Beta 3 subunit of vitronectin receptor is present in osteoclast adhesion structures and not in other monocyte-macrophage derived cells.

The distribution of extracellular matrix receptors in human osteoclasts has been studied; a beta 3 integrin is colocalized with vinculin and talin in the podosomes of osteoclastoma giant cells and not in macrophages from the same source.

Osteoclast-type giant cell tumor of the endometrium. An immunohistochemical study.

We present a rare case of a 55 year old female with an osteoclast-type giant cell tumor of the endometrium associated with leiomyoma and adenomyosis. Multinucleated giant cells and mononuclear stromal cells reacted with vimentin and alpha-1-antichymotrypsin (AACT) using the immunoperoxidase method. Epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and keratin exhibited negative immunoreaction in these tumor cells. Our immunohistochemical results do not support the epithelial origin of an osteoclast-type giant cell tumor and mesenchymal derivation appeared more likely, suggesting histiocytic origin.

Steroid receptors and giant cell tumor of bone.

The cell of origin and giant cell tumor remains unknown, but on the basis of most experimental evidence it is probably a mesenchymal cell showing some macrophage characteristics. The clinical features which have led people to suggest that this tumor may be a steroid receptor positive lesion are tenuous at best. Early histochemical data suggesting a presence of estrogen and progesterone receptors in giant cell tumor have not been substantiated by further studies. Immunohistochemical techniques have not identified estrogen receptors in giant cell tumor. Multiple biochemical techniques have failed to identify clinically significant levels of estrogen or progesterone receptors in giant cell tumor.

Immunohistochemistry: a useful adjunct in the evaluation of malignant cutaneous spindle cell tumors.

We used immunohistochemistry to evaluate four cytologically malignant cutaneous neoplasms on the face or neck of elderly individuals. All four lesions were composed of a dermal proliferation of spindle and pleomorphic giant cells. Differential diagnosis included spindle cell carcinoma, atypical fibroxanthoma, malignant melanoma, leiomyosarcoma, and angiosarcoma. All four neoplasms were strongly immunoreactive for vimentin and negative for cytokeratin, S100 protein, desmin, and factor-VIII-related antigen. Focal immunoreactivity for lysozyme and/or a1-antichymotrypsin was seen in the giant cells of each lesion. These results supported the diagnosis of atypical fibroxanthoma in each instance. Immunohistochemical staining can provide useful information for distinguishing among malignant cutaneous spindle cell tumors.

Granulocyte macrophage colony-stimulating activity production by cultured human thymic nonlymphoid cells is regulated by endogenous interleukin-1.

Supernatants of cultured human thymic nonlymphoid cells were assayed for granulopoietic factors using cultures of low density bone marrow mononuclear cells (LD-BMMC). Thymic nonlymphoid cell-conditioned medium (TNLC-CM) supported vigorous myeloid colony growth of LD-BMMC, and of LD-BMMC depleted of T lymphocytes and/or monocytes. Colony stimulating activity (CSA) in TNLC-CM was abrogated by a highly specific neutralizing antiserum against recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). TNLC-CM also enhanced colony growth in LD-BMMC stimulated by colony stimulating activity from a giant cell tumor culture (GCT). The enhancing activity of TNLC-CM, unlike its CSA activity, required the presence of adherent cells in the marrow cell culture. The addition of anti-interleukin-1 (anti-IL-1) antibody to TNLC-CM inhibited the GCT-enhancing activity, but not the CSA. When the anti-IL-1 immunoglobulin was added directly to cultures of thymic nonlymphoid cells, GM-CSF production was completely inhibited, and the GCT enhancing activity was neutralized. We conclude that an intercellular regulatory network exists in cultured thymic explants in which GM-CSF expression is induced by IL-1. In this system, the granulopoietic effect of IL-1 derives not from a direct effect on myeloid progenitors, but from its ability to recruit CSA production by other cells.

Prostaglandin synthesis by osteoid osteoma and osteoblastoma.

Osteoid osteomas are characterized clinically by a pattern of nocturnal pain which is exquisitely sensitive to salicylates. Etiology for the pain has been ascribed by previous investigators to the presence of nonmyelinated nerve fibers or to the effect of prostaglandins. In an effort to corroborate the potential role of prostaglandins in mediating the pain associated with this tumor, we have determined the concentration of prostaglandins E2, F2 alpha, 6-keto-F1 alpha, and thromboxane B2 utilizing radioimmunoassay of extracts of homogenated tumor tissue. Results were compared with similar extracts of normal bone and a variety of other osseous tumors. The increased concentrations of prostaglandin E2 found in cases of osteoid osteoma and osteoblastoma confirm studies of explants of these tumors previously recorded in the literature.

Calcitonin receptors of human osteoclastoma.

Osteoclast-rich cultures were prepared by disaggregation of osteoclastomas (giant cell tumour of bone) and settlement onto glass or plastic surfaces. Autoradiography using [125I]-salmon calcitonin ([125I]-sCT) revealed specific binding only to multinucleate giant cells (osteoclasts) and a minor population of mononuclear cells. [125I]-sCT competitive binding studies indicated a Kd of 5 x 10(-10) M and receptor number of approximately 1 million sites/osteoclast. sCT treatment resulted in a dose-dependent rise in cAMP (EC50 10(-10) M). Homogenates of an osteoclastoma also demonstrated specific binding of [125I]-sCT. Chemical cross-linking of a labelled synthetic sCT derivative. [125I]-[Arg11,18,Lys14]-sCT, using disuccinimidyl suberate, resulted in labelling of a receptor component of approximate Mr 85-90,000. The multinucleate giant cells (osteoclasts) of human osteoclastomas possess large number of CT receptors which exhibit the same binding kinetics and apparent Mr as those of other CT target cells.

Breast carcinoma with stromal multinucleated giant cells--a light microscopic, histochemical and ultrastructural study.

A rare form of infiltrating ductal carcinoma of the breast containing numerous benign stromal multinucleated giant cells (MNGC) is described. Giant cell tumours of the breast are usually the result of stromal metaplasia or fusion of malignant cells or occur as extraskeletal giant cell tumours. Benign multinucleated cells in breast carcinoma, however, are a very unusual phenomenon and have been said to arise from the fusion of mononuclear cells, in response to increased vascularity. The present investigation by light and electron microscopy, in part, supports an origin for the multinucleated giant cells from mononuclear cells, but immunohistochemistry surprisingly failed to confirm this observation. Also, the formation of the multinucleated giant cells did not show any direct relationship with tumour vascularity.

Histochemical, immunohistochemical and ultrastructural investigations of giant cell tumors of bone.

The origin and characteristics of so-called stromal cells (stromal cell) and the osteoclast-like giant cell series of 19 cases of giant cell tumor (G.C.T.) of bone were studied. Immunohistochemically, two interesting cases were found. The stromal cells of one case were alpha-1-antitrypsin positive and those of the other case were alpha-1-antichymotrypsin positive. The histiocytic stromal cells of the latter case seemed to be surely neoplastic since they showed mild to moderate cell atypism. There were foci consisting of fibroblastic cells or osteoid and osteoblasts within the tumor. Those cells in the foci were apparently continuous with the surrounding stromal cells, and they were, therefore, also considered to be neoplastic. These findings strongly indicate that the stromal cells originate from the undifferentiated mesenchymal cells in the bone marrow and may differentiate to osteoblastic, fibroblastic, and histiocytic cells. All cells of these three series were not stained for a high stable form of acid phosphatase (SAPhase). SAPhase activity was demonstrated only in osteoclast-like giant cells and some mononuclear cells, which are recently believed to be non-neoplastic. Therefore, the cell atypia of SAPhase negative stromal cells is considered to have a prognostic value.

Characterization of cells from human giant cell tumors of bone.

In vitro cell culture techniques were used to identify and characterize the individual cell types present in human giant cell tumors of bone. Three major cell types were identified based on morphologic characteristics, patterns of specific cell surface antigens, presence of receptors for hormones, and cell products. One population consisted of mononuclear cells that expressed monocyte-macrophage markers. These cells lacked receptors for skeletal hormones and did not persist in culture. Distinct from these cells was a population of mononuclear cells that proliferated in culture and most likely represented the neoplastic element of the tumor. These cells phenotypically resembled connective tissue stromal cells, i. e., they did not express macrophage surface antigens and they produced collagens (Types I and III). They also possessed receptors for parathyroid hormone. The final population of tumor cells consisted of multinucleated giant cells. These cells lacked monocyte-macrophage surface antigens and possessed receptors for calcitonin, a phenotypic marker for osteoclasts. These studies illustrate that in vitro cell culture techniques can be employed to identify and characterize the cell populations of tumors of skeletal tissues, and demonstrate the usefulness of these cell culture models for investigating the biology of bone tumors.

[The relationship between cell kinetics and histological features of giant cell tumor of the bone].

This study was undertaken to clarify the relationship between the proliferative activity and histological findings of the giant cell tumor (GCT) of bone by means of an epi-illumination cytofluorometer (NIKON SPM-RF1-D). Fresh tissues of GCT were surgically obtained from two cases. In both cases, small pieces of tumor tissues were obtained from several different regions based on the macroscopic characteristics of the cut surface, and processed for single cell preparation using enzymatic method. These isolated cells were smeared and stained with acridine orange, and then analyzed cytofluorometrically to determine simultaneously DNA and RNA contents of the individual cells. The results showed that the proliferative activity of tumor cells was much higher in the regions composed of both many histiocytic stromal cells having polygonal or ovoid shape and many multinucleated giant cells, than either in the regions composed of fibrocytic stromal cells accompanying abundant collagen fibers or in the regions composed of foamy cells.

Grading of bone tumors by analysis of nuclear DNA content using flow cytometry.

We studied 217 consecutive tumors of bone by flow cytometric analysis of nuclear DNA concentration after staining with propidium iodide. A diagnosis and histological grade (benign, low-grade, or high-grade sarcoma) were assigned to each tumor on the basis of staging data (with the exception of the forty-six giant-cell tumors, which, although indistinguishable histologically, were divided according to the flow cytometric pattern into two distinct groups), and we quantitatively studied the flow cytometry data to assess the percentages of cells in diploidy, tetraploidy, or aneuploidy. When compared, the mean values for the flow cytometric data for the three grades showed significant differences. Criteria were established for the three classes of tumors: for benign tumors, less than 11 per cent tetraploidy and no aneuploidy; for low-grade sarcomas, more than 11 per cent and less than 17 per cent tetraploidy, and no aneuploidy; and for high-grade tumors, either more than 17 per cent tetraploidy or aneuploidy. Tests for compliance for all groups of tumors (excluding the forty-six giant-cell tumors)--benign, low grade, or high grade--were significant for most of the benign lesions (with the exception of chondroblastoma and fibrous dysplasia) and for the high-grade sarcomas (with the exception of round-cell tumors). The low-grade sarcomas did far less well, based principally on the failure of the low-grade chondrosarcomas, chordomas, and adamantinomas to comply with the criteria. An attempt to assess the value of the system as a predictor of metastases showed that a low percentage of diploid cells (less than 75 per cent) and the presence of an aneuploid peak correlated statistically with the development of metastatic disease, but the usefulness of this observation could not be fully assessed because of multiple variables, associated principally with treatment.

Giant granular cell tumor of the suprasellar area: immunocytochemical and electron microscopic studies.

We describe a case of a granular cell tumor (GCT) of the suprasellar region with an 11-year history in a 26-year-old woman. The computed tomographic scan showed a midline, contrast-enhancing, noncalcified mass. The biopsy was diagnosed as GCT. The tumor was treated with radiation therapy. At necropsy, a large, homogeneous GCT surrounded by gliosis was found. The tumor cells were filled with granules positive for periodic acid-Schiff, diastase-resistant. The cells did not contain glial fibrillary acidic protein or S-100 protein. Electron microscopy showed tumor cells filled with innumerable lysosomal structures. No intermediate filament was found within the cytoplasm. The tumor cells were not surrounded by a basement membrane. Based on this study and on our review of the literature, the suggestion that GCT has a multicellular origin is upheld.

[Trace elements of bone tumors]. / Mikroélementy opukholei kostei.

Due to activation analysis involving the use of neutrons from a nuclear reactor, the concentrations of 11 trace elements: scandium, iron, cobalt, mercury, rubidium, selenium, silver, antimony, chrome, zinc and terbium in intact bone and skeletal tumors were measured. 76 specimens of bioptates and resected material of operations for bone tumors and 10 specimens of normal bone tissue obtained in autopsies of cases of sudden death were examined. The concentrations of trace elements and their dispersion patterns in tumor tissue were found to be significantly higher than those in normal bone tissue. Also, the concentrations of some trace elements in tumor differed significantly from those in normal tissue; moreover, they were found to depend on the type and histogenesis of the neoplasm.

Microspectrophotometric quantitation of DNA in bone tumors with giant cells (osteoclastoma, osteosarcoma and chondroblastoma).

A microspectrophotometric study of DNA content was carried out on cells from three types of bone tumor--osteoclastoma, chondroblastoma, and osteosarcoma--in all of which the formation of multinucleated giant cells occurs. Giant cells of osteoclastic type were present in all the tumors, with contents of DNA which were constant, uniform and diploid in character for each nucleus individually considered. Since there were no nuclei with reduced or increased content of DNA, mitotic proliferation or gemmation can be excluded. Instead, the evidence suggests the formation of giant cells through a mechanism of cellular fusion. In contrast, the stromal cells of the osteoclastomas and the chondroblastomas gave evidence of DNA synthesis, thus proving their proliferative capacity in both tumors. The osteosarcomas showed a very irregular distribution of DNA, and generally the nuclear content of DNA exceeded the diploid DNA content.

Dysgerminoma with giant cells. A case report with immunoperoxidase.

A 15-year-old female with a positive pregnancy test was found to have a large ovarian tumor. Histology revealed a pure dysgerminoma with unusual giant cells, reminiscent of syncytiotrophoblast. PAP immunoperoxidase to the beta subunit of human chorionic gonadotropin (HCG) was performed on tumor sections. HCG was demonstrated within and confined to the giant cells. All studies for alpha-fetoprotein were negative. The use of immunoperoxidase in the evaluation of tumor markers and in the management of this unique tumor is discussed.