Extraosseous primary and recurrent giant cell tumors: Transforming growth factor-β1 and -β2 expression may explain metaplastic bone formation

Giant cell tumor (GCT) of bone is a locally aggressive neoplasm with a high incidence of recurrence, usually at the site of previous osseous involvement. Primary and recurrent intraosseous lesions typically are lytic and do not show evidence of tumor-associated osteogenesis. Rarely, GCT recurs or is primary within soft tissue, and not infrequently, these extraosseous lesions show metaplastic bone formation that is visible radiographically. The authors report two recurrent and one primary case of extraosseous GCT, all of which exhibited significant deposits of metaplastic bone localized to the periphery of the lesions. In situ hybridization showed messenger RNA (mRNA) for transforming growth factor β1 (TGF-b1) and transforming growth factor β2 (TGF-β2) in neoplastic stromal cells and osteoclast-like giant cells within the recurrent and primary extsaosseous tumors as well as in active osteoblasts on the surfaces of recently formed spicules of metaplastic bone. In situ hybridization also revealed mRNA for TGF-b1 and TGF-β2 in primary intraosseous tumors from these cases and from four cases in which neither extraosseous recurrence nor osseous metaplasia was identified. In the microenvironment of the extraosseous soft tissue, production of these osteoinductive growth factors by GCT may have a paracrine effect on mesenchymal progenitor cells, thereby stimulating the osteoblastic differentiation and metaplastic bone formation associated with these lesions.