Despite unremarkable postoperative day 1 (POD1) examination findings, the patient presented on postoperative week 3 with a painless central scotoma and worsening floaters.

Her visual acuity was 20/400 OD and intraocular pressure was normal.

There was no external hyperemia or chemosis, and the anterior chamber was deep and quiet with no cells or flare.

On dilated fundus examination, there were 15 to 20 cells per high-power field (using a 1 × 1-mm2 high-intensity incidental slit beam) and a white macular lesion with disc edema and scattered intraretinal and peripapillary hemorrhages and mixed venous and arterial sheathing.

Optical coherence tomography of the macula showed atrophy, full-thickness hyperreflectivity, and a residual epiretinal membrane (Figure).Color fundus photograph (A) of the right eye demonstrating white macular lesion and optic disc edema with scattered intraretinal and peripapillary hemorrhages and vascular sheathing (white arrowheads).

Diluted triamcinolone acetonide (TA) was used to stain the posterior hyaloid.

After removal of 25-gauge trocar cannulas, subconjunctival TA and ceftazidime was injected.

Owing to cystoid changes in the central macula, a short-acting gas tamponade with sulfur hexafluoride was used to tamponade any cystoid abnormalities that may have been unroofed.


Current ophthalmic medications included topical prednisolone acetate, 1%, in the right eye 6 times per day.

The patient reported no improvement with the treatment.

On examination, his best-corrected visual acuity was 20/80 OD and 20/20 OS.

Pupils were reactive without relative afferent pupillary defect, and intraocular pressures were 18 mm Hg in the right eye and 11 mm Hg in the left eye.

A slitlamp biomicroscopic examination of the right eye revealed grade 2 to 3 diffuse central corneal edema and folds (Figure 1).

The anterior chamber was deep and the posterior chamber intraocular lens was in good position within the capsular bag.

Although the view to the posterior pole of the right eye was hazy owing to corneal edema, dilated fundus examination findings were unremarkable.

Examination of the left eye revealed a few guttate.


His active medical problems included atrial flutter on anticoagulation, antisynthetase syndrome (which was diagnosed based on the presence of autoantibodies against aminoacyl-tRNA synthetase), fever with negative infectious workup results, and interstitial lung disease that was managed with azathioprine.

Two weeks before the onset of sudden vision loss, the patient developed a rapidly evolving purpuric rash on his hands and feet that progressed to digital ischemia (Figure 1A).

B, Montage fundus photograph of the left eye shows frosted branch angiitis with preretinal hemorrhages over the disc (arrowhead) and macula (arrowhead), intraretinal hemorrhages, perivenular exudates, and sheathing.On ophthalmic examination, visual acuity was 20/20 OD and hand motions OS (baseline from 2 weeks prior was 20/20 OU), with a briskly reactive right pupil and a left afferent pupillary defect.

Left eye examination revealed 2 or more anterior chamber cells, preretinal hemorrhage, frosted branch angiitis with diffuse intraretinal hemorrhages, and perivascular exudates (Figure 1B).

Fluorescein angiography results revealed extensive vascular nonperfusion and late perivenular leakage.

The right eye was normal.Laboratory workup results revealed an erythrocyte sedimentation rate of 85 mm per hour, C-reactive protein levels of 2.53 mg/dL (to convert to milligrams per liter, multiply by 10), negative antineutrophil cytoplasmic antibodies test result, antinuclear antibodies, cryoglobulins, syphilis serology, tuberculosis testing, and transthoracic echocardiogram.

Skin biopsy results showed medium vessel vasculitis.

He was treated with intravenous methylprednisolone, which was completed 3 days before the onset of loss of vision and transitioned to treatment with azathioprine, 150 mg, and prednisone, 80 mg, that he was taking at the time of his vision loss.Cutaneous and retinal vasculitis.

A, Purpuric rash involving the left foot.


He had no history of malignant neoplasm or chemical exposure.

He denied having fever, chills, fatigue, night sweats, or weight loss.

Physical examination findings demonstrated numerous erythematous, indurated nodules involving the surface of his head, neck, torso, and extremities, without ulceration or scarring (Figure, A and B).

Findings of systemic reviews were unremarkable, and there was no lymphadenopathy or peripheral nerve enlargement.

Complete blood cell count with differential results were normal (white blood cell count, 6060/μL, normal range, 4500-10 000/μL; absolute neutrophils, 3070/μL, normal range, 1800-8300/μL [to convert cell counts to ×109/L, multiply by 0.001]).

Serum lactate dehydrogenase level was elevated (279 U/L, normal range, 100-240 U/L [to convert to μkat/L, multiply by 0.0167]).

Biopsies from skin nodules (Figure, C) and bone marrow were obtained.Skin lesions on the patient with widespread, erythematous, indurated nodules involving his head and neck (A) and trunk (B).

C, Histologic findings demonstrate diffuse dermal infiltrates, extending to the subcutis, with sparing of the upper papillary dermis (original magnification ×20).

The infiltrates are characterized by immature myeloid cells (inset, original magnification ×400).


His medical history was significant for several episodes of upper respiratory infection during the previous winter season, and he previously had an adenotonsillectomy several years prior and bilateral ear tubes placed 1 year before presentation.

The mass had been slowly enlarging and he had been experiencing mild intermittent pain, but no additional symptoms were reported.

Physical examination showed a mildly tender, nonmobile, left parotid mass near the angle of the mandible with no overlying skin changes or drainage around the mass.

There was no lymphadenopathy or other lesions noted in the neck area, and cranial nerve VII was fully intact.

Ultrasonography results of the neck showed a left 1.5-cm preauricular nodular mass with internal and marginal vascularity.

A neck magnetic resonance imaging study without contrast performed at an outside institution revealed the 1.5-cm heterogeneous intraparotid nodule that was predominantly isotense to glandular tissue on T1 images with vague hypointensity of a small irregular central region, as well as vague hyperintensity on T2 images.

He subsequently underwent fine needle aspiration biopsy to assess the lesion, which demonstrated benign-appearing salivary gland tissue and clusters of myoepithelial cells.

Gross examination of the specimen demonstrated a 1.6 × 1.5 × 1.1–cm tan-white, well-circumscribed lesion that was partially surrounded by salivary gland parenchyma (Figure, A).

A, Serial sections of the intraparotid mass demonstrate a well-demarcated solid nodule with tan-white, glistening cut surfaces.

B, Microscopic examination shows a multilobulated, complex lesion with prominent stromal fibrosis and collections of ductal structures with varying degrees of cystic change (hematoxylin-eosin).

C, Acinar cells with brightly eosinophilic intracytoplasmic granules (hematoxylin-eosin).

The mass was continuing to enlarge, and the patient’s pain was increasing in that area, so the decision was made to perform left superficial parotidectomy with preservation of the facial nerve.

Intraoperatively, the left parotid mass was noted to be just below the lower branches of the facial nerve.

The excised parotid mass was sent to the pathology department for analysis.

Histologic examination of the nodule was performed (Figure, B and C).Gross and histologic findings.


Her medical history included systemic lupus erythematosus, antiphospholipid antibody syndrome, and external hemorrhoids.

Six months before admission, she underwent a deceased donor kidney transplant.

Her immunosuppressive regimen at the time of dermatologic evaluation consisted of prednisone, 5 mg daily, and mycophenolate mofetil, 500 mg twice daily.On admission, she was afebrile and normotensive; laboratory results were notable for an elevated creatinine level of 1.43 mg/dL (reference range, 0.40-1.30 mg/dL) (to convert to micromoles per liter, multiply by 88.4) and thrombocytopenia (platelet count, 92 × 103/μL [reference range, 140-440 × 103/μL] [conversion to ×109 per liter is 1:1).

She developed diarrhea 1 day after admission.

Stool antigen test results for cryptosporidium, giardia, and rotavirus were negative.

Polymerase chain reaction (PCR) test results for campylobacter, norovirus, salmonella, shigella, Shiga toxin–producing Escherichia coli 1 and 2, Vibrio cholerae, and Yersinia enterocolitica in the stool were negative.

Antigen and toxin test results for Clostridium difficile in the stool were positive.Total body skin examination was notable for 1- and 3-cm tender, round perianal ulcers with a clean base.

A biopsy specimen of a perianal ulcer border was obtained for histopathologic analysis (Figure, B-D).Clinical and histologic images of multiple perianal ulcers.

A, Two round ulcers, each with well-demarcated borders, were present perianally.

A smaller, third ulcer was also noted in the intergluteal cleft.

B, Microscopic examination of the punch biopsy on low magnification reveals epidermal ulceration and mixed dermal inflammation (hemoxylin-eosin.

C, On higher magnification, the epidermis lacks viral cytopathic changes but there are enlarged dermal fibroblasts and endothelial cells (hemoxylin-eosin).

One month before presentation, she was hospitalized for acute cellular transplant rejection managed with systemic corticosteroids, belatacept, mycophenolate mofetil, and tacrolimus therapies.

Another 4-mm round ulcer was present at the superior intergluteal cleft (Figure, A).


The patient had immigrated to Israel 9 years before admission.

She was adamant that the lesion had been present since early childhood but had gradually increased with a recent appearance of foul-smelling otorrhea.

Bloody otorrhea from the external auditory canal was seen.

On examination, the auricle was markedly enlarged, edematous, and encircled by an erythematous, indurated plaque partially covered with a fine scale (Figure 1A).

Diascopy revealed an “apple jelly” appearance.

There was no local or distant lymphadenopathy; general physical examination findings were unremarkable.A, Clinical findings at presentation in 2008 showed an enlarged and edematous auricle encircled by an indurated erythematous plaque.

B, Biopsy specimen showed superficial and deep diffuse granulomatous dermatitis (hematoxylin-eosin).

C, Higher magnification demonstrated classic tuberculoid granuloma with histiocytes and Langhans giant cells surrounded by lymphoplasmacytic infiltrate (hematoxylin-eosin).Results of routine laboratory investigations, including complete blood cell count, biochemical profile, liver function tests, and chest radiography, were normal.

An intradermal Mantoux test induced a 20-mm induration.

Histopathologic evaluation of the cutaneous lesion revealed noncaseating granulomatous dermatitis involving the dermis (Figure 1B).

High magnification demonstrated tuberculoid dermal granulomas composed of histiocytes and Langhans giant cells surrounded by lymphoplasmacytic infiltrate (Figure 1C).

Results of polarized light examination and periodic acid–Schiff, Ziehl-Neelsen, Giemsa, Gram, and Grocott methenamine silver stains were negative for microorganisms.

Image resolution was digitally enhanced.


She had no specific medical or family history and had no treatment.

A resting electrocardiogram (ECG) while symptomatic showed a wide QRS complex rhythm at a rate of 81 beats per minute (Figure 1A).

After a short walk, symptoms disappeared and another ECG was recorded (Figure 1B).

Physical examination and transthoracic echocardiography results were normal.Twelve-lead electrocardiogram at rest during symptoms (A) and after walk test with symptoms resolution (B).


She had sustained a left radius fracture 6 months prior, which resulted in deconditioning and poor appetite.

Past medical history included chronic nondeforming rheumatoid arthritis, hypothyroidism, and colon adenocarcinoma resected 10 years prior.

Her medications were prednisolone (1 mg/d) and levothyroxine.On examination, she was afebrile, with blood pressure 90/46 mm Hg; pulse, 90/min and regular; and respirations, 18/min.

Her diet consisted of mostly vegetables, and she lost 4 kg (8.8 lb) during this time.

Two months prior, she developed postprandial nonbloody diarrhea that occurred 5 times daily.

Two weeks prior, a pruritic rash in her extremities emerged.

She had no fever, night sweats, or abdominal pain.

Glossitis and a scaly pruritic rash with an erythematous brawny peeling base on her neck and extremities were noted (Figure).

Body mass index was 16.8 (calculated as weight in kilograms divided by height in meters squared).

She was alert, cognitively intact, and appeared emaciated.

Findings on cardiovascular, pulmonary, abdominal, and neurologic examinations were unremarkable.Left, Dorsum of the hands, exhibiting symmetric scaly eruption.

Right, Bilateral lower extremities showing ruptured bullae on an erythematous brawny peeling base.Laboratory studies showed mild hyponatremia (132 mmol/L) and an otherwise normal basic metabolic panel.

Other laboratory values were as follows: C-reactive protein, 0.58 mg/dL; erythrocyte sedimentation rate, 23 mm/h; total protein, 4.8 g/dL; and albumin, 1.8 g/dL.

Her white blood cell count was 7200/μL (66.5% neutrophils, 30.4% lymphocytes); hemoglobin level, 9.9 g/dL; mean corpuscular volume, 96 fL; and platelet count, 332 000/μL.

Results of liver function tests, coagulation tests, urinalysis, thyroid function tests, measurement of serum vitamin B12 and folic acid levels, and cosyntropin stimulation tests were normal.

Serum copper level was 46 μg (reference range, 66-130 μg) and zinc level was 23 μg (reference, ≥80 μg).

Abdominal computed tomography revealed no abnormalities.


Six days prior, he had presented with an inferior stromal infiltrate with an overlying epithelial defect, diffuse corneal edema, and a small hypopyon with no hemorrhage in the anterior chamber (Figure 1A).

He also had patchy iris hemorrhages with no transillumination defects and areas of conjunctival ulceration nasally and temporally.

While evaluating the new defect, the patient was also noted to have dull conjunctival reflexes and bulbar conjunctival lesions in both eyes (Figure 1B).

Additionally, both eyes had patchy interpalpebral results on lissamine green staining of the conjunctiva and clinically significant punctate epithelial erosions of the cornea with fluorescein staining.

Corneal cultures grew Streptococcus pneumonia.

He initially responded well with improvement of the stromal infiltrate and overlying epithelial defect.

However, on day 6 of treatment, he had a new larger epithelial defect and subepithelial bullae in an adjacent location but no infiltrate.

Treatment with hourly topical vancomycin at 14 mg/mL and tobramycin at 25 mg/mL, as well as 1000 mg of oral valacyclovir 3 times a day, was initiated.

Given these findings, a presumed herpes zoster sine herpete1 with secondary bacterial infection was suspected.


Her medical history was significant for hypothyroidism, treated with levothyroxine, as well as 2 forms of hematologic malignancy: retroperitoneal extranodal marginal zone lymphoma and indolent-phase T-cell prolymphocytic leukemia.

She had received no treatment for her hematologic malignancies, as she had been asymptomatic since her diagnoses 6 years prior.Ophthalmological examination revealed 27 mm of bilateral proptosis, conjunctival injection, chemosis, and bilateral lower eyelid retraction (Figure 1A).1 Visual acuity, color vision, and pupillary responses were normal.

Extraocular motility was full in all positions of gaze, and there was no associated pain.

Von Graefe sign (delayed descent of the upper eyelid with initiation of downgaze) and lagophthalmos were absent.

Results of slitlamp examination and dilated fundus examination were normal, including the appearance of both optic nerves.A, Clinical photograph at presentation; bilateral proptosis, lower eyelid retraction, chemosis, and conjunctival injection are present.

There is mild temporal retraction of both upper eyelids.

B, Radiographic images documenting marked enlargement of all extraocular muscles bilaterally.

The lateral rectus is especially enlarged on both sides.

Using a measurement technique described by Dagi and colleagues,1 the maximal diameter of each extraocular muscle in this patient was as follows: right inferior rectus, 8.0 mm; right medial rectus, 9.1 mm; right superior muscle group, 9.7 mm; right lateral rectus, 9.3 mm; left inferior rectus, 8.1 mm; left medial rectus, 9.5 mm; left superior muscle group, 10.0 mm; and left lateral rectus, 9.6 mm.

There is sparing of anterior tendinous insertions (arrowheads) of each medial rectus (MR) and lateral rectus (LR).

However, the anterior portion of the muscle belly (brackets) appears uninvolved compared with the posterior portion, causing an acute taper of the muscle that is similar in shape to an amphora (inset).An orbital computed tomography scan revealed marked enlargement of all extraocular muscles (Figure 1B).


Her medical history included hypertension and right-sided trigeminal neuralgia.

On examination, her visual acuity with habitual correction had decreased to 20/60 OD and 20/40 OS from 20/30 OU 2 years prior.

A slitlamp examination revealed normal conjunctivae, nuclear sclerosis cataracts in both eyes, and deep and quiet anterior chambers.

On a dilated fundus examination, there was 2+ vitreous cell and floaters in both eyes and a blonde fundus in both eyes.

Optical coherence tomography imaging confirmed cystoid macular edema (CME) in both eyes; the right eye had cystoid spaces in the inner nuclear, outer plexiform, and outer nuclear layers, and the left eye had small cystoid spaces in the inner nuclear layer (Figure, A and B).

Fluorescein angiography showed leakage of the optic nerve in the right eye, with petaloid leakage in the macular right eye worse than in the left eye.

A uveitis workup had unremarkable or negative results for a basic metabolic panel, a complete blood cell count with a differential, Quantiferon gold test, Lyme antibody tests, an angiotensin-converting enzyme level, a serum erythrocyte sedimentation rate, and chest radiography.

Additionally, 4 months prior, the patient developed trigeminal neuralgia, with a magnetic resonance image with contrast of the brain revealing an enhancing mass in the right middle cranial fossa, extending into the Meckel cave and abutting the right trigeminal nerve (Figure, C).A, Optical coherence tomography (OCT) image showing the right eye had cystoid spaces in the inner nuclear, outer plexiform, and outer nuclear layers.


At the time of IAC, she had an upper respiratory tract infection (coughing, congestion, rhinorrhea, fever [temperature of 38.9 °C]).

On postoperative day 3, she returned to the emergency department with left eye swelling, continued fever, and poor oral intake.

On physical examination, her temperature was 40.2 °C, and periorbital swelling and erythema were present without drainage.

Dilated fundus examination at the bedside showed the known large retinoblastoma tumor.

A large exudative retinal detachment was noted, which was not present prior to treatment.

Blood bacterial culture testing showed no growth, respiratory viral testing revealed rhinovirus, and results of comprehensive metabolic testing were unremarkable.

Complete blood cell count showed mild leukopenia (2700/μL [to convert to ×109 per liter, multiply by 0.001]) and anemia (hemoglobin, 9.2 g/dL [to convert to grams per liter, multiply by 10]) but were otherwise within reference ranges.

Computed tomography scan of the orbits, recommended by the on-call general ophthalmologist, demonstrated preseptal and periorbital soft tissue swelling and edema with subtle retrobulbar stranding, without substantial proptosis, along with retinal detachment (Figure, B).

B, Orbital computed tomography on presentation, demonstrating preseptal and periorbital soft tissue swelling and edema with subtle retrobulbar stranding along with retinal detachment (arrowheads).

On postoperative day 1, her temperature reached 39.4 °C, and she was diagnosed as having bilateral acute otitis media and discharged with amoxicillin therapy.

She was admitted for intravenous fluids for her noted dehydration.A, Clinical appearance of the child on presentation, showing unilateral periorbital swelling and erythema.

There was no substantial proptosis or orbital masses.


Previously, he had been well, with morphological remission found on a recent bone marrow biopsy.

The patient had no significant dermatological history, except an allergy to cashew nuts and a prior episode (6 mo) of urticaria during a platelet transfusion that had resolved with 1 dose of oral antihistamine.

The patient’s medications included ondansetron, aprepitant, prednisolone, and oxycodone (supportive care initiated with chemotherapy), and long-term posaconazole and trimethoprim/sulfamethoxazole treatment.Lesions were noted on day 2 of the fourth cycle of a chemotherapy regimen comprising fludarabine, cytarabine, and filgrastim (G-CSF).

Initially present over the distal limbs, palms, and soles, the lesions progressed to the proximal limbs and lower trunk during 24 hours (Figure, A and B).

The patient developed a fever, which we extensively investigated.

C, Hematoxylin-eosin–stained specimen showing leukocytoclastic neutrophilic infiltrate in deeper dermis, around appendage structures and coiled eccrine glands, and into the interstitium.The results of a complete examination of blood drawn at lesion onset demonstrated a total white cell count of 6330/μL (to convert to 109/L multiply by 0.001) with absolute neutrophil count of 6140/μL, more than the previous day’s counts of 3210/μL and 1720/μL, respectively.

The blood film demonstrated increased neutrophil granulation with a left shift.

Intravenous cefotaxime was commenced, but because no infectious source was identified, the fever was thought to be secondary to cytarabine.A and B, Clinical images showing erythematous plaques and nodules on patient’s palm and forearm.

A punch biopsy from the upper arm was performed (Figure, C).


He reported an edema of the lower lip that resolved spontaneously the day before.

He had no dyspnea nor dysphagia, but did have a discrete dysphonia.

Neck swelling was global, bilateral, and painless, and was most severe on the left side.

There was a rash, the border of which was marked with a felt pen.

Nasofibroscopy results showed a normal airway with a posterior pharyngeal wall bulging.

Oropharyngeal and oral cavity examination results were normal, with no trismus.A contrast-enhanced computed tomography (CT) scan showed a large retropharyngeal fluid accumulation of 2 × 10 × 6 cm that extended laterally to the vascular spaces, especially on the left side (Figure, A and B).

This was associated with infiltration of the mediastinal fat and a thin left pleural effusion.

There was no vascular thrombosis or dental abnormality.

Hyperleukocytosis levels were 12 000/mL.

We did not have the result of the C reactive protein assay.Cervical computed tomography scan of the sagittal (A) and axial (B) planes.

In the sagittal plane, there is retropharyngeal fluid accumulation, and in the axial plane, there is fluid accumulation in the retropharyngeal and vascular spaces with fat infiltration.

The patient had no traumatic or iatrogenic triggers.


His complex medical history included factor V Leiden deficiency requiring therapeutic anticoagulation, heart failure with atrial fibrillation, and chronic obstructive pulmonary disease associated with 110-pack-year smoking history.

He denied chills, fever, neck stiffness, new medications, otalgia, sick contacts, trismus, and use of an angiotensin-converting enzyme inhibitor.

On examination, the patient had substantial dysphonia, fullness in the left submandibular region, and ecchymosis of the lateral left neck extending toward the midline.

Laboratory studies demonstrated an international normalized ratio of 16.4, a prothrombin time of 118.1 seconds, and a partial thromboplastin time of 81.4 seconds.

Contrast-enhanced computed tomography performed in the emergency department revealed a large, intermediate-density, modestly enhancing, left-sided submucosal lesion extending from the nasopharynx inferiorly to the glottis with encroachment on the airway (Figure).

Flexible fiberoptic laryngoscopy demonstrated a large submucosal mass extending from the left posteroinferior nasopharyngeal wall to the left lateral and posterior pharyngeal walls, obstructing the view of the left supraglottis, glottis, and piriform sinus.

The right side of the epiglottis was ecchymotic and edematous.

The mass extended farther along the aryepiglottic fold to involve the arytenoid and interarytenoid space, as well as the false vocal fold on the left.

The vocal cords were only partially visualized.

Given the important laryngoscopy findings, the decision was made to proceed with awake fiberoptic nasotracheal intubation in the operating room to secure the patient’s airway.Contrast-enhanced computed tomography of the neck in the coronal (A) and axial (B) views demonstrating a large, predominantly left-sided, obstructive, submucosal, upper airway lesion extending from the nasopharynx to the glottis.


She was born after an uncomplicated pregnancy and delivery, and her growth and development were appropriate for her age.

No associated symptoms such as fever, anorexia, or weight loss were noted.

Physical examination revealed multiple skin-colored and erythematous follicular papules, 1 to 2 mm in diameter, distributed in a segmental pattern on the right side of the forehead, as well as the dorsum and tip of the nose.

A small, excoriated plaque was also noted on the right malar area (Figure 1A).

No mucosal lesions were present, and the rest of the physical examination findings were unremarkable.

A complete hematological and biochemical survey, including blood cell count, liver and renal function tests, C-reactive protein levels, thyroid function, rheumatoid factor, and antinuclear antibodies, disclosed no abnormalities.

Representative histopathological features are shown in Figure 1B and C.Multiple skin-colored and erythematous follicular papules are seen coalescing into a linear plaque involving the patient’s forehead, as well as the dorsum and tip of the nose (A).

Two skin punch biopsies were taken from the forehead and nose.

Two skin punch biopsies were taken from the forehead and nose (B and C).


The patient’s medical history was significant for dermal melanocytosis of the right hip and mid back, increased head circumference (97th percentile), and expressive language delay.

There was no family history of congenital birthmarks or neurofibromatosis type 1 or 2.Physical examination revealed a well-appearing boy with normal vital signs and Fitzpatrick type III skin type.

The child's mother reported that, on discovery, the plaque was initially 1 × 1 cm and had since grown in size with the child.

She was uncertain if the plaque was present at birth.

On the left lower back, there was a 15 × 5-cm indurated skin-colored to yellow, firm, multinodular plaque with hypertrichosis, extending from the midline to the left lower flank (Figure, A).

There were additional blue-gray patches on the back and right hip, as well as a small café au lait macule on the right lower back.

Limited neurologic examination was within normal limits.

A 4-mm punch biopsy was performed for further diagnostic evaluation (Figure, B-D).A, Large, well-defined, firm yellow to skin-colored multinodular hypertrichotic plaque on the left lower back.

B, Hematoxylin-eosin staining demonstrates diffuse dermal infiltration of spindle cells, predominantly encircling terminal folliculosebaceous units (original magnification ×4).

C, Higher-power magnification highlights a mix of partially fusiform melanocytes and dendritic cells with glassy, eosinophilic cytoplasm (hematoxylin-eosin, original magnification ×40).

D, Immunohistochemical staining reveals diffuse and periadnexal S100 positivity in the mid to deep dermis (original magnification ×4).


He denied taking any medications or recent international travel.

A few days prior to presentation, he had developed palpitations, chest discomfort, and lower-extremity swelling.

In the emergency department, he had a normal blood pressure with an irregular heart rate at 104 beats per minute.

On examination, he had bilateral basilar crackles and traces of lower extremity edema.

An electrocardiogram revealed that he was experiencing atrial flutter.

A computed tomographic angiogram showed an acute pulmonary embolism, multiple bilateral pulmonary nodules, mediastinal lymphadenopathy, and a right atrial mass.

He then underwent a transthoracic echocardiogram with 2-dimensional speckle-tracking strain, which revealed a 4.5 × 3.6 × 3.1-cm pedunculated right atrial mass attached to the interatrial septum near the fossa ovalis (Figure 1A; Video).

Left ventricular function was noted to be reduced and cardiac mechanics by 2-dimensional speckle-tracking strain were markedly abnormal, suggesting a more diffuse myocardial process (Figure 1B).A, Transthoracic echocardiogram image with 4-chamber view visualizing the right atrial mass measuring 4.5 × 3.6 × 3.1 cm.

B, Bull’s-eye plot showing globally abnormal longitudinal strain of −2.24%.

EndoGLS indicates endocardial global longitudinal strain; myoGLS, myocardial global longitudinal strain.


Six weeks prior, he fell from a ladder and had right nondisplaced medial malleolar and comminuted talar fractures.

Erythema without warmth was present over the right ankle and dorsomedial foot, along with nontender, nonpalpable purpura over the dorsum of the foot and scattered petechiae over the right lower leg (Figure).

On current presentation, his temperature was 38.2 °C (100.8 °F); heart rate, 88/min; respiratory rate, 18/min; and blood pressure, 102/65 mm Hg.

He was well appearing with normal cardiopulmonary and abdominal examinations.

There was trace right lower extremity edema localized to the ankle and normal pedal pulses.

The fractures were managed nonsurgically in a controlled ankle movement boot, with resolution of swelling and bruising.


Her medical history included a red blood cell transfusion as a child and 2 uncomplicated pregnancies.The lesions started as small papules on the dorsal right great toe and left third toe that gradually spread across the dorsum of her feet over the following 12 months.

On serologic testing, the patient was negative for HIV and positive for hepatitis C virus (HCV).

An over-the-counter antifungal ointment was unhelpful.

The lesions did not improve, and her foot pain worsened.

She continued to have 6 of 10, dull, constant pain that was nonradiating, improved when she soaked her feet in water, and worsened with any type of topical pressure or wrapping.

Physical examination revealed multiple well-circumscribed, scaly plaques with cobblestone surfaces on the dorsal aspects of the forefoot and midfoot bilaterally.

Findings were more severe on the right and left hindfoot (Figure, left panel).

A punch biopsy of the right foot lesion revealed psoriasiform epidermal hyperplasia, parakeratosis, eosinophils, papillary dermal inflammation, and intraepidermal necrosis (Figure, right panel).Left, Dorsal aspects of bilateral forefoot and midfoot of a 32-year-old Nigerian woman.

Her primary care physician completed a biopsy, diagnosed verruca plantaris, and prescribed topical salicylic acid twice daily for 4 weeks.

Subsequent treatment with topical liquid nitrogen cryotherapy was ineffective.Three months after cryotherapy, the patient presented to the dermatology clinic regarding the lesions on her feet.

The patient stated that the lesions had been stable in size for the previous 6 months, without bleeding, discharge, or change in color.


He reported forgetfulness and word-finding difficulties for 3 years but performed all activities of daily living independently and was generally healthy.

Physical (including neurologic) examination, basic laboratory studies, and brain magnetic resonance imaging results were normal.

The Short Test of Mental Status (STMS) score was 33 (maximal attainable score of 38 indicates best performance).

Neuropsychological assessment showed average to above-average performance in all cognitive domains, accounting for age and education.

Results of his genetic testing for APOE were reported as follows: “This individual possesses an apolipoprotein E genotype (3 and 4) that indicates, with high specificity, that Alzheimer’s disease is the cause of or a contributor to the observed dementia.”Obtain a brain fluorodeoxyglucose positron emission tomography (FDG-PET) scan.Order cerebrospinal fluid (CSF) testing for Alzheimer disease biomarkers.Reassure and address patient’s concerns and follow up in 1 year.

His father and maternal great aunt developed dementia in their 70s.


He had emigrated from Ghana 2 years before but denied any illness there.

His visual acuity without correction was 20/20 OD and 20/20 OS, although he had to manually elevate his eyelids to see the Snellen chart.

He had no movement of the right eye past midline in elevation, adduction, depression, and abduction and no movement of the left eye past midline in elevation, depression, and abduction, with 50% deficit of adduction.

His external examination results were notable for a margin reflex distance 1 of −4 mm OU and a levator function of 0 OU.

On funduscopic examination, his optic nerves were sharp and pink without atrophy, maculae and retinal vasculature were normal, and peripheral retina appeared normal without pigment abnormalities.


Two days later, she was admitted to the hospital for headaches and vomiting; her temperature was 40 °C, and her blood pressure and pulse were normal.

Two days later, she developed worsened headaches and blurry vision, prompting an ophthalmology evaluation.

An examination was remarkable for listlessness, a thickened erythematous and nonbulging right tympanic membrane, and significant right-sided hearing loss.

Laboratory studies showed leukocytosis and thrombocytosis.

A computed tomography scan of the head with intravenous contrast found no abnormalities.

She began treatment with intravenous ceftriaxone and vancomycin.

An examination was remarkable for visual acuities of 20/20 OU, symmetric pupils without a relative afferent pupillary defect, and bilateral abduction deficits worse in the right eye.

She had bilateral optic disc swelling with obscuration of all borders and a peripapillary halo, as well as vessel obscuration (stage 3 papilledema1) without peripapillary hemorrhages.

Magnetic resonance imaging and venography of the head with and without intravenous contrast were performed (Figure 1).Magnetic resonance T1 images post–intravenous gadolinium infusion.

A, Coronal view of right sigmoid sinus thrombosis next to the ear.

Empty delta sign, a triangular area of enhancement with a low-attenuating center that represents the thrombosis, is shown (arrowhead).

B, Axial view of bilateral confluent mastoiditis (arrowheads), greater on the right.

She began treatment with oral amoxicillin.


He had experienced painless decrease of vision in both eyes for 6 years but did not seek medical care.

He had had hypertension for 3 years, with amlodipine taken regularly.

A sibling developed uremia in their 30s.

A parent died of kidney failure in their 40s.

On results of an ophthalmic examination, his best-corrected visual acuity was 20/50 OD and 20/40 OS, without visual field defects, dyschromatopsia, or relative afferent pupillary defect.

Neurologic examination findings were unremarkable except for mild cognitive impairment.

Fundus fluorescein angiography showed retinal vasculitis (Figure, A).

Enhanced magnetic resonance imaging (MRI) of the brain showed diffuse white matter hyperintensities—leukoencephalopathy—with multiple ring-enhancing lesions (Figure, B).

Results of routine blood tests were significant for kidney insufficiency (proteinuria, 3.47 g of protein in 24 hours; estimated glomerular filtration rate, 38.5 mL/min).

Angiotensin-converting enzyme level and serum tumor marker findings were normal.

Infection panel screenings for hepatitis, HIV, syphilis, tuberculosis, and parasites were negative.

Antinuclear antibodies and antineutrophil cytoplasmic antibodies were negative.

Whole-body positron emission tomographic/computed tomographic (PET/CT) imaging detected no hypermetabolic changes.

The cerebrospinal fluid (CSF) profiling, including cytologic analysis, was normal.

Culture of the CSF and blood was negative for bacteria and fungus.Representative ophthalmic and neuroimaging results.

The arrowheads indicate perivascular fluorescein leakage and hyperfluorescence of the vessel walls; the asterisk indicates the nonperfusion area.

B, This enhanced magnetic resonance image (MRI) shows the ring-enhancing lesions (arrowheads).

No other accompanying symptoms were reported.

A, Fundus fluorescein angiography findings in the right eye.


His ocular history included cataract surgery in the left eye, followed by yttrium-aluminum-garnet capsulotomy 2 months before his referral.

Of note, he had recently undergone Mohs surgery and subsequent reconstruction for squamous cell carcinoma in situ of the lateral canthus in the fellow eye; he also had a medical history of multiple skin malignant neoplasms.Slitlamp examination findings were notable for a grayish cornea opacity that appeared to be lusterless, abutting the nasal limbus and extending into the visual axis (Figure 1A).

His best-corrected visual acuity was 20/40 OS, and the patient reported that his vision had waxed and waned over several months.

There was no apparent conjunctival erythema or appreciable feeder vessels at the limbus.

The rest of the examination findings, including the fundus, were unremarkable.

Anterior segment optical coherence tomography (AS-OCT) indicated that the hyperreflective corneal lesion did not involve the cornea stroma (Figure 1B).Examination findings at presentation.

A, Slitlamp photograph of the left cornea revealing a translucent gray, lusterless lesion that extends into the visual axis.


He had a distant history of actinic keratoses on the scalp treated with liquid nitrogen but otherwise denied previous skin cancer.

Examination of the scalp revealed male pattern baldness, diffuse actinic damage, and multiple thick, yellow-brown crusts overlying erosions with purulent drainage (Figure 1).

A wound culture was performed and grew methicillin-sensitive Staphylococcus aureus.

Five months earlier he began treatment with cetuximab, binimetinib, and encorafenib, complicated by a grade 1 acneiform eruption that was managed with doxycycline hyclate and topical hydrocortisone and clindamycin phosphate.

Oncologic therapy was withheld pending further evaluation of the scalp eruption.


She had a history of a laryngeal tracheoesophageal fissure, intestinal hernia, and hearing loss because of an ossicular malformation.

From age 10 years, she was unable to catch up with conversation of curry smell.

Olfactory tests were performed, and T&T olfactometry1 results showed severe hyposmia (5.4/5.4; detection threshold/odor recognition threshold).

On the card-type odor identification test, Open Essence,2 she only identified menthol correctly.

Her Self-Administered Odor Questionnaire3 score was 20%.

Her visual analog scale4 score was 10 for odor but 100 for taste.

There were no unusual nasal findings on endoscopy or computed tomography.

Because we suspected a congenital olfactory disorder, we recommended magnetic resonance imaging (MRI), which showed olfactory bulb (OB) atrophy (Figure, A).A, Coronal short-tau inversion recovery magnetic resonance imaging (MRI) of the olfactory bulb shows that the olfactory fissure remains aerated, but the olfactory bulb is slightly atrophied on both sides (arrowheads).

There were no dysplastic signs in the frontal gyri.

B and C, An axial MRI T2-weighted image of the pelvis shows vaginal defects and bilateral 1 layer–differentiated uterine rudiments (arrowheads) that were 35 mm on the left and 37 mm on the right.

Both ovaries are normal (equivalent to Mullerian duct anomaly class I).The patient also confirmed that she had not started menstruating.

The results showed an atypical reaction to the insulin tolerance test.

However, the results for adrenocorticotropic hormone/cortisol corticotropin-releasing hormone load test, diurnal variation, and urine accumulation were normal.

The luteinizing hormone (LH)/follicle-stimulating hormone (FSH) values were normal as determined by LH-releasing hormone load tests.

After consulting the pediatric department, an endocrine test was performed.

She was subsequently referred to the gynecology department.


Her last dose of ipilimumab was 2 months prior, and she was scheduled to receive pembrolizumab with doxorubicin, carboplatin, and prednisone for treatment of her underlying malignant tumor.

The rash started as an erythematous papule on her right arm 2 months after initiation of a new immunotherapy regimen, then gradually enlarged and spread to involve both legs (Figure, A and B).

She denied any new systemic symptoms associated with onset of the rash.

She returned to the clinic 3 weeks later with resolution of pruritus but enlarging lesions.

Physical examination revealed erythematous annular plaques without scale on her right arm and bilateral legs.

C, Hematoxylin and eosin stain demonstrating superficial and deep perivascular and interstitial inflammation.

D, Hematoxylin and eosin stain demonstrating numerous scattered eosinophils.

A 4-mm punch biopsy was obtained from the patient’s right arm (Figure, C and D), and she was prescribed fluocinonide, 0.05%, ointment.

For management of her rash, the patient was prescribed betamethasone dipropionate, 0.05%, ointment (augmented).A, Erythematous annular plaques without scale on the left lower leg.

A recent trial of oral terbinafine for possible tinea corporis yielded no improvement.

B, Erythematous annular plaques without scale on the right lower leg.


The division of dermatology was consulted for evaluation of lesions on the face, chest, back, and arms that were gradually increasing in size and number over the past year.

Physical examination revealed leonine facies with madarosis and an eschar on the nasal dorsum (Figure, A).

The lesions were nontender and nonpruritic.

The patient had a muffled voice and reported shortness of breath with exertion.

Red-to-brown dome-shaped papules coalescing into plaques were present on the upper extremities.

Cervical and axillary lymph nodes were palpable.

Results of laboratory investigation demonstrated marked leukocytosis with a white blood cell count of 77.5 × 103/uL with 76.5% lymphocytes.

No blasts were present on peripheral smear.

Computed tomography of the chest, abdomen, and pelvis demonstrated multiple enlarged mediastinal, axillary, subpectoral, abdominopelvic, and inguinal lymph nodes.

Small pulmonary nodules were also detected.

A punch biopsy was obtained from the right arm (Figure, B, C, and D).A, Infiltrative plaques and nodules obscuring normal facial architecture.

B and C, Histopathologic images show normal epidermis with dense diffuse dermal lymphoid infiltrate composed of small to medium cells with irregular nuclear contours (hematoxylin-eosin stain).

D, Immunohistochemistry shows diffusely positive cyclin D1 staining.


Emergency department evaluation noted a heart rate of 64 beats per minute, blood pressure of 173/90 mm Hg, and a temperature of 37.1 °C.

An electrocardiogram showed a sinus rhythm with complete heart block (CHB) and a narrow QRS junctional escape at 65 beats per minute (Figure, A).

Investigation revealed an erythrocyte sedimentation rate of 30 mm/h (normal limits, 0-15 mm/h) and a C-reactive protein level of 6.3 mg/dL (reference range, 0.0-1.0 mg/dL [to convert to milligrams per liter, multiply by 10.0]).

Tests for kidney function, hepatic function, a complete blood cell count, troponin T levels, creatine kinase levels, thyrotropin levels, antinuclear antibodies, and rheumatoid factor had normal results, and tests for anti–streptolysin O and anti–DNAse B titers, Lyme IgG and IgM titers, Coxiella burnetti and Bartonella serologies, Epstein-Barr virus serology, and cytomegalovirus quantification had negative results.

A transthoracic echocardiogram showed no structural abnormalities, while fluorine 18–labeledfluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET–CT) showed a small focal area of FDG uptake in the region of the membranous septum (Figure, B).

A CT showed no hilar adenopathy or pulmonary parenchymal abnormalities.

Over the next 48 hours, the patient’s junctional rhythm accelerated to 90 beats per minute with ventriculoatrial block before acutely degenerating to a narrow complex escape rhythm of 45 beats per minutes associated with lightheadedness (Figure, C).A, A rhythm strip at presentation with a sinus rhythm with complete heart block.


She was born in 1973 at 38th week of gestation followed by a normal delivery (weight, 3.15 kg and head circumference, 42 cm) to nonconsanguineous parents.

The head size was normal at birth, and no other abnormalities were seen during her infancy.

At age 2 years, her parents noticed that she had delayed motor and language milestones.

She experienced a progressive developmental delay such as reduction of head growth, loss of acquired communication, and loss of motor functions between ages 9 and 12 years.

She was referred to us at age 40 years with the characteristic features of growth deceleration (height, 142 cm; weight, 22 kg; body mass index, 11 [calculated as weight in kilograms divided by height in meters squared]), apraxia, left-sided hemiplegia, spasticity, sleep apnea, constipation, osteoporosis, hypoalgesia, and repetitive hand tapping (Video).

The electrocardiogram showed sinus rhythm with T wave inversion (V3-V6), and echocardiography showed mild cardiomegaly.

Blood reports showed anemia (hemoglobin level of 9.1 g/dL; to convert to grams per liter, multiply by 10) and low levels of high-density lipoprotein cholesterol (47 mg/dL; to convert to millimoles per liter, multiply by 0.0259).

The brain magnetic resonance imaging studies showed a diffuse reduction in the corpus callosum involving splenium and enlarged right ventricle, resulting in cerebral lateral ventricular asymmetry (Figure, C).A, Characteristic features of a 42-year-old woman with microcephaly.

The severity of scoliosis increased with age, and she became a wheelchair user at age 18 years.

There was no history of autistic behavior, vision or hearing impairments, or epilepsy.

C, Magnetic resonance imaging of the patient with reduced volume of corpus callosum (arrowhead), sagittal view.


His medical history was notable for atopic dermatitis and diarrhea in infancy that prompted allergy testing at age 6 months; he was subsequently diagnosed with milk, egg, and peanut allergies.

His parents avoided feeding him these foods, providing him only soy-based milk and formula, with improvement of dermatitis, until age 1 year.

Since then his diet had consisted of multiple rice milk feeds daily, supplemented only with pureed fruits and vegetables, pasta, snack puffs, and sunflower butter.

The patient had no history of meconium ileus or family history of cystic fibrosis.

Following an upper respiratory tract infection 1 month prior, he developed disseminated red, scaly patches and a progressive eruption of hyperpigmented and hypopigmented patches of skin.

He had occasional nonbloody loose stools but no fevers or vomiting.

Although he was otherwise well, his growth had fallen from the 75th to the 25th percentile for height and weight over the preceding 9 months, and he could speak only 2 words.

There was no recent travel and no changes to the home environment.On presentation, the patient was irritable, with normal vital signs.

He displayed prominent scrotal swelling and pitting edema of the legs bilaterally.

Skin examination was notable for erythematous, denuded patches with peeling scale and reticulate hyperpigmentation, accentuated on the abdomen, back, diaper area, and extensor extremities (Figure; left panel).

Notably, his skin also demonstrated widespread patches of hypopigmentation, with an accompanying band of hypopigmentation proximally at the site of newest hair growth (Figure; right panel).Physical examination findings at presentation.

Left, Right abdomen, back, buttock, and thigh.


In the emergency department, the patient’s temperature was 36.7 °C (98.1 °F); blood pressure, 121/82 mm Hg; pulse, 74/min; respiratory rate, 15/min; and oxygen saturation, 99% on room air.

Physical examination revealed petechiae within a poorly demarcated erythematous patch on the left dorsal foot (Figure 1, left panel), splinter hemorrhages on the right thumbnail (Figure 1, center panel), and petechial macules on the palms and soles, most numerous on the distal digits.

There was no murmur or plop on cardiac auscultation.

Neurologic examination findings were significant for left eye nystagmus and inability to adduct the right eye on left gaze, consistent with right-sided internuclear ophthalmoplegia.

A computed tomography (CT) scan of the head showed 2 acute infarcts in the right cerebellum.

Results of laboratory testing were notable for mild leukocytosis (12.2 × 109/L), mild thrombocytosis (439 × 109/L), and elevated troponin level (4.4 ng/mL); results of a comprehensive metabolic panel and the remainder of the complete blood cell count were normal.

An electrocardiogram showed T-wave inversions in lead V2, consistent with a non–ST-segment elevation myocardial infarction.

Transthoracic echocardiogram and cardiac CT angiography (Figure 1, right panel) were performed.Findings at presentation.

Right, Computed tomography angiography of the heart.

LA indicates left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle.


Multiple prior office visits with referring ophthalmologists during which eyes were dilated showed normal results.

Clinical examination revealed 180° of left interior subconjunctival hemorrhage with overlying conjunctival elevation and mild fullness of the left lower eyelid (Figure 1A).

Fixation was central, steady, and maintained bilaterally, with full ocular motility and absence of appreciable proptosis.

Penlight anterior segment examination demonstrated normally formed anterior segment structures without inflammation or hyphema in either eye, although the left eye exhibited a small intraocular lightly pigmented lesion at the 5-o'clock limbus.

Examination under anesthesia (EUA) was deemed appropriate and further demonstrated normal intraocular pressures bilaterally.

Handheld slitlamp examination localized the left eye 2-mm limbal lesion on the posterior corneal surface.

The surrounding corneal and iris structures were normal appearing without evidence of vascularization.

Ultrasound biomicroscopy was used to further evaluate both the intraocular lesion and better characterize the left lower eyelid fullness.

This demonstrated no iris, angle, or ciliary body involvement by the intraocular lesion.

A 10-MHz contact B-scan examination showed a large inferior orbital lesion measuring more than 17 mm in the anterior-to-posterior dimension (Figure 1B).


The patient had no history of frequent sinusitis, trauma, or exposure to chemicals, but he did note poor dentition.On examination, visual acuity was 20/25 OD and 20/20 OS.

Worsening edema prompted his primary care physician to initiate a course of oral methylprednisolone and amoxicillin-clavulanic acid, which did not alleviate the symptoms.

Because of persistent swelling, he was referred for further evaluation.

The patient denied fevers, chills, purulent drainage, otalgia, or odynophagia.

Pupils were reactive, extraocular motility was full, and intraocular pressure was 19 mm Hg OD and 16 mm Hg OS.

Exophthalmometer readings were 21 mm OD and 18 mm OS with a base of 120 mm.

Inspection of the right upper eyelid was remarkable for a 2.2-cm fluctuant mass with surrounding erythema that was tender to palpation.

Computed tomography (CT) of the face and head demonstrated a right supraorbital abscess with mass effect resulting in right hypoglobus, multiple communicating channels through inner and outer tables with cortical breakthrough in the frontal sinus, and advanced dental caries that communicated directly with the maxillary sinus owing to cortex erosion (Figure).Coronal sections of a computed tomographic image of the orbits with intravenous contrast.

There is a 2.2-cm right supraorbital abscess with mass effect on the right globe leading to a hypoglobus (arrowhead).

The abscess has a direct communication with the right frontal sinus.

One of the channels that directly communicates with the right supraorbital abscess shows adjacent cortical breakthrough.


Otherwise, her condition was managed conservatively for presumed viral conjunctivitis.She self-presented 6 days later with intermittent visual blurring, mild eyelid swelling, and conjunctival chemosis.

The intraocular pressure (IOP) was raised (26 mm Hg) and was treated with a topical β-blocker.

An inflammatory or allergic etiology was suspected; therefore, topical corticosteroids and a prostaglandin analogue were also prescribed.One week later at planned follow-up, the patient had dilated and tortuous bulbar blood vessels (Figure 1).


She had an unremarkable ocular and medical history.

She had no associated fever, chills, upper respiratory tract symptoms, lethargy, or changes in behavior.

External examination revealed mild left-sided ptosis, axial proptosis, and upper eyelid fullness with no mass or tenderness to palpation (Figure, A).

On examination, visual acuity was fix-and-follow in each eye.

Pupils were round, symmetric, and reactive to light without an afferent pupillary defect.

Ocular movements were full, and the patient had grossly full visual fields to confrontation.

Slitlamp and fundus examination results were unremarkable, and there was no left optic nerve edema or pallor.

Magnetic resonance imaging (MRI) of the orbits revealed a left intraconal mass that was isointense relative to rectus muscles on T1-weighted images and hypointense with a hyperintense rim on T2-weighted images (Figure, B).A, Clinical photograph showing left upper eyelid fullness (arrowhead) and mild axial proptosis.

B, Axial T2-weighted magnetic resonance image (MRI) of orbits with contrast showing a left intraconal hypointense mass with a hyperintense rim and peripheral enhancement (arrowhead) exerting mass effect on the intraconal contents.


Her medical history was remarkable for congestive heart failure and schizophrenia.

The patient reported symptoms of joint and musculoskeletal pain and fatigue but denied fever, sore throat, abdominal pain, and kidney stones.

Neck examination revealed no meaningful findings except right thyroid enlargement.

Results of laboratory evaluation demonstrated normal white blood cell count, borderline hypercalcemia (10.6 mg/dL), and elevated parathyroid hormone level (208 pg/mL).

She underwent ultrasonography at an outside facility, and results demonstrated a 2.2-cm dominant right thyroid nodule with additional smaller thyroid nodules.

Findings of preoperative technetium-99m (Tc-99m) sestamibi planar and single-photon emission computed tomographic/computed tomographic (SPECT/CT) imaging (Figure, A) were nonlocalizing for a parathyroid adenoma and showed increased uptake in the dominant right thyroid nodule (Figure, B).

Results of an ultrasound-guided biopsy of the thyroid nodule demonstrated a benign colloid nodule with cystic changes.

Computed tomography with intravenous contrast was obtained, and findings were initially reported as negative except for right multinodular goiter.

However, on additional review, a well-circumscribed fat density mass measuring 3.0 × 2.3 × 1.1-cm was identified in the right retropharyngeal space posterior to the hypopharynx (Figure, C).A, Results of single-photon emission computed tomography/computed tomography (SPECT/CT) demonstrated relatively low radiopharmaceutical uptake superior to the expected area of the parathyroid glands.

B, Findings of technetium-99m sestamibi SPECT/CT demonstrated increased radiopharmaceutical uptake in the previously identified dominant right inferior thyroid nodule (white arrowhead).

C, A CT neck scan with contrast showing a mass in the right retropharyngeal space with complex internal areas of increased attenuation (red circle).


The patient’s history was notable for an 8-year history of right maxillary first premolar impaction.

The patient denied any drainage from the site but reported worsening swelling and pain over the past several weeks.

On physical examination, there was noted intraoral swelling involving the buccal and palatal aspects of the posterior maxilla.

The lesion was soft and fluctuant with no appreciable drainage.

Findings from computed tomography of the head demonstrated a relatively spherical 4-cm growth of the right anterior maxilla abutting the maxillary sinus and orbital floors, and enclosing an impacted premolar at the superior margin of the growth (Figure, A).

There was no proptosis or visual field changes associated with the lesion.

An incisional biopsy was performed via an intraoral approach, and results demonstrated a thickly encapsulated proliferation of odontogenic epithelial cells with pseudoglandular elements (Figure, B and C).

Following diagnostic confirmation, the patient was taken to the operating room, and a midface (Weber-Ferguson) incision was used to access the maxillary lesion for complete removal.A, Sagittal computed tomography (CT) of the head and neck demonstrating an expansile, 5.0-cm mass enclosing an impacted first maxillary premolar (white arrowhead).

B, Neoplastic proliferation of swirls and anastomosing cords of odontogenic epithelium with formation of psuedoglandular structures (black arrowheads; hematoxylin-eosin).

C, High-powered view of ductlike structures (black arrowhead; hematoxylin-eosin).


Two weeks after treatment initiation, multiple tender nodules developed over the palms and interphalangeal joints, and flexion contractures continued (Figure, A).

Results of autoimmune serology, including antinuclear antibody, C3 and C4, rheumatoid factor, and Scl-70 antibody tests, were negative.

There was an absence of nailfold capillary changes and distal digital pitting.The patient was treated with nonsteroidal anti-inflammatory drugs, systemic steroid therapy, and disease-modifying antirheumatic drugs (ie, hydroxychloroquine), but symptoms persisted.

Results of the CT demonstrated bilateral ovarian tumors with highly suspect peritoneal metastases.A, Clinical image of erythematous and edematous changes of bilateral hands and multiple nodules on palms and interphalangeal joints.

B and C, Hematoxylin-eosin–stained specimen showing increased fibroblasts with fibrosis from dermis to subcutis.


The patient described the spontaneous onset of the lesion and reported no previous history of trauma or any other systemic symptoms; he had previously applied a topical antifungal cream but observed no lesion improvement.

Physical examination revealed a nonindurated and well-defined 10 × 8-cm reddish-brown annular plaque with peripheral ecchymosis.

Two biopsy specimens were obtained from different areas of the lesion for immunohistochemical studies; vascular channel endothelial cells were positive for CD31, CD34, and D2-40 and negative for human herpesvirus 8 (HHV-8) (latent nuclear antigen) and Wilms tumor 1 (WT1).

Serologic tests for HIV and hepatitis B and C were negative.Clinical image of the left axilla showing an asymptomatic, reddish hematomalike plaque with a brownish peripheral border.


Four years ago while pregnant, she had recurrent endocarditis complicated by severe symptomatic mitral regurgitation, but she was successfully brought to term and had a cesarean delivery.

Post partum, her symptoms resolved, but she had persistent marked mitral regurgitation related to a severely deformed posterior leaflet.

She wished to have another child, and after extensive counseling she elected to undergo a complex redo MV repair (annuloplasty) 2 years ago.

She developed perioperative atrial fibrillation but declined anticoagulation and has not had further arrhythmias.

She had mild exertional dyspnea, a right ventricular (RV) heave, and elevated jugular venous pulsation.

Serial transthoracic echocardiograms have demonstrated normal biventricular function and pulmonary pressures.

Her postoperative MV gradient was 10 mm Hg (heart rate, 90 beats per minute [bpm]) and has been stably elevated since surgery.At presentation, the patient was 19 weeks pregnant at presentation.

Transthoracic echocardiogram demonstrated normal biventricular function, mild RV dilation, RV systolic pressure of 84 mm Hg, normal left atrial size, and mean MV gradient of 18 mm Hg at a heart rate of 97 bpm.

Transesophageal echocardiogram revealed mean MV gradient of 21 mm Hg at a heart rate of 100 bpm (Figure).

She strongly desired this pregnancy and declined termination.A, Color wave doppler demonstrating a mean mitral valve gradient of 21 mm Hg at a heart rate of 100 beats per minute.

B, Three-dimensional mitral valve area (1.22 cm2) as measured by planimetry.


Initially, she experienced fever and sore throat.

The mother reported that the patient lost 3.2 kg in 2 months, without any chills or night sweats, difficulty swallowing or breathing, change in voice, abdominal pain, recent travel, or exposure to animals or pets.Magnetic resonance imaging (MRI) demonstrated extensive unilateral right-sided neck adenopathy, the largest nodes measuring approximately 4 cm at level IB; an approximately 2-cm destructive mass involving the left maxillary malar eminence; and additional lesions involving the T4 vertebra and upper sternum (Figure, A and B).

Physical examination findings demonstrated minimally tender and nonmobile 4-cm right submandibular space swelling.

Laboratory examination findings were significant for leukocytosis with neutrophilia (white blood cell count, 19.8 K/μL; neutrophil count, 18.2 K/μL [to convert to ×109/L, multiply by 0.001]), anemia (hemoglobin level, 9.6 g/dL [to convert to g/L, multiply by 10.0]), elevated erythrocyte sedimentation rate (>130 mm/h), and elevated C-reactive protein level (3.1 mg/dL [to convert to mg/L, multiply by 10]).

Ultrasonography revealed multiple enlarged hyperemic lymph nodes within the right side of the neck, the largest measuring 3.4 × 2.4 × 2.1 cm in the submandibular space.

Ultrasonography at 1-month follow-up revealed interval enlargement of the lymph nodes, which appeared rounded in shape, without preservation of internal architecture.

Fluorodeoxyglucose 18F-labeled positron emission tomography with computed tomography (FDG PET/CT) demonstrated extensive FDG-avid right-sided cervical lymphadenopathy and innumerable FDG-avid lytic foci involving the axial and appendicular skeleton (Figure, C).A, Postcontrast T1-weighted fat-suppressed magnetic resonance imaging (MRI) of the brain demonstrated an approximately 2-cm destructive mass involving the left malar eminence of maxilla with homogeneous enhancement.

B, Axial T2-weighted fat-suppressed MRI through the neck demonstrated unilateral right-sided neck adenopathy.

C, Fluorodeoxyglucose F18-labeled positron emission tomography whole-body imaging demonstrated avid right cervical lymphadenopathy and innumerable avid foci involving the axial and appendicular skeleton.

She was treated with oral antibiotics without improvement.


The ceritinib was then shifted to crizotinib, 500 mg/day, when the reimbursement of crizotinib as a first-line therapy was approved by Taiwan's National Health Insurance system.Three weeks after the first dose of crizotinib, the patient developed a dry cough without fever or purulent sputum.

There was no significant finding on physical examination except mild crackles over the right lung field, although chest radiography results showed a new consolidation lesion over the right upper lobe.

A chest computed tomography (CT) scan showed a right upper lobe lung mass with multiple lymphadenopathies (N3), and bone scan and brain magnetic resonance imaging results showed multiple metastatic foci.

Meanwhile, the results of mycobacterial and bacteriologic surveys were unremarkable.

The tumor marker carcinoembryonic antigen level decreased from an initial 14.76 to 0.71 ng/mL (reference range, 0-5.00 ng/mL [to convert to micrograms per liter, multiply by 1]).

A CT scan was arranged, and developing lung cancer with lymphangitic carcinomatosis was highly suspected by the radiologist (Figure, A).

A bronchoscopy with bronchial brushing and biopsy was performed, and no pathogen was identified.A, The comparison of the chest computed tomographic (CT) scan of the new consolidation lesion (red arrowheads) mimicking recurrence (right panel) with the primary tumor (yellow arrowhead) in the initial CT scan (left panel).

Granulomatous inflammation or sarcoid-like reaction with predominant T-cell infiltration (hematoxylin and eosin stain, magnification ×200) and less B cell infiltration.

The patient received ceritinib, 450 mg/day, and his tumor and brain and bone metastatic lesions subsequently decreased in size.

B, Microscopic findings of a CT-guided biopsy (left panel) and CT scan after resuming ceritinib treatment (right panel).

A biopsy was performed, and the pathologic report showed a poorly differentiated lung adenocarcinoma with ROS1 rearrangement identified by immunohistochemical staining (clone: D4D6; H-score: 280) and further confirmative fluorescence in situ hybridization.

Inset: double immunohistochemical staining showing abundant T cells (CD3, red staining; red arrowheads) and rare B cell infiltration (CD20, brown staining; yellow arrowhead).


His prenatal course was complicated by maternal drug use, hepatitis C, and lack of routine prenatal care.

At the age of 5 weeks, a swollen right eye with a foggy cornea and conjunctival vascular anomaly were noted.

A soft, mobile, right parotid mass had doubled in size.Ocular B-scan ultrasonography revealed a large subretinal lesion with multiple intralesional, hyperechoic foci extending temporally from the optic disc to the periphery.

Intraocular pressure of the right eye was elevated to 31 mm Hg (normal pressure, <20 mm Hg).

Parotid ultrasonography demonstrated a lobulated solid vascular mass measuring 2.1 cm.

Results of magnetic resonance imaging (MRI) showed an intraocular mass in the right eye, with faint contrast enhancement thought to represent intratumoral calcification or hemorrhage, and a well-circumscribed, 3.1-cm, right superficial parotid mass with faint enhancement (Figure 1).

18F-fludeoxyglucose–positron emission tomography (FDG-PET) showed hypermetabolic masses at the posterior aspect of the right globe, the lateral aspect of the orbit, and the right parotid gland.

Computed tomography of the chest, abdomen, and pelvis provided no evidence of distant metastasis.

Cerebral spinal fluid analysis and examination of a bone marrow biopsy specimen showed no suspicious findings.

A pathological specimen from the parotid gland featured small blue cells with a fine chromatin granular pattern and complete loss of integrase interactor 1 (INI-1).Axial magnetic resonance image showing a right orbital mass (arrowhead) with faint contrast enhancement.

The infant was referred to the ophthalmology and otolaryngology service.


Medications included liraglutide, metformin, apixaban, sotalol, metoprolol, levothyroxine, venlafaxine, lisinopril, ranitidine, and magnesium oxide (400 mg, 2 times/d).

Her blood pressure was 148/68 mm Hg, heart rate 96/min, and weight 106.4 kg.

Her prior serum magnesium levels ranged from 1.4 mg/dL to 1.6 mg/dL and a recent hemoglobin A1c level was 10.8%.

Following baseline blood testing (Table), the patient collected a 24-hour urine sample after discontinuing magnesium supplements for 24 hours.Evaluate for alcoholism as the cause of hypomagnesemia.Improve glycemic control due to urinary magnesium loss from polyuria.Start insulin to promote magnesium reabsorption at the proximal convoluted tubule.Stop ranitidine due to concern for reduced gastrointestinal magnesium absorption.


Following neoadjuvant chemoradiotherapy, low anterior resection, and 6 cycles of adjuvant FOLFOX therapy (fluorouracil, leucovorin, and oxaliplatin), he had developed a lung metastasis (KRAS wild type) 1 year later.

He subsequently developed multiple lung metastases treated with palliative local interventions (lobectomy, radiofrequency ablation) and 4 lines of chemotherapy.

He had no shortness of breath or noisy breathing, dysphagia, voice change, or hemoptysis.

After 9 months, contrast computed tomography restaging scans noted a new, 1-cm posterior subglottic lesion of unclear origin (Figure, A).

A partial response was maintained without evidence of progression of lung disease.A, An axial computed tomographic image reveals a new posterior subglottic lesion (pink arrowhead) of unclear etiology.

The differential diagnosis based on imaging included a mass vs inspissated mucus.

Examination using distal-chip flexible laryngoscopy revealed a 1-cm, broad-based, exophytic mass along the posterior wall of the subglottis with prominent vasculature.

No other anatomic abnormalities in the upper aerodigestive tract or cervical lymphadenopathy were noted.

Examination revealed a subglottic mass that did not extend inferiorly beyond the caudal aspect of the cricoid cartilage.

Owing to symptomatic lung disease, he was enrolled in a clinical trial (NCT03502733) following informed consent and achieved a confirmed partial response.

The decision was made to proceed to the operating room for definitive endoscopic biopsy under general anesthesia (Figure, B).

The mass was debulked and sent to pathology for analysis, including hematoxylin-eosin and immunohistochemical staining (Figure, C).

B, In the operating room, the larynx was exposed with a Lindholm laryngoscope, and a Hopkins rod-lens endoscope was used to photograph the lesion under apneic conditions.

C, Photomicrograph (original magnification ×20) of a section of the mass stained for CDX2 via standard immunohistochemical techniques.Otolaryngology was consulted to assess the lesion.


She was standing and laying out a blanket for her dog before passing out.

She denied prodromal symptoms and reported this was her first syncopal episode.

She reported a few episodes of dizziness in the couple days prior to presentation but denied chest pain, shortness of breath, palpitations, or the recent use of illicit drugs or new medications.

Shortly after arrival at the emergency department, she had a 50-second run of polymorphic ventricular tachycardia.

Her vital signs and the results of her physical examination were normal.

Troponin levels, thyroid levels, and the results of a complete blood cell count and metabolic panel were all normal.

The results of imaging studies, including echocardiography, computed tomography (CT) pulmonary angiography, and brain CT, were also unremarkable.

Coronary angiography found no evidence of obstructive coronary disease.

The results of the urine toxicology test were negative.


Her medical history was unremarkable, and she had no allergies.

She had been well until 2 hours before the flight home, when at the Havana airport, she developed generalized weakness, increased sweating, severe nausea, and vomiting.

In flight, she had lethargy, vomiting, and urinary incontinence.

On arrival to the emergency department, she was stuporous and required intubation.

Her muscle tone was normal, and she had mild proximal muscle weakness with occasional bilateral upper extremity and lower extremity fasciculations and jerky movements.

Initial laboratory tests showed a hemoglobin level of 10.9 g/dL (reference range, 12.0-15.2 g/dL [to convert to grams per liter, multiply by 10.0]), a creatinine level of 1.31 mg/dL (reference range, 0.51-1.08 [to convert to micromoles per liter, multiply by 88.4]), and a pH of 7.22 with a normal anion gap.

Serum electrolyte levels; a white blood cell count; levels of glucose, creatine kinase, lactic acid, and thyrotropin; coagulation studies; and liver function tests had normal results.

An electrocardiogram showed sinus bradycardia at 53 bpm and borderline QT interval prolongation (QTc; 465 milliseconds).

A urine toxicology screen had negative results for acetaminophen, salicylates, opiates, barbiturates, benzodiazepines, cocaine, and ethanol.

Cerebrospinal fluid was clear, with normal levels of glucose, total protein, and white blood cells and negative microbiology and cytology testing results.

A malaria smear and antigen test, respiratory viral assay, and cultures of cerebrospinal fluid, blood, and urine had negative results.

Computed tomography of the head showed bilateral hyperdensity of the globus pallidi (Figure 1).

Her blood pressure was 99/61 mm Hg; pulse, 80 bpm; temperature, 37.6 °C; and oxygen saturation, 99% on room air.

Involuntary facial muscle twitching was noted.

Deep tendon reflexes were normal, with flexor plantar responses.

Within several hours, her level of consciousness improved spontaneously, and she was extubated.


The patient reported headaches and loss of vision in the right eye, which started several months earlier.

She had no history of trauma, neurosurgical procedures, or lumbar puncture.Examination findings were notable for visual acuities of 20/30 OD and 20/20 OS with an approximate correction of −6.50 D. An afferent pupillary defect of 2+ was detected in the right eye, and color vision was diminished in both eyes (1/13 Ishihara plates OD, 5/13 OS).

Findings on slitlamp examination were normal.

Applanation tonometry revealed an intraocular pressure of 10 mm Hg in both eyes.

Findings on dilated fundus examination were notable for small, tilted discs without pallor, hyperemia, or elevated margins; tilting of the nerves precluded estimation of cup-disc ratio.

Automated 24-2 Humphrey visual field testing revealed diffuse depression in the right eye (mean deviation, −26.97 decibels [dB]) and a dense inferior nasal defect in the left eye (mean deviation, −8.05 dB) (Figure).Optic disc photographs of the right (A) and left (B) eyes show small, tilted optic nerves with peripapillary atrophy but no hemorrhage, edema, hyperemia, or pallor.

The temporal edge of the optic nerve is designated by the black arrowhead; the edge of the scleral crescent, by the white arrowhead; and the edge of peripapillary atrophy with hyperpigmentation, by the yellow arrowhead.

Selective laser trabeculoplasty and application of 4 topical agents in both eyes reduced intraocular pressure to the high single digits, yet visual field deterioration had continued.

Her ocular history was notable for open-angle glaucoma in both eyes, diagnosed 3 months previously.


Her medical history was unremarkable apart from an allegedly benign breast nodule resection in her teenage years.

In addition, her father died of metastatic cutaneous melanoma at 83 years old.Clinically, there was an ill-defined, infiltrated plaque with a normochromic, exophytic nodule on her scalp vertex measuring 4.2 × 3.8 cm (Figure, A).

She was born with the lesion but noticed some growth following a minor local trauma a couple of months prior to seeking medical evaluation.

The patient denied local inflammation, purulent discharge, and systemic symptoms.

It had a waxy surface with irregular transverse furrows and overlying alopecia.

Dermoscopic evaluation findings revealed a homogeneous yellow hue with no visible vascular or pigmented structures and absence of follicular ostia.

The lesion was firm and mildly tender to the touch and seemed adherent to the underlying bone.

B, Paramedian sagittal gadolinium-enhanced T1-weighted brain magnetic resonance imaging (MRI).

C, Cellular infiltration in the reticular dermis (hematoxylin-eosin, original magnification ×100).

D, Monomorphic cells in a syncytial configuration surrounding collagen bundles (hematoxylin-eosin, original magnification ×400).

A brain magnetic resonance imaging was performed for further elucidation (Figure, B), as well as a punch biopsy (Figure, C and D).A, Clinical image of the lesion on the scalp.


She had a 25-year history of bulimia and was purging almost daily.

She reported an inability to go more than 3 days at a time without purging and noted a reduction in the pressure and size of her lesions with respite from these daily episodes.

The patient first noticed these lesions 15 years ago in association with a subconjunctival hemorrhage on the left side.

She denied any vision changes or pain but did report a sensation of pressure in the location of the lesions, which was relieved when prone.

An orbital magnetic resonance image obtained at the time of that episode demonstrated a 2 × 0.6-cm focus of enhancement along the inferior and inferolateral palpebral tissues anterior to the left globe, suggestive of lymphangioma, hemangioma, or vascular malformation without other focal abnormalities.

The anterior segment examination showed bilateral superior (Figure, A) and inferior (Figure, B) large dilated blood vessels underlying the palpebral conjunctivae.

Complete ophthalmic and orbital examinations revealed no other abnormalities.Eyelids of the patient demonstrating vascular lesions visible within the palpebral tissue at the time of presentation.

A, Atypical vascular dilation along the superior peripheral arcade of the right eye.

B, Atypical vascular dilation along the inferior palpebral arcade of the left eye.


Surgical drainage was performed, but the swelling persisted.

Two months later, nontender preauricular fullness was noted, which prompted the patient to seek a second opinion.

The left upper eyelid was thickened (Figure 1A).

Eyelid eversion was not possible in the clinic because of mass effect, but a small portion of the tumor was visualized at the supranasal eyelid margin.

A nontender left preauricular mass of 1 cm in diameter was palpable.

In the interim, magnetic resonance imaging of her orbit and parotid glands revealed focal enhancement in the left upper eyelid and superficial lobe of the left parotid gland.

She was referred to us for diagnosis and treatment.On examination, visual acuity was 20/20 in the right eye and 20/30 in the left eye.

Ocular motility was full, and proptosis was absent.

The remainder of the findings on eye examination were unremarkable.

After eyelid eversion in the operating room, the mass measured 35 mm in basal diameter and 5 mm in thickness and demonstrated an amelanotic appearance with a hairpin-shaped vascular pattern suggestive of an epithelial tumor (Figure 1B).A, External photograph demonstrating left upper eyelid fullness.

B, Everted left upper eyelid showing a diffuse, multinodular tarsal mass with hairpin-shaped vessels.


At presentation she had a 3-week history of a striking pruritic and generalized cutaneous eruption.

The patient otherwise felt well and denied fever, malaise, insect bites, or starting new drug treatments.

Except for leukopenia and a slightly elevated C-reactive protein level, results of other routine blood and urine tests were unremarkable.

Physical examination revealed an erythematous eruption composed of small indurated and edematous papules (Figure, A and B).

Confluent papules leading to large urticariform plaques, some with annular configuration, were present on the flanks, lower legs, breasts, and scalp.

Hyperpigmented patches and focal areas of bruiselike discoloration were seen adjacent to acute lesions.

Mucous membranes, palms, and soles were spared.

B, Large erythematous plaques involving the scalp and ear.

C, Hematoxylin-eosin–stained histologic specimen showing a superficial and deep dermal perivascular and interstitial mononuclear infiltrate with numerous eosinophils (original magnification ×40).

D, Higher magnification of C showing an abundant number of eosinophils in the infiltrate (original magnification ×400).

A biopsy specimen was obtained (Figure, C and D).A, Erythematous indurated and edematous papules and plaques on the thighs with some residual discoloration.


She was born in Guatemala and had immigrated to the US approximately 1 year ago, without subsequent international travel.

She was somnolent and confused without focal neurologic deficits.

On examination, she was afebrile (36.8 °C) and hemodynamically stable, with heart rate 70/min and blood pressure 95/53 mm Hg.

Serum white blood cell count was elevated to 14.9 ×109/L (86% segmented neutrophils, 9% lymphocytes, 5% monocytes, 0% basophils/eosinophils).

A computed tomography scan of her brain was notable for diffuse ventriculomegaly and sulcal effacement consistent with hydrocephalus and cerebral edema.

Laboratory analysis of cerebrospinal fluid (CSF) obtained from the ventriculostomy was notable for 40 red blood cells/mm3; 3 nucleated cells/mm3; protein level, 11 mg/dL; and glucose level, 73 mg/dL.

Magnetic resonance imaging (MRI) of the brain with and without contrast demonstrated ventriculomegaly of the lateral and third ventricles, with a 0.4 × 0.4 × 0.6–cm nonenhancing lesion obstructing the aqueduct of Sylvius (Figure 1A).

No abnormal meningeal enhancement or parenchymal lesion was identified.

Repeat MRI demonstrated resolved hydrocephalus, a patent aqueduct of Sylvius, and the aforementioned nonenhancing lesion now located in the fourth ventricle (Figure 1B).Left, Sagittal T2-weighted noncontrast magnetic resonance imaging (MRI) image at presentation.

Given her diminished level of consciousness, a ventriculostomy was placed emergently.

On hospital day 5, in the midst of an ongoing infectious diseases workup, the measured intracranial pressure and rate of CSF drainage from the ventriculostomy suddenly decreased.

Right, Sagittal T2-weighted noncontrast MRI image obtained on day 5 after sudden decrease in intracranial pressure and cerebrospinal fluid drainage.


He was taking amlodipine (5 mg daily) and ipratropium bromide nasal spray twice daily.On examination, he was afebrile.

Over the same period, he also developed thickened, brittle, and discolored fingernails and toenails.

More recently, he developed progressive exertional dyspnea and edema of both lower extremities.

He had yellow discoloration and thickening of his fingernails and toenails (Figure 1A).

He had partially nonpitting edema of the lower extremities (Figure 1B).

Heart rate was 66/min; blood pressure, 132/72 mm Hg; respiratory rate, 18/min; and oxygen saturation by pulse oximetry, 97% on room air.

Auscultation revealed diminished breath sounds at the lung bases but no rhonchi or crackles.

Percussion of the lung bases and vocal resonance were normal.

Cardiac and abdominal examination findings were unremarkable.A, Yellow discoloration and thickening of fingernails and toenails.

B, Partially nonpitting edema of the lower extremities with a positive Stemmer sign (difficulty pinching the skin on the dorsum of the toes), suggestive of lymphedema.Laboratory testing revealed normal complete blood cell count, comprehensive metabolic panel, and thyrotropin level.

Erythrocyte sedimentation rate was 2 mm/h; C-reactive protein level was 0.1 mg/dL.

Antinuclear antibody (ANA) was positive (1:160, nucleolar pattern), but results of testing for antibodies to extractable nuclear antigens and double-stranded DNA were negative.

He had mildly low C3 complement level (63 mg/dL [reference range, 79-152 mg/dL]), but normal C4 complement level (20 mg/dL [reference range, 16-38 mg/dL]).

A chest radiograph performed within the last 6 months to evaluate his chronic cough did not reveal any obvious cardiopulmonary disease.

He had no joint pain or swelling and no chest pain.


His diarrhea was nonbloody, woke him up from sleep, was accompanied by crampy abdominal pain, and was not associated with nausea or vomiting.

His physical examination results revealed normal vital signs and a mildly tender abdomen with hyperactive bowel sounds, but no peritoneal signs.

His laboratory workup results were notable for severe hypokalemia and hypomagnesemia, as well as positive fecal lactoferrin and elevated fecal calprotectin levels of 646 μg/g.

His infectious workup results were unremarkable.

A computed tomography scan of the abdomen/pelvis revealed diffuse long-segment wall thickening involving nearly the entire terminal ileum (Figure, A).

An ileocolonoscopy revealed erythematous and congested mucosa with scattered erosions and ulcerations throughout the examined terminal ileum (Figure, B).

The diarrhea persisted despite treatment with combinations of loperamide, atropine/diphenoxylate, colestipol, and tincture of opium.

He required repeated intravenous infusions for fluid and electrolyte repletion.


She had been treated for glaucoma for approximately 1 year.

Her medical history included hyperlipidemia, obesity, and prior cataract surgery in both eyes.

On examination, best-corrected visual acuity was 20/20 OD and 20/80 OS.

The patient’s pupils were equal, round, and reactive to light without a relative afferent pupillary defect.

Intraocular pressure was 11 mm Hg bilaterally without medication.

Slitlamp findings were notable for patent peripheral iridotomies, open angles on gonioscopy, and an asymmetrically enlarged cup-disc ratio with mild pallor of the left optic nerve.

Color vision was decreased in the left eye.

Visual field (VF) testing as well as ganglion cell layer (GCL) segmentation by optical coherence tomography (OCT) were obtained for both eyes (Figure 1).Optical coherence tomography ganglion cell layer thickness map shows nasal thinning of the right eye (A) and diffuse thinning of the left eye (B).

In the right eye, the relative thinning within the nasal macula compared with the temporal macula suggests injury to the papillomacular bundle.

In the left eye, the diffuse thinning suggests diffuse optic nerve injury (Heidelberg Spectralis; Heidelberg).

Review of systems was negative for previous episodes of eye pain, redness, or emesis.


He noted a medical history of hyperthyroidism, coronary artery disease, hypertension, and type 2 diabetes mellitus.

He also noted a history of substantial blood glucose elevation after taking oral prednisone.A review of systems had negative results, including the absence of joint pain, fevers, chills, weight loss, and rashes.

After strabismus surgery, he was noted to have a nonhealing conjunctival epithelial defect inferiorly, which later developed underlying scleral thinning.

His best-corrected visual acuity was 20/20 OD and counting fingers OS, and his intraocular pressures were 13 mm Hg OD and 4 mm Hg OS.

Slitlamp examination of the left eye revealed marked inferior redness, including large-caliber episcleral vessels and scleral thinning that was greatest inferonasally (Figure 1A).

There was an epithelial defect overlying the thinned sclera, scleral tenderness to palpation, 16 to 25 cells per high-power field in the anterior chamber, and iris neovascularization.

The view to the posterior pole was hazy, and B-scan ultrasonography revealed an inferior retinal detachment (Figure 1B).

He was being treated with topical moxifloxacin, 0.5%, every 2 hours in the left eye.

Examination of the right eye had unremarkable results.A, Slitlamp photograph of the left eye demonstrates focal scleral thinning inferonasally.


He denied any pain, swelling, or paresthesia, and his medical history was unremarkable.

A consultation with a dentist 1 year prior revealed an impacted mandibular canine (No.

Clinical examination revealed fullness on the mentolabial fold but no gross facial asymmetry or mental nerve paresthesia.

Intraorally, there was an expansile mass of the left anterior mandible with ill-defined margins, which crossed the midline and obliterated the gingivolabial sulcus.Results of dental cone beam computed tomography imaging revealed a 4.3 × 4.0-cm radiolucent mandibular lesion with an unerupted mandibular canine in the center of the lesion, cortical destruction, and root deviation of teeth Nos.

Histological sections from the resection demonstrated nests and cords of polygonal cells with clear to eosinophilic cytoplasm embedded in a dense collagenous stroma (Figure, B).

The lesion was centered in the cortical bone (Figure, C) and extended into the surrounding mucosa (Figure, D), fibroadipose tissue, and skeletal muscle.

Perineural invasion was identified (Figure, E), and lymphovascular invasion was absent.

Immunohistochemistry findings revealed the tumor cells were positive for p40.

Fluorescence in situ hybridization  studies demonstrated an EWSR1 gene rearrangement in 60% of the tumor cells (Figure, F).A, Dental cone beam computed tomography (CT) scan showing 4.3 × 4.0-cm radiolucent lesion in the anterior mandible with impacted mandibular canine at the center of the lesion.

B, Nests and cords of polygonal cells with clear to eosinophilic cytoplasm (hematoxylin-eosin stain).

C, Lesion centered in the bone (hematoxylin-eosin stain).

D, Tumor cells extending beyond the cortex of the mandible to involve the gingival mucosa (hematoxylin-eosin stain).

E, Perineural invasion is present (hematoxylin-eosin stain).

An incisional biopsy was performed, and the patient underwent radical mandibular resection 2 months later.


Her medical and family history was unremarkable.

The lesion started as a small eczematous, pink-to-brown plaque.

As the lesion was asymptomatic and slow growing, she did not initially seek treatment.

Recently, the color of the lesion had changed to an alarming dark brown color (Figure, A).

No breast mass or lymphadenopathy was observed.

A skin biopsy specimen was obtained and submitted for further histopathologic analysis.A, Clinical presentation of pigmented plaque in the axilla with well-demarcated margins.

B, Histologic findings revealed an intraepidermal neoplasm consisting of pagetoid cells, characterized by round, pale, vacuolated cytoplasm, and large pleomorphic nuclei (hematoxylin-eosin; original magnification ×200).

C, Immunohistochemical findings showed positive staining for EMA (original magnification ×200).

D, The lesion was surrounded by numerous reactive dendritic HMB-45–positive melanocytes scattered among the tumor cells (original magnification ×200).


There were no systemic complaints, history of arthropod bite, immunosuppression, travel abroad, or contact with animals in the recent past.

Physical examination revealed a skin-colored, firm, nontender, freely mobile 2 × 1.5-cm nodule with overlying normal skin on the right occipital region of the scalp (Figure, A).

No other cutaneous lesions were present.A, Clinical photograph shows a 2 × 1.5-cm skin-colored nodule on the occiput.

A nodular lesion surrounded by a fibrous capsule is seen in the dermis with cross-sections of many parasites along with pink material in the nodule (hematoxylin-eosin, original magnification ×2).

C, The parasite morphology depicts a thick cuticle, well-developed inner muscular layer, tubular structures containing microfilariae, and necrotic debris (hematoxylin-eosin, original magnification ×20).

Cross-sections of parasites were present, surrounded by a fibrous capsule (Figure, B).

The cuticle demonstrated a wavy pattern of longitudinal ridges on its outer surface (Figure, D).

The fibrous capsule contained mixed inflammatory infiltrate of lymphocytes, eosinophils, histiocytes, and plasma cells.

Findings of slitlamp examination and fundoscopy of the eyes were normal.

Findings of routine hematologic and biochemical investigations were normal.

No microfilaria was seen in peripheral blood.

Findings of chest radiography and abdomen ultrasonography were unremarkable.

D, Higher magnification shows spinous processes on the outer surface of the cuticle (hematoxylin-eosin, original magnification ×20).The nodule was completely excised and sent for histopathologic examination, which revealed a nodule in the dermis with an unremarkable epidermis.

The parasite showed an outer cuticle, muscle layer underneath, and gravid uterus filled with microfilariae (Figure, C).


Despite having taken multiple courses of oral antibiotics, he saw no improvement in his symptoms.

Over the course of 3 months, the patient went on to notice swelling and redness of his left ear (Figure 1A) that would resolve and recur every few weeks.Clinical photographs demonstrating auricular chondritis (A) and saddle nose deformity (B).Bothered by his hoarse voice and sore throat, he consulted a private otolaryngologist, who performed a nasoendoscopy, the results of which showed severe Reinke edema and chronic laryngitis.

In addition, his hoarseness of voice worsened during a 2-week span and was now associated with difficulty breathing when he laid supine.

He was unable to speak a full sentence without drawing a deep, labored breath.

In our otolaryngology clinic, physical examination results revealed a saddle-nose deformity, left pinna perichondritis, and a soft inspiratory stridor.

Laboratory test results showed elevated C-reactive protein levels of 143 mg/L, erythrocyte sedimentation rate of 97 mm/h, and a microcytic hypochromic anemia of hemoglobin level of 12.1 g/dL (to convert to grams per liter, multiply by 10).

He was treated with a short course of oral prednisolone that alleviated all his symptoms.However, on cessation of oral steroids, the patient noticed a saddle-shaped deformity on his nose (Figure 1B) that appeared without any antecedent trauma.


She had no relevant medical history, was not taking any systemic or ocular medications, and denied a history of floaters.

The patient denied any known history of sickle cell disease or trait and any family history of sickle disease.

Her visual acuity was 20/40 OU, and her intraocular pressure was 18 mm Hg OU.

An anterior segment examination was unremarkable in both eyes.

Ophthalmoscopy findings were notable for a vitreous hemorrhage in the right eye.

Salmon-patch intraretinal hemorrhages were noted in the temporal peripheral retina of both eyes (Figure 1).

Widefield fluorescein angiography revealed retinal capillary nonperfusion of the peripheral retina with neovascularization elsewhere, in a sea fan–like pattern, in both eyes.

Scatter laser photocoagulation was performed on the nonperfused temporal retina in the right eye, and the left eye was observed.A, Fundus photograph of the right eye with media opacity consistent with vitreous hemorrhage and, in the far temporal retinal area, evidence of ischemia and vascular attenuation and ghosting.

There is also evidence of multiple salmon-patch hemorrhages (arrowheads).


Both parents had a history of latent tuberculosis infection treated after immigrating to the US from Syria shortly after the patient’s birth.

The patient’s pediatrician diagnosed him with reactive airway disease and adenotonsillar hypertrophy.

He was sent to the emergency department, where he was stridulous and afebrile with a normal white blood cell count and an elevated erythrocyte sedimentation rate.

He was referred to the otolaryngology clinic, where flexible laryngoscopy revealed diffuse upper airway lymphoid hyperplasia and supraglottic edema.

A computed tomography scan of the neck revealed diffuse edema and contrast enhancement of the nasopharynx, oropharynx, hypopharynx, and supraglottis.

A chest radiograph was normal.The patient was taken urgently to the operating room for direct microlaryngoscopy (Figure 1A and B) and intubated.

Results of biopsies and cultures of the tonsils, adenoids, and supraglottis revealed diffuse non-necrotizing granulomas (Figure 1C) and oropharyngeal flora with negative acid-fast bacilli and Grocott methenamine silver stains.

During this time, he had a normal angiotensin-converting enzyme (ACE) level and normal titers for antinuclear antibody (ANA), cytoplasmic antineutrophilic cytoplasmic antibody, perinuclear antineutrophilic cytoplasmic antibody, antimyeloperoxidase antibody, antiproteinase 3 antibody, anti–double-stranded DNA antibody, Smith antibody, Sjogren antibodies, and histoplasma antibodies.

He also had normal results on tuberculin purified protein derivative and interferon-γ release assay (QuantiFERON; Qiagen).A, View with laryngoscope blade in vallecula, revealing only a profoundly swollen epiglottis.

He remained intubated, and treatment with systemic corticosteroids and antibiotics was initiated.

B, View with laryngoscope blade beneath epiglottis, revealing edema and distortion of supraglottic structures that obscured the glottis (* indicates left arytenoid; **, right aryepiglottic fold; ***, right arytenoid).

C, Supraglottic biopsy specimen demonstrating non-necrotizing granulomas in a background of lymphoid tissue; hematoxylin-eosin stain, original magnification ×200.


Her immunizations were up to date, and she had had an uncomplicated prenatal and delivery course.

Her ocular history and family history were unremarkable.

On examination, the patient’s visual acuity was 20/25 OU and pupillary responses and intraocular pressures were normal.

The anterior segments were normal, the lenses were clear, and there was no inflammation in either eye.

On a dilated fundus examination, the vitreous was clear bilaterally.

A single, superonasal, white retinal mass with no visible calcification or subretinal fluid was present in the right eye (approximately 2.5 disc diameters away from the optic nerve), with associated retinal pigment epithelium changes at the edge of the lesion (Figure 1) and a normal optic disc and posterior pole.

The left posterior segment was normal.Right eye fundus photograph at presentation: ultra-widefield image obtained in the clinic.

Peripheral image artifacts include the nose and eyelashes (inverted).