We provide an overview of imaging, histopathology, genetics, and multidisciplinary treatment of giant cell tumor of bone (GCTB), an intermediate, locally aggressive but rarely metastasizing tumor. Overexpression of receptor activator of nuclear factor κB ligand (RANKL) by mononuclear neoplastic stromal cells promotes recruitment of numerous reactive multinucleated giant cells. Conventional radiographs show a typical eccentric lytic lesion, mostly located in the meta-epiphyseal area of long bones. GCTB may also arise in the axial skeleton and very occasionally in the small bones of hands and feet. Magnetic resonance imaging is necessary to evaluate the extent of GCTB within bone and surrounding soft tissues to plan a surgical approach. Curettage with local adjuvants is the preferred treatment. Recurrence rates after curettage with phenol and polymethylmethacrylate (PMMA; 8%–27%) or cryosurgery and PMMA (0%–20%) are comparable. Resection is indicated when joint salvage is not feasible (e.g., intra-articular fracture with soft tissue component). Denosumab (RANKL inhibitor) blocks and bisphosphonates inhibit GCTB-derived osteoclast resorption. With bisphosphonates, stabilization of local and metastatic disease has been reported, although level of evidence was low. Denosumab has been studied to a larger extent and seems to be effective in facilitating intralesional surgery after therapy. Denosumab was recently registered for unresectable disease. Moderate-dose radiotherapy (40–55 Gy) is restricted to rare cases in which surgery would lead to unacceptable morbidity and RANKL inhibitors are contraindicated or unavailable.

Approximately one in five patients with giant cell tumor of bone presents with a pathologic fracture. However, recurrence rates after resection or curettage differ substantially in the literature and it is unclear when curettage is reasonable after fracture. We therefore determined: (1) local recurrence rates after curettage with adjuvants or en bloc resection; (2) complication rates after both surgical techniques and whether fracture healing occurred after curettage with adjuvants; and (3) function after both treatment modalities for giant cell tumor of bone with a pathologic fracture. We retrospectively reviewed 48 patients with fracture from among 422 patients treated between 1981 and 2009. The primary treatment was resection in 25 and curettage with adjuvants in 23 patients. Minimum followup was 27 months (mean, 101 months; range, 27–293 months). Recurrence rate was higher after curettage with adjuvants when compared with resection (30% versus 0%). Recurrence risk appears higher with soft tissue extension. The complication rate was lower after curettage with adjuvants when compared with resection (4% versus 16%) and included aseptic loosening of prosthesis, allograft failure, and pseudoarthrosis. Tumor and fracture characteristics did not increase complication risk. Fracture healing occurred in 24 of 25 patients. Mean Musculoskeletal Tumor Society score was higher after curettage with adjuvants (mean, 28; range, 23–30; n = 18) when compared with resection (mean, 25; range, 13–30; n = 25). Our observations suggest curettage with adjuvants is a reasonable option for giant cell tumor of bone with pathologic fractures. Resection should be considered with soft tissue extension, fracture through a local recurrence, or when structural integrity cannot be regained after reconstruction. Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Giant cell tumours (GCT) of the synovium and tendon sheath can be classified into two forms: localised (giant cell tumour of the tendon sheath, or nodular tenosynovitis) and diffuse (diffuse-type giant cell tumour or pigmented villonodular synovitis). The former principally affects the small joints. It presents as a solitary slow-growing tumour with a characteristic appearance on MRI and is treated by surgical excision. There is a significant risk of multiple recurrences with aggressive diffuse disease. A multidisciplinary approach with dedicated MRI, histological assessment and planned surgery with either adjuvant radiotherapy or systemic targeted therapy is required to improve outcomes in recurrent and refractory diffuse-type GCT.Although arthroscopic synovectomy through several portals has been advocated as an alternative to arthrotomy, there is a significant risk of inadequate excision and recurrence, particularly in the posterior compartment of the knee. For local disease partial arthroscopic synovectomy may be sufficient, at the risk of recurrence. For both local and diffuse intra-articular disease open surgery is advised for recurrent disease. Marginal excision with focal disease will suffice, not dissimilar to the treatment of GCT of tendon sheath. For recurrent and extra-articular soft-tissue disease adjuvant therapy, including intra-articular radioactive colloid or moderate-dose external beam radiotherapy, should be considered.

Background: The rate of recurrence of giant cell tumor of bone is decreased by use of adjuvant treatments such as phenol, liquid nitrogen, or polymethylmethacrylate (PMMA) during curettage. We assessed recurrence and complication rates and functional outcome after curettage with use of phenol and PMMA, liquid nitrogen and PMMA, and liquid nitrogen and bone grafts. Methods: We retrospectively compared the relative effectiveness of treatment of giant cell tumors of bone at two tertiary centers with a regional function from 1990 to 2010. The 132 (of 201) patients who met the inclusion criteria had a mean age of thirty-three years (range, eleven to sixty-nine years). Treatment assignment depended purely on the center, with primary treatment consisting of curettage with use of phenol and PMMA (n = 82) at one center and with use of either liquid nitrogen and PMMA (n = 26) or liquid nitrogen and bone grafts (n = 24) at the other center. Recurrence and complication rates were determined, and functional outcome was assessed on the basis of the Musculoskeletal Tumor Society (MSTS) score. Results: The mean duration of follow-up was eight years (range, two to twenty-two years). Recurrence rates were comparable among the groups (28% for phenol and PMMA, 31% for liquid nitrogen and PMMA, and 38% for liquid nitrogen and bone grafts; p = 0.52). Soft-tissue extension increased the recurrence risk (hazard ratio [HR] = 2.1, 95% confidence interval [CI] = 1.1 to 4.0, p = 0.024). The complication rate was 33% after use of liquid nitrogen and bone grafts, 27% after liquid nitrogen and PMMA, and 11% after phenol and PMMA (p = 0.019); complications included osteoarthritis, infection, postoperative fracture, nonunion, transient nerve palsy, and PMMA leakage. The complication risk was increased by the presence of a pathologic fracture (HR = 4.1, 95% CI = 1.7 to 9.5, p = 0.001) and use of liquid nitrogen (HR = 3.9, 95% CI = 1.5 to 10, p = 0.006 for liquid nitrogen and bone grafts; HR = 3.1, 95% CI = 1.1 to 8.6, p = 0.028 for liquid nitrogen and PMMA). The mean MSTS score was 26 (range, 8 to 30) and was comparable among all three groups (p = 0.52). Conclusions: Recurrence rates were comparable for treatment with phenol and PMMA, liquid nitrogen and PMMA, and liquid nitrogen and bone grafts. Complication rates were higher after use of liquid nitrogen. The functional outcome was excellent in all three cohorts. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Tors, and clinical relevance of osteoarthritis on radiographs after curettage and application of PMMA for the treatment of giant cell tumors around the knee. Methods: This retrospective single-center study included fifty-three patients with giant cell tumor around the knee treated with curettage and PMMA between 1987 and 2007. The median age at the time of follow-up was forty-two years (range, twenty-three to seventy years). There were twenty-nine women. Radiographic evidence of osteoarthritis was defined, preoperatively and postoperatively, as Kellgren and Lawrence grade 3 or 4 (KL3-4). We studied the influence of age, sex, tumor-cartilage distance, subchondral bone involvement (≤3 mm of residual subchondral bone), subchondral bone-grafting, intra-articular fracture, multiple curettage procedures, and complications on progression to KL3-4. Functional outcomes and quality of life were assessed with the Short Form-36 (SF-36), Musculoskeletal Tumor Society (MSTS) score, and Knee injury and Osteoarthritis Outcome Score (KOOS). Results: After a median duration of follow-up of eighty-six months (range, sixty to 285 months), six patients (11%) had progression to KL3, two (4%) had progression to KL4, and one had preexistent KL4. No patient underwent total knee replacement. The hazard ratio for KL3-4 was 9.0 (95% confidence interval [CI] = 2.0 to 41; p = 0.004) when >70% of the subchondral bone was affected and 4.2 (95% CI = 0.84 to 21; p = 0.081) when the tumor-cartilage distance was ≤3 mm. Age, sex, subchondral bone-grafting, intra-articular fracture, multiple curettage procedures, and complications did not affect progression to KL3-4. Patients with KL3-4 reported lower scores on the KOOS symptom subscale (58 versus 82; p = 0.01), but their scores on the other KOOS subscales, the MSTS score (21 versus 24), and the SF-36 (76 versus 81) were similar to those for the patients with KL0, 1, or 2 (KL0-2). Conclusions: Seventeen percent of patients with giant cell tumor around the knee had radiographic findings of osteoarthritis after treatment with curettage and PMMA. A large amount of subchondral bone involvement close to articular cartilage increased the risk for osteoarthritis. The function and quality of life of the patients with KL3-4 were comparable with those for the patients with KL0-2, suggesting that radiographic findings of osteoarthritis at the time of intermediate follow-up had a modest clinical impact. Treatment with curettage and PMMA is safe for primary and recurrent giant cell tumors, even large tumors close to the joint. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence....