He had hypertension, diabetes, hyperlipidemia, and obesity and was a current smoker.

His medications included carvedilol, furosemide, lisinopril, metformin, and aspirin but no testosterone or herbal supplements.

Family history was significant for a sister with brain cancer, diagnosed in her 40s.

On physical examination, his vital signs were within normal limits; his body mass index, calculated as weight in kilograms divided by height in meters squared, was 53.

At the 2-o’clock position of the left breast, 3 cm from the nipple, there was a 3.5 × 3.0–cm firm mass.

The right breast was normal without masses, and there was no palpable axillary lymphadenopathy.

He underwent a bilateral diagnostic mammogram, which showed a partially obscured mass in the left upper outer quadrant with linear extension to the nipple (Figure, left panel).

Targeted ultrasound showed a 2.0 × 1.6 × 1.6–cm irregular hypoechoic mass (Figure, right panel).Left, Mediolateral view of the diagnostic mammogram of the left breast.

Right, Targeted ultrasound of the left breast.


He did not take medication over the past 3 months.

There was no relevant family medical history.

At that time, no diagnosis was found and the lesions disappeared following treatment with corticosteroids.

The patient reported fever and rhinorrhea in the few days preceding the emergency consultation.

At the clinical examination, the patient had several macules and desquamatory lesions on the mucosa of the oral cavity, lips, and penis, and he had hemorrhage lesions of the eye sclera (Figure).

The skin of the patient was unremarkable.

The nasofibroscopy results showed generalized desquamatory lesions of the upper aerodigestive tract mucosa affecting the laryngeal and vocal fold mucosa (Figure).

There was no dyspnea and the airway was clear.

Desquamatory injuries were found on vocal folds and ventricular bands (A); iris (B); lips and oral mucosa (C); and epiglottis (D).

There was a moderate laryngeal mucosa hypertrophy related to the inflammatory reaction.

Dermatopathologic analysis, biology, serology, and biopsy were performed.Lesions of eye, oral, and upper aerodigestive tract mucosa.

The patient revealed that he had a similar but less severe clinical event 5 years previously.


He had no notable medical history except stable asthma.

He also complained of recurrent epistaxis.

On physical examination, nasopharyngoscopy showed a pedunculated mass with a smooth mucosal surface arising from the roof of the nasopharynx.

Computed tomographic (CT) imaging (Figure, A and B) revealed a midline, well-defined, pedunculated polypoid lesion with areas of calcifications in the nasopharynx, measuring approximately 1.2 × 1.5 × 2.0 cm.

Results of other investigations after surgery were negative for cancer, including magnetic resonance imaging (MRI) of the neck and thyroid ultrasonography.

In addition, no residual tumor or systemic metastasis was observed on positron emission tomography (PET)-CT results.

There was no evidence of recurrence at 12-month postoperative follow-up.A and B, Computed tomography images with contrast enhancement reveal a 1.2 × 1.5 × 2.0-cm soft-tissue–density mass (white arrowheads) with multiple nodular calcifications (red arrowhead) in the nasopharynx.

C and D, Lesional histopathologic images (hematoxylin-eosin) show tumor cells arranged in papillary structures with fibrovascular cores (asterisk).

An endoscopic resection via retrovelar approach using a 70-degree endoscope combined with transnasal approach was performed under general anesthesia.

The mass was completely resected with its stalk and with adequate surgical margin.

Histopathological results (Figure, C and D) showed that the tumor cells were arranged in papillary structures with fibrovascular cores and these cells also had nuclear grooves.

Nuclear grooves (black arrowheads) in these cells were also identified.


His medical history included hypertension treated with captopril and a remote history of psoriasis.

The lesions initially only involved his lips and nasal bridge, and appeared 5 months prior while he was living on a ranch in Mexico.

Physical examination demonstrated several dry, crusted skin lesions with blistering and ulceration, and shallow erythematous ulcerations of his oral mucosa.

Results of flexible fiberoptic laryngoscopy demonstrated erythematous and ulcerative lesions with surrounding leukoplakia involving the base of tongue, glossoepiglottic fold, lingual and laryngeal surfaces of the epiglottis, and aryepiglottic folds (Figure, C and D).

Serum antigen testing for blastomyces, histoplasmosis, syphilis, HIV, hepatitis B virus, hepatitis C virus, human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, varicella zoster virus, human polyomavirus 2, and West Nile virus were performed, and all results were found to be negative.

Enzyme-linked immunosorbent assay serological testing was subsequently performed, and results demonstrated elevated levels of antidesmoglein 1 immunoglobulin G (IgG) and antidesmoglein 3 IgG.A, Lesions involving the patient’s nose and lower lip.

B, Direct immunofluorescence staining for immunoglobin G of an intralesional biopsy at magnification ×34 demonstrating autoantibody deposition in a lacelike pattern localized to the intracellular matrix of the stratified squamous epithelium.

C, Bullous lesion involving the epiglottis (black arrowhead).

D, Bullous lesions involving the left posterior true vocal fold, left false vocal fold, and right vestibule (black arrowheads).

The lesions did not respond to treatment with an unknown oral antibiotic.

Internal medicine, otolaryngology, and dermatology departments were consulted.

A QuantiFERON-TB Gold test was obtained, and results were found to be positive.

A biopsy of the skin lesion was obtained from the edge of the lesion found on the patient’s back (Figure, B).


Her medical history was unremarkable except for allergic rhinitis.

She reported no associated fevers, chills, dryness of mouth, nausea, vomiting, dysphagia or odynophagia.

On physical examination, she had slight enlargement of the left submandibular gland, which was not tender on palpation.

Ultrasonography results revealed normal submandibular and parotid glands bilaterally without any mass or calcifications.

Blood examinations and basic metabolic panel results were all within normal limits.

The areas of webbing were broken up with irrigation, and at the end of the procedure steroid instillation and irrigation were performed.

Sialoendoscopy of the left submandibular duct was performed under general anesthesia.

The patient was found to have a cast at the opening of the Wharton duct, which was removed and sent for pathological evaluation (Figure).

Using sialoendoscopy with saline irrigation, the entire duct was examined up to the hilum of the gland.

There were areas of mild partial webbing without complete obstruction.

There were no complications during or after the procedure.Hematoxylin-eosin–stained histological slide of the cast showing numerous eosinophils.


She had undergone an uncomplicated Descemet stripping automated endothelial keratoplasty (DSAEK) for Fuchs endothelial dystrophy in the right eye 5 months before, which improved her corrected-distance visual acuity to 20/20 OD.

She denied any history of ocular trauma or cold sores, and she was taking dexamethasone, 0.1% drops 4 times a day.At presentation, her corrected-distance visual acuity was 20/60 OD.

Slitlamp examination revealed a right inflamed conjunctiva with circumcorneal hyperemia, 2 mm × 2 mm epithelial defect with a small infiltrate at the temporal cornea, 2+ cells in the anterior chamber with a 1-mm hypopyon, and a peculiar graft-host interface haze with crisscross pattern (Figure, A).

Corneal scrapes were performed and samples were sent for microscopy with Gram staining, culture, and sensitivity testing.

One day later, there was no improvement in the graft-host interface haze, and results of microbiological investigations, including donor rim culture, were all negative.

Slitlamp photography demonstrating an inflamed right eye with diffused stromal haze in crisscross pattern at the graft-host interface and a mild opacity at the temporal host cornea.

B, In vivo confocal micrograph demonstrating diffuse hyperreflective crisscross changes at the graft-host interface (at the depth of 598 μm).

The patient was admitted on that day and commenced taking topical cefuroxime, 5%, and gentamicin, 1.5%, drops every hour around the clock, and topical steroid was discontinued.

In view of the clinical dilemma, an in vivo confocal microscopy was performed to aid the diagnosis (Figure, B).A, Right eye after Descemet stripping automated endothelial keratoplasty.


He was born and raised in Mexico prior to his immigration to the United States 5 years before presentation.

He worked as a farmer and denied recent illnesses, contacts with illnesses, alcohol or tobacco use, and having pets.

He complained of a gradual decline in his vision bilaterally over the past 2 years.

He denied flashes, floaters, or eye pain but endorsed a chronic cough.

His visual acuity was 20/60 OD and 20/40 OS with normal intraocular pressures.

His slitlamp examination results were notable for mild nuclear sclerosis in both eyes and were negative for conjunctival or corneal lesions.

He had round, reactive pupils and no anterior chamber inflammation in either eye.

Dilated fundus examination results revealed a few pigmented anterior vitreous cells, a normal optic disc, and flat and large yellowish chorioretinal lesions with overlying pigment scattered throughout the macula and periphery in the right eye (Figure).

He had no known ocular or medical history and took no systemic medications.


The patient’s medical history was remarkable for hypertension and asthma.

He denied smoking, drinking alcohol, and using recreational drugs.

His medications included losartan, albuterol, and fluticasone.

He had woken up earlier that morning with normal visual acuity, but his visual acuity had progressively worsened to the point that he was unable to work.

He denied additional symptoms, other than mild tearing.

Per his ophthalmologist, his visual acuity improved with a −10 diopter lens, but his intraocular pressure was elevated to between 30 and 40 mm Hg OU.

On examination, his visual acuity was 20/400 OU (while wearing prescription lenses, −2.75 + 1.00 × 090 OD and −2.50 + 1.00 × 081 OS).

His best-corrected visual acuity was 20/25 OU (manifest refraction, −12.00 + 1.75 × 097 OD and −10.75 + 0.25 × 050 OS).

Sensorimotor and external examination results were normal.

A slitlamp examination revealed mild diffuse vasodilation and temporal chemosis, clear corneas, shallow anterior chambers, and clear lenses in both eyes.

A gonioscopic examination showed no angle structures in either eye.

Results of an undilated fundus examination was unremarkable.

A, B-scan on initial presentation showed no masses and shallow choroidal effusion.

The patient was sent to the emergency department, where the authors’ consultation team evaluated him.

A review of symptoms was otherwise negative.

Figure 1 shows ultrasonographic images of his eyes.Images on initial presentation.


He had a distant history of right temple melanoma that was excised with clean margins and accompanied by a negative sentinel lymph node biopsy result.On examination, he was found to have a best-corrected visual acuity of 20/20 OD and 20/40 OS, with a normal pupillary response and intact color vision bilaterally.

He reported several eyeglass prescription changes in the left eye over the past 2 years and frequent ipsilateral tearing.

He had a mild limitation of left abduction and supraduction.

He had 5 mm of relative left proptosis, with moderate resistance to retropulsion of the left globe.

No change in globe position was appreciated with systolic pulsations or the Valsalva maneuver.

Anterior segment examination results were normal bilaterally.

Dilated fundus examination results of the left eye revealed an abnormality of the posterior pole (Figure 1A), which was confirmed on fluorescein angiography (Figure 1B).Color fundus photograph (A) and fluorescein angiography (B).

He denied ocular discomfort, headaches, or double vision.


Physical examination revealed ptosis, modest restriction of ocular motility in all directions bilaterally, and esotropia with left hypertropia in the primary gaze.

Muscle strength was 5/5 on hip flexion and extension bilaterally.

There was no weakness with repetitive and sustained testing of power.

Workup revealed elevated creatine kinase (1222 U/L; reference range, 24-195 U/L [to convert to μkat/L, multiply by 0.0167]), aldolase (24.5 U/L; reference range, <8.1 U/L [to convert to μkat/L, multiply by 0.0167]), and C-reactive protein levels (106 mg/L; reference range, <5 mg/L [to convert to nmol/L, multiply by 9.524]).Acetylcholine receptor binding and modulating antibody levels were elevated (0.69 nmol/L [reference range, <0.3 nmol/L] and 48% [reference range, 0%-20%], respectively).

Results of the striated muscle antibody titer were also abnormal (1:160; reference range, <1:40).

Blood test results were negative for acetylcholine receptor blocking and muscle-specific receptor tyrosine kinase antibodies.

Nerve conduction studies showed a normal response to repetitive nerve stimulation.

Single-fiber electromyography was pathologic and revealed an abnormal mean consecutive difference in more than 50% of the tested pairs (Figure, B), and no blocking was seen.

He enrolled in a phase 1 clinical trial (NCT03299946) using neoadjuvant cabozantinib plus nivolumab followed by definitive resection for patients with locally advanced disease.A, Magnetic resonance image of the abdomen shows a liver mass.

A biopsy was performed, and pathology results were consistent with a well-differentiated hepatocellular carcinoma.

B, On single-fiber electromyography, the mean consecutive difference of the tested pairs was abnormal, and there was no blocking.Five weeks after the first dose of nivolumab, he developed diplopia and myalgia that mostly affected proximal muscle groups.

Myopathic action potentials were not present.


Her breast cancer was diagnosed in 2007 as stage IA estrogen-receptor positive, progesterone-receptor negative (ER+, PR−), and human epidermal growth factor 2 (ERBB2; formerly HER2) negative, initially treated with lumpectomy plus left breast radiotherapy followed by doxorubicin, cyclophosphamide, paclitaxel, and anastrazole.

Later, progressive liver metastasis and repeat biopsy with equivocal ERBB2 testing led to treatment with capecitabine plus trastuzumab.On presentation to the ophthalmologist, her visual acuity was reduced to only being able to count fingers (worse than 20/400) OD and 20/40 in the left eye (OS).

She reported not experiencing any headache, photophobia, diplopia, or eye pain.

Visual acuity was 20/25 bilaterally at her last eye examination, 1 year prior.

Ocular motility, pupillary response, and intraocular pressure were normal for each eye.

On slit lamp examination, the anterior segment of each eye was normal, without inflammation or blood.

In 2017, metastases were found in the lumbar spine and lung and treated with fulvestrant and palbociclib plus left brachial plexus radiotherapy.


She lost 50.8 kg from the time of the procedure to presentation, her body mass index at presentation was 23, and her preoperative comorbidities were in remission.

She was under some financial stress after recently losing her job, and reported drinking 2 to 6 beers within a 2-hour period on the weekends.

She took a gummy multivitamin sporadically and self-reported a daily total calorie intake of less than 500 kcal and less than 20 g of protein.

She did not have any nausea, abdominal pain, or change in bowel habits, but her periods had been more irregular over the past 2 to 3 months and, when present, lasted for 7 to 10 days.

She also noted a tingling sensation in her hands and feet.

On physical examination, although she reported having paresthesias in her fingertips and toes, her neurological examination findings were nonfocal.

She exhibited bilateral flattening of the temporalis muscle and thenar eminence.

Her vital signs were normal, and serum tests were ordered (Table).This patient has iron deficiency anemia in the setting of polycystic ovarian syndrome.The patient has both iron and vitamin B12 deficiencies.


The patient had a history of rectal carcinoma with lymph node metastasis and 2 years prior had received low anterior resection plus postoperative chemotherapy (6 cycles of oxaliplatin, calcium folinate, and tegafur).

A physical examination revealed well-defined, firm, indurated plaques on the vulva with nodules on the surface (Figure 1A).

A biopsy of the left vulva was performed (Figure 1B and C).A, Well-defined, firm, indurated plaques on the vulva.

B and C, A biopsy of the left vulva was performed for evaluation (hematoxylin-eosin).


The lesions were never ulcerated or inflamed, but hemorrhage occurred occasionally after rubbing.

At 3 years of age, scarlike macules appeared on the occipital scalp and coalesced to form a larger plaque with sparse hair.

Simultaneously, multiple brown-red, dome-shaped papules developed on the nose and gradually evolved to involve the cheeks.

Rubbery plaques also developed on the sacrococcygeal area, along with hypopigmented patches on the right buttock.

The patient has no systemic symptoms or mental impairment and denied a family history of genetic disease.Physical examination revealed a group of unevenly distributed skin–colored-to-pink, discrete, coalescing papules superimposed on a firm plaque on the occipital scalp (Figure, A).

A biopsy specimen was obtained from one of these papules (Figure, B, C, and D).

Another biopsy from a facial papule demonstrated features of angiofibroma.A, Clinical photograph shows a firm plaque with superimposed papules and decreased hair density.


His medical history was significant for adenosine deaminase–deficient severe combined immunodeficiency (ADA-SCID), which had been managed since childhood with twice weekly intramuscular injections of pegademase bovine enzyme replacement, thrice weekly trimethoprim-sulfamethoxazole for Pneumocystis prophylaxis, and monthly infusions of intravenous immunoglobulin.

Although most were asymptomatic, the patient was concerned about the ongoing appearance of new lesions and the associated pain that some lesions were causing.

Physical examination revealed 9 smooth-surfaced, skin-colored to hyperpigmented, 0.5- to 1.5-cm atrophic papules and plaques that exhibited the buttonhole sign on palpation (Figure, A).

The multicentric lesions were located on the left knee, left thigh, bilateral chest, and back.

Punch biopsies of lesions on his trunk and extremities were sent for histopathological examination with hematoxylin-eosin (H&E) staining (Figure, B and C), immunohistochemical (IHC) studies, and molecular evaluation with reverse transcription polymerase chain reaction.A, The patient presented with 2 distinct, smooth-surfaced, 0.5- to 1.0-cm atrophic plaques with overlying hyperpigmentation on the left thigh.

Both lesions exhibited the buttonhole sign on palpation.

B and C, Histopathology shows poorly circumscribed hypercellular proliferation of spindle cells occupying the lower reticular dermis with lacelike infiltration of the subcutaneous fat (hematoxylin-eosin).

The somewhat whorled, uniform appearing spindle cells with mildly hyperchromatic, elongated, wavy nuclei surrounded by pale cytoplasm.

Mitotic figures and nuclear pleomorphism are uncommon.


He had psoriasis for 30 years, for which he was taking steroids intermittently, and hypothyroidism for 4 years, for which he was taking levothyroxine.

The patient denied confusion, memory problems, hallucinations, and sleep disturbance.

His examination results were significant for psoriatic skin lesions and purple stria in the abdomen and both calves.

Undulating wavelike movements were visible on the muscle surface of the abdomen and calves (Video).

The remaining general and neurological examination results were normal.

Laboratory test results, including creatine kinase, thyrotropin, antinuclear antibodies, paraneoplastic antibodies (includes Hu, Yo, Ri, CV2, Ma2, and amphiphysin antibodies), were normal.

Chest computed tomography results were normal.


The patient was diagnosed as having vasospastic angina (VA); diltiazem and glyceryl trinitrate were prescribed, and an implantable cardioverter-defibrillator (ICD) was implanted.Two months later, she presented with similar symptoms to another hospital; her ICD had not delivered a shock.

The electrocardiogram showed asystole with pacemaker spikes not followed by QRS complexes.

Given her history of VA, we started nitroglycerin infusion, which resulted in return to normal sinus rhythm after 5 minutes with a palpable peripheral pulse.Despite the intensification of therapy with isosorbide mononitrate and concomitant use of amlodipine, diltiazem, and benzodiazepine, the patient experienced another episode of asystole and multiple episodes of asymptomatic ST-T changes in the coronary care unit.

Cardiopulmonary resuscitation was initiated and was followed with coronary angiography, which showed significant 3-vessel stenosis that completely resolved after nitroglycerin injection.

Angiography was again performed and showed severe spasm of all coronary vessels that resolved after nitroglycerin administration (Figure).

Medical treatment was intensified by adding verapamil and a statin to the regimen.Total occlusion of all coronary arteries during cardiac arrest (A) that was completely resolved after nitroglycerin administration (B).Four months later, the patient was admitted to our center in an unconscious state.

Because she was not carrying her medical records, she was immediately transferred to the catheterization laboratory.

Cardiopulmonary resuscitation was started, but after 10 minutes of resuscitation there was no response.


Physical examination was notable for tenderness over the nasal bones.

Computed tomography (CT) scan of the head without contrast revealed nasal bone fractures and an incidental 7-mm tissue density within the posterior aspect of the left sphenoid sinus (Figure 1A) with an apparent dehiscence of the posterior wall and possible communication with the intracranial extra-axial spaces and brain parenchyma.

A magnetic resonance imaging scan with contrast was recommended to further characterize the lesion which showed a transosseous T1 dark, T2 bright multilobulated mass measuring 2.1 × 1.4 × 1.3 cm with heterogeneous enhancement on postcontrast imaging extending into the sphenoid sinus.

Pathological analysis revealed sheets of neoplastic, vacuolated, “soap bubble–like” cells with a myxoid background (Figure 1B).A, Sagittal computed tomography (CT) scan showing 7 mm tissue density within the posterior aspect of the left sphenoid sinus.

B, Sheets of neoplastic, vacuolated, physaliphorous cells with a myxoid background (original magnification ×40).

An endoscopic transnasal approach was used to obtain a tissue biopsy specimen.


A polypoid lesion was identified at the left lateral nasal wall.

Noncontrasted computed tomography showed a hyperdense mass involving the left medial canthus extending through the nasolacrimal duct into the left nasal cavity.

On examination, there was a palpable subcutaneous nodule 1 cm inferior to the left medial canthus with normal overlying skin.

On nasal endoscopy, residual tumor was visible at the anterior aspect of the lateral nasal wall.

Computed tomography showed postoperative changes with enhancement of left medial canthus extending into nasolacrimal duct and along the lateral nasal sidewall (Figure, A).A, Coronal view of contrast-enhanced maxillofacial computed tomography obtained after initial biopsy and before resection showing tumor involvement of lateral nasal sidewall and nasolacrimal duct.

Microscopic examination showed sheets of monomorphic undifferentiated tumor cells with interspersed areas of abrupt squamous differentiation and keratinization (Figure, B and C).

The patient underwent endoscopic left maxillary antrostomy, ethmoidectomy, and biopsy of mass, with results of pathology analysis showing poorly differentiated squamous cell carcinoma.

The tumor appeared to originate from left lateral nasal wall, with involvement of nasal floor and extension into the orbit and periorbita.Histologically, the tumor extensively eroded maxillary bone, with abundant necrosis and widespread involvement of surgical margins.

Immunohistochemical (IHC) staining was positive for cytokeratin 5/6 and p63, and negative for Epstein-Barr virus, p16, CD45 (leukocyte common antigen), and synaptophysin.

The patient was referred to a tertiary care facility for further treatment.

B and C, Hematoxylin eosin–stained histologic sections of tumor after resection showing bony invasion by sheets of undifferentiated cells (B) and focal areas of abrupt keratinization (C).The patient subsequently underwent left medial maxillectomy via lateral rhinotomy approach, with resection of residual tumor.


Medical history included corrective lens replacement surgery in early childhood and a family history of childhood hearing loss in the patient’s maternal grandfather.

The patient failed a school-administered hearing screening as well as a subsequent hearing screening performed by his pediatrician.

According to his mother, the patient had struggled with his hearing, often failing to respond to vocalizations and requiring statements to be frequently repeated.

Physical examination revealed no effusions, while formal audiological testing revealed restricted middle ear mobility and bilateral moderately severe mixed hearing loss rising to normal hearing sensitivity in both ears (Figure, A).

A noncontrast computed tomography (CT) scan of the temporal bones revealed bilateral enlargement of the vestibular aqueducts (Figure, B), fistulous communication between the internal auditory canal (IAC) and the basal turn of the cochlea (Figure, C), and a bulbous dilation of the IAC (Figure, D).

He reportedly passed his newborn hearing screening and his mother had no serious hearing concerns prior to his failed school screening.

Given the family history of childhood-onset hearing loss, genetic testing was performed and revealed genetic mutation of the POU3F4 gene.


She reported the sensation of eye fullness and denied pain.

Brain magnetic resonance imaging (MRI) results revealed a thickening and enhancement of the pituitary gland, stalk, and hypothalamus.

The abnormal imaging findings improved on subsequent MRIs without treatment.

Surveillance pituitary MRIs remained stable.

Four years later, MRI results (Figure) revealed bilateral T1 and T2 low-intensity intraconal soft tissue masses with avid enhancement on postcontrast images.

The optic nerves were encased with no evidence of infiltration of the nerves, vascular structures, or extraocular muscles.

Her best-corrected visual acuity was 20/20 OU.

Her pupils were symmetric and responded to light and near effort; there was no relative afferent pupillary defect.

The results of testing with an Amsler grid and Ishihara color plates were normal.

Her visual fields were full to confrontation.

The optic nerves and retina were normal bilaterally.

There was bilateral periorbital swelling and proptosis.

Exophthalmometry measurements on a base of 92 were 17 mm on the right and 19 mm on the left.

Applanation tonometry results were 12 mm Hg on the right and 15 mm Hg on the left.

Extraocular motility examination results revealed substantial (−3) deficits in both eyes.


He had no history of hearing loss or pigmented skin lesions.

He had no past ocular history or prior ophthalmic examinations.

Color vision was severely diminished in the right eye, as determined by Ishihara color plates, and he had no detectable stereoacuity, as determined by Titmus testing.

Intraocular pressure and extraocular movements were normal.

He had a mild relative afferent pupillary defect in the right eye but no strabismus or nystagmus.

The cycloplegic refraction was +2.50 + 0.50 × 100 OD and +2.00 sphere OS.

Results of an anterior segment slitlamp biomicroscopy examination showed no abnormalities.

Results of a dilated retinal examination showed a large, elevated, homogenous, gray mass in the macula of the right eye with temporal pallor of the optic disc (Figure, A).


He took no medications and denied prior surgery, eye trauma, or pain.

He experienced left temporal field loss when lifting heavy objects.

His best-corrected visual acuity was 20/25 OD and 20/30 OS.

The only abnormalities on bilateral eye examination were 1+ levels of anterior vitreous cells and trace levels of posterior vitreous cells in the left eye, without vitreous haze, and a left retinal detachment extending from 1:30 to 10:00 o’clock, with macular involvement and without visible retinal tears.

There were 360° left choroidal detachments.Optical coherence tomography showed choroidal thickening in both maculae.

Fluorescein angiography (FA) of the right eye gave normal results.

On B-scan ultrasonography, there was a subclinical choroidal detachment superonasally in the right eye.

An ultrasonographic image confirmed the detachments in the left eye (Figure 1B).

The findings of a prior magnetic resonance image of the brain, chest radiographic image, and computed tomographic image of the chest were unremarkable.

Test results for syphilis, tuberculosis, bartonella, and toxoplasma were negative, as were test results for inflammatory markers, quantitative serum proteins, and immunoglobulins.Images of the left eye at baseline.

A, Midphase fluorescein angiography of the left eye.

There are multiple peripheral areas of punctate hyperfluorescence.

Leakage is more pronounced posteriorly around the nerve.

There is scattered blockage of background fluorescence owing to retinal pigment epithelium mottling, which creates a leopard-spot pattern.

A retinal detachment is seen inferiorly with tortuous vessels and nonfluorescent subretinal fluid.

B, A B-scan ultrasonographic image of the left eye in the longitudinal 6 o’clock meridian demonstrates retinal detachment and a nonserous choroidal detachment superiorly.

The optic nerve shadow is seen inferiorly.

The detachment was mapped to extend from 1:30 to 10:00 o’clock and involve the macula.

The maximum height of the choroidal detachment was 3.4 mm.

Three weeks later, his best-corrected visual acuity worsened to 20/50 OS.

A posterior sub-Tenon injection of 40 mg of triamcinolone acetonide was given, along with tapering doses of oral prednisone for 6 more weeks.

Figure 1A depicts the FA image of the left eye.

No retinal tear was visualized.The patient started receiving 60 mg of oral prednisone  daily.


He had been diagnosed with type 1 diabetes 5 years prior and had never been examined for diabetic retinopathy.

At the initial examination, his hemoglobin A1c level was 11.0% (to convert to the proportion of total hemoglobin, multiply by 0.01), suggesting a lack of compliance with his diabetic treatment regimen.

His best-corrected visual acuity (BCVA) was 20/100 OS and 20/60 OD.

On examination of the left eye, the anterior segments were unremarkable, with no neovascularization of the angle or iris.

However, there was considerable retinal thickening, substantial capillary nonperfusion in the macular area, and a large area of disc neovascularization (in more than one-third of the disc area), with leakage on the disc associated with prepapillary neovascularization, as confirmed by fluorescein angiography (Figure 1A).

Optical coherence tomography confirmed retinal thickening in the macular area (central subfield thickness [CST], 805 μm), with cystoid abnormalities throughout the retinal layers as well as subretinal fluid (Figure 1B).A, Large prepapillary neovascular complex, nonperfusion in the macula and the periphery, and central subfield involvement of the macular edema is visible.

Arrowheads indicate neovascularization of the disc (pink) and nonperfusion (blue).


At the moment of impact, she was wearing her seat belt, the airbag deployed, and an intense flexion-extension head movement occurred.Best-corrected visual acuity was 20/125 OD and 20/63 OS.

Intraocular pressure was 19 mm Hg OD and 20 mm Hg OS.

Slitlamp examination revealed no palpebral hematoma, and the anterior segment was found to be normal.

On the fundus bilaterally, we only noted an alteration of the foveal reflection, with neither retinae commotio nor hemorrhages.

Macular optical coherence tomography (OCT) showed bilateral macular edema with cystoid abnormalities (Figure 1).

An epiretinal membrane also was noted in the left eye (Figure 1B).Optical coherence tomography showed bilateral macular edema with cystoid abnormalities.

Central subfield thickness was 696 μm in the right eye and 392 μm in the left eye.


The patient first noticed a rapidly expanding, itchy, painful nodule, which measured 3 cm in diameter, 5 months prior to presentation (Figure, B).Lesion appearance at the first visit (A) and 5 months earlier (B).

C, Hematoxylin-eosin stain, magnification ×20.The patient reported decreased appetite with weight loss of 7 kg over 5 months and denied fever, itching aside from the lesion, vomiting, or bowel alterations.

On physical examination, there were no other cutaneous lesions though multiple ipsilateral axillary lymph nodes, and enlarged supraclavicular and cervical lymph nodes were present.

All other physical and laboratory findings were unremarkable.

Owing to intense and continuous pain from the lesion, she began opioid treatment with oxycodone/naloxone association at an initial dose of 5 mg/2.5 mg twice a day and titrated to 10 mg/5 mg twice a day after a week to achieve pain control.Abdominal ultrasonography revealed only a left adrenal gland mass, consistent with adenoma.

A skin punch biopsy of the lesion was obtained (Figure, C).


He did not have chest pain or any other symptoms.


She had no history of neonatal respiratory distress, nasal congestion, persistent urticaria, joint laxity, or illicit drug use.

She denied a family history of liver cirrhosis, chronic obstructive pulmonary disease (COPD), or cystic fibrosis.

Her cough was productive of yellow-green sputum and treated with antibiotics on multiple occasions, which provided some alleviation of her symptoms.

Examination revealed scattered wheezes and rhonchi on auscultation.

Pulmonary function testing demonstrated a severe obstruction with a forced expiratory volume at 1 second (FEV1) of 0.79 L (28% of predicted), forced vital capacity (FVC) of 1.64 L (47% of predicted), FEV1:FVC ratio of 48%, and a reduced diffusing capacity for carbon monoxide of 8.74 mL/min per mm Hg (23.75% of predicted), which was consistent with emphysema.

Chest radiography followed by computed tomography (CT) of the chest showed lower lobe predominant emphysema and bronchiectasis (Figure).Computed tomography of the chest.


He had not received any prior treatment for the lesions.

On examination, there were hypopigmented and hyperpigmented reticulated patches and thin, atrophic plaques covering more than 10% of the total body surface area involving the axilla, groin, and flanks bilaterally (Figure, A).

No cervical, axillary, or inguinal lymphadenopathy was noted.

Results from a comprehensive review of systems was unremarkable.

Results from a complete blood cell count, erythrocyte sedimentation rate, and blood chemistry analyses were normal.

A 6-mm punch biopsy specimen from the right flank was obtained for histopathological examination (Figure, B).

Immunohistochemical analysis was also performed (Figure, C and D).A, Hyperpigmented reticulated patches with central hypopigmentation on the right axilla.

B, Lesional punch biopsy specimen obtained from the right flank (hematoxylin-eosin stain).

C and D, Immunohistochemical analysis (positivity stain, original magnification ×100).


He was taking finasteride, montelukast, enalapril, and metoprolol.

His medical history was significant for right total reverse shoulder replacement 5 years prior.

There was no warmth, thrills, or pulsations across the affected area.

The patient complained about a mild tingling sensation within the lesion.

The patient could not think of any triggers or causes for his condition and denied any aggravating or alleviating factors as well as any treatment attempts.

Complete review of systems yielded negative results except for easy bruising.

Apart from the previously described lesion, his physical examination was unremarkable, and he had full range of motion of his right shoulder.

A punch biopsy of the slightly indurated papule from the involved area on the right biceps was completed (Figure, C and D).A and B, An irregularly linear, rusty-brown, atrophic, streaklike plaque extends from the tip of the right shoulder to the right biceps, where it ends in arborizing purple plaque with scattered, slightly indurated, irregular papules within it.

C, Hematoxylin-eosin staining demonstrates a dermal infiltrate arranged in nodules with clefting between nodules; some inflammatory aggregates are also seen within dilated vessels.

D, Immunohistochemical staining for CD68 antigen reveals that the infiltrate is composed mostly of histiocytes.


The patient was an active smoker (1 pack per day) with an unremarkable family history.

He began pembrolizumab therapy.After starting treatment, the patient began to notice slowly worsening painless, nonpruritic, diffuse dark gray skin, nail beds, and eye discoloration (Figure).

Physical examination revealed palpable right axillary lymphadenopathy.

A positron emission tomography scan showed a hypermetabolic right axillary lymph node that measured 5 × 5 cm as well as multiple liver lesions, the largest of which measured 8 cm.

The results of a core needle biopsy specimen from the right axillary lymph node were consistent with malignant neoplasm, with immunohistochemistry staining positive for S100, HMB-45, and MART-1.

The results of laboratory studies revealed normal electrolytes, normal kidney function, mild elevation of liver function, and mild anemia with a hemoglobin level of 12 g/dL (for SI unit conversion, multiply by 10.0 to convert to liters).

Computed tomography of the chest, abdomen, and pelvis showed worsening hepatic metastases and right axillary adenopathy.


Two weeks later, she presented to the emergency department (ED) after receiving several shocks from the device during the early morning, waking her up from sleeping.

Postprocedure chest radiography results showed appropriate device placement.

Postimplant interrogation results showed appropriate device function.

Physical examination results revealed no signs of decompensated heart failure.

Device interrogation results showed shock therapies delivered postimplant on days 3, 5, 6, and 10.

Repeated chest radiography at the ED showed appropriate device location, lead pin, and an absence of subcutaneous air trapping at the proximal and distal sense electrodes.Surface electrogram recorded by subcutaneous implantable cardioverter defibrillator from one of the events.

The device was programmed with a conditional shock zone of 200 beats per minute and a shock zone of 230 beats per minute.

The patient was discharged the day after implant.

There were no reported symptoms associated with shortness of breath, chest pain, or syncope.

The surface electrogram from the events, recorded at a paper speed of 25 millimeters per second and an amplitude of 2.5 mm/mvV) is shown in Figure 1.

Recorded at a paper speed of 25 millimeters per second and an amplitude of 25 mm/mV.


She reported no constitutional symptoms or any history of tobacco or alcohol use.

The lesion waxed and waned but never completely healed; however, it greatly increased in size over 3 weeks before presentation.

She reported constant, severe stabbing pain, right otalgia, and occasional swelling that caused oral dysphagia.

On examination, the mass was a 3 × 2-cm, exophytic and raised, plateaulike lesion on the right dorsolateral tongue with approximately 1 to 2 cm of surrounding induration (Figure, A).A, Right lateral tongue lesion at presentation.

B, Spindled-cell proliferation with palisaded areas (Verocay bodies) and an associated inflammatory infiltrate with abundant eosinophils (hematoxylin-eosin, original magnification ×20).A biopsy was obtained that demonstrated ulceration, pseudoepitheliomatous hyperplasia, and abundant acute and chronic inflammation replete with eosinophils.

The differential based on the biopsy included traumatic ulcerative granuloma with stromal eosinophilia and ulceration due to drug- or infection-related sources.

In addition, the possibility of an unsampled submucosal mass with overlying ulceration was suggested by the pathologist who interpreted the biopsy findings.


He had been diagnosed a year earlier with HIV infection and hepatic tuberculosis.

Baseline CD4 count was 7 cells/μL, and following treatment with HAART (highly active antiretroviral therapy) consisting of dolutegravir, emtricitabine, and tenofovir-disoproxil-fumarate, he achieved full virological suppression; however, CD4 counts remained low at 31 cells/μL.

He had completed 12 months of directly observed therapy with ethambutol, moxifloxacin, and rifabutin—a liver-sparing regimen—owing to toxic effects from the first-line regimen 1 month prior to admission.

Physical examination revealed evidence of perforation of the hard palate (Figure, A).

A computed tomographic scan of the chest revealed necrotic lymph nodes, and a palatine biopsy was performed (Figure, B and C).A, Clinical view of the perforation of the hard palate.

B, Low-power microscopic view of a biopsy specimen from the hard palate (hematoxylin-eosin).

C, Oil immersion image of the same tissue shown panel B stained with Grocott methenamine silver.


His ocular history included nonclearing vitreous hemorrhage in the right eye requiring pars plana vitrectomy, panretinal photocoagulation, multiple treatments with intravitreous bevacizumab, and cataract extraction with placement of an intraocular lens (IOL) into the capsular bag approximately 4 years ago.

Examination of the anterior segment at that time was unremarkable.At his current visit, visual acuity with the previous correction had been reduced to 20/150.

At his routine follow-up visit 2 weeks prior, the proliferative diabetic retinopathy was quiescent, and his Snellen visual acuity was 20/20 OD with manifest refraction of −1.50 + 0.25 × 180.

Repeated manifest refraction of the right eye was −4.00 + 1.50 × 166, resulting in a visual acuity of 20/25.

Intraocular pressure of the right eye was 10 mm Hg by Goldmann applanation tonometry.

Evaluation of the posterior segment, including dilated fundus examination and optical coherence tomography (OCT) of the macula, showed stability compared with previous results.

Imaging of the anterior segment with OCT is shown in Figure 1.


Medical history was significant for Sjögren syndrome, for which she was taking hydroxychloroquine sulfate.

Family history was negative for corneal disease.On initial presentation to the clinic, the best-corrected visual acuity of the patient was 20/150 OD and 20/40 OS.

She was found to have bilateral, gray-white, irregular, poorly circumscribed, linear and nummular central and peripheral corneal opacities, confined primarily to the subepithelium and focally to the underlying anterior stroma (Figure 1A).

The epithelium itself and deeper corneal stroma were spared, and the remainder of her anterior segment and fundus examination results were within normal limits.

Anterior segment optical coherence tomography documented deposition of hyperreflective material in the subepithelium with trace deposition in the anterior stroma (Figure 1B).

Evaluation of the patient's children showed no evidence of corneal disease.A, Right eye gray-white, irregular, linear and nummular central and peripheral corneal opacities.

B, Hyperreflective deposits in the subepithelium (black arrowhead) with trace deposit in the anterior stroma (white arrowhead).

Ocular history was notable for neovascular age-related macular degeneration under good control with intravitreal injections in the right eye and intermediate dry age-related macular degeneration in the left eye.


One month after presentation, the patient developed worsening photophobia, and his visual acuity declined to 20/50 OS.

On ophthalmic evaluation, visual acuity was 20/20 OS, intraocular pressure was 13 mm Hg OS, and slitlamp examination of the left eye demonstrated a clear, intrinsically vascularized, cystic lesion extending into the anterior chamber from the peripheral superonasal iris (Figure 1A).

The base of the lesion was surrounded by iris atrophy and corectopia was noted.

The remainder of the ocular examination was unremarkable.

Examination of the right eye was also unremarkable.

Ultrasonographic biomicroscopy of the anterior segment demonstrated a large, cystic lesion incorporated in the iris of the left eye with a thickness of 2.2 mm and a maximum radial extent of 6.1 mm (Figure 1B).A, Slitlamp photograph of the iris cyst in the superonasal periphery of the left eye.

B, Ultrasonographic biomicroscopy of the anterior segment in the left eye with longitudinal orientation at the 10-o’clock position.Given the patient’s excellent visual acuity and no documented evidence of growth, the lesion was initially monitored closely.

The iris lesion was noted to have grown, with maximum thickness measuring 3.5 mm and with radial extension now involving the visual axis.

The referring clinician initially suspected traumatic iridodialysis and vitreous prolapse.


The patient had a history of congestive heart failure, cleft lip surgery as an infant, and right eye amblyopia.

She reported occasional floaters and flashes in the right eye but denied any ocular complaints in the left eye.

On examination, her visual acuity measured 3/200 OD and 20/30 OS, stable compared with her baseline.

Her intraocular pressure was 18 mm Hg OD and 14 mm Hg OS.

Right eye slitlamp biomicroscopy showed an irregular pupil, aphakia, and a pigmented mass behind the temporal iris (Figure 1A).

Ophthalmoscopic examination results revealed a subluxed white cataractous lens in the inferior vitreous base (Figure 1B).

An evaluation of the left eye yielded normal results aside for a moderate cataract.

B-scan ultrasonography results showed the 2 masses described previously; both were moderately reflective, oval, and separate from the wall of the eye.

Ultrasonography biomicroscopy (UBM) confirmed that the temporal mass and the inferiorly subluxed lens were separate from the iris and ciliary body and were similar to each other in size, shape, and density.A, Anterior fundus photograph of the right eye shows a dark mass behind the pupil temporally.


She had a medical history significant for a renal transplant performed 4 years prior.

She received induction with alemtuzumab and maintenance immunosuppression with tacrolimus and mycophenolate.

On admission, the patient developed left eye pain and slurred speech.

Physical examination revealed expressive aphasia, partial left abducens nerve palsy, decreased motor strength in her right upper and lower extremities, and right-sided pronator drift.

Laboratory evaluation showed a white blood cell count of 9.6 K/μL (reference range, 4.5-11.0 K/μL), and a lactic acid dehydrogenase level of 547 U/L (reference range, 160-450 U/L).

Cerebrospinal fluid analysis revealed a white blood cell count of 51 cells/μL (reference range, 0-5 cells/μL) with 92% lymphocytes, a glucose level of 76 mg/dL (reference range, 40-70 mg/dL), and a protein level of 136 mg/dL (reference range, 12-60 mg/dL).

A computed tomography (CT) scan of the brain showed multifocal vasogenic edema around the left lentiform nuclei, left temporal occipital white matter, and right parietal white matter, with mass effect causing near complete effacement of the third ventricle and subsequent rightward midline shift.

Magnetic resonance imaging of the brain revealed multiple ring-enhancing lesions (Figure, A).

A fluorine 18 fluorodeoxyglucose positron emission tomography/CT demonstrated increased focal fluorodeoxyglucose activity throughout the brain only.

She was not on any antiviral therapies prior to presentation.

The patient underwent a biopsy of the right posterior temporal lobe (Figure, B and C).A, Ring-enhancing lesions are visible.

B, A lesional biopsy specimen of the brain was obtained (hematoxylin-eosin, original magnification ×400).

C, Immunohistochemical stain of CD20 (original magnification ×400).


He had no other medical conditions, took no medications, and was sexually monogamous with his wife, who was asymptomatic.The patient was hemodynamically stable and had a normal respiratory examination.

Two days later, he returned with worsening oral lesions, painful phonation, poor oral intake, odynophagia, and new painful penile lesions.

He denied any abdominal pain, diarrhea, rectal bleeding, weight loss, arthralgia, fatigue, vision changes, or skin rashes.

He reported a similar episode of widespread oral lesions 18 months earlier that was less severe and self-resolving.

He had a fever (39.4°C) on presentation, but his temperature abated overnight and he remained afebrile for the rest of the admission.

His superior and inferior lips had extensive well-circumscribed erosions and ulcerations with erythematous edges, crusting, and a gray-white base (Figure, left).

Lesions extended into the buccal mucosa and soft palate.

A genital examination showed similar lesions on the penis, with scalloped borders (Figure, right).

There were no skin lesions, lymphadenopathy, or hepatosplenomegaly.Left, Extensive well-circumscribed oral lesions limited to the mucosa in a 28-year-old man.

Right, Similar lesions with scalloped borders on the distal shaft and glans of the penis in the same patient.Results of laboratory tests from the emergency department were normal, and a chest radiograph showed no evidence of pneumonia.

Results of further testing for antinuclear antibodies, erythrocyte sedimentation rate, C-reactive protein level, HIV, HSV serology, syphilis, chlamydia, and gonorrhea were negative.

Bacterial and viral cultures of the oral and penile lesions were also negative.

Serum enzyme immunoassay for Mycoplasma pneumoniae IgM was positive at 1280 U/mL.

He was diagnosed with herpes simplex virus (HSV) and discharged home with acyclovir.


She had a medical history of hypertension and palmar and axillary hyperhidrosis.

She denied double vision, ptosis, headache, and weakness.

On examination, she appeared well and her blood pressure was 128/78 mm Hg; heart rate, 76/min; and respiratory rate, 13/min.

Visual acuity was 20/20 in both eyes, there was no ptosis, and extraocular movements were full.

Pupillary examination revealed anisocoria that was more pronounced in bright lighting conditions (Figure).

The right pupil measured 6 mm in the dark and 3 mm in the light, whereas the left pupil measured 9 mm in the dark and 8 mm in the light.

The left pupil was poorly reactive to light and to a near target.

Slitlamp examination revealed normal-appearing anterior chambers without any signs of intraocular inflammation.

Cranial nerve function was otherwise normal.


He immigrated to the United States as an adult more than 20 years before presentation.

He reported a 4-month history of nonproductive cough, 5-kg weight loss, and fatigue.

His temperature was 37°C, heart rate was 78/min, respiratory rate was 17/min, and blood pressure was 158/95 mm Hg.

A chest radiographic image suggested cardiomegaly and a computed tomographic scan demonstrated a moderate to large pericardial effusion.

A pericardial drain was placed and pericardial fluid was sent to the laboratory for evaluation.

Initial pericardial fluid study results are presented in the Table.

Empirical treatment for tuberculosis was initiated.


He had no history of chronic abdominal pain.

Past surgical history was noteworthy for emergency exploratory laparotomy and splenectomy for blunt trauma 14 years prior.

He stated that “I think I have a kidney stone blocking my kidney” but denied nausea, vomiting, fever, dysuria, hematuria, or weight loss.

Physical examination revealed a comfortable-appearing patient in no acute distress.

His temperature was 36.8°C; pulse, 77/min; and blood pressure, 125/86 mm Hg.

Abdominal palpation elicited only mild epigastric tenderness without masses or rebound.

There was no costovertebral angle tenderness.Laboratory data revealed normal levels of serum urea nitrogen and creatinine and normal liver function.

A complete blood cell count showed leukocytosis (15 300/μL with 54% neutrophils, 38% lymphocytes, 8% monocytes); hemoglobin level, 15.5 g/dL; and hematocrit, 45.2%.

Urinalysis revealed no red or white blood cells and was negative for leukocyte esterase and nitrate.


She subsequently developed multiple asymptomatic pink papules on the trunk and extremities.

Clinical examination revealed scattered pink papules with a white firm center and dark brown core scattered throughout the chest, abdomen (Figure, A and B), back, groin, and upper and lower extremities.

Laboratory workup was significant for leukopenia with neutropenia, anemia, and thrombocytopenia.

Creatinine and transaminase levels were within normal limits.

The patient was afebrile and was receiving broad-spectrum antibiotic, antifungal, and antiviral treatment for a prior episode of neutropenic fever.

A punch biopsy from the left flank was obtained for hematoxylin-eosin staining, and a punch biopsy from the left leg was sent for tissue and fungal culture.

Histopathological analysis was subsequently performed (Figure, C and D).A, Multiple papules on the abdomen.

C and D, Hematoxylin-eosin–stained lesional specimens.


The patient had experienced a weight loss of 6 kg during the last 3 months.

Within the last month, the patient’s thyroid became enlarged, and she developed anorexia and abdominal discomfort.

The verrucous plaques also involved the conjunctiva, lips, and gingiva (Figure 1B).

Laboratory test results revealed remarkably elevated levels of carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 125, tissue polypeptide antigen and carbohydrate antigen 242.

Biopsy specimens of lesions on the axillae and lips both revealed a papillary structure with hyperkeratosis.

An endoscopic examination and computed tomographic scan of the abdomen were performed.Axilla with velvety, hyperpigmented skin (A) and verrucous plaques on the lips and gingiva (B).


Social history was significant for 25 pack-years of smoking.

The onset was gradual and started on the lower extremities and gradually extended to involve the lower trunk.

The rash was associated with mild discomfort.

The patient denied itching, weeping, or bleeding from the rash.

She denied any constitutional symptoms (weight loss, fever, night sweats), joint pains, history of blood in urine, periorbital edema, and recent intake of medications or herbal medications.

Physical examination revealed multiple well-defined, coalescent, erythematous, palpable, purpuralike lesions that were predominantly present over the trunk and lower extremities (Figure, A and B).

Laboratory test results at presentation included a hemoglobin level of 11.2 g/dL (to convert to g/L, multiply by 10), mean corpuscular volume of 84 fL, erythrocyte sedimentation rate of 72 mm/h, and a lactate dehydrogenase level of 412 IU/L.

Hepatic and renal function levels were within normal limits.

Hepatitis B and C and HIV profiles were negative.

A chest radiograph showed a 2-cm lesion in the upper lobe of the left lung.

A computed tomographic scan of the chest showed a spiculated mass in the same region along with mediastinal lymphadenopathy.

An ultrasound of the abdomen showed bilateral adrenal masses.

A lesional skin biopsy specimen was obtained (Figure, C).Coalescent, erythematous, palpable lesions on the lower extremity (A) and trunk (B).


Her family history was notable for hypertension, and no other systemic diseases were reported.

The pain started at rest, was 10 of 10 in severity, and was not alleviated by changing position.

She also experienced concomitant nausea and diaphoresis.

On physical examination, her blood pressure was 115/76 mm Hg, heart rate was regular at 72 beats per minute, respiratory rate was 20 breaths per minute, and oxygen saturation level was 98% on room air.

Physical examination also revealed mild bibasilar crackles and jugular venous distention, and no murmurs or lower extremity edema.

Laboratory test results demonstrated an elevated troponin, and the 12-lead electrocardiogram showed marked ST-segment elevations in leads V2 to V5 (Figure, A).

The ST-segment elevation myocardial infarction (STEMI) pager was activated, and the patient was transferred urgently to the catheterization laboratory.

Coronary angiography of the patient’s left anterior descending coronary artery was performed, and the findings are depicted in the Figure, B.A, Twelve-lead electrocardiogram.


She had developed a recurrence for which she had just completed 3 cycles of treatment with carboplatin.

She also had a history of anxiety, hypertension, and pterygium, and she was taking gabapentin, lorazepam, prochlorperazine, metoprolol succinate, bromfenac and ketorolac ophthalmic solution, and aprepitant.

Her local dentist had prescribed an antibiotic and performed a tooth extraction in the area 6 months prior with no improvement in symptoms.

Ultimately, her pain became persistent and radiated to the right lower lip.

Intraoral examination revealed a 1.5 × 1.0-cm firm, erythematous gingival mass in the area of missing right mandibular second bicuspid and first molar with buccal and lingual expansion (Figure 1A).

The right mandibular first bicuspid was grade 3 mobile.

A periapical radiograph was obtained, and results showed a diffuse, poorly demarcated radiolucency measuring approximately 1.2 × 0.8 cm (Figure 1B).

Findings from an incisional biopsy of the mass showed an infiltrative tumor (Figure 1C).

Tumor cells were positive for CK7, PAX8, and WT-1, and negative for CK20 and TTF-1 (Figure 1C, inset).A, A 1.5 × 1-cm gingival mass is distal to the right mandibular first bicuspid.

B, Diffuse, poorly demarcated radiolucency is seen in the area of the missing right mandibular second bicuspid and first molar (arrowheads).

C, Multiple nests of round to ovoid epithelial cells form ducts (hematoxylin-eosin stain, original magnification ×100).


He had been taking prophylactic emtricitabine-tenofovir daily and had received his last diphtheria booster 2 years prior to presentation.

Owing to the odynophagia, he had presented to the emergency department for dehydration.

At that time, he was febrile to 101°F and denied any dysphonia or dyspnea.

The results of a rapid Streptococcus test, recent HIV screen, and a rapid plasma reagin test were all negative.

He denied any genital lesions or symptoms at that time.

On physical examination, there was no cervical lymphadenopathy, and there were no genital lesions.

Flexible fiber-optic nasopharyngoscopy showed ulcerative lesions with exudate and erythema extending diffusely along the base of tongue, oropharynx, nasopharynx, hypopharynx, and epiglottis (Figure 1).

Treatment with amoxicillin clavulanate over several days had not prevented a worsening of his symptoms.


Her history also included chronic gastroesophageal reflux disease and a 14-pack-year smoking history.

She initially presented 3 months prior with upper respiratory symptoms, which continued to worsen despite oral antibiotic therapy.

Her cough became productive with white, frothy phlegm that was accompanied by fever, wheezing, hoarseness, and fatigue.

Her dyspnea worsened in the supine position.Flexible laryngotracheoscopy results revealed diffuse, white-to-yellow pseudomembranous changes involving the glottis and supraglottis (Figure, A), posterior tracheal wall, and left mainstem bronchus with skip lesions in the subglottis and distal 1 cm of the trachea (Figure, B).

Glottic mobility was limited in both abduction and adduction with substantial airway obstruction.

Computed tomographic findings revealed posterior tracheal wall thickening with the loss of the fat plane between the trachea and esophagus, and a moderate to severe obstruction within the distal left mainstem bronchus.

Biopsy results are shown in Figure, C.Laryngoscopic images demonstrate pseudomembranous plaques lining supraglottis and glottis (A) and posterior wall of the trachea (B).

Supraglottic biopsy demonstrates branching organisms superficial to squamous epithelium (original magnification ×400) (C).


The patient did not have any noteworthy rhinological symptoms on review.

Preoperative magnetic resonance imaging examination of the sella revealed a left-sided pituitary microadenoma (Figure, A) and lobulated polypoid soft tissue masses in the superior nasal cavities arising from the olfactory clefts.

These lesions demonstrated avid post–contrast enhancement with small areas of cystic change and heterogeneously hyperintense T2 signal.

There was mild widening of the olfactory clefts, particularly on the left side (Figure, B).

The intervening nasal septum was intact, and there was no intracranial extension.

He later underwent nasal endoscopy, and results showed tan-colored polypoid lesions emanating from the olfactory clefts of both nasal cavities (Figure, C).

Biopsy findings revealed submucosal proliferation of seromucinous and respiratory epithelial glands (Figure, D).A, An incidental polypoid-enhancing mass in the nasal cavity demonstrating avid post–contrast enhancement (yellow arrowheads) was observed on the magnetic resonance imaging examination.

The white arrowhead points to the pituitary adenoma.

B, Widening and remodeling of the olfactory clefts (yellow arrowheads) was also observed on the magnetic resonance imaging examination.

C, The incidental polypoid-enhancing mass in the nasal cavity (yellow arrowheads) as seen on nasal endoscopic analysis.

D, Results of the nasal cavity mass biopsy (original magnification ×100) revealed submucosal proliferation of bland-appearing seromucinous and respiratory epithelial glands.


Her medical history was notable for a growth hormone–producing pituitary macroadenoma for which she underwent surgical resection 2.5 years prior to presentation, followed by γ-knife radiosurgery (50 Gy) 6 months after the initial surgical procedure.

She also had a history of congenital hip dysplasia.

Medications included cabergoline, levothyroxine, ethinyl estradiol/drospirenone, and pasireotide.Her visual acuity was 20/20 OU.

The double vision occurred every day, multiple times throughout the day, and was provoked after looking to the right.

Her pupils were equal in size with no relative afferent pupillary defect.

Automated perimetry was full in both eyes.

The anterior and posterior segments were normal in both eyes.

On initial examination, the eye movements were full, with no ocular deviation in primary, right, or lateral gazes.

However, on returning to a primary gaze from a sustained right-gaze position, a large angle exotropia was present, and on attempted left gaze, there was a limitation of adduction of the right eye (Figure).

After 10 to 15 seconds, the exotropia resolved, and eye movements returned to normal.A, Eye positions in right gaze, and B, eye positions in primary gaze.

After sustaining a right gaze position for 10 to 15 seconds (A) and then returning to primary gaze (B), there is a large-angle right exotropia.


He had an unremarkable medical and ocular history and had not sustained any ocular trauma.

He described a painless, reddish mass in his lateral conjunctiva, which had been present since birth.

He was asymptomatic aside from rare episodes of pink tears in his right eye, and the lesion did not bother him cosmetically.

He noted no blurry vision, diplopia, or pain with eye movements.

His visual acuity was 20/20 OU, and there was no proptosis, ptosis, or afferent pupillary defect.

Extraocular muscle movements were intact, and his intraocular pressure was 15 mm Hg OU.

There was no change in lesion size observed with the Valsalva maneuver.

A slitlamp examination revealed an 8-mm, round, fluctuant, vascular, multifocal mass involving the bulbar and palpebral conjunctiva near the lateral canthus (Figure).


The lesion was followed closely and throughout a series of visits, the lesion and fluid continued to progress, the visual acuity worsened to 20/200, and the tumor mass extended closer to the fovea (Figure 1).

Visual acutiy was 20/60 OD and 20/20 OS.

Intraocular pressures and anterior segment examination findings were normal.

Fundus examination revealed orange, subretinal mass with associated subretinal fluid in the posterior pole.

The mass measured 15 mm in basal diameter with a thickness of 6.4 mm on B-scan ultrasonography.Large choroidal vascular mass of inferotemporal right choroid.

Note large choroidal mass on B-scan ultrasonography.


His medical history was significant for pyruvate dehydrogenase deficiency, and his family history was notable for glaucoma in his grandmother.

He was being treated by the neurology department for his pyruvate dehydrogenase deficiency with thiamine, vitamin C, and oxaloacetate.

He had exotropia and amblyopia of the left eye.

His systemic symptoms included hyperhidrosis and episodes of hand tremors, ataxia, and dysarthria that occur every 2 to 3 years.Best-corrected visual acuity was 20/40 −2 OD and 20/100 +2 OS, with a relative afferent pupillary defect in the left eye.

Intraocular pressure (IOP) was 16 mm Hg OU, and pachymetry was 611 μM OD and 592 μM OS (normal mean [SD], 542.4  [33.5] μM).

He identified 8/8 OD and 3/8 OS Ishihara color plates.

His nuclear sclerotic cataracts were not consistent with visual acuity in both eyes; his anterior segment examination was otherwise within normal limits.

His dilated examination was normal except for cupping and pallor in both eyes with a supratemporal optic nerve pit in the right eye.

The optic discs and automated perimetry are shown  in the Figure.

Optical coherence tomography (OCT) of the retinal nerve fiber layer showed a mean thickness of 64 μM OD and 47 μM OS (normal mean [SD], 97.3 [9.6] μM), and OCT of the macula showed perifoveal thinning with normal foveal thickness in both eyes.A and B, Fundus photographs show cupping with optic nerve pallor in both eyes and a supratemporal optic nerve pit in the right eye (arrowhead).

He was diagnosed as having glaucoma 6 months prior to presentation owing to optic nerve cupping and visual field deficits on automated perimetry and was taking latanoprost.

He had an exotropia with full range of motion in both eyes.


He was diaphoretic and had poor dentition.

His vital signs were temperature, 38.4°C (101.1°F); blood pressure, 94/40 mm Hg; heart rate, 116/min; and respiratory rate, 26/min.

A soft S1 was present on cardiac examination, and crackles were auscultated in basilar lung fields bilaterally.

A bedside transthoracic echocardiogram was performed, the patient was transferred to the intensive care unit, and a transesophageal echocardiogram was obtained (Figure 1).Transesophageal echocardiogram obtained from the patient in diastole on the midesophageal long-axis view.

Three sets of blood cultures from different sites were obtained.

Cardiology, cardiac surgery, and infectious disease physicians were consulted.


The patient first noticed papules on his forehead 1 year prior to presentation that spread to his face, trunk, and extremities.

He had mild dysphagia and severe joint pain in his hands and wrists, with carpal tunnel of his right wrist.

Additionally, his daily activities were impaired owing to decreased mobility.

During clinical evaluation, he denied cough, shortness of breath, chest pain, Raynaud phenomenon, fevers, night sweats, weight loss, seizures, or confusion.Physical examination revealed diffuse skin-colored to pink papules coalescing into plaques on the entire face, with exaggerated skin folds of the forehead (Figure, A), glabella, periocular regions, and superior cutaneous lip.

This was accompanied by swelling and erythema of both ears.

On his extremities and trunk, he had diffuse infiltration of the skin, with exaggerated skin folds (Figure, B), decreased finger flexion, and four-fifths grip strength.

C, Hematoxylin-eosin stain image from the punch biopsy featuring fibroblastic proliferation from the papillary to the reticular dermis (original magnification ×40).

D, Hematoxylin-eosin and Alcian blue stain image featuring mucin deposition in the reticular dermis.Notable laboratory results included a normal level of thyroid-stimulating hormone, macrocytic anemia, normal creatinine and calcium levels, and a monoclonal spike on a serum protein electrophoresis test.

Serum free light chains revealed normal κ free light chains, λ free light chains, and a normal κ/λ ratio.

Immunofixation results revealed IgG λ monoclonal gammopathy.

Skin sensation was intact.A, Clinical image of the exaggerated skin folds of the forehead and glabella.

B, Clinical image of the wrist and hand depicting the exaggerated skin folds and decreased finger flexion.


He had a 16-year history of diabetes mellitus that was being treated with metformin.

Physical examination revealed reddish brown hyperkeratotic papules 1 to 10 mm wide on the front and back of the left leg from knee to ankle.

Removal of the scales caused slight bleeding.

Hematological and biochemical test results were unremarkable.

The rest of the physical examination findings were unremarkable.

A lesional skin biopsy was performed (Figure 1B and C).A, Clinical image of the reddish brown hyperkeratotic papules on the front of the left leg.

B and C, Hematoxylin-eosin–stained lesional skin biopsy specimens revealing compact hyperkeratosis, epidermal atrophy, and bandlike lymphocyte infiltrate in the superficial dermis.

There was no history of another endocrine disorder or malignant neoplasm.

There was no family history of similar cutaneous findings.


He described transient episodes of expressive speech difficulties, paroxysmal dizziness, and involuntary nonsuppressible jerks of the right arm, which occurred without warning and were associated with mild disorientation.

Video electroencephalography (EEG) captured the movements (Figure, A).

They consisted of involuntary, synchronous contractions of the right face, arm, and leg that were sustained for a few seconds before muscle relaxation occurred (Figure, B and C; Video).

There was no epileptic abnormality that correlated with the movements on EEG, and head magnetic resonance imaging was unremarkable.A, Electroencephalogram (EEG) during the event (bipolar montage, 60-Hz filter, 7-uV/mm sensitivity).

C, Patient position while experiencing an involuntary, sustained contraction of the right lower face, arm, and leg lasting almost 2 seconds before spontaneous resolution.

The event took place during the time span marked with red vertical lines on the EEG and did not show a clear change from baseline rhythm.

Muscle artifacts are seen prior to and during the event.

The movements were not elicited by action or exertion.


She previously received a diagnosis of viral conjunctivitis at an outside institution and was treated with topical prednisolone acetate without improvement before presenting to our institution.

On examination, visual acuity was 20/25 OD and hand motions OS.

A relative afferent pupillary defect was present on the left in the setting of left optic atrophy from the patient’s locally invasive meningioma.

Confrontational visual fields were otherwise full in the right eye.

Intraocular pressures were within normal limits in both eyes.

Hertel exophthalmometry was notable for 3 mm of proptosis on the right.

Slitlamp examination demonstrated 3 to 4+ meibomian gland dysfunction in both eyes, but with prominent conjunctival injection in the right eye only.

Dilated funduscopy revealed scattered intraretinal hemorrhages (IRHs) and cystoid macular edema (CME) in the right eye, which was also seen on optical coherence tomography (Figure 1).

Vital signs, complete blood cell count, and the results of thyroid function tests were within reference ranges.

Magnetic resonance imaging and magnetic resonance angiography of the brain and orbits with and without contrast showed a stable size of the meningioma and were otherwise normal.A, Color fundus photograph of the right eye showing scattered intraretinal hemorrhages and a blunted foveal light reflex.


Her medical history was notable for hypertension and type 2 diabetes.

Family history was positive for hypertension in her mother, prostate cancer in her father, and ductal carcinoma in situ in her daughter.

She was a current daily smoker at presentation.

Over the previous 5 months, the patient had experienced gradual onset of binocular, horizontal diplopia and ptosis of the left upper eyelid.

Her symptoms were constant, without fluctuation during the day.

An ophthalmologic examination revealed a visual acuity of 20/25 OD and 20/30 OS.

Pupillary, intraocular pressure, and dilated fundus examinations were unremarkable.

Abduction was severely restricted in the left eye, but it did not elicit pain, and extraocular muscle movements were otherwise full.

There was substantial resistance to retropulsion of the left eye.

Bilateral blepharoptosis, with more severity on the left side, was noted.

The margin-to-reflex distance 1 was 2 mm on the right and 0 mm on the left.

A 3.5-mm left enophthalmos was noted compared with the right side, and there was hollowing of the left superior sulcus.

There were no neurological deficits and no pain.

There was no history of trauma or prior surgery of the eye.


He had a history of herpetic keratitis and cataract surgery 2 years prior, both in the right eye, complicated by postoperative bullous keratopathy without treatment.

The patient noted a corneal scar after the cataract surgery that gradually thickened over the ensuing 6 months.

In our office, his examination in the right eye was notable for hand motion visual acuity and a pearly white, raised, 10 × 10-mm, gelatinous, corneal lesion with both intrinsic and feeder vessels (Figure 1A).

There was no view of the anterior segment.

Ultrasound biomicroscopy showed a hyperechoic opacity on the surface of the cornea, with maximal thickness of 1.5 mm.

A cleft was noted between the lesion and the cornea (Figure 1B).

There was no extension posteriorly into the anterior chamber, iris, or ciliary body.A, Slitlamp external photograph of right-eye corneal lesion showing prominent elevation and both intrinsic and feeder vessels.

B, Ultrasound biomicroscopy showing hyperechoic anterior corneal lesion with hypoechoic cleft labeled centrally.

The lesion did not involve any other adjacent structures.


She was diagnosed with Hodgkin lymphoma at 35 weeks’ gestation, and 1 week later she underwent cesarean delivery.

Laboratory test results revealed a white blood cell count of 1.6 ×103 cells/mm3, with an absolute neutrophil count of 500 cells/mm3 and a total bilirubin of 0.3 mg/dL (to convert to μmol/L, multiply by 17.104), which was unchanged from the baseline total bilirubin.Clinical photograph of the patient’s back shows scratch marks that appeared after diffuse pruritus.Prior to the diagnosis of Hodgkin lymphoma, she was receiving routine prenatal care, and the only complication was pruritus without a rash that developed during the first trimester.

She was evaluated for right supraclavicular adenopathy that was unresponsive to antibiotics during the third trimester.

On day 15 of cycle 1, she presented with linear, hyperpigmented streaks and welts on her arms, back, and legs.

Intense, diffuse pruritus had developed within 24 hours of the patient’s first day of treatment, and her symptoms were poorly responsive to antihistamines and topical steroids.

Pruritus was followed by the appearance of dark scratch marks as demonstrated in the Figure.

Findings from a lymph node biopsy were consistent with classic Hodgkin lymphoma, nodular sclerosis subtype.

Staging imaging revealed bilateral supraclavicular jugular chain, paratracheal and mediastinal lymphadenopathy, and the erythrocyte sedimentation rate was 67 mm/h.

At 3 weeks’ postpartum, she began chemotherapy (cycle 1, day 1) with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD).

She was diagnosed with stage II, unfavorable-risk Hodgkin lymphoma.


The lesions had started a month previously as red nodules on the left axilla, ipsilateral chest, and back.

Twenty days later, he developed edema in the left upper limb.

There was diffuse erythema and edema on the left upper limb, leading to difficulty in limb movement (Figure, A).

While being evaluated for the cutaneous lesions, the patient was diagnosed with AIDS and began antiretroviral therapy.On examination, 6 erythematous, firm, subcutaneous nodules were present on the left side of the chest, abdomen, and left upper limb, varying in size from 2 × 2 cm to 4 × 4 cm (Figure, A).

Multiple dilated superficial vessels were present on the posterior aspect of the left arm and ipsilateral chest wall.

Left axillary lymph nodes were grossly enlarged, firm, nontender, and nonmatted, with the largest lymph node measuring 6 × 4 cm.

The patient’s CD4 cell count was 141/μL (to convert to ×109/L, multiply by 0.001), and his HIV load was 504 473 copies/mL.

B, Skin biopsy sample showing infiltration with lymphoid cells and few histiocytes in the subcutaneous tissue (hematoxylin-eosin, original magnification ×400).

C, On immunohistochemical analysis, these cells showed nuclear positivity for c-Myc (c-Myc, original magnification ×400).

A skin biopsy sample was obtained from the plaque and sent for histopathologic examination (Figure, B and C).A, Multiple erythematous indurated plaques and nodules confined to the left side of the chest and abdomen with axillary lymphadenopathy and upper limb edema.


He had no history of drug use or cardiac events.

The heart sounds were normal, and bilateral ankle edema was present.

On physical examination, he had warm extremities.

His blood pressure was 100/60 mm Hg, heart rate was 130 beats/min, respiratory rate was 24 breaths/min, and pulse oximetry was 98% on ambient air.

There were bibasilar rales on lung auscultation.

Laboratory tests revealed hyponatremia (sodium, 124 mEq/L [to convert to millimoles per liter, multiply by 1]), a compensated metabolic acidosis with a bicarbonate concentration of 14 mEq/L (to convert to millimoles per liter, multiply by 1), and a lactate concentration of 82.0 mg/dL (to convert to millimoles per liter, multiply by 0.111).

The D-dimer level was 0.0003 μg/mL (to convert to nanomoles per liter, multiply by 5.476), and the pro–brain-type natriuretic peptide level was 6062 pg/mL (to convert to nanograms per liter, multiply by 1).

Echocardiography (Video 1 and Video 2) revealed a left ventricular ejection fraction of 50%.

The electrocardiogram on presentation is shown in the Figure.


The mass was soft, mobile, and compressible in midline level IA, measuring 7 cm and posterior-superiorly displacing the tongue.

The mass was visible as a clear blue lesion in the floor of the mouth and was nontender.

Computed tomographic (CT) scan of the neck with IV contrast was performed (Figure).

The patient was taken to the operating room for a successful combined intraoral and transcervical approach to excision.Computed tomographic images.


Social history included routine cocaine use 10 years ago.

Associated symptoms included epistaxis and left-sided epiphora.

Physical examination demonstrated substantial erythema and edema of the left infraorbital region and left nasal sidewall and purulent nasal secretions (Figure 1A).

Endoscopic nasal examination revealed substantial swelling of the left nasal vestibule completely obstructing the left naris, swelling of the left nasolacrimal duct orifice, nearly total septal perforation with areas of necrotic bone, and no identifiable intranasal landmarks except for a remnant of the left middle turbinate (Figure 1B).

Laboratory evaluation revealed a white blood cell count of 12 300/μL with normal neutrophil count; erythrocyte sedimentation rate of 83 mm/h; and a C-reactive protein level of 134 mg/L.

A maxillofacial computed tomographic (CT) scan demonstrated cartilaginous and anterior osseous nasal septal perforation and left nasal and preseptal soft-tissue thickening with associated periosteal reaction of the nasal process of the maxilla.A, Periorbital and nasal cellulitis.

Prior to presentation, she had been treated as an outpatient with multiple rounds of oral antibiotics and steroids for presumed sinusitis without improvement.

(To convert white blood cells to ×109/L, multiply by 0.001; C-reactive protein to nanomoles per liter, multiply by 9.524.)


One week after symptom onset, she remained febrile (maximum temperature, 39.6°C [103.2°F]) and the rash spread to her palms and soles, with some progression to pustules (Figure, left panel).

She developed right knee pain, followed by pain in other joints.

Two weeks after symptom onset, she presented to a local emergency department, reporting inability to stand due to severe joint pain.

Approximately 3 weeks after symptom onset, she presented to the emergency department again with persistent fever, worsening arthralgia, back pain, and progressive purpuric and pustular rash.

White blood cell count was 12 100/μL (reference range, 4000/μL-10 000/μL), with 84% neutrophils.

Urinalysis results and levels of serum electrolytes and liver enzymes were within normal limits.

She was presumptively diagnosed with a viral illness and discharged home with supportive care.

Results of tests for sexually transmitted infections and respiratory viruses were negative.


On examination, she had a large, palpable, nontender right gluteal mass.

Results of laboratory studies were within normal limits.

Computed tomography (CT) revealed an 11-cm heterogeneous lipomatous tumor involving the right gluteal musculature (Figure).Axial (left) and coronal (right) computed tomography images of patient’s right gluteal mass.


Prior to presentation, he had been treated for herpes zoster with famciclovir for 1 week, during which the lesions kept developing and were accompanied with irregular fever (maximum temperature, 39°C).

Physical examination revealed edema on both eyelids; multiple papules, blisters, and crusted erosions with thin exudation on his right cheek and neck; and erythematous plaques and tense blisters and bullae on his back and on the dorsal surface of both hands (Figure 1B).

A full laboratory workup was performed for autoantibodies for systemic lupus erythematosus (SLE), pemphigus, and bullous pemphigoid; skin and bone-marrow biopsies and direct immunofluorescence were performed; and immunohistochemichal analysis, a swab of exudation, and bacterial, fungal, and atypical mycobacterial cultures from blood and tissue were also examined.A, Edema on both eyelids; multiple papules, blisters, and crusted erosions with thin exudation on right cheek and neck.


Eleven years earlier, she had been diagnosed with left breast carcinoma and had undergone a mastectomy with subsequent radiotherapy and chemotherapy.

Seven years later, she had been found to have left supraclavicular lymph nodes metastasis and had undergone a surgical excision.

On presentation for the current problem, the patient experienced pain on palpation, but denied fever, chills, or other symptoms.

A physical examination revealed violaceous swelling with telangiectasia and necrosis on the forehead, eyelids, nose, and cheek, predominantly involving the left side of the face (Figure 1).

A biopsy of the lesion was performed for histopathological analysis (Figure 2).A, A full image and B, a three-quarters image of the face, showing telangiectatic, swelling erythema mainly involving the left side of the forehead, eyelids, nose, and cheek.


His medical history included hepatitis C, cirrhosis, and an orthotopic liver transplant (OLT) 3 years prior that was subsequently treated with tacrolimus, 5 mg, and mycophenolate, 750 mg, twice daily.

Five weeks after treatment with CHOP chemotherapy, the patient presented with an acute-onset abdominal skin eruption without fever or pain.

Physical examination revealed confluent indurated violaceous papules and plaques coalescing into an annular pattern encircling the healed OLT incisional scar with central sparing (Figure 1A).

A 4-mm punch biopsy specimen was obtained for histopathological evaluation (Figure 1B and C) and bacterial and fungal cultures.A, Confluent, indurated, violaceous papules and plaques coalescing into an annular pattern encircling the well-healed orthotopic liver transplant incisional scar.

B, Hematoxylin-eosin staining of the punch biopsy shows an atypical, hyperchromatic infiltrate present throughout the superficial and deep dermis.

C, High magnification reveals crushed but markedly atypical-appearing lymphoid cells with nuclear hyperchromasia and scant amounts of cytoplasm.

Multiple mitotic and apoptotic figures are easily identified.

He was subsequently instructed to stop use of mycophenolate and decrease use of tacrolimus to 0.25 mg daily, then treated with 1 cycle of CHOP chemotherapy (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone) and lenalidomide, resulting in symptomatic and radiologic improvement.

A computed tomographic scan of the abdomen and pelvis showed possible abdominal wall cellulitis, so treatment with piperacillin-tazobactam and vancomycin was empirically started.

The gastric wall mass was found to be associated with plasmablastic posttransplantation lymphoproliferative disorder (pPTLD).

Approximately 2½ years after the transplant, the patient developed gastric outlet obstruction secondary to an infiltrative gastric wall mass.


The patient had reportedly always walked on the outside of his feet and had been considered clumsy when compared with other children but had no history of motor delays.

Family history revealed a mother with diminished reflexes, hand tremor, and balance issues with a prior inconclusive electromyogram  and nerve conduction study.

A younger brother with attention-deficit/hyperactivity disorder also had similar gait abnormalities.

Symptoms lasted approximately 60 minutes each before completely resolving; prior to the day of the events, he had never experienced similar phenomena.

Initial examination following the second event revealed mild-to-moderate dysarthria, pes planovalgus and tight achilles tendons bilaterally, and decreased vibratory and fine touch sensation from the great toe up to the mid shin bilaterally.

Reflexes were absent at the patella and achilles bilaterally.

Bilateral dorsiflexion weakness was present (4 of 5).

There were otherwise no motor deficits, muscle atrophy, or lateralizing neurologic abnormalities.On arrival, the patient underwent a stroke/transient ischemic attack workup.

Results of a comprehensive metabolic panel, complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, and a coagulation panel were within normal limits.

Computed tomography angiogram demonstrated no evidence of extra or intracranial dissection.

Magnetic resonance imaging of the brain with and without contrast (Figure) demonstrated symmetric, bilateral, restricted diffusion, with T2 hyperintensities in the supratentorial white matter and corpus callosum.

Lumbar puncture was obtained and revealed normal cell counts and no oligoclonal bands or evidence of infection.A, Diffusion-weighted imaging sequence demonstrating bilateral, symmetric, restricted diffusion of the supratentorial white matter (corresponding hypointensity noted on apparent diffusion coefficient sequences).

B, T2 sequence demonstrating bilateral and symmetric increased signal in the supratenorial white matter–sparing U-fibers.


His right eye had experienced an episode of blurry vision 4 months previously that had spontaneously improved over a few weeks.

Two weeks before presentation, he experienced blurry vision in his left eye and received a diagnosis of vasculitis based on fluorescein angiography (FA) findings.

Over the next 2 weeks, he experienced a rapid worsening of vision in both eyes and presented to the Illinois Eye and Ear Infirmary.

In the absence of other signs or symptoms of syphilis, he was scheduled to undergo a lumbar puncture later that day.On presentation, his visual acuity was counting fingers OD and 20/300 OS, with manifest refraction to 20/60 OS only.

He had no afferent pupillary defect and his intraocular pressures were healthy.

The anterior segment examination yielded normal results without evidence of anterior chamber inflammation.

A dilated fundus examination was notable for mild vitritis of both eyes, mild hyperemia of the right optic nerve, and a large white lesion that encompassed the nerve and macula of both eyes.

Fluorescein angiography results revealed multiple hyperfluorescent lesions in late frames (Figure 1).A, Color fundus photograph of the left eye shows  a large placoid lesion in the macula.

He was referred to a rheumatologist and received high-dose oral prednisone therapy for presumed autoimmune vasculitis.

During an interview, he noted that the laboratory workup results had recently come back as notable for a mildly reactive fluorescent treponemal antibody absorption test.

showing multiple areas of hyperfluorescence in the macula and periphery with peripheral vascular leakage.


She had a 4-year history of Behçet disease (BD), and her condition had been stabilized with thalidomide.

She denied any other neurologic symptoms, such as headache, nausea, vomiting, seizures, and paresis.

Humphrey visual fields showed complete visual field loss in the right eye and peripheral visual field defects in the left eye.

Intraocular pressure was 21 mm Hg OD and 19 mm Hg OS.

Fundus examination revealed papilledema in both eyes (Figure 1A).

No obvious sign of optic disc ischemia or active uveitis was observed by fundus fluorescein angiography bilaterally.

Her anterior segment was normal in both eyes except for relative afferent pupillary defect in the right eye.

Cranial nerve examination was otherwise unremarkable.

Magnetic resonance imaging of the brain showed no remarkable abnormalities except for partially empty sella (Figure 1B).

Results of laboratory testing regarding systemic infection were negative, and her serum D-dimer level was normal.A, Fundus photograph of the right eye indicated papilledema, disc congestion, venous distension, and macular exudates.

Her optic neuropathy of BD had been treated with high-dose intravenous methylprednisolone for 4 days followed by oral prednisone for a month without improvement.Her best-corrected visual acuity was no light perception OD and 20/20 OS.


Bilateral lateral rectus muscle recession for exotropia was performed 4 years before this presentation.

Medical history was otherwise unremarkable.

The patient was born full term after a normal pregnancy and delivery, with normal growth assessments.

The patient was performing well in school.On examination, her best-corrected visual acuity was 20/40 OD and 20/40 OS, which was stable from previous visits.

There was a residual intermittent exotropia of 4 prism diopters bilaterally.

Findings on slitlamp examination of the anterior segment were unremarkable.

A single, 1-cm, oval, lightly pigmented macule with irregular borders was noted on her right upper arm.

Dilated fundus examination revealed eccentric, yellow-clear, preretinal lesions in the maculas of both eyes.

Optical coherence tomography revealed hyperreflective areas on the surface of the macula with a spiculated appearance, projecting anteriorly into the vitreous.


The patient had an ocular history of bilateral cataract surgery in 2016, a medical history of thyroid cancer with thyroidectomy in 1990, and stage IIIc lobular carcinoma of the right breast with mastectomy of the right breast in 2008.On examination, her visual acuity was 20/80 OD and 20/30 OS.

The ptosis was first noticed 3 weeks prior to presentation and had gradually worsened.

Pupils were equal in size and reactive without an afferent pupillary defect.

Intraocular pressures were 21 mm Hg OD and 16 mm Hg OS.

Assessment of the extraocular motility demonstrated moderate limitation to up gaze of the right eye and full ductions of the left eye.

External examination confirmed right upper eyelid ptosis without substantial proptosis.

On slitlamp examination, eversion of the right upper eyelid revealed a solid, superior bulbar conjunctival mass measuring 10 mm in diameter (Figure 1A).

B-scan ultrasonography demonstrated an extraconal, noncompressible lesion of orbital tissue (Figure 1B).

A computed tomographic scan showed nonspecific, increased soft-tissue density in the superior and anterior orbit.A, External photograph of the right eye demonstrating an elevated conjunctival lesion.

She denied any acute changes in her health and review of her systems was unremarkable.


He had not received medical care in 20 years and had no known medical diagnoses, but his social history was notable for consumption of approximately 12 alcoholic beverages per day.

His ocular history was notable for left-eye enucleation from recent trauma.

He initially presented to his local ophthalmologist with right eye redness, pain, and photophobia for 1 week.

On referral, his visual acuity was 20/100 OD, and his intraocular pressure was 16 mm Hg.

Anterior examination revealed a diffusely hazy cornea with a blunted light reflex.

A large, well-demarcated epithelial defect with substantial underlying stromal loss was seen in the inferonasal periphery (Figure).

The stroma was 40% thinned without infiltrate.

The epithelium was heaped up along the lesion borders.

The conjunctiva demonstrated hyperemia, which was more prominent around the corneal lesion, although there was no discharge.

A dilated ophthalmoscopic examination was unremarkable.

Bacterial (aerobic and anaerobic) and fungal cultures were obtained, and the patient started receiving topical moxifloxacin.

The cultures were negative after 1 week, but the patient did not demonstrate signs of clinical improvement.

A complete blood cell count, metabolic panel, and serum test results (for antinuclear antibodies, peripheral antineutrophil cytoplasmic antibodies, cytoplasmic antineutrophil cytoplasmic antibodies,  rheumatoid factor, and anti–cyclic citrullinated peptide) were unremarkable.


Medical history included medulloblastoma treated with irradiation of the brain and spine at age 2 years.

He was also treated for several seemingly similar lesions on the face and scalp and had a family history of similar cutaneous lesions reported in 2 brothers and 1 niece.Figures show crusted erythematous papules and plaques adjacent to the surgical excision scar within a prior irradiation field on the head and neck (A) and erythematous and hyperpigmented papules and plaques overlying diffuse postsurgical scarring within a prior irradiation field on the back (B).

He also received radiation therapy for a meningioma of the posterior fossa in adulthood.


However, after 11 cycles of nivolumab, the patient presented with progressive painful reddening and swelling of the left thigh.

There was no deterioration of the general condition, no fever, no change in current medication, and no recent cold exposure.

Clinical examination revealed diffuse erythematous induration of the upper thigh expanding to the lower left abdominal area, as well as multiple small palpable subcutaneous nonindurated nodules on the ipsilateral gluteal region and leg (Figure, A).

Fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) detected multiple FDG-active lesions in both lower extremities and the lumbar region; a previously described left iliac lymphadenopathy was partially regressed (Figure, B).

A diagnostic biopsy specimen of the left thigh revealed a lobular lymphocytic panniculitis with dense infiltrate of mainly lymphocytes and plasma cells with no signs of vasculitis (Figure, C and D).

Direct immunofluorescence and blood analysis showed an absence of specific autoimmune antigens (test results for α-1 antitrypsin, antinuclear antibody, anti-Sjögren syndrome–related antigen, and anti-Sjögren syndrome–related antigen B were all unremarkable).A, Localized erythematous brownish induration seen on the upper thigh.

One year later she underwent inguinal lymphadenectomy for macrometastasis followed by adjuvant immunotherapy with ipilimumab, a monoclonal antibody that targets cytotoxic T-lymphocyte antigen 4.

Owing to local disease progression, treatment escalation with combined immunotherapy (ipilimumab and nivolumab, an anti–PD-1 [programmed cell death 1]) antibody was initiated.

Apart from immunotherapy-induced thyroiditis, the treatment was well tolerated.

Arrowheads correlate with the most prominent clinical findings.

B, Radioactive fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) reveals multiple subcutaneous lesions in both lower extremities, the lumbar region, and on the ipsilateral lower leg with high FDG uptake highly suggestive of (in transit) metastasis.

C and D, Lesional skin biopsy samples obtained from the proximal left thigh show normal epidermis and dermis with patchy infiltrate of the deep subcutaneous fat (hematoxylin-eosin stain).

Green arrows indicate the plasma cells, and blue arrows indicate the lymphocytes.


She had undergone mechanical mitral valve replacement and aortic dissection repair 2 months prior to presentation.

On physical examination, she was found to have elevated jugular venous pressure, bilateral rales in her lungs, and reduced intensity of the mitral valve closure sound, and her international normalized ratio was subtherapeutic (1.5).

An echocardiographic image showed a mean gradient of 12 mm Hg across the mitral valve, suggesting valve stenosis.

Fluoroscopy showed restricted mobility of the leaflets (Video 1).

Transesophageal echocardiography showed a large thrombus on the mechanical mitral valve, along with a small new dissection flap in the aortic root (Figure and Video 2).