Two years before our examination, her visual acuity had been 20/200 OD and 20/60 OS.

At our initial evaluation, her visual acuity was 20/300 OD and 20/250 OS.

Optic nerve atrophy was noted, with no optociliary collaterals.

Imaging of the retinal nerve fiber layer showed thinning in both eyes.

Automated perimetry demonstrated general constriction of visual fields and bilateral central scotomas.

Ocular motility was full, without pain, and orthotropic.

Two years prior, initial magnetic resonance imaging (MRI) of the brain and orbits with and without contrast was read as normal.

Retrospectively, those images were reviewed and noted to be limited due to artifact from dental braces and a lack of fat suppression.

Two years prior, lumbar puncture revealed normal opening pressure.Complete blood cell count with differential was negative, as were test results for erythrocyte sedimentation rate, fluorescent treponemal antibody absorption, antinuclear antibody, angiotensin-converting enzyme, and serum neuromyelitis optica antibodies.

Whole-exome genome sequencing was negative for genes associated with neurofibromatosis type 1 and type 2.

After removal of dental braces, MRI of the brain and orbits with and without contrast demonstrated thickening and nodular enhancement of bilateral perioptic nerve sheaths extending up to the orbital apex.

Patchy T2-weighted hyperintensity was noted within the bilateral optic nerves (Figure).A, T1-weighted fat-suppressed image demonstrates thick, nodular, circumferential enhancement in the bilateral optic sheaths.


She denied a history of severe acne or other inflammatory skin disorders.

The patient had no health problems and only had a distant medical history of an appendectomy and an oophorectomy.

The only medication she was taking was hydroxychloroquine 200 mg twice daily that was initiated as treatment of her LPP and did not improve the appearance or symptoms of her facial papules.

On physical examination, she had numerous 1-mm skin-colored grouped monomorphic noninflammatory papules on the bilateral temples, the bilateral cheeks, and the chin.

A 3-mm punch biopsy specimen was obtained for histopathologic examination of a representative lesion on the right chin (Figure, B and C).A, Clinical photograph shows numerous grouped 1-mm skin-colored monomorphic noninflammatory papules on the left cheek and chin.

B and C, Histology of a 3-mm punch biopsy specimen of a lesion on the right chin using a hematoxylin-eosin stain.


She was previously diagnosed with hidradenitis suppurativa and treated with surgical excision and split-thickness skin grafting of the genitocrural folds with graft failure.

Over the past 1.5 years, she had been admitted to the hospital on multiple occasions for cellulitis around the wounds, which responded to intravenous antibiotics, and she had received a diverting sigmoid colostomy and indwelling urinary catheter to decrease wound contamination.

Just prior to presentation, she received adalimumab for 3 months without clinical improvement.

On physical examination there were linear moist, eroded, exophytic, condyloma-like plaques of the bilateral submammary folds (Figure, A), intergluteal cleft, and under the abdominal apron.

There were ulcers of the bilateral genitocrural folds, as well as vulvar edema (Figure, B).

The lips, oropharynx, and ostomy were unremarkable.

Similar plaques were present in the bilateral submammary fold, under the abdominal apron and in the intergluteal cleft.

B, Clinical photograph of linear ulcers of the genitocrural folds, vulvar edema, and an indwelling urinary catheter.

A wedge biopsy specimen of a submammary plaque was obtained, and histopathology was performed (Figure, C and D).A, Clinical photograph shows a submammary representative linear condyloma-like ulcerated plaque, as well as secondary irritant contact dermatitis from application of topical medications.

C, Hematoxylin-eosin stain of a biopsy specimen from the submammary plaque.

D, High-power image from the same specimen.


He had previously been treated with various topical glucocorticosteroids and antibiotics without improvement.

The family history was negative for skin disease.

The physical examination revealed multiple disseminated erythematous papules, petechial hemorrhages, and yellowish crusts on the scalp (Figure, A).

The patient did not show any other obvious abnormalities, but his mother reported occasional otitis media.

The remaining skin and mucosal surfaces, as well as neck, axillary, and inguinal lymph nodes, were unremarkable.

Routine blood examinations revealed no pathological findings.

A whole-body magnetic resonance imaging (MRI) scan showed 2 osteolytic lesions on the right frontoparietal skull (Figure, B).

A punch biopsy specimen of an erythematous papule on the scalp was obtained and stained with hematoxylin-eosin for histopathological analysis (Figure, C).

In addition, immunohistochemical stainings were performed (Figure, D).A, Clinical photograph shows multiple disseminated erythematous papules, petechial hemorrhages and yellowish crusts on the scalp.

B, Contrast-enhanced T1-weighted axial magnetic resonance image shows osteolytic lesions in the frontotemporal skull.

C, Histopathological analysis of a punch biopsy of the scalp demonstrates a subepidermal infiltrate consisting of large cells with kidney-shaped nuclei, solitary lymphocytes, and eosinophilic granulocytes.

D, The infiltrate stained positively for CD1A.


His parents also reported atypical social and language development, disrupted sleep, and persistent impulsivity with attempts to elope.The patient had a complex medical history that was marked by prematurity at 32 weeks, slow postnatal growth, and severe gastroesophageal reflux.

His pediatrician documented a normal neurological examination without dysmorphology or congenital anomalies.A developmental evaluation revealed delays in motor function and language development notable by age 2 years.

Tantrums were unpredictable and often resulted in severe head-butting.

The parents stated that he played repetitively, lining up toy cars and spinning their wheels.

He did not seek or give comfort to others when distressed.

He had tactile hypersensitivity but pain hyposensitivity, flicked light switches repetitively, and mouthed objects.In the office, the patient showed a minimal response to clinicians’ social overtures and poor eye contact.

He replayed videos on a smartphone while laughing, spinning around, and flapping his hands.

He did not respond to prompts for joint engagement and no imaginative play was observed.

When the videos stopped, he repeatedly climbed onto chairs and jumped off.

Testing results revealed clinically significant scores on the Autism Diagnostic Observation Schedule.

Cognitive testing results showed that his IQ was below average but was likely an underestimate due to noncompliance.

He attended a 0 to 3 program with intensive speech therapy and then moved to a self-contained preschool classroom with a 1:1 staff-to-student ratio.

He received school-based speech, occupational, and physical therapies.


The patient’s medical history was otherwise unremarkable and she had no known history of atopic dermatitis.

Physical examination revealed well-demarcated desquamative patches with scales on both distal feet, showing a sandal appearance.

No local heat, swelling, or discharge from the skin lesions was noted.

A fungal smear skin test with potassium hydroxide preparation was performed on the lesion, which showed negative findings.Well-defined hyperkeratotic desquamation on both feet, representing a sandal appearance.


The patient had a history of hyperlipidemia.

Results of examination revealed a palpable mass of about 15 cm in the left paraumbilical region.

The patient had a normal right testis but a missing left testis.

Results of a computed tomography scan of the thorax, abdomen, and pelvis revealed large intraperitoneal and retroperitoneal masses.

The intraperitoneal heterogenous mass was 20 × 15 × 11 cm, with linear calcifications (Figure 1).

There was a right moderate hydronephrosis.

The retroperitoneal mass was homogeneous, with associated lymphadenopathy encircling the aorta, inferior mesenteric artery, and both renal arteries.

A large left supraclavicular lymph node and left inguinal lymph node were also detected.

There was no metastasis identified elsewhere.

Serum lactate dehydrogenase was elevated at 1358 U/L (to convert to microkatals per liter, multiply by 0.0167), β human chorionic gonadotrophin was elevated at 1485 mIU/mL (to convert to international units per liter, multiply by 1.0), and α fetoprotein levels were normal.A computed tomography scan of the thorax, abdomen, and pelvis showing large intraperitoneal and retroperitoneal masses.

The intraperitoneal heterogenous mass was 20 × 15 × 11 cm, with linear calcifications.


The patient reported undergoing an appendectomy at age 23 years and having ulcerative colitis since he was aged 30 years.

He had received treatment (mesalazine and corticosteroids) for inflammatory bowel disease that had been discontinued.Physical examination revealed paraumbilical ecchymosis (Figure 1A), general abdominal tenderness, and distension.

He described abdominal trauma caused by the bicycle handlebar.

Body temperature, blood pressure, and heart and respiratory rates were normal.

Laboratory test findings did not show abnormalities except for the leukocyte count (12 300 cells/μL [to convert to ×109/L, multiply by 0.001]); hemoglobin and hematocrit levels were within the reference ranges.

An abdominal computed tomographic (CT) scan, performed immediately, revealed a pneumoperitoneum and free fluid in the lower quadrants of the abdomen (Figure 1B).Preoperative workup.

B, Abdominal computed tomography (CT) scan: coronal cut showing free fluid (white arrowhead) and pneumoperitoneum (red arrowheads).


Visual acuity was 20/400 in the left eye, improved to 20/100 with pinhole.

Slitlamp examination revealed a small, nasal corneal scar, a small iris defect, iris heterochromia, and a cataract with overlying pigment (Figure 1A).

Dilated funduscopic examination of the left eye demonstrated vitritis and a hazy view of the retina due to the opacity of the media.

A color fundus photograph of the eye showed opacity of the media secondary to the cataract and vitritis and a slightly pale optic nerve.

Fluorescein angiography (Figure 1B) demonstrated early hyperfluorescence of an inferotemporal chorioretinal lesion that increased slightly during the course of the study, consistent with possible leakage.

There were multiple hypofluorescent dots throughout the retina and an appearance of segmentation of the vessels with slightly decreased venous filling and late staining.

A computed tomography scan of the eye and orbit revealed a hyperdense foreign body located along the inferior aspect of the vitreous, approximately at the 5 o'clock position, abutting the retinal surface.

Ultrasonography B scan revealed a highly reflective material causing posterior shadowing at the 5 o’clock position.A, Cataract with overlying pigment (yellow arrowhead).


The kidney transplant was performed 4 years previously presumably secondary to diabetic nephropathy, and the patient was receiving daily 5 mg of oral prednisone and 1500 mg of mycophenolate mofetil hydrochloride.

The patient denied significant ocular history before this episode of vision loss.

On examination, his visual acuity was counting fingers OD at 2 ft and 20/20 OS.

Intraocular pressures were measured at 15 mm Hg OD and 14 mm Hg OS, and normal pupillary and anterior segment examination findings were noted in each eye.

The patient had several large pigment epithelial detachments (PEDs) with associated tears and scrolling of the retinal pigment epithelium (RPE) seen on enhanced-depth imaging optical coherence tomography in the right eye (Figure 1A).

Intravenous fluorescein angiography demonstrated several large window defects with hyperfluorescence in the regions of the RPE tears in the late phase (Figure 1B).

Indocyanine green angiography was also performed and did not reveal any hyperfluorescent regions.A, Enhanced-depth imaging optical coherence tomography (OCT) of a foveal cross-section at presentation shows a serous retinal detachment and a retinal pigment epithelium tear with scrolled edges seen along the Bruch membrane inferiorly in the image and the other edge of the tear seen attached to the retina at the top left.


She was otherwise well and had no history of tuberculosis or underlying immunocompromise.

Three days after initial presentation, the patient developed acute binocular horizontal diplopia and disorientation.A, Color fundus photograph revealed bilateral swollen, hyperemic optic discs with multifocal choroidal lesions.

Her best-corrected visual acuity was 20/80 OD and 20/60 OS.

Ophthalmoscopy revealed bilateral swollen, hyperemic optic discs with multifocal yellowish choroidal lesions located at the midperiphery and posterior pole of the retina.

The lesions varied in size, ranging from one-fourth to twice the diameter of the optic disc.

Punctate areas of choroiditis were also seen along the temporal arcades (Figure 1A).

Results of fundus fluorescein angiography showed bilateral early hypofluorescence, with late staining and leakage from the optic discs.

Results of systemic examination were normal, except for coarse crepitations of the right lung.

The erythrocyte sedimentation rate was elevated, at 80 mm/h, as was the C-reactive protein level, at 20.2 mg/L (to convert to nanomoles per liter, multiply by 9.524).

Chest radiograph showed consolidation in the right lower zone (Figure 1B).

However, results of tuberculin skin test, sputum for acid-fast bacilli, and sputum culture were negative.


Her ocular history included narrow angles and ocular hypertension that were managed with laser peripheral iridotomy and topical antiglaucomatous medications in both eyes.

During subsequent visits to the clinic, pigmentation was also noted in the auricles of both ears (Figure 1B).External photographs taken at initial presentation.

On examination, her visual acuity was 20/25 OD and 20/20 OS, with intraocular pressure of 21 mm Hg OD and 21 mm Hg OS.

Slitlamp examination demonstrated mild cataract with narrow angles, with patent laser peripheral iridotomy in each eye.

Ophthalmoscopic examination demonstrated peripheral paving-stone degeneration in the right eye and peripheral retinal pigmentary abnormalities in both eyes.


The baby was an otherwise healthy girl born at full term.

Her perinatal history was significant only for a positive maternal test for group B Streptococcus agalactiae, which was treated prior to delivery.Results of the initial examination were significant for conjunctival hyperemia or vasodilation of the right eye, with a 3 × 4-mm central corneal ulcer.

The patient had received a diagnosis of conjunctivitis at 6 days of life but failed to respond to treatment with topical erythromycin ophthalmic ointment, 0.5%.

Results of spinal ultrasonography demonstrated spinal cord tethering at L4, preventing lumbar puncture and collection of cerebrospinal fluid for culture.Two days later, the patient’s right eye developed a hypopyon, and its intraocular pressure was elevated (Figure).

Results of B-scan ultrasonography showed no posterior chamber involvement.

Corneal cultures for bacteria, fungi, and herpes simplex virus were obtained.

Results of another B-scan ultrasonography showed a normal posterior segment without inflammation.

Treatment with topical polymyxin B sulfate-trimethoprim and intravenous ampicillin, cefepime hydrochloride, and acyclovir sodium was initiated.

The topical antibiotic eyedrops were changed to fortified vancomycin hydrochloride, 50 mg/mL, and tobramycin sulfate, 14 mg/mL, and topical timolol maleate, 0.5%, and dorzolamide hydrochloride, 2.0%, were added.

Owing to concern for systemic involvement of group B S agalactiae, herpes simplex virus, and other infectious causes, the patient was admitted to the children’s hospital for a full sepsis workup.

Anterior chamber fluid was sent for culture.


He had no other pertinent medical history and no relevant ocular history other than anisometropia, for which he wears a corrective contact lens in his right eye.

At his initial ophthalmology visit, his best-corrected visual acuity was 20/40 OD and 20/20 OS.

In both corneas, he had numerous multicolored, highly refractile crystals located primarily in the subepithelium and anterior stroma (Figure 1).

No deposits were noted in the retina of either eye on funduscopic examination.External slitlamp examination of the left eye shows extensive subepithelial and anterior stromal crystals.

Similar findings were seen in the right eye.


He was otherwise asymptomatic and had no physical limitations.

He had never smoked, and results of his physical examination were normal.

Results of complete blood cell counts, basic metabolic panel, and liver function tests were all within normal limits.

A chest radiograph revealed a 10 × 9-cm lobulated left lower lobe mass.

Examination of a biopsy specimen showed a primary adenocarcinoma with an immunohistochemical profile of CDX2 positive, CK20 positive, TTF-1 negative, and napsin A negative.

His EGFR (OMIM 131550), ALK (OMIM 105590), and ROS1 (OMIM 165020) genes were wild type, and results of testing for programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) were 0%.

Results of upper gastrointestinal tract endoscopy and colonoscopy did not reveal any evidence of a primary malignant neoplasm.

Positron emission tomography showed no evidence of mediastinal lymphadenopathy or extrathoracic disease.

Surgical margins were negative for involvement, with no large vessel or perineural invasion seen.

Five sampled lymph nodes were negative for involvement.

Given the patient’s excellent performance status, he underwent a mediastinoscopy with left lower lobe lobectomy.

Results of postoperative pathologic testing showed a 13-cm adenocarcinoma with similar immunohistochemical markers as in the prior biopsy specimen.

Repeat pathologic interpretation was performed (Figure).Initial pathologic testing of a left lower lobe biopsy specimen (hematoxylin-eosin stain, original magnification ×100).


Her medications included 125 mcg digoxin daily and 2.5 mg apixaban twice daily.On presentation, she was afebrile.

She experienced severe pain over the left hip.

She denied any head trauma or loss of consciousness but described occasional palpitations.

Her blood pressure was 168/96 mm Hg, her heart rate was 88 beats per minute, and her respiratory rate was 18 breaths per minute.

Physical examination showed no gross physical deformity.

The trachea was midline and the neck was supple, without any engorged veins.

Lung sounds were clear to auscultation bilaterally.

Precordial palpation revealed a nonpalpable apex beat.

Heart sounds were appreciated loudest over the right parasternal area.

No S3, murmur, rub, or gallop were present.

The 12-lead electrocardiogram showed marked right axis deviation with poor R wave progression across the precordial leads V1-V6 (Figure 1).Standard 12-lead electrocardiogram shows upright R wave in avR and R wave regression across the precordial leads.

Radiography of the hip showed a femoral neck fracture, and she was scheduled for emergent hip arthroplasty.


She had a remote 2 pack-year smoking history.

She was prescribed antibiotics and steroids by her family physician, which initially provided intermittent, symptomatic improvement; however, she ultimately experienced a progressive decrease in tactile sensation on her face, anosmia, and changes in her right peripheral vision.

Sinus computed tomography (CT) and neck magnetic resonance imaging (MRI) revealed a large expansile mass arising from the right side of the skull base and nasopharynx with extension into the pterygopalatine fossa, masticator, parapharyngeal, retropharyngeal, and carotid spaces.

In addition, imaging showed involvement of the right posterior orbit with erosion of the posterior maxillary sinus wall, anterior and middle cranial fossa with erosion through the cribriform plate, and cavernous sinus.

Physical examination revealed slight right-sided facial fullness, grossly intact extraocular motion, decreased vision in the right lateral field, and palpable bilateral level 2 neck lymph nodes.

Flexible laryngoscopy revealed a right-sided lobulated mass involving the medial middle turbinate, posterior septum, and nasal floor, as well as the posterior aspect of the maxillary sinus extending superiorly to the nasopharynx and skull base posteriorly.

The mass extended into the left superior nasopharynx and superior septum.

In-office biopsy specimens were obtained and revealed a primitive small round cell tumor with the following immunohistochemical (IHC) staining profile: diffusely positive for desmin, myogenin, and CD56; focally positive for low-molecular-weight kininogen (LMWCK), p63, and S-100; and negative for AE1/AE3, CK 5/6, CK7, CK20, p40, chromogranin, SOX10, HMB45, CD99, and CD20 (Figure 1).Histopathologic images.

A, Nests of primitive small round blue cells surrounded by fibrovascular septa.


A noncontrast computed tomographic (CT) scan of the abdomen demonstrated splenomegaly, ascites, and a retroperitoneal mass posterior to the pancreatic head.

Fine-needle aspiration from the retroperitoneal mass and ascitic fluid revealed no malignant cells.

The patient subsequently developed a left-sided lateral chest wall hematoma, and, in retrospect, it was thought that the retroperitoneal mass was actually a hematoma because multiple follow-up studies demonstrated the mass steadily decreasing in size.

Echocardiography showed right atrial and ventricular dilatation and increased thickness of the interventricular septum.

Laboratory tests showed elevated results for serum-free λ light chain and proteinuria levels and altered liver function tests but a normal coagulation profile.

Routine surveillance noncontrast CT imaging of the neck demonstrated a submucosal soft-tissue mass containing few punctate calcifications centered in the epiglottis with clinically significant narrowing of the oropharyngeal and supraglottic laryngeal airways by the enlarged epiglottis (Figure).Computed tomographic images show a soft-tissue mass containing punctate calcifications centered on the epiglottis.


She had not experienced hypertension, vertigo, sleep apnea, hyperthyroidism, hearing loss, head trauma, history of ear infections, otorrhea, rhinorrhea, ear surgery, or family history of ear problems.

She reported constant pulsatile tinnitus with a whooshing quality for 4 years.

Factors exacerbating her symptoms included holding her breath and turning her head to the left.

She reported that compression of her right neck and turning her head to the right decreased the loudness of the tinnitus.

The external auditory canals were clear bilaterally.

Tympanic membranes were intact and mobile bilaterally.

There was no evidence of any vascular masses in the middle ear space.

Results from testing with tuning forks were normal.

Toynbee stethoscope revealed a bruit in the right ear that could be stopped with gentle compression of the right side of the neck.

An audiogram showed hearing within normal limits with slight air-bone gaps present at 250, 1000, and 3000 Hz on the right and within normal limits on the left.

Speech reception threshold on the right was 10 dB with a word recognition score of 100% bilaterally.

The tympanogram result revealed type A bilaterally, and acoustic reflexes were all present.

A computed tomographic (CT) temporal bone scan was completed (Figure 1).Computed tomographic images of the right temporal bone.


His medical history was significant for obstructive sleep apnea, gastroesophageal reflux disease, a right ear skin cancer excised by a dermatologist, and coronary artery disease with angina on stress test.

He described the pain as “electric” and “stabbing.” He reported no numbness of the region and had not experienced any other symptoms, including new neck masses.

His physical examination revealed a well-healed excision site of the right ear without new skin lesions.

He had full strength of the shoulder and no numbness of the right ear or cheek.

Palpation of the lateral neck demonstrated a mass running along the lateral border of the sternocleidomastoid (SCM) muscle.

Magnetic resonance imaging (MRI) showed an elongated enhancing tubular structure along the lateral surface of the right SCM muscle (Figure 1).A and B, Anterior to posterior coronal fat-saturated T1-weighted postcontrast magnetic resonance imaging (MRI) with an enhancing tubular mass of the right side of the neck (yellow arrowhead) that extends posterior and deep to sternocleidomastoid (SCM) (blue arrowheads).

C, Axial T1-weighted postcontrast MRI with an enhancing tubular mass (blue arrowheads) that extends posterior and deep to the SCM (blue arrowheads) (white arrowhead indicates external jugular vein).


His sister had diabetes mellitus and a similar rash in her axillae.

Physical examination revealed irregularly thickened skin of the right axilla (Figure 1, left) and right lateral area of the neck (Figure 1, right) containing hyperpigmentation, hypopigmentation, multiple acrochordons (skin tags), malodorous crust, and areas of maceration and erosion.

It was worse during the summers, and blisters sometimes developed.

Further examination of the skin revealed pseudofolliculitis barbae in the submental and mandibular regions bilaterally.

The nails, oral cavity, and mucosal membranes appeared normal.

The patient performed indoor manual labor as a maintenance engineer and had no significant sun exposure.

A biopsy of right axillary skin was performed (Figure 2).Left, Rash of right axilla.


She was born full term to a primigravid mother, who had an uncomplicated pregnancy.

On examination, the baby was alert and healthy appearing, although her sclerae were icteric.

At parturition, the baby presented in occiput posterior position and remained partly crowned for more than 24 hours of maternal labor.

Birth weight was 3.13 kg (15th percentile), head circumference was 31 cm (<1 percentile), and Apgar score was 9 of 9.

The baby’s head had a markedly elongate vertex, which the neonatal intensive care unit team diagnosed as cephalohematoma.

On day 5 of life, her serum total bilirubin and conjugated bilirubin were 20.5 mg/dL (>95 percentile) and 0.3 mg/dL (to convert to micromoles per liter, multiply by 17.104), respectively.

The vertex of her scalp was uniformly boggy, soft, and edematous, extending beyond suture lines, consistent with a diagnosis of caput succedaneum.

Beneath the mat and extending laterally in both directions was a deep, 8 × 1-cm, trenchlike ulcer with no drainage (Figure 1B).

The girl was hospitalized for 1 day of phototherapy before being discharged home weighing 2.95 kg (−5.75%).

Wound culture samples were sent for analysis, and she was given empirical intravenous clindamycin hydrochloride.

Finally, due to failure to progress, the baby was delivered by urgent cesarean delivery.

She was exclusively breastfed.She was admitted to our hospital for evaluation of the scalp.

On the right occiput, there was a mat of hair and thick serosanguineous crust adhering to the scalp (Figure 1A).

It was nontender to palpation.A, Serosanguineous crust adhering to occipital scalp of a neonate.

Prior to removing this crust it was being treated as an open ulcer.

B, Trenchlike linear ulcer revealed after removal of the crust.


He had a history of keratosis pilaris on the lower legs and was otherwise well with no fevers, recent upper respiratory infections, abdominal pain, vomiting, or diarrhea.Physical examination showed a man in no apparent distress.

The patient was well until 2 days prior to hospitalization when he developed bilateral lower extremity edema.

The day prior to admission, he developed painful pink lesions on both legs.

There was also a background of pinpoint folliculocentric papules on leg and thighs consistent with keratosis pilaris.

There was 2+ pitting edema of the lower extremities.

On the bilateral anterior legs were scattered tender, pink to purple nodules, and plaques (Figure, A).

A punch biopsy specimen was obtained for histopathology and microbiology cultures (Figure, B-D).

Routine complete blood cell count and complete metabolic panel had results within normal limits.A, Clinical photograph shows scattered pink to purple nodules and plaques on the bilateral lower extremities.

B, C, and D, Histopathologic images of a biopsy specimen (hematoxylin-eosin).

B, Subcutaneous tissue with superficial and deep, dermal and perivascular inflammation, fibrosis, and fat necrosis.

D, Dense neutrophilic infiltration of subcutaneous fat associated with fat necrosis and deposition of granular basophilic material (arrowhead).

He had not applied any topical medications to his legs or had recent exposure to hot tubs or fish tanks at the home.


The lesions previously resolved with topical corticosteroids but flared soon after treatment discontinuation.

Some papules became pruritic and extended to the waist and anterior trunk in the past month.

Physical examination revealed multiple hypopigmented, flat-topped papules on the back, waist, and inframammary area without genital involvement (Figure, A).

Most lesions were folliculocentric under close inspection.

Dermoscopy revealed central keratin plugs and some foci of structureless, whitish, and homogenous areas with surrounding erythema (Figure, B).

The results of laboratory tests for antinuclear antibody and hyperglobulinemia were negative.

A biopsy specimen was obtained from the back for histologic analysis (Figure, C).A, Multiple hypopigmented, atrophic, keratotic, and folliculocentric papules are seen on the trunk.

B, Dermascopic findings included 2 foci of central keratin plugs and another ill-defined, whitish, and homogenous area with surrounding erythema.

C, Histopathologic examination of a biopsy specimen (hematoxylin-eosin, original magnification ×100).

No family history of similar lesions was recorded.


In addition, the parent reported that, at birth, the patient failed multiple hearing tests and that he had small kidneys.

The parent noted that clear fluid drained from this bump when the patient ate.

Upon physical examination, the patient was noted to have a preauricular sinus and ear pit as well as a skin-colored papule on the antitragus of the right ear.

He also had a pedunculated, skin-colored papule on the right lateral neck.Photograph of infant’s lateral neck depicting skin-colored papule with clear drainage.


The pain had no associated nausea, vomiting, or obstipation.

On examination, he was afebrile and had a normal heart rate but was notably hypotensive.

His physical examination showed an abdomen that was soft but diffusely tender without rebound or guarding.

Blood testing revealed an elevated creatinine level of 1.7 mg/dL (to convert to micromoles per liter, multiply by 88.4), an elevated lactate level of 29.7 mg/dL (to convert to micromoles per liter, multiply by 0.111), an international normalized ratio of 4.6, a lowered hemoglobin level of 10.7 g/dL (to convert to grams per liter, multiply by 10), and a lowered hematocrit level of 27.2%; all other results were unremarkable.

Given his coagulopathy, low hematocrit level, and abdominal pain, a computed tomography angiogram was performed to rule out bleeding (Figure 1).A, Axial cross-section computed tomography without contrast of the abdomen and pelvis revealed gallstones in the neck of the gallbladder, high-density material within the lumen, and free intraperitoneal fluid.

He was given 2 L of crystalloid, and his blood pressure responded appropriately.


In 2014, he experienced angina that resolved following placement of a drug-eluting stent in his LAD.

He reported dyspnea on exertion and left leg claudication at 23 m. At rest, his blood pressure was 146/65 mm Hg measured on the right arm and 85/50 mm Hg on the left arm.

Physical examination was notable for a diminished left radial pulse.

Coronary angiography via the left femoral artery is displayed in the Figure.


He initially presented to his primary care physician reporting unintentional weight loss, fevers, and subacute visual decline.

Subsequent ophthalmic examination revealed mild anterior and posterior inflammation, raising suspicion for panuveitis.

He was pseudophakic with bilateral mild anterior chamber inflammation, moderate vitreous haze, and inferior vitreous condensations.

The posterior pole demonstrated bilateral diffuse retinal pigment epithelial alterations with a prominent leopard spot pattern and focal choroidal pigmented lesions.

Macular subretinal fluid tracked to the inferior periphery in both eyes (Figure 1A).

Optical coherence tomography confirmed bilateral subretinal fluid and retinal pigment epithelial irregularity (Figure 1B); nummular hypoautofluorescent lesions were interspersed within areas of hyperautofluorescence on autofluorescence imaging.

The optic disc and peripheral vasculature leaked on fluorescein angiography.

B-scan ultrasonography also showed diffuse choroidal thickening with focal choroidal thickening consistent with the pigmented choroidal lesions.

Ultrasonographic biomicroscopy revealed ciliary cysts associated with anterior thickening of both ciliary bodies.A, Optos photograph of the left eye demonstrating diffuse retinal pigment epithelial alterations in a leopard spot pattern (white arrowhead) and focal choroidal pigmented lesions, as well as subretinal fluid that tracks to the inferior periphery.

However, a right upper lobe lung mass noted on the chest radiograph proved to be T2N2M0 stage III non–small-cell lung cancer on biopsy.On presentation to us, the patient’s visual acuity was 20/150 OD and 20/200 OS, but improved to 20/70 OU with pinhole.

Results of laboratory tests for sarcoidosis, Lyme disease, and syphilis were negative.


He had no history of contact lens use, ocular trauma, or ocular surgery.

His only other medications were oral vitamin D and folic acid.

He had no other symptoms other than occasionally noticing a sensation of a foreign body in that eye and denied any changes in his vision.

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

Intraocular pressure was 16 mm Hg OD and 23 mm Hg OS.

The lesion measured 6.5 × 2.5 mm and was firm, nonvascular, slightly mobile, and located on the superotemporal portion of the bulbar conjunctiva (Figure 1).

It was purulent in appearance, but no material was expressed with attempted incision and drainage at the slitlamp.

A culture was positive only for Propionibacterium acnes.

Tests for herpes simplex, cytomegalovirus, and Epstein-Barr virus polymerase chain reactions were negative.External slitlamp photograph showing conjunctival lesion at presentation.

He was initially treated with topical antibiotics followed by a course of oral sulindac, 200 mg twice daily, without any improvement.


Examination with the patient under anesthesia with fluorescein angiography (Figure 1) revealed significant peripheral retinal avascularity, circumferential vascular loops at the border of vascular and avascular retina, and arteriovenous anastomoses in both eyes.


Her other medical history was unremarkable.Six months prior to presentation, workup at her local hospital for the transient vision loss revealed an enhancing right orbital mass on magnetic resonance imaging (Figure, A).

She reported 5 episodes, each lasting a few minutes and all occurring on awakening.

Further inquiry revealed that symptoms always developed after using her electronic reader tablet in dim lighting while lying on her left side.

Notably, the patient reported immediate resolution of vision loss on turning on the lights.

She denied headaches, visual aura, or neurologic symptoms.

Carotid ultrasonography and head magnetic resonance angiography showed no abnormalities.

Magnetic resonance imaging 3 months later showed a stable mass without change in size or appearance.A, T1-weighted magnetic resonance image (MRI) of the orbit with contrast shows a well-circumscribed, enhancing soft-tissue lesion in the right orbit superomedially (arrowhead).

B, Computed tomographic (CT) scan of the orbit with contrast shows the mass (arrowhead); no change noted on Valsalva maneuver.On examination, visual acuity was 20/25 OD.

Pupils, intraocular pressure, and motility were unremarkable.

Anterior segment examination showed mild cataract and dry eye.

Posterior pole examination revealed evidence of posterior vitreous detachment and normal optic nerves with 0.2 cup-to-disc ratio in each eye.

The retina was flat without evidence of whitening or Hollenhorst plaques.

Normal retinal nerve fiber and ganglion cell layer thickness were observed in each eye on optical coherence tomography.


He had been diagnosed as having an orbital capillary hemangioma at 3 months of age after orbital magnetic resonance imaging (MRI), which had reportedly revealed an orbital mass with enlarged extraocular muscles.

He was treated with oral propranolol with no improvement.On examination, the patient had inferior displacement of the left globe with a severe limitation of supraduction and a mild limitation of horizontal movement in the left eye.

He was unable to maintain fixation with the left eye.

Results of modified Krimsky testing showed 6 prism diopters (PD) of exotropia and 16 PD of left hypotropia.

Retinoscopy disclosed a cycloplegic refraction of +2.00 diopters (D) in the right eye and +6.00 D in the left eye.

Thyrotropin, thyroxine, and thyroid-stimulating immunoglobulin levels were all within reference ranges.

Repeated MRI with coronal images showed massive enlargement of the superior, inferior, and medial rectus muscles (Figure 1).

The medial rectus mass extended nasally to produce bowing of the lamina papyrecea, with no extension into adjacent structures.

The enlarged extraocular muscles were hypointense on T1- and T2-weighted sequences.

An abnormal curvilinear signal in the intraconal fat was isointense with muscle (Figure 1).A, Coronal T1-weighted magnetic resonance imaging (MRI) of both orbits shows enlarged inferior, medial, and superior rectus muscles with an isointense curvilinear signal in the intraconal fat (arrowhead).


Several days after YAG capsulotomy for posterior capsule opacification, his left eye had become red and painful and his visual acuity had declined to counting fingers.

The macular edema improved with 4 times daily topical prednisolone acetate and ketorolac tromethamine.After 2 months, the patient reported recurrent pain, redness, and decreased visual acuity.

A subsequent vitreous tap and injection of intravitreal vancomycin hydrochloride (1.0 mg) and ceftazidime (2.25 mg) were performed.

His visual acuity was 20/20 OD and 20/160 OS improving to 20/120 OS with pinhole.

His intraocular pressure was 32 mm Hg OD and 20 mm Hg OS.

The results of ophthalmic examination of the left eye were notable for pigmented keratic precipitates, a rare anterior chamber cell, 2+ (ie, 16-25 cells per field) anterior vitreous cells, epiretinal membrane, and cystoid macular edema.

Tuberculosis, sarcoidosis, syphilis, and HLA-B27 laboratory test results were negative.

At that time, the visual acuity in the left eye was 20/200E at 2 ft, and there were 4+ (ie, >50 cells per field) anterior chamber cells, a layered hypopyon and 2+ anterior vitreous cells.

Inflammation improved but persisted after vitreous tap and injection of intravitreal vancomycin hydrochloride (1.0 mg) and ceftazidime (2.25 mg) followed by intravitreal triamcinolone acetonide.

Vitreous cultures yielded no growth.Six months after the patient’s symptoms began, he presented to our clinic.


Medications were switched to levetiracetam, and a tapering dose of steroid was prescribed.

Her skin lesions slightly improved.Two months later, she developed diffuse urticarial lesions of varying sizes over the old plaques.

The T cell receptor γ gene (TRG) rearrangement analysis by polymerase chain reaction (PCR) was negative.The plaques and nodules worsened over a 6-month period, becoming more numerous and increasing in thickness, especially on the face, and early leonine facies developed (Figure 1B).

These lesions were well-defined with demarcated borders and were minimally pruritic at the time.Given that her condition worsened despite changing her medication, the lesions were biopsied and analyzed, and the results were inconclusive, demonstrating atypical lymphoid infiltrate.

The results from analysis of a second biopsy specimen showed dense band-like lymphoid infiltrate in the superficial dermis with mild epidermotropism.

As her condition continued to worsen, a third biopsy specimen was obtained, and the result was consistent with the suspected diagnosis.


Thirty-day event monitoring showed sinus tachycardia during episodes of palpitation.

Physical examination was unremarkable, except for sinus tachycardia.

Laboratory test results were all within normal limits.

The electrocardiogram showed sinus rhythm and early repolarization changes (Figure, A).

The transthoracic echocardiogram is shown in Figure, B, and Video 1.

The left ventricular ejection fraction was between 56% and 60%.

The estimated pulmonary artery systolic pressure was 24 mm Hg.

A transesophageal echocardiogram was also performed (Video 2 and Video 3).A, Electrocardiography showing sinus rhythm and early repolarization changes.


He had no reported respiratory issues at birth and no feeding difficulties.

His symptoms included gasping and apneic episodes at night, as well as nighttime nasal congestion.

Nasal endoscopy in clinic revealed a firm, mobile mass in the nasopharynx.

Magnetic resonance imaging of the brain revealed a 21 × 14 × 18-mm irregular, but well-defined, heterogeneously enhancing mass in the left nasopharynx with increased perfusion (Figure, A).

Final pathologic results demonstrated keratinizing squamous cysts and collections of ductal structures set within a myxoid stroma, with small nests of primitive mesenchyme (Figure, C and D).

He had been evaluated by an outside otolaryngologist, who had scheduled an adenoidectomy.

Given the vascularity of the tumor, the boy underwent preoperative embolization with interventional radiology.

He was subsequently taken to the operating room, where endoscopic resection of the mass and division of the pedicle were performed without complication (Figure, B).

Intraoperatively, he was found to have a nasopharyngeal mass, and thus surgery was aborted.


He stated that he had recently bitten his cheek and had since experienced increasing spontaneous pain and swelling.

There was no obvious swelling extraorally.

Oral examination revealed an erythematous, 15 × 10-mm lesion of the buccal mucosa, adjacent to the maxillary first molar.

The lesion was hard and produced a small amount of bleeding with palpation (Figure 1).


She was initially prescribed a muscle relaxant without notable improvement.

Physical examination revealed a mild firmness in the left submandibular area.

The mucosa of the oral cavity and floor of mouth was normal.

Cranial nerve function, including tongue mobility and sensation, was also normal.

Contrast-enhanced computed tomography (CT) demonstrated a 1.7 × 1.5 × 1.4-cm mass, adjacent to the left submandibular gland.

Scattered, nonenlarged lymph nodes were observed (Figure, A).

Histopathologic findings showed spindle cell neoplasm with morphologic features and no malignant neoplasm identified (Figure, C).

Results from immunohistochemical analysis were positive for S100 (Figure, D) and negative for smooth muscle actin, CD34, and pankeratin.A, Contrast-enhanced computed tomographic (CT) image.

The patient underwent surgical exploration with left submandibular gland excision and resection of the left submandibular mass (Figure, B).

An ultrasonography-guided fine needle aspiration biopsy was nondiagnostic owing to an inability to obtain sufficient tissue.

B, Submandibular mass after removing the left submandibular gland.

C, Hematoxylin-eosin–stained frozen section of the mass.

D, Positive S-100 immunohistochemical stain.


This mass underwent progressive growth during the first year but subsequently stabilized.

Despite causing occasional pruritus, the lesion was otherwise asymptomatic.

A shave biopsy specimen revealed islands of large epithelioid cells with increased mitotic index surrounded by a dense lymphocytic infiltrate (Figure, B and C).

The tumor cells expressed p16 (Figure, D) and epithelial membrane antigen (EMA), p63, and CK903, and were negative for prostate-specific antigen, CDX2, thyroid transcription factor 1, S-100, chromogranin, synaptophysin, and CD56.

In situ hybridization for Epstein-Barr virus (EBV) was negative.

Otolaryngology referral was sought to rule out a head or neck primary neoplasm.

With the exception of the cutaneous neoplasm, the findings from the otolaryngologic examination were unremarkable.

A screening chest computed tomographic (CT) image showed multiple right lung nodules, the largest of which measured 2.4 cm in diameter.

A biopsy of this pulmonary nodule showed a well-differentiated adenocarcinoma with lepidic pattern, and further workup revealed an intestinal tumor as the primary source.

Positron emission tomography and CT imaging demonstrated a mildly fludeoxyglucose F 18–avid superficial supraclavicular soft-tissue mass but no primary head or neck malignant neoplasm or local nodal metastases.

A wide local excision of the cutaneous mass and a right level Vb neck dissection were performed.

Clinical observation was recommended.A, 6.5 × 2.5-cm erythematous, raised, nontender lesion localized to skin without underlying tethering.

B, Carcinoma and rich lymphoplasmacytic infiltrate (original magnification ×200).

C, Carcinoma showing anaplasia and atypical mitoses (arrowhead) (original magnification ×400).

The final pathology report showed residual neoplasm with negative margins and 5 negative lymph nodes.


She was prescribed proton pump inhibitor (PPI) therapy with esomeprazole 40 mg, which she took daily, 30 minutes before breakfast.

She had no dysphagia, gastrointestinal bleeding, weight loss, anemia, or exertional chest pain.

Over-the-counter antacids provided incomplete benefit.

Her heartburn did not improve and continued to bother her daily despite adding famotidine at bedtime.Esophagogastroduodenoscopy (EGD) results, with esophageal mucosal biopsies, were normal.

Twenty-four-hour ambulatory reflux monitoring was performed after acid suppressive medications were discontinued for 1 week (Table).

She was referred for esophageal physiologic testing for possible gastroesophageal reflux disease (GERD).


She was diagnosed 6 years ago with recurrent poorly differentiated serous ovarian carcinoma and underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, with multiple regimens of chemotherapy, most recently with ixabepilone and bevacizumab.

Complications included a large bowel obstruction, for which she underwent a transverse loop colostomy 3 years ago.The nodule first appeared 1 year prior.

It appeared to increase in size after contact with fecal matter and decrease in size after cleaning of the ostomy site, although it never resolved completely.

She reported no pain at the site but described mild burning with fecal-induced irritation.

She noted “pus-like” drainage from the nodule and received several courses of antibiotics.Examination revealed a 3-cm firm, pink to violaceous, irregularly shaped multilobulated nodule with a central 1-cm ulcer with undermined borders, overlying an erythematous base (Figure).

The nodule was rock-hard, with a friable yellow-red plaque between the nodule and ostomy site.

The stoma was red, moist, and well-perfused.


He was otherwise healthy, with no other underlying conditions, and he was taking no medications.

He had no history of atopic dermatitis or other eczematous dermatoses.

His family medical history was relevant only in that his mother had systemic lupus erythematosus.On physical examination, there were several erythematous annular patches on the abdomen (flanks and periumbilical region), lower back, groin, wrists, and legs (Figure, A).

The lesions showed slightly raised red-brown borders and a clear center in some patches with no visible scaling, hypopigmentation, induration, or atrophy.

There were no associated extracutaneous symptoms.

Results of laboratory studies including complete blood cell count, biochemical analysis, complement levels, antinuclear antibodies, anti-Ro, anti-La, anti-ribonucleoprotein, anti-Smith, and anti-dsDNA antibodies, as well as serologic testing for syphilis and hepatitis B and C virus, were all normal or negative.

A punch biopsy specimen was obtained for histopathologic evaluation (Figure, B and C).A, Clinical image shows several erythematous annular patches on the flanks and periumbilical region.

B, Histopathologic analysis of a punch biopsy sample from the abdomen showing superficial lymphocytic infiltrates in the papillary and superficial reticular dermis.

C, There are also prominent vacuolar changes at the dermoepidermal junction, and in some areas mild lymphocytic exocytosis.


She had moved to Canada from China 30 years ago and was unsure about tuberculosis (TB) exposure and Bacillus Calmette–Guérin vaccine status.

Her medical history included atrial fibrillation, type 2 diabetes mellitus, dyslipidemia, cerebrovascular disease, hypertension, and Parkinson disease.

The first lesion appeared as an erythematous papule, which grew and subsequently ulcerated.

Within a few months, she developed other indurated plaques on her legs.

The ulcer was painful on palpation, but the plaques were mostly asymptomatic.

Physical examination showed a 5 × 4-cm, well-demarcated, oval ulcer with a violaceous, dusky border and central yellow fibrin mixed with granulation tissue on the left lateral aspect of the calf (Figure, A).

There were numerous violaceous to dull red, indurated plaques on the posterior aspect of the legs (Figure, B).

Wound cultures were negative for bacteria, mycobacteria, and fungi (Figure, C and D).


She denied use of heating pads, space heaters, or other forms of external radiation.

Physical examination showed several discrete, erythematous, scaly papules admixed with light brown reticulated macules and patches (Figure, A and B).

Punch biopsy specimens were obtained for further evaluation (Figure, C and D).A, Light brown macules and patches on the back show a strikingly reticular pattern.

B, Discrete erythematous and scaly papules and overlying hyperpigmented patches are shown.

C, Histopathologic examination shows eosinophilic spongiosis with interface dermatitis, dyskeratosis, and neutrophilic exocytosis (hematoxylin-eosin, original magnification ×20).

D, Prominent dermal melanophages are present (hematoxylin-eosin, original magnification ×20).

She was treated with potent topical corticosteroids and oral prednisone, with no improvement.

Before evaluation in our department, the patient had undergone a skin biopsy that showed spongiotic dermatitis, had patch testing that was reportedly negative, and received a diagnosis of atopic dermatitis.


C, T2-weighted axial MRI at the basal ganglia level showing remarkable progression of the lesions in the right basal ganglia and thalamus with heterogeneous high signal intensity and multicystic change (arrowhead).There was no history of tumors elsewhere, and his family history was unremarkable.

Sixteen months earlier, the patient was admitted to a hospital for weakness of the left fingers and mild spasticity of the left lower extremity.

Slight weakness in the left lower extremity was detected 3 months later.

Neurological examination revealed distal left hemiparesis, left facial palsy, and decreased pinprick sensation in his left face and extremities.

Magnetic resonance imaging (MRI) at the time revealed a suspicious lesion in the right basal ganglia (Figure, A).

In addition, carotid and intracranial angiography revealed no abnormalities (not shown).

Magnetic resonance imaging revealed nonhomogeneous hyperintensity on T2-weighted images in the right basal ganglia without mass effect (Figure, B).

Atrophy of the right cerebral hemisphere and right cerebral peduncle was observed (not shown).

A, T2-weighted axial brain magnetic resonance imaging (MRI) at the basal ganglia level performed 16 months before the current hospitalization showing slight hyperintensity at the right putamen and posterior limb of the internal capsule (arrowhead).

B, T2-weighted axial MRI performed 13 months before the current hospitalization showing moderate hyperintensity at the right basal ganglia without mass effect (arrowhead).

On MRI, the lesion appeared larger than before (Figure, C), with remarkable heterogeneous enhancement (not shown).

Human chorionic gonadotropin (HCG) levels in both serum and cerebrospinal fluid (CSF) were normal.

A hormone assay disclosed normal pituitary function.

The patient was subsequently admitted to our hospital for further evaluation.


No other relatives had hearing impairment.The child was born full term without complications.

Growth and language skills were appropriate for age.

Hearing screening at birth and the repeated auditory evaluations at follow-up had normal findings.

The physical examination was unremarkable except for some midfacial features consisting of a lateral displacement of the inner canthi of the eyes with a broad nasal root, small nostrils, and medial eyebrow flare (Figure, A).

The same midfacial anomalies were observed in his father (Figure, B), in whom a hypopigmented patch on the left arm and bright blue eyes were also noticed.

Both parents were diagnosed with profound, nonprogressive sensorineural hearing loss within the first year of life.

A homozygous mutation in the connexin 26 gene (GJB2 [OMIM 121011]) was found in the mother, whereas the father remained without a causative diagnosis.

Visual acuity and kidney function were normal, and no skeletal deformities were appreciated in the child or his father.The child and his father demonstrate a lateral displacement of the inner canthi.


She received a diagnosis of UC 6 years earlier and has taken mesalamine to control UC.

Review of systems was notable for diarrhea; however, she denied hematochezia, melena, emesis, fevers, or changes in urination.Her last colonoscopy was 3 years ago, and UC without evidence of dysplasia was confirmed.

Otherwise, her medical history was unremarkable.

Family history was negative for inflammatory bowel diseases and gastrointestinal malignancies.

She was discharged a week before this admission for a UC flare that was managed with prednisone.

Her abdomen was tender to palpation in the left lower quadrant, which was soft and nondistended.The patient’s complete blood cell count and comprehensive metabolic panel results were unremarkable.

She started receiving piperacillin/tazobactam but began to have increased abdominal pain, emesis, and inability to tolerate oral intake.

On examination, she was afebrile with normal vital signs.

Computed tomographic scan of the abdomen/pelvis demonstrated a thickened colon from the middescending colon to the rectosigmoid.

There was also a 2.7-cm intramural abscess in the descending colon.

A repeated computed tomographic scan performed 4 days after the original scan demonstrated that the intramural mass had increased to 3.5 cm and was partially obstructing the descending colon.

She underwent a colonoscopy, which demonstrated multiple areas of inflammation in the rectum through the descending colon (Figure 1).

Nothing proximal to the midtransverse colon was visualized because of a large fecal burden.


During his hospitalization, he was noted to have persistent fevers of unclear origin and neutropenia.

The findings of a previous inpatient eye examination performed 3 weeks earlier were unremarkable.

Dilated fundoscopy revealed multiple yellow-white subretinal lesions with associated hemorrhages and vitritis in the left eye (Figure 1).Left eye fundus photograph shows multiple creamy white subretinal lesions with associated hemorrhages and optic nerve head edema.

He was already admitted for induction chemotherapy after a relapse of his acute lymphoblastic leukemia.

He was receiving prophylactic cefepime and amphotericin B prescribed by the infectious diseases service.

Up to this point, the results of multiple systemic cultures were negative other than a skin biopsy specimen of a concerning papular rash that was noted to yield Candida tropicalis.

Anterior segment examination findings were unremarkable.


His ocular history included exotropia and amblyopia in the right eye.

Severe pain was noted with supraduction and infraduction of the right eye.

The bullet passed through a wooden door before entering the patient’s right orbit.

An examination revealed normal pupillary light reflexes, a visual acuity of 20/70 OD and 20/40 OS, and normal color vision OU.There was 3 mm of proptosis in the right eye, as well as right-sided periocular ecchymosis.

An entry wound was visible inferior to the right medial canthus, and the right upper and lower eyelids had full-thickness lacerations involving the canaliculi.

The patient had a large-angle alternating exotropia, as well as mild supraduction, infraduction, and adduction deficits in the right eye.

A slitlamp examination of the right eye revealed a normal anterior segment, while a mild vitreous hemorrhage, extramacular retinal whitening, and a subretinal hemorrhage in the inferonasal periphery was noted on ophthalmoscopic examination.


Her medical history was negative for diabetes, hypertension, dyslipidemia, and smoking.

Her only medication was oral contraception (OCP).

The patient’s uncorrected visual acuity was 20/20 OU, and intraocular pressures were 14 mm Hg OD and 15 mm Hg OS.

Confrontational visual fields and results of external eye examination were normal.

She had full ocular motility and no afferent pupillary defect.

Results of the right eye fundus examination were unremarkable (Figure, A).

The left eye (Figure, B) had tortuosity and dilation of all branches of the retinal vein, disc edema, scattered intraretinal hemorrhages, and nasal macula nerve fiber layer infarcts.

The vitreous was clear, macula flat, and there was no retinal neovascularization.

Results of optical coherence tomography confirmed the absence of cystoid macular edema and demonstrated nerve fiber layer thickening and hyperreflectivity, consistent with a nerve fiber layer infarct.A, Right fundus photograph demonstrating absence of vessel tortuosity and dilation, disc edema, infarcts, and hemorrhages.


A review of systems was remarkable for unintentional weight loss, night sweats, and cough with scant sputum.

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

Intraocular pressure, pupillary reaction, and ocular motility were normal.

The right eye had normal anterior and posterior segment examination findings.

The left eye was notable for mostly superior conjunctival and scleral hyperemia with dilated scleral vessels and associated scleral thinning with a conjunctival epithelial defect (Figure 1).

The results of posterior examination of the left eye were normal.

Results of serologic tests, including Treponema pallidum particle agglutination assay, HIV, hepatitis B and C, Lyme antibody, rheumatoid factor, and anticyclic citrullinated peptide, were negative.

Angiotensin-converting enzyme level, uric acid level, erythrocyte sedimentation rate, complete blood cell count, and basic metabolic panel results were within normal limits.

The results of proteinase 3–antineutrophil cytoplasmic antibody (ANCA) testing and interferon γ release assay using QuantiFERON-TB gold (QFT) (Qiagen) were positive.

Chest computed tomography revealed tiny, scattered solid pulmonary nodules that were too small to characterize according to the radiology department.

The patient was referred to the infectious diseases clinic, where the results of sputum culture and polymerase chain reaction for Mycobacteria tuberculosis were negative.


He reported a small mass in the right scrotum that was evaluated 5 years previously and was reassured to be a nonmalignant lesion.

Physical examination was notable for a distended abdomen with a palpable left abdominal mass.

Testicular examination revealed an approximately 1-cm firm right spermatic cord nodule.

Laboratory tests showed lactate dehydrogenase levels of 818 U/L (to convert to μkat/L, multiply by 0.0167), with no significant β-human chorionic gonadotropin and α-fetoprotein levels.

Computed tomography (CT) of the abdomen (Figure, A and B) revealed innumerable masses throughout the abdomen and pelvis, with the largest measuring 17.5 × 14 × 14 cm and a 3.9-cm enhancing lesion in the left hepatic lobe, and a small amount of ascites.

Testicular sonogram disclosed a 1.5-cm right epididymal cyst.

Percutaneous biopsy and histologic examination of the dominant left abdominal mass revealed neoplastic cells (Figure, C) that were positive for cytokeratin, desmin but negative for S100.

Fluorescence in situ hybridization (FISH) was positive for EWS-WT1 rearrangement.A, Coronal view and B, sagittal view contrast-enhanced computed tomographic imaging revealed innumerable abdominopelvic masses.

Blue arrowheads indicate the dominant mass and the red arrowhead indicates the liver mass.

C, Hematoxylin-eosin stain (original magnification ×40).


Her risk profile included a family history of sudden cardiac death: her cousin died unexpectedly in his mid-40s while playing football.

A physical examination showed no remarkable findings.

Her systolic blood pressure was 125 mm Hg, diastolic blood pressure was 70 mm Hg, and resting heart rate was 52 beats/min.

Portions of her electrocardiogram (Figure 1A) and 24-hour Holter monitoring trace (Figure 1B) are shown.

Echocardiographic findings included mildly impaired systolic function (left ventricular ejection fraction, 45%-50%) but were otherwise normal.


He reported no antecedent neck trauma or neck infection, nor any history of swelling during childhood.

He experienced dyspnea, limitation of neck movements, and neck tightness owing to the bulkiness of the lesion.

The swelling had been present for approximately 12 months, and the growth was gradual and continuous.

Contrast-enhanced T1- and T2-weighted magnetic resonance imaging (MRI) revealed a 15 × 7-cm homogenous ovoid bilobulated cystic mass in the left lateral region of the neck with displacement of the surrounding musculature and vascular structures but no sign of invasion.

The imaging of the lesion revealed fibrous septae in the central and inferior parts, with extension to the supraclavicular region (Figure, A and B).

After written informed consent was obtained, the patient underwent total excision of the cystic mass through an apron flap incision combined with T-incision for preservation of cranial nerve XI and sternocleoidomastoid muscle (Figure, C).A, T1-weighted magnetic resonance image (MRI) shows a homogenous ovoid bilobulated hypointense cystic mass in left parapharyngeal area and posterior cervical region, extending to the supraclavicular triangle.

B, T2-weighted MRI demonstrates thin-walled, markedly hyperintense cystic mass indenting neighboring structures.

C, Cervical mass with preservation of the vital structures of the neck.


She presented to her rhinologist for follow-up 6 weeks after surgery reporting improved nasal obstruction and olfaction, but complained of 2 weeks of throat pain and swelling.

Two weeks later her symptoms returned, now accompanied by new-onset snoring and nasal obstruction.

Physical examination revealed bilateral tonsillar erythema, exudate, tenderness, and peritonsillar edema.

Nasal endoscopy revealed nasopharyngeal soft-tissue swelling with mucopurulent secretions on the left side.

She was referred for a computed tomographic scan with contrast, which showed a rim-enhancing, multilocular hypodense collection extending from the left nasopharynx inferiorly to the level of the right palatine tonsil (Figure 1).

Intraoperative endoscopy revealed ulceration and necrotic debris in the nasopharynx and oropharynx.

She was prescribed amoxicillin–clavulanic acid for presumed tonsillitis and began to improve.

On the basis of the radiographic findings, she was taken to the operating room urgently.

Culture and biopsy specimens were obtained.


However, her medical history was otherwise unremarkable.

The lesions were first reported when she was 5 years of age and gradually increased in size.

There was significant bilateral exophthalmos (the left eye was more pronounced), with visual changes, and dental malocclusion.

On clinical examination, the lesions were hard in consistency with normal overlying skin.

However, there were no clinical signs of endocrinopathy.

A skeletal survey showed no involvement of other bones.

The patient’s serum calcium, phosphate, alkaline phosphatase, thyroid, and parathyroid hormone levels were within normal limits.

A computed tomographic (CT) examination of the craniofacial skeleton was performed (Figure).Noncontrast axial bone algorithm computed tomographic images of the facial bones.


His remaining medical, surgical, family, and social history was noncontributory.

He was otherwise healthy and exhibited no constitutional complaints.

Examination showed a healthy-appearing child with left abducens nerve palsy and an afferent pupillary defect.

There was no chemosis, exophthalmos, or enophthalmos.

Findings from nasal endoscopy were unremarkable.

A computed tomographic scan of the sinuses without contrast showed a well-circumscribed posterior-medial extraconal mass extending into the orbital apex with smooth, nonaggressive bony remodeling and expansion of the left superior orbital fissure with further dorsal extension into the left cavernous sinus (Figure, A).

Magnetic resonance imaging of the orbits showed that orbital component was inseparable from medial rectus muscle.

Tumor also resulted in lateral displacement and compression of the left optic nerve (Figure, B).

The patient underwent an image-guided left endoscopic orbital decompression with biopsy of the orbital mass.

Representative hematoxylin-eosin–stained sections are shown in the Figure, C and D. The tumor was negative for FUS (FUsed in Sarcoma; also termed TLS, Translocated in LipoSarcoma)-CHOP (C/EBP HOmologous Protein; also termed DDIT3, DNA Damage-Inducible Transcript 3) fusion oncogene on fluorescent in situ hybridization (FISH).A, Axial cut of noncontrast computed tomographic (CT) scan of facial bones.

B, Axial cut of T1-weighted magnetic resonance image (MRI).

C and D, Representative hematoxylin-eosin–stained histologic sections of the lesion.


Her medical history was significant for streptococcal glomerulonephritis and 2 prior kidney transplants.

Her medications included prednisone, tacrolimus, and mycophenolate mofetil.

In the few months before presentation, she experienced partial nail loss and her nail had become painful with intermittent drainage.

Physical examination of the left second fingernail showed a tender ulcerated nodule encompassing the nail bed with near-complete nail loss and purulent drainage (Figure 1, left).

The specimen was analyzed by histopathology with hematoxylin-eosin staining and once again showed a pyogenic granuloma–like response characterized by proliferating blood vessels in a background of fibrosis and reactive plasmacytic infiltration (Figure 1, right).

Careful inspection of the pyogenic granulomatous process at higher power demonstrated atypical epithelioid and spindled cells adjacent to blood vessels.Left, Physical examination of left second fingernail.

A previous biopsy showed a pyogenic granuloma, and she had been treated with curettage and electrodessication.

A nail biopsy was repeated by performing a 4-mm punch through the nail bed.


Three weeks later, he presented again with abdominal pain.

A computed tomography (CT) scan demonstrated fluid collections adjacent to the ascending colon and bowel wall thickening with intestinal pneumatosis consistent with ischemic bowel.

Superior mesenteric vein thrombosis was redemonstrated on CT scan.

One day following surgery, a CT scan demonstrated a new left femoral vein thrombosis and pulmonary embolism.

He was diagnosed with superior mesenteric vein thrombosis with mesenteric ischemia and treated with partial small bowel resection and 2 weeks of enoxaparin while hospitalized.

An intravenous course of piperacillin-tazobactam was started, and an exploratory laparotomy with bowel resection was performed.

Postoperatively, intravenous heparin was started.


A diagnosis of multibacillary leprosy was considered previously in another health care facility for which multidrug therapy with rifampicin, 600 mg/mo, dapsone, 100 mg/d, and clofazimine, 50 mg/d, was administered for 6 months.

The lesion had started on the left foot as a painful blister that eventually ruptured to form an ulcer, which subsequently progressed.

During this time, multiple hypopigmented asymptomatic lesions appeared on his face and scalp.

On physical examination, an 8 × 6-cm ulcer was noted on the lateral aspect of the dorsum of the left foot (Figure, A).

The ulcer was well defined with regular margins, and the floor was covered by a yellowish slough.

Perilesional tenderness and pitting edema were observed.

Multiple ill-defined, hypopigmented patches of various sizes were present on the scalp and face (Figure, B).

Inguinal lymph nodes on both sides were enlarged, nontender, and movable.

Peripheral nerve trunks were not thickened, and peripheral arteries could be easily palpated.

C, Histologic analysis showing acute ulceration of the epidermis with granulation tissue and infiltrating neutrophils and macrophages (hematoxylin-eosin, original magnification ×100).

There was no appreciable clinical improvement.

Lesional appendages and sensations were preserved.

Skin punch biopsy specimens were obtained from the ulcer (Figure, C and D) and a hypopigmented facial lesion.A, Nonhealing ulcer.

B, Ill-defined hypopigmented macules on the left side of the face.


The asymptomatic patch had slowly enlarged since initial onset, but remained confined to the single extremity.

Physical examination revealed agminated and discrete erythematous macules as well as interspersed fine, reticulated telangiectases over the right pretibial leg (Figure, B).

No edema or warmth of the affected area was observed, and there was no evidence of mucosal, conjunctival, or nail involvement.

Findings on review of systems were negative for bleeding tendencies or hypercoagulability.

A punch biopsy was performed (Figure, C and D).A, Reticulated, blanchable, salmon-colored patch on the pretibial leg.

B, Individual fine, telangiectatic erythematous macules identified on closer inspection.

C, Concentric deposits of hyaline material surround dilated and markedly thickened capillaries within the papillary dermis (original magnification ×200).

D, Perivascular hyaline deposits are highlighted strongly by periodic acid–Schiff stain (original magnification ×200).


His medical history was significant for primary hyperparathyroidism 6 years prior to presentation, for which the patient refused therapeutic management.

The patient was cachectic and exhibited significant muscular weakness.

Clinical examination revealed a large tumor on the distal part of the right fourth finger (Figure, A) that had gradually enlarged in recent months.

Radiography revealed complete lysis of the underlying phalanx and periosteal bone resorption in the phalangeal tuft band.A, The patient initially presented with a large tumor on the distal part of the right fourth finger.

B, Histopathology shows numerous giant cells with multiple osteoclastlike nuclei, and (C) giant multinucleated cells dispersed in contact with fibers associated with the presence of a few small vessels.Laboratory evaluation revealed hypercalcemia at 3.6 mmol/L (reference range for total calcium, 2.05-2.55 mmol/L [to convert to mg/dL, divide by 0.25]), hypophosphatemia at 0.65 mmol/L (reference range for phosphate, 0.87-1.45 mmol/L), and elevated serum parathyroid hormone at 380 pmol/L (reference range, 1.6-6.9 pmol/L [to convert to ng/L, multiply by 1.355]).

A chest radiograph revealed an important and unexplained deformation of the ribs.We performed a 3-mm punch skin biopsy on the tumor and performed histopathological analysis (Figure, B and C).


The mother stated that the patient was born with normal-appearing dark hair that fell out days after birth.

This was replaced with “peach fuzz,” with no subsequent regrowth of normal hair.

On physical examination, short, brittle terminal hairs of varying lengths covered the entire scalp.

Follicular hyperkeratosis and perifollicular erythema were present, most prominently on the parietal and occipital scalp (Figure, A).

Mild perifollicular keratotic papules were noted on the posterior upper arms.

Teeth and nails showed no abnormalities.

Her eyebrows and lashes were not affected.

Results of trichography are shown (Figure, B).Photograph of a young patient with hair loss depicts shortened, thin hairs on the scalp of a child with follicular hyperkeratosis.

Light microscopy of hair shaft at 4 × magnification shows a beaded appearance.

Family history was significant for similar hair loss in the patient’s maternal grandmother and maternal cousin.

The patient had otherwise normal development.


He complained about abdominal pain and had vomited twice.

The next day, his vomiting persisted, especially after oral intake.

At physical examination, according to the Advanced Pediatric Life Support protocol, he had normal vitals results with pain during palpation of the left abdominal region without guarding.

His hemoglobin level was 12.3 g/dL (to convert to grams per liter, multiply by 10) (normal value, 10.5-16.1 g/dL), amylase 68 U/L (to convert to microkatals per liter, multiply by 0.0167) (normal value, <85 U/L), and lipase 25 U/L (normal value, <60 U/L).

A plain chest radiography result showed no signs of traumatic injury.

Abdominal ultrasonography results showed a bowel loop with a thickened wall in the left abdominal region with no free abdominal fluid.

He was admitted to the pediatric ward for close observation.

Computed tomography with oral and intravenous contrast was performed (Figure 1).Computed tomography, axial reconstruction (A) and coronal reconstruction (B).


A transvaginal ultrasonographic scan confirmed normal intrauterine gestation with a vital embryo.

On examination she had tenderness in the RIF with a positive Blumberg sign; blood testing showed leukocyte count 10 450/μL (to convert to ×109/L, multiply by 0.001) without any shift, C-reactive protein 1.29 mg/dL (to convert to nanomoles per liter, multiply by 0.331), and hemoglobin 11.4 g/dL (to convert to grams per liter, multiply by 10).

Three days later she returned to the emergency department with recurrent pain; the clinical and ultrasonographic findings were unchanged, without evidence of complicated appendicitis, intra-abdominal fluid collection, or abscess.

A transabdominal ultrasonographic scan showed a tubular structure in the RIF consistent with a mildly inflamed appendix and stratification of the appendiceal wall (7 mm in the proximal and 11 mm in the appendiceal distal tract).

A small amount of free fluid was present in the Douglas pouch.

Working diagnosis was uncomplicated appendicitis and initial conservative management was amoxicillin clavulanate because of the potential risks of miscarriage associated with performing an avoidable appendectomy and general anesthesia during early gestation.

The surgeon on call requested an urgent magnetic resonance imaging (MRI) investigation (Figure 1).Magnetic resonance imaging showed the gestational chamber and a normal intrauterine pregnancy as well as the presence of a tubular structure in the right iliac fossa (RIF) (A) and what appeared to be an inflamed, thickened appendix (9.83 mm in the proximal appendix) (B).

The patient initially improved and was discharged home 2 days later with an Alvarado score of 4; oral antibiotic therapy was continued.

The patient was admitted to the surgical ward and given intravenous antibiotics.

In the next 48 hours the symptoms and pain did not resolve, although inflammatory markers were low and the patient was not septic.


This patient was recently discharged from the hospital for West Nile virus (WNV) encephalitis (confirmed seropositive for IgM and IgG antibodies against WNV).

Polymerase chain reaction analyses detected no DNA for Epstein-Barr virus, BK virus, cytomegalovirus, or herpes simplex virus types 1 and 2.

Neither HIV antibody nor antigen was detected.

Cerebrospinal fluid culture analysis findings were normal.

She received supportive treatment and made a full recovery.The patient’s corrected visual acuity was 20/20 OU, and her intraocular pressure was 14 mm Hg OU.

Anterior segment examination findings were unremarkable for both eyes.

Dilated fundus examination revealed microaneurysms, a dot-blot hemorrhage, and scattered, deep, white, chorioretinal lesions in the posterior pole and periphery that were more numerous in the right than left eye (Figure 1A).

Fluorescein angiography showed chorioretinal lesions with central hypofluorescence and peripheral hyperfluorescence (Figure 1B).A, Deep, white, creamy lesions (arrowheads) are observed in the posterior pole of the right eye.

The dot-blot hemorrhage inferior to the fovea is secondary to nonproliferative diabetic retinopathy.


One day prior, she developed a new-onset right facial palsy in addition to bilateral eyelid, lip, and feet swelling.

Ophthalmologic evaluation revealed visual acuities of 20/20 OD and 20/800 OS.

The left eye showed a relative afferent pupillary defect and decreased color vision.

Extraocular movements, confrontation visual fields, and intraocular pressures were within normal limits.

Anterior segment examination was unremarkable in both eyes.

Dilated fundus examination revealed optic nerve head edema and peripapillary hemorrhages bilaterally, greater in the left eye than in the right eye (Figure 1).

Scattered peripheral hemorrhages were present, consistent with thrombocytopenia at the time.Clinical photograph demonstrating optic nerve head edema.

A, Fundus photograph of the right eye demonstrating lymphomatous optic nerve infiltration and peripapillary hemorrhages.


Her ocular history included myopia with a spherical equivalent of −5.50 OD and −4.00 OS, normal-tension glaucoma controlled with latanoprost in both eyes, and mild cataracts.

Systemic medical history included use of aspirin, 81 mg/d, and a multivitamin.

She frequently consumed alcohol; however, she denied smoking or recreational drug use.

She denied any known allergies, and findings of review of systems were unremarkable.Best-corrected visual acuity was 20/20 OU.

Extraocular movements were intact, and pupils were round and reactive with no afferent pupillary defect.

Intraocular pressure by pneumotonometry was 16 OD mm Hg and 19 mm Hg OS, and visual fields by confrontation were full in both eyes.

Anterior segment examination showed 1+ nuclear sclerosis in both eyes.

Dilated fundus examination revealed a posterior vitreous detachment and tilted optic nerves with adjacent myopic crescents in both eyes.

A small, yellowish orange discontinuity was found in the inferior peripapillary region of the optic conus in the right eye (Figure, A).

The macula was flat with a sharp foveal reflex, and the peripheral retina was unremarkable in both eyes.Color fundus photography (A) and optical coherence tomography (B) of peripapillary changes.

The color fundus image demonstrates a yellow-orange region inferior to the optic nerve, with arrowheads denoting the full extent of the peripapillary intrachoroidal cavitation.


Two weeks later, he developed pain and redness while receiving a steroid taper, and examination revealed episcleritis and a small scleral depression temporally.

Topical prednisolone therapy was increased; however, during subsequent weeks, his pain intensified.

His baseline visual acuity was count fingers OD.

The day after treatment, the patient was comfortable with an intraocular pressure of 23 mm Hg.

Transscleral cyclophotocoagulation (TSCPC) was recommended over filtering surgery because of extensive conjunctival scarring and lagophthalmos.

Transscleral cyclophotocoagulation was performed with 19 spots (1300-1500 mW) at 3 seconds each, without audible pops, and sparing the superotemporal quadrant.


She had a history of tobacco use and stopped smoking cigarettes in the 1970s.

Physical examination and laryngoscopy findings confirmed a painless lesion on the left side of the palate and immobility of the left vocal cord.

The PET scan results showed focal fludeoxyglucose F 18 localization within the known oral cavity SCC (Figure 1A) and in a small, level IIA lymph node, located lateral to the upper right internal jugular vein.

There was unexpected, prominent, metabolic activity in the medial and asymmetrically enlarged left vocal cord (Figure 1B).A, Positron emission tomography reveals focal fludeoxyglucose F 18 uptake in biopsy-confirmed squamous cell carcinoma of the left palatal graft margin (arrowhead).

Each malignant neoplasm was locally resected and the patient was also treated with adjuvant radiotherapy for the last episode.

She remained asymptomatic, and a routine surveillance clinical examination uncovered a sixth lesion at the margin of a palatal graft.The patient’s medical history was also noted for a total thyroidectomy in the 1950s, complicated by recurrent laryngeal nerve injury.

Her oncologic history began 16 years ago with diagnosis and local resection of a lesion on the palate.

Cancer recurrence at the left buccal mucosa was identified and excised 10 years later.

She then was diagnosed with 3 recurrences of SCC in rapid succession.

Positron emission tomography (PET) was performed to assess extent of disease and to plan treatment.


He had no relevant medical history and was taking no medications.

He denied smoking, drugs, or alcohol abuse.

The patient reported an incremental decline of daily activities because of progressive muscle weakness.

He denied chest pain, orthopnea, and paroxysmal nocturnal dyspnea.

Physical examination was significant for normal heart sounds with bilateral basal rales on lung auscultation and swollen lower extremities with trace edema.

Bloodwork revealed a mildly elevated alanine aminotransferase level of 77 U/L (normal level, <41 U/L; to convert to microkatals per liter, multiply by 0.0167) and aspartate aminotransferase level of 47 U/L (normal level, <38 U/L; to convert to microkatals per liter, multiply by 0.0167).

Cardiac profile showed normal troponin-I levels, mildly elevated brain-type natriuretic peptide level of 142 pg/mL (normal level, <125 pg/mL; to convert to nanograms per liter, multipy by 1), and elevated serum creatine kinase level of 666 U/L (normal level, 20-200 U/L; to convert to microkatals per liter, multiply by 0.0167) and creatine kinase–MB fraction level of 10 ng/mL (normal level, <6.7 ng/mL; to convert to micrograms per liter, multiply by 1).

Echocardiography showed global hypokinesia with a left ventricular ejection fraction (LVEF) of 35%.

The right ventricle was moderately dilated with impaired systolic function.

Family history was significant for early death of his maternal uncle who had congestive heart failure.

His younger brother also had progressive weakness but no dyspnea.

Electrocardiogram  (ECG) on presentation is shown in Figure 1, which has not changed compared with an ECG a year before presentation.


She denied a history of localized trauma, substance abuse, or prior endonasal surgery.

Examination revealed a nontender, 8-mm, pink-red, soft, fleshy growth just posterior to the membranous septum near the nostril apex.

Histopathological analysis demonstrated a well-circumscribed submucosal lesion comprised of bland, round, syncytial cells, arranged in a concentric fashion around variably sized slit-like vascular spaces, a minority of which were staghorn in appearance (Figure, A-C).

No significant perivascular hyalinization was identified.

The overlying nasal mucosa and surrounding submucosal glands were unremarkable.

Immunohistochemical stains demonstrate the cellular population to be strongly positive for smooth-muscle actin (SMA), muscle-specific actin, and CD34 (Figure, D), but negative for B-catenin and epithelial membrane antigen.Histopathology of asymptomatic septal mass shows (A) a well-circumscribed, unencapsulated lesion based in the submucosa with an intact overlaying squamous and respiratory mucosa (hematoxylin-eosin); (B) bland, vaguely spindled cells arranged around prominent thin-walled vessels with a “staghorn” branching configuration (hematoxylin-eosin); (C) the lesional cells are oval to spindle-shaped with abundant cytoplasm and ill-defined cell borders (hematoxylin-eosin); (D) the lesional cells are stained diffusely with myoid markers, including smooth-muscle actin and muscle-specific actin (muscle-specific actin stain).


Tobacco history was minimal and distant, and alcohol use was social only.

Physical examination, including flexible nasolaryngoscopy, was notable for a large smooth nonulcerated right base of tongue mass with almost complete pharyngeal airway obstruction, and a 4-cm right level II lymph node.

Computed tomography (CT) imaging revealed a 3-cm base of tongue–lingual tonsil mass with multiple right Ib, IIa, and II/III nodes, the largest of which was 2.0 cm by 3.0 cm.

Awake tracheotomy and direct laryngoscopy with biopsy of right base of tongue mass lesion was performed.Histological analysis showed sheets and clusters of small round-oval uniform cells with minimal cytoplasm, granular chromatin pattern, and prominent nuclear molding (Figure, A) with positive immunoreactivity for cytokeratin (CK) 7 (Figure, B) and synaptophysin (Figure, C); a high mitotic rate was also exhibited (Figure, D).

The cells were negative for CK 5 and 6, CK 20, NUT, p63, and chromogranin.

Polymerase chain reaction (PCR) detected human papillomavirus (HPV) 16 DNA and did not detect HPV 6, 11, and 18 DNA.Histopathological analysis of the tongue lesion shows (A) sheet-like growth pattern with Azzopardi-type crush artifactual distortion of the neoplastic cells (original magnification ×100) (the insert shows round-oval compact molded nuceli, a high nuclear:cytoplasmic ratio, and granular chromatin pattern without conspicuous nucleoli [original magnification ×400]); B, cytokeratin 7–positive immunoreactivity (original magnification ×200); C, synaptophysin-positive tumor cells (original magnification ×200); and D, a high proliferation rate by Ki-67 staining (original magnification ×200).


Approximately 1 month prior he had been admitted to the hospital and treated for meningitis.

At the otolaryngologist’s office, the patient stated that he had not experienced otalgia, otorrhea, tinnitus, or vertigo.

During his hospital course, a computed tomographic (CT) scan of his head revealed a lytic lesion of the left occipital bone.

His examination revealed clear nasal discharge and a normal otoscopic finding.

His audiogram demonstrated normal sloping to moderate sensorineural hearing loss with type A tympanometry result on the right and type A on the left.

His word recognition score was 100% bilaterally.

To evaluate for a skull base defect and cerebrospinal fluid (CSF) leak, a noncontrast CT scan of the temporal bones was obtained (Figure, A and B).

This demonstrated a large area of bony destruction and osteolysis involving the left occipital bone.

A T2-weighted MRI sequence showed a lesion, isointense to CSF, with thinning of the bony cortex (Figure, C and D).

Based on the imaging, the differential diagnosis included metabolic, infectious, or metastatic lesions to the bone.A and B, Noncontrast temporal bone computed tomographic images.

C, T2-weighted fast imaging using steady state acquisition magnetic resonance imaging sequence demonstrating a signal isointense to cerebrospinal fluid in the left occipital bone.

After treatment with intravenous antibiotics and steroids, his neurologic examination results returned to baseline, and he was discharged home.

Magnetic resonance imaging (MRI) was deferred to the outpatient setting.

The collection of nasal discharge for β-2 transferrin analysis was attempted, but insufficient quantity was obtained.

D, Reformatted postcontrast T1 image shows the herniation of nonenhancing meninges through the defect.


She was of Italian, German, and Slovak ancestry.

She had a history of congenital horizontal nystagmus, which was pendular, ie, occurring in 2 phases of equal speed (Video).

She had fair skin, platinum white hair (Figure 1, left panel), and blue eyes.

Best-corrected visual acuities were 20/60 bilaterally.

The irides were blue, although by retro-illumination with a light beam perpendicular to the iris plane, they appeared reddish-pink (Figure 1; eFigure in the Supplement).Left, Hypopigmented platinum hair.

Right, Hypopigmented eyelashes, and iris lucency on retro-illumination.

At age 24 years, she underwent resection of a cutaneous melanoma (stage T1bN1a) from the upper chest, with no signs of recurrence or metastasis.


She had no history of immunosuppression.

She denied fevers, joint pain, joint stiffness, inciting trauma, or recent outdoor activity.

Results of a recent complete blood cell count and comprehensive metabolic profile were unremarkable.

Physical examination showed a single 25-mm, firm, dome-shaped subcutaneous nodule with central ulceration on the lateral aspect of the right fifth digit (Figure 1).

There was no erythema, edema, fluctuance, induration, or lymphangitis surrounding the lesion.

No lymphadenopathy was present.Dome-shaped subcutaneous nodule with central ulceration on the lateral aspect of the right fifth digit.


Treatment with griseofulvin and clotrimazole had not improved the rash.

One day prior to presentation he had developed a fever and was diagnosed with otitis media in the emergency department.

Acetaminophen, ibuprofen, and amoxicillin were used for treatment, but the child was receiving no other medications.Physical examination revealed multiple annular, indurated, dusky red plaques with central clearing and trailing scale ranging from 1 to 6 cm in diameter on his trunk (Figure, A and B).

A 4-mm punch biopsy of the largest lesion on his back was performed and sent for histopathologic examination (Figure, C).A and B, Annular dusky red indurated plaques on the right flank with central clearing and trailing scale.

Scattered café au lait macules and annular dusky red indurated plaques with central clearing and trailing scale on the back.

C, Hematoxylin-eosin stain (original magnification ×40) demonstrates perivascular and periadnexal infiltrate.

D, Hematoxylin-eosin stain (original magnification ×400).


Her medical history was notable for essential thrombocytosis, which had been complicated by portal vein thrombosis, and she had been receiving treatment with hydroxyurea and rivaroxaban for the past 2 years.

Despite worsening cutaneous disease, she otherwise felt well and denied associated fevers, weakness, weight loss, myalgias, arthralgias, or other constitutional symptoms.Physical examination revealed atrophic and reticulated violaceous plaques with a striking photoaccentuated distribution on the patient’s dorsal hands and forearms (Figure, A).

Scaly, violaceous plaques were also present on the thenar eminences and radial aspects of her first 2 fingers bilaterally (Figure, B).

Prominent poikiloderma was seen on her sun-exposed chest and neck, and a large, stellate ulcer was present on her left distal lower leg (Figure, C).

A lesional skin biopsy was performed on the patient’s left forearm (Figure, D).A, Clinical photograph of violaceous reticulated plaques on the dorsal aspect of the hands.

B, Clinical photograph of violaceous, scaly plaques on the thenar and radial aspects of the thumb and second digit (mechanic hands).

C, Clinical photograph of a shallow ulcer with stellate margins on the left distal lower leg.

D, Histopathology (hematoxylin-eosin stain, original magnification x100).


Her medical history was significant for 5 strokes over the past 6 years and Raynaud syndrome for the past 2 years.

In the past, despite extensive workup, no definitive diagnosis had been established.

Annular patches of violaceous erythema forming an irregular net-like pattern were noted on her trunk and extremities (Figure, A and B).

The patient stated that these skin changes had appeared 2 years prior.

Complete blood cell count, liver function tests, creatinine, C-reactive protein, erythrocyte sedimentation rate, and urinalysis results were normal.

Antinuclear antibodies and complement C3 and C4 levels were unremarkable.

Antiphospholipid antibody and lupus anticoagulant screening results were repeatedly negative and no evidence of thrombophilia was found.

Magnetic resonance imaging showed acute dot-like diffusion anomalies in the medial and posterior cerebral artery-supplied areas, as well as old stroke residues (Figure, C).

Transesophageal echocardiography showed no abnormalities.

A skin biopsy sample was taken from the patient’s left thigh (Figure, D).A, Patient’s lower back and buttocks and, B, thighs and upper calves show generalized, irregular, violaceous, net-like erythema.

C, Magnetic resonance imaging of the brain showing old stroke residues.

D, Hematoxylin-eosin stain (original magnification ×10).


Brain magnetic resonance imaging during second attack: resolution of the initial left frontal lobe lesion now with T2-weighted and FLAIR recovery hyperintensity in the left parietotemporal region (C) with associated patchy enhancement (D).She presented again, 15 months later, with 2 weeks of dysarthria and progressive ataxia without change in mental status.

The patient received pulse dose corticosteroids (intravenous solumedrol, 30 mg/kg per dose every 24 hours) for 5 days with resolution of her truncal ataxia during hospitalization.

Brain magnetic resonance imaging (MRI) revealed T2-weighted and fluid-attenuated inversion recovery changes with associated patchy enhancement in the brainstem, left frontal lobe, left cingulate gyrus, and left parietal lobe without restricted diffusion (Figure, A and B).

Cervical spine imaging results were negative.

Cerebral spinal fluid (CSF) study results were unremarkable (red blood cell count, 0 × 106/µL [to convert to ×1012/L, multiply by 12]; white blood cell count, 0/µL [to convert to ×109/L, multiply by 0.001]; glucose, 61 mg/dL [to convert to millimoles per liter, multiply by 0.0555]; and total protein, 19 g/dL [to convert to grams per liter, multiply by 10]), and CSF cytologic test results were negative for malignancy.

She was diagnosed with acute demyelinating encephalomyelitis (ADEM) and received 5 days of high-dose intravenous corticosteroids followed by a 1-month course of oral prednisone with improvement back to baseline in 3 weeks.Brain magnetic resonance imaging during initial presentation: T2-weighted and fluid-attenuated inversion recovery (FLAIR) hyperintensity in the left frontal lobe (A) and associated enhancement on T1-weighted postcontrast imaging (B).

Subsequent brain MRI revealed resolution of the prior supratentorial involvement and new T2/fluid-attenuated inversion recovery changes with patchy enhancement in the brainstem and a large new lesion in the left parietotemporal area (Figure, C and D).

Head magnetic resonance angiography findings were unremarkable.

The CSF studies revealed a mild lymphocytic pleocytosis (white blood cell count of 11/µL with 3 neutrophils, 6 lymphocytes, and 2 monocytes) with 1 red blood cell, glucose level of 57 mg/dL, and total protein level of 39 g/dL.

The results of the CSF viral polymerase chain reaction studies, including cytomegalovirus, varicella-zoster virus, herpes simplex virus, enterovirus, and Epstein-Barr virus, were negative.

The CSF bacterial culture returned without growth.

The results of tests for the CSF oligoclonal bands and IgG index were negative.

The results of serum cell-based aquaporin 4 antibody tests were negative.

She was discharged with a month-long oral prednisone taper starting at 20 mg/d.

When tapered down to prednisone, 5 mg every other day, she developed a right facial droop with recurrent ataxia.


The patient reported the presence of a stable red lesion since he was 7 years old; however, over the preceding month, this lesion developed new black spots within it.

There was no associated pain, pruritus, or bleeding.

His family history was notable for dysplastic nevus syndrome in his father and melanoma in a paternal uncle and cousin.On examination of the right lower back, there was a cluster of 1-mm flat purple-black papules coalescing into a 1.5 × 1.0-cm oval plaque with surrounding erythema (Figure, A).

On reinspection of the lesion at a subsequent visit, the morphology had significantly changed; there were 1-mm skin-colored to pink thin-walled vesicles clustered within a 1.5 × 1.0-cm oval telangiectatic plaque (Figure, B).A, Flat purple-black papules coalescing into an oval patch with surrounding erythema.

B, Skin-colored to pink thin-walled vesicles making up an oval telangiectatic patch.


The patient denied history of local trauma, and his family history was negative regarding breast or ovarian cancers.

The patient had no history of liver disease, hormonal therapy, or radiation to the chest wall.

The physical examination disclosed an obese man with no signs of hypogonadism or liver failure.

There was a 3 × 4-cm hard, irregular, mobile nodule in the retroareolar area of the right breast, tethered to the overlying skin but not fixed to the underlying muscle.

There were no other masses on the chest wall.

The ipsilateral lymph nodes were palpable.

Right mediolateral oblique mammography (Figure, A) and computed tomography scan of the chest (Figure, B) are shown.A, Right mediolateral oblique view of male breast showing a breast mass and axillary lymph nodes.

B, Computed tomography of the chest showing the right breast mass involving the skin but not the pectoralis muscle.