GCT is one of the most common benign bone tumors,characterized by high incidence of local recurrence. the pathogenesis,pathology,clinical presentation and treatment options will be discussed.

1. Giant cell tumors of long bones
By
Ahmad M. Shahin, M.D.
Prof. and head of orthopedic department
Chief of bone oncology and reconstruction unit
Elmenofia university
EGYPT

2. Giant cell tumor
((GCT
Is a benign neoplastic lesion
locally osteolytic without matrix calcification
Arise in the metaepiphyseal region of long bones
Histologically it is consisted of three cell types;
mononuclear histiocytic cells ,multinucleated giant
cells that resemble osteoclast and neoplastic
stromal cells
•

4. The high incidence of local recurrence
to 65%) and the tendency to give % 0 )
metastasis in rare cases raised the
question of the nature of these tumors
A aggressive Benign? Or Locally
? malignant

5. The pathogenesis and etiology of giant cell
tumor of bone
In the primary culture characteristic multinucleated giant cells and •
mononuclear cells were coexisted
The values of interleukin 1 and prostaglandin E2 in the obtained from •
. the primary culture were high
In subcultures, multinucleated giant cells were not persisted and only •
stromal cells were visible and the values of IL-1 and PGE2 were much
lower
the exposure of the passaged stromal cells to the medium containing IL- •
1 stimulated the stromal cells to produce PGE2 and proteolytic enzymes
These findings demonstrated that coexistence of multinucleated giant •
cells with mononuclear cells should be needed for the tumor
Komiya S et.al from Japan
•

6. The nature of giant cell tumor of bone
Cell culture experiments with GCT cells revealed that •
stromal cell to be the proliferating component of the
GCT
The monocyte and the multinucleated giant cell, were lost
•
after a few cell culture passages
stromal cells secrete a variety of cytokines and •
differentiation factors, including MCP1, ODF, and MCSF
Wülling M, Engels C, Jesse N, Werner M, Delling G, Kaiser E. Hamburg,
Germany
•

7. These molecules are monocyte chemoattractants and are •
essential for osteoclast differentiation, suggesting that the
stromal cell stimulates blood monocyte immigration into
tumor tissue and enhances their fusion into multinucleated
. giant cells
The multinucleated giant cell is able to resorb bone leading to
extended osteolysis
This new model of GCT genesis supports the hypothesis that the
stromal cell is the neoplastic component
whilst the monocytes and the multinucleated giant cells are just
reactive components of this tumor

8. The histopathological parameters
The mitotic count •
The presence or absence of nuclear atypia •
The degree of cellularity •
present Conventional mitotic figures are
. restricted to mononuclear cells
If atypical forms or strong nuclear atypia is
noted, a secondary sarcomatous malignancy is
almost always

9. Jaffe and Lichtenstein
– Grade 1 •
, No appreciable a typism of the stormily cells ,mitoses are few •
•
-Grade 2 •
Stromal cells may be slightly or strikingly atypical but not sufficiently to
diagnose frank malignancy
abnormal mitotic figures may be found •
•
-Grade 3 •
Frankly and obviously malignant with capacity to metastasize •
•

10. Netherlands Committee on Bone
. Tumours
•
•
•
•
•
According to the latter grading system,
Grade 1 and 2 are considered as being ,
Grade 3 as borderline malignant,
Grade 4 as malignant tumours.
Grade 4 tumours show histological overlap
with malignant fibrous hystiocytoma of bone.
In this grading system mitoses, pleiomorphism of the spindled
mononuclear cells, giant cells and the individual size of the
giant cells will be taken into account

11. In this grading
system
Mitoses,
pleiomorphism
of the spindled
mononuclear cells,
giant cells and the
individual size of the
giant cells will be
.taken into account

12. Most important is
the mitotic activity.
When mitoses are occasional
observed the risk of developing
recurrences and pulmonal
. metastases is neglectable
If more than 1 mitosis is present
per 1 high power field, patients
are significantly at risk for
developing recurrence and
(pulmonal metastases (23%

13. Grading of giant cell tumours
according to the Netherlands
.Committee on Bone Tumors

14. ,grade 1: 4%
grade 2: 88%
grade 3: 5%
grade 4: 3%
.

15. Enneking
Stage 1-one with a surrounding rim of reactive bone without •
deformation or expansion
Stage 2-the margin is irregular and the overlying cortex •
.expanded or deformed
Stage 3-is one with no clear defined margin , cortical •
. destruction and soft tissue extension

16. Campanacci et.al
well circumscribed with minimal cortical-1
thinning
moderately expansible with moderate to-2
severe thinning of adjacent cortex
no longer contained by a reactive rim of bone-3

17. HIGH RISK GCT
Recurrent GCT •
GCT in the pelvis, sacrum, spine •
GCT extend to joint or soft tissue •
GCT with pathological fracture •

18. Treatment
Radical amputation in 1800's •
[ Curettage and bone graft 1912 [Bloodgood •
Intralesional curettage preserves the bone anatomy •
The main problem with intralesional curettage was the high •
incidence of local recurrence rate that varied from 25% to
50%
Wide resection was advised to have a better local control •
however this procedure was associated with impaired the
limb function as it scarifies a significant segment of bone
Recently Enhancement of intralesional procedures with •
liquid nitrogen, acrylic cement, phenol, hydrogen peroxide
had been advocated with encouraging results

19. Intralesional curettage
For all grade 1 or 2 lesions that had no intra- •
articular extension
High speed burr •
Pulsatile lavage •
hydrogen peroxide •
Phenol Cauterization 80% •
Reconstruction with bone graft /composite •
bone graft bone cement/ bone cement

20. Wide resection
Wide resection was advised in grade 3 lesions, •
tumors with extensive bone destruction,
impossible joint salvage, or in expandable
bones
Reconstruction options include ostearticular •
allograft, resection arthrodesis, arthroplasty

21. GCT is an osteolytic mass in
the epiphysis leading to
cortex thinning and
expansion

64. A
B

65. C

66. C

67. Malignant giant cell tumor
Is defined as a sarcoma arising in association with a 
well documented giant cell tumor, either
synchronously or at the site of a previously
documented giant cell tumor
Difficulty in separating benign from malignant has 
lead to such unfortunate terms as borderline
malignant and tumors of uncertain malignant
Potential 

81. Local Recurrence
Location •
Nature •
Presence of fracture •
Local therapy •
Tumor grade •

82. Location
,Goldenberg et. Al 1970 •
,Harness and Mankin 2004 •
O,Donnell et.al 1994
Reported high incidence of local recurrence •
with distal radius lesions treated with
curettage
They recommended more aggressive •
treatment for Grade 3 lesions at distal radius

84. Kremen et.al.2012
Reported no difference in the
incidence of local recurrence among
distal radius GCT compared to GCT
recurrence in other regions of the
body

85. Author
Primary
Recurrent
O Donnell
25%
-
Malawer
2.6%
38%
Turcotte
12%
35%
Kremen
11%
22%
McDonald
34%
-
Our series
23.5%
42.8%

86. Prosser et. al 2005, Turcotte et. al.2002
Reported increased risk of local recurrence •
among patients with recurrent GCT of bone
In this series there was increased risk in •
patients with recurrent GCT cmopared to
.primary tumors
However there was no difference between •
.recurrent and re-recurrent lesions

87. The pathology of recurrent tumors was •
identical to that of the initial lesions and
does not represent biologically more
aggressive lesions

88. Phenol as an adjuvant
Phenol induces tumor necrosis with few •
adverse effects
Some authors reported little effect of phenol on
recurrence
However others did report decreased local
recurrence rate with its use
In this study we did find decreased rate of local
recurrence with phenol cauterization

89. Bisphosphonates reduce local recurrence in •
:extremity giant cell tumor of bone
A case–control study •
a
Department of Orthopaedics and •
Traumatology, Prince of Wales Hospital,
Shatin, Hong Kong

90. The use of bisphosphonates as an anti-. •
osteoclastic agent in the management of
osteolytic bone metastases is well accepted.
Furthermore in vitro studies have shown that
bisphosphonates also induce apoptosis in GCT
stromal cells

91. Adjuvant zoledronic acid in ‘high risk’
Giant Cell Tumour of bone (GCT)
- A randomized phase II study
Study title •
•
(Adjuvant zoledronic acid in ‘high risk’ Giant Cell Tumour of bone (GCT
•
–A randomised phase II studyPrincipal Investigator •
J.R. Kroep •
Number of centres •
3 •
Proposed countries •
Netherlands: Dutch Orthopaedic Oncology Group / Giant cell tumour
group of EuroBoNet
•