Next-Generation Sequencing Reveals a New Class of Melanocytic Neoplasms With Hybrid Genomic Features of PEM Including Protein Kinase R 1 Alpha Gene Inactivation and Spitz Tumor-Defining Protein Kinase Fusions

Jeffrey Zhao, Nathaniel Lampley, Sarah Benton, Shantel Olivares, Bin Zhang, Andrew Roth, Anastasiya Boutko, Artur Zembowicz, Pedram Gerami

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)568-574
Number of pages7
JournalAmerican Journal of Dermatopathology
Volume44
Issue number8
DOIs
StatePublished - Aug 1 2022

Keywords

  • BRAF
  • Carney complex
  • PEM
  • Spitz melanoma
  • Spitz nevus
  • Spitz tumor
  • atypical nevus
  • cutaneous melanoma
  • epithelioid blue nevus
  • fusions
  • malignant Spitz tumor
  • melanoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Dermatology

Fingerprint

Dive into the research topics of 'Next-Generation Sequencing Reveals a New Class of Melanocytic Neoplasms With Hybrid Genomic Features of PEM Including Protein Kinase R 1 Alpha Gene Inactivation and Spitz Tumor-Defining Protein Kinase Fusions'. Together they form a unique fingerprint.

Cite this