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kenza-ily

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JAMA_Chen2024

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https://jamanetwork.com/journals/jamadermatology/fullarticle/2548257

A healthy woman in her 20s presented with a 5-month history of a painful erythematous eruption over her bilateral thighs. She reported that the eruption was worsening during the winter months. She had not experienced any fevers, chills, joint pains, recent weight loss, or any other constitutional symptoms. She was a nonsmoker and took no medications. A review of her social history revealed that she was working at a horse stable and rode for many hours a day. On physical examination, distributed over the bilateral posterior lateral thighs, there were several arcuate to circinate erythematous to violaceous plaques. There were also several focal areas of ulceration with overlying scale-crust (Figure, A and B). A biopsy was performed during this initial visit (Figure, C and D). What Is Your Diagnosis?

Erythema annulare centrifugum

Subacute cutaneous lupus erythematosus

Palisaded neutrophilic and granulomatous dermatitis

Equestrian perniosis

D. Equestrian perniosis

D

Equestrian perniosis

Histopathologic examination of the biopsy specimen revealed a superficial perivascular and periadnexal infiltrate of predominantly lymphocytes with interface change. Scattered necrotic keratinocytes were also present. There was also an increased amount of interstitial mucin. Given these findings and the clinical history, the patient was determined to have equestrian perniosis.The patient decreased her riding hours and wore looser, warmer clothing. She reported substantial clinical improvement with resolution of her rash.Equestrian perniosis is a rare variant of perniosis that typically involves the lateral thighs and buttocks of female horseback riders.1,2 This entity was first described in detail by Beacham et al3 in 1980; they described 4 women in Virginia who were avid horseback riders, often riding in extreme cold and high winds during the winter. As with classic perniosis, equestrian perniosis is a disease characterized by tender erythematous to violaceous papules or plaques induced by cold exposure. Blistering and ulceration can be seen in severe cases. Consistently reported factors contributing to the development of this condition include tightly fitted and poorly insulated clothes under exposure to cold temperature, humidity, and wind. It should also be noted that this particular eruption is not limited to only horse enthusiasts, but other individuals wearing tight-fitting clothing exposed to cold for long periods of time (eg, motorcycle riders or hikers).4,5Histologic findings in equestrian perniosis generally mirror perniosis itself and may appear similar to connective tissue diseases, such as lupus erythematosus. Such histologic hallmarks of perniosis include dermal edema, vascular endothelial cell edema, a superficial and deep lymphocytic perivascular or perieccrine infiltrate, and vacuolar changes at the basement membrane.2 However, in equestrian perniosis, there seems to be rare or no papillary dermal edema and an inflammatory infiltrate extending into the subcutaneous fat,6 which had led some authors to originally report this entity as equestrian panniculitis. Notwithstanding, it would seem that the term equestrian perniosis is more appropriate because the histologic characteristics of the disease are more akin to those of perniosis, being a primary dermal inflammatory process with a deeper extension into the subcutaneous fat.7Although the literature on this subject is relatively sparse, with only a handful of case reports, one recent epidemiological survey8 from Finland suggests that it may be more common than presumed, finding that a quarter of respondents (comprised of that country’s Equestrian Federation) had panniculitis-like symptoms. Other associated factors among this group were smoking, tight-fitting clothing, age older than 35 years, and longer duration of riding. Indeed, because lesions tend to be self-limited and are seen only in a select group of individuals, this may be an underreported occurrence overall.The present case of equestrian perniosis is the first, to our knowledge, to exhibit such a striking clinical picture with an annular to polycyclic configuration. This may serve to highlight the role of medium-sized vessels in the development of this condition, much as they are in livedo racemosa, owing the circular and net-like appearance to the distribution of a deeper central “feeder” vessel. This is an anatomic location that is especially susceptible to effects of low temperature given the insulation of the blood vessels by surrounding fat. Cold itself can cause increased viscosity and lower blood flow rates in the superficial venous plexus.9 Recently, cold agglutinins have been described in association with equestrian perniosis, further supporting the hypothesis of impaired blood circulation as a root cause of this condition.10Treatment of equestrian perniosis is generally unnecessary because the condition is self-limited. With rewarming and time, lesions tend to resolve spontaneously. However, recurrence is common. Patients who have experienced this condition should be advised to wear looser-fitting, insulated clothing when they choose to go out riding in the cold. The addition of a topical or oral steroid, or oral vasodilating agents, such as nifedipine and pentoxifylline, may be considered if behavior modification alone does not improve the condition.

Dermatology

A healthy woman in her 20s presented with a 5-month history of a painful erythematous eruption over her bilateral thighs. She reported that the eruption was worsening during the winter months. She had not experienced any fevers, chills, joint pains, recent weight loss, or any other constitutional symptoms. She was a nonsmoker and took no medications. A review of her social history revealed that she was working at a horse stable and rode for many hours a day. On physical examination, distributed over the bilateral posterior lateral thighs, there were several arcuate to circinate erythematous to violaceous plaques. There were also several focal areas of ulceration with overlying scale-crust (Figure, A and B). A biopsy was performed during this initial visit (Figure, C and D).

what is your diagnosis?

What is your diagnosis?

Palisaded neutrophilic and granulomatous dermatitis

Erythema annulare centrifugum

Equestrian perniosis

Subacute cutaneous lupus erythematosus

c

female

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2553745

A man in his 50s presented with a 2-month medical history of painful, gradually expanding ulcers on the left lower leg. The lesions started spontaneously as erythematous tender papules with white purulent discharge. He recently failed a course of amoxicillin and trimethoprim-sulfamethaxazole initiated by his primary care physician. He reported a medical history of rheumatoid arthritis (RA), chronic obstructive pulmonary disease, chronic kidney disease, and heavy tobacco use. The patient denied any recent changes to his medications or recent travel. No other household members were affected.Physical examination of the left lower extremity revealed a 2.5-cm keratotic plaque with central ulceration that expressed a straw-colored fluid. The limb was dusky with scattered hyperpigmented patches and surrounding erythema (Figure, A and B). Both lower limbs exhibited pitting edema of 1+ severity, and negative Homans sign bilaterally for deep vein thrombosis. Fungal and bacterial culture samples were negative. Rheumatoid factor was elevated at 198 IU/mL, and other laboratory data were noncontributory. A punch biopsy specimen was obtained from the edge of the lesion (Figure, C and D).A, Left pretibia on initial visit. B, Left pretibia at 7-day follow-up. C, Periodic acid–Schiff stain (original magnification ×4). D, Hematoxylin-eosin stain (original magnification ×20). What Is Your Diagnosis?

Blastomycosis

Pyoderma gangrenosum

Atypical mycobacterial infection

Ecthyma gangrenosum

B. Pyoderma gangrenosum

B

Pyoderma gangrenosum

Histopathologic examination (Figure, C and D) showed ulceration with papillary dermal edema and pan neutrophilic infiltrate, accompanied by prominent hemorrhage. Periodic acid–Schiff stain results were negative. Deep tissue culture results were negative for bacterial, acid-fast bacilli, and fungal organisms. These findings were consistent with pyoderma gangrenosum (PG). The patient was successfully treated with intralesional triamcinolone and triamcinolone 0.1% cream.Pyoderma gangrenosum is an uncommon cutaneous condition that is histopathologically defined by an intense dermal neutrophilic infiltrate. It is a diagnosis of exclusion because underlying infection, malignant abnormality, vasculitis, or trauma must be ruled out. Clinically, it presents as a severely painful rapidly expanding nodule or pustule that often ulcerates.1,2Current literature suggests that the pathogenesis of PG is multifactorial and related to neutrophil dysfunction, inflammation, and genetics.2 Impaired neutrophil chemotaxis and phagocytosis are also implicated in conditions associated with PG such as inflammatory bowel disease (IBD) and rheumatoid arthritis.2,3 It has been suggested that patients with PG have a high concentration of T helper 17 cells compared with regulatory T cells, an imbalance seen in IBD patients as well.4 There have been reported cases of PG associated with use of granulocyte stimulating factor, which also suggests a neutrophilic eitiology.5 Pyoderma gangrenosum has also been linked to numerous hematologic conditions including multiple myeloma, leukemia, and lymphoma.2,6 More than 50% of PG patients have either IBD, RA, or a hematologic condition.1,3,6 Our patient had a known history of rheumatoid arthritis, and had an elevated rheumatoid factor at evaluation.There is no standard treatment for PG, and treatment is often unsuccessful. Topical steroids are often used as a first-line treatment, but supporting evidence is limited owing to minimal randomized control trials.5,7 Although PG lesions can exhibit pathergy, we chose to use intralesional triamcinolone over oral medication owing to the small size of the lesion and the patient’s reluctance to start systemic therapy. Other common treatments include topical tacrolimus, oral dapsone, minocycline, cyclosporine, and tumor necrosis factor α (TNF-α) inhibitors. Lesions associated with rheumatoid arthritis tend to have a worse prognosis and fair better with TNF-α inhibitors.2,6 Tumor necrosis factor α inhibitors should also be considered in IBD associated PG. When a patient with PG has a chronic inflammatory condition, biologics will improve systemic symptoms and should be used early for best outcomes.8,9 This patient is responding well to local steroid treatment and, as of now, does not require systemic therapy.Accurate and timely diagnosis of PG is often difficult and involves excluding multiple entities. Even though the pathology of PG is nonspecific, biopsy procedures are essential for ruling out conditions that clinically may appear similar, such as vasculitis and malignant abnormalities. Although not common, PG should be included in the differential diagnosis of high-risk patients to avoid improper treatment, including unnecessary antibiotics and surgery, as well as to assure an appropriate workup. The association with systemic conditions warrants a rheumatologic and hematologic workup in addition to screening for inflammatory bowel disease.

Dermatology

A man in his 50s presented with a 2-month medical history of painful, gradually expanding ulcers on the left lower leg. The lesions started spontaneously as erythematous tender papules with white purulent discharge. He recently failed a course of amoxicillin and trimethoprim-sulfamethaxazole initiated by his primary care physician. He reported a medical history of rheumatoid arthritis (RA), chronic obstructive pulmonary disease, chronic kidney disease, and heavy tobacco use. The patient denied any recent changes to his medications or recent travel. No other household members were affected.Physical examination of the left lower extremity revealed a 2.5-cm keratotic plaque with central ulceration that expressed a straw-colored fluid. The limb was dusky with scattered hyperpigmented patches and surrounding erythema (Figure, A and B). Both lower limbs exhibited pitting edema of 1+ severity, and negative Homans sign bilaterally for deep vein thrombosis. Fungal and bacterial culture samples were negative. Rheumatoid factor was elevated at 198 IU/mL, and other laboratory data were noncontributory. A punch biopsy specimen was obtained from the edge of the lesion (Figure, C and D).A, Left pretibia on initial visit. B, Left pretibia at 7-day follow-up. C, Periodic acid–Schiff stain (original magnification ×4). D, Hematoxylin-eosin stain (original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Atypical mycobacterial infection

Pyoderma gangrenosum

Ecthyma gangrenosum

Blastomycosis

b

male

51-60

White

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2565795

A man in his 60s with diabetes underwent biopsy for an asymptomatic shiny indurated plaque on the right plantar foot, which had been slowly growing for the past year. The patient was then referred to a dermatology specialist for further treatment. The patient reported no fevers, chills, weight loss, or night sweats. He had long-standing, intermittent dyspnea on exertion, but no baseline shortness of breath, orthopnea, or bilateral lower extremity edema. The patient had occasional numbness in both legs in stocking distribution, attributed to diabetic neuropathy. Physical examination revealed a 4.5 cm waxy, nontender, smooth-surfaced, cobblestoned plaque located in the sulcus between the second and fourth toes (Figure, A). A biopsy specimen obtained by the patient’s podiatrist was sent to the dermatopathology laboratory for review.A, Clinical presentation revealed smooth-surfaced cobblestoned plaque that was asymptomatic. B, Hemotoxylin-eosin stain (original magnification ×100) results show a diffuse infiltrate of pale eosinophilic material with prominent clefts. C, Congo red stain (original magnification ×200). What Is Your Diagnosis?

Pseudolymphoma

Elephantiasis nostras verrucosa

Plantar cerebriform collagenoma

Nodular amyloid

D. Nodular amyloid

D

Nodular amyloid

The biopsy specimen demonstrated large amounts of globular eosinophilic material in the dermis that contrasts sharply with brighter pink collagen bundles and scattered plasma cells. Positive Congo red stain results confirmed the presence of amyloid protein (Figure, B and C).The patient underwent an extensive evaluation for hematological malignant abnormalities in coordination with hematology/oncology specialists as well as assessment of cardiac and renal involvement. Serum protein electrophoresis results were negative for paraprotein although κ and λ were elevated. A complete blood cell count with differential, urinalysis, metabolic panel, and liver function test results were normal. Echocardiogram results were unremarkable. He will be followed up by dermatology and hematology specialists to monitor for clinical or laboratory evidence of systemic disease.Primary cutaneous nodular amyloidosis is a rare disorder characterized by the localized accumulation of light-chain amyloid protein, secreted by lesional plasma cells. This is in contrast to the more common cutaneous lichen and macular amyloidosis, in which the amyloid protein derives from keratin.The morphological presentation of nodular amyloidosis is that of localized, waxy, infiltrated nodules or plaques with typical distribution of lower extremities, face, scalp, and genitals. Lesions are typically asymptomatic but can be pruritic.1 Because the clinical and pathological appearance of nodular amyloidosis can be indistinguishable from that of systemic amyloidosis, systemic involvement must be excluded in order to make the correct diagnosis. Systemic amyloidosis can result in a restrictive cardiomyopathy, proteinuria up to nephrotic range, hepatomegaly, as well as peripheral and autonomic neuropathy.2Even when distinguished from systemic amyloid, patients with localized disease require continued monitoring owing to the possibility of progression to systemic involvement. While early studies estimated this risk at around 50%, larger and more recent case series have shown progression to occur in roughly 7% of patients.1 The disease has been more rarely associated with other concomitant indolent hematologic malignant diseases.3 In addition to malignant abnormality, nodular amyloid has been reported to occur with systemic autoimmune diseases, such as Sjogren syndrome and limited scleroderma.4,5Several reports have attempted to determine the clonality of plasma cells in nodular amyloid lesions. Plasma cells appear to be clonal; except in cases associated with Sjogren syndrome where both monoclonal and polyclonal infiltrates have been described.4,6 In monoclonal cases, nodular amyloid can be thought of as etiopathogenically similar plasmacytoma, with nodular amyloidosis displaying a much sparser plasma cell infiltrate but one in which the cells have a much greater secretory capacity.Nodular amyloidosis can also be understood as a manifestation of a group of disorders characterized by isolated, tissue-specific deposition of amyloid, typically of light-chain composition, by local collections of secretory monoclonal plasma cells. These disorders, referred to as amyloidomas, have been shown to occur in the central nervous system, bone, as well as a variety of levels within the respiratory and genitourinary tracts.7,8Given the rarity of cases, no standard modality exists for treatment of nodular amyloidosis. Reports span the use of surgical excision, electrodesiccation and curettage, cryotherapy, dermabrasion, and ablative lasers.9

Dermatology

A man in his 60s with diabetes underwent biopsy for an asymptomatic shiny indurated plaque on the right plantar foot, which had been slowly growing for the past year. The patient was then referred to a dermatology specialist for further treatment. The patient reported no fevers, chills, weight loss, or night sweats. He had long-standing, intermittent dyspnea on exertion, but no baseline shortness of breath, orthopnea, or bilateral lower extremity edema. The patient had occasional numbness in both legs in stocking distribution, attributed to diabetic neuropathy. Physical examination revealed a 4.5 cm waxy, nontender, smooth-surfaced, cobblestoned plaque located in the sulcus between the second and fourth toes (Figure, A). A biopsy specimen obtained by the patient’s podiatrist was sent to the dermatopathology laboratory for review.A, Clinical presentation revealed smooth-surfaced cobblestoned plaque that was asymptomatic. B, Hemotoxylin-eosin stain (original magnification ×100) results show a diffuse infiltrate of pale eosinophilic material with prominent clefts. C, Congo red stain (original magnification ×200).

what is your diagnosis?

What is your diagnosis?

Elephantiasis nostras verrucosa

Nodular amyloid

Pseudolymphoma

Plantar cerebriform collagenoma

b

male

61-70

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2593859

A 16-year-old boy with autism presented with 4 weeks of progressive bilateral lower extremity edema, ecchymosis, and arthralgias severe enough to prevent ambulation. Associated symptoms included fatigue, decreased appetite, abdominal discomfort, and intermittent scleral icterus noted by his mother. One week prior, a dentist diagnosed acute necrotizing gingivostomatitis based on gum inflammation and bleeding, prompting treatment with metronidazole and penicillin. There was no history of trauma, fevers, hematuria, or hematochezia or family history of coagulation disorders. His medical history was significant for seizures and behavioral disturbances managed with stable doses of lamotrigine and chlorpromazine. On physical examination, he was nonverbal but in no visible distress. There was hemorrhagic gingivitis (Figure, A) without cervical lymphadenopathy, and the bilateral lower extremities had marked asymmetric pitting edema, large ecchymoses on the thighs, ankles, and feet (Figure, B), and scattered petechiae (Figure, C). His lower extremities were tender to palpation and he resisted passive ranging of his joints.A, Markedly edematous and friable gingiva. B, Ecchymoses on the lateral ankle. C, On the lower leg, perifollicular hemorrhage and corkscrew hairs (arrowhead) are present.Initial laboratory workup revealed microcytic anemia with hematocrit level of 22.8% (to convert to proportion of 1.0, multiply by 0.01), mean corpuscular volume of 75.9 µm3 (to convert to femtoliters, multiply by 1), white blood cell count of 5.9/µL (to convert to ×109 per liter, multiply by 0.001), platelet count of 248 ×103/µL (to convert to ×109 per liter, multiply by 1), elevated erythrocyte sedimentation rate of 52 mm/h (to convert to millimeters per hour, multiply by 1), and C-reactive protein level of 5.5 mg/L (to convert to nanomoles per liter, multiply by 9.524), with hypoalbuminemia of 3.4 g/dL (to convert albumin to grams per liter, multiply by 10), but normal creatine kinase level of 83 U/L (to convert to microkatals per liter, multiply by 0.0167), and unremarkable activated partial thromboplastin time and international normalized ratio. Ultrasonography of the lower extremities showed soft tissue swelling without thrombosis. Lower extremity magnetic resonance imaging/magnetic resonance angiography showed diffuse round mildly enhancing bone marrow lesions without vascular changes. What Is Your Diagnosis?

Leukemia

Henoch-Schonlein purpura

Scurvy

Granulomatosis with polyangitis

C. Scurvy

C

Scurvy

A detailed dermatologic examination revealed perifollicular petechiae with overlying hyperkeratosis and corkscrew hairs, raising concern for scurvy. This diagnosis was confirmed later in his hospital stay when his vitamin C level was reported as undetectable. On further questioning, it was noted he ate an extremely limited diet of mainly crackers and peanut butter with no fruits or vegetables, which put him at risk for vitamin deficiencies, including vitamin C.Inadequate or irregular vitamin C intake under the recommended daily allowance of 90 mg1 can lead to scurvy within 8 to 12 weeks.2 Pediatric populations at risk for scurvy in developed countries are those with neuropsychiatric conditions that lead to behaviorally restricted diets, including autism, as was demonstrated in this case.3 The restrictive diets of children with autism may be attributed to sensory hypersensitivities related to the texture of food or aversion to new experiences.4The multisystem involvement of scurvy demonstrates the multiple functions that vitamin C has in the body. These include hydroxylation of collagen, biosynthesis of carnitine and norepinephrine, the metabolism of tyrosine, and amidation of peptide hormones.5 These roles of vitamin C explain the myriad of manifestations in our patient including perifollicular hemorrhage, gingival bleeding and edema caused by diminished blood vessel integrity, corkscrew hairs due to reduced disulfide bonding, and normocytic normochromic anemia related to reduced iron absorption and bleeding.6Magnetic resonance imaging (MRI)/magnetic resonance angiography was performed in our patient because it was unclear whether his extensive lower extremity swelling could be explained solely by scurvy. His MRI showed numerous diffuse-enhancing osseous lesions and significant subcutaneous edema, which shares some similarities to previously published descriptions on MRI findings in scurvy in children.7The diagnosis of scurvy can be made clinically by observing symptomatic improvement after oral vitamin C replacement or a vitamin C plasma concentration of less than 0.2 mg/dL.8 Leukemia, Henoch-Schonlein purpura, and granulomatosis with polyangitis can all present with similar symptoms to scurvy. In our patient, leukemia was unlikely with an isolated anemia and normal white blood cell count and platelet levels. Henoch-Schonlein purpura and granulomatosis with polyangitis are both types of small vessel vasculitis, and the cutaneous findings in these conditions are typically palpable purpura, while this patient had petechiae only in a perifollicular distribution with distinctive associated hyperkeratosis. Furthermore, the lack of renal involvement or other organ involvement made Henoch-Schonlein purpura and granulomatosis with polyangitis unlikely.Oral 750-mg daily vitamin C replacement was started in our patient and improved bruising, gingival bleeding, and perifollicular hemorrhage noted within 2 to 3 days. Rapid improvements with vitamin C replacement are typical in scurvy. The patient was discharged with nutritionist support and adequate vitamin supplementation. At follow-up 6 weeks later, his petechiae, ecchymoses, and arthralgias had resolved. Repeat MRI showed marked improvement in subcutaneous edema and resolving osseous lesions.This case highlights the importance of being aware of the prominent nondermatologic manifestations of vitamin C deficiency. This patient had several subspeciality consultations, numerous laboratories, and MRI/magnetic resonance angiography while awaiting the vitamin C level to return. Detection of the dermatologic clues, with recognition that there can be impressive extracutaneous manifestations, should lead to prompt treatment with rapid improvement and prevent unnecessary workup.This case demonstrates several important points. First, dietary deficiencies should be considered in children with developmental delays. Second, physical examination may reveal the classic findings of gingival bleeding, perifollicular hyperkeratosis, and corkscrew hairs, but vitamin C deficiency can also manifest with systemic features including arthralgias, anemia, and marrow lesions. Third, vitamin C deficiency improves rapidly with oral replacement therapy but holistic nutritional support is also prudent. Last, prompt recognition of the cutaneous and systemic manifestations of vitamin C deficiency can prevent a delay in diagnosis and unnecessary workup.

Pediatrics

A 16-year-old boy with autism presented with 4 weeks of progressive bilateral lower extremity edema, ecchymosis, and arthralgias severe enough to prevent ambulation. Associated symptoms included fatigue, decreased appetite, abdominal discomfort, and intermittent scleral icterus noted by his mother. One week prior, a dentist diagnosed acute necrotizing gingivostomatitis based on gum inflammation and bleeding, prompting treatment with metronidazole and penicillin. There was no history of trauma, fevers, hematuria, or hematochezia or family history of coagulation disorders. His medical history was significant for seizures and behavioral disturbances managed with stable doses of lamotrigine and chlorpromazine. On physical examination, he was nonverbal but in no visible distress. There was hemorrhagic gingivitis (Figure, A) without cervical lymphadenopathy, and the bilateral lower extremities had marked asymmetric pitting edema, large ecchymoses on the thighs, ankles, and feet (Figure, B), and scattered petechiae (Figure, C). His lower extremities were tender to palpation and he resisted passive ranging of his joints.A, Markedly edematous and friable gingiva. B, Ecchymoses on the lateral ankle. C, On the lower leg, perifollicular hemorrhage and corkscrew hairs (arrowhead) are present.Initial laboratory workup revealed microcytic anemia with hematocrit level of 22.8% (to convert to proportion of 1.0, multiply by 0.01), mean corpuscular volume of 75.9 µm3 (to convert to femtoliters, multiply by 1), white blood cell count of 5.9/µL (to convert to ×109 per liter, multiply by 0.001), platelet count of 248 ×103/µL (to convert to ×109 per liter, multiply by 1), elevated erythrocyte sedimentation rate of 52 mm/h (to convert to millimeters per hour, multiply by 1), and C-reactive protein level of 5.5 mg/L (to convert to nanomoles per liter, multiply by 9.524), with hypoalbuminemia of 3.4 g/dL (to convert albumin to grams per liter, multiply by 10), but normal creatine kinase level of 83 U/L (to convert to microkatals per liter, multiply by 0.0167), and unremarkable activated partial thromboplastin time and international normalized ratio. Ultrasonography of the lower extremities showed soft tissue swelling without thrombosis. Lower extremity magnetic resonance imaging/magnetic resonance angiography showed diffuse round mildly enhancing bone marrow lesions without vascular changes.

what is your diagnosis?

What is your diagnosis?

Scurvy

Leukemia

Henoch-Schonlein purpura

Granulomatosis with polyangitis

a

male

11-20

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2571532

A man in his 40s was referred from jail with abdominal pain for 5 days. The pain was constant in the hypogastric region, with no radiation. He did not have bowel movements for 5 days but passed gas normally. He did not complain of nausea or vomiting. He denied substance abuse or addiction.The abdomen was soft with hypogastric tenderness. There was no abdominal distension, guarding, or rebound tenderness. Neither hernia nor surgical scars were seen on examination, and vital signs and results from laboratory tests were normal. An axial contrast computed tomography (CT) scan of the abdomen was performed (Figure 1).A, A computed tomography scan of the abdomen did not show abnormal intestinal air-fluid levels nor free peritoneal air. B, A computed tomography scan revealed that the rectum was not empty. What Is Your Diagnosis?

Gastrointestinal obstruction due to adhesion band

Gastrointestinal obstruction due to internal hernia

Body packing

Fecal impaction due to opium addiction

C. Body packing

C

Body packing

A CT scan of the abdomen showed multiple substance packs throughout the gastrointestinal (GI) tract without free air, abnormal air-fluid levels, or hernias. Therefore, the final diagnosis was GI tract obstruction due to body packing. Laparotomy was considered, and 14 packs were removed. Extraction failed because of tight adherence between a big pack in the rectum and the rectal mucosa, so the rectum was opened and the big pack was removed successfully. The operation site was repaired following the insertion of an ileostomy. After the procedure, an abdominal CT scan confirmed the clearance of the GI tract. He was discharged after 15 days and has been in good condition during follow-up.Body packers tend to traffic illicit drugs by swallowing the substance or inserting it into the rectum or vagina. Body packers are also called swallowers, internal carriers, couriers, or mules.1 Condoms, balloons, plastic bags, or fingers of latex gloves are used for wrapping drugs (Figure 2),2 which allows them to cross country or prison borders.3 Body packers are usually referred to the emergency department for the forensic analysis of drugs or to be assessed for overdose, intestinal obstruction, or bleeding.4 The patient may present to the emergency department with typical respiratory, cardiovascular, neurological, or gastrointestinal signs and symptoms of acute drug intoxication or may be completely asymptomatic.3Multiple ingested drug packs were extracted from the patient’s small and large bowels.After stabilization, it is necessary to evaluate the patient for GI tract obstruction, as this occurs in 5% to 25% of patients, and to search for vaginal or rectal packages.3,5Plain radiography and contrast abdominal CT scans are used to detect packs and complications. Plain abdominal radiography is the most common modality for abdominal investigation of suspected body packers, but there is a risk of false-negative (eg, nonopaque materials for packaging) and false-positive (eg, bladder stones, other calcifications, or coprostasis) results.Asymptomatic patients are treated conservatively. The administration of activated charcoal does not change patients’ clinical outcome, so it is not recommended.5 The treatment of choice in asymptomatic patients is whole-bowel irrigation with polyethylene-glycol until the GI tract is cleared and confirmed by imaging, if this option is not contraindicated.5 Indications for surgical therapy include signs of intoxication, bowel obstruction, a long intestinal passage (ie, passage takes more than 48 hours), gastric outlet syndrome, and GI tract ulceration or bleeding.

Surgery

A man in his 40s was referred from jail with abdominal pain for 5 days. The pain was constant in the hypogastric region, with no radiation. He did not have bowel movements for 5 days but passed gas normally. He did not complain of nausea or vomiting. He denied substance abuse or addiction.The abdomen was soft with hypogastric tenderness. There was no abdominal distension, guarding, or rebound tenderness. Neither hernia nor surgical scars were seen on examination, and vital signs and results from laboratory tests were normal. An axial contrast computed tomography (CT) scan of the abdomen was performed (Figure 1).A, A computed tomography scan of the abdomen did not show abnormal intestinal air-fluid levels nor free peritoneal air. B, A computed tomography scan revealed that the rectum was not empty.

what is your diagnosis?

What is your diagnosis?

Gastrointestinal obstruction due to internal hernia

Body packing

Fecal impaction due to opium addiction

Gastrointestinal obstruction due to adhesion band

b

male

41-50

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2580490

A previously healthy, fair-skinned professional golfer aged 69 years with a history of frequent outdoor sun exposure presented to the surgery clinic with a mass on his left upper back, which he first noted 1 year ago as a small nodule on his back. It grew rapidly throughout the past year, becoming increasingly painful and bleeding easily with light contact. Clinical examination revealed an 8 × 6 × 4-cm multilobulated, purplish lesion that was fungating and friable (Figure 1). He also had a palpable, hard mass in the left axilla. He had no other lesions elsewhere on his body. A punch biopsy of the back mass revealed immunohistochemistry strongly positive for S-100, MART-1, and HMB-45. Computed tomographic and positron emission tomographic scans demonstrated a fludeoxyglucose-avid lesion on the back extending into the subcutaneous fat and fludeoxyglucose-avid uptake in the left axilla.An 8 × 6 × 4-cm multilobulated, purplish lesion on the back that was fungating and friable. What Is Your Diagnosis?

Cavernous lymphangioma

Nodular basal cell carcinoma

Squamous cell carcinoma

Nodular melanoma

D. Nodular melanoma

D

Nodular melanoma

Cavernous lymphangiomas usually arise during infancy, with the most common sites being the neck and head. They appear as painless swellings that can be flesh-colored, blue, or red lesions and may ulcerate. They can be surgically removed but often regrow, creating a therapeutic challenge. However, angiogenesis has been reported to be inhibited successfully with sirolimus.1Nodular basal cell carcinoma is the most common skin cancer and often has rolled, pearly edges with a central ulceration, tends to grow slowly, and usually does not metastasize.2 On histological examination, there are nests of basaloid cells, with palisading strands of the cells at the periphery and haphazard arrangement of the central cells as well as a hyperchromatic nucleus with little cytoplasm.Squamous cell carcinomas usually occur on sun-exposed locations, may produce keratin resulting in a scaly or hornlike appearance, and may ulcerate and bleed.3 On histological examination, there are nests, sheets, and strands of atypical keratinocytes originating in the epidermis and infiltrating into the dermis. Immunohistochemistry shows keratin expression with a high molecular weight and epithelial membrane antigen.Melanomas represent only 4% of all dermatologic cancers but account for 80% of skin cancer–related deaths.4 Nodular malignant melanoma is common in fair-skinned persons and on sun-exposed areas of the body.5 Wide local excision is the treatment for primary melanoma, with resection margins based on lesion thickness (1-cm margins for melanomas less than 2 mm thick and 2-cm and 3-cm margins for lesions greater than 2 mm and 4 mm thick, respectively).6 Wide local excision has been shown to reduce recurrence rates, although there is no statistically significant effect on survival. Patients with Clark level 5 melanoma are associated with 5-year survival rates of 25% or less.7 Melanoma is almost 100% curable when diagnosed early but has poor survival when metastatic.8 Adjuvant interferon alfa has been approved since 1996 based on the results of the Eastern Cooperative Oncology Group 1684 trial9 of patients with stage IIB or III melanoma, which showed the benefit of high-dose interferon alfa on both relapse-free and overall survival.In this patient, histological examination showed atypical melanocytes within the epidermis and dermis. Immunohistological stains can show S-100, MART-1, and HMB-45 as well as other immunohistological markers. The patient underwent a wide local excision of the back mass and a left axillary lymph node dissection. Histological examination of the back mass revealed it was malignant nodular melanoma with vertical growth, tumor-infiltrating lymphocytes, and Clark level 5 with invasion into the subcutaneous fat (Figure 2). Left axillary dissection revealed enlarged, matted lymph nodes. However, histopathological examination revealed only sinus histiocytosis without evidence of any malignancy. Malignant nodular melanoma with vertical growth, tumor-infiltrating lymphocytes, and Clark level 5 with invasion into the subcutaneous fat was found on histological examination.The patient declined to undergo skin graft coverage for the lesion and allowed the wound to heal by secondary intention. At 11-month follow-up, he remained free of recurrence or metastatic disease on clinical and positron emission surveillance, has a completely healed wound, and has returned to golfing with no effect on his swing.

Surgery

A previously healthy, fair-skinned professional golfer aged 69 years with a history of frequent outdoor sun exposure presented to the surgery clinic with a mass on his left upper back, which he first noted 1 year ago as a small nodule on his back. It grew rapidly throughout the past year, becoming increasingly painful and bleeding easily with light contact. Clinical examination revealed an 8 × 6 × 4-cm multilobulated, purplish lesion that was fungating and friable (Figure 1). He also had a palpable, hard mass in the left axilla. He had no other lesions elsewhere on his body. A punch biopsy of the back mass revealed immunohistochemistry strongly positive for S-100, MART-1, and HMB-45. Computed tomographic and positron emission tomographic scans demonstrated a fludeoxyglucose-avid lesion on the back extending into the subcutaneous fat and fludeoxyglucose-avid uptake in the left axilla.An 8 × 6 × 4-cm multilobulated, purplish lesion on the back that was fungating and friable.

what is your diagnosis?

What is your diagnosis?

Nodular basal cell carcinoma

Cavernous lymphangioma

Squamous cell carcinoma

Nodular melanoma

d

male

61-70

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2580528

A woman aged 44 years with no significant medical history presented with increasing exertional dyspnea and fatigue. Transthoracic echocardiography showed an atrial septal defect, and transesophageal echocardiography confirmed a 1.2-cm secundum atrial septal defect with bidirectional shunting without a clear superior rim. A computed tomographic (CT) pulmonary angiogram showed a dilated pulmonary artery consistent with pulmonary hypertension (Figure 1A).A, Computed tomographic (CT) pulmonary angiogram showing a dilated pulmonary artery size in compare to the aorta size. B, Coronary angiogram revealing diffuse narrowing of the left main coronary artery at its origin.Right and left heart cardiac catheterization was performed. During coronary angiography, the patient was noted to have diffuse 90% to 95% narrowing of the left main coronary artery at its origin (Figure 1B; Video). The left anterior descending and left circumflex arteries were normal in caliber and appearance.The question arose whether the left main coronary artery stenosis represented an anatomic anomaly, a spasm, or a combination. Intracoronary nitroglycerine was administered with no change in angiographic appearance of the left main coronary artery. The patient then developed deep ST-segment depressions associated with chest and throat pain. The catheter was re-engaged, and additional intracoronary nitroglycerine was administered with the resolution of ST-segment depression and pain.The patient then developed ventricular tachycardia requiring cardioversion and intravenous amiodarone and lidocaine. The patient became unstable with recurrent episodes of ventricular tachycardia/fibrillation requiring cardiopulmonary resuscitation. An intra-aortic balloon pump was emergently placed, and the patient was intubated.Emergent stenting of the left main coronary arteryEmergent closure of the atrial septal defect What Would You Do Next?

Emergent coronary artery bypass graft surgery

Emergent stenting of the left main coronary artery

Emergent closure of the atrial septal defect

Emergent pulmonic valve balloon valvotomy

Left main coronary artery compression syndrome

B

Emergent stenting of the left main coronary artery

B. Emergent stenting of the left main coronary arteryA decision was made for emergent stenting of the left main coronary artery (LMCA). A 3.5 × 15-mm everolimus drug-eluting stent was placed. Preintervention stenosis was 90% TIMI 3 flow, and postprocedure stenosis was 0% TIMI 3 flow. A longer stent needed to be placed to decrease the risk of embolization, considering the higher risk of embolization in the absence of atherosclerosis. Intravascular ultrasonography to optimize the position of the stent was not done because the procedure was performed emergently.Atrial septal defect (ASD), a persistent interatrial communication, is one of the most common adult congenital heart defects, diagnosed in roughly 1 of 1000 adults. While very small ASDs may remain asymptomatic, patients with moderate to large defects develop symptoms in their 30s through 50s, including dyspnea, fatigue, decreased exercise tolerance, recurrent pulmonary infections, right-side heart failure, atrial tachyarrhythmias, and paradoxical embolism. About 16% of patients with ostium secundum ASDs are reported to develop pulmonary hypertension.Significant coronary artery disease is reported in 3% to 9% of adult patients undergoing evaluation for ASD.1,2 In addition, extrinsic compression of the LMCA by an enlarged pulmonary artery is recognized in 5% to 18% of patients with ASD.3-5 Experimental studies6 suggest that an acute increase in pressure of a nondilated, nonhypertensive pulmonary artery is not sufficient to cause LMCA compression; hence, this phenomenon appears to be associated with vascular remodeling and dilatation. The presenting features may include angina, syncope, myocardial infarction, arrhythmia, and even left ventricular dysfunction and cardiogenic shock.5 The diagnostic modalities include cardiac catheterization (best seen in the 45° left anterior oblique view with 30° cranial projection), especially in conjunction with intravascular ultrasonography, and noninvasive modalities, such as CT coronary angiography and cardiac magnetic resonance imaging. Factors known to be linked to LMCA compression are pulmonary trunk diameter and the ratio of the pulmonary trunk diameter to the aortic diameter.7While coronary artery bypass grafting is the treatment of choice for patients with unprotected LMCA atherosclerotic disease, percutaneous intervention is recommended in those with anatomic conditions associated with a low risk of percutaneous coronary intervention procedural complications and in those with increased risk of surgical complications.7 Previous case reports suggest that extrinsic LMCA compression is a low-risk condition, and most studies report safe and successful stenting. Both bare metal and drug-eluting stents have been used. Drug-eluted stenting of atherosclerotic LMCA disease has been associated with a 0.7% rate of restenosis and a 0.9% rate of thrombosis. Extrinsic LMCA compression likely has a lower restenosis rate, considering the absence of atherosclerotic disease; however, long-term follow-up data are lacking. Treatment of the underlying cause of pulmonary hypertension may decrease the pulmonary artery pressures and diameter.The patient recovered and was discharged home. She underwent CT coronary angiography, which showed the LMCA was normal, in position, and impinged upon by the enlarged pulmonary artery. The CT angiogram confirmed the diagnosis of LMCA compression syndrome (Figure 2). Eventually, the patient underwent successful elective bovine pericardial patch repair of the atrial septal defect.Two views revealing a stented left main coronary artery impinged upon by enlarged pulmonary artery. CT indicates computed tomographic.

Cardiology

A woman aged 44 years with no significant medical history presented with increasing exertional dyspnea and fatigue. Transthoracic echocardiography showed an atrial septal defect, and transesophageal echocardiography confirmed a 1.2-cm secundum atrial septal defect with bidirectional shunting without a clear superior rim. A computed tomographic (CT) pulmonary angiogram showed a dilated pulmonary artery consistent with pulmonary hypertension (Figure 1A).A, Computed tomographic (CT) pulmonary angiogram showing a dilated pulmonary artery size in compare to the aorta size. B, Coronary angiogram revealing diffuse narrowing of the left main coronary artery at its origin.Right and left heart cardiac catheterization was performed. During coronary angiography, the patient was noted to have diffuse 90% to 95% narrowing of the left main coronary artery at its origin (Figure 1B; Video). The left anterior descending and left circumflex arteries were normal in caliber and appearance.The question arose whether the left main coronary artery stenosis represented an anatomic anomaly, a spasm, or a combination. Intracoronary nitroglycerine was administered with no change in angiographic appearance of the left main coronary artery. The patient then developed deep ST-segment depressions associated with chest and throat pain. The catheter was re-engaged, and additional intracoronary nitroglycerine was administered with the resolution of ST-segment depression and pain.The patient then developed ventricular tachycardia requiring cardioversion and intravenous amiodarone and lidocaine. The patient became unstable with recurrent episodes of ventricular tachycardia/fibrillation requiring cardiopulmonary resuscitation. An intra-aortic balloon pump was emergently placed, and the patient was intubated.Emergent stenting of the left main coronary arteryEmergent closure of the atrial septal defect

what would you do next?

What would you do next?

Emergent stenting of the left main coronary artery

Emergent coronary artery bypass graft surgery

Emergent closure of the atrial septal defect

Emergent pulmonic valve balloon valvotomy

a

female

41-50

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2525530

A man in his 30s presented to the emergency department with sudden voice change, odynophagia, and left-sided neck pain following a single sneeze. He experienced a popping sensation during the sneeze followed by neck stiffness 15 minutes later. He did not have associated shortness of breath, hemoptysis, or other pertinent medical history. He had no history of trauma, surgery, or intubation. On physical examination, his vital signs were stable with normal oxygen saturation on room air. His voice was rough and without stridor. Anterior neck examination revealed tenderness over the thyroid notch and left side of the laryngotracheal complex. There was no palpable crepitus. Flexible laryngoscopy was performed, which showed hematoma of the left true vocal fold and laryngeal surface of the epiglottis with normal vocal fold movement and complete glottic closure (Figure, A).Hematoma of the left true vocal fold and laryngeal surface of the epiglottis. B, CT indicates computed tomography. What Is Your Diagnosis?

Ruptured vocal fold hemangioma

Rupture of laryngocele

Thyroid cartilage fracture

Traumatic intubation

C. Thyroid cartilage fracture

C

Thyroid cartilage fracture

Given the presence of pain and hematoma noted on laryngoscopy, a computed tomographic (CT) study of the neck was obtained, which showed a left nondisplaced vertical paramedian fracture of the thyroid cartilage (Figure B). The patient was treated conservatively with a methylprednisolone taper (starting dose of 20 mg) and voice rest. At his follow-up 2 weeks later, there was complete return of vocal quality and resolution of neck pain and odynophagia. Fiber-optic exam demonstrated near-complete resolution of the left true vocal fold edema and ecchymosis.The most frequent cause of thyroid cartilage fracture is blunt trauma to the neck, as seen in motor vehicle crashes, sports injuries, and strangulation. Nontraumatic thyroid cartilage fracture is exceedingly rare, and to our knowledge has been reported in the medical literature on only 4 occasions.1-4 All reported cases have involved male patients in their third to fifth decade. In all cases, including the present, the fracture occurred following a sudden increase in subglottic pressure from sneeze or cough. Odynophagia and dysphonia were present in all described cases.Symptoms and signs may include dysphagia, and swelling or crepitus overlying the thyroid cartilage. On flexible laryngoscopy, all patients displayed some degree of supraglottic and/or glottic edema with normal vocal fold movement. Of the 4 cases with imaging, all showed either a nondisplaced or minimally displaced paramedian fracture of the thyroid. Every patient had full resolution of their symptoms and physical examination findings with conservative treatment consisting of voice rest, steroids, and, in some cases, antibiotics.Previous reports have proposed hypotheses to explain this rare entity. Sneezing and coughing result in a sudden increase in subglottic pressure against a closed glottis. This mechanism of injury is fundamentally different from external trauma because fracture occurs from barotrauma exerting force outward as opposed to external trauma exerting force inward. It has been proposed that the patients who have sustained thyroid cartilage may have an underlying defect predisposing them to injury.3 Fenig and colleagues4 surmise that the mineralization and ossification process may have been abnormal in these patients. They4 further state that this process differs between males and females and, therefore, may explain the male predominance seen in these case reports. Thyroid cartilage in males ossifies earlier and more extensively than thyroid cartilage in females. Perhaps the patients in these reports have more extensively ossified thyroid cartilage compared with their peers. Alternatively, regions of highly ossified cartilage abutting nonossified cartilage could create areas susceptible to fracture with sudden increase in upper airway pressure.Nontraumatic fracture of the thyroid cartilage is an extremely rare entity. Patients giving a history of sneeze or cough followed by the acute onset of dysphonia, odynophagia, dysphagia, or neck pain warrant careful examination, including laryngoscopy and imaging. In most cases, assuming the fracture is nondisplaced, these patients can be treated conservatively with voice rest with full resolution of their symptoms.

General

A man in his 30s presented to the emergency department with sudden voice change, odynophagia, and left-sided neck pain following a single sneeze. He experienced a popping sensation during the sneeze followed by neck stiffness 15 minutes later. He did not have associated shortness of breath, hemoptysis, or other pertinent medical history. He had no history of trauma, surgery, or intubation. On physical examination, his vital signs were stable with normal oxygen saturation on room air. His voice was rough and without stridor. Anterior neck examination revealed tenderness over the thyroid notch and left side of the laryngotracheal complex. There was no palpable crepitus. Flexible laryngoscopy was performed, which showed hematoma of the left true vocal fold and laryngeal surface of the epiglottis with normal vocal fold movement and complete glottic closure (Figure, A).Hematoma of the left true vocal fold and laryngeal surface of the epiglottis. B, CT indicates computed tomography.

what is your diagnosis?

What is your diagnosis?

Ruptured vocal fold hemangioma

Rupture of laryngocele

Thyroid cartilage fracture

Traumatic intubation

c

male

31-40

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2526367

A man in his 30s presented with a 1-year history of recurrent episodes of unilateral high-pitched “clicking” in his right ear followed by vertigo that lasted 3 to 4 seconds. He reported no perceived association between these episodes and breathing and head position, and denied precipitation of symptoms with exposure to loud sound or pressure change. He had not experienced hearing loss, aural fullness, autophony, or headache. On physical examination, objective, intermittent, clicking tinnitus at a frequency of 1 click per second was noted on placement of a stethoscope in close proximity to the right ear. The tinnitus coincided temporally with the patient’s complaints but was nonsynchronous with pulse. Results from prior imaging including a computed tomographic (CT) scan of the head with multiplanar reconstruction (Figure, A, C, and D), were normal. Steady state tympanometry showed mildly decreased compliance of the tympanic membrane when the patient reported hearing the clicking sensation. The patient was tentatively diagnosed as having tensor tympani and stapedius myoclonus and after discussion of treatment options, he decided to undergo middle ear exploration for muscle sectioning. The incidental findings observed during middle ear exploration are shown in the Figure, B.A, Computed tomographic (CT) image of the head using bone window. B, Intraoperative photograph of incidental surgical findings. C, Multiplanar oblique coronal reconstruction of computed tomographic image. The inset shows the plane of reconstruction in an oblique coronal view longitudinal with the petrous pyramid. D, Computed tomographic image of the head using bone window. What Is Your Diagnosis?

Paraganglioma

Persistent stapedial artery

Cholesteatoma

Dehiscent carotid canal

B. Persistent stapedial artery

B

Persistent stapedial artery

Persistent stapedial artery (PSA) is a rare vascular anomaly of the middle ear. Estimates of its occurrence in the general population range from 0.02% to 0.48%.1,2 While most cases of PSA are asymptomatic or found incidentally, they may occasionally cause symptoms, such as pulsatile tinnitus, hearing loss, vertigo, and vomiting. Unilateral PSA is more commonly described in the literature; however, several bilateral cases of PSA have also been reported.3,4The stapedial artery is associated with the second branchial arch. It usually involutes by the 10th week of gestation and does not normally persist in postnatal life. However, during its existence, it plays important roles in the development of the stapes superstructure, the foramen spinosum, and the carotid system and its branches.The stapedial artery originates from the root of the hyoid artery (future caroticotympanic artery). It passes through the obturator foramen of the stapes, after which it branches into a superior supraorbital division and an inferior maxillomandibular division.2,5,6 The former becomes the middle meningeal artery, whereas the latter anastomoses with the ventral pharyngeal artery to form the maxillary artery. It is about this anastomosis that the foramen spinosum develops. Failure of this anastomosis to form or failure of the stapedial artery to regress results in PSA and hypoplasia or aplasia of the foramen spinosum.In the most common variant, the hyoidostapedial variation of PSA, the stapedial artery arises from the petrous portion of the internal carotid artery (Figure, C). The PSA enters the anterior hypotympanum, where it is closely related to the cochlear promontory. It courses through the obturator foramen (Figure, B) and joins the facial nerve at the tympanic segment (Figure, A). It then exits the fallopian canal approximately 2 mm posterior to the geniculate ganglion to supply the middle meningeal artery territory.2 On CT imaging, PSA appears as a linear soft-tissue density signal that overlies the promontory and passes between the crura of the stapes.7 The horizontal portion of the fallopian canal is usually widened to accommodate both the stapedial artery and facial nerve.Despite its rarity, clinicians should be aware of the possibility of PSA. Patients with PSA may present with symptoms as described herein, and the presence of the stapedial artery can complicate middle ear surgery. Risk of injury to the vessel is particularly high during myringotomy and, because of its course through the obturator foramen, during stapedectomy or stapedotomy for otosclerosis. Laser coagulation and bipolar cautery have been used to successfully remove the artery without injury to surrounding structures.2Persistent stapedial artery has been reported to be coincident with other head and neck malformations as well as congenital syndromes. Microtia, ossicular chain defects, facial nerve aberrancies, and vascular anomalies are among the most common.3,7 There have also been case reports of PSA in patients with Patau and Pascual-Castroviejo type 2 syndromes.8,9The patient in this case underwent pressure equalizer tube placement in the clinic and subsequent middle ear exploration with muscle sectioning for question of spasm. Intraoperatively, the PSA was found incidentally, and so stapedius tenotomy was not performed; however, tensor tympani sectioning was completed without complication. Findings from a follow-up audiogram and tympanometry 6 weeks postoperatively were normal; however, the patient continued to experience clicking tinnitus. After discussion of the risks and benefits PSA coagulation, he declined further treatment. Although this patient experienced symptoms only in the right ear, review of the CT scan reveals absent spinosum foramina bilaterally (Figure, D), raising the possibility of an additional left-sided PSA. Conventional or CT angiography more definitively elucidates the presence of PSA; however, in this case no additional imaging or interventions were planned because the patient relocated.

General

A man in his 30s presented with a 1-year history of recurrent episodes of unilateral high-pitched “clicking” in his right ear followed by vertigo that lasted 3 to 4 seconds. He reported no perceived association between these episodes and breathing and head position, and denied precipitation of symptoms with exposure to loud sound or pressure change. He had not experienced hearing loss, aural fullness, autophony, or headache. On physical examination, objective, intermittent, clicking tinnitus at a frequency of 1 click per second was noted on placement of a stethoscope in close proximity to the right ear. The tinnitus coincided temporally with the patient’s complaints but was nonsynchronous with pulse. Results from prior imaging including a computed tomographic (CT) scan of the head with multiplanar reconstruction (Figure, A, C, and D), were normal. Steady state tympanometry showed mildly decreased compliance of the tympanic membrane when the patient reported hearing the clicking sensation. The patient was tentatively diagnosed as having tensor tympani and stapedius myoclonus and after discussion of treatment options, he decided to undergo middle ear exploration for muscle sectioning. The incidental findings observed during middle ear exploration are shown in the Figure, B.A, Computed tomographic (CT) image of the head using bone window. B, Intraoperative photograph of incidental surgical findings. C, Multiplanar oblique coronal reconstruction of computed tomographic image. The inset shows the plane of reconstruction in an oblique coronal view longitudinal with the petrous pyramid. D, Computed tomographic image of the head using bone window.

what is your diagnosis?

What is your diagnosis?

Persistent stapedial artery

Paraganglioma

Cholesteatoma

Dehiscent carotid canal

a

male

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2529738

A woman in her 70s presented with a cervical tracheal mass measuring 1.6 × 1.3 cm found incidentally on magnetic resonance imaging for cervical spine pain. She had not experienced dyspnea, hoarseness, dysphagia, hemoptysis, or chest pain. Flexible fiber-optic nasolaryngoscopy demonstrated a smooth hypervascular mass arising from the posterior membranous trachea (Figure, A). The patient underwent tracheostomy and complete excision via a transtracheal approach. The patient was decannulated on postoperative day 5. Histopathologic images are shown in the Figure, B-D. What Is Your Diagnosis?

Superior laryngeal nerve schwannoma

Carcinoid tumor

Glomus tumor

Paraganglioma

C. Glomus tumor

C

Glomus tumor

A glomus tumor is a rare mesenchymal pericytic neoplasm that consists of cells that resemble the modified smooth muscle cells of a normal glomus body. A normal glomus body functions in thermoregulation and is responsible for regulating blood flow on the skin surface. Glomus tumors represent 2% of all soft-tissue tumors and typically occur in areas with a high concentration of glomus bodies, such as the dermis and subcutaneous tissues.1 Extracutaneous glomus tumors are rare.The first tracheal glomus tumor was reported in 1950 by Hussarek et al,2 and fewer than 30 cases of tracheal glomus tumors have been reported in the literature to date.3-5 Most tracheal glomus tumors are found to arise from the posterior membranous trachea where vessels and mucus glands are rich.3 Most cases (82%) are in the mid to lower trachea, with only 18% in the upper trachea.3 The most common presenting symptoms are cough, hemoptysis, and dyspnea.3,6 Tumors tend to grow and extend into the tracheal lumen but rarely invade or extend extratracheally.7Glomus tumors are histologically composed of 3 different components: glomus cells, vasculature, and smooth muscle cells.1 Depending on the predominance of each of these components, glomus tumors can be classified as solid tumors, which are the most common (75%), glomangiomas (prominent vascular component) (20%), or glomangiomyomas (prominent vascular and smooth muscle components) (5%).1 The histopathological architecture consists of branching vasculature lined with endothelial cells and surrounded by nests and sheets of glomus cells (Figure, B).1 Glomus cells are uniformly round or ovoid cells with a lightly eosinophilic cytoplasm and well-delineated cell borders (Figure, C). Glomus cells stain positive for smooth muscle actin (Figure, D) and vimentin but are negative for endocrine and epithelial markers, including synaptophysin, chromogranin, desmin, cytokeratins, and S-100.1,3,6,8 The differential diagnoses can include carcinoid tumors, paragangliomas, and hemangiopericytomas. Carcinoid tumors have neuroendocrine features, are positive for cytokeratin and chromogranin, and do not express smooth-muscle actin.7 Paragangliomas have immunoreactivity with synaptophysin, chromogranin, and S-100. Hemangiopericytomas consist of spindle-shaped cells that stain positive for vimentin, but smooth-muscle differentiation is less common.9Most glomus tumors are benign, but approximately 1% are reported to be malignant.1 Malignancy is suggested by size greater than 2 cm, atypical mitotic figures, or a moderate to high nuclear grade, and more than 5 mitotic figures per 50 high-powered fields.10 A biopsy specimen from this patient had no significant pleomorphism or increased mitotic activity, suggesting a benign glomus tumor.Treatment consists of surgical resection, with the most common type of resection being tracheal resection with primary reanastamosis.3 Endoscopic resection has also been reported.3,7 However, given the vascularity of glomus tumors, if one is suspected, endoscopic biopsy can be dangerous owing to the risk of hemorrhage. In this case, we initially visualized the mass endoscopically via direct laryngoscopy. The mass was at the level of the cricoid cartilage and first tracheal ring. We then made a tracheotomy incision between the cricoid and first tracheal ring and created an inferiorly based Björk flap. The entire mass was easily visualized and excised under direct visualization through that incision without need for a tracheal resection. The patient was decannulated prior to hospital discharge and at 4 weeks after surgery had a patent trachea with no evidence of residual disease.

General

A woman in her 70s presented with a cervical tracheal mass measuring 1.6 × 1.3 cm found incidentally on magnetic resonance imaging for cervical spine pain. She had not experienced dyspnea, hoarseness, dysphagia, hemoptysis, or chest pain. Flexible fiber-optic nasolaryngoscopy demonstrated a smooth hypervascular mass arising from the posterior membranous trachea (Figure, A). The patient underwent tracheostomy and complete excision via a transtracheal approach. The patient was decannulated on postoperative day 5. Histopathologic images are shown in the Figure, B-D.

what is your diagnosis?

What is your diagnosis?

Paraganglioma

Glomus tumor

Carcinoid tumor

Superior laryngeal nerve schwannoma

b

female

71-80

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2533655

A man in his 70s with long-standing diabetes, coronary artery disease, and chronic renal failure presented with edema of the right lower leg and suspected venous thrombosis (which was not confirmed by subsequent Doppler ultrasonography). Blood tests revealed serious iron deficiency anemia (hemoglobin level, 8.6 g/d [86 g/L]) and a positive result for a fecal occult blood test. His appetite was intact; he had not lost weight; and no dysphagia, stomach pain, or stool irregularity was reported. Initially, we performed an upper endoscopy that revealed normal esophageal mucosa with folding of the posterior esophageal wall through the entire length of the esophagus. Distal ending of the folding was not clearly seen in forward viewing, but in retroflexion, a necrotic polypoid lesion was observed protruding from the esophagogastric junction. A computed tomographic scan of the chest with oral contrast revealed an esophageal intraluminal tubular mass of soft-tissue density, about 15 mm in diameter originating just below the pyriform recessus and extending through the esophagus in the stomach lumen for about 20 mm (Figure 1). The patient was referred to an ear, nose, and throat specialist who performed esophagoscopy of the hypopharynx with the patient under endotracheal anesthesia.Intraluminal tubular mass extending through the entire esophagus. CT indicates computed tomographic. What Is Your Diagnosis?

Squamous papilloma

Gastrointestinal stromal tumor

Fibrovascular polyp

Lipoma

C. Fibrovascular polyp

C

Fibrovascular polyp

After identifying the pedicle of the mass, the surgeon was able to per-orally resect a long, pedunculated, V-shaped polyp with a 7-cm-wide stalk originating from the left aryepiglottic fold, descending behind the cricoid cartilage to the esophagus (Figure 2, A and B). The pathology report described 19.0 × 8.0 × 2.5-cm giant fibrovascular hypopharyngeal polyp with apical ulceration consisting of a mixture of fibrous and lipomatous elements with abundant vascularization, covered mostly by normal squamous epithelium. (Figure 2, C).A, V-shaped 18-cm-long hypopharyngeal polyp with 7-cm wide stalk and apical ulceration. B, Histopathological image. C, Giant hypopharyngeal polyp drawn out through the mouth intraoperatively. Giant esophageal and hypopharyngeal polyps are benign tumors rarely encountered in clinical practice. About 110 cases of large (>5 cm) pedunculated polyps of the esophagus and hypopharynx have been reported.1,2 Most originate from the upper third of the esophagus; only a few cases of giant hypopharyngeal polyps have been described to date and only 1 case arising from the pharyngoepiglottic fold.3,4 The most frequent symptom is progressive dysphagia, followed by regurgitation of the mass into the mouth with the risk of aspiration into the airways. Other symptoms include pharyngeal globus, weight loss, gastroesophageal reflux, odynophagia, and infrequently melena and anemia.2 As in this case, the latter 2 symptoms were a result of ulceration of the apical part of the polyp owing to contact with the acidic gastric contents. Fibrovascular polyps can be confused with intramural lesions or overlooked completely if the polyp is in contact with the esophageal wall because its surface can resemble normal esophageal mucosa. Malignant degeneration of these polyps rarely occurs.1 Most polyps larger than 8 cm are surgically removed by an abdominal or cervical approach, although endoscopic resection of large esophageal polyps has been reported.5-7 As for giant hypopharyngeal polyps, peroral excision is also an option if the stalk of the polyp is visualized completely, thus reducing morbidity significantly.8

General

A man in his 70s with long-standing diabetes, coronary artery disease, and chronic renal failure presented with edema of the right lower leg and suspected venous thrombosis (which was not confirmed by subsequent Doppler ultrasonography). Blood tests revealed serious iron deficiency anemia (hemoglobin level, 8.6 g/d [86 g/L]) and a positive result for a fecal occult blood test. His appetite was intact; he had not lost weight; and no dysphagia, stomach pain, or stool irregularity was reported. Initially, we performed an upper endoscopy that revealed normal esophageal mucosa with folding of the posterior esophageal wall through the entire length of the esophagus. Distal ending of the folding was not clearly seen in forward viewing, but in retroflexion, a necrotic polypoid lesion was observed protruding from the esophagogastric junction. A computed tomographic scan of the chest with oral contrast revealed an esophageal intraluminal tubular mass of soft-tissue density, about 15 mm in diameter originating just below the pyriform recessus and extending through the esophagus in the stomach lumen for about 20 mm (Figure 1). The patient was referred to an ear, nose, and throat specialist who performed esophagoscopy of the hypopharynx with the patient under endotracheal anesthesia.Intraluminal tubular mass extending through the entire esophagus. CT indicates computed tomographic.

what is your diagnosis?

What is your diagnosis?

Fibrovascular polyp

Squamous papilloma

Gastrointestinal stromal tumor

Lipoma

a

male

71-80

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2569669

A 64-year-old man was referred to our clinic for suspected central retinal vein occlusion (CRVO) in his right eye. He had experienced blurred vision of the right eye for 2 months; medical history included hypercholesterolemia. Best-corrected visual acuity was 20/80 OD and 20/20 OS. The anterior segment was normal and intraocular pressure was 16 mm Hg in both eyes. Dilated fundus examination of the right eye revealed a normal optic disc, mild venous engorgement, and widespread peripheral dot-blot retinal hemorrhages mainly located in the temporal midperiphery (Figure 1A). No spontaneous retinal arterial pulsation was noted. Examination findings of the left eye were unremarkable. Fluorescein angiography in the right eye showed delayed venous filling, mild perifoveal leakage, and scattered microaneurysms in the temporal sector (Figure 1B).A, Montage color fundus photograph of the right eye at presentation shows mild venous dilation and midperipheral dot and blot hemorrhages mostly located in the temporal sectors. B, Fluorescein angiography frame (2 minutes, 3 seconds) shows multiple microaneurysms in correspondence of the dot-blot retinal hemorrhages and a barely visible perifoveal vascular leakage. What Would You Do Next?

Observe

Perform panretinal photocoagulation

Obtain carotid Doppler

Refer to cardiology

Unilateral ocular ischemic syndrome

C

Obtain carotid Doppler

This patient was referred to us with a provisional diagnosis of CRVO. However, the optic disc was not swollen, the hemorrhages were in the midperiphery, and microaneurysms were present. Furthermore, the extent of vision loss was not consistent with the severity of features observed on funduscopy or optical coherence tomography (Figure 2). The right macula was only mildly and diffusely thickened and the absence of hemorrhages or exudates in this region was striking. We suspected insufficient flow through the retinal artery with the obstruction located in the carotid artery. Ultrasonographic carotid examination confirmed our suspicion, showing complete obstruction of the internal carotid of the right side and an echogenic atheroma in the proximal internal carotid of the left side.Optical coherence tomography at presentation shows a mild diffuse macular thickening on the color retinal thickness map (A) and a preserved foveal contour on the scan passing through the fovea (B). ETDRS indicates Early Treatment Diabetic Retinopathy Study.In 1963, Hedges1 first described a case of a 48-year-old man with peripheral dot and blot hemorrhages and dilated retinal veins and attributed these findings to retinal hypoxia induced by carotid artery insufficiency. In the same year, Kearns and Hollenhorst2 also reported the presence of venous dilation in association with midperipheral dot-blot and flame-shaped hemorrhages, and microaneurysms in 5% of their patients with unilateral stenosis or occlusion of the internal carotid artery and named the condition venous stasis retinopathy. Subsequently, it was observed that in case of carotid artery insufficiency, the signs of ischemia may be present in both the anterior and the posterior segments of the eye, and these have been eventually referred to as ocular ischemic syndrome (OIS).3 Atherosclerosis of the common or internal carotid arteries is the main cause of OIS.3 Other causes include dissecting aneurysm of the carotid artery, giant cell arteritis, fibrovascular dysplasia, Takayasu arteritis, aortic arch syndrome, Behçet disease, and trauma.4Common presenting visual symptoms of OIS may include amaurosis fugax, gradual or sudden functional loss, and pain. However, the clinical presentation is variable and might be confused with that of CRVO.3 As opposed to eyes with CRVO, in eyes with OIS, a light digital pressure on the eyelid may induce retinal arterial pulsations, which may also be spontaneously observed.3 A prompt recognition of OIS is critical because it may be the first manifestation of carotid artery disease,3 as in this case.The patient was urgently referred to a vascular surgeon.

Ophthalmology

A 64-year-old man was referred to our clinic for suspected central retinal vein occlusion (CRVO) in his right eye. He had experienced blurred vision of the right eye for 2 months; medical history included hypercholesterolemia. Best-corrected visual acuity was 20/80 OD and 20/20 OS. The anterior segment was normal and intraocular pressure was 16 mm Hg in both eyes. Dilated fundus examination of the right eye revealed a normal optic disc, mild venous engorgement, and widespread peripheral dot-blot retinal hemorrhages mainly located in the temporal midperiphery (Figure 1A). No spontaneous retinal arterial pulsation was noted. Examination findings of the left eye were unremarkable. Fluorescein angiography in the right eye showed delayed venous filling, mild perifoveal leakage, and scattered microaneurysms in the temporal sector (Figure 1B).A, Montage color fundus photograph of the right eye at presentation shows mild venous dilation and midperipheral dot and blot hemorrhages mostly located in the temporal sectors. B, Fluorescein angiography frame (2 minutes, 3 seconds) shows multiple microaneurysms in correspondence of the dot-blot retinal hemorrhages and a barely visible perifoveal vascular leakage.

what would you do next?

What would you do next?

Refer to cardiology

Perform panretinal photocoagulation

Obtain carotid Doppler

Observe

c

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2578712

An African American woman in her 50s presented for recent-onset blurred vision in both eyes for 2 months. She endorsed mild photophobia but denied pain, redness, tearing, or discharge. There was no history of oral/genital ulcers, rashes, or atopy. Her medical history was significant for hypertension, asthma, hepatitis C, and essential tremor. Her medications include lisinopril, albuterol sulfate, and amantadine hydrochloride. She denied any previous ocular surgical procedures or trauma. She was seen 2 weeks prior and was treated with 400 mg of oral acyclovir sodium 5 times a day and sodium chloride, 5%, ointment 4 times a day. Her central corneal thickness at that time was recorded at 798 μm OD and 827 μm OS.Her best-corrected visual acuity at presentation was 20/70 OD and 20/50 OS. Her extraocular motility, pupils, and confrontation visual fields were normal. Intraocular pressures were 7 and 9 mm Hg OD and OS, respectively. An anterior segment slitlamp examination was significant for central bilateral stromal edema, Descemet folds, microcystic edema, and endothelial guttae in both eyes (Figure). There were no keratic precipitates, and the anterior chamber did not show cells or flare. Conjunctiva was white and quiet. No abnormalities were noted during an ophthalmoscopic examination. Her central corneal thickness was found to be 833 μm OD and 925 μm OS.Slitlamp photograph at presentation showing corneal edema in the left eye. Corneal edema was similar in both eyes. What Would You Do Next?

Bilateral Descemet stripping endothelial keratoplasty

Corneal topography

Observe

Discontinue treatment with amantadine

Amantadine-associated endothelial toxicity

D

Discontinue treatment with amantadine

Amantadine has been shown in several case reports and studies to cause bilateral corneal edema secondary to endothelial toxicity, which may or may not be reversible.1-8 Elimination of all potential toxic agents is needed to determine the cause of the endothelial failure and resultant corneal edema. The patient had received 200 mg of amantadine for the past year, with an increase in the dose to 300 mg 7 months ago. It is also important to rule out herpetic disease as a potential cause of endothelial dysfunction. The patient was receiving acyclovir for 2 weeks without improvement in symptoms and had worsening corneal edema.Descemet stripping endothelial keratoplasty is not the best answer because we are not certain of the source or cause of the edema. Transplantation without identifying a causative etiology could lead to graft failure. Corneal topography would not be helpful in this case, although serial pachymetry would be useful to follow. Observation is not warranted because her corneal edema was worsening.Amantadine is an antiviral agent used in the management of influenza A but also has been used for patients with Parkinson disease, tardive dyskinesia, essential tremor, and fatigue and for patients with multiple sclerosis.5 Several case reports and studies have reported various ocular adverse effects including vision loss, mydriasis, superficial punctuate keratitis, punctate subepithelial opacification, epithelial, and stromal edema.1The exact etiology is unknown; however, drug hypersensitivity and dose-related effects are 2 proposed etiologies for endothelial toxicity.7 Endothelial toxicity has developed in patients weeks to years after starting the medication (on doses between 100 and 400 mg).2,3,7,8 Corneal edema and visual acuity are reversible in most cases after discontinuation of the medication; however, irreversible damage has been reported.3 This endothelial damage is also seen in corneal graft tissue in patients who continue to use amantadine after Descemet stripping endothelial keratoplasty.4A surveillance study at the Veteran Health Administration looked at the relationship between corneal edema or Fuchs dystrophy and amantadine use. While only a small percentage of patients (0.27%) developed corneal edema, the relative risk of developing corneal edema with amantadine use was 1.7, with one-third of patients developing symptoms within 1 month.6Chang et al7 found that patients taking amantadine had a significantly lower endothelial cell density, a lower hexagonality, and a greater coefficient of variation compared with the age-matched control group. In addition, a longer duration of treatment and a higher cumulative dose of amantadine were associated with lower endothelial cell counts.7The patient had bilateral corneal edema caused by toxicity from amantadine. For patients with bilateral corneal edema, it is important to rule out Fuchs corneal dystrophy, herpetic keratitis, endothelial corneal dystrophies, and drug toxicities. Early diagnosis could prevent irreversible corneal damage.After a discussion with the neurology team, treatment with amantadine was discontinued, and the edema resolved (central corneal thickness at 3 months was 541 and 545 μm OD and OS, respectively). The patient’s vision returned to 20/20 OU.

Ophthalmology

An African American woman in her 50s presented for recent-onset blurred vision in both eyes for 2 months. She endorsed mild photophobia but denied pain, redness, tearing, or discharge. There was no history of oral/genital ulcers, rashes, or atopy. Her medical history was significant for hypertension, asthma, hepatitis C, and essential tremor. Her medications include lisinopril, albuterol sulfate, and amantadine hydrochloride. She denied any previous ocular surgical procedures or trauma. She was seen 2 weeks prior and was treated with 400 mg of oral acyclovir sodium 5 times a day and sodium chloride, 5%, ointment 4 times a day. Her central corneal thickness at that time was recorded at 798 μm OD and 827 μm OS.Her best-corrected visual acuity at presentation was 20/70 OD and 20/50 OS. Her extraocular motility, pupils, and confrontation visual fields were normal. Intraocular pressures were 7 and 9 mm Hg OD and OS, respectively. An anterior segment slitlamp examination was significant for central bilateral stromal edema, Descemet folds, microcystic edema, and endothelial guttae in both eyes (Figure). There were no keratic precipitates, and the anterior chamber did not show cells or flare. Conjunctiva was white and quiet. No abnormalities were noted during an ophthalmoscopic examination. Her central corneal thickness was found to be 833 μm OD and 925 μm OS.Slitlamp photograph at presentation showing corneal edema in the left eye. Corneal edema was similar in both eyes.

what would you do next?

What would you do next?

Discontinue treatment with amantadine

Corneal topography

Observe

Bilateral Descemet stripping endothelial keratoplasty

a

female

51-60

African American

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2579927

A Hispanic woman in her 60s presented to the oculoplastics clinic with a 1-week history of pain, redness, and swelling in the medial aspect of the right periorbital region. Her medical history included sarcoidosis, type 2 diabetes, hypertension, and coronary artery disease. Her ocular history included pseudophakia and proliferative diabetic retinopathy in both eyes; she had also undergone pars plana vitrectomy and panretinal photocoagulation in both eyes. Seven days prior to presentation, an ophthalmologist prescribed the patient oral amoxicillin-clavulanate, 500 mg 3 times daily, and topical antibiotics. However, her symptoms persisted and eventually worsened. She reported increasing swelling and pain in the affected region. She denied changes in vision, eye pain, or pain with eye movements. The patient’s best-corrected visual acuity was 20/60 OD and 20/50 OS, her pupils were reactive, extraocular motility was full and painless, and intraocular pressures were 18 mm Hg in both eyes. External examination revealed an erythematous, tender, firm mass in the medial periorbital area (Figure, A). Results of anterior slitlamp examination and dilated fundus examination were unremarkable. Contrast-enhanced computed tomographic imaging of the maxillofacial region was performed and showed a peripherally enhancing mass in the affected area (Figure, B).A, External photograph demonstrating a firm, tender, erythematous mass located in the medial periorbital area. B, Contrast-enhanced maxillofacial computed tomographic scan showing a peripherally enhancing mass (arrowhead) in the medial aspect of the right periorbital region.Perform magnetic resonance imaging of the orbits and maxillofacial regionPrescribe topical and systemic antibiotics and recommend use of warm compresses without planned surgical or procedural intervention What Would You Do Next?

Perform a biopsy of the mass

Perform magnetic resonance imaging of the orbits and maxillofacial region

Perform endoscopic dacryocystorhinostomy and prescribe antibiotics

Prescribe topical and systemic antibiotics and recommend use of warm compresses without planned surgical or procedural intervention

Acute dacryocystitis with abscess formation

C

Perform endoscopic dacryocystorhinostomy and prescribe antibiotics

This patient has acute dacryocystitis with abscess formation, as evidenced by the characteristic swelling, erythema, and tenderness in the inferomedial aspect of the periorbital region (specifically, at or below the level of the medial canthal tendon). The presence of an abscess is supported by results of computed tomographic imaging as well as the clinical history of failed systemic and topical antibiotic therapy. Acute dacryocystitis with abscess formation can be treated in several ways, although an essential element of treatment is drainage of the abscess. Prescription of topical and systemic antibiotics and recommendation to use warm compresses without planned surgical or procedural intervention, which are additional necessary components of the medical management of this condition, is incomplete because it does not include drainage of the abscess. Magnetic resonance imaging is unlikely to add additional information beyond that provided by results of the computed tomographic imaging, and a biopsy is not indicated.Congenital or acquired nasolacrimal duct obstruction can result in tear stagnation and subsequent infection and inflammation within the lacrimal sac, known as dacryocystitis. Serious consequences of dacryocystitis include recurrent conjunctivitis, endophthalmitis, postseptal or preseptal cellulitis, formation of an abscess, and formation of a cutaneous fistula. Risk factors of acquired nasolacrimal duct obstruction include mechanical obstruction (eg, dacryoliths or foreign body), trauma, prior sinonasal surgery, sinusitis, nasal septum deviation, inferior turbinate hypertrophy, spread of infection (eg, conjunctivitis or orbital cellulitis), malignant infiltration, inflammatory disease (eg, sarcoidosis, granulomatosis with polyangitis, mucous membrane pemphigoid, or Stevens-Johnson syndrome), and idiopathic stenosis.1-3 Women, especially those who are postmenopausal, are more commonly affected.1 Culture results suggest that the most commonly isolated gram-positive organisms include Staphylococcus and Streptococcus species, and the most commonly isolated gram-negative organisms include Haemophilus influenza and Pseudomonas aeruginosa.1,4 Anaerobic and fungal organisms also may be isolated on culture.Initial treatment of acute dacryocystitis without formation of an abscess consists most commonly of culturing, warm compresses, and topical and systemic antibiotics with subsequent dacryocystorhinostomy (externally or endonasally) after resolution of the acute infection. However, in the setting of formation of an abscess, a drainage procedure is required. External dacryocystorhinostomy is typically not performed for drainage of an abscess because of the risk of exacerbation of inflammation and formation of a cutaneous fistula and is instead deferred until after the acute infection has resolved. In contrast, evidence suggests that endonasal, endoscopic dacryocystorhinostomy is a viable and effective alternative for drainage of an abscess in acute dacryocystitis.5,6 Success rates may be as high as 90% and symptoms, such as pain and swelling, may resolve more quickly with endoscopic dacryocystorhinostomy than with delayed external dacryocystorhinostomy.5This patient underwent endoscopic dacryocystorhinostomy and bicanalicular intubation with a silicone tube. Intraoperative cultures revealed methicillin-resistant Staphylococcus aureus. She was discharged home to complete a course of oral antibiotics. After the procedure, she achieved resolution of her infection with no recurrence.

Ophthalmology

A Hispanic woman in her 60s presented to the oculoplastics clinic with a 1-week history of pain, redness, and swelling in the medial aspect of the right periorbital region. Her medical history included sarcoidosis, type 2 diabetes, hypertension, and coronary artery disease. Her ocular history included pseudophakia and proliferative diabetic retinopathy in both eyes; she had also undergone pars plana vitrectomy and panretinal photocoagulation in both eyes. Seven days prior to presentation, an ophthalmologist prescribed the patient oral amoxicillin-clavulanate, 500 mg 3 times daily, and topical antibiotics. However, her symptoms persisted and eventually worsened. She reported increasing swelling and pain in the affected region. She denied changes in vision, eye pain, or pain with eye movements. The patient’s best-corrected visual acuity was 20/60 OD and 20/50 OS, her pupils were reactive, extraocular motility was full and painless, and intraocular pressures were 18 mm Hg in both eyes. External examination revealed an erythematous, tender, firm mass in the medial periorbital area (Figure, A). Results of anterior slitlamp examination and dilated fundus examination were unremarkable. Contrast-enhanced computed tomographic imaging of the maxillofacial region was performed and showed a peripherally enhancing mass in the affected area (Figure, B).A, External photograph demonstrating a firm, tender, erythematous mass located in the medial periorbital area. B, Contrast-enhanced maxillofacial computed tomographic scan showing a peripherally enhancing mass (arrowhead) in the medial aspect of the right periorbital region.Perform magnetic resonance imaging of the orbits and maxillofacial regionPrescribe topical and systemic antibiotics and recommend use of warm compresses without planned surgical or procedural intervention

what would you do next?

What would you do next?

Perform endoscopic dacryocystorhinostomy and prescribe antibiotics

Prescribe topical and systemic antibiotics and recommend use of warm compresses without planned surgical or procedural intervention

Perform magnetic resonance imaging of the orbits and maxillofacial region

Perform a biopsy of the mass

a

female

61-70

Hispanic

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2585122

A girl in her teens with a history of postconcussion syndrome was referred for retinal evaluation after failing her vision examination for her learner's permit for driving. She complained of progressively declining, blurred vision for 2 years. She denied floaters, flashes of light, headaches, and eye pain. The patient had a concussion 1 year prior after becoming dehydrated during marching band practice, fainting, and hitting her head on pavement. Her postconcussion symptoms included headaches, dizziness, and dysarthria. The headaches and dizziness resolved but the dysarthria remained. Brain magnetic resonance imaging (MRI) within the last year was normal. She denied acute vision changes after the concussion. Family history was unremarkable for vision loss, glaucoma, inherited retinal degeneration, and autoimmune disease.Best-corrected visual acuity was 20/80 OU. Ishihara testing revealed red-green color deficiency bilaterally. Intraocular pressures, extraocular motility, confrontational visual fields, and pupils were normal. Anterior segment examination was unremarkable. Ophthalmoscopic examination demonstrated mild mottled retinal pigment epithelial abnormalities bilaterally (Figure, A).Right eye multicolor fundus image and retinal spectral-domain optical coherence tomography (SD-OCT). A, Multicolor fundus image demonstrates mild macular mottling. The optic disc and retinal vessels are unremarkable. B, Retinal SD-OCT shows normal foveal contour with disruption and loss of the interdigitation and ellipsoid zones subfoveally.Fundus autofluorescence showed bilateral mild macular hyperautofluorescence likely within normal range without evidence of flecks. Retinal spectral-domain optical coherence tomography demonstrated bilateral disruption of the interdigitation and ellipsoid zones subfoveally (Figure, B). Electroretinogram (ERG) revealed delayed and decreased amplitude responses to 30-Hz flicker with normal dark-adapted responses. Goldmann visual field testing showed mild bilateral nasal constriction.Two months after presentation, the patient returned with new balance difficulties and worsening dysarthria. Horizontal and vertical saccades were markedly slowed bilaterally. What Would You Do Next?

MRI of the brain/orbits with contrast

Genetic testing

Lumbar puncture

Audiogram

Spinocerebellar ataxia 7

B

Genetic testing

When the patient returned with worsening dysarthria, saccadic slowing, and balance difficulties, the differential diagnosis narrowed to conditions producing both slowly progressive vision loss and neurological findings. A unifying diagnosis was sought.A second brain/orbital MRI with gadolinium and lumbar puncture to provide cerebrospinal fluid for an oligoclonal band screen would aid in diagnosing multiple sclerosis (MS). Multiple sclerosis is a common cause of combined vision loss and focal neurological symptoms in young women. However, several factors make MS unlikely. The patient had a normal brain MRI within a year of her visit. Additionally, vision loss in MS is typically acute and occurs over days or weeks rather than progressively over years.1 While saccades can be slow in MS, such as from internuclear ophthalmoplegia, vertical saccades are rarely affected. An audiogram is useful in diagnosing Usher syndrome. The type III subtype can produce progressive vision and hearing loss with balance problems presenting in adolescence.2,3 The vision loss in Usher syndrome, though, initially affects rod photoreceptor function. The ERG showed normal scotopic function.3 Usher syndrome would also not produce the foveal changes found on spectral-domain optical coherence tomography.3Instead, the patient’s dysarthria, balance problems, saccadic slowing, and slowly progressive vision loss associated with cone dystrophy prompted genetic testing for spinocerebellar ataxia 7 (SCA7). Genetic testing demonstrated 65 CAG repeat expansions in ATXN7, consistent with SCA7. Spinocerebellar ataxia 7 is an autosomal dominant subtype of the SCAs.4-7 The expansions cause neuronal dysfunction, leading to cell loss in the retina, cerebellum, and brainstem. An inverse correlation exists between the number of CAG repeats and age at onset.4-6 The symptoms in turn depend on the age at presentation, and earlier onset portends faster disease progression. In infancy and childhood (first decade of life), symptoms include muscle wasting, failure to thrive, and loss of motor milestones.8 In adolescent- and adult-onset cases such as this one, presentation includes ataxia, dysarthria, and dysmetria.4 Importantly, though the disease is inherited in an autosomal dominant pattern, a negative family history does not preclude the diagnosis. A parent may remain asymptomatic or present after an affected child due to genetic anticipation (especially in paternal transmission).5,6In both early- and late-onset cases, visual symptoms include decreases in central visual acuity, defects in color vision, slow saccades, and photophobia.5,6 Progression to blindness occurs earlier with childhood onset. Visual symptoms may occur before, during, or after the presentation of neurological findings.6 Therefore, initial presentation may be limited to ophthalmologic findings with a normal brain MRI. Saccadic slowing may be subtle and requires thorough motility testing as global saccadic slowing points to SCA7.Retinal degeneration is present in almost all patients with SCA7 and differentiates this subtype from the other SCAs. Cone cell degeneration occurs before involvement of rod cells, and ERG reveals cone cell dysfunction.7 Symptoms reflecting cone cell degeneration such as deficits in color vision and abnormal ERG readings may precede retinal degeneration on examination as this case demonstrates.7 On ophthalmoscopy, early changes include subtle arteriolar attenuation and loss of the foveal light reflex.9 With disease progression, atrophic macular changes develop along with pigmentary changes.9 As retinal degeneration advances, rod photoreceptor cells also deteriorate leading to complete blindness.7,9 However, as in this patient, early ophthalmoscopy may be normal even with vision abnormalities.There is no curative treatment for SCA7. Vision loss is progressive. Neurological dysfunction often leaves patients wheelchair-bound. Dysphagia presents a risk of aspiration. In association with occupational, physical, and speech therapy, the patient has continued to attend high school. The patient and her family were referred for additional genetic counseling.

Ophthalmology

A girl in her teens with a history of postconcussion syndrome was referred for retinal evaluation after failing her vision examination for her learner's permit for driving. She complained of progressively declining, blurred vision for 2 years. She denied floaters, flashes of light, headaches, and eye pain. The patient had a concussion 1 year prior after becoming dehydrated during marching band practice, fainting, and hitting her head on pavement. Her postconcussion symptoms included headaches, dizziness, and dysarthria. The headaches and dizziness resolved but the dysarthria remained. Brain magnetic resonance imaging (MRI) within the last year was normal. She denied acute vision changes after the concussion. Family history was unremarkable for vision loss, glaucoma, inherited retinal degeneration, and autoimmune disease.Best-corrected visual acuity was 20/80 OU. Ishihara testing revealed red-green color deficiency bilaterally. Intraocular pressures, extraocular motility, confrontational visual fields, and pupils were normal. Anterior segment examination was unremarkable. Ophthalmoscopic examination demonstrated mild mottled retinal pigment epithelial abnormalities bilaterally (Figure, A).Right eye multicolor fundus image and retinal spectral-domain optical coherence tomography (SD-OCT). A, Multicolor fundus image demonstrates mild macular mottling. The optic disc and retinal vessels are unremarkable. B, Retinal SD-OCT shows normal foveal contour with disruption and loss of the interdigitation and ellipsoid zones subfoveally.Fundus autofluorescence showed bilateral mild macular hyperautofluorescence likely within normal range without evidence of flecks. Retinal spectral-domain optical coherence tomography demonstrated bilateral disruption of the interdigitation and ellipsoid zones subfoveally (Figure, B). Electroretinogram (ERG) revealed delayed and decreased amplitude responses to 30-Hz flicker with normal dark-adapted responses. Goldmann visual field testing showed mild bilateral nasal constriction.Two months after presentation, the patient returned with new balance difficulties and worsening dysarthria. Horizontal and vertical saccades were markedly slowed bilaterally.

what would you do next?

What would you do next?

Genetic testing

Audiogram

Lumbar puncture

MRI of the brain/orbits with contrast

a

female

11-20

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2585031

A woman in her 70s presented with a new 4-cm left upper lobe lung mass with hilar lymphadenopathy. Biopsy results demonstrated a squamous cell carcinoma (SCC) of the lung, and chemoradiotherapy with carboplatin and paclitaxel for stage 3A disease was initiated. An allergic reaction prompted a change to cisplatin-etoposide, which continued as adjuvant chemotherapy after the radiation was complete. At first restaging, a recurrence of disease in the lung was detected, which was treated with cisplatin and gemcitabine for 4 months before she enrolled in a clinical trial (NCT02009449) in which she received combination therapy with pembrolizumab, 2 mg/kg intravenously for 21 days, and an investigational agent, AM0010 (pegylated recombinant human interleukin-10), 10 μg/kg subcutaneously on days 1 through 14 of the 21-day cycle. Three months into treatment, she developed multiple thick, mildly pruritic, yellow hyperkeratotic plaques on her lower extremities (Figure, A). A referral to a dermatology expert was initiated.A, Clinical image showing representative plaque on left leg of patient on initial presentation. B, Shave biopsy of skin (hematoxylin-eosin; original magnification ×10). C, Deeper biopsy demonstrating bandlike lymphocytic infiltration (hematoxylin-eosin; original magnification ×20). What Is Your Diagnosis?

Squamous cell carcinoma

Plaque psoriasis

Hypertrophic lichen planus

Keratoacanthoma

C. Hypertrophic lichen planus

C

Hypertrophic lichen planus

A superficial shave biopsy was performed and the results were initially interpreted as well-differentiated squamous cell carcinoma (Figure, A). Deeper excisional biopsies were performed of the originally biopsied lesion and representative smaller papulonodules. These biopsy specimens demonstrated the classic histopathologic changes seen in hypertrophic lichen planus (HLP) (Figure, B). Hypertrophic lichen planus is a subtype of lichen planus, a common skin eruption characterized histologically by a bandlike (lichenoid) lymphocytic infiltrate in the upper dermis and destruction of the basal layer of the epidermis (Figure, C).After 6 weeks of clobetasol propionate, 0.05%, a high-potency topical corticosteroid, applied under occlusion, near-complete resolution was noted.Antibodies that target the programmed cell death receptor 1 (PD-1) are gaining acceptance in oncology for a variety of neoplasms. Activated T cells express PD-1 as an immune checkpoint receptor to mediate immunosuppression and immune tolerance. Tumor and stromal cells express immunosuppressive PD-1 ligands, PD-L1 and PD-L2. Thus, inhibition of PD-1 and its immunosuppressive ligands increase antitumor T-cell response and disinhibit T-cell tolerance.1 This has emerged as a therapeutic strategy in oncology, and 3 antibody inhibitors have gained US Food and Drug Administration approval since 2014: pembrolizumab, nivolumab, and atezolizumab. Pembrolizumab is approved for melanoma and non–small-cell lung cancer (NSCLC), while nivolumab is approved for squamous and nonsquamous NSCLC, renal cancer, melanoma, and Hodgkin lymphoma; atezolizumab is approved for bladder cancer.Checkpoint inhibition can induce autoimmune responses. Clinical observation of toxic effects from immune checkpoint inhibitors has led to the identification of immune-related adverse events, including dermatologic, hepatic, and gastrointestinal toxic effects. In agents targeting PD-1, a significant percentage of such adverse events appear in the skin,2-6 termed immune-related cutaneous adverse events.5 Lichenoid tissue reactions, eczema, and vitiligo appear to be the most common immune-related cutaneous adverse events with pembrolizumab, with lichenoid reactions observed in 17% of patients in a recent single institution cohort.5 While this patient’s skin reaction developed relatively early on in her treatment course, these events typically occur later in therapy. These immune-related cutaneous adverse events do not seem to be confined to pembrolizumab and are likely a class effect.The protypical lichenoid tissue reaction is lichen planus, a pruritic eruption found in the skin and mucous membranes.7 Clinical findings are polymorphic and range from classic flat-topped polygonal purple papules to bullous, erosive, and hypertrophic variants. Lichen planus has been associated with hepatitis C, medications, and certain dental hardware.7 It is often highly pruritic and symmetric and with a predilection for the lower extremities. A growing consensus suggests the etiology is a result of T-cell–mediated autoimmune damage to basal keratinocytes expressing self-antigens. In animal models, PD-1 pathway inhibition induces T-cell responses against self-antigens, resulting in keratinocyte apoptosis.8 Corticosteroids, whether topical, intralesional, or systemic, are the cornerstone of treatment.Histologically, HLP can mimic squamous cell carcinoma with marked psuedoepitheliomatous hyperplasia, thereby presenting a diagnostic challenge. In this patient, her initial superficial shave biopsy was read as a squamous cell carcinoma. Hypertrophic lichen planus can be distinguished histologically by the presence of a lichenoid lymphocytic infiltrate in the upper dermis with associated pigment incontinence, resulting in destruction of the basal layer of the epidermis. In addition, paucity of atypical keratinocytes and hypergranulosis can help to differentiate HLP from squamous cell carcinoma. This distinction is important, because the morbidity and cost associated with the treatment of HLP is significantly lower than that of squamous cell carcinoma.The development of hypertrophic lichen planus in patients receiving pembrolizumab has emerged as a relatively common toxic effect in checkpoint inhibition,5 much as solitary BRAF inhibition is linked with the emergence of keratoacanthomas and squamous cell cancers.9 Indeed, some have proposed that cutaneous adverse effects are associated with better outcomes.4,10 Whether this is true, and whether they represent more potent immune activation, remains to be determined. Lichen planus and other immune-related cutaneous adverse events are likely to emerge with increasing frequency as the use of PD-1 inhibitors expands and combination therapies are studied. Recognition of cutaneous adverse events associated with this new class of medication is important not only to allow for proper treatment but also to prevent potentially unnecessary surgical and diagnostic procedures.

Oncology

A woman in her 70s presented with a new 4-cm left upper lobe lung mass with hilar lymphadenopathy. Biopsy results demonstrated a squamous cell carcinoma (SCC) of the lung, and chemoradiotherapy with carboplatin and paclitaxel for stage 3A disease was initiated. An allergic reaction prompted a change to cisplatin-etoposide, which continued as adjuvant chemotherapy after the radiation was complete. At first restaging, a recurrence of disease in the lung was detected, which was treated with cisplatin and gemcitabine for 4 months before she enrolled in a clinical trial (NCT02009449) in which she received combination therapy with pembrolizumab, 2 mg/kg intravenously for 21 days, and an investigational agent, AM0010 (pegylated recombinant human interleukin-10), 10 μg/kg subcutaneously on days 1 through 14 of the 21-day cycle. Three months into treatment, she developed multiple thick, mildly pruritic, yellow hyperkeratotic plaques on her lower extremities (Figure, A). A referral to a dermatology expert was initiated.A, Clinical image showing representative plaque on left leg of patient on initial presentation. B, Shave biopsy of skin (hematoxylin-eosin; original magnification ×10). C, Deeper biopsy demonstrating bandlike lymphocytic infiltration (hematoxylin-eosin; original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Hypertrophic lichen planus

Keratoacanthoma

Squamous cell carcinoma

Plaque psoriasis

a

female

71-80

original

https://jamanetwork.com/journals/jama/fullarticle/2592480

A 28-year-old man presented with abdominal pain and diarrhea (10-12 Bristol type 7 stools per day; Bristol scale range, 1-7 [1, separate hard pieces; 7, watery stool])1 after completing a course of azithromycin for pneumonia. He was diagnosed with Clostridium difficile infection (CDI) with a positive stool polymerase chain reaction (PCR) for the toxin B (tcdB) gene. Laboratory studies showed unremarkable results (Table 1). He was successfully treated with a 10-day course of oral metronidazole, and his bowel movement pattern returned to its baseline of 2 to 3 Bristol type 4 stools per day. Six weeks later, he presented with abdominal discomfort for 3 weeks relieved by bowel movements associated with increased stool frequency (4-5 Bristol type 4 stools per day). Vital signs and physical examination were unremarkable and a repeat stool test for C difficile toxin PCR was positive.Diagnose recurrent Clostridium difficile infection (CDI) and prescribe metronidazole.Diagnose postinfectious altered bowel habits with C difficile colonization and recommend a high-fiber diet.Diagnose refractory CDI and consider fecal microbiota transplantation. What Would You Do Next?

Diagnose recurrent Clostridium difficile infection (CDI) and prescribe metronidazole.

Diagnose severe CDI and prescribe vancomycin.

Diagnose postinfectious altered bowel habits with C difficile colonization and recommend a high-fiber diet.

Diagnose refractory CDI and consider fecal microbiota transplantation.

C

Diagnose postinfectious altered bowel habits with C difficile colonization and recommend a high-fiber diet.

Clostridium difficile, the most common nosocomial infection in the United States, is now increasingly being diagnosed in the community.2,3 There are an estimated 453 000 incident CDI cases associated with 29 000 deaths in the United States every year.3 Patients should undergo stool testing for C difficile only in the presence of signs (diarrhea with or without abdominal pain) or clinical or radiographic features (ileus or toxic megacolon) of CDI in the presence of risk factors such as hospitalization and antibiotic exposure, unexplained leukocytosis, or other signs of infection.Testing for C difficile can be performed by detecting C difficile toxin or toxin-producing strains. Single-step nucleic acid amplification tests (NAATs), PCR for the tcdB gene, and loop-mediated isothermal amplification (LAMP) for the tcdA gene are accurate diagnostic modalities for detecting C difficile with high sensitivity (0.87-0.92), specificity (0.94-0.97), positive likelihood ratio (26.89), and negative likelihood ratio (0.11).2,4 However, NAATs do not distinguish C difficile colonization from active CDI because toxin production is not tested.3 Retesting for C difficile within 7 days of a negative NAAT result is not recommended because of a low likelihood of subsequent positive results.4 Approximately 45% of PCR tests become negative after 3 days of CDI antibiotic therapy. Initiating CDI therapy prior to testing may result in false-negative results.5 Testing for cure should not be performed since tests remain positive in 60% of patients after successful treatment.3The Medicare midpoint reimbursement for a stool test for C difficile NAAT is $64.60.6This patient was appropriately tested and treated for CDI when he presented with diarrhea after antibiotic use. Subsequently, he developed abdominal discomfort without watery diarrhea, and repeat C difficile testing was positive. Clostridium difficile stool tests are positive in as many as 3% of outpatients and in 4% to 29% of inpatients without signs of infection.3 These patients should not be treated because antibiotics may further disrupt the gut microflora, and treating patients who have asymptomatic colonization does not prevent future infection.7 Although increased stool frequency in a patient with history of CDI is concerning for recurrent CDI, testing should only be performed in patients having at least 3 Bristol type 6 or 7 stools per day or radiographic evidence of CDI.1 This patient’s symptoms were more consistent with postinfectious altered bowel habits, similar to irritable bowel syndrome and other functional gastrointestinal disorders that occur in 25% of patients after successful CDI therapy.8 If this patient presented again with typical CDI symptoms and objective evidence of disease, treatment would be indicated.9Alternative methods to test for CDI include stool culture and cell cytotoxicity assay, which are used mostly for epidemiological purposes. In clinical practice, PCR is widely used alone or as part of an algorithm (Table 2). A typical multistep algorithm screens for glutamate dehydrogenase antigen (present in most C difficile isolates) using enzyme immunoassay (EIA) followed by EIA testing for toxin A or toxin B. NAAT can be used for confirmation when there is discrepancy between glutamate dehydrogenase and EIA toxin results.4 Multistep algorithms incorporating PCR have good sensitivity (0.68-1.0) and specificity (0.92-1.0), but approaches using only EIA have variable sensitivity (0.32-0.99).4 Patients with a positive PCR result and a negative toxin EIA had outcomes comparable with patients without C difficile by either method.10 Due to limitations from NAAT testing, a multistep test is likely the best strategy for diagnosing CDI.10The patient was advised to increase intake of dietary fiber. His symptoms improved over 8 weeks. He remained symptom free at 2-year follow-up without recurrence.Clostridium difficile testing should be restricted to patients suspected of having C difficile infection (CDI) who have watery diarrhea or clinical or radiographic evidence of ileus or toxic megacolon.Asymptomatic C difficile colonization is a common reason for a false-positive stool result.Stool C difficile testing is not appropriate after treatment of CDI in the absence of symptoms.Postinfectious functional abdominal symptoms occur in 25% of patients with CDI and should be differentiated from recurrent CDI with a careful history.

Diagnostic

A 28-year-old man presented with abdominal pain and diarrhea (10-12 Bristol type 7 stools per day; Bristol scale range, 1-7 [1, separate hard pieces; 7, watery stool])1 after completing a course of azithromycin for pneumonia. He was diagnosed with Clostridium difficile infection (CDI) with a positive stool polymerase chain reaction (PCR) for the toxin B (tcdB) gene. Laboratory studies showed unremarkable results (Table 1). He was successfully treated with a 10-day course of oral metronidazole, and his bowel movement pattern returned to its baseline of 2 to 3 Bristol type 4 stools per day. Six weeks later, he presented with abdominal discomfort for 3 weeks relieved by bowel movements associated with increased stool frequency (4-5 Bristol type 4 stools per day). Vital signs and physical examination were unremarkable and a repeat stool test for C difficile toxin PCR was positive.Diagnose recurrent Clostridium difficile infection (CDI) and prescribe metronidazole.Diagnose postinfectious altered bowel habits with C difficile colonization and recommend a high-fiber diet.Diagnose refractory CDI and consider fecal microbiota transplantation.

what would you do next?

What would you do next?

Diagnose postinfectious altered bowel habits with C difficile colonization and recommend a high-fiber diet.

Diagnose recurrent Clostridium difficile infection (CDI) and prescribe metronidazole.

Diagnose severe CDI and prescribe vancomycin.

Diagnose refractory CDI and consider fecal microbiota transplantation.

a

male

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2546025

A woman in her 30s presented with multiple discrete and clustered blue papules on her face and extremities. The lesions had been present since childhood, but the size of the lesions and the intensity of pain associated with them had recently increased with even light touch causing paroxysms of pain. The pain associated with these papules worsened as the day progressed, and she could not tolerate elastic compression due to excessive pain on compression. Her medical and family histories were unremarkable. Physical examination revealed multiple discrete and agminated blue papules on the face, arms, hands, and thighs with a cobblestoned appearance (Figure 1). On palpation, the papules were exquisitely tender and partially compressible. The patient underwent duplex ultrasonography of representative papules on the thigh, and a skin biopsy specimen of a papule on the thigh was obtained for histopathologic evaluation.Clinically, multiple discrete and agminated blue papules are apparent, nodular, blue cutaneous lesions cobblestone-like in appearance, on the thigh (A) and hand and thigh (B). What Is Your Diagnosis?

Blue rubber bleb nevus syndrome

Venous malformation

Hemangioma

Glomuvenous malformation

D. Glomuvenous malformation (GVM)

D

Glomuvenous malformation

Histopathologic examination of the biopsy specimen revealed dilated, thin-walled vascular spaces lined by cuboidal glomus cells in the dermis and subcutis (Figure 2). The cells were monomorphous and lacked atypical features.Histopathologic papule specimens demonstrate dilated, thin-walled veins surrounded by cuboidal glomus cells (hematoxylin-eosin).The patient underwent duplex ultrasonography of the thigh that showed normal superficial and deep venous systems without reflux, and a subsequent magnetic resonance angiogram excluded arteriovenous communications. After sclerotherapy, the papules did not resolve, and the patient reported increased pain of the treated areas; she elected to pursue surgical excision of 10 symptomatic papules on the thigh. Postoperatively and at last follow-up, she was pain free without evidence of recurrence.Venous anomalies are a group of slow-flow vascular malformations with an estimated incidence of 1 in 10 000. Venous malformations (VMs) account for 95% of patients with venous anomalies.1First described by Masson2 in 1924, GVMs are the most common heritable vascular malformation and account for 5% of VMs. It should be noted that GVMs are a distinct pathologic process from VMs. Most GVMs are inherited in an autosomal dominant fashion, although they also may occur sporadically. This trait tends to show incomplete penetrance that increases with age and has wide heterogeneity, even among affected first-degree relatives. A genetic diagnosis should be considered whenever there is a family history of vascular malformations, particularly multiple lesions.Diagnosing GVMs is challenging; they are often misdiagnosed as hemangiomas or inherited mucocutaneous VMs. Correct diagnosis is imperative because the outcome and treatment for GVMs differ from those of other malformations, especially VMs. Often appearing during childhood or adolescence, GVMs present as pink to deep blue multifocal nodules or plaques, and 78% are located on the extremities.1 They are clinically distinguished from other malformations by their characteristic cobblestoned appearance, pain on palpation, lack of fullness with exercise or dependency, and incompressibility with elastic compression. Histologic findings confirm the diagnosis and are characterized by branching vascular channels lined by endothelial cells interspersed with cuboidal glomus cells with well-defined nucleoli.3The anatomic pathogenesis of familial GVMs is a loss-of-function mutation in the glomulin (GLMN) gene that causes the benign neoplasms to arise from glomus bodies. The glomus unit, also known as the Secquet-Hoyer canal, is responsible for thermoregulatory function and is composed of an afferent artery, an arteriovenous canal, neuroreticular elements, lamella of collagen, and collecting veins.Although treatment for GVMs is largely symptomatic and cosmetic, accurate diagnosis is paramount for planning therapy. Compression often exacerbates GVMs, whereas patients with large VMs generally benefit from external compression. Surgical excision of GVMs is feasible because they are discrete and superficially located, whereas VMs pose a greater surgical dilemma because they are more ill defined and can involve deeper structures. Furthermore, sclerotherapy is more effective in shrinking VMs than GVMs. Ablative therapy with argon, carbon dioxide, and pulsed-dye lasers as well as sclerotherapy have been used to successfully treat GVMs,4-6 although results can vary.7 Surgical excision remains the gold standard treatment for GVMs, but their multifocal nature may necessitate numerous excisions and undesirable scarring.This case illustrates the importance of accurately diagnosing GVMs because the treatment of GVMs differs from other vascular malformations. Because VMs account for the majority of vascular malformations, it is imperative that primary care physicians, dermatologists, and vascular specialists are able to accurately distinguish GVMs to direct appropriate care.

Dermatology

A woman in her 30s presented with multiple discrete and clustered blue papules on her face and extremities. The lesions had been present since childhood, but the size of the lesions and the intensity of pain associated with them had recently increased with even light touch causing paroxysms of pain. The pain associated with these papules worsened as the day progressed, and she could not tolerate elastic compression due to excessive pain on compression. Her medical and family histories were unremarkable. Physical examination revealed multiple discrete and agminated blue papules on the face, arms, hands, and thighs with a cobblestoned appearance (Figure 1). On palpation, the papules were exquisitely tender and partially compressible. The patient underwent duplex ultrasonography of representative papules on the thigh, and a skin biopsy specimen of a papule on the thigh was obtained for histopathologic evaluation.Clinically, multiple discrete and agminated blue papules are apparent, nodular, blue cutaneous lesions cobblestone-like in appearance, on the thigh (A) and hand and thigh (B).

what is your diagnosis?

What is your diagnosis?

Hemangioma

Blue rubber bleb nevus syndrome

Venous malformation

Glomuvenous malformation

d

female

31-40

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2547136

A woman in her 20s presented to our department for treatment of multiple facial papules. The lesions were present since childhood, progressively increasing in number. They involved primarily her face, and, less so, her extremities and trunk. There was no medical history of spontaneous regression. She had a young brother, who had the same papular lesions that had followed the same natural history, displaying a similar bodily distribution although fewer in number. Previous studies and imaging of the 2 siblings had failed to reveal any systemic findings.Physical examination revealed multiple smooth skin-colored and erythematous papules of various size, some with telangiectasia, with a medial but asymmetrical distribution on the face (Figure, A). Identical, less numerous lesions were also present on her hands and back. Three biopsy samples were taken and showed similar findings (Figure, B-D). A, Multiple skin-colored to erythematous asymptomatic facial papules in a woman in her 20s. The papules were present in childhood and were increasing in number. B, Hematoxylin-eosin stain (original magnification ×20). C, Hematoxylin-eosin stain (original magnification ×40). D, Alcian blue stain (original magnification ×10). What Is Your Diagnosis?

Birt-Hogg-Dube syndrome

Hereditary progressive mucinous histiocytosis

Multiple eruptive dermatofibromas

Acral persistent papular mucinosis

B. Hereditary progressive mucinous histiocytosis (HPMH).

B

Hereditary progressive mucinous histiocytosis

The biopsies showed dilated vessels, mucin deposits, in addition to a prominent histiocytic proliferation made of spindle or globular cells, which were CD68 positive, CD1a negative and S100 negative. There were neither abnormal follicular structures as may be seen in trichofolliculoma, nor perifollicular fibrosis. The dermis was much more cellular, with more mucin than what is observed in angiofibromas. Altogether, the familial history, clinical presentation, evolution and histopathology were suggestive of hereditary progressive mucinous histiocytosis (HPMH). Indeed, specimens examined under transmission electron microscopy revealed histiocytes with a cytoplasm rich in characteristic vacuoles. They formed zebra bodies containing stacked transverse lamellae, or, myelin bodies (vacuoles with concentric rings of myelin). No Birbeck granules were noted. The biopsy specimens from the younger brother showed similar histopathologic and electron microscopic features. We treated our patient with ablative CO2 laser (Sharplan, Lumenis industries, 10 watts) with good improvement. The results were maintained at 2 years of follow-up.Hereditary progressive mucinous histiocytosis is considered to be a type of a nonlangerhans cell histiocytosis.1 However, because of its rarity, it has not always been incorporated in classification models. To the best of our knowledge, 22 cases have been described in the literature worldwide. Of these, 17 were familial cases, presumed to present an autosomal dominant pattern of inheritance. The remaining 5 were sporadic cases.Hereditary progressive mucinous histiocytosis seems to present with 2 distinct phases in patients with the inherited variant. The first phase is seen in infancy and is characterized by dermal nodules that can be seen on the scalp, trunk, and extremities. These lesions regress spontaneously.2,3 It is unclear whether the infantile stage is present in all patients. The second phase starts at a later stage, in childhood and up to early adulthood. Papules appear and keep progressing throughout life with no spontaneous resolution.2 They are smooth, skin-colored or erythematous to red brown, ranging from 1 to 10 mm in size. The lesions are generally asymptomatic, although mild pruritus has been occasionally described. Most common locations include face, scalp, hands, forearm and thighs. There is no associated mucosal, visceral, or systemic involvement and the course is benign. As opposed to other diseases on the differential of HPMH, the lack of systemic involvement makes the recognition of this entity particularly important. It allows to reassure patients on their prognosis and avoid unnecessary exams. Alternatively, patients with sporadic HPMH only develop the second phase lesions at a later age, from 30 to 60 years.3-6Reported histological findings are similar, ie, well-circumscribed aggregates of epithelioid and spindled histiocytes in the upper and mid dermis, with mucinous stroma, and dilated vessels.5 In addition, some reports found an increased number of mast cells. Although iron deposits in the dermis have been described, they are not consistently found in all patients.6 The lack of very specific clinical and histological findings makes the diagnosis difficult and often delayed, as was the case in our patient. Clinicopathological differential diagnosis includes dermatofibromas, other nonlangerhans cell histiocytoses, papular mucinosis, and adnexal tumors. Immunohistochemical staining shows a disparity for CD68 with some cases staining positive4,5,7 while others were negative.8-10 The staining is consistently negative for Langerhans cell markers CD1a and S100. The association of unusual histiocytic proliferation with mucin deposits is suggestive of the disease. Findings under electron microscopy are pathognomonic and reveal abundant vacuoles, myelin bodies, and zebra bodies in the cytoplasm of lesional histiocytes.2,8The progressive nature of HPMH differentiates it from nonlangerhans cell histiocytoses that present with lesions that regress spontaneously after a few years, such as multicentric reticulohistiocytosis or generalized eruptive histiocytoma. On the other hand, although nodular histiocytosis also follows a nonremitting course, it tends to have a more generalized distribution, bigger lesions with a central depression reaching up to 5 cm and associated systemic findings.5Treatment has been unrewarding. Topical steroids, cryotherapy, imiquimod, and pulsed dye laser have been tried with unsatisfactory results.2 Thalidomide (100mg/d), used in a woman in her 30s, resulted in a decrease in the size of the lesions while no new papules developed for the treatment duration.4 The best treatment modalities so far seem to be surgical removal or destruction of lesions.

Dermatology

A woman in her 20s presented to our department for treatment of multiple facial papules. The lesions were present since childhood, progressively increasing in number. They involved primarily her face, and, less so, her extremities and trunk. There was no medical history of spontaneous regression. She had a young brother, who had the same papular lesions that had followed the same natural history, displaying a similar bodily distribution although fewer in number. Previous studies and imaging of the 2 siblings had failed to reveal any systemic findings.Physical examination revealed multiple smooth skin-colored and erythematous papules of various size, some with telangiectasia, with a medial but asymmetrical distribution on the face (Figure, A). Identical, less numerous lesions were also present on her hands and back. Three biopsy samples were taken and showed similar findings (Figure, B-D). A, Multiple skin-colored to erythematous asymptomatic facial papules in a woman in her 20s. The papules were present in childhood and were increasing in number. B, Hematoxylin-eosin stain (original magnification ×20). C, Hematoxylin-eosin stain (original magnification ×40). D, Alcian blue stain (original magnification ×10).

what is your diagnosis?

What is your diagnosis?

Acral persistent papular mucinosis

Birt-Hogg-Dube syndrome

Multiple eruptive dermatofibromas

Hereditary progressive mucinous histiocytosis

d

female

21-30

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2548246

A man in his 60s who was a former smoker with a medical history of chronic obstructive pulmonary disease, type 2 diabetes, chronic kidney disease, anemia, and cervical myelopathy experienced low-grade fevers, unintentional 80-pound weight loss, productive cough, and development of cutaneous ulcers over a 6-month period after cervical spine fusion. Two ulcers developed at the surgical site, and 2 similar ulcers developed on his back shortly after cyst excision. He had been recently diagnosed with lung cancer based on computed tomographic (CT) and positron emission tomographic imaging showing an enhancing, hypermetabolic, 7-cm cavitary right upper lobe mass with mediastinal adenopathy. A chest x-ray 6 months prior revealed negative results. A few days after establishing care, he presented to the emergency department with extreme weakness and intolerable pain related to his ulcers. Physical examination revealed an ill-appearing man. In the right upper lobe, there were decreased breath sounds with clear auscultation in the remaining chest. On the right anterior neck were two, 3- to 4-cm tender ulcers extending to the deep subcutaneous fat with erythematous, friable borders (Figure). On his back were 2 similar 2- to 2.5-cm ulcers. Inflammatory markers were notably elevated. A complete autoimmune panel, indirect immunofluorescence assays, enzyme immunoassays for antineutrophil cytoplasmic antibodies (c-ANCA)/proteinase 3, antineutrophil cytoplasmic antibody/myeloperoxidase, a quantiferon gold test, cultures of blood, broncheoalveolar washings, and tissue analysis were performed. Only c-ANCA testing revealed positive results. A CT scan of the sinus showed multiple bony defects and acute and chronic sinusitis. A transbronchial biopsy of the lung and excisional biopsy of the skin bridge between back ulcers were performed.A, Two deep ulcers of the right mid-lower back with erythematous borders. B, Hematoxylin and eosin stain (original magnification × 5). C, Hematoxylin and eosin stain (original magnification × 200). D, Hematoxylin and eosin stain (original magnification × 200). What Is Your Diagnosis?

Disseminated tuberculosis

Paraneoplastic pyoderma gangrenosum

Disseminated nocardiosis

Granulomatosis with polyangiitis

D. Granulomatosis with polyangiitis

D

Granulomatosis with polyangiitis

Histopathologic evaluation of the excisional skin biopsy demonstrated deep ulceration with associated small and medium vessel leukocytoclastic vasculitis, necrosis and abundant infiltrating neutrophils. Transbronchial biopsy results showed acute and necrotizing granulomatous inflammation. Pulse dose corticosteroids and intravenous rituximab were started, which stabilized and improved his condition. At 5-month follow-up, the lung and cutaneous lesions had substantially healed, and no new lesions had developed. No malignant abnormalities of the lungs were present.Granulomatosis with polyangiitis (GPA), formerly called Wegener granulomatosis, is a rare autoimmune disease often associated with c-ANCA and manifests as widespread granulomatous inflammation and necrotizing vasculitis commonly involving the upper and lower respiratory tracts and kidneys.1 Skin involvement can occur in up to 50% of patients, with primary skin lesions presenting up to 25% of the time.2-4 A subset of the primary skin lesions is pyoderma gangrenosumlike ulcers, an initial feature in about 5% of cases.1-9 Other cutaneous manifestations include palpable purpura, papules, vesicles, and bullae.Histologic tissue examination demonstrates small and medium-vessel leukocytoclastic vasculitis with a mixed acute and chronic, necrotizing inflammatory infiltrate with a variable degree of granulomatous inflammation. The histopathologic findings of GPA are not specific and may be seen in infectious or other autoimmune diseases, it is therefore important to consider the distribution of the disease process and laboratory findings. This patient was comprehensively evaluated with a complete autoimmune panel and batteries of studies searching for bacterial (especially mycobacterial), fungal, viral, and parasitic organisms, which eliminated an infectious etiology.Pyoderma gangrenosum, as an idiopathic or paraneoplastic process, was originally in the clinical differential diagnosis. It is a diagnosis of exclusion with potential for misdiagnosis if a true etiology for cutaneous ulceration exists yet is never discovered. The pathology in our case is most consistent with GPA, a sterile vasculitis rather than a sterile neutrophilic dermatosis. The overall diagnosis in this case was multifactorial and based on clinical presentation (ie, sinus and lung involvement), laboratory test results (ie, positive c-ANCA and negative workup for infection, malignant abnormalities, etc), and skin biopsy, all of which pointed to a diagnosis of GPA.Generalized GPA is rapidly progressive with death occurring an average of 5 months after presentation without adequate immune suppressive and/or modulating therapies.10 Therapeutic regimens depend on disease severity, including extent of involvement and degree of end-organ damage. Systemic corticosteroids are first line therapy and are often combined with cyclophosphamide. Additional therapies include tacrolimus and rituximab. As with this patient, recovery is often slow, requiring close clinical follow-up to ensure patient improvement and long-term stability.

Dermatology

A man in his 60s who was a former smoker with a medical history of chronic obstructive pulmonary disease, type 2 diabetes, chronic kidney disease, anemia, and cervical myelopathy experienced low-grade fevers, unintentional 80-pound weight loss, productive cough, and development of cutaneous ulcers over a 6-month period after cervical spine fusion. Two ulcers developed at the surgical site, and 2 similar ulcers developed on his back shortly after cyst excision. He had been recently diagnosed with lung cancer based on computed tomographic (CT) and positron emission tomographic imaging showing an enhancing, hypermetabolic, 7-cm cavitary right upper lobe mass with mediastinal adenopathy. A chest x-ray 6 months prior revealed negative results. A few days after establishing care, he presented to the emergency department with extreme weakness and intolerable pain related to his ulcers. Physical examination revealed an ill-appearing man. In the right upper lobe, there were decreased breath sounds with clear auscultation in the remaining chest. On the right anterior neck were two, 3- to 4-cm tender ulcers extending to the deep subcutaneous fat with erythematous, friable borders (Figure). On his back were 2 similar 2- to 2.5-cm ulcers. Inflammatory markers were notably elevated. A complete autoimmune panel, indirect immunofluorescence assays, enzyme immunoassays for antineutrophil cytoplasmic antibodies (c-ANCA)/proteinase 3, antineutrophil cytoplasmic antibody/myeloperoxidase, a quantiferon gold test, cultures of blood, broncheoalveolar washings, and tissue analysis were performed. Only c-ANCA testing revealed positive results. A CT scan of the sinus showed multiple bony defects and acute and chronic sinusitis. A transbronchial biopsy of the lung and excisional biopsy of the skin bridge between back ulcers were performed.A, Two deep ulcers of the right mid-lower back with erythematous borders. B, Hematoxylin and eosin stain (original magnification × 5). C, Hematoxylin and eosin stain (original magnification × 200). D, Hematoxylin and eosin stain (original magnification × 200).

what is your diagnosis?

What is your diagnosis?

Granulomatosis with polyangiitis

Paraneoplastic pyoderma gangrenosum

Disseminated tuberculosis

Disseminated nocardiosis

a

male

61-70

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2565823

A man in his 50s presented with weakness in the distal right hand and leg and paresthesias of the right hand. Four days before presentation, he experienced sudden, severe neck pain that swiftly progressed to neck stiffness and bilateral shoulder pain. The next day, he noticed weakness in the right arm and leg. The day before hospitalization, the weakness progressed, and he lost the ability to ambulate. Until 18 months ago, he had worked as a clerk, but he retired because of a history of hypertension and diabetes. His family history revealed no neurological disorders, except for a brother who had a brain lesion excised. On examination, he was afebrile, and his vital signs were normal. He was fully alert but had weakness in the right distal arm (medical research council [MRC] grade 3/5) and the right leg (MRC grade 4/5) with sensory impairment to pinprick and temperature in the left leg. Laboratory values revealed an elevated γ-glutamyltransferase level of 615 U/L (reference range, 10-71 U/L). Analysis of the cerebrospinal fluid indicated xanthochromia; normal white blood cell count, 1 cell/µL; red blood cell count, 2.19 × 10/μL; increased glucose level at 133 mg/dL (reference range, 40-80 mg/dL); increased total protein level at 0.10 g/dL (reference range, 0.03-0.05 mg/dL); and increased lactate level at 28.8 mg/dL (reference range, 9.9-21.6 mg/dL). Magnetic resonance imaging (MRI) of the brain and the entire spinal cord revealed patency of the intracranial vessels and multiple abnormal signals throughout the brain on T1-, T2-, and susceptibility-weighted sequences (SWIs) and 1 lesion at the level of the fifth cervical vertebra (Figure).A, Susceptibility-weighted magnetic resonance image (MRI) showing numerous intraparenchymal hypointensities (red arrowheads). B, T1-weighted MRI at the level of the fifth cervical vertebra showing hyperintensity in the right ventral portion of the spinal cord (red arrowhead). C, T2-weighted MRI showing central hypointensity of the spinal cord between the levels of the fifth cervical and seventh thoracic vertebrae (not shown) (red arrowheads).Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy What Is Your Diagnosis?

Amyloid angiopathy

Multiple cavernous malformations

Metastatic melanoma

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

B. Multiple cavernous malformations

B

Multiple cavernous malformations

Brain and spinal cord MRI showed multiple hemorrhages throughout the brain as hypointensities on SWI. T1 and T2 sequences showed various stages of bleeding throughout the brain (not shown) and one acute hemorrhage in the spinal cord (Figure).Because of spinal cord involvement, an amyloid angiopathy was highly unlikely. The other consideration was metastatic melanoma; however, there was no evidence of a mass effect on MRI. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy was another possibility; however, our patient had no evidence of leukoencephalopathy.The spinal T1 hyperintensity at the cervical level was consistent with acute bleeding in the right ventral portion of the spinal cord and the patient’s symptoms. There was a large syrinx cavity underneath the spinal cavernoma that was hypointense on T2 MRI and was consistent with a hematosyrinx, a rare complication of an intraspinal mass. The presentation was consistent with Brown-Sequard syndrome.Neurosurgical exploration of the patient's spinal cord lesion revealed a cavernous malformation. Apparently, the brain lesion his brother had resected was also a cavernous malformation.Developmental abnormalities of the brain and spinal vessels are found in 4% of the population and are known to cause focal neurological deficits. Cerebral cavernous malformations (CCMs) account for 8% to 15% of these abnormalities and are characterized by closely clustered and irregularly dilated capillaries.1 Only 20% of CCMs are familial (FCCMs), which are defined as an autosomal dominant trait with incomplete penetrance. They are characterized by a multiplicity of lesions along the neuroaxis, with an average of 20 in each patient, but they can be innumerable. Mutations in the k-rev interaction trapped protein 1 (KRIT1), MGC4607, and programmed cell death 10 (PDCD10) genes are associated with FCCMs. These genes are encoding proteins that modulate junction formation between endothelial cells.2 Symptomatic spinal involvement occurs in 5.5% of patients with CCM.3The diagnostic method of choice is MRI SWI because it is sensitive to hemoglobin degradation products. Cerebral cavernous malformations appear at the rate of 0.2 lesions per patient-year, with older lesions changing in size.4 The bleeding risk as determined by lesion-years is 1.1% to 2.5% per year. The differential diagnoses include hemorrhagic metastatic lesions, meningiomas, low- and high-grade gliomas, cysticercosis and lipomas.3Up to 60% of all patients with FCCMs are symptomatic. The initial event is a seizure in 55% of patients, cerebral hemorrhage in 32%, and focal symptoms or headache in 13%.5 The mean age at symptom onset is 30 years, but there is no sex prevalence. Supratentorial lesions are associated with seizures and a better prognosis, whereas infratentorial lesions are associated with a worse prognosis and focal neurological deficits.6 Symptomatic lesions should be invasively treated, but the choice between neurosurgical management and stereotactic radiosurgery depends heavily on the lesion location. Nonoperatively managed spinal CCM could have a poor prognosis.7 After symptomatic hemorrhage, 40% of these patients show a full recovery, although 20% die.8 Close clinical and neuroimaging follow-up is recommended, along with genetic counseling for family members.A positive family history indicated a genetic disorder, which was confirmed with molecular diagnostic and histological analysis of the operated tissue. The patient experienced familial cerebral cavernous malformation syndrome with a newly described mutation at c.1820dupA, p.N607Kfs*6 in exon 17 of the KRIT1 gene. The intrasyringeal hemorrhage (Gowers syndrome9) was also present.The patient’s condition deteriorated, and he underwent repeated spine MRI, which showed signs of bleeding into the syrinx on the eighth day (image not shown). He underwent neurosurgical intervention on the 11th day after symptom onset. Intraoperatively, the syrinx cavity appeared to be filled with blood. The postoperative hematosyrinx cavity shrank from 4.5 to 3.7 mm (measured on matched sagittal projections at the level of T3 to T6 on the fourth and eighth days after symptom onset and then at the 21st postoperative day). One month after admission, he was discharged with weakness in the right arm, paraplegia, and a sensory level at the sixth thoracic level.

Neurology

A man in his 50s presented with weakness in the distal right hand and leg and paresthesias of the right hand. Four days before presentation, he experienced sudden, severe neck pain that swiftly progressed to neck stiffness and bilateral shoulder pain. The next day, he noticed weakness in the right arm and leg. The day before hospitalization, the weakness progressed, and he lost the ability to ambulate. Until 18 months ago, he had worked as a clerk, but he retired because of a history of hypertension and diabetes. His family history revealed no neurological disorders, except for a brother who had a brain lesion excised. On examination, he was afebrile, and his vital signs were normal. He was fully alert but had weakness in the right distal arm (medical research council [MRC] grade 3/5) and the right leg (MRC grade 4/5) with sensory impairment to pinprick and temperature in the left leg. Laboratory values revealed an elevated γ-glutamyltransferase level of 615 U/L (reference range, 10-71 U/L). Analysis of the cerebrospinal fluid indicated xanthochromia; normal white blood cell count, 1 cell/µL; red blood cell count, 2.19 × 10/μL; increased glucose level at 133 mg/dL (reference range, 40-80 mg/dL); increased total protein level at 0.10 g/dL (reference range, 0.03-0.05 mg/dL); and increased lactate level at 28.8 mg/dL (reference range, 9.9-21.6 mg/dL). Magnetic resonance imaging (MRI) of the brain and the entire spinal cord revealed patency of the intracranial vessels and multiple abnormal signals throughout the brain on T1-, T2-, and susceptibility-weighted sequences (SWIs) and 1 lesion at the level of the fifth cervical vertebra (Figure).A, Susceptibility-weighted magnetic resonance image (MRI) showing numerous intraparenchymal hypointensities (red arrowheads). B, T1-weighted MRI at the level of the fifth cervical vertebra showing hyperintensity in the right ventral portion of the spinal cord (red arrowhead). C, T2-weighted MRI showing central hypointensity of the spinal cord between the levels of the fifth cervical and seventh thoracic vertebrae (not shown) (red arrowheads).Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

what is your diagnosis?

What is your diagnosis?

Multiple cavernous malformations

Metastatic melanoma

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Amyloid angiopathy

a

male

51-60

White

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2586274

An 18-month-old boy presented to the emergency department with a rash on the left lower extremity. He was fully vaccinated, with routine vaccines at 12 months of age administered in the left thigh. The influenza vaccine was administered 1 week prior to presentation in the left buttock, after which his parents noted a red patch near the site of vaccination. The patch became raised and spread down the left thigh over the course of several days. The rash did not bleed, ulcerate, weep, or appear itchy or painful, though the patient did seem uncomfortable when getting dressed. He had no known sick contacts at day care, exposure to herpes simplex virus, or exposure to new topical products or clothing. His pediatrician prescribed cephalexin and mupirocin for a presumed cutaneous bacterial infection. The eruption continued to spread down his left thigh over the next 2 days, at which point the pediatrician advised the family to go to the emergency department.On examination, the boy was afebrile and well-appearing. There were multiple discrete clusters of monomorphic pink to violaceous papulovesicles with surrounding erythema scattered across the left buttock, thigh, and upper calf, some with central punctate hemorrhagic crust (Figure). The lesions were nontender. There were no skin lesions elsewhere. A test was performed.Discrete clusters of monomorphic pink to violaceous papulovesicles with surrounding erythema. What Is Your Diagnosis?

Microcystic lymphatic malformation

Eczema herpeticum

Herpes zoster

Hypersensitivity reaction

Herpes zoster

C

Herpes zoster

The grouped papulovesicles in a unilateral L3-L5 distribution involving the same extremity in which the varicella-zoster virus (VZV) vaccine was administered raised suspicion for herpes zoster in this patient. Direct fluorescent antibody of a vesicle confirmed the presence of VZV. Because the patient’s eruption was asymptomatic and improving by the time that test results were available, treatment with acyclovir was deferred.Varicella-zoster virus reactivation resulting in herpes zoster is a well-described, but uncommon, occurrence in healthy children immunized with live attenuated varicella vaccine. Average age at onset of herpes zoster is approximately 4 years among vaccinated children.1 Herpes zoster may occur less frequently after vaccination than natural infection, possibly because the attenuated virus is less able to replicate than wild-type virus.1 Approximately 15 to 30 cases of herpes zoster occur per 100 000 vaccinated children per year, corresponding to about 700 to 900 cases per year in the United States.1,2 Risk factors for herpes zoster include receipt of any vaccination within 30 days prior to symptom onset and race reported as white or Asian (compared with black).3 Less than 5% of pediatric patients with herpes zoster have an immunodeficiency or are receiving immunosuppressive therapy.3-5 In addition, long-term follow-up of healthy children with herpes zoster has not demonstrated an increased rate of conditions associated with immune deficiency.6 Thus, evaluation for immune deficiency is not warranted in the setting of herpes zoster in an otherwise healthy child.Herpes zoster classically presents as a painful eruption with true vesicles in a single dermatome. However, atypical presentations are more common following VZV vaccination and are characterized by minimally tender eruptions that may be more papular than vesicular as compared with zoster following natural VZV infection.2 Herpes zoster lesions in vaccinated children can represent reactivation of either vaccine-type VZV or wild-type VZV, which can infect vaccinated children without producing clinical disease and remain latent in multiple sensory ganglia.7,8 Diagnosis can be confirmed by a swab specimen via direct fluorescent antibody or polymerase chain reaction, both of which have a rapid turnaround time. However, increased sensitivity has been demonstrated with polymerase chain reaction testing. Antiviral therapy is not needed in most healthy children. However, treatment may be considered in immunocompromised individuals or those with disseminated disease and would be most effective within the first 72 hours of rash onset.The differential diagnosis for a clustered, vesicular, and erythematous eruption includes lymphatic malformations, hypersensitivity reactions, and eczema herpeticum. The morphology of our patient’s eruption raised concern for a microcystic lymphatic malformation (lymphangioma circumscriptum), which is a benign congenital malformation of dilated superficial lymphatic vessels leading to monomorphic pseudovesicles (appearing to contain clear fluid) often described as “frog spawn” in appearance. While lymphatic malformations can become more prominent after trauma, such as vaccination, the acute time course of this patient’s eruption with no precursor lesion reduced the likelihood of lymphatic malformation. Cutaneous hypersensitivity reactions can have a wide range of clinical appearances and have been reported following vaccination. However, hypersensitivity reactions are usually generalized and pruritic. An early presentation of eczema herpeticum could appear as vesicles in areas affected by atopic dermatitis, but eczema herpeticum tends to be pruritic or painful and rapidly progresses to punched-out erosions with hemorrhagic crust.Here, we describe an atypical presentation of a common clinical entity. Early recognition of herpes zoster can facilitate timely and effective intervention. However, decreased incidence coupled with more atypical findings in vaccinated children makes this diagnosis a clinical challenge that is likely to persist in years to come.

Pediatrics

An 18-month-old boy presented to the emergency department with a rash on the left lower extremity. He was fully vaccinated, with routine vaccines at 12 months of age administered in the left thigh. The influenza vaccine was administered 1 week prior to presentation in the left buttock, after which his parents noted a red patch near the site of vaccination. The patch became raised and spread down the left thigh over the course of several days. The rash did not bleed, ulcerate, weep, or appear itchy or painful, though the patient did seem uncomfortable when getting dressed. He had no known sick contacts at day care, exposure to herpes simplex virus, or exposure to new topical products or clothing. His pediatrician prescribed cephalexin and mupirocin for a presumed cutaneous bacterial infection. The eruption continued to spread down his left thigh over the next 2 days, at which point the pediatrician advised the family to go to the emergency department.On examination, the boy was afebrile and well-appearing. There were multiple discrete clusters of monomorphic pink to violaceous papulovesicles with surrounding erythema scattered across the left buttock, thigh, and upper calf, some with central punctate hemorrhagic crust (Figure). The lesions were nontender. There were no skin lesions elsewhere. A test was performed.Discrete clusters of monomorphic pink to violaceous papulovesicles with surrounding erythema.

what is your diagnosis?

What is your diagnosis?

Hypersensitivity reaction

Microcystic lymphatic malformation

Eczema herpeticum

Herpes zoster

d

male

0-10

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2559961

A man in his 30s presented to his primary care clinician after 2 years of worsening abdominal discomfort and an increasingly large recurrent umbilical hernia. He described early satiety but had no nausea or vomiting. He reported night sweats and a 9.1-kg weight loss over the prior 6 months. His medical history was unremarkable. His social history was notable for a 15-pack-year smoking history and consumption of 6 to 8 beers per night. He had no family history of malignant disease. On examination he had no fever, a reducible umbilical hernia, a palpable left-sided abdominal mass, and significant bilateral lower extremity edema. Laboratory evaluation revealed anemia for which the patient received several blood transfusions, leukocytosis (white blood cell count, 57 000/μL), and hyponatremia (sodium level, 128 mEq/L). He was first referred to the hematology service, and a blood smear showed 74% neutrophils. A bone marrow biopsy specimen showed a hypercellular marrow with a myeloid left shift but no increase in blasts or dyspoiesis. Tests for BCR/ABL and peripheral blood JAK2 mutation were negative. Computed tomography revealed splenomegaly, hydronephrosis, and a 25-cm left-sided retroperitoneal mass (Figure). Surgical consultation was requested.Computed tomographic images. A, A large retroperitoneal mass extending from the upper abdomen into the pelvis. B, A mass encasement of the left kidney. What Is Your Diagnosis?

Adrenocortical carcinoma

Liposarcoma

Lymphoma

Leiomyosarcoma

B. Liposarcoma

B

Liposarcoma

The patient was taken to the operating room and underwent a midline laparotomy. Approximately 500 mL of straw-colored ascites were encountered on entry into the abdomen. Significant splenomegaly and signs of left-sided portal hypertension were apparent. The mass was densely adherent to the body and tail of the pancreas and completely encased the left kidney. The mass was therefore resected en bloc with the distal pancreas, spleen, left kidney, and left adrenal. On postoperative day 0, his leukocytosis resolved (white blood cell count, 6000/μL).Pathologic examination of the retroperitoneal mass identified a largely dedifferentiated liposarcoma (French Federation of Cancer Centers Sarcoma Group [FNCLCC] grade 2) with associated well-differentiated components. The dedifferentiated component of the liposarcoma contained a prominent inflammatory infiltrate with numerous neutrophils and scattered eosinophils and plasma cells (described as an inflammatory malignant fibrous histiocytoma). The spleen showed red pulp expansion by a granulocytic proliferation. The kidney and adrenal gland were surrounded by the sarcoma but were otherwise normal.Retroperitoneal sarcomas are relatively rare tumors, of which liposarcomas are the most common variant. Inflammatory malignant fibrous histiocytoma is an even rarer subtype of liposarcoma. These tumors of mesenchymal origin are associated with a clinically significant systemic leukemoid reaction and contain a predominance of neutrophils and eosinophils. The exceptionally high white blood cell count associated with these masses, which often abruptly normalizes after resection, can easily lead to misdiagnosis as leukemia or infection. Bone marrow biopsy, when performed, can help differentiate leukemia from inflammatory malignant fibrous histiocytoma, in which a hypercellular bone marrow is found but without any monoclonal proliferation.Surgical resection is the principal treatment, and multiorgan en bloc resection is frequently required to obtain complete macroscopic excision of the mass. Chemotherapy is generally not useful. The effectiveness of radiation is controversial, given the absence of randomized clinical trial evidence showing survival benefit. Many still favor its use, especially in cases with the highest risk of recurrence, given the potential of radiotherapy to decrease local recurrence.1 Following surgical resection, a recurrent leukocytosis frequently marks disease recurrence.2 The leukocytosis associated with these masses led some to initially believe that they were of lymphomatous origin, but they are now considered a subtype of dedifferentiated liposarcoma based on immunohistochemical and genomic analysis.3

Surgery

A man in his 30s presented to his primary care clinician after 2 years of worsening abdominal discomfort and an increasingly large recurrent umbilical hernia. He described early satiety but had no nausea or vomiting. He reported night sweats and a 9.1-kg weight loss over the prior 6 months. His medical history was unremarkable. His social history was notable for a 15-pack-year smoking history and consumption of 6 to 8 beers per night. He had no family history of malignant disease. On examination he had no fever, a reducible umbilical hernia, a palpable left-sided abdominal mass, and significant bilateral lower extremity edema. Laboratory evaluation revealed anemia for which the patient received several blood transfusions, leukocytosis (white blood cell count, 57 000/μL), and hyponatremia (sodium level, 128 mEq/L). He was first referred to the hematology service, and a blood smear showed 74% neutrophils. A bone marrow biopsy specimen showed a hypercellular marrow with a myeloid left shift but no increase in blasts or dyspoiesis. Tests for BCR/ABL and peripheral blood JAK2 mutation were negative. Computed tomography revealed splenomegaly, hydronephrosis, and a 25-cm left-sided retroperitoneal mass (Figure). Surgical consultation was requested.Computed tomographic images. A, A large retroperitoneal mass extending from the upper abdomen into the pelvis. B, A mass encasement of the left kidney.

what is your diagnosis?

What is your diagnosis?

Lymphoma

Liposarcoma

Leiomyosarcoma

Adrenocortical carcinoma

b

male

31-40

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2569805

A woman in her 60s presented with acute-onset, diffuse abdominal pain for 24 hours accompanied by nausea and retching. She had no significant medical history and no prior abdominal surgery. In the emergency department, she was afebrile with stable vital signs. Results of her abdominal examination revealed a slight distension and diffuse tenderness to palpation, particularly in the epigastrium and right upper quadrant, but no peritoneal signs. Results of laboratory tests were unremarkable except for mild leukocytosis. Abdominopelvic computed tomography revealed a distended cecum in the left upper quadrant (Figure 1).Computed tomographic images of a dilated cecum in the left upper quadrant (arrowhead). What Is Your Diagnosis?

Cecal volvulus

Internal hernia of the cecum

Intestinal malrotation

Midgut volvulus

B. Internal hernia of the cecum

B

Internal hernia of the cecum

The foramen of Winslow, also known as the epiploic foramen, is bordered by the duodenum, caudate lobe of the liver, and vena cava. The foramen of Winslow is an anatomical communication between the great and lesser peritoneal cavities. Internal hernias through the foramen of Winslow account for 8% of all internal hernias, 30% of which contain the cecum, ascending colon, or terminal ileum.1Cecal herniation through the foraman of Winslow requires a hypermobile cecum, an enlarged foramen, and elongated small-bowel mesentery.1 Patients with a hypermobile cecum may develop other complications, such as cecal volvulus, which is a more common cause of the cecum being in the left upper quadrant. Abdominopelvic computed tomography permits preoperative diagnosis of internal hernia through the foramen of Winslow by demonstrating mesenteric fat and vessels posterior to the portal structures and gas and fluid collection in the lesser sac tapering toward the area of the foramen.2Herniation through the foramen of Winslow is the rarest cause of internal hernias. As a result, current literature consists only of case reports,1-9 with a consensus that all patients with an internal hernia through the foramen of Winslow require timely surgical intervention to prevent potential complications (eg, bowel obstruction or ischemia).10 Surgical techniques, however, vary depending on patient conditions and surgeon preferences.6,7,10This patient underwent an urgent exploratory laparotomy during which the preoperative diagnosis of internal hernia of the cecum through the foramen of Winslow was confirmed. Because the cecum was massively dilated, reduction through the foramen of Winslow was initially not possible. The cecum was first exposed by incising the anterior leaflet of the gastrocolic ligament and then decompressed with an angiocatheter (Figure 2). The hernia contents, including the cecum, appendix, and a portion of the terminal ileum, were then reduced into the greater peritoneum via the foramen of Winslow. The opening of the foramen was closed by approximating the serosal covering of the gallbladder to the retroperitoneum to prevent reherniation. The cecum was inspected and preserved because it did not have any signs of ischemia or serosal tear. An appendectomy was then performed, followed by a cecopexy. The patient was discharged on postoperative day 5 after an unremarkable recovery.Intraoperative image of a distended cecum exposed by incising the anterior leaflet of the gastrocolic ligament.

Surgery

A woman in her 60s presented with acute-onset, diffuse abdominal pain for 24 hours accompanied by nausea and retching. She had no significant medical history and no prior abdominal surgery. In the emergency department, she was afebrile with stable vital signs. Results of her abdominal examination revealed a slight distension and diffuse tenderness to palpation, particularly in the epigastrium and right upper quadrant, but no peritoneal signs. Results of laboratory tests were unremarkable except for mild leukocytosis. Abdominopelvic computed tomography revealed a distended cecum in the left upper quadrant (Figure 1).Computed tomographic images of a dilated cecum in the left upper quadrant (arrowhead).

what is your diagnosis?

What is your diagnosis?

Internal hernia of the cecum

Midgut volvulus

Intestinal malrotation

Cecal volvulus

a

female

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2553791

A woman in her 30s was referred for evaluation of bilateral papilledema. She had no specific chief complaint other than intermittent floaters. A review of systems as well as her medical, family, and social history were unremarkable. She was not taking any medications and did not have any allergies. Best-corrected visual acuity was measured 20/25 OD and 20/20 OS. Extraocular movements were intact and pupils were round and reactive with no afferent pupillary defect. Intraocular pressure by applanation was 18 mm Hg OU. Her anterior segment examination was within normal limits. Examination of her fundus revealed the optic nerves seen in Figure 1. The remainder of her posterior segment was unremarkable.Color fundus photography of the right (A) and left (B) eye demonstrates an elevated optic disc with blurred margins and loss of the central physiologic cup.Order magnetic resonance imaging of the brain and orbitsOrder B-scan ultrasonography or fundus autofluorescence imaging of optic nerves What Would You Do Next?

Order magnetic resonance imaging of the brain and orbits

Order a lumbar puncture with opening pressure

Order B-scan ultrasonography or fundus autofluorescence imaging of optic nerves

Admit the patient and consult neuro-ophthalmology

Bilateral optic nerve head drusen

C

Order B-scan ultrasonography or fundus autofluorescence imaging of optic nerves

Optic nerve head drusen (ONHD) can be mistaken for true papilledema because of its similar presentation of an elevated optic nerve with blurred margins and loss of the physiologic cup. Of the above options, only choice C can correctly identify ONHD. Obtaining a magnetic resonance image (choice A) or performing a lumbar puncture (choice B) would be appropriate in a clinical scenario where suspected increased intracranial pressure requires confirmation. Admitting the patient and consulting neurology is unnecessary in cases of pseudopapilledema secondary to ONHD (choice D).The most important differential diagnosis for ONHD includes true papilledema. All causes of true papilledema share a finding of increased intracranial pressure. Examples include intracranial mass lesions (neoplasms, hematomas, or traumatic injury); changes in cerebrospinal fluid production, absorption, or flow (choroid plexus papilloma, arachnoid granulation adhesions, or obstructive hydrocephalus); obstruction of venous outflow (cavernous or venous sinus thrombosis); cerebral edema; and, as a diagnosis of exclusion, idiopathic intracranial hypertension (pseudotumor cerebri).Multiple theories suggest that ONHD form secondary to axonal dysfunction, although no consensus on an exact mechanism has been reached. In 1968, Seitz1 proposed that drusen were the derivatives of slowly degenerating retinal nerve fibers. Spencer2 believed this degeneration was due to altered axoplasmic transport while Tso3 postulated that it was due to abnormal axonal metabolism. Histopathological studies have revealed ONHD are composed of mucopolysaccharides, amino acids, RNA and DNA, calcium, and iron.4Findings on examination include an elevated optic nerve with irregular borders, lack of hyperemia, and absence of exudates or hemorrhage.4 With age, the drusen often become larger and more visibly distinct.5 Several imaging modalities can also diagnose ONHD, including B-scan ultrasonography, fundus autofluorescence (FAF), computed tomography, and fluorescein angiography.6 Fundus autofluorescence is a noncontact imaging technique that takes advantage of the natural autofluorescent properties of ONHD (Figure 2). B-scan ultrasonography displays ONHD as an acoustic shadow due to its calcium content. Computed tomography imaging and fluorescein angiography can also visualize the calcifications within drusen, though both present more risk to the patient than FAF or B-scan ultrasonography.6Fundus autofluorescence of the right eye reveals an elevated optic disc with irregular borders and the presence of clustered drusen that autofluoresce.The incidence of ONHD has been reported as high as 2.4% from autopsy studies with bilateral findings in a majority of patients.4,7 Optic nerve head drusen is commonly clustered in families with suspected autosomal dominant inheritance and incomplete penetrance.8 Most importantly, ONHD can also be associated with retinitis pigmentosa and pseudoxanthoma elasticum.4Although the deposits can appear impressive, patients are often asymptomatic with no specific visual complaints and diagnosed incidentally. Even so, ONHD is not always benign and may result in visual field defects with potential for progressive vision loss due to optic nerve damage. Therefore, some experts suggest monitoring with serial visual field tests; if progression is noted, patients may be managed with intraocular pressure reduction in an attempt to preserve vision.4The patient was diagnosed with bilateral ONHD via FAF. Visual field testing confirmed significant bilateral defects with annual follow-up showing no progression.

Ophthalmology

A woman in her 30s was referred for evaluation of bilateral papilledema. She had no specific chief complaint other than intermittent floaters. A review of systems as well as her medical, family, and social history were unremarkable. She was not taking any medications and did not have any allergies. Best-corrected visual acuity was measured 20/25 OD and 20/20 OS. Extraocular movements were intact and pupils were round and reactive with no afferent pupillary defect. Intraocular pressure by applanation was 18 mm Hg OU. Her anterior segment examination was within normal limits. Examination of her fundus revealed the optic nerves seen in Figure 1. The remainder of her posterior segment was unremarkable.Color fundus photography of the right (A) and left (B) eye demonstrates an elevated optic disc with blurred margins and loss of the central physiologic cup.Order magnetic resonance imaging of the brain and orbitsOrder B-scan ultrasonography or fundus autofluorescence imaging of optic nerves

what would you do next?

What would you do next?

Admit the patient and consult neuro-ophthalmology

Order B-scan ultrasonography or fundus autofluorescence imaging of optic nerves

Order magnetic resonance imaging of the brain and orbits

Order a lumbar puncture with opening pressure

b

female

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2554925

A 64-year-old man presented with 3 weeks of bilateral anterior uveitis unresponsive to treatment with topical steroids. He was referred to our clinic for worsening uveitis and ocular hypertension. The patient had no ocular history. His medical history was significant for 8 months of bilateral recurrent gingivitis with persistent reactive lymphadenopathy of the head and neck unresponsive to treatment with systemic antibiotics. He denied any constitutional symptoms. His visual acuity was 20/40 OD and 20/200 OS, and intraocular pressures were 17 and 32 mm Hg, respectively. On slitlamp examination, both eyes were markedly hyperemic with diffuse corneal stromal edema, and his anterior chambers were deep with 3+ OD and 4+ OS cell and mixed hypopyon and hyphema in each eye (Figure, A and B). His dilated fundus examination findings were remarkable only for an area of retinal pigment epithelial stippling inferonasal to the macula in the left eye, without any vitritis in either eye. He did not have any skin or mucocutaneous lesions, but he had extensive bilateral preauricular, submental, posterior occipital, and supraclavicular lymphadenopathy. Gram stain and culture of aqueous and vitreous biopsy sample results were negative for infectious and cytologic studies, as were serum human leukocyte antigen B27, tuberculosis, syphilis, and sarcoidosis test results (Figure, C).Slitlamp examination findings of the left eye with hypopyon (A) and iris nodules (B). C, Aqueous cytology (Wright stain). Note the scant cytoplasm containing small, irregular nuclei with inconspicuous nucleoli. What Would You Do Next?

Biopsy of iris nodule

Lymph node biopsy

Prescribe intravitreal vancomycin and ceftrazidime

Obtain bacterial and fungal blood cultures

Intraocular lymphoma

B

Lymph node biopsy

This patient presented with chronic lymphadenopathy and severe, subacute bilateral anterior uveitis, including hypopyon mixed with hyphema and iris nodules. In a patient with lymphadenopathy and ocular inflammation unresponsive to steroid therapy, one must consider infectious uveitis or a neoplastic masquerade syndrome. Infectious uveitides with a subacute or long-term course include herpetic, fungal, and parasitic etiologies. However, he did not have risk factors, systemic manifestations, or other ocular findings consistent with infection. The absence of such features, the patient’s age, and his long-term lymphadenopathy raise suspicion for neoplasia, making the diagnostic value of a lymph node biopsy higher than that of blood cultures. Furthermore, a lymph node is more accessible to biopsy than an iris nodule, especially in the setting of hypopyon and hyphema.Submental lymph node biopsy and peripheral blood flow cytometry were consistent with mantle cell lymphoma (MCL). Magnetic resonance imaging of the brain and lumbar puncture did not reveal additional central nervous system involvement, and positron emission tomographic scan demonstrated subcarinal lymphadenopathy and splenomegaly. Repeat anterior chambers sampling yielded monomorphic, medium-sized round blue cells with clumpy chromatin expressing CD19, CD20, CD5, and monotypic surface κ immunoglobulin, consistent with MCL.Primary central nervous system lymphoma, usually a non-Hodgkin B-cell lymphoma, is the most common intraocular neoplastic masquerade syndrome. In contrast to our case, intraocular lymphoma typically presents with vitreous, retinal, or subretinal involvement, classically featuring “creamy yellow subretinal infiltrates.”1 Mantle cell lymphoma accounts for 2% to 10% of all non-Hodgkin lymphoma and presents at a median age of 60 to 65 years, with lymphadenopathy, splenomegaly, and bone marrow involvement.2,3 However, central nervous system involvement is rare, and intraocular involvement of MCL has been reported in only 6 other cases.3-9 To our knowledge, this patient is the fourth reported case of isolated anterior segment involvement; previous cases have presented with unilateral or bilateral pseudohypopyon (consisting of lymphoma cells), hyphema, or lymphomatous iris infiltration.4-6Patients presenting with intraocular MCL are likely to have systemic MCL suggested by the history and physical examination. The diagnosis may be confirmed by peripheral blood and bone marrow cytology, flow cytometry, and cytogenetics, featuring the hallmark translocation t(11;14)(q13;32).3 Disease stage may be assessed by lumbar puncture, brain magnetic resonance imaging, and whole-body positron emission tomographic scan. Cytology of aqueous or vitreous may be used to confirm ocular involvement.The paradigm of systemic treatment of MCL is rapidly evolving and comprises combination chemotherapy followed by autologous stem cell transplantation.3 Although intraocular MCL responds to systemic chemotherapy alone or in combination with external beam irradiation, adjuvant intravitreal methotrexate or rituximab has been successfully used in cases of ocular involvement.4 The patient underwent systemic chemotherapy and intravitreal methotrexate injection. He achieved ocular and systemic remission (with visual acuity of 20/20 OU after cataract surgery) and awaits autologous bone marrow transplantation.

Ophthalmology

A 64-year-old man presented with 3 weeks of bilateral anterior uveitis unresponsive to treatment with topical steroids. He was referred to our clinic for worsening uveitis and ocular hypertension. The patient had no ocular history. His medical history was significant for 8 months of bilateral recurrent gingivitis with persistent reactive lymphadenopathy of the head and neck unresponsive to treatment with systemic antibiotics. He denied any constitutional symptoms. His visual acuity was 20/40 OD and 20/200 OS, and intraocular pressures were 17 and 32 mm Hg, respectively. On slitlamp examination, both eyes were markedly hyperemic with diffuse corneal stromal edema, and his anterior chambers were deep with 3+ OD and 4+ OS cell and mixed hypopyon and hyphema in each eye (Figure, A and B). His dilated fundus examination findings were remarkable only for an area of retinal pigment epithelial stippling inferonasal to the macula in the left eye, without any vitritis in either eye. He did not have any skin or mucocutaneous lesions, but he had extensive bilateral preauricular, submental, posterior occipital, and supraclavicular lymphadenopathy. Gram stain and culture of aqueous and vitreous biopsy sample results were negative for infectious and cytologic studies, as were serum human leukocyte antigen B27, tuberculosis, syphilis, and sarcoidosis test results (Figure, C).Slitlamp examination findings of the left eye with hypopyon (A) and iris nodules (B). C, Aqueous cytology (Wright stain). Note the scant cytoplasm containing small, irregular nuclei with inconspicuous nucleoli.

what would you do next?

What would you do next?

Biopsy of iris nodule

Obtain bacterial and fungal blood cultures

Lymph node biopsy

Prescribe intravitreal vancomycin and ceftrazidime

c

male

61-70

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2569797

A 77-year-old man with a history of mitral valve replacement, previous coronary artery bypass grafting, atrial fibrillation, and heart failure presented to our clinic for evaluation of worsening exertional dyspnea. In 1998, he underwent mitral valve replacement with a St Jude mechanical prosthesis for severe mitral regurgitation owing to a flail leaflet, with 2-vessel coronary artery bypass grafting. He reported compliance with warfarin therapy for many years.One year ago, he noted the onset of exertional dyspnea that culminated in multiple recurrent admissions for decompensated heart failure requiring intravenous diuretics. While hospitalized, he underwent a cardiac catheterization that demonstrated patent bypass grafts but a profoundly low cardiac output and elevated pulmonary capillary wedge pressure. A transthoracic echocardiogram was performed that suggested the presence of a significantly elevated gradient across his mitral prosthesis. A plain radiography of the chest demonstrated a mechanical prosthesis (Figure 1A). A transesophageal echocardiogram was then performed that demonstrated complete immobilization of 1 mechanical leaflet and impaired excursion of the other leaflet (Figure 1B), with subsequent severe mitral stenosis (Figure 1C) at a baseline heart rate of 82 bpm. He developed worsening hemodynamic instability and refractory pulmonary edema, and a TandemHeart left ventricular assist device was placed for cardiogenic shock.A, Chest radiograph with zoom of the mitral valve prosthesis, demonstrating opening of 1 leaflet from en face view and other leaflet not seen. B, Transesophageal echocardiogram midesophageal view (90°) demonstrating bileaflet mechanical mitral valve prosthesis with immobilized leaflet (left) in systole and diastole. C, Three-dimensional transesophageal echocardiogram midesophageal views of the mitral valve, demonstrating severely restricted leaflet movement of the partially mobile mechanical mitral leaflet with no obvious overlying mass.Administer intravenous unfractionated heparin for presumed prosthetic valve thrombosisAdminister intravenous thrombolysis for presumed prosthetic valve thrombosis What Would You Do Next?

Administer intravenous unfractionated heparin for presumed prosthetic valve thrombosis

Administer intravenous thrombolysis for presumed prosthetic valve thrombosis

Obtain consultation for urgent surgical valve replacement

Start empirical antibiotics for prosthetic valve endocarditis

Prosthetic valve obstruction

C

Obtain consultation for urgent surgical valve replacement

This case highlights the importance of vigilance for prosthetic valve complications, which should be maintained as part of the differential diagnosis for any patient presenting with a prosthetic valve and changes in clinical status. Etiologies for prosthetic valve dysfunction include thrombosis/thromboembolism, pannus formation, endocarditis, or patient-prosthesis mismatch. Suspicion for prosthetic valve obstruction (PVO) is a class I indication for transesophageal echocardiography (TEE).1 Several clinical factors can aid in identifying the cause of PVO including prosthesis type, time from surgery, adequacy of anticoagulation, and previous transprosthetic gradients. The correct identification of thrombotic vs nonthrombotic causes of obstruction is an important step in accurate diagnosis to guide appropriate clinical treatment.2The incidence of mechanical valve obstruction is estimated at 0.1% to 1.3% per patient-year.1,3,4 Risk of thromboembolic events is greater in the early postoperative period (<3 months), with mechanical valves, and with valves in the mitral position; this risk can be augmented by the presence of atrial fibrillation, hypercoagulability, and left ventricular dysfunction.1 Late complications should invoke suspicion for pannus formation as the cause of PVO. Although pannus overgrowth is less common and may occur concomitantly with thrombus in 12% of cases, the classic timing is late in the postsurgical course and should be ruled out when a patient presents with worsening symptoms or transvalvular gradients years after valve operation.3Transesophageal echocardiography is essential for differentiating thrombus from pannus. While the presence of a mass on TEE is more suggestive of thrombus, the identification of a mobile or large (>0.8 cm2) thrombus has prognostic implications because these patients benefit from surgery rather than undergoing thrombolysis.2,5 Restricted leaflet mobility may be observed in both pannus and thrombus-related PVO (Videos 1 and 2). Pannus formation is often annular in location, occurring on the atrial side of mitral valve prostheses. Thus, 3-dimensional TEE is useful in highlighting the etiology of PVO owing to improved ability to detect masses and delineate valve-ring appearance, although its usefulness is limited to case reports.6,7Treatment for PVO includes medical and surgical interventions, the latter of which is associated with a significant mortality risk owing to the attendant repeat valve surgery. While thrombolysis or intravenous anticoagulation is the mainstay of medical therapy, there is a paucity of data to demonstrate the efficacy of these approaches. However, the presence of obstructive symptoms with severe heart failure or large mobile masses should prompt surgical consideration.1 The diagnosis of pannus is also critical for patient treatment because the fibroelastic and collagen overgrowth that drives pannus formation is unresponsive to medical therapy, requiring valve replacement for definitive treatment. Taken together, this patient’s clinical presentation and imaging findings of severe mechanical valve stenosis illustrate the importance of monitoring for prosthetic valve complications.Owing to profound heart failure from an obstructed mitral valve prosthesis, urgent repeat mitral valve replacement surgery was performed. Intraoperative visualization of the mechanical prosthesis demonstrated pannus overlying the immobilized leaflet and acute and subacute organized thrombus adjacent to both leaflets (Figure 2). A bioprosthetic 31-mm St Jude Epic mitral valve was placed without complications (St Jude Medical Inc).Intraoperative pathology of removed mechanical mitral valve, demonstrating significant pannus (white smooth material) and concomitant acute (dark red) and chronic (white-pink) thrombus at the leaflet hinge points.

Cardiology

A 77-year-old man with a history of mitral valve replacement, previous coronary artery bypass grafting, atrial fibrillation, and heart failure presented to our clinic for evaluation of worsening exertional dyspnea. In 1998, he underwent mitral valve replacement with a St Jude mechanical prosthesis for severe mitral regurgitation owing to a flail leaflet, with 2-vessel coronary artery bypass grafting. He reported compliance with warfarin therapy for many years.One year ago, he noted the onset of exertional dyspnea that culminated in multiple recurrent admissions for decompensated heart failure requiring intravenous diuretics. While hospitalized, he underwent a cardiac catheterization that demonstrated patent bypass grafts but a profoundly low cardiac output and elevated pulmonary capillary wedge pressure. A transthoracic echocardiogram was performed that suggested the presence of a significantly elevated gradient across his mitral prosthesis. A plain radiography of the chest demonstrated a mechanical prosthesis (Figure 1A). A transesophageal echocardiogram was then performed that demonstrated complete immobilization of 1 mechanical leaflet and impaired excursion of the other leaflet (Figure 1B), with subsequent severe mitral stenosis (Figure 1C) at a baseline heart rate of 82 bpm. He developed worsening hemodynamic instability and refractory pulmonary edema, and a TandemHeart left ventricular assist device was placed for cardiogenic shock.A, Chest radiograph with zoom of the mitral valve prosthesis, demonstrating opening of 1 leaflet from en face view and other leaflet not seen. B, Transesophageal echocardiogram midesophageal view (90°) demonstrating bileaflet mechanical mitral valve prosthesis with immobilized leaflet (left) in systole and diastole. C, Three-dimensional transesophageal echocardiogram midesophageal views of the mitral valve, demonstrating severely restricted leaflet movement of the partially mobile mechanical mitral leaflet with no obvious overlying mass.Administer intravenous unfractionated heparin for presumed prosthetic valve thrombosisAdminister intravenous thrombolysis for presumed prosthetic valve thrombosis

what would you do next?

What would you do next?

Administer intravenous thrombolysis for presumed prosthetic valve thrombosis

Start empirical antibiotics for prosthetic valve endocarditis

Obtain consultation for urgent surgical valve replacement

Administer intravenous unfractionated heparin for presumed prosthetic valve thrombosis

c

male

71-80

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2583373

A woman in her 60s returned for a 6-month follow-up after undergoing a substernal total thyroidectomy for a T3N0M0 right-sided undifferentiated insular carcinoma that caused dysphagia, dysphonia, and tracheal deviation (Figure, A and B). The procedure was uneventful and well tolerated. Her history of end-stage renal disease precluded postoperative radioactive iodine treatment. Ultrasonography performed at her 3-month follow-up showed no evidence of disease recurrence or local metastasis. Her compressive symptoms had also resolved. Ultrasonography revealed a 1.3 × 1.1 × 1.0-cm hypoechoic mass in the right central compartment and a suspicious lymph node in the right carotid sheath. Fine-needle aspiration confirmed recurrence of a malignant neoplasm in the central compartment; however, the lymph node was not amenable to sampling based on its anatomic location. The patient decided to undergo a right central (level VI) lymph node dissection. Intraoperatively, insular carcinoma was dissected away from the cricothyroid membrane and recurrent laryngeal nerve. In the right central compartment several prelaryngeal and pretracheal nodes were identified and excised. After removal of the most distal of these nodes, a separate pale tan mass 2 cm in diameter was visualized at the level of the thoracic inlet. The mass demonstrated respiratory expansion and retraction. The expansile mass was excised. Histopathologic analysis revealed a cystic mass composed primarily of mucosal cells and sparse fibroconnective tissue (Figure, C and D).A, A large heterogeneously enhancing mass with central necrosis arising from the right thyroid fossa with leftward displacement of the trachea (t). Large air-filled cavity (yellow arrowhead) measuring 20 × 18 × 15 mm and communicating with the right posterolateral aspect of the trachea. Incidental small esophageal diverticulae noted (e). B, Large air-filled cavity (red arrowhead) measuring 20 × 18 × 15 mm and communicating with the right posterolateral aspect of the trachea (t). C and D, Histopathologic images of resected tissue specimen, hematoxylin-eosin. C, Respiratory epithelial lined cyst. Respiratory mucosa with absence of thyroid, lung, smooth muscle, and cartilaginous tissues. What Is Your Diagnosis?

Apical lung bulla/bleb

Tracheocele

Laryngocele

Zenker diverticulum

B. Tracheocele

B

Tracheocele

Tracheoceles and tracheal diverticula are characterized as abnormal outpouchings of respiratory tissue from the tracheal wall. A renowned 19th-century physician, Carl von Rokitansky, was the first to describe tracheal diverticula in 1838 and inferred that they resulted from chronic inflammation of mucous membranes in the respiratory tract.1 They are rare findings, as indicated by a 1953 necroscopic series of 867 patients reporting a prevalence of approximately 1% of the measured population.1 However, most diverticula and tracheoceles lack characteristic symptoms, which makes measurement of incidence within a population particularly challenging.2Although tracheal diverticula and tracheoceles have been reported intermittently since 1838, a clear mechanism for development of these lesions has not been well established. Consensus for terminology differentiating tracheoceles from diverticula does not exist, and the 2 terms have been used interchangeably in the literature to describe the same condition. Grassi and colleagues3 proposed that size should be the main determinant in nomenclature, and a diameter of at least 2 cm across the broadest aspect of the defect should be used for diagnosis of tracheocele. Other authors suggest that a tracheocele is simply a diverticulum that has become air-filled and distended. For the purpose of this case report, and to avoid confusion, we will refer to air-filled tracheal outpouchings as tracheoceles.Two types of tracheoceles have been described in medical texts: acquired and congenital. Each defect differs in etiology, anatomic localization, and histologic characteristics. Congenital tracheoceles are postulated to be a result of aberrant endodermal and cartilaginous embryologic development or remnants of an aborted division of a primary lung bud.4 These lesions are more common in males, are typically found on the right side (approximately 5 cm inferior to the true vocal cords), have an oblique downward trajectory, contain complete tracheal anatomic components (respiratory epithelium, smooth muscle and cartilage), and are often filled with air or mucous.5 In addition, congenital tracheoceles have been reported in association with embryologic airway malformations, such as tracheoesophageal fistula.2Acquired tracheoceles are primarily composed of respiratory mucosa.6 These lesions are a result of mucosal herniation through weakened transverse bands of the trachealis muscle and are believed to occur in response to blunt injury or chronic pulmonary diseases associated with increased respiratory luminal pressure.7 Similar to the congenital defect, acquired tracheoceles are typically right-sided. Conversely, they are most often observed at the level of the posterolateral thoracic inlet.4 It has been postulated that thyroid malignant neoplasm extending into the thoracic inlet may cause chronic cough from persistent tracheal irritation, which could facilitate mucosal herniation through a weak point in the opposing tracheal wall.5Most congenital and acquired tracheoceles are asymptomatic; however, reports have been published of patients presenting with dysphonia, hemoptysis, dyspnea, dysphagia, and chronic tracheobronchitis.2,8 Symptomatic tracheoceles can be managed surgically or conservatively with antibiotics, mucolytics, and airway physiotherapy. Although a small tracheal defect had been visualized on computerized tomography prior to her initial surgery (Figure, A and B), our patient’s dysphonia and dysphagia likely stemmed from compressive effects of her malignant neoplasm based on resolution of her symptoms following the thyroidectomy. Nonetheless, with the anatomic localization of the respiratory lesion to the posterolateral aspect of the trachea and the histopathologic findings of respiratory mucosa with absence of smooth muscle and cartilaginous tissues (Figure, C and D), the diagnosis of acquired tracheocele can accurately be made.This is the third known report of tracheocele accompanying a thyroid carcinoma5,9; however, this case is unique in its lack of correlation to chronic lung disease and asymptomatic presentation. Head and neck surgeons should be aware of these entities, their intraoperative presentation, and how they are successfully treated.

General

A woman in her 60s returned for a 6-month follow-up after undergoing a substernal total thyroidectomy for a T3N0M0 right-sided undifferentiated insular carcinoma that caused dysphagia, dysphonia, and tracheal deviation (Figure, A and B). The procedure was uneventful and well tolerated. Her history of end-stage renal disease precluded postoperative radioactive iodine treatment. Ultrasonography performed at her 3-month follow-up showed no evidence of disease recurrence or local metastasis. Her compressive symptoms had also resolved. Ultrasonography revealed a 1.3 × 1.1 × 1.0-cm hypoechoic mass in the right central compartment and a suspicious lymph node in the right carotid sheath. Fine-needle aspiration confirmed recurrence of a malignant neoplasm in the central compartment; however, the lymph node was not amenable to sampling based on its anatomic location. The patient decided to undergo a right central (level VI) lymph node dissection. Intraoperatively, insular carcinoma was dissected away from the cricothyroid membrane and recurrent laryngeal nerve. In the right central compartment several prelaryngeal and pretracheal nodes were identified and excised. After removal of the most distal of these nodes, a separate pale tan mass 2 cm in diameter was visualized at the level of the thoracic inlet. The mass demonstrated respiratory expansion and retraction. The expansile mass was excised. Histopathologic analysis revealed a cystic mass composed primarily of mucosal cells and sparse fibroconnective tissue (Figure, C and D).A, A large heterogeneously enhancing mass with central necrosis arising from the right thyroid fossa with leftward displacement of the trachea (t). Large air-filled cavity (yellow arrowhead) measuring 20 × 18 × 15 mm and communicating with the right posterolateral aspect of the trachea. Incidental small esophageal diverticulae noted (e). B, Large air-filled cavity (red arrowhead) measuring 20 × 18 × 15 mm and communicating with the right posterolateral aspect of the trachea (t). C and D, Histopathologic images of resected tissue specimen, hematoxylin-eosin. C, Respiratory epithelial lined cyst. Respiratory mucosa with absence of thyroid, lung, smooth muscle, and cartilaginous tissues.

what is your diagnosis?

What is your diagnosis?

Apical lung bulla/bleb

Tracheocele

Zenker diverticulum

Laryngocele

b

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2585375

An infant girl presented to the outpatient clinic with a history of recent-onset hoarseness in her cry. Her parents also reported loud snoring and some retractions during sleep. There was no clinically significant medical or family history. Her birth had been uncomplicated after a term pregnancy. Physical examination revealed mild inspiratory stridor and several light-brown macules approximately 1 cm in size on the patient’s skin. On flexible fiberoptic laryngoscopy (Figure), a supraglottic mass could be seen, but visualization of the full extent of the larynx or the mass was difficult owing to lack of cooperation by this very young patient. The decision was made to obtain a better view under direct laryngoscopy in the operating room. A submucosal lesion of the left aryepiglottic fold extending inferiorly to the level of the arytenoid, and displacing the epiglottis medially, was found. An incision was made through the mucosa, where a firm, whitish mass that bled minimally was noted, and a biopsy specimen was sent for permanent pathologic analysis. A magnetic resonance image was then obtained to assess the full extent of the mass and whether surrounding tissues were involved.A, View of lesion at the level of the epiglottis on direct laryngoscopy. B, View of the vocal folds on direct laryngoscopy. C, T1-weighted sagittal magnetic resonance image (MRI) showing laryngeal lesion. D, Bundles of spindle cells with angulated nuclei in a stroma of variable coarse collagen and loose myxoid matrix (hematoxylin-eosin, original magnification ×4). What Is Your Diagnosis?

Laryngeal sarcoid

Granular cell tumor

Laryngeal rhabdomyosarcoma

Laryngeal neurofibroma

D. Laryngeal neurofibroma

D

Laryngeal neurofibroma

Neurofibromas are aberrant proliferations of the Schwann cells, fibroblasts, and perineural cells of peripheral nerves. They can arise in isolation, but are most commonly associated with neurofibromatosis 1 or 2 (NF1 or NF2). NF1, or von Recklinghausen disease, is the more common and is found in 1 in 2500 to 1 in 3000 births.1 It displays autosomal dominant inheritance, but in 30% to 50% of cases (such as this one) it spontaneously arises from a germline mutation. NF1 typically presents with café-au-lait spots, cutaneous neurofibromas, and skeletal abnormalities, but neurofibromas can form in almost any location.1 NF2 is characterized by bilateral acoustic neuromas. It is rarer, occurring in about 1 in 40 000 births, and is not typically associated with laryngeal neurofibroma.2Laryngeal neurofibroma is a rare presentation of NF1 in the pediatric population, and a very rare cause of hoarseness overall.2,3 As of 2014, there were 63 cases reported in the world literature.3 When they occur, they most commonly affect the supraglottis, although there have been reported cases of epiglottic, subglottic, and hypopharyngeal neurofibromas.3,4 They typically present with obstructive symptoms, such as stridor, dyspnea, and dysphagia.1,3-5 Some patients have nontypical presenting symptoms, such as sleep apnea.6 Diagnosis is made by performing direct laryngoscopy with biopsy. Histologically, there are 2 subtypes of neurofibroma found in the head and neck: plexiform and diffuse. Diffuse neurofibromas are plaquelike enlargements of tissue. Plexiform neurofibromas are characterized by the involvement of numerous adjacent nerve fascicles or multiple components of a nerve plexus.7 Although both subtypes can be found in NF1, plexiform is nearly pathognomonic. Plexiform neurofibromas typically grow slowly and can remain asymptomatic for a long time. However, they can be deeply locally invasive and cross planes of tissue. Plexiform neurofibromas have a 5% risk of malignant transformation.4Laryngeal neurofibroma is treated with surgical resection. Open resection and endoscopic approaches using a carbon dioxide laser have been reported.3,5 The small numbers of these cases make an in-depth comparison of these modalities impossible, but a 2014 literature review3 concluded that endoscopic approaches were a safe initial treatment option and may decrease the need for tracheostomy for airway control after surgery. However, endoscopic approaches may be less useful in cases in which the tumor is deeply invasive or recurrent. Because of the risk of malignant transformation and because incompletely excised tumors often recur, total excision is preferable for smaller, localized lesions. However, in cases of deeply invasive tumors, complete excision may be difficult or impossible. Care must be taken during surgery because the tumor may involve nerve bundles important to laryngeal function.8 In all cases, close follow-up after surgery is essential to monitor for recurrence or malignant transformation.In this case, the patient was treated initially with partial carbon dioxide laser excision, although ultimately further growth led to the need for tracheotomy for protection of her airway. Six months later, the patient underwent open supraglottic partial laryngectomy. The tumor was deeply locally invasive, so complete excision with preservation of laryngeal function was impossible even with an open approach. Regardless, a follow-up direct laryngoscopy and bronchoscopy 4 months later revealed a significantly improved airway, and the patient was able to be decannulated. Swallowing function was preserved and to date she is tolerating a regular, age-appropriate diet. Because of the partial excision, we plan on follow-up monthly with flexible fiberoptic endoscopy for the first year and will perform follow-up direct laryngoscopy 3 months following decannulation. The follow-up interval will be lengthened after the first year. The family was informed of the possibility of recurrent disease and was asked to return immediately for any signs of airway distress.

General

An infant girl presented to the outpatient clinic with a history of recent-onset hoarseness in her cry. Her parents also reported loud snoring and some retractions during sleep. There was no clinically significant medical or family history. Her birth had been uncomplicated after a term pregnancy. Physical examination revealed mild inspiratory stridor and several light-brown macules approximately 1 cm in size on the patient’s skin. On flexible fiberoptic laryngoscopy (Figure), a supraglottic mass could be seen, but visualization of the full extent of the larynx or the mass was difficult owing to lack of cooperation by this very young patient. The decision was made to obtain a better view under direct laryngoscopy in the operating room. A submucosal lesion of the left aryepiglottic fold extending inferiorly to the level of the arytenoid, and displacing the epiglottis medially, was found. An incision was made through the mucosa, where a firm, whitish mass that bled minimally was noted, and a biopsy specimen was sent for permanent pathologic analysis. A magnetic resonance image was then obtained to assess the full extent of the mass and whether surrounding tissues were involved.A, View of lesion at the level of the epiglottis on direct laryngoscopy. B, View of the vocal folds on direct laryngoscopy. C, T1-weighted sagittal magnetic resonance image (MRI) showing laryngeal lesion. D, Bundles of spindle cells with angulated nuclei in a stroma of variable coarse collagen and loose myxoid matrix (hematoxylin-eosin, original magnification ×4).

what is your diagnosis?

What is your diagnosis?

Laryngeal sarcoid

Laryngeal rhabdomyosarcoma

Granular cell tumor

Laryngeal neurofibroma

d

female

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2527093

A woman in her 50s presented with a 5-month history of right submandibular swelling and pain, associated with eating and relieved by gland massage. No saliva was expressed on examination. Computed tomography (CT) and ultrasonography showed normal-appearing submandibular glands and neck soft tissues. A sialogram showed high-grade stricture approximately 3 to 4 cm into the right submandibular duct orifice. Complete stricture prevented evaluation of the proximal duct and intraglandular portions. Sialendoscopy showed a widely patent right submandibular duct proximally with a segmental takeoff, consistent with the Bartholin duct draining into the Wharton duct distal to a blind pouch identified 2.5 cm from the intraoral duct orifice (Figure, A). Despite a Wharton ductoplasty to improve sublingual gland drainage through the Bartholin duct, the degree of scarring at the hilum and inability to further dilate warranted submandibular gland (SMG) excision. Four months after SMG excision, she developed a right floor of mouth lesion after “burning her mouth” with high-temperature food. Magnetic resonance imaging demonstrated a cystic lesion in the right sublingual space following the Wharton duct (Figure, B). Recurrent floor of mouth swelling (Figure, C) was addressed by repeated marsupialization and eventual sublingual gland excision. Pathologic analysis identified fragments of squamous mucosa with inflammation, cystic space, and compressed granulation tissues consistent with mucous extravasation (Figure, D). What Is Your Diagnosis?

Submandibular duct sialocele

Lymphangioma

Mucus retention cyst

Abscess

A. Submandibular duct sialocele

A

Submandibular duct sialocele

Four months after submandibular gland resection, the patient developed a lesion in the right floor of mouth with examination revealing a large, fluid-filled cyst at the end of the Wharton duct, which is consistent with a remnant of the dilated Wharton duct. The differential diagnosis included mucous retention cyst, obstructed submandibular duct remnant, abscess, or a small ranula due to an extravasating pseudocyst of a sublingual gland. The fluid accumulation likely represented a sialocele that resulted from sublingual gland drainage through the Bartholin duct into the submandibular duct after the patent Wharton duct scarred closed, possibly as a result of the exposure to the high-temperature food. The large Bartholin duct emptying into the submandibular duct remnant likely caused a recurrent sialocele. This hypothesis is consistent with the previous sialendoscopic findings of a blind pouch at the 2.5-cm mark into the submandibular duct, suggesting the presence of a large Bartholin duct, draining into the submandibular duct.Treatment then followed with resection of the duct remnant and adjacent sublingual gland removal after initial unsuccessful efforts to cannulate and reopen the remnant duct. Surgical pathologic results demonstrated chronic inflammation of the Wharton duct with Bartholin duct drainage (Figure, D). Postoperatively, the right floor of mouth showed advanced healing with good clear saliva expressed from the left submandibular duct.Sialocele is characterized by the accumulation of extravasated saliva around the secretory tissues of a salivary gland without a defined epithelial lining, granulation, and abundant mucin proteins. In this instance, the thick mucoid contents of the sialocele were consistent with the typically high mucin content secretions of the sublingual gland, and not submandibular secretions, which are thin and serous.1 Notably, the term ranula is often used interchangeably with sialocele in the literature to describe a salivary mucocele often occurring in the floor of mouth associated with major or minor salivary glands. Principle treatments include compresses, medication, successive puncture and aspiration, installation of local drains, or even surgical removal of the affected gland in the absence of adequate clinical response. Sublingual gland drainage through the Bartholin duct may cause recurrent submandibular duct sialocele following submandibular gland excision owing to impaired emptying of the sublingual gland causing sublingual secretions to accumulate in the duct remnant. Although ranulae are common, to our knowledge, this case is the first clinical example delineating this process with sialography, sialendoscopy, magnetic resonance imaging, and histopathologic findings.A recent study2 used adult cadavers to investigate the relationship between the ducts of the submandibular gland and sublingual gland. Four patterns of sublingual and submandibular duct anatomic variation were reported: (1) the sublingual gland has many fine ducts (Rivinus ducts) that secrete in the floor of the mouth; (2) the sublingual gland has a major duct, the Bartholin duct, that joins the Wharton duct; (3) the sublingual gland has its own respective duct that opens separately at its own orifice adjacent to and a short distance from the orifice of the Wharton duct; and (4) the sublingual gland has 2 Bartholin ducts, one which joins the Wharton duct and the other opens at its own orifice near that of the Wharton duct on the floor of the mouth. Mun et al3 concluded that the occurrence of ranula might be related to the ductal variation of the sublingual gland. Using sialendoscopy, we found a secondary duct orifice consistent with Bartholin duct drainage of the sublingual gland into a distally strictured Wharton duct. Presence of Bartholin duct variant may warrant closer postoperative monitoring for recurrent sialocele following submandibular gland resection. Recurrent sublingual sialocele unamendable to marsupialization may be treated successfully with sublingual gland excision.

General

A woman in her 50s presented with a 5-month history of right submandibular swelling and pain, associated with eating and relieved by gland massage. No saliva was expressed on examination. Computed tomography (CT) and ultrasonography showed normal-appearing submandibular glands and neck soft tissues. A sialogram showed high-grade stricture approximately 3 to 4 cm into the right submandibular duct orifice. Complete stricture prevented evaluation of the proximal duct and intraglandular portions. Sialendoscopy showed a widely patent right submandibular duct proximally with a segmental takeoff, consistent with the Bartholin duct draining into the Wharton duct distal to a blind pouch identified 2.5 cm from the intraoral duct orifice (Figure, A). Despite a Wharton ductoplasty to improve sublingual gland drainage through the Bartholin duct, the degree of scarring at the hilum and inability to further dilate warranted submandibular gland (SMG) excision. Four months after SMG excision, she developed a right floor of mouth lesion after “burning her mouth” with high-temperature food. Magnetic resonance imaging demonstrated a cystic lesion in the right sublingual space following the Wharton duct (Figure, B). Recurrent floor of mouth swelling (Figure, C) was addressed by repeated marsupialization and eventual sublingual gland excision. Pathologic analysis identified fragments of squamous mucosa with inflammation, cystic space, and compressed granulation tissues consistent with mucous extravasation (Figure, D).

what is your diagnosis?

What is your diagnosis?

Abscess

Submandibular duct sialocele

Mucus retention cyst

Lymphangioma

b

female

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2541394

A woman in her 20s presented to the emergency department with a 2-week history of progressive sore throat, dysphagia, and fever (38.2°C) that developed into dyspnea, dysphonia, and neck pain on the day of presentation. Initially, she had been treated with oral amoxicillin–clavulanic acid with no improvement. Her medical history included ulcerative colitis (UC) controlled by oral azathioprine for 2 years. She was a nonsmoker. Initial clinical evaluation revealed respiratory distress with respiratory rate of 21 breaths per minute, with oxygen saturation 95% on room air. Her heart rate was 95 beats per minute, her blood pressure was 135/91 mm Hg, and she was pyretic. Further examination with flexible fiberoptic laryngoscopy (Figure, A) showed considerable erythema and edema of the epiglottitis with patchy necrosis partially obstructing the glottis and saliva pooling in the supraglottis. Findings from the remainder of the otolaryngology examination and chest auscultation were normal. Subsequently, oxygen saturation improved to 100% with 3 L per minute of oxygen via nasal prongs. Her initial laboratory findings revealed a white blood cell count of 12 000/μL, absolute neutrophil count of 46%, hemoglobin count of 12.8 g/dL, and a platelet count of 175 000/μL. Her C-reactive protein level was 5 mg/dL (normal level, <0.5 mg/dL). Results from liver function tests and chest radiograph were normal. What Is Your Diagnosis?

Candidosis

Diphtheric laryngitis

Pseudomembranous epiglottitis

Necrotic epiglottitis

D. Necrotic epiglottitis

D

Necrotic epiglottitis

The key to the correct diagnosis is the patient’s condition, the improvement of the initial decreased oxygen saturation, and the laryngoscopic findings that point toward an epiglottitis. Therefore, the patient was admitted and empirically started on intravenous ceftriaxone and metronidazole with regular airway monitoring. The improvement of oxygen saturation and the patient’s stable condition averted the need of urgent intubation or/and tracheostomy. A throat swab was taken and sent for culture analysis. α-Hemolytic Streptococcus pyogenes (GAS)—sensitive to ceftriaxone—was isolated, and the diagnosis of necrotic epiglottitis (NE) was set.Necrotic epiglottitis is an uncommon form of acute epiglottitis. It involves the supraglottis and the adjacent structures, and the patients’ respiratory status may deteriorate rapidly with fatal consequences.1 In fact, clinical symptoms of NE include sore throat, odynophagia, dysphagia, and pyrexia that can progress rapidly to respiratory distress requiring urgent intubation.2 From the 7 cases reported to date, 6 of the previously described patients were urgently intubated, and the seventh patient and our patient could be treated conservatively.1Various microorganisms have been isolated from previous NE cases with most being commensal organisms of the airway. Consequently, it has been suggested that NE can be caused by normal microbial flora in an immunocompromised host.2 Immunodeficiency is thought to be the driving force for the development of NE as it is the common feature of all reported cases. Most patients (6 cases) were neutropenic on presentation.1-6 In 2 cases (including ours) infection with GAS was reported.7 GAS causes invasive and noninvasive infections. The former occur more commonly in immunocompromised hosts in whom GAS penetrates vulnerable tissues.7,8 In the case of the patient described herein, we assume that a common streptococcal pharyngitis aggravated to NE because the patient was immunocompromised.Immunosuppression in our patient was caused by 2 factors, UC and azathioprine intake. In UC, an abnormal mucosal immune response and an increased epithelial cell apoptosis result in a disrupted epithelial barrier function. Subsequently, bacteria invade the defected thinned mucus layer and trigger innate and adaptive immune system.9 Ulcerative colitis is considered to be a systemic inflammatory disorder that may affect also the respiratory system.9 Lung-gut interactions are supported by the common mucosal immunological system concept.9 Azathioprine is used for the treatment of UC because it incites local T-cell apoptosis.10 Azathioprine causes immunosuppression by inhibiting DNA replication and consequently leads to bone marrow suppression and leukopenia.10 The risk of opportunistic infections in these patients is increased.10Another common feature of all reported cases was respiratory distress. Therefore, it is vital to assess the airway status in these patients. In case of upper airway obstruction, the most pertinent clinical sign is stridor, which was absent in our patient. Upper airway obstruction does not improve with medical management, and urgent intubation and/or tracheostomy is warranted. However, dyspnea may be caused by sepsis. Signs of systemic inflammatory response syndrome (SIRS) include pyrexia, tachycardia, tachypnea, and elevated white blood cell count, which are caused by the release of various mediators and were present in our patient. Dyspnea due to SIRS improves with adequate treatment of the underlying cause. Laryngoscopic examination in our patient revealed a superficial partial necrosis of the epiglottis that did not obstruct the glottis. Dyspnea was caused by SIRS and did not deteriorate, possibly because of early identification of the disease, immediate initiation of intravenous antibiotics, and no manipulation of the larynx. Therefore, our patient did not require intubation (Figure, B).In conclusion, NE can occur in immunocompromised patients and can lead to airway compromise needing intubation and/or tracheostomy. The otorhinolaryngologist should be aware of this uncommon clinical condition.

General

A woman in her 20s presented to the emergency department with a 2-week history of progressive sore throat, dysphagia, and fever (38.2°C) that developed into dyspnea, dysphonia, and neck pain on the day of presentation. Initially, she had been treated with oral amoxicillin–clavulanic acid with no improvement. Her medical history included ulcerative colitis (UC) controlled by oral azathioprine for 2 years. She was a nonsmoker. Initial clinical evaluation revealed respiratory distress with respiratory rate of 21 breaths per minute, with oxygen saturation 95% on room air. Her heart rate was 95 beats per minute, her blood pressure was 135/91 mm Hg, and she was pyretic. Further examination with flexible fiberoptic laryngoscopy (Figure, A) showed considerable erythema and edema of the epiglottitis with patchy necrosis partially obstructing the glottis and saliva pooling in the supraglottis. Findings from the remainder of the otolaryngology examination and chest auscultation were normal. Subsequently, oxygen saturation improved to 100% with 3 L per minute of oxygen via nasal prongs. Her initial laboratory findings revealed a white blood cell count of 12 000/μL, absolute neutrophil count of 46%, hemoglobin count of 12.8 g/dL, and a platelet count of 175 000/μL. Her C-reactive protein level was 5 mg/dL (normal level, <0.5 mg/dL). Results from liver function tests and chest radiograph were normal.

what is your diagnosis?

What is your diagnosis?

Diphtheric laryngitis

Necrotic epiglottitis

Pseudomembranous epiglottitis

Candidosis

b

female

21-30

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2556185

A man in his 40s was referred for a 1-year history of decreased vision and the sensation of tunnel vision, which accompanied cognitive decline for the past 2 years. He had a history of renal cell carcinoma and had undergone left nephrectomy 1 year prior with no recurrence. Prior to presentation, his evaluation included brain magnetic resonance imaging and neurologic evaluation with unremarkable results, and he was scheduled to undergo neuropsychological testing.Visual acuity was counting fingers OD, and 20/100 OS. Motility and intraocular pressures were normal. There was a right afferent pupillary defect. Examination of the right eye revealed rubeosis iridis, a clear lens, neovascularization of the optic disc, retinal vasculitis, venous sheathing, and a dusky-appearing peripheral retina. The left eye had a clear lens and a normal fundus on clinical examination. Fluorescein angiography demonstrated a mixed retinal arteritis and phlebitis with extensive retinal and choroidal nonperfusion of the right eye with both retinal and optic nerve neovascularization. The left eye demonstrated patches of active arteritis peripherally with a minimally affected posterior pole (Figure).Fluorescein angiogram at 1 minute demonstrating a mixed occlusive arteritis and phlebitis (yellow arrowhead) with extensive areas of retinal and choroidal nonperfusion (white arrowhead) in the right eye. The posterior pole of the left eye appears unaffected.Check antinuclear antibodies, anticardiolipin antibodies, anti–double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies, and angiotensin-converting enzyme What Would You Do Next?

Panretinal photocoagulation

Check antinuclear antibodies, anticardiolipin antibodies, anti–double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies, and angiotensin-converting enzyme

Administer methylprednisolone, 1 g intravenously daily

Plasmapheresis

Systemic lupus erythematosus vasculitis

C

Administer methylprednisolone, 1 g intravenously daily

The clinical examination results and fluorescein angiography show a mixed occlusive arteritis and phlebitis. The chronicity of this patient's symptoms, as well as the absence of either a vitreous cellular reaction or retinitis, is suggestive of a systemic autoimmune vasculitis. Diagnostic considerations include Wegener granulomatosis, polyarteritis nodosa, and systemic lupus erythematosus (SLE). Given the severity of the systemic vasculitis and worsening neurologic symptoms, prompt initiation of high-dose steroids is the appropriate first step in management to reduce end organ damage from ischemia, especially given concern for concurrently active central nervous system (CNS) disease.1The diagnosis of SLE is based on clinical and laboratory findings. Antinuclear antibodies occur in 95% of cases, but anti–double-stranded DNA antibodies are more specific for the disease.2 In this case, antinuclear antibody testing had positive results with a 1:80 titer, and anticardiolipin screen revealed significantly elevated serum IgA of 65 A phospholipids and IgG of 112 G phospholipids. The anti–double-stranded DNA antibody level was more than 300 IU/mL. This testing confirmed the diagnosis of SLE.Visual loss from SLE vasculitis is an important prognostic indicator of disease severity. Population studies indicate that active CNS disease occurs in 73% of patients with retinopathy, and retinopathy significantly increases the risk of death related to lupus from 10.8% to 34%.3 In many cases, ocular involvement is the presenting symptom of the disease.While initial management of systemic vasculitis involves the initiation of high-dose steroid therapy to treat both ocular and CNS disease, steroid-sparing immunosuppression was initiated for improved long-term disease control.4 Combination therapy with both mycophenolate mofetil and cyclosporine was started concomitantly with corticosteroids for this patient.Plasmapheresis involves the removal, filtration, and replacement of plasma to eliminate circulating immune complexes. In cases such as this with severe vision loss as well as CNS involvement, plasmapheresis has been shown to be effective in restoring vision.5 While this patient did undergo plasmapheresis, this procedure takes time to arrange, and prompt steroid treatment should not be delayed.Panretinal photocoagulation is important in cases of occlusive lupus vasculitis for management of secondary proliferative retinopathy to reduce the risk of vitreous hemorrhage, neovascular glaucoma, and tractional retinal detachment. Panretinal photocoagulation should be considered to treat the anterior and posterior segment neovascularization, and the role of anti–vascular endothelial growth factor therapy may need to be considered as well, but independent of the initiation of corticosteroid treatment, which is needed to control the vasculitis.Over the course of 2 months, this patient's vision improved to 20/200 OD and 20/60 OS with prednisone, 60 mg daily; mycophenolate mofetil, 1500 mg twice daily; and cyclosporine, 100 mg twice daily. During this time, his proliferative retinopathy in the right eye was treated with panretinal photocoagulation. His neurologic symptoms, including confusion, have improved with treatment of his SLE.

Ophthalmology

A man in his 40s was referred for a 1-year history of decreased vision and the sensation of tunnel vision, which accompanied cognitive decline for the past 2 years. He had a history of renal cell carcinoma and had undergone left nephrectomy 1 year prior with no recurrence. Prior to presentation, his evaluation included brain magnetic resonance imaging and neurologic evaluation with unremarkable results, and he was scheduled to undergo neuropsychological testing.Visual acuity was counting fingers OD, and 20/100 OS. Motility and intraocular pressures were normal. There was a right afferent pupillary defect. Examination of the right eye revealed rubeosis iridis, a clear lens, neovascularization of the optic disc, retinal vasculitis, venous sheathing, and a dusky-appearing peripheral retina. The left eye had a clear lens and a normal fundus on clinical examination. Fluorescein angiography demonstrated a mixed retinal arteritis and phlebitis with extensive retinal and choroidal nonperfusion of the right eye with both retinal and optic nerve neovascularization. The left eye demonstrated patches of active arteritis peripherally with a minimally affected posterior pole (Figure).Fluorescein angiogram at 1 minute demonstrating a mixed occlusive arteritis and phlebitis (yellow arrowhead) with extensive areas of retinal and choroidal nonperfusion (white arrowhead) in the right eye. The posterior pole of the left eye appears unaffected.Check antinuclear antibodies, anticardiolipin antibodies, anti–double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies, and angiotensin-converting enzyme

what would you do next?

What would you do next?

Plasmapheresis

Administer methylprednisolone, 1 g intravenously daily

Check antinuclear antibodies, anticardiolipin antibodies, anti–double-stranded DNA antibodies, antineutrophil cytoplasmic antibodies, and angiotensin-converting enzyme

Panretinal photocoagulation

b

male

0-10

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2569439

A 21-year-old woman presented with foggy vision of her right eye that began 5 months prior. She had daily frontal headaches without any associated visual aura, numbness, or weakness. She had a history of “multiple lasers” of her right eye and blindness of her left eye from an unrepaired retinal detachment. Her medical history included a pheochromocytoma, bilateral adrenal gland resection, and a pancreatic cyst. Her father had a history of retinal detachment in his right eye; her 2 siblings did not have any medical or ocular issues.Visual acuity was 20/200 OD and no light perception OS. Anterior segment examination was unremarkable in the right eye and revealed phthisis bulbi of the left eye. Dilated fundus examination of the right eye revealed prominent, engorged, and tortuous vessels with traction extending from the optic disc to the superior peripheral retina. There was an associated thick fibrotic epiretinal membrane extending from the macula to the superior peripheral retina. The retinal arterioles were attenuated and there was thickening of the macula with subretinal fluid found on optical coherence tomography. In the superior retinal periphery, there was an orange, round, circumscribed mass with overlying tractional retinal detachment and numerous other smaller orange masses (Figure 1A). Fluorescein angiography of her right eye showed early hyperfluorescence of the lesions with late leakage (Figure 1B).A, Wide-field scanning laser image of right fundus showing a round mass with an overlying tractional retinal detachment. Associated engorged and tortuous vessels emanate from the optic disc. B, Wide-field scanning laser fluorescein angiographic late-phase frame of right fundus demonstrating late leakage of engorged vessels. What Would You Do Next?

Conduct complete blood cell count

Conduct genetic testing

Refer for magnetic resonance imaging

Perform retinal biopsy

Retinal capillary hemangioma

C

Refer for magnetic resonance imaging

Retinal angiomas are benign vascular hamartomas that are often associated with systemic disease. On fundus examination, a retinal capillary hemangioma (RCH) presents as a round, circumscribed, orange/red mass with prominent tortuous feeder vessels extending from the optic disc.1 Retinal capillary hemangiomas are associated with Von Hippel–Lindau (VHL) disease, an autosomal dominant multisystem cancer syndrome. Retinal lesions are the earliest and most frequent manifestation (present in 49%-68% of cases), but the condition is also associated with life-threatening tumors, including renal cell carcinoma, pheochromocytoma, and cerebellar hemangioblastoma.2On investigation, this patient revealed that her father has VHL, consistent with his history of retinal detachment. Genetic testing for a VHL gene mutation on chromosome 3 and retinal biopsy are not necessary in this case as multiple RCHs are diagnostic for VHL disease; however, genetic counseling may help this patient understand the risk to living relatives and offspring. Genetic testing may be a valuable screening tool for patients with solitary lesions or a negative family history. Approximately 20% of VHL gene mutations are sporadic. Patients with VHL disease and their relatives should be screened for ocular disease and biennial systemic evaluation should include magnetic resonance imaging of the brain, pancreas, and kidneys.2 Lifelong annual screening is recommended in those with VHL disease and VHL gene mutation carriers.3The presence of at least 1 RCH increases the risk for decreased vision, with greatest vision loss found with both juxtapapillary and peripheral locations of RCHs. The most common etiologies of vision loss in VHL disease are subretinal fluid near the macula, epiretinal membranes, or retinal detachments.4 Approximately 20% of patients have at least 1 eye with severe complications due to angiomatous disease.4 Several longitudinal studies have shown progression to bilateral eye involvement in 21.2% to 33% of patients with unilateral disease.3,5,6 Thus, examination of the fellow eye for retinal angiomas is essential throughout the disease course.Fluorescein angiography typically demonstrates early hyperfluorescence of the vascular lesions with progressive leakage. Echography can be used to monitor tumor dimensions, and optical coherence tomography may be used to detect macular subretinal fluid and evaluate treatment response.7Management of retinal angiomas depends on tumor size and location. Laser photocoagulation or cryotherapy may be used to ablate the tumor and/or feeder vessels in RCHs up to 4.5 mm in diameter. Plaque or low-dose external beam radiotherapy may be used for tumors greater than 4.0 mm in diameter and those resistant to photocoagulation or cryotherapy. These approaches may be paired with pars plana vitrectomy if necessitated by an epiretinal membrane or retinal detachment.7This patient had magnetic resonance imaging of the brain and abdomen, which was negative for renal cell carcinoma and cerebellar hemangioblastoma. One month after presentation, she underwent cryotherapy of the retinal angiomas. She later developed new angiomas and a tractional retinal detachment, and the epiretinal membrane progressed to involve the optic disc. Two months after her initial treatment, she underwent pars plana vitrectomy, membrane peeling, endolaser of the angiomas, and air-fluid exchange (Figure 2). On follow-up 4 months afterwards, her visual acuity was 20/800 OD.Wide-field scanning laser image of right fundus 5 months after cryotherapy and 3 months after pars plana vitrectomy, membrane peel, removal of subretinal fluid, and endolaser of the retinal angiomas.

Ophthalmology

A 21-year-old woman presented with foggy vision of her right eye that began 5 months prior. She had daily frontal headaches without any associated visual aura, numbness, or weakness. She had a history of “multiple lasers” of her right eye and blindness of her left eye from an unrepaired retinal detachment. Her medical history included a pheochromocytoma, bilateral adrenal gland resection, and a pancreatic cyst. Her father had a history of retinal detachment in his right eye; her 2 siblings did not have any medical or ocular issues.Visual acuity was 20/200 OD and no light perception OS. Anterior segment examination was unremarkable in the right eye and revealed phthisis bulbi of the left eye. Dilated fundus examination of the right eye revealed prominent, engorged, and tortuous vessels with traction extending from the optic disc to the superior peripheral retina. There was an associated thick fibrotic epiretinal membrane extending from the macula to the superior peripheral retina. The retinal arterioles were attenuated and there was thickening of the macula with subretinal fluid found on optical coherence tomography. In the superior retinal periphery, there was an orange, round, circumscribed mass with overlying tractional retinal detachment and numerous other smaller orange masses (Figure 1A). Fluorescein angiography of her right eye showed early hyperfluorescence of the lesions with late leakage (Figure 1B).A, Wide-field scanning laser image of right fundus showing a round mass with an overlying tractional retinal detachment. Associated engorged and tortuous vessels emanate from the optic disc. B, Wide-field scanning laser fluorescein angiographic late-phase frame of right fundus demonstrating late leakage of engorged vessels.

what would you do next?

What would you do next?

Perform retinal biopsy

Refer for magnetic resonance imaging

Conduct genetic testing

Conduct complete blood cell count

b

female

21-30

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2546173

A 67-year-old woman with a history of peripheral T-cell lymphoma after an allogeneic stem cell transplant (SCT) presented with 3 days of fever, weakness, and dyspnea.She was diagnosed with stage IV peripheral T-cell lymphoma 3 years prior and was initially treated with gemcitabine, vinorelbine, and doxorubicin. Her disease recurred 1 year later, and she underwent haplotype-matched allogeneic SCT 8 months prior to admission. Two months prior to admission, she developed graft-vs-host disease requiring high-dose prednisone, rituximab, and intravenous immunoglobulin. At the time of admission, she was receiving prednisone (40 mg/d) and tacrolimus for graft-vs-host disease and prophylaxis of infection with levofloxacin, valacyclovir, posaconazole, and thrice weekly dapsone. The patient lived with her family, including her son who recently had a cough. She was born in the Philippines and immigrated to the United States 3 decades prior. She denied recent travel.On examination, her temperature was 38.3° C, pulse of 115 beats/min, blood pressure of 110/50 mm Hg, respiratory rate of 24 breaths/min, and an oxygen saturation of 90% on room air. Cardiopulmonary examination revealed tachycardia, increased work of breathing and bibasilar crackles without wheezes. Her laboratory studies revealed a white blood cell count of 4.2 × 106/mL (normal range, 3.4-10 × 106/mL), hemoglobin of 10.3 g/dL (normal range, 12-15.5 g/dL [to convert g/dL to g/L, multiply by 10]), platelets of 45 × 106/mL (normal range, 140-450 × 106/mL), and creatinine of 1.2 mg/dL (normal range, 0.5-1.0 mg/dL [to convert mg/dL to μmol/L, multiply by 88.4]). A chest radiograph demonstrated bilateral opacities without pleural effusion or pneumothorax. Initial empirical treatment included vancomycin, cefepime, azithromycin, and oseltamivir. On hospital day 2, she was intubated for hypoxemic respiratory failure. Computed tomography (CT) of the chest was performed (Figure, A) and compared with a study 2 weeks prior when she was asymptomatic (Figure, B).A, Computed tomographic (CT) chest image obtained on admission demonstrates diffuse bilateral ground glass opacities with interlobular septal thickening. B, Computed tomographic chest image from 2 weeks prior demonstrates nearly normal lungs.Add trimethoprim and sulfamethoxazole and corticosteroids for Pneumocystis jiroveci pneumoniaSwitch vancomycin to linezolid for refractory methicillin-resistant Staphylococcus aureus pneumonia What Would You Do Next?

Add amikacin to cover multidrug-resistant Acinetobacter

Add trimethoprim and sulfamethoxazole and corticosteroids for Pneumocystis jiroveci pneumonia

Switch vancomycin to linezolid for refractory methicillin-resistant Staphylococcus aureus pneumonia

Add liposomal amphotericin B to cover mucormycosis

Pneumocystis jiroveci pneumonia (PJP)

B

Add trimethoprim and sulfamethoxazole and corticosteroids for Pneumocystis jiroveci pneumonia

The differential for diffuse ground-glass opacities on chest CT includes certain infectious etiologies, pulmonary edema, diffuse alveolar damage owing to infection or drugs, and diffuse alveolar hemorrhage. We considered infectious etiologies to be most likely given this patient’s profound immunosuppression, which included respiratory viruses (eg, parainfluenza, influenza, respiratory syncytial virus, metapneumovirus), cytomegalovirus, PJP, and Mycoplasma pneumoniae.1 Among the provided answers, B is correct because the other infections are unlikely to present with diffuse ground-glass opacities on chest CT.In addition to her broad-spectrum coverage, she was started on intravenous TMP/SMZ (10 mg/kg/d) with methylprednisolone for PJP, as well as intravenous ganciclovir for possible cytomegalovirus. A broad respiratory viral panel returned negative for common respiratory pathogens. Blood, sputum, and urine cultures were negative, as were tests for Legionella, blastomycosis, and histoplasmosis. The serum β-D-glucan was more than 500 pg/mL (normal level, <60 pg/mL), galactomannan index was 0.15 (normal index, <0.5) and lactate dehydrogenase was 590 U/L (normal level, <199 U/L [to convert U/L to μkat/L, multiply by 0.0167). A cytomegalovirus polymerase chain reaction returned at 2110 IU/mL, increased from 721 IU/mL 2 weeks prior. Bronchoscopy revealed numerous cyst forms on methenamine silver stain, consistent with Pneumocystis jiroveci.Despite treatment with high-dose TMP/SMZ and methylprednisolone, her respiratory and hemodynamic status did not improve, and she remained on multiple vasopressors. Her course was complicated by persistent respiratory failure owing to persistent infection and/or acute respiratory distress syndrome. She died on hospital day 48.Infectious pulmonary complications after SCT remain a significant cause of morbidity and mortality.2 The incidence of pneumonia 1 year after SCT ranges from 18% to 26% depending on the type of SCT.3 When an organism is identified, the most common culprits are bacterial (22%) and viral (21%) causes.3 Infection with PJP is less common (0.5%-5%), especially with prophylactic agents, but can occur.3-6 Graft-vs-host disease, lymphopenia, and age increase the risk of pneumonia.3,5,6 Despite treatment, death due to PJP in post-SCT patients is 30% to 50%.3,7 Poor prognostic factors include radiographic evidence of diffuse lung involvement and prolonged steroid use.7The National Comprehensive Cancer Network guidelines recommend PJP prophylaxis for at least the first 6 months after allogeneic SCT and in patients receiving T-cell depleting agents or high-dose steroids.8 Studied regimens include TMP/SMZ, dapsone, atovaquone and pentamidine.9 Trimethoprim and sulfamethoxazole is the preferred agent in high-risk patients (ie, those receiving high-dose steroids),8 barring any absolute contraindications such as renal failure, severe cytopenias, or sulfa allergies. Patients receiving thrice-weekly dapsone vs TMP/SMZ have a higher relative risk (18.8) of developing PJP, but daily dapsone may be equally effective, though should be reserved for low-risk patients.4,10This patient was taking dapsone because of a historic allergy to sulfa (documented prior to SCT) which had been dosed thrice weekly. The case illustrates that PJP breakthrough in post-SCT patients still occurs despite prophylaxis, particularly in patients taking thrice-weekly dapsone, an inferior regimen when compared with daily dapsone and daily or thrice-weekly TMP/SMZ. The index of suspicion for PJP must remain high for patients with suppressed cellular immunity, especially in patients with imaging findings demonstrating diffuse bilateral ground glass opacities. Importantly, this case underscores that the type, dose, frequency, and adherence to prophylaxis affect overall protection.

Oncology

A 67-year-old woman with a history of peripheral T-cell lymphoma after an allogeneic stem cell transplant (SCT) presented with 3 days of fever, weakness, and dyspnea.She was diagnosed with stage IV peripheral T-cell lymphoma 3 years prior and was initially treated with gemcitabine, vinorelbine, and doxorubicin. Her disease recurred 1 year later, and she underwent haplotype-matched allogeneic SCT 8 months prior to admission. Two months prior to admission, she developed graft-vs-host disease requiring high-dose prednisone, rituximab, and intravenous immunoglobulin. At the time of admission, she was receiving prednisone (40 mg/d) and tacrolimus for graft-vs-host disease and prophylaxis of infection with levofloxacin, valacyclovir, posaconazole, and thrice weekly dapsone. The patient lived with her family, including her son who recently had a cough. She was born in the Philippines and immigrated to the United States 3 decades prior. She denied recent travel.On examination, her temperature was 38.3° C, pulse of 115 beats/min, blood pressure of 110/50 mm Hg, respiratory rate of 24 breaths/min, and an oxygen saturation of 90% on room air. Cardiopulmonary examination revealed tachycardia, increased work of breathing and bibasilar crackles without wheezes. Her laboratory studies revealed a white blood cell count of 4.2 × 106/mL (normal range, 3.4-10 × 106/mL), hemoglobin of 10.3 g/dL (normal range, 12-15.5 g/dL [to convert g/dL to g/L, multiply by 10]), platelets of 45 × 106/mL (normal range, 140-450 × 106/mL), and creatinine of 1.2 mg/dL (normal range, 0.5-1.0 mg/dL [to convert mg/dL to μmol/L, multiply by 88.4]). A chest radiograph demonstrated bilateral opacities without pleural effusion or pneumothorax. Initial empirical treatment included vancomycin, cefepime, azithromycin, and oseltamivir. On hospital day 2, she was intubated for hypoxemic respiratory failure. Computed tomography (CT) of the chest was performed (Figure, A) and compared with a study 2 weeks prior when she was asymptomatic (Figure, B).A, Computed tomographic (CT) chest image obtained on admission demonstrates diffuse bilateral ground glass opacities with interlobular septal thickening. B, Computed tomographic chest image from 2 weeks prior demonstrates nearly normal lungs.Add trimethoprim and sulfamethoxazole and corticosteroids for Pneumocystis jiroveci pneumoniaSwitch vancomycin to linezolid for refractory methicillin-resistant Staphylococcus aureus pneumonia

what would you do next?

What would you do next?

Switch vancomycin to linezolid for refractory methicillin-resistant Staphylococcus aureus pneumonia

Add liposomal amphotericin B to cover mucormycosis

Add amikacin to cover multidrug-resistant Acinetobacter

Add trimethoprim and sulfamethoxazole and corticosteroids for Pneumocystis jiroveci pneumonia

d

female

61-70

White

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2546654

A 69-year-old man with a history of relapsed acute myeloid leukemia (AML) monocytic type presented with intermittent fever and fatigue 2 months after allogeneic stem cell transplantation (SCT). Post-SCT bone marrow biopsy specimen analysis at day 30 showed no evidence of leukemic cells and 99.5% donor cells. His home medications included acyclovir, fluconazole, and cyclosporine. Temperature on admission was 103.1° F, and other vital signs were unremarkable. Vancomycin and cefepime were started for possible infection. Complete blood cell counts with differential counts showed no evidence of peripheral blasts. Laboratory and imaging work-up—including chest radiographs, blood culture, fungal culture, urinalysis, sputum culture, respiratory viral panel, fungitell and galactomannan assay, coccidioidomycosis serology, and cytomegalovirus and human herpesvirus 6 polymerase chain reaction assays—were all negative. The patient was discharged with oral antibiotics after being afebrile for 72 hours. Thereafter, he had 2 more emergency department visits and was readmitted for recurrent fever. A thorough physical examination revealed 2 nonpruritic skin bumps on the right forearm and left calf that both measured 1.0 cm × 1.5 cm. Both bumps were soft without pigmentation or ulceration. Pathologic sampling of the respective lesions revealed a diffuse infiltration of large mononuclear cells with high nuclear-to-cytoplasmic ratio (Figure, A and B). Immunohistochemistry staining was positive for CD4 cells and myeloperoxidase (Figure, C and D)A and B, Histologic evaluation of the skin biopsy specimens. C and D, Immunohistochemical analysis. What Is Your Diagnosis?

Methicillin-resistant Staphylococcus aureus skin infection

Candida tropicalis

Leukemia cutis

Disseminated coccidioidomycosis

C. Leukemia cutis (LC)

C

Leukemia cutis

Post-SCT extramedullary relapse of AML is very rare with an incidence of 0.02% to 20.00% and may occur in an isolated fashion or in combination with medullary relapse.1 Myelomonocytic and monocytic subtypes are most commonly associated LC,2,3 and its incidence is higher in pediatric population. Most of the LC cases are described in patients with AML; however, it can also develop in myelodysplastic syndrome, accelerated phase of chronic myeloid leukemia, and acute lymphoblastic leukemia.4The common sites of extramedullary AML are skin, bone, periosteum, soft tissue, and lymph nodes.5 Other commonly reported sites are those with less rigorous immune surveillance including testes, ovaries, and the central nervous system.5 Therefore, patients may present with soft tissue masses or lymphadenopathy and life-threatening complications such as spinal cord compression and extremity paresis.5 Cutaneous manifestations in LC are characterized by infiltration of leukemic cells into epidermis or dermis, causing single-to-multiple erythematous nodular or papular lesions that may be accompanied by ecchymosis, palpable purpura, bullous lesions, erythroderma, or ulcers. Most patients who received allogeneic SCT require post-SCT immunosuppressive agents to prevent graft-vs-host disease. Therefore, differential diagnoses of new skin lesions associated with recurrent fever are broad—including bacterial, viral, or fungal infection, and disease relapse—rendering LC a diagnostic challenge, especially when the marrow exam is negative.Risk factors associated with extramedullary relapse include French-American-British AML subtypes M4/M5 (hazard ratio [HR], 2.5; P = .02), age 18 years or younger (HR, 3.3; P = .006), pre-SCT extramedullary leukemia (HR, 4.6; P < .001), and refractory disease at the time of SCT (HR, 2.6; P = .02)1. Other cytogenetic abnormalities including del(5q) (32.1%), monosomy 7 (10.8%), trisomy 8 (10.4%), trisomy 4 (4.4%), del(20q) (2.4%), monosomy 16 (2.3%), and trisomy 11 (2.2%) are frequently associated with extramedullary leukemia6; however, their significance in the post-SCT relapse setting remains to be answered. The pathogenesis of extramedullary infiltration is ill-defined. Extramedullary migration is presumably initiated by altered expression of adhesion molecule that allows for the separation of leukemic cells from the bone marrow and mobilization into blood circulation.6 In a prior study7 of 331 patients with de novo AML, the CD56 positivity (defined as at least 20% of blasts expressing CD56 on flow-cytometry) was shown to be associated with significantly higher rate of extramedullary disease compared to CD56 negativity (53.1% vs 29.2%; P = .01), suggesting that CD56 may mediate extramedullary migration or tissue invasion. However, there was no significant intergroup difference in leukemic skin infiltration (3.1% vs 3.1%; P > .99), questioning the role of CD56 in LC pathogenesis7.Two-years overall survival rate in patients with extramedullary relapse was shown to be 11% to 38%, and the prognosis depends on the presence of concurrent medullary disease. Solh et al8 reported a significantly better 6-month survival rate in patients with isolated extramedullary relapse (69%) compared with those with medullary relapse (27%) or combined medullary and extramedullary relapse (8%).There is no standard treatment established for LC. Since graft-vs-leukemia effect plays an important role for cutaneous disease control, tapering immunosuppressive agents should be considered as an initial approach in patients without active graft-vs-host disease.6 In patients with good performance status and younger age, systemic chemotherapy could be a reasonable option as a next step. Previous retrospective study in 257 patients with AML and post-SCT extramedullary relapse showed nominally longer median survival with systemic chemotherapy compared with no treatment (120 vs 25 days)1. Adding donor lymphocyte infusion into the systemic chemotherapy resulted in further improvement in median survival (226 vs 120 days).1 Therefore, donor lymphocyte infusion should be strongly considered if it is available. In patients who are not eligible for intensive chemotherapy, DNA hypomethylating agents such as azacitidine could be an alternative option as shown in a recent case study.9 Hypomethylating agents induce leukemic cell differentiation as well as increase the expression of the human leukocyte antigen and tumor-associated antigens, which may potentiate the graft-vs-leukemia effect.10 In our patient, cyclosporine was tapered and azacitidine (75 mg/m2/d for 7 days) was started based on his poor performance status. The patient completed total 4 cycles of azacitidine treatment, and his disease is currently stable and has been for 8 months.

Oncology

A 69-year-old man with a history of relapsed acute myeloid leukemia (AML) monocytic type presented with intermittent fever and fatigue 2 months after allogeneic stem cell transplantation (SCT). Post-SCT bone marrow biopsy specimen analysis at day 30 showed no evidence of leukemic cells and 99.5% donor cells. His home medications included acyclovir, fluconazole, and cyclosporine. Temperature on admission was 103.1° F, and other vital signs were unremarkable. Vancomycin and cefepime were started for possible infection. Complete blood cell counts with differential counts showed no evidence of peripheral blasts. Laboratory and imaging work-up—including chest radiographs, blood culture, fungal culture, urinalysis, sputum culture, respiratory viral panel, fungitell and galactomannan assay, coccidioidomycosis serology, and cytomegalovirus and human herpesvirus 6 polymerase chain reaction assays—were all negative. The patient was discharged with oral antibiotics after being afebrile for 72 hours. Thereafter, he had 2 more emergency department visits and was readmitted for recurrent fever. A thorough physical examination revealed 2 nonpruritic skin bumps on the right forearm and left calf that both measured 1.0 cm × 1.5 cm. Both bumps were soft without pigmentation or ulceration. Pathologic sampling of the respective lesions revealed a diffuse infiltration of large mononuclear cells with high nuclear-to-cytoplasmic ratio (Figure, A and B). Immunohistochemistry staining was positive for CD4 cells and myeloperoxidase (Figure, C and D)A and B, Histologic evaluation of the skin biopsy specimens. C and D, Immunohistochemical analysis.

what is your diagnosis?

What is your diagnosis?

Disseminated coccidioidomycosis

Methicillin-resistant Staphylococcus aureus skin infection

Candida tropicalis

Leukemia cutis

d

male

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2585958

An 84-year-old woman with a history of chronic kidney disease, prior stroke, and hypertension was admitted with a 2-week history of spontaneous subcutaneous ecchymoses and hematomas. She did not have any history of bleeding disorders, preceding trauma, or other precipitating factors such as recent heparin exposure, surgical procedures, underlying liver disease, or receipt of anticoagulation agents. There was no family history of hematologic disorders.Her vital signs were normal. Physical examination showed large ecchymoses on the left arm, right shoulder, left anterior chest wall, and flank. Initial laboratory results showed isolated severe anemia. Computed tomographic imaging showed a large soft-tissue hematoma in the left chest wall without evidence of internal hemorrhage. Test results for other causes of anemia were unremarkable. Laboratory values and mixing study results are shown in the Table.The patient has a common clotting factor inhibitor.The patient has an extrinsic clotting factor inhibitor.The patient has an intrinsic clotting factor inhibitor.The patient does not have a clotting factor inhibitor. How Do You Interpret These Test Results?

The patient has a common clotting factor inhibitor.

The patient has an extrinsic clotting factor inhibitor.

The patient has an intrinsic clotting factor inhibitor.

The patient does not have a clotting factor inhibitor.

C

The patient has an intrinsic clotting factor inhibitor.

The mixing study is a relatively simple procedure performed in the hemostasis laboratory by mixing the patient’s plasma with normal pooled plasma in a 1:1 ratio. Clotting tests will result in normal values when at least 50% of the activity of the involved coagulation factors is present.1 If the underlying problem is a factor production deficiency, mixing the patient’s plasma 1:1 with normal pooled plasma that contains 100% of the normal factor level will result in a level that is greater than or equal to 50% in the mixture. In this scenario, the prothrombin time or partial thromboplastin time will be normal, indicating a factor production deficiency. Failure to correct the clotting time in the mixing study indicates presence of an inhibitor. Some inhibitors take time to inhibit clotting factors in the normal pooled plasma. When this occurs, the 1:1 mix will have a normal coagulation when tested immediately but will yield an abnormal test result when incubated for 1 to 2 hours at 37°C. The Medicare midpoint reimbursement is $7.26 for a prothrombin time mixing study and $11.05 for a partial thromboplastin time mixing study.2 Despite some limitations, the mixing study helps guide further testing by determining whether coagulation factor testing or inhibitor testing should be performed next.The isolated prolonged partial thromboplastin time led to a differential diagnosis of inadequate levels of factors VIII (antihemophilic factor [AHF]), IX (plasma thromboplastin component [PTC]), or XI (plasma thromboplastin antecedent [PTA]) in the intrinsic pathway. The partial thromboplastin time mixing study did not correct, which suggests the presence of an acquired inhibitor. Individual clotting factor assays revealed reduced factor VIII activity (<5%) with a high titer for factor VIII inhibitor.Acquired hemophilia results from development of autoantibodies to the coagulation factors. Antibodies to factor VIII are the most common type of acquired hemophilia. Risk factors include older age, pregnancy or the postpartum state, rheumatologic disorders, malignancy, and drug reactions. However, no underlying disorder was present in 46% of cases based on a population-based study.3 The mainstay of treatment is control of bleeding and elimination of the inhibitor. Prednisone and the addition of cyclophosphamide, along with other immunosuppressants, have been studied, but no therapy is clearly superior.4Occasionally, mixing studies are not definitive, especially when a partial thromboplastin time is mildly prolonged and corrects with mixing. In this case, performing both selected factor activity assays and lupus anticoagulant screening can identify whether this prolonged partial thromboplastin time is from a nonspecific inhibitor such as a lupus anticoagulant or a factor deficiency—with factors VIII and IX being the most common.The patient received a transfusion with packed red blood cells and was treated with factor VIII inhibitor bypassing activity (anti-inhibitor coagulant complex is the name of the plasma-derived concentrate) to overcome the inhibitor. The patient simultaneously began treatment with a combination of prednisone, 1 mg/kg per day, and cyclophosphamide for immunosuppression to eradicate the inhibitor. At 4-week follow-up, the inhibitor was still detectable by factor VIII inhibitor assay. However, the titer continued to decline and factor VIII activity improved. The patient did not have further bleeding and her hemoglobin level normalized. The etiology of the inhibitor was not identified, but older age is the most common risk factor for clotting factor inhibitors.Isolated prolonged partial thromboplastin time may indicate deficiencies in intrinsic factor or the presence of an acquired intrinsic clotting factor inhibitor.The purpose of a mixing study is to determine whether an abnormal coagulation test is due to deficiency of a coagulation factor or an inhibitory antibody.Results of a mixing study can be used to determine whether further testing should be performed to identify a deficient factor or a factor that lacks activity.

Diagnostic

An 84-year-old woman with a history of chronic kidney disease, prior stroke, and hypertension was admitted with a 2-week history of spontaneous subcutaneous ecchymoses and hematomas. She did not have any history of bleeding disorders, preceding trauma, or other precipitating factors such as recent heparin exposure, surgical procedures, underlying liver disease, or receipt of anticoagulation agents. There was no family history of hematologic disorders.Her vital signs were normal. Physical examination showed large ecchymoses on the left arm, right shoulder, left anterior chest wall, and flank. Initial laboratory results showed isolated severe anemia. Computed tomographic imaging showed a large soft-tissue hematoma in the left chest wall without evidence of internal hemorrhage. Test results for other causes of anemia were unremarkable. Laboratory values and mixing study results are shown in the Table.The patient has a common clotting factor inhibitor.The patient has an extrinsic clotting factor inhibitor.The patient has an intrinsic clotting factor inhibitor.The patient does not have a clotting factor inhibitor.

how do you interpret these test results?

How do you interpret these results?

The patient does not have a clotting factor inhibitor.

The patient has an extrinsic clotting factor inhibitor.

The patient has an intrinsic clotting factor inhibitor.

The patient has a common clotting factor inhibitor.

c

female

81-90

original

https://jamanetwork.com/journals/jama/fullarticle/2579844

A 34-year-old woman presenting to the clinic reported having thickened toenails for more than 20 years. She had used an over-the-counter antifungal cream intermittently to treat pruritus of her feet. Her father and sister had similar, but less severe, toenail problems. She had no history of dandruff, skin problems, or joint pains. Her medical history was significant for asthma, but she had been symptom free for more than 7 years without medications. She reported no pain in the nails or difficulty ambulating. The patient, a stay-at-home mother, denied prior toenail trauma, frequent sports activities, or hyperhidrosis of the feet. She had undergone no previous diagnostic tests or treatment for her toenails. Physical examination revealed thickening, yellow discoloration, and subungual hyperkeratosis of all 10 toenails (Figure, panel A). Scale was present on the plantar surface skin and in the web spaces (Figure, panel B). Examination of the fingernails, scalp, and skin was normal.A, Appearance of toenails on left and right feet. B, Plantar surface of both feet.Reassure the patient that no treatment is necessaryPerform a diagnostic test to clarify the diagnosis What Would You Do Next?

Treat with an oral antifungal

Reassure the patient that no treatment is necessary

Treat with a topical antifungal

Perform a diagnostic test to clarify the diagnosis

Onychomycosis

D

Perform a diagnostic test to clarify the diagnosis

The key to the diagnosis was the presence of subungual hyperkeratosis and plantar scale, suggesting the diagnosis of onychomycosis. Although onychomycosis is the most common nail disorder, approximately one-half of all nail dystrophies are attributable to other etiologies, both benign and malignant1; therefore, the diagnosis should not be made by history and physical examination alone. The diagnosis of onychomycosis can be confirmed using 1 of 3 routine methods. First, direct microscopy of nail scrapings with potassium hydroxide is a rapid in-office test that determines the presence or absence of fungal hyphae. Second, nails can be clipped, placed into 10% buffered formalin, and sent for histopathologic analysis with periodic acid–Schiff (PAS) staining. Third, nail scrapings can be sent to a central laboratory for fungal culture to identify the causative organism.Onychomycosis is a fungal infection of the nail unit and the most common nail disorder.2 The dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes cause the most cases in the United States. Internists and primary care physicians are often the first to encounter nail dystrophies and are well positioned to make a definitive diagnosis and initiate prompt treatment. Onychomycosis may contribute to local pain, paresthesias, and even difficulty walking. Risk factors for onychomycosis include trauma, hyperhidrosis, tinea pedis, psoriasis, peripheral artery disease, and diabetes. Physical examination typically shows white or yellow staining of the nail plate and nail bed hyperkeratosis leading to onycholysis (detachment of the nail plate from its bed). With prolonged disease, nail plate dystrophy with thickening, crumbling, and ridging may develop. The diagnosis of onychomycosis is made using these key findings from the history and physical, with a laboratory confirmation. Empirical treatment of nail dystrophies should not be routinely performed, because the differential diagnosis includes benign inflammatory conditions such as lichen planus and psoriasis, infections attributable to bacteria and human papillomavirus, subungual exostoses, and malignant neoplasms such as squamous cell carcinoma and melanoma.3 Empirical treatment may be considered in immunosuppressed patients, for whom prompt treatment is critical. Since patients with onychomycosis may experience physical, social, and emotional sequelae from disease progression, treatment options should be discussed. The decision to treat with oral vs topical medication vs observation is based on the number of nails affected and extent of infection, prognostic factors (immunosuppression, diabetes), medication interactions, prior treatment failures, efficacy, and cost.3-5Systemic treatment options approved by the US Food and Drug Administration (FDA) for toenail onychomycosis include itraconazole6 and terbinafine.7 These medications are metabolized by CYP450 and have important drug-drug interactions. Monitoring of alanine aminotransferase levels is suggested for patients receiving these systemic therapies.6,7 Oral medications are generally more effective than topical therapies and are used for more severe cases of onychomycosis (see eTable in the Supplement).FDA-sanctioned topical therapy for toenail onychomycosis includes ciclopirox (8% lacquer),8 tavaborole (5% solution),9 and efinaconazole (10% solution).10 Topical therapies are generally reserved for patients with less than 50% nail surface area involvement, nail thickness less than 3 mm, and no more than 3 to 4 nails affected. Patients should be advised to avoid use of nail polish, since efficacy of topical therapies with nail polish is unknown.Patients should be counseled prior to initiating therapy that even if a mycological cure is attained, a clinically normal nail may be not possible, particularly when the disease affects the nail matrix or when concurrent nail psoriasis is present.The diagnosis of onychomycosis was confirmed with a PAS stain of nail clippings that demonstrated fungal hyphae and a culture growing T rubrum. The patient completed a 12-week course of terbinafine (250 mg daily) and was advised that clinical improvement would take 1 to 1.5 years as the nail continued to grow. Six months after completing therapy, physical examination showed a reduction in subungual hyperkeratosis and an increase in clear nail.

General

A 34-year-old woman presenting to the clinic reported having thickened toenails for more than 20 years. She had used an over-the-counter antifungal cream intermittently to treat pruritus of her feet. Her father and sister had similar, but less severe, toenail problems. She had no history of dandruff, skin problems, or joint pains. Her medical history was significant for asthma, but she had been symptom free for more than 7 years without medications. She reported no pain in the nails or difficulty ambulating. The patient, a stay-at-home mother, denied prior toenail trauma, frequent sports activities, or hyperhidrosis of the feet. She had undergone no previous diagnostic tests or treatment for her toenails. Physical examination revealed thickening, yellow discoloration, and subungual hyperkeratosis of all 10 toenails (Figure, panel A). Scale was present on the plantar surface skin and in the web spaces (Figure, panel B). Examination of the fingernails, scalp, and skin was normal.A, Appearance of toenails on left and right feet. B, Plantar surface of both feet.Reassure the patient that no treatment is necessaryPerform a diagnostic test to clarify the diagnosis

what would you do next?

What would you do next?

Treat with a topical antifungal

Treat with an oral antifungal

Perform a diagnostic test to clarify the diagnosis

Reassure the patient that no treatment is necessary

c

female

31-40

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2538521

A man in his 70s presented to the clinic with a split in the right fifth fingernail for the past 10 years. He reported paroxysmal, intermittent pain that was exacerbated by cold weather. He fractured the digit more than 30 years earlier. Physical examination revealed distal nail plate splitting with accompanying longitudinal erythronychia (Figure, A) and tenderness on palpation of the nail unit. Magnetic resonance imaging revealed a nail matrix lesion (Figure, B), which was excised using a transungual approach with partial nail avulsion. The specimen was analyzed by histopathology (Figure, C and D). What Is Your Diagnosis?

Amelanotic melanoma

Onychopapilloma

Glomus tumor

Squamous cell carcinoma in situ

C. Glomus tumor

C

Glomus tumor

Histopathological examination showed a circumscribed dermal nodular tumor (Figure, C), with monomorphic cells with pale to eosinophilic cytoplasms and round to oval central nuclei associated with small caliber vascular channels (Figure, D), diagnostic of a glomus tumor (glomangioma). Eight weeks following surgery, the patient reported that his symptoms, including pain and cold sensitivity, resolved.Glomus tumors are benign neoplasms derived from cells of the glomus body, a specialized arteriovenous shunt involved in temperature regulation.1 Glomus bodies are highly distributed in the fingertips, thus accounting for the high frequency of tumors in this region. In fact, glomus represent 1% to 5% of hand tumors and are most commonly located in the subungual region.2 They typically present as solitary tumors less than 1 cm in women aged between 30 and 50 years.3 The presence of multiple glomus tumors in the digits should raise suspicion for neurofibromatosis type 1.4Subungual glomus tumors may present with a classic triad of symptoms: pinpoint tenderness, severe pain, and cold hypersensitivity.5 On physical examination, a small, round, bluish nodule may be visible through the nail plate or a longitudinal red band may be evident in the plate. Several tests may be helpful for diagnosis: (1) Love test, where pinpoint pressure will provoke exquisite pain in the area of the tumor, with absence of pain in the surrounding nail. This test has a high sensitivity, but low specificity. (2) Hildreth test, in which a tourniquet is applied to the associated limb and inflated. The test is positive if the nail pain decreases with inflation, and recurs with deflation. This test has high sensitivity and specificity. (3) The cold sensitivity test, in which the affected hand is submerged in cold water, is positive if pain is elicited around the lesion.6Imaging is helpful in the diagnosis of glomus tumors. X-ray examination reveals bone erosions in 50% of patients. Doppler ultrasound examination can detect glomus tumors 2 mm in diameter and color duplex Doppler sonography has even higher sensitivity and specificity. Magnetic resonance imaging identifies tumors as small as 2 mm in diameter, which is enhanced by use of gadolinium injection.7The treatment of choice for suspected symptomatic glomus tumors is complete excision, which may be performed through a transungual5 or a lateral subperiosteal approach.8 An advantage of the subungual approach is that nail avulsion allows for adequate exposure of the tumor, while reducing the risk of local recurrence.5 Unfortunately, recurrence may still occur and nail dystrophy is common. Alternatively, the lateral subungual technique preserves the nail unit and reduces the risk of permanent nail dystrophy, but is difficult to perform when the tumor is localized centrally instead of laterally.8Therefore, bluish to erythematous discoloration of the nail or longitudinal erythronychia, combined with pinpoint tenderness, paroxysmal pain, and cold hypersensitivity, should prompt imaging and/or excision. It is important to remember that some cases of erythronychia may be of malignant origin, including squamous cell carcinoma and malignant melanoma.9

Dermatology

A man in his 70s presented to the clinic with a split in the right fifth fingernail for the past 10 years. He reported paroxysmal, intermittent pain that was exacerbated by cold weather. He fractured the digit more than 30 years earlier. Physical examination revealed distal nail plate splitting with accompanying longitudinal erythronychia (Figure, A) and tenderness on palpation of the nail unit. Magnetic resonance imaging revealed a nail matrix lesion (Figure, B), which was excised using a transungual approach with partial nail avulsion. The specimen was analyzed by histopathology (Figure, C and D).

what is your diagnosis?

What is your diagnosis?

Glomus tumor

Amelanotic melanoma

Onychopapilloma

Squamous cell carcinoma in situ

a

male

71-80

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2541900

An African American woman in her 30s with no medical history presented with a 4-year history of diffuse progressive proliferation of dark papules. The patient noted that the lesions initially began on her thighs and rapidly multiplied throughout her skin. Some of the lesions were pruritic and when scratched could be removed, leaving behind a hyperpigmented macule. The patient described a sunburn several weeks prior to the initial eruption. She was taking no medications and these lesions were unchanged throughout an uncomplicated pregnancy. There was no personal or family history of melanoma or eruptive nevi. On physical examination, she had hundreds of 1- to 2-mm dark brown-black monomorphic papules throughout her trunk, extremities, palms, face, tongue, and sclera (Figure, A). No lymphadenopathy was present. Findings from laboratory tests, including a complete blood cell count, comprehensive metabolic panel, and computed tomography of the chest, were unremarkable. A punch biopsy was performed for histopathologic examination (Figure, B-D).A, Photograph of left thigh shows diffuse 1- to 2-mm dark brown-black macules and papules. B and C, Punch biopsy of right arm shows a circumscribed proliferation of pigmented epithelioid melanocytic nests, located primarily at tips of rete ridges. Moderate cytologic atypia is present. Superficial papillary dermis shows prominent pigment incontinence. No mitotic figures are seen. Kamino bodies were not visualized. D, Melan-A immunostain shows low pagetoid migration of melanocytes with a lack of melanocytic confluence at the dermal-epidermal junction. What Is Your Diagnosis?

Superficial spreading melanoma

Eruptive disseminated Spitz nevi

Dermatosis papulosa nigra

Metastatic melanoma

B. Eruptive disseminated Spitz nevi

B

Eruptive disseminated Spitz nevi

The punch biopsy specimens from the right arm show a circumscribed proliferation of pigmented epithelioid melanocytic nests, located primarily at tips of rete ridges. Moderate cytologic atypia is present (Figure, C). Melan-A immunostain demonstrates low pagetoid migration of melanocytes with a lack of melanocytic confluence at the dermal-epidermal junction (Figure, D). No further molecular or immunodiagnostic studies were performed because the patient lacked insurance coverage.The patient was referred to a primary care physician and gynecologist. Age-appropriate cancer screenings had normal results. Today, her skin lesions persist, but she reports no new lesions. She is otherwise in excellent health.Spitz nevi typically present as pink-to-red or brown-to-black papules, often on the face or extremities. Spitz nevi are classified as 3 distinct variants, listed in order of decreasing prevalence: solitary, agminated (grouped), and eruptive disseminated Spitz nevi (EDSN). To date, only 20 cases of EDSN have been reported in the literature.1Eruptive disseminated Spitz nevi is most common in the third decade of life, with a mean age of onset of 23 years.2 The etiology is unknown, but previous case reports have cited sunburn, pregnancy, intravenous drug use, operative stress, and autoimmune disease as possible inciting factors.3Malignant transformation of EDSN has not been described. Previous case reports suggest that it is reasonable to follow up EDSN patients with observation only.2,4,5 In several cases, regression of many lesions over several years has been reported.4 Excision is neither cosmetically beneficial nor feasible, given the multitude of lesions. Liquid nitrogen, electrodessication, laser ablation, and imiquimod have proven unsuccessful treatments.6,7 No satisfactory treatment exists for this cosmetically challenging condition.Diagnostically, Spitz nevi have been controversial since Spitz first described them in 1948. Spitz called the neoplasms “benign juvenile melanoma,” yet one of her 13 original cases died from metastatic disease. For 40 years thereafter, Spitz nevi were believed to be completely benign, and metastatic disease fell under melanoma classification. In 1989, however, Smith and colleagues8 showed that Spitz nevi can have atypia with regional nodal metastasis but still maintain benign behavior. Some authors believe that Spitz nevi should belong to an intermediate “melanocytoma” category between nevus and melanoma with suggestion for sentinel lymph node biopsy for difficult cases. This concept has critics; a recent systematic review of published reports of sentinel lymph node biopsy failed to demonstrate any prognostic value in atypical Spitz tumors.9Histopathologically, the lesions are symmetric well-circumscribed nests of melanocytes. The melanocytes show enlarged nuclei and abundant eosinophilic cytoplasm. There may be clefting between melanocyte nests and the overlying epithelium. The dermal mitotic rate and distance of mitotic bodies from the lesion’s deep edge are used to differentiate a melanoma from a Spitz nevus, along with immunostaining for Ki-67 and HMB-45; however, this distinction is often difficult to make, and the diagnosis in some cases may be equivocal. Misdiagnosis of EDSN as a melanoma has occurred, and 1 unfortunate patient with EDSN received 10 cycles of chemotherapy.5The inherent difficulty of accurately distinguishing between Spitz nevi and melanoma necessitates development of novel diagnostic genetic markers. Previous studies have shown BRAF and HRAS mutations in solitary Spitz nevi. However, a recent study of 37 Spitz nevi in a patient with EDSN failed to show BRAF, HRAS, NRAS, or KRAS mutations, making the characterization elusive to researchers.1 Another study demonstrated the presence of kinase fusion oncogenes ROS1, NTRK1, or ALK in the majority of Spitz nevi and a large proportion of spitzoid melanomas.10 Further study of the genetic alterations present in this rare disease is warranted to hasten diagnosis and offer targeted therapy.

Dermatology

An African American woman in her 30s with no medical history presented with a 4-year history of diffuse progressive proliferation of dark papules. The patient noted that the lesions initially began on her thighs and rapidly multiplied throughout her skin. Some of the lesions were pruritic and when scratched could be removed, leaving behind a hyperpigmented macule. The patient described a sunburn several weeks prior to the initial eruption. She was taking no medications and these lesions were unchanged throughout an uncomplicated pregnancy. There was no personal or family history of melanoma or eruptive nevi. On physical examination, she had hundreds of 1- to 2-mm dark brown-black monomorphic papules throughout her trunk, extremities, palms, face, tongue, and sclera (Figure, A). No lymphadenopathy was present. Findings from laboratory tests, including a complete blood cell count, comprehensive metabolic panel, and computed tomography of the chest, were unremarkable. A punch biopsy was performed for histopathologic examination (Figure, B-D).A, Photograph of left thigh shows diffuse 1- to 2-mm dark brown-black macules and papules. B and C, Punch biopsy of right arm shows a circumscribed proliferation of pigmented epithelioid melanocytic nests, located primarily at tips of rete ridges. Moderate cytologic atypia is present. Superficial papillary dermis shows prominent pigment incontinence. No mitotic figures are seen. Kamino bodies were not visualized. D, Melan-A immunostain shows low pagetoid migration of melanocytes with a lack of melanocytic confluence at the dermal-epidermal junction.

what is your diagnosis?

What is your diagnosis?

Eruptive disseminated Spitz nevi

Superficial spreading melanoma

Dermatosis papulosa nigra

Metastatic melanoma

a

female

0-10

African American

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2544683

A man in his 20s presented with a large, verrucous plaque on his right calf (Figure, A). The lesion initially appeared as a small, bluish plaque at a young age and had gradually increased in size with subsequent development of wartlike features. Aside from minor local pain and pruritus, the patient reported history of recurrent infections as well as oozing and bleeding after minimal trauma. Physical examination revealed soft, compressible nodules overlying a friable verrucous plaque in a linear distribution involving the length of the right calf with minimal tenderness on palpation. No other lesions were found on the body. A deep punch biopsy specimen was obtained and sent for histopathological examination (Figure, B and C).A, Clinical photograph of extensive verrucous plaque on the right calf. B, Biopsy specimen demonstrating epidermal verrucous hyperplasia, acanthosis, papillomatosis, and hyperkeratosis overlying dilated vessels in the dermis (hematoxylin-eosin, original magnification ×4). C, Deeper section showing similarly dilated vessels in the deep dermis to the base of the specimen, indicating the probability of deeper extension (hematoxylin-eosin, original magnification ×4). D, Negative D2-40 stain. What Is Your Diagnosis?

Malignant melanoma

Verruca vulgaris

Angiokeratoma circumscriptum

Verrucous hemangioma

D. Verrucous hemangioma

D

Verrucous hemangioma

The biopsy specimen revealed epidermal verrucous hyperplasia with irregular papillomatosis, acanthosis, and hyperkeratosis. Localized areas of dilated vessels were seen in the deep dermis to the base of the specimen, suggesting deeper extension. These findings were consistent with the diagnosis of verrucous hemangioma.1 Treatment options such as surgical excision were discussed; however, due to the extent of the lesion, radiation therapy was considered to debulk the lesion prior to surgery.Verrucous hemangiomas are rare, congenital, progressive vascular tumors that usually appear at birth or during childhood. The lesions present as dark red or bluish-purple plaques most commonly on the lower extremities in a unilateral distribution. They can be solitary or grouped in a linear or serpiginous orientation, with satellite lesions commonly seen.1,2 Initially they resemble other cutaneous hemangiomas, but verrucous features gradually develop after repeated traumas or infections.3 In addition to recurrent infections, verrucous hemangiomas are associated with bleeding, oozing, and pain.1,3 They do not resolve spontaneously and continue to enlarge.1 Dermoscopic features include a blue-white veil, dark round lacunae, and complete absence of a pigment network.4 Histopathologically, verrucous hemangiomas exhibit epidermal acanthosis, papillomatosis, and hyperkeratosis with dilated, capillary-sized blood vessels extending into the deep dermis and subcutis.1,2 Vascular thrombosis can also be seen.2The differential diagnosis varies depending on the stage of progression of the lesion. Early verrucous hemangiomas appear clinically similar to infantile hemangiomas or vascular malformations. In contrast to infantile hemangiomas, verrucous hemangiomas continue to grow and do not spontaneously resolve.2 As they develop verrucous features, they begin to resemble angiokeratomas.2 Although the clinical presentation should raise suspicion for verrucous hemangioma, the definitive diagnosis is made histopathologically. The extension of blood vessel abnormalities into the subcutaneous tissue is observed in verrucous hemangiomas, whereas the blood vessel abnormalities seen in angiokeratomas are limited to the superficial dermis.1,2 A deep punch biopsy is required to differentiate angiokeratoma circumscriptum from verrucous hemangiomas, as they can appear similar in superficial sections.1Immunohistochemical markers such as Wilms tumor-1 (WT-1), Glut-1 have attempted to accurately identify the nosology of these lesions to differentiate between vascular malformation and tumor. Wilms tumor-1 is expressed in vascular tumors but not vascular malformations.5 Glut-1 is negative in most vascular tumors and malformations but is positive in infantile hemangiomas.5 One group studied verrucous hemangiomas and angiokeratomas together and found that 29 out of 30 were Wilms tumor-1negative; however, the investigators did not differentiate between the 2 diseases, which may have skewed the results.6 Conversely, a study of 13 verrucous hemangiomas found that all stained positive for Wilms tumor-1 and Glut-1.5 Another study found that only 7 out of 11 verrucous hemangiomas were positive for Glut-1.7 D2-40 (Figure, D), a marker for lymphatic endothelium, is expected to be negative in verrucous hemangiomas.5Verrucous hemangiomas are difficult to treat because of their deep vascular component. Wide and deep surgical excision is the mainstay of therapy,4,8 but up to 33% of lesions recur.2 Large lesions present a surgical dilemma and may require skin grafting2 or serial excisions.3 Other treatment options such as electrocautery2 and laser therapy9 may yield some benefit in smaller lesions. The pulsed dye laser is effective in superficial lesions, and combining it with the longer wavelength Nd:YAG laser is ideal for deeper lesions. The carbon dioxide laser can reduce the hyperkeratotic component.9 One study found that the best treatment outcomes occurred when combining surgery with lasers.10 In cases with considerable progression, as seen in our patient, angiography is a suitable option to consider before deciding on invasive treatment.2,10

Dermatology

A man in his 20s presented with a large, verrucous plaque on his right calf (Figure, A). The lesion initially appeared as a small, bluish plaque at a young age and had gradually increased in size with subsequent development of wartlike features. Aside from minor local pain and pruritus, the patient reported history of recurrent infections as well as oozing and bleeding after minimal trauma. Physical examination revealed soft, compressible nodules overlying a friable verrucous plaque in a linear distribution involving the length of the right calf with minimal tenderness on palpation. No other lesions were found on the body. A deep punch biopsy specimen was obtained and sent for histopathological examination (Figure, B and C).A, Clinical photograph of extensive verrucous plaque on the right calf. B, Biopsy specimen demonstrating epidermal verrucous hyperplasia, acanthosis, papillomatosis, and hyperkeratosis overlying dilated vessels in the dermis (hematoxylin-eosin, original magnification ×4). C, Deeper section showing similarly dilated vessels in the deep dermis to the base of the specimen, indicating the probability of deeper extension (hematoxylin-eosin, original magnification ×4). D, Negative D2-40 stain.

what is your diagnosis?

What is your diagnosis?

Malignant melanoma

Angiokeratoma circumscriptum

Verrucous hemangioma

Verruca vulgaris

c

male

21-30

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2578652

An 11-year-old boy with a history of asthma and constipation presented with 6 weeks of intermittent, worsening lower back pain. His pain was mild to moderate, woke him from sleep, and limited his physical activity. He had previously been referred to orthopedics by his pediatrician owing to multiple presentations for the same complaint. The patient denied recent trauma, fevers, weight loss, cough, rash, or sick contacts. He was born in the United States with no recent travel. According to outpatient records, his height had been unchanged for the last 2 years.A physical examination showed a well-appearing young boy with unremarkable heart, lung, and abdominal findings. There was mild tenderness to palpation of the lumbar spine, and mild pain elicited with flexion and extension of his back. His strength was 4/5 in bilateral lower extremities, with otherwise normal neurological examination findings.He had a white blood cell count of 6.2 × 103/µL (to convert to ×109 per liter, multiply by 0.001), a hemoglobin level of 10.9 g/dL (to convert to grams per liter, multiply by 10.0), and a platelet count of 611 × 103/µL (to convert to ×109 per liter, multiply by 1.0), with a normal peripheral smear result. The results of a complete metabolic panel were unremarkable, and so were his lactate dehydrogenase and uric acid levels. He had an erythrocyte sedimentation rate of 80 mm/h and a C-reactive protein level of 20 mg/L (to convert to nanomoles per liter, multiply by 9.524).In the emergency department, a radiograph of his chest (Figure, A) revealed a right paravertebral mass, destruction of left seventh rib, a compression fracture of T8, and bony erosion of L1 vertebra. A computed tomographic (CT) scan (Figure, B) revealed paravertebral abscesses with T8 compression and destruction. Mediastinal and hilar lymphadenopathy was noted on imaging but are not shown.A, Radiograph of the chest reveals a right paravertebral mass (left arrowhead), destruction of the left seventh rib (top right arrowhead), a compression fracture of T8 (middle right arrowhead), and bony erosion of L1 vertebra (bottom right arrowhead). B, Computed tomographic scan reveals paravertebral abscesses (left arrowhead) with T8 compression and destruction (right arrowhead). What Is Your Diagnosis?

Ewing sarcoma

Tuberculous spondylitis

Discitis

Pyogenic osteomyelitis

B. Tuberculous spondylitis

B

Tuberculous spondylitis

After reviewing the images, the orthopedic and neurosurgical teams were concerned for spinal cord compression due to tuberculous spondylitis or malignancy. A CT-guided needle biopsy of L1 was performed, after which the patient was started on steroids for spinal cord compression. His back pain quickly improved. Preliminary results of the biopsy yielded granulomas and multinucleated giant cells. Owing to high suspicion for tuberculosis (TB), the patient was treated with rifampin, isoniazid, pyrazinamide, and ethambutol (ie, RIPE therapy). Purified protein derivative (tuberculin) was used after initiation of steroids, and he had a 0-mm induration at 48 hours; however, at 72 hours, he had an induration of more than 10 mm. The results of an interferon gamma release assay were indeterminate. Three acid-fast bacterial Gram stains of nasogastric aspirates were negative for TB; however, cultures of the same samples and a culture from the biopsy confirmed pansensitive Mycobacterium tuberculosis 4 to 8 weeks later. The boy’s treatment was changed to rifampin and isoniazid for a total of 12 months of therapy.Ultimately, the patient received a diagnosis of both tuberculous spondylitis and miliary TB. A full investigation by the US Department of Health revealed that a teacher at the child’s school had received a diagnosis of the same strain of TB and is thought to have been the source of infection.Among children, back pain without a history of trauma is uncommon and always necessitates further evaluation.1 In the case of this patient, the persistent focal back pain, the failure of expected growth, and the pain waking him from sleep were all red flags. Oncologic etiologies such as Ewing sarcoma and osteosarcoma were considered because they can originate in the spine, although they are rare.2 Osteomyelitis and discitis are unlikely given the appearance of the bone and lung findings.Tuberculous spondylitis (Pott disease) is the most common form of skeletal tuberculosis, occurring in 1.7% of the world’s population.3 It can be a difficult diagnosis to make in children and often takes weeks or months to confirm. Diagnosis is often delayed owing to the subacute nature of symptoms, particularly in areas where TB is not endemic.4 In cases for which there is high suspicion for TB, it is important to begin therapy as soon as possible. Tuberculous spondylitis is thought to be caused by the hematogenous spread of primary TB3 but can also occur from a contiguous disease or the lymphatic spread of a nearby pleural disease. It typically presents with lower thoracic and upper lumbar back pain,3,5 which is usually present for weeks, months, or even years. Associated symptoms include muscle spasms, rigid or erect posture, weight loss, and fevers.3The gold standard of diagnosis is a culture of infected tissue, either by surgical biopsy or CT-guided needle biopsy.4,6 An interferon gamma release assay is only 84% sensitive for skeletal tuberculosis, although it is 95% specific.7 Acid-fast bacterial stains are often negative for skeletal TB,7 although cultures are positive up to 75% of the time.7 At the time of diagnosis of tuberculous spondylitis, about 50% of patients have concomitant pulmonary TB.8 Tuberculous spondylitis is treated medically with RIPE therapy,9 but surgical intervention may be warranted for patients with significant kyphosis, spinal involvement, or neurological deficits.5,10Patients with TB who are from endemic areas should be under suspicion for having tuberculous spondylitis, but this diagnosis should also be considered for children without known risk factors. For patients with tuberculous spondylitis, it is imperative to use a multidisciplinary approach (using the orthopedics, neurosurgery, and infectious disease departments and the US Department of Health).

Pediatrics

An 11-year-old boy with a history of asthma and constipation presented with 6 weeks of intermittent, worsening lower back pain. His pain was mild to moderate, woke him from sleep, and limited his physical activity. He had previously been referred to orthopedics by his pediatrician owing to multiple presentations for the same complaint. The patient denied recent trauma, fevers, weight loss, cough, rash, or sick contacts. He was born in the United States with no recent travel. According to outpatient records, his height had been unchanged for the last 2 years.A physical examination showed a well-appearing young boy with unremarkable heart, lung, and abdominal findings. There was mild tenderness to palpation of the lumbar spine, and mild pain elicited with flexion and extension of his back. His strength was 4/5 in bilateral lower extremities, with otherwise normal neurological examination findings.He had a white blood cell count of 6.2 × 103/µL (to convert to ×109 per liter, multiply by 0.001), a hemoglobin level of 10.9 g/dL (to convert to grams per liter, multiply by 10.0), and a platelet count of 611 × 103/µL (to convert to ×109 per liter, multiply by 1.0), with a normal peripheral smear result. The results of a complete metabolic panel were unremarkable, and so were his lactate dehydrogenase and uric acid levels. He had an erythrocyte sedimentation rate of 80 mm/h and a C-reactive protein level of 20 mg/L (to convert to nanomoles per liter, multiply by 9.524).In the emergency department, a radiograph of his chest (Figure, A) revealed a right paravertebral mass, destruction of left seventh rib, a compression fracture of T8, and bony erosion of L1 vertebra. A computed tomographic (CT) scan (Figure, B) revealed paravertebral abscesses with T8 compression and destruction. Mediastinal and hilar lymphadenopathy was noted on imaging but are not shown.A, Radiograph of the chest reveals a right paravertebral mass (left arrowhead), destruction of the left seventh rib (top right arrowhead), a compression fracture of T8 (middle right arrowhead), and bony erosion of L1 vertebra (bottom right arrowhead). B, Computed tomographic scan reveals paravertebral abscesses (left arrowhead) with T8 compression and destruction (right arrowhead).

what is your diagnosis?

What is your diagnosis?

Tuberculous spondylitis

Pyogenic osteomyelitis

Discitis

Ewing sarcoma

a

male

11-20

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2553473

A man in his 40s training for weight-lifting presented with new-onset progressive dizziness, lightheadedness, and shortness of breath. His medical and family history as well as review of other systems were unremarkable. Physical examination revealed a positive Kussmaul sign and pulsus paradoxus but no cardiac murmurs. There was no pedal edema, clubbing, or cyanosis. An electrocardiogram demonstrated sinus tachycardia. Results of a complete blood cell count and biochemical panel were within reference ranges. A chest radiograph revealed convexity on the right heart border suggestive of cardiomegaly (Figure 1A). Echocardiography demonstrated normal cardiac chambers and valves. However, an echogenicity was noted compressing the superior vena cava and right ventricle. The patient subsequently underwent computed tomographic imaging of the chest that revealed a large, 16.2 × 6.8 × 5.6-cm anterior mediastinal mass compressing the right cardiac structures, particularly the superior vena cava. The mass consisted mostly of fat attenuation, but was interspersed with nodular densities (Figure 1B). Tumor marker levels, including α-fetoprotein, lactate dehydrogenase, and β-human chorionic gonadotropin, were within reference ranges. Chest imaging. A, Radiograph showed a convexity on the right heart border and cardiomegaly. B, Tomographic examination revealed a large, anterior mediastinal mass with fat attenuation interspersed with nodular soft tissue elements (asterisk). What Is Your Diagnosis?

Thymoma

Thymolipoma

Mediastinal lipomatosis

Myelolipoma

B. Thymolipoma

B

Thymolipoma

Thymolipomas are underrecognized and often misdiagnosed benign neoplasms of the anterior mediastinum.1 These neoplasms are confused with mediastinal lipomatosis, thymoma, or myelolipoma.2 Thymolipomas often present as very large, anterior mediastinal masses and exert compression on the cardiac structures. They tend to hang down either side of the pericardium, molding to the mediastinal structures.3 However, due to the predominant fat density, thymolipomas are difficult to diagnose on plain film. Chest tomography is the investigative procedure of choice; the pathognomonic finding is the predominant fat attenuation mixed with nodular elements that represent thymic tissue. Thymolipomas are distinct from thymomas, which do not have fatty elements, and mediastinal lipomatosis, which does not have these nodular elements. Thymolipomas are never associated with elevated tumor markers, including β-human chorionic gonadotropin, α-fetoprotein, or lactate dehydrogenase, differentiating them from germ cell tumors. Thymolipomas tumors can be mistaken for myelolipomas, which are very rare. On gross morphologic examination, thymic nests in thymolipomas are salmon-colored and dispersed throughout the predominantly fatty tumor (Figure 2). Histologic analysis of thymolipomas shows mature fat and thymic tissue with lack of Hassall corpuscles and intervening areas of fibrosis. In contrast, myelolipomas reveal hallmark bone marrow elements on histologic examination.4 Thymolipomas have been proposed to develop due to regression of a hyperplastic thymus, lipoma formation within thymic tissue, or hamartoma formation in the thymus.5Gross analysis. Cut section reveals a predominantly fatty tumor with islands of salmon-colored nests representing thymic tissue (black asterisks).This patient presented with presyncope and dyspnea likely resulting from caval compression. Most patients remain asymptomatic until the tumor is large enough to exert a mass effect on adjacent structures. The most common presenting symptoms are dyspnea and chest pain. The incidence of myasthenia gravis associated with thymolipoma has been reported6,7 as between 2.8% and 50%. Thymolipomas have also been associated8 with other autoimmune disorders, including hypogammaglobulinemia, aplastic anemia, and Graves disease. Timely surgical excision of thymolipomas is the treatment of choice and results are excellent. Complete R0 resection has been well documented using minimally invasive thoracoscopic resection.9 Robot-assisted resection has been shown10 to result in less operative blood loss, decreased length of stay, and decreased postoperative complications with superior results compared with the standard transsternal approach. This patient underwent robot-assisted mediastinal mass resection and was discharged on postoperative day 1. There was no recurrence or symptoms 1 year following resection.

Surgery

A man in his 40s training for weight-lifting presented with new-onset progressive dizziness, lightheadedness, and shortness of breath. His medical and family history as well as review of other systems were unremarkable. Physical examination revealed a positive Kussmaul sign and pulsus paradoxus but no cardiac murmurs. There was no pedal edema, clubbing, or cyanosis. An electrocardiogram demonstrated sinus tachycardia. Results of a complete blood cell count and biochemical panel were within reference ranges. A chest radiograph revealed convexity on the right heart border suggestive of cardiomegaly (Figure 1A). Echocardiography demonstrated normal cardiac chambers and valves. However, an echogenicity was noted compressing the superior vena cava and right ventricle. The patient subsequently underwent computed tomographic imaging of the chest that revealed a large, 16.2 × 6.8 × 5.6-cm anterior mediastinal mass compressing the right cardiac structures, particularly the superior vena cava. The mass consisted mostly of fat attenuation, but was interspersed with nodular densities (Figure 1B). Tumor marker levels, including α-fetoprotein, lactate dehydrogenase, and β-human chorionic gonadotropin, were within reference ranges. Chest imaging. A, Radiograph showed a convexity on the right heart border and cardiomegaly. B, Tomographic examination revealed a large, anterior mediastinal mass with fat attenuation interspersed with nodular soft tissue elements (asterisk).

what is your diagnosis?

What is your diagnosis?

Mediastinal lipomatosis

Thymolipoma

Thymoma

Myelolipoma

b

male

41-50

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2547676

A 67-year-old man was evaluated for lower gastrointestinal tract bleeding. He had been transferred from an outside institution with rectal bleeding requiring blood transfusion. The result of an upper gastrointestinal endoscopy performed at the referring institution was normal. A colonoscopy had been performed at the referring institution, but visualization was poor, with fresh blood and clots noted in the ascending colon. Endoscopic treatment of a right colon arteriovenous malformation with active bleeding was attempted. This was unsuccessful and bleeding persisted. The patient underwent urgent angiography and embolization of a right colic artery branch (Figure 1B). At angiography, no blush or bleeding vessel was evident. The decision to embolize the right colic branch was based on the endoscopic findings and the presence of pooling contrast in the cecum noted on a computed tomographic angiogram (Figure 1A) performed at the referring institution. He had no further bleeding episodes. Twenty hours after the procedure, he reported abdominal pain. Findings from computed tomographic scan of the abdomen and pelvis obtained at this time were unremarkable. He was treated with antibiotics and observed. He progressed to develop abdominal distension, vomiting, and significant right lower quadrant tenderness during the next 2 days.A, Computed tomographic angiogram showing pooling of contrast in right colon (yellow arrowhead), B, Selective embolization of right colic artery with a gel foam slurry.Prolonged ileus secondary to retained intraluminal old blood What Is Your Diagnosis?

Right colon ischemia

Endoscopic perforation

Prolonged ileus secondary to retained intraluminal old blood

Diverticular perforation

A. Right colon ischemia

A

Right colon ischemia

Lower gastrointestinal tract bleeding has an incidence of 36 of 100 000 in the population.1 Although most cases of colonic bleeding are self-limiting, patients with a drop in hemoglobin levels of at least 2 g/dL (to convert to grams per liter, multiply by 10) or requiring a 2-unit blood transfusion should be evaluated urgently.1 The presence of active bleeding within 4 hours of examination, aspirin use, hypotension (systolic blood pressure <115 mm Hg), tachycardia (heart rate >100 beats/min), and the presence of at least 2 additional medical comorbidities are clinical factors that are predicative of severe bleeding.2 The most common causes of lower gastrointestinal bleeding are diverticulosis, anorectal disease, and ischemic colitis.1,3 Vascular ectasia and arteriovenous malformations are a relatively uncommon cause of rectal bleeding, making up just 3% of cases in 1 series.1 Approximately 75% of angiodysplastic lesions involve the right colon.3Urgent colonoscopy with rapid bowel preparation is effective in making a diagnosis and allows therapeutic intervention. Early endoscopy has been associated with a shorter hospitalization, mainly from earlier diagnosis.4 Large-volume bleeding and inability to cleanse the bowel limit the usefulness of this procedure.In patients where colonoscopy is inadequate or cannot be performed and where bleeding is significant, angiography with intervention is a useful diagnostic and therapeutic modality. Technological advances allow superselective embolization of distal arterial branches, increasing success of the intervention and reducing complications.5 Angiography with superselective embolization is effective with immediate hemostasis achieved in 96% of patients and rebleeding within 30 days occurring in 22% of patients. However, the potential for serious complications is significant, with a reported rate of 17%. The most common major complication from the procedure is bowel infarction.5 In a series reporting on outcomes after superselective angioembolization for lower gastrointestinal hemorrhage, bowel ischemia occurred in 7 of 11 patients treated.6 A second retrospective series of 265 patients reported a postembolization ischemia rate of 3%.7In this patient, worsening abdominal pain, distension, and localized peritonitis at 48 hours after selective angiography and embolization raised strong suspicion for a diagnosis of bowel ischemia with infarction. The other diagnostic possibilities are less likely, although a delayed presentation of an endoscopic perforation with peritonitis remains an important differential diagnosis. The patient’s clinical picture warranted operative exploration. At diagnostic laparoscopy, a necrotic cecum and ascending colon were noted (Figure 2). Blood in the gastrointestinal tract can give the bowel wall a dark appearance, which may be confused with ischemia, especially in patients with ongoing brisk hemorrhage. However, in this case there was an obvious difference in color between the necrotic right cecum and distal transverse colon. Other abnormal findings that suggested the diagnosis of bowel necrosis were the presence of hemorrhagic peritoneal fluid and significant mesenteric and retroperitoneal inflammation. However, no perforation was noted. A laparoscopic-assisted right hemicolectomy with a primary ileocolic anastomosis was performed.

Surgery

A 67-year-old man was evaluated for lower gastrointestinal tract bleeding. He had been transferred from an outside institution with rectal bleeding requiring blood transfusion. The result of an upper gastrointestinal endoscopy performed at the referring institution was normal. A colonoscopy had been performed at the referring institution, but visualization was poor, with fresh blood and clots noted in the ascending colon. Endoscopic treatment of a right colon arteriovenous malformation with active bleeding was attempted. This was unsuccessful and bleeding persisted. The patient underwent urgent angiography and embolization of a right colic artery branch (Figure 1B). At angiography, no blush or bleeding vessel was evident. The decision to embolize the right colic branch was based on the endoscopic findings and the presence of pooling contrast in the cecum noted on a computed tomographic angiogram (Figure 1A) performed at the referring institution. He had no further bleeding episodes. Twenty hours after the procedure, he reported abdominal pain. Findings from computed tomographic scan of the abdomen and pelvis obtained at this time were unremarkable. He was treated with antibiotics and observed. He progressed to develop abdominal distension, vomiting, and significant right lower quadrant tenderness during the next 2 days.A, Computed tomographic angiogram showing pooling of contrast in right colon (yellow arrowhead), B, Selective embolization of right colic artery with a gel foam slurry.Prolonged ileus secondary to retained intraluminal old blood

what is your diagnosis?

What is your diagnosis?

Diverticular perforation

Right colon ischemia

Prolonged ileus secondary to retained intraluminal old blood

Endoscopic perforation

b

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2546165

A man in his 60s presented with subacute vision loss in his right eye for the prior 3 weeks. His medical history was significant for diabetes without retinopathy and radial keratotomy in both eyes for moderate myopia. The patient had undergone 2 ureterorenoscopies over a 2-week period with laser fragmentation for nephrolithiasis. A ureteral stent was placed followed by systemic ciprofloxacin. The patient’s urinary symptoms subsequently improved. In the ensuing days to weeks after these urologic procedures, the patient reported fever, weakness, and decreased appetite, which resolved spontaneously after several days but resulted in persistent weight loss of approximately 15 lb. Three months following this episode, visual symptoms developed.On examination, visual acuity was 20/400 OD and 20/20 OS. Intraocular pressure, pupils, visual fields, and ocular motility were normal. On slitlamp examination of the right eye, trace conjunctival hyperemia was present, the anterior chamber had occasional cells, the lens had mild nuclear/cortical cataract, and the anterior vitreous had 2+ cells. Dilated fundus examination of the right eye showed grade 2 vitreous haze, mild optic disc edema, scattered elevated white chorioretinal lesions—some with mild surrounding intraretinal and subretinal hemorrhage—and a prominent macular lesion (Figure 1). In the left eye, there were 3 small white chorioretinal lesions inferiorly and no other abnormalities.Dilated fundus examination of the right eye demonstrated vitreous haze, mild optic disc edema, and an elevated white chorioretinal lesion (arrowhead) in the macula, surrounded by mild intraretinal and subretinal hemorrhage.Initiate uveitis workup and begin topical glucocorticoid therapy What Would You Do Next?

Intravitreal injection with vancomycin and ceftazidime

Initiate uveitis workup and begin topical glucocorticoid therapy

Obtain urinalysis

Perform diagnostic pars plana vitrectomy

Endogenous fungal endophthalmitis

C

Obtain urinalysis

The differential diagnosis is limited for bilateral, elevated, white chorioretinal lesions with vitritis. Infectious causes include fungi, syphilis, tuberculosis, or other bacteria. Inflammatory causes include idiopathic uveitis, sarcoidosis, Behçet disease, sympathetic ophthalmia, and multifocal choroiditis.Urinalysis provides results quickly after a sample is submitted and, given the patient’s recent history and systemic symptoms, is the most appropriate next step in evaluation. Injection of anti-infectious agents may be warranted but not until an aqueous or vitreous biopsy is assessed for the pathogenic organism. Pars plana vitrectomy is unnecessary, invasive, and expensive. A uveitis workup alone is not appropriate for initial diagnostic evaluation.Infectious endophthalmitis was suspected, so a vitreous culture was obtained and intravitreal vancomycin, ceftazidime, and voriconazole were injected. Blood cultures were also collected. Blood and vitreous cultures revealed no microbial growth. Blood tests for syphilis (rapid plasma reagin and treponemal antibody tests) and tuberculosis (quantiFERON gold) were normal. However, a urinalysis of cloudy urine showed an elevated white blood cell count of 122 cells per high-power field and branching yeast with budding within 2.5 hours of specimen collection, consistent with a fungal (Candida) urinary tract infection. The patient began receiving oral fluconazole (200 mg twice daily for 6 months).Fungi are the most common causes of endogenous endophthalmitis, and Candida albicans is the most frequently cultured organism.1C albicans chorioretinitis appears as a creamy-white lesion resembling a “fluff ball,” involving the retina and choroid and extending into the vitreous cavity.2 The lesion is usually well-circumscribed, less than 1 mm in diameter, located in the posterior pole, and associated with localized overlying vitritis.3 Vascular sheathing of the retinal vessels and iridocyclitis may also be present. Multiple yellow-white vitreous abscesses in a row are also classic and referred to as “string of pearls.”3Diagnosis of endogenous fungal endophthalmitis (EFE) is usually clinical. Cultured fungus from the vitreous, blood, or urine may confirm the diagnosis, but the yield from culture is often low owing to prolonged culture times and confinement to the retina/abscess.2Oral fluconazole is the most commonly used drug for EFE. It has a long half-life, penetrates the vitreous well, and has no reported ocular toxicity.4 When systemic and intravitreal antifungal therapy is insufficient for disease control, pars plana vitrectomy may help prevent further decline, but persistent infection often results in extensive involvement of the vitreous, scarring and fibrosis, choroidal neovascularization, and traction retinal detachment.1,5Endogenous endophthalmitis from a genitourinary source has been previously reported. Two case reports described bilateral EFE; one described shock wave lithotripsy and placement of a ureteral stent and bladder catheter in a patient with chronic cystitis,6 and the other described a patient after a urinary tract infection complicated by ureterolithiasis with obstructive hydronephrosis and septic shock.7 One case of unilateral EFE in a patient with a history of recurrent urinary tract infections, nephrolithiasis, hydronephrosis, and ureteral stents has also been reported.5 In all 3 cases, chorioretinal lesions resulted in macular scarring and significant vision loss despite intravitreal antifungal administration and pars plana vitrectomy. Antibiotic use, diabetes, indwelling catheters, and advanced age have been suggested as risk factors for endophthalmitis after urologic procedures, which were present in these patients.1Repeated urinalysis 2 weeks after starting fluconazole treatment did not demonstrate any fungi. The lesions resolved in both eyes after 4 weeks, leaving vitreous debris and minimal scarring (Figure 2) and a visual acuity of 20/80 OD and 20/20 OS.Dilated fundus examination of the right eye demonstrated resolution of the macular chorioretinal lesion (arrowhead) with minimal associated scarring. There was persistent vitreous debris.

Ophthalmology

A man in his 60s presented with subacute vision loss in his right eye for the prior 3 weeks. His medical history was significant for diabetes without retinopathy and radial keratotomy in both eyes for moderate myopia. The patient had undergone 2 ureterorenoscopies over a 2-week period with laser fragmentation for nephrolithiasis. A ureteral stent was placed followed by systemic ciprofloxacin. The patient’s urinary symptoms subsequently improved. In the ensuing days to weeks after these urologic procedures, the patient reported fever, weakness, and decreased appetite, which resolved spontaneously after several days but resulted in persistent weight loss of approximately 15 lb. Three months following this episode, visual symptoms developed.On examination, visual acuity was 20/400 OD and 20/20 OS. Intraocular pressure, pupils, visual fields, and ocular motility were normal. On slitlamp examination of the right eye, trace conjunctival hyperemia was present, the anterior chamber had occasional cells, the lens had mild nuclear/cortical cataract, and the anterior vitreous had 2+ cells. Dilated fundus examination of the right eye showed grade 2 vitreous haze, mild optic disc edema, scattered elevated white chorioretinal lesions—some with mild surrounding intraretinal and subretinal hemorrhage—and a prominent macular lesion (Figure 1). In the left eye, there were 3 small white chorioretinal lesions inferiorly and no other abnormalities.Dilated fundus examination of the right eye demonstrated vitreous haze, mild optic disc edema, and an elevated white chorioretinal lesion (arrowhead) in the macula, surrounded by mild intraretinal and subretinal hemorrhage.Initiate uveitis workup and begin topical glucocorticoid therapy

what would you do next?

What would you do next?

Initiate uveitis workup and begin topical glucocorticoid therapy

Obtain urinalysis

Intravitreal injection with vancomycin and ceftazidime

Perform diagnostic pars plana vitrectomy

b

male

61-70

White

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2547102

A boy aged 17 years presented after noticing that his right pupil was off-center. He had a high hyperopic refractive error, and the magnification of his spectacle lenses highlighted the eccentric pupil. He had no associated symptoms of decreased vision, ocular pain, diplopia, glare, or haloes and had no history of ocular infection, surgical procedure, or trauma. His mother, also hyperopic, previously underwent prophylactic laser iridotomy for anatomically narrow, occludable angles.Best corrected visual acuity was 20/20 OU, with a manifest refraction of +7.75 −1.00 × 170 OD and +7.75 −1.25 × 010 OS. Slitlamp examination confirmed mild corectopia in the right eye, along with 4 clock hours of iridocorneal touch nasally and a “hammered silver” appearance to the involved cornea (Figure 1). On examination via gonioscopy, there were high peripheral anterior synechiae (PAS) above the Schwalbe line in this area, while the remaining angle was deep without PAS. The left eye was normal. Intraocular pressures were 15 mm Hg OD and 14 mm Hg OS. Pachymetry testing revealed symmetric central corneal thicknesses of 577 μm OD and 582 μm OS. Both optic discs appeared healthy, with a cup-disc ratio of 0.2. There were no visual field defects.Slitlamp photography showed the right eye had mild corectopia and iridocorneal touch nasally.Test the aqueous fluid for Human herpesvirus 1 What Would You Do Next?

Start pilocarpine eyedrops

Test the aqueous fluid for Human herpesvirus 1

Obtain specular microscopy

Recommend genetic testing

Iridocorneal endothelial syndrome

C

Obtain specular microscopy

The clinical presentation is consistent with a diagnosis of essential iris atrophy, a subtype of iridocorneal endothelial (ICE) syndrome. Iridocorneal endothelial syndrome is a proliferative endotheliopathy with deposition of an abnormal basement membrane extending across the angle and over the iris.1 Its distinguishing feature is progressive atrophy and hole formation of the iris. The condition is usually unilateral and predominantly affects women in early to middle-aged adulthood. Patients frequently present with blurred vision or a noticeable change in the pupil, but the condition is occasionally diagnosed on routine examination.Specular microscopy is an important diagnostic tool in the evaluation of this condition, particularly in early or uncertain cases.1,2 Gross central endothelial changes are found in patients with minimal PAS, suggesting that these changes are primary in nature, rather than secondary to iridocorneal adhesions.3 In this patient, specular microscopy confirmed endothelial cell loss in the right eye, and the surviving endothelium showed rounding of cell borders and early intracellular dark areas (Figure 2). The endothelial cell count was 2146 cells/mm2 OD compared with 3115 cells/mm2 OS. In more advanced disease, there are ICE cells with dark cell surfaces surrounded by light boundaries. The resulting appearance of the reversal of the light/dark pattern is pathognomonic for ICE syndrome.4 There is no direct correlation between the degree of endothelial abnormality and the development of corneal edema.5 Other potentially useful tests include confocal microscopy and ultrasound biomicroscopy for the visualization of the endothelium and angles, when corneal edema prevents specular and gonioscopic views.Specular microscopy showed the right eye had endothelial cell loss with rounding of cell borders and early intracellular dark areas.In patients with ICE syndrome who require corneal surgical intervention, favorable short-term outcomes may be achieved with penetrating or endothelial keratoplasty. However, in the long term, these patients often require repeated procedures to maintain corneal clarity. Approximately 50% of patients with ICE syndrome develop glaucoma, which tends to be worse in patients with essential iris atrophy and Cogan-Reese syndrome.6-8 Glaucoma may occur earlier than expected based on gonioscopy, as trabecular meshwork dysfunction precedes PAS formation.6 These eyes are frequently resistant to medical therapy and require multiple surgical procedures. A study9 on outcomes after glaucoma operations found that at 5 years, trabeculectomy with antifibrotic agents had a survival of 29% and glaucoma drainage implants had a survival of 53%.This patient showed no evidence of glaucoma and required no treatment. Miotics are ineffective for medical treatment. Based on the findings of unilateral PAS and endothelial changes in an otherwise normal eye, serologic workup was not indicated. Essential iris atrophy is an acquired condition with no known genetic basis.Although this patient had relatively mild involvement, it is important to note that ICE syndrome is a progressive disorder. Slitlamp examination and gonioscopy should be performed at regular intervals to monitor for development or progression of glaucoma or corneal edema. Although there are no known preventive measures, early diagnosis and surveillance may increase the likelihood of favorable outcomes in these patients.

Ophthalmology

A boy aged 17 years presented after noticing that his right pupil was off-center. He had a high hyperopic refractive error, and the magnification of his spectacle lenses highlighted the eccentric pupil. He had no associated symptoms of decreased vision, ocular pain, diplopia, glare, or haloes and had no history of ocular infection, surgical procedure, or trauma. His mother, also hyperopic, previously underwent prophylactic laser iridotomy for anatomically narrow, occludable angles.Best corrected visual acuity was 20/20 OU, with a manifest refraction of +7.75 −1.00 × 170 OD and +7.75 −1.25 × 010 OS. Slitlamp examination confirmed mild corectopia in the right eye, along with 4 clock hours of iridocorneal touch nasally and a “hammered silver” appearance to the involved cornea (Figure 1). On examination via gonioscopy, there were high peripheral anterior synechiae (PAS) above the Schwalbe line in this area, while the remaining angle was deep without PAS. The left eye was normal. Intraocular pressures were 15 mm Hg OD and 14 mm Hg OS. Pachymetry testing revealed symmetric central corneal thicknesses of 577 μm OD and 582 μm OS. Both optic discs appeared healthy, with a cup-disc ratio of 0.2. There were no visual field defects.Slitlamp photography showed the right eye had mild corectopia and iridocorneal touch nasally.Test the aqueous fluid for Human herpesvirus 1

what would you do next?

What would you do next?

Recommend genetic testing

Test the aqueous fluid for Human herpesvirus 1

Obtain specular microscopy

Start pilocarpine eyedrops

c

male

11-20

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2551689

A woman in her 30s with no significant medical history presented with a 1-month history of worsening “bulging,” redness, and mild pain in her right eye. She also reported intermittent, binocular diplopia. Results from a review of systems were otherwise negative, and she had not experienced recent trauma. She was started on topical antihypertensive drugs for elevated intraocular pressure (IOP) in the affected eye (30 mm Hg) and referred to our institution. On examination, visual acuity was 20/20 in both eyes with subjective red desaturation OD. Pupils were equal and without afferent pupillary defect. Confrontation visual fields were full. Intraocular pressures were 24 mm Hg OD and 12 mm Hg OS. Hertel exophthalmometry showed 4.5 mm of relative proptosis OD. She had limitation of her extraocular muscles in nearly all fields of gaze OD, with the most obvious limitation occurring in abduction. She had decreased sensation to light touch in the right cheek (cranial nerve V2). There were no orbital bruits. Ocular examination revealed diffuse conjunctival injection OD with tortuous, dilated, corkscrew-shaped blood vessels (Figure, A). Dilated fundus examination revealed mild optic nerve hyperemia and mild vascular tortuosity OD. Vital signs and results from complete blood cell count and thyroid function tests were normal. Computed tomography and magnetic resonance imaging, angiography, and venography of the brain and orbits revealed extraocular muscle enlargement and enhancement and a dilated superior ophthalmic vein OD. There was no mass, abscess, or arteriovenous fistula (Figure, B). What Would You Do Next?

Orbital biopsy

Start systemic corticosteroids

Start systemic antibiotics

Order catheter cerebral angiography

Carotid-cavernous fistula

D

Order catheter cerebral angiography

When treating a red, proptotic eye, it is important to consider the possibility that the pathologic abnormality may be intracranial rather than intraorbital. Dilation of the superior ophthalmic vein on imaging and impairment of the maxillary (V2) branch of the trigeminal nerve, as in this case, localize abnormality to the cavernous sinus (which contains cranial nerves III, IV, V1, V2, and VI), causing secondary orbital signs and symptoms. This is in contrast to primary orbital disease (eg, orbital cellulitis, orbital inflammatory syndrome, thyroid eye disease, orbital tumor). The constellation of findings in our patient, including V2 impairment, elevated intraocular pressure, dilated and tortuous conjunctival vessels, and evidence of orbital congestion, including proptosis, extraocular muscle enlargement, and a dilated superior ophthalmic vein, led us to strongly suspect a carotid-cavernous fistula (CCF), despite the absence of this finding on magnetic resonance angiography. This patient therefore underwent catheter cerebral angiography (answer choice D), which confirmed an indirect, type D, CCF characterized by an abnormal communication between the cavernous sinus and meningeal branches of both the internal and external carotid arteries. Answer choices A, B, and C are inadequate given that the clinical and radiographic findings did not strongly support a neoplastic, inflammatory, or infectious process.Carotid-cavernous fistula is a condition describing an abnormal communication between the carotid artery and the cavernous sinus. It is divided into 2 broad categories: (1) direct, or type A, and (2) indirect, dural, or types B, C, and D.1 Direct CCFs are high-flow fistulas and most commonly occur after trauma. Indirect CCFs are low-flow fistulas and most commonly occur spontaneously. Indirect CCFs may present quite variably or insidiously and are often initially misdiagnosed as other conditions, including thyroid eye disease, orbital inflammatory syndrome, or chronic conjunctivitis.Direct and indirect CCFs are capable of producing similar clinical manifestations, although indirect CCFs generally tend to have less severe and acute presentations. Possible findings include mild pain, unilateral (or less frequently, bilateral) proptosis, pulsatile exophthalmos,2 orbital bruit,3 abnormal ocular motility (secondary to impaired function of cranial nerves III, IV, or VI), exposure keratopathy, neurotrophic keratopathy from V1 neuropathy, conjunctival chemosis and injection (manifesting as dilated, tortuous, corkscrew-like vessels), elevated IOP, glaucoma, optic disc swelling, venous stasis retinopathy, retinal vascular occlusions, and choroidal effusion.4 The gold standard for diagnosis is catheter cerebral angiography, although less invasive neuroimaging may also be helpful. Importantly, as shown by this case, certain CCFs, particularly indirect CCFs, may be missed unless catheter cerebral angiography is performed.Endovascular embolization is the treatment of choice for both direct CCFs and those indirect CCFs that fail to spontaneously close or are vision threatening.2,5,6 After treatment, elevated IOP often returns to baseline within 2 days, but orbital congestion and ophthalmoparesis often require 1 to 4 weeks to return to normal.2Our patient successfully underwent endovascular embolization at the time of her cerebral angiogram. Within 2 days of treatment, her vision subjectively improved, IOP returned to normal, proptosis decreased, conjunctival injection decreased, and ophthalmoparesis had markedly improved.

Ophthalmology

A woman in her 30s with no significant medical history presented with a 1-month history of worsening “bulging,” redness, and mild pain in her right eye. She also reported intermittent, binocular diplopia. Results from a review of systems were otherwise negative, and she had not experienced recent trauma. She was started on topical antihypertensive drugs for elevated intraocular pressure (IOP) in the affected eye (30 mm Hg) and referred to our institution. On examination, visual acuity was 20/20 in both eyes with subjective red desaturation OD. Pupils were equal and without afferent pupillary defect. Confrontation visual fields were full. Intraocular pressures were 24 mm Hg OD and 12 mm Hg OS. Hertel exophthalmometry showed 4.5 mm of relative proptosis OD. She had limitation of her extraocular muscles in nearly all fields of gaze OD, with the most obvious limitation occurring in abduction. She had decreased sensation to light touch in the right cheek (cranial nerve V2). There were no orbital bruits. Ocular examination revealed diffuse conjunctival injection OD with tortuous, dilated, corkscrew-shaped blood vessels (Figure, A). Dilated fundus examination revealed mild optic nerve hyperemia and mild vascular tortuosity OD. Vital signs and results from complete blood cell count and thyroid function tests were normal. Computed tomography and magnetic resonance imaging, angiography, and venography of the brain and orbits revealed extraocular muscle enlargement and enhancement and a dilated superior ophthalmic vein OD. There was no mass, abscess, or arteriovenous fistula (Figure, B).

what would you do next?

What would you do next?

Start systemic antibiotics

Order catheter cerebral angiography

Start systemic corticosteroids

Orbital biopsy

b

female

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2552683

An otherwise healthy white man in his 40s was referred to the cornea service for decreased vision in the setting of a white cataract in his left eye. The patient reported the acute onset of foreign body sensation in his left eye while splitting wood 1 year prior. He attended a hospital emergency department at that time and was diagnosed with a corneal abrasion and treated with topical antibiotics. He stated that his vision initially returned to normal after treatment, but had subsequently worsened. He complained of tearing, photophobia, and burning in the left eye.The visual acuity was hand motions OS with a grossly constricted visual field by confrontation. The intraocular pressure was normal. The anterior segment examination revealed mild edema of the cornea, a shallow anterior chamber, iris heterochromia (Figure 1A), and an intumescent white cataract with pigment deposition on the anterior lens capsule. The cataract precluded visualization of the fundus. B-scan ultrasonography did not reveal masses, retinal detachment, or foreign body (Figure 1B).Heterochromia iridis. A, External photograph displaying significant heterochromia. B, B-scan ultrasonography image of the left eye.Computed tomography scan of the orbits without contrastMagnetic resonance imaging of the orbits without contrastPhacoemulsification with intraocular lens placement in the left eye What Would You Do Next?

Observation

Computed tomography scan of the orbits without contrast

Magnetic resonance imaging of the orbits without contrast

Phacoemulsification with intraocular lens placement in the left eye

Intraocular metal foreign body with resultant siderosis bulbi

B

Computed tomography scan of the orbits without contrast

Ocular siderosis refers to degenerative changes caused by iron toxicity, while siderosis bulbi describes the effects of an iron intraocular foreign body (IOFB).1 Siderosis bulbi most commonly results from retention of a ferrous IOFB after traumatic penetration of the globe. Siderosis can also result from radiologically occult foreign bodies in the cornea,2 lens,3 or sclera.4 Systemic iron overload is a very rare cause of ocular siderosis.5The clinical signs of siderosis bulbi include corneal stromal rust deposits, heterochromia iridis, mydriasis, anterior subcapsular cataract, and retinal degeneration with associated electroretinographic abnormalities in the affected eye. Long-standing siderosis may be associated with cystoid macular edema, widespread retinal pigmentary abnormalities, and attenuation of the retinal vessels, mimicking the appearance of retinitis pigmentosa.1Frequently an IOFB can be detected via ophthalmoscopy. In cases where the fundus cannot be directly examined, or when an IOFB cannot be detected by ophthalmoscopic examination but the clinical history and associated finding are suggestive of a metallic IOFB, ophthalmic imaging is warranted. Radiography, computed tomography, and B-scan ultrasonography are usually diagnostic.1 However, siderosis has been reported arising from radiologically undetectable foreign bodies.2-4 Ophthalmologists should maintain a high index of suspicion for siderosis despite normal imaging in the setting of a suggestive clinical history or examination. Computed tomography of the orbits with 1-mm sections or thinner should be performed to assess for metallic IOFB. Observation would not be advised in this patient with signs and symptoms of ocular siderosis and severe visual loss. Magnetic resonance imaging would be inappropriate in the case of a suspected metallic IOFB; the magnetic field induced by magnetic resonance imaging could mobilize the foreign body resulting in further tissue damage. Lastly, while lens removal may eventually be required, proceeding with cataract extraction before diagnostic testing for ocular siderosis could delay a definitive surgical procedure and prolong irreversible, ongoing toxic effects.While there is general consensus that metallic IOFBs should be surgically removed, some controversy exists regarding the timing of surgery. Advocates of immediate surgical removal cite a 5% to 13% incidence of infective endophthalmitis in eyes with retained IOFB,6 as well as risk of progressive retinal metallotoxicity. Early retinal toxic effects may be reversible, with recovery of electroretinography b-wave amplitude following IOFB removal in cases of likely mild, early-onset toxic effects. If the diagnosis of ocular siderosis is not certain, and no other indication for surgical removal exists, careful observation including serial electroretinography assessments may be acceptable in cases with preserved vision and normal retinal electroretinographic function.7The patient was referred to the retina service for evaluation. Orbital computed tomography revealed a metallic IOFB in the anterior aspect of the inferior vitreous (Figure 2). The patient was advised to undergo pars plana vitrectomy, lensectomy, and IOFB removal. The patient failed to attend surgery and, despite multiple attempts, could not be contacted.Metallic intraocular foreign body. Computed tomography of the left eye revealed focal hyperdensity in the anterior inferior aspect of the vitreous (red circle) consistent with a metallic foreign body within the posterior segment.

Ophthalmology

An otherwise healthy white man in his 40s was referred to the cornea service for decreased vision in the setting of a white cataract in his left eye. The patient reported the acute onset of foreign body sensation in his left eye while splitting wood 1 year prior. He attended a hospital emergency department at that time and was diagnosed with a corneal abrasion and treated with topical antibiotics. He stated that his vision initially returned to normal after treatment, but had subsequently worsened. He complained of tearing, photophobia, and burning in the left eye.The visual acuity was hand motions OS with a grossly constricted visual field by confrontation. The intraocular pressure was normal. The anterior segment examination revealed mild edema of the cornea, a shallow anterior chamber, iris heterochromia (Figure 1A), and an intumescent white cataract with pigment deposition on the anterior lens capsule. The cataract precluded visualization of the fundus. B-scan ultrasonography did not reveal masses, retinal detachment, or foreign body (Figure 1B).Heterochromia iridis. A, External photograph displaying significant heterochromia. B, B-scan ultrasonography image of the left eye.Computed tomography scan of the orbits without contrastMagnetic resonance imaging of the orbits without contrastPhacoemulsification with intraocular lens placement in the left eye

what would you do next?

What would you do next?

Magnetic resonance imaging of the orbits without contrast

Phacoemulsification with intraocular lens placement in the left eye

Computed tomography scan of the orbits without contrast

Observation

c

male

41-50

White

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2553878

A woman in her mid-60s with end-stage lung disease secondary to systemic sclerosis and pulmonary hypertension underwent bilateral sequential lung transplantation without cardiopulmonary bypass through a clamshell thoracotomy. The immediate postoperative course was uneventful, and she was weaned off oxygen support. On postoperative day 10, she developed seizures when walking and was immediately intubated. Brain imaging revealed a new intracerebral hemorrhage in the right frontal and left occipital lobes, with narrowing of the internal carotid, basilar, posterior cerebral, and right posterior communicating arteries, suggestive of vasospasm or vasculopathy. Subsequently, she developed hypoxemia and hypotension associated with acute pulmonary edema and new cardiomegaly (Figure 1A). An electrocardiogram showed nonspecific ST changes with T-wave inversion (Figure 1B), and serum levels of troponin and creatine phosphokinase were negative. Transesophageal echocardiography revealed new dilation of the left ventricle (LV), with an ejection fraction of 10%, functional mitral regurgitation, anterior and apical akinesis, and basal hypokinesis (Video 1, Video 2, and Video 3). The right ventricle (RV) was distended, with moderate tricuspid regurgitation. Recent pretransplantation coronary angiography did not reveal atherosclerosis. Her cardiopulmonary status rapidly worsened, with cardiogenic shock and refractory hypoxemia (arterial blood pH, 7.12; arterial partial pressure of oxygen, 43 mm Hg; and partial pressure of carbon dioxide, 56 mm Hg), despite mechanical ventilation (rate, 24/min; tidal volume, 6 mL/kg; fraction of inspired oxygen, 100%; and positive end-expiratory pressure, 15 cm H2O), neuromuscular blockade, and administration of inotropes.Patient workup. A, Chest radiographs were obtained on the morning of postoperative day 10 before (left) and after (right) the onset of pulmonary edema. B, An electrocardiogram shows nonspecific ST changes and T-wave inversion. What Is Your Diagnosis?

Myocardial infarction

Pulmonary embolism with cardiogenic shock

Noncardiogenic pulmonary edema

Takotsubo cardiomyopathy

D. Takotsubo cardiomyopathy

D

Takotsubo cardiomyopathy

The management of Takotsubo cardiomyopathy is usually supportive care.1 Inotropes are avoided because they can worsen stress-induced myocardial injury.2 A patient with refractory biventricular failure and pulmonary edema can be supported using venoarterial extracorporeal membrane oxygenation (VA-ECMO).3 During VA-ECMO, blood is drained from the right atrium and returned to the aortic circulation after being oxygenated. This simultaneously improves systemic oxygen delivery and decompresses both ventricles to restore chamber geometry, perhaps facilitating cardiac recovery. However, VA-ECMO was not an option for this patient because her recent transplantation eliminated the bronchial circulation, making both lung allografts dependent on pulmonary blood flow. Specifically, the native human lungs are perfused through both the pulmonary artery (PA) and bronchial circulation. The most commonly practiced technique of bilateral lung transplantation includes anastomosing the donor and recipient bronchus, PA, and atrial cuff of the ipsilateral pulmonary veins, but without reestablishing the bronchial circulation. Therefore, VA-ECMO, which bypasses the pulmonary circulation, carries a risk of ischemia in fresh allografts. To maintain oxygen delivery in the systemic and pulmonary circulation, we combined LV support with an LV assist device (LVAD) through the right axillary artery (Impella-CP; Abiomed) and RV and respiratory support through a right internal jugular vein–PA dual-lumen cannula connected to an ECMO circuit (Protek-Duo; CardiacAssist Inc). In addition, a percutaneous intra-aortic balloon pump was placed through the left femoral artery to improve coronary perfusion, set at 1:2 augmentation to reduce competition with the outflow jet of the LVAD (Figure 2). This configuration decompressed both ventricles, improved coronary and cerebral perfusion, provided oxygenated blood flow to the allografts, and addressed gas exchange. Systemic anticoagulation was avoided because of the brain bleed.Biventricular and respiratory support. A, Chest radiograph shows position of Imprella device serving as left ventricular (LV) assist device (L), Protek-Duo cannula serving as both right ventricular (RV) assist device (R) and extracorporeal membrane oxygenation, and intra-aortic balloon pump (P). B, Schematic illustrating position of the LV and RV assist devices. Deoxygenated blood is drained via Protek-Duo cannula from the right atrium through the outer lumen into a centrifugal pump and an oxygenator and returned back through the inner lumen directly into the main pulmonary artery. Hence, it provides both gas exchange and RV support, as well as oxygenated blood to the fresh pulmonary allografts. The Impella device served as an LV device, draining blood from the left ventricle and ejecting it into the ascending aorta across the aortic valve.This case posed some unique challenges. The patient required LV support to manage pulmonary edema and maintain cerebral perfusion due to the intracranial hemorrhage and vasospasm, and RV support to maintain perfusion of fresh lung allografts. We chose to initiate mechanical LV support with an LVAD and RV support combined with venovenous extracorporeal membrane oxygenation. For RV support, we chose the dual-lumen cannula because it drains blood from the right atrium and ejects into the proximal PA, thereby unloading the RV while delivering oxygenated blood to the lungs.4 This approach allowed us to achieve normal levels of systemic and PA perfusion and maintain oxygenation independent of the intrapulmonary shunt, as well as to discontinue sedation and mobilize the patient, which is important because early ambulation may benefit patients with cardiorespiratory failure.5 As a bridge to recovery or transplantation, the configuration of biventricular support we describe (Figure 2) can allow ambulation while providing biventricular and gas exchange support in patients with refractory cardiorespiratory failure.The hemodynamic status of the patient improved with resolution of her pulmonary edema. The dual-lumen cannula and intra-aortic balloon pump were removed after 36 hours, and the LVAD support was discontinued on day 4 after initiation of extracorporeal cardiopulmonary support. Her mitral regurgitation resolved, and biventricular function recovered (LV ejection fraction, 68%). There was no progression of the intracranial hemorrhage, and the patient demonstrated no neurological deficits.

Cardiology

A woman in her mid-60s with end-stage lung disease secondary to systemic sclerosis and pulmonary hypertension underwent bilateral sequential lung transplantation without cardiopulmonary bypass through a clamshell thoracotomy. The immediate postoperative course was uneventful, and she was weaned off oxygen support. On postoperative day 10, she developed seizures when walking and was immediately intubated. Brain imaging revealed a new intracerebral hemorrhage in the right frontal and left occipital lobes, with narrowing of the internal carotid, basilar, posterior cerebral, and right posterior communicating arteries, suggestive of vasospasm or vasculopathy. Subsequently, she developed hypoxemia and hypotension associated with acute pulmonary edema and new cardiomegaly (Figure 1A). An electrocardiogram showed nonspecific ST changes with T-wave inversion (Figure 1B), and serum levels of troponin and creatine phosphokinase were negative. Transesophageal echocardiography revealed new dilation of the left ventricle (LV), with an ejection fraction of 10%, functional mitral regurgitation, anterior and apical akinesis, and basal hypokinesis (Video 1, Video 2, and Video 3). The right ventricle (RV) was distended, with moderate tricuspid regurgitation. Recent pretransplantation coronary angiography did not reveal atherosclerosis. Her cardiopulmonary status rapidly worsened, with cardiogenic shock and refractory hypoxemia (arterial blood pH, 7.12; arterial partial pressure of oxygen, 43 mm Hg; and partial pressure of carbon dioxide, 56 mm Hg), despite mechanical ventilation (rate, 24/min; tidal volume, 6 mL/kg; fraction of inspired oxygen, 100%; and positive end-expiratory pressure, 15 cm H2O), neuromuscular blockade, and administration of inotropes.Patient workup. A, Chest radiographs were obtained on the morning of postoperative day 10 before (left) and after (right) the onset of pulmonary edema. B, An electrocardiogram shows nonspecific ST changes and T-wave inversion.

what is your diagnosis?

What is your diagnosis?

Takotsubo cardiomyopathy

Pulmonary embolism with cardiogenic shock

Noncardiogenic pulmonary edema

Myocardial infarction

a

female

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2492613

A man in his 30s presented with a steady 5-year progression of facial asymmetry and new-onset left-sided facial weakness, pain, and otalgia. Physical examination revealed no palpable parotid mass and no overlying skin changes. Neurologic examination showed incomplete left eye closure with a grade 5 of 6 on the House-Brackmann scale. Treatment with steroids and antiviral agents marginally improved facial strength and allowed eye closure. Magnetic resonance imaging showed subcutaneous nodules focally infiltrating the superficial parotid gland with evidence of perineural spread along the labyrinthine segment of CN VII. Fine-needle aspiration (FNA) with ultrasonographic guidance was nondiagnostic. An open excisional biopsy demonstrated dense subcutaneous tissue overlying and invading the parotid gland. Intraoperative frozen section revealed a spindle cell tumor. A superficial parotidectomy with facial nerve dissection and preservation was performed. Histopathologic examination revealed a subcutaneous mass with stellate extension into and around the parotid gland. The tumor consisted of bland fusiform tumor cells in a storiform pattern near inconspicuous hyalinized vessels (Figure, A and B). Immunohistochemical staining demonstrated diffuse positivity for CD34 (Figure, C), positivity for bcl-2, and negativity for CD99 and S-100. Fluorescent in situ hybridization (FISH) further characterized the tumor with a translocation t(17;22)(q21;q13) and corresponding COL1A1/PDGFB fusion protein (Figure, D).A-C, Histopathologic images. A, Tumor infiltrating around and within the parotid gland. B, Fusiform tumor cells arranged in a storiform pattern. C, Tumor cells strongly positive for CD34. D, Image from FISH studies. What Is Your Diagnosis?

Solitary fibrous tumor

Dermatofibrosarcoma protuberans

Malignant melanoma

Spindle cell carcinoma

B. Dermatofibrosarcoma protuberans

B

Dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing, locally aggressive primary soft-tissue tumor with a high rate of local recurrence. Commonly presenting as a painless plaque, it often progresses to form a nodule. Initially fixed within the dermis, the tumor follows a radial growth pattern in finger-like projections, eventually invading underlying structures, and potentially ulcerating the epidermis.1 More often occurring on the trunk or the proximal extremities, 10% to 15% of DFSP affect the head and neck. This is a locally aggressive tumor; metastatic behavior is rare. Typically occurring between ages 30 and 50 years, there is a slight male predominance and a notable predilection in African Americans.2Without a known history of DFSP, FNA is unlikely to yield diagnostic results3 owing to the inherent difficulty of acquiring suitable cellularity from a densely fibrotic mass, as illustrated by the present case. The histologic features of DFSP are those of a monotonous storiform architecture of uniform bland spindle cells, centered in the dermis and locally infiltrative.4 The tumor cells are immunoreactive for CD344 and bcl-2 and negative for S-100. The cytogenetic abnormality in DFSP is manifested as translocation t(17;22)(q22;q13). This results in fusion of COL1A1 (also located at 17q21) and PDGFB genes.4 The resultant fusion gene disallows normal repression of transcription and translation of PDGFB. The case presented herein meets all these diagnostic criteria, including the helpful and sometimes necessary use of FISH noted recently by Karanian et al.5The standard of care for DFSP is surgical resection with negative margins. In the head and neck region, the highest cure rate with lowest morbidity is achieved using Mohs surgery in selected cases.2 Imatinib, a tyrosine kinase inhibitor known for its specificity for c-KIT (gastrointestinal stromal tumor) and BCR-ABL (chronic myelogenous leukemia), also works on PDGFB.6 A 2001 study7 found that imatinib inhibits growth of DFSP in mice. Case reports summarized by Malhotra and Schuetze1 demonstrate up to 75% tumor shrinkage. Rutkowski et al8 reported partial response to imatinib in 6 of 11 cases of DFSP, while the remaining cases remained stable. A multicenter clinical trial demonstrated a median tumor shrinkage of 31.5%, but such response was not definitively correlated with presence of the characteristic translocation.9 The role of imatinib in locally advanced disease or neoadjuvant therapy is becoming well-established. Some DFSP cases (8%) fail to demonstrate this translocation.6 In such cases, the medication’s potential therapeutic benefit may not occur.DFSP is unusual in the head and neck. In a recent review2 of 1443 cases, 227 were noted in this region (16%). The present case most likely originated in the subcutaneous tissue and dermis overlying the parotid gland, not within the gland itself, eventually infiltrating the parotid gland. Cho et al10 in 2008 reported a case of DFSP originating in the parotid gland. In this case, attachment to the subcutaneous tissue and facial nerve involvement would require a complete resection of the overlying skin, remaining parotid gland, and facial nerve up to the geniculate ganglion for tumor eradication. Demonstration of the characteristic gene rearrangement COL1A1-PDFGB t(17;22)(q21;q13) by FISH, unique to DFSP, both confirmed diagnosis and allowed for directed adjuvant medical therapy (imatinib) as an alternative to further invasive surgery.In conclusion, we have described a case of DFSP invading the parotid gland. DFSP-specific cytogenetic abnormality allowed both accurate diagnosis and directed medical therapy with imatinib. Since the initiation of imatinib, the patient has experienced improved facial nerve function. The mass has decreased in size and in enhancement based on examination and imaging, respectively.

General

A man in his 30s presented with a steady 5-year progression of facial asymmetry and new-onset left-sided facial weakness, pain, and otalgia. Physical examination revealed no palpable parotid mass and no overlying skin changes. Neurologic examination showed incomplete left eye closure with a grade 5 of 6 on the House-Brackmann scale. Treatment with steroids and antiviral agents marginally improved facial strength and allowed eye closure. Magnetic resonance imaging showed subcutaneous nodules focally infiltrating the superficial parotid gland with evidence of perineural spread along the labyrinthine segment of CN VII. Fine-needle aspiration (FNA) with ultrasonographic guidance was nondiagnostic. An open excisional biopsy demonstrated dense subcutaneous tissue overlying and invading the parotid gland. Intraoperative frozen section revealed a spindle cell tumor. A superficial parotidectomy with facial nerve dissection and preservation was performed. Histopathologic examination revealed a subcutaneous mass with stellate extension into and around the parotid gland. The tumor consisted of bland fusiform tumor cells in a storiform pattern near inconspicuous hyalinized vessels (Figure, A and B). Immunohistochemical staining demonstrated diffuse positivity for CD34 (Figure, C), positivity for bcl-2, and negativity for CD99 and S-100. Fluorescent in situ hybridization (FISH) further characterized the tumor with a translocation t(17;22)(q21;q13) and corresponding COL1A1/PDGFB fusion protein (Figure, D).A-C, Histopathologic images. A, Tumor infiltrating around and within the parotid gland. B, Fusiform tumor cells arranged in a storiform pattern. C, Tumor cells strongly positive for CD34. D, Image from FISH studies.

what is your diagnosis?

What is your diagnosis?

Solitary fibrous tumor

Spindle cell carcinoma

Malignant melanoma

Dermatofibrosarcoma protuberans

d

male

0-10

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2492614

A young boy presented to the pediatric otolaryngology clinic with bilateral conductive hearing loss (CHL) and delayed speech development. Examination revealed normal otoscopic findings, and an audiogram demonstrated moderate low-frequency CHL of 45 dB in the right ear and mild 30-dB CHL in the left ear with a normal tympanogram (Figure, A). Two sets of tympanostomy tubes were placed the year before his initial visit for presumed otitis media–related CHL, but his hearing did not improve. An axial computed tomographic (CT) scan performed at that time was interpreted as normal. Owing to concerns of visual changes and possible associated genetic cause for hearing loss (HL), magnetic resonance imaging (MRI) was ordered 1 year after initial presentation and showed no central or peripheral otologic abnormalities. A genetic evaluation revealed no abnormalities. Follow-up audiograms at 3 and 6 months showed similar persistent CHL despite normal otoscopy results. The patient and family decided to treat the CHL with bilateral hearing aid amplification and a frequency modulation (FM) system at school. After 30 months of persistent CHL with an unknown etiology, a repeated CT scan of the temporal bones was performed (Figure, B and C). Operative intervention vs amplification was discussed, and the patient and family decided to continue with hearing aids because he had improved performance in school. Surgical treatment will be considered in the future if there is a decline in hearing.A, Right-sided (45-db) and left-sided (30-db) conductive hearing loss in low frequencies (arrows). O and X indicate right and left air conduction, respectively; opening and closing brackets, right and left bone conduction, respectively. B and C, Axial computed tomographic (CT) scans of the temporal bones. What Is Your Diagnosis?

Bilateral otosclerosis

Bilateral malleus fixation

Bilateral tympanosclerosis

Bilateral malleoincudal subluxation

B. Bilateral malleus fixation

B

Bilateral malleus fixation

The most common cause of CHL in the pediatric population is middle ear effusion following otitis media. Other causes of CHL are rare in pediatrics and include obstruction at the external ear (eg, canal atresia) or middle ear (eg, cholesteatoma, ossicular chain abnormality). These causes are often associated with physical examination findings and should be considered in children with persistent HL after appropriate initial treatment of otitis media–related CHL with observation for at least 3 months and tympanostomy tubes if there is no improvement.1 Persistent CHL that is not related to middle ear effusion should be evaluated with imaging of the temporal bones and a genetic workup to evaluate for syndromic HL.2 Imaging may help to localize pathologic abnormalities to the external or middle ear. In this patient, a normal tympanic membrane was visualized, and while a tympanosclerosis can cause similar patterns of CHL on audiogram as seen in this patient, we suspected a congenital ossicular chain abnormality in the setting of a normal tympanic membrane. Dislocation of the malleoincudal joint was also a possibility but was unlikely without a history of antecedent trauma. A repeated dedicated CT scan of the temporal bones confirmed the diagnosis of bilateral isolated fixation of the malleus head to the epitympanum (Figure, B and C).Bony fixation in the middle ear space can occur at any level of the ossicular chain. It may be acquired or congenital. The acquired form occurs through repeated episodes of infectious middle ear disease. The congenital form of ossicular fixation most frequently occurs at the stapes in the form of otosclerosis. This is rare in children, and reports of congenital middle ear abnormalities in children demonstrate that there are often multiple anomalies.3 Stewart and Downs4 reviewed congenital CHL and found that only 3 patients of 54 had isolated, nonsyndromic middle ear abnormalities. Isolated fixation of the malleus is the least common form of ossicular chain fixation,5 and it occurs in 0.4% to 1.6% of all cases of CHL and is often unilateral.6-9Audiometric evaluation in the patient demonstrated persistent bilateral CHL greater than 30 to 35 dB after tympanostomy tube placement. In otitis media–related CHL, the expected level of hearing loss is less than 35 dB HL, which helped raise suspicion for ossicular chain abnormalities. The bilateral nature of his condition makes the diagnosis difficult, however, because bilateral conditions often represent otitis media.Imaging was performed early in the disease process with a CT scan and MRI, yet it did not reveal any abnormalities initially. This may be due to subtle ossicular abnormalities, such as malleus head fixation being beyond the limits of resolution of conventional CT scans, or failure to capture representative cuts of the pathologic abnormality. This diagnosis is made based on imaging findings; thus, communication with a neuroradiologist for unusual cases of HL is important.There are a variety of described ways in which to treat CHL caused by malleus head fixation. Surgery is often advised if the HL is severe and there is no benefit from hearing aid amplification. The bilaterality of this patient’s disease complicates the decision for surgery owing to the risk of worsening hearing in the setting of compromised hearing in the opposite ear. Different techniques exist with similar results in hearing improvement.10 He received bilateral hearing aids and an FM system at school, which provided him with benefit; thus, surgery was declined.Herein, we present a case of bilateral isolated congenital malleus fixation that highlights the importance of broadening the differential for CHL in the pediatric population and reviews the necessary workup with genetic evaluation and imaging.

General

A young boy presented to the pediatric otolaryngology clinic with bilateral conductive hearing loss (CHL) and delayed speech development. Examination revealed normal otoscopic findings, and an audiogram demonstrated moderate low-frequency CHL of 45 dB in the right ear and mild 30-dB CHL in the left ear with a normal tympanogram (Figure, A). Two sets of tympanostomy tubes were placed the year before his initial visit for presumed otitis media–related CHL, but his hearing did not improve. An axial computed tomographic (CT) scan performed at that time was interpreted as normal. Owing to concerns of visual changes and possible associated genetic cause for hearing loss (HL), magnetic resonance imaging (MRI) was ordered 1 year after initial presentation and showed no central or peripheral otologic abnormalities. A genetic evaluation revealed no abnormalities. Follow-up audiograms at 3 and 6 months showed similar persistent CHL despite normal otoscopy results. The patient and family decided to treat the CHL with bilateral hearing aid amplification and a frequency modulation (FM) system at school. After 30 months of persistent CHL with an unknown etiology, a repeated CT scan of the temporal bones was performed (Figure, B and C). Operative intervention vs amplification was discussed, and the patient and family decided to continue with hearing aids because he had improved performance in school. Surgical treatment will be considered in the future if there is a decline in hearing.A, Right-sided (45-db) and left-sided (30-db) conductive hearing loss in low frequencies (arrows). O and X indicate right and left air conduction, respectively; opening and closing brackets, right and left bone conduction, respectively. B and C, Axial computed tomographic (CT) scans of the temporal bones.

what is your diagnosis?

What is your diagnosis?

Bilateral malleus fixation

Bilateral tympanosclerosis

Bilateral malleoincudal subluxation

Bilateral otosclerosis

a

male

11-20

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2503117

A man in his 50s presented with intermittent dysphagia to solid foods, dry cough, foreign-body sensation in the throat, and dyspnea on effort for 4 months. His medical history included hypertension and chronic rhinosinusitis. On oral endoscopic examination, mild bilateral hyperemia of the tonsillar area and posterior pharyngeal wall were noted. The base of tongue was normal. Fiber-optic laryngoscopy revealed a reddish, 2-cm supraglottic lesion involving medially the free margin of the suprahyoid epiglottis (Figure, A). The neoplasm appeared highly vascularized on narrowband imaging (Figure, B). For this reason, before attempting an incisional biopsy, contrast magnetic resonance imaging (MRI) was performed. The MRI scan revealed an oval, 2.2-cm hypervascular mass arising from the free border of the suprahyoid epiglottis, which extended along the right aryepiglottic fold. The mass appeared to be capsulated, with regular margins, and did not show laryngeal deep tissues invasion. We proposed to the patient a surgical excision that could have been transoral or open according to the quality of exposure (which would be evaluated in general anesthesia). After evaluating the optimal exposure using a Crowe-Davis retractor, a transoral excision using the da Vinci robotic system was performed. The postoperative course was uneventful, and patient did not develop complications. On the second postoperative day, pain was fully controlled with oral medications, and the patient tolerated oral intake. He was discharged on the second postoperative day.A, Endoscopic examination of the supraglottic larynx revealing reddish supraglottic neoplasm arising from the free epiglottic border. B, Narrowband imaging of highly vascularized supraglottic neoplasm. What Is Your Diagnosis?

Supraglottic hemangioma

Supraglottic paraganglioma

Rhabdomyoma of the epiglottis

Laryngeal squamous papilloma

B. Supraglottic paraganglioma

B

Supraglottic paraganglioma

Paragangliomas are neuroendocrine neoplasms of neural origin.1 They are situated adjacent to sympathetic or parasympathetic nerves, and they produce a variety of neuroendocrine products. Laryngeal paragangliomas (LPs) are rare, and to date fewer than 90 cases have been recognized.2 LPs show a female preponderance (male to female ratio, 1:3) and tend to occur during the fourth to sixth decades of life. The sites of distribution are supraglottic (82%), subglottic (15%), and glottic (1%). About 2% show a malignant biological behavior.2Hoarseness or dysphagia are the commonest presenting LP symptoms, and usually it presents as a submucosal laryngeal mass.1 Depending on the size of the tumor, stridor, dysphagia, foreign-body sensation, and dyspnea are observed.2 In this patient, dyspnea on effort was present because the mass promoted the epiglottis collapse during inspiration.Preoperative LP histological diagnosis is preferable. However, superficial biopsies are inconclusive because LPs are usually covered by healthy mucosa. Deeper biopsies can cause complications because these lesions are highly vascular.3Currently, the diagnostic imaging modality of choice for laryngeal paragangliomas is MRI with gadolinium enhancement.2 It is preferred over computed tomographic scanning unless information about cartilage destruction is needed. Preoperative angiography with embolization is useful in minimizing bleeding during surgery, especially for larger LPs.4 If imaging provides sufficient evidence of LP (or any other vascular tumor), surgical excision is recommended. In this patient, we performed a surgical excision without preoperative embolization because the lesion spreading was superficial and limited to the free epiglottic border.The histopathological architecture of LPs is composed by chief cells (type I cells) and sustentacular cells, arranged in a characteristic alveolar or Zellballen pattern.1,2,5 The chief cells are more numerous and contain catecholamine-bound neurosecretory granules, whereas the sustentacular cells (type II cells) are devoid of neurosecretory granules and are characteristically located at the periphery of Zellballen.5 Zellballen pattern are also seen in typical and atypical carcinoid, malignant melanoma, and medullary carcinoma of thyroid and are not specific for paragangliomas.5 However, a differential diagnosis of LP is possible basing on the immunohistochemical expression of neuroendocrine markers (chromogranin, synaptophysin, and neuron-specific enolase), epithelial markers, S-100, HMB45, and melan-A.5Surgery is the treatment of choice.2 The goal of surgery is tumor eradication with respect to the surrounding normal tissues and maximal preservation of laryngeal function. However, most LPs are treated surgically using different open-approach techniques. Transoral techniques are not recommended, especially in larger neoplasms, because of increased risk of postoperative bleeding and recurrence owing to poor exposure and limited hemostatic control using the carbon dioxide laser.3In this patient, the well-encapsulated tumor was well exposed6,7 and entirely removed using the da Vinci system, preserving the healthy surrounding tissues without postoperative complications. Both the false and true vocal folds were preserved, as there was no sign of tumor invasion. At the 6-month follow-up we did not observe any sign and symptoms of recurrence.

General

A man in his 50s presented with intermittent dysphagia to solid foods, dry cough, foreign-body sensation in the throat, and dyspnea on effort for 4 months. His medical history included hypertension and chronic rhinosinusitis. On oral endoscopic examination, mild bilateral hyperemia of the tonsillar area and posterior pharyngeal wall were noted. The base of tongue was normal. Fiber-optic laryngoscopy revealed a reddish, 2-cm supraglottic lesion involving medially the free margin of the suprahyoid epiglottis (Figure, A). The neoplasm appeared highly vascularized on narrowband imaging (Figure, B). For this reason, before attempting an incisional biopsy, contrast magnetic resonance imaging (MRI) was performed. The MRI scan revealed an oval, 2.2-cm hypervascular mass arising from the free border of the suprahyoid epiglottis, which extended along the right aryepiglottic fold. The mass appeared to be capsulated, with regular margins, and did not show laryngeal deep tissues invasion. We proposed to the patient a surgical excision that could have been transoral or open according to the quality of exposure (which would be evaluated in general anesthesia). After evaluating the optimal exposure using a Crowe-Davis retractor, a transoral excision using the da Vinci robotic system was performed. The postoperative course was uneventful, and patient did not develop complications. On the second postoperative day, pain was fully controlled with oral medications, and the patient tolerated oral intake. He was discharged on the second postoperative day.A, Endoscopic examination of the supraglottic larynx revealing reddish supraglottic neoplasm arising from the free epiglottic border. B, Narrowband imaging of highly vascularized supraglottic neoplasm.

what is your diagnosis?

What is your diagnosis?

Supraglottic hemangioma

Laryngeal squamous papilloma

Rhabdomyoma of the epiglottis

Supraglottic paraganglioma

d

male

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2516463

A man in his 20s presented for further evaluation of an elevated serum ionized calcium level (6.28 mg/dL; reference range, 4.56-5.32 mg/dL) found incidentally during a routine examination 5 months prior. He had a several-year history of joint, back, and abdominal pain; constipation; fatigue; and depression. Laboratory workup revealed a normal intact parathyroid hormone (PTH) level (50 pg/mL; reference range, 13-88 pg/mL) and a slightly elevated 24-hour urinary calcium level (314 mg/d; reference range, 25-300 mg/d). A technetium Tc-99m sestamibi scan showed no definitive lesion but demonstrated a small focus of possible increased tracer uptake near the mid-pole of the left thyroid lobe (Figure, A, arrowheads). No abnormal masses were readily identifiable by ultrasonography or contrast-enhanced computed tomography (CT) of the neck. He underwent a parathyroid exploration and excision of a soft, ovoid tissue, believed to be a slightly enlarged left inferior parathyroid gland (120 mg; 1.0 × 0.6 × 0.3 cm). Intracytoplasmic fat vacuoles were evident on intraoperative touch preparation. Histological examination of permanent sections showed a thinly encapsulated parathyroid tissue (Figure, B) with approximately 30% displaying myxoid stromal change and focal presence of interspersed adipocytes (Figure, C, yellow arrowhead) bordered by a rim of compressed gland containing abundant stromal fat (Figure, C, blue arrowhead). Examination at higher power showed chief cells in lobules, nests, and focal trabeculae with occasional clusters of clear and oxyphil cells (Figure, C and D).A, Technetium Tc-99m sestamibi scan with sodium iodide I-123 subtraction. Columns 2 to 4 show delayed images at 30 minutes, 1 hour, and 2 hours. B-D, Histopathologic images (hematoxylin-eosin) of thinly encapsulated parathyroid tissue. What Is Your Diagnosis?

Hyperplastic parathyroid

Parathyroid lipohyperplasia

Parathyroid lipoadenoma

Parathyroid carcinoma

C. Parathyroid lipoadenoma

C

Parathyroid lipoadenoma

Parathyroid lipoadenoma is an exceedingly rare cause of primary hyperparathyroidism and is histologically characterized by polygonal chief cells with a few nests of oxyphil cells in the abundance of mature adipocytes.1 This pathologic entity was first described by Ober and Kaiser2 in 1958 as a parathyroid hamartoma, because it was believed to be nonfunctioning and serum calcium and PTH levels were not measured. Abul-Haj et al3 described a similar pathologic finding with endocrine functionality in 1962 and coined the term parathyroid lipoadenoma. To date, 59 cases have been reported in the literature, with patient ages ranging from 24 to 94 years and a female to male ratio of 1.4:1.4 Of note, several cases have demonstrated ectopic lipoadenomas in the mediastinum, and a recent report5 described a unique case of a double parathyroid lipoadenoma. To our knowledge, there have been no cases reported in association with multiple endocrine neoplasia syndromes.Preoperative localization of lipoadenomas by diagnostic imaging is often difficult owing to the high fat content of the tumor, as illustrated in this case. In the largest case series to date,4 ultrasonography successfully localized 50% of cases, and 3-dimensional, single-photon emission CT with sestamibi tracing and planar sestamibi was able to localize 71.4%. Our report highlights the challenges faced in the preoperative evaluation of primary hyperparathyroidism secondary to a lipoadenoma with a normal ultrasonography and CT with a technetium Tc-99m sestamibi scan showing a low target-to-background signal ratio.On gross examination, these tumors are typically lobulated, yellow-tan masses that vary greatly in size, ranging from less than 200 mg, as in our case, to 420 g, the largest reported. Microscopically, most cases display a predominance of chief cells in a fatty stroma with only a small minority showing a definitive capsule and a rim of normal parathyroid as described herein. Owing to the high fat content of these tumors, they can easily be mistaken for normal parathyroid tissue on intraoperative frozen section. Similar histologic features can be found in parathyroid lipohyperplasia, an entity distinguished by lipoid changes usually affecting all 4 glands.6 However, this is an extremely rare variant, with even fewer cases reported than parathyroid lipoadenomas. Evaluation of intracytoplasmic fat droplets on touch preparation can be beneficial during an intraoperative parathyroid consultation. Normal parathyroid glands typically display large intracytoplasmic fat vacuoles, which are reduced to absent in adenomas and hyperplastic glands.7 As evidenced in this case, the diagnosis of lipoadenoma on touch preparation can be difficult owing to the cytologic sampling of normal lobulated parathyroid tissue adjacent to the tumor. Also, frozen section diagnosis of lipoadenoma can be challenging, owing to the presence of stromal fat within the parathyroid adenoma. In this case, because of the presence of intracytoplasmic and stromal fat, the pathologic diagnosis of lipoadenoma was not considered in the intraoperative setting.A decrease in the intraoperative measurement of PTH more than 50% within 10 minutes of gland excision has been previously shown to be a reliable predictor of the successful removal of a parathyroid adenoma.8 Given the difficulty of differentiating normocellular parathyroid tissue from lipoadenoma on frozen section, intraoperative measurement of PTH can significantly aid in the diagnosis of this tumor4,9 and was beneficial in this case, as the serum concentration decreased from 56 pg/mL to 6 pg/mL. Because parathyroid lipoadenomas are not always readily detectable on diagnostic imaging and can be difficult to differentiate from normal adipose tissue on gross examination, it is essential that the surgeon is aware of this entity to avoid a failed or unnecessary bilateral neck exploration.

General

A man in his 20s presented for further evaluation of an elevated serum ionized calcium level (6.28 mg/dL; reference range, 4.56-5.32 mg/dL) found incidentally during a routine examination 5 months prior. He had a several-year history of joint, back, and abdominal pain; constipation; fatigue; and depression. Laboratory workup revealed a normal intact parathyroid hormone (PTH) level (50 pg/mL; reference range, 13-88 pg/mL) and a slightly elevated 24-hour urinary calcium level (314 mg/d; reference range, 25-300 mg/d). A technetium Tc-99m sestamibi scan showed no definitive lesion but demonstrated a small focus of possible increased tracer uptake near the mid-pole of the left thyroid lobe (Figure, A, arrowheads). No abnormal masses were readily identifiable by ultrasonography or contrast-enhanced computed tomography (CT) of the neck. He underwent a parathyroid exploration and excision of a soft, ovoid tissue, believed to be a slightly enlarged left inferior parathyroid gland (120 mg; 1.0 × 0.6 × 0.3 cm). Intracytoplasmic fat vacuoles were evident on intraoperative touch preparation. Histological examination of permanent sections showed a thinly encapsulated parathyroid tissue (Figure, B) with approximately 30% displaying myxoid stromal change and focal presence of interspersed adipocytes (Figure, C, yellow arrowhead) bordered by a rim of compressed gland containing abundant stromal fat (Figure, C, blue arrowhead). Examination at higher power showed chief cells in lobules, nests, and focal trabeculae with occasional clusters of clear and oxyphil cells (Figure, C and D).A, Technetium Tc-99m sestamibi scan with sodium iodide I-123 subtraction. Columns 2 to 4 show delayed images at 30 minutes, 1 hour, and 2 hours. B-D, Histopathologic images (hematoxylin-eosin) of thinly encapsulated parathyroid tissue.

what is your diagnosis?

What is your diagnosis?

Parathyroid carcinoma

Parathyroid lipoadenoma

Parathyroid lipohyperplasia

Hyperplastic parathyroid

b

male

21-30

original

https://jamanetwork.com/journals/jamaoncology/fullarticle/2537187

A man in his 30s with no medical history reported a 2-year history of waxing and waning pruritic papules involving his left popliteus, contralateral popliteus, groin, and penis with each lesion occurring at different time points. He was initially evaluated by an infectious disease physician and a local dermatologist, who had intermittently prescribed empirical antibiotics (clindamycin hydrochloride and doxycycline calcium) for a presumptive clinical diagnosis of methicillin-resistant Staphylococcus aureus (MRSA) infection for more than 1 year with minimal response. Because no objective data including wound culture or biopsy were obtained during his prior evaluations, he sought an alternate clinical consultation given the appearance of new violaceous ulcerated lesions over his right lateral proximal calf (Figure, A) despite his actively taking doxycycline. He endorsed spontaneous healing of previously involved sites despite the absence of antibiotic exposure but denied constitutional complaints, recent travel, or high-risk behavior. His physical examination was unremarkable for hepatosplenomegaly or systemic adenopathy. Laboratory evaluation including complete blood cell count, peripheral blood cultures, MRSA swab, human immunodeficiency virus/human T-cell lymphotropic virus testing, flow cytometry, and Lyme disease titers had unremarkable results. Pathologic sampling of the lesions revealed V-shaped perifascicular infiltrative large lymphocytes with abundant amphophilic cytoplasm and prominent nucleoli (Figure, B and C). Lesional cells exclusively involving the dermis stained positive for CD30, leukocyte common antigen, CD2, TIA-1, and CD4 and negative for CD7, CD8, CD43, CD56, and programmed cell death protein 1. Scattered B lymphocytes were PAX5 positive and CD20 positive. Ki-67 level was 87%. Scattered dermal dendritic and Langerhans cells were S100 positive. T-cell receptor (TCR) gene rearrangement testing had negative results. Systemic imaging did not reveal extracutaneous involvement, and screening endoscopy for upper and lower gastrointestinal involvement had unremarkable results.A, Photograph of right lateral proximal calf shows violaceous ulcerated nodule. B and C, Biopsy of the lesion revealed V-shaped perifascicular infiltrative large lymphocytes with abundant amphophilic cytoplasm and prominent nucleoli hematoxlyn-eosin, original magnification ×2 and ×20, respectively). What Is Your Diagnosis?

Adult T-cell leukemia-lymphoma

Primary cutaneous anaplastic large-cell lymphoma

Lymphomatoid papulosis

Transformed mycosis fungoides and Sézary syndrome

C. Lymphomatoid papulosis

C

Lymphomatoid papulosis

Lymphomatoid papulosis (LP) is characterized by chronic and recurrent cutaneous papules and nodules that spontaneously regress without treatment.1 The disease is more common in males, with a median age of 50 to 55 years at diagnosis. The life span of skin lesions typically ranges from 4 to 8 weeks but may last up to several months. Lesions are usually less than 2 cm in diameter and may occur in a solitary pattern or multiple crops involving any part of the body. Some patients have associated pruritus, which may heal with scar formation; however, accompanying constitutional symptoms are absent in most cases. Early lesions typically show a limited number of perivascular lymphocytes; however, large atypical cells accumulate in the advanced lesions.1 Furthermore, neutrophilic infiltration is frequently observed in the epidermis of the involved lesions.1Lymphomatoid papulosis is classified as a primary cutaneous CD30-positive T-cell lymphoproliferative disorder along with primary cutaneous anaplastic large-cell lymphoma (ALCL).2 Accordingly, LP is uniformly positive for CD30, and may be positive for CD25, CD71, CD3, CD4, CD8, and HLA-DR depending on subtypes.1 There are 6 major histopathologic subtypes (types A-E, LP with 6p23.5 rearrangement).3 Type A, the most common subtype, is characterized by a wedge-shaped infiltration of large atypical CD30-positive and inflammatory cells resembling Hodgkin lymphoma. Type B and C lesions show small and large atypical CD30-positive cell infiltration resembling mycosis fungoides (MF) and ALCL, respectively. Type D is characterized by epidermotropic infiltration of atypical CD30-positive/CD8-positive lymphoid cells resembling primary cutaneous cytotoxic T-cell lymphoma, and type E shows angiocentric infiltration of CD30-positive/CD8-positive small to large pleomorphic cells in dermis and blood vessels.3CD30 has been shown to interact with CD30L to activate the nuclear factor–κB pathway regulating cell death and proliferation in active B and T cells, but the mechanistic role of CD30 in LP remains unexplained.4 Other chromosomal and genetic abnormalities such as aneuploidy have been identified in LP although t(2;5)(p23;q35) translocation, a characteristic marker of systemic ALCL, is typically absent in LP.5 The underlying mechanisms of spontaneous regression in LP are largely unknown, although several hypotheses, including low and high expression of antiapoptotic and proapoptotic B-cell lymphoma 2 family proteins and higher apoptotic vs proliferation ratio, have been suggested.6Owing to variability in the results of histopathologic analysis depending on evolutionary course of disease, LP is often misdiagnosed. As well, the histologic patterns and immunophenotypes largely overlap with other cutaneous lymphoid malignant neoplasms such as primary cutaneous ALCL, transformed MF, Sézary syndrome, and adult T-cell leukemia and lymphoma. Because benign skin lesions from pityriasis lichenoides, lymphomatoid drug eruption, viral infection, and insect bites can mimic LP, a thorough history and physical examination, viral serologic testing, and expert pathologic review are essential in differentiating LP from other benign disease. Clinical features pointing toward a disorder other than LP include constitutional complaints, lymphadenopathy, and organomegaly. Moreover, molecular workup such as TCR gene rearrangement, flow cytometry, immunohistochemical staining, and cytogenetic testing is essential to differentiate LP from other malignant neoplasms including ALCL, MF, Sézary syndrome, and T-cell leukemia and lymphoma.The life expectancy of patients with LP is similar to that of the general population, but 10% to 25% develop other types of lymphoid malignant neoplasms such as MF (61%), cutaneous ALCL (26%), Hodgkin lymphoma (4%), and chronic lymphocytic leukemia (4%).7 Male sex, subtypes B and C, and TCR-γ gene rearrangement have been shown to be associated with increased risk of lymphoma.7,8 Although the mechanisms of transformation remain elusive, monoclonal TCR gene rearrangement has been identified in both cutaneous lesions of LP and associated lymphoid malignant cells, supporting the clonal relationship between these 2 entities.9Asymptomatic patients with LP do not need treatment, and a watch-and-wait strategy is reasonable for them. Our patient remains on active surveillance without any new lesions at the time of publication. In symptomatic patients with extensive disease, oral methotrexate is the treatment of choice and efficacious at weekly doses of 5 to 25 mg.10

Oncology

A man in his 30s with no medical history reported a 2-year history of waxing and waning pruritic papules involving his left popliteus, contralateral popliteus, groin, and penis with each lesion occurring at different time points. He was initially evaluated by an infectious disease physician and a local dermatologist, who had intermittently prescribed empirical antibiotics (clindamycin hydrochloride and doxycycline calcium) for a presumptive clinical diagnosis of methicillin-resistant Staphylococcus aureus (MRSA) infection for more than 1 year with minimal response. Because no objective data including wound culture or biopsy were obtained during his prior evaluations, he sought an alternate clinical consultation given the appearance of new violaceous ulcerated lesions over his right lateral proximal calf (Figure, A) despite his actively taking doxycycline. He endorsed spontaneous healing of previously involved sites despite the absence of antibiotic exposure but denied constitutional complaints, recent travel, or high-risk behavior. His physical examination was unremarkable for hepatosplenomegaly or systemic adenopathy. Laboratory evaluation including complete blood cell count, peripheral blood cultures, MRSA swab, human immunodeficiency virus/human T-cell lymphotropic virus testing, flow cytometry, and Lyme disease titers had unremarkable results. Pathologic sampling of the lesions revealed V-shaped perifascicular infiltrative large lymphocytes with abundant amphophilic cytoplasm and prominent nucleoli (Figure, B and C). Lesional cells exclusively involving the dermis stained positive for CD30, leukocyte common antigen, CD2, TIA-1, and CD4 and negative for CD7, CD8, CD43, CD56, and programmed cell death protein 1. Scattered B lymphocytes were PAX5 positive and CD20 positive. Ki-67 level was 87%. Scattered dermal dendritic and Langerhans cells were S100 positive. T-cell receptor (TCR) gene rearrangement testing had negative results. Systemic imaging did not reveal extracutaneous involvement, and screening endoscopy for upper and lower gastrointestinal involvement had unremarkable results.A, Photograph of right lateral proximal calf shows violaceous ulcerated nodule. B and C, Biopsy of the lesion revealed V-shaped perifascicular infiltrative large lymphocytes with abundant amphophilic cytoplasm and prominent nucleoli hematoxlyn-eosin, original magnification ×2 and ×20, respectively).

what is your diagnosis?

What is your diagnosis?

Primary cutaneous anaplastic large-cell lymphoma

Transformed mycosis fungoides and Sézary syndrome

Lymphomatoid papulosis

Adult T-cell leukemia-lymphoma

c

male

0-10

original

https://jamanetwork.com/journals/jama/fullarticle/2569762

A 62-year-old woman presented with a 6-month history of hair thinning, itchy scalp, and cold sensitivity. She reported no fatigue, depression, memory problems, dry skin, or constipation. She had hyperlipidemia for which she took fish oil and red yeast rice extract. Heart rate was 80/min and body mass index was 31 (calculated as weight in kilograms divided by height in meters squared). Physical examination demonstrated a thyroid gland of normal size and consistency without palpable nodules. Deep tendon reflexes were normal. Her laboratory values are reported in the Table.The patient has subclinical hyperthyroidism and does not need a repeat testing of a thyroid-stimulating hormone (TSH) level.The patient has subclinical hypothyroidism and does not need a repeat testing of a TSH level.The patient has subclinical hypothyroidism and should have the TSH level repeated in 1 to 3 months. How Do You Interpret These Test Results?

The patient has overt hypothyroidism.

The patient has subclinical hyperthyroidism and does not need a repeat testing of a thyroid-stimulating hormone (TSH) level.

The patient has subclinical hypothyroidism and does not need a repeat testing of a TSH level.

The patient has subclinical hypothyroidism and should have the TSH level repeated in 1 to 3 months.

D

The patient has subclinical hypothyroidism and should have the TSH level repeated in 1 to 3 months.

Serum thyroid-stimulating hormone (TSH) is the initial screening test for primary thyroid dysfunction. TSH is a glycoprotein hormone produced by the pituitary gland. It stimulates the thyroid gland to secrete thyroid hormones, which regulate tissue metabolism. TSH assays are named historically by generation; third-generation assays are widely used and have a detection limit of 0.01 mIU/L as compared with first- (1 mIU/L) and second-generation assays (0.1-0.2 mIU/L).1 The 2016 Medicare midpoint reimbursement for TSH is $30.93.2Serum TSH is reliable in the outpatient setting and is more sensitive and specific than free thyroxine (free T4) for diagnosing thyroid dysfunction. A free T4 level can be added if the serum TSH is abnormal. In suspected secondary hypothyroidism, TSH is inadequate for diagnosis, and both serum TSH and free T4 should be measured. Serum TSH is not reliable in diagnosing thyroid dysfunction in hospitalized patients with severe nonthyroidal illness. TSH remains the preferred test during pregnancy and in situations affecting thyroid hormone–binding proteins.A serum TSH above the upper reference limit with a normal free T4 level indicates subclinical hypothyroidism, which has a prevalence of 4.3% to 8.5%.3 Mild TSH fluctuations may occur in patients without thyroid disease with subsequent normalization. The diagnosis of subclinical hypothyroidism is only applicable when thyroid function has been stable for 1 month, the hypothalamic-pituitary-thyroid axis is normal, and there is no recent or ongoing severe illness.4Upon presentation, the patient had mild TSH elevation (between the assay upper limit and 10 mIU/L), hair thinning, cold sensitivity, and elevated levels of low-density lipoprotein and total cholesterol. These symptoms are not specific to hypothyroidism, and their relationship to her thyroid status is unclear. The elevated TSH level indicates subclinical hypothyroidism, which occurs in approximately 15% of adults older than 65 years.3 Although the free T4 level was not measured in this patient, the TSH was too low for a diagnosis of overt hypothyroidism, which would require a level greater than 10 mIU/L. Mild TSH elevations may not reflect thyroid dysfunction and may be a normal manifestation of aging.3 There is controversy over the appropriateness of diagnostic testing and treatment in this setting.5There are no alternative diagnostic testing approaches for subclinical hypothyroidism. However, a single serum TSH result may not be a reliable indicator because of transient fluctuations.6 Thus, observation with a repeat serum TSH in 1 to 3 months without treatment is acceptable. Prior to TSH, nonspecific tests were used to diagnose hypothyroidism, including basal metabolic rate, sleeping heart rate, and Achilles reflex time. The presence of thyroid peroxidase antibody (TPOAb) suggests underlying autoimmune thyroid disease. The TPOAb test slightly improves prediction of progression to overt hypothyroidism at 4.3% per-year progression with subclinical hypothyroidism and elevated TPOAb titers and 2.6% per-year progression with subclinical hypothyroidism and normal TPOAb titers.7A free T4 level was not obtained during the initial evaluation. Treatment was started with 25 µg of levothyroxine prescribed by the patient’s primary care physician. Her itchy scalp improved, and her bowel movements became more regular without changes in other symptoms. Her TSH was 2.75 mIU/L after 3 months of levothyroxine. Her lipid profile remained unchanged with a total cholesterol level of 250 mg/dL, triglycerides of 53 mg/dL, high-density lipoprotein of 90 mg/dL, and low-density lipoprotein of 149 mg/dL.Upon endocrinology consultation, a TPOAb test showed normal results (<20 IU/mL). Levothyroxine was discontinued. Placebo-controlled trials of levothyroxine therapy in patients with subclinical hypothyroidism do not demonstrate improved symptoms.8,9 Although subclinical hypothyroidism is associated with an adverse lipid profile, studies investigating the effect of levothyroxine therapy on lipids have shown mixed results, with a small benefit of uncertain clinical significance.8,9 Lifestyle modifications and lipid-lowering therapy are reasonable options for this patient’s hyperlipidemia.Patient follow-up continues without levothyroxine therapy and no recurrence of symptoms has occurred. Spontaneous resolution of subclinical hypothyroidism is common, occurring in 46% of individuals with TSH concentrations of 4.5 to 7.0 mIU/L when retested 2 years later.6 TSH concentrations 4 months later and annually thereafter were 5.14 mIU/L, 3.05 mIU/L, 3.78 mIU/L, 2.75 mIU/L, and 4.14 mIU/L.Subclinical hypothyroidism is defined as an elevated serum TSH with normal free thyroid hormones. However, a single serum TSH result may not be a reliable indicator of subclinical hypothyroidism and repeat testing should be performed in 1 to 3 months.Treatment of subclinical hypothyroidism with TSH values of less than 7 mIU/L is usually deferred due to high rates of spontaneous reversion to euthyroidism.Randomized trials are needed to determine the long-term risks and benefits from treatment of subclinical hypothyroidism.

Diagnostic

A 62-year-old woman presented with a 6-month history of hair thinning, itchy scalp, and cold sensitivity. She reported no fatigue, depression, memory problems, dry skin, or constipation. She had hyperlipidemia for which she took fish oil and red yeast rice extract. Heart rate was 80/min and body mass index was 31 (calculated as weight in kilograms divided by height in meters squared). Physical examination demonstrated a thyroid gland of normal size and consistency without palpable nodules. Deep tendon reflexes were normal. Her laboratory values are reported in the Table.The patient has subclinical hyperthyroidism and does not need a repeat testing of a thyroid-stimulating hormone (TSH) level.The patient has subclinical hypothyroidism and does not need a repeat testing of a TSH level.The patient has subclinical hypothyroidism and should have the TSH level repeated in 1 to 3 months.

how do you interpret these test results?

How do you interpret these results?

The patient has subclinical hypothyroidism and should have the TSH level repeated in 1 to 3 months.

The patient has overt hypothyroidism.

The patient has subclinical hyperthyroidism and does not need a repeat testing of a thyroid-stimulating hormone (TSH) level.

The patient has subclinical hypothyroidism and does not need a repeat testing of a TSH level.

a

female

61-70

original

https://jamanetwork.com/journals/jama/fullarticle/2565727

A 47-year-old man with a history of severe Crohn disease was admitted for elective colectomy. He experienced nausea and vomiting in the 2 weeks prior to surgery. Although the surgical procedure was uneventful, the postoperative period was complicated by an enterocutaneous fistula that required further surgical intervention. One week after the second operation, he reported an “inability to visually focus on objects” and excruciating, burning pain in the lower limbs, both proximally and distally. On evaluation, the patient was alert and interactive, afebrile, and had no neck rigidity. A primary gaze upbeat nystagmus was present, with superimposed gaze-evoked nystagmus in all directions (Video). The remainder of the cranial nerve examination was normal. He had neither motor deficits nor coordination problems. Sensory examination revealed hyperalgesia and allodynia in the lower extremities. Bilateral ankle reflexes were diminished. He could not recall 3 items after a 5-minute delay. The results of laboratory tests, including a complete blood cell count and comprehensive metabolic panel, were all within reference ranges. Magnetic resonance imaging (MRI) of the brain showed abnormal signals of both medial thalami (Figure).Axial fluid-attenuated inversion recovery magnetic resonance imaging of the brain showing bilateral medial thalamic hyperintensity. These areas demonstrated restricted diffusion on diffusion-weighted imaging (not shown). What Would You Do Next?

Start intravenous acyclovir

Start intravenous thrombolysis

Start parenteral thiamine

Start systemic corticosteroids

Wernicke encephalopathy

C

Start parenteral thiamine

The key to the diagnosis in this case is that the patient’s symptoms developed in circumstances known to predispose to nutritional deficiencies, namely, gastrointestinal surgical procedures, parenteral nutrition, recurrent vomiting, and diarrhea. The comorbidity of Crohn disease could have also contributed to the patient’s malnourished state.The combined occurrence of mental status changes and ocular abnormalities points toward a thiamine deficit, presenting as Wernicke encephalopathy.1 Upbeat nystagmus—the first symptom in this case—is a centrally mediated phenomenon attributable to lesions from the medulla to the thalamus.2 The abrupt onset, in conjunction with anterograde amnesia, suggested a possible thalamic insult. Findings from MRI of the brain confirmed the neurologic localization and supported the diagnosis: symmetric lesions of the medial thalami are common neuroimaging findings of Wernicke encephalopathy.1Immediate treatment with parenteral thiamine is needed in suspected cases of Wernicke encephalopathy because any delay can result in permanent brain damage and even death.1 Initiating acyclovir for herpes encephalitis without first performing a lumbar puncture would not be appropriate. Moreover, the possibility of encephalitis or meningoencephalitis is unlikely given the absence of fever, headache, meningeal signs, or leukocytosis. Intravenous thrombolysis, as might be considered for acute ischemic stroke, is not indicated in this case. Bilateral thalamic vascular lesions are rare and usually result from deep cerebral venous thrombosis, anatomical variations (eg, occlusion of the artery of Percheron, a solitary trunk that supplies the paramedian thalami and rostral midbrain bilaterally), and predisposing risk factors.3 This patient was a nonsmoker, did not use illicit drugs, had no known heart disease, and did not have diabetes. The presence of restricted signal on diffusion-weighted imaging, as detected in this patient, is possible in Wernicke encephalopathy and does not represent an ischemic insult.4 Systemic corticosteroids would be considered for treatment of immune-mediated encephalitis but are not indicated in this case, because they could potentially exacerbate neurologic symptoms of Wernicke encephalopathy by inducing hyperglycemia.1,5Wernicke encephalopathy is a catastrophic, yet treatable, neurologic disease that results from thiamine (vitamin B1) deficiency.1,5,6 This condition is increasingly seen following bariatric5 and other abdominal surgery, prolonged parenteral feeding, and comorbid gastrointestinal diseases,1,6 rather than the classic setting of alcoholism. However, Wernicke encephalopathy remains a clinical, often underrecognized, diagnosis, since no definitive diagnostic test exists. The classic triad of ataxia, ophthalmoplegia, and altered mental status is rarely present1,6 and was not present in this case. Although the leg pain experienced by the patient could have been thalamic in nature, given the abrupt onset and prompt response to treatment, it was more likely a concurrent neuropathy attributable to thiamine deficiency (“dry beri beri”). Dejerine and Roussy described thalamic pain attributable to infarction in 1906,7 but bilateral thalamic pain has only been described twice8 and never in patients with Wernicke encephalopathy.A high index of suspicion may allow prompt diagnosis and treatment of Wernicke encephalopathy. Additional studies to be considered in elusive cases are MRI of the brain and measurement of serum thiamine levels,1 although treatment should not be delayed while waiting for laboratory confirmation of thiamine deficiency.9 Patients with Wernicke encephalopathy should receive high doses of parenteral thiamine (500-1500 mg daily in 3 divided doses).1,9 Early treatment prevents evolution into Korsakoff syndrome, a chronic anterograde and retrograde amnesia that responds poorly to thiamine.1Immediate treatment with parenteral thiamine (200 mg, 3 times daily) was initiated, and after 24 hours the patient’s condition began to improve. Allodynia completely resolved after 1 week and nystagmus gradually diminished, but mild anterograde amnesia persisted. Repeat MRI of the brain performed 10 days after the initial presentation revealed normal findings.

General

A 47-year-old man with a history of severe Crohn disease was admitted for elective colectomy. He experienced nausea and vomiting in the 2 weeks prior to surgery. Although the surgical procedure was uneventful, the postoperative period was complicated by an enterocutaneous fistula that required further surgical intervention. One week after the second operation, he reported an “inability to visually focus on objects” and excruciating, burning pain in the lower limbs, both proximally and distally. On evaluation, the patient was alert and interactive, afebrile, and had no neck rigidity. A primary gaze upbeat nystagmus was present, with superimposed gaze-evoked nystagmus in all directions (Video). The remainder of the cranial nerve examination was normal. He had neither motor deficits nor coordination problems. Sensory examination revealed hyperalgesia and allodynia in the lower extremities. Bilateral ankle reflexes were diminished. He could not recall 3 items after a 5-minute delay. The results of laboratory tests, including a complete blood cell count and comprehensive metabolic panel, were all within reference ranges. Magnetic resonance imaging (MRI) of the brain showed abnormal signals of both medial thalami (Figure).Axial fluid-attenuated inversion recovery magnetic resonance imaging of the brain showing bilateral medial thalamic hyperintensity. These areas demonstrated restricted diffusion on diffusion-weighted imaging (not shown).

what would you do next?

What would you do next?

Start parenteral thiamine

Start intravenous acyclovir

Start intravenous thrombolysis

Start systemic corticosteroids

a

male

41-50

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2532613

A man in his 40s presented with a 2-year history of multiple asymptomatic lesions on the face and neck. The lesions were round, hypopigmented macules and were symmetrically distributed in the affected area. The patient reported that the macules had appeared on his cheeks 2 years earlier and had gradually coalesced (Figure). The size of the lesions ranged from approximately 2 to 3 mm to 25 mm in diameter. There was no hair growth at the site of the lesions, and the patient reported no symptoms. He was treated for tinea versicolor, without success. A skin biopsy was performed to rule out some kind of morphea.A, Hypopigmented macules on the face and neck. B, Absence of hair growth in the affected area. C, Hematoxylin-eosin staining (original magnification ×10). D, Hematoxylin-eosin staining (original magnification ×20). What Is Your Diagnosis?

Guttata hypomelanosis

Vitiligo

Tumors of the follicular infundibulum

Tuberculoid leprosy

C. Tumors of the follicular infundibulum

C

Tumors of the follicular infundibulum

Histopathologic findings revealed a plate-like subepidermal tumor extending horizontally under the epidermis with multiple cord-like connections to the overlying epidermis. These neoplastic cords consisted of clear or pale epithelial cells, whose cytoplasm showed strong staining for periodic acid-Schiff owing to the accumulation of glycogen. The stroma was formed by fibrous connective tissue. Marked elastosis was also observed in the dermis surrounding the tumor.These findings were consistent with a diagnosis of multiple tumors of follicular infundibulum (TFI).Tumors of follicular infundibulum is a rare benign cutaneous adnexal neoplasm. Despite its name, the tumor shows isthmus rather than infundibular differentiation, and the neoplastic epithelium is similar to that of the outer root sheath at the level of the isthmus.The clinical manifestations of TFI are generally classified as solitary or eruptive. The most common form is a solitary lesion, which typically appears in middle-aged women. It presents as an asymptomatic scaly papulonodular lesion that measures up to 1 to 2 cm and resembles basal cell carcinoma or seborrheic keratosis.1 The eruptive or multiple form diagnosed in our case is rare, and is much less common than the solitary form.2 In most of the reports to date, eruptive TFI has been described as symmetrically distributed tumors with variable degrees of scaling and hypopigmented macules and papules with irregular or angulated borders confined to the face, neck, and upper trunk. There have also been rare reports of lesions on the extremities and buttocks. The tumors are usually asymptomatic.The differential diagnosis is challenging as TFI resemble many other dermatologic conditions. When faced with a patient with hypopigmented macules, the differential diagnosis should include tinea versicolor, pityriasis alba, vitiligo, tuberculoid leprosy, and idiopathic guttate hypomelanosis.The definitive diagnosis is provided by the histopathological study because clinical findings are insufficient. Histopathological findings consist of a plate-like fenestrated subepidermal tumor with anastomosing epithelial cords protruding into the dermis. One of the main characteristics is the presence of a network of elastic fibers surrounding the base of the tumor that is not present in other benign follicular tumors. Ductal structures can be observed in the epithelial cords. Histologically, TFI should be differentiated from basal cell carcinoma, superficial fibroepithelial tumor of Pinkus, trichilemmoma, inverted follicular keratosis, and pilar sheath acanthoma.3Eruptive TFI has been reported in association with Cowden disease, nevus sebaceous, trichilemmoma, Schöpf-Schulz-Passarge syndrome, actinic keratosis, junctional melanocytic nevus, desmoplastic malignant melanoma, and epidermal inclusion cysts. Our patient reported no symptoms and associated tumors were ruled out. In 1 report4 of a patient with more than 100 lesions, the authors reported the transformation of 2 tumors into basal cell carcinoma.Many treatments have been described for TFI but none of them have been successful.5 They include topical steroids, topical retinoic acid, topical keratolytics, topical imiquimod, etretinate, cryotherapy, curettage and excision, and ablative laser therapy. Our patient was treated with topical retinoic acid but showed no improvement at 3 months.Tumors of follicular infundibulum should be contemplated in a patient with hypopigmented macules that do not respond to treatment based on clinical diagnosis, particularly when these are located on the head and neck. Familiarity with the clinical and histopathologic features of this tumor can greatly facilitate diagnosis.

Dermatology

A man in his 40s presented with a 2-year history of multiple asymptomatic lesions on the face and neck. The lesions were round, hypopigmented macules and were symmetrically distributed in the affected area. The patient reported that the macules had appeared on his cheeks 2 years earlier and had gradually coalesced (Figure). The size of the lesions ranged from approximately 2 to 3 mm to 25 mm in diameter. There was no hair growth at the site of the lesions, and the patient reported no symptoms. He was treated for tinea versicolor, without success. A skin biopsy was performed to rule out some kind of morphea.A, Hypopigmented macules on the face and neck. B, Absence of hair growth in the affected area. C, Hematoxylin-eosin staining (original magnification ×10). D, Hematoxylin-eosin staining (original magnification ×20).

what is your diagnosis?

What is your diagnosis?

Tuberculoid leprosy

Vitiligo

Tumors of the follicular infundibulum

Guttata hypomelanosis

c

male

0-10

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2546558

A 42-year-old African American male presented with a 7-month history of fatigue, exertional dyspnea, arthralgias, hand swelling, tender ulcerations, hair loss, and a 50-pound weight loss. He had been hospitalized 6 months prior for hypoxia. Chest computed tomography (CT) showed hilar lymphadenopathy, interstitial thickening, and perilymphatic ground glass opacities. Bronchoscopy revealed plaquelike lesions, and transbronchial nodal aspiration of mediastinal nodes was negative for carcinomas and/or granulomas. Prednisone was initiated for presumed sarcoidosis. Antineutrophil cytoplasmic antibodies, antinuclear antibodies, angiotensin-converting enzyme, rheumatoid factor, and Aspergillosis antigen were negative and/or normal. The patient was referred for a second opinion.On presentation he had symmetric swelling of metacarpophalangeal joints (MCPs) and interphalangeal joints (IPs), preventing fist formation. Dorsal MCPs had ulcers distal fingers were dyspigmented and atrophic, capillaroscopy was normal, and palmar IP creases had ulcerated lichenoid papules (Figure, A and B). Oxford Scale muscle strength was 5 of 5 throughout. Auscultation revealed bibasilar rales. He had normal aldolase levels (4.5 U/L [to convert to μkat/L, multiply by 0.0167]), depressed creatine kinase (32 U/L), hyperferritinemia (1543 ng/mL), and T lymphocytopenia (absolute CD3, CD4, and CD8 counts, 328 μL, 233 μL, and 85 μL, respectively); the patient also had anti-SSA (Ro) antibodies, and immunoglobulin G anticardiolipin antibodies (19.5 units). The patient tested negative for HIV, anti–Scl-70 antibodies, anti–β2-glycoprotein 1 antibodies, lupus anticoagulant, cryoglobulins, and anti–Mi-2 antibodies; prothrombin time, partial thromboplastin time, and tissue thromboplastin were normal.A, Edematous hands with crusted ulcers and surrounding hyperpigmentation overlying dorsal metacarpophalangeal joints and interphalangeal joints. B, Ulcerating papules with crust located in the palmar creases of the priximal interphalangeal joints and distal interphalangeal joints. C, Histopathology. D, Chest computed tomography.Antimelanoma differentiation associated gene 5 clinically amyopathic dermatomyositis What Is Your Diagnosis?

Sarcoidosis and/or lymphoma syndrome

Immunoglobulin G4-related disease

Antimelanoma differentiation associated gene 5 clinically amyopathic dermatomyositis

Systemic lupus erythematosus

C. Antimelanoma differentiation associated gene 5 clinically amyopathic dermatomyositis

C

Antimelanoma differentiation associated gene 5 clinically amyopathic dermatomyositis

Histopathology of a biopsy specimen of the patient’s distal digit (Figure, C) revealed orthokeratosis with rare lymphocytes at the dermal/epidermal junction, minimal basal vacuolar change, and pigment incontinence. A diffuse vasculopathy with fibrin thrombi was observed within the deep dermal vessels.Pulmonary function tests showed restrictive disease with decreased diffusing capacity of the lungs for carbon monoxide (33% predicted). Chest CT revealed worsening interstitial lung disease (ILD) (Figure, D). Currently, the patient is being treated with hydroxychloroquine 400 mg/d, prednisone 60 mg/d, mycophenolate mofetil 1 g/d, and aspirin 81 mg/d. Malignancy workup is negative. Recently, the patient developed the heliotrope sign. Antimelanoma differentiation associated gene 5 (anti-MDA5) antibody levels have been sent. Profound T lymphopenia is being evaluated by the hematology and oncology departments but may be dermatomyositis-related.Dermatomyositis is an autoimmune connective tissue disease characterized by chronic inflammation and subsequent destruction of skin and muscle. Patients with clinically amyopathic dermatomyositis (CADM) lack clinical signs of myositis for at least 6 months after cutaneous findings arise. Approximately 19% to 35% of patients with dermatomyositis1-3 have autoantibodies to the melanoma differentiation-associated gene. Many of these patients have CADM. Identification of patients with anti-MDA5 dermatomyositis is important because they are more likely to develop rapidly progressive ILD, which can be fatal. Pulmonary function tests should be performed to identify potential ILD in patients with anti-MDA5 dermatomyositis.4In contrast to ILD associated with classic dermatomyositis, CADM-associated ILD is more acute, aggressive, recalcitrant to treatment, and fatal.3,5,6 In one study, 74% patients who were MDA-5 positive developed rapidly progressive ILD, 33% of whom died within 6 months.7 High-resolution chest CT often reveals ground glass opacities and consolidation in the lower lobes; in contrast, patients who are MDA-5 negative tend to have a predominance of reticular opacities.8 Identification of MDA-5 antibodies may warrant earlier, more aggressive treatment, particularly when other poor prognostic factors for pulmonary outcomes such as elevated anti-MDA antibody titers, T lymphocytopenia, and hyperferritinemia are present.5-7 In limited, small studies,3 it was found that patients with anti-MDA5 dermatomyositis have a lower incidence of internal malignancies compared with those with classical dermatomyositis.The MDA-5 test is not widely available, potentially delaying diagnosis and intervention. Patients with dermatomyositis who are positive for the MDA-5 antibody have a cutaneous phenotype distinct from classic cutaneous signs of dermatomyositis and often present with tender palmar papules (including in the creases), cutaneous ulcerations, diffuse arthralgias, arthritis, hair loss, edematous hands, and oral mucosal pain.3 Palmar papules show vasculopathy on histology with vascular fibrin or perivascular inflammation.3In this patient, respiratory symptoms preceded cutaneous findings of MDA-5−positive dermatomyositis; generally, the opposite is true.9 This patient also presented with normal aldolase and depressed creatine kinase levels; typically, patients who are anti-MDA-5 positive have an elevated aldolase level with normal creatine kinase levels.3 However, both cutaneous and histopathological findings best support a diagnosis of anti-MDA-5 dermatomyositis.Our patient had 2 episodes of antecedent pneumonia, supporting the existing hypothesis that infection may trigger anti-MDA5 dermatomyositis through up-regulation of an immunogenic form of the MDA5 gene.2,3 This gene up-regulates interferon type 1, which has vasculopathic effects, potentially explaining cutaneous ulcers in such patients.3

Dermatology

A 42-year-old African American male presented with a 7-month history of fatigue, exertional dyspnea, arthralgias, hand swelling, tender ulcerations, hair loss, and a 50-pound weight loss. He had been hospitalized 6 months prior for hypoxia. Chest computed tomography (CT) showed hilar lymphadenopathy, interstitial thickening, and perilymphatic ground glass opacities. Bronchoscopy revealed plaquelike lesions, and transbronchial nodal aspiration of mediastinal nodes was negative for carcinomas and/or granulomas. Prednisone was initiated for presumed sarcoidosis. Antineutrophil cytoplasmic antibodies, antinuclear antibodies, angiotensin-converting enzyme, rheumatoid factor, and Aspergillosis antigen were negative and/or normal. The patient was referred for a second opinion.On presentation he had symmetric swelling of metacarpophalangeal joints (MCPs) and interphalangeal joints (IPs), preventing fist formation. Dorsal MCPs had ulcers distal fingers were dyspigmented and atrophic, capillaroscopy was normal, and palmar IP creases had ulcerated lichenoid papules (Figure, A and B). Oxford Scale muscle strength was 5 of 5 throughout. Auscultation revealed bibasilar rales. He had normal aldolase levels (4.5 U/L [to convert to μkat/L, multiply by 0.0167]), depressed creatine kinase (32 U/L), hyperferritinemia (1543 ng/mL), and T lymphocytopenia (absolute CD3, CD4, and CD8 counts, 328 μL, 233 μL, and 85 μL, respectively); the patient also had anti-SSA (Ro) antibodies, and immunoglobulin G anticardiolipin antibodies (19.5 units). The patient tested negative for HIV, anti–Scl-70 antibodies, anti–β2-glycoprotein 1 antibodies, lupus anticoagulant, cryoglobulins, and anti–Mi-2 antibodies; prothrombin time, partial thromboplastin time, and tissue thromboplastin were normal.A, Edematous hands with crusted ulcers and surrounding hyperpigmentation overlying dorsal metacarpophalangeal joints and interphalangeal joints. B, Ulcerating papules with crust located in the palmar creases of the priximal interphalangeal joints and distal interphalangeal joints. C, Histopathology. D, Chest computed tomography.Antimelanoma differentiation associated gene 5 clinically amyopathic dermatomyositis

what is your diagnosis?

What is your diagnosis?

Antimelanoma differentiation associated gene 5 clinically amyopathic dermatomyositis

Immunoglobulin G4-related disease

Systemic lupus erythematosus

Sarcoidosis and/or lymphoma syndrome

a

male

41-50

African American

original

https://jamanetwork.com/journals/jamadermatology/fullarticle/2526258

A man in his 60s presented with a 2-month history of painful, occasionally pruritic, fixed erythema on the abdomen. In addition, the patient suffered from a splenic marginal zone lymphoma with bone marrow infiltration, had a history of splenectomy, and an IgM-κ paraproteinemia. His hematologic condition was considered stable by his physician, who had also been treating the patient for hepatitis C with ledipasvir-sofosbuvir for 3 months. On examination, there was a warm erythema on most of the abdomen, which appeared distended owing to hepatitis-induced ascites (Figure, A). Laboratory results showed an elevated but stable white blood cell count of 19.04 × 103µL (reference range, 3.6-10.5 × 103µL), a recent rise of C-reactive protein levels to 179 mg/L (reference range, 0-5 mg/L), as well as a rise of IgM levels from 1060 mg/dL to 2220 mg/dL (reference range, 34-248 mg/dL) within the past year. A biopsy procedure was performed on the abdomen (Figure, B-D).A, Light red erythema on most of the abdomen. B, Interstitial infiltrate of deeply eosinophilic cells in the entire dermis and adjacent subcutis. Hematoxylin-eosin staining (original magnification ×2). C, Hematoxylin-eosin staining (original magnification ×40). D, Original magnification ×10. What Is Your Diagnosis?

Wells syndrome

Cutaneous amyloidosis

Crystal-storing histiocytosis

Erysipelas

C. Crystal-storing histiocytosis

C

Crystal-storing histiocytosis

The biopsy results showed a diffuse interstitial infiltrate of deeply eosinophilic cells in the entire dermis and the adjacent subcutis (Figure, B). On higher magnification, these cells presented densely packed nonpolarizable intracytoplasmatic crystals (Figure, C). Additionally, there was a sparse perivascular and periadnexal lymphocytic infiltrate with plasma cells. Immunohistochemical analysis demonstrated reactivity of the crystal-laden cells to CD68 (Figure, D) and CD163, confirming their histiocytic nature. The plasma cells were strongly reactive to IgM and showed a monoclonal expression of κ immunoglobulin light chain by in situ hybridization. The crystals were negative for κ and λ, but did show focal reactivity to IgM by immunohistochemical analysis. After treatment with systemic antibiotics and topical steroids the C-reactive protein levels decreased to 36 mg/L (reference 0-5 mg/L), but the skin condition remained unchanged. At that point the patient was referred to a hematologic clinic for further evaluation.Crystal-storing histiocytosis (CSH) is a rare condition characterized by the accumulation of eosinophilic nonpolarizable crystals in histiocytes representing intracytoplasmic immunoglobulins in most cases. It may be localized, affecting only 1 site, most frequently the head and neck region, especially the orbit, followed by the lung, bone marrow, and kidney. The generalized variant implicates different organs, is less frequent, and almost always involves the bone marrow. Occurrence in the skin is uncommon.1,2In most cases CSH is associated with overexpression of monoclonal immunoglobulins owing to a plasma cell or lymphoplasmacytic neoplasm, such as multiple myeloma, lymphoplasmacytic lymphoma, or another B-cell lymphoma, as well as monoclonal gammopathy of undetermined significance. Only rarely occurrence with inflammatory conditions, such as rheumatoid arthritis, pulmonary infections, and Crohn’s disease has been reported. Although the pathogenesis is not entirely elucidated, the accepted concept is that immunoglobulins are phagocytized by macrophages, digested, and put in lysosomal storage in their crystallized form. Investigations with mass spectrometry have suggested that immunoglobulin alterations and/or defects in the ability of histiocytes to process immunoglobulins might play a role.2,3 In the majority of cases a monoclonal immunoglobulin of κ light chain without any preference of a heavy chain type is detected in the serum. The crystals themselves have displayed variable reactivity to κ or λ as well as to IgA, IgM and/or IgG using immunohistochemical analysis. Negative results have also been reported and explained by antigen-masking owing to crystallization or considered an artifact of fixation.2,4,5 Set apart from immunoglobulin induced CSH are exceptional reports where crystals are of nonimmunoglobulin origin. In this group cutaneous lesions were associated with Charchot-Ledyen crystals in hypereosinophilic syndrome and silica crystals following injection of a silica sclerosing agent for hernia repair.1To our knowledge, 7 patients (3 male, 4 female) with primary cutaneous immunoglobulin-associated CSH have been described in the literature, disposing very heterogeneous clinical features. Three cases showed swelling of the periorbital region5-7 with yellow discoloration in 2.6,7 Additional symptoms included swelling of the face,6 the submandibular and parotid region,5 an extended plaque-like swelling with verrucous surface on the anterior chest and adjacent neck,8 and subcutaneous tumors on the cheek, trunk, axilla, and upper arm measuring up to 8 cm in diameter.4,5 One patient had scaly crusted papules on the upper and mid back and displayed features of Grover disease and CSH in the same biopsy.7 This was the only case where pruritus was reported. Three patients had multiple myeloma,6-8 3 lymphoplasmacytic lymphoma,4,5,7 and 1 extranodal marginal zone B-cell lymphoma.2 Our patient showing painful and pruritic erythema on the abdomen and splenic marginal zone lymphoma contributed to the clinical heterogeneity of the cutaneous CSH.Follow-up was reported in 4 of 7 cutaneous CSH cases. During chemotherapy for their hematologic condition, CSH completely resolved in 1 patient,6 while the second patient showed a 50% reduction of lesions.8 Another patient was free of symptoms after treatment with methylprednisolone, 1 g, for 3 consecutive days.5 The patient with coinciding Grover disease showed no cutaneous lesions after 4 weeks using topical emollients.7The prognostic significance of CSH remains unclear, although it has been suggested that generalized CSH is associated with a worse prognosis than is localized.1,3,7 Irrespective of the prognostic implications of CSH, awareness and recognition of the disease are important, as correct diagnosis and treatment may unravel an unknown hematologic malignant disease. In cases where no associated disease can be detected, close follow-up is recommended considering that CSH may occasionally predate the hematologic condition.

Dermatology

A man in his 60s presented with a 2-month history of painful, occasionally pruritic, fixed erythema on the abdomen. In addition, the patient suffered from a splenic marginal zone lymphoma with bone marrow infiltration, had a history of splenectomy, and an IgM-κ paraproteinemia. His hematologic condition was considered stable by his physician, who had also been treating the patient for hepatitis C with ledipasvir-sofosbuvir for 3 months. On examination, there was a warm erythema on most of the abdomen, which appeared distended owing to hepatitis-induced ascites (Figure, A). Laboratory results showed an elevated but stable white blood cell count of 19.04 × 103µL (reference range, 3.6-10.5 × 103µL), a recent rise of C-reactive protein levels to 179 mg/L (reference range, 0-5 mg/L), as well as a rise of IgM levels from 1060 mg/dL to 2220 mg/dL (reference range, 34-248 mg/dL) within the past year. A biopsy procedure was performed on the abdomen (Figure, B-D).A, Light red erythema on most of the abdomen. B, Interstitial infiltrate of deeply eosinophilic cells in the entire dermis and adjacent subcutis. Hematoxylin-eosin staining (original magnification ×2). C, Hematoxylin-eosin staining (original magnification ×40). D, Original magnification ×10.

what is your diagnosis?

What is your diagnosis?

Crystal-storing histiocytosis

Cutaneous amyloidosis

Erysipelas

Wells syndrome

a

male

61-70

White

original

https://jamanetwork.com/journals/jamaneurology/fullarticle/2537552

A man in his 30s presented with a 5-day history of vomiting, followed by lethargy and confusion. Two years prior, he was hospitalized with coma with no identifiable precipitant and an extensive workup done at that time only revealed an elevated ammonia level of 233 µg/dL (to convert to µmol/L, multiply by 0.714); etiology remained unclear but he improved with lactulose. Prior to this admission, he was working in a restaurant, did not ingest any drugs or mushrooms, and had no operations and no family history of similar problems. He was found to have hyperammonemia to 239.5 µg/dL and respiratory alkalosis (pH level, 7.482; partial pressure of carbon dioxide, 27.3 mm Hg, and partial pressure of oxygen, 109 mm Hg [to convert to kPa, multiply by 0.133]; and bicarbonate, 20.2 mEq/L [to convert to mmol/L, multiply by 1]). Liver and kidney function were normal (protein, 6.4 g/dL, and albumin, 3.4 g/dL [to convert to g/L, multiply by 10]; direct bilirubin, 0.1 mg/dL, and indirect bilirubin, 0.8 mg/dL [to convert to µmol/L, multiply by 17.104]; alkaline phosphatase, 38 U/L, aspartate aminotransferase, 22 U/L, and alanine aminotransferase, 42 U/L [to convert to µkat/L, mutiply by 0.0167]). His mental status rapidly declined despite treatment with lactulose, necessitating intubation. Head computed tomography and cerebrospinal fluid analysis were unrevealing. Ammonia levels progressively increased to 1120.5 µg/dL, requiring hemodialysis and sodium phenylbutyrate, which did not lead to significant clinical improvement. On hospital day 6, he developed continuous myoclonus due to status epilepticus (Figure 1A), which was refractory to treatment with lorazepam and levetiracetam as well as continuous midazolam, lorazepam, and propofol infusions. Plasma amino acids and urine organic acids were requested. Continuous venovenous filtration hemodialysis and carnitine treatment were started because of concern for inborn errors of metabolism. Within a few hours of transfer, his ammonia level peaked to 1960 µg/dL and he lost all brainstem activity due to diffuse cerebral edema (Figure 1B).A, Electroencephalography (EEG) showing diffuse polyspike complexes consistent with myoclonic seizures. B, Head computed tomography showing diffuse cerebral edema, obliteration of basal cisterns, and transtentorial and tonsillar herniation. What Is Your Diagnosis?

Reye syndrome

Urea cycle disorder

Fatty acid oxidation disorder

Organic acidemia

B. Urea cycle disorder

B

Urea cycle disorder

In the absence of liver disease, hyperammonemia should trigger a search for nonhepatic causes (Figure 2). It can be caused by medications, surgical procedures, and infections with urease-producing bacteria. Fatty acid oxidation defects, organic acidemias, and urea cycle disorders (UCDs) cause hyperammonemia. Fatty acid oxidation defects are associated with hypoglycemia and ketosis, which were absent in our patient. The lack of significant acidosis excludes organic acidemias. These 2 disorders are rare in adulthood. Ornithine transcarbamylase deficiency (OTCD), a UCD, was considered in our patient as it commonly presents in adulthood. Serum amino acid and urine organic acid testing showed elevated serum glutamine (21.2 mg/dL) and urine orotic acid (28 mmol/mol of creatinine) and low serum citrulline (0.05 mg/dL) and ornithine (0.34 mg/dL). This fulfills the criteria for diagnosis of OTCD.3 In patients with proven OTCD, a pathogenic mutation is detected in only 80% of patients.4 Pathogenic mutation in OTC was detected in codon 81, which had a nucleotide substitution and insertion (c.81T>CT), resulting in amino acid change p.Ser81Pro and frameshift. This is not a previously known pathogenic mutation but is deleterious; a deletion at the same codon site has been reported as pathogenic.4Approach to hyperammonemia. Information derived from studies by LaBuzetta et al1 and Wong et al.2 CPS1 indicates carbamoyl phosphate synthetase 1; GI, gastrointestinal; OTC, ornithine transcarbamylase; TPN, total parenteral nutrition.Urea cycle disorders typically present in the neonatal period with vomiting and lethargy, which can rapidly progress to coma and death. They result from deficiency or absence of any of the following: carbamoyl phosphate synthetase 1, ornithine transcarbamylase, argininosuccinate synthase, argininosuccinate lyase, or N-acetyl glutamate synthase. Partial deficiency may present in adults with acute life-threatening encephalopathy and hyperammonemic crisis leading to refractory elevation of intracranial pressure, status epilepticus, and ultimately death. Plasma amino acid and urine organic acids differentiate among the UCDs (Figure 2). The most common UCD is OTCD. It is X-linked and largely affects males, but heterozygous women may manifest symptoms. Brain magnetic resonance imaging in OTCD can show extensive cortical involvement with the insular and cingulate cortices.5

Neurology

A man in his 30s presented with a 5-day history of vomiting, followed by lethargy and confusion. Two years prior, he was hospitalized with coma with no identifiable precipitant and an extensive workup done at that time only revealed an elevated ammonia level of 233 µg/dL (to convert to µmol/L, multiply by 0.714); etiology remained unclear but he improved with lactulose. Prior to this admission, he was working in a restaurant, did not ingest any drugs or mushrooms, and had no operations and no family history of similar problems. He was found to have hyperammonemia to 239.5 µg/dL and respiratory alkalosis (pH level, 7.482; partial pressure of carbon dioxide, 27.3 mm Hg, and partial pressure of oxygen, 109 mm Hg [to convert to kPa, multiply by 0.133]; and bicarbonate, 20.2 mEq/L [to convert to mmol/L, multiply by 1]). Liver and kidney function were normal (protein, 6.4 g/dL, and albumin, 3.4 g/dL [to convert to g/L, multiply by 10]; direct bilirubin, 0.1 mg/dL, and indirect bilirubin, 0.8 mg/dL [to convert to µmol/L, multiply by 17.104]; alkaline phosphatase, 38 U/L, aspartate aminotransferase, 22 U/L, and alanine aminotransferase, 42 U/L [to convert to µkat/L, mutiply by 0.0167]). His mental status rapidly declined despite treatment with lactulose, necessitating intubation. Head computed tomography and cerebrospinal fluid analysis were unrevealing. Ammonia levels progressively increased to 1120.5 µg/dL, requiring hemodialysis and sodium phenylbutyrate, which did not lead to significant clinical improvement. On hospital day 6, he developed continuous myoclonus due to status epilepticus (Figure 1A), which was refractory to treatment with lorazepam and levetiracetam as well as continuous midazolam, lorazepam, and propofol infusions. Plasma amino acids and urine organic acids were requested. Continuous venovenous filtration hemodialysis and carnitine treatment were started because of concern for inborn errors of metabolism. Within a few hours of transfer, his ammonia level peaked to 1960 µg/dL and he lost all brainstem activity due to diffuse cerebral edema (Figure 1B).A, Electroencephalography (EEG) showing diffuse polyspike complexes consistent with myoclonic seizures. B, Head computed tomography showing diffuse cerebral edema, obliteration of basal cisterns, and transtentorial and tonsillar herniation.

what is your diagnosis?

What is your diagnosis?

Reye syndrome

Fatty acid oxidation disorder

Organic acidemia

Urea cycle disorder

d

male

31-40

original

https://jamanetwork.com/journals/jamapediatrics/fullarticle/2553100

A previously healthy 7-year-old girl presented with fever, sore throat, bilateral conjunctival hemorrhage, periorbital edema, and eyelid ecchymoses (Figure). The illness began 1 week prior with low-grade fever and back pain. The following day, she developed periorbital swelling and subjective high fever. The back pain resolved, but she complained of fatigue, stiffness in her limbs, and sore throat. A rapid antigen detection test from a throat swab was positive for group A Streptococcus, so she was given an “antibiotic shot,” presumably penicillin. She developed a mild cough and had several episodes of vomiting and diarrhea. She presented for reevaluation when she developed eyelid ecchymoses and conjunctival hemorrhage. Four days prior to the onset of illness, she had completed a 10-day course of amoxicillin for acute otitis media.A 7-year-old girl with periorbital edema, ecchymosis, and bilateral conjunctival hemorrhage.A physical examination revealed a febrile patient with bilateral conjunctival hemorrhages, periorbital edema, and eyelid ecchymoses. She had tonsillar hypertrophy with erythema and exudates. Her liver and spleen were mildly enlarged. Laboratory tests showed leukocytosis with a white blood cell count of 16.7 000/μL (to convert to ×109 per liter, multiply by 0.001) with a predominance of lymphocytes, mild thrombocytopenia (platelet count, 108 × 103/μL [to convert to ×109 per liter, multiply by 1.0]), elevated aminotransferases (alanine aminotransferase, 232 U/L [to convert to microkatals per liter, multiply by 0.0167]; aspartate aminotransferase, 261 U/L [to convert to microkatals per liter, multiply by 0.0167]), γ-glutamyltransferase (265 U/L), conjugated bilirubin (2.3 mg/dL [to convert to microkatals per liter, multiply by 0.0167]), and lactate dehydrogenase (2116 U/L [to convert to microkatals per liter, multiply by 0.0167]). A throat culture grew group A Streptococcus. What Is Your Diagnosis?

Streptococcal pharyngitis

Epstein-Barr virus infection

Neuroblastoma

Viral hepatitis

B. Epstein-Barr virus infection

B

Epstein-Barr virus infection

Epstein-Barr virus (EBV) serological results indicated acute EBV infection (viral capsid antigen IgM 1:160, IgG 1:5120). Although the patient had a positive rapid antigen detection test for group A Streptococcus, she received adequate treatment with intramuscular penicillin and continued to have symptoms, suggesting that the positive result represented colonization, not infection. In addition, the patient completed a 10-day course of amoxicillin for otitis media 4 days prior to illness onset. A computed tomographic scan did not reveal neuroblastoma infiltration of the periorbital bones, and this diagnosis often is characterized by unilateral periorbital ecchymosis accompanied by ptosis and proptosis. Viral hepatitis in children does not present with periorbital edema and ecchymosis, and the patient’s hepatitis serological results were consistent with hepatitis B immunization.With supportive care, the patient improved with resolution of fever and periorbital ecchymoses, and minimal periorbital edema at the time of hospital discharge. In outpatient follow-up, signs and symptoms of illness had resolved, and laboratory results were normal.Epstein-Barr virus is a widely disseminated herpesvirus that is spread by intimate contact (eg, saliva or blood). Most infections are subclinical.1 Antibodies to EBV have been found in all age groups with a worldwide distribution; 90% to 95% of adults are seropositive.2For children, acute EBV infection is commonly asymptomatic; however, it can affect many organs in the body.3 For older children and adults, the most common presentation is that of infectious mononucleosis, with fever, sore throat, generalized fatigue, cervical adenopathy, and hepatosplenomegaly.2 For young children, respiratory and gastrointestinal symptoms are common.4,5 Skin manifestations such as maculopapular rash, purpura or ecchymoses from thrombocytopenia, and icterus due to hepatitis or hemolytic anemia occur infrequently.5 Periorbital edema is observed in approximately 15% of children with primary infection4 and usually manifests as transient bilateral upper-eyelid edema in the first few days of illness.6Acute EBV infection can affect almost any segment of the eye, but follicular conjunctivitis is the most common manifestation.7 Less frequently, oculoglandular syndrome, keratitis, optic neuritis, uveitis, and dacryoadenitis can occur.8 Periorbital ecchymosis and conjunctival hemorrhage associated with acute EBV infection have not previously been reported in children. It is reasonable to assume that these signs and symptoms occurred in this patient owing to mild thrombocytopenia temporally associated with vomiting.Most patients with mild illness due to EBV are unlikely to be identified because they do not seek medical attention or because EBV is not considered in the differential diagnosis. Patients with typical EBV infection can be a diagnostic challenge because signs and symptoms are not sensitive or specific.1 The differential diagnosis for primary EBV infection includes disease caused by human immunodeficiency virus, human herpesvirus 6, cytomegalovirus, and Toxoplasma gondii.2A definitive diagnosis of EBV infection can be made by testing for viral capsid antigen (VCA)–specific IgM and IgG, and anti-EBV nuclear antigen antibodies.2 Anti-VCA IgM antibodies often are detected at the time of presentation and disappear within 4 to 8 weeks. Anti-VCA IgG antibodies are detectable in high titer during early onset of infection and persist at reduced levels throughout life. Anti-EBV nuclear antigen antibodies indicate past infection and appear weeks to months after onset of illness. Polymerase chain reaction is used for the detection of EBV in tissues and fluids in immunocompromised children or those with complicated illnesses, but it is not recommended for the evaluation of immunocompetent patients.Management of EBV infection is supportive. There is insufficient evidence of a clinically relevant benefit to recommend standard corticosteroid treatment for severe pharyngitis.2 Corticosteroids may be considered for patients with upper airway obstruction, meningoencephalitis, thrombocytopenia, or hemolytic anemia.2,3 A number of antiviral drugs have in vitro activity against EBV, but none have yet shown significant clinical efficacy, and therefore they are not currently recommended for treatment.1,2

Pediatrics

A previously healthy 7-year-old girl presented with fever, sore throat, bilateral conjunctival hemorrhage, periorbital edema, and eyelid ecchymoses (Figure). The illness began 1 week prior with low-grade fever and back pain. The following day, she developed periorbital swelling and subjective high fever. The back pain resolved, but she complained of fatigue, stiffness in her limbs, and sore throat. A rapid antigen detection test from a throat swab was positive for group A Streptococcus, so she was given an “antibiotic shot,” presumably penicillin. She developed a mild cough and had several episodes of vomiting and diarrhea. She presented for reevaluation when she developed eyelid ecchymoses and conjunctival hemorrhage. Four days prior to the onset of illness, she had completed a 10-day course of amoxicillin for acute otitis media.A 7-year-old girl with periorbital edema, ecchymosis, and bilateral conjunctival hemorrhage.A physical examination revealed a febrile patient with bilateral conjunctival hemorrhages, periorbital edema, and eyelid ecchymoses. She had tonsillar hypertrophy with erythema and exudates. Her liver and spleen were mildly enlarged. Laboratory tests showed leukocytosis with a white blood cell count of 16.7 000/μL (to convert to ×109 per liter, multiply by 0.001) with a predominance of lymphocytes, mild thrombocytopenia (platelet count, 108 × 103/μL [to convert to ×109 per liter, multiply by 1.0]), elevated aminotransferases (alanine aminotransferase, 232 U/L [to convert to microkatals per liter, multiply by 0.0167]; aspartate aminotransferase, 261 U/L [to convert to microkatals per liter, multiply by 0.0167]), γ-glutamyltransferase (265 U/L), conjugated bilirubin (2.3 mg/dL [to convert to microkatals per liter, multiply by 0.0167]), and lactate dehydrogenase (2116 U/L [to convert to microkatals per liter, multiply by 0.0167]). A throat culture grew group A Streptococcus.

what is your diagnosis?

What is your diagnosis?

Streptococcal pharyngitis

Epstein-Barr virus infection

Neuroblastoma

Viral hepatitis

b

female

0-10

White

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2542662

A man in his early 40s was referred for surgical evaluation following abnormal imaging obtained during workup of recent left-sided chest discomfort and longstanding dyspnea on exertion. A large air-fluid level was seen on a recent chest roentgenogram, and subsequent computed tomographic scans of his chest were obtained (Figure 1). The only medical history reported was a previous umbilical hernia repair. On further discussion, it was discovered that he was involved in a motorcycle crash many years ago. Other than a brief loss of consciousness, no significant injuries were sustained per the patient’s report. He did undergo a formal trauma evaluation at that time; however, the radiographic images and medical records were no longer available. In addition to complaints of dyspnea and chest discomfort, the patient reported 5 to 6 episodes of small-volume emesis over the last 6 months. He denied any other gastrointestinal symptoms, such as heartburn, dyspnea, or constipation. The results of his examination were unremarkable, with the exception of bowel sounds being heard on auscultation of the left chest. What Is Your Diagnosis?

Type IV hiatal hernia

Congenital diaphragmatic hernia

Blunt traumatic rupture of the diaphragm

Diaphragm eventration

C. Blunt traumatic rupture of the diaphragm

C

Blunt traumatic rupture of the diaphragm

This patient’s presentation was consistent with a diaphragmatic hernia or some other diaphragm disorder. The representative computed tomographic images reveal multiple abdominal viscera (stomach, small bowel, colon, spleen, and pancreas) herniated into the left chest with near-complete left-lung atelectasis (Figure 1A). Differential diagnoses included type IV hiatal hernia, congenital diaphragmatic hernia, diaphragm eventration, diaphragm paralysis, and blunt traumatic rupture of the diaphragm with delayed diagnosis. Complaints of dyspnea are common with each of these disorders owing to the intrathoracic displacement of abdominal contents with resulting restricted lung volumes. Chest radiography demonstrating air-fluid levels above the expected level of the diaphragm is also suggestive of any of these diagnoses. A detailed history and additional imaging are therefore required to determine the correct diagnosis.Computed tomography with reformatted, multiplanar images is currently the diagnostic modality of choice to detect and localize diaphragmatic defects.1,2 In this case, the selected images reveal a central left-diaphragm defect (Figure 1B), which was confirmed intraoperatively (Figure 2). Congenital diaphragmatic hernias are uncommon in adults and are found in distinctly different locations.3 Morgagni hernias result from anterior defects, typically to the right of the midline. Bochdalek hernias result from posterior diaphragmatic defects, most commonly on the left in adults. Type IV hiatal hernias can also present with impressive herniation of multiple viscera. However, herniation through a widened esophageal hiatus and upper gastrointestinal complaints are typically observed. The diaphragm is elevated but intact in cases of eventration and diaphragm paralysis.Laparoscopy of left diaphragm defect after reduction of bowel, with stomach and spleen not yet fully reduced.Acute blunt traumatic rupture of the diaphragm occurs in roughly 5% of blunt traumas, the majority resulting from motor vehicle crashes.4 This diagnosis can be challenging, particularly in cases of right-sided injury, conservatively managed blunt trauma, and multiple traumas with other life-threatening injuries.1,2 Imaging technique, clinicians’ awareness of the possibility for occult diaphragm injury, and extent to which suspicion of injury is investigated affect the odds of correctly diagnosing blunt traumatic rupture of the diaphragm. Approximately 15% of cases are diagnosed in a delayed fashion, sometimes years after injury.5,6 Therefore, a history of thoracoabdominal trauma, regardless of how trivial, should raise suspicion of a late-presenting blunt traumatic rupture of the diaphragm. Larger defects are more likely to cause respiratory compromise owing to herniation of multiple viscera, whereas obstructive symptoms resulting from incarcerated bowel are more likely with smaller defects.7In this case, herniated contents were reduced laparoscopically. A left-sided minithoracotomy was necessary to maintain reduction of abdominal viscera while primary repair with pledgetted, nonabsorbable suture was performed. The patient was discharged home on postoperative day 6 with a chest tube for drainage of a persistent pleural effusion. The tube was removed in the clinic 1 week later. Recovery was otherwise uncomplicated. The patient reported resolution of symptoms and improved exercise capacity at long-term follow-up.

Surgery

A man in his early 40s was referred for surgical evaluation following abnormal imaging obtained during workup of recent left-sided chest discomfort and longstanding dyspnea on exertion. A large air-fluid level was seen on a recent chest roentgenogram, and subsequent computed tomographic scans of his chest were obtained (Figure 1). The only medical history reported was a previous umbilical hernia repair. On further discussion, it was discovered that he was involved in a motorcycle crash many years ago. Other than a brief loss of consciousness, no significant injuries were sustained per the patient’s report. He did undergo a formal trauma evaluation at that time; however, the radiographic images and medical records were no longer available. In addition to complaints of dyspnea and chest discomfort, the patient reported 5 to 6 episodes of small-volume emesis over the last 6 months. He denied any other gastrointestinal symptoms, such as heartburn, dyspnea, or constipation. The results of his examination were unremarkable, with the exception of bowel sounds being heard on auscultation of the left chest.

what is your diagnosis?

What is your diagnosis?

Type IV hiatal hernia

Diaphragm eventration

Blunt traumatic rupture of the diaphragm

Congenital diaphragmatic hernia

c

male

41-50

original

https://jamanetwork.com/journals/jamasurgery/fullarticle/2544829

A 61-year-old man presented with a progressive shortness of breath for 1 week. He was diagnosed with myocardial infarction 1 month earlier at another hospital and a coronary intervention was performed with 1 drug-eluted stent put in the left anterior descending artery. Progressive dyspnea at rest was noted in recent days. Review of systems and family history were unremarkable. Physical examination revealed tachycardia and tachypnea. His heart rate was 138 beats/min and respiratory rate, 25 breaths/min. Blood pressure was 92/58 mm Hg. Chest auscultation revealed bilateral rales. Heartbeat was regular, but with faint S1 and S2. The extremities were cold, while no pitting edema was found. Laboratory findings were within normal limits. Twelve-lead electrocardiography demonstrated persistent ST-T segment elevation in V2 to V6 leads. Transthoracic echocardiography showed a hypoechoic mass around the apical region (Figure 1A). Computed tomography of the chest revealed a large crescentic hypodense lesion surrounding the anterolateral wall of the left ventricle and apex (Figure 1B).A, Transthoracic echocardiography, apical 4-chamber view, showing a hypoechoic mass (arrowhead). LA indicates left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. B, Computed tomography of the chest, axial view, showing a hypodense lesion surrounding the anterolateral wall of the left ventricle and apex (arrowhead). What Is Your Diagnosis?

Pseudoaneurysm due to free wall rupture

Apical aneurysm with thrombus formation

Postinfarction hemorrhagic pericarditis

Intramural hematoma

D. Intramural hematoma

D

Intramural hematoma

The patient later underwent explorative sternotomy, and no pericardial hematoma was found. The anterolateral wall of the left ventricular myocardium was replaced by a thick transmural hematoma with extensive necrosis (Figure 2). There was no mural thrombus inside the left ventricle cavity. Diagnostic coronary angiography performed before the operation demonstrated that the stent at the proximal site of the left anterior descending artery was patent. However, the downstream blood flow was very poor, reflecting extensive transmural infarction of the left ventricle myocardium. Such a large territory of necrosis might be related to delayed reperfusion or reperfusion injury after coronary intervention. Because of the large area of transmural necrosis of the left ventricle with poor cardiac output, end-stage ischemic cardiomyopathy was diagnosed. The patient was put on the transplant waiting list. He died several days later.The anterolateral wall of the left ventricle myocardium was replaced by a thick transmural hematoma with extensive necrosis (arrowheads).Intramyocardial hemorrhage is a rare but known complication following myocardial infarction, coronary intervention, or ventriculography.1,2 The diagnosis is typically made by echocardiography and magnetic resonance imaging.3 The hemorrhage demonstrates well-demarcated bright signal under T1-weighted magnetic resonance imaging.4 However, with transmural hemorrhagic necrosis, the border of the epicardium or endocardium is absent. Differentiation among pericardial hematoma, intramyocardial hemorrhage, or intracavity thrombus by noninvasive imaging is challenging. Sometimes the correct diagnosis cannot be made without explorative operation. Nevertheless, it is important to be aware of the possibility of intramyocardial hemorrhage. Surgical removal of pericardial hematoma with chamber compression has low operative risks and a good outcome.5 In contrast, evacuation of intramyocardial hemorrhage will result in a large defect of the myocardium and may not have better efficacy than medical treatment.

Surgery

A 61-year-old man presented with a progressive shortness of breath for 1 week. He was diagnosed with myocardial infarction 1 month earlier at another hospital and a coronary intervention was performed with 1 drug-eluted stent put in the left anterior descending artery. Progressive dyspnea at rest was noted in recent days. Review of systems and family history were unremarkable. Physical examination revealed tachycardia and tachypnea. His heart rate was 138 beats/min and respiratory rate, 25 breaths/min. Blood pressure was 92/58 mm Hg. Chest auscultation revealed bilateral rales. Heartbeat was regular, but with faint S1 and S2. The extremities were cold, while no pitting edema was found. Laboratory findings were within normal limits. Twelve-lead electrocardiography demonstrated persistent ST-T segment elevation in V2 to V6 leads. Transthoracic echocardiography showed a hypoechoic mass around the apical region (Figure 1A). Computed tomography of the chest revealed a large crescentic hypodense lesion surrounding the anterolateral wall of the left ventricle and apex (Figure 1B).A, Transthoracic echocardiography, apical 4-chamber view, showing a hypoechoic mass (arrowhead). LA indicates left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. B, Computed tomography of the chest, axial view, showing a hypodense lesion surrounding the anterolateral wall of the left ventricle and apex (arrowhead).

what is your diagnosis?

What is your diagnosis?

Intramural hematoma

Pseudoaneurysm due to free wall rupture

Apical aneurysm with thrombus formation

Postinfarction hemorrhagic pericarditis

a

male

61-70

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2535220

A teenaged boy awakened 2 days prior to presentation with a few skin lesions, which rapidly spread to the rest of his right eyelids (Figure 1). The rash caused a burning sensation; otherwise, he was feeling well. He was not taking any regular medication. His visual acuity was 20/20 OU. Examination revealed clusters of target lesions on the right upper and lower eyelids. There were papillae in the upper palpebral conjunctiva and follicles and a few pustules in the lower palpebral conjunctiva. The cornea was unremarkable with no staining, and results of a dilated ophthalmoscopy examination were normal. Ocular movements were full, and there was no proptosis. A few solitary lesions were found scattered on his nose and right cheek; however, his body was not affected. He had a tender right submandibular lymphadenopathy but was apyrexial.A healthy teenaged boy presented with multiple target lesions and erythema on his right eyelids. What Would You Do Next?

Observe

Prescribe oral flucloxacillin

Prescribe oral aciclovir

Prescribe oral cimetidine

Human herpesvirus 1, or Herpes simplex virus type 1 infection (HHV-1)

C

Prescribe oral aciclovir

This teenaged boy presented with periocular target lesions. The abrupt eruption suggested a hypersensitivity reaction.1 An infection was likely the cause, given the prodromal symptoms and submandibular lymphadenopathy with conjunctivitis. Herpes simplex virus is the most commonly identified etiology, accounting for more than half of adult patients.2 In children, Mycoplasma pneumonia and fungal infection are more frequent.3 The lesions on this patient were not waxy papules or umbilicated, which would have suggested Molluscum contagiosum virus.Early treatment with aciclovir has been demonstrated to lessen and reduce the duration of skin lesions.4 The patient took 200 mg of oral aciclovir 5 times daily and guttae chloramphenicol 4 times daily for a week. A week later, the lesions had scabbed over (Figure 2) and the conjunctivitis had resolved. The eye was quiet, and there was no corneal involvement. The scabs started to shed in the second week. He felt well, and the lymphadenopathy had resolved.Scabs formed in place of the previous target lesions, and the conjunctival papillae and follicles resolved 9 days after the lesions first erupted.After using polymerase chain reaction, we detected HHV-1 from swabs of the lesions. The result of the bacterial swab was normal, as were the results of the blood tests.The eyelid lesions caused by HHV-1 are consistent with a delayed-type hypersensitivity reaction.2 The herpetic DNA fragments are transported to the skin sites by peripheral blood mononuclear cells and expressed on keratinocytes. This leads to the recruitment of HHV-1–specific CD4+ helper T cells, which respond to the viral antigens by producing interferon-γ. The latter upregulates cytokines and chemokines that amplify an acute cutaneous inflammatory cascade.2Primary HHV-1 infection usually presents in the unilateral facial area supplied by the maxillary division of the trigeminal nerve.5 The findings for this patient of greater upper papillary and lower follicular reactions on the palpebral conjunctivae also corresponded with a published report.6 It is important to check for corneal involvement; as many as 17% of patients with HHV-1 can be affected.6Herpes simplex virus remains latent within the trigeminal ganglion after its initial infection, and one of the main issues is that a quarter of patients can have a recurrence after the primary disease, of which up to 50% occur within 2 years.7 Topical aciclovir applied to the skin lesions does not appear to prevent herpes-associated multiforme lesions.8 However, 400 mg of acyclovir twice daily has been shown to be effective in the reduction of recurrent disease.9 Other options include 500 mg to 1 g of valaciclovir per day or 125 to 250 mg of famciclovir per day, which offer greater oral bioavailability than aciclovir and can be used in patients who do not respond to aciclovir.10 The antiviral dose may be tapered once the patient is free of recurrence for 4 months and eventually stopped.In summary, HHV-1 eyelid infections can present with various lesion types and severity, such as in this otherwise healthy teenaged boy. Early antiviral treatment should be commenced to reduce the duration of the cutaneous disease.After a week, the conjunctival follicles settled and the target lesions began to scab over. These lesions completely resolved at 1 month.

Ophthalmology

A teenaged boy awakened 2 days prior to presentation with a few skin lesions, which rapidly spread to the rest of his right eyelids (Figure 1). The rash caused a burning sensation; otherwise, he was feeling well. He was not taking any regular medication. His visual acuity was 20/20 OU. Examination revealed clusters of target lesions on the right upper and lower eyelids. There were papillae in the upper palpebral conjunctiva and follicles and a few pustules in the lower palpebral conjunctiva. The cornea was unremarkable with no staining, and results of a dilated ophthalmoscopy examination were normal. Ocular movements were full, and there was no proptosis. A few solitary lesions were found scattered on his nose and right cheek; however, his body was not affected. He had a tender right submandibular lymphadenopathy but was apyrexial.A healthy teenaged boy presented with multiple target lesions and erythema on his right eyelids.

what would you do next?

What would you do next?

Prescribe oral aciclovir

Prescribe oral cimetidine

Observe

Prescribe oral flucloxacillin

a

male

11-20

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2540511

A 7-year-old boy with a history of Klinefelter syndrome presented to the pediatric glaucoma service with a 4-year history of intense intermittent photophobia. During the office evaluation, the patient had an uncorrected visual acuity of 20/30 OD and 20/25 OS but was extremely photophobic and would not cooperate with any additional examination. An examination under anesthesia was performed. Intraocular pressures by Tono-Pen XL (Reichert) under light sedation were 13 mm Hg OD and 12 mm Hg OS. Axial lengths by echography were 23.7 mm OD and 23.9 mm OS. Retinoscopy showed bright reflexes in both eyes. Anterior segment examination of each eye showed normal eyelids and lashes, conjunctiva, anterior chamber, iris, and lens. The examination of the cornea of each eye was significant for punctate keratitis in the epithelial and subepithelial layers that stained lightly with fluorescein (Figure). The corneal diameters were normal, and there was no evidence of Haab striae or stromal scarring. The ophthalmoscopic examination was unremarkable.RetCam photograph demonstrating punctate keratitis in the epithelial and subepithelial layers of the cornea. What Would You Do Next?

Schedule an electroretinogram

Perform corneal cultures

Start topical steroids and cyclosporine A eyedrops

Observe

Thygeson superficial punctate keratitis

C

Start topical steroids and cyclosporine A eyedrops

Klinefelter syndrome is a genetic disorder characterized by an extra X chromosome in males. Affected males have lower testosterone production, which might have a noticeable effect on appearance (eg, small testicles, reduced muscle mass, reduced body and facial hair, and enlarged breast tissue), as well as learning and behavioral disorders. While there are no known associations between Thygeson superficial punctate keratitis (TSPK) and Klinefelter syndrome, this patient’s presentation was confounded by mild developmental delay, hyperactivity, and behavioral problems associated with Klinefelter syndrome.1 The intermittent, chronic, severe photophobia out of proportion to cursory clinical examination along with poor cooperation from the child can occasionally lead the physician to attribute the findings to nonorganic causes and miss the diagnosis.Thygeson superficial punctate keratitis was first reported by Phillips Thygeson, MD, in 1950, who described a chronic, bilateral, punctate epithelial keratitis characterized by remissions and exacerbations.2 Patients with TSPK often present with bilateral tearing, photophobia, foreign body sensation, irritation, and occasional blurring of vision during exacerbations. It affects patients of all ages, with no predilection for sex or race/ethnicity.3,4 When the disease is active, slitlamp examination reveals an oval or round conglomerate of coarse, granular, slightly elevated, white-to-gray dots in the central cornea that stain minimally with fluorescein, with little or no hyperemia of the conjunctiva. When inactive, the lesions can disappear or persist as subepithelial opacities that do not stain.4,5 The time course of exacerbations and remissions is highly variable, with the average duration ranging from 3 to 7.5 years,2,3,5 although atypical cases with durations of more than 40 years have been reported.6The pathophysiology of TSPK remains unclear, although viral and immunologic components have been implicated.5,7 However, most viral cultures, electron microscopy studies, and polymerase chain reaction analyses have shown no evidence of viral DNA.7 Thygeson superficial punctate keratitis has also been associated with HLA-DR3, suggesting an altered immune response as a cause for the chronic course of exacerbations and remissions of the disease.5Many therapies for TSPK have been tried in the past with unsuccessful outcomes. Antibiotics and antivirals have been shown to be ineffective.7,8 Topical lubricants help alleviate clinical symptoms but do not hasten resolution of the acute episode. Therapeutic extended-wear soft contact lenses provide an alternative treatment, but they may expose the patient to the potential complications of contact lens wear. Currently, topical low-dose corticosteroids are considered the mainstream treatment.2,8 However, chronic dependence can lead to steroid-associated adverse effects, such as cataract and glaucoma. Recent studies9 have reported good outcomes with the use of cyclosporine A as an adjuvant first-line treatment. Patients may start receiving both medications simultaneously, with subsequent steroid taper as symptoms are controlled. Continued treatment with cyclosporine A will protect patients from recurrences, with the benefit of fewer adverse effects compared with corticosteroids.9,10 In the absence of nystagmus or abnormalities on dilated fundus examination, an electroretinogram would most likely be nonrevealing. Corneal cultures are indicated in cases of corneal ulceration or discharge, neither of which were present in this patient. Because of the recurrent nature of the symptomatic photophobia, observation would not be an appropriate management for this patient.In summary, TSPK is an uncommon chronic condition that could be potentially underrecognized. Most patients can be successfully managed with a low-dose topical steroids and cyclosporine A, with an excellent long-term visual prognosis.After initiating steroid and cyclosporine A therapy, this patient’s photophobia significantly improved. He was instructed to taper the steroid over the course of 1 month and to continue cyclosporine for 6 months. After 6 months of cyclosporine therapy, the patient denies photophobia, and his corneas remain clear.

Ophthalmology

A 7-year-old boy with a history of Klinefelter syndrome presented to the pediatric glaucoma service with a 4-year history of intense intermittent photophobia. During the office evaluation, the patient had an uncorrected visual acuity of 20/30 OD and 20/25 OS but was extremely photophobic and would not cooperate with any additional examination. An examination under anesthesia was performed. Intraocular pressures by Tono-Pen XL (Reichert) under light sedation were 13 mm Hg OD and 12 mm Hg OS. Axial lengths by echography were 23.7 mm OD and 23.9 mm OS. Retinoscopy showed bright reflexes in both eyes. Anterior segment examination of each eye showed normal eyelids and lashes, conjunctiva, anterior chamber, iris, and lens. The examination of the cornea of each eye was significant for punctate keratitis in the epithelial and subepithelial layers that stained lightly with fluorescein (Figure). The corneal diameters were normal, and there was no evidence of Haab striae or stromal scarring. The ophthalmoscopic examination was unremarkable.RetCam photograph demonstrating punctate keratitis in the epithelial and subepithelial layers of the cornea.

what would you do next?

What would you do next?

Schedule an electroretinogram

Start topical steroids and cyclosporine A eyedrops

Perform corneal cultures

Observe

b

male

0-10

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2542213

A woman in her 30s presented 2 weeks after cesarean delivery complaining of bilateral blurred vision, photophobia, headache, and nausea. Her postoperative course had initially been complicated by the development of a transverse sinus thrombosis on postoperative day 4, for which she was treated with anticoagulation.Over the next several days, she experienced marked worsening of her headaches, nausea, and blurred vision. She also noticed subjective fevers, weakness, and spasticity in her left upper and lower limbs, along with right ear pain and decreased hearing. Repeated magnetic resonance imaging and venography of the head and neck demonstrated worsening of the cerebral venous sinus thrombosis, now extending into the right sigmoid sinus and jugular vein. Additionally, opacification of the mastoid air cells on the right side was noted, consistent with mastoiditis. Physical examination revealed otitis media on the right side.Ophthalmologic examination showed a visual acuity of 20/30 OD and 20/20 OS; color plates were 8 of 8 bilaterally, and there was no afferent pupillary defect. Motility and confrontational visual fields were without abnormality. Dilated fundus examination showed edema of the optic nerves bilaterally. Spectralis MultiColor fundus images were obtained (Figure, A), as well as traditional spectral-domain optical coherence tomography images (Figure, B).Optical coherence tomography (OCT) of the patient’s optic nerves prior to lumbar puncture. Continue anticoagulation and monitor closely in an outpatient clinical settingContinue anticoagulation, prescribe oral antibiotics, and monitor closely in an outpatient clinical setting What Would You Do Next?

Continue anticoagulation and monitor closely in an outpatient clinical setting

Continue anticoagulation, prescribe oral antibiotics, and monitor closely in an outpatient clinical setting

Perform an immediate lumbar puncture

Perform an urgent radical mastoidectomy

Lateral venous sinus thrombosis

C

Perform an immediate lumbar puncture

Dural sinus thrombosis may result in grossly elevated intracranial pressure. In the setting of bilateral papilledema, headaches, and nausea, it is important to quantify the elevation of intracranial pressure to aid in determining whether to continue medical therapy or to move to surgical intervention. Lumbar punctures also may be therapeutic on a temporary basis until decisions can be made about a more permanent cerebrospinal fluid diversion procedure.Ipsilateral mastoiditis suggests that the patient may be developing a septic venous sinus thrombosis, requiring aggressive intravenous antibiotic therapy (oral antibiotics are insufficient), as well as anticoagulation and intracranial pressure–lowering surgery. Outpatient observation is inappropriate because often these individuals are very systemically ill and require close monitoring. If the patient fails to defervesce within 24 hours, urgent radical mastoidectomy should be considered; however, this is not a first-line treatment.Cerebral venous thromboses (CVTs) are characterized by elevated intracranial pressure, focal neurological deficits, seizures, and encephalopathy.1 Neuro-ophthalmologic manifestations may include papilledema (with retinal nerve fiber layer edema), visual field defects, decreased central visual acuity, and diplopia.2Septic lateral sinus thrombosis is a condition associated with mastoiditis and causes a clinical presentation of classic CVT with a systemic inflammatory response syndrome, including fever, tachycardia, tachypnea, and/or leukocytosis.3 Diagnosis requires imaging, most often magnetic resonance imaging and venography.Treatment of CVT begins with anticoagulation to prevent propagation of clots and to allow recanalization of thrombosed vessels. In otogenic septic lateral sinus thrombosis, control of the infection and antibiotics are critical to early treatment.4 In the antibiotic era, death due to septic lateral sinus thrombosis is rare; however, neurologic sequelae can result. Elevated intracranial pressure from CVT can be treated medically, with cerebrospinal fluid shunting, or in severe cases with decompressive craniectomy.5Severe papilledema occurs with CVT secondary to substantially elevated intracranial pressure. Elevated intracranial pressure can result in permanent optic nerve dysfunction if left untreated, so the ophthalmologist must work closely with the neurosurgical team to guide the timing of intervention. Some authors have published good results for visual recovery following optic nerve sheath fenestrations.6,7Using the different depths of penetration due to the different wavelengths of blue, red, and green light, multicolor optical coherence tomography is a new technology for evaluation of the fundus and optic disc by providing topographic maps of the inner, mid, and deep retinal layers. Subtle changes in nerve head architecture may be seen that are not at all visible with fundus examination or photography with monochromatic light, and may be a useful tool in monitoring response to therapies.A lumbar puncture revealed an opening pressure of 430 mm of water with an otherwise normal fluid analysis. During the lumbar puncture, a lumbar drain was placed. The patient’s symptoms improved for 2 days. The lumbar drain was then clamped, and symptoms quickly returned. Mechanical cerebrospinal fluid diversion dependence prompted neurosurgery to implant a permanent ventriculoperitoneal shunt, which was tolerated well.Oral anticoagulation was continued and the patient was treated with intravenous vancomycin and ciprofloxacin for mastoiditis, because of the concern for septic lateral sinus thrombosis. Otolaryngology was consulted and performed a myringotomy.The patient’s visual symptoms improved and she had an uneventful postoperative course. She was discharged home with a prescription of oral anticoagulation and has had no return of symptoms.

Ophthalmology

A woman in her 30s presented 2 weeks after cesarean delivery complaining of bilateral blurred vision, photophobia, headache, and nausea. Her postoperative course had initially been complicated by the development of a transverse sinus thrombosis on postoperative day 4, for which she was treated with anticoagulation.Over the next several days, she experienced marked worsening of her headaches, nausea, and blurred vision. She also noticed subjective fevers, weakness, and spasticity in her left upper and lower limbs, along with right ear pain and decreased hearing. Repeated magnetic resonance imaging and venography of the head and neck demonstrated worsening of the cerebral venous sinus thrombosis, now extending into the right sigmoid sinus and jugular vein. Additionally, opacification of the mastoid air cells on the right side was noted, consistent with mastoiditis. Physical examination revealed otitis media on the right side.Ophthalmologic examination showed a visual acuity of 20/30 OD and 20/20 OS; color plates were 8 of 8 bilaterally, and there was no afferent pupillary defect. Motility and confrontational visual fields were without abnormality. Dilated fundus examination showed edema of the optic nerves bilaterally. Spectralis MultiColor fundus images were obtained (Figure, A), as well as traditional spectral-domain optical coherence tomography images (Figure, B).Optical coherence tomography (OCT) of the patient’s optic nerves prior to lumbar puncture. Continue anticoagulation and monitor closely in an outpatient clinical settingContinue anticoagulation, prescribe oral antibiotics, and monitor closely in an outpatient clinical setting

what would you do next?

What would you do next?

Perform an immediate lumbar puncture

Continue anticoagulation, prescribe oral antibiotics, and monitor closely in an outpatient clinical setting

Continue anticoagulation and monitor closely in an outpatient clinical setting

Perform an urgent radical mastoidectomy

a

female

31-40

original

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2543474

A man aged 51 years was admitted to the internal medicine service with a recent history of left-sided hemibody paresthesia, dysphagia, and ataxia. He also reported a single episode of binocular diplopia that lasted for 1 day and resolved spontaneously. Otherwise, his medical history was unremarkable.On physical examination, there was mild right-sided ptosis and miosis. Pain and temperature sensation were not evaluated. After instilling 10% topical cocaine eyedrops, the right pupil did not change its size whereas the left pupil dilated by 2 mm, supporting a diagnosis of right-sided Horner syndrome. With the exception of delayed initiation of saccades, extraocular motility was full, and there was no nystagmus.Perform a lumbar puncture and measure opening pressure and cerebrospinal fluid compositionOrder magnetic resonance imaging and magnetic resonance angiography of the brain and cervical spinePerform an apraclonidine test to confirm diagnosis of Horner syndromeOrder tests for erythrocyte sedimentation rate, C-reactive protein level, and syphilis serologies What Would You Do Next?

Perform a lumbar puncture and measure opening pressure and cerebrospinal fluid composition

Order magnetic resonance imaging and magnetic resonance angiography of the brain and cervical spine

Perform an apraclonidine test to confirm diagnosis of Horner syndrome

Order tests for erythrocyte sedimentation rate, C-reactive protein level, and syphilis serologies

Lateral medullary syndrome

B

Order magnetic resonance imaging and magnetic resonance angiography of the brain and cervical spine

B. Order magnetic resonance imaging and magnetic resonance angiography of the brain and cervical spineThe patient’s multiple neurologic symptoms prompted urgent imaging of the brain and were likely localized to the brainstem. In all patients with Horner syndrome, angiography imaging of the neck (computed tomography angiography or magnetic resonance angiography) should also be performed to fully evaluate the sympathetic chain and to specifically rule out a carotid artery dissection. Apraclonidine testing is not used in the setting of acute Horner syndrome, as the adrenergic denervation hypersensitivity can take a few weeks to develop. Lumbar puncture and serologic testing could be indicated in subsequent workup, but they should be performed after neuroimaging.Brain magnetic resonance imaging demonstrated restricted diffusion within the right medulla consistent with the recent (10 days or less) infarct (Figure). There was a flow void within the posterior inferior cerebellar artery, which likely represented a thrombus or an embolus within this vessel.A, Apparent diffusion coefficient map demonstrates abnormal diffusion restriction within the right medulla (arrowhead), consistent with an acute infarct. B, Diffusion-weighted imaging sequence on magnetic resonance imaging shows high signal within the right medulla (arrowheads). Wallenberg syndrome, the eponym for lateral medullary syndrome, arises from the infarction of the lateral medulla and is usually secondary to atherothrombosis, embolism originating from the heart, or arterial dissection.1 Atherosclerosis is more likely to be found in older patients with vascular risk factors, arterial dissection is more common in younger patients and can either be spontaneous or associated with trauma, and embolism should be contemplated in patients with valvular disease or arrhythmias.2,3Wallenberg syndrome is usually caused by the compromise of the ipsilateral vertebral artery and, occasionally, the posterior inferior cerebellar artery.3 The syndrome is characterized by impaired pain and temperature sensation of the ipsilateral face and contralateral trunk and limbs, ipsilateral central Horner syndrome, and ipsilateral ataxia, dysarthria, and dysphagia.2,3 Crossed hemisensory disturbances are reported in 90% of cases in large case series, making this finding highly sensitive.1,4,5 Patients often complain of vertigo and sensations of environmental tilt; they will report that the room is tilted upside down or to the side.3 Another common symptom is lateropulsion of the body and of the oculomotor system; patients will describe a sensation of being pulled toward the side of the lesion, and when asked to fixate straight ahead, eyes will move toward the side of the lesion.2,3 Nystagmus can be part of the syndrome and can be horizontal, torsional, or both. Ocular tilt reaction, skew deviation, abnormal smooth pursuits, and saccades are also often present.2,3While most patients with Wallenberg syndrome will present to an emergency department rather than the ophthalmologist’s office, ocular symptoms can be dominant, and thus, ophthalmologists should be familiar with this condition. Prompt recognition of the lateral medullary infarction is of utmost importance, as treatment options are time sensitive. This syndrome is usually associated with a good prognosis, with most patients recovering with minimal sequelae at 6 months.1,6The patient was referred to a stroke prevention clinic and received anticoagulation. His left-sided hemibody paresthesia, dysphagia, and ataxia progressively improved during his admission. No further episodes of diplopia developed.

Ophthalmology

A man aged 51 years was admitted to the internal medicine service with a recent history of left-sided hemibody paresthesia, dysphagia, and ataxia. He also reported a single episode of binocular diplopia that lasted for 1 day and resolved spontaneously. Otherwise, his medical history was unremarkable.On physical examination, there was mild right-sided ptosis and miosis. Pain and temperature sensation were not evaluated. After instilling 10% topical cocaine eyedrops, the right pupil did not change its size whereas the left pupil dilated by 2 mm, supporting a diagnosis of right-sided Horner syndrome. With the exception of delayed initiation of saccades, extraocular motility was full, and there was no nystagmus.Perform a lumbar puncture and measure opening pressure and cerebrospinal fluid compositionOrder magnetic resonance imaging and magnetic resonance angiography of the brain and cervical spinePerform an apraclonidine test to confirm diagnosis of Horner syndromeOrder tests for erythrocyte sedimentation rate, C-reactive protein level, and syphilis serologies

what would you do next?

What would you do next?

Perform a lumbar puncture and measure opening pressure and cerebrospinal fluid composition

Perform an apraclonidine test to confirm diagnosis of Horner syndrome

Order tests for erythrocyte sedimentation rate, C-reactive protein level, and syphilis serologies

Order magnetic resonance imaging and magnetic resonance angiography of the brain and cervical spine

d

male

51-60

original

https://jamanetwork.com/journals/jamacardiology/fullarticle/2546888

A woman in her 50s was referred for evaluation of progressive shortness of breath over several months. No history of clinically significant fever was noted. The electrocardiogram showed ST-segment elevation in leads I, aVL, II, III, aVF, and V3-6 (Figure 1A), which was accompanied by fluctuating elevation of troponin-T levels (1.2-12.0 ng/mL). Angiography showed no evidence of coronary artery disease. Transthoracic echocardiography demonstrated restricted diastolic filling with a low left ventricular ejection fraction (40%). Treatment for heart failure was initiated. Cardiac magnetic resonance (CMR) imaging was then scheduled. Late delayed enhancement images showed a striking sawtooth pattern of hyperenhancement in the left ventricular epicardium (Figure 1B) and right-sided enhancement of the anteroseptum. Extensive myocardial edema was noted in the left ventricle via T2-weighted short tau inversion recovery imaging (Figure 1C). Chest and abdominal computed tomography (CT) showed no inflammatory changes or lymphadenopathy. Serum angiotensin-converting enzyme (ACE) levels were not elevated. The brain natriuretic peptide level was elevated (1550 pg/mL).A, Electrocardiogram with ST-segment elevation in leads I, aVL, II, III, aVF, and V3-6. B, Delayed enhancement cardiac magnetic resonance (CMR) images show a sawtooth pattern of hyperenhancement in the epicardium of the left ventricle (arrowheads). C, T2-weighted short tau inversion recovery image from CMR shows extensive high signal intensity over the entire left ventricle, indicative of myocardial edema.Perform positron emission tomographic/CT imaging to guide steroid treatmentPerform serum and urine immunofixation and light chain determination What Would You Do Next?

Conduct close follow-up and provide medical treatment

Perform positron emission tomographic/CT imaging to guide steroid treatment

Initiate steroid pulse therapy

Perform serum and urine immunofixation and light chain determination

Acute giant cell myocarditis

C

Initiate steroid pulse therapy

C. Initiate steroid pulse therapy for acute giant cell myocarditisAll 4 of the options listed herein can induce electrocardiographic changes, troponin elevation, and severe diastolic dysfunction. Options A and D can be excluded based on the patterns of cardiac damage observed via CMR imaging. Takotsubo cardiomyopathy is not characterized by delayed enhancement.1 Cardiac amyloidosis is the most common identifiable cause of restrictive cardiomyopathy and usually presents with low voltage on the limb leads. Delayed enhancement imaging typically demonstrates diffuse subendocardial, but not epicardial, left ventricular hyperenhancement, and no edema is observed.2The clinical manifestations and examination findings raised the possibility of myocarditis or sarcoidosis. Both conditions present with abnormal ST-T changes, troponin elevation, and diastolic dysfunction in the acute phase. Both can present with epicardial hyperenhancement in a noncoronary pattern.3,4A biopsy was performed on the anteroseptum. Biopsy specimens from the right ventricular endocardium showed extensive fibrosis with large multinucleated giant cells (Figure 2A). Some multinucleated giant cells exhibited a typical unstructured “asteroid body” (Figure 2B). Myocardial biopsy specimens also demonstrated that the interstitial space adjacent to degenerating myocytes was increased, without the presence of epithelioid cells or caseous necrosis (Figure 2C). Infiltrating eosinophils, lymphocytes, and monocytes indicated an acute inflammatory process.Histopathologic images of biopsy specimens, hematoxylin-eosin. A, Biopsy specimens from the endocardium of the right ventricle showed extensive fibrosis with large multinucleated giant cells (arrowheads). B, A typical unstructured “asteroid body” was found in the multinucleated giant cells (arrowhead). C, Myocardial biopsy specimen showing increased interstitial space adjacent to the degenerating myocytes, without epithelioid cells or caseous necrosis. Infiltrating eosinophils (arrowhead), lymphocytes, and monocytes indicated an acute inflammatory process.The characteristic “asteroid body” can be found in both giant cell myocarditis and sarcoidosis.5 Isolated cardiac sarcoidosis is recognized clinically in less than 10% of patients, but with the finding of such extensive epicardial hyperenhancement on CMR, normal serum ACE level, lack of nodular changes on chest CT, and absence of epithelioid cells or caseous necrosis on multibiopsy samples, the patient was finally diagnosed as having acute myocarditis, specifically giant cell myocarditis.Giant cell myocarditis is the most lethal form of myocarditis. The average time from symptom onset to death or transplantation in giant cell myocarditis is only 5 months. Historically, most patients die before being placed on a transplant list. Future studies devising noninvasive strategies for early disease diagnosis are needed. The patient subsequently received steroid pulse therapy and immunosuppressive therapy but died within 1 month of presentation.

Cardiology

A woman in her 50s was referred for evaluation of progressive shortness of breath over several months. No history of clinically significant fever was noted. The electrocardiogram showed ST-segment elevation in leads I, aVL, II, III, aVF, and V3-6 (Figure 1A), which was accompanied by fluctuating elevation of troponin-T levels (1.2-12.0 ng/mL). Angiography showed no evidence of coronary artery disease. Transthoracic echocardiography demonstrated restricted diastolic filling with a low left ventricular ejection fraction (40%). Treatment for heart failure was initiated. Cardiac magnetic resonance (CMR) imaging was then scheduled. Late delayed enhancement images showed a striking sawtooth pattern of hyperenhancement in the left ventricular epicardium (Figure 1B) and right-sided enhancement of the anteroseptum. Extensive myocardial edema was noted in the left ventricle via T2-weighted short tau inversion recovery imaging (Figure 1C). Chest and abdominal computed tomography (CT) showed no inflammatory changes or lymphadenopathy. Serum angiotensin-converting enzyme (ACE) levels were not elevated. The brain natriuretic peptide level was elevated (1550 pg/mL).A, Electrocardiogram with ST-segment elevation in leads I, aVL, II, III, aVF, and V3-6. B, Delayed enhancement cardiac magnetic resonance (CMR) images show a sawtooth pattern of hyperenhancement in the epicardium of the left ventricle (arrowheads). C, T2-weighted short tau inversion recovery image from CMR shows extensive high signal intensity over the entire left ventricle, indicative of myocardial edema.Perform positron emission tomographic/CT imaging to guide steroid treatmentPerform serum and urine immunofixation and light chain determination

what would you do next?

What would you do next?

Perform serum and urine immunofixation and light chain determination

Conduct close follow-up and provide medical treatment

Perform positron emission tomographic/CT imaging to guide steroid treatment

Initiate steroid pulse therapy

d

female

51-60

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2486997

A woman in her 30s presented with a 3-month history of painful swelling of the left hard palate and cheek. The growth also caused malocclusion and ipsilateral upper lip numbness. She reported no recent trauma; no difficulty speaking, breathing, or swallowing; no epistaxis, nasal congestion or nasal drainage; and no recent fevers. She did have a history of recent pericoronitis, but several courses of antibiotics were unhelpful. Physical examination revealed a submucosal growth centered on the mesial aspect of the left maxillary alveolus. Transnasal endoscopy was unremarkable. Contrasted computed tomographic and magnetic resonance imaging showed a heterogeneously ossified lesion filling the left maxillary sinus, with local destruction of hard palate and alveolar bone (Figure, A and B). Positron emission tomographic scans highlighted the fluorodeoxyglucose-avid nature of both the tumor and associated cervical lymphadenopathy. A biopsy showed a tumor with lobular architecture, an incomplete peripheral ossified rim (Figure, C), and focal areas of osteoid matrix. Higher power showed atypical cells with increased mitotic activity in a myxoid stroma (Figure, D). Immunostains were negative for S100, pankeratin AE1/AE3, SMSA, and GFAP.A, Computed tomographic (CT) image of the head, coronal view. B, Magnetic resonance image (MRI) of the face, coronal view with contrast. C, Histopathologic image. D, Histopathologic image. Arrows indicate mitotic figures. What Is Your Diagnosis?

Chondroblastic osteosarcoma

Chondrosarcoma

Malignant mixed tumor of salivary gland

Malignant ossifying fibromyxoid tumor

D. Malignant ossifying fibromyxoid tumor

D

Malignant ossifying fibromyxoid tumor

The initial differential diagnosis comprised malignant and benign neoplastic masses of the hard palate and/or maxillary alveolus because previous treatments for infectious causes had been ineffective. Common alveolar tumors include odontogenic masses, chondroid and/or osteoid tumors, and minor salivary gland neoplasms. Intraoral biopsy of the lesion provided the final diagnosis of a malignant variant of ossifying fibromyxoid tumor (OFMT).OFMTs are rare neoplasms, first described by Enzinger et al1 in 1989. Although this example occurred in the maxilla, OFMTs most often occur in the extremities and trunk. Specific tumor histogenesis is controversial, with no agreed-on cell of origin.2 In head and neck OFMTs, the mean patient age at presentation is 46.8 years, with a male to female ratio of 1:0.63.3 Previous case examples of head and neck OFMTs describe subcutaneous and/or submucosal growths of the oral cavity, neck, scalp, lips, and nasal vestibule, as well as a metastatic nodule near the thyroid gland.3,4 Patients rarely report pain, often living with the lesions present for years prior to presentation.3Computed tomographic imaging may demonstrate a peripherally ossifying, locally destructive tumor that may be cystic owing to internal hemorrhage (Figure, A). Magnetic resonance imaging may show areas of low signal owing to calcification, ossification, or hemosiderin deposits (Figure, B).5Histopathologic findings in this case revealed cellular lobules with moderately atypical mononuclear cells in a predominately myxoid stroma (Figures, C and D). More typical tumors display a similar lobular architecture, but with predominately bland, low-grade spindled cells in a reticular growth pattern.6 An incomplete rim of metaplastic bone is found in 63% to 80% of OFMTs and was also present in this tumor (Figure, C).2-4 Although the tumor showed focal osteoid matrix production, no overt cartilaginous matrix was seen, arguing against a chondroblastic osteosarcoma. In addition, the lobular architecture of the tumor was more in keeping with ossifying fibromyxoid tumor than osteosarcoma (Figure, C).6The morphologic features of this case combined with the elevated mitotic index (≤23 mitotic figures per 50 high-power fields), high cellularity, and nuclear atypia fulfill the criteria proposed by Folpe et al2 for an atypical or malignant variant of ossifying fibromyxoid tumor. Fulfilling this criteria correlates with elevated metastatic risk; however, no distant disease was present 3 months postoperatively.2 In addition, this tumor’s myxoid extracellular matrix is typical in malignant and atypical OFMTs compared with the more fibromyxoid to fibrous stroma found in benign variants.7Immunostains for a variety of high and low molecular weight keratins, S100, SMSA, desmin, and p63 were all negative in the neoplastic cells of this tumor, excluding carcinoma, mixed tumor, myofibroblastic or smooth muscle differentiation, or a glial neoplasm.6 Some OFMTs can show positivity for desmin and S-100, and cytokeratin and GFAP expression is variable. In this case the immunohistochemical profile combined with the morphologic features secured the diagnosis of atypical or malignant OFMT. NextGen sequencing and fluorescence in situ hybridization tests have shown recurrent gene rearrangements of PHF1 in up to 80% of OMFTs as well, but such biomarkers are still considered experimental and were not performed in this case.7Treatment for malignant and typical OMFTs is surgical resection, after full-body imaging to rule out metastatic disease. Perioperative chemoradiation is common owing to the similarity of OMFT with soft tissue sarcomas, but no specific regimen has been agreed on. Locoregional recurrence is possible in a minority of cases. Kondylidou-Sidira et al3 found that of 71 tumors, 15 recurred at least once. Larger cohorts report local recurrence rates at 20% to 27%,4 with metastatic lesions present in 4.2% to 16% of cases.2,3 Prognosis with OMFTs, both typical and malignant variants, seems to be favorable but outcomes data are lacking owing to the rarity of the disease.2,3

General

A woman in her 30s presented with a 3-month history of painful swelling of the left hard palate and cheek. The growth also caused malocclusion and ipsilateral upper lip numbness. She reported no recent trauma; no difficulty speaking, breathing, or swallowing; no epistaxis, nasal congestion or nasal drainage; and no recent fevers. She did have a history of recent pericoronitis, but several courses of antibiotics were unhelpful. Physical examination revealed a submucosal growth centered on the mesial aspect of the left maxillary alveolus. Transnasal endoscopy was unremarkable. Contrasted computed tomographic and magnetic resonance imaging showed a heterogeneously ossified lesion filling the left maxillary sinus, with local destruction of hard palate and alveolar bone (Figure, A and B). Positron emission tomographic scans highlighted the fluorodeoxyglucose-avid nature of both the tumor and associated cervical lymphadenopathy. A biopsy showed a tumor with lobular architecture, an incomplete peripheral ossified rim (Figure, C), and focal areas of osteoid matrix. Higher power showed atypical cells with increased mitotic activity in a myxoid stroma (Figure, D). Immunostains were negative for S100, pankeratin AE1/AE3, SMSA, and GFAP.A, Computed tomographic (CT) image of the head, coronal view. B, Magnetic resonance image (MRI) of the face, coronal view with contrast. C, Histopathologic image. D, Histopathologic image. Arrows indicate mitotic figures.

what is your diagnosis?

What is your diagnosis?

Chondroblastic osteosarcoma

Malignant ossifying fibromyxoid tumor

Malignant mixed tumor of salivary gland

Chondrosarcoma

b

female

31-40

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2498964

A man in his 60s presented with positional shortness of breath and sensation of airway obstruction of 3 to 4 months’ duration, with acute increase in symptoms over 4 days. He described the need to cough to clear the airway, but coughing provided no relief. He noted some relief when bending at the waist or lying prone. Flexible fiber-optic laryngoscopy revealed a large, irregular pedunculated mass on the left anterior false vocal fold (Figure, A and B). The mass was seen to ball-valve in and out of the glottis with respiration. The position of the mass was discussed with the anesthesiology team, who felt comfortable performing prone intubation. Preparations for emergency tracheotomy were made. In the operating room, with the patient, the anesthesia unit performed flexible fiber-optic laryngoscopy and advanced the endotracheal tube into the trachea over the flexible bronchoscope. A video laryngoscope was used to ensure that advancing the tube would not shear the mass. The patient was turned supine, and microdirect laryngoscopy was performed. The mass originated from a stalk in the left anterior ventricle. It was removed with microscissors. Pathologic examination (Figure, C and D) revealed a 1.7 × 1.3 × 1.0-cm mass with a papillary-like architecture, expansion of the submucosa by benign mature adipose tissue, and variable amount of fibrous tissue. There was mild chronic submucosal inflammation without squamous epithelial proliferation.A, Direct laryngoscopic image of mass. B, Direct laryngoscopy with retraction of mass to view stalk. C, Hematoxylin-eosin, original magnification ×40. D, Hematoxylin-eosin, original magnification ×200. What Is Your Diagnosis?

Lipoma

Vocal cord polyp

Squamous papilloma

Adenoid cystic carcinoma

A. Lipoma

A

Lipoma

Benign tumors of the larynx are relatively uncommon. The most common ones seen include papilloma, chondroma, and neurofibroma, with others seen less frequently.1 Common symptoms of laryngeal tumors include airway obstruction (stridor and dyspnea), globus, cough, voice changes, snoring, and excessive accumulation of salivary secretions.2A rare benign laryngeal neoplasm is a laryngeal lipoma, accounting for about 0.1% of all benign laryngeal tumors.3 Laryngeal lipoma was first described in 1854 by Holt et al; since that time approximately 115 cases have been reported.3 Below the clavicles, lipomas are more common in obese women older than 40 years; however, in the head and neck region, men in their seventh decade are most commonly affected.2 Lipomas are slow-growing tumors that are clinically asymptomatic until they grow large enough to cause symptoms owing to physical discomfort and compression on surrounding anatomical structures. Endoscopic appearance ranges from a submucosal mass to a pedunculated intraluminal projection.2Laryngeal lipomas almost exclusively arise from the supraglottic larynx, which differs from the glottis and subglottis in the presence of subepithelial fat. Lipomas of the hypopharynx are slightly more common than those of the larynx, again related to the fat content of the region.2 Differential diagnosis of a well-circumscribed laryngeal mass includes hyperplastic mucosal polyp, mucus retention cyst, laryngocele, lymphatic malformation, benign tumor (eg, lipoma, hemangioma, adenoma, schwannoma), and sarcoma.4While progressive airway obstruction is a relatively common symptom of laryngeal lipoma, to our knowledge, positional obstruction, as described in this case, has not been reported. Such ball-valve obstruction has been reported with foreign-body obstruction and in a few cases of benign laryngeal neoplasms, including a pedunculated papilloma and a solitary fibrous tumor.5,6 Two cases exist in the literature of a large lipomas causing suffocation due to regurgitation into the hypopharynx.3Prone intubation was required because the patient had to lay prone to prevent the mass from obstructing the airway, and there was concern that mask ventilation would cause the same problem. Prone anesthesia is occasionally required in spinal, ophthalmologic, and head and neck reconstruction surgery, though very rarely in other surgical specialties. In most cases, however, the airway is secured first in standard position.7Treatment for laryngeal lipoma is surgical. Small tumors, such as the one in this case, can be removed endoscopically with cold or laser techniques.4 For larger tumors, external surgical approaches, piecemeal resection, and transoral dissection have been described.3,8,9 Tracheotomy may be necessary to avoid fatal airway obstruction. If the lesion is a benign lipoma, complete excision is adequate. Histologic evidence of atypia requires follow-up owing to a 53% recurrence rate.10 If the lesion is found to be a liposarcoma, radiotherapy should be considered.3We present the rare case of ball-valve airway obstruction secondary to a pedunculated laryngeal lipoma. To the best of our knowledge, neither laryngeal lipoma as a cause of ball-valve airway obstruction nor benign laryngeal neoplasm as an indication for prone intubation have not been reported. Prone intubation, a rarely used technique, was successfully performed and allowed for safe airway management for complete resection of the mass. Laryngeal lipomas are slow-growing and often asymptomatic until large enough to cause clinically significant obstruction of the airway, as in this patient. While laryngeal lipoma is a rare occurrence, it can present in unusual ways, including with positional airway obstruction.

General

A man in his 60s presented with positional shortness of breath and sensation of airway obstruction of 3 to 4 months’ duration, with acute increase in symptoms over 4 days. He described the need to cough to clear the airway, but coughing provided no relief. He noted some relief when bending at the waist or lying prone. Flexible fiber-optic laryngoscopy revealed a large, irregular pedunculated mass on the left anterior false vocal fold (Figure, A and B). The mass was seen to ball-valve in and out of the glottis with respiration. The position of the mass was discussed with the anesthesiology team, who felt comfortable performing prone intubation. Preparations for emergency tracheotomy were made. In the operating room, with the patient, the anesthesia unit performed flexible fiber-optic laryngoscopy and advanced the endotracheal tube into the trachea over the flexible bronchoscope. A video laryngoscope was used to ensure that advancing the tube would not shear the mass. The patient was turned supine, and microdirect laryngoscopy was performed. The mass originated from a stalk in the left anterior ventricle. It was removed with microscissors. Pathologic examination (Figure, C and D) revealed a 1.7 × 1.3 × 1.0-cm mass with a papillary-like architecture, expansion of the submucosa by benign mature adipose tissue, and variable amount of fibrous tissue. There was mild chronic submucosal inflammation without squamous epithelial proliferation.A, Direct laryngoscopic image of mass. B, Direct laryngoscopy with retraction of mass to view stalk. C, Hematoxylin-eosin, original magnification ×40. D, Hematoxylin-eosin, original magnification ×200.

what is your diagnosis?

What is your diagnosis?

Vocal cord polyp

Adenoid cystic carcinoma

Squamous papilloma

Lipoma

d

male

61-70

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2503115

A woman in her 40s had experienced dizziness and headache to the vertex with left retro-orbital irradiation for 1 year. She referred only to minor head trauma 15 years earlier. Findings from a physical examination were negative, while nasal endoscopy showed diffuse mucous rhinorrhea. A CT scan of the paranasal sinuses showed complete opacification of the left sphenoid sinus, a double-lined appearance of the sinus walls (an inner bony sclerotic layer and a thin external one) (Figure, A), and 2 bony defects of the sphenoid sinus walls next to the cavernous sinus along the floor (Figure, B). An MRI scan showed a concentric multistratified appearance of the sinus content. On T2-weighted images (Figure, C), a hyperintense line peripheral layer consistent with fluid retention, an irregularly thick hypointense line, consistent with the sclerotic bone visible on CT, a crescent-shaped heterogeneous material in the lower part, and a black oval area in the upper part of the sinus were identified. After gadolinium administration, volumetric interpolated breath-hold examination (VIBE) sequences revealed very intense enhancement of the oval black area in the upper part of the sinus, with no contrast enhancement of the remainder of the sinus (Figure, D). On paracoronal images, there was no cleavage plane between the hyperenhancing area in the sphenoid sinus and the bright signal of the internal carotid artery (ICA) in the cavernous sinus.Intrasphenoid pseudoaneurysm of the internal carotid artery What Is Your Diagnosis?

Fungus ball

Intrasphenoid pseudoaneurysm of the internal carotid artery

Cerebrospinal fluid leak with sinusitis

Hypervascular metastasis from thyroid cancer

B. Intrasphenoid pseudoaneurysm of the internal carotid artery

B

Intrasphenoid pseudoaneurysm of the internal carotid artery

Intrasphenoid pseudoaneurysm of the ICA (ICPA) is a rare entity that should be included in the differential diagnosis of isolated sphenoid sinus diseases, which encompass inflammatory lesions (sphenoiditis, fungal ball, mucocele, sphenochoanal polyps), skull base defects with cerebrospinal fluid leakage or meningo(encephalo)cele, neoplasms (inverted papilloma, epidermoid carcinoma, fibrous dysplasia, rabdomyosarcoma, chordoma), and vascular lesions (pseudoaneurysm).1 ICPA is mostly posttraumatic or postsurgical, whereas spontaneous forms are less frequent.1,2Maurer triad (history of craniofacial trauma, delayed massive epistaxis, and unilateral visual disturbances) represents the classic clinical presentation of ICPA.3 Nasal obstruction,4 headache,2 hematemesis,5 palpebral chemosis,6 ptosis,6 extraocular muscle palsy,2 and reduction or loss of pupil reflex2,7 even loss of consciousness and coma,3,6 have also been reported. However, trauma or concomitant diseases can cause some of these symptoms. Diagnosis can also occur serendipitously.8However, the appearance on CT or MRI of an intrasphenoid ICPA can be misrecognized as a fungus ball or long-lasting mucocele.2 In this patient, digital subtraction angiography (not shown) confirmed the diagnosis; an occlusion test, which showed a good vascular compensation of contralateral vessels to ICA occlusion, was also performed.Imaging plays a key role in differential diagnosis. The 6 ICPAs reported by Saket et al2 all appeared as hyperdense expansile intrasinusal masses on unenhanced images, and bony defects were always present (acute, subacute, or chronic fractures) in the posterior or lateral sphenoid sinus walls. By MRI, a central area of T2 hypointensity (flow-void effect in the perfused ICPA portion) and a heterogeneous/stratified T1 hyperintensity within the peripheral thrombus were constant features.In the present case, imaging findings differed for the absence of hyperdensity on unenhanced CT and the presence of an almost complete hyperostotic envelope. The patient’s clinical history was not clearly suspicious because epistaxis was absent and the reported minor trauma dated back many years. It is conceivable that the ICPA initially grew through a cortical defect (posttraumatic or congenital) of the skull base, which triggered remodeling and neo-ossification, further promoted by ICPA pulsation. The slow growth and bone remodeling caused the bubble-like appearance at imaging of the surrounding hyperostotic bony wall.Treatment of nonruptured ICA (pseudo)aneurysm includes extracranial or intracranial bypass, clipping, endovascular procedures (covered stents, coiling, and flow-diverter stents), ICA occlusion, and endoscopic wrapping with grafts. Treatment should aim to exclude the lesion from blood flow; for ruptured forms this is best achieved by ICA occlusion.9The patient underwent an endovascular coiling of the lesion and subsequent ICA occlusion (not shown). This procedure allowed formation of an obstructing thrombus inside the lesion. One month later, she underwent surgery to drain and marsupialize the surrounding fluid collections after removal of the residual lesion. The neck of ICPA, filled by thrombosed remnants, scar tissue, and intravascular coils, was shown to have pierced through the posterolateral wall of the sinus. A Hadad-Bassagasteguy flap was used to cover the defect and boost healing.Definitive histopathological examination was consistent with the concentric multistratified MRI appearance: the envelope was described as “bony tissue with reactive appearance,” and from periphery to center the following was visible: (1) hyperintense layer (fluid retention within the residual air space), (2) hypointense irregularly thick layer (ICPA bony walls), (3) heterogeneous crescent-shaped avascular tissue (mural thrombus), and (4) hypointense central area (the ICPA lumen) (Figure, D).Although intrasphenoid ICPA is rare, its symptoms and imaging findings should be promptly recognized because of its relatively high mortality rate (about 30%) if left untreated.10 Exclusion from blood flow by ICA occlusion represents first-line treatment. Sinus surgery is indicated in case of concomitant benign lesions (mucocele, fungus ball) or when it compresses nearby structures. However, selected small ICPAs may not require further treatment other than coiling.

General

A woman in her 40s had experienced dizziness and headache to the vertex with left retro-orbital irradiation for 1 year. She referred only to minor head trauma 15 years earlier. Findings from a physical examination were negative, while nasal endoscopy showed diffuse mucous rhinorrhea. A CT scan of the paranasal sinuses showed complete opacification of the left sphenoid sinus, a double-lined appearance of the sinus walls (an inner bony sclerotic layer and a thin external one) (Figure, A), and 2 bony defects of the sphenoid sinus walls next to the cavernous sinus along the floor (Figure, B). An MRI scan showed a concentric multistratified appearance of the sinus content. On T2-weighted images (Figure, C), a hyperintense line peripheral layer consistent with fluid retention, an irregularly thick hypointense line, consistent with the sclerotic bone visible on CT, a crescent-shaped heterogeneous material in the lower part, and a black oval area in the upper part of the sinus were identified. After gadolinium administration, volumetric interpolated breath-hold examination (VIBE) sequences revealed very intense enhancement of the oval black area in the upper part of the sinus, with no contrast enhancement of the remainder of the sinus (Figure, D). On paracoronal images, there was no cleavage plane between the hyperenhancing area in the sphenoid sinus and the bright signal of the internal carotid artery (ICA) in the cavernous sinus.Intrasphenoid pseudoaneurysm of the internal carotid artery

what is your diagnosis?

What is your diagnosis?

Fungus ball

Hypervascular metastasis from thyroid cancer

Intrasphenoid pseudoaneurysm of the internal carotid artery

Cerebrospinal fluid leak with sinusitis

c

female

41-50

Black

original

https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2507064

A man in his 30s from Burma presented with a slow-growing right facial mass after resection 14 years prior. His medical history was significant for atopic dermatitis. He had no previous treatment with radiation or immunosuppressive medications. On examination, he had a surgical scar, an indurated malformed auricle, a superficial right parotid mass infiltrating the overlying skin, and a 1.5-cm postauricular node. Facial nerve function was normal. Postgadolinium magnetic resonance imaging (MRI) showed infiltration into the cartilaginous tissue of the external auditory canal and ipsilateral cervical adenopathy (Figure, A). Serum laboratory test results revealed an eosinophil count of 1109 cells/μL (reference range, 50-350 cells/μL), and an IgE level of 5.44 μg/mL (reference range, <0.27 μg/mL). Flow cytometry was negative for signs of leukemia or lymphoma. Fine-needle aspiration (FNA) revealed a mixed leukocyte population and was negative for malignant neoplasm, necrosis, and granulomatous disease. An excisional biopsy of the postauricular node was performed. Within the lymphoid tissue there was prominent follicular hyperplasia and a diffuse infiltrate of eosinophils (Figure, B). There was an increase in small blood vessels within the germinal centers. While some follicles had well-defined mantle zones, others demonstrated a spectrum of lytic changes accompanied by intrafollicular infiltrates of eosinophils (Figure, C). The stroma was densely fibrotic with perivascular sclerosis (Figure, D).A, Magnetic resonance image (MRI) of a right parotid mass and pathologic preauricular and retroauricular lymph nodes. B-D, Histopathologic images, hematoxylin-eosin. What Is Your Diagnosis?