Giant Cell Tumour of Bone

 

GCT distal tibiaGCT hip GCT humerus

 

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

 

GCT Distal Femur Xray

 

GCT knee 1GCT knee 2

 

GCT humerus 1GCT wrist

 

GCT fingerGCT toe

 

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

 

GCT Distal Femur MRI0001GCT Distal Femur MRI0002

 

GCT hip 1GCT hip 2

 

GCT hum MRI 1GCT hum MRI 2

 

CT

 

GCT CT 1GCT CT 2GCT CT 3

 

GCT wrist CT 1GCT wrist CT 2

 

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 tumour 1Brown tumour 2

Brown's tumour in hyperparathyroidism

 

Histology

 

Giant Cell Tumour Histology Nephron GNU Free Documentation License Version 1.2 httpwww.gnu.orgcopyleftfdl.html

 

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

 

Tsukamoto et al CORR 2020

- 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

 

Traub et al Eur J Cancer 2016

- 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

 

Vumedi video

 

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

 

GCT cement 1GCT cement 2

 

GCT knee 1GCT knee 2

 

Tibia GCT 2Tibia GCT 1

 

Results

 

Aoude et al Bone Joint J 2023

- 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

 

GCT hip 1GCT hip 2GCT hip 3

 

GCT femur 1GCT femur 2GCT femur 3

 

GCT hip 1Hip GCT 2HIp GCT 3

 

Distal Radius

 

GCT DRGCT DR CT

 

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

 

DR GCTDR GCT allograft DR GCT AllograftDR GCT allograft wrist subluxation

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

 

Wang et al Int Orthop 2021

- 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

 

Itkin et al J Clin Oncol 2018

- 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

 

Liu et al J Bone Oncol 2020

- 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%