The Transformation Rate of Moles (Melanocytic Nevi) Into Cutaneous Melanoma

Abstract

Background: Moles, or melanocytic nevi, are both markers of an increased risk of cutaneous melanoma and direct precursor lesions. Recent strategies to reduce the burden of advanced disease have focused on early detection and ongoing surveillance of moles for malignant degeneration. Inherent in this approach is the notion that moles exhibit a certain risk of transformation into melanoma; however, this risk is unknown.Objective: To estimate the risk of moles transforming into cutaneous melanoma. Design:We first constructed a model of transformation based on the assumption that the minimal number of moles turning into cutaneous melanoma per year is roughly equivalent to the number of melanomas diagnosed each year with associated nevic components. The annual risk was then calculated as the number of moleassociated melanomas diagnosed in 1 year (stratified by 10-year age groups) divided by the number of moles in a the same 10-year age group. We also estimated the cumulative risk during the lifetime of an individual mole by using a modification of the standard life table method.Results: The annual transformation rate of any single mole into melanoma ranges from 0.0005% or less (ie, Յ1 in 200000) for both men and women younger than 40 years to 0.003% (about 1 in 33000) for men older than 60 years. The rate is similar between men and women younger than 40 years but becomes substantially higher for men older than 40 years. For a 20-year-old individual, the lifetime risk of any selected mole transforming into melanoma by age 80 years is approximately 0.03% (1 in 3164) for men and 0.009% (1 in 10800) for women. Conclusions:The risk of any particular mole becoming melanoma is low, especially in younger individuals. However, since moles can disappear, ones that persist into old age have an increased risk of malignant degeneration. For young people with innumerable moles and no other associated risk factors, systematic excision of benignappearing lesions would be of limited benefit.

p15 Expression Differentiates Nevus from Melanoma

“…5,6,11 Although these growtharrested melanocytes can exhibit senescent features, the mitotic arrest is not permanent, since almost half of melanomas likely arise from nevi that have acquired additional changes that restore proliferative capacity. 10,25,26 Genetic changes associated with melanoma formation include inactivation of tumor suppressors such as CDK inhibitors 2A/B, phosphatase and tensin homolog, and cellular tumor antigen p53. Activation of mitotic drivers such as GTPase NRas, protein kinase B, mast/stem cell growth factor receptor Kit, epidermal growth factor receptor, or serine/threonine protein kinases B-raf/c-Raf dimers has also been found.…”

“…7e9 In some studies, approximately 50% of melanomas are seen arising from benign nevi; therefore, it is logical to infer that BRAF(V600E) oncogene-induced senescence (OIS) in nevomelanocytes is reversible. 10,11 OIS is promoted by increased expression of cyclindependent kinase (CDK) inhibitors p16 and p15, encoded by the CDKN2A and CDKN2B loci, respectively, on chromosomal locus 9p21.…”

Malignant Melanoma S3‐Guideline “Diagnosis, Therapy and Follow‐up of Melanoma”

“…This is evidenced by the fact that remnants of melanocytic nevi are found in some melanomas [12]. The risk for malignant transformation of an individual melanocytic nevus is, however, very low [13,14].…”

Literature Update on Melanocytic Nevi and Pigmented Lesions in the Pediatric Population

“…The annual transformation rate of any single melanocytic nevus into melanoma is exceedingly low, estimated at 0.0005 % or less for patients younger than age 40 years [23]; nonetheless, one risk factor for melanoma is a high number of AMN [24]. Children tend to have few AMN, but these lesions increase in number with age until mid-life [25].…”