Giant Cell Tumor — Campanacci Classification

Giant cell tumour of bone (GCT) is a locally aggressive benign bone tumour characterised by multinucleated osteoclast-like giant cells on a background of mononuclear stromal cells. Despite its benign histological classification, GCT has a significant risk of local recurrence and, in approximately 1–3% of cases, can metastasise to the lung. Understanding its behaviour, staging, and surgical management is fundamental to musculoskeletal oncology practice.

• Incidence: approximately 1–2 per million per year; accounts for approximately 5% of all primary bone tumours and 20% of benign bone tumours
• Age: predominantly young adults aged 20–40 years; rare before growth plate closure (skeletal maturity)
• Female:male ratio: slightly higher incidence in women (1.3:1)
• Most common locations: distal femur (25%), proximal tibia (20%), distal radius (10%) — all epiphyseal and subarticular; always extends to the articular surface or just beneath it after physeal closure
• GCT is an epiphyseal tumour — it arises in the epiphysis after physeal closure; in skeletally immature patients it may begin in the metaphysis but crosses the physis to involve the epiphysis
• GCT of sacrum and spine: less common but important; presents with back pain, neurological deficit; difficult to treat surgically; high recurrence rates
• Paget disease: malignant degeneration of GCT or secondary GCT in Paget bone — important differential in elderly patients

The Campanacci grading system (1987) classifies GCT based on radiographic appearance and is the most widely used system for guiding surgical treatment decisions.

• Campanacci Grade II is the most common presentation — guides most surgical decisions in everyday practice
• Grade III with soft tissue extension: associated with higher recurrence rate; wide resection strongly considered to reduce recurrence risk, particularly at distal radius
• Campanacci grading is based on plain radiographs; CT and MRI add information about cortical integrity and soft tissue extent beyond what plain films show

• Symptoms: joint pain, swelling, limited range of motion; pathological fracture in approximately 10–15% at presentation; neurological symptoms in spinal and sacral lesions
• Plain radiographs: eccentric, lytic, epiphyseal lesion extending to or abutting the articular surface; no calcification; no periosteal reaction (unless fracture); soap-bubble appearance in some; no sclerotic rim in Grade II/III
• CT scan: better defines cortical integrity, soft tissue extension, and lesion matrix — guides Campanacci grading; essential preoperatively
• MRI: defines intramedullary extent, articular involvement, soft tissue mass, and joint congruity; fluid-fluid levels may be present (secondary ABC change — occurs in up to 14% of GCTs); guides surgical approach
• Fluid-fluid levels on MRI: seen in aneurysmal bone cyst (ABC) but also in GCT with secondary ABC change and telangiectatic osteosarcoma — do not assume benign diagnosis from imaging alone; biopsy mandatory
• CT chest: lung metastases in 1–3%; mandatory staging investigation; lung lesions may be late-presenting — surveillance CT required
• Bone scan: assesses polyostotic disease and skip lesions (rare in GCT)

• Histology: mononuclear stromal cells (true neoplastic cells) + multinucleated osteoclast-like giant cells (reactive, non-neoplastic); uniformly distributed giant cells; mitoses may be present in stromal cells but not atypical
• The giant cells are RANKL-positive — express receptor activator of NF-κB ligand; stromal cells drive osteoclast recruitment and bone destruction via RANKL pathway
• H3.3 histone mutation (H3F3A gene, G34W substitution): present in >90% of GCTs — highly specific molecular marker; useful for confirming diagnosis in challenging cases
• Malignant GCT: rare (<1% primary; higher in irradiated tumours); frank sarcomatous transformation; treat as high-grade sarcoma
• Lung metastases from GCT: histologically benign giant cells in lung — can remain stable for years or slowly grow; resection indicated if enlarging or symptomatic; denosumab before metastasectomy now commonly used

The primary surgical strategy for most GCTs is intralesional curettage with adjuvants, preserving the joint whenever possible. Wide resection is reserved for select cases where joint preservation is not feasible or recurrence risk is very high.

Intralesional Curettage + Adjuvant Treatment:

• Technique: thorough curettage of entire cavity; high-speed burr (extended curettage) to remove additional 1–2 mm of residual tumour in bone walls — high-speed burring reduces recurrence rate significantly compared to curettage alone
• Adjuvant methods to further reduce recurrence:

• Cavity filling: PMMA cement (polymethylmethacrylate) preferred over bone graft — provides immediate stability, allows earlier weight bearing, and the exothermic reaction may kill residual tumour cells; also enables easier detection of recurrence on follow-up radiographs (lucent zone at cement-bone interface)
• Bone graft: alternative to cement — better restores bone stock for future revision; slower rehabilitation; recurrence harder to detect on plain radiographs
• Internal fixation: supplementary plate or nail fixation when cortical compromise is significant — prevents pathological fracture; particularly important around the knee

Wide Resection Indications:

• Campanacci Grade III with large soft tissue mass where joint cannot be preserved
• Distal radius GCT with severe bone loss — distal radius resection + wrist reconstruction (allograft, non-vascularised fibula, or wrist fusion)
• Multiply recurrent tumour after adequate curettage
• Expendable bones (proximal fibula, distal ulna, clavicle, ribs)
• Distal radius GCT: wide resection more commonly performed than at other sites — reconstruction with proximal fibula autograft or wrist arthrodesis; higher recurrence risk with curettage at this location

• Denosumab (Prolia/Xgeva): fully human monoclonal antibody against RANKL — blocks osteoclast activation; causes giant cell apoptosis and tumour sclerosis
• Denosumab indications in GCT: unresectable tumour (sacrum, spine, pelvis); preoperative downsizing; recurrent/metastatic GCT; patients refusing surgery
• Mechanism: RANKL expressed on GCT stromal cells drives osteoclast-like giant cell recruitment and bone destruction; denosumab blocks this pathway
• Response: radiographic sclerosis and tumour consolidation — converts lytic lesion to sclerotic; facilitates surgical resection or definitive radiological response
• Dosing: 120 mg subcutaneous monthly (loading doses at day 1, 8, 15); continued until surgery or disease control
• Important: rebound phenomenon on cessation — rapid tumour recurrence after stopping denosumab; taper or transition to surgical treatment before stopping
• Bone densification after denosumab makes curettage technically harder — account for this in surgical planning

• Recurrence rate after intralesional curettage + adjuvant: approximately 15–25%; after wide resection: 5–7%
• Most recurrences within 2 years — serial radiographs every 3–4 months for first 2 years, then 6-monthly to 5 years
• Recurrence management: repeat curettage + adjuvant for Grade I/II; resection for Grade III recurrence or failed multiple curettages
• Lung metastases surveillance: CT chest annually for 5–10 years; benign lung lesions may remain stable for years — resect if growing or symptomatic
• Radiation: historically used; now avoided as primary treatment due to risk of malignant transformation (post-radiation sarcoma); reserved for truly unresectable lesions (sacrum, spine base) where denosumab alone insufficient

• GCT with secondary ABC change: fluid-fluid levels on MRI may suggest pure ABC; biopsy is mandatory — GCT with secondary ABC change requires the same treatment as standard GCT; missing the diagnosis leads to inadequate treatment
• Pathological fracture through GCT: fracture haematoma contaminates tissue planes; some advocate denosumab to allow fracture healing and consolidation before surgery; curettage through fracture haematoma associated with higher recurrence; wide resection is increasingly favoured in fracture cases at distal radius
• Spinal GCT (most commonly sacrum): extremely challenging — wide resection often not feasible; embolisation before surgery reduces intraoperative blood loss; denosumab pre- and post-surgery to reduce recurrence; stereotactic radiosurgery as adjunct for residual disease; high recurrence rates despite aggressive treatment
• H3.3 mutation testing: G34W mutation is >90% specific for GCT — useful in atypical presentations, small biopsies, or when histology is ambiguous; now available in most specialist centres as part of molecular panel
• Cement vs graft: PMMA cement has thermal and possibly cytotoxic effect on residual cells at cavity margin; enables reliable detection of local recurrence as lucent zone at cement interface on serial X-rays; superior to graft for post-operative monitoring; bone graft preferred in young patients where future revision surgery anticipated

• GCT: epiphyseal, lytic, no sclerotic rim (Grade II/III); extends to articular surface; young adult (20–40 years)
• Campanacci Grade I = intact cortex; Grade II = thinned cortex; Grade III = cortex destroyed, soft tissue mass
• Grade II = most common; intralesional curettage + high-speed burr + adjuvant + PMMA cement
• PMMA cement preferred over graft — exothermic reaction, earlier weight bearing, easier recurrence detection
• Distal radius GCT: wide resection more often required — high curettage recurrence rate at this site
• Denosumab: anti-RANKL antibody; for unresectable, recurrent, or metastatic GCT; rebound recurrence on stopping — do not stop without surgical plan
• H3F3A G34W mutation: >90% specific for GCT — molecular diagnostic marker
• Lung metastases in 1–3%: histologically benign; resect if growing; CT surveillance annually for 5–10 years
• Fluid-fluid levels on MRI: not specific for ABC — seen in GCT with secondary ABC change and telangiectatic osteosarcoma; always biopsy
• Recurrence after curettage: 15–25%; most within 2 years — serial imaging mandatory