Denosumab-Treated Giant Cell Tumor of Bone Its Histologic Spectrum and Potential Diagnostic Pitfalls

Giant cell tumor of bone (GCT) is a locally aggressive, rarely metastasizing primary bone neoplasm that occurs most frequently in the epiphysis of long bones of young adults. It is composed of round, oval or elongated mononuclear cells admixed with osteoclast-like giant cells that express receptor activator of nuclear factor- қB (RANK). The mononuclear stromal cells express RANK ligand (RANKL), a mediator of osteoclast activation. Denosumab, a monoclonal antibody that inhibits RANKL reducing tumor-associated bone lysis, has been used to treat selected cases of GCT. We reviewed the clinical records and histologic slides of 9 patients with GCT that had received denosumab therapy and were subsequently surgically treated. There were 5 males and 4 females, aged 20 to 66 (mean 36). Duration of treatment varied from 2,5 to 13 months (mean 5,9). In all cases, different degrees of ossification, fibrosis, depletion of giant cells and proliferation of mononuclear cells were seen. With this combination of changes, denosumab-treated GCT may mimick other lesions such as fibrous dysplasia, juvenile ossifying fibroma, nonossifying fibroma and osteoblastoma. Less frequent but more relevant is the presence of cellular atypia or patterns of ossification that resemble an undifferentiated pleomorphic sarcoma, a conventional osteosarcoma or a low-grade central osteosarcoma. The presence of clinical and radiological response to denosumab along with the lack of high mitotic activity, atypical mitotic figures, extensive necrosis or a permeative pattern of growth, represent clues to achieve a correct diagnosis.