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Biomedical subjects

B Czernobilsky

Publications and source records attributed to B Czernobilsky.

At least 55 records · Page 3Linked to original sources

Dysplastic vulvar nevi.

Of several pigmented vulvar lesions, the dysplastic nevus, a know precursor of malignant melanoma, has been described only twice. Focusing on pigmented vulvar lesions, 18 were excised among approximately 500 unselected parturients. Three lesions showed clinical and histologic characteristics of a dysplastic nevus. The patients with a dysplastic vulvar nevus were 21, 27, and 30 years old, respectively; all three had multiple torso and limb nevi and two had anamnestic features of the dysplastic nevus syndrome. Only one was aware of her vulvar lesion. All dysplastic nevi were brown or black and were larger than 5 mm in diameter. Our cases suggest that dysplastic vulvar nevi may be more frequent than previously thought. We suggest that the puerperium is a suitable time for a definite histologic diagnosis of large-size lesions with variegated pigmentary patterns and irregular borders that occur on the vulvar skin. Likewise, in other patients with suspected dysplastic vulvar nevi, excisional biopsy is recommended.

Adult↗

Ovarian mucinous cystadenoma with leiomyomatous mural nodule.

A case of an ovarian mucinous cystadenoma with a leiomyomatous mural nodule is described. The diagnosis was confirmed by immunohistochemical methods. This is the first report of a mural nodule of leiomyomatous nature, thus widening the histologic spectrum that may be encountered in these lesions.

Cystadenoma↗

Heterogeneity of intermediate filament expression in human testicular seminomas.

Testicular seminoma has in the past been considered to represent a germ cell tumor incapable of further differentiation. In recent years this view has been challenged on the basis of morphologic and chromosomal studies. Moreover, studies of intermediate filaments (IF) of seminoma cells have provided evidence of the capability of seminoma cells to differentiate in different directions. In the present study of the IF protein profile of 26 human testicular seminomas, using frozen as well as formalin-fixed, paraffin-embedded tissues, we report evidence of a heterogeneous differentiation potential inherent in these neoplasms. Thus, in 4 of the seminomas neither cytokeratins nor vimentin were detected; 3 showed vimentin positive cells but no cytokeratins; in 4 seminomas only cytokeratins were detected. In the remaining 15 cases both cytokeratins and vimentin were present, with occasional cells demonstrating coexpression of cytokeratin and vimentin. While the cytokeratins present were mostly of the "simple epithelial type", in 2 instances seminoma cells also contained cytokeratins 4 and 17, normally found in stratified and/or complex glandular epithelia. Furthermore, in 3 cases scattered tumor cells stained for desmin and in 2 other seminomas neurofilaments were identified. All of the cases showed variable positive staining for desmoplakins and desmoglein, indicative of the presence of desmosomes. It can therefore be concluded that, while some seminomas seem to be devoid of IFs, most of them show varied differentiation patterns usually with epithelial features but occasionally also with components commonly regarded as characteristic of myogenic or neurogenic differentiation. These observations may help to elucidate the relationship of seminomas to other germ cell tumors, and also contribute to our understanding of the histogenesis of these neoplasms.

Desmin↗

Quantitative nuclear morphology in the diagnosis of ovarian tumors of low malignant potential (borderline).

Ovarian tumors of low malignant potential or of borderline malignancy are characterized histologically by the association of malignant type of epithelial proliferation with a noninvasive pattern of growth. Because epithelial proliferation relates to features of nuclear morphology and chromatin structure and because of the difficulties to distinguish nuclear atypism seen in borderline malignancy from that in frankly invasive tumors by usual microscopic study, the authors concentrated their studies exclusively on computerized analysis of cell nuclei images. Using specially developed methods of analysis the authors described geometrical, optical, and structural differences among the epithelial and stromal cell nuclei of benign, borderline, and malignant ovarian tumors. The structural differences concern the pattern of chromatin condensation and suggest that the cytokinetic properties of the borderline tumors are intermediate to those of benign and malignant. The results demonstrate that the quantitative evaluations provide objective and reproducible data useful in the differential diagnostic of the borderline malignancy.

Adenoma↗

Alpha smooth muscle actin (alpha-SM actin) in normal human ovaries, in ovarian stromal hyperplasia and in ovarian neoplasms.

An immunohistochemical investigation of alpha-smooth muscle actin (alpha-SM actin) using the monoclonal anti-alpha-SM-1 antibody was carried out in 15 normal ovaries, in three ovaries with stromal hyperplasia and in 27 neoplastic ovaries. In selected cases the pattern of actin isoforms was examined by means of 2 D-gel electrophoresis. In addition, the tissues were stained for vimentin and desmin. In normal ovaries alpha-SM actin was found in the inner cortex and in the theca externa. In ovarian stromal hyperplasia expression of alpha-SM actin was minimal or absent. In primary and metastatic epithelial tumors there was positive stromal staining for alpha-SM actin, especially in the vicinity of epithelial elements. This tended to be more widespread in malignant neoplasms. Thecomas did not express alpha-SM-actin and could thus be differentiated from leiomyomas which stained intensely for alpha-SM actin. Only focal stromal staining of alpha-SM actin was observed in granulosa and germ cell tumors. In all the tissues studied blood vessels were strongly positive for alpha-SM actin. Desmin, although present in the stroma of most of the specimens, was less abundant than alpha-SM actin. We concluded that alpha-SM actin is a component of the normal human ovary where it may contribute to the contractility of its stroma. Its absence in the normal outer cortex and theca interna, and in stromal hyperplasia and thecoma implies that sex hormones do not constitute a stimulus for alpha-SM actin production in the ovary. Among neoplasms it is most widely represented in the stroma of epithelial tumors in which it may reflect stromal stimulation mediated by neoplastic epithelium.

Actins↗

Cytokeratin patterns in the epidermis of human ovarian mature cystic teratomas.

Using a battery of monoclonal antibodies, we investigated the cytokeratin pattern in the epidermides of 12 human ovarian mature cystic teratomas (MCTs) and compared them with those of infant, adult, and fetal skin. Histologically, two types of epidermal layers were identified in the MCTs, a mature layer and an immature layer. The mature layer was similar to the epidermis of infants and adults, while the immature layer resembled stratified nonkeratinizing and metaplastic squamous epithelium. The cytokeratin pattern of the histologically mature epidermis in MCT was either similar to that in infants and adults or was of the fetal type. The cytokeratin expression of the histologically immature epidermis in MCT also showed many similarities to the fetal cytokeratin pattern. We conclude that histologic maturity of the epidermis in MCT is not necessarily expressed by the cytokeratin pattern, which reflects the state of molecular rather than histologic differentiation. Since prognosis in germ cell tumors is usually related to the degree of tissue maturation, our observations raise the possibility that the cytokeratin profile may eventually prove to be a valuable prognostic tool in some of the neoplasms that contain epithelial elements.

Adult↗

Endolymphatic stromal myosis (endometrial low-grade stromal sarcoma) presenting with hematuria: a diagnostic challenge.

In this case of a 41-year-old white woman who presented with hematuria, the diagnosis of metastatic endolymphatic stromal myosis (ESM) in the urinary bladder was reached on the basis of the histologic pattern and with the aid of intermediate filament typing. In the hysterectomy specimen the tumor foci of ESM were of minute size. To the best of our knowledge, this is the first report of such an unusual clinical presentation of this lesion.

Adult↗

Chorangioma. A cytoskeletal profile.

Cytoskeletal typing of five chorangiomas revealed diffuse staining of the blood vessels with antibodies to vimentin and to alpha smooth muscle (alpha-SM) actin, while cytokeratin 18 decorated the blood vessels focally. Focal staining for desmin was observed in two chorangiomas. Blood vessels of the placentas in which these chorangiomas arose stained for vimentin and alpha-SM actin. In addition, there was positive staining for cytokeratin polypeptide 18 in blood vessels within the chorionic plate and anchoring villi, and occasional staining for desmin. The vasculature of the terminal villi lacked cytokeratins. The stromal elements of the chorangiomas stained for vimentin and focally for alpha-SM actin and cytokeratin 18. A similar staining pattern was also found in the placental stroma, with most of the cytokeratin positivity encountered in the chorionic plate and anchoring villi. Blood vessels in extraplacental hemangiomas were devoid of cytokeratins. These results indicate that chorangiomas originate most likely from blood vessels of the chorionic plate and anchoring villi, which, as chorangiomas, are the site of vascular cytokeratin expression.

Actins↗

Malignant mesenchymoma of spermatic cord: a case report with intermediate filament typing.

A malignant mesenchymoma arising in the spermatic cord of a 79-year-old patient is described. The radiologic appearance was that of a predominantly calcified mass. Histologically the tumor was composed primarily of malignant cartilage. In other areas there were spindle-shaped cells and large eosinophilic and multinucleated giant cells. Staining for intermediate filaments revealed vimentin throughout the neoplasm with some areas showing positive staining for desmin, the latter confirming the muscular origin of some of the neoplastic elements. No cytokeratins were identified, effectively ruling out the possibility of a malignant teratoma.

Aged↗

Ovarian tumors in pregnancy.

Thirty-eight women were operated for an ovarian tumor diagnosed during pregnancy, with an incidence of 1/2328 deliveries. The diameter of all tumors was above 5 cm. Of the 31 women operated before delivery, seven were untreated and 24 received supportive progestational therapy. The rate of abortions was 85.7% in the untreated group and 10% in the hydroxy-progesterone-caproate group (HPC) (P less than 0.02). When the women received a total dose of HPC of more than 300 mg, 9 of 10 pregnancies reached term with a live child. Two ovarian malignancies were found, 5.3% of all cases. In 42.9% of the women there were fertility problems later in life. Ovarian tumors during pregnancy should be removed as soon as possible, irrespective of the age of the pregnancy. If fully progesterone therapy is given, the danger of abortions is reduced to a minimum. Prophylactic antibiotic treatment should also be administered.

17 alpha-Hydroxyprogesterone Caproate↗

Expression of intermediate filaments and stromal proteins in granular cell tumor of the tongue.

Intermediate filament subunits as well as components of the extracellular matrix, were localized in three cases of granular cell tumor of the tongue. Of the five intermediate filament families, only vimentin was present within the tumor cells. No labeling was obtained with antibodies to cytokeratin, desmin, neurofilaments, and glial filaments; this suggests that this tumor is not derived from epithelium, muscle, neural, or astrocytic origins, respectively. Immunofluorescent staining of the tissue with antibodies to fibronectin and to collagen indicated that the tumor contained low levels of these extracellular matrix proteins. The results suggest the possible use of antibodies to intermediate filaments as histogenetic markers for the clarification of the origin of tumors whose nature cannot be unequivocally determined by conventional histopathologic methods.

Aged↗

Lactic dehydrogenase, alkaline phosphatase and human chorionic gonadotropin in a pure ovarian dysgerminoma.

Pure dysgerminoma is considered to be a nonsecretary ovarian tumor. In this study serum lactic dehydrogenase, human chorionic gonadotropin, and alkaline phosphatase levels were highly elevated in a 21-year-old woman with unilateral ovarian pure dysgerminoma and fell sharply to normal levels after removal of the tumor. In order to establish the source of these elevated serum enzymes and hormone, the tumor was homogenized and the level of these substances was found to be several times higher than that of normal homogenized ovarian tissue. In addition, the presence of lactic dehydrogenase and alkaline phosphatase in the dysgerminoma cells was shown by histochemical methods. This is the first report providing evidence that pure dysgerminoma contains and secretes enzymes and hormones which may constitute tumor markers useful for the diagnosis and follow-up of patients with this type of neoplasm.

Adult↗

Selective expression of cytokeratin polypeptides in various epithelia of human Brenner tumor.

A human ovarian Brenner tumor presenting a wide spectrum of benign and malignant histologic features was studied for its patterns of intermediate filament expression. All epithelial elements of the tumor, regardless of their morphologic type, contained cytokeratins as their only intermediate filament component. Differences were detected, however, between tumor nests that displayed transitional epithelium and those with squamoid features. These differences were manifested by the presence of cytokeratin 18, in the former type only, and by the abundance of cytokeratins 10/11 in the latter. We also detected mixed epithelial nests in which both features were present, suggesting that the transitional epithelium transforms in polar fashion into squamous epithelium. Examination of cytokeratin patterns found in urothelium and in the surface epithelium of the ovary pointed to certain differences from the Brenner tumor epithelia. The significance of these latter findings with regard to cellular transformation and histogenesis of the Brenner tumor are discussed.

Antibodies, Monoclonal↗

Subtyping of epithelial cells of normal and metaplastic human uterine cervix, using polypeptide-specific cytokeratin antibodies.

The aim of the present study was to explore the histogenesis of metaplastic cells in the human uterine cervix. In a previous study we demonstrated that squamous cervical metaplasia expresses a unique set of cytokeratin polypeptides different from that expressed by the various normal epithelial elements of both the exo- and endocervix. It was thus proposed that the formation of squamous metaplasia represented a new route of differentiation. In the present study we further investigated this aspect by expanding the battery of monoclonal antibodies directed against specific cytokeratin epitopes used for immunohistochemical labelling. The antibodies used were: KS-1 A3, which specifically stains cytokeratin polypeptide no. 13; antibody KS-2.1, which is an anti-cytokeratin reacting with pseudostratified transitional and some simple epithelia; and antibody KS-B17.2 reacting with cytokeratin polypeptide no. 18. Examination of the staining patterns obtained with these antibodies revealed specific staining of ciliated cells with antibody KS-2.1 and of endocervical reserve cells with antibody KS-1A3. In 6 out of 19 cases tested reserve cells were also stained with antibody KS-2.1. These results enabled us to distinguish between at least four types of cells residing within the simple epithelium of the endocervix, namely columnar nonciliated cells, ciliated cells, and two subpopulations of reserve cells. Since metaplasia was positively stained by antibodies KS-1A3 and KS-2.1, we propose that the endocervical reserve cells that express cytokeratin polypeptide no. 13 are most probably the cells from which endocervical metaplasia is derived.

Antibodies, Monoclonal↗

Immunocytochemical study of an endometrial diffuse clear cell stromal sarcoma and other endometrial stromal sarcomas.

Intermediate filament composition was studied in the following endometrial stromal tumors: low-grade stromal sarcoma (endolymphatic stromal myosis), high-grade stromal sarcoma with an associated adenocarcinoma (collision tumor), diffuse clear cell stromal sarcoma and a mesodermal mixed tumor (carcinosarcoma). The tumor cells of the stromal tumors as well as the mesenchymal elements of the mixed mesodermal tumor were decorated exclusively with antibodies to vimentin. Desmin was not demonstrated in these tumor cells. A biochemical study of the cytoskeletal filaments present in the low-grade stromal sarcoma revealed, in addition to vimentin, beta and gamma actin as seen in normal endometrial stroma. Cytokeratins were only identified in epithelial components which were present in some of these tumors. Intermediate filament typing in these endometrial neoplasms contributes to the elucidation of histogenetic problems, may delineate mesenchymal from epithelial elements, may separate muscle from stromal lesions and in one instance helped to define a hitherto unreported diffuse clear cell stromal sarcoma.

Actins↗

Patterns of expression of cytoskeletal proteins in human thyroid gland and thyroid carcinomas.

By two-dimensional gel electrophoresis of proteins insoluble in detergents and high-salt buffer and immunofluorescence microscopy with a panel of polypeptide-specific antibodies to proteins of intermediate filaments (IF) and desmosomes, we have characterized the cytoskeletons of normal human thyroid gland, several kinds of benign lesion (goiter, Hashimoto's and Graves' diseases, adenomas), and the major thyroid carcinomas (follicular, papillary, medullary, and anaplastic). In all these tissues, desmoplakins and cytokeratins 7, 8, 18, and 19 were identified. While cytokeratins 8 and 18 occurred in all epithelial cells and cytokeratin 7 was also rather widespread, cytokeratin 19 occurred in amounts variable between the different types of tissues and in normal thyroid gland was restricted to certain clusters of follicular epithelial cells. Of all samples studied, in none did we detect cytokeratins commonly associated with stratified epithelia such as cytokeratins 4-6, 10, and 13-17, indicating that these are infrequent, if at all present, in such tissues. Coexpression of cytokeratins with vimentin appears to occur constitutively in follicular epithelial cells of normal thyroid gland and is also frequent in the diverse carcinomas, though to various degrees. Medullary carcinomas are exceptional, not only because they express neuroendocrine markers, but also because they coexpress combinations of cytokeratin IFs with neurofilaments and/or vimentin IFs in some cases, but not all. The results are discussed in relation to states of cell differentiation in normal and diseased thyroid gland and with respect to their value in tumor diagnosis.

Cytoskeletal Proteins↗

Distinctive immunohistochemical labeling of epithelial and mesenchymal elements in laryngeal pseudosarcoma.

A laryngeal squamous cell carcinoma in situ with an underlying spindle cell nodule (pseudosarcoma) was immunohistochemically labeled with antibodies to tissue-specific intermediate filament proteins, including desmin, vimentin, and cytokeratin. Two distinct populations of cells were found within the lesion: cytokeratin-positive cells, corresponding to the carcinomatous component of the tumor, and vimentin-positive spindle cells in the subepithelial nodule. In view of the strict specificity of antivimentin and anticytokeratin for cells of mesenchymal and epithelial origin, respectively, it is proposed that the two components of the pseudosarcoma in our case are not morphologic variants of the same tumor, and that the subepithelial nodule represents a mesenchymal lesion. These results can, however, not be extrapolated to other cases since in some the spindle cell component may represent metaplastic epithelial cells. In view of the difficulties encountered in reaching a correct diagnosis in these lesions, it is recommended to use intermediate filament typing to elucidate the nature of the spindle cells in this controversial tumor.

Carcinoma in Situ↗

Desmosomal plaque-associated vimentin filaments in human ovarian granulosa cell tumors of various histologic patterns.

Proteins of intermediate-sized filaments and desmosomal plaques (desmoplakins) of four human ovarian granulosa cell tumors were studied by immunofluorescence and immunoelectron microscopy and by two-dimensional gel electrophoresis of microdissected tissue samples. All tumor cells, irrespective of their specific histologic patterns, contained both vimentin and desmoplakins. Cytokeratin-positive structures were absent or very scant in most tumor regions, but more common in trabecular, insular, macro- and microfollicular structures. Biochemical analysis revealed the presence of Cytokeratin Polypeptides 8 and 18. Desmin filaments, neurofilaments, and glial filaments were not detected. Immunoelectron microscopy showed vimentin filaments attached to desmoplakin-positive plaques of desmosomes. These results indicate that granulosa cell tumors contain true desmosomes, which are associated primarily with vimentin filaments. This phenomenon has so far only been described in meningiomas and in blastema cells of nephroblastomas. Our observations suggest that in most neoplastic granulosa cells one epithelial feature, ie, cytokeratin expression, is greatly reduced, whereas desmosomes are still formed in appreciable frequencies. This unusual constellation of cytoskeletal elements in granulosa cell tumors may be useful in the differential diagnosis from other ovarian neoplasms, especially undifferentiated carcinomas. The importance of the use of antibodies specific for exclusively desmosomal proteins in classifying morphologically ill-defined junctional structures (eg, "rudimentary junctions," "primitive junctions," "desmosome-like junctions") is emphasized.

Aged↗