Ocular Pathology Case Kari Eisley, M.D. PGY3 Pathological images © Charleen T. Chu, 2010.

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Ocular Pathology Case Kari Eisley, M.D. PGY3 Pathological images © Charleen T. Chu, 2010

Clinical History 66 yo white female Presents to ED with right eye redness, drainage and decreased vision x 2 weeks Has a history of mental retardation Eye enucleated (PHS )

Extrascleral Mass Cornea Mass in Anterior Chamb e r Pathological images © Charleen T. Chu, 2010

Intraocular Mass under transillumination Pathological images © Charleen T. Chu, 2010

Retina Detachment Dislocated lens Extrascleral extension Intraocular tumor Subretinal Gel Pathological images © Charleen T. Chu, 2010

Under transillumination Pathological images © Charleen T. Chu, 2010

Sclera Ciliary Body Tumor Extrascleral extension Pathological images © Charleen T. Chu, 2010

Dislocated Lens Anterior Subcapsular Cataract Posterior Polar Cataract Tumor Detached Retina with Subretinal Gel Pathological images © Charleen T. Chu, 2010

Tumor Invasion of Iris Sclera Pathological images © Charleen T. Chu, 2010

Lens Cornea Tumor extension along posterior surface of cornea Pathological images © Charleen T. Chu, 2010

Rubeosis Iridis of fine thin-walled vessels barely larger than the RBCs inside Pathological images © Charleen T. Chu, 2010

Tumor behind the Cornea Cornea Neovascularization Pathological images © Charleen T. Chu, 2010

Immunostain for Ki-67 Proliferation Antigen (Tumor Nuclei are staining red) Pathological images © Charleen T. Chu, 2010

Background staining of macrophage cytoplasm for Ki-67 stain (due to unquenched macrophage peroxidases) as opposed to prior slide where the nuclei are staining. Pathological images © Charleen T. Chu, 2010

Immunohistochemical stain for the melanocyte marker Melan A Tumor Invasion of Subconjunctival Tissue Pathological images © Charleen T. Chu, 2010

Melan A Melanocyte Immunostain Pathological images © Charleen T. Chu, 2010

Immunohistochemical Stain HMB-45 Melanophages Tumor cells with positive HMB-45 Pathological images © Charleen T. Chu, 2010

Uveal Melanoma Incidence: 6 per million per year in adult Caucasians Most common primary intraocular malignancy in adults Peak incidence: 55 years old 94% arise in the choroid, 3% arise on ciliary body, 3% arise in iris Can present with blurred vision, visual field defect, photopsia, or metamorphopsia (but most often are asymptomatic)

Risk Factors Uveal nevus Congenital ocular melanocytosis Dysplastic nevus syndrome Family history of uveal melanoma Xeroderma pigmentosa 97.8% of uveal melanomas are in whites

Signs of Ciliary Body Melanoma on Ocular Exam Sentinel Vessel (dilated episcleral vessel) Low intraocular pressure (>5mmHg difference between eyes) High intraocular pressure from pigment dispersion, melanin-laden macrophages (melanomalytic glaucoma), tumor cells, rubeosis iridis, angle closure Darkly pigmented mass posterior to the pupil –usually are solid but can be cystic Can extend around the circumference of the ciliary body; known as ring melanomas Unilateral Cataract

Differential Diagnosis Choroidal Nevus Conjunctival Melanoma Primary Acquired Melanosis (PAM) Melanocytoma Juvenile Xanthogranuloma Iris Leiomyoma Medulloepithelioma (Diktyoma) Sarcoid nodules (Granuloma) Adenocarcinoma Fuchs adenoma (senile hyperplasia of the ciliary body) Lymphoid Tumor Iridociliary epithelial cysts Other Metastatic Tumor

Classification of Uveal Melanoma Spindle Cell Nevus (benign) Spindle Cell Melanoma –Spindle A (stripe down nucleus) –Spindle B (granular chromatin, larger nucleous) Epithelioid Melanoma –Abundant eiosinophilic cytoplasm, enlarged oval nuclei with prominent nucleolus, cells lack cohesiveness Mixed-Cell Type (Spindle & Epithelioid)

Methods of Spread/Metastasis Distant Spread: Hematogenously –most commonly to liver –Also to lung, bone, skin and CNS Extrascleral extension: –through aqueous channels, ciliary arteries, vortex veins, ciliary nerves, and the optic nerve –can metastasize locally into the orbit and conjunctiva –Axenfeld’s nerve loops (normal posterior cilliary nerve loops visible in the sclera) can be pigmented and confused with extrascleral extension of melanoma Remember – the eye has NO lymph vessels so no lymphatic spread!!

Prognosis Mortality of Ciliary Body Melanoma is 30-50% within 10 years from diagnosis Ciliary Body Melanoma has a worse prognosis than posterior choroidal melanomas, likely due to delayed diagnosis Spindle Cell – Best Epithelioid – Worst Mixed-cell Type – Intermediate With Metastatic disease : < 6 months

Work-Up A-Scan and B-Scan –In tumors more than 3 mm thick, ultrasound has a diagnostic accuracy of over 95% –Ultrasound features Low-to-medium reflectivity Excavation of underlying uveal tissue Shadowing of subjacent soft tissues Internal vascularity An acoustic quiet zone at the base of the tumor (acoustic hollowing) Ultrasound biomicroscopy (UBM) Consider CT orbits for extraocular extension and to help differentiate between detachment and a solid tumor

Metastatic Work-Up Importance: –To determine medical risk of surgery –If metastatic disease is present, enucleation is inappropriate unless the eye is painful Thorough physical, especially to hepatic abdominal region & skin/subcutaneous tissues LFTs, CT/Ultrasound of liver Chest X-Ray

Conjunctival Melanoma vs Ciliary Body Melanoma Clinical exam of conjunctival melanoma –Known history of PAM (esp with atypia) or a nevus –Pigmented area becomes anchored to underlying sclera –No intraocular extension evident Pathologically –No extension through sclera to intraocular tissue Can consider radiologic testing if necessary

Ciliary Body Melanoma Treatment Many factors considered in treatment approach: –Visual acuity of the affected eye –visual acuity of the contralateral eye –intraocular pressure –ocular structures involved –size of the tumor –age and general health of the patient –presence of metastases

Ciliary Body Melanoma Treatment 1.Enucleation has been the preferred treatment for advanced and complicated tumors, especially when other treatment has failed 2.External beam irradiation with either protons or helium ions is a frequently used alternative method to treat medium-size tumors (<10 mm in height and 15 mm in diameter). –Complications include cataract, dry eyes, radiation retinopathy, and rubeosis iridis 3.Plaque brachytherapy is a widely accepted alternative to enucleation for medium-size posterior uveal melanomas –Local recurrence rate of about 12% –Can still get radiation retinopathy but less frequently than external beam 4.Block excision, or sclerouvectomy, is an alternative treatment method for ciliary body melanomas covering less than 4 clock hours of the circumference. 5.If there is extensive orbital extension, consider orbital exenteration Overall, remains controversial adjuvant systemic treatment is not currently advocated without metastases

Metastatic Ciliary Body Melanoma Treatment Systemic chemotherapy is the primary treatment Enucleation is only offered as palliative treatment if the eye is painful