Giant Cell-Rich Tumors of Bone and Soft Tissue

Many benign and malignant bone and soft tissue tumors can contain giant cells in variable amounts. In some tumors, such as tenosynovial giant cell tumor and giant cell tumor of bone, these osteoclast-like giant cells are so prominent and characteristic that their presence has defined the entity. Other examples of bone tumors in which the presence of osteoclast-like giant cells is characteristic include chondroblastoma, aneurysmal bone cyst, nonossifying fibroma, and central giant cell granuloma. These tumors have a distinct pathogenesis, although some parallels can be identified. The osteoclast-like giant cells within these tumors are not the neoplastic component but are nonneoplastic bystanders and part of the tumor microenvironment. Notably, the activation of the colony-stimulating factor 1 (CSF1)-CSF1 receptor (CSF1R) and/or the receptor activator of NFκB ligand-receptor activator of NFκB signaling pathways, best studied in tenosynovial giant cell tumor and giant cell tumor of bone, respectively, appears to be key in attracting macrophages and the formation of osteoclast-like giant cells within the tumor. Among soft tissue tumors, a plethora of tumors have been described to contain variable amounts of giant cells, and the underlying mechanisms are so far less well understood. One exception is the recently described keratin-positive giant cell-rich tumor of soft tissue, which also seems to rely on CSF1-CSF1R signaling to attract giant cells. The CSF1-CSF1R and receptor activator of NFκB ligand-receptor activator of NFκB pathways are suitable targets for nonsurgical interventions, and inhibitors of these pathways are already being used for some entities in clinical practice. These inhibitors inhibit tumor growth and may induce bone formation, although pathologists should be aware when evaluating posttreatment specimens that the neoplastic cells remain unaffected.