Giant cell tumor of bone is a benign tumor with an aggressive behavior. Its typical subarticular location and high recurrence risk can be associated with significant morbidity. Although benign, it can rarely metastasize especially to the lungs. Also, it can be multicentric in less than 1% of patients. Late malignant transformation, although rare, can occur with a very poor prognosis. This series reports on these unusual and challenging features and management considerations of giant cell tumor of bone. This retrospective study included review of the medical records of patients with a confirmed histopathological diagnosis of giant cell tumor of bone. A total of 25 patients (16 females and 9 males) with a mean age of 34.5 years were included; 22 had primary tumors, while 3 were referred with recurrent tumors. Pain was the most common presenting symptom. Most patients had grade III tumors. Tumors around the knee were the most common. Multicentric tumors were detected in three patients. Twenty-three patients (20 primary giant cell tumor of bone and 3 with recurrence) received treatment. Most patients (15/23) were treated with intralesional curettage with or without adjuvants. Seven patients had wide excision. Recurrence was seen in 45% (9/20) of primary giant cell tumor of bone especially with difficult anatomical locations. Most recurrences occurred more than 4 years after treatment. Pulmonary nodules were detected in four patients; two of them showed resolution during follow-up. One patient developed secondary sarcoma transformation with a fatal outcome. Giant cell tumor of bone was more common in females. Long bones were more affected, especially around the knee. Intralesional curettage was the most frequently used treatment. Recurrence was associated with inadequate tumor resection (especially in difficult anatomical location), younger age, male gender, and advanced local tumor grade. Denosumab can be used in the treatment of pulmonary metastasis, multicentric and recurrent giant cell tumor of bone. Due to late recurrence and malignant transformation, a prolonged follow-up is warranted.

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