Melanoma with Loss of BAP1 Expression in Patients with No Family History of BAP1-Associated Cancer Susceptibility Syndrome: A Case Series

Abstract

The presence of multiple BAP1-negative melanocytic neoplasms is a hallmark of familial cancer susceptibility syndrome caused by germline mutations in BAP1. Melanocytic tumors lacking BAP1 expression may also present as sporadic lesions in patients lacking a germline BAP1 mutation. Here, we report histomorphologic and clinical characteristics of cutaneous melanomas with loss of BAP1 expression in 4 patients with no known history of BAP1-associated cancer susceptibility syndrome. The lesions were nodular melanomas composed predominantly of intradermal large epithelioid (Spitzoid) melanocytes with nuclear pseudoinclusions as well as scattered multinucleated cells, arising in association with a typical intradermal nevus. Of the 4 patients, only 1 had recurrence. This patient had multiple recurrences with in-transit and regional lymph node metastases. To the best of our knowledge, this is the first reported series of cutaneous melanomas with loss of BAP1 expression arising in patients without a family history of cancer.