A Histopathological and Immunohistochemical Study of High-Molecular-Weight Cytokeratin, Mitochondrial Protein and Gross Cystic Disease Fluid Protein-15 in Pleomorphic Adenomas-With Special Reference to Epithelial Metaplastic Changes

Pleomorphic adenoma, which is the major histopathological type of salivary gland tumor, shows polymorphous features including proliferating epithelial components with tubulo-ducatal and/or solid nests and mesenchyme-like components with myxomatous, myxo-chondromatous, and/or fibrohyalinized tissues. The process of metaplasia, which involves progressive changes in tissues, results in the transformation of fully differentiated cells of one type into differentiated cells of another type in various organs and diseases. Therefore, metaplastic change is an important morphological factor that determines the individual characteristics and typical histogenesis of various lesions. The purpose of the present study was to investigate metaplastic changes histopathologically and immunohistochemically using antibodies against high-molecular-weight keratin (34βE12), mitochondrial protein (MIT) and gross cystic disease fluid protein-15 (BRST-2) in order to clarify the morphological nature and mechanism of the metaplastic change in pleomorphic adenomas. These antibodies are known to be useful markers of squamous, oncocytic and apocrine-like metaplasia, respectively. Histopathologically, the parenchyma of pleomorphic adenoma consisted of double-layered epithelial elements showing luminal and abluminal arrangements, continuously adjacent to mesenchyme-like elements with myxomatous, myxochondromatous and/or hyalinized tissues. The epithelial parenchyma contained squamous eddies with polygonal cells and/or horny keratin pearls (10/10 cases), eosinophilic cuboidal and/or columnar oncocytic cells (8/10 cases), and also apocrine-like features (3/10 cases). Immunohistochemically, 34βE12-positive cells corresponded to the squamous eddies, whereas MIT- and BRST-2-positive cells corresponded to the eosinophilic, oncocytic cells and apocrine-like cells, respectively. In addition, positive immunoreactivity for 34βE12, MIT and BRST-2 was evident at luminal sites, and 34βE12 was expressed at abluminal sites in this tumor. These results suggest that metaplasia of squamous epithelium is associated with both ductal or luminal differentiation and abluminal differentiation of basal and myoepithelial cells, whereas, metaplastic changes of oncocytes and apocrine cells are related to ductal, luminal proliferation, comprising the typical polymorphous features of pleomorphic adenoma.