HRAS-mutated Spitz nevus on the cheek in a middle-aged man.

© 2012 The Authors. doi: 10.2340/00015555-1264 Journal Compilation © 2012 Acta Dermato-Venereologica. ISSN 0001-5555 Spitz nevus (SN) was first described in 1948, and was referred to as melanoma of childhood (1). Although SNs are benign melanocytic neoplasms, these lesions share many histopathological findings with malignant melanomas (MMs) (2). Despite the diagnostic criteria, the similarities between SNs and MMs make their distinction very difficult even among expert dermatopathologists. Studies using molecular biological techniques, such as loss of heterozygosity analysis, comparative genomic hybridization (CGH), multiplex ligation-dependent probe amplification (MLPA), and DNA sequencing, have provided important clues to the genetic basis of SNs and MMs (3–11). These studies have shown that most MMs have multiple chromosomal aberrations and frequent mutations in oncogenes in the mitogen-activated protein kinase signal transduction pathways, such as BRAF, NRAS and KIT (4, 8, 12). Multiple genetic aberrations, including copy number loss of the CDKN2A gene on chromosome 9p21, are characteristic of MMs (13). However, most SNs have normal karyotypes, whereas increased copies of chromosome 11p associated with mutations in the HRAS gene are found in a minority of cases showing atypical histopathological features (5, 7). HRAS-mutated SNs have been reported to tend to be infiltrative, larger, intradermal and markedly desmoplastic (5, 7). Furthermore, some degree of atypicality could be seen (5, 7). Several histopathological features overlapped those of MMs. To our knowledge, however, there have only been a few reports describing this lesion.