Prognostic value of PD-L1, tumor-infiltrating lymphocytes, and CD117 in vulvovaginal melanoma

Vulvovaginal melanoma represents a rare and aggressive melanoma subtype with distinct mutation patterns, such as a higher frequency of KIT (CD117) mutations, and is associated with poor clinical outcomes. This study investigated the prognostic implications of PD-L1 expression, tumor-infiltrating lymphocytes (TILs), and CD117 expression in patients with vulvovaginal melanoma. A retrospective analysis was conducted on histologically confirmed vulvovaginal melanoma cases diagnosed between January 2010 and December 2020. Immunohistochemical evaluation was performed to assess PD-L1 and CD117 expression, while TIL density was graded using published guidelines. Associations between PD-L1 expression and key clinicopathological features were also evaluated. The primary outcome was disease-specific survival, defined as the interval from diagnosis to death specifically attributable to vulvovaginal melanoma, analyzed using Kaplan-Meier estimates and Cox regression models. Among 47 patients, 70% presented with advanced-stage disease (stage III-IV). PD-L1 expression was detected in 22 patients (47%), and brisk TIL infiltration was observed in 12 patients (26%). PD-L1 positivity correlated with advanced disease stage (p = .002), non-brisk/absent TILs (p = .003), and lymphovascular invasion (p = .047). Kaplan-Meier analysis demonstrated significantly better disease-specific survival in PD-L1-negative tumors (3-year disease-specific survival: 48% vs 18%, p = .008) and in tumors with brisk TIL infiltration (3-year disease-specific survival: 67% vs 21%, p = .003). Combined stratification identified PD-L1-negative/brisk TIL tumors as the most favorable subgroup, while PD-L1-positive/non-brisk/absent TIL tumors exhibited the poorest prognosis (p < .001). In multivariate analysis, PD-L1 expression (HR 1.68, 95% CI 1.10 to 2.55, p = .015), TIL status (HR 0.62, 95% CI 0.43 to 0.89, p = .012), and disease stage (HR 1.85, 95% CI 1.22 to 2.81, p = .004) remained independent prognostic factors. Additionally, CD117 positivity was observed in 30% of tumors (n = 14), although its prognostic significance was not retained in multivariate analysis. The study establishes PD-L1 expression and TIL density as independent prognostic factors in vulvovaginal melanoma, suggesting their potential utility for risk stratification and therapeutic decision-making.