BAP1-Inactivated Melanoma Arising From BAP1-Inactivated Melanocytic Tumor in a Patient With BAP1 Germline Mutation: A Case Report and Review of the Literature

Abstract

:BAP1-inactivated melanocytic tumors represent a subset of epithelioid melanocytic neoplasms resulting from biallelic inactivation of the BAP1 gene and by a driver mutation that activate the MAP kinase pathway, most commonly BRAFV600E. They occur sporadically or, less common, in the setting of BAP1 tumor predisposition syndrome caused by a BAP1 germline mutation that predisposes to several malignancies including cutaneous and uveal melanoma. To date, only few cases of BAP1-inactivated melanomas have been reported. We present a case of a 35-year-old woman presented with a melanocytic lesion microscopically composed of 3 distinct melanocytic populations, suggesting a stepwise progression model to melanoma from a conventional nevus through a melanocytoma stage. This progression was also supported from a molecular viewpoint given BRAFV600E, BAP1, and TERT-p hot spot mutations detected by targeted mutational analysis. Four atypical melanocytic lesions were removed from the patient's back, and the same A BAP1 c.856A>T, p.(Lys286Ter) mutation was detected on either tumoral or normal tissue samples. To the best of our knowledge, this is the first case of BAP1-inactivated melanoma with a documented TERT-p hot spot mutation manifesting as the first presentation of BAP1 tumor predisposition syndrome.

Melanocytic Neoplasm With KIT and APC Mutations: A New Subtype of Melanocytoma?

“…8 The acquisition of further genetic alterations in specific melanoma-related genes can lead to malignant transformation of these lesions. [9][10][11][12] Several small series of unusual melanocytic neoplasms with peculiar molecular findings have been reported, expanding the group of the intermediate-grade melanocytic tumor/melanocytoma. [13][14][15] We herewith report a unique case of a morphologically ambiguous melanocytic proliferation characterized by concomitant KIT and APC mutations (Figs.…”

“…8 The acquisition of further genetic alterations in specific melanoma-related genes can lead to malignant transformation of these lesions. 9–12 Several small series of unusual melanocytic neoplasms with peculiar molecular findings have been reported, expanding the group of the intermediate-grade melanocytic tumor/melanocytoma. 13–15…”