Malignant Transformation of Ocular Melanocytoma to Uveal Melanoma: A Clinicopathologic Review of Three Novel Unsuspected Cases of a Likely Under-Recognized Phenomenon, With Review of the Literature and Molecular Genetic Data

Abstract

PURPOSE

To describe three cases of, and review the current knowledge regarding, malignant transformation of ocular melanocytoma (OM) to uveal melanoma (UM).

DESIGN

Retrospective clinicopathological case series and review of the literature.

METHODS

Clinical records and histopathology from three patients diagnosed with UM arising from a previously unsuspected OM were critically reviewed at a single academic institution. The patients’ demographic information, medical history, presenting clinical signs and symptoms, laboratory results, ancillary (including molecular genetic) testing, and management were collected. A literature review was conducted.

RESULTS

Three novel cases were identified, totaling 18 reported cases of malignant transformation of an OM to UM. The three new cases were diagnosed histopathologically on enucleation specimens for UM, without prior clinical history of OM. Where demographic information was available, ten patients were female and six male, with an average age at presentation of 45.75 years (range 15-69 years). For patients with an initial clinical diagnosis of OM, the interval to diagnosis of melanoma was between 0.25 years and 33 years, with the most common symptoms of evolution to UM being progressive vision loss, ocular pain, and elevated intraocular pressure. Six total cases did not have a previously known history of melanocytoma.

CONCLUSION

OM is rare; malignant transformation of OM to UM is also very uncommon. The incidental histopathological observation of darkly pigmented, polyhedral, magnocellular cells adjacent to or admixed with frank melanoma resulted in immunohistochemical confirmation of a precursor OM in three unsuspected cases, mimicking somewhat the appearance of UM with abundant admixed melanophages. OM may be a precursor to UM in more instances than previously recognized, and further data, as well as careful attention by pathologists, is needed to refine diagnosis and clinical management strategies regarding patients with known OM, especially outside of the optic nerve head.