His medical history was remarkable for diabetes mellitus of 40 years’ duration complicated by end-stage renal disease requiring a renal transplant and ongoing immunosuppression.

His visual acuity was no light perception OD and 20/40 OS.

The right eye exhibited an amaurotic pupil, severe generalized restriction of extraocular movement, and ptosis with poor levator function.

At a base of 104 mm, exophthalmometer measurements were 24 mm OD and 20 mm OS.

The results of a slitlamp examination were noncontributory in both eyes.

A dilated fundus examination revealed a pale optic disc in the right eye and panretinal laser scars in both eyes.

Cranial nerves V and VII-XII were intact bilaterally.

The patient was afebrile, with vital signs within normal limits.

His leukocyte count was 2200 cells/μL (to convert to ×109/L, multiply by 0.001).Noncontrast computed tomography and magnetic resonance imaging of the orbit demonstrated highly attenuating debris and bony irregularities throughout the paranasal sinuses and fat stranding in the right orbital apex (Figure).

Magnetic resonance venography of the head had unremarkable results.

Results of a sinus biopsy by the otolaryngology service demonstrated fungal hyphal elements.

Systemic therapy was initiated, and the otolaryngology service planned urgent surgical nasosinal debridement.

Contrast-enhanced magnetic resonance imaging was withheld pending stabilization in the patient’s renal status.Orbital noncontrast imaging studies.

Noncontrast computed tomography (CT) (A) and magnetic resonance imaging (B), images of the orbit.

Computed tomography demonstrates inflammatory changes of the right medial orbital wall (arrowhead).

Magnetic resonance imaging demonstrates inflammatory changes at the right orbital apex (arrowhead).


There was a family history of cutaneous melanoma in his 2 sisters, daughter, and nephew and breast cancer in his mother and sister.

We completed genetic testing of family members and found no genetic mutations in sera samples to predispose them to melanoma skin cancer or breast cancer.

The main genes tested were the breast cancer type 1 susceptibility (BRCA1), breast cancer 2–DNA repair associated (BRCA2), partner and localizer of BRCA2 (PALB2), checkpoint kinase 2 (CHEK2), and tumor protein p53 (TP53) genes.

A dermoscopic examination of the patient showed a translucent lesion with arborizing vessels and erosion (Figure, B).


She described occasional pain and intermittent bleeding from the site.

Physical examination showed a discrete, reddish-brown, noncompressible, smooth nodule within the umbilicus (Figure, A).

There was no change in size with the Valsalva maneuver.Clinical image and punch biopsy specimen.

A, Smooth reddish-brown nodule within the umbilicus.

B, Low-power view showing glandular and stromal tissue within the dermis (hematoxylin-eosin).

C, Higher-power view demonstrating a spindle-cell stroma with hemorrhage and hemosiderin-laden macrophages (hematoxylin-eosin).

D, Glandular epithelium showing prominent decapitation secretion (hematoxylin-eosin).Histopathologic examination revealed stromal tissue and glandular epithelium within the dermis (Figure, B).

The stroma tissue was characterized by small spindle cells, hemorrhage, and numerous hemosiderin-laden macrophages (Figure, C).

Glandular epithelium composed of basophilic cuboidal cells and showing decapitation secretion was also present (Figure, D).

Computed tomography scan of the abdomen showed a well-circumscribed nodule within the umbilicus without intrabdominal extension or herniation.

Prior treatment with intralesional triamcinolone injections for a presumed keloid yielded no improvement.

Surgical excision followed by umbilical reconstruction was performed.


Her medical history included atrial fibrillation and lung adenocarcinoma (a lung lobectomy was performed 8 years ago).

Bibasilar coarse crackles and pretibial edema were also noted.

Her blood pressure was 112/60 mm Hg, her heart rate was 100 beats per minute, her respiratory rate was 37 breaths per minute, her body temperature was 36.6°C, and her oxygen saturation was 100% while breathing 10 L of oxygen.

A cardiac examination was clinically significant for an irregular rhythm, an increased pulmonic closure sound, and jugular venous distension.

A complete blood count had results within normal limits.

The serum lactate dehydrogenase level was 278 U/L (to convert to microkatal per liter, multiply by 0.0167).

A chest radiographic image showed bibasilar infiltrates.

An electrocardiogram was notable for atrial fibrillation, and echocardiography revealed normal left ventricular function, mild right atrial and ventricular dilatation, and severe tricuspid regurgitation (transtricuspid pressure gradient, 40 mm Hg).

A contrast-enhanced computed tomography image revealed bilateral ground-glass opacities and right basilar consolidations, with no evidence of thromboembolisms (Figure, A).

Para-aortic and inguinal lymphadenopathies were also noted.

The patient began receiving dobutamine and furosemide, but she continuously required 2 to 10 L of oxygen, and further invasive evaluations could not be performed.

Presumptive diagnoses of pulmonary hypertension (PH) and right-sided heart failure were made.

An echocardiogram identified aggravating PH (transtricuspid pressure gradient, 57 mm Hg).

A thorough physical examination identified scaly, crusty genital skin lesions pathologically compatible with extramammary Paget disease.

The patient deteriorated and died despite treatment.

An autopsy was performed (Figure, B).A, The chest computed tomography showed ground-glass opacities (white arrowheads) and consolidative lesions (a yellow arrowhead), but no evidence of thromboembolism was obtained.

B, Hematoxylin-eosin stain of the lung showed proliferation of intimal fibromuscular cells with (yellow arrowheads) or without (black arrowheads) the presence of Paget cells.

Yellow arrowheads show embolized Paget cells.


She had a medical history of end-stage renal disease secondary to autosomal dominant polycystic kidney disease, after renal transplant 5 years prior.

She had concomitant polycystic liver disease and had undergone right hepatectomy and cyst fenestration, plus inferior vena cava (IVC) stent placement for intrahepatic caval compression due to hepatic cysts 9 years earlier.

Initial laboratory evaluation results revealed elevated creatinine levels with concern of renal graft failure.

Physical examination results revealed a blood pressure of 96/65 mm Hg, an elevated jugular venous pressure with blunted Y-descent, Kussmaul sign, and distant heart sounds.

Chest radiography results revealed cardiomegaly and the IVC stent was evident, adjacent to her heart (Figure, A).

Echocardiography (Video 1 and Figure, B) revealed a large circumferential pericardial effusion, diastolic right ventricular collapse, and exaggerated respiratory variation (>25%) in the mitral inflow velocity but a normal inferior vena cava size.Chest radiography and transthoracic echocardiogram illustrating cardiomegaly and pericardial effusion in addition to visualization of the inferior vena cava stent.


The patient chose observation vs further workup at that time.The patient returned 6 months later with worsening symptoms.

There were no respiratory symptoms, and results of a complete head and neck physical examination were unremarkable.

Flexible nasolaryngoscopy was performed and revealed erythema and swelling to the right arytenoid.

Repeat flexible nasolaryngoscopy was performed and revealed significant edema of the right arytenoid extending into the aryepiglottic fold, limiting the mobility of the right vocal fold (Figure 1).

Permanent sections showed unremarkable squamous mucosa.

Flow cytometry revealed mixed inflammatory infiltrate and an increased plasma cell component.

Results of stains for infectious organisms were negative.

A 2-week course of doxycycline was completed for presumed infectious supraglottitis without a change in symptoms.

Microdirect laryngoscopy and biopsy under general anesthesia was performed, and a specimen was sent to the pathology department for permanent section analysis and flow cytometry.

Further immunohistochemical analysis confirmed the diagnosis.

A biopsy and culture of the lesion was then collected in the office and revealed inflammatory disease but ultimately was nondiagnostic.

A full-body nuclear magnetic resonance positron emission tomography/computed tomography scan was performed to rule out systemic disease.


Prior to presentation, she had been prescribed fluticasone and loratadine for allergic rhinitis without resolution of symptoms.

She reported feeling a mass in her right nostril that had not changed in size, as well as associated nasal tenderness to the external nose, worsening pain with exposure to cold temperatures, and frequent sneezing.

On physical examination, her external nose had no visible lesions.

A rhinoscopy revealed normal mucosa with a submucosal, round, firm, tender lesion, measuring approximately 1 cm and located on the right anterior nasal septum.

The patient underwent surgical excision of the septal lesion under general anesthesia for definitive diagnosis.

The specimen measured 1.1 × 0.7 × 0.2 cm and was erythematous, soft, vascular, and adherent, with a broad base to the anterior superior nasal septal mucosa just inferior to the upper lateral cartilage (Figure 1A and B).

The lesion was excised down through the perichondrium.Endoscopic photographs.

A, Intraoperative view and intraoperative photograph of a mucosal lesion on the anterior septum after the initial incision.

B, Elevation with a suction shows attachments to the underlying perichondrium.


He was diagnosed with asthma 2 years earlier when he first started experiencing shortness of breath and had partial relief with inhaled albuterol treatments only.

He had no history of fevers, dysphagia, odynophagia, cough, or allergies.On physical examination, moderately severe dysphonia characterized primarily by roughness with mild breathiness as well as mild inspiratory stridor were noted.

Anterior rhinoscopy demonstrated large, bilateral obstructive nasal polyps.

Flexible laryngoscopy revealed smooth, lobulated masses involving the epiglottis and right aryepiglottic fold.

The epiglottic component extended inferiorly along the petiole, involving and obstructing the anterior glottis.

The vocal fold mucosa was thickened, but bilateral mobility was intact with an adequate posterior glottic airway.Computed tomography demonstrated homogenous, isodense, laryngeal lesions that correlated with the previously mentioned laryngoscopy findings, but also showed subglottic stenosis approximately 2 cm in length secondary to the thickened intraluminal soft tissue (Figure, A).

The cartilaginous laryngotracheal framework was preserved.

The patient was taken to the operating room for direct laryngoscopy with endoscopic airway dilation and laryngeal mass biopsy (Figure, B, C, and D).A, Subglottic stenosis was noted on computed tomography (yellow arrowhead).

Multifocal laryngeal masses were also observed, with the largest mass involving the epiglottic petiole and extending to obstruct the anterior glottis (black arrowhead).

B, The arrowhead points to a smooth, lobulated mass involving the epiglottis and anterior glottis.

C, Cotton-Meyer grade II subglottic stenosis was noted.

D, Laryngeal mass biopsy results showed vacuolated macrophages with bacilli (yellow arrowhead) and eosinophilic inclusions within plasma cells (black arrowhead) (hematoxylin-eosin).


The patient first presented to her dentist with a complaint of “it feels like there is something on the roof of [her] mouth.” She was never aware of the palatal lesion before her initial presentation.

She denied any pain or discomfort from the site, and stated that the increasing size of the mass was what first alerted her to its presence.The extraoral examination results were within normal limits, with no evidence of swelling, expansion, trismus, or lymphadenopathy.

Intraoral examination revealed a focally ulcerated, fluctuant 2.5 × 2 × 1-cm pink-red submucosal swelling in the right palatal mucosa (Figure, A).

The lesion involved almost the entire right side of the hard palatal mucosa and soft palate and terminated at the palatal midline.

Imaging studies were unremarkable.A, A clinical image shows a diffuse, right-sided palatal swelling with a focal ulceration.

B, A photomicrograph shows sheets of large lymphocytes with a moderate amount of cytoplasm and round to oval nuclei containing vesicular chromatin and 2 to 3 small nucleoli (hematoxylin-eosin, original magnification ×200).

The lesional cells stained positively with CD20 (inset) (original magnification, ×400).An incisional biopsy of the lesion was performed and showed fibrous connective tissues infiltrated by inflammatory cells arranged in a diffuse, sheetlike pattern.

The cells were large with a moderate amount of cytoplasm and appeared to be round to oval vesicular nuclei with vesicular chromatin and 2 to 3 small nucleoli (Figure, B).

The cells stained positively with CD45, CD20 (Figure, B, inset), CD79, CD21, BCL6, and BCL2 antibodies.


Importantly, the patient noted that he was capable of a “party trick” which involved puffing out his cheeks to force air into his neck with subsequent decompression of air back into his oral cavity by pushing behind his ear.

This became a habitual behavior, which the patient performed multiple times per day.

C. Frothy air bubbles milked from the parotid duct with external massage of the parotid gland.On evaluation, the patient noted a week of worsening facial swelling, neck pain, dysphagia, and odynophagia.

On examination, there was a tender, fluctuant pocket of the left neck near the angle of the mandible without significant crepitus (Video).

He was discharged after being prescribed oral antibiotics but continued to have worsening symptoms and returned to the outside facility, where a noncontrasted computed tomographic (CT) scan of the neck and chest showed significant subcutaneous emphysema of the neck and mediastinum (Figure, A and B).

Intraluminal air in the left parotid duct with associated pneumoparotid and dissection of air into the left parapharyngeal and masticator spaces.

Pneumoparotid is also noted on the right.

Inferior dissection of subcutaneous emphysema resulting in pneumomediastinum.

Air has dissected around the left common carotid artery near its origin from the aortic arch.

He was subsequently transferred to our facility for additional treatment.A.


Her medical history was notable for keratoconjunctivitis sicca, Hashimoto thyroiditis, and anti–interferon-γ autoantibody syndrome treated with 6 monthly rituximab infusions (375 mg/m2 with 100 mg of methylprednisolone acetate).

Infusions were given weekly for the first 3 weeks and then every 6 to 8 months based on a CD20 count.

This treatment concluded 2½ years before presentation.

In addition, she had a long-standing history of arthralgias with intermittent arthritis treated with hydroxychloroquine, 300 mg/d, that was discontinued 2 years before presentation.

On examination, she had no visual concerns.

Conjunctivas were normal, lenses were clear, and anterior chambers were deep and quiet.

The results from the slitlamp examination showed numerous bilateral, peripheral light brown corneal opacities.

The opacities were located in the far posterior corneae and were present circumferentially (Figure, A).

There was no associated keratitis or corneal neovascularization.

Anterior segment optical coherence tomographic findings showed focal areas of hyperreflectivity anterior to the Descemet membrane.

Confocal microscopy revealed variably shaped, hyperreflective clusters of opacities just anterior to the endothelium (Figure, B).Imaging of the right eye of a patient with rifabutin-related posterior corneal deposits.

She had previously been diagnosed with disseminated Mycobacterium avium complex (MAC) infection requiring 2 years of treatment with rifabutin, 300 mg/d; ethambutol hydrochloride, 1000 mg/d; and clarithromycin in a divided dose, 500 mg twice a day.

A, Slitlamp photograph with arrowhead highlighting one of numerous bilateral peripheral, small corneal light brown opacities.

B, Confocal microscopic image captured at a slightly oblique angle illustrates normal endothelial cells (yellow arrowhead).

Just anterior to the endothelium, the drug deposit appears as variably shaped, hyperreflective clusters of opacities (white arrowhead).


The onset of vision decrease coincided with muscle pain, joint swelling, and headache.

All of the symptoms except blurry vision resolved spontaneously after 3 days.

Over the preceding 5 months, he had had approximately monthly similar episodes consisting of a few days of flulike symptoms and blurry vision, with full recovery between episodes.

At the time of evaluation, the vision was decreased in the left eye, with pain in both eyes and deep throbbing in the back of the left eye.Visual acuity was 20/20 OD and counting fingers at 1 ft OS, with visual field constriction and a relative afferent pupillary defect in the left eye.

The examination of the anterior segment bilaterally was unremarkable, as was the posterior segment examination of his right eye.

However, the fundus examination of the left eye showed extensive optic nerve swelling, with nerve fiber layer hemorrhage at the inferior temporal disc margin and peripapillary subretinal fluid extending to the macula (Figure 1).

Magnetic resonance imaging (MRI) of the orbits showed anterior swelling of the left optic nerve without masses or hyperintensity of the retrobulbar optic nerve.

Brain MRI results were normal.Optic nerve imaging at time of presentation.

Optical coherence tomography (A) and fundus photography (B) of the left optic nerve at time of presentation showing broad optic nerve swelling with nerve fiber layer hemorrhage and fluid extending to macula.


The patient’s medical history was significant for type 2 diabetes diagnosed in her 30s and managed with metformin therapy, hypertension, mild hearing loss, and thyroid cancer that was in remission following thyroidectomy and radiotherapy.

The patient denied exposure to retinotoxic drugs.On examination, her best-corrected visual acuity was 20/20 OU.

The patient reported having difficulty with night driving owing to glare.

The anterior segment examination findings were unremarkable except for trace nuclear sclerosis in each eye.

Dilated fundus examination revealed peripapillary atrophy and scattered macular pigment clumps in each eye.

Fundus autofluorescence imaging showed a reticular pattern of hyperautofluorescence with sparing of the central macula (Figure).

Optical coherence tomography of the macula demonstrated hyperreflective retinal pigment epithelial (RPE) lesions with no intraretinal or subretinal fluid.

Full-field electroretinography (ERG) testing was suggestive of mild cone system dysfunction in each eye.A, Color fundus image of right eye shows scattered deep pigment clumps.

The patient had been told that radioactive iodine therapy damaged her pancreas and predisposed her to diabetes.


Visual acuity was 20/20 OU with normal intraocular pressures.

The results from the slitlamp examination of the right eye were within normal limits (Figure 1A).

Examination results of the left eye demonstrated 2+ diffuse conjunctival hyperemia, 1+ anterior chamber cell, and a vascularized iris infiltrate (Figure 1B).

Results of the dilated fundus examination were within normal limits in both eyes.

Ultrasound biomicroscopy of the left eye demonstrated areas of ciliary body thickening 360° and a thickened iris pupillary margin superiorly and nasally.

A full review of systems was negative for other abnormalities including skin lesions.

The patient had previously been treated with topical corticosteroid therapy, which provided temporary relief of his symptoms.


She reported no medications or comorbidities.

She reported no heartburn, nausea, vomiting, abdominal pain, weight loss, or changes in bowel habits.

Despite taking ranitidine (150 mg twice daily), she continued to have bothersome daily dysphagia, prompting her primary care clinician to order esophagogastroduodenoscopy (EGD).

Results of a recent complete blood cell count were normal.

The EGD showed vertical furrows and circumferential rings in the esophagus (Figure 1A), while the stomach and duodenum appeared normal.

Four biopsies each were taken from the proximal and distal esophagus (Figure 1B).Left, Esophagus at initial esophagogastroduodenoscopy (EGD).

Right, Esophageal biopsy sample from initial EGD (hematoxylin-eosin, original magnification ×400).


C, Histopathologic examination of lesional skin (hematoxylin-eosin).Over the past 5 years, the patient’s medications consisted of metoprolol and acetylsalicylic acid for treatment of established ischemic heart disease.

Nine months prior to being referred to our department, he was given oral furosemide and amiloride and then underwent median sternotomy and coronary artery bypass surgery 2 months later.

Four days after the operation, he developed a red patch at the area of the incision that was accompanied by mild pruritus.

Physical examination findings revealed a 20-cm–diameter plaque that consisted of multiple concentric annular formations with raised erythematous margins and studded with numerous blisters and pustules, some coalescing into lakes of pus (Figure 1A).

Nikolsky sign was not elicited, and oral, ocular, and genital mucosa involvement was absent.

The patient did not report other symptoms, and findings of the overall physical examination were normal.A, A crusted, focally vesiculating, well-demarcated erythematous plaque at the area of median sternotomy.

Over the following months, the lesion showed a marked tendency for centrifugal extension over the chest area.Results of routine laboratory studies, Mantoux test, chest radiography, and chest computed tomography of the area were within the normal range.

Gram stain, periodic acid–Schiff stain, and tissue culture results were negative (Figure 1B and C).

B, Histopathologic examination of lesional skin (hematoxylin-eosin).


The patient initially had improvement in her skin, but she again noticed enlargement of the soft tissue with thickening of the overlying skin on her right cheek and right side of her nose several months later.Clinical examination revealed slightly hyperplastic soft tissue with dilated patulous follicles involving the right medial malar cheek and right nasal ala in addition to deviation of the nasal tip (Figure, A).

The surgical pathology specimens from her septorhinoplasty were obtained and reviewed.A, Clinical image shows facial asymmetry with deviation of the nasal tip.

B, Hematoxylin-eosin stain of an interstitial proliferation of spindle cells within mature adipocytes that extends between bundles of skeletal muscle.

C, Hematoxylin-eosin stain of mature adipocytes that are separated by a proliferation of spindle cells associated with fragments of thickened collagen.

She underwent a septorhinoplasty 6 months prior to presentation because of collapse of her right nasal ala. During the surgical procedure, the surgeon noted a significant amount of submucosal tissue in the right nasal cavity, which was removed; histopathological analysis was performed, and the results were reported as fibroadipose tissue and vascular proliferation.

A skin biopsy was performed at the time of the surgical procedure and was interpreted as sebaceous hyperplasia.

She had been seen by several dermatologists and otolaryngologists and had undergone nondiagnostic skin biopsies.


Bowel and bladder movements were normal.

The child had an older sibling who had no skin ailments, and none of the other family members were affected.On examination, multiple tense, angulated vesicles and bullae on a background of erythema were seen over the face, trunk, and extremities (Figure, A and B).

The lesions initially started over the trunk and subsequently progressed to involve the face, hands, and feet.

The episodes of skin blisters were accompanied by pruritus and redness all over the body.

The ruptured bullae were healing with hypopigmentation with accompanying scarring and discrete milia formation.

Few urticated papules and wheals were seen in isolation over the trunk.

No contractures or webbing of fingers was noted.

A punch biopsy from a vesicle was subsequently performed (Figure, C and D).A, Multiple angulated vesicles and tense bullae over the forehead and chin.

B, Tense bullae over the trunk with superficial erosions and postinflammatory hypopigmentation, which are healing with scarring and discrete milia formation.

Few urticated papules and plaques can also be appreciated.

C, Subepidermal bulla with bandlike mast cell infiltrate in the upper dermis (hematoxylin and eosin stain).

D, Higher magnification showing dense infiltrate of mast cells in the upper dermis.

There was no history of oral erosions or difficulty in feeding.


Her mental state had deteriorated progressively over the previous 12 months, following the death of her father.

On arrival in the United Kingdom, her family claimed asylum and moved into a small apartment in a high-rise building in central London.

Although there was no reported developmental delay, she had struggled academically at school and was bullied for having overweight.

She left school without qualifications at age 16 years and worked as a shop assistant.

She left this job about a year prior to her referral to psychiatry after a period of sick leave following the death of her father.

She was a nonsmoker, did not drink alcohol, and denied illicit drug use.

A paternal relative was reported to have a diagnosis of schizophrenia.

After a period living alone, she had returned to the family home 4 months prior to her presentation and had been noted to be socially withdrawn, preoccupied, and distractible.

Her family subsequently sought advice from the family physician when the patient was noted to be speaking to herself, expressing concerns about people meaning her harm, and professing the belief that she could hear other peoples’ thoughts.The patient had been born in Sierra Leone after a complicated delivery and had traveled to the United Kingdom as a child with her family, who were fleeing from a civil war.

She denied feeling low in mood or suicidal and was objectively euthymic.

She reflected that over the preceding few months, she had experienced a sensation of detachment from her immediate environment, as though it was not real, making her world similar to that of a video game.

She explained this was because 6 was associated with the number of the devil.

She reported hearing her neighbors commenting negatively about her appearance.

On returning home, her paranoia regarding her previous neighbors worsened, resulting in her rarely leaving the house.

There was no comorbid physical illness.On review, the patient was kempt and had overweight.

Eye contact was fleeting, and she presented as anxious, with a degree of psychomotor agitation.

Her speech was normal in rate, volume, and tone, although tangential.

There was no other evidence of thought disorder.

There was some sleep disturbance, with the patient reporting being fearful to go to sleep owing to persecutory beliefs regarding her neighbors.

Her family physician, suspecting a depressive episode, had prescribed citalopram up to a dosage of 40 mg once daily, to no effect.

She reported that in the apartment where she had previously been living, she had realized that something was amiss and had become convinced that the door number of her neighbor’s flat, number 6, signified that they meant her harm.

These distressing experiences prompted her to return to her family home, but she continued to hear her neighbors’ voices making derogatory comments about her appearance and began to hear them commenting on her actions and thoughts in the third person as well.


The patient was admitted with fever of unknown origin with a surge of the inflammatory syndrome and pancytopenia.

He reported night sweats beginning 3 weeks prior associated with fever and unintentional weight loss.

The pleural fluid was transudative and sterile, and the pericardium contained focal lymphoplasmacytic aggregates.

No lymphadenopathy was noted.Laboratory evaluations demonstrated a C-reactive protein level of 133 mg/L (reference range, <10 mg/L); ferritin level of 2607 ng/mL (reference, 30-300 ng/mL); lactate dehydrogenase (LDH) level of 289 U/L (reference, 135-214 U/L); pancytopenia with a hemoglobin level of 9.3 g/dL (reference, 13.3-17.7 g/dL), white blood cell count of 2700/μL (reference, 4000-10 000/μL), and platelet count of 99 ×103/μL (reference, 150-350 ×103/μL); and prerenal acute kidney injury (Acute Kidney Injury Network stage 1) with a serum creatinine level of 1.4 mg/dL (reference, 0.7-1.2 mg/dL).

Results of a comprehensive serologic workup were negative.

Gastroscopy results showed mycotic distal esophagitis.The patient was readmitted 3 weeks later with fever and hypotension without improvement despite broad-spectrum antibiotics and antifungals.

Computed tomography (CT) results showed a splenomegaly without evidence of metastatic disease or lymph node enlargement.

Positron emission tomography (PET)–CT imaging (Figure, A and B) and a bone-marrow biopsy (Figure, C and D) were performed.

A rapidly evolving sepsislike syndrome led to the patient’s death.Fluorodeoxyglucose/positron emission tomography–computed tomography imaging results show diffuse hypercaptation in the bone marrow (A) and spleen (B).

The entire skeleton is highly metabolic, which suggests advanced bone-marrow involvement.

C, Bone-marrow biopsy results show a diffuse infiltrate of large lymphoid cells with scattered residual hematopoietic elements (immunoperoxidase, original magnification ×200).

Attempts to taper immunosuppressive drugs failed because of a recrudescence of the inflammatory syndrome and pericardial effusion.

Considering the increase in ferritin and LDH levels and pancytopenia, a hematologic disease was suspected.

The patient did not report any bone pain.


She reported no family history of sudden cardiac death or unexplained premature death.

When emergency responders arrived, the patient was responsive but groggy.

An electrocardiogram (ECG) in the field demonstrated a regular wide complex tachycardia.

En route to the hospital, 6 mg of adenosine followed by 12 mg of adenosine were administered intravenously, without a change in her rhythm.On arrival to the emergency department, she was in a regular wide complex tachycardia with a heart rate of 225 beats per minute (Figure, A), with an initial blood pressure of 108/77 mm Hg.

Her initial laboratory evaluation revealed hypokalemia (2.8 mEq/L; to convert to millimoles per liter, multiply by 1.0), hypomagnesemia (3.6 mEq/L; to convert to millimoles per liter, multiply by 0.50), and an elevated serum troponin (0.13 nanograms per milliliter; to convert to micrograms per milliliter, multiply by 1.0).

A transthoracic echocardiogram showed normal biventricular size and function.Twelve-lead electrocardiograms (ECGs) obtained on presentation (A) and immediately after electrical cardioversion (B).

After sedation, a synchronized, biphasic, 200-J shock converted her to sinus rhythm with bigeminy (Figure, B), which settled to normal sinus rhythm.

An intravenous amiodarone infusion was administered.

Potassium and magnesium replacement was administered orally and intravenously.


The pregnancy was uncomplicated, and prenatal ultrasonography results were normal.

After spontaneous vaginal delivery at 37 weeks’ gestation, the neonate immediately developed tachypnea, severe retractions, barking cough, hoarse cry, and dusky appearance with oxygen desaturations to 60%, which required continuous positive airway pressure.

The intubating clinician noted a large flesh-colored laryngeal mass and placed a size 3.5 uncuffed endotracheal tube.

Ear, nose, and throat evaluation noted that the neonate was intubated and ventilating easily.

No craniofacial abnormalities or obvious oral cavity, oropharyngeal, or neck masses were present.

Chest radiography was obtained, and results were normal.

Intraoperative evaluation revealed a large submucosal mass involving the left side of the epiglottis, false fold, aryepiglottic fold, and arytenoid that was soft and fluctuant on palpation (Figure 1).Direct laryngoscopy revealed a large mass involving the left side of the epiglottis, false fold, aryepiglottic fold, and arytenoid.

Despite respiratory support, she was intubated within the first hour of life.

The patient was subsequently taken to the operating room for direct laryngoscopy and bronchoscopy.


Ten years later, he developed a second primary tumor in the hypopharynx requiring total laryngectomy and bilateral neck dissection.

He presented with new-onset headaches, left ear pain, and persistent unsteadiness during the previous month.

There was no palpable lymphadenopathy, neurological deficits, or mastoid tenderness, and otoscopic examination results of the tympanic membrane appeared normal.Magnetic resonance imaging of the head showed an enhancing lesion in the left infratemporal fossa (3.4 × 3.4 × 2.8 cm) abutting the cerebellum, and subsequent computed tomographic imaging of the head demonstrated osseous destruction of the left temporal bone extending along the left internal jugular vein (Figure, A).

Fine-needle aspiration of the left mastoid showed atypical spindle cells.

Histopathologic assessment demonstrated myogenin-positive spindle cells with no tumor necrosis (Figure, B and C).

In addition, the tumor expressed desmin-positive and CD34-positive cells.

The tumor focally infiltrated into the fibrous tissue, skeletal muscle, and bone.A, Axial computed tomography of the head and neck demonstrating osseous destruction of the left temporal bone.

B, High-powered view of hematoxylin-eosin stain (original magnification ×40) demonstrating spindle cell morphologic features with admixed fragments of bone (pink-red areas).

C, High-powered view of myogenin stain (original magnification ×40) depicting small-cell or spindle cell morphologic features with rare positive results for myogenin (brown cells).

The patient underwent tumor excision with a left infratemporal approach.

A large mass with rubbery texture was noted, extending into the jugular foramen and adherent to the dura mater without evidence of intradural invasion.

The lower cranial nerves were identified, and the mass was resected to the external wall of the jugular bulb.

The patient tolerated the procedure without complications or neurological deficits.


The infant had no other congenital anomalies and had been meeting all major developmental milestones.

No associated pain or pruritus was noted, and the papule had never bled or produced other fluid or debris.

On clinical examination, a superficial, white-yellow papule was identified on the anterior surface of the neck, situated at the midline superior to the sternal notch.

It measured 6 mm in diameter and was not associated with overlying surface changes or evident discharge.

Dermoscopy results showed scattered telangiectatic vessels over the papule, accentuated peripherally.A smooth, subcutaneous papule with a yellow tint is present above the suprasternal notch and exposed with retraction of skinfolds of the anterior neck.Ultrasonography was performed to further characterize the papule, and imaging results exhibited a superficial cutaneous lesion without evidence of tracking into deeper layers of subcutaneous tissue or fluid collection.

Active nonintervention was recommended, but because of continued parental concern, the lesion was shaved off in clinic and sent for histopathologic evaluation to rule out malignant neoplasm and other morbid diagnoses.


The patient had a history of polycystic ovarian syndrome with insulin resistance and a migraine disorder and reported experiencing 1 to 2 migraine episodes per week since early high school.

She believed that the neck mass made these episodes worse than normal.

After 2 weeks, the neck swelling persisted despite the resolution of other symptoms.

The patient reported new symptoms, including waxing and waning pain that radiated to the back of her neck, headaches, and intermittent dysphagia.

Her physician noted visible swelling in the right neck and clinically interpreted the finding as enlarged lymph nodes associated with the infection.

She also noted periods during which the mass would fluctuate in size.Otolaryngologic examination findings were within normal limits except for a single, nontender, compressible right neck mass deep to the sternocleidomastoid muscle and extending into level V. The patient underwent a computed tomography (CT) scan prior to presentation at the Dartmouth-Hitchcock Medical Center’s otolaryngology clinic.

The scan showed a fatty-appearing tumor within the right carotid space.

Gross pathologic examination demonstrated yellowish-brown, homogenous, lobular adipose tissue covered by a thin, tan, transparent membrane (Figure, A).

Histopathologic examination showed relatively uniform univacuolar and multivacuolated, granular eosinophilic cells with centrally placed nucleoli (Figure, B and C).

B and C, Histologic results show uniform univacuolar to multivacuolated granular eosinophilic cells with centrally placed nucleoli (hematoxylin-eosin).

She was subsequently treated with a course of antibiotics, which did not result in any improvement.

The patient underwent surgical excision, and a mass measuring 8.0 × 6.5 × 4.7–cm was removed from the carotid space (Figure, A).

Additional material from the mass was excised at the level of the base of the skull.

The patient was otherwise previously healthy until she developed an upper respiratory infection.

The mass slowly enlarged over the next 6 months.

In addition, several level II and level III lymph nodes were excised, all of which were found to be benign.A, The 8.0 × 6.5 × 4.7–cm mass was surgically excised from the patient’s carotid space.


Review of systems was positive for fever, tachycardia, odynophagia, productive cough with wheezing, and marked peripheral edema in upper extremities and negative for headache, nausea, vomiting, dysacusis, meningismus, or skin changes.Fundus photographs and optical coherence tomography 4 days from presentation demonstrating bilateral choroidal effusions with serous retinal detachment and white centered intraretinal hemorrhages.

Laboratory test results were remarkable for pancytopenia.

On initial examination, his visual acuity was count fingers at 3 ft in both eyes.

Intraocular pressures were 10 mm Hg OD and 11 mm Hg OS.

Pupils were round and reactive without a relative afferent pupillary defect.

Color plates were 1 of 8 OU, with 50% brightness desaturation in the right eye and no red desaturation.

Slitlamp examination was negative for any signs of inflammation.

Dilated fundus examination demonstrated bilateral choroidal effusions with diffuse serous retinal detachments (RD) involving the macula without vitritis as well as white centered intraretinal hemorrhages along peripapillary and superior and inferior arcade distributions in both eyes (Figure, A).

Optical coherence tomography demonstrated irregular inner retinal surface and subretinal fluid with septae with loss of the ellipsoid zone (Figure, B).

A, Left eye color fundus photograph demonstrates peripheral choroidal effusion with areas of stippled subretinal fluid in the macula, areas of intraretinal hemorrhages scattered throughout the posterior pole as well as far temporal periphery.

Hospital course was complicated by neutropenic fever, receiving cefepime, acyclovir, vancomycin, and voriconazole for prophylaxis.


He had a history of well-controlled type 2 diabetes and diffuse large B-cell lymphoma that was diagnosed 3 years earlier.

The lymphoma was initially treated with chemotherapy, followed by a relapse that required additional chemotherapy and ultimately autologous bone marrow transplant 3 months before presentation.

At the time of presentation, he was taking no immunosuppressive medications and was taking prophylactic acyclovir, 800 mg twice daily, and sulfamethoxazole/trimethoprim (800 mg/160 mg) 3 times weekly.Snellen visual acuity measured 20/40 OD and 20/20 OS.

Intraocular pressure (IOP) measured 24 mm Hg OD and 12 mm Hg OS.

Right eye examination results revealed 1+ anterior chamber inflammation, iris neovascularization, keratic precipitates, vitritis, and a granular necrotizing retinitis (Figure, A).

Left eye examination results were unremarkable.

Fluorescein angiography of the right eye demonstrated panretinal occlusive vasculopathy with severe peripheral nonperfusion (Figure, B).

His white blood cell count was moderately low at 3.1 kilos/μL (to convert to ×109/L, multiply by 0.001; reference range, 4.0-10.0 kilos/μL); a complete blood count and serum chemistry panel were otherwise normal.

Human immunodeficiency virus (HIV) testing results were negative.

An aqueous tap was performed and sent for culture and polymerase chain reaction.A, Wide-field fundus photograph demonstrating vitreous haze, vascular attenuation, macular cotton wool-spots, diffuse intraretinal hemorrhages, and superior granular necrotizing retinitis.


The lack of response to oral prednisone therapy led to suspicion of a possible malignant neoplasm, and the patient was referred for our opinion.The patient’s medical history was notable for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with transformation to large B-cell lymphoma that was treated with rituximab, adriamycin, vincristine sulfate, and prednisone chemotherapy 4 years earlier.

Two years before referral, bladder cancer was diagnosed and was treated surgically and with multiple rounds of intravesical BCG immunotherapy.

The most recent BCG treatment was 5 months before presentation to the Ocular Oncology Service at Wills Eye Hospital, Philadelphia, Pennsylvania.On examination, visual acuity was 20/25 OD and 20/40 OS.

The patient noted redness, pain, and a foreign body sensation on his right eye for 2 weeks.

The chest radiographic findings and blood work results were unremarkable.

Anterior segment examination findings were remarkable for a limbal-based amelanotic lesion of the nasal conjunctiva measuring 5 mm in basal diameter and 1.5 mm thick and fed by large dilated conjunctival and episcleral vessels (Figure 1).

Ocular ultrasonography revealed no intraocular involvement.

The general ophthalmologist prescribed a 3-week course of oral prednisone, 20 mg/d, that reduced surrounding inflammation and pain, but the lesion did not change in appearance.


The patient had an ocular history of herpes simplex (HSV) keratitis with a previous perforation of the right eye repaired with a patch graft, advanced open-angle glaucoma in the right eye, and ocular hypertension of the left eye, and he was receiving brimonidine 3 times a day in both eyes and acetazolamide, 250 mg, 3 times a day.On examination, his visual acuity without correction was 20/200 OD and 20/50 OS, with pinhole acuity measured at 20/80 OD and 20/40 OS.

An external examination revealed severe eczematous skin changes and thinning of the eyebrows and eyelashes.

A slitlamp examination showed madarosis, mild eyelid edema, and conjunctival injection, which were greater in the left eye than the right eye.

His intraocular pressure was 9 mm Hg OD and 42 mm Hg OS.

The right cornea had inferior pannus, scarring, and neovascularization.

The left cornea revealed microcystic edema and central ulceration (Figure 1).

The anterior chambers of both eyes were quiet.

A fundus examination was notable for cup-disc ratios of 0.8 OD and 0.4 OS.Examination at presentation.

External photograph of the right eye with neurotrophic cornea with neovascularization and scarring (A) and external photograph of the left eye with epithelial dendritic lesion with corneal edema (B).Bacterial cultures, a viral polymerase chain reaction, and potassium hydroxide preparations were obtained from the ulcer of the left cornea.

The results of the viral polymerase chain reaction and potassium hydroxide tests were negative, while bacterial cultures had positive results for methicillin-resistant Staphylococcus aureus and Escherichia coli.


Over 2 years, he was prescribed various therapies including prednisone, methotrexate, tumor necrosis factor inhibitors, abatacept, and anakinra; he experienced intermittent improvement in his joint pain but had persistently elevated levels of inflammatory markers.

He continued to experience asymmetric small- and large-joint polyarthralgias and later developed intermittent fevers (temperatures up to 38.3°C [101°F]) along with a 50-lb (22.7-kg) unintentional weight loss over the course of a few months.On examination, there was subtle synovitis in bilateral metacarpophalangeal joints.

Over the next several months, he developed intermittent abdominal pain, steatorrhea, protein-losing enteropathy, and symmetric bilateral lower extremity edema requiring diuresis.

Findings on cardiac, pulmonary, and neurologic examinations were unremarkable.

Laboratory evaluation was notable for a normocytic anemia and elevated C-reactive protein level (7.7 mg/dL [73.3 nmol/L]).

Results of esophagogastroduodenoscopy with gastric biopsies and bone marrow biopsy were unremarkable.

Findings on further workup including transthoracic echocardiography to assess for endocarditis, carotid magnetic resonance angiography to assess for vasculitis, and abdominal fat pad biopsy for amyloidosis were also unremarkable.

Results of infectious stool studies, celiac serology, and fecal elastase testing were normal.

Repeat esophagogastroduodenoscopy (Figure, panel A) was performed, with gastric and duodenal biopsies (Figure, panels B and C).A, Duodenal segment on esophagogastroduodenoscopy.

B, Histologic examination of duodenal mucosa (hematoxylin-eosin, original magnification ×100; sample obtained using cold forceps).


She had immigrated from Chuuk, Micronesia, to Hawaii 10 years ago and had not traveled overseas since.

She denied alcohol use or contact with animals such as pigs.On examination, her temperature was 38.5°C (101.3°F); pulse rate, 104/min; blood pressure, 205/92 mm Hg; and respiratory rate, 33/min with normal saturation.

The pain was sharp, intermittent without radiation, and not exacerbated by eating.

She had no subjective fevers, nausea, vomiting, diarrhea, or weight loss.

Mild conjunctival icterus and a positive Murphy sign were noted.

Laboratory evaluation showed a white blood cell count of 16.4 × 109/L (neutrophils, 87.4%; eosinophils, 0.5% [absolute count, 82/μL]); hemoglobin level, 14.9 g/dL; platelet count, 254 × 109/L; aspartate aminotransferase level, 514 U/L; alanine aminotransferase level, 236 U/L; alkaline phosphatase level, 208 IU/L; total bilirubin level, 2.5 mg/dL; direct bilirubin level, 1.1 mg/dL; and lipase level, 247 U/L.

Results of serologic testing for hepatitis A, B, and C were negative.

Abdominal ultrasound showed no cholecystitis or pancreatohepatobiliary abnormalities.

Magnetic resonance cholangiopancreatography was notable for a linear filling defect within the common bile duct extending through the left hepatic duct (Figure, left panel).

During endoscopic retrograde cholangiopancreatography (ERCP), numerous worms were discovered within the biliary trees, with 1 visible outside the ampulla of Vater (Figure, right panel).Left, Findings on magnetic resonance cholangiopancreatography.


She had experienced a similar eruption at the same site with spontaneous resolution 1 year previously, after she had taken a cold medication containing ibuprofen.

Her medical history was otherwise unremarkable.

She took no prescription medications; however, she did occasionally take over-the-counter ibuprofen.

On examination, she was well-appearing and afebrile.

There were tense confluent blisters in a 4-cm area on and around the lower lip (Figure 1) and no other skin or mucosal lesions.Tense confluent blisters on the lower lip area.


The patient was born and lived in a rural village in Malawi.

Her medical and family history were unremarkable.

Physical examination revealed a polypoid, rubbery tumor measuring 1.5 cm located on her right labium majus, which obliterated the right labium minus (Figure, A).

She did not present with enlarged lymph nodes, and results of the physical examination were otherwise unremarkable.

An incisional lesional biopsy was taken (Figure, B and C).A, Polypoid nodule on the right labium majus obliterating the labium minus.

B-D, Hematoxylin-eosin–stained lesional specimens.

B, Histopathologic analysis of the nodule showed pseudoepitheliomatous hyperplasia with transepidermal elimination of basophilic oval-shaped structures in the epidermis and a dense acute and chronic dermal infiltrate in the dermis.

C, Numerous dermal structures surrounded by a dense acute and chronic inflammatory cell infiltrate with granuloma formation.

D, High-power magnification of the oval parasitic structures with a typical terminal spine.


The patient reported no history of lesions or foreign bodies at this location.

On medical examination, a reddish, smooth, superficial nodule with small dimples and a soft consistency that measured approximately 1.5 cm in diameter was seen on the left earlobe (Figure, A).

A biopsy specimen was obtained for histopathologic analysis (Figure, B and C).A, Clinical photograph of a pruriginous, reddish tumor on the earlobe.

B and C, Histopathologic findings reveal mixed diffuse dermatitis involving the reticular dermis, with small-vessel vasculitis, characteristic sparing of a superficial dermal grenz zone as well as the dilated vessel luminal, and mixed leukocytic infiltrate with eosinophils, lymphocytes, and neutrophils involving the full thickness of the vessel wall (hematoxylin-eosin).


He was a vegetarian, nonsmoker, and nondrinker.

He denied a history of drug addiction.On examination, he was confused.

He had had 2 episodes of seizures that were characterized by tonic head and eye deviation to the left, followed by a brief period of tonic-clonic activity of all 4 limbs and postictal confusion for 10 to 15 minutes.

He had facial flushing and grade III clubbing in his fingers and toes.

His chest and cardiovascular examination results were normal.

The right eye was deviated laterally secondary to right-medial rectus palsy.

His pupil size and pupillary light reactions were normal.

His motor and sensory examination results were normal; however, he had brisk deep-tendon jerks and extensor planter responses.

There were no meningeal signs.His cranial magnetic resonance image showed 2 ring-enhancing lesions in the right frontal and left parietal cortexes, along with surrounding brain edema and mass effects.

Both lesions showed a thin-walled, contrast-enhancing rim with a central liquefaction (Figure, A).

The central liquefaction showed restricted diffusion on diffusion-weighted magnetic resonance images.A, Cranial T1-weighted postcontrast magnetic resonance image showing ring-enhancing lesions in the right frontal and left parietal lobes.

B, Chest radiography showing a radiolucent nodular shadow in left middle lung field.His hemoglobin level was 19.3 grams per deciliter (to convert to grams per liter, multiply by 10.0), his total leukocyte count was 13 500/μL (to convert to cells × 109/L, multiply by 0.001), his hematocrit was 62.4% (to convert to a proportion of 1.0, multiply by 10), and his platelet count was 210 000/μL (to convert to cells × 109/L, multiply by 0.001).

He had normal liver and renal function test results.

An enzyme-linked immunosorbent assay for HIV was nonreactive.

The 2-dimensional echocardiogram did not show any evidence of congenital heart disease.

A radiograph of his chest showed a nodular shadow in the left middle field of the lung (Figure, B).


Two years prior, he had no obvious inducement and gradually developed indifference, glassy eyes, lethargy, and poor memory.

One year prior, the patient’s personality changed dramatically, with notably decreased memory formation but intact short-term memory.

He was short-tempered, irritable, hyperactive, and exhibited slight balance instability while walking.

On admission, physical examination showed unstable balance while walking in a straight line, positive ankle clonus bilaterally, positive Babinski sign bilaterally, positive Chaddock sign bilaterally, positive Romberg sign, and painless lumps of about 8.2 cm in diameter in both Achilles tendons.

Routine laboratory test results showed that the patient’s triglyceride level was elevated at 342.48 mg/dL (to convert to millimoles per liter, multiply by 0.0013 mg/dL; normal levels are considered to be 30.97-150.44 mg/dL).

A brain magnetic resonance imaging (MRI) indicated multiple bilateral, symmetric abnormal signals in the genus of the internal capsules, posterior limbs of internal capsules, cerebral peduncles, pons, and cerebellar dentate nuclei (Figure, A).

Genetic testing indicated a known pathogenic mutation c.1214G>A (p.Arg405Gln; Hom) in the CYP27A1 gene.

An MRI of the ankle joints revealed an enlargement of the left Achilles tendon with abnormal signal, and the right Achilles tendon was circumscribed by a fusiform enlargement with abnormal signal (Figure, B).A, Brain magnetic resonance imaging (MRI) suggested multiple symmetrical abnormal signals (bilateral genus of internal capsule and posterior limbs of internal capsule, bilateral cerebral peduncles, pons, and cerebellar dentate nucleus).


Over a 4-week period, he developed dyspnea with moderate levels of physical activity that were occasionally associated with brief episodes of lightheadedness.

He also reported orthopnea but no paroxysmal nocturnal dyspnea or leg edema.

There was no chest pain, palpitations, cough, fever, or hemoptysis.

He had tachypnea with a respiratory rate of 24 breaths per minute with a normal oxygen saturation, temperature, heart rate, and blood pressure.

A soft (I/VI) systolic murmur with a brief diastolic component was appreciated over the apex.

Jugular venous distension was present; there were no pulmonary rales, abdominal distention, or leg edema.

Workup results demonstrated leukocytosis (white blood cell count, 39 800/μL [to convert to ×109 L, multiply by 0.001]; 15920/μL eosinophils [44%]), with a hemoglobin level of 12.4 g/dL (to convert to grams per liter, multiply by 10) and a platelet count of 153 ×103/μL (to convert to ×109 L, multiply by 1).

A basic metabolic panel yielded normal results and troponin was undetectable.

His chest radiography results were suggestive of pulmonary vascular congestion.

The echocardiogram results demonstrated a normal left ventricular ejection fraction with no substantial wall motion abnormalities.

There was an echogenic band traversing the apical portion of the left ventricle with increased echogenicity compared with the adjacent myocardium (Video).

Representative frames of the echocardiogram are shown in Figure 1.Representative apical 4-chamber view in diastole (A) and systole (B) demonstrating an echogenic band traversing the apical portion of the left ventricle with increased echogenicity compared with the adjacent myocardium.


She had a left vocal fold polyp that was removed 2 months earlier at an outside institution, with benign pathology reported.

However, her voice worsened with therapy, and she returned to the otolaryngology clinic after a few weeks.

Subsequent stroboscopy revealed a hemorrhagic-appearing polyp (2-3 mm).

A larger, 6- to 7-mm, irregular, left vocal fold mass was noted.

Preoperative imaging was nonspecific, revealing a small soft-tissue density along the true vocal fold.

After the final pathology results were obtained, the patient was taken back to the operating room for cordectomy with negative margins.A, The left vocal fold lesion has a hemorrhagic exophytic mass that has prolapsed into the subglottis.

B, Lesional spindled, fibroblastic-myofibroblastic, and inflammatory cells (both plasma cells and lymphocytes) appear in a myxoid background with abundant blood vessels.

The overlying squamous epithelium demonstrates only minimal reactivity with some acanthosis and parakeratosis.

Cellular proliferation was present in a myxomatous and focally fibrous-appearing stroma.

She was sent for preoperative voice therapy, with plans for excision.

The patient was taken to the operating room for excision (Figure, A).

These findings were confirmed at the time of the initial excision.

Even within this field, the denser collagenized stroma interrupts looser edematous areas.

C, Neoplastic, spindled, fibroblastic-myofibroblastic cells have diffuse, strong, granular cytoplasmic staining with the ALK1 (D5F3 clone).

The intralesional blood vessels and inflammatory cells and overlying epithelium do not stain.Pathologic results revealed spindle-shaped cells with variable atypia noted and inflammatory cells, including lymphocytes and plasma cells (Figure, B).

Immunohistochemical analysis revealed that the lesional cells were negative for desmin, S100, P63, and cytokeratin (Figure, C).

They were reactive for vimentin and anaplastic lymphoma kinase 1 (ALK1).

She has had no recurrent disease for the past 3 years.


He had been diagnosed prenatally with cerebellar hypoplasia, so a magnetic resonance imaging study of the brain was performed at 1 month of age.

This study demonstrated an incidental solid, homogenous mass in the subcutaneous fat of the right occiput with irregular borders and infiltration into the paraspinal musculature (Figure, A).

On examination, the upper posterior neck mass was deep to palpation without overlying skin changes.

The arrowhead points to a 1.1-cm × 0.8-cm × 1.7-cm right occipital soft tissue mass with irregular borders and infiltration into the deep paraspinal musculature.

B and C, Hematoxylin-eosin–stained images demonstrating cells with oval nuclei and multiple small nucleoli surrounded by a pale eosinophilic and slightly fibrillary stroma.At 7 months of age, the patient underwent ultrasonography to assess interval change of the lesion, which confirmed a 3.4-cm × 1.6-cm × 3.7-cm mass that had grown proportionally with the patient and was relatively avascular.

Shortly thereafter, the mass was excised en bloc along with a cuff of adjacent posterior neck muscle and subcutaneous tissue.

Histologic examination revealed cells with oval nuclei and multiple small nucleoli surrounded by a pale eosinophilic and slightly fibrillary stroma (Figure, B and C).

Immunohistochemical studies were diffusely positive for glial fibrillary acidic protein and vimentin, and focally positive for S100, NeuN, and synaptophysin.

Grossly, the lesion was firm, round, and white in color with a smooth intact border but no discrete capsule.

The patient had no discomfort, and neck movement was not restricted.A, Axial T2-weighted magnetic resonance imaging of the neck without contrast.


On postoperative day 2, she developed isolated dysphagia and dysphonia.

Her Glasgow Coma Score (GCS) was 11 M5V4E2 on admission, and a computed tomographic (CT) scan showed a right frontal epidural hematoma with a maximum thickness of 19 mm and a volume of 30 cm3 (Figure 1A).

Laryngoscopic examination revealed right vocal cord paralysis (Figure 1B).A, Computed tomographic (CT) image of the head shows a right frontal epidural hematoma.

B, Clinical laryngoscopic image at day 2 shows right vocal cord palsy.

C and D, Computed tomographic images with contrast show a thrombosis of the right sigmoid-jugular complex (yellow arrowheads), which causes acute compression of the recurrent nerve as it follows the course of the cranial accessory nerve then the vagus nerve.

The hematoma was evacuated by neurosurgery, and her GCS improved to 14 postoperatively.


Her medical history included eczema treated with triamcinolone acetonide cream.

Otherwise, the patient had no family history or exposure to tobacco or alcohol.On physical examination, a 2-cm, nontender, mobile retroauricular mass with superficial excoriations was palpable over the right mastoid cortex.

The patient denied bleeding from the mass, ear pain, trauma, fever, fatigue, night sweats, or recent illnesses.

The patient had no hearing deficits and no fistula into the external auditory canal.

There was no palpable head and neck lymphadenopathy.

Serologic studies revealed an elevated absolute eosinophil count of 790/μL  (reference range, <700/μL; to convert to ×109 per liter, multiply by 0.001) and an eosinophilia percentage of 9.7% (reference range, <6.0%).

The T1-weighted postcontrast magnetic resonance imaging of the head and neck showed a heterogeneously enhancing mass with irregular borders in the right retroauricular space, with a tract coursing anteriorly toward the parotid gland (Figure, A).A, Axial T1-weighted postcontrast magnetic resonance image of the head and neck.

B, Lesional specimen of the excised mass (original magnification ×10).The excised mass was an enlarged, 2.2 × 1.5 × 2.2-cm lymph node with a smooth, pale core and no hemorrhage or necrosis.

The capsule was moderately thickened by collagen fibrosis with focal areas of interstitial fibrosis.

Reactive follicular hyperplasia was present with prominent eosinophilia in the interfollicular areas and within follicles, forming eosinophilic microabscesses and follicular cysts (Figure, B).

A few small and ill-defined granulomas were present.

Results of Gomori methenamine silver and acid-fast stains were negative.


She had a history of stage IV breast cancer treated with letrozole after a mastectomy 5 years prior.

She had decreased right-sided hearing and tinnitus, a moderate right-sided frontal headache, and an unsteady gait.

She did not have diplopia, facial numbness, or paresthesias.

Over the ensuing 5 years, she had multiple similar presentations that also included facial pain and paresthesias.

On an initial examination, her best-corrected visual acuity was 20/50 OD and 20/25 OS, with dyschromatopsia, relative afferent pupillary defect, and visual-field defects on the right side.

A dilated fundus examination demonstrated a pale right optic nerve.

Magnetic resonance imaging (MRI) of the brain was reported to have normal results, but on review, we noted thickening and enhancement of both optic nerves (with the right eye larger than the left eye) (Figure 1A), cranial nerve III in the right eye, cranial nerve V bilaterally, the pituitary infundibulum, and the hypothalamus, as well as adjacent cavernous sinuses.

Leptomeningeal thickening over the convexities of the anterior frontal lobes was also evident (Figure 1B).

The patient’s cerebrospinal fluid contained a small population of polyclonal CD19+ B cells and CD4+ and CD8+ T cells.

An extensive laboratory workup, including tests for HIV, antinuclear antibodies, anti–double-stranded DNA, antineutrophil cytoplasmic antibodies, serum protein electrophoresis, erythrocyte sedimentation rate, C-reactive protein, complete blood cell count, antiganglioside antibodies, anti–myelin-associated glycoprotein antibodies, and angiotensin-converting enzyme, gave normal results.

A computed tomographic (CT) scan of the thorax and a whole-body positron emission tomography (PET)/CT scan revealed no abnormalities.Initial magnetic resonance imaging of the brain.

B, Leptomeningeal thickening over the convexities of anterior frontal lobes was also evident.Clinically, she initially responded to corticosteroids.

She also developed a chronic small-fiber peripheral neuropathy and was treated with mycophenolate mofetil, cyclophosphamide, and intravenous immunoglobulin at various points.


However, she experienced recurrences of symptoms after therapy discontinuation.

She subsequently started treatment with topical prednisolone acetate, moxifloxacin, and systemic azithromycin.Patient presented with recurrent left eye ptosis, erythema, blepharedema, chronic discharge, and knifelike pain over the past 4 years (arrowhead).Two weeks after the initial consultation, the patient reported persistent but improved symptoms in the left eye.

Her visual acuity was 20/30 OD and 20/100 OS.

Deep superior conjunctival fornices were noted in both eyes (Figure 1), and eversion of the left upper eyelid revealed a pseudomembrane of the tarsal conjunctiva.

Cultures of the copious discharge demonstrated many gram-negative Serratia marcescens.

At this follow-up visit, her visual acuity was 20/30 OD and 20/200 OS.

Previous treatment included topical steroids, antibiotics, and serum tears, with temporary relief.

Additional treatment included weekly bandage contact lenses for many months, which made the left eye pain tolerable.

A dacryocystogram of the left lacrimal system indicated partial dacryostenosis, but compression of the canaliculi and lacrimal sac did not exacerbate discharge.

A prior computed tomography scan of the orbits and sinuses showed no abnormalities.


Her medical history revealed hypertension, type 2 diabetes mellitus, and hyperlipidemia.On examination, her visual acuity was 20/40 OD and 20/30 OS.

The patient first noted an erythematous, tender swelling with yellow discharge, which later evolved to the pigmented mass.

There was a sausage-shaped, darkly pigmented (black), focally ulcerated nodule involving the medial upper eyelid margin and measuring 8 × 6 × 4 mm.

Associated madarosis, eyelid margin notching, and telangiectasia were noted (Figure 1).

The remainder of the anterior segment and a dilated fundus examination were unremarkable.A, The multilobular pigmented mass is noted along the superomedial upper eyelid margin.


He was nonadherent with medications and denied drug and alcohol abuse.On examination, he appeared comfortable.

At presentation, he was experiencing psychosis and being treated in an inpatient psychiatric ward.

On both lower extremities, there was peripheral edema with widespread hematomas, scattered ecchymosis, petechiae, and diffuse perifollicular purpura (Figure).

His blood pressure was 150/67 mm Hg; heart rate, 77/min; temperature, 36.7°C (98.1°F); respiratory rate, 16/min; and oxygen saturation, 99% on room air.

The remainder of the examination was unremarkable.

Laboratory test results showed a normocytic anemia (hemoglobin level, 5.2 g/dL [reference, 13.5-17.5 g/dL]; mean corpuscular volume, 85 fL [reference, 80-100 fL]); normal platelet count (thrombocytes, 285 ×109/L [reference, 150-400 ×109/L]); and a mild leukopenia (leukocytes, 3.9 ×109 [reference, 4.3-10 ×109/L]).

Folic acid level was low (3 nmol/L [reference, ≥5 nmol/L]) and vitamin B12 level was normal (478 pg/mL [reference, 193-982 pg/mL]).

Results for iron panel, reticulocyte count, prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio, liver function tests, and levels of indirect bilirubin, haptoglobin, fibrinogen, and creatine kinase were all within reference range.

Chest radiographs and computed tomography of the head were negative for any acute pathology.

A 12-lead electrocardiogram revealed no abnormalities.


His warfarin had been managed via point-of-care (POC) testing for the past 4 years with a goal international normalized ratio (INR) of 2.0 to 3.0.

His warfarin dosage was 36 mg/wk (3 mg every Wednesday and Saturday and 6 mg all other days) for the past year.

He reported no extra warfarin doses, medication changes, dietary nonadherence, or bleeding.

The Table shows the patient’s laboratory test results.Continue current warfarin dosing and perform a point-of-care (POC) international normalized ratio (INR) test in 1 week.Skip 2 doses of warfarin then resume current dosage and perform a POC INR test in 2 weeks.Skip 2 doses of warfarin, reduce weekly dosage by 10%, and perform a POC INR in 2 weeks.Perform a plasma INR test to confirm POC INR test results.


He had similar symptoms 1 year ago and was diagnosed with and treated for supraventricular tachycardia (SVT).

A subsequent outpatient echocardiogram revealed a structurally normal heart; results of a follow-up electrocardiogram (ECG) were also normal (Figure 1, top).Patient’s baseline 12-lead electrocardiogram (top) and on presentation (bottom).On presentation to the emergency department, the patient’s temperature was 38.2°C; blood pressure, 125/67 mm Hg; and pulse, 241/min.

He had been experiencing sore throat, fevers, and myalgias for the past day.

He became alarmed when he awoke from sleep with strong palpitations and a heart rate greater than 200/min documented on his smartwatch.

Physical examination was notable for an erythematous oropharynx, tonsillar exudates, a tachycardic, regular heart rhythm, and clear lungs.

A modified Valsalva maneuver1 failed to convert the rhythm.

He was subsequently given a series of doses of intravenous adenosine (6 mg, 12 mg, 12 mg), followed by direct current cardioversion at 200 J, which converted the rhythm to sinus for approximately 3 minutes.

Intravenous metoprolol and intravenous diltiazem bolus and drip were then administered, which slowed the heart rate but did not terminate the arrhythmia.


Examination of the rest of the integument, systemic examination, and investigations including fundoscopy, electrocardiogram, and stool examination for occult blood revealed no significant abnormalities.

Dermoscopic examination was performed (polarized mode, Dinolite) as shown in Figure 1B.

B, Polarized dermoscopic image (Dinolite) showing curvilinear brown pigment lines (black arrowhead) with accentuation of normal pigmentary network (green box) without follicular plugging (red circle) or linear vessels (original magnification ×200).

C, Lesional specimen (original magnification ×100) showing clumped eosinophilic elastic fibers (asterisk) in the middermis (inset, original magnification ×40).

We obtained a 4-mm punch biopsy from one of the papules for diagnostic clarification (Figure 1C).A, Coalescent yellowish periumbilical papules.


She had no history of cancer or chronic diseases.

Physical examination did not show adenopathies, hepatosplenomegaly, or other remarkable findings.

Peripheral blood test results were within normal limits.

Tests for tumor markers including cancer antigen (CA) 15-3, carcinoembryonic antigen, CA 19-9, and CA 125 were unremarkable.

No palpable breast masses were identifiable.

Breast ultrasonography and mammography did not reveal parenchymal nodules.

A local steroid therapy was administered, with no benefit.

A biopsy of the skin lesion was performed (Figure, B and C).A, Clinical image of the cutaneous breast lesion shows a large, erythematous, and slightly infiltrated patch in the periareolar region.

B and C, Hematoxylin-eosin–stained lesional specimens show a dense dermal infiltrate of cells with focal epidermis involvement (B) and large atypical cells with scanty cytoplasm (C).


At age 23 years, he began experiencing involuntary orofaciolingual movements and vocalizations.

At age 27 years, he developed dysphagia, dysarthria, and involuntary tongue- and lip-biting.

This oral dyskinesias worsened while eating.

Orofacial dyskinesia (Video 1), involuntary vocalizations, and mild dysarthria were exhibited.

No neuropsychiatric symptoms or seizures were exhibited.Neurological examination results revealed mild cognitive decline, with a Montreal Cognitive Assessment score of 18/30.

His muscle strength and tone were normal, but his deep reflexes were diminished or absent.

The patient’s sensory and coordination examination results were unremarkable, and bilateral Babinski signs were negative.

The patient’s gait was mildly wide based (Video 2).

Laboratory examination results, including blood electrolytes and lactate, liver, kidney, and thyroid function, antinuclear antibodies, ceruloplasmin levels, and vitamin A and E levels were normal.

Routine and biochemical examination results, oligonucleotide band, antibodies against antiaquaporin 4, and autoimmune encephalitis-related antibodies (ie, N-methyl-d-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic, γ-aminobutyric acid-B, leucine-rick glioma inactivated 1, contactin-associated protein 2, and IgLON5) of cerebrospinal fluid were normal.

Creatine kinase (CK) levels were significantly elevated at 2304 U/L (to convert to microkatals per liter, multiply by 0.0167; normal range, 25-200 U/L).

Low-density lipoprotein and apolipoprotein B levels were slightly decreased at 61 mg/dL (to convert to micromoles per liter, multiply by 0.0357; normal range, 80-119 mg/dL) and 58 mg/dL (to convert to grams per liter, multiply by 0.01; normal range, 66-133 mg/dL), respectively.

Acanthocytes were found in the blood smear via Wright staining (Figure, A).

Electrophysiological examination results revealed reduced compound muscle action potential and sensory nerve action potential of bilateral median and ulnar nerves.

Electromyogram results showed neurogenic damage in lower limb muscles.

However, a handkerchief in the mouth markedly reduced involuntary tongue-biting and mouth movements.


This was the second stroke he had in 6 months.

The patient’s other medical problems included well-controlled hypertension and diabetes.

Seven months before this admission, a dual-chamber pacemaker was implanted at an outside institution for sick sinus syndrome.

Device interrogation revealed no atrial fibrillation and normal lead parameters.

Electrocardiogram results showed atrial pacing with capture and intrinsic ventricular conduction.

Magnetic resonance angiography results of carotid, vertebral, and cerebral arteries were normal.

Chest radiography was taken (Figure 1).Chest radiography.

A, In the posterior-anterior projection, the ventricular lead curves more superiorly than usual and lacks the expected indentation as it traverses the tricuspid valve.

B, Lateral projection demonstrates a posterior orientation of the lead that is suspicious for left ventricular placement.


She had a medical history of vomiting and emaciation in her early 40s.

She claimed that her younger brother died of liver cancer and her mother had lost vision because of vitreous hemorrhage and glaucoma.

She denied any history of systemic disorders.On initial examination, best-corrected visual acuity was measured at 0.1 (20/200) OU.

Intraocular pressure was 14 mm Hg OD and 16 mm Hg OS.

Her anterior segment examination results were within normal limits.

Dilated fundus examination demonstrated bilateral vitreous opacity without cells (Figure).

The peripheral residual vitreous cortex in the left eye was as cloudy as the cortex in the right eye.

Fundus was not visible in the right eye and was normal in the left eye.

A bilateral ocular ultrasonography showed normal results except for vitreous opacity.

The patient weighed 37.0 kg and was 155 cm tall.

Mild anemia (hemoglobin level 10.5 g/dL vs a normal range of 11.0-15.0 g/dL [to convert to grams per liter, multiply by 10]) was found in routine blood test results.

Liver and renal functions were normal according to serum test results.

Pars plana vitrectomy (PPV) had been done for her left eye owing to vitreous opacity half a year prior.


His medical history was notable for stage III non-Hodgkin follicular lymphoma in the hilar and axillary nodes, which was asymptomatic and actively monitored by oncology, prostate cancer treated surgically that was in remission, and atrial fibrillation managed with medication (digoxin and warfarin).

There were no other concerning features noted, such as orange pigment or associated subretinal fluid.At presentation, the patient was asymptomatic with no diplopia, pain, constitutional symptoms, or blurred vision.

The choroidal nevus had been observed for the past 2 years; ultrasonography from 2 years prior revealed dimensions of 1.9 (height) × 9.3 (base) mm with medium internal reflectivity.

His best-corrected visual acuity was 20/30 OU.

Pupils were reactive without a relative afferent pupillary defect, extraocular motility was full, and intraocular pressures were normal.

His slitlamp and fundus examination results were unremarkable aside from the choroidal nevus in his right eye, which appeared similar to previous examinations (Figure 1A).

Proptosis, resistance to retropulsion, conjunctival injection, and strabismus were notably absent.

However, a new retro-orbital hypoechoic cavity causing right globe deformation was noted on B-scan ultrasonography (Figure 1B).A, Color fundus photography of the right eye illustrates a hyperpigmented choroidal nevus (arrowhead) in the macula.


On further questioning, the patient reported a 9 pack-year smoking history.

She had no known history of malignant conditions.

She denied recent fevers, chills, weight loss, night sweats, and travel to foreign countries, and she was otherwise feeling well.A, Color fundus photograph of the right eye demonstrates a large, solitary amelanotic choroidal mass (arrowheads) with overlying subretinal fluid.

Her visual acuity with correction was 20/40 OD and 20/25 OS.

Her intraocular pressures were 14 mm Hg OD and 15 mm Hg OS.

A dilated fundus examination of the right eye was notable for an amelanotic choroidal mass with overlying subretinal fluid (Figure 1A).

Results of a dilated fundus examination of the left eye were unremarkable.

Results of fluorescein angiographic imaging of the right eye showed late leakage corresponding to the choroidal mass; the left eye was unremarkable.

Optical coherence tomography demonstrated a choroidal mass with an irregular surface contour and a mild overlying vitreous cell.

On B-scan ultrasonography of the right eye, a superotemporal choroidal mass with an irregular surface contour and medium internal reflectivity was observed (Figure 1B).


The patient had no notable medical history, including dyskeratosis congenita, trauma, sun exposure, radiation exposure, chemical exposure to tar or arsenic or exposure to minerals, chronic immunosuppression, or chronic infection.

Physical examination revealed a subungual nodule with some exudation and crusts.

The distal nail plate had been destroyed and showed onycholysis with obvious separation from the nail bed (Figure, A).

The lesion was initially believed to be an infection; however, results of both mycological and bacteriologic examinations were unremarkable.

Pertinent laboratory results (complete blood cell count, liver panel, kidney panel) were within normal limits.

Lesional biopsy was also performed (Figure, B and C).A, Clinical photograph shows a subungual nodule with exudation and crusts as well as destruction of the distal nail plate with onycholysis.

B, Lesional biopsy results show proliferation of atypical squamous cells invading the dermis.

C, Large atypical squamous cells with hyperchromatic, pleomorphic, and atypical mitosis (B and C, hematoxylin-eosin).


This was accompanied by fever, night sweats, and fatigue.

Her purpuric patches improved initially after the first cycle of chemotherapy; however, in the weeks before the second cycle, they recurred more extensively, involving her right cheek and bilateral ears, arms, and legs.

This time she also experienced pain in those areas as well as lower extremity edema.On presentation to the outpatient infusion suite, she appeared well, and her temperature was 37°C (98.6°F); heart rate, 91/min; blood pressure, 114/58 mm Hg; respiratory rate, 18/min; and blood oxygen saturation, 98%.

Diffuse, symmetric patches and soft, thin plaques of retiform purpura with minimally erythematous borders covered her extremities and acral surfaces, some with overlying bullae (Figure 1).

A complete blood cell count showed an elevated white blood cell count (18 860/μL with 13% neutrophils, 43% lymphocytes, 9% monocytes, 33% others); hemoglobin, 7.2 g/dL; hematocrit, 21.8%; and platelet count, 142 ×103/μL.

Results of a comprehensive metabolic panel were unremarkable.

Fibrinogen level, prothrombin level, and partial thromboplastin time were within normal limits.

She was found to have clinical and radiologic progression of her lymphoma and began receiving R-CHOP (rituximab + cyclophosphamide + doxorubicin hydrochloride + vincristine [Oncovin] + prednisone) chemotherapy.

Blood was sent for cultures.Skin findings on examination of patient’s lower extremities.


He had been treated by a rheumatologist for polyarticular inflammatory arthritis involving the wrists, metacarpophalangeal joints, and proximal interphalangeal joints, as well as fatigue and dyspnea on exertion.

His pulmonary and joint symptoms were relieved by daily oral prednisone and flared with taper below 10 mg. Other medications prescribed included hydroxychloroquine, 400 mg, daily for 18 months and weekly adalimumab injections for 7 months, without improvement.A, Pink-purple papules on the extensor surface of the arms.

The patient reported a 5- to 7-kg weight loss without fever or sweats.

Examination revealed numerous, pink-purple dermal papules on the trunk and extremities, with preference for the extensor surfaces of the arms (Figure, A) and legs.

D, Biopsy results show low CD4 signal and robust CD8 signal (magnification ×20).Pulmonary function testing revealed mild restrictive disease with decreased forced vital capacity and total lung capacity.

Results of a complete blood cell count and metabolic panel; hemoglobin A1c; viral and rheumatologic panels, including HIV blood tests; chest radiograph; high-resolution chest computed tomographic scan; echocardiography; endoscopic studies; hand radiographs; and serum and urine protein electrophoresis were normal or otherwise unremarkable.

The results of lesional skin biopsies obtained from multiple involved sites initially revealed nonspecific granulomatous dermatitis before a diagnostic biopsy was performed (Figure, B, C, and D).


Medical history and family history were unremarkable.

Physical examination revealed grouped and circumscribed, firm, skin-colored, 1- to 3-mm papules with a central punctate dark core (Figure, A and B).

A 4-mm punch biopsy from a papule on the palm was performed (Figure, C and D).A and B, Grouped, dome-shaped, skin-colored, punctate papules with central keratotic plugging localized to the right palm and finger.

C and D, Dilated follicular infundibulum with keratinous core and absent hair shaft (hematoxylin-eosin).

Prior treatments included cryotherapy, pulsed dye laser, and 40% salicylic acid, with partial improvement reported but never complete clearance.


The numbness progressed over 10 months to involve his entire right arm, patches of his left arm, and his distal lower extremities.

He also developed right-hand incoordination and imbalance.

B, A brain coronal T1 postgadolinium MRI from 10 months later with persistent yet evolving enhancement and mild size increase in brainstem lesion and ongoing dural enhancement.He sought neurological reconsultation 9 months later, reporting progressive blurred vision bilaterally, dysphagia, dysarthria, and urinary and bowel urgency.

His gait had worsened, requiring a cane and, for 6 months, a walker.

A magnetic resonance image (MRI) of the brain is shown in Figure 1A.

A complete blood cell count with a differential; liver function testing; tests for HIV, rapid plasma reagin, serum aquaporin-4 antibody, and antinuclear antibodies; and levels of sodium, calcium, creatinine, glucose, thyroxine, and vitamin B12 were unremarkable.

Examinations of the cerebrospinal fluid had normal results twice, including for white blood cell count with a differential, glucose level, total protein level, IgG index, oligoclonal bands, cultures, and cytology testing.A, A brain coronal T1 postgadolinium magnetic resonance image (MRI), showing a lobulated heterogeneously enhancing mass in the brainstem and dural enhancement.

A neurologic examination revealed decreased visual acuity (20/50 OU) with normal pupillary responses and discs; cerebellar dysarthria, dysmetria, and dysdiadochokinesia; and decreased proprioception in the toes with positive Romberg testing.

A follow-up brain MRI (Figure 1B) showed persistent enhancement plus bilateral optic nerve enhancement (not shown).

A physical examination was otherwise unremarkable, except for mild lower-extremity edema.


He was discharged and prescribed ticagrelor, 90 mg twice daily, in addition to his home regimen of aspirin and metoprolol tartrate.

He had no history of syncopal episodes or arrhythmias.

Three months later, he experienced worsening exertional dyspnea and had multiple episodes of syncope.

His baseline transthoracic echocardiogram results demonstrated normal systolic function and no significant valvular disease.

Ambulatory electrocardiogram (ECG) monitoring results showed 31 episodes of high-grade atrioventricular (AV) block (AVB), with ventricular pauses ranging from 3.0 to 13.0 seconds occurring during the day and at night (Figure 1).


The patient did not require positive pressure or intubation, but he had intermittent stridor associated with desaturations.

He had feeding difficulty and failure to thrive.

On physical examination, the newborn had facial dysmorphism, including a broad and flat nasal dorsum and mild micrognathia.

Flexible fiberoptic laryngoscopy revealed a cystic lesion consistent with a vallecular cyst.

A modified barium swallow study demonstrated laryngeal penetration and aspiration of thin and nectar-thick liquids.

A diffuse, soft, palpable mass was present along the right neck.Magnetic resonance imaging (MRI) demonstrated a multispatial mildly enhancing mass within the bilateral retropharyngeal, parapharyngeal, and carotid spaces, with a mildly hyperintense signal relative to muscle on T1-weighted and T2-weighted images and associated restricted diffusion.

The mass was largest on the right side, with convex borders, mild superior displacement of the right parotid gland, and posterior displacement of the right sternocleidomastoid muscle (Figure, A, B).

The T2-weighted MRI also demonstrated a hyperintense, nonenhancing lesion within the base of the tongue consistent with a vallecular cyst.

The thyroid appeared normal and in its expected location, but no thymus was present in the mediastinum.

B, Axial fat-saturated MRI shows the mass (arrowheads), with encasement of the left internal and external carotid arteries.

C, Biopsy results reveal a polymorphic population of lymphocytes, fibroadipose tissue, and a concentric island of squamous cells with central keratinization (arrowhead).

The patient was taken to the operating room for excision of the vallecular cyst, and a fine-needle aspiration biopsy of the right neck mass was performed for cytopathological analysis (Figure, C, D).A, Axial magnetic resonance image (MRI) of the neck shows a mildly hyperintense mass (arrowheads) with posterior displacement of the right sternocleidomastoid muscle.

D, Reference specimen from a study set of the tissue shown in panel C demonstrates islands of squamous cells in a background of small mature lymphocytes (hematoxylin-eosin).


She had no relevant medical, family, or ocular history.

There was no history of trauma or ocular surgery.

One month prior to presentation, she had developed fevers, chills, and coughing.

After several days, she had developed redness, pain, photophobia, and blurry vision in her left eye, and she had subsequently developed similar symptoms in her right eye.

On presentation, her visual acuity was counting fingers OU.

A slitlamp examination revealed mild conjunctival redness, 2+ anterior chamber cell, and flare in both eyes, as well as mild posterior synechiae.

Pigment was present on the anterior lens capsule.

A fundus examination demonstrated a moderate amount of vitreous cell, hyperemia and edema of the optic disc, and retinal detachments in both eyes (Figure).

The detachments were inferior and shifted with the patient’s head position, suggesting serous detachments.

The cornea was clear without keratic precipitates, and there were no iris nodules.


He had no significant medical history aside from documented allergies to β-lactam, macrolide, and cephalosporin antibiotics resulting in rashes, angioedema, and hives.The patient was febrile on admission, and results from chest radiography were consistent with pneumonia.

He complained of a cough, sore throat, and ocular itching.

He denied prior ocular history and reported no visual changes.

Bedside ophthalmic examination revealed bilateral limbus-sparing conjunctival hyperemia that blanched minimally with phenylephrine, bilateral nasal and temporal conjunctival epithelial ulcerations, and inferior forniceal pseudomembranes (Figure, A).

There were no symblephara or eyelid margin defects.

Examination of the face revealed erosions with hemorrhagic crusts on the lip mucosa (Figure, B) but no associated cutaneous lesions or desquamation.

Findings from the remainder of the ophthalmologic examination, including visual acuity, intraocular pressure, and dilated fundus examination, were unremarkable.

Mycoplasma pneumoniae IgG and IgM titers were obtained and found to be within normal limits.A, Peripheral conjunctival ulceration.

Inset, peripheral conjunctival ulceration highlighted with fluorescein under cobalt blue light.


Medical history was otherwise unremarkable.

On examination, his best-corrected visual acuity was 20/20 OU, although his vision was slightly eccentric.

The slitlamp examination of the anterior segment was unremarkable.

Dilated fundus examination revealed subtle bilateral yellow foveal spots.


Her parents noticed the left eye turning out for the past year.

On examination, she fixed and followed with her right eye but not with the left, with 5.0-diopter exophoria at near in the left eye.

Penlight examination results showed left leukocoria.

Intraocular pressure and motility were normal bilaterally.

On subsequent examination under anesthesia, the left optic nerve was obscured by a whitish mass.

While the optic nerve itself was obscured, a pigmented crescent could be seen surrounding it (Figure, A).

Ultrasonography results demonstrated an elevated retinal mass overlying an excavated optic nerve head.

A small focus of hyperechogenicity was noted at the optic nerve head, consistent with calcium (Figure, B).

Fluorescein angiography results demonstrated staining of the central whitish mass, which was obscuring the underlying retinal vessels.

On fluorescein angiography results, no vessels were seen within the central whitish mass itself.A, Retinal fundus photograph of the left eye demonstrating a whitish mass obscuring the optic nerve with a surrounding pigmented crescent.


Her initial symptoms started 1 month after the initiation of nivolumab, which was 1 year prior to the index visit.

Treatment with nonsteroidal anti-inflammatory drugs failed, and the patient had a partial response to intra-articular steroids.

Evaluation showed fixed swan neck deformities in multiple fingers (Figure, A).

There was evidence of chronic synovial hypertrophy with no active synovitis on examination.

The results of a comprehensive autoantibody blood panel, including antinuclear antibody, rheumatoid factor, and anti-citrullinated peptide antibody, were unremarkable.

Plain radiographs of the hands demonstrated diffuse osteopenia, joint space narrowing, and multiple deformities.

Magnetic resonance imaging of both hands revealed multifocal osseous erosions (Figure, B), synovitis, and tenosynovitis.Erosive deforming inflammatory arthritis.

Despite the joint symptoms, nivolumab treatment was continued for a year.

She refused systemic therapies owing to concern about diminishing the effectiveness of nivolumab.

A, Fixed swan neck deformities in multiple fingers (arrowheads).

B, Magnetic resonance images of both hands reveal multifocal osseous erosions (arrowheads).


His only medication was acetaminophen as needed for pain.

He had no fever, skin rash, headaches, vision changes, or urinary symptoms.

He reported occasional bruising around his eyes.

No joint tenderness, warmth, or fluid collections were present, and skin examination was normal.

The presence of raised soft tissue masses around the sternoclavicular joints (Figure, left panel) and scapulae (Figure, right panel) were noted.

Laboratory evaluation revealed normal results for complete blood cell count, erythrocyte sedimentation rate (ESR), and levels of electrolytes, creatinine, and C-reactive protein.

A spot urinalysis showed a protein level of 220 mg/dL (reference range, <26 mg/dL), and a 24-hour urine collection revealed 1.8 g of albumin (reference range, <229 mg/24 h).

Magnetic resonance imaging (MRI) of the shoulders and hips showed synovial and capsular thickening.Left, Soft tissue masses (arrowheads) around the sternoclavicular joints.


He reports no symptoms of hyperglycemia, such as frequent urination, increased thirst, fatigue, or visual changes, and had no known family history of diabetes.

His body mass index (BMI) is 33.9 and his blood pressure is 160/90 mm Hg.

A series of blood tests had recently been obtained (Table).

The patient wants to know if a test could be done in the office to determine if he has diabetes.Perform a laboratory-based glucose test to determine the patient’s glycemic status.Perform a point-of-care (POC) hemoglobin A1c (HbA1c) test via fingerstick to determine the patient’s glycemic status.Perform a laboratory-based HbA1c test to determine the patient’s glycemic status.Do not perform glycemic testing because it is not indicated for this patient.


The patient was otherwise healthy and denied a family history of inherited ichthyosis or atopy.

Multiple nodules appeared on the upper back 1 year previously and gradually increased in number and size.

Physical examination revealed extensive, dry scaly patches on the trunk, arms, and legs.

Several 0.5- to 1-cm, dome-shaped, red papules and nodules were found on the upper back (Figure, A and B).

Mildly enlarged lymph nodes were observed on the cervical, axillary, and inguinal regions.

Results of routine blood tests, biochemistry analyses, and peripheral blood flow cytometry tests were within normal limits.

No atypical cells were found in the peripheral blood.

A biopsy specimen was obtained from the nodules on the patient’s back (Figure, C and D).Clinical images show multiple dome-shaped nodules on the back (A) and extensive, dry scaly patches on the leg (B).

Lesional histopathologic images show small to medium-sized atypical cells, and focal areas of epidermotropism (C, hematoxylin-eosin) and CD4 on immunohistochemical analysis (D) (original magnification ×200).


Although the patient’s surgical course was uncomplicated, several months postoperatively she noted persistent asymptomatic rough areas that she assumed were scars.

Seven years after the second surgery, she was referred to dermatology for improvement of the areas for cosmetic reasons.On physical examination, the patient had well-healed, barely identifiable scars on the inframammary creases and lower breast areas.

Separate from the scars and located on the inferior medial bilateral breasts were 1- to 2-cm slightly erythematous annular atrophic plaques with more involvement of the left breast than the right.

The rims of the lesions were raised with slight white scale and the centers slightly depressed and wrinkled in appearance (Figure 1).Clinical images of the inferior medial bilateral breasts with 1- to 2-cm erythematous annular atrophic plaques with more involvement of the left breast (A) than the right (B).

Five years later, she underwent a bilateral augmentation mammoplasty with removal and replacement of silicone gel implants and major mastopexy with capsulotomy.


In the weeks prior to onset, she traveled to Yosemite National Park but denied any particular infectious exposures or symptoms including rash.

She reported no personal or family medical history.

Although she did consume a variety of nutraceuticals, she denied medication and recreational drug use.On examination, mental status, cranial nerves, and upper extremities were normal.

Lower extremities were significant for her right side having greater pyramidal weakness than the left, with brisk reflexes and right ankle clonus, as well as a sensory level to pinprick at T6.

Magnetic resonance imaging (MRI) of the total spine with and without gadolinium is seen in Figure 1.

Initial investigations were notable for normal complete blood cell count, electrolytes, kidney and liver function, B12, and thyrotropin as well as an unremarkable MRI of the brain.

Three lumbar punctures were performed over the course of the patient’s hospitalization, each with a white blood cell count less than 5 /µL (to convert to ×109/L, multiply by 0.001), normal IgG index, absent oligoclonal bands, normal protein and glucose levels, and benign cytology.

A comprehensive infectious and inflammatory workup including HIV, herpes simplex virus, varicella-zoster virus, Lyme disease, antinuclear antibodies, astrocyte aquaporin-4 autoantibody, myelin oligodendrocyte glycoprotein autoantibody, and serum and cerebrospinal fluid autoimmune panels were negative.

Whole-body positron emission tomography demonstrated hypermetabolism of the midthoracic cord.A, Long-segment, expansile T2 hyperintense lesion spanning C5 through T12 and involving greater than two-thirds of the cord diameter.

The spinal cord is mildly diffusely swollen without an appreciated focal mass.

B, Associated extensive ill-defined enhancement of the spinal cord spanning T3 through T9.


Examination of the jugular venous contour with the patient sitting upright at 90° is shown in Video 1.

Auscultatory findings at the left lower sternal border showed normal S1 and S2 heart sounds with a diastolic sound and no murmurs (Figure 1; Video 2).

Abdominal examination revealed an enlarged, pulsatile liver with smooth edges palpable 4 cm below the costal margin.

Electrocardiography showed resting abnormalities (rightward axis and inferolateral T-wave inversions).

Posteroanterior chest radiography showed normal heart size and clear lungs (Figure 1).

Transthoracic echocardiography was performed, which showed normal left ventricular size and function without valvular abnormalities.A, Phonocardiography from the left sternal border.

B, Upright chest radiography with posteroanterior projection.