Giant cell tumors are relatively uncommon bone tumors that are often benign but can be locally aggressive and cause significant problems.
What are giant cell tumors?
Giant cell tumors (GCTs) are rare, noncancerous (benign) bone tumors. They are characterized by the presence of large cells called "giant cells," along with other types of cells. While they are not cancerous in the traditional sense, meaning they don't typically spread to distant organs, they can be locally aggressive. GCTs most commonly develop near the ends of long bones, especially around the knee. They can also occur in other bones, such as those in the wrist, hip, or spine, but this is less common.
Your doctor may refer to osteoclasts when discussing GCTs. Osteoclasts are specialized cells responsible for bone resorption, which is the process of breaking down bone tissue. They are essential for bone remodeling, growth, and repair. GCTs are characterized by a large number of multinucleated giant cells (hence the name). These giant cells are believed to be osteoclast-like cells or precursors to osteoclasts. This means they share many characteristics with normal osteoclasts and can perform similar functions. The osteoclast-like giant cells within GCTs are highly active in bone resorption. They break down the surrounding bone tissue, leading to the characteristic bone destruction seen in these tumors. This bone destruction contributes to the symptoms of GCTs, such as pain, swelling, and increased risk of fractures.
Despite GCTs being classified as typically benign, in rare cases, around 1 – 5%, GCTs can become cancerous (malignant) or metastasize (spread) to other parts of the body, most commonly the lungs. These are called malignant giant cell tumors.
GCTs need specialized attention from experienced providers. AHN offers a multidisciplinary team of health care providers who understand how to treat GCTs. Our Sarcoma Center of Excellence is a one-of-its kind-facility, providing highly individualized treatment options and care.
AHN Sarcoma Center of Excellence
The AHN Sarcoma Center of Excellence is made up of a team of multiple health care experts walking you through every step of your cancer diagnosis and treatment.
Diagnosis and treatment will usually begin with an appointment with our orthopaedic oncology team. The team works closely with providers amongst different medical specialties including:
- Surgeons
- Medical oncology
- Radiation oncology
- Pathology
- Physical therapy
- Occupational therapy
- Plastic surgery
- Nurse Navigators
At AHN, we strive to make your treatment course as painless as possible. We will take care of appointment scheduling, imaging planning, and other aspects of care coordination for our patients so you have time to focus on healing and recovery.
Giant cell tumor symptoms and signs
Depending on where the giant cell tumor occurs in the body, its size, and location, the signs and symptoms will differ. In some cases, early-stage GCTs may not cause any noticeable symptoms. However, as the tumor grows, it can lead to pain, swelling, limited range of motion, a mass, and in some instances neurological issues. It’s important to talk to your doctor about any persistent changes in your health and body. GCTs can occur throughout the body, so it’s important to understand how the signs and symptoms may show up in other areas of the body.
Fingers and thumbs
Because the bones in the fingers and thumb are relatively small, even a small GCT can cause noticeable symptoms. The specific symptoms and signs may include:
- Pain: Localized pain in the affected finger or thumb. The pain may come and go, or it could be a constant feeling. Some people may experience a worsening pain with activities such as typing, writing or gripping objects.
- Swelling: In those who have GCTs, fingers and thumbs may swell around the joint or along the bone. Some people experience swelling that is tender to the touch or the skin may be red or shiny.
- Stiffness: Sometimes, GCTs can cause difficulty in bending or straightening the finger or thumb and reduced range of motion.
- A noticeable mass: There are instances where a lump or bump can be felt under the skin on the affected finger or thumb.
- Deformity: If the tumor is large or has been present for some time, it can cause a noticeable change or deformity to the thumb or finger.
Hands and wrist
GCTs can occur in the carpal bones (wrist) or the metacarpal bones (palm). The symptoms will vary based on the specific location and size of the tumor. Some signs and symptoms that may occur include:
- Pain: This may be dull or aching pain that is in the wrist or palm. It can also be feel like a sharp pain and may worsen with activities like typing. lifting or gripping.
- Swelling: Visible swelling in the wrist or palm can occur making the area appear larger or distorted and can feel tender when touched.
- Limited range of motion: Difficulty bending the wrist forward and backward or gripping the hand can be signs of GCTs.
- Weakness: Some people experience a weakening in their hand and wrist, making it difficult to grip objects firmly.
- Deformity: If the tumor is large or has been present for some time, it can cause a noticeable change or deformity to the hand or finger.
Spine
Giant cell tumors (GCTs) of the spine are rare but can cause significant problems. Symptoms can vary depending on the tumor's location and extent of growth.
- Back pain: This is a frequent symptom that feels like deep, persistent pain that can worsen with activity or at night.
- Neurological symptoms: When the tumor presses against the spinal cord or nerve roots, patients can experience numbness, tingling, weakness, or paralysis in the arms or legs.
- Changes in bowel or bladder function: While more common in tumors that are in the lower spine, some people experience incontinence, difficulty urinating, or constipation.
- Muscle weakness: If GCTs are on the spine, this can cause difficulty walking, balance problems, or weakness in the arms or legs.
- Stiffness in the back: While a stiff back can be the result of many activities or age, changes or worsening mobility issues can be a sign of GCTs. This can include difficulty bending, twisting, or moving comfortably.
- Spinal deformity: If tumors are present on the spine, they can cause a weakening of the bone that impacts the curvature of the spine.
- Localized tenderness: The spine might feel tender to the touch or with pressure.
- Radiating pain: A person may experience a shooting pain that travels along the nerve pathway of the spine or a pain that radiates down an arm or leg.
Knee
Since giant cell tumors occur at the end of long bones, the knee is a common place for them to develop. Signs and symptoms of GCTs in the knee can include:
- Pain: This is usually the most common presenting symptom. The pain can be mild at first but typically increases over time as the tumor grows. It may be described as a dull ache or a more intense, throbbing pain, especially with activity or at night.
- Swelling: Visible or palpable swelling around the knee joint is another frequent symptom. The swelling may be soft or firm, depending on the size and location of the tumor and its effect on surrounding tissues.
- Limited range of motion: As the tumor enlarges, it can restrict the normal movement of the knee joint, leading to stiffness and difficulty fully bending or straightening the leg.
- Joint effusion: The tumor can irritate the knee joint, causing an accumulation of fluid within the joint space (effusion). This can contribute to swelling and stiffness.
- Tenderness: The area around the tumor may be tender to the touch.
- Pathological fracture: In some cases, the tumor can weaken the bone to the point where a fracture occurs with minimal trauma (pathological fracture). This would cause a sudden onset of severe pain and an inability to bear weight.
- Limping: Due to pain, stiffness, or instability in the knee, the person may develop a limp while walking.
- Neurological symptoms: Though less common, if the tumor compresses nearby nerves, it could lead to numbness, tingling, or weakness in the leg or foot.
Foot
Giant cell tumors in the foot are relatively rare, but it's helpful to know what to look for. Here's an overview of the common signs and symptoms:
- Pain: This is often the most common symptom. The pain may start as mild and intermittent, gradually increasing over time. It can be localized to the tumor site.
- Swelling: You might notice a palpable mass or swelling in the affected area of the foot.
- Limited range of motion: Depending on the tumor's location and size, it can restrict the movement of nearby joints.
- Tenderness: The area around the tumor may be tender to the touch.
- Pathological fracture: In some cases, the tumor can weaken the bone, leading to a fracture with minimal or no trauma. This is less common but possible.
Causes and risk factors
The exact cause of giant cell tumors (GCTs) is unknown, as they occur spontaneously. There are some correlating causes and risk factors that may be linked to GCTs.
Those include:
- Genetic factors: Research suggests that genetic factors may play a role in the development of GCTs. Specifically, mutations in the H3F3A gene have been found in a significant proportion of GCTs. This gene is involved in regulating cell growth and differentiation.
- RANK/RANKL pathway: The RANK/RANKL signaling pathway, which is crucial for bone remodeling, is often found to be dysregulated in GCTs. This dysregulation contributes to the excessive bone resorption characteristic of these tumors.
- Age: GCTs are most commonly diagnosed in individuals between the ages of 20 and 40. They are relatively rare in children and older adults.
- Skeletal maturity: GCTs typically occur after the closure of the growth plates, meaning they are more common in individuals who have reached skeletal maturity.
- Location: While GCTs can occur in any bone, they are most commonly found in the ends of long bones, particularly around the knee joint (distal femur and proximal tibia). Other common sites include the distal radius (wrist) and the sacrum. The occurrence of GCTs in the foot is less common.
Giant cell tumor screening and diagnosis
Since GCTs are relatively rare, there's no routine screening for them in the general population. Diagnosis typically occurs when someone presents with symptoms like bone pain, swelling, or a pathological fracture.
Clinical evaluation
Your doctor will ask about your medical history, including any previous bone conditions, injuries, or family history of bone tumors. They'll inquire about your symptoms: when they started, how severe they are, and what makes them better or worse.Your doctor will also examine the affected area for swelling, tenderness, range of motion, and any neurological deficits (e.g., numbness, weakness) that might indicate nerve compression.
Imaging studies
Imaging is crucial for identifying and characterizing potential GCTs.
- X-rays: Usually the first imaging study performed. X-rays can show a lytic (bone-destroying) lesion in the bone, often with a characteristic "soap bubble" appearance. This appearance isn't unique to GCTs but can raise suspicion. They can also reveal any fractures.
- Magnetic Resonance Imaging (MRI): MRI is the most important imaging modality for diagnosing and staging GCTs. It provides detailed images of the tumor, including its size, location, relationship to surrounding tissues (muscles, nerves, blood vessels), and any soft tissue extension. MRI is also good for detecting early tumors or tumors in difficult-to-visualize locations. It can also help differentiate GCTs from other bone lesions.
- Computed Tomography (CT) Scan: While MRI is generally preferred, CT scans can be helpful in certain situations, particularly for assessing the degree of bone destruction and visualizing the bony margins of the tumor. CT scans are also useful for evaluating lung involvement, if metastasis is suspected (though metastasis is rare in GCTs).
- Bone Scan (Radionuclide Bone Scan): This imaging technique is less commonly used for the initial diagnosis of GCTs, but it can be helpful to determine if there are other lesions in the body or to assess the overall extent of the tumor. GCTs typically show increased uptake on a bone scan.
Biopsy
A biopsy is essential to confirm the diagnosis of GCTs. Imaging can be suggestive, but a biopsy is required to examine the tissue under a microscope and definitively identify the tumor. Types of biopsy include:
- Needle biopsy (core needle biopsy): A needle is inserted into the tumor to extract a small tissue sample. This is usually performed under image guidance (e.g., CT or ultrasound) to ensure accurate placement.
- Open biopsy (incisional biopsy): A small incision is made, and a larger piece of tissue is surgically removed. This is usually performed if a needle biopsy is insufficient or if a larger sample is needed for more detailed analysis. Ideally, the biopsy should be performed by the surgeon who will be performing the definitive resection, as the biopsy site needs to be excised at the time of definitive surgery to avoid seeding the surrounding tissues with tumor cells.
- Pathological examination: A pathologist examines the biopsy sample under a microscope to identify the characteristic features of GCTs, including the presence of multinucleated giant cells (osteoclast-like cells) and mononuclear stromal cells. Immunohistochemical staining (using antibodies to identify specific proteins) is also performed to help confirm the diagnosis and rule out other types of tumors.
Differential diagnosis
It's crucial to differentiate GCTs from other conditions that can mimic their symptoms and appearance on imaging. These include:
- Aneurysmal Bone Cyst (ABC): A benign bone lesion containing blood-filled cavities.
- Chondroblastoma: A benign cartilage-forming tumor.
- Osteoblastoma: A benign bone-forming tumor.
- Brown Tumor of Hyperparathyroidism: A bone lesion caused by excessive parathyroid hormone production.
- Infection (Osteomyelitis): A bone infection.
- Metastatic Bone Disease: Cancer that has spread from another site to the bone (rare in the typical age group for GCTs, but must be considered).
- Osteosarcoma: A bone cancer that typically occurs around the knee or shoulder.
Types and stages of giant cell tumor
While the term "giant cell tumor" often refers to the classic giant cell tumor of bone (GCTB), it's important to recognize that there are other types of lesions that contain giant cells and are classified differently.
Giant cell tumor of bone (GCTB) — Classic Type
This is the most common and most well-known type of giant cell tumor. It's typically a benign but locally aggressive tumor, meaning it doesn't usually spread to distant sites (metastasize) but can destroy the surrounding bone tissue. It's characterized by the presence of multinucleated giant cells (osteoclast-like cells) scattered among mononuclear stromal cells. It usually occurs in the epiphysis (end) of long bones, especially around the knee, in skeletally mature individuals (typically 20 – 40 years old). This is the type that is typically treated with surgery.
Malignant giant cell tumor (MGCT)
This is a rare variant of GCTB where the tumor exhibits aggressive behavior and the potential for metastasis. It's characterized by the presence of malignant (cancerous) stromal cells in addition to the giant cells. MGCT can arise de novo (as a new tumor) or develop from a previously benign GCTB that has undergone malignant transformation. Treatment often involves a combination of surgery (wide resection), radiation therapy, and chemotherapy. The prognosis is generally less favorable than for classic GCTB.
Giant cell containing lesions (not true GCTs)
These lesions contain giant cells but are distinct entities from GCTB and have different causes and treatments. It's crucial to differentiate these from true GCTs to avoid misdiagnosis and inappropriate treatment. Examples include:
- Aneurysmal Bone Cyst (ABC): While ABCs contain giant cells, they are blood-filled cystic lesions and not considered true neoplasms. They are characterized by multiple blood-filled cavities separated by fibrous septa containing giant cells and reactive bone formation. They are treated differently than GCTB.
- Brown Tumor of Hyperparathyroidism: These lesions are caused by excessive parathyroid hormone (PTH), leading to increased bone resorption. They contain numerous giant cells, but the underlying cause is hormonal imbalance. Treatment focuses on addressing the hyperparathyroidism.
- Chondroblastoma: A benign cartilage-forming tumor that can contain giant cells. It typically occurs in the epiphysis of long bones in younger individuals.
- Giant Cell Reparative Granuloma (GCRG): Usually found in the jaws (mandible and maxilla), GCRGs are benign lesions composed of fibrous tissue, hemorrhage, and numerous giant cells. Their cause is not fully understood.
- Osteoblastoma: A benign bone-forming tumor that can sometimes contain giant cells.
- Metastatic giant cell tumor: Rarely, a metastasis from a primary malignancy elsewhere in the body can mimic a giant cell tumor histologically. These would require careful review by a pathologist to differentiate.
Giant cell tumor treatment
The treatment of Giant Cell Tumors (GCTs) has evolved significantly, with a combination of surgical and medical options available. GCTs have a significant risk of recurrence after curettage so close follow-up is essential. Treatment of GCTs is complex and our specialized orthopaedic oncologist is experienced in dealing with bone tumors. Our team approach involves surgeons, radiologists, pathologists, and medical oncologists with a focus on optimal outcomes. Patients may be eligible for clinical trials investigating new treatments for GCTs.
Surgical treatment
If it’s determined that surgery is the best course of treatment, AHN specializes in minimally invasive surgical options that help reduce or remove giant cell tumors. The options that AHN has available include:
- Curettage: This is the traditional and most common surgical approach for GCTs. It involves surgically scraping out the tumor from the bone. An "extended curettage" may involve using high-speed burrs to remove more of the tumor and create wider margins. To further reduce recurrence risk, curettage is often followed by:
- Bone cement filling (PMMA): Filling the cavity with bone cement (polymethylmethacrylate). The cement has a thermal effect that can kill remaining tumor cells and provides structural support.
- Bone grafting: Filling the cavity with bone graft (either from the patient [autograft] or a donor [allograft]). Bone graft encourages new bone growth and can provide long-term stability.
- Chemical adjuvant: Using a chemical adjuvant (like phenol or hydrogen peroxide) after curettage to further eliminate residual tumor cells.
- Wide resection: This involves removing the entire tumor along with a margin of healthy bone. Wide resection is typically reserved for:
- Aggressive tumors affecting the area. o Recurrent tumors after curettage.
- Cases where the tumor has extended into surrounding soft tissues.
- Situations where curettage is technically difficult or would result in significant functional impairment.
- Malignant GCTs that are spreading.
- Reconstruction after resection: After wide resection, the bone defect needs to be reconstructed. Options include:
- Bone grafting: Using bone graft to fill the defect.
- Prosthetic replacement: Using a metal or plastic implant to replace the removed bone segment. This is common when the tumor involves a joint.
- Allograft-prosthetic composite (APC): Combining an allograft with a prosthetic component to restore function and provide a more biological reconstruction.
- Amputation: In very rare cases, amputation may be necessary if the tumor is extremely aggressive, involves vital structures, or if other treatment options have failed.
Denosumab
A monoclonal antibody that targets RANKL, a protein crucial for osteoclast formation and activity.
Radiation therapy
Generally not the primary treatment for GCTs because of the risk of malignant transformation (the tumor turning into a more aggressive cancer) in the long term. However, it may be considered in specific situations:
- Unresectable tumors where surgery and denosumab are not effective.
- Malignant GCTs, often in combination with surgery and chemotherapy.
- Palliative treatment to relieve pain and control tumor growth in advanced cases.
In some cases, arterial embolization can be used before surgery to reduce the tumor's blood supply, making surgery easier and reducing blood loss.
Giant cell tumor FAQs
A giant cell tumor diagnosis can bring about many questions. AHN is here to help give clarity and provide you with treatment options and a care plan that will fit your specific needs. Background knowledge and information can be an asset in your conversations with your care team, and these FAQs are a great place to start.
What is the survival rate for giant cell tumors?
The term "survival rate" is typically used for malignant (cancerous) tumors. Giant cell tumors are usually benign, meaning they are not cancerous. However, they can be locally aggressive and can recur after treatment. Therefore, the focus is less on survival rate and more on the success of treatment in controlling the tumor and preventing recurrence. With appropriate treatment, the prognosis for controlling GCTs is generally good.
Do giant cell tumors need to be removed?
Treatment approaches vary based on the tumor's size, location, and aggressiveness. In many cases, surgical removal (resection or curettage) is the primary treatment, especially if the tumor is causing pain, limiting function, or threatening the stability of the bone. However, some GCTs may be treated with medications (like denosumab) to shrink the tumor before or instead of surgery. The decision to remove a GCT depends on a thorough evaluation by a specialist.
What is the most common site for giant cell tumors?
The most common sites for giant cell tumors are the ends of long bones, particularly around the knee joint. Specifically, the distal femur (the end of the thigh bone near the knee) and the proximal tibia (the end of the shin bone near the knee) are the most frequently affected locations. Other common sites include the distal radius (wrist) and the sacrum.
Can a giant cell tumor turn cancerous?
In rare cases, a giant cell tumor can undergo malignant transformation, meaning it can become cancerous. This is called a malignant giant cell tumor or a giant cell sarcoma. The risk of this transformation is low, but it's an important consideration in the long-term management of GCTs.
What is the prognosis for giant cell tumors?
The prognosis for giant cell tumors is generally good, particularly with appropriate treatment. However, GCTs have a tendency to recur (come back) after treatment, even after complete surgical removal. Regular follow-up is essential to monitor for any signs of recurrence. Factors that can influence the prognosis include the tumor's size, location, aggressiveness, and whether it has recurred after previous treatment.
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Please bring all relevant imaging on CD or through PowerShare with correlating reports for review by our team to your initial appointment.