Giant desmosomes in tumors.

The lengths of desmosomal profiles were measured in sections of tumor tissue from cases of mesothelioma, adenocarcinoma, squamous cell carcinoma, thymoma, and meningioma. Giant desmosomes (length of profile 1 micron or greater than 1 micron) were found in all the above-mentioned tumors except adenocarcinomas. The largest desmosomal profile in adenocarcinoma was approximately 0.8 micron long; the largest in mesothelioma was approximately 2 microns long. Our observations suggest that one of the ways in which giant desmosomes arise is by growth and fusion of adjacent desmosomes. Giant desmosomes may at times help in distinguishing mesothelioma from adenocarcinoma, but this is a rather rare phenomenon. In this study giant desmosomes were found in only 2 out of 10 cases of mesothelioma.

An ultrastructural morphometric study of follicular center lymphocytes: III. The control of lymphocyte nuclear size in reactive hyperplasia and non-Hodgkin's lymphoma.

Since lymphocyte nuclear size and shape play such a key role in the classification of non-Hodgkin's lymphoma (NHL), the mechanisms and nuclear compartments responsible for the control of nuclear size are of fundamental importance to pathologists. To assess the role of condensed chromatin and the interchromatinic region of the nucleus in determining the size of this organelle, morphometric image analysis of total nuclear area and the area occupied by these two compartments was performed on electron micrographs of nuclear profiles from lymphocytes in lymph node biopsies of four cases of reactive lymphoid hyperplasia and ten examples of NHL. Using bivariate linear regression analysis, it was clear that, whether in normal mantle zone and follicular center lymphocytes or in the neoplastic lymphocytes of various NHLs, there is an extremely high correlation (R = 0.96) between the size of the interchromatinic region and the area of nuclear profiles. In contrast, there is a poorer correlation (R = 0.63) between the area occupied by condensed chromatin and nuclear area. The results demonstrate for the first time that even in NHL, where some nuclear features clearly vary from the normal counterpart, the control of nuclear size continues to be largely dependent on a particular subcompartment of the nucleus, the interchromatinic region. How this fact influences the categorization of subtypes of NHL for therapeutic and prognostic purposes will be an essential avenue for further investigation.

Ultrastructural morphometric study of follicular center lymphocytes: II. Analyses of cleaved-cell populations do not support the Lukes-Collins' concept.

Ultrastructural morphometric analysis was carried out on six cases of lymph node biopsies with reactive hyperplasia to establish the frequency and depth of invaginations in nuclear profiles situated in the mantle zones and follicular centers. The frequency distribution of the depth of invaginations was similar in nuclear profiles whether in the small lymphocytes of mantle zones or the small, partially transformed (centrocytes) and fully transformed (centroblasts) lymphocytes of follicular centers. Invaginated and cleaved lymphocytes were not confined to the partially transformed (centrocytic) lymphocytes of follicular centers, and nuclear profiles with invaginations bore no resemblance to those depicted in the Lukes-Collins model. A considerable proportion of mantle zone lymphocyte nuclear profiles had invaginations (ranging from 7.5% to 53.6%) and there was no difference between the frequency of deep indentations or clefts in mantle zone lymphocytes (8.1 +/- 5.4%) and the small unstimulated (9.3 +/- 5.3%) and partially transformed (8.4 +/- 1.4%) lymphocytes in follicular centers. Computer modeling of stylized nuclei with conical indentations indicated that all lymphocytic nuclei likely have multiple invaginations or groove-like creases.

Ultrastructural morphometric study of follicular center lymphocytes: I. Nuclear characteristics and the Lukes-Collins' concept.

A combined ultrastructural and morphometric image analysis study was carried out on the nuclear profiles of follicular center and mantle zone lymphocytes of six cases of reactive hyperplasia in human lymph node biopsies. For accuracy of morphological observations and sampling at low magnifications, sections were mounted on formvar-covered slot grids. Measurements of nuclear profile features of small (untransformed) lymphocytes in mantle zones served as the standard for a supposed unimodal population in each case. Analysis of nuclear profile area values indicated that during lymphocyte transformation in follicular centers nuclei had a gradual and progressive increase in size and that the sampled nuclear profiles in both the mantle zone and follicular center were unimodal. Lymphocyte nuclear shape (contour index) was a more complex, and likely biologically independent, feature than nuclear area in both the mantle zone and follicular center. Nuclear profile contour indexes of mantle zone lymphocytes were more irregular than suspected and in some cases had mean values greater than those of follicular center lymphocytes. Furthermore, the frequency distribution of nuclear contour index was not normally distributed in either the follicular center or mantle zone due to the presence of a small proportion of highly irregularly shaped nuclear profiles in both sites. The results indicated that some premises of existing concepts of follicular center cells and the process of lymphocyte transformation in follicular centers were incorrect and should not be directly extrapolated to the nuclear profile characteristics in non-Hodgkin's lymphoma.

Salivary gland myoepithelioma variants. Histological, ultrastructural, and immunocytological features.

The histological and ultrastructural features of five major salivary gland tumours, which have little or no evidence of duct- or gland-type differentiation in routine sections, are described. Four of the cases have the tumour cells organized as narrow, anastomosing cords of cells separated by a myxoid and vascularized stroma; we have designated such lesions as reticular-type myoepitheliomas. The fifth case has a solid growth pattern and is largely composed of hyaline cells, that is, a plasmacytoid myoepithelioma. Ultrastructurally, one reticular myoepithelioma reveals myoepithelial cell differentiation with microfilament aggregates, while the other three examples are composed of modified myoepithelial cells displaying widened intercellular spaces, prominent synthesis of extracellular glycosaminoglycans, distinct basal lamina development, and obvious accumulations of cytoplasmic intermediate filaments. In electron micrographs, the modified myoepithelial cells of the plasmacytoid variant closely resemble the tumour cells in the reticular form. Three cases had expression of both glial fibrillary acid protein (GFAP) and vimentin, but only one of the myoepitheliomas contained muscle-specific actin. At least focally, each of the cases exhibited a considerable spectrum of cytokeratin filaments. Using double-labeled immunofluorescent microscopy of one reticular variant and the plasmacytoid myoepithelioma, there was individual tumour cell co-expression of GFAP and vimentin focally in the plasmacytoid myoepithelioma, but co-expression of cytokeratins 13, 16 and GFAP were not noted in either case. As expected, co-expression of high- and low-molecular weight cytokeratin filaments was widespread in both myoepitheliomas. Most described myoepitheliomas have a solid growth pattern and are composed of spindle and plasmacytoid cells, but based on cytological features and growth patterns in this series, it is apparent that polygonal-shaped cells with novel architecture can occur in myoepitheliomas. The results also indicate the close relationship between pleomorphic adenoma and such variants of myoepithelioma.

Low magnification transmission electron microscopy in diagnostic pathology.

Transmission electron microscopy examination of selected diagnostic specimens, that is, renal and nerve biopsies, can be greatly facilitated by the implementation of slot grid preparations that are inherently devoid of any grid bars. Such preparations are conducive to screening and photography at both low and intermediate modes of magnification without any apparent loss of resolution. The use of this technique in diagnostic electron microscopy is simplified by sequential en bloc staining with both uranyl and lead salts.

Isolation and characterization of the 'photosynthetic' phosphoglycerate kinase from Beta vulgaris.

1. Phosphoglycerate kinase has been isolated from a photosynthetic plant tissue, Beta vulgaris leaves. The purification procedure is described. 2. The best preparation had no detectable impurity on electrophoresis, and had a specific activity comparable with the same enzyme from other sources. 3. The molecular weight was not distinguishably different from that of the yeast or muscle enzyme, as measured by polyacrylamide-dodecylsulphate electrophoresis. Measurement of aromatic and sulphydryl residues indicated a close similarity with the yeast enzyme. The enzyme appears to have substantially lower isoelectric point than phosphoglycerate kinases from other sources. 4. Kinetic studies indicated that the affinities for the substrates MgATP2- and 3-phosphoglycerate were not significantly different from those of the 'glycolytic' yeast enzyme. There was no evidence that the B. vulgaris enzyme had specific properties making it more suitable for its gluconeogenic rather than glycolytic role.