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

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.

Enhanced expression of podoplanin in oral carcinomas in situ and squamous cell carcinomas.

OBJECTIVE: Podoplanin, a known lymphatic endothelial cell marker, has been reported to be expressed in various types of cancer. To elucidate the expression of podoplanin in precancerous lesions, we examined the immunohistochemical profiles of podoplanin in oral squamous epithelial lesions. METHOD: We studied a total of 298 foci of squamous cell carcinoma (SCC), carcinoma in situ (CIS), epithelial dysplasia, and hyperplastic and/or normal epithelial lesions by immunohistochemistry using D2-40. RESULTS: There was no positivity for podoplanin in normal or hyperplastic epithelia, while all of the CIS and SCC foci stained positive. Approximately one third of the mild dysplasia foci (10 of 36 foci, 28%) and 80% of moderate dysplasia foci (78/98) showed grade 1 positive reactions (positive only in the 1st layer). Grade 2 reactions (up to 4th layer) were seen in 4 of 98 moderate dysplasia foci (4%), 29 of 74 CIS foci (39%), and 3 of 30 SCC foci (10%). Grade 3 reactions (to more than 5th layer) were found in 35 (47%) CIS foci and 26 (87%) SCC foci. CONCLUSIONS: The relationship between the present histological categorization and podoplanin grade was statistically significant. D2-40 expression is considered to be related to the severity of oral precancerous lesions.

Two-phase appearance of oral epithelial dysplasia resulting from focal proliferation of parabasal cells and apoptosis of prickle cells.

BACKGROUND: One of the histologic characteristics of epithelial dysplasias of the oral mucosa is droplet-shaped rete processes resulting from a solid proliferation of basaloid cells. These basaloid cells are suddenly changed into an overlay of parakeratotic cells. However, it is unknown how this characteristic two-phase appearance is generated. METHODS: Formalin-fixed paraffin sections of the oral mucosal specimens with normal, hyperplastic, dysplastic epithelia and squamous cell carcinomas were examined for apoptosis by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method and for lymphoid cells by immunohistochemistry. RESULTS: Apoptotic cells were only located in the keratinized layer of normal/hyperplastic epithelia. However, in epithelial dysplasias, apoptotic cells were scattered in the middle or even in the lower parts of the epithelial layer with frequent vacuolation changes of epithelial cells. Within the epithelial layer of dysplasias, there were increased number of lymphocytes, which were immunopositive for CD45RO, CD8, and CD57- and CD68-immunopositive (+), S-100 protein-positive and major histocompatibility complex (MHC) class II-positive monocytic lineages. They increased in number with the severity of dysplastic degrees, and they were often located in the vicinity of apoptotic epithelial cells, but decreased in carcinomas in situ and invasive carcinomas, which contained fewer numbers of apoptotic figures. CONCLUSION: The findings indicate that intraepithelial infiltrations of both cytotoxic T cells and natural killer cells are closely related to the apoptotic phenomena of prickle cells, which may result in the characteristic 'two-phase appearance' of epithelial dysplasia.