Background: Melanoma is currently the most prevalent malignant neoplasm among adults and represents the second most common cancer in both sexes among individuals aged 0 to 39 years. This retrospective multicenter study delves into the distinctive clinical, anamnestic, histopathologic, and prognostic attributes of melanoma in Adolescent and Young Adults (AYA), defined as patients diagnosed at ≤40 years, across four Italian centers. Methods: Through a computer-based review of clinical records from 1 January 2010 to 30 September 2023, AYA melanomas were contrasted with non-AYA melanomas (>40 years) among 1452 patients. Data on demographics, melanoma localization, histological type, Breslow thickness, ulceration, and sentinel lymph node (SLN) biopsy status were meticulously collected and analyzed. Results: Our analysis revealed a female predominance in the AYA group and a male predominance in the non-AYA group, with significant differences in anatomical localization and histological types between the two. AYA melanomas showed nearly equal trunk and limb involvement, contrasting with the trunk predominance in non-AYA melanomas. While Breslow thickness was similar across both groups, the presence of ulceration and total number of nevi showed no significant difference. Survival analysis indicated a marginally higher Disease-Free Survival (DFS) in AYA patients compared to non-AYA patients, without a significant difference in Overall Survival (OS). Conclusions: This study highlights demographic and clinical distinctions between AYA and non-AYA melanoma patients, underscoring the need for tailored follow-up and treatment strategies. Despite these insights, the heterogeneity of melanoma among young adults calls for further research, including genetic analyses, to fully understand this unique melanoma subgroup. Indeed, AYA melanoma patients could represent a different and specific target for both follow-up and treatments.
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