Abstract
Pleomorphic adenoma (PA), the most common salivary gland tumor, is a benign tumor that carries a risk of malignant transformation to various histologies of carcinoma ex pleomorphic adenoma (CA exPA). Recently, genomic analyses have provided deeper insights into the molecular biology of salivary gland cancers. However, the molecular processes that underlie the progression from PA to CA exPA are largely unknown. In this study, we used RNAseq data from CA ex PA of myoepithelial (n = 24) or salivary duct histology (n = 6), de novo myoepithelial carcinoma (n = 16) and de novo salivary duct carcinoma (n = 10), and compared their constituent immune tumor microenvironments. We found that increasing levels of immune infiltration and activation were associated with a generally lower probability of cancer developing ex-PA, suggesting that immune surveillance may constrain the malignant transformation of benign salivary tumors. More immunologically infiltrated tumors were more likely to have developed de novo. Taken together, these data suggest a role for tumor escape from immune surveillance in the development of CA exPA. The immune-cold microenvironments of CA ex PA tumors may in part explain their more aggressive clinical behavior.
Highlights
Salivary gland cancers (SGCs) are rare, aggressive human malignancies that account for fewer than 5% of all carcinomas arising within the head and neck
Carcinoma ex pleomorphic adenoma (CA exPA) is the result of malignant transformation of the most common benign salivary gland tumor—pleomorphic adenoma (PA)—into malignant histologies such as adenocarcinoma (AC), salivary duct carcinoma (SDC), adenoid cystic carcinoma (ACC), and myoepithelial carcinoma (MECA) [7]
In a logistic regression model controlling for histology type as covariate, we analyzed the association between immunological tumor microenvironment metrics and cancer origin in MECA (n = 24) and SDC ex PA (n = 6) and de novo MECA (n = 16) and SDC (n = 10)
Summary
Salivary gland cancers (SGCs) are rare, aggressive human malignancies that account for fewer than 5% of all carcinomas arising within the head and neck. Carcinoma ex pleomorphic adenoma (CA exPA) is a rare malignant neoplasm of the major salivary glands, accounting for about 3–15% of all SGCs [2, 5], with rising incidence over the past several decades [5, 6].
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