Treatment of Extraosseous Giant Cell Tumor of Bone and Calcitriol-Mediated Hypercalcemia With Denosumab in Paget Disease.

Extraosseous giant cell tumor of bone (GCTB) associated with Paget disease of bone (PDB) is rare. We report a patient aged in their 70s with polyostotic PDB involving the skull, spine, and pelvis, previously treated with bisphosphonates, who presented with symptomatic hypercalcemia (calcium 14.8 mg/dL [3.7 mmol/L]; reference range [RR], 8.6-10.5 mg/dL [2.1-2.6 mmol/L]), kidney injury (creatinine 2.6 mg/dL [230 μmol/L]; RR, 0.4-1.1 mg/dL [35-97 μmol/L]), and a 17.5 cm pelvic mass. Testing showed elevated calcitriol or 1,25-dihydroxyvitamin D (1,25(OH)2D) (57-108 pg/mL [137-259 pmol/L]; RR, 18-72 pg/mL [43-173 pmol/L]), but normal parathyroid hormone and bone-specific alkaline phosphatase (BSAP), arguing against parathyroid autonomy and active osseous PDB. Histopathology showed osteoclast-like giant cells and stromal mononuclear cells without atypia, necrosis, or mitoses. A one-time dose of denosumab 120 mg resulted in normalized calcium (9.0 mg/dL [2.2 mmol/L]) and 1,25(OH)2D (24 pg/mL [57 pmol/L]) and reduced tumor size. Denosumab was continued at a dose of 60 mg every 6 months. After 20 months, calcium and 1,25(OH)2D remained normal, with no tumor regrowth, and BSAP stayed low. This is the first report of 1,25(OH)2D-mediated hypercalcemia in extraosseous GCTB. It responded well to denosumab. Long-term management options are discussed in the context of existing literature.