He attributed these changes to the need for washing hands frequently in the period of the COVID-19 epidemic.

He had no family history of similar skin problems and did not have a history of hyperhidrosis, cystic fibrosis, atopy, or trauma to the hands.Physical examination showed some changes emerged on both hands after water immersion contrasting with any other condition (Figure, A and B).

The lesions occurred as symmetrical white and transparent papules, white keratosis, excessive wrinkling on the dorsum of hands after water immersion and worsened in summer, and remitted in winter.

The lesions gradually aggravated, and the affected area dispersed to wrists and elbows during past the 1.5 years.

We took a skin biopsy specimen from white papules on the right hand, and representative histopathologic features are shown in the Figure, C and D.A and B, After immersing both hands in water for 10 mins, there were symmetrical white papules, white hyperkeratosis spots, and excessive wrinkling on the thenar eminence, wrist flexure of both hands, and dorsum of fingers and hands.

C and D, A skin biopsy taken from white papules after water immersion for 10 mins showed hyperkeratosis, dilated eccrine ducts in the epidermis and dermis, and hyperplasia of the eccrine sweat glanda (hematoxylin-eosin).

He was treated with topical tretinoin ointment intermittently per a diagnosis of chronic eczema at the local clinic with little improvement.


Three days after admission, the patient developed erythema and edematous necrotic plaques of the bilateral ears (Figure, A and B).

The necrosis progressed during the following days, primarily involving the earlobe of the right ear and a large portion of the helix of the left ear.

A punch biopsy specimen was performed (Figure, C and D).

Following admission, he was intubated with prone positioning, and treatment with tocilizumab and dexamethasone was started.

He was also found to have Staphylococcus hemolyticus bacteremia, and treatment with cefepime was initiated.


She also reported dyspnea on exertion, which developed 6 months prior to presentation.

On physical examination, her peripheral oxygen saturation was 95% on room air.

Auscultation of her lungs revealed crackles at the bases bilaterally.

She had normal strength throughout all muscle groups and full range of motion in the joints of her hands.

The palmar surfaces of her hands revealed livedo racemosa, erythema, and retiform purpura; ulcers overlying her phalangeal joint creases and fingertips; and scale and fissures on several digits (Figure).

On the dorsal surfaces there was a large ulcer on the right second metacarpophalangeal joint and erythematous papules over several metacarpophalangeal joints.

Laboratory testing showed a hemoglobin level of 10.5 g/dL and normal creatine kinase level.


Despite 3 days of treatment with an oral antibiotic (cefalexin), her thigh pain and swelling did not improve, and she was readmitted to the hospital and intravenous clindamycin was started.

The following day, her temperature was 39.4 °C (102.9 °F), blood pressure was 86/42 mm Hg, and heart rate was 131/min.

Surgical debridement of the right thigh was performed on hospital day 3.On hospital day 4, a new purple dusky border developed along the wound edge, and the patent underwent a second surgical debridement.

Her right thigh had a deep 9 × 8–cm ulcer with a dusky violaceous border extending 2 to 5 cm from the wound edge (Figure, left), with many 1- to 2-mm pustules (not visible in Figure).

Wound cultures and blood cultures obtained during incision and drainage performed on hospital day 1 were negative for bacterial, mycobacterial, and fungal organisms.

Laboratory testing showed a white blood cell count of 30 000/μL (88% neutrophils); lactate level, 77.5 mg/dL (8.6 mmol/L); and procalcitonin level, 16.1 ng/mL (reference, <0.1 ng/mL).

Histologic examination of the tissue obtained during the second surgical debridement revealed ulceration with extensive neutrophilic inflammation (Figure, right).

Right, Histopathologic examination of excised tissue showing dense dermal neutrophilic infiltration (hematoxylin-eosin, original magnification ×400).

She was transferred to the intensive care unit for presumed septic shock, and her antibiotics were changed to vancomycin and meropenem.

After debridement on hospital day 5, her temperature was 39.8 °C (103.6 °F), and she required vasopressor infusion with norepinephrine for shock.

Stains for microorganisms, and tissue and blood cultures, remained negative.Left, Patient’s right thigh showing characteristic violaceous border surrounding the surgical wound edge after multiple debridements.


She reported no history of facial trauma, recent travel, illicit drug use, or high-risk sexual behavior.

The nasal deformity, which she attributed to use of her CPAP mask, had developed gradually over the past several years.Patient with deformity of the nasal bridge revealed upon removal of face mask.Laboratory testing showed a white blood cell count (WBC) of 7700/uL, hemoglobin level of 13.2 mg/dL, and platelet count of 404 × 103/μL.

However, a deformity of the nasal bridge was noted after she was asked to remove her face mask, which she was wearing as required during the COVID-19 pandemic (Figure).

Radiographs of the hands and wrists performed 1 month prior showed degenerative changes but no bone erosions.

Her vital signs and physical examination findings were normal.

She had no redness, warmth, or swelling of any joints, and her skin examination was unremarkable.

Creatinine was 1.2 mg/dL (baseline, 0.83 mg/dL); erythrocyte sedimentation rate was 43 mm/h (reference range, 0-40 mm/h) and C-reactive protein was 23 mg/L (reference range, 0-10 mg/L).

Her urinalysis had more than 30 white blood cells/high-power field (HPF), more than 30 red blood cells/HPF, and 2+ protein.

Urine sediment microscopy showed red blood cell casts.


The patient endorsed a history of Crohn disease, and his medication had been changed from infliximab to ustekinumab 6 weeks prior owing to persistent intestinal inflammation.Clinical examination revealed bilateral periorbital edema, diplopia with decreased abduction in the right eye and decreased adduction in the left eye, chemosis, proptosis, and conjunctival hyperemia (Figure 1A).

He reported diplopia and pain with extraocular movement.

Visual acuity and neurologic and fundus examination findings were otherwise normal with no sign of optic neuropathy.Patient characteristics at initial presentation.

The yellow arrowhead indicates right lateral rectus muscle enlargement, and the blue arrowhead indicates left medial rectus muscle enlargement.Laboratory investigation showed a mildly elevated erythrocyte sedimentation rate but was otherwise unremarkable.

Levels of antinuclear antibody, antineutrophil cytoplasmic antibodies, IgG4 levels, serum angiotensin-converting enzyme, thyrotropin, and thyroglobulin receptor antibody were all normal.

Orbital computed tomography showed moderate bilateral lateral rectus muscle enlargement and mild enlargement of the left medial rectus muscle (Figure 1B) with mild, homogenous enhancement.Prednisone was started at a dose of 60 mg daily, and the patient’s symptoms resolved; however, eye pain immediately recurred when weaning the prednisone.

An orbitotomy with lateral rectus biopsy was performed, which showed a prominent chronic inflammatory process with infiltrates composed of a mixture of epithelioid histiocytes and small-sized lymphocytes associated with severe muscle atrophy.

There were no constitutional, dermatologic, or neurologic symptoms.

A, External photograph reveals greater chemosis and more pronounced conjunctival hyperemia and eyelid edema of the right eye than of the left eye.

B, Coronal computed tomography (CT) of the orbits.


She was told about these same findings 10 years ago but did not have a repeated eye examination until recently by another retina specialist.

She reported no family history of retinal diseases.

Her best-corrected visual acuity (BCVA) was 20/60 OD and 20/50 OS.

An anterior segment examination was normal.

Dilated fundus examination revealed multiple vitelliform lesions involving the macula and superior macula bilaterally (Figure 1).

Fluorescein angiography revealed staining of these lesions with a pseudohypopyon appearance of the central vitelliform lesion in the left eye.

Optical coherence tomography (OCT) showed hyperreflectance corresponding to the yellow pigment in the vitelliform lesions in the subretinal space.

She initially received anti–vascular endothelial growth factor (VEGF) treatment, but was later referred because of a concern about either the idiopathic or paraneoplastic variant of acute exudative polymorphous vitelliform maculopathy (AEPVM).

Initial workup by her primary care physician was unremarkable for malignancy.


Two weeks later she developed flickering photopsias and a temporal scotoma progressing to a “brown tint” of her vision in her left eye.

Her vision had decreased in her left eye and macular and optic nerve edema were noted and she was subsequently referred to us.

In our clinic, her visual acuity was 20/20 OD and 20/50 OS, and she had normal intraocular pressure, a shallow anterior chamber but open angle in both eyes, a patent LPI in the left eye, and clear crystalline lenses in both eyes.

The rest of her anterior segment was unremarkable.

The posterior examination was notable for shifting subretinal fluid with choroidal detachments without retinal breaks, inflammation, or optic nerve edema and leopard spotting, while her right eye was unremarkable (Figure, A).

Fluorescein angiography was unrevealing, while optical coherence tomography showed shallow subretinal fluid and an irregular and thickened choroid (Figure, B).

Ultrasonography showed an axial length of 20.0 mm, thickened sclera, anteriorly rotated ciliary body, and 360° of ciliochoroidal detachments in both eyes but worse in the left eye.

Results of a systemic laboratory evaluation for infectious and noninfectious disorders were unremarkable.

She was found to have narrow angles in both eyes and a laser peripheral iridotomy (LPI) was performed in her left eye.

Systemic corticosteroids failed to resolve the subretinal fluid and her vision declined.Subretinal fluid and choroidal effusions following a laser peripheral iridotomy.

A, Fundus photography showed substantial choroidal effusions with overlying serous retinal detachments (asterisk).


A focused laboratory evaluation identified a significantly elevated angiotensin-converting enzyme (ACE) level and antinuclear antibody titer, but serum lysozyme, syphilis, and tuberculosis testing had negative results.

The anterior segment was unremarkable in either eye, while the posterior segment examination noted 1+ vitreous cell, asteroid hyalosis, and a multilobulated, serous retinal detachment (RD) in the right eye and trace vitreous cell and a multilobulated, serous RD in the left eye.

Imaging included B-scan, optical coherence tomography, and fundus autofluorescence, which revealed diffuse choroidal and ciliary body thickening, multifocal pockets of subretinal fluid, and speckled hyperautofluorescence and hypoautofluorescence in both eyes (Figure 1).

A review of systems was unremarkable, most notably a lack of any pulmonary symptoms.

To better differentiate between Vogt-Koyanagi-Harada (VKH) syndrome, a lymphoproliferative disorder, or sarcoidosis as the underlying cause of the vitreous inflammation and multilobulated, serous RD in both eyes, a computed tomographic scan was performed.

It showed marked lymphadenopathy throughout the mediastinum and diffuse scleral thickening in both eyes.

The institute’s radiologists believed these computed tomography findings were nonspecific and could be indicative of either sarcoidosis or intraocular lymphoma.Vogt-Koyanagi-Harada syndrome–like presentation of multilobulated pockets of subretinal fluid and choroidal thickening and undulations.

A, Serous retinal detachment (asterisk).


The patient’s medical history was noteworthy for depression, for which she was taking bupropion and fluoxetine, and prior alcohol use disorder, for which she was 3 years sober.

She denied any smokeless tobacco use but endorsed daily electronic cigarette use.The extraoral examination detected bilateral buccal facial swelling of the lower facial third without associated trismus or lymphadenopathy (Figure, A).

Two months prior to presentation, the patient had awoken with bilateral linear “gashes” in her mandibular vestibule that were accompanied by bilateral buccal facial swellings.

Since that day, the facial swelling remained unchanged, and although the mucosal lesions healed, the oral pain persisted.

Small aphthous ulcerations were also present on the right buccal mucosa (Figure, B).

Intraorally, bilateral scarring of the mandibular buccal vestibule was noted with focal areas of ulceration.

An incisional biopsy of the right vestibular lesion was performed, and the specimen showed diffuse plasmalymphocytic infiltrates within the lamina propria.

On higher magnification, noncaseating granulomatous inflammation was observed (Figure, C).

Staining for acid-fast bacilli was negative.Clinical and histologic features of a patient with oral ulceration and facial swelling.

A, Clinical examination shows bilateral buccal swelling.

B, Intraoral examination shows linear vestibular ulcerations with buccolabial aphthous ulcers.

C, Hematoxylin-eosin stain of biopsy specimen of the vestibular ulcerated tissue shows noncaseating granulomatous inflammation (original magnification, ×100).

Acid-fast bacilli staining was negative.


He had no medical history or family history of cancer and was not a smoker.

The patient only returned 3 months later when his hoarseness became worse.

In the absence of other suggestive symptoms, as well as a normal physical examination that did not reveal any enlarged cervical lymph nodes or oropharyngeal or neck mass and an unremarkable nasoendoscopic examination, a diagnosis of laryngopharyngeal reflux was made.

Repeat nasoendoscopy now showed left vocal cord palsy in the paramedian position.

Results of a computed tomographic (CT) scan showed an ill-defined soft tissue mass, which was likely nodal disease, at the left supraclavicular (Figure 1), as well as the prevertebral and paravertebral region, which partially encased the left common carotid, left subclavian, and left vertebral arteries.

A fused positron emission tomography with CT (PET/CT) scan with fluorodeoxyglucose (FDG) tracer was then performed.Coronal view of the computed tomographic scan of the patient’s neck, including the left supraclavicular node (yellow arrowhead) and the left common carotid artery (black arrowhead).

The patient was advised to try conservative management with dietary advice and proton pump inhibitors, and a clinical review was scheduled in 6 weeks.

In the absence of a history of trauma and associated neurological or systemic symptoms, the main concern was an underlying tumor that impinged on the vagus nerve at various points or its recurrent branch.

This was along the expected course of the left recurrent laryngeal nerve and likely accounted for the left vocal cord palsy.

However, the primary site of disease remained unclear.


The patient has a history of rosacea being treated with topical metronidazole gel for flares but was otherwise asymptomatic.

There was no history of any exposure to radiation or arsenic, nutritional deficiency, inflammatory skin disease, or malignant neoplasm.

There was no family history of a similar condition.Examination revealed multiple, submillimeter, skin-colored to yellowish keratotic spiny projections over the aforementioned areas, only on the left side of the body (Figure, A and B).

The papules progressed proximally over the subsequent decade to involve the forearm, arm, scapular area, ankle, shin, and thigh, but only affected the left side of the body.

The patient’s face, palms, soles, and entire right side of the body were spared.

The patient did not have any alopecia, night blindness, or dry eyes or skin.

Punch biopsy from a lesion showed orthokeratosis with parakeratotic columns emerging from an epidermal invagination.

The epidermis was mildly acanthotic and with a normal granular layer.

There was a sparse superficial perivascular lymphocytic infiltrate.

Adjacent hair follicles were unaffected (Figure, C).A, Numerous, submillimeter, skin-colored spiny projections over left foot web spaces were present.

B, Close-up photograph over the left scapular area showed lesions of similar morphologic characteristics.

C, Histologic results showed a parakeratotic column overlying a mildly acanthotic epidermis with a normal granular layer and keratinocyte maturation.

A sparse superficial perivascular lymphocytic infiltrate was present (hematoxylin-eosin).


He also had asthenia and mild intermittent arthralgias.

Physical examination revealed multiple millimetric erythematous to hyperpigmented monomorphic keratotic papules involving the head, trunk, and extremities.

Symmetric annular brown erythematous plaques on the cheeks and temples were also seen.

Laboratory investigations revealed a normal white blood cell count, mild anemia (hemoglobin level, 11.3 g/dL; normal level 12.50-15.50 g/dL; to convert to g/L, multiply by 10.0), hypocomplementemia, and moderate proteinuria.

Autoimmune serology results showed raised levels of antinuclear antibodies (>1:160), anti-Smith antibodies, SSA/Ro antibodies, SSB/La antibodies, and anti-U1RNP antibodies.

Anti-dsDNA antibodies, lupus anticoagulant, rheumatoid factor, IgG and IgM anticardiolipin antibody, and anti-β2 glycoprotein 1 antibody results were negative.

There were no vesicles or pustules (Figure, A and B).

A biopsy specimen obtained from an erythematous papule on the trunk and stained with hematoxylin-eosin is shown in the Figure, C and D.A, Millimetric erythematous to hyperpigmented monomorphic papules involving the trunk.

B, Erythematous papules and symmetric annular brown erythematous plaques on the cheeks and temples.

C and D, Punch biopsy results (hematoxylin-eosin).


On presentation, she was afebrile with cool extremities; her blood pressure was 75/51 mm Hg, heart rate was 147 beats per minute, respiratory rate was 20 breaths per minute, and oxygen saturation was 99% on mechanical ventilation.

Her chest examination revealed bilateral coarse breath sounds and distant heart sounds.

Transthoracic echocardiogram revealed an ejection fraction of 10% with elevated filling pressures and no significant valvular abnormalities.

There was significant hemodynamic improvement within 48 hours; transthoracic echocardiogram was obtained and showed impressive recovery of the left ventricular function to an ejection fraction of 45%.

In the interim, her vitals remained unchanged, but the patient developed hematuria and laboratory parameters suggestive of hemolysis.

Chest radiography showed pulmonary edema, and low-flow alarms sounded on the device console.

Transthoracic echocardiogram showed severe mitral regurgitation (MR), and a transesophageal echocardiogram was performed to evaluate pVAD positioning (Figure and Video).Transesophageal echocardiogram after low-flow alarm on peripheral ventricular assist device console.

Owing to hemodynamic instability, the patient was given venoarterial extracorporeal membrane oxygenation (ECMO) with the peripheral ventricular assist device (pVAD) Impella CP (Abiomed) and was administered high-dose intravenous corticosteroids.

As a result, ECMO was decannulated after 72 hours.

Left pVAD support was maintained alone for another 24 hours.

Endomyocardial biopsy showed lymphocytic viral myocarditis.

A, 2-Dimensional echocardiogram with color Doppler.

B, 3-Dimensional echocardiogram of mitral valve.


The white line indicates the position of the optical coherence tomography scan.Five years prior to presentation, the patient started treatment with latanoprost nightly in both eyes for an enlarged cup-disc ratio presumed due to normal-tension glaucoma.

The patient denied a family history of eye disease.

Examination showed best-corrected visual acuity of 20/50 OD, 20/30 OS, and intraocular pressure of 13 mm Hg OU.

In the right eye, dilated fundus examination and optical coherence tomography (OCT) of the macula revealed subretinal fluid and cystoid spaces within the outer nuclear layer and inner nuclear layer in the nasal macula (Figure 1).

Results of the left eye fundus examination and macular OCT were normal.

In both eyes, the optic cup appeared very deep with a large cup-disc ratio.Color fundus photograph (A) and optical coherence tomography of the macula (B) illustrating intraretinal and subretinal fluid at the nasal macula.

At that time, intraocular pressure was 12 mm Hg OD and 14 mm Hg OS and central corneal thickness was normal.

Visual field and OCT of the retinal nerve fiber layer were without reproducible defects over 5 years of follow-up.


His visual acuity was count fingers OD and 20/70 OS.

Intraocular pressure was 20 mm Hg OD and 16 mm Hg OS.

There were 1+ (10-12 cells/high-power field) anterior chamber cells in both eyes with very hazy posterior pole details in the right eye and minimal vitreous haze in the left eye.

There was a hazy view to the posterior pole in the right eye with disc edema and multiple flame hemorrhages surrounding the nerve.

Examination of the posterior pole in the left eye revealed partial obstruction of all vessels and a complete halo on the disc with numerous flame hemorrhages emanating from and surrounding the optic nerve, along with a few dot blot hemorrhages within the macula (Figure).

His blood pressure was 173/137 mm Hg, but the rest of his vital signs were normal.Widefield color image of the left eye of a 49-year-old man with acute loss of vision.

There is marked hemorrhagic disc edema with flame hemorrhages emanating from and surrounding the optic nerve.


He had undergone trabeculectomy and 5-fluorouracil injection 1 month prior.

His eye pain worsened significantly, and ultrasound biomicroscopy showed scleral thickening (Figure 1A).

His vision continued to decline to counting fingers because of the development of a dense cataract with retrolenticular plaque (Figure 1B).A, Episcleral and scleral thickening (yellow brackets) adjacent to normal tissue (white brackets) on ultrasound biomicroscopy.

On initial examination, his visual acuity was 20/25.

He had diffuse conjunctival hyperemia without bleb purulence or leakage and more than 50 cells per high-power field of a 1 × 1-mm area of light on slitlamp biomicroscopy.

He was admitted to the hospital and started intravenous vancomycin and piperacillin-tazobactam treatment.

He was treated for blebitis with topical fortified antibiotics but subsequently developed vitritis.

He underwent vitreous tap and injection of vancomycin and amikacin followed by pars plana vitrectomy with bleb revision.

Separate vitreous samples from each procedure were sent for Gram stain and bacterial and fungal culture on chocolate and Sabouraud agar with no growth.

B, Retrolenticular plaque (yellow arrowhead) and vitreous debris (white arrowhead) on inferotemporal longitudinal B-scan.


The patient was not immunocompromised and denied any trauma to the area.

In the 2 months prior, he had received multiple rounds of antibiotics from other health care professionals.

The patient presented to our clinic with an isolated right 2-cm fluctuant and tender mass overlying the parotid gland.

The patient denied fevers or systemic symptoms.

Outside computed tomography of the face showed a 3-cm cystic structure in the superficial aspect of the right parotid gland with associated lymphadenopathy.

There was no accompanying cervical lymphadenopathy, and facial nerve function remained fully intact.

Results of laboratory evaluation revealed normal complete blood cell count and erythrocyte sedimentation rate levels with negative infectious workup results for Epstein-Barr virus, cytomegalovirus, HIV, and tuberculosis (TB).

Magnetic resonance imaging showed a 1.9-cm peripherally enhancing, centrally necrotic lesion overlying the superficial right parotid gland with multiple subcentimeter necrotic lymph nodes within the right parotid gland (Figure 1).The T1-weighted, contrast-enhanced, and fat-suppressed axial (A) and coronal (B) magnetic resonance imaging scans demonstrate the enhancing right-sided lesions overlying the distal aspect of the parotid and extending deep into the parotid parenchyma.

An outside health care professional had attempted incision and drainage of the area with negative cultures.


The patient was also being treated with subcutaneous interferon beta 1a for the multiple sclerosis.

When the arm was abducted to 90°, the patient denied pain but described a subtle tightness sensation on the arm.

Physical examination revealed 2 indurated and mobile subcutaneous nodules on the anterior surface of the arm 5 cm distal to the surgical scar, the larger of them measuring 15 mm in diameter (Figure, A) and the smaller of them measuring 4 mm.

An excisional biopsy from the larger lesion was performed (Figure, B-D).A, Clinical image showing indurated and mobile subcutaneous nodule on the anterior surface of the arm.

An excision with 1-cm margins of the left arm demonstrated desmoplastic melanoma with a Breslow thickness of 1 mm, and a left axillary sentinel lymph node biopsy (SLNB) had been performed 3 weeks before under general anesthesia.

Arrowheads highlight a subtle linear plaque adjacent to the nodule.

B, Histopathologic image showing dilated and thrombosed lymphatic vessels in subcutaneous tissue with recanalization (hematoxylin-eosin).

C, Histopathologic image of partially thrombosed vessels.

D, Immunohistochemistry finding was positive for D2-40 (podoplanin).


He had a history of cardiac arrest after receiving adenosine for sustained supraventricular tachycardia and tachycardia-induced cardiomyopathy.

The patient was also noted to have episodes of atrial flutter.

Transthoracic echocardiogram displayed a left ventricular ejection fraction of 63% and mild aortic and mitral regurgitation.

Cardiac magnetic resonance imaging in sinus rhythm showed mild left ventricle thickening (up to 14 mm) and was otherwise normal.

The patient was hospitalized for initiation of sotalol, given that he experienced frequent episodes of atrial arrhythmia.

Figure 1A shows sinus rhythm prior to sotalol initiation.

Figure 1B shows telemetry during administration of sotalol.


He had hit the right side of his head on a table 1 month before symptoms developed, but had no other recent trauma.

The mass had not changed in size, was not tender, and had no other associated symptoms.

His parents had not noticed any change in vision.

At bedside, the patient was playful and in no acute distress.

On examination, he fixed and followed in each eye.

His pupils were equal and reactive to light without afferent pupillary defect.

Both eyes were soft to palpation and his extraocular movements were full.

Externally, his examination was notable for bilateral upper eyelid ecchymosis and edema, as well as a soft, well-circumscribed mass on the right temporal region (Figure 1).

He was also noted to have subconjunctival hemorrhage temporally on the right eye.


His visual acuity was 20/400 OD and 20/20 OS.

The anterior segments were quiet and vitreous was clear in both eyes.

Fundus examination in the right eye revealed a solitary, elevated choroidal lesion with a creamy yellow appearance in the macular region involving the optic disc (Figure 1A).

Ultrasonography confirmed a dome-shaped choroidal mass with intermediate echodensity measuring 14 mm in diameter and 4 mm in thickness (Figure 1B).

Fluorescein angiography demonstrated scattered pinpoint hyperfluorescence of the mass and late leakage of the disc.

Indocyanine green angiography revealed hypofluorescence in both early and late phases.

Optical coherence tomography disclosed a choroidal mass with undulating surface and shallow subretinal fluid.

Magnetic resonance imaging of the orbit revealed an intraocular mass with hyperintensity on T1-weighted and hypointensity on T2-weighted scans with contrast enhancement extending into the adjacent retrobulbar fat, suspicious for scleral invasion.

Blood test results including a complete blood cell count, tuberculosis, syphilis, and angiotensin-converting enzyme were all negative.

There were more pigments overlying the intraocular mass with prominent intraretinal hemorrhage along the optic disc compared with clinical findings at first presentation.A, A fundus photograph revealed a solitary, raised choroidal lesion with a creamy yellow appearance in the macular region extending nasally to the optic disc (area encircled by a dotted line).

The patient then developed gingivitis with a white blood cell count up to 12 350/μL (to convert to ×109/L, multiply by 0.001) in the next 2 weeks that failed to respond to intravenous antibiotics.


The echocardiogram was performed because of an abnormal electrocardiogram demonstrating sinus tachycardia accompanied by high QRS voltage with a strain pattern in the precordial leads.

On physical examination, the patient was 154 cm tall and weighed 38 kg.

The cardiovascular examination was unremarkable.

Neurological examination showed mild cognitive impairment, poor coordination, and muscle weakness of the bilateral lower limbs.

Blood test results revealed impaired glucose tolerance, hypothyroidism, and elevated levels of lactic acid (32.4 mg/dL) and pyruvate acid (1.91 mg/dL; to convert to micromoles per liter, multiply by 113.56).

Review of the transthoracic echocardiogram showed diffuse hypertrophy, moderately decreased contractility of the left ventricle, and increased intramyocardial signal intensity (Video).

On admission, brain magnetic resonance imaging demonstrated cerebellar atrophy.

Cardiac magnetic resonance imaging demonstrated diffuse biventricular hypertrophy and moderately impaired left ventricular systolic function.

A wide range of nodular and band-shaped late gadolinium enhancement was detected in the middle and epicardial layers of the left ventricular myocardium.

Coronary angiography revealed no significant stenoses of the epicardial coronary arteries.

The patient was admitted to the hospital for further evaluation.


Symptoms started a year before, after receiving dental implants for new lower dentures.

The patient noted right upper and lower eyelid swelling most notable in the morning but denied associated fevers, chills, vision changes, dysphagia, headaches, urinary symptoms, or rashes.

Physical examination revealed a 3-cm round fluctuant area lateral to the right lateral canthus, mildly tender to palpation.

No overlying warmth or erythema and no lymphadenopathy.

The patient’s dentures appeared to be well fitting, but mouth opening was at approximately 50% of expected.

Laboratory results included an erythrocyte sedimentation rate (ESR) of 20 mm/h, and normal complete blood cell count, comprehensive metabolic panel results,  and lactate levels.

Findings on magnetic resonance imaging (MRI) (Figure, A) were most consistent with osteomyelitis of the mandible with inflammation of surrounding soft tissues.

Right temporalis muscle biopsy results for Gram stain and culture, fungal stain and culture, and acid-fast bacillus stain were unremarkable.

Additional laboratory test results, including serum IgG4, SPEP, brucella AB, Q fever AB, RF, urinalysis, and microalbumin/creatinine levels, were all unremarkable.

Results for p-ANCA and c-ANCA were negative.

Repeated MRI findings showed progression of the inflammation and new involvement of the temporal lobe dura.

Findings on positron emission tomographic computed tomography (PET-CT) scan showed nonspecific inflammatory changes to the bone, muscle, and brain meninges.

A biopsy of the temporalis muscle, sphenoid wing, and dura was performed (Figure, B).A, Magnetic resonance image (MRI) showing inflammation involving the right mandibular ramus and greater wing of sphenoid with overlying myositis involving masticator space.

The patient’s symptoms did not improve after 7 weeks of empirical intravenous ertapenem followed by 8 weeks of oral cefuroxime and minocycline.


B, Fluorescein angiography of the left eye demonstrating disc leakage (blue arrowhead) and blockage in the region of the macular lesion (pink arrowhead).His medical history included psoriatic arthritis, for which he had been taking adalimumab.

Four months prior to presentation, he had traveled to Costa Rica on vacation and fallen ill with fevers, night sweats, and myalgias.

After returning to the United States, he developed dyspnea with exertion.

He was found to have an ejection fraction (EF) of 20% to 25% with 4-chamber dilation and was diagnosed with cardiomyopathy.

His visual acuity on presentation was 20/20 in the right eye and hand motion only in the left eye.

Examination of the right eye was normal.

Anterior segment examination of the left eye revealed around 30 cells per high-power field of a 1 mm × 1 mm light beam and diffuse stellate-appearing keratic precipitates.

Posterior examination results showed a vitreous cell that precluded a clear view of the posterior pole and inferior snow banking.

Most notable was a large, white, preretinal lesion in the inferior macula and a near-total retinal detachment with no identifiable retinal break and shifting subretinal fluid (Figure).A, Fundus photograph of the left eye showing vitritis, a near-total retinal detachment, and a fluffy, white, lesion in the inferior macula (arrow).

He started a 6-week course of oral ciprofloxacin and his adalimumab was discontinued.


B, Widefield fundus photograph of the left eye showing scattered intraretinal hemorrhage and segmented periphlebitis (white arrowheads) with prominent venous sheathing and tortuosity and optic disc hyperemia (blue arrowhead).At the time of presentation, she had completed RIPE therapy and was taking mycophenolate mofetil with resolution of her ocular manifestations.

She complained of new bilateral lower extremity weakness with associated lower back pain.

Clinical examination results revealed a wide-based Trendelenburg gait with right foot drop and diminished strength of lower extremity flexors.

Laboratory testing results showed a normal white blood cell count, vitamin B12, angiotensin-converting enzyme, lysozyme, C-reactive protein, and antinuclear antibody levels.

She had negative test results for Lyme disease, syphilis, and HIV.

Computed tomography showed small supraclavicular and mediastinal lymph nodes and an enlarged spleen.

Magnetic resonance imaging demonstrated mild lacrimal gland prominence and low thoracic/high lumbar spine and cauda equina nerve roots hyperintensity and abnormal enhancement.

Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis with an elevated protein level, negative syphilis antibody results, and an absence of organisms on acid-fast bacilli smear, Gram stain, and culture.

Given a positive interferon-γ release assay, therapy was initiated with rifampin, isoniazid, pyrazinamide, ethambutol (RIPE) and corticosteroids for presumed tuberculosis.A, Late-frame fluorescein angiography showing hyperfluorescence of the optic nerve head, segmental vascular leakage and staining, and retinal nonperfusion downstream of obliterated vessels (pink arrowheads).

A year prior, she was found to have bilateral panuveitis with occlusive retinal periphlebitis involving all quadrants of the central and peripheral retina with capillary nonperfusion (Figure 1).

Her subsequent workup revealed elevated inflammatory markers and subcentimeter chest and abdominal lymph nodes.


She denied joint pain, fever, fatigue, changes in urine color, use of other topical or systemic medications, or presence of rashes elsewhere.

She was otherwise healthy without other medical history.On physical examination, she was well appearing with numerous 1- to 2-mm monomorphous pustules over background erythema on the medial cheeks, chin, and nose (Figure, A).

She noted mild associated pruritus but denied burning sensation.

The eruptions occurred intermittently, appearing as erythematous papules with prominent pustules, and were exacerbated by sunlight.

On average, her lesions would resolve in 3 to 4 days with only mild background erythema by 5 to 7 days.

Even mild sun exposure would induce the eruption, leading to frequent recurrences in summer months but long periods of remission in the fall through spring.

No nail fold capillary changes or mucosal lesions were observed.

Serum analysis results for antinuclear, anti-SSA/Ro, and anti-SSB/La antibodies were negative.

A 4-mm punch biopsy was taken from a representative lesion along the right jawline (Figure, B-D).A, Pustular eruption of the face characterized by monomorphous 1- to 2-mm pustules over background erythema on the cheeks, chin, and nose appearing less than 24 hours after sun exposure.

Punch biopsy of skin demonstrated intrafollicular (B and C) and subcorneal (B and D) pustule formation (hematoxylin-eosin).

Trials with various broad-spectrum sunscreens in combination with topical and oral antibiotics and topical ivermectin did not prevent flares or mitigate severity of eruptions when they occurred.


The patient had no other significant medical history and denied having a family history of similar lesions.

The papules and nodules appeared to grow as the boy grew, and some pedunculated lesions tended to fall off spontaneously.

Clinical examination findings revealed multiple skin-colored, nontender soft papules of varying sizes protruding from the skin surface on the right cheek, forehead, and jaw, as well as on the anterior surface of the scalp, distributed along Blaschko lines, with sparse vellus hairs and multiple hair follicles on the lesions (Figure, A and B).

However, no hair was observed on the lesion because the patient had shaved the hair on his face.

An incisional biopsy of a pedunculated lesion above the left eyebrow was performed (Figure, B).A and B, Papules, plaques, and nodules on the skin surface of the right cheek (A, B), forehead (B), intercilium (B), and jaw (B).

Presence of sebaceous glands and the perifollicular fibrous sheath within a fibrotic stroma can be clearly seen (hematoxylin-eosin).

White arrowhead indicates the biopsy site (B).

He had not received any prior treatment.


He had no significant history of cardiopulmonary disease.

Physical examination findings, including chest auscultation, were unremarkable.

Measured hemoglobin was 15.3 g/dL (World Health Organization normal range, 13.8-17.2 g/dL).

Chest computed tomographic imaging was unremarkable.


She had traveled to northeastern Brazil 2 months before the onset of the neurological symptoms.On examination, she had a mild right-side hemiparesis with hyperreflexia and hemiataxia.

She denied any history of fever, head trauma, vomiting, diarrhea, abdominal pain, or cough.

She could walk unassisted but presented with a broad base.

She did not present with hepatosplenomegaly of lymphadenopathy.

Her cranial magnetic resonance imaging  showed a T2-weighted fluid-attenuated inversion recovery hyperintense lesion with heterogeneous gadolinium enhancement in the pons (Figure).

There were no signs of diffusion restriction on diffusion-weighted imaging or hemorrhages on susceptibility-weighted imaging.Sagittal gadolinium-enhanced T1-weighted magnetic resonance imaging (MRI) (A) and sagittal T2-weighted fluid-attenuated inversion recovery (FLAIR) (B) showing the extent of the lesion.The laboratory test results showed a hemoglobin level of 15.3 g/dL (to convert to grams per liter, multiply by 10.0), total leukocyte count of 10 390/uL (to convert to ×109/L, multiply by 0.001), of which 1703 (16.4%) were eosinophils, and a platelet count of 284 000/μL (to convert to ×109/L, multiply by 0.001).

The patient’s liver and kidney function test results were normal.

Computed tomography of the chest revealed bilateral patchy pulmonary infiltrates.Cerebrospinal fluid (CSF) analysis showed 640 cells, of which 57% were lymphocytes, 26% were eosinophils, and 13% were monocytes; protein levels were 70 mg/dL, and glucose levels were 46 mg/dL.

Her blood cultures were found to be sterile.


He started antiretroviral therapy with bictegravir/emtricitabine/tenofovir/alafenamide and chemotherapy with rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH).Four weeks after initiation of chemotherapy, the patient developed sudden onset of bright red blood per rectum, tachycardia, and hypotension.

Five weeks later, he developed blurred vision, and visual acuity testing revealed 20/50 vision in the left eye and 20/70 in the right eye.

Physical examination was notable for oral thrush and mild epigastric tenderness.

Results of a fourth-generation HIV Ab/Ag combination assay were positive, and subsequent testing showed a CD4 cell count of 16/mm3 and an HIV viral load greater than 10 million copies/mL.

Computed tomography of the abdomen and pelvis showed thickening of the walls of the stomach, duodenum, and colon as well as multiple masses in the right hepatic lobe measuring up to 6.9 cm in diameter.

Mesenteric computed tomography angiography demonstrated active extravasation in the jejunum from a branch of the superior mesenteric artery.

After unsuccessful coil embolization, he underwent open resection of 40 cm of distal small intestine; pathological examination of a stained section showed acute inflammation of the lamina propria, with crypt epithelial apoptosis and numerous cytoplasmic and nuclear inclusions with an “owl eye” appearance (Figure 1, left panel).

A dilated retinal examination revealed extensive macular hemorrhage in the left eye, with peripapillary whitening and perivascular hemorrhage with whitening along the superior vascular arcade (Figure, right panel).Left, Representative section of patient’s small bowel showing cytoplasmic and nuclear inclusions surrounded by a clear halo (“owl eye” sign, arrowheads) (hematoxylin-eosin, original magnification ×40).

A core biopsy of one of the liver masses demonstrated diffuse large B-cell lymphoma.


Prior to delivery, she underwent diagnostic ultrasound of the right breast, which showed a possible mass in the location of the palpable lesion that was most consistent with a normal island of fibroglandular tissue.

Follow-up mammogram and ultrasound of the right breast (without axillary evaluation) were performed 6 months later, which showed an irregular 17-mm mass with associated pleomorphic calcifications in the same area.

On postbiopsy physical examination, the patient had a palpable 2.5-cm right breast mass at the 3-o’clock position without palpable axillary lymphadenopathy.Surgical treatment with lumpectomy was recommended, and breast magnetic resonance imaging (MRI) was performed prior to surgery to evaluate the extent of disease (Figure).

Axial T2-weighted MRI at the level of the axilla revealed edema surrounding 2 enlarged, morphologically abnormal right level-1 axillary lymph nodes; axial postcontrast T1 fat-saturated MRI of the right breast revealed an irregular mass with irregular margins at the site of biopsy-proven DCIS.

The patient reported receiving her second dose of COVID-19 vaccine (Pfizer-BioNTech) in the right arm the day before the breast MRI.Top, Axial T2-weighted magnetic resonance imaging (MRI) at the level of the axilla.

Pathology showed high-grade, estrogen receptor–positive ductal carcinoma in situ (DCIS).


Medical history included tertiary hyperparathyroidism related to end-stage kidney disease from chronic glomerulonephritis.

The patient had successfully received an ABO-incompatible kidney transplant 1 year ago, but this was complicated by invasive fungal (Volvariella volvacea) infection of the central nervous system.

Medications included tacrolimus (0.5 mg twice daily), prednisolone (10 mg daily), cinacalcet (12.5 mg daily), and voriconazole (500 mg daily).

There was no history of alopecia, oral ulcers, rashes, or Raynaud phenomenon.

She did not report preceding fever, diarrhea, or dysuria.

There was no history of weight loss or anorexia.

On examination, her fingers and toes were symmetrically and diffusely swollen and tender.

There was no rash, enthesitis, psoriatic nail changes, clubbing, or lower limb edema.

The rest of the physical examination was unremarkable.Alkaline phosphatase level was elevated at 640 U/L (10.69 μkat/L) (reference range, 40-130 U/L [0.67-2.17 μkat/L]).

Corrected calcium and parathyroid hormone levels were 10.88 mg/dL (2.71 mmol/L) (reference range, 8.6-10.2 mg/dL [2.15-2.55 mmol/L]) and 23.7 pmol/L (reference range, 1.3-9.3), respectively.

Serum bilirubin, aspartate transferase, alanine transferase, creatinine, and phosphate levels were within reference ranges.

Free thyroxine and thyrotropin levels were normal.

Results of testing for rheumatoid factor and anti-citrullinated protein antibody were negative.

Radiography of her hands was performed (Figure).


He had been admitted for an upcoming bone marrow transplant.

The patient had floaters without flashes and denied any eye pain.

A review of symptoms found chronic fatigue and a new, mild headache beginning a few days prior.

On examination, his visual acuity was 20/50 OU; intraocular pressures were 15 mm Hg OD and 13 mm Hg OS; and pupils were equal, round, and reactive, without a relative afferent pupillary defect.

Extraocular movements, confrontational visual fields, and Ishihara color plates were full.

An anterior segment examination had normal results.

A fundus examination revealed clinically significant peripapillary intraretinal and preretinal hemorrhages obscuring the optic disc margins of both eyes (Figure 1).


His medical history was significant for dyslipidemia for which he took rosuvastatin.

He noticed colors surrounding the dark area that lasted 2 to 3 minutes at a time and occurred multiple times per day.

He also reported feeling lethargic, with polydipsia and a dull mild holocephalic headache during this period.

Ophthalmological examination revealed a visual acuity of 20/20 OU, pupils were equal and reactive to light with no relative afferent pupillary defect, and color vision was normal.

Humphrey 24-2 Swedish interactive threshold algorithm fast visual field testing revealed a right homonymous hemianopia denser inferiorly (Figure, A).

An urgent noncontrast computed tomography (CT) scan of the head was obtained and was normal (Figure, B).


The mass had gradually grown over 2 months and was tender to palpation.

She had an unremarkable ocular and medical history.On examination, visual acuity was 20/20 OD and 20/20 OS.

Ocular motility was full and pupils were equal, round, and reactive to light.

Her examination was notable for a 3-mm subcutaneous, firm, mobile, noncompressible lesion near the lateral canthus of the right eye without overlying erythema, warmth, telangiectasia, or ulceration (Figure 1).

She denied any vision changes, facial trauma, redness, or discharge from the lesion.


The patient had no history of weakness, incontinence, or severe headaches.

Initial presentation was notable for hand motion visual acuity with a 2+ relative afferent pupillary defect on the right; fundus examination revealed grade IV disc edema with obscuration of all major vessels on the disc (Figure, A).

Two weeks after initial presentation, the visual acuity in the right eye progressed to no light perception.

A magnetic resonance image (MRI) of the brain with and without gadolinium contrast was degraded by motion and orthodontic artifact but was suggestive of optic nerve enhancement consistent with optic neuritis.

The second MRI revealed a fusiform expansion of the right optic nerve and enhancement of the orbital, canalicular, and prechiasmatic segments of the right optic nerve, suggestive of an optic nerve glioma.

Repeated MRI showed progression of the lesion with masslike expansion at the chiasm measuring 1.3 cm (anterior-posterior) × 1.5 cm (craniocaudal) × 1.1 cm (transverse).

Results of serology tests and cerebral spinal fluid analysis were negative for infectious and inflammatory etiologies, including syphilis, sarcoidosis, Lyme disease, viral etiologies, multiple sclerosis, and lupus.The patient started treatment with intravenous methylprednisone and plasmapheresis for a presumptive diagnosis of optic neuritis; however, after 3 days there was minimal improvement and a second MRI of the brain and orbits was performed (Figure, B).


The patient reported that when the lesion had begun to appear, approximately 10 years earlier, he had received 2 doses of intralesional steroid via injection on a small bald patch on the vertex.

The patient denied any trauma history and had no history of connective tissue disease nor any evidence of systemic involvement, such as arthralgia, photosensitivity, or skin rashes.

Localized linear hair loss and hair thinning on the left scalp area were observed.

Thereafter, the lesion gradually progressed to the frontal scalp and eventually made a linear furrow on the left side of his forehead.Physical examination revealed 2 long, curved-line, depressed, alopecic patches on the left side of the vertex and frontal scalp area extending to the left eyebrow (Figure, A and B).

The lesions measured (length × width) 7 × 2 cm and 6 × 1 cm, respectively.

Dermoscopic examination of the alopecic area revealed several short vellus hairs, yellow dots, and honeycomb hyperpigmentation; however, broken hairs were not seen.

The result of a hair pull test was negative.

Histopathologic findings of the 2 biopsy specimens were identical (Figure, C and D).A, Clinical image of annular arc from a longitudinally furrowed skin lesion on the left eyebrow and forehead to an alopecic lesion.

B, Clinical image of the bandlike grooved alopecic lesion on the left side of the frontal scalp and vertex.

C, Scanning view shows predominant lymphocytic infiltrates in perifollicular and periappendageal regions of the dermis and lobular panniculitis (hematoxylin-eosin staining).

Skin biopsies were performed on the left side of the vertex and the forehead.


He reported a 5-kg weight loss that he attributed to impaired intake owing to the oral lesions.

Results of a previous intestinal biopsy had shown unspecific findings and absence of apoptosis.

Physical examination revealed whitish edematous lacy patches with erosions on the dorsal and lateral aspects of the tongue and buccal mucosa (Figure, A); skin and nails were not involved.

The result of indirect immunofluorescence (IIF) testing, using monkey esophagus, salt-skin split, and rat bladder as substrates, was negative.

Enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis did not detect any desmoglein-1 or -3, bullous pemphigoid-180 or -230, collagen VII, desmocollin-1 to -3, laminin-332, envoplakin, or periplakin antibodies.

Results were normal for liver function; negative for hepatitis B and C; indicative of hypogammaglobulinemia, with a decreased immunoglobulin (Ig) G serum level of 465 mg/dL (normal, 750-1600 g/L; for g/L, multiply by 0.01); and normal for IgA and IgM levels.

Positron emission tomography revealed a 10-cm hypercapturing extrapulmonary mass (Figure, D).

B, Epidermis with acanthosis, parakeratosis, necrotic keratinocytes, and dermal band lymphocytic infiltrate with effacement of the dermoepidermal junction (hematoxylin-eosin).

C, Fibrogen deposition along the basement membrane.

D, Hypercapturing, heterogeneous mass in the right anterior hemithorax.

A lingual biopsy specimen was obtained for pathologic evaluation and direct immunofluorescence (DIF; Figure, B and C).

Surgical excision of the mediastinal mass was performed; its histopathologic features were consistent with a type AB thymoma, Masaoka-Koga stage 2A.A, Lacy, white erosive lesions on the tongue.

He was also being evaluated for a mediastinal mass detected in radiography of the chest performed for pneumonia.


On presentation, the patient appeared anxious with a heart rate of 101 beats per minute, respiratory rate of 20 breaths per minute, blood pressure of 151/79 mm Hg, and pulse oximetry of 96% in room air.

His cardiopulmonary examination results, complete blood cell count, basic metabolic panel, and cardiac troponins were all within normal limits.

His electrocardiogram on presentation and echocardiogram are shown in Figure 1 and the Video.A, 1-Lead electrocardiogram shows T wave inversions in V1 through V3.


Notably, he had a 4-year history of an asymptomatic papular skin eruption with more lesions developing in the last 4 months.

Three weeks prior, he had developed acute urinary retention.

The patient developed a sudden worsening of weakness in his legs 2 weeks after initial presentation.

These were distributed on the neck, trunk, and limbs, sparing his face, scalp, and genitalia (Figure 1B).

Neurological examination revealed weakness in bilateral lower limbs (Medical Research Council grade 4 on the right and grade 3 on the left), extensor plantar responses, and a sensory level at T6.

Magnetic resonance imaging of his thoracic spine was performed 10 days after the onset of weakness and did not show any signal abnormalities or restricted diffusion.

Cerebrospinal fluid analysis findings were remarkable for elevated protein (0.14 g/dL [to convert to grams per liter, multiply by 10]) but white cell count (5 cells/mm3) and glucose levels (54.05 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) were normal.

Cytology and flow cytometry were negative for malignancy.

Antibodies to aquaporin 4 and myelin oligodendrocyte glycoprotein were not detected.

Repeated thoracic spine imaging showed an area of T2 hyperintensity in the left posterolateral cord at T7, which did not enhance with contrast or show restricted diffusion (Figure 1A).

Findings of extensive workup for malignancy, including full-body computed tomography scan, paraneoplastic antibody panel, and systemic autoimmune diseases (antinuclear antibody, antidouble stranded DNA, and myositis antibody panel), were negative.

The skin papules were biopsied.T2-weighted magnetic resonance imaging (MRI) of the thoracic spine showing an area of hyperintensity in the left posterolateral cord at T7 (A) (arrowhead).

These consisted of hypopigmented papules with central hyperpigmented umbilication and larger papules with typical central atrophic porcelain white scarring (B).

Multiple papules were seen on the patient’s abdomen.


She had no history of recent travel or illicit drug use and was not taking any medications.On examination, her vital signs were normal.

She had no fevers, epistaxis, rhinorrhea, cough, shortness of breath, or hematuria.

She had bilateral scleral injection and swelling and tenderness over the proximal interphalangeal joints bilaterally.

Hemorrhagic vesicles and violaceous papules were present on her ears, nose, arms, and legs (Figure).

She had been prescribed 4 days of prednisone (10 mg/d) without improvement.

Laboratory studies revealed normal complete blood cell count, serum electrolyte levels, and liver enzyme levels.

Urinalysis findings were normal and urine toxicology screen was negative.

Punch biopsy of a papule on the right arm demonstrated a superficial perivascular infiltrate of neutrophils with leukocytoclasia, extravasation of erythrocytes, and fibrin in small blood vessel walls.


She reported neck swelling and an occasional dry cough but no fevers, chills, trismus, headache, dyspnea, chest pain, abdominal pain, fatigue, or rash.

One week prior to presentation, she visited an urgent care clinic for evaluation of pharyngitis and white exudates on her tonsils.

Despite taking antibiotics for 7 days, she had no improvement in her symptoms.

Results of a rapid strep test and heterophile antibody test (monospot) were negative.

One day prior to presentation, the urgent care clinic notified the patient that her throat culture results were negative.On presentation, the patient was in no acute distress and had normal vital signs.

She had bilateral white tonsillar exudates and posterior cervical lymphadenopathy, but no exudate was observed elsewhere in the oral cavity and the uvula was midline (Figure).

There was no axillary or inguinal adenopathy and no hepatomegaly or splenomegaly.

The remainder of the physical examination was normal.

A throat culture was obtained and she was prescribed amoxicillin (500 mg twice daily for 10 days) for possible group A streptococcal infection.


Aside from atopic dermatitis, his medical history was unremarkable.

Best-corrected visual acuity was 20/20 OU.

Slitlamp examination of the right eye disclosed conjunctival hyperemia and ciliary congestion, anterior chamber flare 2+, and a few nongranulomatous keratic precipitates; the left anterior segment was quiet.

Dilated fundus examination revealed 1+ of vitritis (binocular indirect ophthalmoscopy score) in the right eye and swelling of the optic disc in both eyes, to a greater extent in the right eye (Figure, A).

Routine blood tests, including full blood cell count, plasma glucose levels, liver function test, and kidney function test, were performed on the same day and showed a serum creatinine level of 1.57 mg/dL (reference range: 0.5-1.0 mg/dL; to convert to micromoles per liter, multiply by 88.4).

Antibodies anti–Treponema pallidum were tested and the results were negative.Imaging findings at presentation.

A, Color fundus photograph of the right eye shows mild hyperemia and swelling of the optic disc along with moderate venous vessels tortuosity.

B, Late-frame fluorescein angiography of the right eye shows mild dye leakage of the optic disc and no other obvious abnormalities.Spectral-domain optical coherence tomography at presentation showed increased thickness of the retinal nerve fiber layer in both eyes, to a greater extent in the right eye.

Fluorescein angiography revealed dye leakage of the right optic disc (Figure, B); no further abnormalities were found in both eyes.


Recent computed tomography (CT) of the brain, conducted as part of her headache workup, had been reported as normal.On examination, visual acuity was 20/25 OU.

On further questioning, she reported a 1-week history of drooling when eating.

She had no other associated neurological or constitutional symptoms.

Extraocular motility testing demonstrated no abduction of the left eye with corresponding large-angle incomitant esotropia increasing when looking to the left (Figure 1).

There was 2 mm of left upper eyelid ptosis with preserved levator function.

The left pupil was 1 mm smaller than the right in the light, with the difference increasing to 2 mm in the dark.

There was no relative afferent pupillary defect.

Cranial nerve examination demonstrated reduced sensation in the left V1-V3 distribution and mild flattening of the nasolabial fold.

Corneal sensation was slightly decreased on the left.


He had a history of dry eye disease for which he was treated with preservative-free artificial tears.

He also noted a medical history of well-controlled HIV with highly active antiretroviral therapy.

His last CD 4 lymphocyte count was 750 cells/mm3 with an undetectable viral load.

The patient reported having unprotected sexual contact with multiple male partners in the past few years.On examination, his best-corrected visual acuity was 20/20 OU.

Both eyes appeared to be moderately tender to touch.

Intraocular pressure was 12 mm Hg OD and 14 mm Hg OS.

Slitlamp examination demonstrated diffuse scleral injection in both eyes without any scleral thinning.

The redness did not blanch after administration of phenylephrine, 10% (Figure 1).

The rest of the anterior segment examination was within normal limits without any evidence of intraocular inflammation.

Dilated fundus examination was also unremarkable in both eyes.Slitlamp photographs of the right and left eyes show significant diffuse scleral injection, which did not blanch following administration of phenylephrine, 10%.

A review of system produced negative results, including absence of weight loss, fevers, headache, joint pain, respiratory symptoms, or skin rash.


Her ocular history was notable for indiscriminate trauma to her left eye, primary open-angle glaucoma in both eyes treated with dorzolamide hydrochloride and brimonidine tartrate, and pseudophakia in both eyes.

Four years prior, an inferior cystic iris stromal lesion was discovered in the left eye that measured approximately 5 × 2 mm in basal dimensions at the slitlamp.

Visual acuity was 20/20 OD and light perception OS.

Intraocular pressure (IOP) was 15 mm Hg OD and 54 mm Hg OS.

Anterior segment examination of the left eye was remarkable for a large cystic iris stromal lesion from the 2- to 7-o’clock position with iris-cornea touch.

The anterior chamber was shallow in the area of the enlarged cystic lesion with a large amount of pigmented cells.

The pupil was irregular with blood at the pupillary margin.

Her intraocular lens was not visible because of occlusion by a cystic lesion behind the iris (Figure 1).

Fine-needle aspiration was negative for malignancy, and the lesion was managed by close follow-up.Anterior segment photograph of the left eye demonstrating sudden enlargement of a cystic iris stromal lesion from the 2- to 7-o’clock position (arrowheads).


Her ocular history included pseudoexfoliation syndrome and glaucomatous optic neuropathy in the right eye.

Past ocular surgery included uncomplicated trabeculectomy in the right eye treated with mitomycin C (3 months prior) and no ocular surgery history in the left eye.

Her medical history included pulmonary Mycobacterium avium infection secondary to hypogammaglobulinemia.

Computed tomography scan 2 months prior exhibited reactivation and she started treatment with clarithromycin (1000 mg/d), ethambutol (15 mg/kg/d), and rifabutin (300 mg/d).Best-corrected visual acuity was hand motions OD and 20/20 OS.

Intravitreal amikacin and vancomycin were administered after vitreous sampling was performed.

Her visual acuity returned to 20/30.Two months later, she presented again with a similar acute vision loss in the left eye (counting fingers).

Intraocular pressures were 4 mm Hg ODand 13 mm Hg OS.

Anterior segment examination of the right eye showed substantial conjunctival hyperemia and substantial cellular response in the anterior chamber (2 to 3+) along with a 1-mm hypopyon.

There was no leak at the trabeculectomy bleb (negative Seidel test).

B-scan ultrasonography showed no retinal detachment or mass.

Pars plana vitrectomy was performed, including vitreous sampling, and showed very light growth of Staphylococcus aureus in 1 colony on 1 plate, which was highly suspicious for contaminant.

Postoperatively, the patient initiated treatment with topical antibiotics and corticosteroids.

Presumed diagnosis of bleb-related infectious endophthalmitis was made and she was referred for treatment.


Pemigatinib treatment was initiated 2 months prior to the skin findings.

Physical examination revealed retiform purpura with areas of necrosis involving the bilateral lower extremities (Figure, A and B).

A punch biopsy specimen from the right calf was obtained for histopathologic analysis (Figure, C and D).Early reticulated erythematous patches (A) that rapidly progressed to prominent retiform purpura with cutaneous necrosis (B).

Laboratory evaluation demonstrated a mildly elevated D-dimer level at 578 ng/mL fibrinogen-equivalent units, prolonged prothrombin time of 12.7 seconds, elevated phosphorus level at 6.8 mg/dL (of note, phosphorus was 3.1 mg/dL 1 month prior), and normal calcium level and kidney function.

Other laboratory tests to note include cryoglobulin and cryofibrinogen, which both had negative results.

Calcium deposits within wall of a blood vessel in the subcutaneous tissue (C, white arrowhead) and pseudoxanthoma elasticum–like changes with fragmented calcified elastic fibers (D, white arrowheads) in the dermis and subcutaneous tissue (hematoxylin-eosin–stained sections; original magnification ×200).

Within weeks, there was rapid progression with skin necrosis despite treatment initiation with rivaroxaban.


The patient was otherwise healthy and was a never-smoker with no history of hypertension, atherosclerotic disease, or HIV.Physical examination revealed dark violaceous plaques, scattered subcutaneous nodules, and swelling to the mid-shin of the left lower extremity (Figure, A).

The plaques had been present for years, but the patient noted enlargement and darkening for the past 5 years.

The lesions were asymptomatic with no associated pruritus, bleeding, or pain.

There was mild warmth noted, but no palpable bruits.

Complete metabolic panel, complete blood cell count, prothrombin, and serology were negative or within normal limits.

A punch biopsy was performed and submitted for histopathologic analysis (Figure, B).A, Violaceous papules, plaques, and nodules on the left lower shin.

B, Proliferation of superficial and deep vessels, with thickening of the endothelium (hematoxylin-eosin).

C, Magnetic resonance angiogram demonstrating hypervascular soft tissue mass in the left lower extremity.

No treatments or diagnostic workup had been attempted prior to presentation.


He reported episodic breathlessness, cough, and wheezing with expectoration of brownish sputum, exacerbated with exposure to hay dust, in the past 5 years.

He also reported recent-onset headache while reading.

Physical examination revealed a depressed plaque measuring 6 × 4 cm in the right infraorbital region, surrounded by multiple nodules of sizes ranging from 1 × 1 cm to 5 × 1 cm (Figure, A).

The nodules were firm, mobile, and nontender on palpation.

There was proptosis of the right eye with mild restriction of extraocular movements on lateral gaze.

Examination of the oral cavity revealed dental caries, while gingivolabial sulcus was free on bidigital examination.

Respiratory system examination revealed occasional polyphonic wheeze.

Chest radiography imaging showed nodular opacities in right upper zone and bronchiectasis.

Punch biopsy from 1 nodule was sent for histopathological and microbiological examination (Figure, B and C).A, Destructive depressed plaque involving the medial half of the right side of the face surrounded by multiple nodules of varying sizes.


On examination, she was normotensive, afebrile, and clinically euvolemic.

Laboratory testing showed a hemoglobin level of 12.1 g/dL (to convert to grams per liter, multiply by 10), white blood cell count of 9900/µL (to convert to ×109 per liter, multiply by 0.001), erythrocyte sedimentation rate of 76 mm/h, lactate dehydrogenase level of 139 U/L (to convert to microkatals per liter, multiply by 0.0167), and normal coagulation profile.

Serum immunoglobulin quantitation showed normal immunoglobulin (Ig) G, IgA, and IgM levels of 1590 mg/L, 303 mg/L, and 94 mg/L, respectively (to convert to grams per liter, multiply by 0.01).

Blood culture findings were negative.Transthoracic and transesophageal echocardiography (Figure 1 and Video) showed a large echogenic mass on the inferior aspect of the interatrial septum with infiltration of the coronary sinus, anterior mitral valve annulus, and aortic root.

The mass protruded into the left ventricular outflow tract without causing valve obstruction.

Cardiac magnetic resonance imaging confirmed a bilobed interatrial mass measuring 5.6 × 3.1 × 3.8 cm with patchy late gadolinium enhancement of the lesion.

Contrast-enhanced computed tomography showed a left hilar mass encasing the left upper lobe bronchus with extension into the left main pulmonary artery, a nodular soft tissue lesion along the anterior nasal septum, and no abdominal or pelvic disease.


He had immigrated from India to the US 15 years prior and worked as a software engineer.

He last traveled to India 4 years earlier and had negative results for interferon gamma release assay on return.

He reported no smoking history, recent animal contact, or unpasteurized animal product ingestion.His temperature was 38.05 °C; heart rate, 114/min; blood pressure, 132/85 mm Hg; and respiratory rate, 18/min.

There was no spinal or paraspinal tenderness.

Findings on pulmonary and neurologic examinations were normal.

Erythrocyte sedimentation rate was 84 mm/h (reference, <10 mm/h), and C-reactive protein level was 9.4 mg/dL (reference, <0.8 mg/dL).

A chest radiograph showed prominent reticular markings in the left perihilar area, and chest computed tomography showed a 3.2 × 2.6–cm dense consolidation in the left lower lobe (Figure 1, left panel).

Magnetic resonance imaging (MRI) of the spine showed signal abnormality and extensive contrast enhancement within the T6, T7, and T8 vertebral bodies, with sparing of the T6-7 and T7-8 disks (Figure 1, center panel), and a large paraspinal soft tissue mass with spinal cord compression (Figure 1, center and right panel).Case patient imaging studies.

Left, Axial computed tomography of the chest.

Center, Postcontrast sagittal T1-weighted magnetic resonance imaging (MRI).


She had no known family history of polyneuropathy and no history of diabetes, alcohol misuse, known vitamin deficiency, hypothyroidism, or HIV.

A neurological examination demonstrated reduced pinprick sensation in both feet and absent vibratory sensation at the first toes.

Mild weakness of ankle dorsiflexion and absent ankle jerk reflexes were noted bilaterally.

She had a slightly wide-based gait, high-arched feet, and hammer toes.

Nerve conduction studies (NCS) and needle electromyography (EMG) were performed.

The results are shown in Table 1 and Table 2.


His medical history included chronic kidney disease, chronic hepatitis C infection, cirrhosis, ischemic cardiomyopathy with an implantable cardioverter-defibrillator (ICD), and atrial fibrillation with prophylactic apixaban.

He had recurrent staphylococcus bacteremia due to infection of an ICD lead and had been treated for the past 6 months with minocycline, 100 mg twice daily.

He had no history of malnutrition and reported infrequent alcohol use.Physical examination showed dense blue-black skin pigmentation of his forearms, dorsal hands, legs, and dorsal feet, as well as blue discoloration of his sclerae and teeth (Figure 1).

His arms had been purple and bruise-like for several years but turned a near black color 1 month ago.

He had normal-colored nails and oral mucosa.

Laboratory studies showed white blood cell count of 15 800/μL (reference range, 4000-11 000/μL), hemoglobin of 10.7 g/dL (reference, 13.5-17.5 g/dL), platelet count of 58 000/μL (reference, 150 000-400 000/μL), and INR of 1.8 (reference, 0.8-1.1).

Complete metabolic panel showed increased creatinine (1.51 mg/dL; reference, 0.64-1.27 mg/dL) and elevated total bilirubin (1.7 mg/dL; reference range, 0.3-1.2 mg/dL).

His estimated glomerular filtration rate was 40 mL/min/1.73 m2.

He reported no discoloration of his sweat or urine.


She had no history of eye trauma, did not sleep in her CLs, and stopped using CLs at symptom onset.

Of note, she had recently been swimming in a freshwater lake prior to the onset of the ulcer.

One week later, she presented with worsening pain and vision, which prompted referral to our cornea clinic where, 2 weeks after her initial presentation, her best-corrected visual acuity was 20/20 OD and 20/150 OS.

Left-eye examination demonstrated diffuse microcystic corneal edema and stromal thickening with no Descemet membrane folds (Figure 1A).

A 2 × 2-mm stromal opacity was noted paracentrally with no epithelial defects.

The anterior chamber demonstrated 1+ cell.

She was initially treated with topical besifloxacin and followed up daily.

She appeared to improve clinically with resolution of her epithelial defect after 3 days, and topical loteprednol was added.

Results of initial corneal cultures were negative.

Corneal cultures for bacteria, fungi, and acanthamoeba were repeated, and in vivo confocal microscopy (IVCM) was performed on the stromal infiltrate (Figure 1B).

After reviewing the IVCM images, what empirical treatment would you recommend while awaiting the results of the repeated corneal cultures?


Findings of Amsler grid testing were notable for a small area of distortion inferiorly in the left eye.

On examination, her best-corrected distance visual acuity was 20/40 OD and 20/60 OS (baseline 20/40 OU).

Pupils were equally round and reactive, without afferent pupillary defect.

Intraocular pressures (IOPs) were 13 mm Hg in both eyes.

Findings of anterior segment examination were unremarkable.

Findings of dilated fundus examination were notable for cup-disc ratio of 0.9 in the right eye and 0.85 in the left eye with temporal thinning, stable from prior, and new intraretinal thickening in the left eye.

Optical coherence tomography (OCT) imaging of the left eye revealed schiticlike separation of the outer plexiform and outer nuclear layers extending from the temporal edge of the optic nerve head to the fovea (Figure 1A), continuous with the peripapillary nerve sheath.Optical coherence tomography (OCT) of macula demonstrating schisislike separation involving fovea (A) and OCT of optic nerve head, with optic pit marked with an arrowhead (B).


She had no history of longer-term use of medications.

Medical history was positive for bilateral sensorineural hearing loss with cochlear origin as determined by an otolaryngologist and headache since age 35 years.

Her best-corrected visual acuity was 20/20 OD and 20/63 OS.

Fundus examination confirmed the presence of bilateral macular atrophy.

Fundus autofluorescence revealed a fairly symmetric loss of autofluorescence in the macula and in the regions surrounding the optic disc (Figure).

In proximity of these areas of reduced autofluorescence, a speckled fundus autofluorescence pattern of alternating spots of increased and decreased autofluorescence was also noted.

Optical coherence tomography displayed the presence of a bilateral atrophy of the outer retina and retinal pigment epithelium (Figure).

The patient’s family underwent a complete ophthalmologic evaluation, which did not display any alteration.A, Fundus photograph of the right eye demonstrates an area of pallor in the fundus (blue arrowheads) corresponding to the region of macular atrophy.

B, Structural optical coherence tomography (inset image) and green fundus autofluorescence (main image) of the right eye show a macular atrophy that also involves the peripapillary region.

The area of retinal pigment epithelium loss is featured by well-demarcated reduced autofluorescence (pink arrowhead) surrounded by speckled hyperautofluorescent areas (yellow arrowhead).

There was no family history of hearing and vision loss in all immediate family members.


One week later, the patient returned to our department due to multiple episodes of amaurosis fugax in left eye.

Visual acuity was 20/40 OD and 20/20 OS.

Anterior segment, tonometry, and pupillary light reflex were unremarkable.

Ophthalmoscopy of the right eye showed discretely blurred optic disc margins, tortuous and dilated retinal veins, and intraretinal hemorrhages in all quadrants; the left eye was unremarkable.

An optical coherence tomography (OCT) scan showed a cystoid macular edema (CME) in the right eye; the left was unremarkable.

Retinal nerve fiber layer thickness was 133 μm OD and 82 μm OS (reference value, 95.4 ± 10.48 μm).1 A fluorescein angiography was scheduled.

By that time, ophthalmoscopy disclosed a mild optic disc swelling, tortuous venous vessels, and retinal hemorrhages bilaterally (Figure 1).

The OCT scan showed a CME spontaneous resolution in the right eye while the left eye was unremarkable.

Fluorescein angiography revealed a slight delay in venous filling but no capillary nonperfusion areas.

In the left eye, a superficial optic nerve drusen (white arrowhead) was noted.A hypercoagulability and autoimmune workup—including peripheral blood smear, complete blood cell count, serum hyperviscosity, total protein level, protein electrophoresis, factor V Leiden, prothrombin, protein C and S, antithrombin, anticardiolipin, and antineutrophil cytoplasmic antibodies—gave normal results.

A brain angiomagnetic resonance imaging scan was performed, which excluded central thrombosis.

These features were compatible with bilateral nonischemic central retinal vein occlusion (CRVO), with spontaneous reperfusion in the right eye.Fundus photography of the right and left eyes showing slightly elevated and blurred optic disc margins (asterisk), mildly tortuous and dilated retinal vessels (black arrowheads), and intraretinal hemorrhages (pink arrowheads) in all quadrants in both eyes.


At age 8 months, she was treated with right enucleation and left eye radiotherapy (50.4 Gy).

At age 4 years, she developed a recurrence of the retinoblastoma in the nasal cavity and was treated with 4 cycles of vincristine, doxorubicin, and cyclophosphamide followed by 1 cycle of cisplatin, etoposide, and intrathecal cytarabine.Primary care evaluation was prompted by her mother, as the patient had not noticed her lower extremity edema.

She had no fevers, weight loss, shortness of breath, chest pain, abdominal pain, or history of deep vein thrombosis.

Her physical examination was notable for firm, nonpitting edema to the hip.

She did not have any associated tenderness, inguinal lymphadenopathy, or palpable abdominal masses.

Her vital signs were within normal limits and she ambulated comfortably.

Laboratory work results, including a complete blood cell count with a differential, comprehensive metabolic panel, and D-dimer levels, were within normal limits.

Doppler ultrasonography of her right lower extremity showed no deep vein thrombosis.

A computed tomography venogram demonstrated a 4.0 × 3.5 cm mass of likely vascular origin that was extending into the right common iliac vein (Figure).Computed tomography venogram demonstrating a 4.0 × 3.5 cm heterogeneously enhancing lobulated mass (arrowhead) extending into the right common iliac vein.


She first noticed swelling that progressed to pressure and dyspnea while supine.

She reported fatigue but denied pain, voice change, weight loss, hemoptysis, and dysphagia.

A physical examination revealed a visible and palpable fullness to the right neck without overlying cutaneous or sinus tract changes.

Results of a complete blood cell count, a thyroid stimulating hormone test, triiodothyronine and levorotatory thyroxine testing, and a complete metabolic panel were normal.

Ultrasonography showed a 7.9 × 6.3-cm septate cystic mass lateral to the right thyroid gland.

A contrast-enhanced computed tomography scan of the neck demonstrated a large, nonenhancing cystic-appearing lesion abutting the lateral and posterior margins of the right thyroid lobe and extending from the level of the piriform sinus to the thoracic inlet (Figure).

Ultrasound-guided fine-needle aspiration revealed clear fluid with a parathyroid hormone (PTH) level of 67 pg/mL (reference range, <100 pg/mL; to convert to ng/L multiply by 1.00).

A barium swallow study showed no communication between the cyst and the piriform sinus.

Excision in the operating room was performed, and right thyroid lobectomy was necessary because of the intimate association of the lesion to the thyroid lobe.Contrast-enhanced computed tomography scan of the neck with coronal (A) and axial (B) views demonstrating the right cystic neck mass.


The patient’s neck swelling, which initially decreased in size while undergoing chemotherapy, progressively enlarged shortly after concluding treatment.

He underwent magnetic resonance imaging and computed tomography of the neck that showed a clearly defined, bulky supraclavicular mass confined to left neck levels 3, 4, and 5 (Figure).A, Postcontrast coronal magnetic resonance imaging (MRI) demonstrated a bulky, cystic left neck mass at levels 3, 4, and 5.

B, Axial computed tomography (CT) scan with contrast highlighted extensive septations and modularity within the mass.

He was treated with a right radical orchiectomy and 4 cycles of etoposide, ifosfamide, and cisplatin (VIP) chemotherapy with resulting reduction in metastatic tumor burden and normalization of α-fetoprotein and β-human chorionic gonadotropin.


Fifteen months previously, he had undergone allogeneic stem cell transplant (allo-SCT) with a matched related donor for treatment of fms-like tyrosine kinase (FLT3) internal tandem duplication–mutated acute myeloid leukemia (AML).

The patient had been diagnosed with chronic gastrointestinal graft-vs-host disease after a workup for diarrhea.

Physical examination findings revealed no neck masses or abnormalities, but the patient was noted to be severely dysphonic and stridulous.

Results of a restaging bone marrow biopsy 2 weeks prior to presentation showed no evidence of leukemia.

Flexible laryngoscopy findings demonstrated a right vocal fold neoplasm crossing the posterior commissure with associated bilateral vocal fold motion impairment and obstruction of the glottic airway (Figure, A).

Histologic findings demonstrated diffuse infiltrate of large cells with irregular nuclear contours, vesicular chromatin, and prominent nucleoli (Figure, C).

Immunohistochemical stains showed CD33, CD43, and CD117 positivity, with a subset positive for CD7 and myeloperoxidase.

Stains were negative for CD3, CD20, and cytokeratin expression.Evaluation of the larynx from awake flexible laryngoscopy (A) including posterior commissure (A, inset) and operative microlaryngoscopy (B) with biopsy (C; original magnification ×40).

Awake tracheostomy was performed for airway protection, and biopsy of the neoplasm was obtained via operative microlaryngoscopy (Figure, B).


Three months prior, pembrolizumab treatment was stopped because of a widespread morbilliform reaction, which had resolved completely 6 to 8 weeks before admission.

The new widespread, asymptomatic skin eruption had been ongoing for 1 to 2 weeks and appeared different from her pembrolizumab reaction.A complete blood cell count was notable for a normal white blood cell count of 4100/μL, normal absolute neutrophil count of 2940/μL, chronic normocytic anemia (hemoglobin level of 8.2 g/dL), and chronic thrombocytopenia (platelet count of 62 ×103/μL).

Blood culture results showed no growth at 1 week.

Serum β-D-glucan, galactomannan, Coccidioides antibody by complement fixation, and immunodiffusion results were negative.

Respiratory viral panel and SARS-CoV-2 test results were negative.

Total body skin examination findings were notable for widespread, nontender, erythematous patches and thin plaques, some with prominent overlying telangiectases and hyperpigmentation (Figure, A).

A punch biopsy of a representative lesion was performed (Figure, B-D).A, Physical examination findings were notable for widespread erythematous patches and thin plaques, some with prominent overlying telangiectases.

D, CD56 immunostaining labels intravascular atypical cells.

B and C, Hematoxylin-eosin stained section.


His history was notable for nonischemic cardiomyopathy with ejection fraction of 40% and idiopathic pulmonary fibrosis, for which he underwent single-lung transplant 9 years prior.

Following diuresis and medical optimization, repeated echocardiogram showed a newly depressed ejection fraction (30%).

His electrocardiogram (ECG) was notable for alternating QRS morphologies (Figure 1A).

Chest radiography revealed severe right pulmonary fibrosis leading to ipsilateral mediastinal shift and pacemaker lead position unchanged from implantation.

The left ventricular (LV) pacing vector was programmed from LV tip to right ventricular (RV) lead ring.

During pacemaker threshold testing, a change in QRS morphology was observed as the output was reduced (Figure 1B).


About 2 weeks before the ulcerations developed, the patient had been admitted to the hospital for unstable angina, and coronary angiography was performed.

He had also experienced a burning sensation on the right side of his face, but denied headache, shoulder, or jaw pain and visual disturbance.

Neurological examination revealed hypoesthesia of the right side of the face, while cold-warm sensation and motor function were intact.

The erythrocyte sedimentation rate was 82 mm per hour (normal value, less than 15 mm per hour) and the serum C–reactive protein concentration was 107 mg/L (normal value, less than 5 mg/L).

Chest radiography showed bilateral perihilar infiltrates consistent with pneumonia.

Magnetic resonance imaging of the brain revealed an extensive ischemic posterior circulation stroke involving the right occipital lobe, lower cerebellar peduncle, and pontomedullary boundary (Figure, B).Clinical and radiological findings in a man aged 66 years.A, Multiple ulcers limited to the right half of the face.

Immediately after the angiography, the patient developed left-sided hemiplegia and hemianopsia.

B, Magnetic resonance image showing brainstem involvement by the stroke (diffusion-weighted sequence).


She had a history of hyperlipidemia, hypertension, and migraine headaches.

Her medications included atorvastatin, carvedilol, and norethindrone.

Dilated-fundus examination of the right eye showed a single cotton-wool spot (indicating local retinal ischemia), with intraretinal hemorrhage in the inferotemporal quadrant.

Ultrawide-field imaging showed a cotton-wool spot on the left fundus (Figure 1A, right) and a peripheral arterial occlusion in the right eye (Figure 1A, left), and fluorescein angiographic study of the right eye demonstrated an area of blockage corresponding to intraretinal hemorrhage and venous hyperfluorescence (Figure 1B).

The patient was afebrile, with pulse 110 beats/min and blood pressure of 188/99 mm Hg.

Auscultation over the heart apex revealed a holosystolic ejection murmur (grade 2/6).

Laboratory testing showed normal complete blood cell count and thyrotropin level and negative results for autoantibodies against Sm, SSA, SSB, Scl-70, Jo-1, centromere, chromatin, ribonucleoprotein, and antineutrophil cytoplasmic antibodies.

Erythrocyte sedimentation rate was mildly elevated (30 mm/h).

Results of testing for antinuclear antibodies were positive at low titer (1:40, homogenous pattern) with positive dsDNA (5.0 IU/mL; negative if <4.0 IU/mL).

Blood cultures were negative for bacterial or fungal growth after 5 days.

An echocardiogram revealed pedunculated and mobile aortic valve vegetations.


He was otherwise healthy and did not take any regular medications.

Initially, he had horizontal diplopia on the first day that was worse at the end of the day, but this resolved when the right eyelid ptosis became complete.

He denied any difficulty with his speech, swallowing, weakness, or sensory changes.He presented to the emergency department, and the emergency department physician reported a normal neurological examination result apart from the right-sided ptosis and limited eye movements.

He was referred to ophthalmology and had a visual acuity of 20/20 OU.

Both pupils were equal sizes and reactive to light.

He was found to only have a complete limitation of elevation of his right eye and a limitation of abduction in his left eye (Figure).

He was orthophoric in primary position, and there were no eyelid twitches.

Orbicularis oculi strength was reduced on both sides.

A dilated fundus examination had normal results bilaterally.


His extraocular movements were full, and he had no other neurologic deficits.

His visual acuity was 20/400 OD and 20/30 OS, respectively, and his fundi were notable for bilateral optic nerve edema.

Results of recent computed tomography and angiography of the head and neck and magnetic resonance imaging of the brain and orbits were reportedly normal, and lumbar puncture revealed an opening pressure of 26 cm H2O (normal range, 6 to 25 cm H2O) with elevated protein.

He had an afferent pupillary defect in the right eye, and Humphrey visual fields (24-2) showed binasal inferior defects with a superior defect in the right eye that was considered an artifact of testing.

According to the Ishihara color plates test, color vision was full in both eyes.

Fundus examination was remarkable for pallor of both optic nerves, more notably in the right eye, without edema (Figure 1).

The patient was given acetazolamide and referred to neuro-ophthalmology.On examination by neuro-ophthalmology 4 months later, his visual acuity was 20/50 OD and 20/20 OS.


The patient continued to report severe and progressive headaches along with blurred vision.

Magnetic resonance imaging (MRI) of the brain with and without contrast, magnetic resonance angiography of the head, and magnetic resonance venography of the head were obtained and were unremarkable.

The result of a lumbar puncture showed 101 white blood cells per high-power field (75% lymphocytes).

Results of syphilis serologic tests were negative.

There was no afferent pupillary defect, and an anterior segment examination was within normal limits.

A dilated fundus examination showed numerous bilateral creamy-yellow lesions in the peripheral retina with discrete nummular lesions in the posterior pole (Figure 1A).

Fundus autofluorescence showed focal areas of hypoautofluorescence with surrounding hyperautofluorescence in both eyes (Figure 1B).

A review of systems was otherwise unremarkable.A, Left eye.

Yellow placoid chorioretinal lesions extend from the posterior pole to the retinal periphery.

A creamy chorioretinal lesion (blue arrowhead) signifies active disease.

A corresponding lesion (white arrowheads) is visible on both images.

The patient was discharged with suspected viral meningitis.At a follow-up visit in an ophthalmology clinic 1 week after discharge, visual acuity was 20/25 OD and counting fingers OS.


Four weeks following receipt of immunotherapy with ipilimumab and nivolumab, he developed acute abdominal pain in the setting of a rapidly rising lactic acid dehydrogenase levels, prompting hospital admission.

Splenic infarct and portal/splenic vein thrombi were identified as etiologies of his acute pain and were presumed to be secondary to hypercoagulable state of malignancy.Over the next 3 days, he had rising serum creatinine (sCr) levels (baseline, approximately 1 mg/dL [to convert to μmol/L, multiply by 88.4]).

The top differential diagnoses at this juncture included contrast-induced nephropathy or immune checkpoint inhibitor (ICI)–induced acute interstitial nephritis, and empirical high dose steroids were prescribed.Despite observation and steroid treatment, his sCr levels continued to increase over the next 5 days, peaking at 5.8 mg/dL, and the patient progressed into anuric kidney failure, requiring hemodialysis.

Imaging results showed mild disease progression (new ascites and periportal metabolic lymph node).

Ultrasonography results showed abnormal intraparenchymal flow to both kidneys without evidence of kidney artery stenosis.

Urine studies were consistent with prerenal etiology, while the presence of casts suggested acute tubular necrosis.

Nephrotoxic medications (omeprazole/pantoprazole) were discontinued.

One week later, he received encorafenib, a BRAF inhibitor.1 Two weeks later, the patient’s kidney function began to improve, and hemodialysis was discontinued.

The initial workup included ultrasonography and urinalysis.

This prompted a kidney biopsy for definitive diagnosis (Figure).


He took linagliptin, valsartan, and 15 mg of methotrexate weekly.

He was a nonsmoker and consumed very little alcohol.Clinical examination including flexible nasendoscopy revealed multiple shallow ulcers on the posterior wall of the nasopharynx.

He also complained of nasal regurgitation.

There was a large defect involving the entire soft palate on the left.

There was no obvious mass or any exophytic lesion.

The edges of the soft palate defect were smooth and clean (Figure 1).

There was no cervical, axillary, or inguinal lymphadenopathy.

Findings of the remaining head and neck examinations were normal.Results of laboratory investigations, including lactate dehydrogenase level and autoimmune antibody tests, such as antinuclear antibody and antineutrophil cytoplasmic antibody, were negative.

Screening test results for HIV and Treponema pallidum were also negative.

The only positive result was immunoglobulin (Ig) G for Epstein-Barr virus (EBV).

The IgM for EBV was not detected.Magnetic resonance imaging of the head and neck on short tau inversion recovery sequence confirmed the soft palate defect but also showed some thickening and hyperenhancement around the edges of the defect.

There was no demonstrable nasopharyngeal mass.

The hard palate was intact, and there were no significant cervical lymph nodes.

The patient had biopsies taken from the ulcers and edges of the soft palate defect.


Thyroid function test results were normal, and she did not take thyroid medications.

A relative had received a diagnosis of papillary thyroid cancer at age 50 years.

There was no other pertinent family history, including a history of multiple endocrine neoplasia.

Physical examination showed thyromegaly (right greater than left) with an approximately 5-cm palpable nodule in the right lobe.

There was no tenderness or cervical lymphadenopathy.

Ultrasonography results showed a multinodular goiter with a dominant 4.6-cm right thyroid nodule, 1.6-cm left-sided thyroid nodule, and suspect left level IV lymph node.

Ultrasonography-guided fine-needle aspiration biopsy results showed papillary thyroid carcinoma (PTC) (Bethesda VI) with a BRAFV600E variation in the left nodule and lymph node, and atypia of undetermined significance (Bethesda III) with a suspicious Afirma genomic sequence classifier in the right nodule.

Gross examination of the specimen showed a 2.9-cm pale-tan, partially circumscribed, soft nodule in the right thyroid lobe; a 1.4-cm pale-tan, fibrotic, centrally brown nodule in the left lobe; and a 1.8-cm pale-tan, rubbery, partially circumscribed nodule in the isthmus.

Histologic examination of the right thyroid lesion was performed (Figure), with ancillary testing.A, The right-sided nodule showed an organoid zellballen pattern, with sharp demarcation from thyroid tissue (hematoxylin-eosin).

B, At higher magnification, the tumor cells exhibited amphophilic granular cytoplasm, round to oval nuclei, and salt-and-pepper chromatin (hematoxylin-eosin).

She underwent total thyroidectomy with modified left lateral neck dissection.

There was no prior radiation exposure to the head and neck area.


She did not have any known benign inflammatory conditions.

The patient otherwise felt well and denied malaise, weight loss, or any other symptoms.

Physical examination showed indurated plaques with multiple telangiectasias (Figure, A and B) on almost all the surface of the legs.

Except for slightly elevated C-reactive protein levels, the results of other routine blood and urine tests were unremarkable.

A skin biopsy specimen was obtained for histopathology examination (Figure, C and D).A, Indurated violaceous plaques with multiple telangiectasias on the lower limbs.

C, Histopathologic analysis shows large round cells proliferating within dermal blood vessels (hematoxylin-eosin).

D, Round cells with scanty cytoplasm and prominent nucleoli filling a vessel (hematoxylin-eosin).

B, Prominent telangiectasia on the thigh.


Skin examination showed ichthyosiform brownish plaques on his lower extremities and multiple erythematous confluent papules and plaques on his trunk and face (Figure, A and B).

In addition, painful distal and proximal interphalangeal joints were noted for 2 years, and the patient could not clench his fists.

Uveitis in both eyes was also diagnosed by an ophthalmologist.

Microscopic examination of his hair showed no trichorrhexis invaginata or trichorrhexis nodosa.

A skin biopsy specimen was obtained and submitted for further histopathologic analysis (Figure, C and D).A, Diffuse erythematous papules and plaques with mild scaling and some confluence on the face, neck, and trunk.

B, Ichthyosiform rashes predominantly distributed over the lower extremities.

C, Tissue biopsy results revealed multiple circumscribed nests of granulomas that were infiltrating the dermis and subcutis (hematoxylin-eosin).

D, At higher magnification, histologic findings showed noncaseating granulomas with multinucleated giant cells and neutrophil infiltration in the dermis and subcutis (hematoxylin-eosin).

Topical steroid and pimecrolimus were administered, but their effects were limited.


She reported recent physical and emotional stress from work and dizziness 2 days prior to presentation.

A harmonic, musical systolic murmur was heard at the left third intercostal space.

An electrocardiogram (ECG; Figure 1A) showed diffuse ST-segment elevation, most prominently in the anterior precordial leads.

Laboratory evaluation revealed elevated levels of troponin (1.33 ng/mL; normal range: ≤0.016 ng/mL [to convert to micrograms per liter, multiply by 1.0]), brain natriuretic peptide (376.5 pg/mL; normal range: ≤18.4 pg/mL [to convert to nanograms per liter, multiply by 1.0]), creatinine phosphokinase (96 U/L; normal range: 41-153 U/L), and D-dimer (0.68 μg/mL; normal range: ≤1.00 μg/mL [to convert to nanomoles per liter, multiply by 5.476]).

Echocardiography showed left ventricular (LV) wall-motion abnormalities involving the mid and apical segments and an LV apical mass with protruding features.

Noncontrast computed tomography confirmed the high-density LV mass (Figure 1B).

Coronary angiography revealed mild to moderate coronary atherosclerosis without obstructive coronary artery disease.Noncontrast computed tomography and electrocardiogram obtained on initial admission to the emergency department.

A, Electrocardiogram showing diffuse ST-segment elevation with ST depression in aVR and T-wave inversion in leads V1 to V5, with a QTc interval of 494 milliseconds.

The sweep speed was 25 mm/s and 10 mm/mV.

B, Noncontrast computed tomography shows a high-density mass in the left ventricular apex.