Giant-cell tumor (GCT) of bone is a locally aggressive neoplasm with a tendency for recurrence. Rarely, these tumors may be associated with metastasis and sarcomatous behavior1. Management typically involves intralesional curettage and bone-grafting, either with or without adjuvant therapy; some cases necessitate wide resection and/or radiation therapy2,3. Recently, factors known to contribute to osteoclast activation and differentiation have been identified, including tumor necrosis factor-related proteins, osteoprotegerin, and the receptor activator of nuclear factor-κB ligand (RANKL)4. The latter is present in GCT and is thought to result in the recruitment of osteoclasts5-7. Monoclonal antibodies targeting this ligand have recently been applied to the management of GCT8. We present two patients with unusual morphologic and immunophenotypic changes observed in a GCT following denosumab (AMG 162) (RANKL inhibitor) treatment. The patients were informed that data concerning their cases would be submitted for publication, and they provided consent. Case 1. A twenty-nine-year-old man with a history of GCT (6.3 × 5.6 × 3.2 cm) that was resected from the proximal part of the right fibula two years prior returned with a lateral knee mass. Radiographs demonstrated an expansile, lytic mass (5.5 × 3.0 × 2.7 cm) in the previous tumor site. Positron emission tomography (PET)/computed tomography (CT) highlighted this lesion and additionally demonstrated a separate hypermetabolic lesion (3.6 × 2.5 × 2.3 cm) within the soft tissue of the ipsilateral distal part of the thigh (Fig. 1). Based on its location and distance from the previous surgical site, this lesion was considered consistent with a metastasis. Biopsy of both lesions showed a monotonous population of small, bland epithelioid and spindle cells with diffusely present giant cells, confirming the diagnosis of GCT (Fig. 2). Fig. 1 PET/CT highlighting the patient’s (Case …
