A pediatric case of pigmented epithelioid melanocytoma with chromosomal copy number alterations in 15q and 17q and a novel NTRK3‐SCAPER gene fusion

Abstract

Pigmented epithelioid melanocytoma (PEM) represents a group of rare, heavily pigmented melanocytic tumors encompassing lesions previously designated as "animal-type melanomas" and "epithelioid blue nevi." Despite the association of multiple such tumors in the setting of Carney complex, most cases of PEM occur spontaneously as solitary neoplasms in otherwise healthy patients. PEM may arise in both children and adults, and has a known propensity to spread to the regional lymph nodes.Despite this latter finding, recurrence at the biopsy site or spread beyond the lymph node basin is exceptionally uncommon. Although the molecular basis for PEM continues to be characterized, findings to date suggest that this category of melanocytic neoplasia has genetic alterations distinct from those seen in common nevi, dysplastic nevi, Spitz nevi, and melanoma. Herein, we present an in-depth clinical, histopathologic, and molecular analysis of a case of PEM occurring on the scalp of a young African American girl found to have a novel NTRK3-SCAPER gene fusion. K E Y W O R D S melanocytic neoplasms, melanocytic lesions, dermatopathology, pigmented epithelioid melanocytoma, NTRK3 fusion

Roles of TrkC Signaling in the Regulation of Tumorigenicity and Metastasis of Cancer

“…Recent studies have reported that the tyrosine kinase domain of TrkC and ETV6-NTRK3 interacts with the SH2 domain of the Src and PTB domain of IRS-1. Ligand-independent PTK activation of ETV6-NTRK3 and TrkC in breast and colon cancer leads to constitutive activation of the Ras-MAP kinase (MAPK) mitogenic pathway and the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, as well as upregulation of cyclin D1 mediating cell survival [111,113], In addition, its activation by TrkC and ETV6-NTRK3 is mediated via activation of c-Src by using complex formation [130,131]. IRS-1 functions as an adapter protein, linking ETV6-NTRK3 and TrkC for constitutive activation of downstream signals.…”

Melanocytic lesions with blue naevus‐like (dendritic) morphology: an update with an emphasis on histopathological, immunophenotypic, and molecular features

“…Other, less commonly found, fusions in their study were TPR – NTRK1 (6%, 1/16), ALK (6%, 1/16), and MYO5A – NTRK3 (6%, 1/16) 55 . More recently, rare cases of PEM with NTRK3 – SCAPER 56 or HTT – PKN1 57 fusion have also been reported. Only limited data exist on copy number changes in PEMs; Cohen et al 54 .…”

“…failed to detect significant copy number aberrations in their series of 13 cases. More recently, Friedman et al 56 . reported a case with copy number alterations involving chromosomes 15q and 17q.…”

A Rare Case of Primary Cutaneous Signet-Ring Cell Melanoma With Discrepant Findings on Gene Expression Profiling and Chromosomal Microarray Analysis

“…5). Given the discrepant “benign” gene expression score, peculiar cytology, and deceptively low-grade nuclear pleomorphism, additional analysis via chromosomal microarray (via previously described methods 6 ) was pursued. Multiple deleterious segmental gains and losses were detected, which was more indicative of a malignant phenotype and consistent with our impression of a malignant lesion based on the overall histomorphologic and immunophenotypic features.…”