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De novo versus nevus-associated melanomas: Differences in associations with prognostic indicators and survival.
Background: Although 20%-30% of melanomas may be histopathologically “nevus-associated,” implying direct transformation of a nevus into melanoma, the majority of melanomas arise in clinically normal skin with no detectable precursor lesion. We aimed to determine whether nevus-associated and de novo melanomas differ in their associations with histopathologic features and survival. Methods: 1,048 melanoma patients prospectively enrolled in the NYU Melanoma Cooperative Group registry between 1972 and 1982 (NYU1) were analyzed to detect associations between type of melanoma (de novo vs nevus-associated) and age, anatomic site, ulceration, thickness, mitotic index, histological type, stage, and survival. We tested the significant associations in a replication cohort of 1,202 melanoma patients prospectively enrolled between 2002 and 2009 in the NYU Interdisciplinary Melanoma Cooperative Group registry (NYU2). Results: In the NYU1 dataset, de novo melanomas were more likely to be associated with older age (54 vs 47 years, p < 0.01), non-axial location (OR 1.53, p < 0.01), tumor thickness > 1.0mm (OR 1.95, p < 0.01), ulceration (OR 1.61, p = .026), nodular subtype (OR 2.79, p < 0.01), stage > 1 (OR 2.35, p < 0.01), and shorter overall survival (p < 0.01). In the NYU2 replication dataset, de novo melanoma was again significantly associated with older age (61 vs 54 years, p < 0.01), non-axial location (OR 2.29, p < 0.01), tumor thickness > 1.0mm (OR 2.22, p < 0.01), ulceration (OR 2.92 p < 0.01), nodular subtype (OR 2.23, p < 0.01), stage > 1 (OR 2.43, p < 0.01), and shorter overall survival (p < 0.01). In multivariate analysis, de novo histopathology was an independent, poor prognostic indicator in the NYU2 cohort only (HR = 1.69, p < 0.01). The NYU2 cohort has patients with thinner tumors (56.2% have tumors < 1.0mm) compared to the NYU1 cohort (41.8% have tumors < 1.0mm), which may contribute to the differing impact of the de novo histopathology on the survival models for these cohorts. Conclusions: These data suggest that de novo melanomas may be more aggressive than nevus-associated melanomas, and may differ in their molecular pathogenesis. These findings may also have implications for early detection programs.