The patient had a history of uterine fibroids and a right-sided ovarian cyst for 5 years, but she denied symptoms, including abdominal pain, abnormal defecation, abnormal vaginal bleeding, fever, or weight loss.

She had no history of intravenous drug use.

A physical examination was notable for jugular venous pulsations and a grade 3/6 systolic murmur best heard at the fifth intercostal space in the left side of the sternum.

Laboratory studies revealed normal serum chemistry levels.

A complete blood cell count showed a hemoglobin level of 12.7 g/dL (reference, 11.3-15.1 g/dL [to convert to grams per liter, multiply by 10]), a white blood cell count of 7400 cells/μL (reference, 4000-10 000 cells/μL [to convert to cells ×109 per liter, multiply by 0.001]), and a platelet count of 42 × 103 cells/μL (reference, 100 × 103 to 300 × 103 cells/μL [to convert to cells ×109 per liter, multiply by 1.0]).

The prothrombin time was 16.5 seconds (reference, 10-14 seconds); activated partial thromboplastin time, 47.5 seconds (reference, 23-35 seconds); fibrinogen level, 52 mg/dL (reference, 185-350 mg/dL [to convert to grams per liter, multiply by 0.01]); and D-dimer, 5190 μg/mL (reference, <590 μg/mL [to convert to nanomoles per liter, multiply by 5.476]).


After 1 month of ongoing rash, pembrolizumab was discontinued.

Her pruritic eruption persisted over the next 5 months despite treatment with up to 80 mg/d of oral prednisone.

The eruption continued to worsen when the patient was not receiving systemic corticosteroids, with blisters developing 7.5 weeks after their discontinuation, prompting her presentation to the emergency department.On examination, the patient was afebrile and hemodynamically stable.

She had tense bullae and indurated papules and plaques involving the face, trunk, and extremities (Figure, left), and oral mucosal erosions (Figure, right).

She did not report fever during this period.

A shave biopsy performed while the patient was receiving systemic corticosteroids demonstrated spongiotic dermatitis with a mixed-cell infiltrate suggesting an incipient autoimmune bullous process.

Blood pressure was elevated to 136/98 mm Hg; other vital signs were within normal limits.

Laboratory findings were notable for erythrocyte sedimentation rate and C-reactive protein level being elevated to 25 mm/h and 16.8 mg/dL, respectively, with a normal white blood cell count.Patient presentation.

Left, Bullae on bilateral lower extremities.

Results of follow-up direct immunofluorescence (DIF) performed on a sample taken 15 days after steroid discontinuation were negative.


The patient had cardiovascular risk factors including arterial hypertension and a family history of CAD.

With antihypertensive therapy, her blood pressure was 119/79 mm Hg.

Blood lipids were as follows: total cholesterol, 167 mg/dL (abnormal >200 mg/dL); low-density lipoprotein cholesterol, 80 mg/dL (abnormal >100 mg/dL); high-density lipoprotein cholesterol, 55 mg/dL (abnormal <60 mg/dL); and triglycerides, 80 mg/dL (abnormal >150 mg/dL).

A 20% pretest probability of coronary artery disease (CAD) was estimated, considering sex, age, and type of chest pain.1 Functional tests performed 3 months earlier were inconclusive: a stress electrocardiogram (ECG) showed ST-segment depressions at 100 W of −0.2 mV in lead I and −0.15 mV in V5, while stress magnetic resonance (MR) perfusion imaging had negative results.

To evaluate for CAD, she underwent coronary computed tomography (CT) angiography (Figure).Evaluation for the presence of coronary artery disease using computed tomography angiography.

Patient’s imaging: A, right coronary artery (RCA); B, left circumflex coronary artery (LCX); C, left anterior descending coronary artery (LAD); D, LAD displayed as curved multiplanar reformations and 3-dimensional views; and large field of view of an axial slice, E, and coronal slice, F, to identify extracardiac findings.No coronary stenosis.

If symptoms persist, recommend a follow-up CT and perfusion imaging.No coronary stenosis.

Because of the chest pain, recommend further functional testing.No stenosis or plaque.

Because of high negative predictive value, no further testing is necessary.Relevant coronary stenosis cannot be excluded by CT.

Recommend invasive coronary angiography.


Similar symptoms subsequently spread to the left hallux and ankle, and he developed a fever.

Despite many medical consultations and various attempts at treatment with nonsteroidal anti-inflammatories, the patient developed widespread arthritis within the following month, which was predominant in the knee, shoulder, and hip.

In the month before presentation the articular symptoms worsened, the joints had become tender, and ill-defined skin nodules had appeared predominantly on the legs (Figure, A and B).

An acute abdominal pain in the left hypochondrium developed, accompanied by nausea and vomiting, which led to a diagnosis of pancreatitis.

Laboratory test results revealed strikingly high levels of lipase and amylase, as well as normal levels of cancer antigen 19-9.

Bone computed tomography (CT) of the right shoulder and knee demonstrated cortical bone destruction and intraosseous medullary necrosis (Figure, C and D).

The patient was admitted to the hospital and clinical measures relieved the pain.


Her best-corrected visual acuity was 20/25 OD and 20/20 OS.

There was no afferent pupillary defect, her Ishihara color plate findings were 10/10, and extraocular movements were intact in both eyes.

An anterior slitlamp examination had unremarkable findings.

A fundus examination showed hemorrhagic optic disc edema, peripapillary and subfoveal subretinal fluid, tortuous and dilated retinal vasculature, many intraretinal hemorrhages in all 4 quadrants, and far peripheral temporal inner retinal whitening in both eyes (Figure 1A).

Optical coherence tomography demonstrated peripapillary and subfoveal subretinal fluid, intraretinal fluid, and swollen optic nerve heads in both eyes (Figure 1B).

A fluorescein angiogram showed markedly delayed venous filling (1 minute) in all quadrants and far peripheral capillary nonperfusion in both eyes.Images of the right eye at presentation.

B, Optical coherence tomography of the right macula showing intraretinal fluid (arrowheads) and subretinal fluid tracking from the optic disc and involving the fovea (dotted arrow).A workup for the optic nerve edema included magnetic resonance imaging and venography, which showed mild cerebral leptomeningeal enhancement and no occlusive thrombosis.

A lumbar puncture revealed an elevated opening pressure of 50 cm H20 (38 mm Hg; normal range, 6-25 cm H20), an elevated cerebrospinal fluid white blood cell count (41 cells/μL; normal range, 0-5 cells/μL; to convert to cells × 109 per liter, multiply by 0.001), and negative cerebrospinal fluid culture results.

A complete blood cell count found severe anemia (hemoglobin, 3.4 g/dL; normal range, 12.0-15.5 g/dL; to convert to grams per liter, multiply by 10.0), and a peripheral blood smear showed lymphocytosis with predominantly atypical lymphocytes.

Serum protein electrophoresis revealed an IgM level of 5850 mg/dL (normal range, 57-237 mg/dL; to convert to grams per liter, multiply by 0.01).

A, Optic nerve edema (dotted circle), vascular tortuosity (asterisks), intraretinal hemorrhages in all 4 quadrants (solid circles), and far peripheral retinal whitening (arrowheads).


The patient reported that this cyst had been drained 2 years before with resolution of her symptoms.

On examination, she had an approximately 1.5-cm mucosally covered mass on her left lateral pharyngeal wall that was cystlike in appearance.

The remainder of her examination findings were normal.

Contrasted computed tomographic (CT) imaging of her head and neck was obtained, which revealed a pharyngeal cyst that extended to the atlantoaxial joint (Figure, A).

Further magnetic resonance imaging (MRI) of the area was obtained, which demonstrated communication of the cyst with the atlantoaxial joint (Figure, B and C).Computed tomographic (CT) image (A) and magnetic resonance images (MRIs) (B and C) of the neck show a pharyngeal cyst (all images) that is communicating with the left atlantoaxial joint (B) at the level of the second cervical vertebra (C).


On examination, visual acuity was 20/30 OU.

Intraocular pressure (IOP) was 16 mm Hg OD and 41 mm Hg OS.

The anterior segment was normal in the right eye.

Anterior examination of the left eye revealed 10% hyphema.

Two days later, IOP was 16 mm Hg OD and 10 mm Hg OS.

Slitlamp biomicroscopy revealed resolved hyphema and abnormal blood vessels at the superotemporal pupillary margin of the iris, prompting referral for further evaluation.On further examination, visual acuity was 20/40 OD and 20/50 OS, and IOP was 15 mm Hg OD and 16 mm Hg OS.

Slitlamp examination results in the right eye appeared normal, whereas the left eye demonstrated subtle, multifocal ectatic vascular channels arranged circumferentially at the pupillary margin (Figure 1A, arrowheads).

On fluorescein angiography (FA), both the right and left irises displayed multifocal, pinpoint areas of hyperfluorescence at the pupillary margin and was more noticeable on the left iris (Figure 1B, arrowheads).

The remainder of the eye examination was unremarkable, and there was no sign of neovascularization of the retina or disc.A, Slitlamp photograph of the left eye depicting a vascular lesion at the 2 o’clock position in the pupillary margin (inset, arrowheads).

The patient was prescribed cyclopentolate, 1%, and prednisolone acetate, 1%, to reduce inflammation and lower the IOP in the left eye.


Her medical history had negative results for allergic rhinitis, asthma, chronic rhinosinusitis, epistaxis, nasal trauma, or surgery.

The patient denied systemic symptoms, including oral ulcers, sicca, photosensitivity, dermatitis, or arthralgias.

An in-office nasal endoscopy demonstrated synechiae bridging from the septum to the lateral nasal walls, polypoid changes, and yellow crusting bilaterally.Her immune workup showed elevated complement C3 (200 mg/dL) and total hemolytic complement (CH50; >60 U/mL) levels, with otherwise unremarkable levels of C4, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, Sjögren antibodies, angiotensin-converting enzyme, antinuclear antibody, antineutrophil cytoplasmic antibody, bullous pemphigoid IgG antibodies, and quantitative immunoglobulins and IgG subclasses (IgG4, 53 mg/dL [to convert to grams per liter, multiply by 0.01]).

Nasal cultures had positive results for methicillin-resistant Staphylococcus aureus and Bacteroides.

Preoperative computed tomography showed no evidence of paranasal mucosal disease or bone erosion.

An operative endoscopy with elevation of the mucoperichondrial flaps revealed an absence of the quadrangular cartilage caudal struts and irregular, friable tissue along the cartilage and perichondrium.

Surgical pathology examination demonstrated prominent lymphoplasmacytic infiltrate (Figure, A), angiocentric fibrosis with a relative lack of eosinophils (Figure, B), and increased IgG4 absolute count (up to 50 cells per high-power field), although an IgG4-IgG ratio that was only slightly elevated (0.2) (Figure, C and D).Histopathologic findings: A, hematoxylin-eosin (original magnification ×40); B, hematoxylin-eosin (original magnification ×100); C and D, original magnification ×200.


She noted a 5-kg weight loss in the preceding 3 months.

Examination revealed nonreproducible chest tenderness, bibasilar crackles, and no extra heart sounds.

Testing revealed leukocytosis (white blood cell count, 16 900 cells/μL [to convert to × 109 cells/L, multiply by 0.001]) with a differential of 6% neutrophils and 59% eosinophils, an elevated N-terminal pro B-type natriuretic peptide of 3963 pg/mL (reference level, <900 pg/mL [to convert to ng/L, multiply by 1.0]), and an elevated initial troponin T of 0.36 ng/mL, which later peaked at 0.41 ng/mL (to convert to micrograms per liter, multiply by 1.0).

Her C-reactive protein level was 3.09 mg/dL (normal, <0.5 mg/dL [to convert to milligrams per liter, multiply by 10]).

Subsequent plasma flow cytometry demonstrated 65% eosinophils, and a bone marrow biopsy with immunohistochemistry showed eosinophilia without evidence of clonal expansion.

Cardiac magnetic resonance imaging was performed (Figure 1B; Video).A, Normal sinus rhythm with left-axis deviation, low voltages, inferior Q waves, and poor R-wave progression.

A 12-lead electrocardiogram is shown in Figure 1A.


Examination showed coalescing annular, arcuate, and serpiginous red scaling plaques in a concentric pattern diffusely involving the chest, back, and abdomen with extension to proximal extremities (Figure, A and B).

Punch biopsies from the chest (Figure, C and D) and back were obtained for histopathology and tissue culture.

C, Histopathology of skin biopsy from the chest reveals epidermal hyperplasia with spongiosis and parakeratosis (hematoxylin-eosin, original magnification ×400).

There is a superficial dermal and epidermotropic infiltrate of atypical lymphocytes focally distributed along the dermal-epidermal junction and aggregated in Pautrier microabscesses.

Treatment with topical corticosteroids under wet dressings was associated with partial improvement in the eruption and pruritus.A and B, Clinical images show concentric annular, arcuate, and serpiginous red scaling plaques diffusely involving the back and right flank.


He had a history of high myopia and a family history of glaucoma in a female family member.

He denied other prior ocular history, trauma, or eye surgery.

The patient noted 4 years of progressive, decreased, patchy pigmentation of both eyes; constant photophobia; and constant decreased visual acuity.

A review of systems had no remarkable findings, and the patient denied a prodromal viral illness.On presentation, his best-corrected visual acuity was 20/20-2 OD and 20/25 OS, with a refraction of −6.25 OD and −5.50 OS (spherical equivalent).

Gonioscopy showed openness to the ciliary body with 1+ trabecular meshwork pigmentation, without synechiae or angle recession in either eye.

A slitlamp examination demonstrated quiet conjunctiva, clear corneas, deep and quiet anterior chambers, mid-dilated round pupils, patchy iris atrophy, and transillumination defects bilaterally (Figure).

Ophthalmoscopy showed an 0.8 cup-disc ratio without notching bilaterally but had otherwise normal results.

Retinal nerve fiber layer optical coherence tomography showed borderline thinning with normal Humphrey visual fields in both eyes.Anterior segment photographs of the right eye (A) and left eye (B) showing clear corneas, patchy iris atrophy of both irides (arrowheads), and round mid-dilated pupils without posterior synechiae.


Fine-needle aspiration results showed metastatic p16-positive squamous cell carcinoma.

No mucosal primary site was identified with positron emission tomography, computed tomography, or a head and neck examination.

Pathology results revealed a 1.8-cm primary cancer in the right tonsil, and the patient received a stage designation of T1 N1 M0.

The tumor was intracapsular, and all surgical margins were negative.

Imaging results revealed an enhancing structure at the skull base adjacent to the carotid sheath (Figure).Computed tomography of the neck with contrast and the axial (A) and coronal (B) views revealing an enhancing structure at the skull base along the carotid sheath (arrowheads).

The patient underwent direct laryngoscopy with directed biopsies and bilateral tonsillectomy.

Multidisciplinary tumor board discussion concluded that surgical and nonsurgical treatment options were available, and the patient elected to proceed with further surgery, which would entail additional directed biopsies at the primary site with additional resection if necessary and selective neck dissection of levels Ib to IV.

In preparation for the neck dissection, computed tomography of the neck with contrast was obtained.


She had a medical history of patchy hair loss and a violaceous maculopapular rash on the face and upper extremities for 5 years, which was well controlled with topical corticosteroids.

Family history was notable for antiphospholipid syndrome in her mother.

She reported new, sharp headaches in a headband distribution, exacerbated by lights, sounds, and neck flexion.

One week prior to presentation, she experienced a subjective fever and recurrence of the facial rash.

She denied experiencing eye pain, blurry vision, or light sensitivity.

Results of a comprehensive review of systems were otherwise negative.

Best-corrected visual acuity was 20/25 OU.

Results of an anterior segment examination, pupil examination, and tonometry were unremarkable.

During dilated ophthalmoscopy, both eyes revealed diffuse intraretinal hemorrhages in the posterior pole and temporal retinal neovascularization, worse in the right eye with associated macular traction and striae.


She maintained a healthy diet and denied any history of malnutrition, gastrointestinal procedures, recent ocular infections, or chemical exposures.

Her ocular history was notable for cataract extraction with intraocular lens implantation in both eyes.

Ocular hypertension was noted after corticosteroid treatment, and the patient started brimonidine-timolol drops twice daily in the left eye.At presentation, the patient’s corrected distance visual acuity was 20/20 OD and 20/60 OS.

Results of slitlamp examination revealed very mild shortening of the fornix inferonasally in the right eye.

Shortly after cataract surgery in the left eye, performed 1 year prior to presentation, the patient developed cystoid macular edema treated with a sub-Tenon injection of triamcinolone acetonide.


Her medical history included diabetes, hyperlipidemia, and hypertension that were well controlled with simvastatin, chlorthalidone, hydralazine hydrochloride, lisinopril, and verapamil hydrochloride.

She had been taking these medications for 5 years with no new exposures.

Age-appropriate cancer screening was up to date.

Notable symptoms included 4 months of extreme fatigue, 20.4 kg weight loss, and a recent episode of hematochezia.

On hospital day 2, she developed bright red blood per rectum, necessitating transfusion.

She was afebrile and hemodynamically stable, but laboratory evaluation revealed that she had leukocytosis, normocytic anemia, elevated erythrocyte sedimentation rate, hematuria, and proteinuria.

A computed tomography of the chest, abdomen, and pelvis revealed parenchymal lung nodules.

On admission, punch biopsies of the skin were performed for both histological examination and bacterial, fungal, and acid-fast bacterial cultures (Figure, C and D).A, Edematous, ulcerated pink plaques confluent on forehead and cheeks with sharp demarcation at nasolabial fold are shown.

B, Retiform purpuric plaque is shown on the left leg with overlying desquamation.

C and D, Biopsy specimen findings (hematoxylin-eosin).


He also noted bilateral hand pain along the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints and prolonged morning stiffness lasting approximately 45 minutes.

Family history was notable for a brother with osteoarthritis, hypogonadism, and type 2 diabetes.Vital signs were within normal limits (heart rate, 92/min; blood pressure, 136/84 mm Hg; respiratory rate,  16/min; oxygen saturation, 97%; temperature, 37.0 °C).

Musculoskeletal examination revealed swelling of the second, third, and fifth MCP joints and second and third PIP joints bilaterally as well as decreased knee and hip range of motion with minimal knee effusions.

Lower back flexion was decreased with only 4-mm excursion on the modified Schober test.

Results of cardiopulmonary, abdominal, neurologic, and dermatologic examinations were unremarkable.Results of laboratory testing, including complete blood cell count, basic metabolic panel, and liver function tests, were within normal limits, and results for HLA-B27 were negative.

Erythrocyte sedimentation rate was 8 mm/h and C-reactive protein level was 0.5 mg/dL.

A plain radiograph of the hands (Figure, left panel) showed hook-like osteophytes at the second and third MCP joints bilaterally as well as asymmetric joint swelling in multiple MCP and PIP joints.


She denies any significant medical history, takes only multivitamins, and mentions a childhood heart murmur that was never evaluated.On examination, her blood pressure was 125/85 mm Hg, with a heart rate of 71/min and respiratory rate of 18/min.

She has no chest pain but was experiencing heart palpitations a few times per week.

Physical examination revealed a fixed split S2 and a 2/6 systolic murmur at the left upper sternal border.

An electrocardiogram demonstrated sinus rhythm with incomplete right bundle-branch block.

Transthoracic echocardiography demonstrated an enlarged right atrium and right ventricle; results of contrast echocardiography were negative.

A chest radiograph was obtained (Figure 1).


His medical history was significant for hyperlipidemia, familial polyposis, and acute myelogenous leukemia (AML) for which he had undergone an allogenic hematopoietic stem cell transplant 13 months earlier.

The patient had not attempted measures to alleviate the nodules and denied experiencing exacerbating factors or pain.

Cutaneous examination revealed green-gray nodules and plaques on the left and right upper chest (Figure 1).

Bilateral cervical, axillary, and inguinal lymph node chains were negative for adenopathy.

Biopsies of the skin lesions were performed.A, Representative dusky, green-gray nodule located on the upper chest.

B, A prominent green hue is present at the base of a lesion following shave biopsy.


The patient’s medical history was unremarkable besides mild intermittent whole-body itching starting 9 months prior.

Physical examination revealed mild proximal pyramidal weakness of the left leg (Medical Research Council grade 4/5), with brisk reflexes and extensor plantar response as well as hypoesthesia below the T2 level without sphincter disturbances.

In addition, mild decrement in position sense and marked decrement of vibration sense were observed in both lower extremities.

No skin lesions were detected, while cervical and supraclavicular lymph nodes were enlarged.

Multiple enhancing lesions were observed on brain and cervical spine magnetic resonance imaging (MRI) (Figure).

Cerebrospinal fluid (CSF) was acellular, and eosinophils and oligoclonal bands were not detected, while proteins, glucose, and angiotensin-converting enzyme (ACE) levels were within normal range.

Test results for B-cell clones, viral, and fungal infections were all negative.

Routine blood test results were unremarkable besides an elevated eosinophilic count (2.76 K/μL;17.6%).

Antibodies for AQP4, MOG, and paraneoplastic syndromes were not detected.

Whole-body fluorodeoxyglucose positron emission tomography demonstrated generalized lymphadenopathy without any other pathological findings.

Whole-body gallium scan, chest high-resolution computed tomography, and bone marrow biopsy results were normal, while axillary and inguinal lymph node biopsies revealed nonspecific reactive lymphadenopathy.

Parasitic infections were excluded by plasma and CSF antibodies testing with enzyme-linked immunosorbent assay, stool, and lymph node microscopy.

Extensive diagnostic workup for malignancies and systemic autoimmune diseases was also inconclusive.Fluid-attenuated inversion recovery (FLAIR) images presenting bilateral subcortical lesions in the brain (A) and T2-weighted images demonstrating multiple lesions and swelling of the cervical cord (C).


She had poorly controlled hypertension for 10 years.

There was no history of tobacco, alcohol, or drug consumption.

She had mild weight loss but denied symptoms of anorexia, vomiting, heartburn, chest pain, dyspepsia, hematemesis, or hemoptysis.

Chest radiography results before admission revealed multiple exudative foci in both lungs.

Physical examination results on admission showed wheezes and rales in both lung fields and were otherwise normal.

There were no abnormalities on routine blood tests.


Her symptoms started 1 day after she rubbed her left eye with her hands after handling the milky latex (a fluid found in 10% of flowering plants) of a plant in her garden.

She had no recent history of recent eye surgery, eye trauma, cold sores, or new illnesses.On presentation, her visual acuity was 20/40 OD and 20/200 OS.

Her pupils were equal, round, and reactive in both eyes.

Her intraocular pressures were 16 mm Hg OD and 19 mm Hg OS.

On anterior segment examination, she was found to have pinpoint epithelial defects, thickened stroma, and dense Descemet folds, along with a nuclear sclerotic cataract (Figure 1).

Central pachymetry in the left eye measured 706 μm, which was elevated from the mean expected pachymetry values of 540 to 560 μm.

A posterior pole examination was limited by corneal edema, but there was evidence of a vitreous hemorrhage.

The fellow eye had no corneal edema and was pseudophakic, with prior panretinal photocoagulation scars in the peripheral retina.


Three weeks prior, the patient had noted severe left-sided facial pain.

Following a workup with unremarkable results, the patient presented to the Bascom Palmer emergency department for a second opinion.On initial examination, his best-corrected visual acuity was 20/20 OU.

Intraocular pressure, ocular motility, and confrontational visual fields were normal.

There was no axial proptosis or enophthalmos by exophthalmometry.

No afferent pupillary defect was observed.

External examination demonstrated a left-sided ptosis (Figure 1).

Anterior and posterior examination, including of the optic nerve head, had normal results in both eyes.

The cranial nerve, gross motor, and gross sensory examination had otherwise unremarkable results.

He denied any diplopia, decreased vision, or recent trauma.

The patient had previously been evaluated by his primary care physician and referred to a neuroophthalmologist.

During the course of the workup, the patient had undergone computed tomography (CT) of the head and chest, magnetic resonance imaging (MRI) of the brain, and carotid duplex ultrasonography.


Immediately following workup with noncontrast abdominal ultrasonography, he experienced intense flushing and vomiting.

Subsequent contrast-enhanced magnetic resonance imaging identified a 5-cm thoracic paraspinal mass (Figure, A).

Computed tomography–guided biopsy of the paraspinal mass revealed a dense cellular infiltrate on histopathology composed of cells with round nuclei and abundant pale cytoplasm (Figure, B).A, Axial postcontrast T1-weighted magnetic resonance imaging of the spine identifying a paraspinal soft-tissue mass (bracketed by white arrowheads) encasing the descending aorta with neural foramen extension (pink arrowhead).

B, Computed tomography–guided biopsy sample (original magnification ×400) showing a monomorphic infiltrate of small- to medium-sized round cells with uniform angulated nuclei and abundant amphophilic hypogranular cytoplasm.


Four weeks after the transplant, the patient developed acute vision loss of the left eye.

Pain worsened, intraocular pressure elevated into the mid-40s mm Hg, visual acuity waned to no light perception, and intraocular inflammation and subretinal infiltrates continued to worsen, producing nearly closed funnel retinal detachments in both eyes, including developing orbital cellulitis in the right eye despite broad-spectrum antimicrobials.

Visual acuity was 20/20 OD and hand motion OS.

Anterior segment was remarkable for 1+ hyperemia and 4+ anterior chamber (AC) cell in the left eye.

Posterior segment was notable for retinal whitening and occlusive vasculitis in the right eye and more extensive retinal whitening associated with an exudative retinal detachment in the left eye.

Microbial and broad-range polymerase chain reaction (PCR) analysis and culture results of the AC and vitreous were negative as well as numerous blood cultures and serum fungitell.

During this period, the patient remained afebrile; however, the patient’s white blood cell count was uptrending, raising concern for systemic spread of the infection.A, Intraoperative images from the diagnostic vitrectomy and subretinal biopsy performed on the left eye showing substantial hemorrhagic retinitis with subretinal infiltrate (white arrowhead).

Despite broad-spectrum intravenous (ie, vancomycin and piperacillin/tazobactam) and intravitreal antibiotics (vancomycin and ceftazidime), antifungals (amphotericin B and voriconazole), and antivirals (foscarnet), the patient’s visual acuity and intraocular inflammation worsened in both eyes to light perception.

Owing to the diagnostic dilemma, a pars plana vitrectomy with subretinal biopsy was performed in the left eye, and again, microbiological analysis including culture and PCR analysis was inconclusive.

Over a week, the areas of retinal whitening became elevated owing to enlarging subretinal infiltrates (Figure, A) that were nearly kissing in the right eye (Figure, B).


The family reported living in a rural area on the Mediterranean coast.A, Erythematous nodule on the proximal nail fold.

This lesion had started as a light erythema a few months before, initially oriented as a bacterial paronychia or herpetic whitlow and treated with an oral antibiotic (amoxicillin) and antiviral (acyclovir) without improvement.

B, Inflammatory erythematous plaque with a central shiny orange crust on the left index.

C, Diffuse dermatitis with epithelioid granulomas (hematoxylin-eosin stain).

D, Intracellular amastigotes in the dermal macrophages (hematoxylin-eosin stain).Physical examination findings revealed an inflammatory erythematous plaque with a central shiny orange crust on the left index finger (Figure, B).

There were no systemic symptoms or family history of similar lesions.


B, Cytomegalovirus endotheliitis–associated coin-shaped lesion (arrowhead) superior to an F-stamp of the DMEK graft.Five weeks later, there was a painless decrease in BCVA to 20/80.

Small keratic precipitates (KPs) were noted.

Six weeks later, while taking prednisolone 6 times daily, the patient developed new KPs in coin-shaped aggregates (Figure 1B) along with new anterior chamber (AC) inflammation.

Her best-corrected visual acuity (BCVA) improved to 20/40 two weeks later, limited because of a preexisting corneal scar.A, Pre–Descemet membrane endothelial keratoplasty (DMEK) photograph of edema and bullous keratopathy, and superficial scar.

Her intraocular pressure (IOP) increased to 25 mm Hg.

No vitritis or infiltrates were in the graft-host interface or capsular bag.

Because the patient admitted to inconsistent adherence to the topical steroid regimen, rejection was suspected.

Prednisolone acetate, 1%, was increased from 4 times to 8 times daily.

Five days later the KP resolved and a slow taper of the prednisolone was initiated.


She denied nasal disturbance, prior sinus surgery, asthma, or acetylsalicylic acid (aspirin) sensitivity.

Symptoms included a several-year history of frontal pain, pressure, clear nasal discharge, and progressive nontender facial swelling above her glabella.

Symptoms were refractory to treatment with several rounds of oral antibiotics and oral steroids.

Physical examination findings revealed symmetric facial movement with prominent glabellar swelling and soft tissue thickening.

Nasal endoscopy findings revealed a soft tissue mass anterior to the axilla of the middle turbinates bilaterally, with normal-appearing mucosa overlying.

Computed tomography and magnetic resonance imaging (MRI) scans were obtained for further evaluation (Figure, A).

Adjacent soft tissue thickening noted on skin overlying frontal sinus and nasal bones.

B, Hematoxylin-eosin stain (original magnification ×10) results showed lobules of neoplastic cells with whorled architecture (arrowhead).

C, Hematoxylin-eosin stain (original magnification ×20) results showed intranuclear inclusions (arrowhead).

Recommendations were made to proceed to the operating room for biopsy of the nasal mass.

Pathology results revealed uniform, epithelioid cells arranged in a whorled, lobulated growth pattern without atypia, necrosis, increased cellularity, or diffuse growth pattern (Figure, B and C).A, T1-Weighted postcontrast magnetic resonance imaging scan, sagittal view, showed hyperintense soft tissue mass on anterior septum with extension into frontal sinus.


His 3-month posttreatment fluorodeoxyglucose (FDG) positron-emission tomography/CT (FDG-PET/CT) imaging results demonstrated resolution of the activity at the base of tongue mass and the involved cervical lymph nodes, consistent with complete treatment response.In July 2019, the patient presented with a palpable left supraclavicular lymph node.

Biopsy of the mass demonstrated metastatic p16-positive (human papillomavirus [HPV]-related) squamous cell carcinoma.

Examination revealed a large left base of tongue mass filling the vallecula.

Computed tomography (CT) demonstrated an enhancing mass within the left base of tongue and bilateral cervical adenopathy.

Restaging FDG-PET/CT demonstrated avid supraclavicular and anterolateral neck adenopathy.

Additionally, there was moderately intense activity isolated to the left thyroid lobe.

Ultrasonography of the thyroid demonstrated a 4-cm mass within the gland, and subsequent biopsy was performed with immunohistochemistry staining positive for p16, CK5, and p40 and negative for thyroid transcription factor 1 (TTF-1) (Figure, A, B).

C, Lesional specimen showing tumor cells arranged in irregular nests and cords invading the thyroid parenchyma; normal thyroid tissue shown by the arrowhead (original magnification ×4).

The patient was treated with concurrent radiation therapy and cetuximab, completing treatment without breaks in November 2018.

After multidisciplinary review of the case, the patient was offered salvage left modified radical neck dissection and total thyroidectomy.

Surgical pathology confirmed the diagnosis (Figure, C).Fine-needle aspiration of the left thyroid lesion showing sheets and clusters of tumor cells with indistinct cell borders, with immunohistochemical staining positive for p16 (A) and negative for TTF-1 (B) (both panels, original magnification ×20).


Six months prior to presentation, she developed a dull pain in her left calf while climbing stairs.

After climbing 2 flights of stairs, she had to stop and rest for approximately 15 seconds.

The patient’s symptoms worsened and began interfering with her work.

On physical examination, her heart rate was 82/min and blood pressure was 140/89 mm Hg.

Her lower extremities were warm, with strength for femoral, popliteal, dorsalis pedis, and posterior tibial pulses at 2+ bilaterally.

She had no history of spinal degenerative disease and did not have lower extremity arterial bruits, wounds, sensory deficits, edema, or hair loss.


She had no fevers, nausea, vomiting, diarrhea, constipation, blood in the stool, or weight loss.

On examination, her temperature was 36.9 °C; heart rate, 72/min; blood pressure, 132/68 mm Hg; and body mass index, 25 (calculated as weight in kilograms divided by height in meters squared).

Results of complete blood cell count and serum chemistries were unremarkable, with no leukocytosis and normal differential count.

Abdominal examination demonstrated mild distention without fluid wave and mild right lower abdomen and suprapubic tenderness.

Computed tomography (Figure 1) and magnetic resonance imaging demonstrated pelvic ascites and an enhancing lesion at the base of the cecum.

Two attempts at ultrasound-guided paracentesis were nondiagnostic because of acellular specimens.


The medical history was unremarkable, and findings of a review of systems were negative.

The patient had been treated in the past with topical steroids without improvement, and the size of the lesion had continued to grow slowly.

Physical examination findings revealed a solitary, well-circumscribed pink plaque with overlying yellow-white micaceous scale with interspersed punctate hemorrhagic crusts (Figure, A).

Punch biopsy for histopathologic examination was performed, with representative sections shown (Figure, B and C).A, Well-circumscribed pink, scaly plaque on the right elbow.

B and C, Hematoxylin-eosin–stained sections reveal psoriasiform epidermal hyperplasia overlying suppurative granulomatous infiltrates with multinucleate giant cells and rare eosinophilic spheroid forms.


On arrival, his blood pressure was 222/120 mm Hg, which subsequently normalized with administration of his home regimen for hypertension.

The patient noted an elevated blood pressure and took clonidine hydrochloride without effect, so he called emergency medical services.

His chest pressure resolved after administration of sublingual nitroglycerin en route to the emergency department.

Following initial angioplasty, the patient abruptly became hypotensive without chest discomfort despite quick balloon inflations and robust thrombolysis in myocardial infarction grade 3 flow down both the LAD and LCX.

Unfortunately, his blood pressure continued to rapidly decline, and he experienced an asystolic cardiac arrest.

An electrocardiogram showed sinus rhythm with a preexisting left bundle-branch block.

The troponin I level was initially undetectable but subsequently peaked at 1.3 ng/mL (conversion to micrograms per liter is 1:1).

A transthoracic echocardiogram showed normal left ventricular systolic function with regional wall motion abnormalities suggestive of ischemia in the area supplied by the left anterior descending coronary artery (LAD).

The patient was taken to the cardiac catheterization laboratory the following day for further management of his non–ST-segment elevation myocardial infarction.Coronary angiography revealed a high-grade distal left main coronary artery (LM) bifurcation lesion extending predominantly into the LAD (Figure 1A); the remainder of his coronary tree showed no evidence of obstructive disease.

Given the patient’s low SYNTAX (synergy between percutaneous coronary intervention [PCI] with taxus and cardiac surgery) score and preference to avoid surgery, he underwent transradial PCI of the LM-LAD using a provisional approach for the left circumflex coronary artery (LCX).

There was no evidence of coronary dissection or perforation.

The LM-LAD was quickly stented (Figure 1B) as intravenous fluids and escalating doses of intravenous dopamine hydrochloride and epinephrine drips were administered.

Cardiopulmonary resuscitation was initiated and the patient was emergently intubated, but he remained in asystole.Selective left coronary angiography before (A) and after (B) percutaneous coronary intervention (PCI) of the left main coronary artery and the left anterior descending coronary artery.


He reported throat tightness after significant voice use and consistent voice roughness that worsened over several weeks.

The patient continued to report dysphonia and increased vocal effort.

On examination, he had moderate to severe dysphonia with predominant roughness and strain.

Follow-up videostroboscopy findings demonstrated resolution of the fungal laryngitis but revealed residual fullness of the left false vocal fold and appearance of prolapsed ventricular mucosa obstructing the lateral extent of the left true vocal fold.

There was a reduction of lateral excursion of the mucosal wave on the left.

A computed tomography scan with contrast showed no specific abnormalities.

Intraoperatively, there was a firm lesion in the left paraglottic space extending to the lateral aspect of the true vocal fold (Figure, A).

A subtle but similar finding was seen on the right true vocal fold, not causing any mass effect (Figure, B).

Videostroboscopy findings were consistent with fungal laryngitis; a 2-week course of fluconazole was administered.

This revealed a cartilaginous lesion, which was removed using an AcuBlade CO2 laser (Lumenis) and cup forceps until the cartilaginous edge was smooth within the paraglottic space (Figure, C and D).

A direct laryngoscopy for evaluation and treatment was planned.

The histologic specimen showed fragments of cartilage with no nuclear atypia or mitosis (Figure, E and F).

At 3-months’ follow-up, the patient reported improvement in his voice with decreased effort and strain, which correlated with improvement in the Voice Handicap Index score and objective assessment by the clinicians.Direct laryngoscopy intraoperative images demonstrating left lesion (A), right lesion (B), submucosal firm, white mass excised with a CO2 laser (C), and postoperative view (D); hematoxylin-eosin stain of the left lateral vocal fold lesion showing fragments of cartilage (arrow indicates a peripheral thin fibroblastic rim with a transition to mature chondrocytes of the fibroelastic cartilage toward the center of the nodule) (E) and cartilage with mild nuclear atypia without mitosis (F).


The lesion was of unknown duration and was reported by the patient to be asymptomatic, although he did endorse occasional pruritus.

An extraoral examination was performed without any abnormal findings.

On intraoral soft tissue examination, a brown pigmented patch located predominantly on the hard palate was observed.

The lesion had well-defined but irregular borders, measured 2 × 1.2 cm in size, and was nontender to palpation (Figure, A).

Findings of the remainder of the intraoral soft tissue examination were within normal limits.

B and C, Medium-magnification and high-magnification hematoxylin-eosin–stained images demonstrate slender, elongated dendritic melanocytes (marked by arrows) throughout the epithelium.Histologic examination findings revealed soft tissue covered by benign-appearing stratified squamous epithelium, focally spongiotic and acanthotic.

Within the epithelium, numerous benign dendritic melanocytes were identified (Figure, B and C).

The underlying connective tissues were unremarkable.

An incisional biopsy was performed, and the specimen was sent for microscopic diagnosis.A, Intraoral photograph demonstrating the brown pigmented palatal patch with irregular, albeit sharply demarcated borders.


The patient had no significant medical history; prior surgical history was notable for tonsillectomy.

The hypoesthesia was limited to the distribution of the mandibular branch of the left trigeminal nerve (V3).

On review of systems, the patient denied experiencing visual changes, dizziness, headaches, oral or neck pain, voice changes, weight or appetite changes, or swallowing dysfunction; however, he did report biting his lip occasionally due to the numbness.

On examination, there were no palpable masses noted in the head, neck, or face.

Aside from the V3 sensory deficit, the patient had no cranial nerve deficits.

Magnetic resonance imaging of the face revealed a T1 isointense, T2 hyperintense 5.9-cm lesion in the left masticator space, which appeared to be centered in the lateral pterygoid muscle with benign-appearing remodeling of the posterior maxillary wall (Figure).A, The lesion (indicated by the arrow) is isointense on T1-weighted magnetic resonance imaging (MRI) without contrast.

B, The lesion enhances with contrast on fat-suppressed T1-weighted imaging.

C, The mass is hyperintense on the T2-weighted sequence.

D, Computed tomography imaging reveals bony erosion and expansion of the lesion into the maxillary sinus.


No fever, odynophagia, dysphagia, otalgia, or other constitutional symptoms were reported.

Physical examination findings demonstrated a palpable, soft, nontender left level II/III neck mass.

Clinical examination findings of the thyroid and upper aerodigestive tract were unremarkable.

Contrast-enhanced neck computed tomography (CT) showed a large avidly enhancing mass centered at the left carotid bifurcation splaying the internal and external carotid arteries and extending cranially along the cervical internal carotid artery.

The left internal jugular vein was displaced posteriorly.

There was also a smaller mass with similar appearance at the right carotid bifurcation (Figure 1A).

Contrast-enhanced abdominal CT showed several enhancing masses in the liver (not shown).

Based on CT findings, gallium Ga 68 (68Ga) dotatate positron emission tomography (PET)/magnetic resonance imaging (MRI) was performed; results demonstrated intense radiotracer avidity in bilateral carotid space masses, hepatic masses, and numerous CT occult osseous lesions (Figure 1B).A, Axial contrast-enhanced neck computed tomography (CT) demonstrates large left (black asterisk) and small right (white arrowhead) avidly enhancing bilateral carotid space masses.

The left tumor circumferentially encases the left external carotid artery (black arrowhead) and partially encases the left internal carotid artery (yellow arrowhead).

B, Coronal gallium 68 dotatate positron emission tomography/magnetic resonance imaging (PET/MRI) demonstrates intense radiotracer uptake of bilateral carotid space masses (left, black asterisk; right, white arrowhead), hepatic masses (black arrowhead), and CT occult osseous lesions as seen in the right femoral neck (yellow arrowhead).

The patient had been treated presumptively for infection with antibiotics, with no improvement.


His medical history was significant for Crohn disease controlled with monthly injections of ustekinumab (Stelara; Janssen Biotech Inc).

Symptoms of fever, headache, and myalgia began 1 week prior following a tick bite.

While hospitalized, he developed acute bilateral central scotoma.

He was found to be anemic (hemoglobin concentration, 6.7 g/dL; normal concentration, 13.5-17.5 g/dL) (to convert hemoglobin concentration to g/L, multiply by 10), requiring transfusion.

Magnetic resonance imaging of the orbit and brain with and without contrast was unremarkable.

Infectious serology test results for Lyme disease, syphilis, malaria, Anaplasma species, Cryptococcus species, Rocky Mountain spotted fever, and rickettsia were negative.

Rheumatologic serology test results for antinuclear antibodies, including Sjögren anti-Ro and anti-La, anti-DNA, and anti-Smith, were also negative.

Antineutrophil cytoplasmic antibody testing revealed elevated proteinase 3 antibody level.

Polymerase chain reaction results for babesiosis later returned as negative.Ocular examination revealed uncorrected distance acuity of 20/50 OD and 20/60 OS.

Intraocular pressure values were normal, and there was no afferent pupillary defect.

Slitlamp evaluation showed bilateral rare anterior vitreous cell.

Dilated fundus examination revealed bilateral reddened foveal lesions and irregular macular pigmentation.

He was prescribed oral doxycycline hyclate for suspected Lyme disease.

Owing to persistent fever while receiving oral doxycycline hyclate, he was admitted for intravenous administration of doxycycline hyclate, and the fever resolved.

Peripheral blood smear and polymerase chain reaction were performed; empirical therapy of azithromycin, 500 mg daily, plus atovaquone, 750 mg twice daily, was initiated.

In the setting of anemia, infectious-disease consultants raised concern for babesiosis.


He denied having any symptoms of increased intracranial pressure (ICP), including headaches, pulsatile tinnitus, and transient visual obscurations.

Findings on computed tomography of the brain without contrast were unremarkable.

He was then seen by an ophthalmologist who confirmed bilateral severe optic nerve edema and requested magnetic resonance imaging of the brain and orbits without contrast.

It demonstrated signs of increased ICP, including empty sella, posterior flattening of the globes, and widened optic nerve sheaths, but no other abnormalities (Figure 1A).A, Axial T2-weighted magnetic resonance imaging (MRI) showing flattening of the posterior margin of the globes at the insertion point of the optic nerves (white arrowhead) and dilatation of the subarachnoid space along the optic nerve sheaths (yellow arrowhead), which are signs of elevated intracranial pressure.

These findings are symmetrical between the 2 eyes.

B, Fundus photograph demonstrating grade 3 to 4 optic nerve edema of the left eye.

The visualized retinal vessels and retina are normal.

The right eye had a similar appearance.On examination, best-corrected central acuities were 20/20 OD and 20/25 OS.

There was no relative afferent pupillary defect.

Findings of color vision testing with Ishihara isochromatic plates were normal in each eye (17 of 17 plates identified).

Dilated ophthalmoscopic examination revealed severe optic nerve edema bilaterally with normal-appearing macula and retinal vasculature (Figure 1B).

Visual fields (Humphrey 24-2 algorithm) were normal in each eye.

Optical coherence tomography of the peripapillary retinal nerve fiber layer demonstrated increased retinal nerve fiber layer thickness bilaterally (mean of 246 μm OD and 252 μm OS).

Fundus autofluorescence imaging did not demonstrate optic nerve head autofluorescence.


He had a medical history of hypertension, anxiety, and posttraumatic stress disorder, for which he took amlodipine, lorazepam, citalopram, and quetiapine.

He smoked 1.5 packs of cigarettes per day for the past 30 years and had a history of substantial alcohol use, drinking 2 to 3 L of wine per day.

Because of excessive alcohol intake, he only ate 1 meal per day.

His family history was unremarkable for optic nerve conditions or unexplained blindness.On examination, his visual acuity was 20/400 OU, there was no relative afferent pupillary defect, and his anterior segment examination results were normal.

Dilated fundus examination results revealed bilateral optic nerve hyperemia, blurred margins, and subtle telangiectatic vessels on the surface of the optic nerve bilaterally.

Humphrey 24-2 Swedish Interactive Testing Algorithm fast visual field testing showed central scotomas in both eyes (Figure).

Optical coherence tomography results of the macula were normal in both eyes.

Neurological examination results revealed otherwise normal cranial nerves, normal sensation in the extremities, normal reflexes, and normal strength.Humphrey 24-2 Swedish Interactive Testing Algorithm fast visual fields demonstrating central scotomas in both eyes.


Prior surgeries included cataract surgery in both eyes, selective laser trabeculoplasty in both eyes, trabectome in the right eye (NeoMedix), and mitomycin trabeculectomies in both eyes.

Medications included latanoprost in both eyes once daily, dorzolamide-timolol in the right eye twice daily, and brimonidine in the right eye once daily without complications until a few months prior to presentation when netarsudil in both eyes once a day was added for high intraocular pressures of 21 mm Hg OD and 17 mm Hg OS.

Netarsudil was used in both eyes after a monocular trial of netarsudil in the right eye, which was judged successful owing to a 9–mm Hg pressure reduction in the right eye relative to the left eye.

A few weeks later, the patient returned with worsening pain in the right eye, and visual acuity was 20/500 OD and 20/250 OS.

On presentation, his visual acuity was 20/50 OD and 20/200 OS with correction (1 line worse from baseline in the right eye).

Slitlamp examination revealed conjunctival hyperemia and papillae in both eyes.

The right cornea had 1.5 mm of inferonasal microcystoid epithelial edema with neovascularization.

Dorzolamide in the right eye was discontinued.

There was diffuse microcystoid epithelial and stromal edema in both eyes, worsening reticular changes in the right eye (Figure 1), a new inferocentral wavelike superficial opacification in the left eye, and high pressures (28 mm Hg OD and 13 mm Hg OS).A, Netarsudil-associated reticular epithelial edema was most marked inferior nasally in the right eye (white arrowhead), although diffuse microcystoid epithelial and stromal edema were present in both eyes.


On review of systems, she reported hair loss, dryness of the eyes and mouth, and mild esophageal dysphagia.

She reported no oral ulcers, pleuritic chest pain, shortness of breath, hemoptysis, decreased urine output, hematuria, joint pain, fevers, or weight change.On examination, she was afebrile.

Heart rate was 60/min; blood pressure, 100/70 mm Hg; respiratory rate, 18/min; and Spo2, 100%.

Her hands and fingers were mildly edematous, and the fingertips variably showed purple discoloration, distal pitting scars, and ischemic ulcers (Figure, panel A).

There was periungual erythema with dilated nailfold capillaries but no splinter hemorrhages.

She had no evidence of sclerodactyly or proximal skin thickening, with hands and face showing fine wrinkles and normal-appearing skin folds.

Results of initial laboratory studies were notable for white blood cell count 3270/μL; hemoglobin level, 14.5 g/dL; platelet count, 143 ×103/μL; creatinine level, 1.0 mg/dL (88.4 μmol/L); and C-reactive protein level, 0.1 mg/dL.

Computed tomography angiography (CTA) of the bilateral upper extremities showed normal vasculature.

Antinuclear antibodies (ANA) were positive at 1:640 or greater by indirect immunofluorescence in a composite nuclear and nucleolar fine speckled staining pattern (Figure, B).

Subserologic testing showed high positive anti-Ro52 (176; <20), anti-Ro60 (563; <20), and anti–Scl-70 antibodies (786; <20).A, Digital changes observed in patient.


She took no medications and her medical history was significant for a first-trimester miscarriage.

She was a schoolteacher and had not traveled outside of the country in the past 10 years.Physical examination of her lower extremities revealed erythematous and indurated plaques, some with overlying coarse scale (Figure, A and B).

The plaques began around her ankles and spread proximally, reaching the upper thighs by the time of presentation.

She also noted new lesions on her arms and abdomen in the preceding weeks.

The eruption was asymptomatic, and the plaques were preceded by lower extremity edema and weakness, resulting in difficulty ambulating and frequent falls.

The patient also reported allodynia, tingling, and numbness in her lower legs.

Her neurological examination showed symmetric 4/5 strength and decreased reflexes in her lower extremities.

Sensation to light touch and proprioception were diminished below the knee.

Two punch biopsies were performed for histologic review (Figure, C and D).A, Dark brown, coarse, ichthyosiform scale on the bilateral lower legs.

B, Firm pink plaques with overlying coarse scale.

C, Granulomatous inflammation throughout the dermis with mild hyperparakeratosis around a hair follicle (hematoxylin-eosin).

D, Well-formed, epithelioid granulomas (hematoxylin-eosin).


No remarkable medical history was noted.

Physical examination findings revealed a 4 × 2-cm erythematous, violaceous, indurated, scaly plaque with some papules on his right upper eyelid (Figure, A).

Results of routine blood tests and biochemistry analysis were within normal limits.

A biopsy sample was obtained for histopathologic examination (Figure, B).A, A 4 × 2-cm erythematous, violaceous, indurated, scaly plaque with some papules on the right upper eyelid.

B, Lesional specimen (original magnification ×50).

C, High-power magnification of histopathologic examination; arrows indicate atypical lymphocytes (hematoxylin-eosin).

D, Lymphocytic infiltrates predominantly positive for CD4.Histopathologic analysis revealed perifollicular lymphocytic infiltrates around cystically dilated follicular infundibula and exocytosis of atypical lymphocytes into the epithelium, with admixed plasma cells, eosinophils, and multinucleate giant cells (Figure, C).

Alcian blue staining showed focal mild follicular mucin deposition.

Immunohistochemical analysis showed lymphocytic infiltrates positive for CD3, CD4, CD5, and CD7 and negative for CD8, CD20, CD30, CD79a, and CD56 (Figure, D).

The ratio of CD4 to CD8 cells within hair follicles was greater than 7:1.

Monoclonal T-cell gene rearrangement was demonstrated.


She had been diagnosed with hormone receptor–positive right breast cancer 8 years prior and underwent lumpectomy and treatment with an aromatase inhibitor, with remission since.

Five years later, she subsequently developed left inguinal adenopathy, which biopsy results showed was follicular lymphoma.

Magnetic resonance imaging (MRI) of the brain was performed, demonstrating T2 fluid-attenuated inversion recovery hyperintensity in the left occipital and temporal lobes, crossing the corpus callosum and extending into the right occipital lobe without enhancement (Figure).A, Axial T2 fluid-attenuated inversion recovery precontrast magnetic resonance imaging (MRI) of the brain.

B, Axial T1 magnetization-prepared rapid acquisition gradient-echo postcontrast MRI of the brain.

At that time, she was treated with a course of bendamustine and rituximab with subsequent maintenance treatment with rituximab for 2 years.


Two years prior to presentation, the patient was presumptively diagnosed with viral myocarditis at an outside hospital after experiencing a ventricular fibrillation arrest.

He was subsequently scheduled to undergo endomyocardial biopsy but was lost to follow-up.

Two weeks prior to the date of the presenting ECG, he was admitted to the hospital for symptomatic bradycardia and found to be in sinus rhythm with complete atrioventricular block.

A dual-chamber pacemaker was implanted, with active fixation leads placed in the right atrium and right ventricular apex.

An ECG obtained immediately after the procedure showed an atrial-ventricular–paced rhythm.

His vital signs were documented as a blood pressure of 119/69 mm Hg, a heart rate of 51 beats per minute, a respiratory rate of 16 breaths per minute, and an oxygen saturation of 100% on room air.

The postimplantation course was uncomplicated, and he was subsequently discharged.

He presented for routine postprocedure outpatient follow-up, at which time this ECG (Figure 1) was obtained.


On arrival to the hospital, the patient had a computed tomography scan performed; results demonstrated an obstructive laryngeal mass but no signs of local invasion or lymphadenopathy.

Findings of a direct laryngoscopy demonstrated violaceous nodules of the base of the tongue as well as a mass of the infraglottis and subglottis, which was nearly completely obstructing the airway (Figure, A and B).

Full physical examination findings also demonstrated violaceous nodules involving the patient’s lower extremities.

Results of an excisional biopsy demonstrated a subepithelial spindle cell lesion with extravasation of erythrocytes and stained strongly for human herpesvirus-8 (Figure, C).Left base of tongue mass with a violaceous hue (A), obstructive mass of the subglottic airway (B), and subepithelial spindle cell lesion with extravasation of erythrocytes and stained strongly for human herpesvirus-8 (hematoxylin-eosin; original magnification ×10) (C).

The patient was taken urgently to the operating room where an awake tracheostomy was performed without complication.


She had no prior medical or surgical history and took no medications.

Ultrasonography demonstrated a solid and hypoechoic mass, 1.5 × 1.0 × 0.9 cm, in the inferior right parotid gland with minimal vascularity and without extraparotid extension.

Fine-needle aspiration was performed, and the smear was extremely cellular and showed sheets and clusters of bland polygonal epithelial cells admixed with bright pink filamentous matrix.

Abundant bubbly secretion was present within these microcystic spaces, and this material was positive for periodic acid–Schiff (Figure, C).

Immunohistochemically, there was positivity for epithelial membrane antigen, cytokeratin (CK) 7 and CK19, S100 protein, and gross cystic disease fluid protein 15 (GCDFP-15).

Stains for gastrointestinal stromal tumors 1 (DOG1) and p63 were negative.

The patient underwent a right parotidectomy I to IV1 and a level II superselective neck dissection.A, Hematoxylin-eosin, original magnification ×40.

Tumor cells with oval and rounded nuclei with fine chromatin and centrally localized nucleolus, with papillary architecture.

B, Microcystic growth pattern (hematoxylin-eosin, original magnification ×40).

C, The secretory material stains positive for periodic acid–Schiff; original magnification ×20.

Because of the size and location, extracapsular dissection II was carried out.1 The final pathology of the lesion showed histologic findings compatible with salivary gland carcinoma, with microcystic and papillary architecture (Figure, A and B).

There was perineural invasion without evidence of neoplastic emboli in the peritumoral lymphovascular spaces.

The tumor appeared to be contained within the surgical excision margins.


B, Optical coherence tomography showed generalized undulating choroidal thickening in a so-called seasick pattern.A relook at the anterior segment in the left eye revealed a faint conjunctival thickening at the limbus suggestive of lymphoid tumor.

On examination, his visual acuity was 20/20 OD and 20/40 OS.

Intraocular pressures were normal in each eye.

Anterior segment and fundus examination results were normal in the right eye.

In the left eye, the media were clear, and there were multiple patchy, yellow choroidal lesions with obliteration of the normal choroidal vasculature throughout the entire fundus (Figure 1A).

Ocular ultrasonography revealed diffuse ciliochoroidal thickening measuring 2.9 mm in elevation.

Optical coherence tomography disclosed generalized, undulating choroidal infiltration in a seasick pattern, so to speak, given its resemblance to a stormy ocean surface, with overlying draping of the retina in the foveal region (Figure 1B).A, A healthy man in his 60s with decreased visual acuity in the left eye was found to have multiple patchy, yellow choroidal foci with loss of the choroidal vascular detail throughout the entire fundus.

There was no sign of vitritis or retinitis and no history of previous trauma, uveitis, sarcoidosis, or cancer.


The lesion was not painful but was associated with ipsilateral facial numbness.

There was notable hypoesthesia in the distribution of the trigeminal maxillary branch.

On examination, he manifested a 9 × 6-mm ulcerated marginal lesion of the central right lower eyelid with surrounding edema and erythema (Figure 1).

There was no associated lash loss and the region was nontender to palpation.

On examination, his best-corrected visual acuity was 20/20 OU.

The pupils were round and brisk without an afferent pupillary defect.

He manifested full extraocular movements.

The anterior segment examination, applanation tonometry, and dilated fundus examination results were within normal limits.External photograph demonstrating left lower eyelid ulcerated lesion with overlying black eschar and surrounding edema and erythema.

He was seen by an outside ophthalmologist and prescribed oral amoxicillin/clavulanic acid (675 mg/125 mg) and ophthalmic tobramycin for presumed bacterial infection without improvement.


In addition, the right eye had developed 2+ anterior chamber cell, keratic precipitates, and a possible branch vein occlusion.

Her Snellen visual acuities were 20/25 OD and 20/20 OS.

Her intraocular pressures were 21 mm Hg OD and 14 mm Hg OS.

The right eye had a relative afferent pupillary defect and mild optic nerve edema.

To rule out optic neuritis, a magnetic resonance imaging scan of the brain and orbits was obtained; the results were unremarkable.

Six days after symptom onset, her visual acuity decreased to 20/70 OD and the disc edema increased.

At this time the patient was referred to our clinic.

On presentation 1 day later, visual acuity was light perception OD and still 20/20 OS.

The right eye had 3+ anterior chamber cell, inferior keratic precipitates, and 1+ vitreous cell.

The right optic nerve had grade 4 disc edema with flame-shaped peripapillary hemorrhages.

The fundus examination results of the right eye revealed the following superior quadrant retinal findings: extensive intraretinal and preretinal hemorrhages along vessels, arteriolar attenuation and sheathing, venous engorgement, and tortuosity.

The inferior midperiphery had numerous small areas of deep retinal whitening (Figure 1).

Examination results of the left eye were normal.An Optos color photograph of the right eye of a woman in her 40s with grade 4 disc edema and associated flame-shaped peripapillary hemorrhages.

Also noted are diffuse intraretinal and preretinal hemorrhages in the superior peripheral retina.

The retinal arteries are attenuated with box carring throughout the retina.

There is extensive vascular sheathing involving predominantly the retinal venules, which are also dilated and tortuous (arrowhead).


He did not use tobacco, alcohol, or drugs.

His parents and both siblings were reportedly healthy with no history of ocular disease.

The patient reported slowly progressive difficulty with night driving as well as perceiving objects in the periphery over the past 5 years.

The patient was an avid basketball player and was forced to quit recently when he was unable to locate his teammates during play.

His visual acuity was 20/20 OU, with no afferent pupillary defect.

The Farnsworth D-15 dichotomous test results were normal in the right eye and tritan deficient in the left eye.

His intraocular pressure was normal in both eyes.

Refraction revealed hyperopic astigmatism in both eyes.

His anterior examination results were unremarkable with no evidence of intraocular inflammation.

The dilated fundus examination results showed minimal optic nerve pallor, vascular attenuation in both eyes, and a subtle area of increased pigmentation in the superior retina of the right eye only (Figure 1A).

The fundus autofluorescence results showed bilateral peripheral mottled hypoautofluorescence contrasting a ring of hyperautofluorescence around the macula (Figure 1B).

Automated perimetry was reliable and showed symmetrical severe bilateral field constriction with a remaining island of 6° of central vision.Right eye.

A, Widefield photograph (Optos) showing vascular attenuation, with reduced vessel caliber in the macula (asterisks) and vessels sclerosis in the periphery (black arrowhead).

There is a small area of hyperpigmentation in midperiphery just superior to the optic nerve (white arrowhead).


He was not taking any ocular medications, and his only systemic medication was an oral β-blocker.

He was otherwise healthy, and his family history was noncontributory.On a slitlamp examination, multiple brown masses were noted at the pupillary margin in both eyes, encroaching on the central visual axis (Figure).

He was unaware of any recent changes in the size or number of these lesions.

The patient had noticed progressive visual obscuration in his left eye.

His visual acuity measured 20/25 (6/7.5) OU, and his intraocular pressures were 14 mm Hg OU.

There was no inflammation in the anterior chamber or vitreous.


Transbronchial biopsy histopathology showed acute and chronic inflammation, granulation tissue and necrosis, and negative fungal and AFB stains.Two weeks later, the patient reported worsening right-sided chest pain provoked by palpation, right arm movement, and deep inspiration.

She developed hypoxemia and required intubation.

Lung tissue was sent for bacterial, fungal, mycobacterial, and Nocardia cultures and for histopathology.

BAL cultures grew 100 colony-forming units (CFUs)/mL of group B streptococci and 1 CFU/mL of Aspergillus niger.

Results of acid-fast bacilli (AFB) smear and GeneXpert MTB/RIF testing were negative.

Voriconazole was added to her treatment.

Repeat chest CT demonstrated cavitary mass enlargement with possible pleural invasion (Figure 1, left).

A right-sided tension pneumothorax developed and required emergency chest tube placement, which yielded charcoal-colored pleural fluid (Figure 1, right).Left, Computed tomography scan of the chest demonstrating large right upper lobe cavitary lesion, layering debris, and bronchial wall thickening.

Right, Charcoal-black appearance of the pleural fluid seen in the atrium of the patient’s right-side chest tube placed for tension pneumothorax.

She was treated empirically with intravenous vancomycin and piperacillin-tazobactam.

Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy was performed.


The patient provided the report of a skin biopsy performed 2 years before presentation.

She had been treated with topical corticosteroids with no control of the symptoms.

Physical examination revealed erythematous papules, some of them crusted, and some excoriations located over the trunk and upper extremities (Figure 1A).

In addition, some scales and fissures were seen on her lower lip (Figure 1B), sparing the surrounding skin, as well as inner mouth and upper lip.

It was described as indicating spongiotic dermatitis.

A new biopsy sample was taken to rule out actinic cheilitis.A, Clinical image of actinic prurigo in the skin of the patient showing unspecific erythematous papules on the arm.

B, Clinical image of actinic prurigo cheilitis in the patient showing scales, crusts, and fissures on the lower lip.


She was diagnosed as having pancreatic adenocarcinoma in September 2019 after developing right upper quadrant pain and jaundice, which prompted imaging and a subsequent endoscopic biopsy of a pancreatic head mass.

Several hypodense lesions in the apex of her heart were appreciated on review of her previous chest computed tomography scan (Figure 1A).

A subsequent transthoracic echocardiogram (Figure 1B) was obtained and revealed several discrete, partially mobile frondlike masses originating from her cardiac apex.

Both services requested cardiac magnetic resonance imaging for further clarification of her imaging findings.A, An axial slice from the patient’s chest computed tomography with contrast.

B, A 4-chamber view from the patient’s transthoracic echocardiography.

She established oncologic care in Kentucky and received 1 dose of gemcitabine plus nanoparticle albumin-bound (nab)–paclitaxel in early October 2019.

Her infusion port (right sided) was subsequently removed, and she was given 1.5 mg/kg of enoxaparin daily for anticoagulation.After her transfer, the oncology department was consulted regarding treatment options for her pancreatic cancer.

Her posttreatment course was complicated by elevated levels of transaminases, significant fatigue, and an infusion port thrombosis.

The cardiology and cardiothoracic surgery departments were consulted for input pertaining to her case.

The arrowheads denote atypical lesions in the left ventricle of the patient.

The arrowhead denotes the largest of the 3 frondlike masses emanating from the apex of her heart.


His cardiomyopathy followed a diagnosis of myocarditis after repeated putative chest colds and chest pain at age 14 years, at which time the ejection fraction was reported to be 30%.

His chest pain and dyspnea were chronic and had recently increased in frequency.

The results of a graded exercise stress test at 22 years were unremarkable.On examination, he was afebrile.

His heart rate was 68 beats per minute, his blood pressure was 114/77 mm Hg, and his examination was notable for an absence of jugular venous distension, peripheral edema, and murmurs or extra heart sounds.

His electrocardiogram, shown in Figure 1, was notable for right bundle branch block and left anterior fascicular block, unchanged from his electrocardiogram at age 14 years.

Transthoracic echocardiography revealed an ejection fraction of 40%.

An exercise nuclear stress test revealed a fixed, severe apical defect, a partially reversible severe anterior wall defect, moderate global hypokinesis, and severe hypokinesis of the distal anterior wall and apex.

His ejection fraction was estimated to be 32%.


Medical history was notable for coronary artery disease, hypothyroidism, and prostate cancer in remission.On ophthalmic examination, visual acuity was hand motion OU (baseline from 9 months prior was 20/50 OD and 20/30 OS), with briskly reactive left pupil and trace right relative afferent pupillary defect.

He could detect 2/4 gross colors in the right eye and 1/4 gross colors in the left eye.

Confrontation visual fields revealed dense right homonymous hemianopia with additional asymmetric deficits on Goldmann perimetry (Figure 1).

Extraocular movements were full with gaze-evoked nystagmus.

Horizontal vestibulo-ocular reflex, assessed by head impulse testing, was normal.

Slitlamp and dilated fundus examination revealed pseudophakia and mild epiretinal membrane in the right eye and mild nuclear sclerosis in the left eye.Goldmann perimetry (V4e stimulus) of left (A) and right (B) eyes shows right homonymous hemianopia, left inferotemporal visual field loss, and right nasal paracentral visual field loss.Neurologic examination showed full motor strength, decreased vibration sense and proprioception in the feet, positive Romberg sign, and inability to tandem walk.

Mini-Mental State Examination score was 6 of 30.Magnetic resonance imaging brain and orbits with and without contrast and magnetic resonance angiography head and neck were unremarkable.

An electroencephalogram showed no localizing signs.

Serum thiamine, vitamin B12, and thyrotropin levels were normal.

Cerebrospinal fluid composition, infectious studies, cytology, flow cytometry, and paraneoplastic panel showed only mildly elevated protein.


The patient was otherwise asymptomatic, and a complete review of systems was negative.

The results of her physical examination were notable for left-sided blepharoptosis with a palpable mass of the upper eyelid laterally.

Eyelid eversion examination findings showed a yellow nodular lesion along the tarsal conjunctiva (Figure, A).

Histopathologic examination results showed amorphous acellular proteinaceous deposits that positively stained with Congo red (Figure, B, inset).

Polarized microscopy of the deposits showed apple-green birefringence (Figure, B).A, Everted upper eyelid examination results reveal an elevated yellow, waxy mass along the tarsal conjunctiva (arrowhead).

B, Histopathologic appearance of the lesion.

Amyloid deposits show apple-green birefringence under polarized light (original magnification ×10) when stained with Congo red (inset, area with dashed outline) (original magnification ×10).


However, unnoticed by the patient, her BCVA had worsened to 20/200 OD and 20/40 OS.

Similar findings were present in the left eye.One week later, the BCVA worsened to E at 3 feet OD and 20/200 OS.

Her best-corrected visual acuity (BCVA) was 20/30 + 2 OD and 20/20 OS.

Her intraocular pressure, extraocular motility, and pupillary light reactions were normal.

An examination demonstrated trace anterior cells in the right eye; otherwise, the examination had normal results.

An examination demonstrated new subretinal fluid in the macula in the right eye (Figure 1A).

Fluorescein angiography showed peripapillary speckled pinpoint areas of hyperfluorescence in the right eye.

Indocyanine green showed early choroidal vessel hyperfluorescence and several posterior focal hypofluorescent spots in the midphase in both eyes.

Autofluorescence showed patchy hyperautofluorescence in both eyes.

Tuberculosis and syphilis testing had negative results.

A complete blood cell count was unremarkable.

A, Optical coherence tomography of the right eye demonstrates posterior vitreous cells (white arrowheads), subretinal fluid, and choroidal corrugation (yellow arrowheads).

B, Fundus photograph of the right eye demonstrates multifocal, demarcated exudative retinal detachments, including in the macula.

An examination now revealed 2+ vitreous cells and extensive exudative retinal detachments in both eyes (Figure 1B).

Topical prednisolone was started for presumed acute anterior uveitis.One week later, the photophobia had improved.

The topical prednisolone was stopped.Findings on presentation and follow-up.

A diagnosis of central serous retinopathy (CSR) was made.


Her medical history and family history were unremarkable.

A potassium hydroxide preparation had negative results for fungal elements.

An examination found a 1-cm nummular plaque with centralized micaceous scale and a smooth erythematous border on the right lateral lower leg (Figure, A).

Histopathological testing revealed an epidermis featuring elongated rete ridges, keratinocyte enlargement, and a few Civatte bodies, with overlying parakeratotic crust and neutrophilic cell debris.

Marked epidermotropism of atypical lymphocytes with irregular nuclear contours and halos, both singly and in small collections (Pautrier microabscesses) were also observed (Figure, B and C).

Also, lymphocytes were present along the epidermal side of the dermoepidermal junction.

Periodic acid–Schiff stained sections failed to show fungal or yeast elements.

Immunohistochemical staining was markedly positive for CD3, CD5, and CD8 (Figure, D); CD4 reactivity was less robust and mainly restricted to dermal lymphocytes.

Also, CD20 was present in 5% of dermal lymphocytes, and CD30 showed variable staining of 5% of lymphocytes.A, Image of a solitary plaque on the right lateral lower leg.

B, Scanning view with hyperkeratosis, epidermal hyperplasia, and a lichenoid-like lymphoid infiltrate (hematoxylin-eosin).

C, Biopsy results with marked epidermotropism of atypical lymphocytes (hematoxylin-eosin).

D, Biopsy results with robust CD8 signal (magnification ×100).

Prior treatments included triamcinolone ointment and frankincense with no improvement.

A tangential-shave biopsy was performed to characterize the lesion.


In her early 20s the area of hyperpigmentation started to spread slowly over the above-mentioned areas and became more and more intense.

A slight atrophy of the hyperpigmented skin was palpable without any signs of induration.Clinical images show slightly atrophic hyperpigmented macules following the lines of Blaschko on the right side of the (A) trunk and (B) upper arm.

Histopathologic images of punch biopsy specimen show (C) normal epidermis and dermis with a slight hyperpigmentation of the basal epidermis layer (hematoxylin-eosin stain), and (D) preserved elastic fibers in the reticular dermis (Elastic van Gieson stain).The first onset was in her childhood, at the age of 6 years, with a small hyperpigmentation on the right side of her lower chest remaining stable for years.

Intravenous penicillin G therapy with 10 million units 3 times daily over 1 week combined with a UV-A1 phototherapy in 18 sessions with a maximum dose of 40 J/cm2 and a cumulative overall dose of 670 J/cm2 showed no effects.

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


The patient was initially treated for rosacea at an outside hospital with topical 1% metronidazole cream for 1 month without improvement and developed acute facial purpura after 1 day of treatment with oral doxycycline, which was discontinued.

On examination, the patient had asymmetric, centrofacial, erythematous-violaceous indurated telangiectatic and ecchymotic plaques over a phymatous background (Figure, A).

A series of punch biopsies were performed (Figure, B-D).A, Clinical image showing erythemato-violaceous plaques with ecchymotic areas.

B, Histopathologic image showing ectatic vessels with plump endothelia involving the deep dermis and hypodermis (hemotoxylin-eosin).

C, On higher magnification, ectatic vascular channels were lined by atypical plump endothelial cells (hemotoxylin-eosin).

D, Immunohistochemistry was negative for Human herpesvirus 8 (original magnification ×100).

Because of the eruption’s rapid onset and violaceous appearance, as well as empirical treatment failure, the patient was referred for further evaluation.


She had no history of tobacco, alcohol, or drug use.She had hyperhidrosis and tachypnea on admission.

Sudden episodes of painful involuntary spasms first appeared in her abdominal muscles 2 weeks after a cold.

Soon after, spasms spread to all of her axial muscles and both lower limbs.

These paroxysmal episodes lasted a few seconds, occurred up to 20 times a day, and were exacerbated by external stimuli.

Neurological examination results disclosed an abnormal mental status.

She demonstrated marked myoclonus on tactile and acoustic stimulation.

Cranial nerve examination results demonstrated slow saccades.

Motor system examination results revealed a symmetric and severe hypertonia and rigidity throughout her trunk and all 4 extremities.

Further notable occurrences were severe spasms (Figure, A; Video 1) and patella clonus associated with brisk deep tendon reflexes (Video 2).

Extensor plantar responses were present bilaterally.A, Patient experiencing spasms.

B, Electromyography examination of the patient.Laboratory results were significant for an elevated level of thyroperoxidase antibodies (50.85 IU/mL; normal, <5.16 IU/mL) and thyroglobulin antibodies (88.35 ng/mL; normal: <4.11 ng/mL; to convert to micrograms per liter, multiply by 1).

Cerebrospinal fluid testing results revealed normal protein level and cell counts, as well as absent oligoclonal bands or evidence of infection.

Her paraneoplastic panel results were negative.

Cranial and spinal magnetic resonance imaging yielded no abnormalities.

Needle electromyography (EMG) results showed a continuous firing of normal motor unit potentials at rest within the axial and lower limb muscles (Figure, B; Video 3).

A routine electroencephalogram (EEG) showed mild background slowing without periodic discharges.

Computed tomography scan results of the thorax, abdomen, and pelvis were negative.

An electrocardiogram showed sinus tachycardia.

A review of her previous records revealed a diagnosis of Hashimoto thyroiditis 1 month earlier.


The lesions appeared as erythematous nodules on the left leg with tenderness and pruritus and rapidly progressed to both legs.

Marked lower-leg edema was noted 20 days prior to the visit.

She also had an intermittent fever during the past 3 months that did not respond to antibiotic therapy.

The patient’s medical history was unremarkable.Physical examination revealed ill-defined, indurated erythematous-violaceous plaques on the lower extremities with substantial edema (Figure, A and B).

Complete blood cell count revealed a normal white blood cell count with moderate anemia (hemoglobin level, 87 g/L; normal range 115-150 g/L).

Additional laboratory tests demonstrated an elevated level of serum lactate dehydrogenase (749 U/L; normal range 100-240 U/L) (to convert to μkat/L, multiply by 0.0167).

Quantification of Epstein-Barr virus (EBV) DNA in sera showed a high viral load of EBV in peripheral blood (1 800 000 copies/mL, normal range <500 copies/mL).

C, Lesional skin biopsy specimen revealed dilated vessels filled with atypical large lymphoid cells throughout the dermis (hematoxylin-eosin).

A skin biopsy specimen was obtained from a violaceous plaque (Figure, C).A and B, Ill-defined, irregular erythematous plaques with substantial edema of lower extremities.


When at full term, a planned vaginal delivery was complicated by breached position of the fetus, fetal distress, and new onset of fever.

She had progressive dyspnea, mild pulmonary congestion noted on chest radiography, and an elevated brain-type natriuretic peptide level greater than 800 pg/mL (conversion to ng/L is 1:1).

A vascular ultrasound study ruled out deep vein thrombosis in the lower extremities.

A non–electrocardiogram (ECG)-gated computed tomography angiogram showed no pulmonary embolism but was otherwise not diagnostic owing to motion artifacts (Figure 1A).

Physical examination findings showed a new heart murmur.

A transthoracic echocardiogram (TTE) was performed, which showed a normal-sized left ventricle and preserved left ventricular ejection fraction, severe aortic regurgitation (AR), and a mildly dilated aortic root (Figure 1B and Video).

The patient was afebrile at that point, and her white blood cell count was within normal limits.A, Non–electrocardiogram-gated computed tomography angiography.

The delivery was converted to a cesarean birth, which was uncomplicated.

Perioperatively, she had an episode of chest pain that resolved spontaneously.

The patient was transferred to our institution for further treatment.

B, Transthoracic echocardiography shows the aortic root anatomy and aortic regurgitation.


One year prior to presentation, the patient had undergone coronary artery bypass grafting (CABG).

He was discharged with amiodarone and used the medication for 6 weeks.

He did not use amiodarone for the 10 months prior to presentation.

Prior to his CABG procedure, the patient only used a low dose of lisinopril until he began experiencing progressive dyspnea and fatigue.

He was found to have a 5-vessel blockage once he became symptomatic.

His symptoms resolved after the CABG surgery, and he remained otherwise healthy.

He denied any other symptoms, including headache, rash, joint pain, or chest pain.

His medications at time of presentation were aspirin, atorvastatin, and carvedilol.

His best-corrected visual acuity was 20/20 OD and 20/25 OS.

A slitlamp examination revealed bilateral corneal verticillata and numerous fine anterior stromal crystals (Figure).

He had mild nuclear sclerosis in both eyes.


Her home medications were hydrocodone and ibuprofen.

The patient started receiving oral acetazolamide, 500 mg, twice daily for presumed idiopathic intracranial hypertension (IIH) and transferred to our institution.On admission, she was noted to have near-complete vision loss in both eyes, severe postural headaches, and nausea with vomiting.

Visual acuity was hand motion OD and no light perception OS.

Bilateral disc edema was noted on examination, and neuroimaging was obtained.

Noncontrast head computed tomography (CT) and CT angiogram were remarkable only for bilateral optic nerve head abnormalities.

Magnetic resonance imaging was concerning for prominent optic nerves (Figure, A).

There was no evidence of intracranial masses, hydrocephalus, or bleed.

Lumbar puncture revealed cerebrospinal fluid opening pressure of 40 cm of water.

Cerebrospinal fluid protein, glucose, IgG, and oligoclonal band levels were within normal limits.

Fundoscopic examination revealed severe papilledema (Frisen grade 4-5 OD; grade 5 OS).

A magnetic resonance venography was performed and revealed bilateral filling defect of the transverse sinuses, suggestive of bilateral nonocclusive dural venous sinus thromboses (DVST) (Figure, B).


There was right upper and lower eyelid edema with mild erythema and 3 mm of proptosis.

There was trace vasodilation and chemosis of the conjunctiva in the right eye.

The patient’s visual acuity, color vision, and pupillary examination results were within normal limits, and intraocular pressures were 28 mm Hg OD and 20 mm Hg OS.

The extraocular movements and confrontational visual fields were normal.

The remainder of the slitlamp and dilated fundus examination results were within normal limits.

Computed tomography of the orbits and magnetic resonance imaging (MRI) of the brain and orbits showed a large lesion of the right greater wing of the sphenoid bone extending toward the orbital apex with edema and enhancement of the right temporal lobe of the brain (Figure 1).A, Axial computed tomography (CT) of the orbits with contrast shows a large destructive lesion in the right sphenoid bone and anterior aspect of the middle cranial fossa.

B, A T1-weighted magnetic resonance image (MRI) of the brain and orbits without contrast shows the involvement of the right temporal lobe.

The lesion can be seen also involving the right side of the sphenoid bone, orbital apex, and scalp anteriorly.

The patient was previously treated with an oral combination of amoxicillin and clavulanic acid and topical gentamicin therapy without any improvement.

The scale across the bottom of each image is measured in centimeters.


Her medical history was notable for chronic kidney disease and genital herpes simplex virus (HSV).

She reported no history of genital warts, HIV, or inflammatory bowel disease.

The patient felt well otherwise and denied experiencing fevers, chills, sweats, weight loss, or malaise.

A biopsy was performed, and results were consistent with a noninfectious, granulomatous ulcer.

Findings from colorectal surgical evaluation of the internal anal mucosa were negative for malignant neoplasm.At referral, physical examination findings revealed a 5 × 7-cm verrucous, exophytic tumor with scant yellow drainage on the right medial buttock extending to the perianal skin (Figure 1A).

Findings from the remaining skin examination were normal.

Superficial bacterial cultures were obtained from the lesion and grew methicillin-resistant Staphylococcus aureus.

An incisional biopsy was performed for diagnostic clarification (Figure 1B and C).A, Clinical image of 5 × 7-cm verrucous, exophytic tumor with scant yellow drainage on the right medial buttock extending to the perianal skin.

B, Hematoxylin-eosin stain image from the incisional biopsy featuring a hyperplastic epidermis with ulceration, necrosis, and a very dense inflammatory infiltrate.

C, Hematoxylin-eosin stain demonstrating plasma cells composing the infiltrate while the epithelium shows focal multinucleated keratinocytes, some with gray-blue cytoplasm.

Based on the clinical appearance and prior pathologic findings, the patient received treatment of oral antibiotics, intralesional steroids, topical steroids, and immunomodulators, without improvement.


Within 2 months, she developed isolated, painful tumors.

She then received liposomal doxorubicin, although skin involvement continued to progress rapidly, with ulcerating tumors making up as much as 80% of her total body surface area.

She was hospitalized for worsening disease and pain (Figure, A).

Histopathological testing demonstrated an epidermotropic infiltrate of hyperchromatic, convoluted, atypical CD3+, CD4−, and CD8+ lymphocytes with haloed nuclei with basilar tagging and papillary dermal fibrosis.

Studies of T-cell gene rearrangements identified a clonal population.

Blood-flow cytometry did not reveal aberrant T-cell immunophenotypes.

A second biopsy was performed, which was notable for an epidermotropic infiltrate of CD3+, CD4−, and CD8− weak lymphocytes, which were positive for TIA-1, granzymes, and B factor (Bf) 1 and negative for CD30 and CD56.

The results of flow cytometry and imaging were unremarkable.

Repeated histopathologic analysis was done (Figure, B, C, and D).A, Clinical image.

C, Considerable lymphocytic epidermotropism in a pagetoid reticulosis–like pattern without striking Pautrier microabscesses (original magnification ×230).

She was treated initially with topical and intralesional corticosteroids and narrow band UV B phototherapy.

Oral bexarotene was subsequently added for recalcitrant disease.

After an initial favorable response with chlorambucil, she developed expanding ulcerated tumors complicated by a polymicrobial superinfection.

Chlorambucil was discontinued in favor of antimicrobial treatment.


No inciting events, such as arthropod bite or trauma, were noted.

No other cutaneous abnormalities were noted.

A punch biopsy specimen of the left medial forehead was obtained, and histological and immunohistochemical analyses were performed (Figure, B and C).A, Erythematous patch with central inflammatory papules on the forehead.

B, Histopathological results revealed dissecting vascular channels (black arrowheads) and spindle cells (white arrowheads) (hematoxylin-eosin).

C, Immunohistochemical staining revealed CD31 and diffuse expression of FLI-1 and ERG in the vascular and spindle cell components.

She was initially treated for presumed shingles with valacyclovir, cephalexin, gabapentin, and hydrocortisone 2.5% topical ointment with no improvement in appearance or symptoms.


Following a long flight 6 weeks prior, she had developed left calf tightness and pain, followed by shortness of breath for 1 week and then a syncopal event the day of admission.

On physical examination, she appeared anxious, with a temperature of 36.8°C, a heart rate of 102 beats/minute, blood pressure of 128/66 mm Hg, a respiratory rate of 20 breaths/minute, and pulse oximetry of 98% on room air.

Her laboratory results were notable for a troponin level of 0.07 ng/mL (to convert to μg/L, multiply by 1.0), and a fibrin D-dimer level of more than 2000 μg/mL (to convert nmol/L, multiply by 5.476).

Her electrocardiogram on presentation showed sinus tachycardia and was otherwise normal.

Computed tomography of the chest was performed, which showed multiple large bilateral pulmonary emboli (Figure, A), with deviation of the interventricular septum toward the left ventricle.


The patient’s medical history was notable for severe obstructive sleep apnea (OSA) diagnosed in the fall of 2017, when he presented with snoring, progressive daytime fatigue, and several years of migraines.

Since his diagnosis, he had been adherent to use of nightly continuous positive airway pressure (CPAP).

However, he had persistent daytime fatigue and morning headaches.

Several months before presentation, the patient noticed that his bite changed from an overbite to an underbite (Figure, A), which had been attributed to dental malocclusion from his CPAP machine.

On further review of systems, the patient reported growth in his tongue and feet and intermittent swelling with numbness in his hands over the past year.A, Clinical image of the patient, who reported change in bite.

Examination findings of the oropharynx showed an oropharynx score of a Mallampati 4, with 3-plus tonsils and macroglossia without scalloping of the tongue (Figure, B).

Nasopharyngolaryngoscopic examination findings showed that the tonsils did not approximate at midline, with a narrow anterior-to-posterior dimension of the airway owing to macroglossia and no retrognathia.

B, Oral cavity and oropharynx showing macroglossia and bilateral tonsillar hypertrophy.


The patient had an unremarkable medical, surgical, and social history and no known infectious exposures.

After a period of conservative management, he developed a sore throat and fever.

When he presented to our facility, he was found to have an asymptomatically enlarged left level 2/5A neck mass that was nontender and fixed.

His primary care physician initially obtained an ultrasonographic image, which demonstrated a left, level 2 lymph node measuring 4.0 × 1.5 × 2.8 cm.

He subsequently underwent a computed tomographic scan of the neck and chest with contrast, which demonstrated an isolated, enlarged, homogenously enhancing left-neck level 2B lymph node measuring 3.4 × 2.8 × 2.1 cm (Figure 1A).

A white blood cell count and C-reactive protein level were both elevated, at 11 310 cells/μL (to convert to cells × 109 per liter, multiply by 0.001) and 56.2 mg/L (to convert to nanomoles per liter, multiply by 9.524), respectively.

Studies for influenza A and B, HIV, cytomegalovirus, American foulbrood, Bartonella henselae, infectious mononucleosis, and Epstein-Barr virus had negative results.

Fine-needle aspiration and flow cytometry had negative results for lymphoproliferative disorders or a malignant condition.

Intraoperative frozen sections did not show a malignant process.

On final analysis, a pathologic examination of the largest lymph node was performed (Figure 1B).A, Axial computed tomographic (CT) scan of neck with contrast, showing homogenously enhancing 3.4-cm left level 2B neck mass.

The patient then underwent several courses of antibiotic treatment, but the mass persisted.

An ultrasonography-guided needle biopsy was performed.

Given the inconclusive diagnosis, the patient underwent a left neck dissection of levels 2A, 2B, and 5A.


Notably, 2 weeks prior to presentation, she had started taking cobimetinib therapy as part of a clinical trial for her breast cancer.Fundus autofluorescence (A) demonstrating multiple, discrete hyperautofluorescent lesions throughout the posterior pole, concentrated along the superior arcades; spectral-domain optical coherence tomography (B) shows small, localized subretinal fluid pockets at the site of these lesions.

The spots were stationary; she denied any floaters or photopsias.

The onset was simultaneous in both eyes, with no associated eye pain or photophobia.

There was no ocular history, and a recent comprehensive eye examination had normal results.

An anterior segment examination had unremarkable results.

There was no vitritis, and her optic nerves were pink and sharp.

A dilated fundus examination revealed multifocal, hypopigmented, cream-colored spots scattered throughout the posterior pole in both eyes.

These spots were hyperautofluorescent on fundus autofluorescence and localized to the subretinal space (Figure 1).


His parents reported that he had recently been hospitalized for a suspected overdose with the medications atomoxetine, quetiapine, melatonin, fluoxetine, bupropion, and clonazepam, and shortly after, he reported central visual acuity loss.

His medical history included attention-deficit/hyperactivity disorder, depression, generalized anxiety disorder, posttraumatic stress disorder, and learning disabilities.

His medications included atomoxetine, quetiapine, melatonin, and fluoxetine.

The patient was adopted, and a detailed family history was unknown.

A dilated fundus examination with normal results had been documented 6 months prior to our examination.His ocular history was unremarkable.

His biological sister has learning and attention difficulties but had a normal fundus examination result.The patient’s best-corrected visual acuity was 20/50 OD and 20/60 OS.

His intraocular pressure, pupils, extraocular movements, visual fields, and color testing results were normal.

The anterior segments were unremarkable.

The vitreous, optic nerve, and retinal vasculature were normal.

A bilateral maculopathy was present, with focal areas of gray-brown discoloration (Figure 1A).

Optical coherence tomography (OCT) exhibited an intact foveal depression with subfoveal disruption of the ellipsoid layer and hyperreflective material extending into the Henle layer (Figure 1B).

No subretinal or intraretinal fluid was present.A, Fundus photograph of the left eye demonstrates a central maculopathy with focal gray discolored lesions and yellow-orange pigmentation.

B, Scanning laser ophthalmoscopy and spectral-domain optical coherence tomography (SD-OCT) of the same eye reveal ellipsoid zone disruption and vertical hyperreflective bands.