What is the clinical relevance of atypical melanocytic nevi?

The clinical relevance of atypical nevi relates to their association with increased melanoma risk. Several retrospective and prospective case-control studies have established that increasing numbers of atypical nevi confer an independent increasing risk of melanoma ranging from 2- to 71-fold. Patients with atypical nevi and two or more family members with melanoma seem to be at the highest risk for melanoma. Evidence that atypical nevi may be potential precursors of melanoma includes photographically documented examples of change in a preexisting nevus and the observation of histological atypia in proximity to melanomas. About 25% to 50% of melanomas have a histologically associated nevus, and the incidence rate of melanomas arising in association with atypical nevi has been estimated to be ~0.5% to 46%. The most convincing evidence for this association is the demonstration of similar or identical genetic changes in a melanoma and its associated nevus.


Despite the above findings, as well as the documented increased risk of melanoma in patients with atypical nevi, it is important to recognize that most atypical nevi are benign and do not progress to melanoma. In this regard, previous studies have shown that anywhere from 20% to 40% of melanomas arise from a preexisting nevus, 30% to 70% arise de novo and, in almost a quarter, the historical origin cannot be assessed. Therefore, although there is a clear association between nevi and melanoma risk, at present it is not clear whether an atypical nevus is more likely to develop into a melanoma than any other type of nevus. Moreover, it is quite clear that a nevus precursor is not required for the majority of melanomas. It is thought that the discrepancy between melanomas arising in preexisting nevi and de novo melanomas can best be explained by the cancer stem cell theory. In this regard, the risk of melanoma associated with nevi may be due to the potential for secondary mutations within nevi, as well as due to the inherent properties of the stem cell population in individuals with numerous moles.