Clinical, Morphologic, and Molecular Features of Benign and Intermediate-grade Melanocytic Tumors with Activating Mutations in MAP2K1

Mónica Fumero-Velázquez, Michael Hagstrom, Soneet Dhillon, Tara Geraminejad, Shantel Olivares, Michele Donati, Daniel Nosek, Pia Waldenbäck, Dmitry Kazakov, Brandon S. Sheffield, Victor A. Tron, Pedram Gerami*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Activating mutations in MAP2K1 can be seen in benign and intermediate-grade melanocytic neoplasms with spitzoid morphology. We analyzed the clinical, histopathologic, and genetic features for 16 cases of benign and intermediate-grade melanocytic tumors harboring activating MAP2K1 mutations. We compared them to Spitz neoplasms with characteristic Spitz fusions or HRAS mutation. We also compared the mutational pattern of benign and intermediate-grade MAP2K1-mutated neoplasms and melanomas with activating MAP2K1 mutations. Among the 16 cases, the favored morphologic diagnosis was Spitz nevus (8/16), atypical Spitz tumors (6/16), and deep penetrating nevus (2/16). The 2 most common architectural patterns seen included a plaque-like silhouette with fibroplasia around the rete reminiscent of a dysplastic nevus (n=7) or a wedge-shaped or nodular pattern with the plexiform arrangement of the nests aggregating around the adnexa or neurovascular bundle (n=8). The cases with dysplastic architecture and spitzoid cytology resembled dysplastic Spitz nevi. Compared with true Spitz neoplasms, MAP2K1-mutated neoplasms occurred in older age groups and had more frequent pagetosis and a lower average mitotic count. The most common type of mutation in the benign and intermediate-grade cases in the literature involves an in-frame deletion, while, in melanomas, missense mutations are predominant. Benign and intermediate-grade melanocytic neoplasms with activating mutations in MAP2K1 can have morphologic overlap with Spitz neoplasms. A significant proportion of melanomas also have activating MAP2K1 mutations. In-frame deletions are predominantly seen in the benign and intermediate-grade cases, and missense mutations are predominantly seen in melanomas.

Original languageEnglish (US)
Pages (from-to)1438-1448
Number of pages11
JournalAmerican Journal of Surgical Pathology
Volume47
Issue number12
DOIs
StatePublished - Dec 1 2023

Keywords

  • MAP2K1
  • Spitz
  • dermatopathology
  • genomics

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

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