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We performed a systematic analysis of existing studies to determine whether preoperative denosumab reduces the risk of local recurrence for patients with giant cell tumor of bone treated with en bloc resection and to address the optimal duration of preoperative denosumab with respect to the risk of local recurrence after en bloc resection. Denosumab did not decrease the risk of local recurrence after en bloc resection; the proportion of patients with local recurrence was 3.6% (2 of 56) in the en bloc resection with preoperative denosumab group vs 14.2% (40 of 280) in the en bloc resection alone group, with an overall pooled odds ratio of 0.76 ( P =.67). Meta-regression models revealed no association between the duration of preoperative denosumab and the odds of local recurrence after en bloc resection ( P =.83). Administration of denosumab for 3 months before en bloc resection is appropriate for sufficient bone hardening to reduce tumor cell spillage and does not result in denosumab-related complications. [ Orthopedics . 2021;44(6):326–332.]

There are conflicting reports regarding the outcome and effect of denosumab for distal radius giant cell tumor of bone (GCTB). The authors performed this study to evaluate the behavior of distal radius GCTB in relation to the type of treatment and the administration of denosumab. The files of 72 patients with distal radius GCTB treated from 1984 to 2018 were reviewed. Fourteen patients were administered denosumab. Surgical treatment consisted of curettage (25 patients) or resection (47 patients) and allograft or vascularized fibular head graft reconstruction. Median follow-up was 63.1 months (interquartile range [IQR], 35.5–107.1 months). The authors evaluated local recurrences, metastasis, function, and complications. The local recurrence rate was 30.6% at a median of 14.0 months (IQR, 10–19 months), with no difference between curettage and resection. The local recurrence rate was significantly higher in the patients who received denosumab. The metastasis rate was 9.7% at a median of 41.0 months (IQR, 15–114 months), with no difference regarding denosumab administration. Function was significantly better in patients after curettage. The complication rate was 25%; vascularized fibular graft reconstruction was associated with fewer complications. This study found that denosumab increases the risk of local recurrence after curettage, function is better after curettage, and vascularized fibular graft is the optimal reconstruction after resection of distal radius GCTB. [ Orthopedics . 2020;43(5):284–291.]

P53 is the best known tumor suppressor gene. If p53 is mutated, the ability of the cell to sense and repair DNA defects is lost. Failure of this mechanism increases the risk of malignant transformation and tumorigenesis. P53 overexpression is implicated in many carcinomas. P53 alterations appear to be frequent in bone and soft tissue sarcoma and have a strong negative impact on survival in various subtypes of sarcoma like Ewing's sarcoma, synovial sarcoma, and myxoid liposarcoma. There is also evidence in the literature that p53 may be implicated in bone giant cell tumor behavior. The goal of this pilot retrospective study was to detect p53 mutation in giant cell tumor of bone and correlate it with clinical outcome. We analyzed the presence of p53 mutation in 39 patients with giant cell tumor of bone by means of immunohistochemical staining; 8 tumors expressed mutated p53 protein. Seven of them recurred locally ( P P Limitations of this study include the retrospective data collection, the limited number of patients, and the multifactorial nature of the disease; tumor grade, surgical margins, use of adjuvant therapy, and thoroughness of excision may influence the therapeutic outcome. Despite these limitations, this correlation should be further investigated with larger clinical studies. P53 may be used as a marker for the biologic behavior of giant cell tumor of bone.

Giant cell tumor of bone is a locally aggressive tumor with a high local recurrence rate. Several adjuvant therapies have been employed to reduce the recurrence rate, but their effectiveness remains controversial. The authors attempted local administration of zoledronic acid, a nitrogen-containing bisphosphonate that strongly inhibits bone resorption, as an adjuvant treatment for histologically proven giant cell tumor of bone in 5 patients at their institution. After biopsy, 4 patients were treated with local administration of zoledronic acid with artificial bone and 1 was treated with zoledronic acid without artificial bone. Histologic response to the treatment was evaluated with surgically resected specimens. The 4 patients treated with artificial bone showed local control, with histologic tumor necrosis rates of 90%, 90%, 50%, and 10%. Magnetic resonance imaging showed poor gadolinium enhancement, and histologic examination after local zoledronic acid treatment showed tumor necrosis. One patient without artificial bone showed no histologic tumor necrosis and had local recurrence in soft tissue 18 months after tumor resection. A 3-week waiting period between biopsy and zoledronic acid treatment appears reasonable from the histological study. Complication of this therapy was delayed wound healing and it occurred in 2 cases. Taken together, this case series suggests that local administration of zoledronic acid with artificial bone is a potential adjuvant therapy for giant cell tumor of bone. On the other hand, effective local administration of zoledronic acid requires some bone matrix, including artificial bone. Campanacci’s grading is important for predicting the effect of local administration of zoledronic acid. [ Orthopedics. 2015; 38(1):e25–e30.]

Malignant transformation of conventional giant cell tumor of bone is rare and usually occurs with irradiation. This article describes a case of malignant transformation of a giant cell tumor 15 years after initial curettage and bone graft. A 35-year-old man was admitted to the hospital with a recurrent giant cell tumor of the distal femur. On presentation, the patient reported the insidious onset of a dull aching pain in the distal part of the left thigh 4 months prior to admission. Radiographs revealed a destructive lesion in the left distal femur. Needle biopsy revealed recurrence of giant cell tumor with suspected malignant transformation. The patient underwent en bloc resection of the distal femur with adequately wide margins and reconstruction of the knee joint with a prosthesis. Pathological findings showed malignant transformation of a giant cell tumor to high-grade spindle cell sarcoma. Immunohistochemistry showed diffuse and strong p53 expression. A diagnosis of secondary fibrosarcoma was made after discussion. Unfortunately, the tumor proved to be highly resistant to the chemotherapy, and the patient died of multiple lung metastases 14 months after the diagnosis of malignant transformation. What has to be stressed in this case is that any late recurrence must be approached considering the possibility of a secondary induced primary tumor. Because of the rarity of this disease, the effective therapeutic strategy for fibrosarcoma secondary to giant cell tumor is lacking. In addition, identification of the p53 mutation may help in diagnosing cases of potential malignant transformation of giant cell tumor.

Educational Objectives As a result of reading this article, physicians should be able to: 1. Identify at-risk populations for giant cell tumor of bone. 2. Recognize the biology that drives giant cell tumor of bone. 3. Describe modern surgical and adjuvant techniques to effectively treat giant cell tumor of bone. 4. Recognize the complications associated with radiation therapy, poor resection, and adjuvant treatments. Giant cell tumor of bone (GCT) is a benign, locally aggressive bone tumor. Giant cell tumor of bone primarily affects the young adult patient population. The natural history of GCT is progressive bone destruction leading to joint deformity and disability. Surgery is the primary mode of treatment, but GCT has a tendency to recur locally despite a range of adjuvant surgical options. Pulmonary metastasis has been described. However, systemic spread of GCT rarely becomes progressive, leading to death. This review presents the clinicopathologic features of GCT and a historical perspective that highlights the current rationale and contro-versies regarding the treatment of GCT. [ Orthopedics. 2014;37(2):112–120.]

Benign primary bone tumors are commonly treated with intralesional curettage with or without the use of surgical adjuvants. The reconstructive approach to the resulting contained bone defects is controversial, and clinical practice is varied. Synthetic bone substitutes may provide early mechanical support while minimizing the risks of disease transmission, nonunion, infection, and donor-site morbidity. Limited data exists regarding the use of calcium sulfate–calcium phosphate composite bone substitute for this purpose. The authors retrospectively reviewed the clinical outcomes of 24 patients with benign primary bone tumors who underwent intralesional curettage followed by reconstruction with a calcium sulfate–calcium phosphate composite bone substitute. Mean follow-up was 23 months. The most common diagnosis was giant cell tumor of bone. Six patients had upper-extremity tumors and 18 had lower-extremity tumors. Mean preoperative radiographic tumor volume was 41.0 cm 3 . Mean volume of PRO-DENSE (Wright Medical Technology, Arlington, Tennessee) used in each patient was 15.6 cm 3 . Mean time to full weight bearing for all patients was 7.3 weeks. Two patients sustained local tumor recurrences. No postoperative fractures occurred, and no complications occurred related to the use of the calcium sulfate–calcium phosphate composite. One case of deep infection occurred secondary to wound breakdown. The use of a calcium sulfate–calcium phosphate composite was associated with rapid biological integration and an early return to activities of daily living, with no composite-related complications. This technique is a viable option in the reconstruction of cavitary bone defects following intralesional curettage of primary benign bone tumors.

Giant cell tumor of bone is an uncommon benign tumor that frequently recurs locally. Spontaneous malignant transformation of conventional giant cell tumor of bone is rare and usually occurs with irradiation. This article describes a case of malignant transformation of a giant cell tumor 41 years after initial curettage and subsequent resection. A 68-year-old man presented with a 6-month history of left hip pain. He had been diagnosed 41 years previously with giant cell tumor in the left femoral neck treated by simple curettage and bone grafting, followed by resection of the femoral head 1 year later for local recurrence. On presentation, radiographs revealed a destructive lesion in the left proximal femur. Incisional biopsy revealed recurrence of giant cell tumor with suspected malignant transformation. The patient underwent en bloc resection of the proximal femur with adequately wide margins and reconstruction of the hip joint with a prosthesis. Pathological findings showed malignant transformation of a giant cell tumor to osteosarcoma and leiomyosarcoma. No recurrence or metastasis developed during 2-year follow-up. Benign local recurrences usually arise in the first 3 postoperative years, whereas malignant transformation tends to take longer than 3 years. To the authors’ knowledge, the 41-year interval from primary surgery to diagnosis of malignancy for the current patient is the longest interval reported among cases in which patients received no radiation therapy.

Giant cell tumor of bone is locally aggressive and occurs in the meta-epiphyseal region of long bones. Because of its high recurrence rate, local adjuvant therapies such as phenol or liquid nitrogen have been recommended. In the present study, zoledronic acid, a nitrogen-containing bisphosphonate, was administered locally as an adjuvant during a biopsy. An otherwise healthy 43-year-old man presented with pain and swelling in the right knee. Plain radiographs showed an osteolytic lesion of the right proximal tibia. An open biopsy was performed and the intraoperative pathologic diagnosis was giant cell tumor of bone. Following biopsy, the defect was filled with betatricalcium phosphate, and 4 mg of zoledronic acid was locally administered into the tumor lesion. Two months after the biopsy, curettage and bone grafting were performed. Sections were obtained during the curettage for histology to evaluate the response to bisphosphonate treatment. Histologic examination revealed massive tumor cell death in the lesion in which both stromal cells and osteoclast-like giant cells were necrotic. Curettage was performed and the defect was filled with a commercial preshaped hydroxyapatitetricalcium phosphate bone substitute. Eighteen months after curettage, the patient had regained full range of motion and good function of the knee, and radiographs at 18 months after curettage revealed no recurrence of giant cell tumor of bone.

Giant cell tumor is a benign tumor of bone with a predilection for juxta-articular locations. Although not malignant, giant cell tumor often exhibits unpredictable and locally aggressive behavior, and in rare cases can metastasize in the absence of histologic malignancy. Partial tumor necrosis has been infrequently reported within typical giant cell tumor. A 17-year-old girl presented with a right distal femur giant cell tumor associated with complete tumor necrosis on histopathologic analysis. The etiology, prevalence, and implications of complete necrosis in previously untreated giant cell tumor of bone remain unclear, as there are no previously published reports. Despite the complete necrosis evident in our patient, she nonetheless presented with pain. There were no radiographic signs of the necrotic tumor space remodeling with new bone. The patient was treated with standard extended intralesional curetting through a generous cortical window permitting visualization of the entire lesion, and systematic high speed burring and thermal electrocautery ablation of the periphery, followed by micro particulate allogenic bone grafting. At short-term follow-up, she had healed well with no evidence of tumor recurrence. This article presents the first case, to our knowledge, of complete spontaneous tumor necrosis in a previously untreated bone giant cell tumor. Increased understanding of spontaneous tumor necrosis associated with giant cell tumor may help guided future targeted medical and surgical treatment modalities.

Giant cell tumor, a relatively rare, occasionally malignant tumor of bone, remains a difficult therapeutic problem for the orthopedic surgeon. Various treatment options, including curettage alone, curettage with bone grafting, radiation, and curettage with acrylic cementation have been utilized and reported. Therapeutic complications such as infection, recurrence, and loss of support of the articular surface have continued to plague the treatment of giant cell tumors. This article reports the results of 10 consecutive cases of giant cell tumor of bone treated by curettage and methyl methacrylate cementation, followed by bone grafting of the surface of the lesion with demineralized bone matrix to reconstitute the cortex at the site of the tumor. At an average follow up of 36 months, eight patients had an excellent functional result and two had a fair result as scored on the Musculoskeletal Tumor Society rating system. To date, there have been no tumor recurrences or metastases, and all patients have radiographic evidence of healing of the weight bearing cortical surface.

Giant cell tumor of bone is a rare and unpredictable lesion. Standard treatment ranges from surgical curettage to wide resection, with reports of varying oncological and functional results. Twenty-three consecutive cases of giant cell tumor of long bones were treated in 10 years. Fifteen men and 8 women had a mean age of 38 years (range, 17-82 years). Average follow-up was 45 months (range, 12-180 months). The most common tumor sites were the proximal tibia (10 cases), distal femur (8), and distal radius (3). All patients remained free of recurrence at the time of final follow-up. Functional outcomes as evaluated by the Musculoskeletal Tumor Society measure were successful, with an average score of 26.6 points (range, 22-30 points). To avoid local recurrence around the knee joint, we recommend radical intralesional curettage with a high-speed drill burr, adjunctive therapy with cryosurgery, and filling with polymethylmethacrylate. Primary total knee arthroplasty is acceptable for older patients. For giant cell tumor of the upper limb or for young patients, biological reconstruction should be applied.

Twelve samples of giant cell tumor of bone were incubated in the authors' laboratory. The activity of the cells was documented by means of time lapse cinemicrography. The multinuclear giant cells (MGCs) with undegenerating nuclei migrating from the expiants had active ameboid movement and continuously changed their shapes. The majority of them kept splitting themselves into smaller MGCs until mononuclear cells formed, which were indistinguishable from the original stromal cells in morphology and could take up tritiated thymidine as shown by autoradiography. This splitting process of MGCs is mainly responsible for their vanishing in culture. The authors believe that an MGC is one of the true neoplastic elements. MGCs are present merely in the form of a syncytium derived from neoplastic stromal cells. In culture, the factors maintaining the syncytium are lost and the process opposite to cell fusion appears. Therefore, from a morphological view, MGCs and neoplastic stromal cells are homologous.