Fewer Moles May Be Related to Aggressive Melanoma

Caroline C. Kim, MD

It is well known that having multiple moles (ie, >50) is a risk factor for developing melanoma. A new study shows, however, that melanoma can also develop in people with fewer than 50 moles, and when it does, it typically has a more aggressive course.

The study, to be reported at the upcoming 2015 Summer Meeting of the American Academy of Dermatology, suggests that melanomas originating from patients with high nevus (mole) density (HND) and those with low nevus density (LND) may represent two different entities with distinct biologic pathways and aggressive potential.

"While we know having more than 50 moles is a risk factor for developing melanoma, paradoxically patients with fewer moles may develop more aggressive disease," said senior author Caroline C. Kim, MD, director, Pigmented Lesion Clinic and associate director, Cutaneous Oncology Program; Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston.

"The results of our study are important, because people with many moles may be more likely to be educated about their risk for melanoma and referred for skin cancer screening. However, we may be missing patients with fewer moles who may not know that they too are at risk for melanoma, while unaware of warning signs, and may be at risk for more aggressive disease. All patients should be aware of how melanoma is present on the skin and, in particular, patients should look for 'ugly duckling' lesions —any lesion that appears different from anything else on their skin, especially if the lesions are changing," Kim explained in an interview withTargeted Oncology.

"It is important to note that melanomas not only present as darkly pigmented lesions, but can also present as pink and skin-colored lesions. In addition, having a baseline skin examination with a dermatologist will give patients a better understanding of their skin and risk factors for melanoma. Early detection of melanoma is very important, as this relates to a better prognosis, " Kim said.

The study is based on a retrospective chart review of 281 patients with melanoma seen at BIDMC between 2013 and 2014. Of these, 89 had >50 moles (HND) and 192 had <50 moles (LND).

Patients with LND on average had thicker melanomas than those patients with HND (Breslow depth 1.8 mm versus 1.2 mm, respectively;P=.012) and were diagnosed at an older age (51 years versus 41 years, respectively,P<.001). Patients with LND on average had higher mitotic rates (4 mits/mm²versus 2 mits/mm²,P= .05), and their tumors were less likely to be of the superficial spreading subtype and more likely to be of the nodular subtype (P<.05).

In addition, patients with both HND and aplastic/dysplastic nevi (another risk factor for melanoma) when compared with patients with LND were more likely to have a family history of melanoma and to have a melanoma with dark pigmentation, without ulceration, and with a truncal location. Patients with HND and atypical/dysplastic nevi trended toward having a lower incidence of a nonmelanoma skin cancer.

Kim said that this study corroborates findings from a recent study (Ribero S, Davies JR, Requena C, et al. High nevus counts confer a favorable prognosis in melanoma patients.Int J Cancer2015;doi10:1002/ijc.29525), which also found that patients with melanoma and multiple moles had improved survival compared with those with fewer moles.

Future studies are needed to validate this finding and to explore genetic mutations.

"It is likely that the difference between melanomas in patients with more moles versus fewer moles lie within different genetic pathways leading to different aggressive potential. In addition, the role of the immune system in these two patient populations would be another important area to explore, as well as the role of earlier detection for the HND population if they were referred for screening earlier. However, earlier screening is not likely to account for all of the differences found between the tumors of both populations, as the tumors had differences beyond Breslow depth," Kim said.

"Further understanding of the relationship between patient phenotype and tumor genotype could play a role in more accurate patient selection for melanoma screening, help with melanoma diagnosis, and could also play a role in therapeutic decisions," she added.

Kim hopes to continue to further analyze the study findings with genetic profiling of tumors in her patient population.