BRAF and NRAS mutations in spitzoid melanocytic lesions

Douglas R. Fullen, Jenny N. Poynter, Lori Lowe, Lyndon D. Su, James T. Elder, Rajan P. Nair, Timothy M. Johnson, Stephen B. Gruber

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86 Scopus citations


BRAF mutations are common events in a variety of melanocytic nevi and primary cutaneous melanomas. We have previously found BRAF mutations in 82% of nevi, consisting of congenital, common acquired and dysplastic types, and 33% of primary cutaneous melanomas other than the spitzoid type, similar to other published reports. A small number of studies have evaluated Spitz nevi and have failed to detect any lesions possessing a BRAF mutation. Only one study included categories of atypical Spitz nevus and borderline lesions suspected to be spitzoid melanomas, along with classic Spitz nevi and spitzoid melanomas. We examined a spectrum of spitzoid lesions that included 48 Spitz nevi, some with atypical features, seven atypical (borderline) Spitz tumors, and 13 spitzoid melanomas. BRAF mutations were detected in 12 of 68 spitzoid lesions, of which two were spitzoid melanomas and 10 were Spitz nevi. Five of the 10 Spitz nevi with BRAF mutations were altered by more than usual cytologic atypia and/or architectural atypia overlapping with dysplastic nevi, or irritation/ inflammation; one desmoplastic Spitz nevus had a BRAF mutation. These results indicate that a small subset of Spitz nevi, some with atypical histologic features, possess BRAF mutations. Therefore, the BRAF mutational status does not separate all Spitz nevi from spitzoid melanomas and non-Spitz types of melanocytic proliferations, contrary to previous reports.

Original languageEnglish (US)
Pages (from-to)1324-1332
Number of pages9
JournalModern Pathology
Issue number10
StatePublished - Oct 21 2006

Bibliographical note

Funding Information:
This work was supported in part by NCI U01 CA83180 (SBG) and NIH T32 HG00040 (JNP), as well as a generous gift from Lewis and Lillian Becker. JTE and RPN were supported by the Babcock Memorial Trust. JTE is supported by the Ann Arbor Veterans Affairs Hospital.


  • BRAF
  • Melanoma
  • Mutation
  • NRAS
  • Spitz nevi


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