ABSTRACT
BACKGROUND: Although the majority of melanomas demonstrate high rates of mutations in B-RAF or N-RAS that result in constitutive activation of the mitogen-activated protein kinase-signaling pathway, emerging data suggest molecular differences among melanoma subtypes. In this study, the authors evaluated the contribution of B-RAF and N-RAS mutations to the pathogenesis of Spitzoid melanomas. METHODS: In total, 33 Spitzoid melanomas were analyzed for clinical and pathologic characteristics as well as for hot-spot mutations in the B-RAF and N-RAS genes. In the majority of patients (28 of 33 melanomas), the tumors were confined to the skin with no evidence of metastasis (average follow-up, 32.5 mos). There were five metastasizing melanomas (5 of 33 tumors) with regional or systemic spread. RESULTS: Of 33 Spitzoid melanomas, only 1 showed the V600E mutation in the B-RAF gene (1 of 33 tumors; 3%). It was noteworthy that none of the metastatic Spitzoid melanomas (0 of 5 tumors; 0%), of which 2 resulted in fatal outcomes, demonstrated mutations in B-RAF or N-RAS. CONCLUSIONS: In contrast to the majority of cutaneous melanomas, activating hot-spot mutations in B-RAF or N-RAS were not involved in the pathogenesis of Spitzoid melanoma. These data suggested that Spitzoid melanoma is a distinct form of melanoma with unknown genes and/or signaling pathways involved in its development.
