Do all melanomas develop from atypical nevi?

In the past, the development of melanoma has been modeled as a stepwise process from a cutaneous melanocyte through nevus through atypical nevus stages to melanoma in situ and eventually invasive melanoma. However, around 40% to 75% of melanomas develop in normal skin de novo, and, of those melanomas that develop in association with a preexisting nevus, <50% of the nevi are atypical. At present it is difficult to determine whether an atypical nevus is any more likely to become a melanoma than any other nevus or isolated melanocyte. Moreover, it is now clear that a preexisting nevus is not required for a melanoma to develop. 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. Therefore, although there is a clear association between nevi and melanoma risk, only a portion of this risk may be related to the acquisition of genetic mutations within the nevi. The majority of the risk may be associated with the inherent properties of melanocyte stem cell populations in individuals with numerous nevi.

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