No abstract

Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cavity tumor. In this study, we examined the basis for the activity of PD-1-based immune checkpoint therapy that is being explored widely in head and neck cancers. Using multispectral imaging, we systematically investigated the OTSCC tumor microenvironment (TME) by evaluating the frequency of PD-1 expression in CD8+, CD4+ and FoxP3+ tumor-infiltrating lymphocytes (TIL). We also defined the cellular sources of PD-L1 to evaluate the utility of PD-1:PD-L1 blocking antibody therapy in this patient population. PD-L1 was expressed in 79% of the OTSCC specimens examined within the TME. Expression of PD-L1 was associated with moderate to high levels of CD4+ and CD8+ TIL. We found that CD4+ TIL were present in equal or greater frequencies than CD8+ TIL in 94% of OTSCC, and that CD4+ FOXP3neg TIL were co-localized with PD-1/PD-L1/CD68 more frequently than CD8+ TIL. However, both CD4+PD1+ and CD8+PD1+ TIL were anergic in the setting of PD-L1 expression. Overall, our results highlight the importance of CD4+ TIL as pivotal regulators of PD-L1 levels and in determining the responsiveness of OTSCC to PD1-based immune checkpoint therapy.

Mammary Analog Secretory Carcinoma (MASC) is a new entity of malignant salivary gland tumors that morphologically resembles mammary secretory carcinoma and carries the identical ETV6-NTRK3 fusion gene. We report our first case of MASC in Japan occurring in the parotid gland of a 37-year-old female patient with a t (12; 15) (p13; q25) translocation. Histologically, the tumor was composed of monomorphic cuboidal cells with low-grade vesicular nuclei and pale eosinophilic cytoplasm, and formed microcystic and tubular spaces with periodic acid-Schiff-positive secretion. Immunohistochemically, the tumor cells tested positive for cytokeratin, vimentin, and S-100 protein. MASC is a morphological mimicker of acinic cell carcinoma, but is a distinct neoplasm characterized by a specific chromosomal translocation. An accumulation of similar case studies is mandatory in order to clarify biological behaviors.