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.

Nuclear morphology and morphometry of B-lymphocyte transformation. Implications for follicular center cell lymphomas.

One of the major tenets of current non-Hodgkin's lymphoma classifications is the relationship of morphologic subtypes to stages in the sequence of normal B-lymphocyte transformation occurring in the germinal follicle. To test this hypothesis, quantitative morphometric image analysis was carried out on in vivo and in vitro samples of mouse splenic lymphocytes in which transformation was induced by bacterial lipopolysaccharide (LPS), a specific B-cell mitogen. The results were compared with a similar analysis of germinal center lymphocyte populations of normal human spleen. In the in vivo mouse model, initial stages of B-cell transformation were detectable as early as 4 hours after LPS injection, and the process was essentially fully developed by 48-72 hours. Quantitative evaluation revealed that the majority of nuclear profiles were nearly spherical or only slightly eccentric and that no major alteration in nuclear contour occurred during any phase of the progressive increase in nuclear size following mitogen-induced lymphocyte transformation. In fact, in this system, B lymphocytes with a nuclear profile cleft of greater than or equal to 0.4 mu accounted for only 3% of the combined unstimulated and LPS-activated population assessed (N = 9936). This compared with normal human spleen, in which 16% of germinal center lymphocyte populations had similarly cleft nuclear profiles. Sequential alterations in the organization of condensed chromatin occurred concomitant with gradual nuclear enlargement during mitogen-induced mouse spleen lymphocyte transformation. A comparative morphologic and morphometric assessment of nuclear profiles of lymphocyte populations in germinal centers of normal human spleen provides indirect evidence for a similar pattern of nuclear alterations in human B lymphocytes. Autoradiographic data obtained from LPS-activated mouse splenic lymphocytes indicate that nuclear morphologic aspects of the transformation process can occur entirely within the G1 phase of the cell cycle. The results of this study suggest that subtypes of non-Hodgkin's lymphoma largely composed of neoplastic lymphocytes with extensively convoluted or cleft nuclei do not reflect a morphologic stage in the transformation of normal lymphocytes. In addition, the heterogeneous nuclear forms of follicular center cell lymphocytes would appear to result from parallel transformation processes involving cleaved and noncleaved nucleated lymphocytes and not the sequential pathway proposed by Lukes and Collins.