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

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.

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.

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/mm² (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).

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.