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Melanotic Lesions of the Eye

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Presentation on theme: "Melanotic Lesions of the Eye"— Presentation transcript:

1 Melanotic Lesions of the Eye
Charleen T. Chu, M.D., Ph.D. Division of Neuropathology University of Pittsburgh April 2002 Time spent preparing talk April 4, pm-4:30 pm April 15, 9 am-10:30, 3-4 April 16 3 am-5 am April 16 9 am-11 am, 12-1pm April am, 3-5 pm, 9-12 pm April 18, 10:30-11:30 am April pm April 23 8:30-11:00 am April 24, 2:20-4:30, pm Prior lecture, 2 h 3/20 2 h 3/22 1.5 h 3/28 Copyright ©2002 CT Chu

2 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

3 Uvea (“grape”) Evisceration specimen
year old man with pain in right eye. Is this from a dark skinned or light skinned person, or can you tell? W(Can’t tell) Why does the eye have such a heavily pigmented middle layer? (They function to keep stray light rays that enter the eye from interfering with image formation) Evisceration specimen

4 Melanin producing cells - Embryology
Pigmented epithelia Neuroepithelium of embryonic optic cup Stromal melanocytes Neural crest - similar to those found in skin

5 2-4 weeks - Invagination of optic cup
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

6 Iris © 2002 CT Chu © 2002 CT Chu

7 Ciliary Body © 2002 CT Chu © 2002 CT Chu

8 Retina and choroid © 2002 CT Chu

9 RPE and Choroidal Melanocytes
Pigment epithelium Bruch’s membrane What is Bruch’s membrane (RPE BM stroma and vascular BM) Stromal melanocytes Modified from Yanoff & Fine, ©1996 Mosby-Times Mirror Int.

10 Case 1 58 year old man with serous detachment of the retina B A C
What might be the most relevant prognostic feature? year old man with presumed choroidal melanoma and serous detachment of the retina, OS. Spindle B with microscopic transscleral extension. HMB +. Probably vortex vessel, ciliary nerve

11 Case 1 © 2002 CT Chu © 2002 CT Chu

12 Choroidal Melanoma, Spindle B Type
with transcleral extension along an emissary channel (vortex vein)

13 Choroidal Melanoma Most common intraocular tumor
Classic mushroom shape - rupture into vitreous If metastatic - tend to go to _________. LIVER Prognosis Largest dimension, particularly along base Extension into canal of Schlemm, emissary channels Cytology Location

14 DDx: Diffuse uveal thickening?
year old male. Diffuse uveal melanoma ciliary body and choroid- mixed epithelioid and spindle B type. Invasion of trabec mesh, and multiple emissary vessels to near the scleral surface DDx: Diffuse uveal thickening?

15 DDx Diffuse Uveal Thickening
Diffuse, flat melanoma of the choroid Metastatic carcinoma Lymphoid/leukemic infiltrates Sympathetic uveitis Vogt-Koyanagi-Harada syndrome Phacoanaphylactic uveitis DDx: SO - spare overlying retina, relative sparing of choriocapillaris,, Vogt-Koyanagi-Harada syndrome - uveitis, alopecia, meningoencephatlitis HLA-Bw22J. Dalen Fuchs’ nodule - histiocytes, prolif epithelial cells like cannon balls seen in all inflamm uveitis including TB, characteristic of SO

16 Epithelioid Spindle A - grooves Spindle B - nucleoli
<< Modified from Yanoff & Fine, ©1996 Mosby-Times Mirror Int. Spindle A - grooves © 2002 CT Chu Epithelioid © 2002 CT Chu Yanoff mixed cell type Spindle B - nucleoli

17 Case 2 84 year old woman with blind eye and 2 week history of eye pain and inflammation. Mass detected by ultrasound FNA performed

18 © 2002 CT Chu Case 2 PHC FNA - mixed spindle A and epithelioid melanoma 40x-digital Vanox. Goes with PHS

19 © 2002 CT Chu © 2002 CT Chu 99-4751 84 year old woman 16 x 17 x 18 mm
2x2x0.5 brown plaque 12: mm anterior to optic nerve - most likely a posterior ciliary nerve Material submitted in part 2 by surgeon as suspicious was hemorrhage (? Site of needle aspirate?)

20 Necrotic Choroidal Melanoma (with residual epithelioid and spindle A cells) and Transcleral Extension

21 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”

22 Uveal melanoma - location
Tumors of the iris - ______ prognosis Tumors of the posterior temporal pole - _______ prognosis Tumors of the ciliary body and the peripheral choroid - ______ prognosis better better worse Early detection Proximity to meshwork and related structures Why?

23 Anterior ciliary artery, venous drainage from meshwork, ciliary nerves
© 2002 CT Chu Anterior ciliary artery, venous drainage from meshwork, ciliary nerves Vortex vein does have vortex vein invasion of the inferior nasal vortex vein that was associated with a slight density of the sclera Short and long posterior ciliary arteries Modified from Apple & Rabb, Ocular Pathology, © 1998 Mosby-Year Book

24 Epibulbar Mass This one happens to be a ciliary body melanoma that invaded Schlemm’s canal, collector channels, and shows subconjunc spread. Modified from Yanoff & Fine, ©1996 Mosby-Times Mirror Int.

25 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

26 Nerve with associated melanocytes
Images modified from Yanoff & Fine, ©1996 Mosby-Times Mirror Int. Nerve with associated melanocytes Melanoma exiting through anterior scleral canal

27 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

28 Case 3 80 year old woman Corneal transplant
Expulsive choroidal hemorrhage © 2002 CT Chu Trauma - post penetrating or blunt, anemia, TTP, hypotony, Valsalva Can occur when IOP abruptly reduced - perforated corneal ulcer, catarac, keratoplasty, scleral bucking, filtering, PPV Risk factors include glaucoma, increased axial length, elevated IOP, AS, elevated intraoperative pulse

29 Case 3 © 2002 CT Chu

30 Case 3 © 2002 CT Chu

31 Your diagnosis? What if this was a 55 year old African American man?
What if this lesion measured 16 x 10 mm? Data from a case presented by Ray Font EOPS 99

32 What if I told you this is then classic location for this tumor?
Modified from Yanoff & Fine, ©1996 Mosby-Times Mirror Int.

33 Melanocytoma (Magnocellular Nevus)

34 Bleached slide - H&E What special technique might be helpful for demonstrating benign cytology? Image courtesy of Bruce Shields, presented EOPS ‘99

35 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

36 Melanocytoma - Clinical Characteristics
10 times more likely to occur in dark-skinned 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

37 Multiple iris nevi associated with NF2 (Lisch Nodules)
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.

38 Case 4 Orbital exenteration for morpheaform BCC
© 2002 CT Chu Orbital exenteration for morpheaform BCC Dark fundus spot in the bcc patient © 2002 CT Chu

39 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 Gardner’s familiar polyposis of the colon

40 Reactive hyperplasia of the RPE
© 2002 CT Chu © 2002 CT Chu 80 year old woman History of expulsive choroidal hemorrhage during corneal transplant Reactive hyperplasia of the RPE

41 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 Get images of Fuchs’ adenoma, reactive PE hyperplasia, osseus metaplasia Show also potential confusion on bug stains

42 Reactive PE Proliferation
TRAUMA LONG-STANDING OCULAR INFLAMMATION LONG-STANDING DIABETES Retinitis pigmentosa Homocystinuria Ringschwiele or demarcation line Get images of Fuchs’ adenoma, reactive PE hyperplasia, osseus metaplasia Show also potential confusion on bug stains

43 Neoplastic transformation of uveal epithelia is very rare.
© 2002 CT Chu © 2002 CT Chu Neoplastic transformation of uveal epithelia is very rare.

44 What type(s) of neoplasms arise from pigmented uveal epithelia?

45 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 Stains - PAS and alcian blue

46 Images courtesy of Barbara Streeten (presented EOPS’99)
PAS

47 Pigment epithelia Stromal melanocytes Optic cup Neural crest
Present at birth Develops after birth Cuboidal epithelial cells, tight jxns, coarse granules (melanin and lipofuscin) Solitary, dendritic cells, fine dusty granules Always darkly pigmented (except albinos) Vary in size, number, and melanin content Reactive proliferations Neoplastic proliferation Medulloepithelioma - from non pigmented ciliary body epithelium Adenoma/adenocarcinoma Nevus, Melanoma

48 Case 5 © 2002 CT Chu 46 year old man with a cystic conjunctival lesion

49 Compound cystic melanocytic nevus of the conjunctiva
Modified from Yanoff & Fine, ©1996 Mosby-Times Mirror Int.

50 Conjunctival Nevi Junctional Compound Subepithelial Blue
Congenital melanocytosis (African & Asian) Melanosis oculi - ipsilateral conj & uveal Nevus of Ota - ipsilateral skin, conj & uveal

51 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

52 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)

53 © 2002 CT Chu © 2002 CT Chu

54 Case 5 72 year old man with pigmented areas on the conjunctiva.
© 2002 CT Chu 72 year old man with pigmented areas on the conjunctiva. Status post multiple biopsies

55 © 2002 CT Chu

56 Images modified from Yanoff & Fine, ©1996 Times Mirror Int.
Benign acquired melanosis Unilateral flat pigmentation of conj and periph cornea - completely flat pigmentation rarely is malignant Images modified from Yanoff & Fine, ©1996 Times Mirror Int.

57 Primary Acquired Melanosis with Marked Atypia (Stage IB2)

58 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

59 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)

60 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)

61 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

62 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

63 © 2002 CT Chu © 2002 CT Chu

64 © 2002 CT Chu © 2002 CT Chu

65 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

66 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 Spread via ipsilateral preauricular, submandibular, or cervical lymph nodes DDX - extraocular extension of uveal tumor, metastasis

67 © 2002 CT Chu © 2002 CT Chu © 2002 CT Chu S-100 © 2002 CT Chu

68 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


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