PD Lecture 1999 - University of Pittsburgh
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Transcript PD Lecture 1999 - University of Pittsburgh
Melanotic Lesions of the Eye
Charleen T. Chu, M.D., Ph.D.
Division of Neuropathology
University of Pittsburgh
[email protected]
April 2002
Copyright ©2002 CT Chu
Pigmented Cells of the Eye
Eyelid and Conjunctiva
– Neural crest derived melanocytes
Uvea (“grape”) or tunica vasculosa
– Middle layer of the globe
– Iris, ciliary body, choroid
– Epithelial and stromal compartments
Uvea (“grape”)
Evisceration specimen
Melanin producing cells Embryology
Pigmented epithelia
– Neuroepithelium of embryonic optic cup
Stromal melanocytes
– Neural crest - similar to those found in skin
Migration of neural crest
derived stromal melanocytes
continues after birth
2-4 weeks - Invagination
of optic cup
Images modified from Apple & Rabb, Ocular Pathology 5th ed, © 1998 Mosby-Year Book
Iris
© 2002 CT Chu
© 2002 CT Chu
Ciliary Body
© 2002 CT Chu
© 2002 CT Chu
Retina and choroid
© 2002 CT Chu
RPE and Choroidal Melanocytes
Pigment epithelium
QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
Stromal melanocytes
Modified from Yanoff & Fine,
©1996 Mosby-Times Mirror Int.
Bruch’s
membrane
Case 1
58 year old
man with
serous
detachment of
the retina
What might be
the most relevant
prognostic
feature?
A
B
C
Case 1
© 2002 CT Chu
© 2002 CT Chu
Choroidal Melanoma, Spindle B Type
with transcleral extension along an
emissary channel (vortex vein)
Choroidal Melanoma
Most common intraocular tumor
Classic mushroom shape - rupture into vitreous
LIVER
If metastatic - tend to go to _________.
Prognosis
–
–
–
–
Largest dimension, particularly along base
Extension into canal of Schlemm, emissary channels
Cytology
Location
DDx: Diffuse uveal thickening?
DDx Diffuse Uveal Thickening
Diffuse, flat melanoma of the choroid
Metastatic carcinoma
Lymphoid/leukemic infiltrates
Sympathetic uveitis
Vogt-Koyanagi-Harada syndrome
Phacoanaphylactic uveitis
<< Modified from Yanoff & Fine,
©1996 Mosby-Times Mirror Int.
Epithelioid
Spindle A - grooves
© 2002 CT Chu
Spindle B - nucleoli
© 2002 CT Chu
Case 2
84 year old woman with blind eye
and 2 week history of eye pain and
inflammation.
Mass detected by ultrasound
FNA performed
Case 2
© 2002 CT Chu
© 2002 CT Chu
© 2002 CT Chu
Necrotic Choroidal Melanoma (with
residual epithelioid and spindle A cells)
and Transcleral Extension
Choroidal Melanoma - cytology
Spindle A, Spindle B, Epithelioid, Necrotic
– Most are mixed
– Significant epithelioid component - worse prognosis
Spindle only - 22% death rate
Necrotic, mixed, epithelioid - 62% death rate
– Infarcted tumors can cause significant ocular
inflammation >> misdiagnosis in “blind painful
eyes”
Uveal melanoma - location
Tumors of the iris - ______
better prognosis
Tumors of the posterior temporal pole better prognosis
_______
Tumors of the ciliary body and the
worse prognosis
peripheral choroid - ______
Early detection
Proximity to meshwork and
related structures
Anterior ciliary
artery, venous
drainage from
meshwork, ciliary
nerves
Vortex vein
© 2002 CT Chu
Short and long
posterior ciliary
arteries
Modified from Apple & Rabb, Ocular
Pathology, © 1998 Mosby-Year Book
Epibulbar Mass
QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
Modified from Yanoff & Fine,
©1996 Mosby-Times Mirror Int.
DDx of Pigmented Epibulbar Masses
Conjunctival nevus or melanoma
Extraocular extension of uveal melanoma
Foreign body
“Pigment spots of the sclera”
– Recurrent nerve loop of Axenfeld
Hematoma
Images modified from Yanoff & Fine,
©1996 Mosby-Times Mirror Int.
QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
Nerve with associated
melanocytes
Melanoma exiting
through anterior scleral
canal
Pigment spots of the sclera
People with dark irises
Located 3-4 mm from the limbus
Collections of melanocytes associated
with:
– Anterior ciliary vessel
– Intrascleral nerve loop of Axenfeld
Conjunctiva remains freely mobile over the
pigment spot and nerve remains painful after
anesthesia
Case 3
80 year old woman
Corneal transplant
Expulsive choroidal hemorrhage
© 2002 CT Chu
Case 3
© 2002 CT Chu
Case 3
© 2002 CT Chu
Your diagnosis?
What if this was a 55 year old African
American man?
What if this lesion measured 16 x 10 mm?
What if I told you this is then classic
location for this tumor?
QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
Modified from Yanoff & Fine,
©1996 Mosby-Times Mirror Int.
Melanocytoma
(Magnocellular Nevus)
Bleached slide - H&E
What special
technique might
be helpful for
demonstrating
benign
cytology?
Image courtesy of Bruce Shields, presented EOPS ‘99
Suspect melanocytoma
Maximally pigmented
Uniform, polyhedral cells
Low N/C ratio
Typically affect inferior temporal aspect
of optic disc (but can occur anywhere in
uvea and sclera)
Skin tone of patient
Melanocytoma - Clinical Characteristics
10 times more likely to occur in darkskinned individuals
In contrast, uveal melanomas are 15
times more likely to occur in Caucasians
Benign lesion with low malignant
potential
– 15% will enlarge over time, can locally
infiltrate choroid and optic nerve beyond
lamina cribosa
Caveat: choroidal melanomas can invade optic disc
QuickTime™ and a
Photo - JPEG decompressor
are needed to see this picture.
Modified from Yanoff & Fine, Ocular Pathology ©1996
Mosby-Times Mirror Int.
Multiple iris nevi
associated with NF2
(Lisch Nodules)
Modified from Okazaki & Scheithauer, Slide Atlas of
Neuropathology © 1991 Gower Medical Pub.
Case 4
Orbital exenteration
for morpheaform BCC
© 2002 CT Chu
© 2002 CT Chu
RPE hypertrophy
Melanotic RPE nevus, benign “melanoma” of
the RPE of Reese and Jones
Round or oval, jet black, flat lesion
Can be surrounded by halo or contain punched
out yellow, depigmented patches
Hypertrophy of RPE cells, increase in size of
melanosomes
May be associated with Gardner’s syndrome - 4
or more RPE hamartomas early marker 5q21
© 2002 CT Chu
© 2002 CT Chu
Reactive hyperplasia of the
RPE
Reactive PE Proliferation
Pseudoneoplastic proliferations
– “Invasion” of neural retina
– Intravitreal extension of papillary cords and nests of
pigmented and nonpigmented epithelia with
abundant BM material
– “Fuchs’ adenoma” - of pars plicata
Drusen
Metaplasia
– Fibrous - macular scarring in ARMD
– Osseus
Reactive PE Proliferation
TRAUMA
LONG-STANDING OCULAR
INFLAMMATION
LONG-STANDING DIABETES
Retinitis pigmentosa
Homocystinuria
Ringschwiele or demarcation line
© 2002 CT Chu
© 2002 CT Chu
Neoplastic transformation of uveal epithelia is very rare.
What type(s) of neoplasms arise
from pigmented uveal epithelia?
Pleomorphic Adenoma,
Adenocarcinoma of the ciliary body
Tubulo-papillary or vacuolated solid pattern,
Variable pigmentaion
Nuclear atypia common, mitoses rare
Vimenin, S-100, low MW keratins,
Sparse stroma (BM and hyaluronic acid)
CA - histologic dx, locally invasive, rare
extrascleral extension, and no distant mets
Images courtesy of Barbara
Streeten (presented EOPS’99)
PAS
Pigment epithelia
Stromal melanocytes
Optic cup
Neural crest
Present at birth
Develops after birth
Cuboidal epithelial cells, tight Solitary, dendritic cells,
jxns, coarse granules (melanin fine dusty granules
and lipofuscin)
Always darkly pigmented
(except albinos)
Reactive proliferations
Vary in size, number,
and melanin content
Neoplastic proliferation
Adenoma/adenocarcinoma
Nevus, Melanoma
Case 5
46 year old
man with a
cystic
conjunctival
lesion
© 2002 CT Chu
Compound cystic melanocytic
nevus of the conjunctiva
Modified from Yanoff & Fine,
©1996 Mosby-Times Mirror Int.
Conjunctival Nevi
Junctional
Compound
Subepithelial
Blue
Congenital melanocytosis (African & Asian)
– Melanosis oculi - ipsilateral conj & uveal
– Nevus of Ota - ipsilateral skin, conj & uveal
Melanocytic nevus
50% associated with epithelial buds & cysts
– Cysts may be so prominent to simulate
lymphangioma clinically
– Can have “feeder vessels”
Inflammed nevus of puberty - nevus
enlarges because of lymphoplasmacytic
infiltration +/- germinal centers
– DDx lymphoid tumor, regressing melanoma
Warning signs
Overwhelming majority of nevi stable
But 20-25% melanomas arise from nevi
– Nevi rare in palpebral and forniceal conj.
– Base of nevus does not encroach the cornea
– Cysts tend to be uniformly distributed; look
closely are regions where solid tissue
obliterates cysts at one end of lesion
– Pagetoid spread of melanocytes
–Junctional component should end with
subepithelial component (except in children - early phase
of maturation from junctional to compound)
© 2002 CT Chu
© 2002 CT Chu
Case 5
© 2002 CT Chu
72 year old man with pigmented areas on the conjunctiva.
Status post multiple biopsies
© 2002 CT Chu
Images modified from Yanoff & Fine, ©1996 Times Mirror Int.
Primary Acquired Melanosis with
Marked Atypia (Stage IB2)
PAM IB vs. Junctional nevus
May be identical histologically
Basilar hyperplasia, basilar nesting, and
intraepithelial nesting can be seen in both
Pagetoid spread is not seen in nevus
PAM - > 30 year old, mean age is 40-47
Caveat: Conjunctival melanomas can arise in
teenagers
PAM
Unilateral, middle-aged or elderly white
pts.
Can wax and wane in size, pigmentation
Need to evert eyelids to chart extent of
involvement, does not respect cornea
Extends beyond palpebral fissure, in
contrast to lentigo/freckle (sun exposure)
PAM Staging
IA without atypia
IB with atypical melanocytic hyperplasia
– 1. Mild to moderate
– 2. Severe (“melanoma in situ”)
IIA with superficially invasive melanoma
IIB with invasive melanoma (>1.5 mm)
Primary acquired melanosis
PAM without atypia (IA)
– 8% recurrence
– 0 progressed to melanoma
PAM with atypia (IB)
– 61% recurrence
• incomplete excision, involvement of cornea
– 46% progression to malignant melanoma
• 20% if mild atypia, basilar hyperplasia pattern
• 90% if atypical melanocytes distant from jxn
(nests or pagetoid)
• 75% if epithelioid cells
Primary acquired melanosis
PAM with superficially invasive
melanoma (< 1.5 mm) (IIA)
– Generally nonlethal if excised
– Jakobiec et al. suggest cut off of 0.8 mm
PAM with invasive melanoma (IIB)
– Generally lethal
• Pagetoid growth pattern - more sensitive than
tumor thickness
• Unfavorable location (palpebral, forniceal,
caruncle, invasion of cornea)
• > 5 mitoses/10 HPF, lack of inflammation
© 2002 CT Chu
© 2002 CT Chu
© 2002 CT Chu
© 2002 CT Chu
Potential pitfalls
for overcalling invasion
Bulbous basilar nests simulating invasion
Melanophages - central or eccentric nuclei
without nucleoli after bleaching
Tangential sectioning
– surgeon may submit fixed on a cucumber slice
– corneal margin, deep margin, other margins
Pseudoglands and epithelial cysts
– Goblet cells or compressed rim of keratinocytes
Goblet cells can take up melanin
Conjunctival melanomas
75% associated with PAM
– Confused with nevus, SCC, can
simultaneously involve conj and lid skin
– Usually progress within 6 yrs. Not after 10.
20-25% associated with compound nevus
Spread via ipsilateral preauricular,
submandibular, or cervical lymph nodes
DDX - extraocular extension of uveal tumor, metastasis
© 2002 CT Chu
•
© 2002 CT
Chu
S-100
© 2002 CT Chu
© 2002 CT Chu
Secondary melanosis
Radiation
Addison’s, Pregnancy
Arsenic, Thorazine
Chronic conjunctivitis
“Racial” melanosis
Pathologically, how
do these differ from
primary melanosis?
Nonproliferative conditions with increased
melanin transfer to keratinocytes