Giant Cell Tumor

Giant Cell Tumor

G. Petur Nielsen, MD

Andrew E. Rosenberg, MD

A giant cell tumor involving the distal femur shows a geographic lytic lesion with extension to the subchondral plate. The margins are well defined and nonsclerotic with cortical thinning medially.

Giant cell tumor of bone arising in the distal femur is predominantly red-brown, involves the metaphysis and distal diaphysis, and extends into the epiphysis to the subchondral plate.



  • Giant cell tumor (GCT)


  • Osteoclastoma


  • Benign but locally aggressive neoplasm composed of cytologically banal, oval or polyhedral mononuclear cells admixed with numerous, evenly distributed, osteoclast-like giant cells



  • Mononuclear cells are neoplastic cells of possible osteoblast phenotype that induce formation of osteoclast-type giant cells by expressing receptor activator of NF-κΒ (RANK) ligand

    • Osteoclast-type giant cells express receptor RANK, which binds to RANK ligand on surfaces of mononuclear cells



  • Incidence

    • Represents approximately 5% of primary bone tumors

      • Represents approximately 20% of benign bone tumors

  • Age

    • Develops in skeletally mature individuals during 3rd-5th decades of life

    • Rarely occurs in children

  • Gender

    • Females are affected slightly more frequently than males


  • Vast majority arise in epiphyseal-metaphyseal region of long tubular bones

  • Tumors in patients with open growth plates are often centered in metaphysis and abut epiphyseal plate

    • Rarely arise in diaphysis

  • In almost 1/2 of cases, GCT develops around knee, with predilection for distal femur, followed by proximal tibia and distal radius

  • Uncommon sites include vertebral bodies, short tubular bones of hands and feet, craniofacial bones, and patella

    • Many giant cell tumors of bone that arise in craniofacial skeleton occur in setting of Paget disease of bone

  • Usually solitary

    • 1% of cases are multifocal, and these often affect bones of hands and feet


  • Pain, swelling, pathologic fracture in minority of cases


  • Surgical approaches

    • Usually treated by thorough curettage

    • En bloc resection for large tumors with little residual structural bone

  • Drugs

    • Preliminary studies with RANK ligand inhibitors such as denosumab seem to be effective and may possibly supplement radiation treatment and surgery in difficult cases

      • Tumor locally recurs if drug therapy is discontinued

  • Radiation

    • Can be used in surgically inaccessible tumors, when surgical treatment would result in significant
      morbidity, or when medical problems preclude surgical intervention


  • Local recurrence rate approximately 25% for patients treated with curettage, usually within 3 years

  • Although GCT of bone is classified as a benign neoplasm, it is well recognized that 1-2% eventually metastasize, primarily to lungs

    • Metastatic deposits frequently cured by resection

    • Metastatic disease can also be treated with RANK ligand inhibitors such as denosumab

    • Metastases occur more frequently in patients with pathologic fracture or following multiple curettages for recurrent disease

  • Uncommon complication is development of sarcoma within a GCT

    • This may occur de novo, develop in a locally recurrent tumor, or happen following radiation therapy


Radiographic Findings

  • Large, lytic, intramedullary and frequently eccentric

  • Usually extends from metaphysis to subchondral bone plate

    • Very large tumors may involve adjacent diaphysis, focally destroy cortex, and invade into neighboring soft tissues

  • May expand bone and elevate periosteum

    • Results in thin periosteal shell of reactive bone, which may be incomplete

  • Medullary margins are well defined, may have “motheaten” appearance, and are usually not sclerotic

  • Cystic degeneration is common secondary finding (aneurysmal bone cyst-like changes)

  • After RANKL inhibitor therapy, tumor shows increased sclerosis/bone formation

MR Findings

  • Low to intermediate signal on T1- and T2-weighted images

  • T1 is better to see intramedullary component of tumor

  • T2 is better to evaluate extraosseous component of large tumors and to identify any cystic changes (fluid-fluid levels)

CT Findings

  • Tumor is lytic with well-defined borders

Bone Scan

  • Increased uptake on technetium scan


General Features

  • Friable, hemorrhagic, red-brown

  • Solid or focally cystic

  • Erodes cortex

  • Well-delineated margins within medullary canal and in neighboring soft tissues

Sections to Be Submitted

  • 10 cassettes for curettage specimens

  • Resection specimens: Bone and soft tissue margins, minimum of 1 section per cm of tumor


  • Typically range from 5-15 cm in dimension


Histologic Features

  • Mononuclear stromal cells are diagnostic and neoplastic component of tumor

  • Numerous multinucleated osteoclast-like giant cells are scattered evenly throughout tumor

    • Number of nuclei in any individual cell variable but may be as many as 50 or more

  • Mononuclear cells appear to grow in a syncytium, have ill-defined cell borders, and little eosinophilic cytoplasm

  • Tumor cell nuclei are round or ovoid, vesicular, have central nucleoli, and are morphologically identical to nuclei of giant cells

  • Mononuclear cells may be mitotically active and can show variable degrees of cytologic atypia

    • Atypia may be prominent in areas admixed with previous hemorrhage and fibrin deposition

  • Foci of necrosis and vascular invasion may be present

  • Tumor can demonstrate benign fibrous histiocytomalike areas that are devoid of classic mononuclear and osteoclast-type giant cells

  • Other secondary changes commonly encountered in GCT include hemosiderin deposits, aggregates of foamy macrophages, cystic changes, and reactive bone formation

  • Following RANKL inhibitor therapy, giant cells disappear, mononuclear tumor cells decrease, and bone formation increases

  • Soft tissue recurrence is frequently surrounded by shell of reactive bone

Ultrastructural Features

  • Abundant dilated rough endoplasmic reticulum, well-developed Golgi apparatus, mitochondria, and occasional lipid droplets

    • None of these features are specific for GCT of bone



  • Giant cells have immunoprofile similar to macrophages

  • Osteoclast-type giant cells stain for RANK

  • Many of stromal mononuclear tumor cells stain for RANKL, indicating that they may have osteoblastic phenotype

  • Mononuclear tumor cells show nuclear staining for p63


Nonossifying Fibroma/Benign Fibrous Histiocytoma

  • Most GCTs have areas that resemble benign fibrous histiocytoma or nonossifying fibroma

    • Areas are composed of banal spindle cells arranged in storiform pattern with scattered osteoclast-like giant cells

  • Spindle cell component is frequently located at periphery of tumor and is not diagnostic of GCT

  • True nonossifying fibroma/benign fibrous histiocytoma does not have characteristic giant cell tumor-like areas


  • Seen in skeletally immature individuals with an open growth plate and is centered in epiphysis

  • Mononuclear cells do not resemble nuclei of osteoclast-type giant cells as seen in GCT of bone

  • “Chicken wire” calcifications and chondroid areas frequently seen in chondroblastoma and are not present in GCT of bone

  • Mononuclear cells in chondroblastoma stain for S100 but are usually negative for p63

Giant Cell Reparative Granuloma/Brown Tumor

  • Contains clusters of osteoclast-type giant cells around area of hemorrhage

    • In contrast, in GCT of bone, giant cells are usually evenly distributed

  • Proliferating cells are spindle-shaped and do not resemble nuclei of osteoclast-type giant cells

Aneurysmal Bone Cyst

  • Difficult to distinguish between primary aneurysmal bone cyst and cystic GCT of bone

  • In cystic GCT of bone, characteristic morphologic areas must be present

  • FISH for t(16;17) present in primary aneurysmal bone cyst may be helpful

Giant Cell-Rich Osteosarcoma

  • Tumor grows with an infiltrative pattern

  • Contains cytologically malignant mononuclear cells


Clinically Relevant Pathologic Features

  • Lytic lesion in distal long bone extending to subchondral area in an adult is characteristic

Pathologic Interpretation Pearls

  • Proliferation of mononuclear cells and evenly distributed osteoclast-type giant cells

    • Nuclei of mononuclear cells identical to those of osteoclast-type giant cells

  • If a needle biopsy looks like fibrous histiocytoma, think possible GCT


1. Klenke FM et al: Giant cell tumor of bone: risk factors for recurrence. Clin Orthop Relat Res. 469(2):591-9, 2011

2. Thomas D et al: Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 11(3):275-80, 2010

3. Lee CH et al: Gene expression profiling identifies p63 as a diagnostic marker for giant cell tumor of the bone. Mod Pathol. 21(5):531-9, 2008

4. Rock MG et al: Secondary malignant giant-cell tumor of bone. Clinicopathological assessment of nineteen patients. J Bone Joint Surg Am. 68(7):1073-9, 1986

5. Rock MG et al: Metastases from histologically benign giantcell tumor of bone. J Bone Joint Surg Am. 66(2):269-74, 1984

Image Gallery

Imaging Features

(Left) A giant cell tumor of bone involving the distal femur image demonstrates a lytic, subarticular, and geographic lesion. There is neither reactive sclerosis nor internal matrix. The medial condyle is slightly expanded with the cortex being blurred image. (Right) Coronal T2-weighted MR image shows a giant cell tumor involving the distal femur. The tumor is welldefined and heterogeneous with a dark rim, extending to the subchondral plate. The adjacent marrow is normal.

(Left) A lytic giant cell tumor in the distal lateral femur with irregular, geographic, and sclerotic margins image is seen. The lateral cortex is penetrated, and there is a pathologic fracture image with surrounding periosteal new bone formation. (Right) Coronal CT scan shows a giant cell tumor of the distal femur that is lytic, uniformly hypodense, and subarticular image with sclerotic margins. There is a fracture through the lateral cortex and condyle image with intraarticular extension.

(Left) Radiograph of a giant cell tumor of bone arising in the distal femur shows a vague geographic lytic lesion. The proximal margin has a “moth-eaten” appearance and ill defined image. The distal medial margin has a sclerotic rim image. There is endosteal thinning of the distal lateral cortex. (Right) T1-weighted coronal MR image of a giant cell tumor of bone clearly shows the extent of the lesion. The tumor is heterogeneous in signal intensity with a thin, dark rim. The adjacent marrow is normal.

Clinical and Imaging Features

(Left) Radiograph of a giant cell tumor of the distal femur shows a lytic lesion with thinning and penetration of the anterior cortex image. The distal margin has a thin, sclerotic rim image, and the proximal margin is ill defined image. (Right) Sagittal T2-weighted MR image of a giant cell tumor of the distal femur shows a well-defined heterogeneous lesion with cortical penetration anteriorly and a small soft tissue component image. Note the focal cortical thinning posteriorly image.

(Left) Radiograph shows a giant cell tumor of bone involving the proximal subarticular lateral tibia. The lateral cortex appears destroyed, but the medial margin is better defined image. (Right) Coronal T1-weighted MR image of a giant cell tumor of bone shows expansion of the lateral portion of the tibia; the tumor is confined by a thin shell of periosteal new bone image. The medial margin shows the dark rim characteristic of giant cell tumor image.

(Left) This patient has a giant cell tumor of the proximal tibia that presented as a painful mass. The tumor is multinodular and bulges the overlying skin in multiple areas. In areas, the attenuated skin is erythematous. (Right) Radiograph of a giant cell tumor of the proximal subarticular tibia shows a “blow-out” lesion with expanded medial and lateral cortices and a geographic distal margin image. The lytic tumor extends up to the base of the subchondral bone plate image.

Imaging and Gross Features

(Left) Specimen radiograph of a giant cell tumor of bone involving the proximal tibia shows a multiloculated, subarticular lesion with focal areas of cortical expansion image, internal septation image, and a well-demarcated distal margin image. (Right) Gross photograph of a giant cell tumor of bone arising in the proximal tibia shows that the tan-yellow tumor extends to the articular cartilage and has broken through the cortex laterally with a thin layer of periosteal new bone image.

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Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Giant Cell Tumor

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