Acquired Precursor Lesions and Phenotypic Markers of Increased Risk for Cutaneous Melanoma

Continued advances in our understanding of the etiology, biology, and genetics of melanoma are likely to help curtail the rising incidence of melanoma. Likewise, progress in our understanding of the morphology of early melanoma and its growth dynamics together with continued development of effective therapies for advanced disease is likely to help decrease the morbidity and mortality rate associated with this cancer. This chapter will elucidate the factors that predispose individuals to melanoma and examine lesions that are considered to be potential melanoma precursor lesions. By identifying these high-risk patients and lesions, it is the hope that targeted interventions can be implemented to permit for the early detection of melanoma or for the prevention of this tumor. The phenotypic markers associated with a heightened risk of melanoma include the presence of many nevi and particularly of Clark nevi (large acquired nevi); the presence of BAP1-inactivated melanocytic tumors, as well as other phenotypic risk factors such as fair skin type, hair color, and eye color; and the presence of freckles and lentigines. While no obligate melanoma precursor lesions have yet been identified, there are some lesions, such as congenital nevi, that appear to have a higher than expected incidence of associated melanoma. The management of these high-risk patients and lesions will also be discussed.