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Type: Thesis
Title: Immunocharacterisation of giant cell lesions of the jaws
Author: Hoshyar, Ramesh Mohammad Alizadeh
Issue Date: 1997
School/Discipline: Dept. of Dentistry
Abstract: Many bone and soft tissue tumors and tumor-like lesions are characterised by the presence of a variable number of multinucleated giant cells. Diagnosis of these giant cell lesions, in particular those arising in bone such as central giant cell granuloma and giant cell tumor, is based on an evaluation of the clinical history of the patient, together with the radiological and histologic findings. The occurrence of the central giant cell granuloma is largely confined to the jaws. However, isolated cases of this lesion in the small tubular bones of the hands and feet, facial bones and the skull have been reported. Giant cell tumors occur mainly in the long bones and although infrequent, they have also been reported in the jaws and other sites in the cranial skeleton. Although many of central giant cell granulomas may be distinguished from giant cell tumors on a histologic basis, these lesions are often difficult to differentiate using conventional histologic methods as they can exhibit a variety of morphological appearances and, with the common feature of numerous multinucleated giant cells, may closely resemble each other. Therefore, identification of histologic parameters that could distinguish central giant cell granulomas from giant cell tumors would be valuable in planning optimal therapy. Furthermore, the origin and nature of the cellular components in giant cell lesions has not been satisfactorily established and is still debatable Therefore, further characterisation of these lesions is necessary before their pathogenesis can be determined. The aims of the present study were to: a. Perform a retrospective clinical analysis on a subset of giant cell lesions taken from a South Australian population. b. Further evaluate the antigenic profile of the cellular components of giant cell lesions of the jaws using a panel of monoclonal and polyclonal antibodies, and enhanced antigen retrieval techniques using microwave fixation. c. Further investigate the possible differences between the antigenic profile of the cellular components of the giant cell lesions occurring in the jaws and those of extragnathic sites. A total of 55 cases of giant cell lesions were recovered from archives. The histories of all cases were reviewed and pertinent data regarding age, sex and site of the lesions were tabulated, analyzed and compared with international frequency studies. For the antigenic profile studies, 38 formalinfixed and paraffin-embedded specimens (20 peripheral giant cell granulomas, 15 central giant cell granulomas, and 3 giant cell turners) were sectioned at 5 J..lrn intervals and immunoincubated using microwave antigen retrieval methods. Sections were immunostaine1d using avidin-biotin-peroxidase complex immunohistochemical techniques, with a panel of markers including CD68, MAC 387, CD34, HAM 56 and Factor Xllla. Immunoreactivity was semi-quantitatively graded on a- to+++ scale. The approximate percentage range of cells reacting positively (in the one section) to each antibody was also evaluated in order to assess uniformity of staining. Results revealed that the age and site distribution of South Australian cases of central giant cell granuloma, and gender distribution of South Australian cases of central and peripheral giant cell granuloma, showed some differences from those reported by other investigators. This may have reflected sampling differences. In the immunohistochemical study, multinucleated giant cells exhibited a strong positive reaction for CD68, thus supporting the view of their origin from macrophages. However, the giant cells did not stain for MAC 387 and HAM 56, supporting the concept that these cells may be a subset of specialized giant cells derived from the mononuclear phagocyte system, such as osteocl asts. The positive reaction of mononuclear stromal cells for CD68, MAC 387 and HAM 56 suggests that these cells originate from the macrophage (or the mononuclear phagocyte system). This relationship was reinforced by the strong positive reaction of mononuclear stromal cells to the dermal dendrocytic marker, Factor Xllla. Endothelial cells reacted positively for CD34 and HAM 56. The blood vessels located deeper within the giant cell lesions stained as intensely for these antibodies as those at the periphery of the lesions. There were no obvious differences between the immunostaining patterns of the cellular components of central and peripheral giant cell granuloma. Except for the increased vascularity of giant cell tumor, no major differences were found in the immunostaining patterns between the central giant cell granuloma and the giant cell turner. Whereas further work needs to be done comparing the vascularity of these lesions. the results of this study support the view that central giant cell granuloma and giant cell tumor represent part of a spectrum of a single disease process and that differentiating central giant cell granulomas from giant cell turners remains a difficult diagnostic exercise.
Advisor: Pierce, Angela M
Wilson, David F
Dissertation Note: Thesis (MDS) -- University of Adelaide, Dept. of Dentistry, 1998
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