Definition
Benign, locally aggressive primary bone tumour
- pulmonary metastasis 3% (usually associated with recurrence after surgery)
- malignant transformation 1%
Biologically and clinically distinct from tenosynovial giant cell tumour
Vastly different natural history and treatment
Epidemiology
5% of primary bone tumours
Aged 20 - 40
Pathophysiology
Overexpression of receptor activator of nuclear factor κB ligand (RANKL)
- promotes recruitment of numerous reactive multinucleated giant cells
- resorption of bone
Campanacci Staging
| Stage I: Latent (15%) | Stage II: Active (70%) | Stage III: Aggressive (15%) | Malignant |
|
Sclerotic Rim Asymptomatic Inactive on bone scan Histologically benign |
Expanded cortex but no breakthrough Symptomatic Often have pathological fracture Active on bone scan Histologically benign |
Rapidly growing mass Cortical perforation, soft tissue mass Symptomatic Extensive activity on bone scan Histologically benign |
Rare Sarcomatous lesion contiguous with benign GCT |
Clinical
Joint pain
Pathological fracture common presentation - 20%
Location
85% meta-epiphysis of long bones
10% axial skeleton (sacrum, vertebral bodies)
5% small bones hand and feet
Multiple giant cell tumours rare
- consider Brown's tumours / hyperparathyroidism
- histology findings very similar
X-ray
Eccentric, sharply demarcated lytic lesion
- no sclerosis around lesion
- narrow zone of transition
- metaphysis, extending into epiphysis
- no mineralization
MRI
Low signal intensity T1 / high signal intensity T2
Areas of ABC seen in 10 - 14%
Look for signs of grade III: soft tissue extension
CT
Differential diagnosis
ABC / UBC
Chondroblastoma - adolescents / areas of calcification
Clear cell sarcoma
Osteosarcoma
Synovial cyst / geode in osteoarthritis
PVNS
Osteomyelitis (brodies abscess)
Brown's tumour
Brown's tumour in hyperparathyroidism
Histology
Two Cell Types
A. Neoplastic rounded mononuclear osteoclast precursor cells and spindle-shaped mononuclear neoplastic “stromal” cells
B. Reactive multinucleated osteoclast-like giant cells causing bone resorption
Natural HIstory
Recurrence 18%
- increased risk with soft tissue extension
- reduced by use of cement
- reduced by wide resection, but associated with higher morbidity
Lung metastasis 4%
- increased by local recurrence
Malignant transformation 1 - 2%
Management
Staging
Biopsy usually performed
Options
1. Currettage + bone graft / cement
2. Wide excision + allograft / arthroplasty
3. Adjuvant treatment - Denosumab
Recurrence
Zuo et al World J Surg Oncol 2013
- systematic review
- 1293 patients
- reduced recurrence with use of cement in comparison to bone graft
- systematic review of Denosumab
- evidence of increase rates of recurrence with Denosumab pre-operatively
- may be biased by increased use of Denosumab in Type III
Denosumab
Indicated for GCT of bone, no role in tenosynovial GCT.
Human monoclonal antibody (mAb)
- inhibits tumor-associated bone lysis
- RANKL pathway
- pre-operative treatment
May allow surgical downstaging
- surgically unsalvageable / surgical treatment high morbidity
- arthrodesis or arthroplasty in young patients
Results
- prospective study of 20 patients with GCT
- pre-operative treatment with Denosumab
- pain relief in the first month
- improved radiological response with improved subchondral and cortical bone
- increased intra-lesional resection and joint preservation
- no effect on recurrence
Rutkowski et al Ann Surg Oncol 2015
- 222 patients at risk for wide resection treated with Denosumab
- allowed joint preservation in 96% of those thought to require joint replacement
- allowed joint preservation in 86% of those thought to require wide resection / arthrodesis
- recurrence rate 15%
Complications
Chawla et al Lancet Oncol 2019
- 532 patients with GCT treated with denosumab
- serious adverse events in 26%
- 3% jaw necrosis
- 1% anemia / 1% atypical femur fracture / 1% hypercalcaemia
Bisphosphonates
Results
Deslivia et al Malays Orthop J 2023
- systematic review of pre- and postoperative bisphosphonates
- evidence of lower recurrence rates with few complications
Currettage and Cement +/- local application phenol / liquid nitrogen
Indication
Joint salvage feasible
Technique
Open approach
- bone window
- remove tissue with curette
- saucerisation with high speed burr
- consider phenol / liquid nitrogen application
- cement (works by thermal necrosis), in addition to structural support
Results
- 354 GCT's treated surgically
- recurrence after curettage 18%
Knochentumoren et al JBJS Am 2008
- 384 cases
- recurrence significantly reduced by the use of cement
Wide resection and Allograft / Prosthesis Reconstruction
Indications
- extensive soft tissue tumour
- extensive cortical destruction
- impossible joint salvage
- multiple recurrence / failure bone cement
Distal Radius
Abuhejleh et al Eur J Orthop Traumatol Surg 2020
- 57 patients with GCT's of distal radius
- 29% (10/34) recurrence with intra-lesional treatement but no complications
- 4% (1/23) recurrence with wide resection / arthrodesis but 30% complication rate
- increased risk recurrence for Grade 3
- wide resection / arthrodesis should be reserved for grade 3
Koucheki et al Eur J Orthop Traumatol Surg 2023
- systematic review of 13 studies and 373 patients
- increased local recurrence with intralesional versus en-bloc resection
- especially Grade 3
- increased complications and poorer function with en-bloc resection
Distal radius GCT treated with en bloc resection and allograft reconstruction, followed by late wrist subluxation
Lung metastasis
Associated with local recurrence after treatment
Low mortality rate
Metastasis does NOT imply malignancy
Incidence
- retrospective study of 310 patients
- 5.8% developed pulmonary metastasis
- 89% of patients had local recurrence of GCT after treatment
Ebeid et al J Clin Orthop Trauma 2021
- 15/466 (3.2%) incidence of pulmonary metastasis
- incidence 10% in recurrent GCT
- systematic review of metastatic GCT
- before widespread treatment with denosumab
- 26 case series with 242 patients
- overall survival 87% at 7 years
- spontaneous regression in 4.5%
Malignant transformation
Incidence
1 - 2%
Types
Primary: benign GCT with areas of sarcomatous transformation
Secondary: occur at sites of previously managed GCT
Imaging
Grade III with cortical destruction and soft tissue extension
Chawla et al Lancet Oncol 2019
- 532 patients
- 4 patients (1%) sarcomatous transformation
- retrospective study of 1365 GCT in database
- malignant transformation 2.3%
- secondary most commonly osteosarcoma
- 5 year survival primary 56%
- 5 year survival secondary 40%