Benign and Intermediate-grade Melanocytic Tumors with BRAF Mutations and Spitzoid Morphology: A Subset of Melanocytic Neoplasms Distinct from Melanoma

Jeffrey Zhao, Sarah Benton, Bin Zhang, Shantel Olivares, Sepideh Asadbeigi, Klaus Busam, Pedram Gerami*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The current classification of Spitz neoplasms in the World Health Organization (WHO), Fourth Edition defines Spitz neoplasms as melanocytic proliferations with characteristic Spitz morphology and a Spitz-associated genomic fusion or HRAS mutation. In contrast, melanocytic neoplasms with BRAF mutations are considered typical of common acquired nevi, dysplastic nevi, and melanomas from intermittent sun-damaged skin. However, increased utilization of ancillary testing methods such as BRAFV600E immunohistochemistry and sequencing studies have made apparent a subgroup of benign-grade and intermediate-grade melanocytic neoplasms with Spitzoid morphology that harbor BRAFV600E mutations. We refer to these cases as BRAF mutated and morphologically Spitzoid (BAMS) nevi and tumors. Two experienced dermatopathologists reviewed a series of 36 BAMS nevi/tumors. Cases in which a diagnosis of melanoma was favored were excluded. The histomorphologic, clinical, and molecular findings were assessed by immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing using validated gene panels. Characteristics of BAMS nevi/tumors were compared with a control set of Spitz tumors with previously reported fusion proteins. BAMS nevi/tumors had a decreased proportion of Kamino bodies (P=0.03) and a higher proportion of cytoplasmic pigmentation (P<0.00001). There were no differences in other morphologic features such as the silhouette, epidermal hyperplasia, pagetosis, and cytologic atypia compared with fusion-induced Spitz tumors. In 6/17 cases where next-generation sequencing studies were available, recurrent mutations in the KMT gene family were seen. This was higher than the proportion of such mutations seen in fusion Spitz tumors and lower than the frequency in cutaneous melanoma.

Original languageEnglish (US)
Pages (from-to)476-485
Number of pages10
JournalAmerican Journal of Surgical Pathology
Volume46
Issue number4
DOIs
StatePublished - Apr 1 2022

Keywords

  • Spitz neoplasm
  • Spitz nevi
  • ancillary testing
  • genomics
  • next-generation sequencing

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Fingerprint

Dive into the research topics of 'Benign and Intermediate-grade Melanocytic Tumors with BRAF Mutations and Spitzoid Morphology: A Subset of Melanocytic Neoplasms Distinct from Melanoma'. Together they form a unique fingerprint.

Cite this