Two Congenital Cases of Pigmented Epithelioid Melanocytoma Studied by Fluorescent in situ Hybridization for Melanocytic Tumors: Case Reports and Review of These Recent Topics

Abstract

The term ‘pigmented epithelioid melanocytoma’ (PEM) has recently been proposed as a nosological framework grouping lesions formerly known as animal-type melanomas, sporadic epithelioid blue nevi and Carney complex-associated epithelioid blue nevi. Congenital PEMs have been reported extremely rarely and their prognosis is poorly known. Four-color fluorescent in situ hybridization (FISH) for melanocytic lesions is a recent method developed to assess the malignant potential of ambiguous melanocytic lesions. Here we describe 2 cases of congenital epithelioid and strongly pigmented melanocytic lesions consistent with PEM. No BRAF gene mutation was found in the 2 cases. FISH for melanocytic lesions was also performed. The first case proved entirely negative, whereas the second one showed a positive zone with an extra copy of chromosome 6. The prognosis and management of PEM are discussed, with a review of the available data on the history, demographics, molecular alterations and histopathological aspects of this entity. PEM seems to represent a unique low-grade melanocytic tumor with a limited potential of metastasis to lymph nodes, but a favorable long-term clinical course. The published data about FISH for melanocytic tumors, and especially PEM, are reviewed. Four-color FISH may be a useful tool to assess more accurately the prognosis of these tumors.

Generalized congenital epithelioid blue nevi (pigmented epithelioid melanocytomas) in an infant: Report of case and review of the literature

“…The clinical workup for our patient revealed absence of pathogenic variants in the PRKAR1A gene and also no candidates identified on trio whole exome sequencing. It should be noted that germline PRKAR1A testing was not performed in the prior published reports . Our case demonstrated a slightly elevated proliferative index at 10% to 20% of the MART‐1 positive cells, despite a lack of identifiable dermal mitotic figures.…”

“…A few cases of congenital EBN and PEM occurring in young children have been reported in the literature to date; these are summarized in Table . The majority have been solitary cases, while our case and three others showed multiple lesions.…”

“…14 Blue nevi can also present similarly to EBN/PEM, but lack epithelioid cells that contain vesicular nuclei, often have other types of melanocytes, and have a reduced likelihood of multiple lesions being present. 8,15,16 A few cases of congenital EBN and PEM occurring in young children have been reported in the literature to date [5][6][7][8][17][18][19][20][21][22] ; these are summarized in Table 1. The majority have been Molecular abnormalities can also help distinguish EBN from common blue nevi and other entities.…”

“…4 Congenital cases of EBN are rarely reported. [5][6][7][8] Herein, we describe a patient with multiple congenital EBN without germline pathogenic PRKAR1A mutation or pathogenic mutations identified in other genes on whole exome sequencing.…”

Identification of HRAS mutations and absence of GNAQ or GNA11 mutations in deep penetrating nevi

“…28 Other than the previously mentioned study, molecular analysis has been limited on these lesions and is comprised mainly of fluorescence in situ hybridization or BRAF mutation assessment of small case numbers, none of which demonstrated discernible chromosomal aberrations. 29,30 Our study is the first to analyze epithelioid blue nevi for HRAS, GNAQ, and GNA11 mutations. The presence of GNAQ mutations in a subset of epithelioid blue nevi further confirms categorization of these lesions as true blue nevic variants.…”