CD8/CD4 ratio, CD56, and PD-L1 as prognostic markers in sinonasal mucosal melanoma.

[BACKGROUND] Sinonasal mucosal melanoma (SNMM) is an aggressive malignancy with limited prognostic markers. This study aimed to determine whether immune markers, including the CD8 to CD4 lymphocyte ratio, CD56-positive lymphocytes, and PD-L1 expression, provide prognostic information beyond established clinicopathological factors.

[METHODS] We retrospectively reviewed 67 patients with surgically treated SNMM at two tertiary medical centers in Taiwan between 2004 and 2023. Standard histopathologic parameters and immunohistochemical assessments of the CD8/CD4 ratio, CD56-positive lymphocytes, and PD-L1 expression in tumor and stromal immune cells were evaluated. Disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier estimates and multivariable Cox proportional hazards models.

[RESULTS] The median patient age was 62 years, and 60% were male. During a median follow-up of 42 months, 63% of patients experienced recurrence, and 54% died of the disease. An increased CD8/CD4 ratio and the presence of CD56-positive lymphocytes were associated with better DSS (5-year DSS, 64.3% vs. 32.1% and 70.1% vs. 35.8%, respectively), whereas PD-L1 positivity was associated with shorter RFS (5-year RFS, 28.6% vs. 54.3%). In multivariable analysis, mitotic activity of ≥ 10/mm (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.12-4.78) and PD-L1 positivity (HR 1.92, 95% CI 1.01-3.67) independently predicted worse outcomes, while an increased CD8/CD4 ratio remained associated with improved DSS (HR 0.48, 95% CI 0.23-0.99).

[CONCLUSIONS] Immune markers, particularly the CD8/CD4 ratio and CD56-positive lymphocytes, were significantly associated with survival outcomes independent of traditional histopathologic factors. Incorporating immune profiling into risk stratification may improve prognostication and guide the development of immune-targeted strategies in SNMM.