete removal of the cartilaginous cap can increase the risk of tumor recurrence.7,8 In addition, transformation of solitary osteochondromas into malignant tumors, such as chondrosarcoma and osteosarcoma, may occur. Although the exact risk of malignant changes is not known, the incidence may be about 1% in solitary osteochondromas.9

General

A woman in her 60s presented with a 10-year history of oropharyngeal discomfort and recent episodes of snoring and obstructive sleep disturbance. Although she had been experiencing a gradually increasing lumpy feeling on swallowing for at least 6 months, she did not experience of dysphagia, dyspnea, or pain. Physical examination revealed a mass measuring approximately 4 × 3 cm and covered with normal mucosa on the posterior oropharyngeal wall. This tumor was firm, nontender, and firmly adherent (Figure, A). Computed tomography (CT) showed a segmented bony lesion located at the odontoid process and the body of the C2 vertebra (Figure, B). This mass showed high signal intensity with a hypointense rim in both T1- and T2-weighted magnetic resonance images (MRI) (Figure, C and D, respectively). Polysomnography was performed and showed an apnea-hypopnea index of 58.7/h and a minimal oxygen saturation of 76%, which led to a diagnosis of obstructive sleep apnea. The mass was considered causative of obstructive sleep apnea. Hence, we performed total excision of the mass using a per-oral approach.A, Photograph of an oropharyngeal mass. B, Computed tomographic image showing a segmented bony lesion located at the odontoid process and the body of the C2 vertebra. C, T1-weighted magnetic resonance image (MRI) of an oropharyngeal mass. D, T2-weighted MRI of an oropharyngeal mass.

what is your diagnosis?

What is your diagnosis?

Osteoid osteoma

Osteochondroma

Exuberant osteophytes

Diffuse idiopathic skeletal hyperostosis

b

female

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2110986

A teenage girl presented with a 3-month history of a gradually enlarging soft palate mass associated with a change in her voice. She had no associated pain, difficulty swallowing, or difficulty breathing. She was otherwise healthy, with no medical or surgical history. Findings from her physical examination were unremarkable with the exception of a 2 × 2-cm firm, nontender, submucosal posterior soft palate mass just left of the uvula. There was no overlying ulceration or discoloration. Flexible nasopharyngoscopy was normal. Prior to presentation, a computed tomographic scan and biopsy had been performed at an outside hospital. Magnetic resonance imaging (MRI) of the face with contrast was also performed (Figure, A-C). Imaging showed a well-circumscribed solid lesion with no evidence of infiltration of soft-tissue structures, the pterygopalatine fossa, or palatine nerve foramina. There was no cervical lymphadenopathy. The lesion was resected via a transoral approach and was easily dissected from the surrounding tissue (Figure, D). The overlying mucosa was spared. What Is Your Diagnosis?

Mucoepidermoid carcinoma

Pleomorphic adenoma

Hemangioma

Granular cell tumor

B. Pleomorphic adenoma

B

Pleomorphic adenoma

Of all salivary gland neoplasms, only 3% to 5% occur in children and adolescents.1 These lesions may be benign or malignant and may show epithelial/myoepithelial, mesenchymal, or mixed differentiation. Pleomorphic adenoma (PA), also known as “benign mixed tumor,” is benign and shows a mixture of epithelial/myoepithelial and mesenchymal elements. It is the most common benign minor salivary gland tumor in children. A review of the literature by Ritwik and Brannon2 demonstrated that PA represented 42 of 49 pediatric benign minor salivary gland tumors (85.7%), with myoepithelioma, cystadenoma, and sialadenoma papilliferum accounting for the remainder. The female to male ratio was 2.8:1, the mean age was 12 years, the mean size was 2.4 cm, and the palate was the most common minor salivary gland location. These lesions typically presented as a painless, firm, submucosal mass.2The differential diagnosis for a mass in a child’s soft palate includes benign and malignant salivary gland tumors, hemangioma, granular cell tumor, hematolymphoid tumors, and metastases. Radiologic imaging narrows the differential by defining an intraglandular vs extraglandular location, detecting malignant features, and assessing local extension, invasion, and nodal metastasis. The mass in the patient described herein was centered in the soft palate and completely separate from the hard palate, effectively excluding consideration of odontogenic and other lesions with a propensity for bone. This made the most likely diagnosis that of a minor salivary gland neoplasm, with pleomorphic adenoma being most common.Extrapolation of imaging data from all salivary tumors (primarily adult parotid tumors) suggests that lesions such as the one seen in this patient, with a marked T2 hyperintensity are typical of a minor salivary gland lesion, such as pleomorphic adenoma (Figure, A).3 The central T2 hypointensity of this lesion may have reflected the microscopically confirmed areas of lesional heterogeneity or sequelae of the prior biopsy. Mucoepidermoid carcinomas, however, may also have T2 hyperintensity with areas of T2 hypointensity, without the overtly aggressive imaging features such as perineural spread or invasion of adjacent structures, resulting in an overlap in appearance with pleomorphic adenoma.4In the pediatric population, the most common malignant tumors of the minor salivary glands include mucoepidermoid carcinoma and acinic cell carcinoma. Advanced imaging, such as diffusion-weighted MRI, can assist with discriminating between benign and malignant minor salivary gland tumors. In this patient, the palate lesion did in fact demonstrate high diffusivity favoring benignity (Figure, C).5 Despite these advanced imaging tools, certainty is difficult in any single case, making surgical excision with pathologic evaluation crucial for diagnosis. Specifically, pleomorphic adenomas contain variable degrees of both salivary duct and cartilage differentiation. Heterologous elements, such as bone or adipose tissue, may also occur.6 Most pleomorphic adenomas harbor a chromosomal translocation involving the PLAG1 or HMGA2 gene, either of which creates an abnormal fusion gene that causes or contributes to dysregulated growth.7 The tumor reported herein had fusion of the PLAG1 gene at chromosome 8q12 with an unknown partner at chromosome 10q14, a previously unreported chromosomal translocation.Treatment of PA of the minor salivary gland is complete excision, which provides both a diagnostic and therapeutic purpose. When discussing the procedure with the patient and family, it is important to consider the risk of recurrence. This risk ranges from 0% to 13%; therefore, long-term follow-up of at least 5 years is recommended.2,8

General

A teenage girl presented with a 3-month history of a gradually enlarging soft palate mass associated with a change in her voice. She had no associated pain, difficulty swallowing, or difficulty breathing. She was otherwise healthy, with no medical or surgical history. Findings from her physical examination were unremarkable with the exception of a 2 × 2-cm firm, nontender, submucosal posterior soft palate mass just left of the uvula. There was no overlying ulceration or discoloration. Flexible nasopharyngoscopy was normal. Prior to presentation, a computed tomographic scan and biopsy had been performed at an outside hospital. Magnetic resonance imaging (MRI) of the face with contrast was also performed (Figure, A-C). Imaging showed a well-circumscribed solid lesion with no evidence of infiltration of soft-tissue structures, the pterygopalatine fossa, or palatine nerve foramina. There was no cervical lymphadenopathy. The lesion was resected via a transoral approach and was easily dissected from the surrounding tissue (Figure, D). The overlying mucosa was spared.

what is your diagnosis?

What is your diagnosis?

Granular cell tumor

Pleomorphic adenoma

Hemangioma

Mucoepidermoid carcinoma

b

female

11-20

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2118563

A man in his 60s presented for further evaluation of a right inguinal and scrotal lesion (Figure 1). The rash initially started 4 years prior as a dime-sized, pink, scaly area in the right inguinal crease and was pruritic. Results of a biopsy at the time were consistent with lichen simplex chronicus, and treatment with topical steroids was initiated. Since then, the rash had failed to resolve and the affected area had increased in size to its present dimensions. The patient had a history of prostate cancer treated with prostatectomy 4 years previously without evidence of recurrence and melanoma of the posterior neck treated with wide local excision, in addition to non–insulin-dependent diabetes mellitus and hyperlipidemia controlled with oral medications. He does not smoke and has been in a monogamous marriage for more than 30 years. Examination revealed a multifocal scaly, pink-red beefy plaque in the right inguinal crease extending from the superior aspect of the scrotum to the gluteal crease measuring approximately 6 × 7 cm in total area with some areas of excoriation and superficial open wounds. An additional area of macular erythema extended superiorly along the inguinal crease toward the medial thigh. No lymphadenopathy of the inguinal region was noted. What Is Your Diagnosis?

Fungal infection

Extramammary Paget disease

Bowen disease

Lichen sclerosis

B. Extramammary Paget disease

B

Extramammary Paget disease

Repeated biopsy revealed epidermal infiltration by Paget cells, which are large vacuolated cells with vesicular nuclei and foamy pale cytoplasm (Figure 2).1 Immunohistochemical stains were positive for cytokeratin 7 and carcinoembryonic antigen and negative for prostate-specific antigen and S100 protein.2 These findings are pathognomonic for extramammary Paget disease (EMPD) and distinguish it from Bowen disease, or squamous cell carcinoma in situ, which typically arises in the penis and appears as a gradually enlarging, well-demarcated, velvety plaque.3 Human papillomavirus infection is a risk factor. Cells are typically cytokeratin 7 and carcinoembryonic antigen negative and p63 positive. Lichen sclerosis, a chronic inflammatory skin disease characterized by atrophic white plaques,3 typically occurs women’s anogenital area but has been reported in men and children and is treated with topical corticosteroids.4 Histologic features include a thinned epidermis; inflammation and altered fibroblast function lead to fibrosis of the papillary dermis.3 In a diabetic patient with a persistent rash nonresponsive to steroids, a fungal infection such as candida or tinea cruris can persist in the absence of antifungal therapies and be diagnosed by fungal culture.Extramammary Paget disease is an intraepithelial neoplasm affecting areas rich in apocrine sweat glands. Whereas Paget disease occurs most often in the nipple, EMPD is most common in the vulva of women and penoscrotal area of men 50 to 80 years old. It is usually associated with pruritus and has an insidious onset, presenting as an erythematous, pruritic plaque that may become ulcerated, scaly, or eczematous. Many patients are treated for eczema for years prior to definitive diagnosis. Other differential diagnoses include superficial spreading melanoma, neuroendocrine carcinoma, mycosis fungoides, psoriasis, leukoplakia, eczema, or intraepidermal spread of visceral carcinoma.2Surgery is the standard treatment for EMPD, with an emphasis on obtaining negative margins to control the disease.1,2,5 Intraoperative frozen sections and Mohs surgery have been used to decrease the positive margin rate and risk of recurrence with good results.6 The extent of resection required to obtain negative margins is often much greater than the visible area of involvement of the disease, and frozen sections must be systematically performed. Workup should also include a computed tomographic scan of the abdomen and pelvis because EMPD may be associated with an underlying abdominal or genitourinary cancer (ie, colorectal, prostate, bladder, or kidney), although the frequency of this association is not consistently reported.1,2 Some centers also screen for a secondary cancer with chest x-ray, cystoscopy, colonoscopy, and serum prostate-specific antigen level. Lymph node dissection is indicated if clinical or pathologic lymph node metastases are present, and sentinel lymph node biopsy can be considered in cases of invasive disease.7 Hegarty et al1 reported a difference in median survival in patients with invasive disease compared with those with intraepidermal EMPD of 14.5 vs 55 months, respectively. Although the optimal regimen and timing have not been established, tumor responses have been described with several chemotherapy agents including mitomycin, vincristine sulfate, cisplatin, fluorouracil, and docetaxel for invasive disease.5 Radiation therapy is considered an alternative treatment when there are contraindications to surgical excision or when patients decline surgery. However, due to varying reports of effectiveness, its utility as a monotherapy is uncertain.8,9In summary, patients with pruritic, macular plaques unresponsive to topical therapies should undergo biopsy for definitive diagnosis. A benign initial diagnosis but worsening symptoms should prompt repeated biopsy. Once EMPD is diagnosed, an underlying cancer should be ruled out and surgical excision scheduled.Our patient underwent wide local excision with frozen section margin control with a scrotal advancement flap for reconstruction. Final pathologic analysis revealed focal microinvasion (depth, <0.5 mm) with negative margins.

Oncology

A man in his 60s presented for further evaluation of a right inguinal and scrotal lesion (Figure 1). The rash initially started 4 years prior as a dime-sized, pink, scaly area in the right inguinal crease and was pruritic. Results of a biopsy at the time were consistent with lichen simplex chronicus, and treatment with topical steroids was initiated. Since then, the rash had failed to resolve and the affected area had increased in size to its present dimensions. The patient had a history of prostate cancer treated with prostatectomy 4 years previously without evidence of recurrence and melanoma of the posterior neck treated with wide local excision, in addition to non–insulin-dependent diabetes mellitus and hyperlipidemia controlled with oral medications. He does not smoke and has been in a monogamous marriage for more than 30 years. Examination revealed a multifocal scaly, pink-red beefy plaque in the right inguinal crease extending from the superior aspect of the scrotum to the gluteal crease measuring approximately 6 × 7 cm in total area with some areas of excoriation and superficial open wounds. An additional area of macular erythema extended superiorly along the inguinal crease toward the medial thigh. No lymphadenopathy of the inguinal region was noted.

what is your diagnosis?

What is your diagnosis?

Lichen sclerosis

Bowen disease

Extramammary Paget disease

Fungal infection

c

male

61-70

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2107541

A man in his 50s who previously underwent renal transplantation for polycystic kidney disease presented with worsening chronic malaise, fatigue, dyspnea, early satiety, and abdominal distention with extreme discomfort. An abdominal magnetic resonance image is shown in Figure 1A. Given the symptoms and magnetic resonance imaging findings, the patient was eventually taken to the operating room. Laparotomy exposed a giant multinodular mass (Figure 1B).A, Abdominal magnetic resonance image. B,Intraoperative photograph of the giant multinodular mass occupying most of the upper abdomen. What Is Your Diagnosis?

De novo kidney graft tumor

Recurrence of polycystic kidney disease

Polycystic liver disease

Caroli disease

C. Polycystic liver disease

C

Polycystic liver disease

Polycystic liver disease is a genetically heterogeneous disease that can predispose the patient to a combination of renal and liver cysts or yield isolated liver cysts alone.1 The diseased liver gradually enlarges as it is replaced by cysts (Figure 1). Isolated polycystic liver disease rarely produces symptoms or complications; however, unusually severe hepatomegaly could cause various symptoms, including mass effect.2 For severe symptoms, liver transplantation is performed as a definitive treatment.3In this case, the patient had extreme discomfort from the mass effect of the disease. His liver function, however, was minimally affected. The patient underwent living-donor liver transplantation because his low Model for End-Stage Liver Disease score did not prioritize him high on the waiting list. Intraoperative photographs (Figure 1B and Figure 2) show the patient’s massively enlarged polycystic liver. A normal-appearing gallbladder can be seen (Figure 2). The resected liver measured 65 × 51 × 21 cm and weighed 16.3 kg. Findings from the pathologic examination showed cystic transformation of up to 75% of the liver parenchyma. Unfortunately, a primary graft failure not related to the etiology of the patient’s disease developed postoperatively and eventually resulted in his death.Intraoperative photograph of the massively enlarged polycystic liver occupying most of the upper abdomen. The gallbladder has a normal appearance. In considering the possible alternative diagnoses, the polycystic kidneys are resected during the renal transplantation and the disease does not recur in the donor kidney. The imaging findings and appearance of the mass in this case are not consistent with de novo renal graft tumor or Caroli disease.

Surgery

A man in his 50s who previously underwent renal transplantation for polycystic kidney disease presented with worsening chronic malaise, fatigue, dyspnea, early satiety, and abdominal distention with extreme discomfort. An abdominal magnetic resonance image is shown in Figure 1A. Given the symptoms and magnetic resonance imaging findings, the patient was eventually taken to the operating room. Laparotomy exposed a giant multinodular mass (Figure 1B).A, Abdominal magnetic resonance image. B,Intraoperative photograph of the giant multinodular mass occupying most of the upper abdomen.

what is your diagnosis?

What is your diagnosis?

Polycystic liver disease

De novo kidney graft tumor

Caroli disease

Recurrence of polycystic kidney disease

a

male

51-60

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2130711

A woman in her 30s was referred for evaluation of a large splenic cyst identified on a computed tomographic (CT) scan. She had previously lived in Beijing, China. In 2011, she was evaluated in a Chinese clinic for abdominal bloating and moderate left upper quadrant pain; she was offered a splenectomy, but she declined and pursued a second opinion at a hospital in the United States in 2012. During that evaluation, the patient reported that she had run in areas with dog feces on the ground and had eaten sheep meat (notably, not organ meat); she denied consuming canine meat. Results of serologic tests for Echinococcus antibody IgG were negative. Results of a CT scan were remarkable for a 9.7 × 9.0 × 10.5-cm anterior cyst and a smaller posterior cyst measuring 4.6 × 4.7 × 3.8 cm, both with rim calcifications (Figure 1).A large splenic cyst with calcified capsule is present in the anterior aspect of the spleen, with a smaller cyst in the posterior aspect of the spleen, also with calcified capsule. Arrowheads indicate the location of the cysts. Under higher resolution, debris is noted within the larger cyst. What Is Your Diagnosis?

Congenital cyst

Splenic abscess

Cystic metastasis to the spleen

Echinococcal disease

D. Echinococcal disease

D

Echinococcal disease

Echinococcal disease is seen in areas in which the intermediate host— sheep— and the definitive host— canines— are in close proximity. The highest prevalence of the disease is seen in South America, Asia, and parts of Africa; in the United States, it is most commonly found in immigrants. Echinococcus granulosus is a cestode that survives within an accidental host—humans, who become hosts through contact with infected canine feces or ingesting infected sheep organ meat. The cestode forms cysts with large fluid collections and septations; daughter cysts may also be present. The liver is the most common site of infestation (55%-70%), followed by the lungs and spleen (2.5%).1 The disease is often asymptomatic, and while infection in childhood is common, the slow-growing cestode is often diagnosed in adulthood. When symptoms manifest, they are commonly caused by compression of adjacent structures; the presenting symptom is frequently a dull ache. Patients may also experience dyspepsia or constipation.1Initial workup should include CT scan and serologic tests for echinococcal titers. Findings on CT scan supportive of echinococcal disease include a nonenhancing mass that may be cystic or solid. Following the death of the helminths, a calcified wall may develop (Figure 1). Serologic studies have a relatively high sensitivity and remain positive until 1 year after the organism has been cleared. However, there is a high false-negative rate in extrahepatic disease.2 Despite the availability of CT imaging and serologic studies, Moro and Schantz3 suggested that calcification, presence of daughter cysts, and patient history are useful in establishing a diagnosis. The importance of diagnosing and treating echinococcal disease is because of the possible complications, which include infection, rupture, and fistulization. Broadly, rupture of the cyst leads to potentially fatal anaphylaxis. Specifically, of concern in a large splenic cyst is the likelihood of traumatic rupture. Splenectomy has therefore become the criterion standard of treatment4; however, antihelminthic drugs are used as adjunctive therapy. Recently, spleen-preserving therapy has become increasingly common, especially in children. Spleen-preserving operations are reserved for solitary, small, and superficial cysts.5 While isolated splenic hydatidosis is uncommon, the spleen is the third most common location of echinococcal cysts, and recognizing the risk factors and presentation are paramount to diagnosing this disease and preventing potentially fatal complications (Figure 2).Spleen in situ after mobilization and lysis of adhesion. The white area over the anterior aspect of the spleen is the capsule of the larger cyst. The posterior cyst was identified after the vessels were divided. The spleen and cysts were removed en bloc without violating their capsule.In this patient, a CT scan revealed multiple cysts, which the literature reports are generally not amenable to laparoscopic removal because laparoscopic removal is reserved for small superficial cysts.6 Similarly, the puncture, aspiration, injection, and reaspiration technique was not indicated because the serologic test results for echinococcal titers were negative. However, the US Centers for Disease Control and Prevention reports that false positives are common, especially if the cyst is located within the lungs, brain, or spleen.5 Simple antihelminthic treatment was deemed insufficient owing to the possibility of traumatic rupture and subsequent anaphylaxis. Because of strong suspicion for echinococcal disease and location and size of the cysts, the decision was made to proceed with open splenectomy. The patient was treated preoperatively with albendazole and praziquantel. Diphenhydramine and corticosteroids were in the operating room during the procedure in the event of rupture. The smaller cyst seen on CT scan was found to be an accessory spleen; this was also removed. Pathologic examination of the cysts showed no evidence of echinococcal disease; hence, the cyst was determined to be a primary epithelial cyst. The presence of a cystic structure within the accessory spleen, patient’s travel history, and echinococcal false-positive rate make inactive echinococcal disease a likely diagnosis.

Surgery

A woman in her 30s was referred for evaluation of a large splenic cyst identified on a computed tomographic (CT) scan. She had previously lived in Beijing, China. In 2011, she was evaluated in a Chinese clinic for abdominal bloating and moderate left upper quadrant pain; she was offered a splenectomy, but she declined and pursued a second opinion at a hospital in the United States in 2012. During that evaluation, the patient reported that she had run in areas with dog feces on the ground and had eaten sheep meat (notably, not organ meat); she denied consuming canine meat. Results of serologic tests for Echinococcus antibody IgG were negative. Results of a CT scan were remarkable for a 9.7 × 9.0 × 10.5-cm anterior cyst and a smaller posterior cyst measuring 4.6 × 4.7 × 3.8 cm, both with rim calcifications (Figure 1).A large splenic cyst with calcified capsule is present in the anterior aspect of the spleen, with a smaller cyst in the posterior aspect of the spleen, also with calcified capsule. Arrowheads indicate the location of the cysts. Under higher resolution, debris is noted within the larger cyst.

what is your diagnosis?

What is your diagnosis?

Splenic abscess

Echinococcal disease

Congenital cyst

Cystic metastasis to the spleen

b

female

31-40

Chinese

original

https://jamanetwork.com/journals/jama/fullarticle/2208783

A woman in her 30s presented with gradually worsening abdominal pain and was found to have hyponatremia. A glioma of the optic chiasm was treated 20 years prior with chemotherapy and radiation. Sequelae included chronic headaches, anterior hypopituitarism, and hydrocephalus necessitating a ventriculoperitoneal shunt. Medications included analgesics, cyclobenzaprine, sumatriptan, ondansetron, divalproex sodium, gabapentin, furosemide, somatotropin, potassium chloride, vitamin D, and estrogen. Haloperidol was recently added. Blood pressure was 125/87 mm Hg. Mucosae were moist and jugular venous pressure was not well seen. Her cardiopulmonary and abdominal examinations were normal, peripheral edema was absent, and sensorium was clear. Table 1 shows initial laboratory data. How Do You Interpret These Test Results?

The patient has hypovolemic hypotonic hyponatremia.

The patient has euvolemic hypotonic hyponatremia.

The patient has hypervolemic hypertonic hyponatremia.

The patient has hypervolemic hypotonic hyponatremia.

B

The patient has euvolemic hypotonic hyponatremia.

A low plasma or serum sodium concentration usually indicates an excess of water relative to total body sodium and potassium. Thus, hyponatremia is a measure of water imbalance.1 Plasma sodium concentration measurements can be unreliable in the presence of severe hyperlipidemia or hyperproteinemia (pseudohyponatremia). When plasma has large amounts of other osmotically active organic solutes (eg, glucose or mannitol), true hyponatremia can occur even if the plasma is hypertonic. Therefore, in the presence of hyponatremia, hypotonicity can be confirmed by measuring plasma osmolality. Assessing the extracellular fluid volume is next undertaken to narrow the differential diagnosis. Finally, urine chemistry values can help identify the etiology and guide management (Table 2).Failure to excrete excess water generally results from an inability to suppress secretion of arginine vasopressin (antidiuretic hormone, ADH) and/or a decrease in effective arterial blood volume (EABV). Transient vasopressin increases may be triggered by pain, nausea, or the postoperative state. Persistent increases in vasopressin levels occur in the syndrome of inappropriate antidiuretic hormone secretion (SIADH; alternatively, the syndrome of antidiuresis2) or with certain medications, commonly fluoxetine or sertraline, carbamazepine, vincristine, or cyclophosphamide.2 Hypovolemic and hypervolemic disorders (eg, heart failure or cirrhosis) often decrease EABV and increase vasopressin levels.3 Decreased EABV in these disorders stimulates sodium and water reabsorption along the proximal nephron, reducing delivery to the diluting segment (the thick ascending limb of the Henle loop and the distal convoluted tubule). Normally, sodium chloride reabsorption in the thick ascending limb of the Henle loop and the distal convoluted tubule produces dilute tubular fluid necessary for water excretion. Reduced distal delivery of sodium limits the volume of electrolyte-poor urine that can be generated. Hyponatremia from reduced EABV (ie, hypovolemic or hypervolemic but not euvolemic) is characterized by low urinary sodium concentration (eg, <30 mEq/L),2 reflecting the increased proximal tubular sodium reabsorption (Table 2). Hypervolemic hyponatremia caused by renal failure is identified by abnormal creatinine.According to 2014 Medicare data,4 national fee limits for plasma and urine sodium and osmolality testing are each less than $10.The low plasma sodium concentration suggested relative water excess, which was confirmed by the low plasma osmolality. Physical examination was consistent with euvolemia because of no primary features establishing hypervolemia, peripheral edema, ascites, or hypovolemia. In euvolemic hyponatremia, the distribution of excess water is shared between the extracellular compartment and the much larger intracellular compartment, so edema is not present. Rarely, massive water intake causes hyponatremia by overwhelming a normal urinary diluting mechanism; this is characterized by maximally dilute urine (eg, urine osmolality <100 mOsmol/kg). In this case, the urine osmolality was not maximally dilute, indicating an inappropriate renal response to the water excess. The absence of a urine sodium level of less than 30 mEq/L corroborated the assessment of euvolemia.2 Therefore, this patient has euvolemic hypotonic hyponatremia. The etiology is likely SIADH attributable to the haloperidol or a central nervous system lesion.Plasma sodium concentration and osmolality are the only laboratory measures for detecting water excess or deficit. Occasionally, secondary adrenal insufficiency or severe hypothyroidism can produce euvolemic hypotonic hyponatremia, and tests of thyroid and adrenal function can be ordered. Either test might show abnormal results in this individual with known hypopituitarism.Because the patient was minimally symptomatic, she was treated with fluid restriction and haloperidol was discontinued. However, her plasma sodium concentration declined further. When the sum of the urine sodium and potassium is lower than the plasma sodium level, the patient is excreting electrolyte-free water and should improve if fluid intake is 1 L per day or less and urine flow is adequate (>1.5 L/d). If the sum of the urine sodium and potassium exceeds the plasma sodium level, as in this case, hyponatremia may worsen, despite fluid restriction, unless the underlying disorder is corrected.5 The patient therefore required oral sodium chloride, which resulted in a gradual increase in the plasma sodium concentration.6In the presence of hyponatremia, hypotonicity is confirmed by a plasma osmolality value of less than 270 mOsm/kg.True (ie, hypotonic) hyponatremia usually results from elevated antidiuretic hormone or decreased effective arterial blood volume.Hyponatremia due to reduced effective arterial blood volume is characterized by a urinary sodium concentration <30 mEq/L.

Diagnostic

A woman in her 30s presented with gradually worsening abdominal pain and was found to have hyponatremia. A glioma of the optic chiasm was treated 20 years prior with chemotherapy and radiation. Sequelae included chronic headaches, anterior hypopituitarism, and hydrocephalus necessitating a ventriculoperitoneal shunt. Medications included analgesics, cyclobenzaprine, sumatriptan, ondansetron, divalproex sodium, gabapentin, furosemide, somatotropin, potassium chloride, vitamin D, and estrogen. Haloperidol was recently added. Blood pressure was 125/87 mm Hg. Mucosae were moist and jugular venous pressure was not well seen. Her cardiopulmonary and abdominal examinations were normal, peripheral edema was absent, and sensorium was clear. Table 1 shows initial laboratory data.

how do you interpret these test results?

How do you interpret these results?

The patient has hypervolemic hypertonic hyponatremia.

The patient has hypovolemic hypotonic hyponatremia.

The patient has euvolemic hypotonic hyponatremia.

The patient has hypervolemic hypotonic hyponatremia.

c

female

31-40

original

https://jamanetwork.com/journals/jama/fullarticle/2203781

An 82-year-old man presented with intractable pruritus of several months’ duration and a skin eruption. He reported being diagnosed with dermatitis herpetiformis more than 20 years ago and receiving sulfapyridine and dapsone for treatment. He stopped taking these medications because of limited benefit and concern about nephrotoxicity. Since then, he was treated with periodic courses of oral antibiotics and oral corticosteroids. Recently, extensive skin disease and pruritus developed. He noted 20 years of chronic diarrhea, which improved with a gluten-free diet, in addition to chronic renal insufficiency, hypothyroidism, and aortic stenosis. Physical examination revealed diffuse erosions with grouped papules and vesicles on his bilateral extremities, elbow and knee extensors, chest, back, buttocks, face, and scalp (Figure 1). Examination also revealed extensive excoriations, as well as superficial honey-colored crusts. A few possible burrows were noted on his wrists.Grouped papules, vesicles, and erosions of chest and elbow extensors (left) and back (right; inset is a close-up view).Obtain complete blood cell count and creatinine level What Would You Do Next?

Examine for infestation with scabies

Obtain complete blood cell count and creatinine level

Perform skin biopsy and direct immunofluorescence

Obtain a chest radiograph

Dermatitis herpetiformis and celiac disease

C

Perform skin biopsy and direct immunofluorescence

The key clinical feature to establish the diagnosis is the intensely pruritic, grouped vesicular rash in the setting of chronic diarrhea. In contrast, scabies presents with pruritic papules and burrows and is confirmed by obtaining burrow scrapings to examine microscopically for mites, eggs, or scybala (feces). Patients with new-onset generalized pruritus without a rash need evaluation for liver and kidney disease, malignancy, and lymphoproliferative disorders. This patient had a skin eruption; thus, obtaining laboratory studies and a chest radiograph is less helpful. Bullous dermatoses, such as dermatitis herpetiformis, are diagnosed through skin biopsy and direct immunofluorescence. Specifically for dermatitis herpetiformis, the biopsy for direct immunofluorescence should be perilesional. There was high suspicion of dermatitis herpetiformis in this case, confirmed with biopsy, direct immunofluorescence, serologic studies, and genetic haplotype testing.An autoimmune bullous skin disease, dermatitis herpetiformis typically presents at age 30 to 40 years, with a slightly higher prevalence in male patients.1 Clinical manifestations include intensely pruritic vesicles and bullae in a grouped, symmetrical distribution, most commonly over the extensor surfaces of the extremities, back, buttocks, scalp, and neck.2 The associated pruritus often leads to destruction of primary lesions.The diagnosis of dermatitis herpetiformis is confirmed by histopathologic evaluation, direct immunofluorescence studies, and serologic testing. Lesional skin biopsies show neutrophilic microabscesses. Perilesional biopsies used for direct immunofluorescence show granular deposits of IgA at the dermoepidermal junction (Figure 2). IgA tissue transglutaminase antibodies (tTG) are seen using serologic testing. Additional autoantibody testing includes endomysial and gliadin antibodies.2 Genetic testing for haplotypes HLA-DQ2 and DQ8 can also help determine if the patient is genetically susceptible.3Representative direct immunofluorescence of dermatitis herpetiformis, using fluorescent tagged IgA antibodies showing green fluorescence of IgA in a stippled pattern within dermal papillae. Dermatitis herpetiformis is considered a cutaneous manifestation of gluten sensitivity and thus has a clear relationship to celiac disease. Both are mediated mainly by IgA autoantibodies triggered by dietary gluten. The major autoantigens are tTG in celiac disease and epidermal transglutaminase in dermatitis herpetiformis.4 In persons predisposed to gluten sensitivity, these autoantigens, when coupled with gluten, cross-react with the IgA antibodies. Their deposition in tissues leads to initiation of an inflammatory response and, in the case of dermatitis herpetiformis, dermoepidermal junction breakdown and vesicular formation.2 In contrast to celiac disease, in which only some patients have skin disease, intestinal involvement is virtually universal in patients with dermatitis herpetiformis. The degree of this involvement varies, but most cases are clinically mild or subclinical.5 Small bowel biopsy may be used to elicit the degree of intestinal involvement and rule out lymphoma, which has increased incidence in dermatitis herpetiformis.6 Dermatitis herpetiformis also has been associated with other autoimmune conditions, such as thyroid disorders.7 A gastroenterologist confirmed the diagnosis of celiac disease in our patient and ruled out small bowel lymphoma. This patient also had a history of thyroid disease.The cornerstone of treatment for both dermatitis herpetiformis and celiac disease is strict adherence to a gluten-free diet, which leads to resolution of skin and intestinal lesions. Systemic therapy with dapsone or sulfapyridine is recommended as an initial adjunct because improvement of skin disease may take months to years to resolve with a gluten-free diet alone.2 The most common adverse effects of dapsone and sulfapyridine are hematologic; renal effects are rare but have been reported. This patient’s severe skin disease warranted starting adjunctive systemic therapy, but he was not interested and his comorbidities discouraged dapsone use. He restarted a gluten-free diet and topical corticosteroids. Remarkably, he showed significant improvement within a few weeks. All patients with dermatitis herpetiformis and celiac disease require long-term follow-up with management of flares, laboratory testing when taking systemic therapy, and monitoring for malnutrition, other autoimmune conditions, and signs of lymphoma.

General

An 82-year-old man presented with intractable pruritus of several months’ duration and a skin eruption. He reported being diagnosed with dermatitis herpetiformis more than 20 years ago and receiving sulfapyridine and dapsone for treatment. He stopped taking these medications because of limited benefit and concern about nephrotoxicity. Since then, he was treated with periodic courses of oral antibiotics and oral corticosteroids. Recently, extensive skin disease and pruritus developed. He noted 20 years of chronic diarrhea, which improved with a gluten-free diet, in addition to chronic renal insufficiency, hypothyroidism, and aortic stenosis. Physical examination revealed diffuse erosions with grouped papules and vesicles on his bilateral extremities, elbow and knee extensors, chest, back, buttocks, face, and scalp (Figure 1). Examination also revealed extensive excoriations, as well as superficial honey-colored crusts. A few possible burrows were noted on his wrists.Grouped papules, vesicles, and erosions of chest and elbow extensors (left) and back (right; inset is a close-up view).Obtain complete blood cell count and creatinine level

what would you do next?

What would you do next?

Obtain a chest radiograph

Obtain complete blood cell count and creatinine level

Examine for infestation with scabies

Perform skin biopsy and direct immunofluorescence

d

male

81-90

original

https://jamanetwork.com/journals/jama/fullarticle/2190967

A 91-year-old woman with a history of hypertension, hypercholesterolemia, and stage 3 renal insufficiency presented for a routine office visit. She reported no chest pain, dyspnea on exertion, presyncope, orthopnea, paroxysmal nocturnal dyspnea, or pedal edema.Physical examination demonstrated blood pressure of 140/76 mm Hg and a heart rate of 72/min. Carotid upstrokes were slightly delayed with a transmitted murmur. Lungs were clear bilaterally. Cardiac examination demonstrated a regular rate and rhythm, normal S1, 3/6 harsh, late-peaking systolic murmur that radiated to the carotids with soft A2, 2/4 diastolic decrescendo murmur at the left lower sternal border, and 2/6 holosystolic murmur at the apex. Distal pulses were 2+ bilaterally. There was no edema.A 2-D and Doppler transthoracic echocardiogram (TTE) was performed to assess valvular function (Table; Interactive).The patient has functional mitral regurgitation secondary to a dilated cardiomyopathy.The patient has moderate aortic valve stenosis with the severity overestimated by Doppler measurements.The patient has severe aortic valve stenosis with preserved left ventricular systolic function. How Do You Interpret These Test Results?

The patient has functional mitral regurgitation secondary to a dilated cardiomyopathy.

The patient has obstructive hypertrophic cardiomyopathy.

The patient has moderate aortic valve stenosis with the severity overestimated by Doppler measurements.

The patient has severe aortic valve stenosis with preserved left ventricular systolic function.

D

The patient has severe aortic valve stenosis with preserved left ventricular systolic function.

TTE readily allows for assessment of cardiac chambers size, wall thickness, regional and global systolic function, and valvular morphology and motion. Doppler techniques facilitate assessment of blood flow velocity and measurement of peak transvalvular velocity and time-velocity integrals. Using the simplified Bernoulli equation (pressure gradient = 4 × velocity2), peak pressure gradient is derived from the measured peak transvalvular velocity and the mean pressure gradient is derived from the time-velocity integral. Stenotic valve area is calculated using the continuity equation, which assumes that blood volume is constant across the lesion of interest and a second measurable orifice (eg, left ventricular outflow tract and aortic valve). Valve regurgitation may be evaluated as well, using a composite of quantitative and qualitative Doppler data.TTE has become the initial test of choice for the evaluation of heart murmurs because of its accuracy, noninvasiveness, widespread availability, and relatively low cost (US, $400-$500). It is the criterion standard for aortic stenosis assessment (recommendation class 1; level of evidence B).1 Cutoff reference values for aortic stenosis severity are reported in the Table.In this patient, Doppler study showed that the peak velocity across the aortic valve was 5.4 m/s, corresponding with a calculated peak gradient of 117 mm Hg (see continuous-wave Doppler tracing through the aortic valve in the Interactive). The mean gradient was 70 mm Hg, and the continuity equation–estimated aortic valve area was 0.8 cm2 (0.5 cm/m2). TTE showed mild symmetric left ventricular hypertrophy with normal left ventricular diameter and preserved ejection fraction, which suggests that the aortic stenosis was the dominant lesion because regurgitant lesions lead to left ventricular dilation with normal wall thickness. All Doppler values, in the presence of a thickened or deformed aortic valve morphology, are consistent with severe aortic stenosis (see TTE clip in the Interactive).Rather than the calculated valve area, the 2014 American Heart Association/American College of Cardiology guidelines emphasize the measured valve peak jet velocity and the mean gradient to classify aortic stenosis severity. This approach minimizes errors due to miscalculations and properly stratifies aortic stenosis prognosis. The risk of heart failure, death, or valve replacement surgery increases when the peak aortic velocity is greater than 4 m/s.2 Some patients with aortic stenosis have increased risk at lower gradients,2 particularly those with left ventricular systolic dysfunction or smaller hearts, situations in which left ventricular stroke volume is reduced (<35 mL/m2). In these cases, aortic stenosis severity is more appropriately assessed by estimated aortic valve area. Low-dose dobutamine stress echocardiography may help stratify severity.TTE has largely replaced invasive cardiac catheterization for the assessment of aortic stenosis severity because of its high accuracy, modest cost, and noninvasiveness. In cases in which coronary angiography is performed for preoperative coronary artery disease assessment, avoiding retrograde crossing of the deformed aortic valve reduces subclinical stroke risk.3 Multidetector computed tomography,4 cardiovascular magnetic resonance,5 transesophageal echocardiography,6 and 3-D echocardiography7 can accurately measure the aortic valve area and other valvar lesions, but are reserved in aortic stenosis for situations in which the Doppler beam cannot be aligned with the flow or the 2-D imaging of the valve mobility or morphology is discordant with Doppler data.The patient was seen 4 months later, after being admitted to the hospital with pneumonia. She improved but was not functioning at full energy level. Because of the change in clinical status, another TTE was performed that showed mild global left ventricular hypokinesis (ejection fraction, 45%), moderate mitral regurgitation, and moderate pulmonary artery systolic hypertension, with no change in aortic stenosis peak gradient or valve area severity.Based on the presence of severe aortic stenosis with heart failure and signs of cardiac dysfunction, the patient was referred for elective coronary angiography and aortic valve intervention.8 Angiography demonstrated no significant coronary artery disease and 1 month later, she underwent transcatheter aortic valve implantation with no complications. One year postintervention, the patient has improved energy level and exercise capacity and continues to live independently.Doppler TTE is recommended in the initial evaluation of patients with known or suspected aortic stenosis to confirm diagnosis and determine the need for treatment.Peak aortic valve velocity greater than 4 m/s identifies most patients with hemodynamically severe aortic stenosis.Aortic stenosis severity should be determined from aortic valve area in patients with a reduced stroke volume.In patients with aortic stenosis in which the Doppler beam cannot be aligned parallel with the flow or the valve mobility or morphology is discordant with the Doppler data, severity may be assessed with alternative imaging modalities.

Diagnostic

A 91-year-old woman with a history of hypertension, hypercholesterolemia, and stage 3 renal insufficiency presented for a routine office visit. She reported no chest pain, dyspnea on exertion, presyncope, orthopnea, paroxysmal nocturnal dyspnea, or pedal edema.Physical examination demonstrated blood pressure of 140/76 mm Hg and a heart rate of 72/min. Carotid upstrokes were slightly delayed with a transmitted murmur. Lungs were clear bilaterally. Cardiac examination demonstrated a regular rate and rhythm, normal S1, 3/6 harsh, late-peaking systolic murmur that radiated to the carotids with soft A2, 2/4 diastolic decrescendo murmur at the left lower sternal border, and 2/6 holosystolic murmur at the apex. Distal pulses were 2+ bilaterally. There was no edema.A 2-D and Doppler transthoracic echocardiogram (TTE) was performed to assess valvular function (Table; Interactive).The patient has functional mitral regurgitation secondary to a dilated cardiomyopathy.The patient has moderate aortic valve stenosis with the severity overestimated by Doppler measurements.The patient has severe aortic valve stenosis with preserved left ventricular systolic function.

how do you interpret these test results?

How do you interpret these results?

The patient has moderate aortic valve stenosis with the severity overestimated by Doppler measurements.

The patient has functional mitral regurgitation secondary to a dilated cardiomyopathy.

The patient has obstructive hypertrophic cardiomyopathy.

The patient has severe aortic valve stenosis with preserved left ventricular systolic function.

d

female

91-100

original

https://jamanetwork.com/journals/jama/fullarticle/2174005

A 55-year-old man presenting to the emergency department reported blurry vision in his right eye during the past week. He also noticed rhythmic pulsing sounds in both ears during the past month. Past medical history was significant only for well-controlled hypertension treated with irbesartan (300 mg daily) and poor vision in the left eye for many years attributable to presumed inactive ocular histoplasmosis.On presentation, the patient appeared well, with blood pressure of 140/70 mm Hg and a regular heart rate of 75/min. Best corrected visual acuity was 20/200 (right eye) and counting fingers at 1 foot (left eye). Direct ophthalmoscopy revealed severe bilateral optic disc edema, peripapillary hemorrhages, and absent spontaneous venous pulsations (Figure 1). Findings from a full neurologic examination were otherwise normal. Findings from a plain computed tomography (CT) scan of the head were normal apart from multiple bony sclerotic lesions seen in the calvarium, skull base, and C1 vertebra.Optic nerve photographs demonstrating severe bilateral optic disc edema with peripapillary hemorrhages.Perform lumbar puncture with patient in upright position to measure opening pressure and examine cerebrospinal fluid (CSF) componentsOrder magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbits What Would You Do Next?

Perform skeletal survey

Perform lumbar puncture with patient in upright position to measure opening pressure and examine cerebrospinal fluid (CSF) components

Order magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbits

Perform serum and urine protein electrophoresis

Papilledema due to cerebral venous sinus thrombosis (CVST)

C

Order magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbits

C. Order magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbitsPapilledema is defined as edema of the optic nerve heads due to increased intracranial pressure.1 The etiology can be broadly categorized into entities that cause an increase in brain volume, blood volume, or cerebrospinal fluid (CSF) volume.2 In this patient, after a plain CT scan of the head demonstrated no signs of hemorrhagic stroke or an intracranial mass, the next most appropriate step in the diagnosis was an MRI and MRV to assess the optic nerves and to rule out venous obstruction, most commonly caused by CVST. Computed tomography does not provide enough information about the details of the orbital and intracranial anatomy but is a useful imaging modality to assess the dural venous sinuses. Magnetic resonance imaging is important to rule out subtle compressive lesions and assess for enhancement of the optic nerves, which can occur with inflammatory processes that cause breakdown of the blood-brain barrier.If no cause can be found on neuroimaging, the next step in the diagnostic workup of patients with suspected papilledema is a lumbar puncture performed in the lateral decubitus position (because normative data exist only for this position) to measure the opening pressure and assess CSF constituents. An elevated opening pressure (>25 cm H2O) would confirm papilledema; an opening pressure that is not elevated would point to other causes of bilateral optic disc edema. These causes include inflammatory optic neuropathies such as idiopathic demyelinating optic neuritis, infiltrative optic neuropathies such as central nervous system lymphoma, and ischemic optic neuropathies such as that caused by giant cell arteritis. Choices A and D may be important in a subsequent metastatic workup but are not as critical as obtaining neuroimaging in this patient.Cerebral venous sinus thrombosis occurs when thrombosis is present in the dural venous sinuses, which drain blood from the brain.3 In a multinational prospective observational study the most common causes of CVST were thrombophilia, either genetic or acquired, and oral contraceptives.4 Other less common causes include hematologic conditions (anemia, polycythemia, or thrombocythemia), central nervous system infections, pregnancy, and malignancy.4,5 Isolated intracranial hypertension is often the presenting manifestation of CVST.6 Therefore, all patients presenting with symptoms and signs of increased intracranial pressure, such as papilledema, should be carefully evaluated with a neuroimaging study that includes venography. Patients who have long-standing papilledema may lose vision because of atrophy of the retinal ganglion cells, which underscores the importance of early detection and treatment.This patient’s MRV imaging revealed the presence of CVST (Figure 2), and a lumbar puncture revealed an elevated opening pressure greater than 50 cm H2O with normal CSF constituents. The bony sclerotic lesions seen on the initial CT scan of the head raised concern for metastatic prostate cancer, and further testing revealed an elevated prostate-specific antigen level (751 ng/mL). Computed tomography urography demonstrated an irregular filling defect within the distal right ureter, which was later confirmed to be adenocarcinoma of the prostate. A thrombophilia panel was negative. Thus, the patient’s venous sinus thrombosis was likely the result of a hypercoaguable state secondary to malignancy.Magnetic resonance venography demonstrating filling defects in the right transverse sinus (white arrowhead) and in the superior sagittal (yellow arrowhead) and right sigmoid (blue arrowhead) sinuses.Dilated fundus examination revealed findings of macular edema and diffuse retinal hemorrhages in addition to papilledema. Patients with recent-onset papilledema usually have normal central visual acuity unless there is associated macular edema. In this patient, central visual acuity in his right eye was decreased due to macular edema related to extension of fluid from the optic nerve head. His hypercoaguable state also led to retinal vein occlusions confirmed with intravenous fluorescein angiography, which was responsible for the diffuse retinal hemorrhages.The patient was prescribed a therapeutic dose of enoxaparin as well as acetazolamide to help reduce his intracranial pressure. He was referred to oncology and began treatment with degarelix for metastatic prostate cancer.

General

A 55-year-old man presenting to the emergency department reported blurry vision in his right eye during the past week. He also noticed rhythmic pulsing sounds in both ears during the past month. Past medical history was significant only for well-controlled hypertension treated with irbesartan (300 mg daily) and poor vision in the left eye for many years attributable to presumed inactive ocular histoplasmosis.On presentation, the patient appeared well, with blood pressure of 140/70 mm Hg and a regular heart rate of 75/min. Best corrected visual acuity was 20/200 (right eye) and counting fingers at 1 foot (left eye). Direct ophthalmoscopy revealed severe bilateral optic disc edema, peripapillary hemorrhages, and absent spontaneous venous pulsations (Figure 1). Findings from a full neurologic examination were otherwise normal. Findings from a plain computed tomography (CT) scan of the head were normal apart from multiple bony sclerotic lesions seen in the calvarium, skull base, and C1 vertebra.Optic nerve photographs demonstrating severe bilateral optic disc edema with peripapillary hemorrhages.Perform lumbar puncture with patient in upright position to measure opening pressure and examine cerebrospinal fluid (CSF) componentsOrder magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbits

what would you do next?

What would you do next?

Perform skeletal survey

Perform serum and urine protein electrophoresis

Perform lumbar puncture with patient in upright position to measure opening pressure and examine cerebrospinal fluid (CSF) components

Order magnetic resonance imaging (MRI) or magnetic resonance venography (MRV) of the brain and orbits

d

male

51-60

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/1938931

A white man in his 30s with a 7-year history of severe, mechanical, low back pain and long-standing mental depression was referred to the dermatology department for evaluation of an asymptomatic cutaneous ulcer that had developed over the past year. Physical examination disclosed a large and deep, irregularly shaped, cutaneous ulcer on the dorsum of his right forearm. Necrotic tissue and muscle exposure was seen at the base of the ulcer (Figure, A). Woody induration of skin on both forearms and on the abdominal region was also observed. Bilateral contracture of deltoid, triceps, and biceps muscles was noted. Active and passive range of motion was restricted at the shoulders and elbows. No signs of joint inflammation were seen. At the time of consultation, the patient was taking oral treatment with duloxetine hydrochloride, clonazepam, oxcarbazepine, fentanyl, sulpiride, zopiclone, omeprazole magnesium, and baclofen. He also admitted to self-administering subcutaneous injections of meperidine, 100 mg 4 times per day, for the past 3 years, at different sites, including the deltoid areas and abdomen. Growth from culture specimens taken from the ulcer was negative for bacteria, mycobacteria, and fungal organisms. His serum creatinine kinase level was raised (192 U/L; reference range, 0-174 U/L), but test results for complete blood cell count; erythrocyte sedimentation rate; antinuclear antibody, rheumatoid factor, aspartate aminotransferase, alanine aminotransaminase, and aldolase levels; and serum electrophoresis were all within normal limits. A wedge biopsy from the indurated skin of the abdominal region was performed (Figure, B and C). (To convert creatinine kinase to microkatals per liter, multiply by 0.0167.)A, Clinical photograph of the large, deep, irregularly shaped, cutaneous ulcer on the dorsum of the right forearm. Three small ulcers are seen adjacent to the larger ulcer. B and C, Histologic images of a wedge biopsy specimen from the indurated skin of the abdominal region (hematoxylin-eosin). B, Original magnification ×10. C, Original magnification ×40. What Is the Diagnosis?

Pyoderma gangrenosum

Fibrosis and ulceration caused by meperidine

Localized scleroderma (morphea)

Mycobacterium haemophilum infection

B. Fibrosis and ulceration caused by meperidine

B

Fibrosis and ulceration caused by meperidine

Histopathological findings demonstrated lobular panniculitis, with subcutaneous fat lobules showing necrotic adipocytes and dense inflammatory infiltrates composed mainly of foamy histiocytes. Severe fibrosis involved the deep dermis and subcutaneous septa. Foreign-body giant cells and macrophages with large, foamy cytoplasm engulfing the lipids from necrotic adipocytes were also seen. There was no evidence of thrombosis or vasculitis. No polarizable foreign material was identified. Stains for micro-organisms were negative. Results from a muscle biopsy specimen taken from the deltoid muscle ruled out muscle involvement. The history of meperidine injection and the characteristic clinical and histopathological findings led to the diagnosis.The meperidine injections were discontinued, and the patient was referred for alternative pain management and psychiatric counseling. Topical hydrogels and films were prescribed for the ulcer, and intensive physical therapy was started for the stiffness. Three months later the ulcer had almost healed, but his mobility had improved only slightly.Meperidine, also known as pethidine, is a synthetic analgesic opioid. It is prescribed as hydrochloride salt in tablets, as syrup, or as intramuscular, subcutaneous or intravenous injection. Cutaneous complications of parenteral opioid abuse are varied and include soft-tissue indurations, puffy hand syndrome, hypertrophic scars, calcifications, hyperpigmentation, and skin infections.1,2 Diagnosis is often difficult because drug-dependent patients often deny use of the drug. Furthermore, the clinical appearance may be bizarre and not fit any known dermatosis.The clinical features in our patient, however, are so distinctive that diagnosis can be suspected from these findings alone. Diffuse expansive fibrosis extending well beyond the injection sites and asymptomatic irregular-shaped ulcers often reaching the muscle have been described in relation to several opioids, including pentazocine,1,3 methadone,4 desomorphine,5 and meperidine.6,7 The lesions usually begin as multiple nodules, most commonly located on accessible areas, including the buttocks and thighs. Eventually, they progress to fibrosis and develop into multiple sclerodermoid plaques that extend to the underlying fascia and muscle. Large, deeply penetrating ulcers may develop on the plaques. Patients with severe dermal and muscular involvement may present with severe restriction of mobility and functional disability, sometimes simulating a neuromuscular disorder.Histopathologically, the lesions are characterized by a lobular panniculitis associated with extensive dermal and septal fibrosis. The inflammatory infiltrate is usually granulomatous with fat necrosis and pseudocystic cavities surrounded by foamy histiocytes and giant multinucleated cells. Lipophagic granulomas and thrombi of small blood vessels may also be present. A foreign-body crystalline material is occasionally seen inside multinucleated giant cells under polarized microscopy.8 Muscle involvement is characterized by replacement of muscle fibers with fibrous tissue and variable amounts of inflammatory infiltrate.The exact mechanism of these cutaneous and muscular manifestations is unknown. Repetitive trauma, vascular thrombosis, endarteritis, vasoconstriction or fibrosis stimulated by the opioids themselves are some of the mechanisms that have been proposed.1,7 A recent report9 of successful naltrexone therapy for the treatment of chronic ulcers caused by opioid injections may support the latter hypothesis.Differential diagnosis should be made with other sclerodermoid disorders, such as scleroderma and eosinophilic fasciitis. When muscle is involved, infiltrative or end-stage inflammatory myopathies, muscular dystrophy, and stiff-man syndrome should also be considered. A history of drug abuse, the clinical pattern of distribution, the lack of systemic involvement, and laboratory and histological findings allow the correct diagnosis to be made.The cornerstone of treatment is to stop opioid use, but patients should also receive psychiatric counselling and alternative treatment for the chronic pain to prevent relapses of this condition.

Dermatology

A white man in his 30s with a 7-year history of severe, mechanical, low back pain and long-standing mental depression was referred to the dermatology department for evaluation of an asymptomatic cutaneous ulcer that had developed over the past year. Physical examination disclosed a large and deep, irregularly shaped, cutaneous ulcer on the dorsum of his right forearm. Necrotic tissue and muscle exposure was seen at the base of the ulcer (Figure, A). Woody induration of skin on both forearms and on the abdominal region was also observed. Bilateral contracture of deltoid, triceps, and biceps muscles was noted. Active and passive range of motion was restricted at the shoulders and elbows. No signs of joint inflammation were seen. At the time of consultation, the patient was taking oral treatment with duloxetine hydrochloride, clonazepam, oxcarbazepine, fentanyl, sulpiride, zopiclone, omeprazole magnesium, and baclofen. He also admitted to self-administering subcutaneous injections of meperidine, 100 mg 4 times per day, for the past 3 years, at different sites, including the deltoid areas and abdomen. Growth from culture specimens taken from the ulcer was negative for bacteria, mycobacteria, and fungal organisms. His serum creatinine kinase level was raised (192 U/L; reference range, 0-174 U/L), but test results for complete blood cell count; erythrocyte sedimentation rate; antinuclear antibody, rheumatoid factor, aspartate aminotransferase, alanine aminotransaminase, and aldolase levels; and serum electrophoresis were all within normal limits. A wedge biopsy from the indurated skin of the abdominal region was performed (Figure, B and C). (To convert creatinine kinase to microkatals per liter, multiply by 0.0167.)A, Clinical photograph of the large, deep, irregularly shaped, cutaneous ulcer on the dorsum of the right forearm. Three small ulcers are seen adjacent to the larger ulcer. B and C, Histologic images of a wedge biopsy specimen from the indurated skin of the abdominal region (hematoxylin-eosin). B, Original magnification ×10. C, Original magnification ×40.

what is the diagnosis?

What is your diagnosis?

Pyoderma gangrenosum

Localized scleroderma (morphea)

Fibrosis and ulceration caused by meperidine

Mycobacterium haemophilum infection

c

male

0-10

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2019960

A man in his 60s presented with a slowly enlarging, painful mass on his buttock. He recalled that a small lesion had appeared approximately 8 months prior, and over the past several months he had noted significant growth and pain. A nonpruritic rash had also become apparent on his forearms and thighs. Physical examination showed a 2-cm macerated pedunculated growth on the left buttock within the intergluteal cleft (Figure, A). An erythematous rash was noted on the forearms and thighs with fine scale present at the wrists.A, Photograph of a 2-cm macerated pedunculated growth on the left buttock. B, Histopathologic image of an exophytic growth on the buttock with marked epidermal hyperplasia (hematoxylin-eosin, original magnification ×40). C, Histopathologic image of immunohistochemical staining for spirochetes (original magnification ×400).A shave biopsy specimen of the exophytic growth on the buttock revealed marked epidermal hyperplasia (Figure, B) with a dense dermal infiltrate containing lymphocytes and plasma cells. What Is The Diagnosis?

Condyloma acuminata

Condyloma lata

Verrucous herpes simplex virus

Granuloma inguinale

B. Condyloma lata

B

Condyloma lata

Immunohistochemical staining for spirochetes identified sheets of organisms throughout the lesion (Figure, C). A rapid plasma reagin test was strongly positive for antibodies and Treponemapallidum–specific testing confirmed the diagnosis. The patient was diagnosed as having secondary syphilis with condyloma lata and was treated with benzathine penicillin, 2.4 million U intramuscular injection in a single dose, and his lesions resolved completely over the following weeks.Syphilis is a sexually transmitted disease caused by T pallidum, a microaerophilic spirochete.1 The Centers for Disease Control and Prevention estimates that, annually, 55 400 people in the United States are newly infected with syphilis.2 The infection is transmitted through direct contact with syphilitic lesions, which can be on the external genitalia, vagina, anus, rectum, lips, and in the mouth.1,3 Transmission can occur during vaginal, anal, or oral sexual contact, and the incubation period ranges from 10 to 90 days.1,4 It is divided into primary, secondary, latent (early and late), and tertiary stages.5 In the primary stage, there is often appearance of a chancre at the point of inoculation.5 The chancre is often described as painless, most of the time unnoticed, lasting 3 to 6 weeks, regardless of treatment.1,4 However, without treatment, primary disease may progress to the secondary stage, which has many clinical manifestations. Lesions of secondary syphilis can appear during the healing phase of the chancre or several weeks after its healing.1 The rash can be papular, nodular, erythematous, scaly, psoriasiform, or plaquelike and usually well demarcated, nonpruritic, and affect the trunk, face, and extremities.4,5Along with the more characteristic widespread lesions, secondary syphilis more uncommonly manifests with lesions of condyloma lata, which are of particular interest because they may be confused with condyloma acuminata, keratoacanthoma, squamous cell carcinomas, and atypical pyogenic granulomas.6 Condyloma lata are smooth, flat, moist, flesh-colored, or hypopigmented, macerated papules, plaques, or nodules.7,8 The common sites involved are the genital and anal areas, making them even more difficult to distinguish from condyloma acuminata. In nonmucosal sites, such as the axillae, umbilicus, nape of the neck, and thighs, condyloma lata may be hypertrophic.8Other symptoms of secondary syphilis can include fever, lymphadenopathy, pharyngitis, patchy alopecia, headaches, weight loss, myalgia, and fatigue.5 Rarely, it may cause other issues, including acute meningitis, hepatitis, renal disease, arthritis, periostitis, optic neuritis, iritis, and uveitis.8Serological diagnosis is through nontreponemal tests (venereal disease research laboratory and rapid plasma reagin) and treponemal tests (treponemal pallidum particle agglutination and fluorescent treponemal antibody absorption test).4,5 Direct visualization may be achieved through dark field microscopy, silver stains (Warthin-Starry), and immunohistochemical staining of lesions tissue.4,5 The results of tissue staining should be corroborated by serology to confirm the diagnosis of syphilis.

Dermatology

A man in his 60s presented with a slowly enlarging, painful mass on his buttock. He recalled that a small lesion had appeared approximately 8 months prior, and over the past several months he had noted significant growth and pain. A nonpruritic rash had also become apparent on his forearms and thighs. Physical examination showed a 2-cm macerated pedunculated growth on the left buttock within the intergluteal cleft (Figure, A). An erythematous rash was noted on the forearms and thighs with fine scale present at the wrists.A, Photograph of a 2-cm macerated pedunculated growth on the left buttock. B, Histopathologic image of an exophytic growth on the buttock with marked epidermal hyperplasia (hematoxylin-eosin, original magnification ×40). C, Histopathologic image of immunohistochemical staining for spirochetes (original magnification ×400).A shave biopsy specimen of the exophytic growth on the buttock revealed marked epidermal hyperplasia (Figure, B) with a dense dermal infiltrate containing lymphocytes and plasma cells.

what is the diagnosis?

What is your diagnosis?

Condyloma lata

Condyloma acuminata

Verrucous herpes simplex virus

Granuloma inguinale

a

male

61-70

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2020884

A 40-year-old man, who resided in the eastern part of India, was referred to us from the department of otorhinolaryngology for evaluation of a nonhealing ulcer on the tongue present for the last 4 months. The lesion had started as a small painless mass on the right lateral aspect of the tongue, which gradually grew and subsequently ulcerated. It was asymptomatic except for causing mild difficulty in eating. The patient could not recall any history of trauma or tongue bite preceding the lesion. He denied consuming tobacco or alcohol regularly. He had type 2 diabetes mellitus for 2 years, which was well controlled with oral hypoglycemic agents. The patient had no systemic complaints. There was no history of high-risk behavior for human immunodeficiency virus (HIV) acquisition. On physical examination, there was a single well-defined ulcer measuring 2 × 2 cm on the right lateral aspect of tongue with a clean base and irregular and elevated heaped-up margins (Figure 1A). There was no underlying induration, friability, or bleeding on manipulation. The rest of the oral cavity was normal. A 3-mm punch biopsy from the edge of the ulcer was taken and sent for histopathological examination (Figure 1B and C).A, Tongue ulcer. B, Biopsy from the ulcer showing a mixed cell infiltrate (hematoxylin-eosin, original magnification ×40). C, Intracellular yeast forms within the histiocytes (original magnification ×100). What Is the Diagnosis?

Squamous cell carcinoma

Primary oral histoplasmosis

Mucosal leishmaniasis

Tubercular chancre

B. Primary oral histoplasmosis

B

Primary oral histoplasmosis

The biopsy specimen showed a dense diffuse infiltrate of lymphocytes, histiocytes, epithelioid cells, giant cells, plasma cells, eosinophils, and neutrophils. Many histiocytes and giant cells contained intracellular yeasts with a surrounding halo (Figure 1B and C). Special stains (Grocott-Gomori methenamine-silver nitrate and periodic acid–Schiff) highlighted the fungal forms.Tissue used for a fungal culture on Sabouraud dextrose agar was negative. Results from all investigations toward finding systemic involvement were negative. Findings from serologic testing for HIV-1 and HIV-2 were negative. The patient was started on therapy with itraconazole, 400 mg/d. The ulcer decreased to less than half its size within 6 weeks (Figure 2) and completely healed in 8 to 10 weeks.Almost complete healing of the ulcer after 6 weeks of itraconazole therapy.Histoplasmosis, also known as Darling disease, is caused by Histoplasma capsulatum, a dimorphic fungus. Though it occurs worldwide, it is endemic in the Ohio and Mississippi river valleys in the United States. It occurs infrequently in India, and most of the cases have been reported from the Gangetic belt, with a few cases from South India.1 The infection is asymptomatic in 95% of cases but gets disseminated usually in immunosuppressed individuals, although sometimes immunocompetent individuals can be affected as well. One could argue that type 2 diabetes mellitus could have predisposed our patient to the infection. However, there are only isolated case reports of primary cutaneous histoplasmosis in patients with diabetes.2Mucocutaneous lesions are commonly seen in the disseminated form of the disease. Oral involvement, seen in 30% to 50% of cases of disseminated histoplasmosis, can be the first sign of disseminated infection, but as a sole manifestation it is rare. Tongue, palate, and buccal mucosa are usually affected.3 Isolated involvement of the oropharynx in immunocompetent individuals, as the only feature, has been reported rarely in the literature.3-7 Oropharyngeal lesions are often accompanied by lesions in the larynx.8 The lesion is a firm, painful ulcer with heaped-up edges. The ulcer may be mistaken for a malignant neoplasm because of the heaped-up edges.3 Other differential diagnoses include tubercular or syphilitic chancre, mucosal leishmaniasis, and other deep mycosis-like blastomycosis. In the absence of any clinical clue to the diagnosis, the definitive diagnosis rests on demonstration of the organism in the tissue or isolating in culture. The tissue cultures can be negative for Histoplasma in more than 90% of self-limiting or asymptomatic infections.9Histoplasma is identified as small intracellular yeast forms 2 to 4 μm in size, with a surrounding clear halo within macrophages. Interestingly, it can be confused with Leishman-Donovan bodies seen in leishmaniasis; however, the presence of kinetoplast helps to differentiate it from Histoplasma. Moreover, a mixed cell infiltrate of lymphocytes, plasma cells, and eosinophils can be seen as a nonspecific feature in all the infectious possibilities considered. Itraconazole should be administered in mild to moderate disease, whereas for severe disease, administration of liposomal amphotericin B for an initial 1 to 2 weeks followed by oral itraconazole is recommended.10Because histoplasmosis is often not suspected as a cause of solitary oral ulcer, a strong clinicopathological correlation is necessary to arrive at the correct diagnosis. A differential diagnosis of histoplasmosis should be considered for a nonhealing oral ulcer even in the absence of predisposing factors.

Dermatology

A 40-year-old man, who resided in the eastern part of India, was referred to us from the department of otorhinolaryngology for evaluation of a nonhealing ulcer on the tongue present for the last 4 months. The lesion had started as a small painless mass on the right lateral aspect of the tongue, which gradually grew and subsequently ulcerated. It was asymptomatic except for causing mild difficulty in eating. The patient could not recall any history of trauma or tongue bite preceding the lesion. He denied consuming tobacco or alcohol regularly. He had type 2 diabetes mellitus for 2 years, which was well controlled with oral hypoglycemic agents. The patient had no systemic complaints. There was no history of high-risk behavior for human immunodeficiency virus (HIV) acquisition. On physical examination, there was a single well-defined ulcer measuring 2 × 2 cm on the right lateral aspect of tongue with a clean base and irregular and elevated heaped-up margins (Figure 1A). There was no underlying induration, friability, or bleeding on manipulation. The rest of the oral cavity was normal. A 3-mm punch biopsy from the edge of the ulcer was taken and sent for histopathological examination (Figure 1B and C).A, Tongue ulcer. B, Biopsy from the ulcer showing a mixed cell infiltrate (hematoxylin-eosin, original magnification ×40). C, Intracellular yeast forms within the histiocytes (original magnification ×100).

what is the diagnosis?

What is your diagnosis?

Primary oral histoplasmosis

Tubercular chancre

Mucosal leishmaniasis

Squamous cell carcinoma

a

male

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2196034

A man in his 30s presented with a fishhook injury to his left eye and lower eyelid after fishing in Everglades National Park. His visual acuity was hand motions, and intraocular pressure measurement was deferred in that eye. Findings from examination of the left eye showed a penetrating injury with a 3-pronged barbed fishhook, with 1 prong lodged in the anterior chamber and another lodged in the lower eyelid (Figure 1). The status of the crystalline lens was unclear owing to corneal edema. No hypopyon was visualized. The patient was brought to the operating room for removal of the fishhook, closure of the cornea and eyelid lacerations, and injection of intracameral antibiotic drugs.External photograph showing a 3-pronged treble hook lodged in the cornea and lower eyelid; visual acuity is hand motions.Back-out technique: remove the fishhook in a retrograde manner through its entry woundAdvance-and-cut technique: rotate the hook anterogradely, clip the barb, and back out the hook retrogradely through the entry woundNeedle-cover technique: use the bevel of a large bore needle through the entry wound to engage and “cover” the barb, then withdraw togetherCut-and-push-through technique: cut the lure, make a corneal exit wound next to the distal end of the hook, and rotate the hook through the exit wound What Would You Do Next?

Back-out technique: remove the fishhook in a retrograde manner through its entry wound

Advance-and-cut technique: rotate the hook anterogradely, clip the barb, and back out the hook retrogradely through the entry wound

Needle-cover technique: use the bevel of a large bore needle through the entry wound to engage and “cover” the barb, then withdraw together

Cut-and-push-through technique: cut the lure, make a corneal exit wound next to the distal end of the hook, and rotate the hook through the exit wound

Penetrating ocular fishhook injury

D

Cut-and-push-through technique: cut the lure, make a corneal exit wound next to the distal end of the hook, and rotate the hook through the exit wound

A cut-and-push-through technique would likely minimize damage to the anterior chamber. A barbed hook, if removed in a retrograde manner, can cause significant tissue damage. An advance-and-cut technique would require significant manipulation of the fishhook in the anterior chamber, which could cause damage to the lens given the gauge of the hook. A needle-cover technique would cause damage to the cornea and has, to our knowledge, only been used for posterior segment penetrating fishhook injuries.Fishing is a popular recreational sport worldwide, with fishing-related ocular injuries constituting 20% of sports-related ocular trauma in the United States.1 It is important to note whether the fishhook is barbed, the number and location of these barbs, and the number of prongs (Figure 2A) in determining one’s surgical approach. Three general methods for approaching ocular fishhook injuries have been described (listed in answer choices A-C) (Figure 2).2,3 The back-out technique may be best suited for barbless hooks. Advantages of the advance-and-cut technique include a controlled exit wound and minimal enlargement of the entry wound. However, this approach requires additional manipulation of the hook in the anterior chamber, especially if the proximal end is short. In our case, a large contaminated lure necessitated preoperative clipping of the lure, and the remaining proximal end was too short for a safe advance-and-cut technique. Moreover, the large gauge of the hook would make intraoperative clipping challenging. The needle-cover technique, reported for use in the posterior segment,3 was not applicable in our case given the gauge and the location of the fishhook.A, Treble hook (left), barbed fishhook (center), and double-barbed fishhook (right). B, Back-out technique, in which the fishhook is rotated retrogradely through the wound. C-E, Advance-and-cut technique: the fishhook is rotated anterogradely through exit wound, the barb is cut, and the fishhook is rotated retrogradely through entry wound.In this case, we used a novel cut-and-push-through technique. The fishhook was first clipped using large wire clippers, which can be found in orthopedic surgical trays, to separate the lure and allow for sterile ophthalmic preparation (eFigure, A, in the Supplement). The anterior chamber was filled with viscoelastic; an exit wound was then made in the temporal cornea using a paracentesis blade (eFigure, B) and the entire barbed hook was rotated through the exit wound using 2 curved hemostats (eFigure, C-D) (Video). Intracameral antibiotic drugs were given, and the prong in the lower eyelid was removed. At the 6-week follow-up, the patient’s visual acuity had improved to 20/25 (eFigure, F).The prognosis for corneal and anterior chamber large fishhooks is generally poor, but good visual acuity outcomes are possible. In a cohort of 63 patients with open globe injuries caused by fishhooks, cited in the US Eye Injury Registry, about 50% had visual acuity greater than 20/200, with 12% achieving visual acuity greater than 20/40.1 However, in a separate case series, more than 75% of patients were able to attain visual acuities of 20/30 or better.2,4 As with any ruptured globe repair, the patient should be followed up closely for complications of the ocular trauma, including endophthalmitis, traumatic cataract, and retinal detachment. Five cases of endophthalmitis have been reported after fishhook injury.2,5 The surgical approach should be determined on a case-by-case basis, depending on the location of the entry and, if present, exit wounds, the type of fishhook, the surgical instruments available, and the comfort of the surgeon with various techniques, with the goal to minimize additional trauma and corneal scar formation.A cut-and-push-through technique for management of penetrating ocular barbed fishhook injuries should be considered in the armamentarium of surgical approaches when encountering a penetrating fishhook injury. Also, the importance of eye protection to patients when engaging in or observing this popular sport should be stressed.

Ophthalmology

A man in his 30s presented with a fishhook injury to his left eye and lower eyelid after fishing in Everglades National Park. His visual acuity was hand motions, and intraocular pressure measurement was deferred in that eye. Findings from examination of the left eye showed a penetrating injury with a 3-pronged barbed fishhook, with 1 prong lodged in the anterior chamber and another lodged in the lower eyelid (Figure 1). The status of the crystalline lens was unclear owing to corneal edema. No hypopyon was visualized. The patient was brought to the operating room for removal of the fishhook, closure of the cornea and eyelid lacerations, and injection of intracameral antibiotic drugs.External photograph showing a 3-pronged treble hook lodged in the cornea and lower eyelid; visual acuity is hand motions.Back-out technique: remove the fishhook in a retrograde manner through its entry woundAdvance-and-cut technique: rotate the hook anterogradely, clip the barb, and back out the hook retrogradely through the entry woundNeedle-cover technique: use the bevel of a large bore needle through the entry wound to engage and “cover” the barb, then withdraw togetherCut-and-push-through technique: cut the lure, make a corneal exit wound next to the distal end of the hook, and rotate the hook through the exit wound

what would you do next?

What would you do next?

Needle-cover technique: use the bevel of a large bore needle through the entry wound to engage and “cover” the barb, then withdraw together

Back-out technique: remove the fishhook in a retrograde manner through its entry wound

Cut-and-push-through technique: cut the lure, make a corneal exit wound next to the distal end of the hook, and rotate the hook through the exit wound

Advance-and-cut technique: rotate the hook anterogradely, clip the barb, and back out the hook retrogradely through the entry wound

c

male

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2196035

A woman in her 30s presented to the hospital with decreased vision in both eyes, confusion, and ataxia for 3 weeks. She had undergone gastric bypass surgery 3 months before presentation, which was complicated by a gastric ulcer and stricture. She had lost 34.5 kg since the procedure. Other medical history included hypothyroidism and thyroidectomy for thyroid cancer diagnosed 10 years ago. Her medication regimen included levothyroxine sodium and occasional bariatric chewable vitamins. She denied alcohol or tobacco use or drug abuse. Her best-corrected visual acuity was 20/200 OD and 20/400 OS. Her pupils were equally reactive, with no relative afferent pupillary defect. There was a mild abduction deficit in both eyes as well as prominent upbeating nystagmus. The amplitude of the nystagmus increased in upgaze and dampened with downgaze. She was unable to read the control plate of the Ishihara test. Findings from an anterior segment examination were unremarkable. Findings from a dilated fundus examination revealed disc edema in both eyes with peripapillary nerve fiber layer thickening and large intraretinal hemorrhages (Figure).A and B, Initial presentation of large intraretinal hemorrhages and disc edema in the left and right eye, respectively. What Would You Do Next?

Lumbar puncture

Magnetic resonance imaging and/or venography

Intravenous vitamin therapy

Intravenous corticosteroids

Wernicke encephalopathy with ocular manifestations

C

Intravenous vitamin therapy

Wernicke encephalopathy (WE) is best known by the classic triad of mental confusion, gait ataxia, and eye movement abnormalities (nystagmus and ophthalmoplegia). However, all 3 symptoms rarely occur in the same patient, leading to underdiagnosis of this condition. Confusion is the most common symptom, followed by ataxia and abnormal eye movement.1,2 The oculomotor abnormalities are well documented, but the fundus findings are underreported. Carl Wernicke’s original document from 1881 described a patient with bilateral optic neuritis with massive swelling and many streak hemorrhages. The intraretinal hemorrhages bear a resemblance to those seen in patients with Leber hereditary optic neuropathy, which suggests that mitochondrial dysfunction at the level of the retinal capillary endothelium might be responsible for the hemorrhages.3 However, to our knowledge, this finding and its proposed mechanism is not commonly discussed in the literature.Wernicke encephalopathy remains primarily a clinical diagnosis. Neuro-ophthalmic signs associated with WE consist of both horizontal and vertical gaze-evoked nystagmus, weakness or paralysis of the lateral recti muscles and weakness or paralysis of conjugate gaze, and optic neuropathy.4 Laboratory evaluations and neuroimaging can be helpful in unclear cases, but these should never delay prompt treatment with thiamine hydrochloride (vitamin B1) supplementation. Typical magnetic resonance imaging findings include high signal intensity on T2 sequences in the bilateral medial thalami and periventricular regions of the third ventricle.5 Vitamin B1 and α-transketolase serum levels are 2 laboratory tests that may indicate vitamin B1 deficiency, but there are no absolute levels that determine who is at risk for developing WE.The major barrier to proper diagnosis is a low index of suspicion, particularly in patients without alcoholism. Although most commonly seen in individuals with chronic alcoholism, WE has been found in a variety of other conditions, such as anorexia nervosa, bariatric surgery, forced starvation, hyperemesis gravidarum, and prolonged parenteral feeding. The human body is able to store between 30 and 50 mg of vitamin B1 at a time, and these reserves can be depleted in as little as 4 to 6 weeks,6 hence the recent surge of cases with the increasing popularity of bariatric procedures.Diagnostic evaluation to confirm the diagnosis should never take priority over actual thiamine supplementation. When untreated, WE can result in the most feared complication—Korsakoff syndrome. This disorder occurs in up to 85% of survivors and is characterized by severe retrograde amnesia with prominent confabulations. Without proper treatment, Korsakoff syndrome can lead to death in up to 20% of cases.With proper treatment, recovery of ocular manifestations can be rapid. Horizontal nystagmus can resolve within minutes, and gaze palsies often take 1 to 2 weeks for full recovery. However, central vestibular nystagmus may persist for several months.4 Once memory impairment occurs, only 20% of patients will experience full recovery.Lumbar puncture can be conducted after vitamin supplementation to rule out infectious processes, such as meningitis and increased intracranial pressure. Intravenous corticosteroids (choice D) would actually harm the patient because this treatment might elevate serum glucose levels; hyperglycemia can worsen WE without prior thiamine supplementation.With the recent increase in bariatric procedures, WE is likely to be seen with increasing frequency. Thus, the constellation of malnutrition from any cause with ocular motility dysfunction or nystagmus should prompt the physician to consider vitamin B1 deficiency as a cause. The presence of optic disc edema and intraretinal hemorrhages does not exclude WE as a diagnosis because they remain some of the more underreported features of the disease.7The patient started receiving intravenous thiamine on arrival. Three days after initiating therapy, her visual acuity had improved to 20/30 OU, her sensorium had cleared, and her abduction deficit had resolved. Her nystagmus, however, persisted and continued to be a source of frustration for the following 2 months. Findings from the dilated fundus examination 3 weeks after presentation revealed near-complete resolution of the intraretinal hemorrhages and disc edema, but her visual acuity had declined to 20/70 OU. This reduced visual acuity was likely caused by oscillopsia due to the nystagmus, with an element of impaired cognition and cooperation. She continues to take 100 mg of oral thiamine daily.

Ophthalmology

A woman in her 30s presented to the hospital with decreased vision in both eyes, confusion, and ataxia for 3 weeks. She had undergone gastric bypass surgery 3 months before presentation, which was complicated by a gastric ulcer and stricture. She had lost 34.5 kg since the procedure. Other medical history included hypothyroidism and thyroidectomy for thyroid cancer diagnosed 10 years ago. Her medication regimen included levothyroxine sodium and occasional bariatric chewable vitamins. She denied alcohol or tobacco use or drug abuse. Her best-corrected visual acuity was 20/200 OD and 20/400 OS. Her pupils were equally reactive, with no relative afferent pupillary defect. There was a mild abduction deficit in both eyes as well as prominent upbeating nystagmus. The amplitude of the nystagmus increased in upgaze and dampened with downgaze. She was unable to read the control plate of the Ishihara test. Findings from an anterior segment examination were unremarkable. Findings from a dilated fundus examination revealed disc edema in both eyes with peripapillary nerve fiber layer thickening and large intraretinal hemorrhages (Figure).A and B, Initial presentation of large intraretinal hemorrhages and disc edema in the left and right eye, respectively.

what would you do next?

What would you do next?

Intravenous corticosteroids

Intravenous vitamin therapy

Lumbar puncture

Magnetic resonance imaging and/or venography

b

female

31-40

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2174551

Following 2 days of cough and congestion, an otherwise healthy full-term 5-week-old neonate developed difficulty breathing and apnea requiring cardiopulmonary resuscitation. He was transported to a local emergency department. Following a difficult orotracheal intubation with multiple attempts, the infant was transferred to a pediatric intensive care unit with a presumptive diagnosis of bronchiolitis. During the next 2 days, he was weaned off mechanical ventilation and received oxygen via the nasal cannula. He began feeding orally and was transferred to the general inpatient floor. At the time of transfer, the patient was noted to have choking with feeds as well as a large volume of clear oral secretions that required frequent suctioning. Based on these clinical findings, oral food and fluids were withheld from the patient and a fluoroscopic video swallowing study (FVSS) was performed (Figure 1 and Video). What Is Your Diagnosis?

Gastroesophageal reflux

Tracheoesophageal fistula

Esophageal perforation

Aspiration

C. Esophageal perforation

C

Esophageal perforation

The FVSS demonstrated a perforation of the proximal oropharynx/esophagus with contrast filling a false lumen posterior to the esophagus. During the imaging study, the barium was noted to extend along the lower cervical and upper thoracic levels, with a distinct entry and exit point.An FVSS helps to distinguish between a wide differential diagnosis in the choking infant. The appearance seen on this infant’s study was diagnostic of esophageal perforation. Other diagnoses considered on the differential for a choking infant might have been distinguished by this study. Gastroesophageal reflux events can be seen on the FVSS, noted as passive regurgitation into the upper esophagus following swallowing. Tracheoesophageal fistulas can be diagnosed on FVSS if contrast is seen passing from the esophagus into the trachea below the level of the vocal cords. Vocal cord paralysis can be seen with traumatic intubations and can lead to aspiration. Although vocal cord paralysis cannot be visualized on the FVSS, aspiration would appear as contrast passing through the vocal cords and into the lungs. Finally, a laryngocele, an outpouching of the laryngeal ventricles, can cause choking. This would be apparent on the FVSS as a collection of contrast above the vocal cords.The patient remained stable with no signs of respiratory distress or sepsis. To facilitate feeding, a nasojejunal tube was placed under fluoroscopic guidance to prevent accidental placement into the false lumen and feeding into the mediastinum. All nasopharyngeal suctioning below the pharynx was terminated to avoid further trauma to the area. The patient received intravenous piperacillin/tazobactam as prophylaxis for mediastinitis. The pediatric otolaryngology service was consulted for management.Shortly thereafter, the patient was taken to the operating room where he underwent microlaryngoscopy and bronchoscopy (Figure 2A). This study confirmed the presence of a large false tract on the right, posterior to the true esophagus. The tract ended in a blind pouch. Owing to the location and appearance of the esophageal defect, the patient was diagnosed as having an iatrogenic perforation caused by intubation.A, A nasogastric tube is shown entering the esophageal inlet in an endoscopic photograph of the postcricoid region. A large false tract is clearly visible to the right posterior of the esophagus, which ends in a blind pouch. B, In follow-up, a nasogastric tube is seen entering the esophageal inlet. The previously seen false tract has completely healed.Esophageal perforation is rare in children, with only 8 cases at 1 pediatric hospital in a 15-year period.1 Esophageal perforations are potentially life threatening and may quickly lead to mediastinitis and/or sepsis in the absence of treatment.1,2 For that reason, broad-spectrum antibiotics are recommended.3 Esophageal perforations may be spontaneous (eg, Boerhaave phenomena), traumatic, or, most commonly, iatrogenic. Iatrogenic etiologies include complications of esophageal dilatation, endoscopy, enteric tube insertion, endotracheal intubation, and respiratory suction-catheter use.1,2In adults, esophageal perforations are most commonly treated via a surgical approach.3 Increasingly, children are being successfully treated though nonoperative management.1,4,5In our patient, the perforation was successfully managed via a conservative approach. Through direct visualization in the operating room, a repogle suction tube was placed in the blind pouch and placed to low continuous suction to keep the cavity free of secretions. This tube was slowly withdrawn approximately 0.5 cm every 2 days to allow upward healing of the perforation from the dependent portion.Oral food and fluids were withheld from the infant during the period of healing and feeding was done through a nasojejunal tube. Prophylactic antibiotics were continued for the duration of healing. The esophagus was revisualized both directly and via esophagram at approximately 1 and 2 weeks after the initial diagnosis. These studies confirmed progressive healing. Ten days after the initial diagnosis, the infant had complete healing of the esophagus and was able to resume oral feedings (Figure 2B). An FVSS performed prior to discharge showed no abnormality.

Pediatrics

Following 2 days of cough and congestion, an otherwise healthy full-term 5-week-old neonate developed difficulty breathing and apnea requiring cardiopulmonary resuscitation. He was transported to a local emergency department. Following a difficult orotracheal intubation with multiple attempts, the infant was transferred to a pediatric intensive care unit with a presumptive diagnosis of bronchiolitis. During the next 2 days, he was weaned off mechanical ventilation and received oxygen via the nasal cannula. He began feeding orally and was transferred to the general inpatient floor. At the time of transfer, the patient was noted to have choking with feeds as well as a large volume of clear oral secretions that required frequent suctioning. Based on these clinical findings, oral food and fluids were withheld from the patient and a fluoroscopic video swallowing study (FVSS) was performed (Figure 1 and Video).

what is your diagnosis?

What is your diagnosis?

Tracheoesophageal fistula

Gastroesophageal reflux

Esophageal perforation

Aspiration

c

male

0-10

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2089140

A woman in her 60s presented to the hospital because she felt abdominal pain and increasing asthenia during the previous 4 months. She reported a weight loss of 40 kg during the previous 12 months concomitant with depression. The patient had a history of cardiac arrhythmia, hypertension, and sigmoidectomy for diverticulitis. Medications included lasilix, amlodipine, amiodarone, and atenolol.On examination, the patient appeared well. Her vital signs were normal. The abdomen was soft without distension. A positive Murphy sign was observed. Her white blood cell count was 11400/μL (to convert to ×109/L, multiply by 0.001), her hemoglobin level was 11.5 g/dL (to convert to g/L, multiply by 10.0), and her platelet count was 233 ×103/μL (to convert to ×109/L, multiply by 1.0). The C-reaction protein level was elevated to 41 mg/L (to convert to nmol/L, multiply by 9.524). The results of renal and liver function, coagulation, blood level of electrolytes, total protein, albumin, antigen carcino embryonnaire, carbohydrate antigen 19-9, carbohydrate antigen 125, and β2 microglobulin tests were normal. The patient had a normal esophagogastroduodenoscopy and colonoscopy. Ultrasonography revealed a 10 × 8-m mass in the right hypochondrium. Abdominal computed tomography scan revealed a thickened gallbladder wall infiltrating the liver parenchyma. There were 3 perihepatic lymph nodes. Magnetic resonance imaging showed a greatly enlarged gallbladder with a thickened wall without invading adjacent structures, a continuous mucosal line, and a hypoattenuated intramural nodule (Figure 1). What Is Your Diagnosis?

Carcinoma of the gallbladder

Acute cholecystitis

Xanthogranulomatous cholecystitis

Lymphoma

C. Xanthogranulomatous cholecystitis (XGC)

C

Xanthogranulomatous cholecystitis

Xanthogranulomatous cholecystitis was first described by McCoy et al1 in 1976. It is a benign and uncommon variant of chronic cholecystitis characterized by focal or diffuse destructive inflammation of the gallbladder.2 Showing a low incidence of all inflammatory diseases of the gallbladder (0.7%-13.2%), it occurs mostly in middle-aged and elderly persons.3 The origin and pathogenesis of XGC are related to gallbladder obstruction and bile stasis. The combination of inflammation and bile extravasation in the gallbladder wall leads to a formation of xanthogranulomas similar to that produced in experimental pyelonephritis.4 There is an overlap between XGC and gallbladder carcinoma. The preoperative and intraoperative differential diagnosis of XGC from cancer still remains a challenge to the practicing surgeon, especially when associated with inflammatory involvement of surrounding tissues.It is important to consider XGC to avoid an unnecessary mutilating radical surgery, particularly in elderly individuals with comorbidities.5 The clinical presentation and biological examinations for XGC are not specific and resemble those of acute or chronic cholecystitis. Nevertheless, some morphologic features are highly suggestive of XGC including intramural hypoattenuated nodules, a diffused thickened gallbladder wall, an intact mucosal line, and the absence of obstructive features.6-8 These features do not systematically coexist. The frozen section should be done before proceeding with mutilating surgery.9The diagnosis of XGC is confirmed by the anatomical examination that indicates XGC by a thickened gallbladder wall that is yellowish and granular. Microscopically, the gallbladder is diffusely infiltrated by macrophages containing lipofuscin, lipid material, and bile pigment.4 Cholecystectomy is the treatment of choice for XGC, either complete or partial.10 Xanthogranulomatous cholecystitis creates difficulty at laparoscopy, with more than 80% of conversion to open laparotomy.2 Therefore, any preoperative suspicion of XGC should cause the clinician to consider open cholecystectomy.The patient underwent an open operation. The complete abdominal exploration showed an enlarged gallbladder with high tension and thickening of the gallbladder wall without adhesion to adjacent tissues or signs of malignancy (Figure 2). The intraoperative frozen section was conducted and included lymph nodes. There were no signs of malignant tumor. Owing to our clinical impression, imaging studies, intraoperative findings, and the frozen-section investigation, a simple cholecystectomy with a partial liver wedge resection was performed (Figure 3). An urgent pathological examination was requested and confirmed the diagnosis.An enlarged gallbladder with high tension and thickening of the gallbladder wall without adhesion to adjacent tissues or signs of malignancy.

Surgery

A woman in her 60s presented to the hospital because she felt abdominal pain and increasing asthenia during the previous 4 months. She reported a weight loss of 40 kg during the previous 12 months concomitant with depression. The patient had a history of cardiac arrhythmia, hypertension, and sigmoidectomy for diverticulitis. Medications included lasilix, amlodipine, amiodarone, and atenolol.On examination, the patient appeared well. Her vital signs were normal. The abdomen was soft without distension. A positive Murphy sign was observed. Her white blood cell count was 11400/μL (to convert to ×109/L, multiply by 0.001), her hemoglobin level was 11.5 g/dL (to convert to g/L, multiply by 10.0), and her platelet count was 233 ×103/μL (to convert to ×109/L, multiply by 1.0). The C-reaction protein level was elevated to 41 mg/L (to convert to nmol/L, multiply by 9.524). The results of renal and liver function, coagulation, blood level of electrolytes, total protein, albumin, antigen carcino embryonnaire, carbohydrate antigen 19-9, carbohydrate antigen 125, and β2 microglobulin tests were normal. The patient had a normal esophagogastroduodenoscopy and colonoscopy. Ultrasonography revealed a 10 × 8-m mass in the right hypochondrium. Abdominal computed tomography scan revealed a thickened gallbladder wall infiltrating the liver parenchyma. There were 3 perihepatic lymph nodes. Magnetic resonance imaging showed a greatly enlarged gallbladder with a thickened wall without invading adjacent structures, a continuous mucosal line, and a hypoattenuated intramural nodule (Figure 1).

what is your diagnosis?

What is your diagnosis?

Acute cholecystitis

Lymphoma

Carcinoma of the gallbladder

Xanthogranulomatous cholecystitis

d

female

61-70

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2091771

A 2-day-old girl (weight, 3.7 kg) developed abdominal distention and vomiting after feeding. Her Apgar scores at 1 and 5 minutes were 7 and 9, respectively. The infant’s postnatal course was remarkable for a febrile episode that was presumed to be due to chorioamnionitis in the mother and for which antibiotic treatment was initiated. Findings from the prenatal ultrasound, most recently conducted at 33 weeks’ gestation, were normal. The infant was active and well perfused, with a soft but distended abdomen and right-sided labial swelling. Findings from the remainder of her examination were unremarkable.An abdominal radiograph revealed dilated small-bowel loops (Figure 1A). Radiography of the upper gastrointestinal tract with water-soluble contrast showed a normal pattern of rotation. Results of a suction rectal biopsy revealed ganglion cells to be present. Serial abdominal radiographic images showed retained contrast in the terminal ileum 6 days following the gastrointestinal series (Figure 1B).A, Abdominal radiograph showing distended small-bowel loops with absent gas in the colon and rectum. B, Delayed radiography of the upper gastrointestinal tract with water-soluble contrast demonstrating retained contrast in the terminal ileum 6 days after initial radiography. What Is Your Diagnosis?

Cecal duplication

Small-bowel volvulus

Infantile leiomyosarcoma

Ovarian cyst with torsion

D. Ovarian cyst with torsion.

D

Ovarian cyst with torsion

The infant underwent exploratory laparotomy on the eighth day of life. Findings from the laparotomy are shown in Figure 2. A right-sided ovarian cyst measuring 6 cm in diameter was torsed and adherent to multiple small-bowel loops. The fallopian tube and round ligament were stretched across the terminal ileum, causing a complete small-bowel obstruction. The ovarian torsion occurred prenatally, with inflammation and dense adhesions occurring in the right lower quadrant. Surgery consisted of an ileocolectomy and right-sided salpingo-oophorectomy. The infant was fed and discharged per routine on postoperative day 7.Distended small-bowel loops (superiorly) with 6 × 6–cm, torsed, gangrenous, chocolate-colored, right-sided ovarian cyst (inferiorly).Neonatal ovarian cysts are uncommon.1 Most neonatal ovarian cysts are simple follicular cysts that remain asymptomatic and regress spontaneously.2 Larger or complex ovarian cysts may result in complications, most commonly torsion.3 Ovarian torsion has been reported to cause intestinal obstruction.4 The intestinal obstruction results from 1 of 2 mechanisms: (1) mass effect or (2) adhesions due to the inflammatory reaction occasioned by antenatal torsion, as in our case.4The classic signs of intestinal obstruction are bilious vomiting and abdominal distention. This may be attributed to a number of conditions, including malrotation, intestinal atresia, and Hirschsprung disease. To our knowledge, the associated finding of unilateral labial swelling has not been described in association with intestinal obstruction caused by ovarian torsion. Unilateral labial swelling in neonates is typically attributed to the residual effects of maternal estrogen or inguinal hernia. In this case, we believe that the ovarian cyst torsed with round ligament occlusion led to lymphovenous congestion, causing right-sided labial swelling.Treatment of ovarian cysts is controversial. Observation of simple asymptomatic cysts of less than 5 cm has been advocated. This poses a risk of future torsion.5 Larger neonatal ovarian cysts may be managed with aspiration or excision by open or laparoscopic techniques.Considering the rarity of this complication, it seems prudent to observe most neonates with antenatally diagnosed ovarian cysts. Intestinal obstruction in the presence of unilateral labial swelling should raise one’s suspicion of ovarian cyst with torsion as a possible cause.

Surgery

A 2-day-old girl (weight, 3.7 kg) developed abdominal distention and vomiting after feeding. Her Apgar scores at 1 and 5 minutes were 7 and 9, respectively. The infant’s postnatal course was remarkable for a febrile episode that was presumed to be due to chorioamnionitis in the mother and for which antibiotic treatment was initiated. Findings from the prenatal ultrasound, most recently conducted at 33 weeks’ gestation, were normal. The infant was active and well perfused, with a soft but distended abdomen and right-sided labial swelling. Findings from the remainder of her examination were unremarkable.An abdominal radiograph revealed dilated small-bowel loops (Figure 1A). Radiography of the upper gastrointestinal tract with water-soluble contrast showed a normal pattern of rotation. Results of a suction rectal biopsy revealed ganglion cells to be present. Serial abdominal radiographic images showed retained contrast in the terminal ileum 6 days following the gastrointestinal series (Figure 1B).A, Abdominal radiograph showing distended small-bowel loops with absent gas in the colon and rectum. B, Delayed radiography of the upper gastrointestinal tract with water-soluble contrast demonstrating retained contrast in the terminal ileum 6 days after initial radiography.

what is your diagnosis?

What is your diagnosis?

Small-bowel volvulus

Cecal duplication

Infantile leiomyosarcoma

Ovarian cyst with torsion

d

female

0-10

original

https://jamanetwork.com/journals/jama/fullarticle/2130295

After 5 days of nausea and vomiting, a man in his 60s with advanced, refractory diffuse large B-cell lymphoma involving the abdomen presented to the emergency department. The patient noted chronic, left-sided abdominal pain related to his lymphoma and normal passage of stool and flatus. He reported no other illnesses and was taking only esomeprazole. He was afebrile and normotensive with a pulse rate of 104/minute. A large, firm, tender mass located near the umbilicus was palpable in his abdomen, but there was no rigidity or rebound tenderness. Laboratory studies (Table) showed an elevated lactate level of 6.3 mmol/L (reference range, 0.7-2.2 mmol/L) (56.8 mg/dL; reference range, 6.3-19.8 mg/dL).A computed tomographic scan of the abdomen showed diffuse lymphadenopathy and a large mesenteric mass abutting multiple segments of the small intestine and encasing the mesenteric vasculature. He received 3 L of intravenous normal saline in the first 24 hours because of concern about volume depletion and sepsis. His tachycardia improved, but blood lactate remained elevated between 4.7-7.2 mmol/L (42.3-64.9 mg/dL). Serial abdominal examination results remained unchanged from the initial presentation.The patient has lactic acidosis from hypovolemic shock.The patient has lactic acidosis from mesenteric ischemia. How Do You Interpret These Test Results?

The patient has lactic acidosis from hypovolemic shock.

The patient has lactic acidosis from lymphoma.

The patient has lactic acidosis from mesenteric ischemia.

The patient has lactic acidosis from sepsis.

B

The patient has lactic acidosis from lymphoma.

Lactic acidosis can occur in the presence (type A) or absence (type B) of tissue hypoperfusion. In diagnosing states of tissue hypoperfusion, blood lactate testing is generally highly sensitive but has poor specificity. In the case of mesenteric ischemia, for example, the sensitivity of elevated lactate levels for establishing the diagnosis is as high as 100%, whereas the specificity is only 42%.1 Thus, it is common to have an elevated lactate level due to reasons other than tissue hypoperfusion, but rare to have a normal lactate level in the presence of tissue hypoperfusion. Therefore, if a patient has tissue hypoperfusion, the patient will almost always have an elevated lactate level. However, an elevated lactate level alone does not ensure that tissue hypoperfusion is present. Obtaining additional clinical information—including history, risk factors, physical examination, and other tests—is necessary to establish an underlying etiology for elevated lactate.Type A lactic acidosis is more common than type B and is associated with sepsis, mesenteric ischemia, and shock. In cases of type A lactic acidosis, tissue hypoperfusion results in anaerobic metabolism and lactate production. Type B lactic acidosis generally occurs in the absence of tissue hypoperfusion and has several etiologies, including: malignancy (usually hematologic malignancies such as leukemia, lymphoma, and multiple myeloma); renal or liver disease; drug or toxin ingestion; or congenital enzyme deficiencies.2-4The pathophysiology of type B lactic acidosis in malignancy is not completely understood. Lactic acidosis in malignancy may be related to high cell turnover rates because cancer cells have high rates of anaerobic metabolism even if adequate oxygenation is present.5 Aberrant insulin-like growth factor signaling and overexpression of the hexokinase type II enzyme in malignant cells may lead to increased glycolytic rates and lactate production.6,7 Thiamine is a coenzyme in aerobic metabolism and its deficiency may also result in increased lactate production.7 Neoplastic infiltration of the liver or kidney can lead to decreased clearance of lactate. Neoplastic infiltration or embolization of the microvasculature can also cause regional hypoperfusion leading to lactate production.7,8In 2014, the midpoint Medicare fee for serum lactate testing was $19.69.9The patient’s low bicarbonate, low Pco2, and marginally acidotic pH on venous blood gas testing suggest primary metabolic acidosis with compensatory respiratory alkalosis. Elevated lactate levels suggest lactic acidosis as the cause of the metabolic acidosis.Elevated blood lactate alone does not provide information on the etiology of lactic acidosis, and therefore the clinical context must be considered. Sepsis was unlikely given that the patient was afebrile, hemodynamically stable, and lacked significant leukocytosis. Furthermore, urinalysis, blood cultures, and diagnostic imaging of the abdomen and chest did not show evidence of infection. Mesenteric ischemia was a concern given tumor encasement of the mesenteric vasculature, however the patient’s abdominal pain did not progress and serial abdominal examinations were unchanged. These would be expected to worsen had there been significant mesenteric ischemia. Given the patient’s known malignancy with extensive tumor burden and relatively benign clinical course, he likely had type B lactic acidosis attributable to lymphoma.There are no definitive tests to diagnose type B lactic acidosis. This diagnosis is one of exclusion based on the overall clinical picture.The patient’s nausea and vomiting were attributed to partial bowel obstruction from his large intra-abdominal tumor burden. His symptoms were controlled with antiemetics and antisecretory agents. Blood lactate remained elevated during his hospitalization. He started palliative chemotherapy, but died several weeks later due to progression of his malignancy. Blood lactate was 3.4 mmol/L (30.6 mg/dL) before his death.Lactic acidosis can occur in the presence (type A) or absence (type B) of tissue hypoperfusion.Type A lactic acidosis is more common than type B. Type B lactic acidosis is a diagnosis of exclusion.Type B lactic acidosis occurs in the absence of tissue hypoperfusion and may be due to malignancy (especially hematologic malignancies), renal or liver disease, drug or toxin ingestion, or congenital enzyme deficiencies.

Diagnostic

After 5 days of nausea and vomiting, a man in his 60s with advanced, refractory diffuse large B-cell lymphoma involving the abdomen presented to the emergency department. The patient noted chronic, left-sided abdominal pain related to his lymphoma and normal passage of stool and flatus. He reported no other illnesses and was taking only esomeprazole. He was afebrile and normotensive with a pulse rate of 104/minute. A large, firm, tender mass located near the umbilicus was palpable in his abdomen, but there was no rigidity or rebound tenderness. Laboratory studies (Table) showed an elevated lactate level of 6.3 mmol/L (reference range, 0.7-2.2 mmol/L) (56.8 mg/dL; reference range, 6.3-19.8 mg/dL).A computed tomographic scan of the abdomen showed diffuse lymphadenopathy and a large mesenteric mass abutting multiple segments of the small intestine and encasing the mesenteric vasculature. He received 3 L of intravenous normal saline in the first 24 hours because of concern about volume depletion and sepsis. His tachycardia improved, but blood lactate remained elevated between 4.7-7.2 mmol/L (42.3-64.9 mg/dL). Serial abdominal examination results remained unchanged from the initial presentation.The patient has lactic acidosis from hypovolemic shock.The patient has lactic acidosis from mesenteric ischemia.

how do you interpret these test results?

How do you interpret these results?

The patient has lactic acidosis from hypovolemic shock.

The patient has lactic acidosis from lymphoma.

The patient has lactic acidosis from sepsis.

The patient has lactic acidosis from mesenteric ischemia.

b

male

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2110947

A 67-year-old woman presented to the emergency department with increasing dyspnea and chest wall tenderness. Two hours prior to presentation, she choked on her food while at dinner and received repeated attempts at the Heimlich maneuver with successful dislodgement of a piece of ham. The choking episode lasted for approximately 10 seconds, during which the patient was unable to speak. She has a history of hypertension and gastroesophageal reflux disease but no history of smoking. On arrival, she was dyspneic and in respiratory distress. Oxygen saturation was 80% with ambient air and improved to 99% with supplemental oxygen delivered via nasal cannula. A 12-lead electrocardiogram showed normal sinus rhythm without acute ST or T-wave changes. Brain natriuretic peptide level was 84 pg/mL. The patient received a chest radiograph and a computed tomographic scan of the chest (Figure). Transthoracic echocardiography demonstrated preserved systolic function, with no evidence of valve disease.Top left, Chest radiograph, posteroanterior view. Top right, Chest radiograph, left lateral view. Bottom, Computed tomography scan of the chest, axial view.Start intravenous antibiotics, intravenous fluid resuscitation, and obtain serum lactate level and blood and sputum culturesStart oxygen, β2-agonist nebulizer treatments, steroids, and oral azithromycin What Would You Do Next?

Start intravenous antibiotics, intravenous fluid resuscitation, and obtain serum lactate level and blood and sputum cultures

Start oxygen, β2-agonist nebulizer treatments, steroids, and oral azithromycin

Start aspirin, β-blocker, and consider cardiac catheterization

Observe and provide supplemental oxygen

Negative-pressure pulmonary edema

D

Observe and provide supplemental oxygen

The key clinical feature is the development of acute noncardiogenic pulmonary edema shortly after relief of an upper airway obstruction, which is consistent with negative-pressure pulmonary edema. This clinical entity was first observed in the pediatric population in association with croup and epiglottitis.1 In 1977, Oswalt et al2 reported acute fulminant pulmonary edema in adults after airway obstruction secondary to tumor, strangulation, and interrupted hanging. Although the mechanism is not fully understood, forceful attempts at inhalation against an obstruction or closed glottis, leading to increased negative intrathoracic pressure and subsequent transudation of fluid into the alveolar space, is thought to be the underlying pathophysiology.In this patient, the repeated Heimlich maneuvers may have contributed to high expiratory pleural pressures, which augmented the total transthoracic pressure changes. Negative-pressure pulmonary edema is more common in the setting of postextubation laryngospasm among young healthy patients who have marked inspiratory effort and are able to generate high negative intrathoracic pressures against an airway obstruction. However, any cause of airway obstruction may potentially lead to the development of this noncardiogenic form of pulmonary edema.There are 2 types of negative-pressure pulmonary edema. Type 1 develops after relief of an acute airway obstruction such as laryngospasm, endotracheal tube obstruction or biting, hanging, strangulation, upper airway tumors or masses, foreign bodies, croup, epiglottitis, near drowning, and choking.3 Type 2 may occur as a result of chronic forms of obstruction such as hypertrophic tonsils, adenoids, or tumors.3 Although complications are rare, there have been reports of bronchoscopic evidence of punctate hemorrhages,4 frank diffuse alveolar hemorrhage,5,6 and death attributable to acute respiratory distress syndrome and multiorgan failure.7 Diagnosis requires a high index of clinical suspicion and a compatible clinical scenario. Physicians should be cognizant of the possibility of negative-pressure pulmonary edema in patients who develop acute dyspnea shortly after a choking incident. Treatment is supportive and includes addressing the underlying etiology, relieving airway obstruction, maintaining a patent airway, and providing adequate oxygenation, which may necessitate the use of positive-pressure ventilation. If recognized early, overly aggressive diagnostic and therapeutic interventions can be avoided. Rapid clinical improvement and resolution is usually seen within 24 to 48 hours.Although aspiration of gastric contents into the airways during vigorous Heimlich maneuvers may induce a chemical pneumonitis, the resulting radiographic opacities typically develop in the most dependent regions of the lung.8,9 Empirical antibiotics would not be indicated unless the patient developed evidence of a bacterial infection.10 The patient has no history of chronic obstructive pulmonary disease and is a nonsmoker. Chest imaging is not suggestive of hyperinflation; moreover, the bilateral opacities make the diagnosis of acute exacerbation of chronic obstructive pulmonary disease unlikely, and thus the use of corticosteroids would be unwarranted. The presence of acute bilateral air space opacities in the setting of recent chest wall trauma from vigorous Heimlich maneuvers raises questions of pulmonary hemorrhage. Without evidence of coronary ischemia, cardiac enlargement, pleural effusions, elevated brain natriuretic peptide level, or systolic dysfunction, the patient’s pulmonary edema is most likely noncardiac in etiology. Negative pressure or postobstructive pulmonary edema may develop soon after relief of an upper airway obstruction and can potentially be life-threatening if not recognized early.After 3 days of supportive therapy, the patient’s clinical condition improved to baseline, with complete resolution of the infiltrates.

General

A 67-year-old woman presented to the emergency department with increasing dyspnea and chest wall tenderness. Two hours prior to presentation, she choked on her food while at dinner and received repeated attempts at the Heimlich maneuver with successful dislodgement of a piece of ham. The choking episode lasted for approximately 10 seconds, during which the patient was unable to speak. She has a history of hypertension and gastroesophageal reflux disease but no history of smoking. On arrival, she was dyspneic and in respiratory distress. Oxygen saturation was 80% with ambient air and improved to 99% with supplemental oxygen delivered via nasal cannula. A 12-lead electrocardiogram showed normal sinus rhythm without acute ST or T-wave changes. Brain natriuretic peptide level was 84 pg/mL. The patient received a chest radiograph and a computed tomographic scan of the chest (Figure). Transthoracic echocardiography demonstrated preserved systolic function, with no evidence of valve disease.Top left, Chest radiograph, posteroanterior view. Top right, Chest radiograph, left lateral view. Bottom, Computed tomography scan of the chest, axial view.Start intravenous antibiotics, intravenous fluid resuscitation, and obtain serum lactate level and blood and sputum culturesStart oxygen, β2-agonist nebulizer treatments, steroids, and oral azithromycin

what would you do next?

What would you do next?

Start intravenous antibiotics, intravenous fluid resuscitation, and obtain serum lactate level and blood and sputum cultures

Start oxygen, β2-agonist nebulizer treatments, steroids, and oral azithromycin

Start aspirin, β-blocker, and consider cardiac catheterization

Observe and provide supplemental oxygen

d

female

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2107766

A 74-year-old white man of British descent with a medical history of atrial fibrillation treated with warfarin presented to a dermatology clinic with multiple dark skin lesions on his neck, chest, abdomen, and upper extremities, as well as dark red lesions in his mouth of 4 months’ duration. During this period, he had been seen by his primary care physician as well as by hematology, dermatology, and cardiology specialists, who had told the patient his lesions were ecchymoses secondary to warfarin anticoagulation.The patient had no history of malignancy or exposure to communicable diseases. He experienced a 15.8-kg weight loss during the past few months but denied any fevers or night sweats. Physical examination revealed numerous slightly raised erythematous nodules throughout the neck, torso, and bilateral upper extremities (Figure, left). Inspection of the oral cavity demonstrated 2 discrete erythematous patches with sharply demarcated borders on the soft palate (Figure, right). The remainder of the physical examination was unremarkable. Laboratory results revealed a prothrombin time of 11.6 seconds, an international normalized ratio of 1.0, a hemoglobin level of 12.1 g/dL, and a platelet count of 106 cells ×103/μL; results of a basic chemistry panel with liver function tests were within normal limits. The skin lesion was biopsied, and results are pending.Left, Erythematous nodules on neck and torso (inset, close view). Right, Erythematous patches with sharply demarcated borders.Order computed tomography imaging of the chest, abdomen, and pelvis What Would You Do Next?

Initiate empirical treatment with a topical steroid

Initiate photodynamic therapy

Order computed tomography imaging of the chest, abdomen, and pelvis

Order a human immunodeficiency virus (HIV) test

Kaposi Sarcoma

D

Order a human immunodeficiency virus (HIV) test

The key clinical feature of this case is the development of multifocal erythematous nodules with a history of unexplained weight loss and unknown HIV status, which raises suspicion for Kaposi sarcoma. Although the patient’s age is consistent with classic Kaposi sarcoma, his significant weight loss and presence of upper extremity as opposed to lower extremity lesions is uncommon with classic Kaposi sarcoma and more typical for AIDS-associated Kaposi sarcoma.Computed tomography imaging of chest, abdomen, and pelvis can evaluate for visceral involvement of Kaposi sarcoma or for other diseases on the differential for Kaposi sarcoma, such as carcinoma cutis and arteriovenous malformations, but would not be the first step in the evaluation of suspected Kaposi sarcoma. Photodynamic therapy is an option for local treatment of some Kaposi sarcoma lesions after the diagnosis is confirmed but would not be first-line treatment for AIDS-associated Kaposi sarcoma. Topical steroids play no role in the treatment of Kaposi sarcoma.First described in 1872, Kaposi sarcoma gained importance after being characterized as an AIDS-defining illness in the early 1980s.1 Presently, approximately 2500 cases occur in the United States yearly.2 Four types of the disease exist based on epidemiologic setting: classic, African endemic, iatrogenic, and AIDS-associated. The classic type has a peak incidence between 50 and 70 years and arises most often among men of Mediterranean descent, whereas the AIDS-associated type tends to have a peak incidence between 20 and 40 years.The pathogenesis of Kaposi sarcoma involves infection with human herpesvirus 8 (HHV-8). Past analysis of the HHV-8 genome revealed proteins that dysregulate intracellular signal transduction pathways, cell cycle, and apoptosis, as well as induce angiogenesis.3 Although coinfection with HIV is not essential for the development of Kaposi sarcoma, the immunosuppression associated with HIV reduces control of HHV-8, of HHV-8–infected tumor cells, or both. Furthermore, the HIV genome encodes proteins that up-regulate expression of HHV-8 gene products and facilitate invasion of HHV-8 into endothelial cells.3Kaposi sarcoma usually presents as multiple purplish-red pigmented cutaneous and mucosal nodules or plaques.1 Lesions characteristically begin on the extremities, increase in size, and spread proximally. AIDS-associated Kaposi sarcoma can be aggressive, notably in patients with low CD4 cell counts, and associated with extensive cutaneous and visceral disease. Weight loss is occasionally seen in AIDS-associated cases as well as in multicentric Castleman disease, a separate AIDS-associated disease that can be linked to HHV-8. Mucosal involvement is most commonly seen within the oral cavity, with a predilection for the hard palate, gingiva, and dorsal tongue, and is associated with a higher mortality rate independent of CD4 level.3,4The diagnosis of Kaposi sarcoma centers around biopsy, revealing proliferating spindle cells and ill-defined vascular channels.5 Immunohistochemical staining for HHV-8 latency-associated nuclear antigen (LANA-1) within spindle cells can confirm the diagnosis. Although the US Preventive Services Task Force and the Centers for Disease Control and Prevention recommend routine screening for HIV in adolescents and adults aged 15 to 65 years, it is essential to test for HIV in patients with confirmed Kaposi sarcoma and unknown HIV status, regardless of age.4 Differential diagnosis of Kaposi sarcoma includes angiokeratoma, arteriovenous malformation, bacillary angiomatosis, blue rubber bleb nevus syndrome, carcinoma cutis, Dabska tumor, melanocytic nevi, melanoma, nodal angiomatosis, pyogenic granuloma, and Stewart-Treves syndrome.Institution of highly active antiretroviral therapy (HAART) is paramount for treating AIDS-associated Kaposi sarcoma.6 However, physicians should be aware of the risk of immune reconstitution inflammatory syndrome (IRIS), which may worsen Kaposi sarcoma because of an unregulated hyperinflammatory state in the presence of high antigen burden and increased immune function after starting HAART.4 Intralesional chemotherapy or radiation therapy is also used in AIDS-associated Kaposi sarcoma for management of large or bulky lesions, and systemic chemotherapy, most commonly with pegylated liposomal doxorubicin, is used in advanced or rapidly progressive cases, as well as in cases of IRIS. Local treatment with laser therapy and photodynamic therapy is more commonly used to treat classic Kaposi sarcoma, but has been used in limited cases in the AIDS-associated type, most often for cosmetic or palliative purposes.7Biopsy of the skin lesion revealed findings consistent with Kaposi sarcoma. A confirmatory test for HIV was positive, with a CD4 count of 106 cells/μL and viral load of 160 310 copies/mL. The patient’s wife, with whom the patient reported to have been sexually monogamous since the 1980s, tested negative for HIV. The patient reported having multiple sexual partners prior to his wife but denied other risk factors for HIV. The patient was referred to an infectious disease specialist and was started on efavirenz + emtricitabine + tenofovir therapy. Several months later, his skin lesions were resolving.

General

A 74-year-old white man of British descent with a medical history of atrial fibrillation treated with warfarin presented to a dermatology clinic with multiple dark skin lesions on his neck, chest, abdomen, and upper extremities, as well as dark red lesions in his mouth of 4 months’ duration. During this period, he had been seen by his primary care physician as well as by hematology, dermatology, and cardiology specialists, who had told the patient his lesions were ecchymoses secondary to warfarin anticoagulation.The patient had no history of malignancy or exposure to communicable diseases. He experienced a 15.8-kg weight loss during the past few months but denied any fevers or night sweats. Physical examination revealed numerous slightly raised erythematous nodules throughout the neck, torso, and bilateral upper extremities (Figure, left). Inspection of the oral cavity demonstrated 2 discrete erythematous patches with sharply demarcated borders on the soft palate (Figure, right). The remainder of the physical examination was unremarkable. Laboratory results revealed a prothrombin time of 11.6 seconds, an international normalized ratio of 1.0, a hemoglobin level of 12.1 g/dL, and a platelet count of 106 cells ×103/μL; results of a basic chemistry panel with liver function tests were within normal limits. The skin lesion was biopsied, and results are pending.Left, Erythematous nodules on neck and torso (inset, close view). Right, Erythematous patches with sharply demarcated borders.Order computed tomography imaging of the chest, abdomen, and pelvis

what would you do next?

What would you do next?

Order computed tomography imaging of the chest, abdomen, and pelvis

Initiate photodynamic therapy

Initiate empirical treatment with a topical steroid

Order a human immunodeficiency virus (HIV) test

d

male

71-80

White

original

https://jamanetwork.com/journals/jama/fullarticle/2107769

A 57-year-old white man presents for evaluation of an asymptomatic elevation in bilirubin detected on a chemistry panel during an annual physical examination. Thirty years ago, he had abnormal liver function tests attributed to use of an unknown medication that resolved when the drug was discontinued. He reports no jaundice, pruritus, or family history of liver disease and takes no medications. He drinks 1 alcoholic beverage daily (≈100 g/week). On physical examination, blood pressure was 108/63 mm Hg, pulse rate was 61 beats per minute, and body mass index (calculated as weight in kilograms divided by height in meters squared) was 23.4. His liver was 7.0 cm by percussion and nontender, sclera were anicteric, there was no stigmata of chronic liver disease, and splenomegaly was absent. The examination was otherwise unremarkable. His laboratory values are reported in the Table. How do You Interpret These Test Results?

Hyperbilirubinemia due to cholelithiasis

Hyperbilirubinemia due to Dubin-Johnson syndrome

Hyperbilirubinemia due to Gilbert syndrome

Hyperbilirubinemia due to hemolysis

C

Hyperbilirubinemia due to Gilbert syndrome

Bilirubin is the normal by-product of the breakdown of hemoglobin. Bilirubin circulates in the blood bound to albumin and is taken up by hepatocytes in the liver. Within hepatocytes, bilirubin is conjugated with glucuronic acid, a process catalyzed by uridine diphosphoglucuronate-glucuronyltransferase (UDP-GT). Conjugated (direct) bilirubin is secreted into bile. This process is normally highly efficient so plasma unconjugated (indirect) bilirubin concentrations remain low. Hyperbilirubinemia can be caused by conditions leading to predominantly unconjugated hyperbilirubinemia and those characterized by predominantly conjugated hyperbilirubinemia (Figure). Diseases that increase the rate of bilirubin formation (eg, hemolysis, dyserythropoiesis), reduce hepatic uptake of bilirubin (eg, medications [gemfibrozil, irinotecan and the protease inhibitors, atazanavir, and indinavir]; portosystemic shunts), or reduce the rate of bilirubin conjugation (eg, Gilbert syndrome) result in increased levels of indirect bilirubin (Figure).The algorithm has not been validated and is based on the authors’ expertise and experience.aIncludes alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase.bIndicates at least 80% of the total bilirubin fraction.Gilbert syndrome, also known as Gilbert-Meulengracht syndrome, is a hereditary condition with incomplete penetrance, characterized by intermittent unconjugated hyperbilirubinemia in the absence of hepatocellular disease or hemolysis.1 Gilbert syndrome is present in 5% to 10% of Western European populations and patients are frequently unaware of their diagnosis.2,3 A genetic variant in the promoter region of the UGT1A1 gene, which encodes for UDP-GT, is associated with Gilbert syndrome and there is an additional thymine-adenine (TA) base pair in the TATA box instead of the normal 6 pairs.2 In Gilbert syndrome, there is a 70% reduction in the liver’s ability to conjugate bilirubin that can lead to intermittent episodes of nonpruritic jaundice, which are precipitated by fasting, infection, and overexertion.3 Several therapeutic drugs including gemfibrozil, irinotecan, atazanavir, and indinavir inhibit UDP-GT activity and can trigger jaundice episodes in Gilbert syndrome.4The diagnosis of Gilbert syndrome as the cause of hyperbilirubinemia should only be made after excluding other liver and hematologic disorders. Patients with Gilbert syndrome are asymptomatic and typically have otherwise normal liver serum chemistries. If the unconjugated bilirubin fraction predominates, hemolytic disorders and rare familial hyperbilirubinemias must be considered. In Gilbert syndrome, the degree of hyperbilirubinemia is typically less than 5 mg/dL and the conjugated bilirubin is typically less than 20% of the total bilirubin fraction.3 The Medicare midpoint reimbursement for a total and direct serum bilirubin is $9.25 for each.5 The cost of UGT1A1 gene analysis ranges from $75 to $103, although it is rarely used for diagnosis.6Gilbert syndrome is the most likely cause of the unconjugated hyperbilirubinemia in the setting of normal liver enzymes and in the absence of medications that reduce hepatic uptake of bilirubin or symptoms suggesting hepatobiliary disease or hemolysis. Dubin-Johnson syndrome is another benign hereditary condition characterized by a predominantly conjugated hyperbilirubinemia but would not explain the unconjugated hyperbilirubinemia.Gilbert syndrome is typically diagnosed in the first 3 decades of life and no specific management is required for most patients. The Gilbert syndrome genotype is associated with an increased risk of gallstones1,7 and adverse reactions to multiple drugs, including chemotherapy.1,4,6,7 It is possible but unclear if elevated serum bilirubin levels protect against cardiovascular or other diseases.8,9 A recent study reported an association of Gilbert syndrome with a 50% reduction in mortality compared with the general population (24 vs 50 deaths per 10 000 person-years).10 Another study suggested that Gilbert syndrome may be associated with an increased risk for breast cancer.1,4Hemolysis and drug-induced hyperbilirubinemia should be excluded. Presence of hemolysis can be evaluated with a peripheral blood smear and levels of lactate dehydrogenase and haptoglobin. Provocation tests, including observing an increase in unconjugated bilirubin after a 48-hour fast, are not recommended.3 The diagnosis of Gilbert syndrome can be made in patients who continue to have normal laboratory results (other than the elevation in serum bilirubin) during the next 12 months. For cases in which diagnostic uncertainty remains, such as total bilirubin of greater than 5 mg/dL, genetic testing for a UGT1A1 mutation can be performed athough this is rarely necessary. Liver or biliary imaging and referral to a specialist are typically not needed. Overtesting may be deleterious to otherwise healthy patients with this benign condition.In this patient, a peripheral blood smear, lactate dehydrogenase, and haptoglobin levels confirmed the absence of hemolysis. Repeat bilirubin measured 6 and 12 months later was elevated and a diagnosis of Gilbert syndrome was made. The patient remains well and follows up with his primary care physician for routine medical care.Gilbert syndrome is a hereditary condition characterized by a 70% reduction in the ability to conjugate bilirubin, resulting in asymptomatic intermittent unconjugated hyperbilirubinemia.Gilbert syndrome is present in 5% to 10% of Western European populations.In Gilbert syndrome, the degree of hyperbilirubinemia is typically less than 5 mg/dL and the conjugated bilirubin is typically less than 20% of the total bilirubin fraction.3Gilbert syndrome is usually a diagnosis of exclusion and can be diagnosed by ruling out intrinsic hepatic disease and hemolytic states.

Diagnostic

A 57-year-old white man presents for evaluation of an asymptomatic elevation in bilirubin detected on a chemistry panel during an annual physical examination. Thirty years ago, he had abnormal liver function tests attributed to use of an unknown medication that resolved when the drug was discontinued. He reports no jaundice, pruritus, or family history of liver disease and takes no medications. He drinks 1 alcoholic beverage daily (≈100 g/week). On physical examination, blood pressure was 108/63 mm Hg, pulse rate was 61 beats per minute, and body mass index (calculated as weight in kilograms divided by height in meters squared) was 23.4. His liver was 7.0 cm by percussion and nontender, sclera were anicteric, there was no stigmata of chronic liver disease, and splenomegaly was absent. The examination was otherwise unremarkable. His laboratory values are reported in the Table.

how do you interpret these test results?

How do you interpret these results?

Hyperbilirubinemia due to hemolysis

Hyperbilirubinemia due to Dubin-Johnson syndrome

Hyperbilirubinemia due to cholelithiasis

Hyperbilirubinemia due to Gilbert syndrome

d

male

51-60

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/1935476

A healthy 60-year-old woman presented with a painless subareolar nodule of her left nipple measuring 2 cm in diameter (Figure, A) that had been present for several months. Screening mammography (Figure, B) performed 4 weeks prior revealed a large grouping of left breast subareolar calcifications extending into the skin and nipple. Follow-up ultrasonography demonstrated no discrete abnormal mass or shadowing but did show multiple echogenic foci consistent with findings on mammography. An incisional biopsy specimen of the mass was obtained and sent for histopathologic evaluation (Figure, C).A, Firm, irregular, subareolar nodule of left nipple measuring 2 cm in diameter. B, Mammography of the left breast. C, Biopsy specimen of the subareolar nodule (hematoxylin-eosin, original magnification ×20). What Is the Diagnosis?

Tubular carcinoma

Syringomatous adenoma of the nipple

Low-grade adenosquamous carcinoma

Florid papillomatosis of the nipple

B. Syringomatous adenoma of the nipple

B

Syringomatous adenoma of the nipple

Histopathologic examination revealed a dermal tumor composed of angulated glands and nests and cords of cells permeating between the muscle bundles of the nipple stroma. There was no perineural growth identified. The neoplastic cells were arranged in 2 layers and exhibited minimal nuclear pleomorphism and scant cytoplasm. The stroma was fibrotic without calcification and keratinous cysts were present. The deepest portion of the tumor was measured to be 3.3 mm below the stratum corneum. Once the results from the histopathologic evaluation were obtained, the patient returned to the clinic and was advised to undergo complete tumor excision.Syringomatous adenoma of the nipple (SAN) is a benign, locally infiltrating neoplasm with similar morphology to tumors of eccrine duct origin.1 Despite its benign behavior, SAN is often misdiagnosed as tubular carcinoma or low-grade adenosquamous carcinoma (LGAC) of the breast owing to similarities in clinical presentation and findings on mammography. Syringomatous adenoma of the nipple typically presents as a 1- to 3-cm unilateral firm mass in the nipple or subareolar region of the breast. Symptoms may include pain, crusting, itchiness, nipple discharge, and/or nipple inversion. All but 2 reported cases of SAN have occurred in women, between the ages of 11 to 76 years.1,2 Radiographic findings of SAN are indistinguishable from carcinoma. Mammography often demonstrates a dense, irregular mass with foci of microcalcifications in the subareolar region, findings that are highly suspicious for malignancy.3Definitive diagnosis requires a biopsy of the tumor and microscopic evaluation. Histopathologic criteria to diagnose SAN include (1) location in dermis and subcutaneous tissue of nipple or areola; (2) irregular, compressed, or comma-shaped tubules infiltrating into smooth muscle and/or nerves; (3) myoepithelial cells around the tubules; (4) cysts filled with keratinous material and lined by stratified squamous epithelium; and (5) no mitotic activity and necrosis.1 Despite these criteria, it remains difficult to distinguish SAN from tubular carcinoma, florid papillomatosis of the nipple (a variant of intraductal papilloma), or LGAC of the breast microscopically because of several common features, but there are certain characteristics unique to each allowing for their differentiation. Florid papillomatosis of the nipple, for instance, typically displays epithelial hyperplasia originating from lactiferous ducts, which causes displacement of the nipple stroma rather than the infiltrative pattern seen in SAN.1 Tubular carcinoma and SAN can show similar patterns of infiltration. However, the presence of squamous metaplasia and mitotic figures, in addition to the absence of myoepithelial cells, help differentiate tubular carcinoma from SAN.1 Although immunohistochemical stains were not used in our patient, they can be useful in differentiating difficult cases of tubular carcinoma. Smooth muscle myosin heavy chain and p63 proteins are frequently used to label and identify myoepithelial cells. Their absence in a specimen further suggests a diagnosis of tubular carcinoma rather than SAN. In addition, the anatomic location of tubular carcinoma is not typically confined to the nipple-areola region, as is the case in our patient.4The differentiation between LGAC and SAN can be subtle owing to the amount of common features on clinical and pathologic examination. However, it remains vitally important to distinguish these 2 lesions due to their difference in metastatic potential. Low-grade adenosquamous carcinoma has a small but well-known potential to metastasize, whereas SAN does not.4 Microscopically, SAN is distinguished from LGAC by its characteristic progression from cysts to small ductules to cords and nests of cells. In addition, LGAC frequently demonstrates a prevalence of squamous differentiation, whereas this is a lesser component of SAN.4Another primary skin tumor confused histologically for SAN is microcystic adnexal carcinoma (MAC). Some consider MACs and SANs to be the same neoplastic entity; however, their clinical behavior is drastically different. Again, there have been no reported cases of metastatic SAN, whereas MACs have shown metastatic potential in various case reports.5-7 In addition, MACs frequently show recurrence after conservative excision, while only a small number of SANs have recurred.4 Despite this difference in clinical behavior, definitive treatment remains the same for both. Treatment of SAN requires complete excision of the mass. There have been no reported cases of recurrence after achievement of negative margins with excision.1 However, those with positive margins on excision demonstrate a high rate of recurrence during a 1- to 6-year follow-up.4 Recurrences are typically managed with local reexcision.In conclusion, SAN is a benign, locally aggressive tumor of the breast that must be considered in any patient who presents with an areolar mass and suggestive findings on mammography. Identification of this benign process is critical to avoid misdiagnosis and subsequent unnecessary surgery and psychological stress.

Dermatology

A healthy 60-year-old woman presented with a painless subareolar nodule of her left nipple measuring 2 cm in diameter (Figure, A) that had been present for several months. Screening mammography (Figure, B) performed 4 weeks prior revealed a large grouping of left breast subareolar calcifications extending into the skin and nipple. Follow-up ultrasonography demonstrated no discrete abnormal mass or shadowing but did show multiple echogenic foci consistent with findings on mammography. An incisional biopsy specimen of the mass was obtained and sent for histopathologic evaluation (Figure, C).A, Firm, irregular, subareolar nodule of left nipple measuring 2 cm in diameter. B, Mammography of the left breast. C, Biopsy specimen of the subareolar nodule (hematoxylin-eosin, original magnification ×20).

what is the diagnosis?

What is your diagnosis?

Tubular carcinoma

Low-grade adenosquamous carcinoma

Syringomatous adenoma of the nipple

Florid papillomatosis of the nipple

c

female

51-60

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/1937724

A 2-year-old girl was referred to our department for skin fragility since early infancy. She had 2 older brothers, and the family had no medical history of note. Physical examination revealed mild xerosis with superficial skin erosions and erythematous residual macules from previous erosions. Some of the lesions had an unusual linear geographic contour and were predominantly located at areas of friction (Figure, A and B). Hair, nails, and mucous membranes were normal. There was no history of blistering. The mother explained that she often found the child peeling off skin with marked facility. Symptoms improved in winter and worsened in summer. Physical and mental developments were normal. Serological markers for celiac disease were negative. A skin biopsy was performed (Figure, C).A, Clinical photograph of a disease outbreak. Skin fragility can be seen as superficial erosions distributed predominantly around the trunk, some with geometric shape. B, Photograph showing localized affectation of the disease. Erythemato-desquamative well-demarcated plaque with peeling borders on right foot. C, Hematoxylin-eosin staining (original magnification ×40) of healthy skin. Remarkable detachment of the entire stratum corneum and mild psoriasiform epidermis hyperplasia with no other significant findings. What Is the Diagnosis?

Kindler syndrome

Dermatitis artefacta

Epidermolysis bullosa simplex superficialis

Peeling skin disease

D. Peeling skin disease

D

Peeling skin disease

A biopsy specimen from normal skin was obtained by rubbing with a pencil eraser. Hematoxylin-eosin staining and immunofluorescence mapping showed complete separation of the stratum corneum with a clean split just above the stratum granulosum. Faint psoriasiform hyperplasia and a mild perivascular and interstitial mononuclear infiltrate were observed in the upper dermis. Results from immunofluorescence mapping were normal for collagen IV and VII, for α6 and β4 integrines and for laminine-332. The subcorneal split is usually the key for the diagnosis of peeling skin disease (PSD).1 A genetic study was performed of the COL7A1 and CDSN genes with polymerase chain reaction technique and automatic sequencing with Big Dye Terminators in the genetic analyzer ABI3100. This test revealed 2 heterozygous mutations not previously described in exon 2 of the CDSN gene, confirming the diagnosis of PSD. The patient is now 5 years old, and her disease is well controlled with hygienic measures and topical treatment.Peeling skin disease, previously called peeling skin syndrome, is a recessively inherited ichthyosiform genodermatoses. It is characterized by skin fragility and chronic or recurrent superficial peeling and is classified as a nonsyndromic ichthyosis.2 Severity is variable. According to its distribution, the disorder is divided into acral and generalized forms. Acral PSD is the result of mutations in the transglutaminase 5 (TGM5) gene.3 Generalized PSD has been subclassified into noninflammatory and inflammatory forms. Mutations in the corneodesmosin (CNDS) gene have been detected in inflammatory forms. This gene codifies the corneodesmosin protein responsible for stabilizing the stratum corneum and its adhesion to the stratum granulosum. The gene of the noninflammatory form is currently unknown.4Diagnosis of PSD is often delayed owing to late presentation in less severe cases. It is possibly considered an underdiagnosed disease because of its low clinical expression and the few cases described in the literature. Diagnosis is made exclusively by genetic study. Peeling skin disease can often be well managed with topical treatments and hygienic measures alone. Oral treatments, such as retinoids, methotrexate, or systemic corticosteroids, have been proposed in severe cases without a sustained clinical response. Prognosis is not well known owing to the limited number of cases, but it seems to improve with age.Differential diagnosis of PSD includes mainly the group of inherited epidermolysis bullosa (EB) disorders. Skin fragility occurs in both entities but histological and direct immunofluorescence findings usually help to differentiate them.5 In EB, the separation of keratinocytes occurs at several levels: basal keratinocyte (EB simplex type), dermoepidermal junction (junctional EB), and superficial dermis (dystrophic EB). In Kindler syndrome the division can be seen in both dermoepidermal junction and superficial dermis.6 However, the separation in PSD is within keratinocytes at the junction of the stratum granulosum and stratum corneum.1 The only indistinguishable subtype of EB according to the level of cleavage is epidermolysis bullosa simplex superficialis.1 Nevertheless, in this form of EB, there are several clinical findings that are usually absent in PSD, such as atrophic scarring, onychodystrophy, and milium cysts.7In conclusion, PSD is a rare and misdiagnosed genodermatosis, classified as a nonsyndromic ichthyosis, which we should suspect in young patients with recurrent or chronic skin fragility and a subcorneal split in the skin biopsy. Although diagnosis can be confirmed only by genetic study, the association of these clinicopathological findings should suggest this diagnosis.

Dermatology

A 2-year-old girl was referred to our department for skin fragility since early infancy. She had 2 older brothers, and the family had no medical history of note. Physical examination revealed mild xerosis with superficial skin erosions and erythematous residual macules from previous erosions. Some of the lesions had an unusual linear geographic contour and were predominantly located at areas of friction (Figure, A and B). Hair, nails, and mucous membranes were normal. There was no history of blistering. The mother explained that she often found the child peeling off skin with marked facility. Symptoms improved in winter and worsened in summer. Physical and mental developments were normal. Serological markers for celiac disease were negative. A skin biopsy was performed (Figure, C).A, Clinical photograph of a disease outbreak. Skin fragility can be seen as superficial erosions distributed predominantly around the trunk, some with geometric shape. B, Photograph showing localized affectation of the disease. Erythemato-desquamative well-demarcated plaque with peeling borders on right foot. C, Hematoxylin-eosin staining (original magnification ×40) of healthy skin. Remarkable detachment of the entire stratum corneum and mild psoriasiform epidermis hyperplasia with no other significant findings.

what is the diagnosis?

What is your diagnosis?

Peeling skin disease

Dermatitis artefacta

Epidermolysis bullosa simplex superficialis

Kindler syndrome

a

female

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/1939415

A healthy woman in her 40s, lactating, 5 months post partum, presented with a 1-month history of enlargement and induration of both breasts (Figure, A). A skin biopsy specimen from the breast was obtained (Figure, B). She was initially diagnosed with mastitis and received several courses of antibiotics for 2 months without improvement. Subsequently she presented with back pain, paresthesias, shooting pain in the mandibular region, and diplopia. All of these conditions improved under treatment with oral corticosteroids, but the breast enlargement continued. Laboratory test results highlighted a hemoglobin level of 7.6 g/dL and a platelet count of 80 000/μL. (To convert hemoglobin to grams per liter, multiply by 10; to convert platelets to number of cells × 109/L, multiply by 1.0.)A, Enlargement and induration of both breasts. B, Histopathologic specimen from the breast (hematoxylin-eosin, original magnification ×40). What is the diagnosis?

Acute lymphoblastic leukemia of the breast

Breast implant foreign body reaction

Severe postpartum mastitis

Burkitt lymphoma of the breast

D. Burkitt lymphoma of the breast

D

Burkitt lymphoma of the breast

A skin biopsy of the breast showed extensive infiltration of the superficial and deep dermis by monomorphic medium-sized cells with scant cytoplasm and rounded vesicular nucleus with fine chromatin and occasional irregularity of the nuclear membrane and numerous mitoses imparting the appearance of a starry sky (Figure, B). The immunophenotype showed CD45+, CD20+, CD10+, bcl-6+, CD43+, TDT−, bcl-2−, CD34−, and EBER− with Ki-67 proportion greater than 95%, all findings compatible with Burkitt lymphoma (BL). The molecular study showed the c-Myc translocation, and cytogenetic analysis showed 8:14 translocation. The patient also demonstrated pleural fluid, cerebrospinal fluid, and bone marrow involvement. Systemic and intrathecal chemotherapy was started, followed rapidly by improvement of the breast induration and the supradiaphragmatic and infradiaphragmatic involvement. At last follow-up, the patient was undergoing further cycles of chemotherapy.Primary lymphomas of the breast are uncommon tumors. There are 2 different clinicopathologic groups: one occurs in young women bilaterally and is often associated with pregnancy or lactation: a Burkitt-type lymphoma. The other clinicopathologic group affects a broad age range, but primarily older woman, and is usually a B-cell non-Hodgkin lymphoma with clinical features identical to carcinoma of the breast. This second type presents as a unilateral mass and has a better prognosis than BL.1,2Burkitt lymphoma is a predominantly extranodal aggressive form of non-Hodgkin lymphoma. It has a predilection for the mandibular area, gastrointestinal tract, kidneys, breast, and ovaries. Bone marrow and the peripheral blood are affected in advanced stages. There is a translocation of the c-Myc gene on chromosome 8 with the heavy or light chain of the immunoglobulin on chromosome 2, 14, or 22.3 Burkitt lymphoma is classified into 3 types: sporadic, endemic, or associated with human immunodeficiency virus. Skin involvement is very rare.4,5Negahban et al6 found a total of 47 cases of BL with breast involvement in the literature. Of these 47 cases, 14 occurred during the lactational period, and 13 occurred during pregnancy. The times of occurrence of the other 20 cases were not defined. Of these 47 cases, 32 occurred bilaterally. The survival rates for primary BL of the breast in the lactation period and in pregnancy were 14.3% and 30.8%, respectively. Most of the lactation-associated BLs (92.8%) were stage I, whereas those occurring in pregnancy were mainly stage IV (61.5%). If the onset of BL is in the breast, then it is often bilateral and massive, and it is usually associated with pregnancy or lactation, which might suggest hormonal influences on its pathogenesis.6There are no randomized clinical trials for adult BL to guide therapy. Treatment is based on small series. CODOX-M-IVAC chemotherapy (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate-ifosfamide, etoposide, high-dose cytarabine, and intrathecal methotrexate) and the CALGB 9251 regimen7 are the most frequently cited in the literature. Radical surgery should be avoided.1The present case is interesting because the diagnosis was reached mostly from a dermatologic evaluation. The patient had been treated previously for mastitis without any response for 2 months. The feature of BL with bilateral breast enlargement and induration during the peripartum period is very characteristic. Any pregnant or lactating women with severe or progressive bilateral breast enlargement unresponsive to anti-inflammatory and antibiotic treatment must be evaluated to rule out BL.

Dermatology

A healthy woman in her 40s, lactating, 5 months post partum, presented with a 1-month history of enlargement and induration of both breasts (Figure, A). A skin biopsy specimen from the breast was obtained (Figure, B). She was initially diagnosed with mastitis and received several courses of antibiotics for 2 months without improvement. Subsequently she presented with back pain, paresthesias, shooting pain in the mandibular region, and diplopia. All of these conditions improved under treatment with oral corticosteroids, but the breast enlargement continued. Laboratory test results highlighted a hemoglobin level of 7.6 g/dL and a platelet count of 80 000/μL. (To convert hemoglobin to grams per liter, multiply by 10; to convert platelets to number of cells × 109/L, multiply by 1.0.)A, Enlargement and induration of both breasts. B, Histopathologic specimen from the breast (hematoxylin-eosin, original magnification ×40).

what is the diagnosis?

What is your diagnosis?

Burkitt lymphoma of the breast

Acute lymphoblastic leukemia of the breast

Severe postpartum mastitis

Breast implant foreign body reaction

a

female

41-50

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2108785

At birth, a full-term newborn was noted to have numerous hypopigmented skin macules on the trunk, scalp, neck, face, back, and limbs after an uncomplicated pregnancy (Figure 1A). The family history was negative for any dermatologic or genetic diseases. A shave biopsy specimen of the right leg was interpreted as papillomatous epidermal hyperplasia consistent with an epidermal nevus. Because of the constellation of findings, an initial diagnosis of linear epidermal nevus syndrome was made. At age 3 months, the patient was referred for ophthalmologic examination owing to a flat, hypopigmented lesion in the left temporal iris noted by the patient’s father. On examination, the patient fixed and followed with both eyes. Pupils, motility, and binocular alignment were normal. Dilated ophthalmoscopic examination revealed a well-demarcated hypopigmented lesion originating from the retinal nerve fiber layer and protruding into the vitreous cavity of the right eye (Figure 1B). A similar lesion was seen along the left inferotemporal arcade (Figure 1C). B-scan ultrasonography revealed a 4.0 × 2.9 × 2.2-mm lesion with no calcification, no retinal detachment, and no choroidal involvement (Figure 1D). Given the suspected iris hamartoma and retinal astrocytic hamartoma, a systemic workup was commenced.A, Dermatologic manifestations. The patient had multiple hypopigmented macules on his scalp, face, neck, back, limbs, and torso (arrowheads). B, A lesion was discovered in the right eye consistent with a retinal astrocytic hamartoma. C, A similar smaller lesion was seen in the left eye. D, B-scan ultrasonography revealed an elevated lesion emanating from the retina with no calcification or choroidal involvement. What Would You Do Next?

Renal ultrasonography and lumbar puncture

Brain imaging and echocardiography

Metastatic workup

Fine-needle aspiration biopsy of ocular lesion

Tuberous sclerosis complex

B

Brain imaging and echocardiography

Brain magnetic resonance imaging revealed cortical and subcortical tubers along with subependymal nodules (Figure 2). The echocardiogram revealed several ventricular masses, with the largest measuring 7 mm in the left ventricle, consistent with cardiac rhabdomyomas. The constellation of findings confirmed a diagnosis of tuberous sclerosis.Brain magnetic resonance imaging revealed multiple lesions, including a tuber in the cortex and subcortical white matter (arrowhead) (A), hyperintense patches in the subcortical white matter and a tuber in the right temporal lobe (arrowhead) (B), and multiple subependymal nodules along the lateral ventricles (arrowheads) (C).Tuberous sclerosis complex (TSC) is a rare disorder affecting cellular proliferation and differentiation that leads to hamartomatous formation in multiple organs, including the brain (tubers and subependymal giant cell astrocytomas), heart (rhabdomyomas), kidney (angiomyolipomas and renal cell carcinoma), skin, and retina.1 Tuberous sclerosis complex exhibits an autosomal dominant inheritance pattern and has been mapped to 2 genetic loci—9q34 (TSC1 [OMIM 605284], which encodes protein hamartin) and 16p13 (TSC2 [OMIM 191092], which encodes protein tuberin)1—but has been attributed to a spontaneous mutation in the majority of cases.2 Most patients are diagnosed between ages 2 and 6 years.Diagnosis of TSC depends on the presence of a certain number of major and minor criteria. Characteristic dermatologic lesions include angiofibromas (adenoma sebaceum), shagreen patches, and ash leaf macules. Ocular manifestations of TSC include iris hypopigmentation, inferior iris colobomas, and retinal astrocytic hamartomas, with the latter being the most common and occurring in approximately 50% of patients and bilaterally in half of these.3 Retinal astrocytic hamartomas manifest as sessile or elevated lesions of the retinal nerve fiber layer and often calcify with age. These types of retinal astrocytic hamartomas have been described: type 1 (semitransparent, flat, no calcification), type 2 (multinodular, calcified lesions with a mulberry-like appearance), and type 3 (combined).4 Less common ocular manifestations include iris hypopigmentation (as seen in this patient) and iris colobomas.3Among patients in whom there is a suspicion of TSC, computed tomography or magnetic resonance imaging of the brain should be performed, along with renal ultrasonography, echocardiography, and ophthalmoscopic examination. Genetic testing can be helpful. Antiepileptic medications are the mainstay therapy for patients with TSC, although appropriate treatment for end-organ pathology is sometimes necessary.A notable facet of this case is the initial diagnosis of linear epidermal nevus syndrome, a condition in which hamartomas are also present. Linear epidermal nevus syndrome is a rare neurocutaneous disorder that manifests with skin lesions, mental retardation, seizures, and movement disorders.5 Hafner et al6 reported that 42% of epidermal nevi are due to mutations in the upstream regulators of the TSC1 and TSC2 genes. Hence, and as this case demonstrates, there can be overlap of the clinical presentation and histopathological characteristics between epidermal nevi and TSC lesions, and care must be taken to differentiate between these diagnoses.7

Ophthalmology

At birth, a full-term newborn was noted to have numerous hypopigmented skin macules on the trunk, scalp, neck, face, back, and limbs after an uncomplicated pregnancy (Figure 1A). The family history was negative for any dermatologic or genetic diseases. A shave biopsy specimen of the right leg was interpreted as papillomatous epidermal hyperplasia consistent with an epidermal nevus. Because of the constellation of findings, an initial diagnosis of linear epidermal nevus syndrome was made. At age 3 months, the patient was referred for ophthalmologic examination owing to a flat, hypopigmented lesion in the left temporal iris noted by the patient’s father. On examination, the patient fixed and followed with both eyes. Pupils, motility, and binocular alignment were normal. Dilated ophthalmoscopic examination revealed a well-demarcated hypopigmented lesion originating from the retinal nerve fiber layer and protruding into the vitreous cavity of the right eye (Figure 1B). A similar lesion was seen along the left inferotemporal arcade (Figure 1C). B-scan ultrasonography revealed a 4.0 × 2.9 × 2.2-mm lesion with no calcification, no retinal detachment, and no choroidal involvement (Figure 1D). Given the suspected iris hamartoma and retinal astrocytic hamartoma, a systemic workup was commenced.A, Dermatologic manifestations. The patient had multiple hypopigmented macules on his scalp, face, neck, back, limbs, and torso (arrowheads). B, A lesion was discovered in the right eye consistent with a retinal astrocytic hamartoma. C, A similar smaller lesion was seen in the left eye. D, B-scan ultrasonography revealed an elevated lesion emanating from the retina with no calcification or choroidal involvement.

what would you do next?

What would you do next?

Renal ultrasonography and lumbar puncture

Fine-needle aspiration biopsy of ocular lesion

Brain imaging and echocardiography

Metastatic workup

c

male

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2108786

A woman in her mid-50s with a history of hyperlipidemia and arthritis presented with recurrent subconjunctival hemorrhages and retinal vascular abnormalities as noted by her general ophthalmologist. Best-corrected visual acuity was 20/20 OU. Results of the pupillary examination, intraocular pressure measurements, motility, and confrontatiol visual field testing were normal in each eye. Findings on the anterior slitlamp examination demonstrated rare anterior chamber cells and mild nuclear sclerotic cataracts in both eyes. Results of the dilated fundus examination (Figure 1) demonstrated bilateral vitreous cells that were not dense enough to obscure retinal vessel details, as well as optic disc hyperemia, arterial attenuation, arterial and venous sheathing, hard exudates, and focal areas of retinal thinning. There was no macular edema in either eye. Results of a complete blood cell count were normal.Fundus photograph of the patient’s left eye at presentation. What Would You Do Next?

Check blood pressure

Check antinuclear antibody level

Check hemoglobin A1c level

Check erythrocyte sedimentation rate

Autoimmune occlusive retinal vasculitis

B

Check antinuclear antibody level

The differential diagnosis of retinal vasculitis includes infectious etiologies such as bacterial and viral infections, malignant etiologies including ocular lymphoma, and autoimmune etiologies including sarcoidosis, systemic lupus erythematosus (SLE), and Sjögren syndrome. In this case, there were no signs of infection or malignant neoplasms on ocular examination. However, results of a fluorescent treponemal antibody absorption test and QuantiFERON Gold test (QIAGEN) and findings on a chest radiograph were negative. The initial workup for this patient’s presentation of vasculitis also included tests for angiotensin-converting enzyme and lysozyme, which also had negative results. Results of the ANA test were positive (1:320). Based on the patient’s clinical findings, history, and results of laboratory evaluation, a diagnosis of autoimmune occlusive retinal vasculitis was made. Results of a subsequent rheumatologic workup also revealed a positive IgM antiphospholipid antibody.Autoimmune occlusive retinal vasculitis should be considered in cases of occlusive vasculopathy in the absence of another known etiology. Our patient had a positive ANA test result and a positive antiphospholipid antibody test result. She did not have definitive extraocular signs of SLE on rheumatologic evaluation.Antiphosphospholipid syndrome (APS) is an autoimmune hypercoagulable state that can lead to arterial and venous occlusive events. It is classically associated with pregnancy complications, including multiple miscarriages.1-3 Occlusive retinal vasculitis due to primary APS occurs independent of underlying systemic disease, whereas secondary APS occurs in association with 1 or more autoimmune conditions, most commonly SLE.4 The diagnosis of APS requires at least 1 vasoocclusive event and 2 positive test results for antiphospholipid antibodies at least 12 weeks apart.1,2 Treatment of primary APS typically consists of systemic anticoagulation, although the risks and benefits must be weighed in each case.5 Secondary APS should be managed with treatment of the underlying autoimmune conditions.There have been reported cases of secondary APS in which retinal vasculitis has improved with systemic immunosuppression.6 However, a review of the literature revealed an association between a severe form of retinal vasculitis in APS and SLE.6 Clinical findings may include retinal exudates, vascular occlusions, capillary dropout, and retinal neovascularization. There is also a risk of cerebral vasculitis in patients with SLE.Our patient was started on a regimen of oral prednisone, 60 mg/d, and was referred for rheumatologic evaluation. Three months after starting prednisone therapy and with a slow taper to 5 mg/d, there was significant improvement in her optic disc hyperemia and retinal vasculitis (Figure 2). Rheumatologic evaluation revealed myalgias and proximal muscle weakness, and further testing was ordered including repeat tests for ANA, anti–double-stranded DNA antibodies, antiphospholipid antibodies, anti-citrullinated protein antibodies, and anti-SSA and anti-SSB antibodies. Results of the ANA test were again positive (1:160), as were results of the antiphospholipid antibody test (94 standard IgM units), as noted above. Results of the remaining tests were negative. Results of subsequent antiphospholipid antibody tests were also positive (113 standard IgM units), confirming the diagnosis of APS.Fundus photograph of the patient’s left eye after initiation of treatment.

Ophthalmology

A woman in her mid-50s with a history of hyperlipidemia and arthritis presented with recurrent subconjunctival hemorrhages and retinal vascular abnormalities as noted by her general ophthalmologist. Best-corrected visual acuity was 20/20 OU. Results of the pupillary examination, intraocular pressure measurements, motility, and confrontatiol visual field testing were normal in each eye. Findings on the anterior slitlamp examination demonstrated rare anterior chamber cells and mild nuclear sclerotic cataracts in both eyes. Results of the dilated fundus examination (Figure 1) demonstrated bilateral vitreous cells that were not dense enough to obscure retinal vessel details, as well as optic disc hyperemia, arterial attenuation, arterial and venous sheathing, hard exudates, and focal areas of retinal thinning. There was no macular edema in either eye. Results of a complete blood cell count were normal.Fundus photograph of the patient’s left eye at presentation.

what would you do next?

What would you do next?

Check antinuclear antibody level

Check blood pressure

Check hemoglobin A1c level

Check erythrocyte sedimentation rate

a

female

51-60