Background/Objectives. Head and neck mucosal melanoma (HNMM) is a rare, aggressive malignancy with poor outcomes and limited evidence to guide prognostication and treatment. A detailed assessment of long-term survival and prognostic factors is needed to inform clinical management and staging. This work aimed to describe outcomes and prognostic factors in HNMM patients treated over 45 years. Methods. This was a retrospective observational cohort study of consecutive patients treated at a tertiary referral center in Italy from 1975 to 2020. Random-forest-based screening informed covariate selection for Cox models. Endpoints were overall survival (OS), disease-free survival (DFS), and post-recurrence DFS (prDFS). Associations with clinical and pathological variables were evaluated using Kaplan–Meier estimates, log-rank tests, and multivariable Cox regression. Results. Among 112 patients (median follow-up, 121.1 months), 3-/5-year OS was 42.8%/28.0%, DFS 20.5%/13.2%, and 1-/3-year prDFS 36.7%/10.9%. Ulceration was associated with worse OS (HR 2.12; 95% CI 1.05–4.26) and DFS (HR 2.23; 95% CI 1.16–4.28). Male sex showed a trend toward poorer OS and DFS. Regional lymph-node treatment correlated strongly with OS and prDFS (overall p < 0.001), with neck dissection indicating unfavorable risk (OS HR 5.22; 95% CI 2.39–11.40). Conclusions. HNMM remains a high-mortality disease with frequent recurrence. Ulceration and nodal involvement were key adverse prognostic factors, while surgery was associated with improved survival. The findings support incorporating ulceration into future staging and highlight the potential for durable control through salvage surgery. Further investigation of treatment intensification, biomarkers, and multimodal strategies is warranted.
Cavalieri et al. (Mon,) studied this question.