Biologic characterization of human bone tumors. III. Giant cell tumor of bone. A combined electron microscopical, histochemical, and autoradiographical study.

The cytogenesis of giant cell tumors of bone was studied in 6 cases by combined electron microscopical, histochemical and autoradiographical investigations. Electron microscopy identified two different types of mononuclear stromal cells: fibroblast-like cells with spindly shape and numerous membranes of the granular ER occur together with macrophages bearing many large lysosomes and a prominent Golgi apparatus. Enzyme histochemical results reflect the same diversity: One portion of mononuclear cells exhibits strong alpha-naphthyl acetate esterase (ANAE) activity, known as a marker for cells of the mononuclear phagocyte system, while the other, fibroblast-like cell type is ANAE negative. Tumor giant cells contain numerous membranes of granular ER, mitochondria, and a few isolated lysosomes. They lack the typical brush border of osteoclasts. Moderate to strong ANAE activity of these giant cells reflects their belonging to the mononuclear phagocyte system. Consequently, the giant cell tumor of bone consists of two different cell types, i.e. fibroblast-like cells and cells of the mononuclear phagocyte system, and so is appraised as a fibrohistiocytic tumor. A new inference from our autoradiographic findings is that tritiated thymidine is incorporated only by mononuclear cells, but not by giant cells. Electron microscopical autoradiography demonstrated that among the mononuclear cells, only fibroblasts are found to proliferate, but not macrophages. Thus, the giant cell tumor of bone is seen as a neoplasm of fibroblastic cells with a strong reactive infiltration of cells from the mononuclear phagocyte system.