Bone & joints
Other tumors
Giant cell tumor of bone

Editorial Board Member: Michael R. Clay, M.D.
Deputy Editor-in-Chief: Debra L. Zynger, M.D.
Jesse Hart, D.O.

Topic Completed: 1 April 2018

Minor changes: 11 February 2021

Copyright: 2003-2021,, Inc.

PubMed search: Giant cell tumor of bone[TI] pathology free full text[sb]

Jesse Hart, D.O.
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Cite this page: Hart J. Giant cell tumor of bone. website. Accessed March 9th, 2021.
Definition / general
  • Benign but locally aggressive primary bone neoplasm composed of mononuclear round to spindle cells with numerous evenly dispersed osteoclast-like giant cells
  • Not the same tumor as giant cell lesion of the small bones
  • Malignancy in giant cell tumor is rare (< 2% of cases) and is more common at older ages (30 - 50 years)
  • Rarely associated with Paget disease of bone (Skeletal Radiol 2007;36:973)
  • May occur in setting of focal dermal hypoplasia (Goltz syndrome) (Genet Couns 2014;25:445)
Essential features
  • Epiphysis and adjacent metaphysis of long bones
  • Evenly distributed giant cells throughout lesion; giant cells are not localized around hemorrhagic areas as in giant cell lesion of small bones, central giant cell granuloma or aneurysmal bone cyst
  • May penetrate cortex and extend into adjacent soft tissue
  • Also called osteoclastoma
  • Primary malignant giant cell tumor of bone: a high grade sarcoma arising in a giant cell tumor of bone at initial diagnosis (uncommon)
  • Secondary malignant giant cell tumor of bone: a high grade sarcoma arising at the site of a treated giant cell tumor of bone after surgery or low dose radiation therapy (more common than primary malignant giant cell tumor of bone)
ICD coding
  • D48.0: Giant cell tumor of bone, NOS (uncertain whether benign or malignant)
  • C40, C41: Giant cell tumor of bone, malignant, primary site
  • Accounts for ~5% of primary bone tumors
  • Ages 20 - 45 (10% of cases between age 15 - 20)
  • Rare if immature skeleton (Sarcoma 2016;2016:3079835)
  • Usually occurs in the epiphysis and adjacent metaphysis of long bones (distal femur, proximal tibia, distal radius, proximal humerus)
  • Other bones (proximal sacrum, vertebrae, skull base) may be involved, and any bone may be affected
  • > 95% are unifocal
  • Uncommon in hands / feet (more likely to be giant cell lesion of the small bones), jaw (more likely to be central giant cell granuloma)
  • Giant cells are not neoplastic
  • The neoplastic cells are primitive, mononuclear mesenchymal stromal cells that appear to be preosteoblasts; they express RANKL and preosteoblast markers (alkaline phosphatase, RUNX2, Sp7, osteoclastin)
  • RANKL on neoplastic preosteoblasts binds RANK (receptor activator of nuclear factor kB) on nonneoplastic macrophage-like osteoclast precursors; in the presence of M-CSF, this promotes osteoclast differentiation and giant cell formation (Bone 2004;34:393)
Clinical features
  • Malignant giant cell tumor: very uncommon; older age than for benign giant cell tumors but same site; usually due to prior giant cell tumor and radiation therapy; to diagnose, must document either prior or coexisting benign giant cell tumor at same location as spindle cell sarcoma
Radiology description
  • Lobulated, expansile osteolytic lesion ("soap bubble" appearance)
  • Pathologic fracture in 5 - 10%
  • May extend to within soft tissues with eggshell ossification at periphery
  • Three radiographic "grades" of giant cell tumor of bone called Campanacci grades after the author who first analyzed a large series of tumors using this grading system (Recent Results Cancer Res 1976;(54):257)
    • Campanacci grade I lesions ("quiescent lesions"): well defined border limited to the medullary cavity; no cortical involvement
    • Campanacci grade II lesions ("active lesions"): well defined border; cortex is thinned and expanded
    • Campanacci grade III lesions ("aggressive lesions"): ill defined margins with cortical destruction and soft tissue extension
Radiology images

Contributed by
Jesse Hart, D.O.

CT scan

 Contributed by
 Mark R. Wick, M.D.

Distal femur MRI

Proximal tibia


AFIP images

Tibial giant cell tumor

Chest radiograph

Prognostic factors
  • Pulmonary metastasis in ~2% of cases; they are very slow growing (nonaggressive) and may spontaneously regress; metastases have same morphology as the bone lesion (Pathol Int 1998;48:723)
  • Local recurrence, a high¬†Campanacci¬†grade and curettage are possible high risk factors for pulmonary metastasis (J Bone Oncol 2017;7:23)
  • Secondary malignancy in giant cell tumor of bone (arising after treatment of a benign giant cell tumor) has a poor prognosis akin to other high grade sarcomas and much worse than primary malignancy in giant cell tumor of bone (Cancer 2003;97:2520)
Case reports
  • Curettage: ~15 - 50% recur after curettage alone (usually within 2 years of curettage)
  • Antiosteoclast agents:
    • Bisphosphonates
    • Denosumab (anti-RANKL monoclonal antibody)
Gross description
  • Well defined borders
  • May be an expansile lesion with cortical thinning or soft tissue extension and a pushing border with a rim of reactive bone (often incomplete)
  • Cut surface may have yellow (xanthomatous), white (fibrous) or hemorrhagic / cystic areas
  • Necrosis may be seen in large tumors
  • Malignant transformation (if present) is often a large, fleshy area with soft tissue invasion
Gross images

Contributed by Mark R. Wick, M.D.

Giant cell tumor of bone

Distal femur

Proximal femur

 AFIP images

Distal femur

Microscopic (histologic) description
  • Numerous osteoclast-like giant cells uniformly distributed throughout tumor; many giant cells are larger than normal osteoclasts with numerous (> 50) nuclei; some areas may have a paucity of giant cells
  • Spindle and round / oval mononuclear cells also present (macrophage-like and primitive mesenchymal cells with poorly defined cytoplasm and mitotic activity which are the neoplastic cells)
  • Highly vascular stroma; may have fibrosis or reactive woven bone (common)
  • Acute hemorrhage, hemosiderin, xanthomatous histiocytes, necrosis (in large tumors) or secondary aneurysmal bone cyst (ABC)-like changes (10% of cases) may be present
  • Vascular invasion at periphery of tumor may be seen; it is associated with lung metastasis but not prognostically significant by itself (Virchows Arch 2010;456:97)
  • Malignant giant cell tumor resembles high grade sarcoma (osteosarcoma, fibrosarcoma, malignant fibrous histiocytoma)
Microscopic (histologic) images

Contributed by Jesse Hart, D.O.

Osteoclast-like giant cells

Areas containing woven bone

With cortical permeation

Xanthomatous histiocytes

AFIP images

Low power

Multinucleated giant cell

Advancing metaphyseal margin

Osseous giant cell tumor

 Contributed by
 Mark R. Wick, M.D.

Multinucleated giant cells

Positive stains
Molecular / cytogenetics description
Differential diagnosis
  • Brown tumor of hyperparathyroidism: occurs in setting of hyperparathyroidism, multifocal; microscopically similar appearance to giant cell tumor of small bones or central giant cell granuloma
  • Central giant cell granuloma: looks like aneurysmal bone cyst or giant cell tumor of small bones but is within the jaw (giant cells are not evenly distributed)
  • Chondroblastoma: occurs in epiphysis (like giant cell tumor of bone) but consists of pavement-like sheets of uniform round polygonal cells with well defined cell membranes, nuclei with longitudinal grooves and (often) pericellular "chicken wire-like" calcification; may have scattered giant cells in lesion
  • Giant cell lesion of the small bones: involves the small bones of hands and feet (uncommon site for giant cell tumor of bone); giant cells are not uniformly distributed, instead they cluster around blood (like in aneurysmal bone cyst)
  • Nonossifying fibroma (NOF): usually skeletally immature; microscopically bland spindle cells (fibroblasts) in short fascicles and storiform arrangements; scattered osteoclast-like giant cells (but not the major feature)
  • Primary aneurysmal bone cyst (ABC): radiologically fluid-fluid levels usually present; microscopically giant cells are clustered around blood filled cysts (not evenly distributed); septae contain bland spindle cells (fibroblasts / myofibroblasts) and woven bone; USP6 gene rearrangement in 70% of cases (not in giant cell tumor of bone)
  • Tenosynovial giant cell tumor: soft tissue tumor with giant cells; giant cells may be sparse or abundant; bone involvement should not be present
Board review style question #1
30 year old woman had a 4.5 cm intramedullary mass in the epiphysis of the distal femur. The microscopic image is from the curettage specimen. Which of the following is true about this entity?
  1. Lesion never demonstrates cortical destruction and soft tissue involvement
  2. Neoplastic cells are the osteoclast-like giant cells
  3. Treatment may include targeted therapy against RANKL
  4. Tumor is a high grade malignancy
  5. Tumor never metastasizes
Board review style answer #1
C.Giant cell tumor of bone. Treatment may include targeted therapy against RANKL.

Reference: Giant cell tumor of bone

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Board review style question #2
45 year old woman had a curettage specimen obtained from the left distal femur 2 years earlier as seen in the image below. The patient underwent radiation therapy for that lesion but now has a radiographically aggressive lesion that was biopsied and diagnosed as high grade undifferentiated pleomorphic sarcoma (biopsy not shown). Which of the following is most likely true?
  1. The 2 lesions are unrelated
  2. High grade sarcoma is considered malignant transformation of the original lesion
  3. Initial curettage specimen was misdiagnosed and should have been read as a high grade sarcoma
  4. MDM2 gene is probably amplified
  5. Patient likely has a metabolic disorder
Board review style answer #2
B.Giant cell tumor of bone. High grade sarcoma is considered malignant transformation of the original lesion.

Reference: Giant cell tumor of bone

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