Prognostic Value of Systemic Immune-Inflammation Index in Mucosal Malignant Melanoma

<b>Background</b>: Mucosal malignant melanoma (MMM) is a rare and aggressive malignancy with a dismal prognosis. While the Systemic Immune-Inflammation Index (SII) has emerged as a prognostic marker in various solid tumors, its specific value in MMM remains undefined. This study investigated the association between pretreatment SII and overall survival (OS) in patients with MMM. <b>Methods</b>: We retrospectively analyzed 106 adults with histologically confirmed MMM treated at six oncology centers in Turkey between 2005 and 2025. The baseline SII was calculated as platelet × neutrophil/lymphocyte counts obtained before definitive treatment. A receiver operating characteristic (ROC) analysis identified an optimal SII cutoff of 776 for overall survival (OS), defining low (<776) and high (≥776) SII groups. <b>Results</b>: Gastrointestinal and head and neck mucosa were the most frequent primary sites, and one-third of patients presented with metastatic disease. The median OS for the entire cohort was 23.3 months. Patients with a high versus low SII had a shorter OS (16.2 vs. 35.2 months; HR 2.71, 95% CI 1.67-4.40; <i>p</i> < 0.001). In multivariable analysis, a high SII (HR 1.88, 95% CI 1.12-3.14; <i>p</i> = 0.016), gastrointestinal primary site (HR 1.99, 95% CI 1.23-3.23; <i>p</i> = 0.005), and metastatic disease at diagnosis (HR 4.01, 95% CI 2.32-6.94; <i>p</i> < 0.001) independently predicted a worse OS. <b>Conclusions</b>: The SII is a novel, independent prognostic biomarker in MMM. Elevated pretreatment SII correlates with aggressive clinicopathologic features and inferior survival. As a readily accessible and cost-effective marker, SII may facilitate improved risk stratification in routine clinical practice for MMM patients.