Divergent pathways of melanoma development: evidence from a Southern European cohort

Nevus counts in the divergent pathway model of melanoma development have been studied mainly in patients in Australia. Our aim was to compare nevus counts and the melanoma subtype for melanomas arising on chronically sun-exposed body versus non-chronically sun-exposed body locations in Southern European patients. This was a retrospective study of prospectively collected data from 2013 to 2023 at a melanoma referral center in Athens, Greece, in patients diagnosed with invasive melanoma of the superficial spreading melanoma (SSM) or nodular melanoma subtype. Multivariate multinomial logistic regression analysis was performed. In 1252 patients with SSM or nodular melanoma, the median age (interquartile range) was 57 (46, 67) years old and 51% were males. Regarding nevus counts, 57.9% of patients had 0-25 nevi (low), while the remaining 42.1% had greater than 25 nevi (high). In multivariate analysis, those with greater than 25 nevi (versus ≤25) were significantly less likely to have melanoma developing on the head/neck (chronically sun exposed body site) [odds ratio (OR): 0.60, 95% confidence interval (CI): 0.38-0.93] or on the lower extremity (OR: 0.63, 95% CI: 0.44--0.87), compared with having melanoma on the trunk (non-chronically sun exposed). Regarding the melanoma subtype, those with SSM versus nodular melanoma subtype were 53% less likely to have melanoma developing on the head/neck (OR: 0.47, 95% CI: 0.30-0.75), compared with the trunk. The melanoma subtype (SSM or nodular melanoma) did not significantly differ across upper extremity (OR: 0.94, 95% CI: 0.59-1.51) or lower extremity (OR: 1.03, 95% CI: 0.66-1.62) locations of melanoma development compared with the trunk. In conclusion, the association of higher nevus counts with melanomas developing on the trunk supports the divergent pathways of melanoma development in Southern European patients. Melanomas on the head/neck were significantly associated with lower numbers of nevi and were more likely to be nodular melanoma subtype.