1. ¹Department of Pathology, University of Michigan, Ann Arbor, MI, USA
2. ²Department of Dermatology, University of Michigan, Ann Arbor, MI, USA
3. ³Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA
4. ⁴Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
5. ⁵Department of Dermatology, The Ann Arbor Veterans Affairs Hospital, Ann Arbor, MI, USA
6. ⁶Department of Otolaryngology, University of Michigan, Ann Arbor, MI, USA
7. ⁷Department of Surgery, University of Michigan, Ann Arbor, MI, USA
8. ⁸Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
9. ⁹Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA

Correspondence: Dr DR Fullen, MD, Departments of Pathology and Dermatology, University of Michigan, M3261, Medical Sciences I, 1301 Catherine, Ann Arbor, MI 48109-0602, USA. E-mail: dfullen@med.umich.edu

Received 3 May 2006; Revised 31 May 2006; Accepted 1 June 2006; Published online 23 June 2006.

Abstract

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.