Giant cell tumor is a benign bone tumor composed of multinucleated giant cells and mononuclear stromal cells. It typically occurs in long bones of adults aged 20-55. While locally aggressive, it has well-defined borders on imaging and grows slowly within bone. Treatment involves curettage with or without adjuvants like cryotherapy or bone grafting to minimize the 25-35% recurrence rate. In rare cases, it can metastasize to the lungs.

1. Giant Cell Tumor
CLAUDIA SANTOSA

2. References

3. Introduction
 Also known as: osteoclastoma.
 Incidence 4% of primary bone tumors.
 Female to male ratio: 1.2 : 1.
 Age: 20-55 yo (peak: 3rd decade)
 The multinucleated giant cells result from fusion of the
proliferating mononuclear cells.
 Distinct, locally aggressive (25%).
 Most frequent site: end of long bones in skeletally
mature individuals (epiphyseal/epiphyseal-equivalent
portions of bone).
 Pathologic fracture is found in 5-10% of cases.
 25-35% GCT recur after simple curettage (typically
within 3 years)

4. Clinical Evaluation
 Pain (3-6 months)
 Activity-related  loss of structurally important bone
and mechanical failure of bone
 At rest/at night  related to tumor growth, periosteal
expansion
HISTORY
PHYSICAL EXAMINATION
 Tenderness to palpation
 Soft tissue swelling
 Sympathetic or direct joint effusion
Pathologic fracture can occur through lytic lesions of long bones,
especially in weight-bearing bones.
Raskin, et al. Giant Cell Tumor of Bone. J Am Acad Orthop Surg 2013;21: 118-126

5. Radiographic Evaluation
 Large, purely lytic mass
 Extends from subchondral bone plate into metaphysis +
epiphysis
 Larger tumor  adjacent diaphysis, focally destroyed cortex,
soft tissue invasion
 Frequently eccentric (even though arise within the
medullary portion)
 Expansile + periosteal elevation (thin periosteal shell)
 Well-defined medullary margins (usually not sclerotic); in
some cases may appear moth-eaten
 Cystic degeneration (extremely hypervascular)  contrast
enhancement
 Dark on T1-weighted, bright on T2-weighted
X-RAY
MRI

6. Radiographic Evaluation
 Well-defined, eccentric, lytic subchondral
lucency.
 Expanded cortex + focal destruction.
 Marginal sclerosis + trabeculation 
occasionally at weight-bearing bone.
 “soap-bubble” appearance.

7. Enneking Classification
(Radiological)
Stage I (Latent) Stage II (Active) Stage III (Aggressive)
10-15% 70-75% 10-15%
Lytic defect limited to
medullary cavity
Lytic defect Lytic defect
Minimal / no cortical
involvement
Thinned, expanded
cortex
Cortex invasion +
extension into
surrounding soft tissue
Clear rim of sclerosis Unclear margins Ill-defined margins
Fine trabeculation ± Fine trabeculation ± Fine trabeculation ±
• This classification has limited usefulness  radiologic features of
aggressiveness do not necessarily correlate with microscopic criteria of
malignancy or clinical behavior of the tumor.
• In many cases, the exact radiologic diagnosis cannot be made.

8. Enneking vs Campanacci
RARE
Raskin, et al. Giant Cell Tumor of Bone. J Am Acad Orthop Surg 2013;21: 118-126

9. Gross Findings
 Soft, friable, fleshy, red-brown with
yellowish area.
 Well demarcated tumor tissue.
 Usually extends to the articular cartilage 
but unlikely to be invaded or perforated.
 Eccentric position in the epiphyseal end +
advancing toward the medullary cavity
(more centrally located).
 Delimited in its periphery by a thin layer of
fibrous and reactive bone tissue.
 Evidence of hemorrhage, cyst formation,
necrosis (more frequent and extensive in
weight-bearing bones.

10. Microscopic Findings (Histology)
 GCT is a mesenchymal tumor; cell origin: fibroblastic-
osteoblastic mononuclear cell (producing type I and II
collagen)
 Moderately vascularized stroma with oval/plump, spindle-
shaped mononuclear cells uniformly interspersed with
multinucleated osteoclast-like giant cells.

11. Microscopic Findings (Histology)
 Giant cells:
 Ovoid, vesicular nuclei + central nucleoli,
tend to be situated in the center of cell and
surrounded by abundant eosinophilic
cytoplasm.
 Mononuclear stromal cells:
 Has an affinity for PTH  can produce ALP
 Round/ovoid vesicular nuclei with central
nucleoli (morphologically identical to nuclei
of giant cells)
 Ill-defined borders
 Little eosinophilic cytoplasm
 May be mitotically active  variable degrees
of cytologic atypia

12. Cytology (FNAB)
2 cell populations:
 Mononuclear cells (predominant)
 Histiocytoid appearance, singly dispersed or in small 3D clusters
 Multinucleated giant cells
 Similar to osteoclasts but usually contain many more nuclei
The cytologic feature of GCT are often obscured by secondary changes, such as
proliferation of fibrous tissue accompanied by foamy histiocytes  need
correlation with clinical and radiologic data to establish correct diagnosis.

13. GCT of Proximal Tibia
A: AP view involving epiphysis
 note expanded contour of
tibia.
B: Gross Findings: expansile red-
brown tumor + yellowish
septations, cortex destroyed,
expanded bone contour
delineated by thin fibrous
capsule.
C: Microscopic: multinucleated
giant cells within a mononuclear
stroma.
E+F: FN aspirates containing
multiple mononuclear stromal
cells and multinucleated
osteoclastic cells.
G: Higher power showing
mononuclear stromal cells with
oval nuclei and discrete nucleoli.

14. Differential Diagnosis
 Giant cell reparative granuloma
 Most frequently occurs in the jaws
 Brown tumor of hyperparathyroidism (Recklinghausen
disease)
 Hypercalcemia, hypophosphatemia, ↑ PTH
 Nonossifying fibroma
 Skeletal immaturity (<15 yo), metaphyseal location
 Irregular distribution of multinucleated giant cells in a more
fibroblastic background
 Giant cell rich osteosarcoma
 Nuclear anaplasia, abnormal mitotic figures, neoplastic osteoid
production
 ill-defined margin
 Aneurysmal Bone Cyst (ABC)
 75% in metaphysis
 Double density fluid-fluid level on CT/MRI
 Chondroblastoma
 Adolescent with open physis
 Histology: chicken wire calcification

15. 2˚ phenomena in
Conventional GCT
• Pulmonary metastases
(benign pulmonary
implants) may develop in
approx. 1-2% patients.
• Typically nodules grow
slowly and are amenable
to surgical excision.

16. Treatment
 Curettage + bone graft (recurrence rate 45%)
 Curettage + cryotherapy (liquid nitrogen) (recurrence
rate <8%)
 Complication: pathologic fracture, vascular injury
 Curettage + chemical adjuvant (phenol, H2O2, bone
cement) (recurrence rate 17%)
 En bloc wide excision with allograft/ prosthetic
replacement
 Recalcitrant/recurrent cases
 Aggressive stage 3 tumors
 GCT in expendable bones (clavicle, distal ulna, proximal
+ mid fibula)
 RANKL inhibitor (denosumab) + bisphosphonates
 Primary tumors that cannot be resected
 Metastatic disease that cannot be surgically controlled

17. GCT in sacrum +
axial skeleton
 3-7% involve the spine.
 Account for up to 4% of vertebral
tumors.
 Most common site within the
sacrum: sacral arch or wing.
 Most common site in spine:
vertebral body (60%).
 Treatment:
 Resection with
marginal/microscopically positive
margin
 ± Embolization (reduce
vascularity)
 ± Radiotherapy
A, CT scan demonstrating GCT of bone at L5. Sagittal
T1- weighted (B), sagittal fat-saturated T2-weighted (C),
and sagittal fat-saturated T1-weighted with gadolinium
(D) MRI images.
Raskin, et al. Giant Cell Tumor of Bone. J Am Acad Orthop Surg 2013;21: 118-126

18. Metastatic GCT
 2% of cases.
 Highest rate of metastasis: wrist, distal radius.
 Considered benign and bear the same histologic
characteristics of the original tumor.
 Metastatic GCT to the lung
 Increase c-myc oncogene
 Treatment: surgical resection (76% survival rate, 17.4%
mortality rate), interferon.

19. Take home message
 GCT is a mesenchymal tumor with characteristic abundant
multinucleated giant cells interspersed with mononuclear stromal
cells.
 Predominant location: metaphyseal-epiphyseal regions of long
bones.
 Typically these tumors are clinically active but relatively slow-
growing and confined to bone with fairly well-defined radiographic
borders.
 In cases in which biopsy is required to confirm the radiological
diagnosis prior to treatment  MRI, bone scan and chest X-ray
need to be done first to evaluate the extent of tumor.
 Radiotherapy is only used in certain cases (eg sacrum, spine) where
it is technically difficult to perform en block excision or complete
curettage.