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Distant metastasis due to heavily pigmented epithelioid melanoma with underlying BRAF V600E, NOTCH1 , ERBB3 , and PTEN mutations
Author(s) -
Motaparthi Kiran,
George Eva V.,
Guo Ruifeng
Publication year - 2019
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.13485
Subject(s) - gnaq , pten , melanoma , bap1 , cancer research , pathology , epithelioid cell , genetic heterogeneity , medicine , erbb3 , tfe3 , biology , v600e , mutation , cancer , phenotype , immunohistochemistry , gene , epidermal growth factor receptor , pi3k/akt/mtor pathway , genetics , gene expression , signal transduction , promoter
Pigment‐synthesizing melanoma (PSM) describes a morphologically and genetically diverse group of melanomas. In contrast, pigmented epithelioid melanocytoma (PEM) encompasses a spectrum of indolent tumors now classified as borderline/intermediate melanocytic tumors. Herein, we report a case of widely metastatic heavily pigmented epithelioid melanoma with fatal outcome in a 36‐year‐old woman. Next‐generation sequencing identified somatic (tumoral) mutations in BRAF V600E, PTEN , NOTCH1 , and ERBB3 . By contrast, GNAQ and GNA11 were wild type. Prkar1α and p16 expression were maintained. Identification of mutations in NOTCH1 and ERBB3 may support the diagnosis of heavily pigmented epithelioid melanoma. In contrast, PRKCA fusion genes and PRKAR1A mutations support the diagnosis of PEM. Given the heterogeneity, potential overlap (loss of Prkar1α expression), and evolving genetic profiles of these two distinct groups of tumors, careful appraisal of molecular profiles in the light of histomorphology and clinical history is necessary for distinction between PEM and PSMs including heavily pigmented epithelioid melanomas, with significant potential impact on prognosis and therapy.