This information has been written for patients, their families and friends and the general public to help them understand more about a rare benign tumour type, known as a giant cell tumour of the bone. This section will detail what a giant cell tumour of the bone is and how this tumour can be diagnosed and treated.
For a downloadable source of this information, please view our 'Downloadable Information Materials' page to view all of our fact sheets.
Giant cell tumours of the bone make up approximately 4-5% of all tumours which start in the bone and occur in an estimated 1 person in every 1,000,000 people per year. This rare, benign (non-cancerous) tumour generally affects those aged 20 to 45 years of age and is most effectively treated by the surgical removal of the tumour.
Giant cell tumours of the bone tend to be benign (non-cancerous), but they can be locally aggressive.
Giant cell tumours of the bone are named due to the way they look under a microscope. Many ‘giant cells’ can be seen, which are cells that have formed due to the joining together (fusion) of several individual cells into one single, larger, cell. This production of giant cells can be seen in other conditions and cancers of the bone, as well as in normal bone. Therefore, confirming the diagnosis of a giant cell tumour of the bone is done after ruling out other giant-cell rich diseases - such as giant-cell rich osteosarcoma(2,3).
This tumour type typically occurs in the long bones of the body, including the thigh bone (the femur), the shin bone (the tibia) and the lower arm bone (the radius). Giant cell tumours of the bone tend to be at the end point of these long bones and are often found next to the joints. The most common location of a giant cell tumour of the bone is around the knee joint — where over 50% of giant cell tumours arise(4). Giant cell tumours of the bone can also start in the pelvis, the spine, the ribs, the skull and the sacrum — which is the base of the spine where it connects to the pelvis(2).
Giant cell tumours of the bone make up 4-5% of all primary tumours which start in the bone. However, for unknown reasons, this tumour occurs 2 to 3 times more often in Southern India and China — where giant cell tumours of the bone make up a much larger 20% of all primary bone tumour cases(1,3).
Some reports show a higher number of giant cell tumour of the bone cases in female patients than male patients(5,6).
80% of all giant cell tumours of the bone occur in patients aged between 20 and 45 years of age — affecting patients who have reached the full development of the skeleton (known as reaching skeletal maturity).
Although this tumour can also affect children and the elderly, this is rare(2,5,6).
Giant cell tumours of the bone grow slowly, and so the symptoms and clinical presentation of this tumour may not start until some time has passed. In some cases, the patient may not experience any symptoms at all — which doctors describe as ‘asymptomatic’(7).
The most commonly reported symptoms of a giant cell tumour of the bone are:
- Bone pain — pain tends to increase when active and improve when the area is rested
- A lump — with or without pain
- Decreased mobility in the joint near to the tumour
- Build-up of fluid in a joint near to the tumour
- Fractures may occur due to the tumour weakening the bone –this is known as a pathological fracture
The location and size of the tumour can affect the symptoms that an individual patient may have. Tumours which develop on the spine, particularly in the sacrum, can lead to symptoms including:
- Back pain
- Neurological effects — such as weakness or numbness in the arms and legs and a sensation of pins and needles(7).
There is no identified cause or known origin of giant cell tumour of the bone. It is thought that these tumours arise spontaneously, without any apparent external cause, risk factor or predisposing factor(7).
The unknown cause of giant cell tumours of the bone has generated a lot of interest in researching this tumour type. This research has led to the hypothesis that a giant cell tumour of the bone can arise as a complication of a bone disorder known as Paget’s disease of the bone(2,6,8). Paget’s disease causes an alteration in the remodelling of the bone, creating weakened and disorderly bone tissue(8). On rare occasions, a giant cell tumour of the bone has been seen to arise secondary to Paget’s disease, and so this area continues to be investigated(6,8). For more information on Paget’s disease of the bone, please visit ‘The Paget’s Association’ at www.paget.org.uk.
A molecule known as RANK-L (or Receptor Activator of Nuclear factor κB ligand) has been investigated as a possible factor which influences the development of giant cell tumours of the bone. RANK-L is expressed in high levels on the giant cells which make up these tumours and many studies suggest this molecule to be responsible for the progression of giant cell tumours of the bone and the breakdown of the bone(3,7,8).
For this reason, a targeted treatment known as Denosumab has been developed to block the function of RANK-L and create a new treatment for giant cell tumours of the bone(7,8).
Patients with different types of tumours arising in the bone are assessed in similar ways. For this reason, diagnostic tests are covered in more detail in our About Primary Bone Cancer information section.
This section aims to provide information on the specific details of diagnosing a giant cell tumour of the bone and to discuss other conditions that may appear diagnostically similar to giant cell tumours of the bone.
The first step in diagnosing any primary bone tumour is usually a trip to the GP. From this, a clinical examination and an X-ray will take place. Diagnosis of a suspected bone tumour usually follows a clinical examination and an X-ray. It is very common to be referred to a bone cancer specialist for a second opinion and confirmation of the diagnosis.
Further tests to confirm the presence of a giant cell tumour of the bone include: CT scans, MRI scans, a biopsy of the bone and blood tests.
More information on X-rays, CT Scans, MRI scans, bone biopsies and blood tests can be found here.
The symptoms of a giant cell tumour of the bone are non-specific and can often appear similar to other conditions, including growing pains, and therefore can be overlooked in the first instance. X-rays, CT (computerised tomography) scans and MRI (magnetic resonance imaging) scans cannot definitively diagnose a giant cell tumour of the bone and cannot predict the progression of the tumour in terms of possible spread to elsewhere in the body, or its risk of returning at a later date(2,4).
For this reason, the most appropriate way of confirming the diagnosis of a giant cell tumour is by taking a biopsy of the bone. A bone biopsy is a specialist procedure that takes a small sample of the tumour so it can be examined by a pathologist under a microscope. The pathologist assesses the cells in the area to determine if they have any abnormalities in their appearance that may suggest the presence of a tumour.
Results from a biopsy can take up to two weeks to analyse and they allow doctors to confirm the presence of a giant cell tumour of the bone.
To learn more about biopsies of the bone please see our About Primary Bone Cancer information section.
However, even with a biopsy, the accurate diagnosis of a giant cell tumour of the bone can still be difficult. Giant cells can be found in many other tumours, or may even be found where there is no tumour at all. Therefore, all other possible diagnoses must be ruled out before a giant cell tumour of the bone diagnosis can be made(3,6,7).
Furthermore, giant cell tumours of the bone often present alongside a substance known as osteoid — which is a component of the bone aiding bone production and development. The presence of osteoid is an important indicator of a common form of primary bone cancer, known as osteosarcoma. Consequently, if osteoid is detected, careful consideration of the tumour type presenting must be made in order to make an accurate diagnosis and provide the individual patient with the best possible treatment plan(7).
AN ALTERNATIVE DIAGNOSIS?
When diagnosing a giant cell tumour of the bone it is important to rule out the presence of various other diseases, or conditions, which may appear in a similar manner to this tumour type in terms of signs and symptoms. It is important the correct diagnosis is made to ensure the treatment provided is suitable.
It can sometimes take a long time to confirm a diagnosis after a biopsy, this is because these tumours are rare and sometimes difficult to identify. Diseases with similar symptoms or signs are known as ‘differential diagnoses’.
Other conditions which can present in the same way as a giant cell tumour of the bone include:
- Giant-Cell Rich Osteosarcoma
This is a type of osteosarcoma (a more common form of primary bone cancer) which can appear similar to a giant cell tumour of the bone as both tumours have a large number of giant-cells and osteoid — a substance making up the bone(4,7). Benign giant cell tumours have the ability to change into an osteosarcoma and so care must be taken when differentiating between the two(6)
- Aneurysmal Bone Cysts
An aneurysmal bone cyst is a non-cancerous, blood-filled cyst which can develop in any bone in the body. These cysts grow in the bone, causing pain and possible fracturing of the bone - which are also seen in giant cell tumours of the bone(6)
- Brown Tumours
These non-cancerous tumours are rare and caused by the presence of an abnormally high level of the parathyroid hormone – known as hyperparathyroidism(7). On X-rays and under the microscope, they appear similarly to giant cell tumours of the bone and are differentiated by the high-levels of parathyroid hormone in brown tumours(7,9).
If a diagnosis of a giant cell tumour of the bone is confirmed, you will need treatment in a bone tumour centre.
For more information on the locations of Bone Cancer Centres please click here.
Although giant cell tumours of the bone are non-cancerous, they have the ability to return at a later date (known as tumour recurrence) as a malignant (cancerous) tumour. The transformation of a giant cell tumour tends to occur if the tumour returns after a patient has received surgery or radiotherapy treatment(10).
Malignant tumours such as an osteosarcoma, fibrosarcoma or malignant fibrous histiocytoma have been known to develop from a giant cell tumour of the bone that has been treated with radiotherapy. The transformation of a benign giant cell tumour to a cancerous giant cell tumour can occur up to 20 years after the initial treatment and emphasises the importance of ensuring the surgical treatment of the tumour is adequate and there is little risk of the tumour returning at a later date (2,10).
As giant cell tumours of the bone often appear near the joints, the main aim of treatment is to remove the tumour, to make sure that it does not return at a later date, while maintaining as much cosmetic and functional normality in the area as possible(1). Giant cell tumours of the bone have a very positive survival outlook of 90%(5,7).
The most common method of treatment for a giant cell tumour of the bone is the surgical removal of the tumour. It is important that this surgery removes the entire tumour to ensure no tumour cells are left behind. The methods of surgery used are curettage or a wide surgical excision of the tumour.
Curettage surgery involves the removal of the tumour by scraping the tumour cells from the area. This is usually followed by ‘bone cementation’ – which aims to destroy any remaining tumour cells and fill the area following tumour removal to strengthen the affected bone. Bone cementation is usually carried out using a substance known as ‘polymethyl methacrylate’ (or PMMA). Other substances may also be used after curettage surgery, including phenol or liquid nitrogen, although it is not known if these reduce the risk of the tumour returning at the later date (known as recurrence)(4,11).
Ultimately, the risk of the giant cell tumour returning is down to the adequacy of the surgical procedure. A more invasive surgical procedure may be carried out if the tumour appears to be more aggressive. This procedure involves the removal of the tumour alongside a small amount of healthy tissue to ensure the whole tumour is removed — this is known as taking a ‘wide surgical margin’(5,11). This procedure lowers the risk of tumour recurrence but has a larger impact of the cosmetic and functional normality of the bone. Therefore, this method is reserved for more aggressive giant cell tumours or giant cell tumours of the bone which continue to return(4).
There are currently no reports that suggest there is benefit to using chemotherapy to treat giant cell tumours of the bone. However, drugs known as ‘bisphosphanates’ are occasionally used with the aim to reduce the risk of tumour recurrence(7).
There is ongoing research into the development of targeted drug therapies, which target a specific molecule that may be overexpressed or mutated in this cancer type and not in healthy cells.
A targeted drug known as Denosumab is commonly used to treat giant cell tumours of the bone, with the aim of destroying the giant cells which make up the tumour. Denosumab directly targets the molecule RANK-L, which is thought to influence the development of a giant cell tumour of the bone(2,3). Inhibiting RANK-L with Denosumab appears to stop the giant cells from destroying the bone, allowing the bone to heal so surgery can be performed with less impact to the cosmetic appearance and functionality of the affected bone.
Denosumab is often used before surgery to improve the surgical removal of the tumour. When a patient is being treated using Denosumab they will undergo regular X-rays to monitor how this drug is affecting the tumour and when the best time to operate would be.
Radiotherapy may be used after surgery to improve the control of the tumour. It may also be used to treat tumours that cannot be operated on due to their location - such as tumours on the spine(7).
However, radiotherapy must be used with caution in this tumour type as radiation can increase the risk of a benign, less aggressive, form of a giant cell tumour transforming to a malignant (cancerous) tumour at a later point in the patients life. This is known as a radiation induced sarcoma. Malignant tumours such as osteosarcoma, fibrosarcoma or malignant fibrous histiocytoma (MFH) have been known to develop from a giant cell tumour of the bone that has been treated with radiotherapy.
For more information regarding treatment procedures, including surgery, chemotherapy and radiotherapy, please visit our About Primary Bone Cancer information page.
The outcome for patients with a giant cell tumour of the bone is very positive if the tumour is controlled and is not at risk of returning at a later date following treatment. This tumour is unlikely to spread to other areas of the body but on rare occasions (less than 6%) it may spread to the lungs or pelvis. However, this is still treatable and does not worsen the patients outlook dramatically(2,5).
Ultimately, it is important that a correct diagnosis is made and the use of surgery or biological therapies, such as Denosumab, are used efficiently to ensure the complete removal of the tumour.
It is important to bear in mind that patients receiving treatment outside of the UK may receive different tests and treatment in accordance to the treatment guidelines set out in that specific country. If you have any questions or concerns regarding this please discuss this with your medical team or contact The Bone Cancer Research Trust for more information.
If you would like more information about giant cell tumours of the bone please contact us.
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Version 2 produced September 2016
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