Aggressive giant cell tumour of bone.
ABSTRACT The surgical treatment of Stage III or aggressive giant cell tumour of the bone, whether to perform intralesional or en-bloc resection, remains controversial. The aim of this study is to identify the effectiveness of en-bloc resection for local control and final oncological outcome of the disease.
The data of 20 consecutive patients with Stage III giant cell tumour were retrospectively reviewed to determine the local control and oncological outcome after treatment with wide resection.
The majority of the patients presented late with mean duration of symptoms of 24 months, and four patients presented with recurrences. All patients were treated with wide resection except for two patients who underwent ablative surgery due to major neurovascular involvement. Ten patients required free vascularised tissue transfer to cover massive soft tissue defect. Local recurrence occurred in one patient who was again treated with wide resection and vascularised flap. Six patients had pulmonary metastases. Two patients with resectable disease were treated with thoracoscopic surgery and they remained disease-free 36 months after surgery. Two patients with multiple lung metastases were treated with chemotherapy and the disease remained non-progressive. The remaining two patients who refused chemotherapy showed radiological progression, and one succumbed to the disease with massive haemoptysis.
Aggressive giant cell tumour of bone should be treated with wide resection for better local control, and treatment of pulmonary metastases is mandatory for overall prognosis.
- [show abstract] [hide abstract]
ABSTRACT: The Author reviews 209 cases of giant-cell tumor (follow-up 3-42 years in 130 cases) and 131 chondrosarcomas (70 central, 50 peripheral, 11 periosteal; follow-up 10-32 years in 63 cases). Giant-cell tumors are graded into three radiographic types (calm, active, aggressive) and three histologic types (typical, aggressive, sarcoma). Chondrosarcomas were also graded into three radiographic and three histologic types (grades I, II, III). Incidence and mutual relationships of radiographic and histologic grades are presented. In recurrences it is possible to observe a progression of malignancy in giant-cell tumor and - more often - in chondrosarcomas. Results are related to the radiographic and histologic grading and to the type of treatment. Indications for treatment are given according to the experience gained from this study. The Author enumerates the surgical techniques he has found most suitable for the conservative treatment of these tumors when resection is indicated.Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer 02/1976;
- [show abstract] [hide abstract]
ABSTRACT: The nine-year experience with sixty patients who had had a giant-cell tumor of a long bone was reviewed to determine the rate of recurrence after treatment with curettage and packing with polymethylmethacrylate cement. The demographic characteristics, including the age and sex of the patient and the site of the tumor, were similar to those that have been reported for other large series. An average of four years (range, two to ten years) after the operation, the over-all rate of initial local recurrence was 25 per cent (fifteen of sixty patients). Patients who had had a tumor of the distal aspect of the radius had a higher rate of recurrence (five of ten) than those who had had a tumor of the proximal aspect of the tibia (seven [28 per cent] of twenty-five) or of the distal part of the femur (three [13 per cent] of twenty-three). Higher rates of recurrence were also noted for patients who had had a pathological fracture (three of six), those who had had a Stage-III tumor according to the classification of Campanacci et al. (six of sixteen), and those who had not had adjuvant treatment with either a high-speed burr or phenol (eight of nineteen). Patients who had had an initial recurrence after packing with cement had a low rate of secondary recurrence when the initial recurrence had been treated with a wide resection or a second intralesional procedure (zero of ten and one of five patients, respectively), after an average of three years (range, ten months to eight years). No patient had a multicentric tumor or metastasis.(ABSTRACT TRUNCATED AT 250 WORDS)The Journal of Bone and Joint Surgery 01/1995; 76(12):1827-33. · 3.23 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: We reviewed the results for forty consecutively seen patients, each of whom had been managed by one surgeon for a giant-cell tumor of bone in an extremity between 1976 and 1990. Twenty patients had been managed with an en bloc resection and twenty, with an intralesional excision of the tumor with adjunctive local insertion of methylmethacrylate or phenol. All patients had been followed for a minimum of two years. Both en bloc resection and intralesional excision were found to be excellent oncological procedures. There were fewer complications and better functional results after the intralesional procedure than following the en bloc resection.The Journal of Bone and Joint Surgery 12/1993; 75(11):1648-55. · 3.23 Impact Factor
Singapore Med J 2006; 47(8) : 2
Singapore Med J 2006; 47(8) : 679
Introduction: The surgical treatment of Stage
III or aggressive giant cell tumour of the bone,
whether to perform intralesional or en-bloc
resection, remains controversial. The aim of
this study is to identify the effectiveness of
en-bloc resection for local control and final
oncological outcome of the disease.
Methods: The data of 20 consecutive patients
with Stage III giant cell tumour were
retrospectively reviewed to determine the
local control and oncological outcome after
treatment with wide resection.
presented late with mean duration of
symptoms of 24 months, and four patients
presented with recurrences. All patients were
treated with wide resection except for two
patients who underwent ablative surgery
due to major neurovascular involvement.
Ten patients required free vascularised tissue
transfer to cover massive soft tissue defect.
Local recurrence occurred in one patient who
was again treated with wide resection and
vascularised flap. Six patients had pulmonary
metastases. Two patients with resectable
disease were treated with thoracoscopic
surgery and they remained disease-free
36 months after surgery. Two patients with
multiple lung metastases were treated with
chemotherapy and the disease remained
patients who refused chemotherapy showed
radiological progression, and one succumbed
to the disease with massive haemoptysis.
The majority of the patients
Conclusion: Aggressive giant cell tumour of
bone should be treated with wide resection
for better local control, and treatment of
pulmonary metastases is mandatory for
Aggressive giant cell tumour of bone
Faisham W I, Zulmi W, Halim A S, Biswal B M, Mutum S S, Ezane A M
School of Medical
Kubang Kerian 16150
Faisham W I, MMed
Zulmi W, MS
Plastic Surgery and
Halim A S, FCCP
Biswal B M, MD,
Lecturer and Head
Mutum S S, MD
Ezane A M, MMed
Dr WI Faisham
Tel: (60) 9 766 3000
Fax: (60) 9 765 3370
Keywords: aggressive giant cell tumour, bone
tumours, giant cell tumour, wide resection
Singapore Med J 2006; 47(8):679-683
Giant cell tumour (GCT) of bone is a benign but
locally aggressive neoplasm, characterised by a
large number of uniformly-distributed osteoclast-
like giant cells in a bland stroma of spindle-shaped
mononuclear cells. Stage III or aggressive giant cell
tumour is a symptomatic, rapidly-growing lesion
that is often associated with spontaneous fracture.
Isotope bone scans show intense activity that often
extends beyond the lytic area on radiograph(1,2).
Magnetic resonance (MR) imaging shows infiltration
of surrounding soft tissue, confirmed histologically
by tumour that has breached the cortex and extended
into the surrounding soft tissue.
Treatment of GCT of bone is basically
surgical intervention by curettage and adjuvant
treatment to eliminate any remnant of tumour, and
reconstruction of osseous defect with bone graft or
methylmetacrylate(3,4). However, the treatment of
Stage III GCT, i.e. whether to perform an intralesional
or en-bloc resection, remains controversial(5,6). The
aim of this study is to identify the effectiveness of en-
bloc resection for local control and final oncological
outcome of the disease.
20 patients with histologically-proven Stage III
GCT seen at our institution between January 1997
and June 2003 were included. The clinical and
radiological records of all the patients were reviewed.
As a part of staging process, routine haematological
and biochemical investigations, MR imaging of the
primary tumour, whole body bone scintigraphy and
computed tomography (CT) of the chest were done.
Tissue diagnosis was obtained in all cases with either
open or trucut biopsy.
Wide resection, which consisted of removal
O r i g i n a l A r t i c l e
Singapore Med J 2006; 47(8) : 3
Singapore Med J 2006; 47(8) : 680
of the tumour en-bloc with a cuff of normal tissue
around the mass, was done according to biological
anatomical barrier and MR imaging features. The
surgical specimens were evaluated for microscopical
extent of tumour at the margins and intramedullary
marrow extension. Serial CT of the chest and whole
body Technetium 99m bone scintiscans were taken
at six-monthly intervals for two years and yearly
thereafter for five years. Optional local radiological
assessments were performed based on symptoms.
The outcome of treatment in terms of local control
and failure were recorded. Final oncological outcome
and presence of pulmonary metastases and major
complication in all patients were documented.
There were 13 male and seven female patients, with
a mean age of 33 years (range 24-58 years). The
location of primary tumours was the distal femur in
five patients, proximal tibia in four, distal radius in
seven, distal ulna in two, and one each in the proximal
fibula and distal tibia. The median follow-up period
for all patients was 30 months, ranging from 12 to 60
months. The most common presenting symptom was
a painful bony swelling that occurred in 18 (90%)
patients. Two patients presented late with arthritic
pain and progressive swelling. Four patients presented
with recurrent disease after primary treatment. Four
patients presented with skin infiltration secondary to
previous surgery and biopsy. 16 patients presented
late before a definitive diagnosis was made (range
six months to nine years), with a mean duration of
symptoms of 24 months (Table I).
Classical histopathological features of GCT
Table I. Series of patients with Stage III giant cell tumour of the bone.
1. M 32 Lt proximal tibia Fibular composite allograft Infection
2. F 24 Lt distal tibia Fibular composite allograft SWD
3. F 23 Rt distal radius Fibular graft SWD
4. F 33 Rt distal femur Endoprosthesis SWD
Rt distal femur
Above knee amputation
Single nodule –
6. M 33 Rt distal radius Fibular graft SWD
Lt proximal tibia
Above knee amputation
>5, both lobes
DOD 6 months –
8. F 32 Lt distal femur Endoprosthesis, free flap SWD
Lt distal femur
Double vascularised fibular
graft knee orthrodesis
>5, both lobes
10. M 41 Lt distal radius Fibular graft SWD
Endoprosthesis, free flap
Double nodule –
Rt distal radius
Vascularised fibular graft
>5, both lobes –
13. M 35 Lt distal radius Fibular graft SWD
14. M 24 Rt proximal tibia Endoprosthesis SWD
Rt proximal tibia
>5, both lobes –
16. M 43 Rt distal femur Endoprosthesis SWD
17. M 28 Rt distal radius Vascularised fibular graft SWD
18. F 33 Rt distal radius Skin infiltration Vascularised fibular graft SWD
19. F 50 Lt distal ulna Skin infiltration Fusion, free tissue transfer SWD
20. M 30 Rt distal ulna Wrist fusion SWD
SWD: survived without disease; DOD: died of disease; Lt: left; Rt: right
Singapore Med J 2006; 47(8) : 4
Singapore Med J 2006; 47(8) : 681
two patients were bridged with combined allograft
and intramedullary vascularised fibular graft
and knee arthrodesis. One patient who had distal
tibial lesion was also treated with allograft fibular
composite for ankle arthrodesis.
Aggressive lesions in distal radius were treated
with a wide resection of margin in all patients.
Vascularised osteocutaneous fibular grafts were
performed in three patients due to massive soft
tissue involvement and skin infiltration. The other
three patients were treated with non-vascularised
autogenenous ipsilateral fibular graft. Resection of
the distal ulnar lesion resulted in wrist instability and
massive soft tissue and skin defect. Osseous stability
was achieved by wrist arthrodesis and pedicle lateral
thigh flap was performed in this case to provide the
soft tissue coverage (Fig. 1).
Local recurrence developed 12 months after
surgery in one patient with a proximal tibial
lesion, which was treated with wide resection and
endoprosthesis reconstruction. The recurrent lesion
was resected with wide margin, and reconstructed
with vascularised latissimus dorsi flap. The patient
was disease-free 24 months after surgery. Another
patient with distal radius lesion developed a single
skin nodule at the dorsal aspect after nine months.
It was resected and the patient remained free of
of the bone were observed in all patients. No
histological evidence of malignant transformation
was seen in any of the cases. Wide margin with
1 cm surrounding normal soft tissue was achieved
in 16 cases and marginal of 1-2 mm in another four
patients. Four patients with ulcers showed infiltration
of the skin and the subcutaneous tissue. Amputation
was the primary mode of surgical treatment in two
patients. One patient presented with metachronous
lesion of distal femur and distal radius. The lesion in
distal femur had massive soft tissue infiltration and
neurovascular infiltration posteriorly that precluded
limb salvage surgery. Another patient presented
nine years after initial diagnosis with aggressive
behaviour and massive soft tissue and neurovascular
Limb salvage surgery was performed in 18
patients (Table I). All surgical specimens were
evaluated for microscopical extension at the tumour
margin and intramedullary marrow extension, and
they were tumour-free in all cases. The osseous
defects following resection of lower limb were
reconstructed with endoprosthesis in seven patients.
In one patient with recurrent tumour, the distal
femur was reconstructed with double vascularised
osteocutaneous fibular graft knee arthrodesis due
to massive tumour infiltration into the quadriceps
compartment. The proximal tibial osseous defects in
Fig. 1 Case no. 20. A 30-year-old man presented with
progressive swelling of distal ulna. There was significant soft
tissue infiltration by a markedly hypervascular tumour. He was
treated with wide resection and wrist fusion. He remained
disease-free three years after surgery. (a) Clinical photograph
shows the large distal forearm swelling. (b) Radiograph shows
expansile lytic lesion with cortical break. (c) Surgical photograph
shows a hypervascular tumour and soft tissue infiltration.
Singapore Med J 2006; 47(8) : 5
Singapore Med J 2006; 47(8) : 682
Six patients had pulmonary metastases, and
four presented with recurrence of lesion after
intralesional surgery. One patient presented after
nine years with locally-aggressive lesion and
another patient had metachronous tumour of distal
femur and radius. Two patients who had single and
double metastatic tumour nodules, respectively,
in the lung underwent thoracoscopical resection.
Both were disease-free at 36 months after surgery.
Two patients who had multiple nodules in the lung
received six courses of adriamycin and ifosfamide.
They remained asymptomatic and showed resolution
with peripheral calcifi cation of pulmonary nodules
The two patients who refused chemotherapy
showed progression of the lung nodules. One
patient subsequently succumbed to the disease at
six months with massive haemoptysis. Two patients
treated with fi bular composite allograft developed
chronic infection, which was controlled with
repeated debridement and antibiotics. Both patients
achieved osseous union 12 months after surgery,
despite developing infections.
GCT is an infrequent and unpredictable bony lesion(7).
Although numerous attempts have been made to
predict the behaviour of GCT, there are no defi nite
biological or histological parameters to determine
the prognosis or aggressiveness of this lesion(8). A
review of the histopathological evaluations in the
patients in this series did not reveal any evidence of
malignant change, despite being locally aggressive.
The aggressive behaviour of GCT seems to occur
more frequently in the oriental population(9,10). In
our patients, GCT not only presented with locally-
aggressive behaviour, it also had higher incidence
of pulmonary metastases.
The treatment for GCT of bone is basically
surgical resection. The decision whether to perform
an intralesional excision (curettage) or en-bloc
resection of the tumour, is based on local tumour
extension(3-5,11). Curettage has been associated with
a high rate of local recurrence that ranges from 22%
to 40%(3-5). Combination with adjuvant treatment,
such as the use of phenol and methylmethacrylate,
reduces the incidence of recurrence to less than
10%(3,4). The local recurrence has been shown to
correlate with aggressiveness of the lesion.
A sequential increase in local recurrence rate
from Stage I to III with 7% in “quiescent”, 26%
in “active”, and 41% in “aggressive” tumours
respectively, has been observed(4). The patients
with multiple local recurrences are more likely to
develop metastases(4). In our series, the patients had
either presented late or had recurrent lesions with
surrounding soft tissue infi ltration. Wide resection
has been shown to be a good alternative for local
control of stage III disease with 5% recurrence(5,6).
Amputation may be a good option for GCT of
Fig 2. Case no. 12. A 28-year-old man presented with recurrent tumour of the distal radius, which was resected and reconstructed
with vascularised fi bular graft. He also had multiple pulmonary metastases that precluded surgical resection. He received six courses
of adriamycin and cisplatin for six months. At present, he is asymptomatic and pulmonary nodules remain static. (a) Axial T1-W MR
image shows distal radius giant cell tumour with massive soft tissue involvement. (b) Postoperative radiograph shows the vascularised
fi bular graft and wrist fusion. Axial CT images (c) at presentation shows multiple pulmonary metastases, and (d) after three years,
shows no progression of pulmonary nodules.
Singapore Med J 2006; 47(8) : 6
Singapore Med J 2006; 47(8) : 683
bone that has an aggressive behaviour, particularly
with massive skin infiltration. However, the local
aggressive behaviour has not been shown to change
the final outcome and prognosis of the patients(4).
This has to be considered in the final treatment.
All patients with skin infiltration in this series had
good local control after wide removal of the skin
together with the tumour and reconstruction with
Biological reconstruction of the osseous defect
should be considered first. This is pertinent as
the disease occurs in younger patients, whose
functional demands are high and who have higher life
expectancies(11). Osteomyocutaneous vascularised
fibular graft is, in our opinion, the best option to
reconstruct the distal radius and provides good cover
over the soft tissue defect. A combination of allograft
constructs with vascularised fibular graft as in a knee
arthrodesis provides early stability and reduces the
long-term complication of allograft. This is also
shown by others investigators(12,13). It enhances healing
and provides almost total biological incorporation
in long-term follow-up. Biological reconstruction
with vascularised fibula osteocutaneous graft or
combination of allograft fibular flap composites is a
good alternative construct for reconstruction of both
osseous and soft tissue defects with better long-term
results as shown in our series.
Endoprosthetic reconstructions provide immediate
stability and allows early mobilisation and weight-
bearing. The advancement and modularity of present
implant have dramatically improved function
with better long-term outcome. It is too early to
predict the outcome of endoprosthesis in our series.
However, in other series, ten- to 15-year survival with
endoprosthesis have been reported in about 70-75%,
despite the young age of the patients in whom the
prosthesis was implanted(14).
Approximately 1-2% of GCT of bone develop
metastases that are histologically identical to the
primary tumour(3,4,15-18). Surgical staging, based
on combination of clinical, radiographical and
pathological findings, has shown that aggressive
lesions and recurrences are found to be main risk
factors for pulmonary metastases(4). Local recurrence
is associated with 6% incidence of metastatic disease,
and in patients without local recurrence, this incidence
is less than 1%(4). The incidence of pulmonary
metastases was higher (30%) in our series. This raises
a question mark about the actual behaviour of GCT in
the oriental population.
The natural history of metastatic pulmonary disease
has been found to be as unpredictable as the primary
tumour(4,7). Solitary and surgically-accessible lesions
can be resected with excellent long-term survival(6,15).
Multiple and asymptomatic lesions may remain
stationary in size, or even spontaneously regress
without therapy. In symptomatic and unresectable
pulmonary metastases, radiotherapy has been reported
with variable results and with the risk of secondary
sarcomatous transformation(6,15). Chemotherapy in
combination with surgery also has a significant value
to control the disease and symptoms in selected
patients(16). The patients with multiple pulmonary
metastases in our series did benefit with six courses
of chemotherapy. They were asymptomatic for
24 months, and serial CT showed a peripheral rim of
calcification and no progression of the lesion.
In conclusion, Stage III GCT of bone is best
managed with wide resection for better local control.
Aggressive treatment of pulmonary metastasis is
mandatory in the management of aggressive GCT.
The prognosis is favourable in patients with
complete surgical resection of pulmonary nodule or
those who have received chemotherapy. The overall
outcome of treatment is good.
1. Campanacci M. Giant-cell tumor and chondrosarcomas: grading,
treatment and results (studies of 209 and 131 cases). Recent Results
Cancer Res 1976; 54:257-61.
2. Enneking WF. Musculoskeletal Tumour Surgery. New York: Churchill
Livingstone, 1983: 87-8.
3. OʼDonnell RJ, Springfield DS, Motwani HK, et al. Recurrence of giant
cell tumors of the long bones after curettage and packing with cement. J
Bone Joint Surg Am 1994; 76:1827-33.
4. Rock MG. Curettage of giant cell tumour of bone. Factors influencing
local recurrences and metastasis. Chir Organi Mov 1990; 75:204-5.
5. Gitelis S, Mallin BA, Piasecki P, Turner F. Intralesional excision
compared with en-bloc resection for giant cell tumors of bone. J Bone
Joint Surg Am 1993; 75:1648-55.
6. Rooney RJ, Asirvatham R, Lifeso RM, Ali MA, Parikh S. Giant cell
tumour of bone. A surgical approach to grade III tumours. Int Orthop
7. Faisham WI, Zulmi W, Mutum SS, Shuaib IL. Natural history of giant
cell tumour of the bone. Singapore Med J 2003; 44:362-5.
8. Jaffe HL, Lichtenstein L, Portis RB. Giant cell tumour of the bone. Its
pathological appearance, grading, supposed variant and treatment. Arch
Pathol 1940; 30:993-1031.
9. Shih HN, Hsu RW, Sim FH. Excision curettage and allografting of giant
cell tumor. World J Surg 1998; 22: 432-7.
10. Sung HW, Kuo DP, Shu WP, et al. Giant-cell tumor of bone: analysis of
two hundred and eight cases in Chinese patients. J Bone Joint Surg Am
11. Muscolo DL, Ayerza MA, Calabrese ME, Gruenberg M. The use of a
bone allograft for reconstruction after resection of giant-cell tumor close
to the knee. J Bone Joint Surg Am 1993; 75:1656-62.
12. Cordeiro PG, Neves RI, Hidalgo DA. The role of free tissue transfer
following oncologic resection in the lower extremity. Ann Plast Surg
13. Krag DN, Klein H, Schneider PD, Goodnight JE Jr. Composite tissue
transfer in limb-salvage surgery. Arch Surg 1991; 126:639-41.
14. Shin D, Choong PFM, Chao EY, Sim FH. Large tumor endoprostheses
and extracortical bone bridging: 28 patients followed 10-20 years. Acta
Orthop Scand 2000; 71:305-11.
15. Kay RM, Eckardt J, Seeger LL, Mirra JM, Hak DJ. Pulmonary metastasis
of benign giant cell tumor of bone. Six histologically confirmed cases
including one of spontaneous regression. Clin Orthop Relat Res 1994;
16. Stewart DJ, Belanger R, Benjamin RS. Prolonged disease-free survival
following surgical debulking and high-dose cisplatin/doxorubicin in a
patient with bulky metastases from giant cell tumor of bone refractory to
standard chemotherapy. Am J Clin Oncol 1995; 18:144-8.
17. Rock MG, Sim FH, Unni KK, et al. Secondary malignant giant-cell
tumor of the bone. Clinicopathological assessment of nineteen patients.
J Bone Joint Surg Am 1986; 68:1073-9.
18. Bertoni F, Present DA, Enneking WF. Giant-cell tumor of bone with
pulmonary metastases. J Bone Joint Surg Am 1985; 67:890-900.