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Biomedical subjects

E Grundmann

Publications and source records attributed to E Grundmann.

At least 37 records · Page 2Linked to original sources
PubMed1989

The cytogenesis of macrophages and osteoclast-like giant cells in bone tumors with special emphasis on the so-called fibrohistiocytic tumors.

Recent investigations have suggested that osteoclasts and osteoblasts belong to different cell systems: osteoclasts originate from hemopoietic stem cells, most probably via precursors of the mononuclear phagocyte system. Osteoblasts, however, arise from local mesenchyme. The present classification of bone tumors issued by the WHO, however, is still based on the assumption of osteoclasts and osteoblasts being merely different manifestations or differentiations of the same basic cell type. Consequently, histiocytes or macrophages as well as osteoclast-like giant cells are interpreted in most bone tumors as an autochthonous component of the tumor. In the present study, this theory is contradicted by histological immunohistological, electron microscopic, and autoradiographic-electron microscopic results on a larger number of osteosarcomas, chondromas, chondrosarcomas, chondroblastomas, aneurysmal bone cysts, giant cell tumors of bone, malignant fibrous histiocytomas, fibrosarcomas, desmoplastic fibromas, Ewing's sarcomas, fibrous dysplasias, nonossifying fibromas, and malignant hemangioenkdotheliomas of bone. In order to elucidate the role of macrophages and osteoclast-like giant cells, different monoclonal antibodies were applied to bone tumor specimens as markers of mononuclear macrophages and giant cells. The concept of what is called fibrohistiocytic tumors should be reconsidered. Immunohistological studies have shown that in malignant fibrous histiocytoma as well as in giant cell tumors of bone only a certain portion of macrophages will react with the highly specific antibodies, whereas the majority of tumor cells are negative. This finding alone suggests that the infiltration of macrophages is a reactive phenomenon. It is in agreement with earlier autoradiographic and electron microscopic investigations on giant cell tumors of bone, confirming that only the fibroblast-like tumors are actually proliferating. These data were verified in the present study with the aid of double labeling immunohistological techniques, using antibodies against mature tissue macrophages and others against a proliferation-associated nuclear antigen. Only the fibroblast-like cells, which do not react with the macrophage-specific antibody, will express the proliferation-associated nuclear antigen. Analogous results were obtained in malignant fibrous histiocytoma. We may infer from these results that the majority of these tumors must be neoplasms of local mesenchyme, mostly in fibroblastic differentiation, while the considerable number of macrophages is seen as a reactive phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Neoplasms↗
PubMed1988

Metastatic patterns of renal carcinoma: an analysis of 687 necropsies.

The metastatic behaviour of renal cell carcinoma has been studied in a series of 687 necropsies. The observations were consistent with the concept of "metastatic inefficiency", in that in 295 cases, including 25 with renal vein invasion, there were no detectable metastases. In the present series, renal vein involvement was not an important prognostic factor in stage 1 or 2 disease. In 73% of cases without lung metastases there were none in other sites, and in 84% of those with lung metastases there were others elsewhere, consistent with a metastatic "cascade" in which metastases first developed in the lungs and were later detected in other organs. However, the observations did not permit discrimination between anatomic cascades, in which other organs were seeded from metastasizing pulmonary metastases, and temporal cascades, in which the other were seeded at the same time as the lungs, but with fewer cancer cells. The patterns of arterial metastasis were consistent with the "seed-and-soil" hypothesis, and a novel index was developed to quantify differential organ "soils". The contralateral kidney was not the best soil for metastases from renal carcinoma. Given the presence of lymph node metastasis, the probability of heamatogenous metastasis is 90%. However, in the absence of nodal metastasis, approximately half the cases had haematogenous metastasis.

Adult↗
PubMed1988

S-100 protein and neuron specific enolase (NSE) expression by chordomas in relation to the composition of their stromal mucosubstances.

The immunoreactivity of S-100 protein and neuron specific enolase (NSE.) was correlated with the composition of stromal glycosaminoglycans in chordomas and human notochords, in a combined histochemical and immunohistochemical study. We found that S-100 protein is negative in notochordal and chordoma cells in the absence of stromal mucosubstances or in the presence of small quantities of hyaluronic acid. The positivity of S-100 immunoreaction was found to be related to the presence of stromal glycosaminoglycans of the chondroitine sulfate A and C type. NSE. was found positive in cells presenting features of high metabolic activity. Consequently S-100 protein and NSE. immunoreactivity cannot have any cytogenetic implications, but they could be considered as markers indicating specific cell-stromal functional interactions.

Chordoma↗
PubMed1988

Flow cytometric analysis of stemline heterogeneity.

The stemline heterogeneity of malignant tumors is closely connected with tumor aneuploidy. Both features can be characterized by either chromosome analysis or DNA cytophotometry. DNA analysis may be performed either by single cell photometry or by flow cytometry, of which the respective advantages and drawbacks are presented. Preliminary results of flow cytometric DNA analysis in malignant neoplasms are discussed; the possibilities of multiparametric measurement for quantitative analysis of various biochemical and antigenic properties in DNA stemlines are considered.

Aneuploidy↗
PubMed1988

[Tumorous space occupying lesions of the scapula. An analysis of preoperative assessment of invasion].

The radiographic and histological morphology of 38 tumors lesions of the scapula are analyzed. Osteochondromas (n = 12), chondrosarcomas (n = 7), plasmacytomas (n = 4) and Ewing's sarcomas (n = 3) were the most frequent neoplasms. The radiographically determined growth rates allowed an estimate of the dignity in all cases. Benign lesions were only observed in the first five decades of life, and were mostly located in the scapular blade. Most tumors found in the acromion and in the glenoid region and all lesions diagnosed in the 6th to the 8th decades of life were malignant. In 63.2% of cases correct diagnosis of the type of lesion present was possible on radiographic examination.

Adolescent↗
PubMed1987

Tumor heterogeneity in osteosarcoma as identified by flow cytometry.

Measurements of the cellular DNA content by flow cytometry were carried out in 25 untreated osteosarcomas to identify the frequency of DNA aneuploidies and heterogeneous DNA stemlines in relation to histopathology. Analyzing multiple specimens from each single tumor (2-16; median, 4), highly malignant osteosarcomas were found to express DNA aneuploidies in 18 of 21 cases (86%) with multiple aneuploid DNA stemlines in 10 cases (48%). In three paraosteal osteosarcomas, no DNA aneuploidy was detected and a significantly lower proportion of cells in S-phase was observed as compared to the highly malignant osteosarcomas (mean 8.6% vs. 18.8%; P less than 0.05). Like in the paraosteal osteosarcomas, no DNA aneuploidy and a low fraction of cells in S-phase was found in the predominant cell population of one of the very rare sclerosing small cell osteosarcomas, which also revealed a second DNA stemline with a DNA index of 2.0. These results demonstrate a high degree of DNA stemline heterogeneity in highly malignant osteosarcomas. The data emphasize the usefulness of DNA measurements for the characterization of bone tumors and indicate the possibility of discriminating highly malignant from low-grade osteosarcomas.

Aneuploidy↗
PubMed1987

Biological characterization of human bone tumors. X. The proliferation behavior of macrophages as compared to fibroblastic cells in malignant fibrous histiocytoma and giant cell tumor of bone.

Seven giant cell tumors of bone and four malignant fibrous histiocytomas were studied immunohistochemically with different monoclonal antibodies to the mononuclear phagocyte system (MPS), to HLA-DR antigens, and to a proliferation-associated nuclear antigen (KI-67), in order to clarify the role of macrophages in these tumors. A part of the mononuclear cells stained positive with antibodies against the MPS. Antibody 25-F-9 against mature tissue macrophages showed the strongest reaction. The osteoclast-like giant cells also stained positive with this antibody. Fibroblast-like stromal cells, however, showed negative reactions to all antibodies against MPS cells. A double-labeling immunohistological technique was used to detect the proliferating cell population in these tumors. The fibroblast-like cells that were negative for MPS markers, were positively labeled with the monoclonal antibody Ki-67 against a proliferation-associated nuclear antigen, whereas a negative reaction to Ki-67 was seen in cells positive with antibodies to the MPS. These results support the concept that macrophages are a reactive population in these tumors, whereas the fibroblast-like mesenchymal cells are the proliferating tumor cells.

Antibodies, Monoclonal↗
PubMed1987

Morphology of pulmonary metastases from osteosarcoma during chemotherapy.

Osteosarcoma is known to metastasize rather early, and even after surgical resection of the primary metastases may occur predominantly in the lung. Administration of polychemotherapy for destruction of micrometastases has served to improve prognosis. Preoperative chemotherapy facilitates the evaluation of regression, another factor of high prognostic relevance. Morphologic analysis of pulmonary metastases developing during chemotherapy is of considerable interest on account of the potential therapy resistance of certain histologic subtypes of osteosarcoma. In the present study pulmonary metastases resected in 20 thoracotomies of 15 osteosarcoma patients were investigated by light microscopy and compared, if possible, to the respective primaries. All patients had received chemotherapy, predominantly according to the COSS 80 and COSS 82 protocols. The histologic picture of a tumor was found to change from the primary to the pulmonary metastasis, a pattern also verified in the lung metastases collected in consecutive thoracotomies from the same patient. Several different subtypes were regularly found side by side in the metastases, but generally no special sensitivity or resistance to chemotherapy could be attributed to any of these subtypes. Our results nevertheless do indicate an increased resistance of anaplastic tumor tissue. The response to chemotherapy agreed in 9 of 10 primaries with that of their metastases.

Adolescent↗
PubMed1987

Flow cytometric DNA analysis of malignant lymphomas with primary bone manifestation.

Malignant lymphomas with primary skeletal manifestation have received controversial evaluation with regard to histological classification and histogenesis. Recent histological and immunohistological studies on the rare bone lymphomas conducted by our team, have shown that they do not differ from primary nodal lymphomas with regard to the spectrum of histological subtypes. The present flow cytometric DNA analysis of paraffin-embedded material from 17 lymphomas documented in the Bone Tumor Registry of Westfalia yielded the following distribution pattern of DNA ploidy: among 12 non-Hodgkin's lymphomas (NHL) (according to the Kiel classification) there was only 1 case of low grade malignancy; this centroblastic-centrocytic lymphoma showed a unimodal diploid DNA histogram. Of 11 highly malignant NHL, 6 were DNA hyperdiploid. Among the 5 cases of Hodgkin's lymphoma, 4 were DNA diploid, (1 nodular sclerosing, 3 mixed types) and one DNA tetraploid (lymphocytic depletion type). Comparison with data from the literature reveals that even with regard to DNA ploidy, malignant lymphomas primarily manifesting in bone do not differ from those of exclusively nodal manifestation.

Bone Neoplasms↗
PubMed1987

Cytostatic effects in osteosarcomas as detected by flow cytometric DNA analysis after preoperative chemotherapy according to the COSS 80/82 protocol.

A total of 20 highly malignant osteosarcomas were studied by DNA flow cytometry after preoperative chemotherapy according to the COSS 80/82 protocol to assess their nuclear DNA content and the impact of chemotherapy on DNA ploidy and proliferation. Of the cases studied, 70% revealed aneuploid DNA stem lines with a median value of 1.67, and a median S-phase proportion of 16.1%. These data differed substantially from the results of a preceding study on untreated osteosarcomas revealing a higher frequency of DNA aneuploidy, higher DNA indices, and higher proportions of cells in S-phase. The pretreated tumors also showed a distinct relation between DNA content and the grade of tumor regression. No aneuploid DNA stem line was found in the responder group-I, whereas group-V (osteosarcomas with more than 50% viable tumor tissue) consisted almost completely of aneuploid DNA populations; all tumors with more than 2 DNA aneuploids were found in the latter group. All populations with a DNA index (DI) over 2.0 were found in the nonresponder groups IV and V, where all DNA aneuploids had an S-phase above 12%. No differences in DNA ploidy or proliferation were found in the various histological subtypes of pretreated osteosarcomas. These data indicate that flow cytometric DNA measurement in osteosarcoma may not only serve as a tumor marker, but also support the evaluation of morphologically established regression grades, thereby verifying the patient's prognosis: a high DI (over 2.0), a high number of DNA aneuploids (more than 2), and a high proliferation (S-phase above 12%) seemed to indicate a poor regression of the primary lesion, which may offer a pretherapeutic way of prognostic evaluation.

Adolescent↗
PubMed1987

Identification of macrophages and smooth muscle cells with monoclonal antibodies in the human atherosclerotic plaque.

Sections of human atherosclerotic plaques, obtained from 21 autopsy cases with various degrees of atherosclerosis, were stained with the indirect immunoperoxidase technique using specific monoclonal antibodies against macrophages and smooth muscle cells. Distinctive results were found in differing stages: Single blood monocytes were observed in diffuse intimal thickening and the foam cells seen in fatty streaks were mostly identified as mature tissue macrophages, while only very few blood monocytes were present. The spindle cells observed in fibroelastic plaques showed positive reactions to antibodies against desmin, which points to their derivation from smooth muscle cells, whereas only a few macrophage-derived foam cells were seen in these lesions. In the complicated lesions the majority of foam cells were macrophage-derived, but there was also a small number of foam cells positive to antibodies against desmin, suggesting a smooth muscle cell derivation. Our results confirm that in human atherosclerotic plaques the majority of the foam cells are obviously macrophage-derived, which emphasizes the important role of macrophages in the morphogenesis of these lesions.

Adolescent↗
PubMed1987

Biologic characterization of human bone tumors IX. Occurrence of macrophages.

Fifty bone tumors were investigated using immunohistological methods for an assessment of the amount and nature of macrophage infiltration. Polyclonal antibodies against lysozyme, alpha 1-antichymotrypsin, and alpha 1-antitrypsin were used as markers, besides certain monoclonal antibodies against blood monocytes and mature tissue macrophages. Particularly high macrophage infiltration was found in malignant fibrous histiocytomas, giant cell-containing osteosarcomas, giant cell tumors of bone, and aneurysmal bone cysts. Moderate infiltrates were seen in some highly malignant osteosarcomas, in fibrosarcoma, and in chondroblastoma. A low macrophage content was observed in some osteosarcomas, in Ewing's sarcomas, chordomas, fibrous dysplasias, aggressive fibromatoses, and cartilage tumors. Osteoclast-like giant cells showed distinctly positive reactions with the monoclonal antibody against mature tissue macrophages. In fibrohistiocytic tumors (MFH, giant cell tumor, non-ossifying fibroma) only macrophages gave positive reactions with those antibodies, whereas the reaction of spindle-shaped tumor cells was always negative. These results strongly indicate that the macrophages found in bone tumors (including those of fibrohistiocytic type) result from reactive infiltration. The autochthonous tumor cells are most probably derived from local mesenchymal cells, and are thus cytogenetically unrelated to the infiltrating macrophages.

Antibodies↗
PubMed1987

Malignant lymphomas with primary bone manifestation.

18 malignant lymphomas with initial manifestation in bone were selected from the Bone Tumor Registry of Westfalia at the Münster Institute of Pathology where they had been documented between 1975 and 1985, and evaluated under clinical, radiological and histological aspects. Non-Hodgkin lymphomas were reclassified according to the Kiel nomenclature. Paraffin-embedded material was subjected to immunohistochemical analysis in order to assess the features that could add to the correct characterization of these lymphomas, and to their differentiation from other round cell tumors of bone. Non-Hodgkin lymphomas (NHL) were more common in the collective than Hodgkin's lymphomas (HL). Of 13 NHL, 2 were of low, 11 of high-grade malignancy. The former comprised one centrocytic and one centroblastic/centrocytic, the latter 7 centroblastic, 2 immunoblastic, and 2 lymphoblastic lymphomas. Seven NHL patients with localized tumors survived up to 11 years (mean survival span: 6 yrs) after local therapy (radiation and/or resection). Another NHL patient, however, had multiple bone lesions, and died within a year. Analysis for leukocyte common antigen was positive in 9/12 NHL cases, reaction with Ki-B-3, a marker of B-lymphocytes, was positive in 7/12 cases. No lymphoma cells were found to react positively with lysozyme, alpha 1-antitrypsin, or alpha 1-antichymotrypsin. It is concluded that localized lymphomas of bone respond well to appropriate local therapy; immunohistochemical investigation may be useful to characterize the true cellular origin of these tumors, and may help to differentiate them from other round cell tumors of bone.

Adult↗
PubMed1987

Rhabdomyosarcomatous component in dedifferentiated chondrosarcoma.

The case of a 57-year-old male is described with an extended bone tumor in the proximal left femur. The tumor is histologically classified as dedifferentiated chondrosarcoma. Immunohistologic examination revealed a strong positive reaction for desmin mainly in the tumor giant cells in the dedifferentiated areas, whereas chondroblasts in the low grade chondrosarcoma areas reacted negatively with desmin. In accordance with some cross striation in polymorphic tumor cells this points to a rhabdomyosarcomatous component in the dedifferentiated portions of the tumors. Thus, in addition to fibrosarcomatous, osteosarcomatous and malignant fibrous histiocytoma-like areas, our case presents another sarcomatous constituent in dedifferentiated chondrosarcoma.

Bone Neoplasms↗