The patient also had a history of lumbar spinal stenosis.

On presentation, blood pressure was 104/73 mm Hg; heart rate, 91/min; respiratory rate, 16/min; and oxygen saturation, 96% on room air.

Physical examination revealed edema to the mid-calf bilaterally, hypoesthesia below the knees, and ankle plantar flexion strength of 3 of 5 based on the Medical Research Council Scale for muscle strength.

Laboratory testing revealed a high-sensitivity troponin level of 52 ng/L (reference, <34 ng/L); brain-type natriuretic peptide, 112 pmol/L (reference, <30 pmol/L); aspartate aminotransferase, 51 U/L (0.85 μkat/L) (reference, 0-35 U/L [0-0.58 μkat/L]); and alanine aminotransferase, 76 U/L (1.27 μkat/L) (reference, 0-45 U/L [0-0.75 μkat/L]).

A chest radiograph showed cardiomegaly without pulmonary vascular redistribution or pulmonary edema.An electrocardiogram revealed normal sinus rhythm, left anterior fascicular block, and down-sloping anterolateral ST segments.

The patient was admitted to the hospital, where electromyography results included reduced amplitude of peroneal nerve action potentials, consistent with axonal sensorimotor polyneuropathy of the bilateral lower extremities.

Coronary angiography showed no coronary atherosclerosis, and cardiac magnetic resonance imaging demonstrated asymmetric left ventricular hypertrophy.

Results of serum protein electrophoresis (SPEP) and serum free light chain testing were normal.

A bone scintigraphy scan using technetium Tc 99m–labeled hydroxymethylene diphosphonate demonstrated increased cardiac uptake (Figure).Anterior (left) and posterior (right) bone scintigraphy scan of the patient.


Her medical history was unremarkable.On examination, her best-corrected visual acuity measured 20/60 OD and  20/25 OS.

The anterior segment showed dilated corkscrew conjunctival vessels (Figure 1), a shallow anterior chamber in the right eye, and nuclear cataract in both eyes.

Pupillary reaction and color vision were normal in both eyes.

Intraocular pressure was 16 mm Hg by Goldman applanation tonometry in both eyes.

Gonioscopy revealed an occludable angle in the right eye without evidence of blood in the Schlemm canal.

Both eyes’ extraocular movements were full and free in all directions of gaze.


A few days before surgery, she noticed a sudden decrease in her left visual acuity measured at 20/80.

Her eye specialist then observed a reverse pupillary block in her left eye and referred the patient to our department.

Slitlamp examination showed a unilateral deepening of the anterior chamber associated with signs of anterior uveitis (ie, keratic precipitates and severe aqueous flare, 3+) and posterior synechiae between the iris and the lens.

In addition, fundus examination revealed an inferior retinal detachment without any associated visible tear.

Intraocular pressure was 15 mm Hg in the right eye and 9 mm Hg in the left eye.

Anterior segment optical coherence tomography images and fundus photographs of both eyes are shown in Figure 1.While anterior segment optical coherence tomography (AS-OCT) and fundus imaging were unremarkable for the right eye, the left anterior chamber was substantially deepened with a backbowing of the iris and an apposition to the lens, leading to a disappearance of the posterior chamber on AS-OCT scan.

An inferior retinal detachment without any associated visible tear was present in the left eye (white arrowheads).

At presentation, no other remarkable medical history was recorded and no precipitating factors identified.


He received nivolumab (anti–programmed cell death 1 checkpoint inhibitor) 9 months prior, obinutuzumab (B-cell lymphoma 2 inhibitor) 3 months later, and 5-mg oral prednisone daily.

On presentation, nivolumab and obinutuzumab treatment was complete.His visual acuity was 20/125 OD and 20/50 OS.

At this time, the active anterior and vitreous cells had resolved.However, 2 weeks later, visual acuity decreased to count fingers in his right eye and hand motions in the left eye.

Ophthalmoscopy revealed bilateral panuveitis with diffuse pigmentary abnormalities.

Fluorescein angiography showed diffuse retinal pigment epithelium loss and late staining of the retinal lesions.

The anterior and vitreous chambers had grade +0.5 pigmented cells.

The ophthalmoscopic examination showed a leopard-spot pattern (Figure 1), and optical coherence tomography showed substantial retinal pigment epithelium and outer retinal layer loss.

Repeat testing for Treponema pallidum, Lyme disease, and HIV was negative.

Results of magnetic resonance imaging of the brain and orbit were negative for leukemic infiltration.A, Ultra-widefield fundus photograph of the right eye showing pigmentary abnormalities (arrowhead) within and peripheral to the macula.

He received 60 mg of oral prednisone daily for 2 weeks with a planned 10-week taper.

However, prednisone was discontinued due to positive Lyme disease exposure 6 weeks later.

A red-free image is depicted in the bottom left corner of the panel.

B, Ultra-widefield fundus autofluorescence image of the right eye showing hypoautofluorescent (pink arrowhead) and hyperautofluorescent patches (blue arrowhead) within and peripheral to the macula.


The patient experienced left jaw tightness, aural fullness, and facial discomfort.

The MRI results demonstrated a well-circumscribed, ovoid mass in the left prestyloid PPS that measured 12 × 15 × 22 mm.

The lesion was isointense on T1-weighted imaging, was hyperintense on T2-weighted imaging, and demonstrated heterogeneous enhancement following gadolinium administration (Figure 1).

A computed tomography–guided fine-needle aspiration was performed, which demonstrated blood, fibrin, and rare mesenchymal cells.

Histopathologic evaluation demonstrated a well-circumscribed, 12-mm mass.Magnetic resonance imaging of the face.

A, Coronal section from a T2-weighted image demonstrates a hyperintense mass in the left parapharyngeal space (PPS).

B, Axial section from a postcontrast T1-weighted image shows a heterogeneously enhancing mass in the prestyloid PPS.

Given her ongoing symptoms, the patient requested surgical resection.

The patient underwent transoral robotic surgery for resection of her PPS mass to achieve definitive diagnosis and treatment.


She was receiving oral antidiabetic agents, and her blood glucose level was 110 mg/dL (to convert to millimoles per liter, multiply by 0.0555).

There was no history of prior COVID-19 infection.

Physical examination findings were consistent with left lower-motor-neuron type of facial nerve palsy.

She was conscious and well oriented, with no other relevant clinical signs or focal neurological deficits.

Magnetic resonance imaging (MRI) of the brain was requested, with clinical suspicion of metastasis in view of mildly elevated CA125 levels.The results of MRI of the brain did not reveal any neuroparenchymal or meningeal lesions.

However, both maxillary sinuses showed mucosal thickening, which was intermediate to hypointense on T2-weighted imaging and hypointense on T1-weighted imaging with postcontrast enhancement.

Computed tomography sections confirmed bony destruction with foci of remodeling involving the walls of the maxillary sinuses (Figure 1).A, Axial T2-weighted magnetic resonance imaging (MRI) shows T2 heterogeneous soft tissue in the maxillary sinus with perimaxillary inflammatory changes (yellow arrowhead).

B, In this axial contrast-enhanced, T1-weighted (T1 + C) image, linear enhancement corresponds to expected course of buccal branch of facial nerve (VII) (white arrow).

The enhancement extends medially and involves the mandibular branch of the trigeminal nerve (V3).

P indicates parotid gland, and the yellow dashed line outlines the edge of the parotid gland.

B and C, The white arrow shows the intercommunication between the auriculotemporal branch of V3 and the intraparotid facial nerve (green marker).

C, Additionally, involvement of enhanced thickening is seen up to the left foramen ovale, without involvement of the trigeminal ganglion.

D, In oblique sagittal images, the thick enhancing branches of the facial nerves within the left parotid gland are seen (orange arrows).

The enhancement of facial nerve extends up to the stylomastoid foramen (SMF) (blue arrow), and there is subtle enhancement along its mastoid segments (MSs).

Iodinated contrast medium was used.Fat stranding and enhancing soft tissue was seen in the retroantral spaces bilaterally as well as the pterygopalatine fossae.

Anteriorly, enhancing soft tissue was present in premaxillary space, from which contiguous linear enhancement was seen extending to left parotid gland—along the expected course of buccal branch of left facial nerve.

The entire extracranial left facial nerve proximal to this showed diffuse enhancement and thickening.

Associated stylomastoid foramen widening was present with subtle enhancement along its mastoid and tympanic segments.

These features were compatible with perineural extension of disease (Figure 1A and B).Additionally, there was involvement of the mandibular branch of the trigeminal nerve via intercommunication between the auriculotemporal branch of trigeminal nerve and the intraparotid facial nerve.

Diffuse enhancement and thickening was seen up to the left foramen ovale, without involvement of the trigeminal ganglion (Figure 1C and D).

She was diagnosed as having recurrent high-grade serous cystadenocarcinoma of the ovary and developed these symptoms after cycle 4 of chemotherapy.


Overall, he was in good health with no underlying systemic diseases.

The intraoral examination revealed an erythematous denuded area of the midline posterior dorsal tongue, with a central nodular component (Figure 1A).

The nodule was firm to palpation and nontender.

The patient was asymptomatic and unaware of the lesion prior to it being discovered by his dentist.

Results of the most recent serologic analysis and urinalysis were also reportedly within normal limits.The extraoral examination was unremarkable, with no skin lesions, asymmetry, redness, swelling, or lymphadenopathy observed.

The remaining oral soft tissue was unremarkable.

Because a biopsy specimen was already obtained, blank slides were requested from the aforementioned institution, and staining was performed in house.A, Clinical examination revealed a pink nodule in the midline dorsal tongue with surrounding atrophic papillae.

B, Hematoxylin-eosin stain of the biopsy specimen showed acellular, amorphous, and eosinophilic material arranged in lobules.Histologic evaluation revealed a piece of soft tissue with normal overlying epithelium.

In the connective tissue, acellular, amorphous, and eosinophilic material arranged in lobules was noted (Figure 1B).

He underwent incisional biopsy at another institution and presented for a second opinion on the diagnosis.


He denied any history of trauma, falls, or occlusive headgear use.

His medical history was significant for atrial fibrillation, receiving anticoagulation medication, and heart failure.On physical examination, numerous nontender violaceous plaques were seen on the forehead and scalp of the patient (Figure, A).

On full skin examination, nonspecific skin-colored plaques were noted on the chest, and a 1.8 × 2.5-cm erythematous plaque was noted on the left lower back.

There was no appreciable lymphadenopathy or hepatosplenomegaly.

Peripheral blood test results revealed a hemoglobin level of 9.1 g/dL, a platelet count of 68 × 103/μL, a white blood cell count of 2800/μL, and an absolute neutrophil count of 1.0/μL.

Lactate dehydrogenase level was 202 U/L.

A 4-mm punch biopsy was performed on the erythematous plaque on the left lower back (Figure, B and C).A, Violaceous plaques on the scalp.

B, Punch biopsy showing a grenz zone and infiltrate extending into deeper dermis (hematoxylin-eosin).

C, Punch biopsy showing cellular infiltrate of basophilic blastoid cells (hematoxylin-eosin).

D, Punch biopsy showing cellular infiltrate with CD123 staining.

(To convert hemoglobin to g/L, multiply by 10.0; platelets to ×109/L, by 1; white blood cell and neutrophil counts to ×109/L, by 0.001; and lactate dehydrogenase to μkat/L, by 0.0167.)


In the previous month, he had received the first cycle of a chemotherapeutic regimen of ixazomib, lenalidomide, and dexamethasone to treat a recurrence of IgG-κ multiple myeloma with a 10-year history.

Physical examination showed annular erythematous plaques of up to 2 cm in diameter, with violaceous and crusted centers on the neck and trunk.

On the right chest, an annular erythematous lesion with 2 zones of color—a central area of purpura and an outer erythematous and edematous ring—was present (Figure, A).

Laboratory investigations found pancytopenia: a white blood cell count of 2.3 × 103/μL (reference range, 3.5-9.8 × 103/μL), hemoglobin levels of 12.1 g/dL (reference range, 13.5-17.6 g/dL), platelet count of 29 × 103/μL (reference range, 130-400 × 103μL), and elevated serum C-reactive protein levels of 3.31 mg/dL (reference range, <0.30 mg/dL).

Granulocyte colony-stimulating factor analogs had not been prescribed to the patient.

Skin biopsy from a lesion on the left chest was performed for histopathological and immunohistochemical analyses (Figure, B-D).A, Clinical image of annular erythematous plaques on the chest.

B, A histopathologic image revealing inflammatory infiltrate of predominantly mononuclear cells in the superficial and mid dermis (hematoxylin-eosin stain).

C, The predominantly infiltrated cells showing large, elongated, vesicular nuclei, single inconspicuous nucleoli, and scant, slightly eosinophilic cytoplasm (hematoxylin-eosin stain).

D, An immunohistochemical image showing myeloperoxidase-positive cells.


He had new-onset daily occipital headache for 1 month of mild to moderate severity and pulsating character.

Occasionally, the headache became severe accompanied by vomiting, photophobia, and phonophobia.

The child had 4 to 5 episodes of generalized tonic-clonic seizures 1 day prior to admission.

He remained unconscious for several hours and spontaneously regained consciousness over 24 hours.

There was no history of fever, weight loss, limb weakness, vision impairment, or any strokelike illness.

His birth and developmental history were unremarkable.On examination, his pulse rate was 80 beats per minute (regular) with all peripheral pulses palpable without any radio-femoral delay.

His blood pressure was 170/110 mm Hg with less than 10 mm Hg difference of systolic and diastolic blood pressure in other limbs.

Abdominal examination revealed abdominal bruit.

Fundus examination revealed papilledema with changes of hypertensive retinopathy.

The cranial nerves, motor, sensory, and autonomic system examination were unremarkable.

There was no evidence of neurocutaneous markers.

His cranial magnetic resonance imaging revealed bilateral white matter hyperintensity that was more marked in the bilateral parieto-occipital region.

Ultrasound of the abdomen revealed a small right kidney and renal Doppler was suggestive of right renal-artery stenosis.

His computed tomography angiography revealed short segment (3 cm) and short circumferential thickening of the descending aorta with right renal artery narrowing (Figure 1).

His repeat cranial magnetic resonance imaging showed significant reduction in the white matter hyperintensities.Maximum-intensity projection computed tomography (CT) angiography abdomen axial section (thickness 7 mm) (A) showing narrowing of whole length of right renal artery and thickened abdominal aortal wall (black arrowhead) and coronal section (B) showing small asymmetrical right kidney and compensatory enlarged left kidney.


He reported no new prescription medications, over-the-counter drugs, or herbal supplements prior to the onset of the exanthem.

He had no history of psoriasis, atopic dermatitis, or other skin disorder, and no recent viral or bacterial infection.

The patient had no fever, night sweats, fatigue, recent unintentional weight loss, shortness of breath, chest pain, nausea, vomiting, or diarrhea.

On presentation, his temperature was 37.1 °C (98.7 °F); blood pressure, 128/86 mm Hg; heart rate, 110/min; and respiratory rate, 30/min.

Physical examination revealed confluent salmon-colored plaques composed of folliculocentric scaly papules across his body with several patches of unaffected skin on his trunk.

The patient had waxy, exfoliative scale on the volar aspect of his hands and feet and thickened, onycholytic nails.

Severe ectropion prevented complete eyelid closure (Figure).

He was referred to the emergency department, where laboratory testing revealed a normal complete blood cell count and normal lactate dehydrogenase level.

The patient was admitted to the hospital and was treated with intravenous fluids and daily wet-wrap therapy with topical triamcinolone ointment (0.1%) applied to his trunk, arms, and legs, followed by a layer of warm, damp gauze and dry, cotton pajamas.Clinical examination at the time of presentation revealed generalized and coalescing salmon-colored plaques with “islands of sparing” on the abdomen (far left); waxy, exfoliative scale on the palms (center left) and soles (center right); and ectropion (far right).


He reported no prior lingual discoloration and did not smoke cigarettes, use chewing tobacco or illicit drugs, or drink alcohol.Elongated filiform papillae and black discoloration of patient’s tongue.

He had tenderness to palpation and decreased range of motion of his right shoulder.

One week after hospitalization, the patient developed asymptomatic black discoloration of the dorsal surface of his tongue (Figure).

His temperature was 37.9 °C (100.2 °F); heart rate, 74/min; and blood pressure, 90/49 mm Hg.

Laboratory testing showed a white blood cell count of 9.6 ×  109/L (reference, 4.0-9.0 × 109/L); C-reactive protein level, 35.6 mg/dL (reference, <0.3 mg/dL), and creatine kinase level, 1036 U/L (17.30 μkat/L) (reference, 60-270 U/L [1.00-4.51 μkat/L]).

Magnetic resonance imaging revealed an effusion and synovial thickening with enhancement in the right shoulder joint and inflammation in the right subscapularis muscle.

Gram stain of the synovial fluid revealed gram-positive cocci in clusters.

Intravenous cefazolin therapy was initiated, and he underwent right shoulder joint arthroscopic irrigation, synovectomy, and surgical drainage for subscapularis pyomyositis.

Blood and synovial fluid cultures grew methicillin-susceptible Staphylococcus aureus, and intravenous cefazolin was continued.


She was otherwise healthy with no history of recurrent pharyngitis.On examination, her vital signs were within normal limits.

Her parents noted the lesion 18 months prior.

It remained stable in size and was asymptomatic.

She denied sore throat, dysphagia, and dyspnea.

She was comfortable with no noted stridor and tolerated her oral secretions.

Her oropharyngeal examination was notable for size 2+ palatine tonsils without exudate and a white mass on the posterior tonsillar pillar.

She did not tolerate palpation of the lesion.

There was no palpable cervical adenopathy, and her lungs were clear to auscultation.

B and C, A keratinizing squamous epithelium with Actinomyces colonization was found overlying pilosebaceous units including hair follicles, arrector pili muscles, and sebaceous glands (hematoxylin-eosin stains).Gross examination revealed a 2.2 × 1.1 × 0.7-cm, pink-tan to purple, rubbery lesion.

Histologic examination demonstrated both ectodermal and mesodermal components.

A keratinizing squamous epithelium with Actinomyces colonization was found overlying pilosebaceous units including hair follicles, arrector pili muscles, and sebaceous glands (Figure, B and C).

The core of the lesion comprised adipose and fibrous tissue.

The stalk was covered with acanthotic squamous epithelium, and the base contained embedded salivary glands.

No laboratory work or imaging were performed.The patient was taken to the operating room for an excisional biopsy.

There, a more thorough gross examination of the lesion was notable for a pedunculated, white rubbery mass arising from the left posterior tonsillar pillar with a narrow mucosal stalk (Figure, A).A, Pedunculated, white rubbery mass arising from the left posterior tonsillar pillar with a narrow mucosal stalk.


Her medical history included Leber congenital amaurosis treated with voretigene neparvovec (Luxturna; Spark Therapeutics) 8 years ago, and acute myeloid leukemia (AML) diagnosed 6 months prior to presentation treated with cytarabine and idarubicin.

She also reported rhinorrhea and lethargy.

A complete blood cell count was ordered, revealing anemia, neutropenia, lymphocytopenia, and monocytopenia in the setting of recent chemotherapy.

Blood cultures were drawn, and results were pending at the time of presentation.Her ophthalmic examination showed visual acuity of 20/800 OD and 20/400 OS, decreased from her baseline of 20/200 OU.

Intraocular pressures were 37 mm Hg OD and 31 mm Hg OS.

Slitlamp examination revealed chemosis, conjunctival hyperemia, and microcystic corneal edema bilaterally.

There were more than 20 cells per high-power field of 1 mm × 1 mm beam, with fibrin bilaterally and 2.5-mm hypopyon in the right eye and 2.7-mm hypopyon in the left eye (Figure 1).

Her latest chemotherapy was 3 weeks before presentation, and a peripherally inserted central catheter (PICC) was removed 2 weeks ago.


Her medical history included esophageal atresia, small bowel obstruction, mild cognitive impairment, low tone, and increased reflexes.

Prenatal history was complicated by insulin-controlled gestational diabetes and polyhydramnios.

Her ocular history was notable for eye movement abnormalities since birth.

She had no family history of ocular disease.On examination, her visual acuity was 20/150 OU and did not improve with correction (right eye, −1.50 [2.00] × 180; left eye, −1.00 [1.50] × 180).

Alternating vertical and torsional nystagmus was noted (Figure 1).

Specifically, 1 eye was noted to rise and intort while the other would fall and extort, followed by reversal of the vertical and torsional components in the opposite eye (Video).

The optic nerve and foveal reflexes were normal in both eyes.

Flash visual evoked potential (VEP) demonstrated strong ipsilateral activity of the occipital lobe.

Results of a previously obtained brain magnetic resonance imaging (MRI) scan were reported as normal.


Four years earlier, he started taking lenalidomide, 10 mg/d (28-day cycle), to treat worsening anemia; after 2 cycles of treatment, he became transfusion independent.

Since then, he has remained stable with the same dose and schedule of lenalidomide without significant adverse effects.

Additionally, the patient also had hypertension and hypercholesterolemia for which he was taking lisinopril and simvastatin, respectively.

The presenting skin lesions developed 1 month before presentation and began as small pustules that rapidly transformed into painful ulcers.

Thus, he was transferred to our facility.Physical examination showed multiple cutaneous ulcers with gray undermined borders and red papules of varying depths involving the chest, back, and upper extremity; lesions were as large as 9 × 15 cm.

A complete blood cell count showed a white blood cell count of 16.2 × 103/μL (to convert to 109/L, multiply by 1.0) with an absolute neutrophil count of 12.7 × 103/μL, hemoglobin level of 9.4 g/dL (to convert to g/L, multiply by 10.0), and platelet count of 262 × 103/μL with no circulating blasts.

Results of additional laboratory studies, including blood culture and tests for herpes zoster virus (via polymerase chain reaction), antinuclear antibody, rheumatoid factor, and antineutrophil cytoplasmic antibody were all negative.

Pathologic sampling from skin lesions demonstrated a dense dermal infiltrate with predominantly neutrophils along with reactive histiocytes, fibroblasts, and angioplasia (Figure, A).

Immunohistochemical staining showed myeloperoxidase-positive neutrophils (Figure, B), histiocytic markers (CD43, CD63, CD168), and CD117-positive mast cells, but no immature myeloid precursors.

Results of Grocott-Gomori methenamine silver staining were unremarkable.A, Hematoxylin-eosin staining shows polymorphonuclear neutrophils admixed with scattered histiocytes and vasculatures with a prominent endothelial lining.

He was treated with valacyclovir for a presumed diagnosis of shingles, but the lesions did not improve.

Cultures from the surgical specimen grew methicillin-resistant Staphylococcus hemolyticus.

However, the lesions continued to worsen despite vancomycin and additional debridement.

Because of suspected necrotizing fasciitis, he underwent incision and drainage of the lesions.


Her medical history was notable for end-stage kidney disease requiring a kidney transplant at age 50 years and a second transplant at age 65 years.

She had received her medical care at outside facilities, the records of which were not available.

She could not recall being given any precise diagnosis but reported having proteinuria since age 7 years.

Her other medical conditions included hyperlipidemia, arterial hypertension, and pulmonary Mycobacterium avium complex infection.

She had 2 healthy adult children.One year after the first kidney transplant, she noted an inferior visual field defect in the left eye and was diagnosed with nonarteritic anterior ischemic optic neuropathy.

Color vision was 14/14 plates for each eye.

There was a left relative afferent pupillary defect.

Confrontation visual field was full for the right eye and demonstrated an inferior defect for the left eye.

External and slitlamp examinations were notable only for bilateral pseudophakia.

Both optic discs were anomalous in appearance, with central excavation in the left eye greater than the right eye (Figure).

The remainder of the posterior pole examination, including the retinal vessels, appeared normal in both eyes.The right optic disc is dysplastic, with a subtle appearance of the peripheral location of blood vessels emanating from the central disc.

There is a central excavation of the left optic disc, with peripherally located blood vessels and the absence of central vessels.

She was taking tacrolimus, amlodipine, atorvastatin, ethambutol, rifampin, and clarithromycin.

Several years later, she underwent uncomplicated bilateral cataract procedures.Visual acuity with distance correction was 20/25 OD and 20/30 OS.


Skin examination revealed a 5-mm bright pink, dome-shaped papule with overlying vessels located at the crown of the scalp (Figure, A).

There was no purulent discharge or overlying skin changes.

B, Hematoxylin-eosin staining of the lesion from biopsy.

Scanning magnification demonstrates dermal-based tumor cells arranged in a vague nodular configuration.

C, Proliferation of tumor cells is present around small vessels with scattered mitoses (black arrowhead) and necrosis (yellow arrowheads) (hematoxylin-eosin).

A shave skin biopsy was performed and submitted for histopathologic analysis (Figure, B-D).A, Bright pink, dome-shaped papule of the scalp crown with overlying vessels measuring 5 mm.


No triggers, such as local infection, insect bite, or trauma, occurred before the appearance of the lesions.

She denied fever, weight loss, or fatigue.

Physical examination showed multiple firm, nonscaly, purple erythematous patches and plaques with irregular borders on her left axilla, medial upper arm, and lateral thoracic region (Figure, A).

No extracutaneous involvement was observed.

A skin biopsy specimen was obtained from the left side of her chest for histopathological examination (Figure, B and C).A, Multiple nonscaly, erythematous-violaceous patches and plaques with irregular borders on the patient’s left axilla, medial upper arm, and lateral thoracic region.

B, Irregularly branched, thin-walled blood vessels dissecting through collagen bundles within the superficial to mid dermis (hematoxylin-eosin).

C, Irregularly branched, thin-walled blood vessels with plump endothelial cells dispersed between thickened collagen bundles without signs of atypia (hematoxylin-eosin).

D, Endothelial cells positive for cluster of differentiation (CD) 31 (CD31).


On admission, vital signs showed blood pressure as 98/66 mm Hg while receiving dobutamine and norepinephrine from the referral hospital, a regular heart rate of 90 beats per minute, a respiratory rate of 22 breaths per minute, peripheral oxygen saturation 96% nasal oxygen at 3 L per minute, and a temperature of 36.7° C. Echocardiography showed reduced left ventricle systolic function (estimated ejection fraction, 34%) and hypokinesia of the anteroseptal, anterior, anterolateral, and septal walls.

Lung ultrasound demonstrated multiple B-lines in both lung fields.

Diagnostic coronary angiography revealed a total occlusion in the left main coronary artery.

Chest radiography during the loading dose of amiodarone showed infiltrates in both lung fields (Figure 1A).

Chest computed tomography showed a reticular pattern predominantly in the perihilar area with consolidation and diffuse ground-glass opacity in both lung fields (Figure 1B).

In addition, hemodynamic evaluation and lung ultrasound showed no congestion and laboratory markers, including a procalcitonin level of 0.01 ng/mL, and ruled out an infectious etiology.

Percutaneous coronary intervention (PCI) was successful in opening the osteal left main and drug-eluting stents were placed in the left main and left anterior descending arteries.Following PCI, the patient had episodes of supraventricular tachycardia and atrial fibrillation with a rapid ventricular response.

Electrical cardioversion was performed and a loading dose of amiodarone was administered.

While in the intensive cardiovascular care unit, maintenance doses of amiodarone were continued because of episodes of paroxysmal supraventricular tachycardia, ventricular tachycardia, and torsaded de pointes.

On the third day of hospitalization, despite adequate diuresis, the chest radiography showed persistent pulmonary edema.


She was otherwise in excellent health and not taking any medications.

She had no family history of syncope or sudden death.

She described several other episodes occurring at rest over the past several weeks.

She denied palpitations, chest pain, and shortness of breath.

Her vital signs and physical examination were unremarkable.

The initial electrocardiogram (ECG) results were normal, but premature ventricular contractions (PVCs) were noted on telemetry.

Shortly thereafter, 2 episodes of fast polymorphic ventricular tachycardia (PVT), 30 minutes apart, were recorded, both lasting less than 4 seconds (Figure 1A).

Laboratory test results including serum potassium and magnesium as well as 3 serial troponin levels were normal.

Echocardiography showed normal left ventricular systolic function without wall motion abnormalities or valvular abnormalities.

Coronary angiography showed a 50% stenosis of the left circumflex artery.

Instant wave-free ratio across the stenosis was 1.0.A, A continuous rhythm strip showing a short episode of polymorphic ventricular tachycardia (PVT), which is initiated by a short-coupled premature ventricular contraction (PVC) identical in morphology and coupling interval to the PVC occurring a few beats earlier.

B, A subsequent electrocardiogram (ECG) showed frequent short-coupled premature ventricular contractions.


She reported no hematemesis, hematochezia, or melena and had no history of abdominal surgery.

On physical examination, her abdomen was distended, tympanic, and slightly tender to palpation diffusely.

On admission to the emergency department, she was afebrile, her blood pressure was 80/60 mm Hg, and heart rate was 122/min.

Blood testing showed a white blood cell count of 10 450/μL (84.1% neutrophils); C-reactive protein level, 9.5 mg/dL; potassium level, 3.0 mEq/L (reference, 3.6-5.2 mEq/L); and creatinine level, 5.57 mg/dL (429.39 μmol/L, up from a baseline level of 0.80 mg/dL [70.72 μmol/L]).

Sodium and liver function values were normal.In the emergency department, she received a 500-mL bolus of intravenous crystalloid fluid and 1 g of intravenous ceftriaxone.

A nasogastric tube was placed and initially drained 300 mL of biliary fluid.A non–contrast-enhanced abdominal computed tomography (CT) scan was performed (Figure 1).Left, Abdominal computed tomography scan showing a thickened gallbladder with air and gallstones adherent to the duodenum, with a suspected fistula tract.


She was a farmer in rural Japan who did not drink alcohol and had been diagnosed with bullous pemphigoid 8 months prior, initially treated with prednisolone (15 mg daily).

Her medications at presentation were prednisolone (8 mg daily) and lansoprazole.

She had experienced 1 episode of dyspnea on exertion 2 weeks before presentation but reported no fevers, cough, wheeze, nausea or vomiting, hematochezia, or melena.

In the emergency department, her temperature was 37.7 °C (99.9 °F); blood pressure, 110/56 mm Hg; heart rate, 125/min; and oxygen saturation, 95% on room air.

On physical examination her lungs were clear to auscultation, and her abdomen was diffusely tender to palpation without rebound.

Skin examination revealed purpuric macules and small thumbprint-like patches on the upper abdomen and central chest (Figure 1).Purpuric macules and thumbprint-like patches (arrowheads) on patient’s upper abdomen and central chest.Laboratory testing showed white blood cell count, 13 600/μL (89.9% neutrophils, 0.2% eosinophils); hemoglobin, 10.9 g/dL; serum sodium, 130 mEq/L (reference, 138-145 mEq/L); creatinine, 0.82 mg/dL (72.49 μmol/L); aspartate aminotransferase, 55 U/L (0.92 μkat/L) (reference, 13-30 U/L [0.22-0.50 μkat/L]); alanine aminotransferase, 54 U/L (0.90 μkat/L) (reference, 7-23 U/L [0.12-0.38 μkat/L]); and erythrocyte sedimentation rate, 31 mm/h (reference, 3-15 mm/h).

Platelet count and prothrombin time were normal.


The patient was taking systemic immunosuppression but recently stopped taking maribavir because of concerns about resistance and was transitioned to cidofovir and CMV immune globulin.

On clinical examination, the visual acuity measured 20/25 OD and 20/20 OS.

Motility, visual fields, and anterior segment examination were normal.

Dilated fundus examination revealed tortuous vasculature, multiple cotton wool spots along the arcades and periphery, and granular, hypopigmented retinal lesions without hemorrhage in the macula and temporal periphery in both eyes (Figure 1A).

Optical coherence tomography showed localized areas of full-thickness retinitis (Figure 1B).

CMV titers indicated viremia at 2.24 million IU/mL.

Despite the patient’s documented UL97 and UL54 mutations, a series of 5 biweekly intravitreal injections of foscarnet and ganciclovir were performed given their vision-threatening lesions.


When she was 36 years old, she underwent a hysterectomy due to abnormal uterine bleeding and was taking estradiol to control postmenopausal vasomotor symptoms for the past 20 years.

Bilateral diagnostic mammography revealed a high-density irregular mass in the left axilla with no nodules, architectural distortions, or microcalcifications in the breasts.

Ultrasonography of the left breast showed a 4.6-cm lobulated mixed cystic and solid left axillary mass.

Contrast-enhanced magnetic resonance imaging showed an enhancing 5.2-cm left axillary mass with no breast lesions (Figure 1A).

The biopsy examination indicated high-grade adenocarcinoma with papillary features (estrogen receptor– and progesterone receptor–positive, ERBB2 [formerly HER2]–negative, and a high Ki67 index).

Positron emission tomography/computed tomography revealed only high uptake in the left axilla region.

The patient was treated at an outside hospital with neoadjuvant dose-dense doxorubicin and cyclophosphamide, followed by weekly paclitaxel for 10 weeks.

She then transferred her care to our center for surgical management.

We requested the pathology slides for review at our laboratory and additional immunostaining was performed, which revealed high-grade adenocarcinoma with tumor cells positive for PAX8 (Figure 1B), p53, and WT1 and negative for GATA3.A, Magnetic resonance image of the breasts shows an enhancing 5.2-cm left axillary mass (arrowhead) but no breast lesions.


His parents denied any medical history of trauma, infection, or surgery.

Physical examination showed a 1.3 × 0.7 × 0.6 cm, yellowish, hump-like mass with hairy surface and cartilage-like consistency on the anterior border of the lower third of the left sternocleidomastoid muscle (SCM) (Figure, A).

Ultrasonography revealed a 1.2 × 1.0 × 0.9 cm, hypoechoic, avascular, bulging nodule with an anechoic tubular structure extending to the subcutaneous fat and reaching the surface of the muscular layer.

Magnetic resonance imaging (MRI) demonstrated a protuberant nodule with diffuse, slight hyperintensity on T1WI; and 2 mild hyperintense foci surrounded by hypointense tissue on fat-suppressed T2WI (Figure, B).

The neck mass was completely excised under general anesthesia in the department of pediatric surgery.

Intraoperatively, the mass extended into the anteromedial fascia of the left SCM and did not involve the deeper neck structures.

Postoperative histopathologic analysis showed normal-appearing epidermis, multiple pilosebaceous follicles, abundant adipose tissue, and 2 centrally circumscribed segments of cartilage in the subcutis (Figure, C).

Van Gieson stain highlighted elastic fibers surrounding individual chondrocytes.A, A yellowish hump-like mass with hairy surface on the anterior-inferior third border of the left sternocleidomastoid muscle (SCM).

B, Transverse T2-weighted, fat-suppressed magnetic resonance image (MRI) revealed a nodular bulge with 2 mild hyperintense foci (arrowheads) surrounded by hypointense tissue.

C, Whole-slide hematoxylin-eosin stain showed normal-appearing epidermis, multiple pilosebaceous follicles, abundant adipose tissue, and 2 centrally circumscribed segments of cartilage (arrowheads) in the subcutis (original magnification ×10).


On examination, there was an easily palpable 3-cm firm, fixed, well-circumscribed left supraclavicular mass without overlying skin changes or cutaneous involvement.

She had no other masses, cervical lymphadenopathy, or systemic symptoms.

In workup for this mass, she initially underwent ultrasound imaging, which demonstrated a hypoechoic mass.

Findings from fine-needle aspiration and core-needle biopsy were inconclusive, demonstrating histiocytes.

Magnetic resonance imaging demonstrated a well-circumscribed mass of mainly soft tissue density with contrast enhancement (Figure 1).Magnetic resonance imaging of the left-sided supraclavicular mass.

T2 sequencing with contrast demonstrates strong enhancement of the mass.Given persistence of the lesion, and inconclusive biopsies, the decision was made to pursue surgical excision.

Pathology confirmed complete excision of a well-circumscribed lesion with peripheral casing of bone, cyst-like spaces filled with serous fluid, walls of spindle-shaped fibroblasts, osteoclast-type giant cells, thin trabeculae of woven bone surfaced with osteoblasts, and scattered macrophages.

There was local infiltration into surrounding skeletal muscle, but no atypical mitoses or pleomorphic cells were identified.

The lesion was positive for USP6 locus rearrangement (17p13.2) on florescence in situ hybridization.

In the operating room, a well-defined 5.5-cm left level V mass was excised.

The mass was found to attach deep to the middle scalene and was fed by several unnamed vessels; however, there was no involvement of the clavicle.


He had undergone multiple evaluations by dermatologists and urologists and had not responded to systemic antibiotics and topical corticosteroids.

Physical examination revealed an erythematous, pinpoint orifice on his glans penis, with peripheral telangiectasias and a linear bluish structure on dermoscopy (Figure, A and B).

Ultrasonography revealed a hypoechoic focal zone on the right side of the glans, with multiple hyperechoic bilaminar structures (Figure, C).

A biopsy was performed (Figure, D).A, Clinical image of glans penis with a pinpoint orifice.

B, Dermoscopy reveals an orifice surrounded by peripheral telangiectasias and an extending bluish linear structure.

C, Ultrasonography of the glans penis demonstrates a hypoechoic focal zone in the parenchyma on the right containing multiple hyperechoic bilaminar tracts (arrowheads) (18 MHz; longitudinal view).

D, Hematoxlyin-eosin stain with original magnification ×100.


Medications included insulin lispro (sliding scale 3 times daily) and insulin glargine (20 units nightly).

He reported a tingling sensation in the affected area but no pruritus or pain.

On physical examination, he was afebrile and had normal vital signs.

His extremities were warm with palpable distal pulses.

Hyperpigmented macules were present on the anterior lower legs below the knees, and tense bullae were present on the anterior aspect of the right lower extremity, dorsal foot surface, and toes (Figure).

There was no surrounding erythema or edema, and findings on the remainder of the skin and mucocutaneous examination were unremarkable.

Laboratory testing revealed a blood glucose level of 375 mg/dL (20.81 mmol/L) and hemoglobin A1c level of 9.8%.

Results of a basic metabolic panel and complete blood cell count were within reference range except for mild anemia (hemoglobin level, 10.9 g/dL).Patient's right lower extremity with bullae and hyperpigmented macules and patches, characteristic of diabetic dermopathy (left).

He had no history of leg trauma and no chemical or extreme temperature exposure.


She took no regular medication and did not smoke.At presentation, her visual acuities were perception of light OD and 20/20 OS.

She also reported a 4-week history of right ear pain and fullness, discomfort over her frontal and maxillary sinuses, and nasal congestion without discharge.

Over the past 2 weeks, she had experienced drenching night sweats, cramps in her quadriceps, and weight loss of 3 kg.

She denied respiratory symptoms, headaches, scalp tenderness, or jaw claudication.

There was a right relative afferent pupillary defect.

Dilated fundus examination showed a cherry red spot in the right macula with hyperreflectivity and thickening of the inner retinal layers on optical coherence tomography (Figure 1A and B).

External eye examination results and ocular motility were normal.

Examination by an otolaryngologist revealed normal tympanic membranes and a dry but otherwise normal nasal mucosa on flexible endoscopy.

Blood tests showed leukocytosis (white blood cell count, 15 000 /µL; to convert to 109 per liter, multiply by 0.001) with neutrophilia (white blood cell count, 12 500 /µL), elevated C-reactive protein (19.4 mg/dL; to convert to milligrams per liter, multiply by 10), elevated plasma viscosity (2.06 mPas), and thrombocytosis (467 ×103/µL; to convert to ×109 per liter, multiply by 1).

Kidney function was within normal limits.

Chest radiograph results were unremarkable.False-color and red-free (inset) fundus photograph of the right eye shows retinal pallor (white arrowheads) with a cherry red spot (yellow arrowhead) in the macula (A).


His medical history included hypothyroidism, psoriasis, and recent diagnosis of multiple myeloma, and he was taking daratumumab and zoledronic acid.

Examination of the right eye was notable for visual acuity of 20/50, reduced ocular motility in all gazes, proptosis, and chemosis.

Examination of the left eye was unremarkable.

Computed tomography of the orbits with contrast demonstrated right preseptal edema and intraorbital fat stranding of the extraconal and intraconal fat without sinus disease.

Nasal endoscopy performed by the otolaryngology service showed no evidence of invasive fungal sinusitis.

After 48 hours, motility, proptosis, and chemosis worsened (Figure 1A).A, External photograph of the right eye demonstrating periocular edema, conjunctival injection, and chemosis.

B, Axial T1 fat-suppressed postcontrast magnetic resonance imaging (MRI) demonstrating proptosis of the right eye with optic nerve straightening, diffuse enhancement of the right intraconal and extraconal fat, and periorbital tissues.Magnetic resonance imaging of the orbits with and without contrast (Figure 1B) was remarkable for proptosis with optic nerve straightening, enhancement of the intraconal and extraconal fat, edema and enhancement of the right extraocular muscles, new thickening of the left sphenoid sinus with internal air-fluid level, and new inflammation of the left masticator space.

The patient received a single dose of intravenous vancomycin and ceftriaxone, then was transitioned to ampicillin-sulbactam for presumed orbital cellulitis.

Under guidance from the infectious disease service, antibiotics were broadened back to vancomycin and ceftriaxone with continued worsening.

He denied eye trauma, dental surgery, or sinus disease.

A follow-up computed tomography of the sinus with contrast showed no evidence of osseous structure destruction to suggest invasive fungal sinusitis.


He had undergone laser retinopexy for retinal tears in his right eye and a scleral buckle and vitrectomy for a retinal detachment in his left eye 1 year earlier.

The patient was discharged taking timolol, dorzolamide, brimonidine, and prednisolone.

The patient started treatment with 500 mg of acetazolamide daily and referred to the glaucoma service for surgical evaluation.Ultrasound biomicroscopy of the left eye demonstrating angle closure (arrowheads).When the patient returned for his glaucoma evaluation 3 days later, he was noted to have loss of appetite, drowsiness, nausea, and malaise.

During this visit, the patient developed acute chest pain and respiratory insufficiency requiring immediate transfer to the emergency department.

Best-corrected visual acuity (BCVA) was 20/40 OD and counting fingers OS.

Intraocular pressure (IOP) was 14 mm Hg in the right eye and 44 mm Hg in the left eye.

Anterior segment examination of the right eye was unremarkable, while ophthalmoscopic examination showed vascular attenuation and treated retinal breaks.

In the left eye, microcystic corneal edema and Descemet membrane folds limited examination, but no residual lenticular fragments or neovascularization of the iris or angle were seen.

Twelve days later, the cornea had cleared and IOP in the left eye improved to 32 mm Hg.

Gonioscopy revealed 360° of anterior synechiae and complete angle closure, which was documented on ultrasound biomicroscopy (Figure 1).

The patient’s intraocular examination was stable bilaterally.


She had a history of substantial sun exposure but no history of skin cancer.

The rash had been present for 3 weeks and had recently worsened.

Her disease had progressed after receiving first-line therapy with palbociclib and anastrozole.

Subsequent treatments with fulvestrant and paclitaxel were also followed by progressive disease.

She received treatment with capecitabine; after 6 weeks of treatment, she developed some redness on her hands and feet that resolved on its own.She then presented to the clinic with pruritic, erythematous, scaly macules and papules on her forearms, faces, chest, and upper back (Figure).

The rash did not respond to treatment with topical clindamycin, oral solumedrol, or doxycycline.

She had locally advanced disease that was invading the skin overlying her right breast and metastatic disease to the thoracic and lumbar spine, liver, and mediastinal, axillary, and retroperitoneal lymph nodes.


Her symptoms were initially most prominent while playing sports and were suspected to be due to asthma or seasonal allergies.

More recently, the patient’s parents noted that she developed stridor while sleeping and while at rest, prompting the family to present for medical attention.Previous workup, including pulmonary function testing, was concerning for an upper airway obstructive process, for which she was referred to otolaryngology.

In-office flexible videostroboscopy revealed a mass in the distal cervical trachea that appeared nearly obstructive.

Chest radiography confirmed the presence of an approximately 1.5-cm, well-circumscribed soft tissue mass within the cervical trachea.Direct laryngoscopy and bronchoscopy were performed in the operating room under general anesthesia.

This demonstrated an exophytic, pedunculated mass that emanated from the anterior wall of the cervical trachea (Figure 1A and B).

The patient was intubated via Seldinger technique to bypass the mass, with a 4.0-mm cuffed endotracheal tube loaded over a 0-degree Hopkins endoscope (Figure 1C).

With the airway secured, attention was turned to excision of the mass.

Lidocaine, 1%, with epinephrine 1:100 000 was injected in a submucosal plane, and laryngeal scissors were used to excise the attachment of the mass from the tracheal wall.

The mass was then resected en bloc and removed with laryngeal cupped forceps.

The attachment site was then ablated with the Coblator (Figure 1D).Intraoperative photographs demonstrating supraglottic view of intratracheal mass (A); exophytic, pedunculated mass emanating from the anterior wall of the cervical trachea (B); endotracheal intubation via Seldinger technique bypassing the mass (C); and cervical trachea following ablation of attachment site (D).


Clinical findings suggested unilateral right middle ear effusion associated with ipsilateral conductive hearing loss.

A high-resolution computed tomography scan of the temporal bone showed a lytic aspect of the right temporal bone extending to the petrous apex and the petrous bone, sparing the otic capsule (Figure 1A).

There was soft tissue opacification of the right mastoid air cells.

It showed a hyperintense T2 signal in the petrous apex and mastoid air cells.

Magnetic resonance imaging also showed signs of Chiari malformation type 1.

There was associated soft tissue partial opacification of the right mastoid air cells.

B, Coronal magnetic resonance imaging of the brain and skull base, T2-weighted images showed a hypersignal in the right mastoid and middle ear with suspected communication through the tegmen.

After an initial observation period, a right tympanostomy tube was inserted.

This confirmed the presence of a cerebrospinal fluid (CSF) leak.The patient was referred to our tertiary referral center hospital.

During the procedure, a clear liquid pulsating from the middle ear was noted, and samples were sent for β-2-transferrine analysis.

The leak settled with conservative management, and imaging of the brain and skull base was performed.

Magnetic resonance imaging of the skull base with contrast was performed (Figure 1B).

There was a suspected communication into the soft tissues of the right neck in the posterior triangle.

After a skull base multidisciplinary discussion, the patient underwent a bone biopsy through a transmastoid approach.A, Axial high-resolution computed tomography scan of the temporal bones at the level of the basal turn of the cochlea showed osteolysis involving the petrous part of the right temporal bone.

The destructive process did not involve the otic capsule.

There was also a hypersignal in the soft tissues of the right neck in keeping with extravasation of cerebrospinal fluid in cervical lymphatics.


She had a medical history of essential thrombocytosis (ET), which was treated with hydroxyurea for 14 years, with a total cumulative dose of approximately 2500 g. She was otherwise reasonably well and denied any other constitutional symptoms.

She did have a medical history of nonmelanoma skin cancer (NMSCa), which had previously been treated surgically.

The ulcerations had slowly increased in number and size over several years and were quite painful (Figure, A-C).

Several tangential shave biopsies were performed to help clarify the patient’s diagnosis.A-C, Clinical findings including widespread photodistributed ulcerated pink papules and plaques on the extremities.

D, Histopathologic findings (hematoxylin-eosin stain).


The patient had consanguineous parents, but no other family member, including her children, had the disease.A, Multiple subcutaneous masses in the occipital and bilateral temporal regions.

At 5 years of age, the patient had developed multiple subcutaneous masses in the occipital and bilateral temporal regions.

Tumors recurred 5 years after surgery, with their size and number gradually increasing with age.

Physical examination revealed scalp masses from 4 to 6 cm in diameter, with hard textures and smooth surfaces (Figure, A), and subcutaneous nodules of 1 × 1 cm to 2 × 2 cm with hard textures on the hands (Figure, B), feet, trunk, and lower extremities.

The patient had no tenderness, swelling, or other skin manifestations.

The diameter of the scalp masses varied from 4 to 6 cm, with hard textures and smooth surfaces.

B, Subcutaneous hard nodules on the hands, ranging from 1 × 1 cm to 2 × 2 cm.

C and D, Large amounts of homogeneous eosinophilic hyaline matrix with scattered fibroblasts.

At age 10, she was diagnosed with neurofibromatosis and underwent surgical resection of the tumors at a local hospital.


A head computed tomography showed a 0.9-cm left subdural hematoma with a mild left to right midline shift.

Her ethanol level was 202 mg/dL (to convert to millimoles per liter, multiply by 0.2171); magnesium, 1.7 mg/dL (to convert to millimoles per liter, multiply by 0.4114); potassium, 4.4 mEq/L (to convert to millimoles per liter, multiply by 1); and ionized calcium, 4.6 mg/dL (to convert to millimoles per liter, multiply by 0.25).

Echocardiography demonstrated a left ventricular ejection fraction of 50% and no regional wall motion abnormalities.

Alternans in T-wave polarity is evident in most leads (especially V3-V6) while alternans in T-wave amplitude is seen in leads II and aVF.

She subsequently underwent embolization of the middle meningeal artery.

As a result, on the 11th day of her hospitalization, she had a burr hole evacuation.

The patient developed cardiac arrest due to ventricular arrhythmias in the emergency department and was successfully resuscitated.

After embolization, however, a worsening rightward midline shift was discovered.

During day 15 of admission, the patient had 3 episodes of torsade de pointes (TdP) while receiving 50 mg of metoprolol succinate daily, and her 12-lead electrocardiogram (ECG) is shown in Figure 1.The 12-lead electrocardiogram obtained on day 15 of admission.


However, suddenly, the patient developed acute onset of dyspnea along with retrosternal chest pain.

On physical examination, her pulse was 70 beats per minute, and blood pressure was 110/70 mm Hg.

The cardiovascular examination showed a loud S1, normal S2, and an opening snap along with a mid-diastolic, soft, rumbling murmur at the apex of the heart.

The electrocardiogram showed normal sinus rhythm with left atrial enlargement.

The echocardiogram showed severe mitral stenosis with a mitral valve area of 0.9 cm2 with a mean (SD) gradient of 20 (4) mm Hg.

There was no evidence of any subvalvular thickening, leaflet calcification, or mitral regurgitation.

The patient was taken for balloon mitral valvotomy (BMV).

A 6F pigtail catheter was placed in the left ventricle via the right femoral artery.

The interatrial septum was punctured using a Mullins sheath and Brockenbrough needle via the right femoral vein.

Entry into the left atrium was made and confirmed with a dye injection.

Her blood pressure at the time of the event was 100/60 mm Hg, pulse was 70 beats per minute, and oxygen saturation was 96%.

The catheter was pulled back into the right atrium, and chest fluoroscopy was performed (Figure; Video).The fluoroscopy image of the patient at the time of dyspnea.


Two years ago, she underwent uncomplicated right cataract surgery at a different center.

Her postoperative course had been complicated by persistent low-grade anterior uveitis for which she received maintenance loteprednol, 0.5%, eye drops on alternate days.

Her medical history was only significant for hypertension, which was well controlled with ramipril.

She denied any ocular trauma or recent travel outside of the country.

Review of systems was unremarkable.Slitlamp photographs of the right eye showing 2 darkly pigmented corneal lesions (A) and the location of the lesion on the right corneal endothelium and stroma (B).

The third lesion is covered by the upper eyelid.On examination, her visual acuity was 20/80 OD and 20/20 OS.

Her intraocular pressures measured 17 mm Hg OD and 15 mm Hg OS.

The right sclera and conjunctiva were white with 3 distinct hyperpigmented corneal lesions affecting the corneal endothelium and stroma (Figure 1B).

There were 2+ cells in the anterior chamber and 1+ vitritis.

She also used latanoprost eye drops at night in both eyes for primary open-angle glaucoma.


He previously received failed systemic and radiation therapy for tumor stage mycosis fungoides (MF).

He had received 11 courses of extended beam radiation therapy, including 3 courses of total skin irradiation of 24 to 30 Gy, and focal irradiation to the left posterior thigh and hip/buttock with 2.5/3 Gy to 12.5/24 Gy, respectively, and the right posterior thigh and hip with 2 Gy to 20 and 26 Gy, respectively.

His post-transplant course was complicated by severe chronic graft vs host disease of the skin, eyes, and gut, for which he received systemic corticosteroid therapy, tacrolimus, methotrexate, and long-term extracorporeal photopheresis.

Three years after the HSCT, he developed chronic ulcerations on the hips, back, and arms at the site of previously irradiated tumors, as well as multiple friable, hemorrhagic, and bleeding nodules on bilateral hips and his forearms while receiving treatment with corticosteroids and extracorporeal photopheresis.

In this latest visit, physical examination revealed recurrent hemorrhagic and friable nodules on his left lateral hip and left lateral buttock (Figure 1).

Similar nodules were noted on his right hip and forearm.

The patient underwent repeated debulking and biopsy.

Positron emission tomography (PET) computed tomography (CT) results did not show evidence of visceral or extracutaneous disease.Recurrent hemorrhagic and friable nodules on the left lateral hip.

He underwent several debulking procedures and excision biopsies of the nodules, which revealed granulation tissue on histology.

He was also treated with micafungin, amphotericin B, levofloxacin, dapsone, acyclovir, pentamidine, penicillin VK, and posaconazole.

Seven years before this visit, he underwent a reduced-intensity, matched, unrelated donor, allogeneic hematopoietic stem cell transplant (HSCT).


Active medical issues included hypertension, very poorly controlled type 2 diabetes, hyperlipidemia, tobacco use, and asthma.

Her brother and father both had a history of chronic orbital swelling.

She also reported bilateral rhinorrhea, congestion, and right frontal and temporal headaches.

Vital signs were unremarkable, and examination of the right eye showed moderate chemosis, injected conjunctiva, and periorbital edema.

Both eyes were proptotic, right worse than left.

She had normal bilateral extraocular movements, pupillary light reflexes, and gross vision.

Computed tomography with contrast revealed bilateral ethmoid and frontal sinus opacification and right worse than left orbital fat stranding (Figure 1A).

Magnetic resonance imaging with contrast demonstrated both enlargement and enhancement of bilateral extraocular muscles, especially the right superior rectus (Figure 1B).

Both orbital and nasal cultures grew methicillin-resistant Staphylococcus aureus.

Orbital biopsy showed nodular lymphoplasmacytic infiltrates without evidence of fungal infection or necrosis (Figure 1C).

Further workup revealed elevated erythrocyte sedimentation rate, C-reactive protein, total IgG, and IgG4 levels and normal white blood cell count, thyroid-stimulating hormone, angiotensin-converting enzyme, lysozyme, antinuclear antibody, and antineutrophil cytoplasmic antibody (ANCA) levels.A, Computed tomography with contrast revealed bilateral ethmoid and frontal sinus opacification and right worse than left orbital fat stranding.

Initially she was started on antibiotic therapy.

Right nasal biopsy, right endoscopic sinus surgery, and right anterior superior orbital tissue biopsy were performed.

Intraoperatively, the sinus mucosa demonstrated only edema and mild secretions, but there was no necrosis or purulence.


Four days after treatment, a white head formed overlying the tumor that erupted through the skin surface (Figure 1).

Thin, cloudy discharge that was not foul-smelling drained from the tumor from posttreatment days 5 to 10, at which point the drainage stopped spontaneously.

Laboratory results on days 5, 9, and 14 demonstrated the absence of leukocytosis, and serial wound cultures failed to demonstrate pathogenic growth.

The patient completed the neoadjuvant immunotherapy and underwent a margin-negative tumor resection without intraoperative or postoperative complications.This photo documents clinical tumor behavior after neoadjuvant immunotherapy treatment.

Throughout, the patient reported no pain and remained afebrile.


Since the initial onset, the bruise and pain had persisted despite icing and resting the area.

She denied any personal or family history of bleeding disorders.On examination, an ill-defined indurated blue-green plaque was noted on the dorsum of the left hand (Figure 1).

Radiography results showed soft tissue swelling but were otherwise unremarkable.

Subsequent magnetic resonance imaging showed a heterogeneously fluid hyperintense and T1 heterogeneously hyperintense lesion measuring approximately 1.6 × 0.5 × 2.9 cm that was centered within the dorsal subcutaneous soft tissue of the hand.


She denied any new medications or exposure to chemotherapy, imaging with intravenous contrast, or recent travel.

The rash initially developed on the patient’s legs 13 days before presentation and subsequently progressed to her feet, arms, hands, and trunk.

Associated symptoms included a burning sensation and occasional pain.

On physical examination, there were numerous erythematous edematous coalescing papules and plaques on the upper and lower extremities and scattered erythematous papules and plaques on the back and buttocks (Figure, A).

Some plaques were annular and polycyclic in configuration, with central hyperpigmentation (Figure, B).

A complete blood cell count was notable for an eosinophilia of 11%, with an absolute cell count of 0.80 ×103/uL.

Results from a comprehensive metabolic panel were normal.

A biopsy was performed on her right thigh for histopathological examination.A, Clinical photographs show numerous erythematous edematous coalescing papules and plaques on the bilateral upper and lower extremities.

Her medical history was notable for endometrial adenocarcinoma status post hysterectomy and recent postoperative radiotherapy (total of 50.4 Gy in 28 fractioned doses), which was completed 4 days after the onset of the rash.

The remainder of her review of systems was unremarkable.

Her chest, abdomen, face, and oral mucosa were clear.

B, Some plaques were annular and polycyclic in configuration with central hyperpigmentation.


On arrival to the emergency department, his vital signs were stable.

Serum electrolyte levels were within normal range and C-reactive protein was less than 6 mg/dL (to convert to milligrams per liter, multiply by 10).

High-sensitivity troponin peaked at 1078 pg/mL.

He continued in sinus rhythm with episodes of nonsustained ventricular tachycardia observed on telemetry, as shown in Figure 1B.

Cardiac catheterization revealed patent coronary arteries.

Cardiac magnetic resonance imaging was remarkable for a dilated right ventricle with moderately reduced systolic function and transmural late gadolinium enhancement with akinesis and dyskinesis involving the right ventricular (RV) free wall and outflow tract extending to the left ventricular (LV) anterior, septal, and apical segments.Electrocardiogram (ECG) and telemetry.

He was administered a 150-mg bolus of intravenous amiodarone, which failed to terminate his arrhythmia.

He ultimately required synchronized cardioversion with a biphasic direct current shock of 100 J.

Emergency medical services found him to be in a wide complex tachycardia.

His initial 12-lead ECG is shown in Figure 1A.

A, Twelve-lead ECG on arrival to the emergency department.


He had no history of tobacco, alcohol, or drug misuse.

In the past month, he felt neck stiffness, accompanied by swelling and persistent dull pain of the upper anterior chest wall, which could be transiently relieved by taking oral ibuprofen.

Six days before admission, the patient’s neck stiffness transited to an endurable dull ache.

When turning his head, there was severe burning pain in the posterior neck and occiput, followed immediately by an electric shocklike numbness on ipsilateral side tongue, which led to a forced head position.

In the past 3 days, with the intensification of neck pain, the patient found pustules on both hands, which gradually increased.

Magnetic resonance imaging of the cervical spine with gadolinium on admission revealed signal abnormality in C1/C2 vertebrae (Figure 1A).

There was tenderness in the right sternoclavicular articulation, upper neck, post aurem, and occiput.

Multiple pustules were seen in the palm and back of both hands (Figure 1B).

Complete blood cell count and liver and kidney function yielded normal results, except for elevated erythrocyte sedimentation rate (ESR) of 93 mm/h and C-reactive protein (CRP) level of 5.5 mg/dL (to convert to milligrams per liter, multiply by 10).

Results of workup for rheumatic and infectious disease, including antinuclear, antineutrophil cytoplasmic and anticardiolipin antibodies, human leukocyte antigen B27, repeated blood cultures, rapid plasma reagin test, Aspergillus galactomannan antigen, brucella, Mycobacterium tuberculosis, and rickettsial antibodies, were all negative.

Cell count, protein, and glucose in cerebrospinal fluid were normal.

Cultures of cerebrospinal fluid revealed no organisms.

Whole-body fluorodeoxyglucose–positron emission tomography/computed tomography revealed no malignancy.Abnormal enhancement of C1/C2 vertebrae with prevertebral and retrodental tissue as well as of the anterior vertebrae at C4/C5 with hyperostotic anterior osteophytes on magnetic resonance imaging (MRI) (A) and multiple pustules on the palm (B).


He was taking no regular daily medications, did not smoke cigarettes, and had no history of oral trauma.

Over the prior 6 months, he reported sexual contact with 1 male partner.

The patient reported no sore throat, dysphagia, hoarse voice, cough, dyspnea, nausea, vomiting, headache, fever, night sweats, weight loss, rash, or genital, rectal, or oral ulcers over the past 6 months.

Physical examination revealed irregular gray-white ulcers with a surrounding erythema on the soft palate, uvula, and tonsils (Figure 1) and nontender bilateral submandibular lymphadenopathy.

His tongue was of normal appearance, and he had no skin lesions or mucosal erosions in the anal or genital areas.Patient presentation showing irregular gray-white pseudomembranous ulcerated plaques on an erythematous base on the soft palate, uvula, tonsils, and posterior pharynx.

These findings developed over the prior week and did not improve after treatment with 3 days of oral cefuroxime.

The white appearance on the tongue is a cotton swab.


His family history was significant for non-Hodgkin lymphoma (mother) and leukemia (mother and maternal grandfather).

He reported intermittent dull pain in his left eye for 1 month that improved with acetaminophen.

On examination, his best-corrected visual acuity was 20/25 OD and 20/200 OS, limited by keratoconus.

Extraocular movements were full, there was no relative afferent pupillary defect, and intraocular pressures were 13 mm Hg OD and 11 mm Hg OS.

Anterior segment examination demonstrated keratoconus with corneal scarring in both eyes and Descemet folds in the left eye.

There were no signs of anterior segment or vitreous inflammation.

Ophthalmoscopic examination revealed an amelanotic area of choroidal thickening (confirmed by optical coherence tomography) overhanging the inferonasal margin of the optic disc with associated subretinal fluid and scattered areas of hyperpigmentation (Figure 1A).

There was an additional, subtle amelanotic elevated lesion under the fovea.

Fundus autofluorescence demonstrated hyperautofluorescence in a leopard-spotting pattern (Figure 1B).

Indocyanine green angiography revealed hypocyanescent lesions inferonasal to the disc and at the fovea.A, Montage color fundus photograph of the left eye demonstrating a 14 × 12 × 2.0-mm nasal peripapillary lesion with mottled overlying areas of hyperpigmentation (arrowheads).


On examination, best-corrected visual acuity was 20/20 OU and intraocular pressures were normal in both eyes at 10 mm Hg.

Slitlamp biomicroscopy of the anterior chamber was within normal limits in both eyes.

Dilated fundus examination revealed normal findings in the right eye and clear vitreous with a subretinal mass in the left eye inferior to the optic disc and measuring 3 × 2 mm in base.

Color fundus photography of the left eye (Figure, A) showed an amelanotic lesion under the retina inferior to the optic disc and 3 mm from the foveola surrounded by a subtle orange halo.

Fundus autofluorescence (Figure, B) showed the lesion to be hyperautofluorescent.

Optical coherence tomography (OCT) imaging of the lesion showed the mass was primarily in the sclera and pushed and thinned the overlying choroid (Figure, C).A, Color fundus photography of the left eye showing a 3 × 2-mm yellow lesion with orange halo 0.5 mm inferior to the optic disc.

B, Fundus hyperautofluorescence of the lesion.


He had a history of metabolic syndrome treated with antihypertensives and oral hypoglycemics.

He had noticed the rash a few days after receiving the second dose of an mRNA COVID-19 vaccine (Moderna).

He denied itching, weeping, bleeding, or discharge from the rash or the nipple.

The physical examination showed a morbidly obese White man.The skin examination showed a 19 × 10-cm pink, fallacious purple color deep-infiltrated papule in the left breast and a similar 15 × 7-cm papule under the left clavicle (Figure, A).

The breast examination was notable for bilateral gynecomastia and inverted left nipple without any palpable lumps.

His laboratory results showed stage 2 chronic kidney disease.

Results of a viral panel including hepatitis A, B, and C and HIV were negative.

The punch biopsy of the skin showed a diffuse island of atypical cells in the dermis (Figure, B).

On immunohistochemical staining, the atypical cells stained positive for CK-7, GATA-3, and PAX-8 (weak focal staining) and negative for estrogen receptor (ER)/progesterone receptor (<1%), TTF-1, SATB-2, CDX-2, and NKX-3.1.

The positron emission tomography–computed tomography scan showed a diffuse, infiltrating fluorodeoxyglucose (FDG)-avid cutaneous lesion on the left chest wall (standardized uptake value, 6.5) and multiple FDG-avid nodes in the axilla (bilaterally), left internal mammary, and left cervical chain.

The core biopsy from the lymph node is shown in the Figure, C.A, Rash on the left chest wall.


On further questioning, he had a similar mass that was treated with liposuction 10 years prior.

His family history was negative for any head and neck benign or malignant disease.

His social history was negative for tobacco or alcohol use.

This patient was not taking any steroid medications.Physical examination showed an enlarged right more than left-sided neck mass.

The growing neck mass was causing solid food dysphagia and difficulty breathing at night.

He did not have any neurological deficits.

It was tense but compressible to palpation.

Flexible fiber-optic laryngoscopy showed a crowded oropharynx with lingual tonsil hypertrophy and narrow oropharynx and hypopharynx.

An outside computed tomography scan showed diffuse symmetric fatty infiltration of the pharynx, larynx, trachea, and esophagus.

A magnetic resonance imaging scan with and without contrast (Figure, A) showed extensive areas of fat deposition within the neck that bilaterally extended from the level of C1 in the retropharyngeal space to the level of the sternal notch.

Given that the patient was symptomatic, surgical intervention was recommended.Preoperative magnetic resonance imaging (A) and gross specimen (B).Surgery was approached like a neck dissection.

The entire specimen was removed, including its capsule, which measured 17.0 × 14.0 × 5.0 cm (Figure, B).

Six months later, a postsurgical magnetic resonance imaging scan showed that the fat prominence had largely been resected.

The patient was seen and evaluated by a local surgical oncologist with a working diagnosis of possible lymphoma.


There was nonconsanguineous marriage of his parents, and no family members had similar lesions.

The patient was otherwise in good general health and without developmental delay.

Some of the eruptions on his trunk had spontaneously resolved with developmental growth.

Physical examination showed generalized, linear hyperkeratotic papules with numerous central small filiform keratotic white spicules and brown plugs on the head, face, neck, trunk, and bilateral upper and lower extremities (Figure, A and B), including his palms and soles along Blaschko lines, accompanied with alopecia of the scalp and eyebrows.

The examination of nails, mucosae, and teeth was unremarkable.

No extracutaneous involvement was observed.

Dermoscopic examination showed many central white spines on the face (Figure, C) and brown cores surrounded by yellow crater-like rings on the right palm.

A skin biopsy specimen was taken from the hyperkeratotic papules with white spicules on his right thigh (Figure, D).A, Generalized, linear hyperkeratotic papules and plaques with numerous white spicules and plugs on the head, face, neck, and both arms are accompanied by alopecia of the scalp and eyebrows.

B, Generalized hyperkeratotic papules with numerous central small filiform keratotic white spicules on the face (close-up view).

C, Dermoscopic examination on the face showing many central whitish spines.

D, Skin biopsy specimen taken from the right thigh showing hyperkeratosis, acanthosis, and parakeratotic columns overlying the dilated epidermal invaginations, as well as thinner granular layers and dilated eccrine ostia and acrosyringia under the parakeratotic columns (hematoxylin-eosin).


These lesions started as itchy, weepy, reddish papules and plaques, which gradually progressed to form ulcers and were associated with pain and pus discharge.

They did not heal completely after multiple courses of topical as well as systemic antibiotics, antifungals, and steroids.

She frequently experienced scaling and greasiness on her scalp, which was treated with shampoos and topical steroids.

She also complained of polyuria and polydipsia for the past 4 years.General examination revealed multiple mobile, firm, nonmatted, and nontender lymph nodes in cervical and inguinal region.

On systemic examination, hepatomegaly (2 cm below the right costal margin) was seen.

There was also bilateral enlargement of the parotid area, which was tender on palpation.

Cutaneous examination revealed yellowish greasy scales on the scalp, suggestive of seborrheic dermatitis.

Erythematous edematous papules were present over the retroauricular areas and the inframammary folds (Figure, A).

On examination of external genitalia, deep ulcers were observed in the bilateral inguinal folds, resembling knife-cut ulcers (Figure, B).

Similar lesions were present over the junction of labia majora and labia minora and were associated with yellowish pus discharge.


Current medications included carvedilol, 25 mg, twice daily and apixaban, 5 mg, twice daily.

Review of prior physician encounters revealed reports of lightheadedness and electrocardiograms (ECGs) with atrial fibrillation with ventricular rates of 40 to 50 beats per minute.

An ECG (Figure, A) showed atrial fibrillation with an irregular ventricular rate of around 60 beats per minute, right bundle branch block (RBBB), and left posterior fascicular block (LPFB).Comparison of current (A) and past (B) electrocardiogram (ECG) findings.Telemetry revealed heart rates of 50 to 60 beats per minute, which did not change with activity.

Findings of echocardiography were unremarkable.


His medical history was significant for thyroid cancer treated with total thyroidectomy resulting in a chronic left accessory nerve injury, type 2 diabetes, hypertension, and gout.

His medications were metformin, allopurinol, perindopril, thyroxine, and rabeprazole.

He had no history of smoking and drank 3 glasses of wine per week.

His family history was unremarkable.Examination revealed significant wasting of proximal and paraspinal muscles with a flexed spine posture in the upright position (Figure 1A).

He reported a 20-kg weight loss and numbness to the ankles.

He had symmetric Medical Research Council grade 4/5 weakness of neck flexion, shoulder abduction, elbow flexion and extension, and hip flexion and extension bilaterally.

He had weakness of left shoulder elevation and winging of the left scapula secondary to the accessory nerve injury.

Pinprick sensation was reduced in both feet.Lateral profile of the patient (A) revealing a flexed spine posture (camptocormia) with marked generalized muscle atrophy.

B, A Gömöri trichrome stain of frozen left vastus muscle (original magnification ×400) reveals 3 atrophic muscle fibers with a patchy granular appearance (red arrowheads).Metabolic, endocrine, autoimmune, and infectious screens had unremarkable findings.

A myositis panel demonstrated low-positive Mi2 antibodies.

Serum electrophoresis and immunofixation identified a small immunoglobulin G (IgG) κ paraprotein with normal findings on bone marrow biopsy.

A whole-body positron emission tomography scan was normal.

Nerve conduction studies revealed a mild axonal sensorimotor polyneuropathy.

Concentric needle electromyography showed no spontaneous activity with widespread small, brief, polyphasic units, particularly in proximal and axial muscles, consistent with a myopathic process.

Because the patient’s symptoms were worsening, a second muscle biopsy of vastus lateralis was performed.

His deep tendon reflexes were normal and symmetric.

An initial deltoid muscle biopsy did not show evidence of myopathy.


She described infrequent abrupt awakenings with a sensation of breathlessness but reported no witnessed apnea.

She had fatigue but no headaches or excessive daytime sleepiness.

Her blood pressure was 182/97 mm Hg, oxygen saturation was 98%, and body mass index was 51.3 (calculated as weight in kilograms divided by height in meters squared).

The remainder of her physical examination findings were normal.

Laboratory evaluation revealed a serum bicarbonate level of 24 mEq/L (reference range, 23-29 mEq/L).

The patient underwent home sleep testing using a home sleep test device.

Results are presented in the Table.Advise use of a wedge pillow to avoid sleeping in the supine position.


He also had mild chronic macular edema in both eyes after remote cataract surgery and vitrectomy with membrane peel in both eyes.

Two years prior, he underwent Baerveldt tube shunt in his left eye, and his IOP since surgery had been 8 to 14 mm Hg.

Ophthalmic medications on presentation were timolol eye drops twice daily, brinzolamide-brimonidine eye drops 3 times daily, bimatoprost eye drops every night at bedtime, bromfenac eye drops once daily, and fluorometholone eye drops twice daily in both eyes.During his visit, the patient complained of severe physical exhaustion, syncopal episodes, dysphagia, and sinus congestion.

On external examination, he had diffuse facial edema and erythema without proptosis.

Slitlamp examination showed mild chemosis and hyperemia in both eyes and a patent Baerveldt tube ostium in the midanterior chamber with normal bleb morphology without a tense capsule.

A 24-2 Humphrey visual field showed new glaucoma progression in the left eye (Figure 1).A, A 24-2 Humphrey visual field (HVF) of the left eye after tube shunt showed superior and inferior arcuate defects.

The mean deviation (MD) was −8.57 dB; pattern standard deviation (PSD), 6.53 dB; and visual field index (VFI), 81%.

B, Two years later, 24-2 HVF showed worsening defects.


The swelling worsened over the following 3 weeks despite use of warm compresses and a course of doxycycline prescribed by his outside eye care professionals.

He had progressive binocular diplopia and right periorbital pain, swelling, and redness.

Blurriness of the right eye that started the week before presentation eventually caused enough concern that the patient presented to his local emergency department where magnetic resonance imaging (MRI) of the brain and orbits revealed an intraconal mass (Figure, A).

He then came to our institution’s emergency department for urgent ophthalmology consultation.A, Magnetic resonance imaging (MRI) axial T1 orbit fat-suppressed postcontrast image shows a right retro-orbital intraconal lesion (asterisk) with intrinsic T1 hyperintensity but without fat saturation or enhancement.

The lesion causes proptosis (difference between the dotted lines) and posterior globe flattening (white arrowheads).

B, B-scan ultrasonography of the right eye shows a well-circumscribed and homogenous lesion with low internal reflectivity (asterisk) sitting directly behind the globe (left).

There is a possible thin septation (white arrowheads).His examination revealed a visual acuity of 20/60 OD and 20/20 OS, intraocular pressures of 24 mm Hg and 17 mm Hg in the right and left eyes, respectively, and a normal pupil examination without a relative afferent pupillary defect.

His right eye had 5-mm relative proptosis, hyperglobus, supraduction deficit, conjunctival injection, grade IV optic disc edema, and choroidal folds.

An ultrasonography examination revealed a 2.0 × 2.5-cm echolucent avascular lesion (Figure, B).


Computed tomography (CT) of the neck with contrast at his initial hospital admission was concerning for suppurative lymphadenitis.

Results of subsequent workup—including Haemophilus, tetanus, and pneumococcal antibody titers; QuantiFERON-TB Gold test; serum IgG, IgM, IgA, and IgE levels; absolute lymphocyte count; neutrophil phenotype and function; angiotensin-converting enzyme level; HLA-B27 test; and antinuclear antibody level—were within normal limits.

Magnetic resonance imaging of the neck with gadolinium contrast demonstrated bilateral, bulky, enlarged cervical lymph nodes, as well as enhancing nodules in the left laryngeal ventricle (2.3 × 1.6 × 1.2 cm), right false vocal cord, and right tracheal wall (0.6 × 0.4 cm).

Findings from nasal endoscopy, awake flexible laryngoscopy, and operative microlaryngoscopy revealed yellow submucosal masses in the left nasal cavity, left laryngeal ventricle, and right trachea, as well as left vocal cord paresis (Figure, A).

Histopathologic examination revealed a prominent infiltrate of benign-appearing histiocytes with numerous forms showing emperipolesis and some nuclei showing distinct central nucleoli.

Immunohistochemical staining in these cells was positive for S100 and negative for CD1a.A, Awake flexible laryngoscopy showing a yellow mucosal mass in the left laryngeal ventricle.

Despite incision and drainage, and intravenous ampicillin and sulbactam, his cervical lymphadenopathy persisted.

Biopsies were taken of the tracheal, laryngeal, and nasal cavity masses, and an excisional biopsy was taken of a left cervical lymph node (Figure, B).


Subsequently, the practitioner referred the patient to an otolaryngologist.The patient denied any enlarged lymph nodes, fevers, fatigue, rash, weight loss, or abnormal gastrointestinal symptoms and had no noteworthy medical history.

He reported mild alcohol consumption, denied any cigarette or illicit substance use, and endorsed engaging in oral and anal intercourse.A physical examination was notable for bilateral raised leukoplakia on the tongue; it was larger on the right side than the left and had a slightly hairy appearance.

He stated that the pain was exacerbated by spicy foods.

He had initially presented to a primary care practitioner, was prescribed clotrimazole lozenges, and reported mild initial improvement followed by symptom progression.

The lesion was tender to touch and could not be scraped off (Figure 1A).

The lips and oral mucosa were without lesions, masses, or ulcers.

The patient had no cervical lymphadenopathy.

The findings of the physical examination were otherwise unremarkable.A, Clinical image of the right anterolateral tongue showing a 1 × 3 cm plaque over tongue mucosa.

Left lateral tongue (not shown) had multiple gray papular lesions with similar appearance.

B, Hematoxylin-eosin stain of right tongue biopsy specimen revealing prominent lymphoplasmacytic infiltrate involving squamous mucosa; no cellular atypia is seen among lymphocytes.A biopsy procedure of the right oral tongue lesion was performed, and hematoxylin-eosin staining of the specimen revealed dense perivascular plasmacytic infiltration and neutrophilic inflammation (Figure 1A).


On clinical examination, visual acuity measured 20/70 + 1 in the right eye and 20/100 in the left eye, while she previously had visual acuity of 20/25 in each eye on examination 8 years prior.

Motility, visual fields, and anterior segment examination results were normal.

Dilated fundus examination revealed subtle reddish geographic irregularities at the level of the retinal pigment epithelial at a nasal juxtafoveal location in both eyes.

The optic discs, vessels, and periphery were normal.

Near-infrared (IR) imaging highlighted the irregularities in both eyes (Figure 1).Near-infrared imaging of the right eye (A) and left eye (B) demonstrates juxtafoveal irregularity.

The foveal regions have subtle juxtafoveal geographic areas (white arrowheads), mostly nasal to the foveal center in both eyes (A > B).


She denied experiencing a stressful event recently, and no habitual pulling of hair was observed by her family.

Since the age of 1 year, the girl had begun to have frequent hair loss without pulling.

Her mother also found that her hair grew to approximately the same maximum length down to the upper neck without trimming.

Her scalp hair was relatively normal in terms of density and length at birth.

On clinical examination, diffuse, short, sparse, lanugolike, black hair over the scalp was found (Figure, A and B).

The surface of the scalp was smooth without inflammatory changes or focal alopecic patches.

No involvement of eyebrows, eyelashes, nails, teeth, or body hair was found.

Her intellectual performance was normal at presentation and no developmental delay had ever been noted.

C, Punch biopsy showed a mild lymphocytic perifollicular infiltrate and increased telogen hair with decreased anagen-to-telogen ratio (hematoxylin-eosin staining, magnification 2x).The hair pull test was positive with predominately anagen hair extracted.

Light microscopy of scalp hair shafts revealed no structural abnormalities, such as cuticular damage, twisting, bending, or miniaturization.

Blood levels of ferritin, zinc, and hemoglobin were normal.

A punch biopsy from the alopecic area of the scalp was performed (Figure, C).

Family history regarding hair loss was unremarkable.A and B, Diffuse, sparse, and abnormally short hair over the entire scalp is shown.


The patient had no remarkable medical or family history and was not concurrently being treated with any medications.

She had been previously diagnosed with eczema and treated with topical steroid ointments and oral compound glycyrrhizin tablets, which had no obvious effect.Clinical images of keratotic papules diffusely distributed on an extremity, original (A) and magnified (B).Laboratory investigations, including routine blood, liver and kidney function, antistreptolysin O, C-reactive protein, antinuclear antibody, and rheumatoid factor tests, disclosed no abnormal findings.

The lesions consisted of scattered, erythematous, annular papules measuring up to 5 mm wide (Figure 1).

Further examination revealed a few asymptomatic brown flat papules scattered on her face; the palms, soles, and oral mucosa were not involved.

A biopsy specimen was obtained for histopathologic examination.


He had never smoked, was physically active, and did not take any medications.

His Lp(a) level was elevated at 136 nmol/L and his coronary calcium score of 137 Agatston units was notable and placed him in the 94th percentile for his age (Figure 1).

He had no traditional risk factors for ASCVD and no cardiac symptoms or limitations.

His 10-year ASCVD risk was estimated at 1.6% (low risk) based on the pooled cohort equations (PCEs); however, he had 2 risk-enhancing factors: South Asian ancestry and a FHx of premature ASCVD.

His father had a myocardial infarction at age 39 years, and, importantly, his older brother had angioplasty with multiple stents at age 43 years.

Additionally, multiple male cousins on his father’s side had coronary artery disease, the details of which were unspecified.Owing to his striking FHx of premature ASCVD, he underwent screening for elevated lipoprotein(a) [Lp(a)] and obtained a coronary calcium score.


The patient had become progressively disabled and had been using a wheelchair for 4 years prior to presentation.

Ataxia was seen on finger-to-nose and heel-knee-shin tests.

Neurological examination showed gaze-evoked horizontal nystagmus in both directions along with slow saccades and gaze restriction in both vertical and horizontal planes.

Tone was normal in all 4 limbs but stretch reflexes were absent and plantar fascia were mute.

Ankle inversion with bilateral hammertoes was noted.

Electromyography revealed sensory neuronopathy.

On brain magnetic resonance imaging (MRI), diffuse cerebellar atrophy was noted along with T2 hyperintensities in bilateral middle cerebellar peduncles, cerebellar white matter, pons, and bilateral thalamus (Figure).

Psychiatric treatment was commenced for her severe anxiety but did not relieve the fear of falling.Magnetic resonance brain images showing T2 fluid-attenuated inversion recovery hyperintensities.


She reported no precipitating factors for the pain and had no history of pregnancy, abdominal surgery, or abdominal trauma.

Over the previous 2 years, the patient had experienced similar intermittent episodes of abdominal pain lasting approximately 1 week.

She had no associated nausea, vomiting, diarrhea, hematochezia, bloating, or anorexia.

During palpation of this 1-cm area, the pain increased when she lifted her head and tensed her abdominal muscles.

Results from laboratory tests, upper endoscopy, colonoscopy, and an abdominal computed tomography scan performed 1 year prior to presentation were normal.In the emergency department, her vital signs were normal and her body mass index was 20.4 (calculated as weight in kilograms divided by the square of height in meters).

Abdominal examination revealed no rigidity or guarding; however, a 1-cm point of maximal tenderness was identified in the left lower abdominal quadrant (Figure).


Six days prior to presentation, multiple vesiculobullous lesions appeared on his palms and soles.

Three days later, he developed erythema; vesicles and erosions on his face, trunk, and limbs; erosions on his lips and oral mucosa; eyelid swelling; and blisters on his anal mucosa.On presentation, his temperature was 38.7 °C (101.7 °F); heart rate, 125/min; blood pressure, 98/50 mm Hg; and oxygen saturation, 98% on room air.

Physical examination revealed bilateral exudative conjunctivitis and white exudates on his tongue, posterior pharynx, and buccal mucosa.

Erosions with overlying dried blood were noted around his eyes, lips, and anal mucosa.

He had targetoid erythematous papules on his face and vesiculobullous lesions on his torso and extremities (Figure).

Auscultation of his lungs revealed bilateral crackles.

Laboratory testing showed a white blood cell count of 15 000/μL (82% neutrophils); erythrocyte sedimentation rate, 39 mm/h; and C-reactive protein level, 57.1 mg/L.

A computed tomography scan of the chest revealed bilateral lower lobe infiltrates.

Azithromycin (10 mg/kg daily, intravenously) was started.Patient presentation.

A, Erosions with overlying dried blood around the lips and targetoid erythematous papules on the face.

B, Vesiculobullous lesions on the trunk and arms.

C, Vesiculobullous lesions on the palms.


Seven days prior, she inadvertently broke aseptic technique when tightening a leaking connection of her PD catheter tubing.

Physical examination revealed diffuse abdominal tenderness.

On presentation, she was afebrile and had normal vital signs.


Five months after surgery, he presented to the otolaryngology clinic with 3 weeks of mild odynophagia and dysphagia.

It was noted that the patient had a prominent posterior pharyngeal wall, subtle asymmetry of vocal fold motion, and pooling of secretions in the left pyriform (Video 1).

During the next 6 months, he gradually developed shortness of breath and stridor, and eventually presented to the emergency department in respiratory distress requiring intubation for 2 days.

Shortly after extubation, laryngeal examination showed fullness of the posterior pharyngeal wall and severely limited vocal fold abduction bilaterally (Figure 1A; Video 1).

A modified barium swallow study showed intermittent laryngeal penetration without aspiration (Video 2).

Although the patient was unable to tolerate magnetic resonance imaging, a soft tissue computed tomography scan of the neck with contrast revealed a well-positioned plate with no evidence of fluid collection in the setting of a normal leukocyte count.


The mass had been present for decades and multiple prior office visits with referring ophthalmologists, most recently 4 years prior, showed the mass remained stable in size.The patient’s ocular history included cataract extraction with intraocular lens placement and retinal tear of the right eye and cataract of the left eye.

Visual acuity without correction was 20/20 OD and 20/25+ OS.

Intraocular pressures were normal.Slitlamp examination of the right eye was unremarkable, and the left eye had a raised pigmented iris lesion without prominent internal vasculature and with mammillations on the surface (multiple small smooth dome-shaped protuberances on the surface of the tumor).

There were large pigment granules on the surface of the tumor and on the adjacent iris surrounding the mass (Figure 1A).

There was no ectropion uvea or iris neovascularization.

There were mild nuclear sclerotic changes across the lens in the left eye.

Ultrasound biomicroscopy showed a homogeneous intrinsic iris solid tumor with a height of 1.4 mm and basal diameter of 4.1 mm, without angle or ciliary body involvement (Figure 1B).Color slitlamp photograph shows a pigmented iris mass (note both the mammillations [black arrowheads] as well as the pigment granules stuck on the tumor surface [white arrowheads]) (A); ultrasound biomicroscopy shows solid, echogenically homogeneous iris stromal tumor with high internal reflectivity (B).

Review of systems was negative for any recent changes in health, weight loss, fever, or night sweats.


His medical history was remarkable for mild anemia because of untreated hemorrhoids.

He denied systemic complaints such as weakness, fever, night sweats, or weight loss.

Physical examination revealed numerous symmetrically distributed, well-defined, erythematous skin nodules on his back, buttocks, and limb extensors (Figure, A).

Prominent lymphadenopathies on bilateral cervical, axillary, and inguinal lymph nodes were noted, with the largest lymph node measuring approximately 5 × 2 cm.

Laboratory tests were significant for atypical lymphocytes in the peripheral blood (count up to 6%), an elevated CD4+/CD8+ lymphocyte ratio (9.21; normal range, 0.7-3.1), moderate anemia (hemoglobin level, 8.7 g/dL; normal range, 11.5-15.0 g/dL [to convert to g/L, multiply by 10.0]), a high erythrocyte sedimentation rate (35 mm/h; normal range, 0-25 mm/h), and cryoglobulins composed of mixed polyclonal immunoglobulins.

The platelet count (161 × 103/μL; normal range, 125-350 × 103/μL [to convert to ×109/L, multiply by 1.0]) and lactate dehydrogenase (217 U/L; normal range, 100-240 U/L [to convert to μkat/L, multiply by 0.0167]) were normal.

Quantification of Epstein-Barr virus (EBV) DNA showed high loads of virus in the peripheral blood (846 copies/mL in serum, 27 700 copies/mL in lymphocytes; normal range, <500 copies/mL).

B, Skin biopsy sample showed infiltration of atypical lymphocytes and histiocytes with proliferation of high endothelial venules (hematoxylin-eosin).

C, In situ hybridization was positive for Epstein-Barr virus in the skin.

Oral glucocorticoids did not show any therapeutic effect.

A biopsy specimen from a skin nodule was sent for histopathologic examination (Figure, B).A, Physical examination showed widespread, symmetrically distributed, well-defined nodules on the trunk and extremities.


He reported occasional alcohol intake, and there was no history of tobacco-related habits or oral trauma.

Intraoral examination revealed multiple yellowish to erythematous papules and verrucous cobblestone-like plaques on the mucosal surface on both sides of his tongue (Figure, A and B).

The skin of the face, neck, arms, and other sun-exposed areas did not reveal any associated lesions.

The results of laboratory investigations, including a complete blood cell count, serum chemistry panel, liver and kidney function test, C-reactive protein levels, lipid profile, and serum and urine electrophoresis disclosed no abnormalities.

C and D, Circumscribed eosinophilic, amorphous fissured masses in the subepithelial connective tissue (hematoxylin-eosin).

With the clinical suspicion of squamous cell carcinoma, an incisional biopsy was performed (Figure, C and D).Yellowish plaques in a cobblestone pattern on the right (A) and left (B) side of the tongue.