Giant Cell Tumor of Bone

Key Points:


A benign, but locally aggressive tumor with the potential to metastasize to the lungs.  Giant cell tumors of bone (GCTB) appear as a lytic lesion that originates in the metaphysis and most often extends into the epiphysis.  Histologically, GCTB is characterized by large numbers of multi-nucleated giant cells with even distribution throughout a stroma of mononuclear histiocytic cells. The nuclei of both the giant cells and the mononuclear cells will be morphologically identical. GCTB may develop secondary aneurysmal bone cyst formation. It is common to have several mitotic figures as well as necrosis present in benign lesions. The diagnosis of malignant transformation is made only when there is overt cellular atypia as well as atypical mitotic figures throughout. 
Most common locations in order of decreasing incidence: distal femur > proximal tibia > distal radius > proximal femur > proximal humerus > distal tibia.


Clinical Findings:

Patients often present with insidious and progressive pain at the site of the lesion. Range of motion of the adjacent joint may be decreased and a palpable mass may be present. Occasionally, patients present with a pathologic fracture and an inability to bear weight.

Imaging Studies:

Plain radiographs demonstrate a metaphyseal-epiphyseal, lytic lesion with a thin sclerotic border that may extend to the articular surface. These lesions can have an aggressive appearance with a wide zone of transition, cortical erosion and breakthrough with a soft tissue mass, as well as periosteal reaction. There is usually no visible matrix within the lesion. The presence of an intra-lesional matrix may suggest a cartilage or bone-forming tumor. The diagnosis can often be made based on plain films and the clinical picture. 
The differential diagnosis for a lytic lesion in a young patient includes: chondroblastoma, degenerative subchondral cyst, aneurysmal bone cyst, non-ossifying fibroma, giant cell-rich osteosarcoma, or telangiectatic osteosarcoma. 
MRI with and without contrast is the preferred modality of additional imaging. MRI often demonstrates a heterogenous mass due to hemosiderin deposition throughout the tumor. The lesion will primarily have low T1 signal, increased T2 signal and post-contrast uptake consistent with a solid mass. 
A CT scan may demonstrate intra-lesional matrix and cortical breakthrough which may suggest a more malignant lesion or cartilage/bone forming tumor. CT is not as helpful for diagnosis.
Chest radiographs or a CT scan of the chest should be obtained to rule out metastatic disease to the lungs. 


The treatment for GCTB is primarily surgical. Simple curettage has shown to have unacceptable recurrence rates > 50%. At this time, standard treatment includes open extended curettage with an additional form of local adjuvant therapy. These lesions are commonly filled with polymethyl methacrylate (PMMA). “Extended Curettage” consists of the use of a high speed burr plus use of an adjuvant such as phenol, EtOH, liquid nitrogen, or argon laser. The use of the exothermic reaction of PMMA as an adjuvant is debated. It is important to be aware that liquid nitrogen carries an increased risk of fracture after use. 
With use of local adjuvants after extended curettage, recurrence rates range from 5-20%.  Recurrence can be treated with repeat curettage and adjuvant therapy.
Ultimately, if lesions grow too large or recurrences occur that are not amenable to repeat extended curettage, treatment requires resection with reconstruction. Malignant lesions are treated similarly to other malignant lesions like osteosarcoma with wide excision and reconstruction. 
Medical treatment is based on the underlying pathogenesis associated with the predominance of osteoclast-like giant cell. While bisphosphonate therapy was previously utilized, monoclonal antibodies against RANKL are now preferred.  Denosumab has been shown to improve symptoms and decrease tumor bulk. At this time, the use of Denosumab is reserved for recurrences or lesions in anatomic locations that are not amenable to surgery (spine and sacrum). Current studies are looking at the neoadjuvant use of Denosumab prior to curettage and cementation. There are reports of malignant transformation in patients treated with denosumab. There is also a risk of inducing osteonecrosis of the jaw. Chemotherapy does not play a role in the treatment of GCTB unless the tumor undergoes malignant transformation. 
Radiation is generally not recommended. The use of radiation has been shown to increase the risk of malignant transformation. Radiation is reserved for tumors in locations that are not amenable to surgical resection such as those in the spine or sacrum.


Lung metastases occur in approximately 4% of patients with GCTB. Lung metastases demonstrate variable behavior ranging from sessile to aggressive growth. The metastases are histologically identical to the primary lesion. Lung metastases are treated with surgical resection or medical therapy for multiple and/or unresectable lesions.  Chest imaging (either CT or radiographs) at diagnosis and at regular intervals (radiographs) after diagnosis is recommended. [MOU1]The National Comprehensive Cancer Network guidelines recommend chest imaging every 6 months for the first two years and then annually for a total of 5 years. 
Recurrent GCTB, if amenable to surgery, should undergo repeat extended curettage with added medical therapy. Consideration should also be given to excision with reconstruction depending on size and amount of destruction.
Pathologic fracture
Pathologic fractures can be treated with extended curettage performed at time of fracture fixation.

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1. Bocklage, Therese. Bone and Soft Tissue Tumor: A multidisciplinary Review with Case Presentations. “Osteoclastic giant cell rich tumors of bone,” pgs. 496-507. London, UK. JP Medical Ltd., 2014. Print
2. Cheong, David and Letson, Douglas. “Giant Cell Tumor of Bone,” Orthopaedic Knowledge Update: Musculoskeletal Tumors Ed. 3. Rosemont, IL: American Academy of Orthopaedic Surgeons, 2014. Print.

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Andrew Haus MD