Bone Sarcomas & Subtypes

This is basic information about bone sarcoma and the parts of the body it may affect.

About Bones

The adult human skeletal system is made up of 206 bones. Bones protect the internal organs, allow people to stand upright, and attach to muscles, which allow movement. Bones are connected to other bones by bands of tough, fibrous tissue called ligaments. Cartilage covers and protects the joints where bones come together. Bones are hollow and filled with bone marrow, which is the spongy, red tissue that produces blood cells. The cortex is the hard, outer portion of the bone.

Bone consists of collagen, which is a soft, fibrous tissue, and calcium phosphate, a mineral that helps harden and strengthen the bone. There are 3 types of bone cells:

  • Osteoclasts: Cells that break down and remove old bone.
  • Osteoblasts: Cells that build new bone.
  • Osteocytes: Cells that carry nutrients to the bone.

About Bone Sarcoma

Cancer can start in any part of any bone. Cancer begins when healthy cells in the bone change and grow out of control, forming a mass called a tumor. A bone tumor can be cancerous or benign.

A cancerous tumor is malignant, meaning it can grow and spread to other parts of the body. A malignant tumor can destroy the bone and spread to nearby tissue. If these bone tumor cells get into the bloodstream, they can spread to other parts of the body, especially the lungs, through a process called metastasis.

A benign tumor means the tumor can grow, but it will not spread to other parts of the body. Even though a benign tumor does not spread outside the bone, it can grow large enough to press on surrounding tissue, weaken the bone, and cause the bone to fracture.

There are different types of connective tissue cancers of the bone:

  • Chondrosarcoma is cancer of the cartilage. It is more common in adults.
  • This type of bone sarcoma typically starts in part of the spinal cord.
  • Ewing sarcoma and osteosarcoma.These are 2 of the most common types of bone sarcoma. They mainly occur in children and young adults. Ewing sarcoma is unusual in that it can occur in bone or soft tissue. Refer to the guide to soft-tissue sarcoma for Ewing sarcomas that occur in soft tissue. Refer to the guide to osteosarcoma to learn more about osteosarcoma.

It is rare for soft-tissue sarcoma to begin in the bone, but when it does, it can cause different types of cancer, such as:

  • Undifferentiated pleomorphic sarcoma (UPS). UPS is an uncommon bone tumor, most closely related to osteosarcoma (see above). UPS of bone is usually found in adults. An arm or leg, especially around the knee joint, is the most common place for UPS to appear. This type of soft-tissue sarcoma is also more common among adults, particularly during middle age. It most often begins in the thighbone.
  • Sarcoma of Paget’s disease of the bone. Paget’s disease of the bone generally occurs in older adults. It involves the overgrowth of bony tissue and frequently affects the skull. If Paget’s disease develops into cancer, it is usually an osteosarcoma. However, this is uncommon.

There are other cancers that start in bone marrow, such as myeloma or leukemia. These are different from bone sarcoma.

Subtypes of Bone Sarcoma:

Adamantinoma

This is a very rare tumor of cells that are associated with bone formation in a process that may be similar to the cells responsible for forming teeth. The latter cells can form cancers of the lower jaw more than the upper jaw, termed ameloblastoma. Adamantinoma nearly always affects the tibia, and is treated with surgery. Rare cases can travel elsewhere in the body, at which point chemotherapy is used to increase survival rates.

Reference: SARC

Chondrosarcoma

Conventional chondrosarcoma can be a difficult tumor to treat. It often arises in older patients, and often in the pelvis. As a result, people with multiple medical diagnoses are put in the position of requiring a very large operation with a high risk of post-operative complications, with subsequent loss of function. For chondrosarcomas that arise in other sites, surgery can be less risky and represents the standard of care. There is often a significant risk of tumor recurrence where it started.

People with metastatic disease often do not respond well to chemotherapy. Grade 1 chondrosarcomas almost never metastasize and are now called “atypical cartilaginous tumor”, grade 2 chondrosarcomas have only a 10-15% risk of metastasis, and grade 3 chondrosarcomas have a two-thirds or higher risk of metastasis. As a result, some people with grade 3 chondrosarcomas are treated with adjuvant chemotherapy. A version of chondrosarcoma called clear-cell chondrosarcoma has an intermediate risk of metastasis, but treatment is typically surgery alone.

Dedifferentiated Chondrosarcoma

This more aggressive version of chondrosarcoma typically occurs in adolescence and in people over age 60. It shows features of both chondrosarcoma and a less differentiated tumor, such as UPS (undifferentiated pleomorphic sarcoma), which does not show even a hint of relatedness to the chondrosarcoma. This version of chondrosarcoma has a high risk of recurrence, even greater than that of grade 3 conventional chondrosarcoma (described above).

Mesenchymal Chondrosarcoma

This rare bone tumor shows a mixture of aggressive small round blue cells mixed with more typical lower-grade chondrosarcoma. It usually affects people between 15 and 30, and has a high risk of recurrence. The benefit of chemotherapy is not known, though chemotherapy is often used. The typical chemotherapy drugs that are used in the adjuvant setting (or metastatic setting, for that matter) are the drugs used for Ewing sarcoma and similar sarcomas.

Reference: SARC

Chordoma

Chordoma is a tumor that appears very similar to the fetal cells that form the new spine, the notochord. The relationship to development of the bone while the fetus is growing in the uterus is hard to understand, since tumors of this sort typically only arise in people over 50. It typically occurs at the base of the skull, or in the sacrum (the very base of the spine in the pelvis), where surgical removal is often not possible. This is one tumor that can respond to radiation designed to cure even tumors that are not surgically removable, and is a tumor for which treatment with proton-beam radiation may be better than other forms of radiation therapy. Though there are no approved drugs to treat chordoma, some drugs approved for other cancers can be used for people with recurrences of their chordoma.

Reference: SARC

Craniofacial Osteosarcoma

Osteosarcoma of the bones of the Jaw and Skull are relatively rare and represent less than 10% of all osteosarcomas. They typically occur in patients between the ages of 20 and 40 and have the same occurrence rate between males and females. The bones most commonly affected are the mandible (jaw bone) and the maxilla (cheek bone). Because they are located in the head and neck, they tend to be diagnosed earlier and can remain localized for longer periods of time; however, they are more difficult to remove surgically and therefore local recurrence is common.

Treatment of malignant osteosarcoma in the skull bones is similar of classic osteosarcoma. It should include preoperative chemotherapy. This is extremely important due to the limited margins available for surgical excision.

Ewing Sarcoma

Ewing sarcoma is actually several types of sarcomas known as the Ewing Family of Tumors. In the U.S., there are approximately 250 cases diagnosed a year, generally in children and young adults under the age of 30. This is the third-most-common sarcoma of bone and second most common in children. The same tumor occurs in the soft tissue of adults more than it occurs in bone. It can be found in any bone, but is most common in the bones of the lower body such as the pelvis, tibia (shin), fibula (shin), and femur (thigh).

Ewing sarcoma is often associated with a chromosomal translocation between genes EWS and FLI1 on chromosomes 22 and 11. Although Ewing is classified as a bone cancer, the type of cells it originates in is not completely known, which is why as mentioned above, occasionally Ewing sarcoma may occur in soft tissues. Peripheral Primitive Neuroectodermal Tumor (peripheral PNET) is a rare tumor that has the same translocation, and is now considered to be identical to Ewing sarcoma. The Ewing Family of Tumors (EFT) includes Ewing sarcoma of bone, extraosseous Ewing, and peripheral PNET. It is not known what causes the tumor, although it is more likely to occur in people of European descent. It is an aggressive cancer and is treated with a combination of surgery, radiation, and chemotherapy, with a good outcome for many cases.

Without chemotherapy, the cure rate is at best 10%, but with chemotherapy, a cure rate of up to 75% in children and 50-60% in adults is seen. Surgery and radiation are also commonly used as treatment for the primary tumor to achieve the highest possible cure rate. Ewing sarcomas can appear in any site of the body. When they recur, it is most commonly in the lungs and bones.

Reference: SARC

Giant Cell Tumor of Bone

Giant-cell tumor of bone typically occurs between ages 20 and 40, and has a unique appearance under the microscope. It typically occurs in the knee or lower spine. It is treated by scraping out the tumor and treating the tumor cavity with cement (which heats up and destroys tumor tissue) or with liquid nitrogen (freezing and thawing the tumor in place, often killing remaining cells). A bone graft is often used to try to reconstruct the area. In some cases, the tumor can be removed as one piece without damaging other tissues, and in these cases a bone graft may be performed as well. Conventional giant-cell tumors have a risk of recurrence where they start and have a low but real possibility of metastasis to the lungs. Giant-cell tumors must be differentiated from aneurysmal bone cysts. For giant-cell tumors of bone that have recurred, the new agent denosumab can delay further recurrence, though it is not believed to be curative by itself.

Reference: SARC

Multifocal Sclerosing osteosarcoma

Multifocal sclerosing osteosarcoma is an extremely rare form of osteosarcoma. It tends to occur in children less than 10 years old and represents less than 3% of all primary osteosarcomas. It is an aggressive tumor which presents as a single painful tumor, much like other types of osteosarcoma. However further tests looking for metastases reveal tumor in virtually all of the skeleton.

Since all the bones of the body are involved surgery is usually not an option, except to relieve pain. Aggressive chemotherapy can lead to a remission; however, multiple tumors eventually progress and mortality approaches 100%.

Osteosarcoma

Osteosarcoma (Osteogenic Sarcoma) is a malignant (cancerous) bone tumor that occurs predominantly in adolescents and young adults. Osteosarcoma typically affects adolescents and young adults generally occurs in bones around the knee joint, though any bone of the body can be affected.It accounts for approximately 5% of the tumors in childhood. Although any bone of the body can be affected, the bones most frequently involved are the large bones of the upper arm (humerus) and the leg (femur and tibia). In children and adolescents, 80% of these tumors arise from the bones around the knee. It is slightly more common in males than females. It is the most common primary malignant bone tumor with the exception of myeloma. Although osteosarcoma is a common malignant bone tumor, it is still rare with less than 1,000 new cases each year in the United States. Due to its rarity, it is imperative that patients with proven or suspected osteosarcoma have an initial evaluation by an orthopedic oncologist familiar with the management of this disease. This evaluation should be done prior to the initial biopsy, since an inappropriately performed biopsy may jeopardize a limb-sparing procedure.

Osteosarcoma occurs in adolescents at the time they are most rapidly growing in their most rapidly growing bones; therefore, it is suspected that rapid bone growth may play a role in the development of osteosarcoma. Additionally, some evidence suggests that chronic bone injury can increase the risk for osteosarcoma. When osteosarcoma occurs in adults over age 40 it is usually associated with a pre-existing condition such as Paget’s disease.

The initial symptoms include pain, often in and around the knee, especially in tumors on the tibia or femur. The pain typically worsens over time and is not related to the time of day. Swelling and tenderness typically occur late in the course of osteogenic sarcoma, followed by a large soft tissue mass appearing. A screening of serum alkaline phosphatase levels may be done. These levels are high in approximately 45-50% of patients with osteosarcoma; therefore it cannot be used alone to diagnose the disease.

Osteosarcoma must be diagnosed by biopsy. Because the disease commonly spreads (metastasizes) to other parts of the body, especially the lungs, chest x-rays, lung tomograms, CT scans of the chest , and an x-ray skeletal survey or bone scan may be done before treatment. This process is called staging. There are three groups used to describe the extent of the disease: Localized – the cancer cells have not spread beyond the bone or nearby tissue. Metastatic – the cancer cells have spread from the bone where the cancer began to other parts of the body (commonly the lungs, however it can spread to other bone). Recurrent – the cancer has come back after it has been treated. It may come back to the original site of the tumor or another part of the body.

Surgery is the primary method of treatment. This can be either an amputation or limb-sparing procedure. A limb-sparing procedure is when a surgeon removes the tumor and a block of surrounding tissues to ensure clean (cancer free) margins around the tumor. The surgeon then reconstructs the limb using prosthetic devices, bone grafts or other reconstructive techniques. These procedures are highly specialized and are usually performed by an orthopedic oncologist. In general 70-90% of osteosarcomas of the limb can be treated by a limb-sparing procedure and do not require amputation; therefore, before undergoing an amputation, it is recommended that the patient seek the advice of an orthopedic oncologist.

Surgery is usually followed by a course of chemotherapy using one or more anti-cancer drugs. Some clinical trials have shown that adjuvant chemotherapy ( chemotherapy given when no clear evidence of cancer can be found i.e. after the tumor is removed) may be helpful in preventing the relapse or recurrence of the disease. Other trials suggest that there is no difference in outcome between pre-operative chemotherapy or adjuvant chemotherapy. Standard drugs include doxorubicin and cisplatin in adults and the same two drugs with high-dose methotrexate in children, adolescents, or young adults.

Recurrences typically occur in the lungs. Surgical removal of lung metastases from a primary osteosarcoma is a standard of care when there is a small number of lung nodules that can be removed safely, and can be associated with a 30-35% cure rate. Osteosarcomas occur commonly in familial syndromes associated with sarcoma, such as Li-Fraumeni syndrome (involving a mutation in the p53 gene), retinoblastoma (involving a mutation in the Rb gene), and Rothmund-Thomson syndrome.

Reference: SARC

Osteosarcoma in Paget’s Disease

Paget’s disease affects approximately 3% of the population over the age of 60. It is characterized by abnormal growth of new bone cells leading to multiple bone deformities. Approximately 1% of patients with Paget’s disease develop primary bone sarcoma. The tumors usually arise in the pelvis, femur, or humerus. They typically are large and very destructive making surgery difficult. At the time of diagnosis, the cancer has often metastasized to the lungs. Amputation is sometimes necessary.

Patients with suspected osteosarcoma arising in Paget’s disease should receive a bone scan and x-ray of all identified tumors. Additionally, a CT scan of the chest should be done to rule out metastases to the lungs. Treatment is the same as fully malignant osteosarcoma arising in a younger population. Patients with preoperative chemotherapy, radical surgery of the tumor, followed by post-operative chemotherapy have the best prognosis. Tumors arising in the skull and spine are sometimes inoperable. In this instance patients are typically given chemotherapy and radiation therapy to control and shrink the tumor. Great care must be taken during chemotherapy treatments since many older patients have impaired kidney function.

Parosteal osteosarcoma

Parosteal osteosarcoma is a low-grade tumor that arises on the surface of the bone without lifting off the surface connective tissue of bone (periosteum). It rarely penetrates the center of the bone and rarely becomes a highly malignant osteosarcoma. It accounts for approximately 4% of all osteosarcomas and is slightly more common in females than males. It is different than classic osteosarcoma in that it typically arises in adults between the ages of 20 and 40. It has a better prognosis than classic osteosarcoma with an overall survival rate of 75% to 85%. It has a very slow rate of metastases (spreading).

Parosteal osteosarcoma is most commonly found on the femur, behind the knee (72% of all cases). It usually presents itself with minimal pain and tenderness and in its typical location behind the knee there may be some restriction in movement of the knee joint.

Surgery with wide margins is the standard treatment for parosteal osteosarcoma, either by amputation or limb-sparing surgery. Because they are located at the end of the bone, are typically low grade, and lack local invasiveness, they are often amenable to limb-sparing procedures. Grade III parosteal lesions usually require chemotherapy because of the risk of metastases.

Reference: SARC

Periosteal osteosarcoma

Like parosteal osteosarcoma, periosteal osteosarcoma is an uncommon tumor arising on the surface of the bone, most commonly the tibia. It is a high grade tumor composed of malignant cartilage. It occurs in a younger age group and is even more common among females than males than parosteal osteosarcoma. Because periosteal osteosarcoma is more likely to metastasize than the parosteal, some oncologists treat this tumor more aggressively with combination therapy such as surgery and chemotherapy.

Post-irradiation Osteosarcoma

Radiation Induced Osteosarcoma is a rare form of osteosarcoma which occurs in people who have undergone radiation therapy treatments for other diseases. The average length of time before these tumors appear is 10 years following radiation. The younger the patient is at the time of radiation, the higher the risk of osteosarcoma. Additionally, evidence suggest that patients who receive higher doses of radiation are at a higher risk of developing osteosarcoma than patients who receive lower doses of radiation.

Post-irradiation osteosarcomas are most commonly located in the spine, pelvis, hips and shoulders. People with retinoblastoma, a malignant tumor of the eye, are at a higher risk of developing post-irradiation osteosarcoma due to a defect in the RB gene.

Symptoms of postirradiation osteosarcoma are painful swelling in and around the area of radiation. A biopsy must be performed in order to diagnose the disease. Once the diagnosis is made, staging of the tumor is done using bone scan, CT scan or MRI. Additionally a CT scan of the lungs should be done to rule out metastases to the lungs.

The treatment of postirradaition sarcoma is similar to classic osteosarcoma. It usually included preoperative chemotherapy, surgery and followed by postoperative chemotherapy. Surgery can be difficult when tumors are in and around the spine and therefore preoperative chemotherapy to shrink the tumor is crucial. Due to this challenge, the prognosis for postirradiation osteosarcoma is worse than that for classic osteosarcoma.

Cancer that has spread to the bone

This section contains information about primary bone sarcoma, which is cancer that begins in the bone. In general, primary bone sarcoma is uncommon. It is much more common for other cancers, such as breastlung, or prostate cancers, to spread to the bone. Cancer that started in another area of the body and has spread to the bone is called metastatic cancer, not bone cancer or bone sarcoma. For example, lung cancer that has spread to the bone is called metastatic lung cancer.

 

Reference: the Cancer.Net Editorial Board, 04/2020

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