Ultrastructural morphology and cellular differentiation in acinic cell carcinoma.

Acinic cell carcinomas, in some instances, contain a component of intercalated duct cells. However, the manner in which this element is integrated within the more obvious acinar cells, as well as the role neoplastic intercalated duct cells play in determining morphologic patterns in acinic cell tumors, has not been fully investigated. Ultrastructural study and immunostaining with antibodies to cytokeratins and to S-100 protein carried out in nine cases of parotid acinic cell carcinoma suggest two basic differentiation patterns. In three cases, the lesions were essentially composed of acinar cells (with variation in the number and form of secretory granules), and one of these tumors was unique in having ultrastructural evidence of differentiated myoepithelial cells. In the second group of six cases, there was light microscopic, ultrastructural, and immunohistochemical evidence of a significant component of intercalated duct cells. By means of both immunostaining (intercalated ducts were positive for keratin and S-100 protein; acinar cells were negative for both antigens) and electron microscopy, flattened-to-cuboidal intercalated duct cells were noted to enclose and, presumably, to be involved in the formation of microcystic spaces. Acinic cell carcinomas with a more solid growth pattern contained groups of intercalated duct cells positive for keratin and S-100 protein. Ultrastructurally, these cells were organized into well-formed ducts related to nests of acinar cells. Acinic cell carcinoma is another class of salivary gland tumor in which there can be an integrated proliferation of intercalated duct and acinar cells and, infrequently, of myoepithelial cells, all organized in a simulation of the intercalated duct-acinar unit of the normal salivary gland.

Nuclear morphologic and morphometric analyses of nodular poorly differentiated lymphocytic lymphoma: assessment of small cleaved nuclei.

Comparative analytic measurements of nuclear parameters in normal and neoplastic lymphocytes are limited. In the present morphometric study lymphocyte nuclear features in 21 cases of nodular poorly differentiated lymphocytic lymphoma (NPDLL) were assessed with respect to the theoretical aspects of some non-Hodgkin's lymphoma (NHL) classifications. The mean nuclear area of the lymphocytes in NPDLL is generally within the range of the areas of unstimulated (mature) lymphocytes of mantle and follicular regions of lymph nodes with reactive hyperplasia. On this basis, the neoplastic lymphocytes in NPDLL do not reflect, at least cytologically, the antigen-activated, transforming lymphocytes of normal follicular centers. All measured nuclear parameters of small, unstimulated lymphocytes of neoplastic follicles suggest that major proportions of this component are also part of the neoplastic cohort. Sectional nuclear profiles in NPDLL are much more irregular in shape and have a higher percentage of invaginations than normal lymphocytes. However, only 4 to 5 per cent of nuclear profiles in NPDLL are of sufficient depth to be termed clefted. Serial section reconstruction of both normal and neoplastic lymphocytes indicates the degree to which the numbers of invaginated or clefted nuclei are underestimated in the examination of histologic sections. For example, the 4 to 5 per cent of nuclear profiles with clefts in histologic sections of NPDLL actually represent about 25 to 30 per cent of the lymphocyte population. On the basis of computer modeling of stylized nuclei with simple invaginations of varying depths and serial section reconstruction of normal and neoplastic nuclei, it is likely that all lymphocyte nuclei have some form of nuclear membrane invagination and that in poorly differentiated lymphomas these invaginations may be single and multiple discrete indentations or linear, branching grooves. Assessment of the ratio of nuclear invagination depth to nuclear diameter in normal and neoplastic lymphocytes indicates that transforming normal lymphocytes in follicular centers do not undergo a phase of increased nuclear clefting and that this ratio is somewhat greater in lymphocytes in NPDLL than in follicular center lymphocytes. However, the latter effect is not due to increased depth of nuclear invaginations in NPDLL, but rather results from the fact that mean nuclear diameter in this subtype of NHL is considerably smaller than that of normal lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Non-Hodgkin's lymphoma classification: ultrastructural morphometric studies for the quantification of nuclear compartments in situ.

The condensed chromatin distribution in the nuclei of lymphocytes in non-Hodgkin's lymphoma (NHL) is a key element, along with nuclear size and shape, in the classification of this disease for therapeutic and prognostic purposes. This report describes the ultrastructural comparative quantification of the condensed chromatin and the interchromatinic (nuclear matrix or euchromatin) region in the nuclei of mitogen-stimulated human peripheral T lymphocytes and mouse spleen B lymphocytes, human germinal center lymphocytes, and lymphocytes in ten cases of NHL of a variety of subtypes. The sequential morphologic nuclear changes induced in lymphocytes by mitogens are reflected in human germinal center lymphocyte populations. The common features include the changes in the distribution and volume of condensed chromatin aggregates, as well as the fact that the major increments in nuclear volume during lymphocyte transformation result from increases in the volume of the interchromatinic region. In all subtypes of NHL analyzed morphometrically, subpopulations of lymphocytes were identified in which mean nuclear, condensed chromatin, and interchromatinic volumes were more or less equivalent to those of normal lymphocyte subsets in germinal centers in reactive hyperplasia. However, in NHL the abnormal cytologic characteristics of the nucleus result, at least in part, from a complex interplay of condensed chromatin distribution and amount, and the size of the interchromatinic region. Further complexity is introduced by the fact that in NHL these two nuclear compartments can independently be normal, increased, or reduced in size. Morphometric quantification of lymphocytes in NHL indicates that the interchromatinic (matrix) region of the nucleus is the key element in establishing the nuclear volume of neoplastic lymphocytes. The structural and functional, ribonucleoprotein interchromatinic region of the nucleus was visualized in normal and neoplastic lymphocytes by regressive uranyl-EDTA staining. Quantitative morphometric analysis indicates that the cytologic appearance of neoplastic lymphocytes, even within subtypes of NHL, is heterogeneous and that condensed chromatin quantity and distribution may be more critical than nuclear size in distinguishing between certain subtypes of NHL. Improvements in the classification of NHL will occur only with understanding of the alterations in the biologic mechanisms controlling gross nuclear organization and the morphologic events of the various differentiation pathways available to antigen-stimulated lymphocytes.

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.

Pleomorphic adenoma, I: Ultrastructural organization of "epithelial" regions.

Twenty-four major and minor salivary gland pleomorphic adenomas were studied ultrastructurally to determine the growth patterns, organization, and cytologic modifications of the proliferating neoplastic cells. In compact and highly cellular regions, two cell types--luminal epithelial and myoepithelial--could often be identified; their organization mimicked that of the normal salivary gland duct or acinar unit. Results of the study indicate that the principal proliferating tumor cell is a structurally modified myoepithelial cell that frequently shows squamous differentiation. At the immediate margins of cellular regions of many tumor cells, gradual dedifferentiation of modified myoepithelial cells with a loss of squamous features occurs, although in some cells the squamous features are retained to varying degrees. Within cellular regions, the earliest development of matrix occurs in relation to small, basal lamina-lined extracellular spaces between myoepithelial-like cells. Modifications of such intercellular spaces are helpful in tracing the development of myxoid zones and the evolution of cell types in this unique region. The authors postulate that salivary gland pleomorphic adenomas result from the neoplastic transformation of the complete ductal-acinar unit rather than from one particular ductal "reserve" cell.

Pleomorphic adenoma, II: Ultrastructural organization of "stromal" regions.

Findings from an ultrastructural study of 24 major and minor salivary gland pleomorphic adenomas suggest that the principal cell type in the myxoid and chondromyxoid regions of these tumors is a structurally modified myoepithelial cell. This interpretation is based on findings in the transitional zone between myxoid regions and compact cellular areas that have a ductal-acinar organization, that is, are composed of luminal epithelial and modified myoepithelial cells. Survey-type low-power electron micrographs allowed appreciation of the original orientation of the major proliferating component of these tumors to the perimeter of ductal-acinar units. The low-power electron micrographs also revealed residual features of this organization, the early development and subsequent sequential alteration of matrix compartments as tumor cells became increasingly separated by extracellular products, and a variety of myoepithelial cell modifications, such as squamous and chondroid metaplasia, resulting from neoplastic induction. According to the authors' interpretation, modified myoepithelial cells in myxoid and chondromyxoid regions form a continuum with similar tumor cells in transitional and solid areas, forming what can be visualized as markedly expanded and merging ductal-acinar units that tend to converge with similarly altered adjacent neoplastic ductal-acinar units. Thus, a multiplicity of processes are involved in the formation of the complex and varied histologic patterns that characterize pleomorphic adenomas.

Synovial sarcoma arising in an anatomical bursa.

In previous studies, the origin of synovial sarcoma directly from synovium has not been satisfactorily established. This case report describes the light and electron microscopic features of a biphasic synovial sarcoma occurring within the popliteal fossa. At surgery, a cystic mass was identified in relationship to the semitendinosus tendon at the anatomical site of the semitendinosus bursa. The tumour originated from the inner surface of the bursa as multiple papillary projections with no evidence of extension beyond the capsule of the bursa. Portions of the synovial surface were hyperplastic but otherwise normal. The findings indicate that biphasic synovial sarcoma can arise directly from synovium and support the hypothesis of a mesenchymal histogenesis for this tumour.