chondroitin-sulfates and Adenoma--Pleomorphic

The tumor matrix of salivary pleomorphic adenoma (PA) is characteristically rich in glycosaminoglycans (GAGs), which contribute to its complex histoarchitecture. This study evaluated the microscopic localization of various GAGs in 17 PAs, using a panel of anti-GAG monoclonal antibodies and biotinylated hyaluronic acid (HA)-binding protein. Both epithelial and mesenchymal-like tissues were confirmed to contain GAGs. Luminal epithelial cells mostly lacked GAGs, whereas GAGs were seen both in the cytoplasm and cell membrane of non-luminal epithelial cells. In addition, small intercellular accumulations of GAGs were often present in solid epithelial areas, implying the epithelial origin of GAGs. GAGs did not appear to be a main component of the hyaline matrix. The myxoid region was consistently stained for both chondroitin 6-sulfate (CS-6) and HA but variably for chondroitin 4-sulfate (CS-4), dermatan sulfate (DS) and keratan sulfate (KS); heparan sulfate (HS) was not detected. The chondroid region showed increased staining for CS-6 but reduced staining for HA when compared with the myxoid region. In addition, CS-4, DS and KS were seen both in chondroid cells and the territorial matrix, whereas HS was present only in the cells. It is suggested that GAGs in PA are mainly produced by non-luminal cells and influence the proliferation, differentiation, secretory activity and shape of tumor cells, thus contributing to the morphological diversity of this tumor.

Topics: Adenoma, Pleomorphic; Antibodies, Monoclonal; Cell Differentiation; Cell Division; Cell Membrane; Cell Size; Chondroitin Sulfates; Cytoplasm; Dermatan Sulfate; Epithelial Cells; Epithelium; Extracellular Matrix; Glycosaminoglycans; Heparitin Sulfate; Histocytochemistry; Humans; Hyaluronic Acid; Immunohistochemistry; Keratan Sulfate; Mesoderm; Salivary Gland Neoplasms

One of the common histopathologic features of pleomorphic adenoma (PA) and adenoid cystic carcinoma (ACC) of the salivary gland is the abundant accumulation of glycosaminoglycans (GAGs). To study a relationship between the histologic distribution of GAGs and the morphologic pattern of salivary gland tumors, we carried out immunohistochemical and biochemical analyses of GAGs on 16 cases of PA and three cases of ACC. Immunohistochemically, several GAG fractions such as chondroitin-6-sulfate, unsulfated chondroitin sulfate, and keratan sulfate were seen mainly at the plasma membrane of both PA and ACC cells and of myoepithelial cells of normal salivary glands. Most of these GAG-positive cells were distributed in solid and chondromyxoid parts of PA and in the cellular part of ACC. Biochemical GAG analysis of both PA and ACC, separated into nonsulfated and sulfated fractions by two-dimensional electrophoresis, revealed high concentrations of chondroitin sulfate in both neoplasms, but the concentration of hyaluronic acid, was significantly higher in PA than in ACC. The results show that the concentration of hyaluronic acid, a major nonsulfated GAG fraction, was significantly higher in PA than in ACC and, therefore, this difference may be useful in the differentiation of the two neoplasms.

Topics: Adenoma, Pleomorphic; Adult; Aged; Carcinoma, Adenoid Cystic; Chondroitin Sulfates; Glycosaminoglycans; Humans; Immunoenzyme Techniques; Immunohistochemistry; Microscopy, Immunoelectron; Middle Aged; Parotid Gland; Salivary Gland Neoplasms

Pleomorphic adenoma of the salivary gland is classified into two types based on the morphology of the cells and biochemical analysis of glycosaminoglycans. Type 1: the tumors consisted mainly of spindle cells, producing a large amount of mucinous material, and contained not only chondroitin 4- and 6-sulfate and hyaluronic acid but also heparan sulfate. When the tumors of this type were dissociated and cultivated, spindle cells proliferated vigorously as mulitlayer and secreted mucinous substance into the intercellular space. The cells looked like non-epithelial cells in a conventional culture bottle, but showed an epithelial-like arrangement when they were cultivated in sponge matrix or inoculated subcutaneously into mice. Fine fibres stained with orceine or resorcin-fuchsin were observed in the intercellular material both in resected tissue and in culture. Type 2: the tumors consisted mainly of ductal cells, having no mucinous area, and contained little heparan sulfate. When the tumors were cultivated, the growth of epithelial-like polygonal cells was observed in monotonous pattern, producing scanty intercellular substance, and proliferating, as monolayer, much less rapidly than the cells of Type 1.

Topics: Adenoma, Pleomorphic; Cells, Cultured; Chondroitin Sulfates; Extracellular Space; Glycosaminoglycans; Heparitin Sulfate; Histocytochemistry; Humans; Hyaluronic Acid; Microscopy, Electron; Salivary Gland Neoplasms