Giant Cell Tumour of Bone

Giant cell tumour of bone is a locally aggressive primary bone neoplasm composed of neoplastic stromal cells and numerous osteoclast like giant cells. It most commonly affects skeletally mature young adults.

Typical sites are the epiphysis and metaphysis of long bones, particularly:

• Distal femur

• Proximal tibia

• Distal radius

The lesion usually extends to the subchondral bone. Although conventionally classified as intermediate or locally aggressive rather than a conventional high grade sarcoma, it can:

• Destroy bone extensively

• Recur locally

• Metastasise to lung

• Rarely undergo malignant transformation

Campanacci classification

This is the main useful radiographic severity classification.

Grade I

Well defined lesion with intact cortex.

Grade II

Well defined lesion with cortical thinning and expansion but no major cortical breakthrough.

Grade III

Aggressive lesion with cortical destruction and soft tissue extension.

The grade assists operative planning but should not be used as the sole determinant of treatment.

Patients develop:

• Progressive pain near a joint

• Swelling

• Reduced joint movement

• Mechanical weakness

A pathological fracture can be the first presentation. Because the lesion extends near the joint surface, symptoms may initially resemble internal joint pathology. Pulmonary metastases are uncommon but can occur even with histologically conventional GCT.

Plain radiographs: classically demonstrate an eccentric expansile lytic epiphyseal lesion extending toward the articular surface.

A mature GCT generally has little surrounding sclerosis.

MRI: define:

• Subchondral involvement
• Soft tissue extension
• Neurovascular relationships
• Joint involvement

CT chest: obtain for pulmonary staging in aggressive or confirmed disease.

Biopsy is required before definitive treatment.

H3.3 G34W immunohistochemistry can support the diagnosis in appropriate lesions.

Intralesional surgery

For most Campanacci I and II lesions, and selected III lesions in which the joint can be preserved, perform extended intralesional curettage. The quality of curettage determines recurrence risk. Technique should include:

• Large cortical window providing full visual access

• Removal of all gross tumour

• High speed burr extending treatment into cavity margins

• Careful inspection for residual tumour in recesses

Local adjuncts can include:

• Hydrogen peroxide

• Phenol in selected practice

• Argon beam

• Cryotherapy

The evidence does not establish one universally superior local adjunct.

Defect reconstruction

Fill the cavity with:

• PMMA bone cement

• Autologous bone graft

• Allograft

• Bone substitute

PMMA provides immediate structural support and allows recurrent lysis at the cement interface to be recognised relatively easily. In lesions immediately beneath articular cartilage, a layer of cancellous graft beneath the subchondral plate can reduce direct thermal or mechanical stress from cement. Add plate fixation when curettage leaves the bone mechanically weak or pathological fracture risk is high.

Wide resection

Consider en bloc resection when there is:

• Massive cortical destruction

• Nonreconstructible joint surface

• Extensive soft tissue extension

• Repeated local recurrence

• Pathological fracture with gross contamination that prevents reliable curettage

• Anatomical location where recurrence would be catastrophic

Reconstruction can require:

• Endoprosthesis

• Osteoarticular allograft

• Arthrodesis

• Structural graft

Wide resection lowers local recurrence but sacrifices more normal tissue and joint function.

Denosumab

Denosumab blocks RANKL and profoundly suppresses giant cell mediated bone resorption.

Use primarily for:

• Unresectable disease

• Sacral or spinal lesions where surgery would cause major neurological morbidity

• Tumours where initial resection would require highly morbid surgery

A standard regimen is:

Denosumab 120 mg subcutaneously every 4 weeks

with additional doses on:

Days 8 and 15 during the first month.

Provide:

• Calcium supplementation

• Vitamin D supplementation

unless hypercalcaemia is present.

Before treatment:

• Correct hypocalcaemia

• Assess dental health

• Address significant dental infection

Monitor for:

• Hypocalcaemia

• Osteonecrosis of the jaw

• Atypical femoral fracture with prolonged therapy

• Rebound hypercalcaemia after discontinuation, particularly in younger patients

Denosumab does not eliminate the neoplastic stromal cells. It can produce a thick sclerotic shell that makes later tumour boundaries difficult to identify during curettage. Therefore, routine preoperative denosumab before an otherwise straightforward joint preserving curettage should not be automatic. Its role is most valuable when it meaningfully reduces surgical morbidity.

Pulmonary metastases

Small stable pulmonary metastases may behave indolently. Resect progressing or technically suitable pulmonary disease when appropriate. Denosumab can be used for unresectable metastatic GCT.

Surveillance

Local recurrence occurs most frequently during the first several years. Follow with:

• Local radiographs

• Clinical examination

• Chest imaging according to disease severity

Rapid destructive progression during or after denosumab warrants reassessment and repeat biopsy because malignant transformation or an initially missed sarcoma must be considered.