The Prognostic Role of CD8⁺ Tumor-Infiltrating Lymphocyte Density in Head and Neck Mucosal Melanoma.

Abstract

To explore the prognostic role of CD8+ tumor-infiltrating lymphocytes (TIL) density in head and neck mucosal melanoma (HNMM) using an automated, quantitative, immunohistochemistry-based methodology. Retrospective cohort study. Single-institution, tertiary care hospital. Forty-five patients with primary HNMM treated between January 2002 and December 2021 at the University of Pittsburgh were included. For patients with ample primary tumor specimens, CD8⁺ TIL density was quantified using an automated image analysis algorithm on digitized slides. Receiver operating characteristic curves were used to delineate a biomarker cutoff. Survival analysis using the Kaplan-Meier method and Cox proportional hazards was performed with recurrence-free survival (RFS) and overall survival (OS) as endpoints. Thirty-four patients had adequate pathologic specimens available for analysis. CD8⁺ TIL density threshold of 373.6 cells/mm² best delineated patients based on survival outcomes. On log-rank testing, TIL high patients trended toward improved 5-year RFS (p = 0.06) and OS (p = 0.074) when compared to TIL low patients. Using multivariate analysis, high TIL density was significantly associated with improved RFS (hazard ratio [HR] (95% confidence interval [CI]): 0.17 (0.03-0.83), p = 0.028) but not improved OS (HR (95% CI): 0.48 (0.08-2.90), p = 0.4). Tumor characteristics such as advanced nodal staging (HR (95% CI): 13.2 (1.68-104), p = 0.014), and presence of metastatic disease (HR (95% CI): 48.2 (1.94-1196), p = 0.018) were associated with worsened RFS. Automated, digital CD8⁺ TIL density enumeration is a reliable method of assessing TIL density in HNMM patients. High CD8⁺ TIL density is an independent factor associated with improved RFS and trended toward improved OS.