Pathogenesis Analysis of Salivary Gland Tumors Through the Expression of Programmed Death-Ligand 1 (PD-L1)

Abstract

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, followed by Warthin's tumor (WT). In addition to its high frequency, PA also shows metastasis and transformation towards malignancy as carcinoma ex-pleomorphic adenoma (CXPA). While the histogenesis of WT remains unclear, especially given the presence of lymphoid stroma around the developing tumor and the immunological interaction between them. Immune escape is a carcinogenesis mechanism of tumors to avoid the host immune system by producing PD-L1. This study was conducted to determine whether there is an immune escape through the expression of PD-L1 in salivary gland tumors. The tissue sections of PA, CXPA, and WT were stained with Hematoxylin Eosin and immunostained with a rabbit monoclonal recombinant anti-PD-L1 antibody. We observed immunopositive PD-L1 on the cell membrane with or without cytoplasm staining. PA and CXPA expressed PD-L1, accompanied by an anomaly expression of CXPA in several spots at the salivary gland at the surgical border. Therefore, PD-L1 is one of the PA pathways to transform into CXPA through immune escape. WT expressed PD-L1 in the cytoplasm and lymphoid stroma but not on the cell membrane. It is interpreted as positive constitutive, which may have the function of increasing tumor cell growth, while overexpressed PD-L1 in lymphoid stroma is thought to be associated with a poor prognosis of the tumor and is suspected to transform into malignancy, such as B-cell Lymphoma.

Keywords: Carcinoma ex pleomorphic adenoma; Immune escape; PD-L1; Pleomorphic adenoma; Salivary gland tumors; Warthin’s tumor.

Fig. 1

PD-L1 Expression in Salivary Gland Tumors. a Pleomorphic adenoma; b PD-L1 Expression in PA; c Carcinoma ex Pleomorphic adenoma; d PD-L1 Expression in CXPA; e Warthin’s tumor HE; f PD-L1 Expression in WT. a, c, e: HE staining; b, d, f: IHC staining. magnification 100× insert picture 400×)