Mucosal Melanoma Clinical Management and Prognostic Implications: A Retrospective Cohort Study

Simple Summary Mucosal melanoma (MM) is a rare melanoma subtype that affects mucosal surfaces of the head and neck, anorectal region, and vulvovaginal area. Due to its rarity, the management, monitoring, and treatment of MM lack standardization, often relying on protocols designed for cutaneous melanoma (CM). In this retrospective, registry-based cohort study, we analyzed epidemiological and histological data together with the treatments administered to gain insights into the disease's behavior, treatment patterns, and potential predictors of survival. Our findings reveal that lower disease stage, thinner Breslow depth, and surgical resection are associated with improved overall survival, while age, sex, radiotherapy, and BRAF mutant status do not significantly affect survival. Standard systemic management typically includes immunotherapy (anti-PD-1 or anti-PD-1 and anti-CTLA-4). For cases with BRAF or c-KIT mutations, targeted therapies may be considered. The prognosis is unfavorable, with a survival rate of less than 50% at 2 years.Abstract Mucosal melanoma (MM) is an uncommon melanoma subtype affecting mucosal surfaces of the head and neck, anorectal region, and vulvovaginal area. We aimed to present our experience at a tertiary-level hospital regarding MM diagnosis, management, monitoring of progression, mutations, and outcome predictors. We performed a registry-based cohort study including MM cases diagnosed from 2012 to 2022 and retrospectively characterized somatic mutations on BRAF, NRAS and c-KIT. We employed Kaplan-Meier curves, log-rank tests, and Cox regression analysis to explore prognostic factors and survival outcomes in a cohort of 35 patients, mainly women (63%) with a median age of 70 years. Predominantly, MM occurred in the vulvovaginal region (48.6%). At diagnosis, 28.6% had lymph node involvement, and 31.4% also had distant metastasis. Mutations in BRAF and c-KIT were identified in 3/35 (9%) and 2/6 patients (33%), respectively. Surgery was performed in 71.4% of patients, and most received systemic treatment (65.7%). Lower disease stage, thinner Breslow depth, and surgical resection were associated with improved overall survival. Notably, age, sex, radiotherapy, and BRAF mutant status did not affect survival. Standard management typically involves immunotherapy. Cases with BRAF or c-KIT mutations may be considered for targeted therapies. Unfortunately, MM prognosis remains unfavorable, with a less than 50% survival rate at 2 years.