Clinical, phenotypic and oncologic background differences in patients with sporadic, familial and multiple primary melanoma

Background Sporadic Melanoma (SM) refers to patients with a single melanoma and no family history. Multiple Primary Melanoma (MPM) includes individuals with two or more primary melanomas. Familial Melanoma (FM) is defined as melanoma occurring in two first-degree relatives, or in three or more affected family members of any degree. Previous studies describe distinct phenotypic and clinical profiles in each subgroup, and a high proportion of personal and familial cancer history in patients with melanoma. Objective To compare phenotype, clinicopathological features, and oncological history in the three groups. Methods Data from 442 patients were collected and divided into three groups: FM, MPM, and SM. Results The MPM group showed light eye color (p = 0.01), more tan 50 nevi (p = 0.00014), actinic keratoses (p = 0.0025), and melanomas arising from pre-existing nevi (p = 0.0031). FM patients were younger (p = 0.01) and had a higher burden of personal and family cancer history, particularly breast neoplasms (p = 0.01). SM presented ≥ 2 mitoses (p ≤ 0.0001). Multivariate analysis confirmed independent associations specific to each group. Study limitations Long term-follow-up for secondary melanoma is needed for validation. Also, some participants may not recall certain family history. Conclusion Patients with MPM display fair phototypes, numerous nevi, and markers of chronic sun damage, suggesting a central role of phenotype and cumulative UV exposure. In FM, younger age and a higher burden of oncologic history point toward an underlying genetic predisposition. SM is characterized by fewer nevi and aggressive melanomas, reflecting a distinct biological entity. These findings highlight the complex interplay between genetic and environmental factors.