[Differential diagnostic errors of a tumor situated between the spleen and pancreas].
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Biomedical subjects
Publications and source records attributed to D Katenkamp.
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16/30 human storiform-pleomorphic malignant fibrous histiocytomas (MFH) showed a focal pericellular immunostaining for laminin. 14/16 of these laminin-positive tumours additionally revealed an atypical cellular differentiation (desmin- and/or S-100 protein-positive cells). The significance of focal laminin positivity along with atypical, non-entity specific differentiated cells is discussed before the background of laminin as being an indicator and promoter of differentiation in MFH. The limited value of a laminin detection in MFH for solving differential diagnostic questions (MFH versus other poorly differentiated sarcomas with basement membrane formation) has been pointed out.
In searching an animal model to study metastasis formation we used cultured cells of experimental rhabdomyosarcomas and their inoculation tumors in adult nude mice. Supplementing earlier observations (Katenkamp et al. 1987) we found that long-term cultured sarcoma cells induce tumors in adult nude mice which do not metastasize spontaneously but produce lung metastases after repeated incomplete tumor removal. Possible factors and mechanisms responsible for metastasis emergence are discussed. The metastasis model introduced may be apt to study cellular changes at cytogenetic and molecular biological level that occur during tumor progression and metastatic dissemination.
The results with two new enucleation prothesis made of Bioverit are presented. After unilateral enucleation 14 rabbits received bioreactive, 14 rabbits biocompatible and 9 rabbits nylon prostheses. Implantation periods: 1-13 months. The tissue surrounding of the prostheses was studied histologically, the ceramic electron microscopically. Of 28 ceramic prostheses, 26 were adapted very well. Bioverit ist excellently suited as orbital prosthetic material, even half-open implants are possible.
These studies are based on an analysis of 160 spindle cell and/or pleomorphic malignant soft tissue tumors of adults and are aimed at providing an answer to the question of whether or not inflammatory cells in tumor tissue are of prognostic importance with regard to overall survival time. In a univariate analysis, granulocytes and lymphocytes did not show any statistical correlation with survival periods, whereas such correlation was revealed with significance to survival periods by plasma cells and mast cells. With multivariate analysis used and presence of necrotic areas included, only mast cell infiltration remained to be significantly correlated with survival time. Also presented in this paper is a proposed scheme of malignancy grading in which two properly established indicators are scored together with "mast cell infiltration", that is "mitosis count" and "necrosis amount". The three grades of malignancy resulting from this grading procedure are shown to be related with high significance to overall survival time.
Cellular differentiation processes along with formation of extracellular matrix proteins were investigated in methylcholanthrene-induced murine rhabdomyosarcomata. We used primary tumours, allotransplants in nude mice, and the respective tumour recurrences generated by repeated incomplete surgical tumour removal. The expression of the differentiation markers desmin and myoglobin as well as the presence of fibronectin and laminin was ascertained by immunohistochemical methods. The question arises, whether or not correlations between the grade of cellular differentiation (desmin, myoglobin) and extracellular matrix formation (fibronectin, laminin) exist in tumours with striated muscle cell differentiation. The constant relations between cellular differentiation and matrix formation in original tumours also applied to allotransplants and tumour recurrences in which partially modulations of differentiation in comparison with original tumours could be recognized.
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Multifactorial analysis of the prognostic diagnosis of 39 main clinical, morphological and ultrastructural traits in 109 patients with rectum carcinoma is performed on the basis of computer EC-1045/230 program and algorithmic complex. The optimal complex of the traits is established possessing the maximum information value for prognosis of the 2-, 3- and 5-year survival of patients with this tumour. Three rules are formed for the individual prognosis of a favourable and unfavourable issue of the disease after the radical surgery. The value (in %) of these rules for the prognosis was determined: 79,86 and 92% for the 2-, 3- and 5-year survival, respectively. This is the precision with which one or another prognosis can be predicted.
In murine sarcomas induced by 20-methylcholanthrene, histological features of malignant fibrous histiocytoma (MFH) as well as rhabdomyosarcoma were found in the same tumour both at light microscopy and at ultrastructural level. The areas showing rhabdomyomatous differentiation expressed vimentin, desmin, muscle-specific alpha-actinin, and sometimes myoglobin, but in the MFH areas only vimentin was expressed. A series of allografts in athymic mice, using tumour areas of both histological types, showed in every case a mixed pattern of tumour growth, whether the transplanted tissue was of MFH or rhabdomyosarcomatous type. This suggests that the MFH areas in the original experimental sarcomas were modulated disguised rhabdomyosarcomas. The significance of MFH-like areas in non-related soft tissue sarcomas is also discussed.
Rhabdomyosarcomas (RMSs) consist of a mixture of primitive mesenchymal cells as well as cells showing various stages of rhabdomyomatous differentiation. The qualitative and quantitative degree of the rhabdomyomatous differentiation of the cells, evaluated by their morphology and expression of defined structural and functional proteins, is accepted as the basis of diagnosis and is considered to be related to the biological behaviour of RMSs. Therefore we investigated solid experimentally induced murine RMSs, adherent (subconfluent, confluent) cell cultures obtained therefrom, and also suspension cultures and studied the expression of muscular differentiation markers (vimentin, desmin, myoglobin) and the formation of extracellular matrix components (fibronectin, laminin). When we compared solid tumours with adherent cell cultures of decreasing cell densities (confluent up to single cells) and with cells grown in suspension, we found a gradual decline of differentiation ("dedifferentiation"). This decline paralleled the decrease of cell-cell and cell-substrate contacts. In suspension cultures, cells were prevented from interacting with each other and the substratum, no rhabdomyomatous differentiation of the cells took place. If restoration of cellular contacts was allowed, either by adherent growth or by reinoculation into nude mice, the process of dedifferentiation was completely reversible. Consequently, it was demonstrated that the increase of cell-cell and cell-substrate contacts was strongly associated with the appearance or increasing expression of the desmin intermediate filament cytoskeleton and with formation of the extracellular matrix components fibronectin and laminin. The microfilament (F-actin) system was modulated from an impressive stress-fiber system in subconfluent to a dense network in confluent monolayers. The extent of cell-substrate contacts, mediated by extracellular matrix components, and the number of cell-cell interactions are responsible for the capability of a malignant mesenchymal cell, which is able to undergo rhabdomyomatous differentiation, to achieve the various stages of maturation.
Cytokeratin expression was investigated in paravertebral skeletal musculature of 10 d and 18 d old embryos as well as in adult NMRI-mice. The muscular nature of the evaluated tissue was evidenced by their expression of vimentin and desmin. Binding moieties for cytokeratin antibodies (polyclonal and monoclonal) could be demonstrated only in muscle cells of 10 d old embryos. Concerning subtypes, the mouse equivalents of the human cytokeratins Nos. 8, 18 and 19 could be made probable. The importance of the transient cytokeratin expression in murine embryonal skeletal muscle cells is emphasized, because this intermediate filament type is expressed in rhabdomyosarcomas too.
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Methylcholanthrene-induced murine rhabdomyosarcomas and skeletal muscle of 10 and 18 d old murine embryos were investigated by lectin histochemistry (WGA, RCA-I, LCA, Con-A, PSA, UEA-I, PNA) and by immunohistochemistry (vimentin, desmin, myoglobulin). In rhabdomyosarcomas as well as in the developing skeletal muscle a clear trend was visible. A decrease of vimentin positivity and an increase of desmin positivity were associated with a diminution of binding sites for WGA, RCA, and LCA. No binding moieties for these lectin could be demonstrated in myoglobin positive normal and neoplastic rhabdomyomatous cells at all. The homologous expression or absence of markers reflected the cellular variability in rhabdomyosarcomas and may be explained as a phenomenon of different tumor cell maturation. The results show that rhabdomyosarcomatous cells are imitating the normal skeletal muscle development.
Soft tissue sarcomas were induced by 20-methylcholanthrene in NMRI-mice. The tumors were characterized as rhabdomyosarcomas by light and electron microscopy as well as immunohistochemistry (vimentin, desmin and myoglobin expression). Cytokeratins could be demonstrated by a panel of different poly- and monoclonal antibodies in original rhabdomyosarcomas, their allotransplants and the re-established tumors from cell culture in nude mice. The cytokeratin positive tumor cells were arranged in small clusters and/or haphazardly single dispersed in the rhabdomyosarcomas. By means of monoclonal antibodies cytokeratins No. 8 and No. 19 could be evidenced and cytokeratin No. 18 could be made probably. Behind the background of cytokeratin expression in developing fetal cross striated muscle cells our findings are discussed as a reminiscence of embryonal muscle development in these tumors. The significance of cytokeratin expression in rhabdomyosarcomas for diagnostic histopathology is emphasized.
Cellular heterogeneity, a regular property of malignant neoplasms, can constitute the basis for phenotypic shifting in malignant tumors. A disturbance of the balanced interactions as happens as result of all therapy measurements between tumor cell subpopulations and between tumor and host offers the possibility to profound changes on the basis of cellular heterogeneity. As tumor model we used methylcholanthrene-induced murine rhabdomyosarcomas, which were allotransplanted into nude mice. The original as well as the allotransplanted sarcomas were submitted repeated operative tumor mass reductions, comparable to an insufficient tumor surgery in man. The histology and the cellular differentiation were evaluated by light microscopy and immunohistochemical marker expression (vimentin, desmin and myoglobin). Our findings document that primary tumors, their recurrences after incomplete tumor removal, and allotransplants inclusive of their surgically induced recurrences were histologically and immunohistochemically not identical in every case when compared with each other, but despite the experimental procedures they retained basic criteria necessary for the rhabdomyosarcoma diagnosis. Changes in sarcoma histology and cellular marker expression are not only reflected by dedifferentiation but can also comprise differentiation (maturation) processes. After artificial breakdown of intratumoral cellular interactions and tumor/host relations, unknown sarcoma inherent factors directed to retaining basic properties obviously preponderate, at least for the moment, over accidental new cell clones with differing phenotypic characteristics, which could be expected by cellular heterogeneity and would result in a markedly changed tumor.
Seven focal pleural tumours are studied histochemically, immunohistochemically and electron microscopically (EM). A great variety of histological and EM structures was found: areas resembling fibromas, fibrous histiocytomas, hemangiopericytomas, etc. The EM signs of the abortive mesothelial differentiation were found in the tumour cells. The use of the term "localised fibrous mesothelioma" seems to be justified. It is necessary to distinguish morphologically diffuse mesothelioma and localised fibrous mesothelioma that possess different clinical course and prognosis.