PubMed abstract / permitted excerpt

OBJECTIVE: 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. STUDY DESIGN: Retrospective cohort study. SETTING: Single-institution, tertiary care hospital. METHODS: 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, CD8TIL 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. RESULTS: Thirty-four patients had adequate pathologic specimens available for analysis. CD8TIL density threshold of 373.6 cells/mmbest 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. CONCLUSION: Automated, digital CD8TIL density enumeration is a reliable method of assessing TIL density in HNMM patients. High CD8TIL density is an independent factor associated with improved RFS and trended toward improved OS.