A High-grade Sarcoma Arising in a Patient With Recurrent Benign Giant Cell Tumor of the Proximal Tibia While Receiving Treatment With Denosumab

Abstract

Background A giant cell tumor of bone is a primary benign but locally aggressive neoplasm. Malignant transformation in a histologically typical giant cell tumor of bone, without radiotherapy exposure, is an uncommon event, occurring in less than 1% of giant cell tumors of bone. Although surgery is the standard initial treatment, denosumab, a monoclonal antibody drug that inhibits receptor activator of nuclear factor-jB ligand (RANKL), has shown considerable activity regarding disease and control of symptoms in patients with recurrence, unresectable, and metastatic giant cell tumors of bone. Case Description We report the case of a 20-year-old woman with a recurrent benign, giant cell tumor of bone, who had a bone sarcoma develop while receiving denosumab treatment.

Development of high-grade osteosarcoma in a patient with recurrent giant cell tumor of the ischium while receiving treatment with denosumab

“…In August 2015 (1 month after embolization and 2 weeks after beginning denosumab treatment), axial computed tomography showed a continued increase in the size of the osteolytic lesion and sclerotic formation (arrow) in the left body of the ischium. in the three above-mentioned case reports and the present case, respectively (7,8). Our institute previously reported that the latent periods between diagnosis of benign GCTB and diagnosis of secondary malignant GCTB were 16.0, 27.0, 16.3, 22.0, 27.7 and 7.3 years (mean, 19.4 years) in six patients who received neither radiotherapy nor denosumab treatment (13).…”

“…In six cases of secondary malignancy in GCTB after previous radiotherapy, the interval between the start of radiotherapy and diagnosis of the malignancy was 1.7-15.0 years (mean, 8 years) (13). Conversely, in the three above-mentioned case reports and the present case, the interval between the start of denosumab and diagnosis of the malignancy was 0.5-2.5 years (mean, 1.2 years) (7,8). The interval between the start of denosumab and diagnosis of the malignancy is obviously shorter than the interval between the start of radiotherapy and the diagnosis.…”

Giant cell tumours of bone treated with denosumab: histological, immunohistochemical and H3F3A mutation analyses

“…The local recurrence rate was similar in patients previously treated with curettage alone. 1 Previous studies found instances of sarcomatous transformation arising in GCTBs treated with denosumab, 23,24 and there have been several suggestions regarding the ideal length of denosumab therapy and monitoring procedures. 22,[25][26][27] Further studies are required to determine the best therapeutic strategy.…”

Denosumab in patients with giant-cell tumor of bone in Norway: results from a nationwide cohort

“…It is a concern that young patients receive a potentially life-long treatment, considering the risk of long-term side effects and a potential risk of malignant transformation. Sarcomatous transformation of GCTB has been reported during treatment with denosumab, but whether the malignancies were caused by denosumab is unclear [12,13]. Nevertheless, these concerns indicate that surgery should still be the preferred option for resectable tumors.…”