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Biomedical subjects

M Osborn

Publications and source records attributed to M Osborn.

302 records · Page 17Linked to original sources

Mallory body-like inclusions in a hereditary congenital neuromuscular disease.

Subsequent to an earlier report on clinical and light microscopic data, peculiar Mallory body-like inclusions are described in muscle fibers of three genetically linked children. These Mallory body-like inclusions were unlike other well-defined intramuscular inclusions, such as nemaline, cytoplasmic, fingerprint, or sarcoplasmic bodies, but morphologically quite similar to hepatic Mallory bodies, because they were composed of three components: granular material and two types of filaments. Evidence is presented that these inclusions may contain desmin, the intermediate filament type characteristic of muscle. The exclusive appearance of these Mallory body-like inclusions in muscle biopsy specimens from three genetically related children of a large kinship emphasizes the uniqueness of these Mallory body-like inclusions in these muscle fibers as well as the special form of this congenital neuromuscular disorder.

Adolescent↗

[Significance of immunohistologic methods in the differential diagnosis of solid tumors in childhood].

We have investigated 56 histologic and 13 cytologic specimens of malignant round cell tumors of childhood. The immunohistological detection of intermediate filament polypeptides, neuron specific enolase (NSE) as well as leukocyte common antigen (LCA) allows the histological classification of such tumors. Neuroblastomas demonstrate a positive reaction with antibodies to neurofilaments and NSE independent of differentiation. Rhabdomyosarcomas could be labeled by the desmin antibody, while Ewing sarcomas, malignant lymphomas as well as nonmuscular sarcomas only express vimentin. In nephroblastomas the intermediate filament specific antibodies reveal expression of keratin and vimentin in blastema cells, while tubules are only labeled by the keratin antibody. In undifferentiated nephroblastomas, which lack formation of tubules blastema cells are keratin negative and vimentin positive. Thus antibodies to intermediate filaments, LCA and NSE seem to be useful tools to distinguish the so called "round cell tumors" of childhood.

Adolescent↗

Keratin-positive reticulum cells in fine needle aspirates and touch imprints of hyperplastic lymph nodes. A possible pitfall in the immunocytochemical diagnosis of metastatic carcinoma.

Fine needle aspirates and touch imprints of 36 hyperplastic (reactive) lymph nodes were tested for the presence of keratin and desmin. Keratin-positive cells with morphologic characteristics corresponding to extrafollicular (fibroblastic) reticulum cells were found in 18% of the fine needle aspirates and 42% of the touch imprints. The number of keratin-positive reticulum cells varied from 1 to greater than 30 per slide. Desmin-positive cells with similar morphology were found in 23% of fine needle aspirates and 37% of touch imprints, and the number of such cells per slide ranged from 2 to greater than 70. The relatively frequent occurrence of keratin-positive reticulum cells in these preparations from hyperplastic lymph nodes should be taken into account if keratin antibodies are used to search for carcinoma micrometastases.

Biopsy, Needle↗

Immunocytochemistry on fine needle aspirates in paraffin miniblocks.

A simplified method of processing of fine needle aspirates for paraffin miniblocks suitable for both morphologic and immunocytochemical evaluation is described. Aspirates were fixed in ethanol at 4 degrees C, dehydrated in acetone and xylene and embedded in paraffin (58 degrees C). All steps were carried out in a single Eppendorf centrifuge tube; the total process took less than four hours. Deparaffinized sections were stained using the alkaline phosphatase-antialkaline phosphatase technique with monoclonal and conventional antibodies helpful in the differential cytologic diagnosis of alcohol-fixed aspiration biopsy specimens. Antibodies to keratin, vimentin, desmin, neurofilaments, glial fibrillary acidic protein, leukocyte-common antigen, synaptophysin and immunoglobulin kappa and lambda light chains reacted positively on the miniblock material. Since the paraffin miniblocks combine the histologic pattern of the tumor with the differentiation-specific information provided by immunocytochemistry, their use can improve the accuracy of tumor typing in aspirates.

Antigens, CD↗

Intermediate filament typing of tumor cells in fine needle aspirates by means of monoclonal antibodies.

Well-characterized monoclonal antibodies directed against different intermediate filament proteins were used in the typing of tumor cells in 30 fine needle aspiration (FNA) biopsy specimens received for routine cytologic examination to assess the value of intermediate filament typing in FNA cytology. Tumors from sites that included liver, large bowel, pancreas, breast, skin, thyroid, thigh and kidney were examined with monoclonal antibodies specific for either all keratins or keratin subsets, vimentin, desmin or specific neurofilament polypeptides. Intermediate filament typing helped to confirm, revise or refine the diagnoses made by light microscopy and provided information of value in the classification of tumors of uncertain origin.

Antibodies, Monoclonal↗

Neuroendocrine (Merkel-cell) carcinoma of the skin. Cytology, intermediate filament typing and ultrastructure of tumor cells in fine needle aspirates.

The light and transmission electron microscopic findings and the intermediate filament typing of tumor cells from fine needle aspirates of primary, recurrent and metastatic neuroendocrine (Merkel-cell) carcinoma of the skin are described. The tumor cells in the smears coexpressed keratins and neurofilaments and were characterized by "intermediate filament buttons," i.e., buttonlike fragments of cytoplasm of tumor cells, which could be observed either by staining with intermediate filament-specific antibodies using immunofluorescence or by their appearance in hematoxylin-and-eosin-stained smears. These features may help in the differential diagnosis of fine needle aspirates of neuroendocrine carcinomas of the skin.

Adenocarcinoma↗

Diagnostic significance of coexpression of intermediate filaments in fine needle aspirates of human tumors.

A study was undertaken of the diagnostic significance of the coexpression of intermediate filaments in fine needle aspirates of human tumors. Three types of coexpression were found: (1) true coexpression, in which tumor cells simultaneously express more than one intermediate filament protein; (2) pseudocoexpression, in which various tumor cell types from histogenetically different parts of a complex tumor show different results; and (3) false coexpression, in which tumor cells with one or two types of intermediate filaments are present together with benign cells expressing a different filament type. True coexpression of vimentin and keratin was documented in renal cell carcinomas, endometrial carcinomas, certain thyroid carcinomas and Hürthle cell adenomas. Coexpression of keratin and neurofilaments was seen in Merkel cell carcinomas, and coexpression of desmin and vimentin was found in leiomyosarcomas. Keratin, vimentin and neurofilament expression was seen in medullary thyroid carcinomas, and keratin, vimentin and glial fibrillary acidic protein expression was observed in pleomorphic adenomas of the salivary gland. Pseudocoexpression was noted in synovial sarcoma, epithelioid sarcoma, benign cystosarcoma phyllodes of the breast, teratocarcinoma, malignant granular cell tumor, progonoma, Wilms' tumor and triton tumor. Sources of false coexpression are also discussed.

Biopsy, Needle↗

Coexpression of glial fibrillary acid protein, keratin and vimentin. A unique feature useful in the diagnosis of pleomorphic adenoma of the salivary gland in fine needle aspiration biopsy smears.

Positive staining for glial fibrillary acidic protein (GFAP) of tumor cells in fine needle aspirates of 11 of 12 pleomorphic adenomas of the parotid gland is reported. Tumor cells in these neoplasms also coexpressed keratin and vimentin to varying extents. Coexpression of GFAP, keratin and vimentin in tumor cells in aspirates is an unusual feature, so far demonstrated only in pleomorphic adenomas. Thus, intermediate filament typing may help to distinguish: (1) pleomorphic adenomas of the salivary glands from head and neck tumors of nonsalivary gland origin; (2) intracranial metastases of malignant mixed tumors of the salivary gland from gliomas; and (3) pleomorphic adenomas from extracranial gliomas.

Adenoma, Pleomorphic↗

Diagnosis of metastatic renal cell and thyroid carcinomas by intermediate filament typing and cytology of tumor cells in fine needle aspirates.

Coexpression of keratin and vimentin was found in carcinoma cells of 13 fine needle aspirates of metastatic lesions that showed some cytologic features considered to be consistent with a renal or thyroid origin, but in which a large number of other possible primary sites would have to be taken into account on the basis of the morphologic evidence alone. Immunochemistry thus narrowed the cytologic differential diagnosis to thyroid, renal, endometrial and ovarian carcinomas, which are known to show true coexpression of keratin and vimentin. In most cases, clinical data available at the time of the fine needle aspiration supported the thyroid or renal origin of the carcinoma cells found in the aspirates. In two cases, which lacked significant clinical information, the diagnosis of metastatic renal cell carcinoma was provided on the basis of the combined morphologic and immunocytochemical evidence. In these two cases, computed tomography or ultrasonography revealed kidney tumors, which were removed and confirmed histologically to be clear cell carcinomas.

Adenocarcinoma↗

Decisive role of intermediate filament typing of tumor cells in the differential diagnosis of difficult fine needle aspirates.

Thirty-six diagnostically difficult fine needle aspirates from enlarged lymph nodes and malignant soft tissue tumors, containing tumor cells with scanty or no obvious light microscopic features indicative of their differentiation, were assessed by a panel of six cytopathologists. Their diagnoses were recorded and then compared with the definitive diagnosis established by combining the cytologic findings with the results of intermediate filament typing of tumor cells in the smears using monoclonal antibodies specific for each filament type. The results show that use of these antibodies can markedly improve the accuracy of the cytologic diagnosis of tumor type as well as revise or prevent erroneous cytologic diagnoses in difficult cases. This pertains especially to the differential diagnoses of carcinoma versus malignant lymphoma, carcinoma versus malignant melanoma, carcinoma versus sarcoma and squamous carcinoma versus carcinoma of simple epithelia. Intermediate filament typing of tumor cells in aspirates as an objective histogenetic criterium makes the differential diagnosis of the difficult aspirates much more reliable and reproducible, provided that appropriate questions are asked, monoclonal antibodies with well-defined specificities are used and the antigenicity of the intermediate filaments in smears is preserved.

Adult↗

Differential diagnosis of lymph node aspirates by intermediate filament typing of tumor cells.

Twenty-one lymph node aspirates for which a differential diagnosis was difficult or not possible by light microscopy alone were selected for further study by intermediate filament typing. The use of four monoclonal antibodies specific for different keratin subsets or for vimentin resulted in a definitive diagnosis in all instances. The results show that use of these antibodies can improve the accuracy of cytologic diagnosis and provide further evidence that intermediate filament typing can help differentiate (1) malignant melanoma from adenocarcinoma, (2) malignant lymphoma from small-cell anaplastic carcinoma and (3) squamous-cell carcinoma from adenocarcinoma. Intermediate filament typing can also be used to identify very small numbers of carcinoma cells in specimens that are apparently negative for tumor cells by light microscopy. The method is quick, relatively simple, reliable and unambiguous, provided that appropriate questions are asked and antibodies with well-defined specificities are used.

Antibodies, Monoclonal↗

Ultrasound-guided percutaneous fine needle aspiration biopsy of abdominal and retroperitoneal masses. Accuracy of cytology in the diagnosis of malignancy, cytologic tumor typing and use of antibodies to intermediate filaments in selected cases.

The reliability of ultrasound-guided fine needle aspiration biopsy (FNAB) in the detection of intraperitoneal and retroperitoneal malignancies was evaluated in 308 consecutive cases seen between 1979 and 1983. The prevalence of malignant neoplasms was 68.5%. The overall accuracy of FNAB diagnosis was 88.9%, with a sensitivity of 84.4% and a specificity of 98%. The predictive value of positive and negative results were 98.9% and 74.6%, respectively. Additionally, the cytologic results were statistically evaluated with respect to the different sites of the biopsied lesions (including pancreas, liver, kidneys and miscellaneous sites). The overall accuracy was highest for malignant lesions in the liver (96.4%) and in miscellaneous sites (89.5%). Reasons for false-negative results included incorrect areas sampled, limited material due to fibrosis or necrosis and cytologic misinterpretations. The accuracy of cytologic tumor typing with respect to histogenetic origin was 96.8%. Cytologic subclassification was performed with lower accuracy (82.5%), and exact determination of the site of the primary tumor from cytologic criteria alone was possible for 35.7% of carcinomas. In selected cases, routine cytologic examination was supplemented by intermediate filament typing using well-characterized antibodies against cytokeratin, vimentin, desmin and neurofilaments. Examples are shown in which use of this method clearly increased the accuracy of the diagnosis. Only two serious complications (bleeding) of fine-needle aspiration biopsy were encountered in this series.

Antibodies↗