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Biomedical subjects

I Dardick

Publications and source records attributed to I Dardick.

At least 91 records · Page 5Linked to original sources

Primary thyroid thymoma: a distinct clinicopathologic entity.

A 51-year-old man presented with a paratracheal tumor. He had undergone resection of a thyroid tumor 15 years previously; at that time, the histologic diagnosis had been anaplastic carcinoma. When the tumor recurred, the presumptive clinical diagnosis was medullary thyroid carcinoma. Histologic examination revealed a poorly differentiated epithelial tumor with immunoreactivity for keratins, carcinoembryonic antigen, and, focally, S-100 protein. The tumor was negative for calcitonin and thyroglobulin. There were scattered lymphocytes and plasma cells. Ultrastructural examination showed elongated epithelial cells with prominent desmosomes and bundles of cytoplasmic tonofilaments but no secretory granules; amyloid was not present ultrastructurally or histochemically. The characteristic ultrastructural and immunocytochemical features and the clinical behavior of this tumor verify the existence of primary thyroid thymoma. This new primary thyroid neoplasm is of clinical importance, considering the more benign behavior of primary thyroid thymoma than of other tumors in the differential diagnosis of this lesion.

Adult↗

Culture of granulosa cells in collagen gels: the influence of cell shape on steroidogenesis.

The gonadotropic regulation of granulosa cells steroidogenesis in vitro has been shown to be accompanied by cellular rounding. In this study, the possible relationship between cell shape, microtubules, and granulosa cell steroidogenesis in vitro was further explored by culturing (24 h) granulosa cells obtained from antral follicles of pregnant mare's serum gonadotropin-treated rats in either Eagles's Minimum Essential Medium alone (MEM-cells) or in collagen gels (GEL-cells) in the absence or presence of colchicine, a microtubule-depolymerizing agent previously shown to inhibit cell-spreading in vitro. Cellular morphology was assessed by electron microscopy and compared with that seen in vivo. In addition, the influence of the various culture conditions on progesterone and 20 alpha-hydroxy-pregn-4-en-3-one (20 alpha-OH-progesterone) secretion was determined by specific radioimmunoassays. Whereas the majority of granulosa cells in sections of antral follicles appeared rounded in shape, cells cultured in MEM underwent considerable spreading and assumed a variety of shapes at the end of 24 h of culture. GEL-cells, on the other hand, remained rounded and had cellular diameters only slightly larger than those observed in vivo. They also secreted more progesterone (almost 3-fold) and less 20 alpha-OH-progesterone (0.6-fold) than MEM-cells. Colchicine increased the secretion of progesterone (1.6-fold) and 20 alpha-OH-progesterone (1.8-fold) comparably in MEM-cells but had no influence on the secretion of either progestin by GEL-cells. Hence, although colchicine-stimulated progestin secretion by granulosa cell monolayers appeared to reflect increased metabolism of substrate-possibly due to a closer association between lipid droplets and mitochondria, the elevated secretion of progesterone by GEL-cells may have been largely due to a shift in the equilibrium between progesterone and its inactive 20 alpha-reduced metabolite. The high ratio of 20 alpha-OH-progesterone to progesterone secretion seen in MEM-cultured cells may be an adaptation of granulosa cell metabolism to culture as monolayers on plastic or glass surfaces. The morphology of GEL-rather than MEM-cells resembled closely that seen in vivo. This culture method may represent a more physiologic approach to the maintenance of granulosa and other steroidogenic cells in vitro and provide a more appropriate means of assessing cytoskeletal function in the regulation of steroid hormone production.

20-alpha-Dihydroprogesterone↗

Warthin's tumor: an ultrastructural and immunohistochemical study of basilar epithelium.

The cellular characteristics of the basilar epithelium in Warthin's tumor have had limited investigation. Ultrastructural examination of basal cells in 9 Warthin's tumors reveals that in addition to numerous mitochondria these cells possess a rich complement of tonofilaments. However, in three examples there are a proportion of these tonofilament-rich cells that have a narrow band of microfilaments in the peripheral cytoplasm adjacent to the basal lamina. Frozen sections of Warthin's tumor and normal salivary glands, doubly labeled with rhodamine-phalloidin for actin and monoclonal antibody 312C8-1 for cytokeratin 14, show that normal myoepithelial cells of acini and intercalated ducts have both of these filaments, as do a proportion of basal cells in the tumor. There are distinct differences in the cytokeratin polypeptide complement between normal luminal and myoepithelial cells as well as between luminal and basal cells in Warthin's tumor. Differences occur in the cytokeratin profiles between the luminal and basal cells of Warthin's tumor and comparable cells in the normal gland; however, there continue to be some similarities in the cytokeratin polypeptides of myoepithelium and the basal cells of normal salivary ducts and the basal cells of Warthin's tumor. These findings show that basal cells in Warthin's tumor are a mixed population with some capable of differentiating as myoepithelial-like cells, and that this tumor could arise from any level of the normal salivary gland duct system.

Adenolymphoma↗

Adenomyoepithelioma of the breast.

This report describes an additional case of adenomyoepithelioma, a rare neoplasm of the breast. The tumor presented as a well-defined mass and, cytologically, appeared to be benign. Histologically, the tumor demonstrated the characteristic bicellular differentiation of luminal epithelial and myoepithelial cells reported in previous adenomyoepitheliomas of the breast. On the basis of histological and immunological features, this tumor appeared to be the counterpart of the clear-cell (glycogen-rich) adenoma and epithelial-myoepithelial carcinoma of the salivary glands.

Aged↗

Morphological alterations of salivary gland parenchyma in chronic sialadenitis.

Ten cases of chronic nonspecific sialadenitis of the parotid and submandibular glands were studied by a combination of immunohistochemistry (to detect cytoplasmic filaments), morphometry, and electron microscopy in order to assess histological modifications that might reflect on the concepts for the induction of neoplasia in these glands. Histologically, the gradual atrophy of the glandular parenchyma results in the presence of many small ductules. Although structural alterations were apparent at all levels of the secretory/excretory glandular components, and in all types of cells, the fact that many such ductules resulted from gradual dedifferentiation of acinar cells was a major finding. The results suggest that no cell-type in salivary gland can be excluded as having a potential for neoplastic transformation and that the basis for the currently held reserve cell hypothesis is likely incorrect.

Actin Cytoskeleton↗

Immunohistochemistry and ultrastructure of myoepithelium and modified myoepithelium of the ducts of human major salivary glands: histogenetic implications for salivary gland tumors.

The organization of salivary gland ducts, especially the presence or absence of myoepithelial cells, is central to histogenetic approaches to the classification of salivary gland tumors. Striated and excretory ducts are reported to be devoid of myoepithelial cells but do contain basal cells. To investigate the nature of such basal cells, tissue sections of normal human salivary glands were examined by means of immunohistochemical, ultrastructural, and fluorescent microscopic techniques. With the use of a mouse monoclonal anticytokeratin antibody (3 12C8-1) that, in salivary glands, is specific for myoepithelial cells, these cells associated with acini and intercalated ducts were strongly stained, as were the basal cells of striated and excretory ducts in each case. Ultrastructurally, some basal cells of both striated and excretory ducts had narrow, elongated cellular processes or the main portion of the cell containing parallel arrays of microfilaments with linear densities and micropinocytotic vesicles, whereas in other basal cells tonofilament bundles predominated. A similar range of cytoplasmic features existed in myoepithelial cells associated with acinar and intercalated duct cells. In addition, some duct basal cells have a complement of actin filaments similar to classic myoepithelium of acini and intercalated ducts. Striated and excretory ducts of human salivary glands, therefore, contain fully differentiated and modified myoepithelial cells, both of which express a specific cytokeratin polypeptide that is absent from duct luminal and acinar cells. Differentiation patterns in the intralobular and interlobular ducts suggest that these regions of salivary gland parenchyma cannot be excluded as histogenetic sites for the induction of salivary gland tumors in which neoplastic myoepithelial cells have been shown to have a major role.

Epithelium↗

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.

Carcinoma↗

Microtubules and the gonadotropic regulation of granulosa cell steroidogenesis.

The involvement of microtubules in the gonadotropic regulation of granulosa cell steroidogenesis was assessed at the preantral (E2-cells) and antral (PMS-cells) stages of follicular development. The influence of agents that alter microtubule-tubulin equilibrium on basal and FSH-stimulated progesterone production was determined in vitro and compared with that on microtubule integrity and organization using immunofluorescence. Basal and FSH-stimulated progesterone production was approximately 2-fold higher in PMS-cells than in E2 cells. Colchicine and nocodazole, two agents that depolymerize microtubules, significantly stimulated progesterone and 20 alpha-hydroxypregn-4-en-3-one production in PMS-cells. Although progesterone production by E2-cells was increased by nocodazole, the amount produced was considerably less than that produced by PMS-cells. FSH-stimulated progesterone biosynthesis was reduced by colchicine and nocodazole in both cell types. Taxol, an agent that stabilizes microtubules, markedly reduced FSH-stimulated progesterone production in both E2- and PMS-cells, but failed to exert a comparable effect on basal steroid production. A close association existed between the concentrations of colchicine, nocodazole, and taxol that altered basal and/or FSH-stimulated steroidogenesis and those that affected microtubule organization and/or distribution. Whereas granulosa cells appeared flattened with numerous cytoplasmic processes after 24 h of culture in medium alone, they were almost spherical and devoid of projections after culture with these agents. FSH-stimulated cells also occupied less area than controls, although cytoplasmic processes were present. These findings indicate an involvement of microtubules in the regulation of granulosa cell steroidogenesis. It is proposed that one of their roles is to facilitate the movement of cholesterol from lipid droplets to mitochondria, possibly by bringing these cellular inclusions closer together.

20-alpha-Dihydroprogesterone↗

Diffuse epithelial mesothelioma: a review of the ultrastructural spectrum.

Traditionally, diffuse epithelial mesotheliomas are mainly identified at the ultrastructural level by the numerous, long, wavy-appearing surface microvilli. By electron microscopy of a series of diffuse mesotheliomas of varying subtype (epithelial, biphasic, sarcomatous, and poorly differentiated), it can be demonstrated that the differentiation of this specialized surface organelle is quite variable even in well-differentiated lesions. The presence of only a few, scattered, short microvilli does not exclude a diagnosis of epithelial mesothelioma, particularly if historical, surgical, and radiologic findings support this diagnostic conclusion. Indeed, even the complete absence of surface microvilli is compatible with a diagnosis of diffuse epithelial mesothelioma. It is important to become aware of the spectrum of tumor cell differentiation in serosal tumors, as all of the fine structural diagnostic criteria in mesotheliomas are expressed to varying degrees in individual cases.

Adult↗

Ultrastructural heterogeneity in malignant fibrous histiocytoma of soft tissue.

Five soft tissue sarcomas with histological features of malignant fibrous histiocytoma were selected to illustrate their ultrastructural heterogeneity. One case displayed the mixture of fibroblastic and histiocytic cells characteristic of the majority of malignant fibrous histiocytomas. In 1 case the tumor was composed entirely of primitive mesenchymal cells. The other 3 cases showed lipogenic, neurogenic, and "granular-cell" differentiation, respectively. These findings emphasize the important role of electron microscopy in the precise diagnosis and classification of malignant fibrous histiocytoma.

Adult↗

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.

Animals↗

Lymphocyte nuclear morphology in diffuse well-differentiated lymphocytic lymphoma. Comparative morphometry of normal lymphoid tissues, non-Hodgkin's lymphoma, and Hodgkin's disease.

Precise morphologic data on the relationship of diffuse well-differentiated lymphocytic lymphoma (DWDLL) to other non-Hodgkin's lymphomas (NHLs) are lacking in current classifications of lymphomas. Morphometry of plastic-embedded tissues describes details of the mean nuclear parameters and distribution of lymphocyte-types in 14 cases of DWDLL in nodal and extranodal sites. The results indicate that the proportion of small (unstimulated or nontransformed) lymphocytes in DWDLL varies from 50% to 86%. The mean nuclear area of small lymphocytes in DWDLL is either within the size range or somewhat smaller, and many examples are more irregular in shape, than the small lymphocytes in germinal centers that are morphologically comparable with the majority of lymphocytes in DWDLL and mantle zones. The morphologic relationship of DWDLL to other NHLs, Hodgkin's disease, and paracortical, mantle, and germinal center lymphocytes in lymphoid-reactive hyperplasia was established by morphometric analysis of the nuclear profiles of small lymphocytes. The small (nontransformed) lymphocytes in those subtypes of NHL other than DWDLL have abnormally small and more irregular nuclear profiles than those in normal small lymphocytes, or the small-lymphocyte population of Hodgkin's disease. Such findings may be of diagnostic significance to pathologists.

Biopsy↗

Follicular center cell lymphoma. Morphologic data relating to observer reproducibility.

Subjectivity and observer variation in non-Hodgkin's lymphoma continues to plague current classification schemes. It was thought important to assess objectively derived morphometric data to see if three categories of follicular center cell (FCC) lymphomas, follicular small cleaved cell, follicular mixed small cleaved and large cell, and diffuse and nodular large cell, actually fall into distinctly separate classes based on nuclear parameters. Mean nuclear area, contour index and invagination depth of neoplastic lymphocytes, and the percentage of invaginated and clefted nuclear profiles in each example of FCC lymphoma were evaluated by three different approaches. Results obtained from distribution of the morphometric data in scatter diagrams, calculation of the overlap index, and linear regression values, all revealed considerable (but variable) degrees of overlap between the three FCC subtypes regardless of the nuclear parameter employed. Where separation between FCC lymphomas was maximal, although still incomplete, there was no consistent correlation between the nuclear parameter and the pair of FCC lymphomas being compared. At least in terms of nuclear morphological features, non-Hodgkin's lymphomas of FCC type seem to represent a continuum of one disease process. The information provides a basis for understanding some reasons underlying the problem of observer variation in non-Hodgkin's lymphoma.

Cell Nucleus↗

Localized fibrous tumour of serosal surfaces. Immunohistochemical and ultrastructural evidence for a type of mesothelioma.

It is uncertain whether localized lesions of serosal membranes have a kinship to mesotheliomas or are truly fibromatous in nature. Ultrastructural and immunohistochemical investigations were carried out on 12 localized benign and malignant pleural and peritoneal tumours from 10 patients. Electron microscopic findings, including the consistent and non-fibroblastic cellular organization of localized neoplasms, the presence of some form of intercellular junctions in 7 of 10 cases, basal lamina deposition in 3 cases, and polarized microvilli in one case indicated a form of mesothelial differentiation. Using monoclonal and polyclonal antibodies, positive immunostaining of tumour cells for cytokeratin peptides was detected in one case, while antibody to vimentin stained four cases. Light microscopic, ultrastructural and immunohistochemical features of one benign localized serosal tumour, with a unique blend of epithelial and spindle cells, provided further evidence for a histogenic link between localized serosal tumours and diffuse epithelial mesotheliomas. On the basis of the current findings and reports in the literature, it would appear that the majority of localized tumours of serosal membranes are a subset of mesothelioma, while a minority are fibromas.

Adult↗

Adenomatoid tumor of uterus: presentation in endometrial curettings.

A case of adenomatoid tumor of the uterus with an unusual initial presentation is reported. The patient, a 25-year-old female, underwent a dilatation and curettage during investigation for infertility. Endometrial curettings revealed infiltration of the stroma by epithelioid and signet-ring-type tumor cells. Subsequent hysterectomy revealed a large, somewhat ill-defined posterior myometrial tumor that on the basis of histologic, histochemical, and ultrastructural investigation proved to be an adenomatoid tumor with infiltration into the endometrium.

Adenoma↗

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)

B-Lymphocytes↗