Giant cell tumors of long bones
By
Ahmad M. Shahin, M.D.
Prof. and head of orthopedic department
Chief of bone oncology an...
Giant cell tumor
((GCT
Is a benign neoplastic lesion
locally osteolytic without matrix calcification
Arise in the metaepip...
The high incidence of local recurrence
to 65%) and the tendency to give % 0 )
metastasis in rare cases raised the
question...
The pathogenesis and etiology of giant cell
tumor of bone
In the primary culture characteristic multinucleated giant cells...
The nature of giant cell tumor of bone
Cell culture experiments with GCT cells revealed that •
stromal cell to be the prol...
These molecules are monocyte chemoattractants and are •
essential for osteoclast differentiation, suggesting that the
stro...
The histopathological parameters
The mitotic count •
The presence or absence of nuclear atypia •
The degree of cellularity...
Jaffe and Lichtenstein
– Grade 1 •
, No appreciable a typism of the stormily cells ,mitoses are few •
•
-Grade 2 •
Stromal...
Netherlands Committee on Bone
. Tumours
•
•
•
•
•

According to the latter grading system,
Grade 1 and 2 are considered as...
In this grading
system
Mitoses,
pleiomorphism
of the spindled
mononuclear cells,
giant cells and the
individual size of th...
Most important is
the mitotic activity.
When mitoses are occasional
observed the risk of developing
recurrences and pulmon...
Grading of giant cell tumours
according to the Netherlands
.Committee on Bone Tumors
,grade 1: 4%
grade 2: 88%
grade 3: 5%
grade 4: 3%
.
Enneking
Stage 1-one with a surrounding rim of reactive bone without •
deformation or expansion
Stage 2-the margin is irre...
Campanacci et.al
well circumscribed with minimal cortical-1
thinning
moderately expansible with moderate to-2
severe thinn...
HIGH RISK GCT
Recurrent GCT •
GCT in the pelvis, sacrum, spine •
GCT extend to joint or soft tissue •
GCT with pathologica...
Treatment
Radical amputation in 1800's •
[ Curettage and bone graft 1912 [Bloodgood •
Intralesional curettage preserves th...
Intralesional curettage
For all grade 1 or 2 lesions that had no intra- •
articular extension
High speed burr •
Pulsatile ...
Wide resection
Wide resection was advised in grade 3 lesions, •
tumors with extensive bone destruction,
impossible joint s...
GCT is an osteolytic mass in
the epiphysis leading to
cortex thinning and
expansion
A

B
C
C
Malignant giant cell tumor
Is defined as a sarcoma arising in association with a 
well documented giant cell tumor, eithe...
Local Recurrence
Location •
Nature •
Presence of fracture •
Local therapy •
Tumor grade •
Location
,Goldenberg et. Al 1970 •
,Harness and Mankin 2004 •
O,Donnell et.al 1994
Reported high incidence of local recurr...
Kremen et.al.2012
Reported no difference in the
incidence of local recurrence among
distal radius GCT compared to GCT
recu...
Author

Primary

Recurrent

O Donnell

25%

-

Malawer

2.6%

38%

Turcotte

12%

35%

Kremen

11%

22%

McDonald

34%

-
...
Prosser et. al 2005, Turcotte et. al.2002
Reported increased risk of local recurrence •
among patients with recurrent GCT ...
The pathology of recurrent tumors was •
identical to that of the initial lesions and
does not represent biologically more
...
Phenol as an adjuvant
Phenol induces tumor necrosis with few •
adverse effects
Some authors reported little effect of phen...
Bisphosphonates reduce local recurrence in •
:extremity giant cell tumor of bone
A case–control study •
a
Department of Or...
The use of bisphosphonates as an anti-. •
osteoclastic agent in the management of
osteolytic bone metastases is well accep...
Adjuvant zoledronic acid in ‘high risk’
Giant Cell Tumour of bone (GCT)
- A randomized phase II study

Study title •
•

(A...
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt
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GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt

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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.

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GCT of bone presentation by prof.Ahmad shaheen,M.D. prof.of orthopedic surgery ,Egypt

  1. 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. 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 •
  3. 3. 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
  4. 4. 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 •
  5. 5. 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 •
  6. 6. 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
  7. 7. 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
  8. 8. 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 • •
  9. 9. 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
  10. 10. 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. 11. 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%
  12. 12. Grading of giant cell tumours according to the Netherlands .Committee on Bone Tumors
  13. 13. ,grade 1: 4% grade 2: 88% grade 3: 5% grade 4: 3% .
  14. 14. 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
  15. 15. 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
  16. 16. HIGH RISK GCT Recurrent GCT • GCT in the pelvis, sacrum, spine • GCT extend to joint or soft tissue • GCT with pathological fracture •
  17. 17. 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
  18. 18. 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
  19. 19. 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
  20. 20. GCT is an osteolytic mass in the epiphysis leading to cortex thinning and expansion
  21. 21. A B
  22. 22. C
  23. 23. C
  24. 24. 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 
  25. 25. Local Recurrence Location • Nature • Presence of fracture • Local therapy • Tumor grade •
  26. 26. 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
  27. 27. 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
  28. 28. Author Primary Recurrent O Donnell 25% - Malawer 2.6% 38% Turcotte 12% 35% Kremen 11% 22% McDonald 34% - Our series 23.5% 42.8%
  29. 29. 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
  30. 30. The pathology of recurrent tumors was • identical to that of the initial lesions and does not represent biologically more aggressive lesions
  31. 31. 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
  32. 32. 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
  33. 33. 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
  34. 34. 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 •

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