Nevus-Associated and De Novo Melanoma: A Cross-Sectional Study on Prognostic Differences

Background/Objectives: Melanomas may develop de novo or in association with a pre-existing nevus (nevus-associated melanoma, NAM). Whether these subtypes differ in their clinical and biological behavior remains uncertain. We aimed to compare the clinicopathologic features and outcomes of NAM and de novo melanoma (DNM) in a large single-center cohort. Methods: We retrospectively analyzed 378 patients with invasive melanoma diagnosed between 2007 and 2021 at a tertiary referral center. Tumors were classified as NAM when histopathologic continuity with a nevus was present, and as DNM otherwise. Clinical, histologic, and prognostic variables were compared using univariate and multivariate analyses. Results: Of 378 melanomas, 90 (24%) were NAM and 288 (76%) were DNM. Patients with NAM were slightly younger (mean 52 vs. 54 years) and more often presented with tumors on the trunk (65.6% vs. 51.7%). NAMs exhibited lower Breslow thickness (0.55 vs. 0.84 mm), reduced mitotic activity (0.17 vs. 1.21/mm²), and less frequent ulceration (2.2% vs. 9.4%). Distant metastases occurred only in DNM (6.6%). Sentinel lymph node positivity (1.1% vs. 6.3%) and melanoma-specific mortality (0% vs. 0.69%) did not differ significantly. Multivariate analysis identified Breslow thickness and mitotic rate as independent predictors of subtype. Conclusions: NAMs present with more favorable histopathologic features than DNMs, yet long-term outcomes appear similar. These findings support divergent pathways of melanoma development and underscore the need for molecular and imaging studies to refine risk stratification and guide management.