PURPOSE: To describe the principal histopathologic findings in a series of 1,527 globes with uveal melanoma and the relationship of these findings to each other. METHODS: All eyes enucleated in the Collaborative Ocular Melanoma Study (COMS) were examined independently by three ophthalmic pathologists and the findings recorded on a data form. A composite of findings was obtained after adjudication. RESULTS: The diagnosis was choroidal melanoma in 1,527 (99.7%) of 1,532 cases examined. Misdiagnoses were metastatic adenocarcinoma (four) and hemangioma (one). Spindle cell (9.0%), mixed cell (86.0%), and epithelioid cell (5.0%) types were observed. Medium tumors were located more posteriorly than large tumors. Considerable local invasion was seen: rupture of Bruch's membrane (87.7%), invasion of the retina (49.1%), tumor cells in the vitreous (25.2%), vortex vein invasion (8.9%), invasion of tumor vessels by tumor cells (13.8%), and invasion into emissary canals (55.0%). Overall, 81.1% demonstrated local invasion, excluding rupture of Bruch's membrane. Scleral invasion was present in 55.7% of eyes, and extrascleral extension was present in 8.2%. Mitotic activity was significantly reduced in eyes that had received pre-enucleation radiation treatment (P < .001). The number of macrophages in the tumor increased with increased pigmentation (P < .001) and increased necrosis (P < .01). CONCLUSION: The accuracy of diagnosis in the COMS is high, with histopathologic confirmation of the diagnosis at 99.7%. Extensive local invasion of the tumor was seen. Pre-enucleation irradiation significantly reduced the number of mitotic figures. An association was found regarding the presence of macrophages, the level of pigmentation, and degree of necrosis.
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