Salivary Gland Components Involved in the Formation of Squamous Metaplasia

Squamous metaplasia is not an uncommon feature of a number of salivary gland lesions. Arterial ligation of rat submandibular and sublingual salivary glands was used for study of the processes and cell types involved in the development of the squamous metaplasia that occurs in ischemic and infarcted portions of gland parenchyma 6 to 8 days following vessel ligation. Light and electron micrographs show that the principal portion of salivary gland tissue undergoing squamous metaplasia is the acinar-intercalated duct cell complex. Early stages of this process involve a gradual dedifferentiation of acinar cells and hyperplasia of acinar, duct luminal cells, and myoepithelium. Subsequently, both luminal and myoepithelial cells have increasing accumulation of tonofilaments and formation of desmosomes, and centrally located cells may undergo keratinization. Immunohistochemical staining of ischemic salivary gland tissue with developing squamous metaplasia was performed with the use of rabbit antisera to human epidermal and Mallory body cytokeratins. The two antisera gave complementary patterns in normal acini and ducts, with antibody to epidermal cytokeratin (ECK) staining only myoepithelial cells and antibody to Mallory body cytokeratin (MBCK) staining mainly luminal epithelial cells. In early phases of squamous metaplasia (6 days after ligation), antibody to ECK stained central and peripheral (myoepithelial) cells, but by 8 days after ligation only central cells were stained. At 6 days after ligation, a proportion of central cells in squamoid clusters stained with antibody to MBCK, and myoepithelial cells were unstained. By 8 days after arterial ligation, cell clusters exhibiting squamous metaplasia were completely unstained with antibody to MBCK, despite the presence ultrastructurally of numerous tonofilament bundles in both types of cells forming these clusters. The propensity for squamous alteration of acinar-intercalated duct complexes has important connotations for salivary gland tumors such as pleomorphic adenoma and mucoepidermoid carcinoma.