Giant Cell Tumours of Bone

Is it benign or malignant

Henry Soeharno

Singapore General Hospital

Dept of Orthopaedic Surgery

Giant Cell Tumour of bone

First described by Cooper and Travers in 1818

5% of all primary bone tumours

20% of all benign bone tumours

Peak incidence: 3rd – 4th decade

Benign, expansile, locally aggressive, osteolytic tumour

Characterised by presence of numerous giant cells that exhibit the phenotypic features of mature osteoclasts.

Giant Cell Tumour of bone

Occasionally undergo malignant transformation

and metastasis (usually to lungs) occurs in

around 2%

PRIMARY VS SECONDARY

Primary malignant GCT – less that 1%

Secondary malignant GCT – post irradiation or

recurrence (poor prognosis)

Classification

ENNEKING

Stage % Description

I (latent) 15% •Confined totally to bone

•Asymptomatic

•Inactive on bone scan

II (active) 70% •Expanded cortex with no breakthrough

•Symptomatic if pathological fracture

•Active on bone scan

III

(aggressive)

15% •Rapidly growing mass

•Symptomatic

•Extensive activity on bone scan

Malignant rare Sarcomatous lesion contiguous with benign GCT

Classification

Grade Description

1 Intramedullary lesion confined to bone

2 Thinned, expanded cortex

3 Cortical breakout

Campanacci

Management options

SURGERY

Molecular Therapy

Embolisation

Radiation

Surgery

Intralesional ‘extended’ curettage (with or without

adjuncts such as phenol and liquid nitrogen)

Recurrence rates

Curettage alone : 50-60%

Curettage + adjuncts : 10-20%

AIM of surgery : balance between reducing incidence

of local recurrence while preserving local functional

anatomy

Role of adjuncts

High-speed burr

Phenol

Cementation with PMMA – thermal necrosis and

cytotoxic effects

Liquid nitrogen (cryotherapy)– associated with high

incidence of local wound and bone complications

AIM : to ‘extend’ the curettage or intralesional

excision by chemical or physical means

Molecular Therapy

BISPHOSPHONATES

Widely used to inhibit osteolysis in conditions such as

osteoporosis, Paget’s disease and metastatic cancer

Act by inhibiting farnesyl diphosphate synthase, an

enzyme in the mevalonate pathway

Inhibition of osteoclastic formation

Decrease osteoclast resorption

Increased osteoclast apoptosis

Tse et al , Bone 2008

Retrospective case-control study on 44 patients with appendicular GCT between 1998-2004

Intralesional curettage/wide excision followed with

cementation or biological reconstruction.

24 patients received intravenous and oral bisphosphonate peri-operatively

Average f/u was 48 months

1 of 24 pt (4.2%) developed local recurrence vs 6 of 20 in control group (30%), p=0.056

Balke et al, BMC Cancer 2010 24 cases of GCT recruited from four European centers (5

aggressive primary, 7 recurrence and 12 metastatic disease)

Indication, dose and method of administration differed between various centers

Zoledronic acid most commonly used

Follow up period 36-64 months

Results:

Most inoperable sacral/pelvic tumours did not increase in size

No further recurrence was seen in GCTs that had repeatedly recurred in bone and soft tissue

Lung metastasis did not increase in size or number during course of treatment with Bisphosphonate

Molecular and Cellular biology

of GCT Biphenotypic

Osteoclast-like giant cells – RANK

Mesenchymal neoplastic stromal cells - RANKL

Interaction between these cells lead to bone

resorption

Denosumab

Denosumab – a monoclonal antibody that binds RANKL

and directly inhibits osteoclastogenesis

Denosumab

Thomas et al , The Lancet Oncology, 2010

37 patients with recurrent or unresectable GCT enrolled

Most common sites : pelvis, lungs and lower limb

All treated with 120mg Denosumab s/c once a month

for 25 weeks

30 of 35 patients showed tumour response, defined by at

least 90% elimination of giant cells or no radiologic

progression of target lesion

In 1 patient, tumour progression recurred after

Denosumab was discontinued.

Chawla et al, Lancet Oncology 2013

International , open-label , phase 2 trial (282 patients)

3 Cohorts : 1. Unsalvageable CGTB

2. Salvageable – morbid surgery

3. Previous denosumab GCTB study transfer

Results:

Safety analysis:

1% Osteonecrosis of jaw

5% hypocalcaemia

3% hypophosphataemia

1% anaemia, back and extremity pain

96% in cohort-1 had no disease progression (13 mths)

74% in cohort-2 had no surgery and 62% patients who had surgery

underwent a less morbid procedure (9 mths)

? Secondary malignancy following Denosumab therapy

August 2010 Sept 2009

January 2013

DENOSUMAB

5/12 post Denosumab June 2014

July 2009

Santosh et al, 2015.

Case report on a Pseudosarcomatous Spindle cell

Proliferation with Osteoid Matrix Mimicking

Osteosarcoma in a 68 years old female with left

distal radius GCT following Denosumab therapy

Conclusion

GCTB is a benign but locally aggressive bone

tumour with a high propensity for recurrence

Goal of treatment is to achieve local control whilst

preserving function

Denosumab has shown promising results in the

management of unresectable/recurrent GCT

Concern regarding secondary malignancy

following Denosumab therapy warrants further

prospective studies

Thank you