Giant Cell Tumor of Bone

What a giant cell tumor is

Giant cell tumors contain two main cell types: tumor cells (stromal cells) and many large, multinucleated "giant" cells that resemble osteoclasts, the cells that normally break down bone. The tumor cells produce a signal called RANKL, which recruits and activates the giant cells, which then destroy surrounding bone. This explains why the tumor erodes bone and why denosumab, which blocks RANKL, can control it.

Most tumors carry a specific mutation in the H3F3A gene, which helps confirm the diagnosis.

Giant cell tumors make up about 4 to 5% of primary bone tumors. They usually appear after the growth plates have closed.

Where they occur

• Around the knee: lower end of the femur and upper end of the tibia (about 50%)
• Lower end of the radius at the wrist
• Upper end of the humerus at the shoulder
• Sacrum and spine
• Hands and feet, less often

Symptoms

• Pain in the affected area, often near a joint, which gradually worsens and may be present at rest or at night
• Swelling or a palpable mass
• Limited joint movement
• Fluid in the nearby joint
• Pathological fracture: a break through bone weakened by the tumor, sometimes the first sign. See pathological fractures
• Nerve symptoms with spine or sacral tumors: back pain, leg weakness or numbness, bladder or bowel problems

Diagnosis

1. X-ray: shows a well-defined "lytic" (bone-destroying) area at the end of a long bone extending close to the joint surface, often with a "soap bubble" appearance.
2. MRI: shows the extent within bone and soft tissue.
3. CT scan of the chest: checks for lung spread, which happens in about 2 to 5% of cases.
4. Biopsy: a needle or surgical biopsy, ideally at a specialist bone tumor center, confirms the diagnosis and distinguishes it from other conditions such as aneurysmal bone cysts, brown tumors of hyperparathyroidism, or osteosarcoma.
5. Blood tests: including calcium and parathyroid hormone to rule out hyperparathyroidism.

Tumors are graded by how much they have broken through the bone (Campanacci grades 1 to 3).

Treatment

Treatment should be planned by an orthopedic oncology team.

Surgery

• Extended curettage: the tumor is scraped out through a window in the bone. The cavity is treated with a high-speed burr and often chemical or thermal agents (phenol, liquid nitrogen, or cement heat) to kill remaining cells, then filled with bone cement or bone graft. This preserves the joint and is the most common treatment.
• En bloc resection: removal of the whole affected bone segment, used for large, aggressive or recurrent tumors, or when the joint surface is destroyed. Reconstruction may need a joint replacement or bone graft.

Denosumab

Denosumab is a monoclonal antibody that blocks RANKL. It shrinks tumors and allows bone to reform. It is used for:

• tumors that cannot be removed without major disability, such as in the sacrum or spine
• downsizing before surgery in selected cases
• recurrent or metastatic disease

Long-term use requires monitoring for side effects such as low calcium and jaw bone problems (osteonecrosis), and tumors can regrow after stopping.

Other treatments

• Radiation therapy: occasionally for tumors that cannot be removed or controlled otherwise
• Embolization: blocking blood supply to large sacral or pelvic tumors
• Surgery for lung metastases, which often grow slowly

Recurrence and outlook

Giant cell tumors come back locally in about 10 to 25% of cases after curettage, usually within the first 2 to 3 years, so regular follow-up with X-rays or MRI and chest imaging is needed for several years. Recurrences are usually treatable with further surgery. Lung spread is uncommon and usually slow-growing, and survival is generally excellent. Very rarely, a giant cell tumor becomes malignant, particularly after radiation.

Frequently asked questions

Is a giant cell tumor of bone cancer?

Most giant cell tumors are benign, meaning they are not cancer and usually do not spread. However, they are locally aggressive, destroy bone and often recur. A small percentage spread to the lungs, and very rarely they become malignant.

What are the symptoms of a giant cell tumor?

The main symptoms are pain near a joint, especially the knee, that gradually worsens, swelling, reduced joint movement and sometimes a fracture through the weakened bone. Spine or sacral tumors may cause back pain and nerve symptoms.

How is a giant cell tumor treated?

Most are treated with extended curettage, scraping out the tumor and filling the cavity with bone cement or graft. Large tumors may need removal of the bone segment and reconstruction. Denosumab is used for tumors that are difficult to remove or recur.

Can a giant cell tumor come back?

Yes. Local recurrence occurs in about 10 to 25% of cases after curettage, usually within 2 to 3 years. Regular follow-up imaging helps detect recurrence early, and it can usually be treated with further surgery.

Who gets giant cell tumors?

They mostly affect adults aged 20 to 40, after the growth plates have closed, and are slightly more common in women. They are rare in children and older adults.