Melanoma and the Predictive Value of Nevi: Unexpected Findings?

While it is well-established that nevi are the most important risk marker for melanoma,1 it has not been clear to what extent the number or characteristics of nevi may have predictive value in management of melanoma. It has recently been shown that high nevus counts are associated with better melanoma survival, even among patients with positive sentinel lymph nodes (SLN). Although nevus count was not independently predictive of SLN status, higher counts were associated with lower Breslow thickness, less ulceration, and lower mitotic rate.2

Now, research suggests that the number of atypical nevi, rather than total number of nevi, is a stronger predictor of melanoma thickness, especially in patients under age 60.3 The findings could have important implications for patient screening and counseling.

At Last Count

Based on data for 566 patients at two US-based academic sites and an affiliated Veterans Affairs medical center, the presence of more than 50 total nevi was associated with a sharply reduced risk of thick melanoma in individuals under age 60. However, presence of more than five atypical nevi was associated with a risk for thicker melanomas, compared to no atypical nevi.

For the analysis by Geller, et al., subjects were classified according to total nevi counts, as follows:

• 0-20 (66.4 percent)
• 21-50 (20.5 percent)
• >50 (13.1 percent)

Atypical nevi counts were categorized as follows:

• 0 (73.3 percent)
• 1-5 (14.5 percent)
• >5 (12.2 percent)

Researchers report that most melanomas occurred in patients with few nevi and no atypical nevi.

Implications

The current study raises important issues. It should be noted, however, that there may be an unintended bias in the data, given that patients with more nevi may be more likely to seek regular skin screenings from a dermatologist and may, therefore, have melanoma diagnosed early. Nonetheless, the ability to stratify melanoma risk is important not only to encourage early identification and treatment of melanoma (high-risk patients must be especially vigilant to perform skin self-exams and have regular screenings by a dermatologist) but also to support risk reduction efforts for individuals at highest risk. UV avoidance strategies, though necessary for all patients, are especially important for high-risk patients.

Presence of nevi is just one of many risk factors for melanoma well known to both physicians and patients. In fact, nevus density is among six risk factors integrated into a recently validated Melanoma Risk Prediction Model, based on self-assed risk factors. The risk prediction model includes hair color, nevus density, first-degree family history of melanoma, previous nonmelanoma skin cancer, and lifetime sunbed use.4

In light of Geller, et al.’s recently published analysis, dermatologists should continue to encourage regular surveillance of all patients with multiple nevi but now recognize the importance of early melanoma detection especially in individuals with five or more atypical nevi. n

Jonathan Wolfe, MD is an Associate Professor of Dermatology at the University of Pennsylvania.

1. Seykora J, Elder D. Dysplastic nevi and other risk markers for melanoma. Semin Oncol. 1996 Dec;23(6):682-7.

2. Ribero S, Davies JR, Requena C, et al. High nevus counts confer a favorable prognosis in melanoma patients. Int J Cancer. 2015 Oct 1;137(7):1691-8.

3. Geller AC, Mayer JE, Sober AJ, Miller DR, Argenziano G, Johnson TM, Swetter SM. Total Nevi, Atypical Nevi, and Melanoma Thickness: An Analysis of 566 Patients at 2 US Centers. JAMA Dermatol. 2016 Apr 1;152(4):413-8.

4. Vuong K, Armstrong BK, Weiderpass E, Lund E, Adami HO, Veierod MB, Barrett JH, Davies JR, Bishop DT, Whiteman DC, Olsen CM, Hopper JL, Mann GJ, Cust AE, McGeechan K; and the Australian Melanoma Family Study Investigators. Development and External Validation of a Melanoma Risk Prediction Model Based on Self-assessed Risk Factors. JAMA Dermatol. 2016 Jun 8.