Immunoarchitectural Pattern and Its Potential Prognostic Value in Mucoepidermoid Carcinoma

Objectives: To define tumor immunoarchitectural patterns (IPs) and characterize the immune profile in salivary gland mucoepidermoid carcinoma (MEC) toward assessing MEC prognostic significance and implications for immunotherapy. Methods: This study analyzed 41 MEC cases, evaluating the tumor IPs and tumor-infiltrating lymphocyte (TIL) parameters by using whole-slide imaging and AI-assisted assessment. Immunohistochemistry of CD3 and CD8 markers was performed to assess key lymphocyte subpopulations. Results: Immune-rich (I-rich) tumors were characterized by high TIL density and were associated with aggressive tumor behavior, particularly in histological high-grade MEC, with a significant increase in TIL density observed in the inner invasive margin compartment (p < 0.05). I-rich tumor cases were linked to poorer disease-free survival (DFS) (Breslow = 4.686, p = 0.03). Aggressive MEC cases displayed a highly heterogeneous TIL profile, however, no TIL patterns showed a significant impact on DFS (p > 0.05). Conclusions: Despite the high immunogenicity suggested by the abundance of T lymphocytes, the protective role of CD8+ T lymphocytes was not prominent in MEC. I-rich tumors appeared more aggressive and unfavorable MEC cases exhibited high heterogeneity in their TIL profiles. Interrogating the role of TILs in the inner invasive tumor margin may offer a new mechanistic understanding for future immunotherapy discovery.