The Multinucleate Cells in Giant Cell Granulomas of the Jaw Are Osteoclasts

The giant cell granuloma of jaw is a well-vascularised lesion comprising a mononuclear cell infiltrate with a large number of giant cells. It has been suggested that the lesion is reparative in nature, rather than neoplastic, and that the giant cells are phagocytes accumulating in chronic reparative granulation tissue. However, the nature of the multinucleate giant cells never has been established. One possibility is that the constituent giant cells are osteoclasts. The authors assessed expression by the giant cells of several osteoclast-specific characteristics: excavation of bone; motility inhibition by calcitonin (CT); and binding of osteoclast specific monoclonal antibodies. Two tumors were disaggregated and incubated on slices of cortical bone in the presence and absence of CT. Both tumors were found to excavate bone, a function unique to osteoclasts. The giant cells also were responsive to CT, resulting in cytoplasmic quiescence and inhibition of bone resorption. Two osteoclast-specific monoclonal antibodies bound all the giant cells in one central and six peripheral tumors examined immunohistochemically. These results provide strong evidence for the osteoclastic nature of the giant cells. The presence of alkaline phosphatase-positive cells forming woven bone in giant cell granulomas suggests that osteoblasts are present in the lesion. As cells of osteoblastic lineage are known to regulate osteoclastic function, it may be that osteoblasts account for the characteristic infiltration of osteoclasts into giant cell granulomas of jaws, either as part of a reparative response by reactive osteoblasts or as an infiltrate induced by osteoblasts of aberrant function, as suggested for giant cell tumors of bone.