Nevus-associated melanoma: facts and controversies

Nevus-associated melanoma (NAM) is defined on histopathological basis by the coexistence of melanoma and nevus components. Melanomas developing on pre-existing congenital or acquired nevi are usually of the superficial spreading subtype and harbor the BRAFV600E mutation. NAM accounts for almost one-third of melanoma cases As compared to de novo melanoma, NAM develops on younger patients, is more frequently located on the trunk, and is associated with a high nevus count, light eye color and history of frequent sunburns. NAM has been regarded as a model to investigate melanoma origin. Molecular analysis defining the mutation profile of NAM's nevus and melanoma components supported the existence of two pathways of melanoma development, the first not involving clinically visible precursors, the second involving melanocytic nevi as precursors. Concerning diagnosis, dermatoscopy may identify nevus and melanoma components when located side-by-side, but no specific criteria have been described when superimposed. In-vivo reflectance confocal microscopy significantly enhances the recognition of NAM by allowing the detection of nevus remnants when superficially located. Regarding prognosis, NAM is generally thinner and more frequently in-situ than de-novo melanoma. Furthermore, studies reporting survival analysis demonstrated a trend towards better overall, distant-metastasis-free and recurrence-free survival. Although a clinical, phenotypic and molecular profile of NAM has been defined, controversies still exist. In the current review, we widely report and discuss facts and controversies on NAM.