Intraoral salivary lymphoepithelial carcinoma: clinicopathologic and immunophenotypic characterization of 3 cases indicates elevated programmed death-ligand 1 expression

Objective: Intraoral salivary lymphoepithelial carcinoma (ISLEC) is a rare malignancy with programmed death-ligand 1 (PD-L1) expression levels that have been greatly understudied. We examined the clinicopathologic and immunophenotypic characteristics, including PD-L1 levels, of 3 cases of ISLEC. Study Design: We searched the archives of 2 oral and maxillofacial pathology laboratories for specimens diagnosed as ISLEC between 1985 and 2022. We collected patient demographic and clinical data. Immunostaining for AE1/AE3, CK7, CD3, CD20, p16, p53, Ki67, and PD-L1 (SP263), as well as Epstein–Barr virus-encoded small RNAs (EBER) in situ hybridization (ISH) were performed. Results: All 3 cases affected males aged 42 to 84 years (median = 61y) and involved the floor of the mouth, soft palate/uvula, and tongue. The lesions showed diffuse infiltration by non-keratinizing sheets and islands of undifferentiated carcinoma cells with associated dense lymphoplasmacytic inflammation. Immunohistochemically, all tumors showed AE1/AE3 positivity, selective p53 staining, and negativity for CK7 and p16. Ki67 highlighted 20%-80% of lesional cells. The inflammatory infiltrate comprised a mixed population of T and B lymphocytes. EBER ISH was positive in one case. All ISLECs displayed membranous, focal-to-diffuse, PD-L1 staining with tumor proportion score > 95% in two and 40-50% in the third case. Conclusions: The clinicopathologic and immunophenotypic characteristics of the cases we examined highlight the rarity of ISLEC and indicate overall high PD-L1 levels in this type of malignancy, rendering patients with ISLEC potential candidates for targeted α-PD-1/PD-L1 immunotherapy.