Background: Pigmented epithelioid melanocytoma (PEM) is a subtype of melanocytic tumor with frequent involvement of the sentinel lymph node but rare distant metastasis. Rendering a diagnosis and prognosis based on histology can be challenging. Recent genomic studies identified 2 molecular variants of PEM. One variant is characterized by the activation of the mitogen-activated protein kinase pathway and inactivation of the PRKAR1a gene. The other is associated with genomic fusions involving the protein kinase C ( PRKC ) gene family.
Objective: We investigated the molecular and clinicopathologic features of previously unreported PEM cases to improve tumor classification and report new classes of PEM.
Methods: Next-generation sequencing and histomorphologic assessment was performed on 13 PEM cases.
Results: We identified 2 novel PEM classes. Three cases harbored PRKAR1a inactivation and genomic fusions ( ALK , NTRK , and MAP3K8 ). These tumors had overlapping histologic features with pigmented Spitz neoplasms. Three cases had genomic fusions involving PRKCB . These cases had overlapping features with PRKCA fusions but, in 2 cases, had a notable spindle cell component.
Limitations: The overall sample size and amount of clinical follow-up is limited, leaving some uncertainty regarding the expected clinical course of these novel cases.
Conclusions: PRKAR1a-inactivated/Spitz fusion-associated PEMs and PRKCB fusion-associated PEMs represent 2 new molecular classes of PEM.
Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.