Track: Case Reports

Topic: Melanocytic Neoplasms

Abstract:

BAP-1 inactivated melanocytic tumors (BIMT) or melanocytoma are predominantly intradermal nodular proliferations of large epithelioid melanocytes often showing prominent cytologic atypia. BIMT typically arises from a conventional melanocytic nevus with BRAF p.V600E mutation, or more rarely NRAS mutations or RAF1 fusions; thus, a background conventional melanocytic nevus is sometimes observed. Molecularly, they are defined by inactivation of the BAP1 tumor suppressor gene, either via loss-of-function mutations or deletions, typically leading to the characteristic loss of BAP1 nuclear expression by immunohistochemistry. We present a case of BIMT on the ear of a 51-year-old male patient, histologically showing an intradermal nodular proliferation of epithelioid melanocytes exhibiting cytologic atypia and increased mitoses. BAP1 immunohistochemistry showed retained nuclear expression. Due to concern for melanoma (cytologic atypia, increased mitotic count, anatomical site, and patient demographics), subsequent molecular testing was pursued, which revealed an oncogenic missense mutation of BAP1 (p.Gly185Arg) and BRAF mutation, thus confirming the diagnosis of BIMT in this patient. Rare cases of BIMT with characteristic histomorphology but retained nuclear expression of BAP1 have been reported. The proposed mechanism to explain such phenomenon includes a missense mutation affecting the functionality of the BAP1 protein or leading to its rapid degradation, without altering its expression or nuclear localization, and subsequent detection by immunohistochemistry. Our case highlights the importance of histomorphology, and pursuing additional molecular diagnostics, when BAP1 nuclear expression by immunohistochemistry is discordant with morphology.

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Erik Nohr, MD