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Continuing Education Activity

A giant cell tumor of bone (GCTB) is an aggressive osteolytic neoplasm that primarily affects skeletally mature young adults. This tumor can have severe morbidity and mortality if it is not identified and treated in a timely manner. This activity highlights the role of the interprofessional team in evaluating and managing patients with this condition.


  • Describe the etiology of a giant cell tumor of bone.
  • Review the appropriate history, physical, and evaluation of a giant cell tumor of bone.
  • Outline the treatment and management options available for a giant cell tumor of bone.
  • Review the importance of the interprofessional team to improve outcomes for patients affected by giant cell tumor of bone.


The giant cell tumor of bone (GCTB), also known as an osteoclastoma or a myeloid sarcoma, is a benign local aggressive osteolytic neoplasm that primarily affects skeletally mature young adults.[1] These usually arise in the metaphysis and extend into the epiphysis of long bones. While most GCTB are benign, they rarely metastasize to the lungs. Clinically their behavior can be unpredictable. A histopathological exam is needed to confirm the diagnosis. Imaging of the primary site with plain films and CT is the recommended diagnostic approach. A chest CT or chest X-ray is also recommended to evaluate for metastases to the lungs.[2] Treatment is usually curettage or wide resection, with typically a good prognosis. Rarely GCTB can under malignant transformation. These may be primary or secondary. Primary typically occurs adjacent to the benign GCTB while the secondary occurs at the site of treatment (usually radiation therapy). Malignant GCTB has a poor prognosis.


The exact etiology of this tumor is not fully understood. But the mononuclear cells are thought to be derived from primitive mesenchymal cells. These cells express RANKL and have features of osteoblastic progenitors.[3]


A giant cell tumor of bone is a relatively rare neoplasm, accounting for approximately 3 to 5% of all primary bone tumors. It generally affects young adults, with peak incidences in the 20s and 30s, mildly more prominent in females. Risk factors are not fully understood, but there are increased incidents in patients with Paget disease, typically developing in the pelvic or skull bones.[4] These patients will have abnormal laboratory values that manifest as elevated alkaline phosphate levels. Without Paget’s disease, GCTB usually occur as a single lesion that most commonly affects the distal femur and proximal tibia (50 to 65%), followed by the distal radius, sacrum, and vertebral body. While solitary GCTB accounts for the majority of cases, research has also described multicentric GCTBs (less than 1 percent). These tend to be younger patients before epiphyseal closure. If a multicentric GCTB is suspected, a radionuclide bone scan merits considered for further evaluation.


The pathophysiology is not entirely understood but is thought to be caused by the RANK/RANKL signaling pathway overexpression by osteoblast-like mononuclear stromal cells. This overexpression results in the transformation of monocytic pre-osteoclast cells to osteoclast cells. These osteoclasts start absorbing the bone resulting in osteolysis seen with these tumors.[5]


A giant cell tumor of bone is composed of elongated, oval, or polygonal mononuclear cells with a typical uniform distribution. They are often a low-grade tumor even when they appear aggressive on imaging. When there is a lung metastasis, the histology is the same as the primary tumor, and they have an excellent prognosis.

Interestingly, the development of metastasis and locally aggressive behavior is not well predicted by histological grading. Unless it is associated with malignant transformation, there are no malignant cytologic features. Differential diagnosis tends to be broad as it is challenging to interpret histologically. 

H3F3A is found up to 96% of long bone cases and thus can be used to differentiate GCTB from other entities.[6] Taking advantage of this, a monoclonal antibody directed towards the G34W mutated site of H3F3A is the agent for immunohistochemical staining. When the GCTB arises from the long bone, it is positive 95 to 100%.[7] 

Diagnosis: When establishing a diagnosis of GCTB, even with a high degree of suspicion, a biopsy is required to confirm the diagnosis; this is true for any other bone tumor, as suspicious lesions require a thorough evaluation for malignancy. Imaged guided biopsy with ultrasound or CT is the most agreed upon method.

History and Physical

GCTB commonly presents with swelling, limited range of motion, and pain because of the tumor’s proximity to the joint space. Patients often describe the pain as a persistent, deep pain that is not related to an injury. These symptoms commonly arise in the knee since the epiphysis of the distal femur or proximal tibia is the site of the tumor in over 50% of cases. GCTB less commonly affects craniofacial bones, vertebral body, sacrum, and the small hand and feet bones. Interestingly, some patients have no symptoms, often being found incidentally or as a result of a pathological fracture. These fractures occur in approximately 12% of patients diagnosed with GCTB. Rarely GCTB can present with metastatic disease, usually to the lungs.[8]


Several imaging modalities are available for helping establish the diagnosis of a giant cell tumor of bone. They include:

  • Plain radiographs
  • Computed tomography (CT)
  • Magnetic resonance imaging (MRI)
  • Nuclear medicine

On imaging, GCTB tends to have four radiographic findings when located on a long bone. They are usually eccentric, have well defined nonsclerotic margins, and occur at closed growth plates and near the articular surface. Because of the tumor's tendency to metastasize to the lung, the National Comprehensive Cancer Network (NCCN) recommends chest CT.

 X-ray and Computed tomography scan (CT):

On plain radiography and CT, a GCTB appears as a lytic lesion with well-defined, nonsclerotic margins. It is usually eccentric and occurs at the metaphysis. 

Magnetic resonance imaging (MRI):

On MRI, GCTB have low to intermediate signal intensity on T1-weighted images, heterogenous high signal intensity on T2, and demonstrates enhancement.[9]

Nuclear medicine:

Studies using Technetium 99m scintigraphy demonstrates increased radiotracer on delayed images, most prominent in the periphery, while central regions are photopenic.

Treatment / Management

The treatment of choice for patients with a giant cell tumor of bone involving the appendicular skeleton is surgery. The type of surgery depends on the size and area of the tumor and whether there has been a pathological fracture. The surgical options include intralesional curettage (with or without bone cement), en bloc resection, or marginal excision.[10][11] At times more extensive surgery is required. These primarily being when the articular surface is grossly damaged, second recurrence, extraosseous extension, or dislocated pathological fracture. Radiation therapy and denosumab are an effective treatment option for patients who are poor surgical candidates, or the morbidity from the surgery is too high.[12][13]

The goal of treatment is to minimize the morbidity and to maximize the functionality of the affected bone; this was traditionally done by intralesional curettage with the packing of the cavity with corticocancellous bone. Newer methods such as cementation using bone cement (PMMA) is encouraging as it helps with reconstruction and reduces local recurrence. The thinking is that by creating an exothermic reaction resulting in local hyperthermia, inducing necrosis of the remaining GCTB tissue.

Recurrence rates are as high as 50%. Local adjuvants such as aqueous zinc chloride, PMMA, phenol, argon beam coagulation, or cryotherapy have been utilized to reduce these rates.[14][15] Retrospective studies have provided evidence showing reduced recurrence rates (PMMA, the preferred adjuvant). However, this has not had validation through a randomized control trial.[11][16] The most established treatment with satisfactory recurrence is with PMMA and phenol, with much debate about whether combining them is beneficial. If there is a local recurrence, it is treatable with additional curettage and local adjuvant therapy with only a small increased risk in morbidity. The main disadvantage of using PMMA centers upon the long-term effects of cement being adjacent to the articular cartilage and subchondral bone, which was previously shown to lead to degenerative arthritis. It may also cause a radiolucent line to develop at the bone - cement interface that can progress to become an area of osteolysis, while complications from phenol are primarily from chemical burns. If there is a great concern for these complications, the other local adjuvants previously described are options. 

Sacral tumors tend to be more difficult because of their location. The surgery usually has high morbidity primarily because of the proximity of the sacral nerves. Treatment requires a balance of surgery, radiation therapy, and denosumab, and there is also limited evidence of the effective use of arterial embolization.

Spinal tumors also tend to be very difficult to treat, as the goal is complete resection. The best treatment model has not yet been established. Treatment currently is patient-specific, trying to maximize the effectiveness of the surgery without having unacceptable morbidity.[17] Denosumab has been found to be an effective alternative for patients with tumors in high-risk locations that are unresectable. However, there is a lack of consensus about the appropriate indications.[12]

Pulmonary metastases generally are not as aggressive as other solid tumors. However, with reports of fatal cases, surgical resection is the primary treatment. Other options include denosumab therapy, monitoring with chest computed tomography (CT), or whole-lung radiation therapy.

Denosumab – is a monoclonal antibody that works by binding to RANKL, stopping it from activating its receptor, RANK. This action results in inhibiting the function and recruitment of osteoclast-like cells. Denosumab is primarily for patients in the following clinical situations: (1) when expecting significant morbidity from initial surgery, (2) locally recurrence, (3) poor surgical candidate, or (4) high-risk locations. Early reports from a phase II study suggest a recurrence rate of 15% for patients with significant expected morbidity from the initial surgery.

Differential Diagnosis

Differential diagnosis[18]:

  • Brown tumors associated with hyperparathyroidism 
  • Fibrous metaphyseal defects
  • Giant-cell-rich osteosarcoma
  • Metastatic cancer
  • Chondroblastoma
  • Chondromyxoid fibroma 
  • Nonossifying fibroma 
  • Aneurysmal bone cysts  
  • Endocondroma
  • Chondrosarcoma
  • Desmoplastic fibroma


Multiple classification systems for giant cell tumor of bone have been proposed to help with staging. The Campanacci grading system is most common, which stratifies patients based on clinical and radiological appearances:

  • Grade I - Intraosseous lesion with a well-circumscribed border and a boney border that is intact.
  • Grade II - Intraosseous lesion that is more expansile with a thinned cortex but no loss of cortical continuity.
  • Grade III - Extraosseous radiolucent lesion with cortical breakthrough and soft tissue extension.

Unfortunately, this classification system has limited utility as it does not predict local recurrence or metastatic behavior well. Alternatives have been proposed, but none are universally accepted.


The overall prognosis of a giant cell tumor of bone is good, though local recurrence can vary widely. This determination is primarily from the extent of the resection (wide local excision with the lowest rate but higher morbidity) and whether there was the use of an adjuvant in addition to the surgery. A GCTB located near the spinal cord carries a poorer prognosis and has a high rate of local recurrence.[19] Studies have found the recurrence rate as high as 50% for intralesional curettage without a local adjuvant, three-fourths within two years.[14][20] In an effort to reduce recurrence rates, local adjuvants have been used in combination with surgery. Retrospective studies have demonstrated reduced recurrence rates ranging from 13 to 22%; however, there are no randomized trials demonstrating this.[11] There is also interest in using denosumab as an adjuvant following surgery, but further research is still needed.[12] Rarely GCTB can under a malignant transformation, which often has a poorer prognosis. The appropriate frequency of posttreatment surveillance can vary. However, typically, the primary site is imaged with a CT after three months posttreatment, then twice a year for the next two years, and then once a year for a total of five years. The frequency and duration should be tailored based on clinical judgment.


Besides the pathological fractures that can develop as a result of cortex thinning of bone, giant cell tumor of bone has many other complications:

  • Surgery can have significant morbidities resulting in functional compromise. 
  • Denosumab can lead to osteonecrosis of the jaw.[21]
  • Radiation increases the risk of malignant transformation.

Deterrence and Patient Education

Giant cell tumor of bone, also called an osteoclastoma or a myeloid sarcoma, is a relatively uncommon neoplasm characterized by multinucleated giant cells. It primarily affects young adults, age 20 to 30.[1] They usually arise in the long bones of the arms and legs, but can more rarely occur in the sacrum and vertebral body. While generally thought of as benign, it can rarely metastasize to the lungs.[2] Overall, they are clinically unpredictable but usually present with swelling, limited range of motion, and pain. A histopathological exam is needed to confirm the diagnosis. Treatment is usually a curettage or wide resection.[11] The prognosis is overall good, though recurrence can be as high as 50%. However, with the use of adjuvant therapy, studies have shown a reduction in reoccurrences, ranging from 13 to 22%.[14]

Enhancing Healthcare Team Outcomes

The management of patients with giant cell tumor of bone is best when utilizing an interprofessional team that includes primary care doctors, radiologists, pathologists, surgery oncologists, and orthopedists. Oncology trained nurses, pharmacists, and physical therapists should also assist in the case. The patient will often present to his or her primary care doctor for pain or swelling, which should prompt imaging that may identify the lesion. If suspicious for a malignant lesion, a biopsy is required to confirm the diagnosis. After treatment, patients require long term follow-up to evaluate for recurrence. Depending on the location of the lesion, the patient's treatment may vary. If denosumab therapy is necessary, the oncology board-certified pharmacist should consult on the dosing and duration of treatment. If there is excision of bone, rehabilitation is required to regain muscle and joint function. The pharmacist and a pain specialist may manage the pain. Irrespective of the direction of treatment, the oncology specialty nurse will play a significant role, from patient workup, coordinating referrals, assisting in procedures, and counseling patients, while also monitoring progress and reporting to the treating clinician any concerns that arise. Physical therapy may be required to help with ambulation. Open communication between the interprofessional team members is vital to improving outcomes. [Level 5]

This research was supported (in whole or part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author and do not necessarily represent the official view of HCA healthcare or any of its affiliated entities. 

(Click Image to Enlarge)
Osteoclastoma (GCTB)
Osteoclastoma (GCTB)
Image courtesy S Bhimji MD

(Click Image to Enlarge)
Histopathology of GCTB
Histopathology of GCTB
Image courtesy: https://commons.wikimedia.org/wiki/File:Giant_cell_tumour_of_bone_-_high_mag.jpg
Article Details

Article Author

James Kuhn

Article Editor:

Amit Sapra


6/12/2022 9:58:46 AM

PubMed Link:




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