Giant cell tumor of bone (GCTB) is a locally aggressive primary bone tumor classically considered benign but with potential for local recurrence (15-25%), pulmonary metastasis (1-9%, benign metastasizing GCTB), and rare malignant transformation (less than 1% primary, increased with prior radiation). It accounts for 5-10% of all primary bone tumors and 20% of benign bone tumors. Demographics: skeletally mature young adults aged 20-40 (peak 25-35), with slight female predominance (1.3:1). Geographic variation exists, with higher incidence reported in Asian populations.
Anatomic distribution: GCTB typically arises in the epiphyseal region of long bones with extension into metaphysis after physeal closure. Most common sites: distal femur (30%), proximal tibia (20%), distal radius (10%), proximal humerus, sacrum (most common axial site, often more aggressive), and rarely pelvis, spine, hand bones. The 'around the knee' region accounts for 50%. Histology: characteristic triad — (1) numerous large multinucleated osteoclast-type giant cells expressing RANK and TRAP positivity, (2) mononuclear neoplastic stromal cells (the actual neoplastic component, RANKL-expressing, harboring H3F3A G34W or G34L mutation in 90-96%), (3) macrophage-like mononuclear cells. The H3F3A mutation is highly specific (over 95% sensitivity, near 100% specificity) and useful in differential diagnosis from giant cell-rich lesions (aneurysmal bone cyst, brown tumor of hyperparathyroidism, chondroblastoma, non-ossifying fibroma).
Imaging: plain radiographs show eccentric, expansile, lytic, geographic lesion with thin sclerotic rim or no surrounding sclerosis (Lodwick IB/IC). The lesion typically extends to subchondral bone, occasionally penetrating articular cartilage. Soap bubble appearance from internal trabeculation. CT defines cortical thinning and breakthrough. MRI shows low-intermediate T1, heterogeneous T2 with fluid-fluid levels (when complicated by aneurysmal bone cyst component, 14% of cases) and avid contrast enhancement. Campanacci classification: Grade I (latent, intact cortex), Grade II (active, thinned but intact cortex), Grade III (aggressive, cortical breakthrough with soft tissue extension). Diagnosis requires biopsy with histology and ideally molecular confirmation. Treatment depends on grade and resectability. Standard treatment is intralesional curettage with high-speed burr extending margin (mechanical adjuvant), followed by chemical adjuvants (phenol, hydrogen peroxide, ethanol, argon beam coagulation, or cryotherapy with liquid nitrogen) to extend the kill zone, then filling with polymethylmethacrylate (PMMA) cement (provides immediate stability, exothermic reaction, allows imaging surveillance for recurrence) or bone graft. Recurrence rate with curettage and adjuvants is 15-25%, primarily within 2 years. Wide resection (en bloc) is reserved for expendable bone locations (fibula, distal ulna, proximal fibula), large soft tissue extension, or recurrent unresectable. Denosumab (RANKL monoclonal antibody, 120 mg subcutaneous monthly with loading days 8 and 15) is FDA-approved for unresectable disease, surgically morbid disease (sacral, spinal, pelvic), recurrent, and neoadjuvant before resection (reduces tumor size and ossifies tumor enabling less morbid surgery). Pulmonary metastases (most lung) occur in 1-9% of patients, requiring chest CT surveillance every 6-12 months. Pulmonary GCTB lesions are often benign but require resection or denosumab. Malignant transformation (less than 1% primary, more with radiation) presents as high-grade sarcoma requiring oncologic resection plus chemotherapy.