What is a giant cell tumor (GCT)?

From the Guidelines

Giant cell tumor of bone is a rare, typically benign bone tumor that occurs most commonly at the ends of long bones near joints, particularly around the knee, and is characterized by distinctive multinucleated giant cells mixed with mononuclear stromal cells, with a high risk of local recurrence and potential for metastasis to the lungs.

Characteristics of Giant Cell Tumor

• Giant cell tumors (GCTs) are relatively rare, representing 12–15% of primary bone tumors in England, with a higher incidence in Asia 1.
• They usually occur between 20 and 40 years of age and are rare before epiphyseal closure.
• Tumors usually occur at the epiphyses of long bones next to joints but may arise in other bones, and are rarely multicentric.
• Histologically, tumors comprise mononuclear stromal cells with numerous scattered multinucleated giant cells (osteoclasts) recruited by RANK-ligand from stromal cells.

Treatment and Management

• Treatment typically involves surgical removal through curettage (scraping out the tumor) followed by filling the cavity with bone cement or bone grafts, with denosumab being a standard treatment option for unresectable or metastatic GCTs 1.
• In more aggressive cases, complete surgical resection may be necessary.
• Radiation therapy is generally avoided due to the risk of malignant transformation, and should be limited to cases in which surgery leads to unacceptable morbidity and denosumab is ineffective or contraindicated 1.
• Despite treatment, giant cell tumors have a recurrence rate of 15-50%, necessitating long-term follow-up.

Key Considerations

• The tumor's aggressive behavior stems from the overexpression of RANK ligand by stromal cells, which stimulates the formation of osteoclast-like giant cells that break down bone.
• Denosumab use in the preoperative setting for GCTs that are potentially resectable with high morbidity is debated and should be individualized and reserved for complex cases following multidisciplinary discussion 1.
• Potential maxillar and skeletal side effects of denosumab, such as osteonecrosis of the jaw and atypical fractures, need to be monitored.

From the Research

Definition and Characteristics of Giant Cell Tumor

• Giant cell tumor (GCT) of bone is a benign tumor composed of mononuclear stromal cells and characteristic multinucleated giant cells that exhibit osteoclastic activity 2.
• It usually develops in long bones but can occur in unusual locations, with the typical appearance being a lytic lesion with a well-defined but nonsclerotic margin that is eccentric in location, extends near the articular surface, and occurs in patients with closed physes 2.
• GCT can mimic or be mimicked by other benign or malignant lesions at both radiologic evaluation and histologic analysis, and rarely, GCT is associated with histologically benign lung metastases or undergoes malignant degeneration 2.

Clinical Presentation and Treatment

• Most patients present with pain, swelling, joint effusion, and disability in the third and fourth decades of life, with imaging studies being important for tumor staging and radiographic grading 3.
• Extended intralesional curettage with or without adjuvant therapy is the primary treatment choice, with local recurrence seen in ≤ 20% of cases, and a second local intralesional procedure typically sufficient in cases detected early 3.
• Medical therapies include diphosphonates and denosumab, which has been approved for use in osteoporosis as well as breast and prostate cancer metastatic to bone, and can alter the management of GCT of bone, especially in multifocal disease, local recurrences, and bulky central/axial disease 3.

Denosumab Treatment and Its Implications

• Denosumab is a monoclonal antibody against RANK ligand for treatment of giant cell tumor of bone (GCTB), with clinical trials and case series demonstrating its beneficial tumor response and surgical down-staging in patients with GCTB 4.
• However, denosumab may increase the local recurrence risk in patients treated with curettage, and its treatment can result in a cytostatic instead of a true cytotoxic response on neoplastic stromal cells, with concerns about its long-term safety and potential for malignant transformation 4, 5.
• Studies have shown that denosumab can provide long-term disease control for patients with GCTB, with a favorable overall risk to benefit ratio, but its use should be applied with caution due to potential complications such as osteonecrosis of the jaw and atypical femur fracture 5, 6.