Pathologic assessment Reveals limited efficacy of immunotherapy in recurrent high-grade salivary gland carcinomas: A clinicopathologic and genomic study.

Recurrent high-grade salivary gland carcinomas (SGCs) have limited treatment options, and immunotherapy's role remains unclear. This study evaluated radiologic and pathologic responses to immunotherapy in resectable recurrent high-grade SGCs. We retrospectively analyzed 108 patients from a tertiary center: 41 received neoadjuvant immunotherapy, while 67 underwent upfront surgery. Radiologic response (RECIST 1.1) and pathologic response (immune-related criteria) were discordant-34.1 % showed partial radiologic responses, but only 9.8 % achieved partial pathologic responses, with no complete responses. PD-L1 amplification correlated with response (25 % vs. 8.1 % in non-responders, p = 0.042), whereas B2M loss (29.3 % post-treatment, p = 0.032) and TP53/PIK3CA co-mutations (37.8 % in non-responders) were linked to resistance. Survival did not differ between groups (3-year event-free survival: 19.5 % vs. 23.9 %, p = 0.447; overall survival: 26.8 % vs. 31.3 %, p = 0.593). These findings highlight immunotherapy's limited pathologic efficacy in recurrent high-grade SGCs, with response rates lower on pathologic than radiologic assessment. PD-L1 and B2M alterations underscore the need for biomarker-driven strategies. This study provides a foundation for improving outcomes in this aggressive disease.