| Summary: | Equivocal cases of conjunctival subepithelial melanocytic nevus with atypia may on occasion be difficult to distinguish histopathologically and immunohistochemically from melanoma. We describe the clinical presentation and histopathological features of an atypical amelanotic conjunctival nevus, along with its differential diagnosis and pertinent literature review.A 55-year-old Caucasian male presented with an amelanotic epibulbar conjunctival lesion extending onto the cornea, mimicking a pterygium. The histopathological examination of the excision revealed a well-circumscribed subepithelial amelanotic spindle cell melanocytic proliferation with fascicular growth, focal nuclear and cellular enlargement, reverse maturation, less than 1% of cells in cycle, and no mitotic figures. The spindle cells were diffusely immunoreactive to Mart-1, S100, SOX-10, and superficially to MITF and HMB-45. Given the histopathological atypia and ambiguity of stains, the 5-probe fluorescence in situ hybridization NeoSITE (NeoGenomics, Irvine, CA) was performed and found to be normal.The presence of atypia, a sign of pre-malignancy, in amelanotic subepithelial nevi should be suspected, even in cases of presumed pterygia, to ensure that appropriate histopathological evaluation and subsequent management are pursued. Immunohistochemical stains and molecular studies can be crucial in differentiating benign from potentially malignant conjunctival nevi with atypia. Keywords: Conjunctiva, Nevus, Atypia, Melanoma, Histopathology, Immunohistochemistry, Fluorescence in situ hybridization
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