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I Dardick

Publications and source records attributed to I Dardick.

At least 73 records · Page 4Linked to original sources

Comparative histogenesis and morphogenesis of mucoepidermoid carcinoma and pleomorphic adenoma. An ultrastructural study.

Current classifications of salivary gland tumors separate mucoepidermoid carcinoma from other neoplasms on the basis of a number of histological features, in particular the lack of participation of neoplastic myoepithelial cells. However, ultrastructural examination of low- and intermediate-grade mucoepidermoid carcinomas and pleomorphic adenomas reveals many common organizational and cellular features. Of prime importance is the relationship of intermediate cells to the luminal cells in mucoepidermoid carcinomas, which is remarkably similar to that seen between modified myoepithelial cells and luminal cells in pleomorphic adenomas. The results suggest that intermediate cells of mucoepidermoid carcinoma are the counterpart of the modified myoepithelial cells of pleomorphic adenoma. The generally accepted hypothesis that the former tumor develops from an excretory duct reserve cell, while the latter originates from an intercalated duct stem cell does not seem to be valid; pleomorphic adenoma and mucoepidermoid carcinoma appear to be closely related morphologically.

Adenoma, Pleomorphic↗

A review of the proliferative capacity of major salivary glands and the relationship to current concepts of neoplasia in salivary glands.

The classification of salivary gland tumors relies heavily on histogenetic postulates. One of these, the semipluripotential reserve cell theory, suggests that certain reserve cells in specific segments of the duct system of major and minor salivary glands are critical to the development of neoplasms in these glands. However, direct evidence in support of this hypothesis is unavailable. This survey of proliferative capacity in normal salivary gland is based on a review of data in the literature, our observations of DNA synthetic and mitotic activity in developing rat and human salivary gland, and autoradiographic studies of induced cell proliferation in rat salivary gland. Autoradiography of neonatal rat salivary gland after tritiated thymidine administration, and electron microscopy of these tissues, reveals that as well as duct basal cells, luminal cells at all levels of the duct system and even acinar cells are capable of DNA synthesis and mitosis. Indeed, in such studies, more luminal than basal cells are seen in mitosis. In adult rat salivary gland induced to undergo hyperplasia, more acinar cells than intercalated duct cells are in the S phase of the cell cycle. However, cycling cells were observed even in striated ducts and, importantly, both basal and luminal cells of major interlobular excretory ducts are also labeled. Similar findings are present in fetal and adult human salivary glands. From such observations, it is evident that dividing cells are not limited to basal cells of excretory ducts and luminal cells of intercalated ducts, so that there is no support for the semipluripotential bicellular reserve cell hypothesis. However, there is considerable evidence for a multicellular theory of tumor histogenesis; that is, any of the multiplicity of cell types in normal salivary gland have the potential to give use to any of the various types of tumor occurring in this organ.

Animals↗

Ki-1-positive non-Hodgkin's lymphomas. An immunophenotypic, ultrastructural, and morphometric study.

The authors studied four cases of diffuse, large cell non-Hodgkin's lymphomas with strong Ki-1 expression to determine if they shared characteristic ultrastructural or morphometric features in common. The tumor cells in these lymphomas all had very abundant cytoplasm, which often showed a concentration of organelles, especially mitochondria and Golgi apparatus, in regions next to nuclear concavities. One case had very complex cytoplasmic membrane projections resembling a "microvillous" lymphoma. These ultrastructural features combined with the frequent reniform nuclei and scattered lysosomes suggested histiocyte differentiation. However the immunophenotype was variable, more often showing "activation" markers and abnormal T-cell marker patterns. The mean nuclear area for all cases was between 38.3 +/- 12.7 to 42.3 +/- 16.2 microns2, roughly twice the size of the small lymphocyte population. The nuclear contour index, a measure of irregularity of the nuclear membrane, ranged from 4.75 +/- 0.86 to 6.36 +/- 1.89 (a circle is 3.54). These nuclear parameters are comparable in size to those of previously measured large cell lymphomas but exhibit more nuclear irregularity than most. Ki-1 lymphomas appear to represent a somewhat diverse group of tumors of lymphoid origin that exhibit some hybrid features of histiocytes.

Adult↗

Basal epithelial cells of human prostate gland are not myoepithelial cells. A comparative immunohistochemical and ultrastructural study with the human salivary gland.

The hypothesis that basal epithelial cells of the human prostate are of myoepithelial origin was investigated using immunohistochemical and ultrastructural methodologies. The immunohistologic analyses show significant phenotypic differences between prostatic basal cells and myoepithelial cells of the salivary gland. Although both cell types stain intensely with the 312C8-1 monoclonal antibody, only true myoepithelial cells demonstrated significant amounts of muscle-specific actin as decorated by the HHF35 monoclonal antibody. Furthermore, using double-labeling experiments, the prostatic basal cells were strongly decorated with a fluorescein-tagged basal cell-specific keratin but were negative with the rhodamine-tagged phalloidin, a chemical that binds specifically to actin microfilaments. Ultrastructural studies also showed an absence of thin microfilament bundles, dense bodies, and micropinocytotic vesicles in the prostatic basal cells. The current investigations show that the prostatic acini do not have a basal myoepithelium. Although some authors have suggested a stem cell role for prostatic basal cells, the weight of experimental work argues against this hypothesis. The exact role of the basal epithelial cells of the prostate is not known, although they may serve endocrine, paracrine, or other regulatory functions and may be involved in modulating signals between prostatic stroma and epithelium.

Actins↗

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.

Cell Nucleus↗

A pseudo-malignant Warthin's tumor presenting with facial nerve paralysis.

Facial nerve paralysis, in association with a parotid mass, is generally considered pathognomonic of malignancy. However, nine cases of paralysis with benign tumors have been reported: four in association with a pleomorphic adenoma, three with a Warthin's tumor and one with an oncocytoma. The details of these cases are described and an additional case of Warthin's tumor causing a facial paralysis is reported. In all four cases of Warthin's tumor the pathology is similar, with inflammation, fibrosis and necrosis, especially in areas surrounding branches of the facial nerve. In view of the 10 cases reviewed herein, it is suggested that the pathology be confirmed at the time of surgery and every effort made to preserve facial nerve function.

Adenolymphoma↗

Ultrastructural study of acinar and intercalated duct organization of submandibular and parotid salivary gland.

According to some current hypotheses, the morphology and organization of the intercalated duct/acinar interface of salivary gland have implications for the induction of tumors in this organ. However, this region has received limited detailed investigation. To study the organization of the terminal ductal segments of salivary gland, conventional transmission electron microscopy of human parotid and submandibular glands and canine submandibular gland was combined with 3-dimensional observations of polymer casts of the canine submandibular ductal system; the latter were prepared by retrograde injection of acrylic resin via the main excretory duct with subsequent digestion of the gland tissue. The division of intercalated ducts, into first- and second-order branches, and acinar arrangement is more complex than previously suggested. The entire surface of each elongated second-order intercalated duct is covered with acini projecting in all directions. In the human gland, some acini abut directly on the intercalated duct surface, whereas others are connected by a short stalk of intercalated duct cells; in comparison with canine submandibular gland, the latter may be a modification producing a third-order of the intercalated duct unit. All of these features combine to produce a highly efficient secretory apparatus with a large proportion of acinar cells to each intercalated duct.

Animals↗

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.

Actins↗

A case of a Ki-1 large cell anaplastic lymphoma with ultrastructural features.

A 29-year-old woman first presented in 1982 with a large cell lymphoma, initially thought to be of histiocytic origin on the basis of prominent sinus infiltration. She had a complete response to chemotherapy, but relapsed in 1987. Histologically, a repeat biopsy was identical to the first. Immunocytochemically, there was strong reactivity with Ki-1 antibody and histiocyte lineage markers, but all specific T cell markers were negative. Southern blot hybridization demonstrated a clonally rearranged band with the T cell receptor (T beta) probe. Ultrastructurally, the cells showed sparse organelles except for prominent paranuclear Golgi apparatus, frequent reniform nuclear indentations, and ruffled cytoplasmic membranes. This case appears to represent a Ki-1-positive lymphoma with the hybrid features of an activated T lymphocyte and a histiocyte.

Adult↗

The measurement of surface area of endometriotic implants by morphometric analysis.

There are numerous staging methods for the assessment and evaluation of endometriosis both before and after treatment. Present systems rely on subjective criteria that are prone to bias and error. This report describes an objective technique for the measurement of surface area of pelvic endometriotic implants that is both accurate and reproducible. Six patients with endometriosis underwent laparoscopy and were staged using the Revised American Fertility Society criteria; the lesions were photographed simultaneously. These patients were then treated with either danazol or Nafarelin acetate for 6 months before a second-look laparoscopy. Using coded photographic slides, implants were measured using computerized morphometric analysis. An accurate record of the number and surface area of the lesions was obtained before and after treatment. The mean surface area of individual lesions and the total visible disease per patient fell by 89 and 82%, respectively. The mean number of lesions per patient actually rose by 30% as a result of fragmentation into smaller plaques. These data suggest that morphometry may be more valuable in the assessment of endometriotic implants than are all previously described staging systems.

Endometriosis↗

Nuclear antigens in neoplastic lymphocytes of B cell and T cell non-Hodgkin's lymphomas.

Gross nuclear morphology is a major diagnostic feature in the identification of subtypes of non-Hodgkin's lymphoma (NHL). The authors have shown that the size, shape, and chromatin distribution of the lymphocyte nuclei vary extensively both within and between samples of a subtype, and have proposed that the variations may reflect qualitative and quantitative differences in extrachromatinic components. To test this hypothesis, the organization of individual nuclear antigens in NHL and in reactive hyperplasia biopsies was examined by immunofluorescence labeling of frozen sections with previously characterized monoclonal antibodies. The results have been correlated with observations of the staining patterns produced by the antibodies in mitogenically stimulated human peripheral blood lymphocytes. Labeling pattern and intensity with each antibody were consistent between preparations of blood lymphocytes, and all four antibodies labeled all blood lymphocyte samples tested. In contrast, only 15% of the 53 biopsies were labeled by all four antibodies, although all were stained by anti-peripherin, nearly 80% by I1, and almost 60% by PI1. Antibody PI2 labeling was detected in only 20% of the samples. Variation in labeling intensity was equally extensive both within and between biopsy samples. In general, there was little homogeneity between samples of an NHL subtype as to which antigens were detected, their labeling intensity, or their pattern of intranuclear distribution. These observations are consistent with earlier reports of significant diversity in the morphology of nonchromatin components in such samples. The data support the proposition that the heterogeneity of gross nuclear morphology in nuclei of NHL biopsies may be due in part to disordered expression or abnormal organization of nuclear proteins.

Antibodies↗

Intermediate filament expression in normal parotid glands and pleomorphic adenomas.

A comparative immunohistochemical study of intermediate filament expression in normal parotid glands and pleomorphic adenomas (PA) was performed using material fixed in a modified methacarn fixative. The normal myoepithelial cells of acini stained only with monoclonal antibodies 312C8-1 (cytokeratin (CK) 14) and 4.62 (CK 19) while myoepithelial/basal cells of ducts also reacted with antibodies 8.12 (CK 13, 16), 8.60 (CK 10, 11, +/- 1), and PKK1 (CK 7, 8, 17, 18). Normal duct luminal cells showed a different CK profile, reacting consistently with ECK, a polyclonal antibody to epidermal prekeratin (CK 3,6), and monoclonal antibodies 4.62, PKK1 and 8.60. In PA, tumour cells at the periphery of ducts, in solid areas, and at the edge of myxoid regions all had CK profiles similar to normal myoepithelial/basal cells except that antibody 4.62 was generally negative. Vimentin and glial fibrillary acidic protein (GFAP) were uniformly negative in normal parotids but showed variable (often strong) reactivity with some cells in chondroid, myxoid and solid areas of PA. A surprising feature of most PA was the variability of CK subtype expression not only from one case to another but also within morphologically similar areas of the same specimen. These results suggest that the morphology of PA is the result of diversity of tumour cell differentiation rather than the processes implicit in a reserve cell histogenetic model.

Adenoma↗

Characterization of cytoskeletal proteins in basal cells of human parotid salivary gland ducts.

From previous immunofluorescent, immunohistochemical and ultrastructural studies, myoepithelial cells have been reported to be absent from the striated and excretory ducts of human salivary gland. Yet recently, certain anti-cytokeratin monoclonal antibodies which specifically label the myoepithelium of salivary gland acini and intercalated ducts have also been found to stain basally situated cells in both striated and excretory ducts. In this study, we have used eight samples of normal human parotid gland (methacarn-fixed and frozen sections) to establish if basal cells of striated and excretory ducts have the cytoskeletal protein complement (actin and cytokeratins) of myoepithelial cells. Using a muscle-specific actin, HHF35, not only is the myoepithelium of acini and intercalated ducts stained in all cases, but stellate and spindle shaped cells are also detected all along the inter- and intralobular striated ducts in four of the eight examples. With double-labeled frozen sections and fluorescent microscopy, the actin-specific probe, phalloidin, and the myoepithelial-selective anti-cytokeratin 14 antibody, 312C8-1, confirm that the striated duct does have a population of basal cells with the cytoskeletal protein make-up of myoepithelium. The monoclonal antibody 8.12 (specific for cytokeratin 13 and 16) also stains some basal cells of striated and excretory ducts, as well as luminal cells of ducts at all levels, but does not label the myoepithelium of acini and intercalated ducts. Both the anti-cytokeratin antibodies and the actin-detecting mechanisms reveal that the basal cell population of striated and excretory ducts is more heterogeneous, and likely functionally more complex, than has been realized previously. Such findings are not in agreement with certain aspects of current theories of the histogenesis of salivary gland tumours.

Actins↗

Polymorphous low-grade adenocarcinoma: a case report with ultrastructural findings.

A specimen of a polymorphous low-grade adenocarcinoma of minor salivary gland origin in the nose, originally diagnosed as an adenoid cystic carcinoma, was examined by electron microscopy. The tumor cells forming narrow, anastomosing trabecular cords in histologic sections were almost exclusively well-differentiated myoepithelial cells when examined with the electron microscope. Adenoidal regions within and between the columns of tumor cells resulted from the production of excessive amounts of basal lamina and glycosaminoglycans. In one focal region, glandular lumina were formed within the trabecular cords and more solid regions of the tumor. By both immunohistochemistry (anticytokeratins and anti-S 100 protein) and electron microscopy, transitions from the principal tumor cells comprising the trabecular cords (myoepithelial cells) to luminal epithelial cells could be detected. Since the patient is free of recurrence or metastases 7 years after limited surgical resection of the tumor, the designation of polymorphous low-grade adenocarcinoma seems quite appropriate.

Adenocarcinoma↗

Morphologic studies of lymphocyte nuclei in follicular and diffuse mixed small- and large-cell (lymphocytic-histiocytic) lymphoma.

Twelve examples of mixed small- and large-cell lymphoma (eight follicular, one follicular and diffuse, and three diffuse) were investigated morphometrically using plastic-embedded tissue in order to study nuclear characteristics of lymphocyte populations in this form of non-Hodgkin's lymphoma (NHL) and to test morphologic bases for current NHL classification systems. This study illustrates that there are many inaccuracies, illusions, and misconceptions in the morphologic criteria currently used to classify mixed small- and large-cell lymphoma. A principal finding was that lymphocyte nuclear profiles in mixed-cell lymphomas tend to be smaller in size (P less than .005) and more irregular in shape (P = .0001) than the morphologically similar counterparts in germinal centers of lymph nodes with reactive hyperplasia. Intercase comparison of mixed small- and large-cell lymphomas revealed a considerable range of mean nuclear area values, some of which were within the size range of normal, small lymphocytes. At the magnifications used for morphometric assessment, a high proportion of lymphocyte nuclear profiles had shallow invaginations, but only a limited number of profiles (4% to 14%) had deep (cleaved) indentations. Contrary to current definitions for this subtype of NHL, lymphocytes with "small" nuclei had the same proportion of the nuclear diameter occupied by nuclear invaginations as lymphocytes with "large" nuclei and, in fact, mean nuclear invagination depth was shallower in "small" nuclei than in "large" nuclei. Furthermore, regardless of whether it is nuclear area or shape that is evaluated, lymphocytes in mixed-cell lymphoma do not separate into two populations of small-cleaved and large noncleaved cells. Morphometry reveals that only four of the 12 examples of mixed small- and large-cell lymphoma had a proportion of the lymphocytes in the size range of fully transformed germinal center lymphocytes that exceeded 25%, and none of the cases approached 50% even though the population of lymphocyte nuclei appearing "transformed," and therefore "large," ranged from 28% to 57%. Such results indicate that the large, noncleaved and cleaved component, as seen in histologic sections of mixed small- and large-cell lymphoma, do not have nuclei of uniform size and many, in fact, are not actually large. The morphometric findings indicate reasons for the poor observer reproducibility in classifying this subtype of NHL.

Cell Nucleus↗