The patient developed a rash on the dorsal aspect of his hand half a year ago without any pain or itching discomfort and denied any history of injury or exposure to suspected pathogens prior to onset.

After self-medication with topical herbal medicine, the lesions gradually spread to the forearm and fused into plaques, and ulcers often recurred on the surface.

Physical examination revealed large, firm, mildly swollen erythematous plaques on the back of the left forearm with purulent discharge and crusting (Figure, A).

Results of routine laboratory investigations, including complete blood cell count, biochemical profile, and chest radiography, were normal.

B, Hyperkeratosis, pseudoepitheliomatous hyperplasia, and lymphohistiocytic infiltrate with neutrophils, plasma cells, and a small amount of multinucleated giant cells in the dermis (hematoxylin-eosin).

He denied any systemic symptoms and concerns.

A biopsy specimen was taken for pathological examination (Figure, B-D).A, A large, firm, mildly swollen erythematous plaque with purulent discharge and crusting on the back of the left forearm.


The patient currently smoked 30 cigarettes per day and had a 20 pack-year history of smoking.

He was taking no daily medications and had no family history of cardiovascular disease.

Two days earlier, he reported a similar 20-minute episode of chest pain and diaphoresis.

On admission to the ED, the patient was asymptomatic.

Blood pressure was 102/74 mm Hg, heart rate was 84/min, and oxygen saturation was 100% on room air.

His physical examination results were unremarkable.

Laboratory testing produced the following results: troponin T, 16 ng/mL (reference, <14 ng/mL); creatine kinase (CK), 82 U/L (1.37 µkat/L) (reference, <190 U/L [<3.17 µkat/L]); CK-MB, 16 U/L (reference, <24 U/L); low-density lipoprotein (LDL) cholesterol, 106 mg/dL (2.75 mmol/L) (reference, <130 mg/dL [<3.37 mmol/L]); and high-density lipoprotein (HDL) cholesterol, 38 mg/dL (0.98 mmol/L) (reference, >35 mg/dL [>0.91 mmol/L]).

His initial electrocardiogram (ECG) is shown in Figure 1.Biphasic T waves in leads V2 and V3 on patient’s initial electrocardiogram.


Two weeks later, the patient presented to the ED for another episode of acute, painless, right proptosis, and the VA had decreased to 20/40 OD.

The VA was 20/20 OU, with a persistent, mild, nonreducible, nonpulsatile proptosis unrelated to Valsalva maneuver but associated with extraocular movement limitation in upgaze.

Visual acuity (VA) was 20/32 OD and 20/20 OS.

Anterior-segment and fundus examination results were normal.

Magnetic resonance imaging (MRI) of the orbits revealed a right retro-orbital hemorrhage.

No etiology could be identified on the image.

MRI showed a right retrobulbar hemorrhage.

Systemic corticosteroid therapy was again prescribed for 48 hours with rapid resolution of the visual impairment but incomplete resolution of the proptosis.One month later, the patient presented to our ophthalmology department.

The proptosis decreased, and the patient was discharged.After 6 months, complete ophthalmologic examination was performed again; VA was 20/20 OU, and there was no remaining proptosis.

There was no contributory medical history, recent trauma, or surgery.

Systemic corticosteroid therapy (methylprednisolone, 1 mg/kg per day) was prescribed for 48 hours.


She had been taking 60 mg of oral prednisone; topical prednisolone acetate, 1%; and oral ibuprofen for 10 days without relief.

Three years prior, sinus pressure symptoms led to magnetic resonance imaging that revealed a nasal sinus mass.

Ultrasound biomicroscopy revealed an elevated and tender uveal-episcleral lesion.

Visual acuity was 20/30 in the left eye and 20/25 in the right eye.

She was suspected of being a steroid responder due to elevated intraocular pressure bilaterally.

Biopsy demonstrated a histiocytic infiltrate with emperipolesis, consistent with Rosai-Dorfman-Destombes (RDD) disease.

Timolol-dorzolamide topical drops were initiated.

Staging evaluations showed no other sites of RDD disease.Pretreatment.


The patient was lost to follow-up and re-presented 5 months later with an enlarged crusting and ulcerating lesion of the right temple/brow (Figure 1A).

He had mild proptosis in the right eye and right lower eyelid retraction.

On review of history, maxillofacial magnetic resonance imaging (MRI) with and without contrast done 5 months prior to presentation showed a 5.9 × 5.3 × 3.7-cm mass centered at the right temple that tracked along the right lateral orbital wall as well as an enhancing right intraparotid lymph node.

On ocular examination, best-corrected visual acuity was 20/100 OD and 20/125 OS due to cataracts, pupils reacted normally without afferent pupillary defect, and ocular motility was full.

Orbicularis strength was intact and symmetric in both eyes.

MRI of the orbits, face, and neck with and without contrast showed a 6.1 × 5.7 × 4.0-cm mass with erosion through the right sphenoid wing, involvement of the lacrimal gland, and abutment of the lateral rectus (Figure 1B).

In discussing treatment strategies for the orbital component of the disease, the patient was strongly against an orbital exenteration.A, External photograph showing a large right brow mass with overlying crust after the patient was lost to follow-up and re-presented 5 months later.


She had a history of cutaneous nodular melanoma in the right arm.

Ocular history was positive for cataract surgery bilaterally.

After cataract surgery in the right eye, an asymptomatic vision loss was noted and the cause was attributed to the presence of choroidal neovascularization (CNV), for which the patient underwent intravitreal anti–vascular endothelial growth factor (anti-VEGF) injections.Examination showed a best-corrected visual acuity of 20/60 OD and 20/20 OS, unremarkable anterior segment findings, and intraocular pressures of 12 mm Hg OU.

A fundus examination in the right eye revealed scarce pigmented cells in the anterior vitreous, a dark-pigmented epiretinal membrane, and an area of retinal hyperpigmentation in the inferior temporal arcade corresponding to the CNV (Figure 1).

Optical coherence tomography imaging revealed a hyperreflective structure on the surface of the inner retina with increased macular thickness, compatible with the described epiretinal membrane (Figure 1).Fundus examination in the right eye revealed scarce pigmented cells in the anterior vitreous, a dark-pigmented epiretinal membrane (white arrowheads), and an area of retinal hyperpigmentation in the inferior temporal arcade corresponding to the choroidal neovascularization (black arrowhead).

In April 2018, axillary lymphadenectomy was performed for local recurrence and the patient started treatment with an immune checkpoint inhibitor (ICI) pembrolizumab, without further local or metastatic evidence of the tumor.

Tumor staging was classified as T3N0M0 in August 2017, at the time of diagnosis and excision.


Three years prior, she was diagnosed with a solitary HCC and underwent surgical resection with curative intent.

Pathology revealed poorly differentiated HCC, 16 cm in largest dimension, with large vein involvement (T3bNXM0, R0 resection).

The patient underwent expectant observation.

One and a half years prior to the current presentation, laboratory results revealed an elevated α-fetoprotein (AFP), and cross-sectional imaging revealed multiple lung nodules consistent with metastases.

She was treated with nivolumab every other week and attained a biochemical (baseline, 212.2 ng/dL; best response, 3.3 ng/dL) and radiographic complete response.In the current presentation, the patient reported nonradiating epigastric pain of moderate intensity for 1 month.

Associated symptoms included nausea, anorexia, and water brash without emesis.

Review of systems was positive for unchanged chronic abdominal bloating and negative for other constitutional or gastrointestinal symptoms.

Laboratory results, including liver function tests, amylase, lipase, and AFP, were within normal limits, and hepatitis B virus polymerase chain reaction was undetectable.

Computed tomography with multiphasic liver protocol showed new enlarged mesenteric nodes and diffuse thickening of the gastric body (Figure, A).

Esophagogastroduodenoscopy (EGD) identified diffuse inflammation and ulcerations in the gastric body and antrum (Figure, B).

Biopsy specimens showed chronic and active mixed inflammatory infiltrate, including intraepithelial lymphocytosis (Figure, C).

No overt viral cytopathic effects were observed, and immunostaining results for Helicobacter pylori, cytomegalovirus, and adenovirus were negative.A, Coronal view of restaging computed tomography of chest, abdomen, and pelvis with contrast.

The yellow circle notes borderline enlarged mesenteric nodes inferior to the stomach, and the yellow arrowheads show thickened gastric body wall.

B, Gross appearance of the gastric mucosa visualized via upper endoscopy, which showed diffuse inflammation and ulceration in the gastric body and antrum.

C, Biopsy of the gastric mucosa showed marked chronic and active intraepithelial infiltration of lymphocytes (blue arrowheads) and neutrophils (yellow arrowhead) and associated glandular epithelial injury with withered glands and gland dropout (red circle) (original magnification ×100).


He had a medical history of myocardial infarction, sleep apnea, Ménière disease, and congenital cataract.

The patient used atorvastatin and acetylsalicylic acid, did not smoke, and reported drinking 2 glasses of wine daily.

Furthermore, he did not report otalgia, otorrhea, a recent episode of Ménière disease, or other ear, nose, and throat or systemic symptoms.

The lesion was hard and painful during palpation (Figure 1A).

Otoscopy of the left ear revealed a yellow-whitish calcareous lobular mass located in the mesotympanum anterior to the malleus with an intact tympanic membrane.

Otoscopy results for the right side were normal.Conductive hearing loss of the left ear because of a middle ear mass, seen on otoscopy (A) and on computed tomography (CT) (B).Pure-tone audiometry results showed a left-sided mixed hearing loss with a pure tone average of 110 dB HL and bone conduction levels at approximately 60 dB HL.

The tympanogram showed a normal A-type curve with a normal to low middle ear compliance of 0.5 mm on the left side.

Computed tomography (CT) imaging of the middle ear showed a heterogeneous hyperdense round mass of 5.5 mm in the left middle ear with a close relation to the malleus, eardrum, and tegmen (Figure 1B).

There were no other abnormalities in the mastoid, ossicular chain, facial nerve canal, or surrounding blood vessels.


Her parents stated that her stridor began acutely at 4 months of age without any inciting illness or event.

The stridor was worse with agitation but was without positional exacerbation.

The family reported that the stridor had remained stable since onset.

Her parents noted mild dysphagia but denied shortness of breath, cyanosis, or apnea.

Laboratory test results revealed acute COVID-19 infection.

Physical examination was unremarkable other than mild inspiratory stridor.

Findings from bedside flexible laryngoscopy revealed intact vocal fold motion bilaterally with glottic competence.

No supraglottic or glottic masses were identified.

Anterior-posterior neck and chest radiography demonstrated narrowing and tortuosity of the trachea with displacement to the right proximal to the thoracic inlet and diffuse patchy heterogenous airspace opacities (Figure, A).

Subsequent neck ultrasonography and computed tomography scan demonstrated a 3.2 × 2.0-cm low-density lesion abutting the trachea and hypopharynx at the level of thoracic inlet, with rightward displacement of the trachea and larynx (Figure, B-D).

Operative laryngoscopy, bronchoscopy, and esophagoscopy revealed extrinsic compression of the trachea, right mainstem bronchus, and esophagus with rightward deviation of the trachea and esophagus.

No mucosal tract was identified.A, Narrowing and tortuosity of the trachea with rightward deviation on anterior-posterior neck radiograph (arrowhead delineates tracheal deviation).

B, Echogenic cystic lesion on ultrasonogram.

C and D, Low-density lesion abutting the trachea and pharynx with rightward deviation of the trachea and larynx on coronal and axial neck computed tomography (black arrowheads delineate tracheal deviation; yellow arrowheads depict the lesion).


The mass had been present since birth but had slowly grown larger in the previous 2 years.

On physical examination, a 2.5 × 1.5-cm, nontender, blue, soft, cystic mass was observed in the right postauricular area.

There were no fistular openings around the auricle or in the external auditory canal (EAC), and there were no additional cysts, sinuses, or fistulas at the right neck from the hyoid bone and chin to the EAC.

On temporal bone computed tomography, a 2.5 × 1.5-cm, hypodense, oval-shaped cystic mass was revealed at the subcutaneous fat layer superoposterior to the right auricle.

On temporal magnetic resonance imaging (MRI), an oval cystic mass was revealed at the same location, with high signal intensity on both T1-weighted and T2-weighted images and low signal intensity on enhanced T1-weighted fat suppression and T2-weighted short T1 inversion recovery images (Figure, A-D).

The cyst contained keratinous debris (Figure, E).

E, Hematoxylin-eosin staining showed a cyst composed of keratinizing stratified squamous epithelium, hair follicles, and sebaceous glands.

In surgery, the well-demarcated cystic mass was completely excised.

Yellowish fluid leaked out of the cyst during excision.

On histopathologic examination, the cyst was lined by keratinizing stratified squamous epithelium with hair follicles and sebaceous glands.

There was no recurrence 6 months after surgery.A-D, Magnetic resonance imaging showed a 2.5 × 1.5-cm, oval cystic mass at the subcutaneous fat layer superoposterior to the right auricle with high signal intensity on both T1-weighted and T2-weighted images and low signal intensity on enhanced T1-weighted fat suppression and T2-weighted short T1 inversion recovery images (in order from the left).


The patient had been treated previously with steroids and amoxicillin for the presumptive diagnosis of chronic laryngitis but reported no improvement in symptoms.

She also reported odynophonia, globus sensation, and mild dysphagia to solids.

Laboratory workup was positive for elevated antinuclear antibodies and erythrocyte sedimentation rate and was consequently referred to our institution.On presentation, the patient had only minimal dysphonia.

Interestingly, the patient denied any shortness of breath.

She underwent a transnasal flexible laryngoscopy that demonstrated a severely edematous epiglottis, posterior pharyngeal wall, aryepiglottic folds, and arytenoids (Figure, A).

The vocal folds were difficult to visualize but seemed normal in appearance and mobility.

Stroboscopy could not be performed because of obstruction from the prolapsing arytenoids.

Results of laboratory testing revealed normal levels of all components of a comprehensive metabolic panel, thyroid-stimulating hormone, and angiotensin-converting enzyme.

The patient’s erythrocyte sedimentation rate was elevated to 75 mm/h (reference range, 0-15 mm/h).

Findings of chest radiography were normal.

An esophagram showed no evidence of reflux esophagitis and a computed tomography of the neck showed edema of the supraglottis with some edema in the posterior hypopharyngeal wall.A, Awake flexible laryngoscopy image of the edematous epiglottis, arytenoids, and posterior pharyngeal wall.

B, High-magnification of hematoxylin-eosin staining reveals well-formed noncaseating granulomas (arrowheads) with lymphoid reaction visible around the granulomas.Subsequently, the patient underwent a direct laryngoscopy with laryngeal biopsy.

Pathology results demonstrated hyperplastic squamous mucosa with submucosal chronic inflammation and fibrosis and were negative for high-grade dysplasia and carcinoma; scattered nonnecrotizing granulomas in the subepithelium were also observed (Figure, B).


Other physical examinations as well as his medical and family histories were unremarkable.

The skin lesions continued to progress and worsened after scratching.

Physical examinations revealed disseminated erythematous papules, hypertrophic plaques approximately 1 to 2 cm in diameter, and dome-shaped nodules with excoriated whitish or pink centers on the scalp, chest, abdomen, back, waist, and extremities (Figure, A and B).

Subsequent examinations of the mucosal membranes appeared normal.

Peripheral eosinophils, serum total immunoglobulin E level, enzyme-linked immunosorbent assay (ELISA) test for HIV, and results of other routine laboratory tests were within normal ranges or negative.

A biopsy specimen was taken from one of the skin lesions on his right forearm for histopathological examination and direct immunofluorescence (DIF) testing (Figure, C and D).A and B, Clinical images showed disseminated erythematous papules, hypertrophic plaques approximately 1 to 2 cm in diameter, and dome-shaped nodules with excoriated whitish or pink centers on the back, waist, and extremities.

C, A biopsy specimen taken from the right forearm showed marked hyperkeratosis, acanthosis with irregular elongation of the rete ridges, fibrotic dermis, and perivascular lymphocytic infiltrate (hematoxylin-eosin).

D, Direct immunofluorescence revealed linear deposition of immunoglobulin G along the basement membrane zone.

The patient had been initially diagnosed with nodular prurigo at a local hospital and treated with various topical steroids and oral antihistamines for 2 months, without significant improvement.


The patient was born at full term via spontaneous vaginal delivery; the birth mother had not received prenatal care.

Neither the birth mother nor the infant had any known history of environmental or occupational exposure to hazardous substances.

The paternal family medical history was unremarkable; maternal family medical history was unknown.Physical examination revealed numerous bright red macules, papules, and plaques ranging in size from 1.0 × 1.0 mm to 2.2 × 2.3 cm, many of which had hemorrhagic crust and dark scale (Figure, A and B).

The guardian reported first noticing the papules at birth.

During the following months, the papules grew in number and size, involving the head and neck, trunk, extremities, right palm, mons pubis, and buttocks.

At the height of severity, the patient had 39 lesions, some of which were associated with ulceration and bleeding.

Additional examination findings included retrognathia, thickened maxillary frenulum, and anterior ankyloglossia.A, Irregularly shaped red vascular plaque (2.2 × 2.3 mm) with overlying scale, dark crusting, and a dark blue component with surrounding (1.0-3.0 mm) red papules.

B, Numerous bright-red macules and papules (1 × 1 mm-3 × 3 mm) and 1 vascular red nodule (1.6 × 1.1 cm) on the left lateral neck with dark overlying crusting.

C, Low-power view of histopathology findings demonstrating epidermal hyperplasia and an upper dermal vascular proliferation (hematoxylin-eosin section).


He did not complain of headaches, facial numbness, dysarthria, facial droop, dysphagia, or limb weakness or numbness.

There was no history of joint pain or constitutional symptoms.Neurological examination revealed a nonfatigable partial left-eyelid ptosis, left-eye hypotropia at primary position, and impaired left eye supraduction (Figure 1) with a nonreactive left pupil on direct and consensual light reflexes.

There were no other cranial nerve deficits.

Limb reflexes, motor testing, and sensory testing results were normal, and the plantar responses were flexor.Top left (looking right and up), middle left (looking right), bottom left (looking right and down), center (primary position), top right (looking left and up), middle right (looking left), and bottom right (looking left and down).

The images demonstrate left-eye hypotropia and left-eyelid ptosis at the primary position and impaired left-eye supraduction worse at lateral gaze on extraocular movements.Laboratory evaluation showed a normal fasting serum glucose level, thyroid function test result, and erythrocyte sedimentation rate.

Anti–double-stranded DNA, antinuclear antibodies, and HIV test results were negative.

Repetitive nerve stimulation did not show any decremental response and anti-acetylcholine receptor antibodies were negative.

A computed tomography (CT) angiography of the circle of Willis did not show any aneurysms and a routine magnetic resonance imaging (MRI) of the brain did not show any infarcts or masses.


His medical history was noncontributory, except for allergic rhinitis, for which he was prescribed fexofenadrine pro re nata.

He also reported redness of his right eye with watery discharge.

He developed a skin rash affecting his trunk, limbs, and genitalia within the previous week.

Examination of his right eye revealed erythematous swollen eyelids.

A slightly raised dome-shaped umbilicated nodule, of approximately 3 mm, was present on his medial one-third lower eyelid margin, with a similar lesion developing on the corresponding upper eyelid margin (Figure).

A vesicular lesion was also present on the caruncle and there was global conjunctival hyperemia, mostly pronounced nasally and around the lesions (Figure, B).

There were no signs of corneal involvement, and the anterior chamber was quiet.

Results of fundus examination in both eyes were normal.

No preauricular or submandibular lymph node involvement was noted, but cervical lymph nodes were enlarged.

The pharynx was erythematous and swollen with white pus patches.

The skin lesions were dome-shaped papules, round, pinkish-white in color, surrounded by an erythematous area.

Full blood cell count and tests for HIV, AIDS, and syphilis were ordered.

Conjunctival swabs and eyelid vesicle fluid were taken for polymerase chain reaction testing.


His history included full-term birth by cesarean delivery from an uncomplicated pregnancy.

He had healthy, nonconsanguineous parents.The ocular examination showed a visual acuity of 20/20 OU with no anterior segment abnormalities.

He reported no present or past ocular symptoms and had negative findings on a review of systems.

Findings of dilated fundus examination of the right eye were within normal limits.

In the left eye, a white, translucent solid lesion with calcification was noticeable in the inferonasal quadrant (Figure, A).

The lesion measured approximately 1.6 mm in height, exhibited mild underlying chorioretinal changes, and had associated 3 vitreous seeds (Figure, A).

There were no signs of internal vascularization or vitritis.

Optical coherence tomography confirmed an intraretinal location and calcified deposits within the lesion (Figure, B).A, Left eye fundus photograph showing the white retinal lesion and vitreous seeds (arrowheads).

B, Optical coherence tomography confirming an intraretinal tumor with calcification (asterisks).

Scan noise due to the lesion’s peripheral location.


Ocular history included high hyperopia and amblyopia, and abnormal foveal contour was discovered when he was aged 3 years.

Best-corrected visual acuity was 20/50 in the right eye and 20/30 in the left.

Pupils were round and reactive to light, and intraocular pressure and anterior segment examination were within normal limits.

Dilated fundus examination revealed blunted foveal reflexes and abnormal vasculature in the inferonasal quadrant of the right eye.

Fluorescein angiography displayed symmetric bilateral circular areas of hypofluorescence around the macula and irregular fovea with no leakage (Figure 1A).

Color fundus photography showed symmetric bilateral mottling of the retinal pigment epithelium in the periphery (Figure 1B).

Spectral-domain optical coherence tomography on initial examination showed an abnormal foveal contour with loss of the foveal pit and intraretinal cystoid cavities within the inner nuclear layer.


At the time of initial presentation to her local retina specialist 1 week following her cataract surgery, the patient had severe pain and redness.

Her ocular history was notable for recent cataract surgery 5 weeks prior to presentation that was complicated by endophthalmitis.

A normal funduscopic examination was documented prior to cataract surgery.

An examination revealed a 2-mm hypopyon and dense vitreous haze with no view of the retina.

Examination showed a deep and quiet anterior chamber with a well-positioned intraocular lens without any plaques or deposits on the lens capsule.

Dilated ophthalmoscopic examination demonstrated improvement in the vitreous debris with 1+ vitritis and numerous superficial, round, white lesions spread throughout the fundus in all 4 quadrants and in the macula (Figure 1A).

Optical coherence tomography verified the preretinal location of the lesions (Figure 1B).A, Fundus photograph of the left eye at presentation shows vitreous debris with numerous white lesions throughout the retina.

She was treated for presumed endophthalmitis with a vitreous tap and intravitreal injections of vancomycin (1 mg/0.1 mL), ceftazidime (2.2 mg/0.1 mL), and dexamethasone (0.4 mg/0.1 mL).

The vitreous sample obtained at the time of treatment grew Staphylococcus caprae susceptible to vancomycin.At time of examination in our clinic 4 weeks following treatment, the patient was receiving topical steroid and cycloplegic drops.


The patient had recently immigrated from rural Moldova 1 month prior to presentation, where she had exposure to farm animals, including dogs and cats.

She had not traveled to any other countries.Painful and pruritic lower eyelid lesion with a vermiform appearance (arrow) (A).

The lesion resolved after 1 month, but she developed redness and swelling of the inner part of her right conjunctiva the next day (Figure 1B).

She denied any vision changes, eye pain, eye discharge, or systemic symptoms, such as fevers, chills, night sweats, weight loss, or diarrhea.

This was followed by an elevation in the bulbar conjunctiva with whitish linear opacities within the lesion (B).Ophthalmological examination showed a best-corrected visual acuity of 20/40 OU and intraocular pressures of 17 OD and 18 OS.

Pupils were equal and reactive to light.

On slit-lamp examination of the right eye, there was diffuse conjunctival vasodilation and hyperemia that was worse nasally.

There was a cystic elevation of the bulbar conjunctiva nasally with whitish linear opacities within the lesion (Figure 1B).

There was no anterior chamber or vitreous inflammation.


She denied having any symptoms, tenderness, numbness, or facial nerve weakness.

Physical examination revealed a mass in the buccinator space that was smooth, was nontender to palpation, and had no overlying cutaneous changes.

A contrast-enhanced maxillofacial computed tomography scan demonstrated a 1.8 × 1.8 × 1.9-cm rounded, well-circumscribed lesion at the anterior aspect of the left masticator space (Figure 1).

The mass was abutting the parotid duct, which did not appear dilated, and appeared to have a peripheral rim of hyperenhancing soft tissue with a central cystic/necrotic component.

Results of ultrasound-guided fine-needle aspiration revealed rare epithelial cells with degenerative changes and inflammatory cells present.

Findings from a core biopsy demonstrated a spindle cell neoplasm of uncertain origin.

On immunostaining, spindle cells were CK8/18, S100, and SOX10 negative; myosin and smooth muscle actin (SMA) negative; and CD31 negative.

However, STAT6 staining was diffusely positive.Axial view of the contrast-enhanced maxillofacial computed tomography scan demonstrating the left cheek mass (arrowhead).


On physical examination, the patient presented a grade VI peripheral left facial paralysis.

On audiometry, normal hearing sensitivity in the right ear and a severe to profound sensorineural hearing loss with poor word recognition score in the left ear were noted.

Findings from the rest of the clinical examination were within normal limits.Results of cerebral magnetic resonance imaging (MRI) and temporal bone computed tomography (CT) revealed a left internal auditory canal mass, measuring 13×12 mm, developed at the expense of nerve VII, with a dilation of the various portions of the facial nerve with extension to its distal branches.

It presented a hypointensity on T2, isointensity on T1, and was strongly enhanced after the injection of gadolinium.

This mass was responsible for the enlargement of the internal auditory canal and was in close contact with the left middle cerebral fossa, without intraparenchymal extension (Figure 1A and B).A, Cerebral MRI T1-weighted contrast-enhanced image showing the mass.

B, Temporal bone CT scan showing the mass.

Arrowheads indicate the abnormal facial nerve.


The patient lived in Southern California but had visited Kenya for an extended trip a few years prior.

Review of systems was negative for fevers, night sweats, weight loss, headache, vision changes, respiratory distress, or arthralgias.

On the left nasal dorsum and medial cheek, there was a 3 × 4 cm violaceous plaque with focal purulent drainage.

Within several weeks, the lesion rapidly expanded into a vegetative, freely draining plaque covering the cheeks and glabella and approaching the medial canthi (Figure, B).

Computed tomography revealed findings consistent with abscess that did not involve the orbits, sinuses, or bone.

Chest radiography results were unremarkable.

Punch biopsy specimens were obtained for histopathological analysis and tissue cultures (Figure, C).

Tissue culture results at 2 weeks remained negative, and a QuantiFERON-TB Gold test result was negative.A, Violaceous plaque on the nose and left cheek.

B, Rapid progression of the lesion involved the cheeks and glabella, with substantially worsening drainage at 6-week follow-up.

C, Punch biopsy of lesion showing suppurative and granulomatous dermatitis (hematoxylin-eosin).

D, Posttreatment, there was improvement of the lesion from initial presentation, but substantial residual facial scarring remained.


On physical examination, the patient showed a rhythmic tachycardia with a rate of 178 beats/min and blood pressure of 130/80 mm Hg.

The 12-lead electrocardiogram (ECG) revealed a regular tachycardia with a rate of 178 beats/min; no obvious P waves were recognizable (Figure 1A).

The QRS complexes displayed 2 different morphologies occurring with a definite allorhythmic distribution: pairs of beats exhibiting complete right bundle branch block (RBBB) and QRS duration of 140 milliseconds followed by a third beat with normal configuration and QRS duration of 70 milliseconds.

This trigeminal variation in intraventricular conduction occurred without any change in cycle length and was maintained.

Numbers within the tracing indicate the R-R intervals (in milliseconds).

The variability in ventricular cycle lengths results from small changes in both the P-P and P-R intervals.

Adenosine administration quickly slowed the ventricular rate allowing recognition of an atrial tachycardia with a rate of 178/min and a 2:1 atrioventricular (AV) ratio (Figure 1B).A, Regular supraventricular tachycardia with right bundle branch block aberration disappearing every third beat.


His medical and family histories were unremarkable.

Six months prior, he found his palms could not make full contact with each other (the “prayer sign”).

He had not been able to fully clench his fists for 2 months or squat for the past 10 days.

No erythema, edema, or sclerotic skin plaque had been found on his limbs or trunk.

On examination, he showed bilateral limited mobility of interphalangeal (hands), metacarpophalangeal, wrist, interphalangeal (feet), metatarsophalangeal, and ankle joints (Video).

No muscular atrophy or sclerodactyly was found.

The prayer sign (Figure 1A) and the “groove sign” (Figure 1B) were observed.

Blood test results indicated eosinophilia (absolute eosinophil count, 1300 μL; reference, <500μL [to convert to ×109/L, multiply by 0.001]), elevated erythrocyte sedimentation rate (ESR, 31 mm/h; reference, <15 mm/h) and C-reactive protein (CRP, 3.01 mg/dL; reference, <0.8 mg/dL [to convert to mg/L, multiply by 10]).

Liver and kidney function tests, creatine kinase level, electrolyte level, thyroid function, globulin concentration, and antinuclear antibody (ANA) level were unremarkable.

Electrocardiogram, cervical spine magnetic resonance imaging, and plain radiographs of hands, wrists, feet, and ankles were normal.

Nerve conduction studies performed in all 4 limbs were normal.

Electromyography (EMG) showed spontaneous activities in muscles of limbs, including fibrillation potentials and positive sharp waves (1+ or 2+).

Myotonic discharges were seen in bilateral extensor digitorum.A, The patient’s bilateral palms and fingers could not make full contact due to the limited mobility of interphalangeal and metacarpophalangeal joints.

B, Linear depression (arrowheads) was seen along the course of superficial vein when limb was elevated.


At age 4 years, she developed white oral plaques that resolved with oral nystatin.

Approximately 6 months later, the oral plaques recurred, her toenails became thickened and yellowed, and red plaques appeared on both feet and lower legs.

Over the following years, she received intermittent 3- to 6-month courses of daily itraconazole for recurrent skin, nail, and oral mucosal abnormalities, which typically recurred within 6 to 12 months of discontinuing itraconazole.

Her last dose of itraconazole was approximately 2 years prior to presentation.

On physical examination, the patient had white, moist, nonadherent plaques in the oral mucosa and moist red fissures at bilateral oral commissures (Figure, left panel).

She also had thickened, yellowed toenails and scaly erythematous plaques on her lower legs and feet bilaterally (Figure, right panel).

Results of complete blood cell count with differential were normal, as were results of measurement of serum IgG, IgA, IgM, and IgE levels and analysis of CD3, CD4, and CD8 T-cell subsets.

Potassium hydroxide wet mount preparation of skin scrapings from the lower extremities demonstrated fungal elements.

Fungal culture of the skin scrapings grew Candida albicans.Patient presentation.

After 3 months of daily oral itraconazole, her skin, nail, and oral mucosal abnormalities resolved for approximately 1 year.

Left, White plaques in the oral mucosa and angular cheilitis.

Right, Thickened, yellowed toenails and scaly erythematous plaques on both lower legs and feet.


She reported 2 months of increasing right-sided blurry vision and a sensation of eye dryness.

She was found to have incomplete eyelid closure by her primary care physician, who initiated artificial tear lubrication and bedtime eyelid taping with partial symptom improvement.Clinical examination revealed 20/25 visual acuity OD with full extraocular motility and normal intraocular pressure.

She was noted to have right upper eyelid retraction (Figure 1A) with substantial static upper eyelid lag on downgaze (Figure 1B).

She had 1-mm right lagophthalmos with incomplete blink.

Frontalis and orbicularis oculi strength were intact.

She was measured to have a 2-mm relative right enophthalmos and no resistance to retropulsion.

A review of patient photographs from 2 years prior showed symmetric bilateral eyelid appearance without retraction.Right upper eyelid retraction (A) with substantial static eyelid lag on downgaze (B).


He had a history of stage 3B melanoma treated with ipilimumab complicated by grade 3 colitis refractory to high-dose corticosteroids and infliximab requiring colectomy and stomal hernia after hernia repair.

His medical history was notable for hypertension controlled with metoprolol.

He denied any changes in vision, flashes, floaters, eye pain, or eye redness.

His mother had a history of breast cancer but otherwise family history was unremarkable.Visual acuity was 20/20 OD and 20/25 OS.

Intraocular pressure was 16 mm Hg OD and 15 mm Hg OS.

Anterior segment examination showed inferior corneal endothelial pigmentation in the right eye (Figure, A) and trace nuclear sclerotic cataracts in both eyes.

Dilated ophthalmoscopy was unremarkable.

Four-mirror gonioscopy in the right eye showed an open angle, normally pigmented trabecular meshwork, and a well-demarcated pigmented brown lesion without extension into the angle (Figure, B).

He denied a history of trauma, intraocular surgery, or inflammation in the eyes.

Serial positron emission tomography/computed tomography scans showed no evidence of metabolically active disease.

He did not have ectropion uvea, corectopia, or feeder vessels.


At age 3 years, he presented to the clinic with a persistent cheek and orbit lesion, dense amblyopia, large-angle monocular esotropia and hypertropia, and proptosis of the left eye.

A repeated magnetic resonance image showed persistent orbital involvement causing medial displacement of the lateral rectus muscle and mass effect on the globe (Figure 1B).Infantile hemangioma prior to treatment.

An ophthalmic evaluation at an outside hospital was concerning for amblyopia because of anisohypermetropia, greater on the left, and a left esotropia and hypertropia.

A magnetic resonance image revealed an orbital mass surrounding the left lateral rectus muscle with mass effect on the globe and extension into the eyelid, pterygopalatine fossa, and cheek.Given the risk of amblyopia, the patient underwent 2 embolization and debulking procedures of the orbital and cheek components of the lesion, which were positive for glucose transporter 1 on pathology.

The left extraocular muscle showed inability to abduct past midline (Figure 1A).

A, Left abduction deficit (asterisk) from complex infantile hemangioma involving the orbit, pterygopalatine fossa, and cheek.

Arrowhead indicates cheek component of hemangioma.

B, Magnetic resonance imaging orbits axial image (postgadolinium, T1) showing enhancing orbital component (arrowhead).

He was diagnosed with a capillary hemangioma, and propranolol was started at age 1 month with progression despite dosage increases.

Topical timolol was tried without improvement; oral prednisolone decreased the size of the lesion, but was poorly tolerated and discontinued.

However, the esotropia abruptly worsened after the second debulking.

He had a pink macule on his left cheek at birth, which became raised and discolored around age 3 to 4 weeks.


The lesions gradually enlarged and coalesced into large plaques and nodules.

Mild erosions occurred occasionally on the surface of the lesions.

She denied having fever, fatigue, chills, night sweats, or weight loss.Physical examination demonstrated ill-defined, indurated erythematous-violaceous patches, nodules, and plaques involving the surface of her head and face with sporadic erosion and brownish crusts (Figure, A).

The findings of systemic reviews were unremarkable, and there was no lymphadenopathy.

The complete blood cell count revealed normal white blood cell count.

The biopsy from an erythematous nodule displayed sheets of medium to large mononuclear cells infiltrated in the dermis, some of which filled and expanded apparent dermal blood vessels and had large, irregular, pleomorphic nuclei (Figure, B).

The initial immunohistochemical stain revealed the tumor cells were positive for CD3 and negative for CD20, AE1/AE3, CK20, chromogranin A, and melan-A.

The Ki-67 labeling index was 70%.A, Ill-defined, indurated erythematous-violaceous patches, nodules, and plaques on the head and face with sporadic erosion and brownish crusts.

B, The biopsy showed dilated vessels expanded by cohesive clusters of large atypical lymphoid cells (hematoxylin-eosin staining).

C, Immunohistochemical staining of D2-40 highlighted the exclusively lymphovascular location of the lymphoma.

In addition, some neoplastic cells formed a balloon appearance.


Five years before this otolaryngology evaluation, the patient developed diffuse skin plaques with erythema and was subsequently diagnosed with hypopigmented cutaneous T-cell lymphoma (CTCL, mycosis fungoides type).

Owing to significant worsening of his symptoms 4 months before his evaluation, a biopsy of his cutaneous lesions was performed to rule out progression of CTCL (Figure 1).

Physical examination demonstrated large annular plaques with peripheral hyperpigmentation of the body.

There were also confluent, indurated pink plaques with slightly raised edges along the forehead, malar eminence, and scalp.

The nasal septum demonstrated an inverted V deformity with compromise of the keystone junction.

Nasal passages were obstructed with thick mucus and synechiae formation, nearly obstructing the entire nasal passage bilaterally.A, Fite acid-fast stain of cutaneous lesion identifying pink bacilli (original magnification ×100).

The patient was treated with a regimen of narrowband UV-B phototherapy and triamcinolone cream, which he has continued for 4 years.

B, Hematoxylin-eosin stain of the same cutaneous lesion showing poorly formed granulomas (original magnification ×40).


She was breastfeeding her 10-month-old, had no history of alcohol use, and had a remote history of hookah use.

She was a Southern California native with travel history to Pakistan, Turkey, Jordan, Israel, Qatar, and Dubai 5 years prior to symptom onset.

One month prior to onset, she drove from Los Angeles, California, to Houston, Texas.

She denied recent unintentional weight loss, cough, fever, night sweats, chills, stridor, dyspnea, dysphonia, or rash.On examination, her vital signs were within normal limits, and physical examination revealed a small right tonsillolith, mild tonsillar erythema that was worse on the right side, and a mobile 2-cm, right level 2 lymph node that was slightly tender to palpation.

Laboratory evaluation was notable for an elevated eosinophil count and positive Epstein-Barr immunoglobulin G. Her white blood cell count and mononucleosis spot test result were within normal parameters.Her symptoms persisted despite treatment with penicillin, azithromycin, and steroids from her primary physician and amoxicillin-clavulanate, sinus rinses, fluticasone propionate, and azelastine spray from an otolaryngologist to treat any contributing postnasal drainage and tonsillitis.Flexible transnasal videolaryngoscopy revealed a lesion on the laryngeal surface of the right epiglottis passing midline extending to the right aryepiglottic fold, but not involving the true vocal cords (Figure 1A).

Given inconclusive office biopsy results, direct laryngoscopy with biopsy was performed, showing extensively inflamed squamous mucosa with ulceration, granulation tissue, pseudoepitheliomatous hyperplasia, and atypia (Figure 1B).A, In-office laryngoscopy showing an ulcerative, papillomatous lesion on the laryngeal surface of the right epiglottis that passed midline and extended to the right aryepiglottic fold but did not involve the true vocal cords.

B, Laryngeal biopsy specimen demonstrating extensively inflamed squamous mucosa with ulceration, granulation tissue, pseudoepitheliomatous hyperplasia, and atypia, with background chronic granulomatous inflammation.


He denied any history of dysphagia, odynophagia, fevers, unintentional weight loss, cough, or reflux symptoms.

There was no prior history of smoking, head and neck surgeries, or radiation exposure.

He was treated for asthma with inhaled steroids by his primary care physician without improvement in symptoms.

On physical examination, the patient was stridulous and considerably hoarse.

Subsequent videostroboscopy revealed severe laryngeal mucosal edema, most significant in the false vocal folds, interarytenoid, and postcricoid regions (Figure 1A).

There was right true vocal fold immobility with compensatory squeeze of the false vocal folds and an absent mucosal wave.

Computed tomographic (CT) scan of the neck with contrast showed irregularity along the free edges of the true vocal folds but no evidence of a neoplasm or cervical lymphadenopathy.

The patient underwent urgent direct laryngoscopy with biopsy, which showed edematous, irregular, friable laryngeal mucosa with significant airway narrowing.

Laryngeal biopsy findings are shown in Figure 1, B and C.A, Laryngeal videostroboscopic image.

B, Hematoxylin-eosin stain.
C, Grocott methenamine silver stain.


The child had an older sibling with no skin ailments, and no other family members were affected.

The lesions started on the left foot and subsequently progressed to involve the face, trunk, and extremities, with distal interphalangeal joint deformity of both hands (Figure, A).

Parents reported decreased oral intake, decreased activity, and delayed motor development.A, Nodules on the right hand and joint deformity.

The child weighed 8 kg (normal, 13-15 kg) and was 87 cm (normal, 91-95 cm) in length.

B and C, Histopathological images show a granulomatous pattern, numerous foamy cells, marked collagen degeneration, and mucin deposition (hematoxylin-eosin stain).

D, Comma-shaped curvilinear tubular structures (yellow arrowhead).On examination, dozens of tough to hard subcutaneous skin-colored nodules ranging from 0.5 to 5 cm in diameter were observed on both sides of the nose and parts of both wrists, the knees, elbows, ankles and hips, and the trunk.

Symmetrical beaded subcutaneous nodules were observed in the bilateral auricles, while the mucous membrane was not involved.

In addition, a physical examination revealed horizontal nystagmus and voice hoarseness.

The distal interphalangeal joints of both hands were stiff with limited extension.

The interphalangeal joints of the third through fifth distal segments of both feet were slightly bent.

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

A magnetic resonance imaging study of the brain showed volume loss in the parietooccipital region.

Ultrasonographic evaluation of metacarpophalangeal joints showed multiple hypoechoic nodules on the skin of the hands.

Radiography showed deformities of the interphalangeal joints with soft tissue swelling.


The patient’s medical history was otherwise unremarkable.

The patient denied any known preceding triggers or trauma to the area of the rash.

Review of systems was negative for any new or worsening constitutional, respiratory, or gastrointestinal symptoms.

Examination findings were notable for firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk (Figure, A and B).

There was no appreciable skin tightening in the affected areas.

Complete blood cell count with differential was unremarkable.

Lesional punch biopsy specimens were obtained (Figure, C and D).A, Clinical image of firm, red-brown plaques without overlying scale on the proximal upper extremities and anterior trunk.

B, Clinical image of nodular plaques on the right shoulder and chest.

He had tried treating with topical aloe, without improvement.

C and D, Lesional punch biopsy specimens (hematoxylin-eosin).


Past medical history included schizophrenia, hypothyroidism, and supraventricular tachycardia.Her examination demonstrated normal visual acuity in both eyes.

She reported difficulty opening her jaw, pain when chewing, and a 2.3-kg weight loss.

The week prior, she experienced left-sided ptosis that persisted for 2 days and subsequently resolved.

Extraocular motility demonstrated limitation of elevation and abduction bilaterally (Figure 1).

Results of dilated fundus examination were normal, and the remainder of her neurologic examination results were normal.

Her eye movements and ptosis did not change with fatiguability, rest, or an ice-pack test.

Investigations revealed a C-reactive protein level of 292 mg/L (normal, <10 mg/L; to convert to milligrams per deciliter, divide by 10) and erythrocyte sedimentation rate of 93 mm/h (normal, <30 mm/h).

A lumbar puncture demonstrated normal opening pressure, cell count, and glucose and protein levels.

Magnetic resonance imaging with contrast of the brain demonstrated diffuse edema and enhancement of the scalp, skull base, neck, and paraspinal soft tissues, as well as T2 hyperintensity and enhancement of the extraocular muscles bilaterally.

An additional test was obtained, and a diagnosis was made.Extraocular movements on presentation.

She denied vision changes, eye pain, scalp tenderness, and myalgias.

Examination reveals deficits in elevation and abduction of both eyes not conforming to a cranial nerve distribution.


She had pseudophakia with an otherwise normal anterior segment examination in each eye.

Fundus examination was remarkable for macular PEDs and SRF in each eye.

There was an epiretinal membrane in the left eye.Optical coherence tomography (OCT) in the right eye disclosed a central PED with SRF that extended beyond the inferior border of the PED (Figure, A).

Hyperreflective foci, suggestive of vitelliform material, were visible on the photoreceptors.

OCT in the left eye demonstrated 2 PEDs in the parafovea (Figure, B).

SRF was present with overlying thickening of the photoreceptors.

Fluorescein angiography revealed punctate hyperfluorescent staining within the body of the PEDs in each eye.

There was no evidence of leakage in either eye.

Fundus autofluorescence displayed dispersed, speckled hyperautofluorescence corresponding to the potential vitelliform material and SRF in the right eye.

A, A 3000-μm-diameter pigment epithelial detachment with a 30-μm layer of subretinal fluid overlying the pigment epithelial detachment and a 140-μm layer of subretinal fluid inferior to the pigment epithelial detachment.

There are hyporeflective pockets within the pigment epithelial detachment possibly representing fluid.

B, Two 500-μm pigment epithelial detachments with subretinal fluid and thickening of the photoreceptors in the left eye.

Ocular history included presumed exudative age-related macular degeneration.

Central serous chorioretinopathy was also suspected secondary to the presence of yellow subretinal deposits located within an inferior macular detachment in the right eye.Visual acuity was 20/40 OD and 20/25 OS.

Review of the autofluorescence 3 years prior revealed boat-shaped hyperautofluorescence located in the most inferior aspect of the SRF in the right eye.Optical coherence tomography with corresponding autofluorescence image is shown in each eye.

Hyperreflective deposits on the photoreceptors are suggestive of vitelliform deposits (arrowheads).


Her medical history included neonatal seizures.

Both parents were healthy and denied consanguinity.

The patient has 3 half sisters, all of whom are healthy.A, Fundus autofluorescence discloses attenuated, narrow vasculature and diffuse peripheral patchy hypoautofluorescence.

She was initially evaluated at an outside institution and was found to have bilateral symmetric vision loss with nyctalopia.

The patient did not receive any ophthalmological care until 2 years later, when she was seen for marked vision loss and was noted to have a BCVA of light perception in both eyes.When she presented to the pediatric retina service, she demonstrated poor mentation and was unable to recall simple things such as the name of her siblings.

At that time, her best-corrected visual acuity (BCVA) was 20/70 OU.

The anterior segment examination and intraocular pressures were within normal limits.

Fundus autofluorescence disclosed attenuated, narrow vasculature and diffuse peripheral patchy hypoautofluorescence (Figure 1A).

Color fundus photography showed optic disc pallor, attenuated retinal vasculature, prominent choroidal markings, and central retinal atrophy with diffusely mottled pigmentation (Figure 1B).

Optical coherence tomography displayed decreased retinal thickness, more prominent in the inner layers, and hyper-reflective dots in the outer retinal layers.

Family history included unilateral vision loss in her paternal grandmother in her late 20s.

B, Color fundus photograph displays optic disc pallor, attenuated retinal vasculature, prominent choroidal markings, and central retinal atrophy with diffusely mottled pigmentation.


Her symptoms began after relocation to California and occurred more frequently at her home.

However, she could not discern any environmental or dietary triggers.

She reported pruritus and swelling, which were usually moderate but occasionally severe, prompting several emergency department visits.

During an emergency department visit, she was diagnosed with acute parotitis based on clinical and radiographic findings of diffuse gland edema, without salivary stones or masses.

A differential blood cell count revealed 10% eosinophils (normal, <6%) and an absolute eosinophil count 500/µL (to convert to ×109/L, multiply by 0.001).

Titers for antinuclear antibodies, rheumatoid factor, anti-Ro (SS-A), and anti-La (SS-B) were negative.Sialendoscopy of her right parotid and left submandibular glands found no obstructing stones or strictures.

An open biopsy of the right parotid tail revealed nonspecific inflammatory changes and otherwise normal parenchyma.

Further histologic examination of the surgical specimen revealed substantial periductal inflammatory infiltrate with eosinophils, as seen in the Figure.Medium-powered (A) and high-powered (B) field from the superficial parotid gland (hematoxylin-eosin).

Her symptoms responded to oral prednisone bursts and diphenhydramine, but not to second-generation antihistamines or montelukast.Her workup included immune serology and total immunoglobulin (Ig) E measurements, all of which were within normal limits.

Concurrent steroid irrigation did not provide any substantial benefit.

Given the frequency and severity of her symptoms along with multiple treatment failures, she opted to undergo a right superficial parotidectomy, which proceeded without complications.


On physical examination, there was a nontender 4-cm mass in the left submandibular region with no overlying skin changes.

Ultrasonography results showed an avascular cystic structure with internal debris and a single thin septation.

Contrast-enhanced computed tomography (CT) of the neck soft tissue revealed a 3-cm low attenuation, nonenhancing, cystic-appearing mass that elevated the submandibular gland to the level of the parapharyngeal fat space with medial extension of the lesion into the tongue musculature.

The walls were thin except for mildly thickened capsule along the posterior aspect of the lesion (Figure, A and B).

Fluid that aspirated from the cyst was serous, and cytology showed mature and anucleate squamous cells with acute inflammation.

At age 12 months, the mass was excised via neck dissection.

A, Axial: the blue arrowhead indicates extension into the tongue musculature, the yellow arrowhead indicates focally thickened capsule posteriorly, and the white arrowhead indicates a displaced sternocleidomastoid muscle.

B, Coronal: the black arrowhead indicates an elevated left submandibular gland, and the white arrowhead indicates a normal right submandibular gland.

C, Axial T2-weighted magnetic resonance image showing marked interval enlargement of the multiseptated cystic mass.

A lateral component at the level of the sternocleidomastoid muscle was completely excised.

An intraoperative rupture of the thin capsule caused some spillage of cystic contents that were milky white in some areas and mucinous in others.Contrast-enhanced computed tomography images.

Her parents reported no fevers, constitutional symptoms, or enlargement of the mass.

Further analysis 8 months after the initial CT via contrast-enhanced magnetic resonance imaging (MRI) showed a large, multiseptated cystic structure (Figure, C); the capsule of the wall was mildly thickened and was contrast enhancing.


The lesion had appeared without an identifiable cause, and for the previous 2 months, the patient had applied topical corticosteroids and antifungals with no improvement.

Physical examination revealed an ill-defined, nonindurated, erythematous-violaceous plaque that was slightly raised but with an atrophic appearance (Figure, A).

A skin biopsy was obtained for histopathology examination (Figure, B-D).A, Clinical image of the left calf showing an ill-defined, erythematous-violaceous plaque with an atrophic appearance.

B, Band-like vascular proliferation in the upper dermis with no grenz zone (hematoxylin-eosin).

C, Round vascular channels lined by a single layer of endothelial cells without atypia (hematoxylin-eosin).

D, CD34 immunostaining labels endothelial cells.


The patient fell asleep and his girlfriend tried to wake him, but he started shaking and slumped over on the ground.

He denied confusion afterward but did not feel well with nausea, flushing, chest tightness, and a rapid heart rate.

About 10 minutes later, he had a second syncopal episode for 2 to 3 minutes with more than 20 muscle jerks.

On presentation at the emergency department, he was afebrile, blood pressure was 120/59 mm Hg, heart rate was 85 beats per min, respiratory rate was 16 breaths per min, and oxygen saturation was 96% on room air.

His cardiac examination revealed normal heart sounds with no murmurs.The electrocardiogram (ECG) was performed early on arrival in the emergency department (Figure).

Transthoracic echocardiography revealed an ejection fraction of 54%, mild right ventricular (RV) dilation (RV diameter, 4.1 cm), and no significant valvular abnormalities.

Cardiac magnetic resonance imaging showed no RV abnormalities and qualitatively normal RV function.

Brain magnetic resonance imaging and electroencephalogram  were obtained, both of which results were normal.

Neurology consultation was obtained with concern for an epileptic seizure event surrounding the recurrent syncopal episodes.

On further questioning, patient reported having a second cousin with sudden cardiac death of uncertain etiology in his early 20s.Initial electrocardiogram on presentation in the emergency department.


On physical examination, the patient had normal vital signs, mild diffuse abdominal tenderness without rebound or guarding, and bluish pigmentation along his gingival margin (Figure, panel A).

Blood testing showed alanine aminotransferase level 51 U/L (0.85 μkat/L; reference range, 7-23 U/L [0.12-0.38 μkat/L]), aspartate aminotransaminase 68 U/L (1.14 μkat/L; reference range, 13-30 U/L [0.22-0.50 μkat/L]), total bilirubin 3.2 mg/dL (54.73 μmol/L; reference range, 0.4-1.5 mg/dL [6.84-25.66 μmol/L]) and direct bilirubin 0.9 mg/dL (15.39 μmol/L; reference range, 0.0-0.4 mg/dL [0.0-6.84 μmol/L]).

Hemoglobin level was 8.7 g/dL with a normal mean corpuscular volume, and ferritin level was 637.9 ng/mL (reference range, 39.9-465 ng/mL).

Blood testing revealed normal lactate dehydrogenase, haptoglobin, iron, vitamin B12, folate, zinc, and copper levels, and results of urinalysis were normal.

A peripheral blood smear demonstrated small, bluish-purple punctate inclusions in erythrocytes (Figure, panel B).

Results of upper and lower endoscopy and abdominal-pelvic computed tomography performed within the past 3 months were unremarkable.A, Dark blue lines along patient’s upper gingival margins.


Medical history was notable for mild obesity (body mass index of 30 [calculated as weight in kilograms divided by height in meters squared]).Visual acuity was 20/20 OU, with briskly reactive pupils OU and no relative afferent pupillary defect.

Automated visual fields demonstrated subtle enlargement of the blind spots.Fundus photography demonstrating bilateral grade 1 optic disc edema.On neurologic examination, she had moderate weakness of dorsiflexors at the ankles bilaterally as well as toe extensors and everters.

There was large and small fiber sensory loss distally in the legs.Findings of magnetic resonance (MR) imaging and MR venography of the head were unremarkable.

Ophthalmoscopic examination revealed blurring and elevation of the nasal margins of the optic disc consistent with grade 1 optic disc edema in both eyes (Figure).

Optical coherence tomography showed an elevated mean peripapillary retinal nerve fiber layer thickness of 170 μm OD and 150 μm OS.

Electromyography suggested a brachial plexopathy.

Lumbar puncture showed a normal opening pressure of 170 mm Hg with a cerebrospinal fluid protein of 113 mg/dL and 2 nucleated white blood cells.

Serum studies were notable for a thrombocytosis of 479 × 103/μL (to convert to × 109/L, multiply by 1) and an elevated quantitative monoclonal IgA λ-protein level of 492 mg/dL (to convert to grams per liter, multiply by 0.01).


Several days into her hospital course, she developed acute-onset severe bilateral periorbital swelling, chemosis, and ophthalmoplegia as well as occasional flushing and palpitations.

Her best-corrected visual acuity was 20/70 in both eyes.

Pupils, intraocular pressure, and color vision were normal.

She had bilateral proptosis to 20/21 mm by Hertel exophthalmometer, −3 restriction of extraocular movements in all directions of gaze, diffuse punctate epithelial erosions, and mechanical lower lid entropion secondary to severe chemosis in both eyes (Figure 1A).

Anterior segment examination and dilated ophthalmoscopy results were otherwise unremarkable.A, External photograph on initial presentation demonstrating bilateral periorbital swelling, chemosis (yellow arrowhead), and lower lid entropion (white arrowheads).

B, Coronal T1 fat-suppressed postcontrast orbital magnetic resonance imaging (MRI) with nodular heterogenous enhancement of bilateral extraocular muscles.

IR indicates inferior rectus; LR, lateral rectus; MR, medial rectus; SO, superior oblique; SR, superior rectus.Magnetic resonance imaging of the brain and orbit with contrast revealed bilateral and symmetric tendon-sparing extraocular muscle enlargement of all extraocular muscles (EOMs) with nodular heterogenous enhancement (Figure 1B).


His best-corrected visual acuity was 20/20 OD and 20/30 OS with intraocular pressures of 20 mm Hg OD and 26 mm Hg OS.

The anterior segments showed well-positioned posterior chamber intraocular lens implants with open posterior capsules.

Dilated fundus examination revealed a small peripheral hypoautofluorescent chorioretinal scar in the right eye.

In the left eye, there was trace vitreous haze and 2+ anterior vitreous cell.

Multifocal chorioretinal scars extended from the left optic nerve into the macula in each quadrant (Figure 1).

These lesions showed variable hypoautofluorescence and hyperautofluorescence.

On indocyanine green angiography (ICGA), the confluent hypoautofluorescent lesions showed loss of the choriocapillaris and prominent large choroidal vessels, whereas the mottled hypoautofluorescence and hyperautofluorescent lesions appeared to block the underlying fluorescence.

Routine laboratory testing was unremarkable except for a positive interferon-gamma release assay for Mycobacterium tuberculosis.

A chest radiograph was normal.Fundus photograph of the left eye demonstrating multifocal outer retinal lesions with variable pigmentation extending from the optic nerve to the equator with sparing of the foveal center.

The referring physician was treating him with prednisolone eye drops for cystoid macular edema after recent left Nd:YAG capsulotomy.


Local antiglaucoma therapy with a fixed-combination prostaglandin and β-blocker was used regularly in both eyes owing to long-standing primary open-angle glaucoma.

Uneventful cataract surgery with phacoemulsification and in-the-bag insertion of an intraocular lens was performed 10 years earlier in both eyes.

Best corrected visual acuity (BCVA) was 1.0 and 0.5 (Snellen equivalent, 20/20 and 20/40) OD and OS, respectively.

His manifest refraction revealed a difference of −0.75 D sphere compared with his own preexisting glasses in the right eye.

IOP was 24 mm Hg in the right eye and 18 mm Hg in the left eye.Slitlamp examination revealed a milky substance in the retrolental space, more pronounced in the right eye (Figure) but evident in both.

The rest of the slitlamp examination was unremarkable with moderate superficial punctate keratitis owing to ocular surface disease, an anterior chamber depth of Van Herick grade 4 (peripheral anterior chamber depth >1 corneal thickness), an absence of anterior chamber inflammation, and a moderate amount of Elschnig pearls in both eyes.Right eye with milky-opaque substance (between white arrowheads) in the retrolental space and distension of the capsular bag.


Her history was notable for phthisis in her left eye due to a left orbit clear cell sarcoma with metastatic disease, after surgical excision and radiation, with recent enrollment in a palliative immunotherapy research protocol.

One day later, her mental status improved, and she reported central blurry vision in her right eye.

On examination, her visual acuity was 20/40 in this eye, she had normal intraocular pressure, and there was no evidence of anterior chamber or vitreous cells.

Dilated fundus examination revealed segmental areas of venous sheathing (Figure 1A) in the right eye and was not possible in the left eye owing to phthisis.

An optical coherence tomography scan of the right eye revealed hyperreflective changes along the outer plexiform and outer nuclear layers, small intraretinal cysts, and disruption of the ellipsoid and especially the interdigitation zone (Figure 1B).A, Color fundus photograph of the right eye at the time of presentation demonstrating segmental areas of venous sheathing (white arrowheads).

After completing 2 days of broad-spectrum intravenous antibiotics and antivirals for presumed septic meningitis, her laboratory and imaging results returned negative and she was transitioned to intravenous methylprednisolone (1 mg/kg).


One month later, he presented to a local emergency department with diffuse abdominal pain.

Symptoms began 6 weeks earlier and had been intermittent in nature.

He had also experienced fatigue, night sweats, decreased appetite, and weight loss for 6 weeks.

He otherwise denied having fevers, myalgias, nausea, vomiting, diarrhea, or easy bruising.

A fine-needle biopsy of an enlarged left-sided cervical lymph node yielded benign results.

Physical examination revealed bilateral cervical, axillary, and inguinal lymphadenopathy in addition to mild diffuse abdominal pain.

Laboratory results revealed a hemoglobin level of 13.1 g/dL (to convert to g/L, multiply by 10), a white blood cell count of 6.4 × 103/μL, and a platelet count of 404 × 103/μL  (to convert to × 109/L, multiply by 1) in addition to negative results for HIV, hepatitis B virus, and hepatitis C assays.

Additional workup results were notable for elevated levels of interleukin (IL) 10 (1091 pg/mL), IL-6 (3.1 pg/mL), C-reactive protein (4.9 mg/dL [to convert to mg/L, multiply by 10]), and erythrocyte sedimentation rate (79 mm/h).

A computed tomography scan of the neck, chest, abdomen, and pelvis further revealed extensive cervical, supraclavicular, retroperitoneal, pelvic, and inguinal lymphadenopathy, with extensive inflammation and fat stranding adjacent to these enlarged nodes.

Positron emission tomography–computed tomography further demonstrated fluorodeoxyglucose-avid lymph nodes above and below the diaphragm.

The patient then underwent excisional biopsy of an enlarged right cervical lymph node (Figure).A, Proliferation of slitlike blood vessels (hematoxylin-eosin).

B, The lymphoid follicle shows regression, with onion-skinning of mantle zone lymphocytes and hypervascularity (hematoxylin-eosin).

Scattered atypical plasma cells are present.


The skin lesion was nail sized when first noticed 1½ years earlier, then gradually developed over the 8 months prior to presentation.

The patient denied any associated fevers, weight loss, or night sweats.

Physical examination revealed a slightly reddish verrucous mass with translucent papules and plaques on the right temple, about 5 cm in diameter, with surface hemorrhagic crust in the side adjacent to right eyebrow arch (Figure, A).

The lesion was nontender with no purulent discharge and no severe necrotic changes.

There was no hepatosplenomegaly or superficial lymphadenopathy.

Laboratory tests, including blood cell counts, urinalysis, and kidney and hepatic panels, revealed no abnormalities.

A skin biopsy was performed and submitted for histopathologic analysis (Figure, B-D).A, A slightly reddish verrucous mass with translucent papules and plaques on the right temple.

B, The histological examination showed papillomatous epidermal hyperplasia, edema of dermal papillae, and neoplastic infiltration consisting of small round blue cells with alternating areas of dense and loose cellularity (hematoxylin-eosin).

C, Small, round blue cells were observed in the dermis with round, fusiform, or oval hyperchromatic nuclei, conspicuous nucleoli, and scant cytoplasm (hematoxylin-eosin).

D, Tumor cells were positive for MyoD1 (original magnification ×400).


Dermatology was consulted for input on the cause of the ulcers, which had been ongoing for approximately 6 months prior; individual lesions lasted 1 to 3 weeks before self-resolving.

Examination revealed exquisitely tender, ovoid, punched-out ulcerations of the inferior lip and scrapeable white plaques on the tongue (Figure, A), right buccal mucosa, and external anal mucosa (Figure, B).

A punch biopsy from 1 of the perianal ulcers was performed (Figure, C and D).A, Healing oval punched-out ulceration of inferior lip and white plaques on tongue consistent with thrush.

B, Two ovoid, punched-out ulcerations of the external anal mucosa.

C, Hematoxylin-eosin staining of perianal lesion showed mixed infiltrate of histiocytes, neutrophils, lymphocytes, and eosinophils, with prominent admixed large and atypical cells at high power.

D, Epstein-Barr virus–encoded RNA staining showed scattered positivity in some cells.

During admission in the intensive care unit, treatment with broad-spectrum oral antibiotics for presumed infection and oral fluconazole for thrush led to improvement in the patient’s medical condition, but the ulcers persisted.


After recovering from anesthesia in the postanesthesia care unit, he experienced headache, facial numbness, inability to open both his eyes, and inability to move both eyes in any direction.He had a known enhancing central skull base lesion in sella turcica with compression of the optic chiasm and mild mass effect on the pons that was felt to be a pituitary macroadenoma (Figure).

After symptom onset, the mass was hyperintense on T2-weighted images (not shown).During the bedside examination in the postanesthesia care unit, he was noted to have complete bilateral ptosis.

He had decreased sensation to light touch and pinprick in the V1/V2 distribution of the trigeminal nerve bilaterally.

Vestibulo-ocular reflex did not overcome the ophthalmoplegia.

His baseline examination before the cystectomy showed visual acuity of 20/20 OU with intact extraocular movements and unremarkable confrontational fields, although a mild bitemporal hemianopia was seen on automated visual fields.T1-weighted coronal magnetic resonance imaging (MRI) with contrast shows a 4.9 × 4.6 × 5.2-cm sellar/parasellar lobulated mass with homogenous enhancement before symptom onset (A), which became 5.3 × 5.1 × 5.3 cm and had loss of enhancement after symptom onset (B).

The mass caused superior displacement of the optic chiasm and had extension into the cavernous sinus bilaterally.

The mass also extended posteriorly and deformed the anterior aspect of the pons (not shown).

His visual acuity was 20/20 OU with full visual fields on confrontational visual field testing.

The right and left pupils were 5 mm and 6 mm in size, respectively, in both light and dark.

There was no pupillary response to light or accommodation.

Intraocular pressure was normal in both eyes.

The patient was unable to move either eye in any direction on extraocular motility testing.

Magnetic resonance imaging (MRI) was obtained 12 hours after symptom onset redemonstrating the large sellar mass, which no longer had central enhancement (Figure).


Her last intravenous heroin use occurred 9 days prior to presentation.

She was not taking any prescription or herbal medications and had not been prescribed suppressive antiviral medication for chronic HBV infection.

She reported no history of travel outside the US and no raw meat ingestion.

Her vital signs, mentation, and physical examination were normal except for scleral icterus (Figure).

Results of blood testing were negative for hepatitis C virus RNA, anti–hepatitis A IgM, and HIV antibody.

Other selected laboratory values are shown in the Table.


Twelve months prior, he experienced a self-limited episode of right eye pain and redness, and 2 months later, a similar episode occurred in his left eye.

He reported no fevers, chills, headaches, visual changes, hearing loss, hoarseness, shortness of breath, wheezing, chest pain, arthralgias, or rash.

Physical examination revealed normal vital signs, and no abnormalities on nasal, cardiopulmonary, joint, and skin examination.

His left eye had scleral erythema, and the cartilaginous portion of his left ear was swollen and erythematous (Figure).Left, erythematous and edematous patch on the patient’s left sclera.

Right, auricular erythema of the left external ear, with sparing of the earlobe.Laboratory testing revealed a white blood cell count of 4200/μL, hemoglobin level of 12.9 mg/dL, and platelet count of 142 000/μL.

Erythrocyte sedimentation rate (ESR) was 53 mm/h (reference range, 0-15 mm/h), and C-reactive protein was 135 mg/L (reference range, 0-8 mg/L).


She denied experiencing pain, diplopia, muscle weakness, dysarthria, dysphagia, difficulty breathing, or other neurologic deficits.On examination, corrected visual acuity was 20/20 bilaterally, with normal color vision, visual fields, intraocular pressure, extraocular movements, alignment, and pupils.

External examination was notable for left upper eyelid ptosis (Figure 1), with a margin-to-reflex distance 1 of 3.5 mm on the right and 0.5 mm on the left, intact levator function, and no fatiguability on sustained upgaze.

There was no evidence of eyelid edema, erythema, or tenderness to palpation.

There were no palpable adnexal masses or orbital rim deformities, but there was mild fullness in the left superior sulcus and mildly increased left-sided resistance to retropulsion.

However, Hertel exophthalmometry did not reveal any relative proptosis.

No lacrimal gland abnormalities or conjunctival masses were seen with upper eyelid eversion.

There was no palpable preauricular or cervical lymphadenopathy.

Slitlamp and fundus examination findings were normal.

Serological testing results for antiacetylcholine receptor antibody were negative.Clinical photograph of both eyes showing left upper eyelid ptosis.

Margin-to-reflex distance 1 was 3.5 mm on the right and 0.5 mm on the left.


Her medical history included untreated hyperprolactinemia manifested by galactorrhea and oligomenorrhea.

She did not take any medications, smoke, or drink alcohol.On examination, visual acuity was 20/20 in each eye.

She denied any other neurologic symptoms.

There was no relative afferent pupillary defect.

There was minimal limitation in infraduction in the left eye with corresponding left hypertropia (Video), which was worse in left gaze and right head tilt.

Ophthalmoscopy findings were normal in each eye.


The patient was referred to a cornea specialist for further evaluation and treatment.Because of the COVID-19 pandemic, specialty evaluation occurred 10 weeks later at which time the patient complained of progressive vision loss in the right eye.

There was no recent ocular trauma or intraocular surgery.

At the time of the initial examination, visual acuity was 20/50 in the right eye and 20/20 in the left eye, with a refraction of −1.50 diopters (D) sphere in both eyes.

Examination was notable for a superonasal area of pigmentation with elevation of the conjunctiva and an inferotemporally subluxed PCIOL in the right eye.

Results of the fundus examination were reported to be normal in both eyes and the anterior examination of the left eye was notable for only a well-positioned PCIOL.

Visual acuity measured hand motion in the right eye with normal intraocular pressure.

The PCIOL was subluxed inferotemporally with vitreous prolapse into the anterior chamber (Figure 1A).

A 4 mm × 3.1-mm superonasal pigmented scleral lesion was also noted (Figure 1B).

The examination of the left eye was remarkable only for a well-centered PCIOL and iris transillumination defects.A, Slitlamp photography of the right eye showing the inferotemporal intraocular lens implant subluxation (arrowhead).


The patient was nonverbal at baseline and exhibited restrictive and repetitive behaviors.

His diet consisted exclusively of cookies, apples, potato chips, and Gatorade.

His mother noticed him frequently rubbing his eyes for several weeks, which she initially attributed to new-onset allergies.

She did not describe any reduction in visual function or ability to perform low-luminance tasks.The patient was admitted and ophthalmology was consulted.

He required an examination under sedation.

His visual acuity could not be determined.

There was no relative afferent pupillary defect in either eye.

The eyelids were mildly erythematous with bilateral eyelash hypertrichosis.

The conjunctiva and cornea appeared dry and leathery bilaterally.

The right cornea was diffusely hazy with a 3-mm paracentral epithelial defect with 60% stromal thinning and a 1-mm infiltrate.

There was a small crescentic fibrin deposit nasally in the right anterior chamber.

The left cornea was diffusely hazy with a 1-mm epithelial defect without stromal thinning (Figure).

Dilated examination showed bilateral grade 3 optic nerve head edema and otherwise normal retinal findings.

Results of magnetic resonance imaging of the brain were normal.Photographs of the right (A) and left (B) eyes reveal a dry and lusterless appearance of the conjunctivae and corneas of both eyes.

Fortified vancomycin eye drops, 25 mg/mL, and tobramycin eye drops, 15 mg/mL, were initiated.


She denied any medical history of vertigo, recent upper respiratory infection, head trauma, or prior otologic surgery.A physical examination revealed no abnormalities on otoscopic evaluation; however, a strongly positive right-sided Dix−Hallpike test was elicited with rotary nystagmus; a subsequent Epley maneuver was performed.

The patient’s symptoms subjectively worsened during the following several days.

Therefore, an audiogram test (Figure 1) and computed tomography (CT) of the temporal bone were performed.Preoperative audiogram reveals a right-sided low- to mid-frequency moderate conductive hearing loss and a bilateral high-frequency sensorineural hearing loss.

dB denotes decibels; HTL, hearing threshold level; SL, sensation level; SRT, speech reception threshold; and TDH, telephonic dynamic headphones.


The patient denied any history of dysphagia, dysphonia, drainage, previous neck surgery, trauma, or recent fever.

There was no significant medical or family history of thyroid disease.

On examination, the mass moved with swallowing.

The patient had normal thyroid stimulating hormone and calcium levels and a parathyroid hormone (PTH) level of 63 pg/mL.

Neck ultrasonography revealed a well-circumscribed anechoic lesion with a diameter of 5.9 cm in the right thyroid lobe without any internal solid nodularity or septation.

A neck computed tomography (CT) scan revealed an intrathyroidal lesion extending inferiorly to 3 cm above the angle of Louis causing tracheal compression and displacement (Figure, A).

Pathologic examination confirmed a normal right thyroid lobe, a normal right parathyroid gland, and a cystic lesion at the inferior pole with no evidence of malignant disease in the specimen.

The tissue inside the lesion stained positive for PTH.A, A neck CT scan showing an intrathyroidal mass causing tracheal compression and is in close proximity to the right common carotid artery and right internal jugular vein.

The patient underwent right hemithyroidectomy to relieve tracheal compression.

A near-infrared autofluorescence (NIRAF) camera yielded a homogenously dim lesion (Figure, B).

B, A NIRAF image of the surgical field showing right thyroid lobe, a right parathyroid gland, and a homogenously dim capsulated lesion of interest.


She had a history of coronary artery disease and prior myocardial infarction that was treated with warfarin.

She denied any personal or family history of cancer.

A physical examination revealed no erythema or tenderness of the parotid.

Her cranial nerves were intact, specifically the right facial nerve and its branches.

The oral mucosa was intact with no epithelial lesions.

Urinalysis results revealed slight hematuria.

Her international normalized ratio (INR) was 4.4.

Contrast-enhanced computed tomography (CT) revealed an ill-defined infiltrative mass centered in the deep lobe of the right parotid with extension into surrounding soft tissue spaces (Figure, A).

A follow-up CT was performed 6 weeks later (Figure, B).A, Axial contrast-enhanced computed tomography (CT) reveals an ill-defined, infiltrative lesion centered in the deep lobe of the right parotid gland.


Her medical and family histories were unremarkable.

Her parents denied drug injection or trauma history.

The lesion initially occurred as an erythema in the neck and progressed centrifugally to the nape and submandibular areas.

Atrophy was observed in the center of the lesion, surrounded by an erythematous border, with underlying blood vessels being visible deep to the atrophy (Figure, A).A, Atrophy in the center of the lesion, surrounded by an erythematous border, with underlying blood vessels deep to the atrophy.

B, A biopsy specimen taken from the edge of the depressed lesion showing normal epidermis and dermis, no inflammatory cell infiltration within the dermis, and somewhat diminished subcutaneous fatty tissue (hematoxylin-eosin).

C, The same specimen at a greater magnification (hematoxylin-eosin).

D, Ultrasonographic findings showing markedly thinner subcutaneous fat of the skin (thickness of thinner region, 0.08 cm).Cervical lymph nodes were palpable bilaterally.

Tactile responses within the depressed as well as surrounding areas were normal.

Other physical examinations were without abnormalities.

Results of routine laboratory tests, HIV test, serological test of antibodies for Borrelia, and antinuclear antibody test were within normal limits or negative.

After obtaining informed consent from her parents, a biopsy specimen was taken from the edge of the depressed lesion for histological examination.


Skin lesions developed 2 months earlier and progressively spread.

She reported abdominal discomfort, weight loss, and vaginal bleeding.

A solid mass on her lower abdomen that had been palpable about 10 years prior had rapidly increased in size within the past few months.

Physical examination revealed erythematous plaques on the right chest and flank without warmth.

Punch biopsy of a lesion from the chest was sent for histopathological examination (Figure, B and C).A, Erythematous plaques involving the right chest and flank at the initial presentation.

B and C, Large atypical cells with clear or eosinophilic cytoplasm forming papillary and glandular architectures are present in the deep dermis; lymphovascular invasion was observed in the superficial and deep dermis (hematoxylin-eosin).

D, Contrast-enhanced computed tomographic scan of the abdomen and pelvis showing a large heterogeneous mass in the right rectus abdominis muscle (blue arrowhead) and cystic lesion in the left ovary (pink arrowhead).


His medical history comprised unexplained sensory hearing loss, hyperlipidemia, and osteoarthritis.

Family history was negative for movement or developmental disorders.

At age 23 years, he had bilateral cataract surgery, and over the last 2 years, he developed worsening stiffness and walking difficulties with frequent falls.

He reported features of rapid eye movement (REM) sleep behavior disorder, restless legs syndrome (RLS), visual daytime hallucinations, and rapid cognitive decline.

His neurologic examination showed hypomimia, symmetrical bradykinesia, and rigidity of the extremities without tremors (Video).

There was full range of eye movements with large-amplitude saccadic intrusions on smooth pursuit in all directions.

Neuropsychological assessment revealed significant abnormalities in cognitive functioning, affecting verbal and nonverbal cognitive skills (ie, speed of information processing, visuospatial skills, verbal and visual memory loss, executive skills).

Mini-Mental Status Examination score was 26 of 30 points.

Laboratory and cerebral spinal fluid testing (ie, paraneoplastic antibodies Hu, Yo, Ri, CV2, Ma2, amphiphysin, glutamic acid decarboxylase, N-methyl-d-aspartic acid, LGI1, and Caspr2, 14-3-3 protein) were normal.

Cranial magnetic resonance imaging (MRI) showed mild frontal and parietal atrophy.

An electroencephalogram demonstrated slowing in keeping with moderate generalized encephalopathy.

Total-body positron emission tomography (PET) using fluorine 18 (18F) fluorodeoxyglucose (FDG) as a tracer showed no FDG-avid lesions; however, a subsequent brain-specific FDG-PET/MRI revealed hypometabolism throughout the left cerebral hemisphere and crossed cerebellar diaschisis (Figure 1).

He was given levodopa/benserazide (up to 200 mg/50 mg 4 times daily) without improvement on his Unified Parkinson Disease Rating Scale scores.

Therefore, his dopaminergic medication was ceased.

As the patient’s cognitive function and parkinsonism had deteriorated rapidly, a brain biopsy of the left frontal cortex was done.


He reported no new medications or recent infection.

His temperature was 37.5 °C (99.5 °F); heart rate, 102/min; blood pressure, 98/72 mm Hg; respiratory rate, 12/min; and oxygen saturation, 94% on room air.

His skin examination revealed 3 tender, nonfluctuant 10-cm scalp plaques with overlying hemorrhagic crust and necrosis on an erythematous indurated base (Figure, left panel).

Similar-appearing papules and plaques were present on the dorsal surfaces of his hands.

The remainder of his physical examination was normal.Left, 10-cm tender plaque on the patient’s scalp, with overlying hemorrhagic crust and necrosis on an erythematous indurated base.

Right, Tissue sample from punch biopsy of patient’s hand shows papillary dermal edema, a dense dermal neutrophilic infiltrate, blister formation, and red cell extravasation (hematoxylin-eosin, original magnification ×400).Blood testing revealed a hemoglobin level of 7.1 g/dL; white blood cell count, 2000/μL; and platelet count, 105 000/μL.

Results of vitamin B12, folate, and iron studies were within normal limits.

Erythrocyte sedimentation rate was 85 mm/h and C-reactive protein level was 147 mg/L.

A peripheral blood smear demonstrated no blast forms.

Computed tomography scan of the chest, abdomen, and pelvis with intravenous contrast performed on the day of presentation showed no infiltrates, mass, lymphadenopathy, or pulmonary embolus but revealed an acute deep vein thrombosis (DVT) involving the left common and external iliac veins and distal inferior vena cava.

The patient declined hospital admission, and treatment with apixaban was started.Punch biopsies of the scalp and left hand revealed a dense dermal neutrophilic infiltrate with marked edema without vasculitis (Figure, right panel).


She took no prescription medications and reported no recent use of over-the-counter medications, including nonsteroidal anti-inflammatory drugs.

Twelve days after the booster vaccination, she developed pruritic wheals on her face and bilateral, transient eyelid swelling.

Over the next week, a pruritic rash spread over her neck, chest, trunk, and arms; each lesion faded without scarring within 24 hours.

She did not experience lip, tongue, or neck swelling; shortness of breath; wheezing; chest pain; or palpitations.

Application of pressure to her forearm in a circular motion using a pen cap elicited wheal and flare lesions (Figure, left panel).

On physical examination, performed 17 days after the onset of rash, her vital signs were normal.

Wheal and flare lesions developed on her upper eyelids during the examination and resolved after approximately 30 minutes (Figure, right panel).

Light pressure applied to her skin with a tongue depressor elicited wheal and flare lesions within 3 to 5 minutes.Wheal and flare lesions on patient’s forearm (left) and eyelids (right).The patient had no history of atopy, urticaria, angioedema, or food or drug allergy and no recent infections.

She had no tongue, lip, or throat swelling, and her lungs were clear to auscultation bilaterally.

She had not experienced adverse effects after the first 2 vaccine doses on January 17 and February 5, 2021.


His histology results showed a 5-cm Warthin tumor, with a focus of nodular oncocytic hyperplasia in the adjacent parenchyma and reactive intraparotid lymph nodes.He presented to the ear, nose, and throat clinic and complained of pain in the operative site of 6 months duration.

This occurred intermittently once a week and lasted for a few minutes each time.

It was associated with a small lump over the left neck, and the pain was worse on touch and head turning.

On examination, there was a 3-mm nodularity palpated deep to the neck wound along the mid sternocleidomastoid muscle.

It was associated with focal tenderness.

A magnetic resonance imaging (MRI) scan was performed, and the results showed no focal lesion in either parotid glands or at the area of interest over the left sternocleidomastoid muscle.

The patient was counseled for an excisional biopsy of the left neck nodule.

His facial nerve function was otherwise normal, and sensation in the ear lobe was intact.

The intraoperative photograph of the neck and the excised specimen is shown in Figure 1.Intraoperative photograph of the left lateral neck and the excised specimen.

The black arrowhead indicates left neck lesion, the white arrowhead the external jugular vein.


Her history was notable for bilateral colobomas involving the iris, optic nerve, and retina; congenital cataracts after lensectomy of the left eye; retinal detachment with proliferative vitreoretinopathy of the left eye requiring a scleral buckle and silicone oil; and intractable glaucoma in the left eye requiring a superior trabeculectomy, an inferotemporal Ahmed tube implant, and multiple diode cyclophotocoagulation treatments.

The patient presented 9 months after the last cyclophotocoagulation procedure.At presentation, she was taking dorzolamide-timolol, brimonidine, netarsudil, and latanoprost for her left eye.

There was a left hypertropia of more than 45° by Hirschberg test.

Best-corrected visual acuity was 20/80 OD and light perception OS.

Intraocular pressures (IOPs) were 11 mm Hg OD and 20 mm Hg OS.

Examination of the left eye revealed a large, firm, pink subconjunctival mass inferotemporally near the Ahmed valve (Figure 1).

The anterior chamber was deep with fine silicone oil bubbles superiorly.

The aphakic left eye revealed a well-positioned tube.

Because of the high risk of retinal redetachment, the silicone oil was retained throughout the glaucoma procedures.


The patient noted floaters in her right eye, which prompted an ophthalmology consultation.

Inflammatory markers were elevated with an erythrocyte sedimentation rate greater than 130 mm/h and a C-reactive protein level of 1.48 mg/dL (to convert to milligrams per liter, multiply by 10).

On bedside examination, her near visual acuity was J1+ (Snellen equivalent, 20/20 OU), and color vision was full in both eyes; the patient’s intraocular pressure, pupils, extraocular movements, and confrontational visual fields were all unremarkable.

Dilated examination revealed grade I and II optic disc edema in the right and left eyes, respectively, and peripapillary hemorrhage in the right eye.

Optical coherence tomography was obtained 3 days after initial consultation, which confirmed bilateral disc edema, more pronounced in the left eye than the right eye (Figure 1), and 24-2 Humphrey visual field examination in both eyes was normal.

Magnetic resonance imaging (MRI) of the brain and orbits with and without contrast and lumbar puncture were obtained, and results showed diffuse signal abnormality in the bone marrow compartment and findings suggestive of papilledema.

Magnetic resonance venography did not reveal thrombosis.

Opening pressure during lumbar puncture was 37 cm H2O (upper limit of normal, 28 cm H2O); all cerebrospinal fluid (CSF) viral serology test results were negative, and glucose level and red and white blood cell counts were all within normal limits.

CSF protein was slightly decreased at 10.4 mg/dL, and CSF cytospin findings were unremarkable.Optical coherence tomography of the right (A) and left (B) optic discs showing edema (mean retinal nerve fiber layer thickness, 158 μm and 187 μm in the right and left eye, respectively).


The patient underwent right-sided ptosis repair at another hospital less than 1 year earlier without improvement.

Best-corrected visual acuity was 20/30 OU, and pupil examination revealed no anisocoria or afferent pupillary defect.

External examination revealed a margin reflex distance 1 (MRD1) of 0 mm OD, 4 mm OS without fatigability in extended upgaze (Figure 1A).

The patient had a small exotropia in primary gaze with a −2 supraduction deficit.

An ice pack was applied in the clinic to the ptotic eyelid for 2 minutes, which led to a 1.5-mm improvement (Figure 1B) in ptosis and no appreciable change in strabismus.


Her ocular history included bilateral cataract surgery 5 years prior.

She had no history of tobacco use.On examination of the left eye, visual acuity was hand motion, and intraocular pressure was 8 mm Hg.

Suspicious retinal detachment and intraocular mass were identified, which raised concerns for choroidal melanoma.

No symptoms or signs were reported in the right eye.

The anterior segment showed diffuse conjunctival chemosis of yellow hue, low-grade aqueous reaction, and pseudophakia (Figure 1A).

On the fundus evaluation, large pockets of subretinal fluid suggested choroidal effusion based on marked fluid shifting with head position.

B-scan ultrasonography confirmed 4-quadrant choroidal hemorrhage and partially mobile serous retinal detachment.

B-scans also exhibited a solid lesion from the 6- to 10-o’clock meridians with irregular shape and variable internal reflectivity, measuring 5.8 mm in height.

In the interim, she received oral steroids aiming to contain the abundant exudation and topical atropine for pain, evolving with minimal clinical improvement on these features.Coloration changes in the left eye associated with choroidal hemorrhage and an intraocular solid lesion.

Magnetic resonance imaging was requested to delineate the mass from the surrounding clot (Figure 1B).

B, The arrowhead indicates the lesion and the asterisk, the adjacent clot.

Review of systems yielded negative results, including for ocular trauma, jaundice, and cutaneous melanoma.


Two weeks later, she developed progressive bilateral lower extremity numbness, pain, weakness, and imbalance, prompting emergent evaluation.

Magnetic resonance imaging (MRI) findings demonstrated extensive spinal cord edema extending from T2 to the conus and a posterior ring-enhancing intramedullary lesion at T9 to T10 without any mass effect (Figure 1).

Lumbar puncture showed no malignant cells.

Positron emission tomographic-computed tomographic (PET/CT) scan demonstrated multifocal intensely F-fluorodeoxyglucose (FDG)-avid disease, but only mild uptake from T9 to T12 and no definitive FDG-avidity at the intramedullary lesion.

Of note, there was enhancement of the previously irradiated T11 vertebral body metastasis, and adjacent vertebrae demonstrated marrow hyperintensity on T1-weighed noncontrast imaging.

In November 2020, she underwent posterior lateral stabilization of C7-T4 for a T2 vertebral body metastasis causing cord compression, followed by postoperative stereotactic body radiation therapy to T2 to T3 (35 Gy/5 fractions) in January 2021.

In February 2021, she received palliative radiation therapy (20 Gy/5 fractions) to T9 to T12 for a T11 vertebral body metastasis with epidural extension.

From January to August 2021, she was treated with gemcitabine, and in September 2021, she received her first dose of liposomal doxorubicin.

Because the intramedullary lesion appeared atypical for malignant disease given the lack of mass effect, she was prescribed high-dose steroids while further workup was pursued.

In 2020, she relapsed in the liver and spine.

Her symptoms remained stable with steroid treatment and a plan was made to repeat an MRI of the spine in 6 to 8 weeks.A, T1-weighted postgadolinium sagittal image demonstrating an enhancing spinal intramedullary lesion (blue arrowhead).


The patient’s medical history included anxiety, depression, emphysema, hyperlipidemia, migraines, and pseudoseizures.

She denied prior head trauma and had no pertinent surgical history.

The patient reported that the facial and jaw symptoms had evolved gradually over the past 5 years and that multiple medical therapies had provided only minimal relief of pain.

On physical examination, the patient had normal body habitus and reported bilateral tenderness of the temporomandibular joints and paresthesia of the right trigeminal nerve in the V2 and V3 distribution with intact masseteric nerve and symmetric facial nerve.

Audiometric evaluation showed normal hearing bilaterally.

Magnetic resonance imaging (MRI) revealed a cystic mass in the right side of infratemporal fossa (ITF) that was nonenhancing on T1 sequencing with contrast and hyperintense on T2 (Figure 1A).