Further testing led to a diagnosis of HIV/AIDS, and at that time she was started on highly active antiretroviral therapy (HAART) therapy as well as bactrim prophylaxis.

She had presented 3 months prior with neurologic and vision changes and was diagnosed as having varicella zoster encephalitis and cytomegalovirus retinitis.

Physical examination revealed left-sided facial fullness and a left-sided violaceous, vascular-appearing lesion involving the left maxillary gingiva (Figure, A).

The patient was afebrile, her white blood cell count was 3300/μL, and her CD4 count was 210 μg/mL.

Magnetic resonance imaging (MRI) of the face revealed a poorly enhancing mass arising from the left maxilla and extending into the left maxillary sinus (Figure, B).

Histologic analysis and immunophenotype of the specimen showed a dual population of lymphoma cells with plasmablasts having large vesicular nuclei and centrally located eosinophilic nucleoli and “plasmacytic” cells with comparatively smaller darker nuclei and smaller scanty nucleoli (Figure, C).

Immunohistochemical expression was strongly positive for CD138 (Figure, D) and Epstein-Barr virus–encoded small nuclear RNA (EBV-EBER), and the Ki-67 index (marker of mitotic division) was greater than 90%, negative for CD45, CD20, HHV-8, TdT, CD34, PAX5, CD3, CD99, ALK-1, and CD30.

An incisional biopsy was undertaken, during which excessive bleeding was encountered.


Palpation detected a smooth, soft, and fluctuant mass in his left supraclavicular region.

Fiberscopic examination of the pharynx and larynx revealed no abnormalities.

Contrast-enhanced computed tomography (CT) demonstrated a poorly circumscribed, heterogeneous, and cystic mass near the sternocleidomastoid muscle (SCM).

The SCM around the tumor was thickened, suggesting invasion of the SCM.

There was no continuity between the tumor and the thyroid gland (Figure, A).

Magnetic resonance imaging revealed a poorly marginated, heterogeneous, and partially tubular mass.

Fine-needle aspiration cytology revealed cystic elements but no atypical cells.

Positron emission tomography showed hypermetabolism (maximum standardized uptake value, 1.6) in the mass, but no other hypermetabolic foci.

At surgery, the tumor was attached to the medial side of the origin of the left SCM.

No extensive adhesions were observed, and dissection of the tumor from the adjacent tissues was straightforward.

The lesion measured 2.5 × 3.0 × 4.0 cm, was a solitary well-circumscribed roundish nodule with a thin capsule, and its cut surface had a yellowish white homogeneous surface (Figure, B).

Pathological examination revealed that the mass comprised an irregular combination of squamous epithelial and spindle cells, with a mature adipose tissue component (Figure, C and D).

Immunohistochemical analysis revealed that the epithelial component was diffusely positive for cytokeratin AE1/AE3.A, Contrast-enhanced neck computed tomographic (CT) image.

C and D, Histopathologic images, hematoxylin-eosin.


He had not experienced prior nasal trauma or surgery and had quit smoking 30 years ago.

He also reported intermittent right-sided epistaxis occurring multiple times per day.

At the outside institution, a nasal mass was found on examination and biopsied.

Endoscopic examination showed a dark, soft-tissue mass filling the right nasal cavity.

Computed tomography (CT) of the sinuses revealed opacification of the right nasal cavity with tissue protruding into the nasopharynx and complete opacification of the right maxillary, anterior ethmoid, and frontal sinuses (Figure, A and B).

Histopathologic analysis from both the outside hospital and our institution revealed sheets of atypical, pleomorphic epithelioid cells, some with prominent pigment (Figure, C).

Immunohistochemical stains were positive for HMB-45 (Figure, D) and S-100.A and B, Noncontrast computed tomographic images of the paranasal sinuses.

The patient underwent surgical resection.

Removal of the mass required a right medial maxillectomy, septectomy, and excision of the right nasolacrimal duct via endoscopic approach.

Resection also necessitated removal of the anterior maxillary sinus wall via Caldwell-Luc procedure.

He was referred to our office for further management.


He had a history of gastroesophageal reflux disease and allergic rhinitis.

His medications included esomeprazole, fluticasone nasal spray, and supplemental cholecalciferol.

Physical examination revealed multiple ecchymoses on the extremities and abdomen but was otherwise unremarkable.

Laboratory evaluation showed a white blood cell count of 2.4 × 103/µL, with 13% neutrophils, 32% lymphocytes, 1% monocytes, 0% eosinophils, 0% basophils, and 54% blasts.

Hemoglobin level was 10.3 g/dL, and platelet count was 20 × 103/µL.

Prothrombin time was 14.5 seconds; international normalized ratio, 1.4; partial thromboplastin time, 27 seconds; D-dimer level, 2.524 μg/mL (13.82 nmol/L); and fibrinogen level, 68 mg/dL (2 μmol/L).


There was no history of weight loss, hypertension, medication use, or a family history of genetic syndromes such as von Hippel-Lindau.

She reported increasing symptoms possibly affected by stress, left lateral recumbent position, and physical activity.

Physical examination revealed a body mass index of 25.9, blood pressure of 112/74 mm Hg, and a heart rate of 82 beats/min without cardiac or renal artery murmurs or skin lesions.

Laboratory tests were performed (Table 1).


She reported that the mass had been present for 2 to 3 weeks and was increasing in size.

It was not painful but bled when she brushed her teeth or ate sharp foods, which made it difficult to eat.

She had no fevers, no trauma to the area, and no history of a similar condition.Vital signs included a temperature of 36.4°C, blood pressure of 106/57 mm Hg, and heart rate of 93/min.

Physical examination revealed a 3 × 5–cm soft, compressible, nodular mass on the upper right gum line adjacent to the lateral incisors (Figure).

The mass was friable, pedunculated, and covered with a thin white film.

There was some gingival erythema near the adjacent teeth but no lymphadenopathy.

The examination results were otherwise unremarkable.


She experienced no symptoms of weight loss, headache, sweating, palpitations, pallor, anxiety, menstrual abnormalities, or mood changes; had no known history of cancer or hypertension; and was not taking any medications.

On physical examination, her blood pressure was 135/73 mm Hg, and her heart rate was 82/min.

There was no truncal or facial obesity, acne, striae, hirsutism, or proximal muscle weakness.

Laboratory analysis showed normal blood cell counts and levels of electrolytes, liver enzymes, and lactate dehydrogenase.

Further biochemical evaluation revealed normal levels of plasma and urinary cortisol, serum aldosterone and 17-hydroxyprogesterone, and urinary metanephrines.

A computed tomography (CT) scan revealed a 5.5 × 4.3–cm left adrenal tumor with heterogeneous appearance, a hypodense central area, and irregular margins, with a density of 36 Hounsfield units (HU).

Relative and absolute adrenal washout values (a measure of the disappearance of contrast media from a mass after 10 minutes) were 23% and 47%, respectively.


He was found to have scattered petechiae and hemorrhagic vesicles, with most concentrated on the hands and feet (Figure, A and B).

Palpable purpura were noted across the extremities.

Several lesions were studded with pustules.

He had an enlarging bulla on his left wrist.

An abrasion on his left elbow was attributed to his recent falls.

He underwent a stroke workup, including transesophageal echocardiography (TEE), results of which were negative.

One was sent for histopathological examination, and the other was sent for fungal, bacterial, and mycobacterial cultures.

A bacterial culture swab was obtained from the tense bulla on his left wrist.A, Pustule on dorsal surface of fingers.

B, Acral eruption on the dorsal surface of the foot.

C and D, Skin biopsy specimens, hematoxylin-eosin.

C, Specimen from the dorsal side of the right foot.

D, Focal ulceration and underlying vascular thrombosis with extramural fibrin deposition.

On presentation to the emergency department, he received antibiotics owing to a concern for aspiration pneumonia.

The infectious disease department was also consulted, and the patient was given broad-spectrum antibiotics owing to concern about endocarditis.

He was noted to have a progressing cutaneous eruption during his admission, and the dermatology department was consulted.

As part of his dermatological workup, two 4-mm punch biopsy specimens were obtained (Figure, C and D).


The patient did not smoke and denied any medical history of chronic rhinosinusitis.

The lesion bled with minimal trauma but did not obstruct his breathing.

Physical examination revealed a 1-cm, nontender, exophytic, verrucous, skin-colored plaque on the right nasal vestibule (Figure, A and B).

C, Histologic sections display papillary fronds with slender fibrovascular cores that are lined by nonkeratinizing squamous epithelium (original magnification ×200).

D, Higher magnification shows mucin-containing goblet cells.

Neither cytologic atypia nor atypical mitotic figures are present (original magnification ×400).

A diagnostic shave biopsy specimen was taken after informed consent was obtained (Figure, C and D).A and B, An exophytic, verrucous, and skin-colored plaque on the right nasal vestibule.


She recalled having a small abrasion on her left leg before wading waist-deep in search of trout.

Prior to presentation, she was unsuccessfully treated by 3 different physicians for allergic contact dermatitis and cellulitis.

Physical examination revealed erythematous, crusted, edematous plaques and pustules with weeping of yellow exudate on the left leg (Figure, A).

Plaques extended from the lower mid-shin to the thigh in a sporotrichoid spread, ending with a palpable enlarged lymph node in the left groin.

The patient reported no history of cutaneous eruptions on her legs or feet, and there was no obvious thickening, yellowish discoloration, or subungual debris of the fingernails or toenails on examination.

A laboratory work-up, potassium hydroxide scraping (Figure, C), and punch biopsies for histopathologic analysis and fungal, bacterial, and atypical mycobacterial tissue cultures were performed.A, Erythematous, crusted, edematous plaques and pustules on the left leg prior to definitive treatment.

Attempted treatments included topical and oral corticosteroids, trimethoprim-sulfamethoxazole, ceftriaxone, doxycycline, and clindamycin.

Following 1 month of failed treatment, she presented to the dermatology clinic.

B, Near complete resolution of pustules and resultant postinflammatory hyperpigmentation after definitive treatment.

C, Potassium hydroxide scraping taken from the left leg.


The eruption was accentuated in the inguinal folds, antecubital fossae, and popliteal fossae.

Physical examination revealed a strikingly symmetrical eruption of erythematous, edematous, annular plaques with superimposed small pustules at the periphery, and associated desquamation (Figure, A and B).

Laboratory evaluation was significant for leukocytosis with neutrophilia (26000 μL; to convert to × 109 per liter, multiply by 0.001).

Neutrophil levels were 66.7% (to convert to proportion of 1.0, multiply by 0.01), and lymphocyte levels were 9.9% (to convert to proportion of 1.0, multiply by 0.01).

C-reactive protein and erythrocyte sedimentation rate levels were within normal limits.

Test results for anti-DNase B antibodies, a respiratory viral panel, and blood and throat cultures were all negative.A, Right arm with erythematous edematous plaque with superimposed pinpoint pustules and associated superficial desquamation.

B, Bilateral buttocks with well-demarcated, erythematous plaques with pustules at the periphery.

Superficial desquamation is present at the superior aspect of the buttocks.

C, Hematoxylin-eosin stain (original magnification × 20).There was no ocular or mucosal involvement and no lymphadenopathy.

There was no family history of psoriasis.Biopsy of the left thigh revealed a subcorneal pustule with underlying neutrophilic spongiosis, with associated psoriasiform epidermal hyperplasia and rare individually necrotic keratinocytes.

There was edema of the papillary dermis and a mild superficial perivascular lymphocytic infiltrate with scattered neutrophils (Figure, C).


She underwent a tonsillectomy at age 5 years.

She smoked for 1 year but quit 20 years before this presentation.

There was no family history of malignancy.

On further inquiry, the patient acknowledged right shoulder pain that had been progressing over 5 months and leading to a limited mobility of the right upper extremity.Cross-sectional computed tomography demonstrating a mass of the right shoulder (arrowhead).Her comorbidities included hypertension, morbid obesity, fibromyalgia, and obstructive sleep apnea dependent on positive pressure ventilation.

There was fullness involving the right scapula.

After ruling out acute coronary syndrome or pulmonary embolus, a computed tomography scan of her thorax revealed lytic lesions of the sternum and second rib and a large mass involving the right scapula (Figure 1).

On examination she was morbidly obese with a body mass index (calculated as weight in kilograms divided by height in meters squared) of 63.

Laboratory testing included comprehensive metabolic panel and complete blood cell count results within the normal range, except for a calcium level of 10.4 mg/dL (for millimoles per liter, multiply by 0.25) (reference range, 8.4-10.2) and alkaline phosphatase level of 400 U/L (for micokatals per liter, multiply by 0.0167) (reference range, 36-126).

She was referred to our Cancer Center with a diagnosis of a metastatic giant cell tumor.

A computed tomography–guided biopsy of the mass gave a broad differential.


The lesion progressively developed several days after an unintentional exposure to blood with a blade used to drain an abscess of the oral cavity.

A soft tissue abscess of the digit appeared 7 days after the initial trauma.

Forty-eight hours after surgery, pustules appeared.

One year later, the surgeon presented with prodromal burning pain of the same index finger, and a similar soft tissue abscess recurred after 48 hours at the same site of the original lesion with a small painful vesicle progressively developed (Figure, B).A, Clinical aspect of the index finger 2 days after the second surgery.

The bacteriological samples were found to be sterile.

Antibiotic therapy combining amoxicillin and clavulanate was started, without any significant improvement.

Surgery was performed urgently, with excision of the wound entrance and washing of the flexor tendon sheath.

An antibiotic regimen with amoxicillin/clavulanate was prescribed.

The surgeon was hospitalized for infusions combining piperacillin/tazobactam and teicoplanine, carried out over 72 hours.

An oral antibiotic regimen with amoxicillin/clavulanate (3 g every 24 hours) was prescribed for 10 additional days.

The patient presented a deep wound induced by the bistoury piercing of the index finger pulp of the right hand, with a disrupted epidermal barrier.

Both the patient who was operated on and the surgeon were negative for human immunodeficiency virus and hepatitis B/C virus testing.

Bacteriological swabs were performed in the same time.

Further drainage and washing of the sheath were repeated (Figure, A).

The lesions completely resolved within 2 weeks.

B, Recurrence of the soft tissue abscess.


Her medical history was remarkable for type 2 diabetes (which was well-controlled with insulin), and a review of systems found that she had not experienced headache, pain, or neurologic complaints.

Fluorescein angiography was deferred because of her pregnancy.A and B, Fundus photographs demonstrating macular edema, prominent flame hemorrhages, and a mild tortuosity of the retinal venules.

Her blood pressure was 102/54, and her best-corrected visual acuity was 20/50 OD and 20/40 OS without afferent pupillary defect, motility disturbance, or intraocular pressure abnormalities.

A fundus examination was remarkable for bilateral hyperemic discs and macular edema and subretinal fluid, with numerous flame-shaped hemorrhages in 4 quadrants without microaneurysms, exudates, or neovascularization (Figure).

There was no evidence of intraocular inflammation.

C, Spectral-domain optical coherence tomography (OCT) of the right eye with subretinal fluid and macular edema.

Central macular thickness, 1095 μm.A complete blood cell count, antithrombin III, protein C, prothrombin mutation, antiphospholipid, anticardiolipin, diluted Russell viper venom test, and antinuclear antibody testing results were within normal limits.


He had been treated approximately 4 months prior at an outside facility for cerebral infarct with resultant right lower extremity weakness.

He had no history of head trauma or surgery.

On presentation, he complained of headache and nasal congestion but denied diplopia or rhinorrhea.

Findings from the ophthalmologic examination revealed bilateral visual acuity of 20/100 with intact visual fields.

Findings from a head and neck examination were otherwise within normal limits, with cranial nerves III to XII intact.

Computed tomography (CT) of the sinuses with image guidance protocol revealed a 5.6 × 2.7 × 2.0-cm, well-circumscribed expansile mass occupying the left petrous apex and sphenoid sinus (Figure, A).

Magnetic resonance imaging (MRI) demonstrated that this mass was heterogeneous on T1-weighted images (Figure, B) and hyperintense on T2-weighted images.

The mass did not enhance with gadolinium.

The position of the internal carotid artery was not obviously displaced in either a posterior or anterior direction (Figure, A and B).

Therefore, it was not entirely clear from imaging if this lesion originated in the petrous apex or sphenoid sinus.

The patient was taken to the operating room in conjunction with the neurosurgery team for an endoscopic, transnasal approach to this lesion.

A wide sphenoidotomy was performed, and a cystic mass was identified within the sphenoid sinus (Figure, C).

On entering the capsule, a golden-brown fluid was encountered (Figure, D).


Pertinent medical history included obesity, type 2 diabetes mellitus, allergic rhinitis, and chronic lymphocytic leukemia (CLL).

The CLL had been treated successfully with chemotherapy and had been in remission for the past 6 years.

He had previous complaints of left-sided aural pressure and intermittent clear otorrhea that were unsuccessfully treated at another center with 2 sets of pressure equalization tubes (PETs) and 3 courses of ototopical antibiotics.

In the month before presenting to us, the otorrhea had turned bloody.

He had not experienced fever, malaise, weight loss, lymphadenopathy, skin lesions, or vertigo.

The only notable finding from the physical examination was a hypomobile left tympanic membrane with an anterior-inferior PET plugged by granulation tissue.

Facial nerve function was normal bilaterally.

Audiometry results demonstrated a left moderate sloping to profound mixed hearing loss and speech discrimination score of 68%.

A fine-cut, temporal bone computed tomographic (CT) scan was obtained, which demonstrated near-complete opacification of the left mastoid air cells, and middle ear (Figure, A).

Bulky soft tissue was removed from the middle ear and mastoid.

The patient underwent a left tympanomastoidectomy for continuing otorrhea.

Cytopathologic examination revealed numerous, small, basophilic cells (Figure, B).

Immunostaining showed that the cells were CD20 positive (Figure, C) and CD3 negative (Figure, D).A, Coronal computed tomographic (CT) scan showing near-total opacification of the left mastoid air cells.

B-D, Histopathologic images, original magnification ×40.

B-D, Histopathological images, original magnification ×40.

B, Biopsy specimen demonstrating homogenous, small basophilic cells.

C, Positive immunostaining with anti-CD20 antibodies.


Treatment of allergic rhinitis with cetirizine and intranasal fluticasone had provided only partial relief.

There was no associated history of diplopia or worsening visual acuity.

She had not experienced facial trauma or sinus surgery.

On examination, there was proptosis and periorbital edema of the left eye without any restriction of extraocular movements.

The left supraorbital area was tender to palpation, with no abnormal masses appreciated.

A computed tomographic (CT) scan demonstrated extensive thickening of the left frontal bone, extending over the entire roof of the orbit posteriorly (Figure, A and B).

Changes within the frontal sinus were consistent with a soft-tissue component of the mass.

Subsequent magnetic resonance imaging (MRI) (Figure, C and D) showed markedly hypertrophic bone in the frontal region and a homogeneously enhancing lesion within the left frontal sinus that was hyperintense on T2-weighted images, with left extraconal superior orbital and left frontal intracranial extension with dural enhancement.

A combination above-and-below approach combining unilateral frontal sinusotomy with a trephination was performed.

Abnormal tissue appearing in the left frontal sinus was removed, along with diseased tissue that extended into the orbital roof and orbit.

Specimens were sent for pathologic evaluation, and findings demonstrated bony spaces containing lobules and whorls of spindle cells.A and B, Preoperative computed tomography (CT).

A, Extensive thickening of the left frontal bone.

B, Soft-tissue component in left frontal sinus.

C and D, Magnetic resonance imaging (MRI).

D, Lesion within the left frontal sinus, with superior orbital and intracranial extension.


He reported a 2-day history of left-sided jaw pain preceding the swelling but had no other clinically significant history.

Physical examination showed trismus, rightward tracheal deviation, and a hoarse voice.

The left side of his neck was diffusely swollen without palpable fluctuance, induration, or a discrete mass.

A complete blood cell count revealed no abnormalities.

A contrast-enhanced computed tomographic (CT) scan of the neck showed a large hyperdense mass interposed between the left common carotid artery and the hypopharynx (Figure, A-C).

There was resultant lateral deviation of the left common carotid artery and medial deviation on the supraglottic larynx and hypopharynx, resulting in airway compromise.

Of note, the density of the mass was identical to that of the adjacent vasculature.

There was extensive edema surrounding the primary abnormality.

Additional findings include periapical dental abscesses in 2 teeth (Figure, D).


A review of his systems was significant for bilateral lower leg swelling, a rash of the torso, painful “bumps” on his neck, reduced hearing abilities, and tinnitus.His medical history was significant for human immunodeficiency virus, controlled with antiretroviral therapy (Strilbild; Gilead Sciences Inc).

He was homosexual, did not smoke, and denied intravenous drug use.His best-corrected visual acuity was hand motion OD and 20/20 OS.

There were no associated feelings of pain, flashes, or floaters.

His cluster of differentiation 4 count was 600, and his viral load was undetectable.

No afferent pupillary defect was apparent.

His intraocular pressures were 19 mm Hg in OU.

His external and anterior segment examinations were within normal limits.

The posterior segment of the left eye was unremarkable.

A physical examination revealed a tender lymphadenopathy of the posterior neck and a maculopapular rash of the torso.

Right eye optical coherence tomography was performed (Figure 1B).A, A fundus photograph illustrates a yellowish placoid lesion.

B, Optical coherence tomography demonstrates an irregular thickening of the retinal pigment epithelium layer with small nodular elevations.

Figure 1A shows the findings of the posterior segment examination of the right eye.

The remainder of the examination was unremarkable.


He denied any medication use and had no previous history of ocular surgery or known ophthalmic disorders.On examination, visual acuity with correction was 20/400 OD and 20/100 OS.

Intraocular pressure was within normal limits.

Both pupils were briskly reactive without an afferent pupillary defect.

Dilated fundus examination of both eyes revealed peripapillary retinal whitening emanating from the optic nerve and encroaching into the macula, more pronounced in the right eye (Figure 1A).

Late-phase frames of fluorescein angiogram in both eyes revealed hypofluorescence corresponding to the areas of retinal whitening and obscuring the choroidal fluorescence in these areas, along with nasal peripapillary hyperfluorescence in the areas of retinal whitening (Figure 1B).Fundus photograph (A) and late-phase frame fluorescein angiography (B) of the right eye.

Arrowheads indicate areas of retinal opacification.


Visual acuity was 20/25 OD, and intraocular pressure was 39 mm Hg OD.

A pigmented iris lesion was noted, spanning from the pupillary margin to the anterior chamber angle, with several satellite lesions (Figure 1A).

Gonioscopy showed a pigmented mass infiltrating the anterior chamber angle from the 2-o’clock position to the 5-o’clock position, with extensive pigmentation of the remaining angle structures.

Anterior segment optical coherence tomography demonstrated a hyperreflective lesion invading into the anterior chamber angle.

Ultrasound biomicroscopy revealed a mid-low reflective anterior ciliochoroidal lesion measuring 4.4 mm in height and 14.5 × 9.1 mm in largest basal dimensions, centered in the nasal quadrant and extending circumferentially from the 12-o’clock position to the 7-o’clock position (Figure 1B).

Examination of the posterior pole and of the fellow eye was unremarkable.

Contrasted computed tomography scans of the chest, abdomen, and pelvis were performed, along with baseline liver enzymes, which revealed no evidence of metastatic disease.Clinical appearance of the lesion.

A, Slitlamp photograph of a pigmented iris lesion distorting the pupil, with nasal sentinel vessels.


Laboratory data are summarized in the Table.

Bone marrow karyotyping revealed a normal karyotype; 46 XX [20].

Multigene polymerase chain reaction (PCR) testing of the bone marrow identified a 44–base pair (bp) internal tandem duplication in the FLT3 gene (OMIM 136351), with an allelic ratio of 0.57 (range, 0.01 to >100).

No other mutations on the panel (CEBPA, NPM1, KIT, IDH1, and IDH2) were detected.The patient is more likely to have a worse prognosis.The patient’s prognosis is unaffected because the length of the duplication is small.The patient’s prognosis is unaffected because of low mutation burden.Gene sequencing is needed to identify the exact mutation and prognosticate.

He was diagnosed with acute myeloid leukemia (AML) complicated by leukostasis.


Medical history included glaucoma, gastroesophageal reflux disease, and osteoarthritis.

His home medications included lansoprazole, probiotics, vitamin B12, folic acid, vitamin D3, prednisone (10 mg/d), and timolol eye gel.

He had no sick contacts or recent travel and reported no alcohol or tobacco use.On examination, the patient was afebrile and normotensive, with a pulse of 88/min.

The rash improved initially but recurred at the 10-mg/d prednisone dosing.

He had an erythematous rash, characterized by a combination of palpable purpura and petechiae extending from the axilla to the lower abdomen, back, and lower extremities (Figure 1A).

The face, neck, chest, upper extremities, and oral and nasal mucosa were spared.

The abdomen was nontender, with a healed postoperative scar.

Cardiopulmonary and musculoskeletal examination results were unremarkable.Left, Cutaneous findings on physical examination.

Right, Punch biopsy of rash on lower abdomen (hematoxylin-eosin, ×200).Laboratory tests revealed normal blood cell counts and normal values for renal and hepatic panels.

Urinalysis showed microscopic hematuria (6-10 red blood cells) and 1+ proteinuria.

A spot urine protein-to-creatinine ratio on morning void was 1.17 mg/mg creatinine.

Six weeks ago, he underwent sigmoid colon resection with fistula repair.

He was prescribed prednisone when the rash first presented (starting at 30 mg/d and decreased by 10 mg every 4 days).

For the past year, he had recurrent episodes of diverticulitis complicated by colovesical fistula.

He had no fever, abdominal pain, dysuria, or urinary frequency.


She was a current smoker, was taking oral contraceptives, and delivered a healthy infant (2.5 months prior).

One week later, she had new-onset ascites and diffuse abdominal pain.

The patient was not jaundiced, but her abdomen was distended without rebound or guarding.

An ultrasound of her right upper quadrant showed hepatic vein thrombosis that was confirmed by magnetic resonance imaging of the abdomen.

A laboratory workup and bone marrow biopsy were performed (Table).


The patient reported that these asymptomatic lesions had been present since her adolescence, and she was easily bruised with minimal trauma since birth.

There was no family history of similar cutaneous findings.Clinically, arciform to annular plaques surround white atrophic patches on the left antecubital fossa (A), and skin atrophy is apparent on the dorsal aspects of the hands (B).

C, Histopathologically, a punch biopsy specimen from a papule on the left arm was analyzed with Verhoeff–van Gieson stain (original magnification ×100).On close inspection, the plaques were found to be composed of individual 2- to 4-mm keratotic papules surrounding white atrophic patches.

Physical examination also revealed remarkable skin atrophy on the dorsal aspects of her hands (Figure, B) and feet.

The patient’s skin was generally pale and translucent with visible veins, especially on the chest and abdomen.

The face appeared to be emaciated, with a pinched nose, thin lips, sunken cheeks, and prominent eyes.

A punch biopsy specimen from an individual papule from the left arm was obtained and analyzed under Verhoeff–van Gieson stain (Figure, C).


The patient was born at 38½ weeks by normal spontaneous vaginal delivery.

His medical history was notable for tongue tie from birth.

The lesion had been present since loss of the umbilical stump at 1 week of life.

It bled easily with Valsalva maneuver or trauma.

On examination, he was an alert and healthy-appearing child.

The umbilicus demonstrated a bright red, friable, 5-mm papule (Figure, A).

A shave biopsy specimen was obtained for histologic examination (Figure, B and C).A, Clinical photograph of the red friable papule in the umbilicus.

B and C, Hematoxylin-eosin–stained shave biopsy specimen showing an ulcerated epidermis, colonic mucosa, and granulation tissue (B, original magnification ×2.7; C, original magnification ×10).

The lesion was treated as an infantile hemangioma with timolol by an outside dermatologist and as an umbilical pyogenic granuloma with silver nitrate by the patient’s pediatrician, with minimal improvement.


His medical history included alcohol abuse and cognitive impairment.

Purpura and ecchymoses, initially periorbital, progressed over the previous 12 months.

Examination demonstrated waxy yellow papules and plaques with purpura in the periocular, neck, axillary, trunk, and inguinal regions (Figure, A).

Investigations revealed anemia, abnormal liver function test results, and renal impairment with moderate proteinuria.

The patient’s serum protein electrophoresis (SPEP) and immunofixation urine protein electrophoresis test results were normal.

B, Punch biopsy specimen (hematoxylin-eosin, original magnification × 4).

C, Punch biopsy specimen stained with Congo red (original magnification × 10).

D, Punch biopsy specimen under polarized microscopy (original magnification × 10).

Subsequently, a 4-mm punch biopsy specimen was obtained (Figure, B-D).A, Waxy yellow discoloration of the skin with papules and purpura in the periorbital region.


He was a construction supervisor and had daily contact with moist earth.

No relevant family history was reported.

The muscle weakness started from the right lower limb and gradually spread to the upper limb and contralateral side.

Urinary retention developed 1 month later.

The symptoms ameliorated in the first week but thereafter deteriorated with fever.

The cranial nerve was intact, but he had quadriplegia with a Medical Research Council muscle scale grade of 0 of 5 power, decreased tendon reflexes, and bilateral positive Babinski sign.

Pinprick and vibration sensation were markedly impaired below the nipples.

Multiple enlarged cervical lymph nodes could be palpitated.

The skin was extraordinarily dry, and a pigmentation of 10 mm in diameter at the T2 vertebrae, just on the midline of the back, was noticed.

Total blood T-cell count (CD3+) was 1643/uL (to convert to ×109 per liter, multiply by 0.001), and the patient had a CD4+/CD8+ ratio of 0.89.

Results of blood testing for human immunodeficiency virus, syphilis, and tuberculosis were negative.

Cerebrospinal fluid testing revealed pleocytosis (72 cells/uL; mononuclear cells, 59 of 72), elevated protein concentration (200 mg/dL), and a decreased glucose level (36.0 mg/dL [to convert to millimoles per liter, multiply by 0.0555]), but no organisms were identified on Gram stain or on stain for acid-fast bacilli.

Pulmonary computed tomography showed enlarged lymph nodes in mediastinum and axillary regions.

Results from magnetic resonance imaging of the brain were normal, while magnetic resonance imaging of the cervical spine revealed multiple intramedullary lesions with enhancement (Figure 1).Magnetic resonance imaging of the cervical spine.

Multiple intramedullary lesions and enlarged lymph nodes with strong enhancement were revealed.

The subcutaneous abscess beneath the pigmentation on the back is also shown.

Inset, photograph of the skin lesion on the back.

Because he was suspected of having tubercular meningomyelitis, he received an antituberculosis regimen plus dexamethasone (10 mg daily) for 10 days.

He had no history of central nervous system injury or drug overuse.


The patient’s history was otherwise unremarkable, he had no recent travel outside the United States, and his vaccinations were up to date.On physical examination, the patient had multiple pale, nontender papules distributed over the anterior third of his tongue (Figure).

His mother reported that multiple masses would develop and resolve spontaneously over the course of days to weeks.

The lesions were usually white and the size of a pinhead, and located on the anterior portion of the tongue.

Occasionally they would grow in size and progress to red-filled vesicles that did not burst or bleed.

No other masses were noted to the remainder of his oropharynx.

He was afebrile and had no signs or symptoms of airway obstruction.Multiple discolored masses located on the anterior surface of the tongue.

The timing of the lesions was not associated with fever or other rashes.


His family members and caregivers accompanied him.

At physical examination the patient was pale, sweaty, peripherally hypoperfused, tachypnoeic, and dehydrated, and the abdomen was extremely distended, diffusely tympanic, and tender at palpation.

His blood pressure was 90/70 mm Hg, his heart rate was 114 beats per minute, his oxygen saturation was at 90%, his arterial blood gas pH level was 7.43, his partial pressure of carbon dioxide was 32, his partial pressure of oxygen 68, his laceration lactate level was 5.0, and his white blood cell count was 24 000 mm3.

A plain abdominal radiograph showed a huge colonic distension (Figure 1A).

A computed tomography scan with multiplanar reconstruction was also performed (Figure 1B).A, A plain abdominal x-ray shows a huge colonic distension and a clear coffee-bean-like or “bent inner tube” sign is visible.

B, A computed tomography scan with multiplanar reconstruction.


Her medical history was significant for heavy smoking, reflux, and surgical procedures including a right inguinal hernia repair, total abdominal hysterectomy, and bilateral salpingo-oopherectomy, all more than 5 years prior.

She reported a failure to pass stool or flatus since the onset of symptoms.

She denied hematochezia, melena, or hematemesis.

On examination, she had a distended and tympanic abdomen with tenderness, guarding, and rebound in the epigastrium and right upper quadrant.

Vital signs and standard laboratory test results were unremarkable.An upright abdominal plain radiograph showed a distended, thickened stomach and multiple dilated loops of small bowel with air-fluid levels.

Contrast-enhanced computed tomography demonstrated a focal area of mixed fat density involving the distal small bowel concerning for a lead point with adjacent mesenteric fat stranding (Figure 1).

The scan also revealed multiple bilateral lung nodules.Computed tomography of abdomen.

A, Coronal view demonstrating obstructing intraluminal lesion (arrowhead).

B, Transverse view demonstrating obstructing intraluminal lesion (arrowhead).

The patient was subsequently taken to the operating room for exploratory laparotomy and found to have an obstruction in the distal ileum.


The electrocardiogram showed several premature ventricular contractions.

Results of 30-day Holter monitoring were obtained, and more than 5000 premature ventricular contractions were recorded, including occasional polymorphic ventricular couplets.Transthoracic echocardiography showed normal left ventricular internal dimensions and systolic function.

All valves were structurally normal with trace mitral and tricuspid regurgitation.

A treadmill exercise stress test demonstrated 2 mm horizontal ST-segment depression in inferior and apical leads with exercise.

Cardiac catheterization of the left side of the heart was performed (Figure, A) and can be viewed in the Video.Retrograde filling of the right coronary artery emptying into the main pulmonary artery (A) and a medium-sized area of moderate stress-induced ischemia throughout the right coronary artery territory (B).


He was subsequently tried on various statins, but owing to hip pain thought possibly because of these agents, a rise in liver enzymes, and persistently elevated LDL-C, he was referred to the Boston Medical Center Lipid Clinic Fasting lipid profile in December 2013 on no lipid-lowering agents included an LDL-C level of 232 mg/dL.

He restarted atorvastatin at 40 mg daily because it was determined that his hip pain was more likely because of arthritis than statin therapy.

The adherence and effectiveness of lipid-lowering therapy were then routinely monitored by measuring direct LDL-C levels, which dropped to 113 mg/dL in June 2014 and 115 mg/dL in October 2015, respectively.

Interestingly, his directly measured LDL was 115 mg/dL in October 2015, but a calculated LDL-C was 170 mg/dL in December 2015.

Repeat fasting lipid profiles with simultaneously calculated and directly measured LDL-C levels, apolipoprotein B (Apo B), and lipoprotein (a) (Lp[a]) were subsequently assessed in April 2016 and June 2016.

They confirmed a marked difference between the direct LDL-C level and calculated LDL-C levels (Table).The marked discordance between the direct and calculated LDL levels is the result of a laboratory error.The patient has familial dysbetalipoproteinemia (type III hyperlipidemia).The marked discordance between the direct and calculated LDL levels is related to the effects of very LDL (VLDL), intermediate-density LDL (IDL), and/or Lp(a).The marked discordance between the direct and calculated LDL levels is the result of excess VLDL cholesterol only.


His medical history was notable for allergic rhinitis and well-controlled type 2 diabetes mellitus.

Physical examination revealed tenderness to palpation over the right nasal bridge and mild right proptosis.

The prior biopsy diagnosis from the area of swelling was inflammatory nasal polyp.

Flexible and rigid nasal endoscopy demonstrated a right-sided exophytic mass visible between the middle turbinate and nasal septum.

Computed tomography showed a large, right-sided mass centered in the ethmoid sinus with expansion into the anterior skull base, anterior cribriform plate, and right medial orbit.

Magnetic resonance imaging showed vascularity in the lesion and early intracranial involvement with transdural spread but no evidence of invasion into the meninges or brain.

The final pathology report showed an infiltrative, low-grade, malignant spindle cell neoplasm with immunoreactivity for BCL2 protein and neural marker, S-100 protein, and focal immunoreactivity for smooth muscle markers SMA and HHF35 (Figure).

Cytoplasmic immunoreactivity for β-catenin was noted, and nonreactive immunostains included CD31, CD34, epithelial membrane antigen (EMA), and CD99.

In addition, there was minimal mitotic activity, and no tumoral necrosis was present.

There was no regional or distant metastasis, and TNM staging was cT4N0M0.Histopathologic photomicrographs of a biopsy specimen from a mass centered in the ethmoid sinus.

C, Tissue section showing strong nuclear and cytoplasmic immunologic staining for S-100 protein.

D, Immunologic staining for smooth muscle actin showing patchy immunoreactivity in tumor cells.

The patient was taken for surgery, and findings from intraoperative frozen section analysis were consistent with a spindle cell neoplasm.

Definitive skull base resection of the mass was deferred until final pathological diagnosis was obtained, given the morbidity with skull base resection.

B, Invagination of respiratory-type epithelium.


Her medical history was significant for herpes zoster and self-limited vertigo approximately 3 years prior.

Her physical examination was remarkable for left-sided facial swelling.

No deficits of the facial or trigeminal nerves were detected.

Magnetic resonance imaging (MRI) was performed (Figure).Magnetic resonance imaging, axial views.

A. T1-weighted image demonstrating a mass lying on the anterior surface of the eroded left mandibular condyle with homogeneous isointensity relative to skeletal muscle.

B, Postcontrast T1-weighted image with fat suppression showing homogeneous, avid enhancement of the mass.

C, T2-weighted image showing homogeneous moderately hyperintense signal.

D, Diffusion-weighted image is significant for marked diffusion restriction.


Fine-needle aspiration was performed twice, each time with inconclusive results.

Computed tomography (CT) of the neck showed a heterogeneous mass located immediately adjacent to the tail of the left parotid.

Pathologic findings revealed a 3.0 × 2.9 × 1.9-cm, encapsulated, tan, soft nodule within the specimen.

The nodule had peripheral cystic spaces as well as focal areas of hemorrhage and a 0.5 × 0.4 × 0.4-cm area of calcification within the periphery.

The entire tumor was confined within a periparotid lymph node, almost completely replacing it.

Histopathologic findings (Figure) showed a mixture of dark, granular, basophilic acinar cells and eosinophilic intercalated ductal cells.

The acinar cells contained periodic acid–Schiff–positive, diastase-resistant intracytoplasmic granules, whereas the ductal cells were both fusiform and cuboidal forming small ductlike structures.

The neoplasm also exhibited focal areas of hyaline sclerosis without necrosis.

He underwent a left superficial parotidectomy with en bloc removal of the mass.


This change prompted a visit to an optometrist, who found a mild decrease in visual acuity and minor cataract in the right eye.

His primary care physician diagnosed his ear pain as acute otitis media and prescribed a course of amoxicillin-clavulanate; however, the young man’s vision continued to deteriorate and became associated with the onset of right eye swelling and forehead tenderness.

The patient had not experienced nasal congestion, epistaxis, weight loss, fevers, or chills.

A repeat eye examination by an ophthalmologist was performed and showed normal peripheral visual acuity with a decrease in central vision and confirmed proptosis.

Physical examination included right eye proptosis and restricted eye movement.

A computed tomographic (CT) scan with contrast of the face showed a small relatively homogenous mass in the right anterior nasal cavity invading the right orbit, and a magnetic resonance image (MRI) with contrast showed a right superior nasal cavity mass, with invasion of the right orbit and right ethmoidal sinus with extension to the overlying soft-tissue scalp (Figure).

A 30° endoscope was used to visualize the superior nasal cavity and revealed a fleshy red soft-tissue mass.

Several biopsy specimens were taken and sent for frozen pathologic evaluation.A, Postintravenous contrast computed tomographic (CT) scan of the face showing a relatively homogenous mass of the right ethmoid complex with invasion of the orbit and extension to the nasal cavity (arrowhead).

B, Fast spin echo (FSE) T2 magnetic resonance image (MRI) of the right ethmoidal/orbital soft-tissue mass (arrowhead).

C, Positron emission tomographic (PET) scan of the face with fludeoxyglucose F 18 showing increased uptake within the right ethmoid air cells and nasal cavity, and in the medial right orbit.


Her ocular history was significant only for refractive error.

Her medical history revealed systemic hypertension, depression, and obesity.

Her current medications included hydrochlorothiazide and fluoxetine.

On review of systems, she endorsed nausea as well as paresthesia in her hands.Neuro-ophthalmic examination revealed visual acuities of 20/20 OD and 20/40 OS, with no pinhole improvement.

With the Amsler grid, she reported significant metamorphopsia in the left eye.

Color vision (Ishihara pseudoisochromatic plates) was within normal limits bilaterally, although it was noted to be slightly slower in the left eye.

Pupils were symmetric with slow responses bilaterally but without afferent defects.

Applanation tonometry revealed pressures of 16 mm Hg OD and 17 mm Hg OS.

Slitlamp examination revealed no cells in the anterior chamber or the anterior vitreous in either eye.

Automated (Humphrey) visual field testing revealed enlargement of the blind spot in the right eye (mean deviation, −2.91 dB) and generalized, nonspecific depression in the left eye (mean deviation, −3.41 dB).

Examination of her fundus was notable for bilateral optic disc swelling (Frisén grade 2 in each eye) as well as unilateral macular exudates, subretinal fluid, and subretinal hemorrhages in the left eye (Figure 1).

Results from brain magnetic resonance imaging with magnetic resonance venography with and without contrast were normal.A, Color fundus photograph demonstrating Frisén grade 2 optic disc edema.


On examination, visual acuity was 20/25 OD with correction, and the superior cornea showed an intact epithelium, mild stromal thinning, and pannus with faint yellow-white subepithelial deposits at the leading edge (Figure 1A).

There were no other abnormalities reported on examination.

B, Appearance of the cornea 1 year later, with more prominent neovascularization and progression of deposits toward the visual axis.A year later, best-corrected visual acuity had decreased to 20/30 OD with against-the-rule astigmatism.

The patient was treated conservatively with lubrication.

Slitlamp photographs of corneal findings.

A, Appearance of the cornea at time of the initial presentation.


Within 24 hours he developed prodromal flu like myalgias and malaise.

After 48 hours, the patient experienced severe bilateral photophobia, conjunctival injection, lacrimation, and blurred vision.

His photophobia peaked at 72 hours but had significantly improved by the time of his initial ophthalmic review 4 days after the infusion.

His uncorrected visual acuities were 6/5 bilaterally.

His intraocular pressures were within normal limits.

An anterior segment examination demonstrated symmetric bilateral nasal sectoral subconjunctival hemorrhages (Figure).

Examination of his anterior chambers revealed a 2+ cell count and 2+ flare count in both eyes without hypopyon or synechiae.

The posterior segment was unremarkable, with no evidence of vitritis, retinitis, or macular edema.Routine investigations returned results of an elevated alkaline phosphatase level (230 U/L) and mild-positive (1:160) antinuclear antibody speckled pattern.

The complete blood cell count and coagulation profile were normal.

The results for extractable nuclear antigen antibodies, antidouble-stranded deoxyribonucleic acid, rheumatoid factor, human leukocyte antigen B27, QuantiFERON-TB Gold (Quest Diagnostics), syphilis serology, elevated serum angiotensin-converting enzyme level, and a chest radiography were all negative.

Topical dexamethasone, 0.1%, and homatropine, 2%, were commenced, with complete resolution of uveitic signs within 2 weeks.

Dexamethasone frequency was initially once hourly for 3 days and was followed by a standard weekly tapering course.


Over subsequent days, he developed right periorbital erythema, edema, and pain, with blisters appearing on the eyelid skin 1 day prior to presentation.On examination, his pulse was 120 beats per minute, blood pressure was 92/62 mm Hg, and temperature was 38.2°C.

The right upper and lower eyelids were warm, erythematous, edematous, and tender, with large fluctuant blisters (Figure, A).

Erythema tracked down the cheek, and there was right cervical lymphadenopathy.

The patient did not cooperate for a visual acuity assessment, but there was no afferent pupillary defect.

Limited penlight examination revealed a normal anterior segment except for 360° conjunctival chemosis.

Noncontrast computed tomography of the orbits demonstrated extensive right preseptal soft tissue swelling and slight enlargement of the right lateral rectus muscle with minimal orbital fat stranding.

The right globe was slightly proptotic (Figure, B).

Laboratory testing revealed a white blood cell count of 32.6 K/µL (to convert to × 109 per liter, multiply by 0.001), with 95% polymorphonuclear lymphocytes.A, External photograph of the right eyelids demonstrates significant erythema and edema with large blisters.


She had no history of dysphagia, dyspnea, recent upper respiratory tract infection, injury, or surgery.

She also had no weight loss, pain, or fever and had no history of tobacco or alcohol use, radiation exposure, family history of thyroid cancer, and no previous thyroid dysfunction.

She had a medical history of high-grade osteosarcoma with areas of leimyosarcoma of the tibia which had been treated with right above-knee amputation and chemotherapy 4 years prior to presentation.

She was followed up in the oncology clinic without any recurrence or metastases.

She was also diagnosed with squamous cell carcinoma of the cervix 2 months earlier and was awaiting surgery.

Thyroid function test results were normal.

Physical examination revealed a palpable nontender, firm mass and no cervical lymphadenopathy.

Computed tomography (CT) of the neck revealed a 6.0 × 3.4 × 4.4-cm calcified left thyroid lobe mass (Figure, A).

Positron emission tomography–computed tomographic (PET-CT) imaging showed increased uptake in the left thyroid gland.

The neoplastic cells were positive for p53, vimentin, and smooth muscle actin, and negative for S-100, thyroid transcription factor-1 (TTF-1), and CD34 (Figure, B).A, Computed tomographic image reveals a calcified mass (blue arrowhead).


He was born by spontaneous vaginal delivery at 36 weeks’ gestational age with a birthweight of 3048 g (6.7 lb) with Apgar scores of 9 and 10.

There were no complications during the prenatal and perinatal periods.

His mother had no history of ringworm infection, positive IgG antibodies against rubella virus and herpes zoster virus, and serology findings negative for human immunodeficiency virus, hepatitis B virus, and syphilis.

His family history was unremarkable.On examination, he had a temperature of 38.0°C, a heart rate of 150/min, and a respiratory rate of 60/min.

Slightly scaly annular erythematous plaques with central atrophy and raised margins were present on the forehead and periorbital areas (Figure).

The remainder of the physical examination was unremarkable.


The GVHD occurred secondary to a bone marrow transplant in 2014 for treatment of chronic lymphocytic leukemia.

One month prior to commencing oral azathioprine therapy, the patient noted the growth of nodules on the genital and perianal region, with 1 ulcerated nodule in the perianal area associated with painless bleeding on trauma.

Additionally, she had sclerodermatous plaques on the lower legs, scarring alopecia on the scalp with minimal hyperkeratosis, nail dystrophy and lichenoid changes, erythematous changes in both feet, and desquamation in the lower legs and on the back and arms suggestive of eczematous or postlichenoid changes as part of her lichenoid GVHD.

The lesions were otherwise asymptomatic.On examination she had several yellow-colored nodules, some of them ulcerated with extrusion of yellow-colored discharge on the left labia majora and on the perianal area with surrounding inflammatory reaction (Figure 1).

Initial investigations revealed a white blood cell count of 13.1 × 103/μL (to convert to billions per liter, multiply by 0.001); however, the results of the rest of her blood tests including the full blood count and electrolytes, urea and creatinine, and liver function tests were otherwise stable and unremarkable.Clinical photographs of cutaneous nodules in a woman with graft-vs-host disease.

A, Multiple erythematous eroded nodules in the perianal area.

B, yellowish nodules located on the left labia majora.

At the time of review she was being treated with oral azathioprine (50 mg twice daily), tacrolimus (0.5 mg twice daily), and prednisone (25 mg daily) therapy.

She was also receiving monthly intravenous immunoglobulin, prophylactic oral fluconazole, acyclovir, sulfamethoxazole-trimethoprim, and penicillin.


She reported a distant history of discoid lupus, and was taking 2 antihypertensives but no other oral or topical medications.

She reported that these appeared 1 to 2 months following placement of the tattoo and were restricted to areas where the artist created pink zones by layering white ink over red ink.

She denied pain, fevers, and chills and had no history of skin cancer.

Physical examination revealed well-demarcated erythematous to violaceous verrucous nodules on the right lateral leg and dorsal foot (Figure 1A).

A punch biopsy specimen from a representative nodule was obtained, with an additional biopsy for tissue culture (Figure 1B).A, Verrucous nodules are restricted to zones of pink pigment within the tattoo, sparing other colors present.

B, Histologic reaction pattern from punch biopsy specimen of right lower leg nodule (hematoxylin-eosin, original magnification ×4).


Six days prior to this admission, she had been hospitalized for a photo-induced flare of acute cutaneous lupus erythematosus (ACLE).

At readmission, she was febrile with a temperature of 101.5°F, and on examination, she had a worsening, exquisitely tender rash with several blisters across her right arm.

Physical examination revealed erythematous plaques with superficial desquamation in the malar distribution of the face, nose, ears, and medial forehead (Figure, A), as well as bilateral extensor arms, chest, posterior neck, and upper back.

Several large bullae were located on the right arm (Figure, B).

Numerous flat and raised 2-zoned atypical targets with dusky centers were appreciated on the forearms, abdomen, back (Figure, C), thighs, legs, palms and soles.A, Dusky malar erythema with focal heme crusting.

C, Diffuse typical and atypical target lesions of the back.

D, High-power view (original magnification 100×) of punch biopsy obtained from left abdomen demonstrating dyskeratosis with superficial perivascular inflammation and interface changes.Hemogram test results revealed a normocytic anemia (mean corpuscular volume, 99 fL; hemoglobin, 11.7 g/dL [to convert to g/L, multiply by 10.0]; hematocrit, 33.4%), in addition to thrombocytopenia (platelet count, 81 K/μL).

Other pertinent laboratories included hypocomplementemia (C3 of 42 mg/dL; C4 of 3 mg/dL), a speckled antinuclear antibody titer of 1:1280, and an antidouble-stranded DNA titer of 1:80, along with positive anti-Smith, antiribonucleoprotein, and SSA/anti-Ro antibodies.

Bacterial blood, urine, stool and cerebrospinal fluid cultures, and a hepatitis panel revealed no infectious source.

Punch biopsy of an abdominal atypical target lesion was performed (Figure, D).


No significant history of illness was noted in the patient or among family members.Neurological examination on admission revealed normal mental status, and the results of cranial nerve examination were normal.

Although these symptoms had resolved after 3 hours’ rest, they recurred 2 hours prior to hospital admission.

In addition, the patient had begun to experience weakness and numbness of his limbs, with more severe symptoms on the right side.

The symptoms began to gradually resolve 2 hours following admission, and normal function had returned within 2 days.

Although the patient had cavus feet, no atrophy was observed in the distal lower limbs (Figure, A).

Muscle strength was classified as grade 4 for the left limbs and grade 3 for the right limbs, according to Medical Research Council criteria, and muscle tone was diminished.

The sensory examination was unremarkable.

Deep reflexes were diminished or absent.

However, bilateral positive Babinski signs were observed.

Results from laboratory examinations, including blood electrolytes, cerebrospinal fluid, and lactate, were normal.

Oligonucleotide bands and aquaporin 4 detection were negative.

Craniocervical computed tomographic angiography results were normal.

Cerebral magnetic resonance imaging (MRI) revealed abnormal bilateral increases in T2 signal and diffusion restriction in the periventricular areas and the splenium of corpus callosum (Figure, B).

Interestingly, a significant reduction of the abnormal signal was noted on MRI 3 months later.

Electrophysiological examination of peripheral nerves revealed extensive bilateral nerve conduction abnormalities.

Significantly reduced motor nerve conduction velocity was also observed in the median nerves (38.3 m per second in the left and 36.5 m per second in the right).A, Image shows patient’s pes cavus.


Her relevant history included a pituitary macroadenoma, which had been resected 30 years prior, followed by radiation.

There was no evidence of subsequent recurrence.

There was no family history of ptosis, ophthalmoplegia, or myopathy.

Diplopia was frequently present after repeatedly changing direction of gaze.

There was no associated headache or ocular or periorbital pain.

She had not noticed any injection of the sclera.

Her family and friends made no comments regarding exophthalmos.

She had not noticed any deficits in axial or appendicular strength, rapid fatigability, or dysphagia.

Her symptoms did not exhibit diurnal variation.

She had not noted any changes in her hair, skin, or nails.

She had no subjective disturbance of thermoregulation.

The patient was a retired English teacher.Examination demonstrated anisocoria (right pupil larger than left), which was accentuated in bright ambient light; mild right ptosis; and mildly restricted supraduction, adduction, and infraduction of the right eye (Video, prepared by N.T.).

The second half of the Video (from 24 seconds on) demonstrates marked restriction of elevation, depression, and abduction in the right eye after eccentric gaze.

The patient’s neurological examination demonstrated a normal level of consciousness, fluent speech, normal comprehension, good attention, normal cranial nerve function aside from the aforementioned deficits, full strength, normal sensation to proprioception and temperature, symmetric reflexes, absence of ataxia, and a stable, narrow-based gait.

A recent contrast-enhanced brain magnetic resonance image showed a stable intracanalicular vestibular schwannoma on the left, which had been monitored for 8 years.


He had a family history of ischemic heart disease (both parents) but no family history of neurological disorder.

He exercised regularly (5 times per week) and consumed 2 to 4 standard drinks per week.

He was a former smoker with a 2-year pack history and denied any illicit drug use.Cognitive testing revealed deficits in executive function and speed of information processing.

When questioned, he described subtle balance problems without falls developing over the past 3 years.

With the exception of profound difficulties with handwriting, motor symptoms did not affect livelihood or activities of daily living.

There was no tremor reported in the nondominant hand or other limbs or symptoms of autonomic dysfunction.

Neither he nor his wife reported any changes in cognitive function.

Examination of eye movements and speech revealed jerky eye pursuit, saccadic dysmetria, and moderate slurring of speech.

Additional motor signs included abnormal handwriting (Figure 1A), bilateral intention tremor, mild rigidity (upper extremities), and moderately impaired heel tapping.

He demonstrated moderate body sway while standing, was unable to stand on 1 foot for more than 10 seconds, and had impaired tandem walking.

B, T2-weighted fluid-attenuated inversion recovery image from brain magnetic resonance imaging showing white matter hyperintensities in the middle cerebellar peduncles.Routine blood test results were normal.

Brain magnetic resonance imaging showed moderate volume loss in the cerebral hemispheres bilaterally as well as the cerebellum and brainstem.

Abnormal signal intensity was noted in the cerebral hemispheric white matter bilaterally, the middle cerebellar peduncles (Figure 1B), the cerebellar white matter, and the pons.

His medical history comprised surgeries of the hand (laceration repair), leg (fracture repair), knee (reconstruction), and ear (stapedectomy); these were not related to the presenting symptoms.

Gait, posture, and walking capacities during a timed 6-m walk were normal.A, Handwriting task from the motor examination showing abnormal handwriting.


Pregnancy was uncomplicated and there was no history of teratogenic exposure or family history of congenital defects.

She was asymptomatic, moving all limbs, urinating, and defecating normally.

These skin changes included a red patch on the central lower back with a soft nodule located on top of the patch.

Additionally, she had a pedunculated red papule positioned on top of the red stain and soft nodule.

Her prenatal screens, including 20-week ultrasonography, were normal.

Ultrasonography of the spine obtained prior to the visit showed no abnormalities.Photograph depicting a red patch with overlying soft nodule and red pedunculated papule in the lower midback of a neonate.


Medications at the time of referral were 1000 mg per day of ursodeoxycholic acid and 2 g of colestipol twice daily for symptomatic relief of pruritus.

She first noted the appearance of periorbital xanthelasmata 2 years after PSC diagnosis (Figure 1A).

Approximately 6 months prior to referral, she developed marked worsening of biliary obstruction, deterioration of liver function, and clinical jaundice (aspartate aminotransferase, 145 U/L; alanine aminotransferase, 111 U/L; alkaline phosphatase, 726 U/L; and bilirubin, 6.7mg/dL), and she noted palmar xanthomata in the creases of her palms and fingers (Figure 1B).

She was normocholesterolemic prior to the diagnosis of PSC (total cholesterol [TC], 188 mg/dL [to convert to millimoles per liter, multiply by 0.0259]).

Following the diagnosis of PSC, she developed moderate hypercholesterolemia (representative TC, 256 mg/dL).

Periorbital xanthelasmata (A, arrowheads) and palmar xanthomata (B, arrowheads) in a patient with severe hypercholesterolemia and primary sclerosing cholangitis.At the time of referral, she had severe hypercholesterolemia (TC, 832 mg/dL; triglycerides, 114 mg/dL [to convert to millimoles per liter, multiply by 0.0113]; and high-density lipoprotein cholesterol, 18 mg/dL; low-density lipoprotein cholesterol was not calculated).

The majority of TC (719 mg/dL) consisted of free cholesterol (518 mg/dL) instead of the usual esterified cholesterol.

Serum phospholipids levels were high (1186 mg/dL), while triglycerides were normal (97 mg/dL).

Fast protein liquid chromatography analysis of serum lipoproteins, after ultracentrifugation to remove very-low-density lipoprotein, indicated the unique composition and distribution of lipid classes in a special form of dyslipidemia known as lipoprotein X (LpX), ie, high unesterified cholesterol and phospholipids in large lipid-containing particles.


She had not experienced otalgia, otorrhea, or tinnitus.

Physical examination revealed a mass obstructing the right external auditory canal and House-Brackmann grade 2 facial nerve weakness on the right.

Audiogram revealed right-sided moderate to profound mixed hearing loss.

Computed tomography revealed a soft-tissue mass emanating from the middle ear involving the facial canal with surrounding bony erosion, including dehiscence of the tegmen, cochlea, bony labyrinth, lateral semicircular canal, and jugular foramen.

The patient underwent transtemporal mastoidectomy and debulking.

Magnetic resonance imaging during embolization revealed intense enhancement in the right middle ear extending from the epitympanum to the hypotympanum with extension into the right external auditory canal (Figure, B).

The mass was adherent to the underlying bone and had invaded the facial canal but not the nerve itself.

However, owing to the mass’s vascularity and significant bleeding, the operation was aborted, and she was sent for embolization (Figure, A).

She returned to the operating room, and the vascular mass was found to extend inferiorly to the jugular bulb and carotid and anteriorly into the eustachian tube.

Immunohistochemical stains of the specimen indicated cells positive for synaptophysin with a sustentacular pattern of cells positive for S-100 (Figure, C and D).A, Mastoidectomy, visualization of vascular mass.

B, T1-weighted axial magnetic resonance image (MRI) showing enhancement of right middle ear extending to external auditory canal.

C, Hematoxylin-eosin, original magnification ×40.

Clusters of cells surrounded by vascular tissue.

D, Synaptophysin stain, original magnification ×40.

Nests of strongly staining neuroendocrine cells separated by vasculature.


His medical history revealed a long-term history of substance abuse with active alcohol and tobacco consumption, chronic obstructive pulmonary disease, and epilepsy (tonic-clonic seizures, badly controlled owing to a lack of adherence to therapy).

This lesion had developed spontaneously 3 months prior to consultation without an identifiable inciting event.

He could recall no trauma and described a slow but progressive increase in the volume of this otherwise asymptomatic lesion.

Clinical intraoral examination of this fully edentulous patient revealed a nontender, mobile, cystic nodule, approximately 1 × 1 cm on the vestibular side of the lower left lip with outflow of a clear serous fluid on palpation (Figure, A).

After hematoxylin-eosin staining, light microscopy revealed an endophytic growing lesion, which consisted of an acanthotic epidermoid epithelium organized in broad papillary folds, with at its periphery an infiltrating border.

At the surface of these papillae, the epithelium was sometimes columnar.

Mucocytes were present, individually dispersed throughout the epithelium, but also organized in small tubuloacinar structures emptying onto the surface.

The epithelium was infiltrated by neutrophils.

Atypia or mitotic figures were absent, and the subepithelial stroma contained normal-appearing seromucous acini (Figure, B and C).A, Clinical presentation of the cystic lesion of the lower left lip.

The papillary fronds lining the interior of the lesion.

The lesion is well demarcated from the subepithelial stroma, and has an infiltrating border.

The cells at the surface of the epithelial folds are columnar.

Mucocytes organized in acinar structures empty on the surface epithelium but are also individually dispersed between the epidermoid cells.

The lesion was excised surgically and the specimen sent for additional histological examination.

B and C, Histopathologic images, hematoxylin-eosin.

C, Detail at the base of one of the papillae.


On presentation, he also reported decreased acuity in his left lower visual field, continued swelling with increasing pain, and worsening trismus.

The patient also reported hypoesthesia of the left maxillary division of the trigeminal nerve.

No purulence or clinically significant bleeding was identified.

Physical examination revealed mild tenderness over a mass that extended inferiorly to the zygoma into the buccal cavity and posterolaterally to the left superior molars.

Fiber-optic scope of the nasopharynx revealed a small lesion posterior to the left middle turbinate.

Contrast-enhanced magnetic resonance imaging of his head, neck, and brain was performed (Figure, B and C).A, Computed tomographic (CT) image shows a uniformly hyperdense mass extending into the left infratemporal fossa with slight extension of the mass through the medial aspect of the posterior wall of the maxillary sinus and widening of the sphenopalatine foramen.

B, Contrast-enhanced magnetic resonance image (MRI) with fat saturation shows a mass with mild punctuate areas of hypointense signal (suggestive of vascularity) terminating in the left buccinator space with extension into the nasal cavity, maxillary sinus and inferior orbital fissure.

C, A heterogenous mass in the left retromaxillary region and infratemporal fossa with hyperintense signal and mild salt-and-pepper appearance consistent with vascularity.

D, Gross specimen is in similar orientation as mass seen in panel B.

He underwent a third maxillary molar extraction and attempted incision and drainage of the area with no improvement in symptoms.

A contrast-enhanced computed tomographic (CT) scan was performed (Figure, A), and the patient was referred to the otolaryngology clinic.


She noted a discretely palpable mass in the left parotid region during these episodes.

The patient returned days later with acutely worsening left facial swelling, which she noticed while straining.

On presentation, she was diagnosed as having malignant hypertension and had a palpable parotid lesion noted on physical examination.

When asked to perform a Valsalva maneuver, she was noted to have more pronounced left facial swelling (Figure, A).

However, at the time of clinic presentation, she had no palpable masses on physical examination.

Ultrasonography performed on the day of initial evaluation revealed no intraparotid masses, lesions, or stones.

A short tau inversion recovery (STIR) image is shown in the Figure, B.

Magnetic resonance angiogram was obtained (Figure, C and D).A, The patient performed a Valsalva maneuver, with increased left parotid gland and neck swelling.

B, Coronal T2-weighted short tau inversion recovery (STIR) image demonstrating a T2 hyperintense lesion measuring 3.7 × 3.4 × 7.4 cm involving the left parotid gland and extending to the left side of the neck.

C and D, T1-weighted, fat-suppressed, gadolinium-enhanced angiography.

C, Arterial section demonstrating no evidence of significant high flow component.

D, Delayed phase demonstrating a homogenous contrast enhancing lesion.

The patient was encouraged to return if she noticed acute return of swelling so that she could be evaluated when symptomatic.


She had a history of upper respiratory tract infection with nasal congestion and discharge being treated with oral antibiotics.

She also recently received a diagnosis of migraines.

Computed tomographic imaging from an outside hospital 3 weeks prior was reported as unremarkable.

The patient had an uncorrected visual acuity of 20/50 OU.

Her pupils were round and reactive without an afferent pupillary defect.

Confrontation visual fields revealed superotemporal, inferotemporal, and superonasal defects in both eyes.

The results of her motility examination showed a complete absence of abduction on both eyes, consistent with bilateral sixth nerve palsy.

The results of a fundus examination showed blurred optic nerve margins nasally (Figure 1).Fundus photographs demonstrating blurred nasal margins of the right (A) and left (B) discs.


He had a history of hypertension and non-Hodgkin lymphoma, which was last treated in 2012 without evidence of recurrence.

The patient was told to follow-up as needed.About 2 months later, the patient called on the telephone to say that he had a new onset of blurry vision and photopsias in the right eye that started about 2 days prior.

His visual acuity was 20/25 OU, and neither fundus was seen to be abnormal.

Optical coherence tomography (OCT) revealed vitreomacular adhesion in the right eye and a macular posterior vitreous detachment in the left.

The anterior segment and the anterior vitreous of his right eye were still clear.

However, an examination of the posterior pole of the right eye revealed a light white, deep subretinal/choroidal ring surrounding the optic nerve, with smaller rings around the edge of the larger ring (Figure, A).

Optical coherence tomography of the right eye revealed loss of the outer retina (more nasal than temporal to the fovea), whereas OCT of the left eye revealed that it was normal (Figure, B).

The results of fluorescein angiography and fundus autofluorescence were both unremarkable (data not shown).A, Fundus photograph of the right eye at the time of presentation shows a white-gray ring centered on the optic nerve.

B, Optical coherence tomography (OCT) of the right eye reveals significant loss of the outer retina, especially nasal to the fovea.

He denied any recent viral-type illness.

The patient was asymptomatic at the time.


He also had associated ear pain, hearing loss, and severe headaches.On presentation, his visual acuity was light perception OD and 20/600 at 1 m OS.

He also had ear drainage with inflamed tympanic membranes and ear tubes in place bilaterally.

The right eye had a 1+ afferent pupillary defect.

A dilated fundus examination revealed grade 2 optic disc edema with an inferior disc hemorrhage in the right eye and grade 1 edema in the left eye.

The remainder of the examination was unremarkable.Laboratory results revealed elevated C-reactive protein levels and erythrocyte sedimentation rates at 78 mg/L and 77 mm/h, respectively, with negative antinuclear antibody test results (to convert C-reactive protein to nanomoles per liter, multiply by 9.524).

His white blood cell count was elevated at 14 910/μL without eosinophilia (to convert to × 109/L, multiply by 0.001).

Cerebrospinal fluid studies were remarkable only for an elevated white blood cell count of 72/μL (79% lymphocytes) and elevated protein level at 97 mg/L, while Gram stain and culture were negative.

Opening pressure was 17 cm H2O.A magnetic resonance venogram with and without contrast ruled out venous occlusions.

Finally, magnetic resonance imaging demonstrated diffuse pachymeningeal (dural-arachnoid) enhancement (Figure) without leptomeningeal (pial) enhancement, left-sided mastoiditis, and subtle optic nerve enhancement.Coronal T1 with gadolinium showing dural enhancement (blue arrowhead) and optic nerve enhancement (white arrowheads).


Review of systems was remarkable for concomitant hearing loss and vertigo for 1 month.

She was alert but confused and disoriented, and she manifested gait imbalance and ataxia.

White blood cell count was elevated at 14 600/μL (to convert to ×109 per liter, multiply by 0.001).

Results from computed tomography of the head were normal, but magnetic resonance imaging of the brain revealed multifocal punctate areas of restricted diffusion.

A lumbar puncture showed lymphocytosis (80%), normal glucose levels, and protein levels greater than 125 mg/dL.

Results from cerebrospinal fluid polymerase chain reaction were negative for herpes simplex virus, varicella zoster virus, and cytomegalovirus.

Results from laboratory tests for hypercoagulable states, antinucleolar antibodies, antineutrophilic cytoplasmic antibodies, human immunodeficiency virus, Lyme disease, and tuberculosis were unrevealing.Ophthalmology was consulted.

Visual acuity was 20/20 OU with normal pupil response, visual fields to finger counting, motility, and intraocular pressure.

Anterior segment biomicroscopy was normal without vitreous cell or haze.

The optic discs were pink with sharp margins.

The macula appeared flat, and there were scattered peripheral retinal hemorrhages and areas of retinal vascular nonperfusion in both eyes.

Optical coherence tomography showed inner retinal thinning with preservation of outer retinal architecture.


In the emergency department, the patient was awake but restless and combative and was subsequently intubated.

He was a restrained driver noted to be awake at the scene of the collision and had to be extracted from the vehicle.

He was hemodynamically stable on route to the hospital.

He was hypotensive on arrival but responded transiently to fluid resuscitation.

Multiple closed long bone fractures of the upper and lower extremities were noted.

The chest radiography (Figure 1A) showed marked elevation of the left hemidiaphragm.

The pelvic radiography revealed an unstable fracture involving bilateral pubic rami and the left sacroiliac joint.

Computed tomography of the head and cervical spine showed no evidence of injury.

The pelvis was splinted in the emergency department.

He remained transiently responsive to fluid resuscitation and was taken for emergent computed tomography.

A computed tomographic scan of the chest (Figure 1B) and abdomen was then performed, and the patient was taken to the operating room.A, single-view supine chest radiography.


Her previous abdominal surgery included a hysterectomy for menorrhagia.

These episodes started approximately 4 years prior, occur approximately every 3 to 4 months, and are associated with crampy abdominal pain.

Colonoscopies were significant only for diverticulosis without a clear source of bleeding.

She had computed tomography of the abdomen and pelvis that showed eccentric and irregular masslike thickening of the sigmoid colon of approximately 7 cm with a wall thickness of 1.4 cm (Figure 1).

Repeat colonoscopy showed an exquisitely painful nodule at the rectosigmoid junction.

There were no stigmata of recent bleed, and biopsy showed normal colonic mucosa.Axial (A) and coronal (B) computed tomography of the pelvis with rectal contrast.

The images show thickening and narrowing of the sigmoid colon (arrowheads).

Although she has been hospitalized, she never required a transfusion.

There is no family history of colon cancer.Physical examination showed no abnormalities.


In the week following her first treatment, the patient reported a few mild morning headaches that improved with acetaminophen.

After receiving 3 cycles of ipilimumab, 3 mg/kg, and nivolumab, 1 mg/kg, and 8 weeks after her first treatment, the patient reported experiencing daily headaches for at least the prior week and a half.

The location of her headaches varied, and there was no associated eye or temple pain.

Also at this time, the patient reported low energy levels and difficulty reading; however, physical examination showed no gross visual field defects.

Laboratory workup conducted 8 weeks after initiating treatment included adrenocorticotropic hormone (ACTH) and cortisol levels that were measured at 25 pg/mL (reference range, 10-60 pg/mL) and 16.8 μg/dL (reference range, 6-24 μg/dL), respectively.

Thyroid-stimulating hormone (TSH) level was 0.82 mIU/L (reference range, 0.5-5.0 mIU/L), which was gradually decreasing compared with 1.41 mIU/L 5 weeks earlier and 1.21 mIU/L 2 weeks earlier.

Her total triiodothyronine level was measured at 73 ng/dL (reference range, 80-200 ng/dL) and free thyroxine level was 1.0 ng/dL (reference range, 0.9-1.7 ng/dL).

Her serum sodium level was measured at 138 mEq/L; 1 week later it was measured at 135 mEq/L (reference range, 135-145 mEq/L).

Contrast-enhanced magnetic resonance imaging (MRI) of the brain was performed for further assessment (Figure).Magnetic resonance imaging (MRI) of the brain obtained 8 weeks after initiating ipilimumab (A-C) and nivolumab treatment and at follow-up (D).


She was previously healthy, did not consume alcohol, and had no personal or family history of liver disease.

She took no prescription medications; however, approximately 6 months prior to the onset of symptoms, she began taking a nutritional supplement (Nature Made Beta Carotene, Otsuka Pharmaceutical) manufactured in Japan and available online in China.

This supplement contained 1.8 mg of beta carotene per tablet, and she had been taking 2 tablets daily for the past 6 months.

She had no other dietary changes during this period, in particular, no increased intake of carrots or other yellow- or orange-colored fruits or vegetables.

Physical examination revealed yellow-orange pigmentation of her palms and soles (Figure).


His only medication was omeprazole (20 mg daily).

He felt well until 6 days prior, when he awoke with diffuse muscle cramps following a strenuous day of moving boxes.

He subsequently developed oliguria that progressed to anuria.

His usual fluid intake had not changed.Physical examination was notable for moist mucous membranes, clear lungs, no lower extremity or periorbital edema, and no jugular venous distension.

Bladder scan showed 50 mL of urine, which was collected via straight catheterization.

Three liters of normal saline was administered, with no further urine production.Laboratory testing revealed a blood urea nitrogen level of 90 mg/dL (32.1 mmol/L) (reference range, 7-21 mg/dL [2.5-7.5 mmol/L]) and creatinine level of 14.1 mg/dL (1246.4 μmol/L) (reference range, 0.6-1.17 mg/dL [53.0-103.4 μmol/L]); baseline levels 3 months prior were 37 mg/dL (13.2 mmol/L) and 3.3 mg/dL (291.7 μmol/L), respectively.

Hemoglobin level was 10.6 g/dL (reference range, 13-17 g/dL); calcium, 8.1 mg/dL (reference range, 8.5-10.1 mg/dL); potassium, 6.2 mmol/L (reference range, 3.5-4.7 mmol/L); and phosphorous 8.8 mg/dL (2.8 mmol/L) (reference range, 2.5-4.9 mg/dL [0.81-1.58 mmol/L]).

Creatine kinase level was within normal limits.

Urinalysis showed minimal albuminuria (100 mg/dL); however, spot urine protein to creatinine ratio predicted 11 139 mg/g (reference range, 0-200 mg/g) proteinuria.

Renal ultrasound showed no hydronephrosis.

Serum protein electrophoresis and immunofixation electrophoresis identified a small monoclonal IgG κ band.

Serum κ free light chain (FLC) level was 20 765 mg/L (reference range, 3.3-19.4 mg/L) with a free κ to λ ratio of 296 (reference range, 0.37-3.1).1 Hemodialysis was initiated and a bone marrow biopsy obtained.Bone marrow biopsy showed a normocellular bone marrow with 10% κ-restricted plasma cells (Figure, left panel).

Immunohistochemical staining demonstrated positivity for the plasma cell marker CD138 (Figure, right panel).Left, Bone marrow biopsy sample (hematoxylin-eosin, original magnification ×400).

Right, Immunohistochemical staining of biopsy sample (immunohistochemical stain for CD138, original magnification ×400).


He was born in the United States but had traveled to Sierra Leone for a period of 3 weeks and had returned 1 week prior to presentation.

He did not take any form of malaria prophylaxis, nor did he use insect repellent while traveling.

He previously received the yellow fever vaccine but not hepatitis A or typhoid vaccination.Physical examination revealed a temperature of 39.3°C, heart rate of 120/min, blood pressure of 119/60 mm Hg, respiratory rate of 32/min, and oxygen saturation of 98% on room air.

The patient was jaundiced, with scleral icterus, and was alert and oriented, although he had a fluctuating attention span and was unable to complete basic tasks.

He was able to localize painful stimuli.

No retinal lesions were present on dilated ophthalmologic examination.

Laboratory tests were notable for a white blood cell count of 5000/μL with 88% polymorphonuclear leukocytes, 1% bands, 5% lymphocytes, 5% monocytes, and 0% eosinophils; hemoglobin level of 9.5 g/dL, and platelet count of 25 ×103/μL.

Sodium level was 132 mEq/L; potassium, 4.0 mEq/L; chloride, 100 mEq/L; carbon dioxide, 15 mEq/L; blood urea nitrogen, 40 mg/dL; and creatinine, 1.5 mg/dL.

Total bilirubin level was 23.9 mg/dL; aspartate aminotransferase, 252 U/L; and alanine aminotransferase, 100 U/L.

A computed tomography scan of the head was unremarkable.

A thin preparation blood smear was obtained (Figure).Thin preparation smear of blood obtained from patient (Wright-Giemsa, original magnification ×100).


Physical examination revealed violaceous plaques, measuring 2 to 3 cm, on the extensor surface of the knees, bilaterally (Figure, B).

Excisional biopsy specimens were obtained (Figure, C and D).A, Multiple asymptomatic erythematous nodules measuring 1.5 to 3.0 cm at presentation.

B, Multiple violaceous plaques measuring 2 to 3 cm on the extensor surface of the knees.

C, Excisional biopsy specimen of a calcaneal nodule (hematoxylin-eosin, original magnification ×20).


She reported no history of pregnancy-related complications.

Physical examination revealed confluent erythema with keratotic papulovesicles distributed on the face and neck (Figure, A).

Honey-colored crusts were present on the left ear and preauricular area.

The chest and inframammary area displayed occasional red, crusted papules.

Laboratory tests revealed an elevated white blood cell count of 17.18 × 103/μL (reference range, 4.50-11.00 × 103/μL).

A shave biopsy specimen and tissue culture were obtained from the center of an umbilicated papule on the neck (Figure, B and C).A, Confluent erythema with papulovesicles on the neck and face.

B and C, Histopathological images, hematoxylin-eosin.

B, Full-thickness epidermal necrosis with focal areas of suprabasal acantholysis with corp ronds, corp grains, and parakeratosis.

C, Multinucleated cells with nuclear molding and margination.


He reported no previous infections or family or personal medical history of autoimmune diseases or psoriasis.

He was previously treated for rheumatoid arthritis, but various arthritis treatments showed no improvements over 1 year.

The patient exhibited no associated fever, analgesia or hypesthesia.

A physical examination showed diffuse infiltration of the face with loss of skin creases and diminished facial hair; all joints of both hands were swollen (Figure, A); multiple asymptomatic nodules without ulceration were present on his upper arms (Figure, B); decreased sensation to pain, temperature and/or touch and neuropathic changes were not found.

Laboratory test results showed a slightly elevated erythrocyte sedimentation rate (27 mm/h) and significantly elevated rheumatoid factor (70.1 IU/mL).

Additional immunology indicators, including C-reactive protein, anticyclic citrullinated peptide, antinuclear antibodies, and globulin levels were normal.

X-ray and joint ultrasound results suggested osteoarthritis, synovitis, flexor tendon tenosynovitis, and bone erosions.

Ultrasound results also indicated enlarged axillary, cervical, and inguinal lymph nodes and an enlarged spleen.

Fundus fluorescein angiography showed uveitis.A, Joints of both hands were swollen.

C, Skin biopsy from the patient’s upper arm nodule demonstrating diffuse infiltrate of foamy histiocytes in the dermis (hematoxylin-eosin stain, original magnification ×100).

D, Numerous acid-fast bacilli (acid-fast stain, original magnification ×400).

B, Multiple asymptomatic nodules on the upper arms.


He served in the military for 4 years, including a 6-month tour in Iraq.

He reported drinking more than 12 beers 2 to 3 times per week.

He was prescribed a selective serotonin reuptake inhibitor (SSRI) but did not find it helpful and so he discontinued it.

He reported numerous traumatic experiences, including frequent receipt of incoming fire, multiple ambushes, and an explosion by an improvised explosive device (IED) that injured several fellow soldiers (see Theme 1, Fear Conditioning, in related Educational Review).1He denied any psychiatric issues prior to his military service, but reported that since returning home “there ain’t a day that goes by that I don’t think about [these experiences].” The thoughts were highly distressing and he had frequent violent nightmares.

He reported intense guilt relating to the belief that he should have detected the IED and been able to protect his colleagues.

He reported a number of triggers (eg, walking down a city street; driving by a shooting range) that reminded him of his experiences in Iraq and induced panic-like symptoms (eg, fear, anxiety, racing heart, and feeling shaky).

He avoided things that reminded him of these events and was reluctant to discuss his history (see Theme 1, Fear Conditioning, in related Educational Review).1He felt numb and withdrawn from others, reported difficulty sleeping, and was always “on guard.” He startled easily and had angry outbursts.

The patient was hopeless at times, but denied suicidal thoughts.

He reported difficulty concentrating and had significant fluctuations in his weight.

He denied any other substance abuse history.The patient was briefly in outpatient treatment while he was still in the military.

While in Iraq he worked as an assault vehicle operator and was involved in frequent foot patrols.

He was referred for psychotherapy but did not keep his appointments (see the last sentence of Theme 1, Fear Conditioning, in related Educational Review).1The patient grew up in the suburb of a small city.


She had 1 week of nonbilious, nonbloody emesis, and “graying out” of her vision only when standing up or sitting down.

Three months after initial presentation, she reported a 9.07-kg weight loss (height 1.57 m; body mass index dropped from 21.3 to 16.8 [calculated as weight in kilograms divided by height in meters squared]), postural lightheadedness, worsening fatigue, muscle weakness, salt cravings, loss of axillary hair, and missed periods for 2 months.

Examination noted normal visual acuities and swelling of both optic discs (Figure, A).

Magnetic resonance imaging and magnetic resonance venography of the head showed no intracranial mass or venous sinus thrombosis.

Lumbar puncture showed an opening pressure of 550 mm of water and normal cerebrospinal fluid (CSF) composition.

Repeated ophthalmic examination showed normal visual acuities and worsening optic disc swelling.The patient presented with papilledema bilaterally (A, right eye shown) patchy tongue darkening (B), and darkening of knuckles and distal fingers (C).

A diagnosis of idiopathic intracranial hypertension was made, and she was treated with acetazolamide.

Headaches initially improved but worsened during the following weeks.


Surgical history consisted of a Blalock-Taussig shunt in early childhood and subsequent TOF repair at age 3 years.

On examination, venous pressure was visualized 4 cm above the clavicle at 45° with a prominent a wave.

An electrocardiogram (Figure 1A) revealed sinus rhythm with a right bundle branch block.

Findings from a transthoracic echocardiogram (TTE) are shown in Figure 1B and Video 1.

Right ventricular diastolic volume index, quantitated by cardiac magnetic resonance, was 161 mL/m2.A, Electrocardiogram showing sinus rhythm, right bundle branch block, right axis deviation, and premature ventricular contractions.

B, Still frame from the transthoracic echocardiogram in parasternal long-axis orientation in diastole.

LA indicates left atrium; LV, left ventricular; RVOT, right ventricular outflow tract.

Auscultatory findings at the left upper sternal border are provided in  the corresponding Audio.


He also reported progressive dysphagia to solids but no dyspnea, otalgia, or weight loss.

Examination revealed very tender right-sided neck fullness of 6 cm.

Laryngoscopic findings were unremarkable.

Computed tomography (CT) with contrast demonstrated a 4.4 × 3.6 × 4.5-cm heterogeneously enhancing mass in the right side of the neck, splaying and completely surrounding both the internal and external carotid arteries (Figure, A).

Scattered lymph nodes were also observed.

On magnetic resonance imaging (MRI), the mass was hyperintense on T2 (Figure, B).

A second 0.9-cm enhancing mass was visualized at the inferior right jugular foramen.

Chest radiography demonstrated no suspicious pulmonary or mediastinal lesions.

He underwent excision of the mass with right-sided neck dissection.

Cranial nerves XI, X, and XII were identified and preserved.

Vascular surgery was performed to make an intraoperative repair, and an intraoperative angiogram demonstrated no dissections or thrombi.

The lesion was suspected to be benign, and the procedure was aborted.

During subadventitial dissection of tumor off the carotid bifurcation, a laceration of the internal carotid artery was noted.

The patient experienced no neurologic sequelae postoperatively.

A specimen was taken of the right-sided neck mass (Figure, C and D).A and B, Imaging of the carotid space.

B, Postcontrast T1 magnetic resonance image (MRI).


He was born at 37 weeks gestation via cesarean delivery and developed noisy breathing and nasal congestion shortly after birth.

On the eighth day of life, the patient returned with noisy breathing, retractions, and poor feeding.

On the 12th day of life, he presented with worsening symptoms.

Physical examination revealed significant distress, retractions, and cyanosis relieved by crying.

Otolaryngological consultation, including fiberoptic nasopharyngolaryngoscopy, was performed, and revealed a right septal deviation.

Flexible nasopharyngolaryngoscopy revealed a large left inferior turbinate and right septal deviation.

A mucosalized mass filling the left nasal cavity was visualized on anterior rhinoscopy, requiring nasal stenting to relieve obstruction.

A maxillofacial computed tomographic (CT) scan demonstrated a 2.0 × 1.6-cm mass in the left mid-nasal cavity, compressing the middle turbinate and lamina papyracea (Figure, A).

The cribriform plate was slightly widened prompting magnetic resonance imaging (MRI), which confirmed a 2-cm heterogeneous mass, isointense on T2 with small hyperintense areas, without intracranial extension (Figure, B).

The infant was treated with topical neosynephrine and fluticasone spray and discharged home.

The mass was smooth, epithelialized, and pedunculated at the anterior aspect of the face of the left sphenoid sinus and medial to the middle turbinate (Figure, C).

Transnasal delivery was performed with a deep margin achieved by resecting the periosteum of the sphenoid (Figure, D).

The patient underwent urgent transnasal endoscopic excision of the mass under general anesthesia.

Histologic examination revealed a lesion characterized by regions of cartilage admixed with irregular areas of chondromyxoid stroma containing spindle cells.


She was prescribed multiple rounds of antibiotics without notable improvement.

Physical examination revealed a submucosal right retropharyngeal mass extending from the level of the soft palate to the postcricoid.

Cranial nerve function and neck range of motion were normal.

Contrast-enhanced computed tomography (CT) demonstrated a 4 × 3 × 3-cm right retropharyngeal mass with narrowing of the pharyngeal airway, subtle permeative destruction and cortical breakthrough of the C2 vertebral body.

Magnetic resonance imaging (MRI) with contrast showed a T2 hyperintense, enhancing mass in the retropharyngeal and prevertebral spaces with marrow replacement of the C2 vertebral body extending to the odontoid (Figure, A).

The patient underwent a combined otolaryngology-neurosurgical procedure with a transoral approach via an inferiorly based myomucosal flap to C1-C3 with microsurgical resection of C2 tumor and corpectomy, placement of the halo device, tracheotomy, and staged interval occiput-C6 posterior spinal fusion (Figure, B).

Results from immunohistochemical analysis were positive for brachyury (Figure, D).

Her postoperative course was uneventful, and she was decannulated prior to hospital discharge.


Examination revealed a firm, immobile, and nontender mass affixed to the underlying right mandible.

Magnetic resonance imaging (MRI) showed a 3.7 × 3.6 × 2.6-cm mass arising from the medial aspect of the right mandibular body with cortical destruction (Figure, A-C).

The mass extended into the submandibular and sublingual spaces.

Magnetic resonance imaging demonstrated a lesion isointense to muscle on T1 sequence, heterogeneously hyperintense with internal foci of decreased intensity on T2 sequence (Figure, D), and homogeneous contrast enhancement.

Results from staging studies, including a bone survey, were negative for metastatic disease.

Core biopsy revealed spindle cell proliferation with abundant intervening collagen but no anaplasia, mitotic activity, eosinophils, or inflammatory components.

Incisional biopsy showed fibroblastic proliferation comprised of slender, uniform spindle cells arranged in fascicles with intervening collagenous stroma and no mitoses.

Results from immunohistochemical analysis were positive for β-catenin and negative for CD34, desmin, and smooth muscle actin.

The patient was negative for familial adenomatous polyposis (FAP) mutations on genetic testing.

The most recent interval MRI, performed 4 years after initial presentation, showed a decrease in the size of the mass to 1.5 cm in the maximum dimension.A and B, T1 precontrast fat-saturated magnetic resonance imaging (MRI) demonstrating a mass (arrowhead) arising from right aspect of the mandible.

C, Axial diffusion weighted imaging of the mass (arrowhead).

D, Axial T2 MRI image demonstrating heterogeneously hyperintense mass (arrowhead).

Chemotherapy with hydroxyurea, 20 mg/kg/d, was initiated and continued for 2 years.

Reconstructive surgery was considered but not pursued given the lesion size.