Abstract
BRCA1-associated-protein-1 (BAP1) inactivated melanocytomas (BIM) are rare melanocytic tumors that may be mistaken for Spitz tumors or melanoma. They can occur sporadically or in association with the BAP1 tumor predisposition syndrome (BAP1-TPDS), which may be complicated by uveal or cutaneous melanoma, mesothelioma, basal cell carcinoma and renal cell carcinoma. Aim of this study was to study the clinicopathologic features, preferentially expressed antigen in melanoma (PRAME) and p16 immunohistochemistry of BIM. Ethical approval was obtained. H&E-stained sections were reviewed. PRAME and p16 immunohistochemistry was performed and clinical follow-up was obtained from patient records. Sixty-five BIM from 38 patients (F:M = 4.4:1) were identified. BIM were typically located on the head and neck and trunk (median size: 0.4 cm). Seven patients with BAP1-TPDS (median age: 25 years) had multiple BIM (median: 5), while sporadic BIM were solitary (median age: 39 years). One of seven patients with BAP1-TPDS developed additional malignancies (mesothelioma and cutaneous spindle cell melanoma) and died of complications of mesothelioma. All other patients are alive and without recurrence of BIM (median follow-up: 42 months). Histopathologically, BIM were composed of intradermal, nodular aggregates of epithelioid melanocytes with low mitotic activity (0-1 mitoses/mm2) and 22% of cases showed severe cytologic atypia. A background conventional nevus was present in 74% of cases. P16 staining was mosaic. PRAME immunohistochemistry was negative in all BIM. BIM are more common in the sporadic setting and behave indolently despite of worrisome cytologic atypia. PRAME and p16 immunohistochemistry are reassuring tools in distinguishing BIM from melanoma.