Ocular Pathology Flashcards
What is the pathology of senile calcific plaque?
• The pathology of senile calcific plaques shows
basophilic calcific deposits in sclera anterior to the
lateral rectus muscle
What is trilateral retinoblastoma?
● Bilateral retinoblastoma + ectopic intracranial
retinoblastoma (pineal gland or parasellar region)
● Histology: numerous round blue cells surrounded
by pink necrotic cells
What is the term for epithelium growing on both sides of the cornea?
● Epithelium growing on both sides of the cornea is
termed epithelial downgrowth
● Most commonly seen from multiple prior surgeries
such as ECCE and PKP
What are the characteristic findings in Peters Anomaly?
● Peters anomaly is characterized by:
○ The absence of Descemet’s membrane
○ Adhesions of iris and lens material to the
posterior surface of the cornea
What are the pathologic findings of ICE Syndrome?
● Corneal edema
● Inappropriate proliferation of endothelium and/or
Descemet’s membrane along anterior segment
structures
What are the characteristic findings in Granulomatosis with Polyangiitis (GPA) and what vessels are involved?
● Chronic sinusitis
● Saddle Nose deformity
● Granulomatous inflammation with necrosis
● Small and medium size blood vessels are usually
involved
What is the most common cause of proptosis in adults?
● Thyroid-associated orbitopathy
● Pathology: muscle bundles separated by fluid and
infiltrated by a mixture of mononuclear
inflammatory cells
<img></img>
What conditions are associated with weakened zonules?
● Congenital
○ Marfan’s
○ Homocystinuria
○ Hyperlysinemia
○ Ehler-Danlos Syndrome
○ Scleroderma
○ Weill-Marchesani
● Other
○ Pseudoexfoliation
○ Prior vitreoretinal surgery
○ History of trauma
○ High myopia
What is the most common extraocular tumor that spreads into the eye via direct extension?
● Squamous Cell Carcinoma of the Conjunctiva
○ Typically mucoepidermoid carcinoma or
spindle cell variant
What is the management of a brown pigmented lesion of the palpebral conjunctiva?
● A brown pigmented lesion of the palpebral
conjunctiva is more likely to be Primary Acquired
Melanosis with atypia which requires immediate
work up with excisional biopsy given its high
malignant potential
What is the presentation, prognosis, and management of lymphangioma?
● Typically present in children in the superior and
nasal quadrant
● Can bleed into themselves causing cysts of blood,
“chocolate cysts”
● Enlarge in association with upper respiratory
infection
● Benign
● Treatment:
○ Observation unless optic nerve compression
or corneal exposure
○ Debulking, complete removal is difficult
What was the main conclusion of the LARGE choroidal melanoma trial?
● Adjunctive radiotherapy did not improve overall
survival
What was the main conclusion of the MEDIUM choroidal melanoma trial?
● Mortality was similar between brachytherapy and
enucleation groups
● Histologically confirmed metastases were found in
approximately 10% patients treated with
enucleation
What was the main conclusion of the SMALL choroidal melanoma trial?
● Mortality was 1% at 5 years with observation only
What cell type produces the myelin sheath of the optic nerve?
● Oligodendrocyte
What is the function of microglial cells?
● “Clean-up” function due to phagocytic activity
What function do astrocytes have?
● Support and nutrition to the optic nerve and retina
What are the similarities and differences between the pathology of pterygia and pingueculae?
● Similarities:
○ Both have fragmented stromal collagen with
basophilic “elastotic” degeneration
○ Degeneration is due to chronic UV light
exposure
● Differences:
○ Pterygia = involves the cornea and
destruction of Bowman’s layer
<img></img>
What is stained by periodic acid-Schiff (PAS) stain?
● Type IV collagen, glycogen, and proteoglycans
What is stained by Prussian blue stain?
● Iron
What is stained by Von Kossa stain?
● Calcium
What is stained by cytokeratin stain?
● Squamous epithelium
What are the favorable and unfavorable risk factors in conjunctival melanoma?
● Favorable:
○ Epibulbar
● Unfavorable
○ Location:
■ Palpebral, caruncle, eyelid margin,
fornix (non-limbal)
○ Invasion into deeper tissues
○ Thickness > 1.8 mm
○ Pagetoid or full thickness intraepithelial
spread
○ Lymphatic invasion
○ Mixed cell type
○ De novo origin
○ Residual involvement at the surgical margin
What is a Mittendorf dot and where is it most commonly located?
● Remnant of the hyaloid artery of primary vitreous
at its attachment to the tunica vasculosa lentis
● Most commonly located inferonasally
What are the criteria of the Reese Ellsworth Classification for retinoblastoma? What is it useful for?
● Classification by:
○ Number
○ Size
○ Location
○ Presence or absence of vitreous seeding
● Used after external beam radiation for RB lesions,
does not give prognostic information
What is stained by Verhoeff-van Gieson Stain?
● Elastin
What is HMB-45 a marker for?
● Marker for melanocytic lesions
What cells does CD3 stain identify?
● T cells
What cells does CD20 stain identify?
● B cells
What does Warthin-Starry stain identify?
● Bartonella henselae
What is the rate of metastasis of conjunctival melanoma?
● 25%
What is the presentation of a ciliary body melanoma?
● Can range from completely asymptomatic to visual loss, photopsias, and visual field loss
What is a dermolipoma and where is it typically located?
● Type of choristoma
● Most commonly in the superotemporal quadrant
● Extends posteriorly into the orbit
What are the average ages of retinoblastoma diagnosis in patients with family history and patients without family history with unilateral or bilateral disease?
● Positive family history: 8 months
● Negative family history, bilateral disease: 12
months
● Negative family history, unilateral disease: 24
months
What is the pathology of a xanthelasma and what systemic problem is it associated with?
● Pathology shows macrophages with large amount
of fatty cytoplasm
● Associated with hyperlipoproteinemia
What happens during a spasm of the near reflex?
● Excessive convergence, accomodation, miosis
● Normal ductions, abduction deficit on version
movements
What stains can be used to visualize acanthamoeba?
● Stains:
○ H&E
○ PAS
○ Calcofluor white
○ Acridine orange
○ Gridley stain
○ Giemsa
Where are Koeppe iris nodules located and what conditions are they associated with?
● Located at the pupillary margin
● Associated with granulomatous uveitis:
○ Sarcoidosis
○ Tuberculosis
○ Syphilis
○ Lyme
What is adenoma sebaceum and what condition is it associated with?
● Facial angiofibromas (red papules)
● Adenoma sebaceum is found in 80-90% of
individuals with tuberous sclerosis which is
inherited in an autosomal dominant pattern
What condition are cerebellar hemangioblastomas associated with and what other problems are associated with this condition?
● Von Hippel Lindau Syndrome
● Also associated with retinal hemangioblastomas
and increased risk of renal cell carcinoma and
pheochromocytoma
What is the structure of the cells in the outer plexiform layer and what pathology can this result in?
● The outer plexiform layer is composed of neuronal
synapses that are obliquely oriented AKA the nerve
fiber layer of Henle
● The oblique orientation in this area accounts for
flower-like (petalloid) pattern of leakage seen on
IVFA for macular edema
What is stained by the Mart-1 immunostain?
● Melanocytes
What histologic features of choroidal melanoma are associated with increased rate of metastasis?
● High mitotic index
● High cell proliferation
● Complex microvascular patterns
● Tumor infiltration
● Lymphocytes
● Trisomy 8
● Monosomy 3
● Predominance of epithelioid cells
What is the difference between a tumor predominantly composed of epithelioid cells versus spindle cells?
● Tumor that is predominantly epithelioid is more
aggressive than a tumor predominantly spindle
cells
What makes up the primary, secondary, and tertiary vitreous?
● Primary: hyaloid artery, vasa hyaloidea propia,
mesenchymal cells, tunica vasculosa lentis
● Secondary: adult vitreous body; replaces primary
around 9th week of gestation
● Tertiary: zonular fibers
What is a choroidal osteoma? What is the epidemiology? What is the classic presentation and hallmark feature?
● Benign bony tumor of the choroid
● Found in young/adolescent patients, commonly in
females, can be bilateral
● Usually near the optic nerve, appears
orange-yellow with pseudopod margins
● When involving the macula: subretinal
neovascularization can negatively impact vision
● Hallmark feature: high amplitude echo on B scan
due to calcification with loss of normal orbital
echoes behind the lesion
What features are unique to sarcoid lesions of the optic nerve compared to sarcoid lesions of the eye itself?
● Sarcoid granulomas of the optic nerve may have
necrosis (caseating granulomas or noncaseating)
What are the features of choroidal melanoma on A scan and B scan?
● A scan: low amplitude internal reflections
● B scan: mushroom shaped mass or dome shaped;
can see invasion through Bruch’s membrane
What are the two growth patterns of retinoblastoma?
● Endophytic: grow from the retinal surface and
project into the vitreous cavity; more associated
with vitreous seeding
● Exophytic: grow underneath the retina and toward
sclera; more associated with serous RD
What is the pathology, appearance, and genetics of Lattice Corneal Dystrophy?
● Pathology: fusiform deposits within the corneal
stroma. Stain red with congo red; see
metachromasia with crystal violet and apple green
birefringence under polarized light
● Cornea has glass-like branching lines in the stroma
● Autosomal dominant inheriteance of TGFB1
mutation
● Of the stromal dystrophies, it has the highest rate
of recurrence in corneal transplant patients
What corneal dystrophies are associated with TGFB1 mutations?
● TGFB1 mutations cause abnormal keratoepithelin
● LARGE
○ Lattice (Type 1)
○ Avellino
○ Reis-Bucklers and Thiel-Behnke
○ Granular (Groenouw type 1)
○ Empty
Rank the stromal corneal dystrophies from highest to lowest rate of recurrence.
● Lattice > Granular > Macular
What percentage of women with choroidal metastases have history of breast cancer?
● 90% of women have been treated for breast cancer
in the past
What percentage of patients with very ischemic CRVO develop NVI/NVA and what is the most important predictive factor?
● High, up to 60%
● Over a mean of 3-5 months after the onset of
symptoms
● Most important predictive risk factor is poor visual
acuity
What is Meretoja syndrome? What gene mutation is it associated with? How does it present?
● Also known as lattice corneal dystrophy type 2, but
is not a true dystrophy due to the systemic
involvement
● Caused by mutation of gelsolin gene
● Presentation: corneal lattice-like changes with
systemic amyloidosis, masked facies,
dermatochalasis, lagophthalmos, pendulous ears,
dry/lax skin, cranial/peripheral nerve palsies,
orthostasis hypotension, cardiac conduction
abnormalities, problems with perspiration
What are the similarities and differences of Reis-Bucklers Corneal Dystrophy and Thiel-Behnke Corneal Dystrophy?
● Both are due to TGFB1 mutations
● Reis-Bucklers: autosomal dominant, painful
recurrent erosions, 1st/2nd decade, affects
Bowman’s layer, more common to have recurrent
erosion episodes and more severe stromal scarring
● Thiel Behnke: also affects Bowman’s layer; has
curly fibers on electron microscopy
What is the appearance of an eosinophil and what pathology are they most commonly associated with?
● Bilobed nucleus with abundant intracytoplasmic
eosinophilic granules
● Found in allergic reaction-type process like vernal
keratoconjunctivitis
What intraocular location is the most common site to have metastases?
● Bilobed nucleus with abundant intracytoplasmic
eosinophilic granules
● Found in allergic reaction-type process like vernal
keratoconjunctivitis
What are Dalen-Fuchs nodules and what conditions are they found in?
● Small, discrete yellowish infiltrate at the level of
the RPE
● Made up of aggregates of inflammatory cells,
usually epithelioid histiocytes, that collect between
the RPE and Bruch’s membrane
● Seen in sympathetic ophthalmia and VKH
What neoplasm is most likely to spread systemically with fine needle aspiration biopsy?
● Retinoblastoma
What is deposited in band keratopathy and what layer is it deposited in? What are the risk factors for band keratopathy? What is the treatment for band keratopathy?
● Calcium hydroxyapatite deposits in Bowman’s
membrane
● Systemic risk factors: hypercalcemia
(hyperparathyroidism, excessive vitamin D intake,
renal failure, milk-alkali syndrome, Paget disease,
sarcoidosis)
● Ocular risk factors: chronic uveitis, phthisis bulbi,
end-stage glaucoma, anterior mosaic dystrophy,
silicone oil tamponade
● Medication induced: steroid phosphate,
pilocarpine containing, mercury based
preservatives
● Rx: EDTA with superficial debridement
What is the process by which a retinal scar is formed?
● For example: after PRP
● Laser demarcation is produced by glial cells (Muller
cells and fibrous astrocytes)
● The internal limiting membrane and Bruch’s
membrane provide plans for glial scarring
● RPE cells undergo fibrous metaplasia giving rise to
dense black clumps seen in retinal scars
What is Masson trichrome used to stain?
● Hyaline in corneal stroma, for example in granular
dystrophy
What substance does Alcian blue stain and what pathology is this associated with?
● Stains acid mucopolysaccaride in corneal stroma
blue
● Used to diagnose Macular dystrophy
What are the three attachment sites of the uveal tract to the sclera?
● Scleral spur
● Internal ostia of vortex veins
● Peripapillary tissue
● This explains the dome-shaped configuration of
choroidal hemorrhages
What are the risk factors for a nevus being a malignant melanoma?
● TFSOM
● Thickness
● Subretinal fluid
● Symptoms
● Presence of orange pigment
● Juxtapapillary location (within 2 disc diameters)
● Absence of drusen or RPE changes
● Hot spots on IVFA
● Homogeneity on ultrasound
● Large size
● Flat lesion diameter of < 10 mm is nearly always
benign
What is snowflake degeneration?
● Long term complication of IOLs made of PMMA
material and an indication for explantation
What is a postoperative complication associated with hydrogel material?
● Calcification
What is a post-op complication of silicone-based IOLs in eyes with asteroid hyalosis?
● Deposits of calcium oxalate after a YAG cap
What is the appearance of nfectious crystalline keratopathy? What is the most commonly associated bacterium? What are the most common comorbidities? What is the treatment?
● Appears as white, branching, crystalline opacities
within the corneal stroma with little to no
associated inflammatory response
● Most common bacterium: strep viridans
● Most common comorbidities: PKP, corticosteroid
use, immunocompromised corneas, contact lens
wear
● Treatment: Stop topical steroid; requires
prolonged use of antibiotics. It is difficult to treat
and often requires repeat PKP or lamellar
keratectomy
What is the treatment for primary acquired melanosis?
● Excision with cryotherapy
What is the difference between UBM and B scan?
● UBM = high resolution (40 microns), high
frequency (50 MHz) penetrates less (4 mm)
● B scan = lower frequency, decreased resolution,
penetrates deeper (4 cm)
What is the pathology behind Giant Cell Arteritis?
● Granulomatous inflammation that destroys the
internal elastic lamina
● Involves medium to large vessels (i.e. posterior
ciliary, ophthalmic arteries)
● Treatment: IV solumedrol 1 g/day x 3-5 days then
PO prednisone with long taper
Marilyn Monroe Always Gets Her Man in LA County
Marilyn - Macular dystrophy
Monroe - Mucopolysaccharide
Always - Alcian blue stain
Gets - Granular dystrophy
Her - Hyaline
Man in - Masson Trichrome stain
L - Lattice dystrophy
A - Amyloid
County - Congo red
What is the other name for type 2 granular corneal dystrophy?
● Avellino dystrophy
What is the other name for type 3 granular dystrophy?
● Reis Buckler dystrophy
What is the most common etiology of anterior capsular fibrosis?
● Posterior synechiae causing hypoxia to lens
epithelium
● Leads to metaplastic response of epithelium, forms
fibrous plaques, mixed in with basement
membrane
What exam components should be included in the initial evaluation of a child with suspected retinoblastoma?
● Visual function
● Slit lamp exam
● Corneal diameter
● IOP
● DFE with scleral depression
● B scan (looking for calcifications)
● MRI brain
● Examination of parents/siblings
In what pathology is lipogranulomatous inflammation seen?
● Typically seen in chalazia
What virus causes molluscum contagiosum? What is the presentation? What is seen on pathology?
● Caused by the pox virus
● Exam shows dome-shaped, waxy nodules with
central umbilication
● Microscopic exam shows abundant granular
eosinophilic cytoplasm with small peripheral
nuclei; Henderson-Patterson corpuscleseosinophilic
inclusion bodies
What is the microscopic appearance of seborrheic keratosis?
● Hyperkeratosis, acanthosis (polygonal or basaloid
squamous cell proliferation), and some degree of
papillomatosis
● Pseudohorn cysts (concentrically laminated
keratin)
What is the microscopic appearance of papilloma?
● Fibrovascular ores with finger-like projections
going away from epidermis, surrounded by
hyperplastic stratified squamous epithelium
What is the histologic appearance of Peters anomaly? How often is Peters anomaly bilateral? How often is it associated with systemic abnormalities? What are some of these abnormalities?
● Histologically shows localized absence of corneal
endothelium and Descemet’s membrane beneath
an area of stromal irregularity
● Associated with iridocorneal adhesions
● Bilateral > 50% of the time
● Associated with systemic abnormalities > 50% of
the time
● Associated with:
○ Axenfeld-Rieger syndrome
○ Congenital rubella
○ Microphthalmia with linear skin defects
○ Pfeiffer syndrome
○ Kivlin Syndrome
○ Trisomies 13-15
What locations of ocular melanoma have the best and worst prognosis? What are the most common and least common locations for uveal melanoma? What are the associated mortality rates of these locations?
● Best prognosis: Iris
● Worst prognosis: ciliary body
● Most common location: choroid
● Least common location: iris
● Mortality rates:
○ Iris = 1-4%
○ Conjunctiva = 25%
○ Choroid = 12-50%
○ Ciliary Body = 30-50%
What chromosome is implicated in retinoblastoma?
● Chromosome 13
What chromosome is involved in neurofibromatosis type 1?
● Chromosome 17
What chromosome is involved in neurofibromatosis type 2?
● Chromosome 22
What chromosome is involved in tuberous sclerosis?
● Chromosome 9 for TSC1 (hamartin)
● Chromosome 16 for TSC2 (tuberin)
What type of tumor is a limbal dermoid? What syndrome is it associated with?
● Choristoma (normal tissue in an abnormal location)
● Associated with Goldenhar syndrome -
oculoauriculovertebral syndrome
○ Ear and mouth malformations
○ Preauricular skin tags
○ Strabismus
<img></img>
<img></img>
What is the difference between charged-particle radiation and brachytherapy in the treatment of uveal melanoma?
● Charged particle radiation delivers more
homogenous dose of radiation to tumor as
compared to brachytherapy
● Charged particle radiation delivers higher dose of
energy to anterior segment leading to high
incidence of NVG and vision loss
● Charged particle radiation is effective primary
therapy for uveal melanomas (unlike conventional
external beam radiation)
What are the layers of the choroid?
● Three main layers (inner to outer)
○ Choriocapillaris
○ Stroma
○ Lamina fusca (suprachoroidal layer)
● Can also be divided as follows:
○ Bruch’s membrane
○ Vascular layers (choriocapillaris, Sattler’s
layer - medium sized vessels, Haller’s layer -
large vessels)
● The choroid is thickest in the posterior pole (0.25
mm) and thinnest anteriorly and peripherally (0.10
to 0.15 mm)
What is the structure of amyloid?
● Final structure is beta-pleated sheet
● Ultrastructure shows nonbranching fibrils with
diameter 75-100 angstroms
What is Grocott-Gomori methenamine silver stain used for?
● Used to stain mucormycosis and other nonseptate
large branching hyphae
● Other useful stains for mucormycosis:
○ H&E
○ PAS
○ Calcofluor white
What are the most common non-ocular tumors located outside the field of any radiation treatment that occur in Rb survivors?
● Osteosarcoma and cutaneous melanoma
What is the pathology of anterior basement membrane dystrophy? What are some of the complications of this dystrophy?
● Pathology shows redundant epithelial basement
membrane, encysted degenerated epithelial cells
● One of the most common hereditary corneal
dystrophies
● Often bilateral
● Complications:
○ Recurrent erosions due to poor adhesion of
corneal epithelium from thickening
basement membrane
○ Problems with LASIK flap creation
What is the pathology of sebaceous carcinoma?
● Foamy cytoplasm within tumor cells
● Pagetoid spread = tumor cells that spread through
the epithelium without well-defined borders of the
area of involvement
● Very similar to chronic blepharoconjunctivitis or
chalazion
What is the most common orbital tissue to be involved in sarcoidosis?
● Lacrimal gland
What is the fixative used for electron microscopy?
● Glutaraldehyde
What is the fixative used for routine histopathologic analysis?
● Formalin
What are absolute ethanol or methanol media used for?
● Crystals (e.g. corneal urate crystals)
What is the fixative used for cytologic preparation?
● Ethyl alcohol
What is the fixative used for immunofluorescence?
● Michel fixative
● Zeus
What is Saccomanno medium used for?
● Liquid specimens or smears (e.g. vitreous biopsies, fine needle aspirates)
What are the acellular layers of the cornea?
● Bowman’s - made of collagen
● Descemet - true basement membrane, collagen
type IV, continuously produced by endothelium,
thickness increases with age
What is the pathologic appearance of Dalen Fuchs nodules and what conditions are they found in?
● Located between RPE and Bruch’s membrane
● Compared of lymphocytes and epithelioid
histiocytes
● Seen in VKH and SO
What is a plexiform neurofibroma and what condition is it associated with?
● Slow growing non-encapsulated lesions consisting
of endoneural fibroblasts, Schwann cells, nerve
axons
● Dermis infiltrated by numerous spindle shaped
cells arranged in ribbons and cords
● Associated with neurofibromatosis type 1 (von
Recklinghausen disease)
What is a seborrheic keratosis and what can it be associated with?
● Well circumscribed, oval, dome shaped to
verrucous benign papillomatous proliferation of
basal cells within epidermis
● Usually pink or brown in color
● “Stuck-on” appearance
● Lesions have cystic collections of keratin
● Pathology shows pseudohorn cysts or cysts line
with acanthotic stratified epithelium
● Sudden appearance of multiple seborrheic
keratoses = Leser-Trelat sign which is associated
with GI adenocarcinoma
What is Muir-Torre Syndrome?
● A syndrome of multiple sebaceous neoplasms in
conjunction with visceral malignancies (GI or GU)
What is Erdheim-Chester Disease?
● Subtype of xanthogranulomatous disease
● Pathology shows foamy histiocytes → Touton giant
cells
● Associated with serious cardiac complications leading
to death
What are the indications for enucleation for treatment of retinoblastoma?
● Tumor that is > 50% of the globe
● Optic nerve involvement
● Anterior segment involvement
What are the three types of giant cells?
● Langhans
● Touton
● Foreign body
What do Langhans giant cells look like on pathology and what conditions are they associated with?
● Horseshoe shaped ring of nuclei around the cell
● Seen in giant cell arteritis and sarcoidosis
<img></img>
What do Touton giant cells look like on pathology and what conditions are they seen in?
● Ring of nuclei that are surrounded by foamy ring of
lipid
● Seen in xanthogranulomatous disease
○ Juvenile X-linked xanthogranuloma
○ Adult onset xanthogranuloma
○ Adult onset asthma
○ Periocular xanthogranuloma
○ Necrobiotic xanthogranuloma
○ Erdheim Chester Disease
<img></img>
What does foreign body giant cells look like on pathology?
● Haphazard arrangement of nuclei within the cells
<img></img>
What is persistent fetal vasculature (PFV)?
● PFV is when the primary vitreous does not regress
leading to fibrovascular mass that produces
tractional forces on variety of ocular structures
● Exert traction on ciliary process thus elongating
them (characteristic PFV)
● How to distinguish from retinoblastoma:
○ PFV are often microphthalmic
○ Retinoblastoma eyes are normal size
