Sarcoma Cancer is a rare disease, often misdiagnosed, often afflicting children and young adults.
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Types of Bone Sarcomas

Introduction

The second group of sarcoma is bone cancer. It is very rare with approximately 2,000 new cases diagnosed in the United States each year. The incidence is slightly higher in males than females and no race has a higher incidence than another, although, Ewings sarcoma is even more rare among African and American blacks. Due to the rarity and severity of bone cancer, a bone cancer specialist such as an Orthopedic Oncologist should be consulted in the treatment of the disease. Visit the Musculoskeletal Tumor Society website to find a sarcoma surgeon.

Bones consist of three types of tissue: compact tissue (the hard outer portion of the bone), cancellous tissue (spongy tissue inside the bone containing the bone marrow), and subchondral tissue (the smooth bone tissue of the joints). Cartilage surrounds the subchondral tissue to form a cushion around the joints.

Bone tumors can be benign (non-cancerous) or malignant (cancerous). Benign bone tumors are rarely life threatening and do not spread within the body; however, they can grow and compress healthy bone tissue. Cancer that develops in the bone is called primary bone cancer. It is differentiated by secondary bone cancer which spreads to the bone from another part of the body. Primary bone cancer is rare with approximately 2,500 new cases diagnosed each year in the United States (this figure includes bone cancer which is not sarcoma).

The most common type of primary bone cancer is osteosarcoma. Because it occurs in growing bones, it is most often found in children. Another type of primary bone cancer is chondrosarcoma which is found in the cartilage. This cancer occurs more often in adults.

Scientists are uncertain what causes bone cancer however they have been able to identify some factors which may put a person at risk. Children, and young adults who have had undergone radiation therapy or chemotherapy for other diseases, are at increased risk for bone cancer. Additionally, adults with Paget's disease which is a disease characterized by abnormal growth of new bone cells have an increased risk of osteosarcoma. There are also some hereditary conditions which can increase the risk of bone cancer.

Symptoms of bone cancer can vary depending on the size and location of the tumor. Pain is the most common symptom. Tumors arising in or around the joints often cause swelling and tenderness. Tumors can also weaken the bones thus causing fractures. Some other symptoms can be weight loss, fatigue and or anemia.

The first step in diagnosing primary bone cancer is a complete medical history and physical examination performed by a physician. The doctor may order a blood test to determine the level of an enzyme called alkaline phosphatase. Approximately 55% of patients with primary bone cancer will have elevated levels of alkaline phosphatase. However, it isn't a completely reliable indicator for bone cancer since growing bones in children will cause the enzyme to be elevated.

X-rays are also used to locate a tumor. If an x-ray suggests a tumor is present then a doctor may require further testing such as a CT scan, Magnetic Resonance Imaging (MRI), or an angiogram. Finally, a biopsy must be performed to determine if cancer is present. A biopsy is a procedure used to remove sample tissue from the tumor. A surgeon, usually an orthopedic oncologist, performs the procedure using a needle or making an incision. During a needle biopsy the surgeon makes a small hole in the bone and removes sample tissue with a small instrument. During an incisional biopsy, the surgeon cuts into the tumor and removes sample tissue. A Pathologist (a doctor specializing in identifying disease) then studies the cells and tissues under a microscope to determine whether the tumor is cancerous.

The treatment of bone cancer depends on the size, location, type and stage of the cancer. Surgery is often the primary treatment. While amputation of a limb is sometimes necessary, using chemotherapy either before or after surgery has allowed physicians to save the limb in many cases. Radiation may also be used alone or in combination with the other treatments.

New and more effective treatments are being developed in clinical trials at many hospitals and cancer centers in the United States.  The most common types of bone sarcomas are described below.


Chondrosarcoma

This is a cancer of that usually grows within a bone or on its surface. It is most typically found in middle-aged adults. Chondrosarcoma is usually a slow-growing tumor and the most common sites are the pelvis, shoulder and the upper part of the arms and legs.
The treatment for chondrosarcoma relies heavily on surgical removal, since there is limited response to radiation and/or chemotherapy. One of the reasons for aggressive treatment is that 10% of low-grade tumors have been reported to develop a much more aggressive biologic behavior, a process called dedifferentiation.


Ewing’s Sarcoma Family of Tumors (EWST)

Note: This section is used with permission from the author, Edward Y. Cheng, M.D., Mairs Family Professor, Department of Orthopaedic Surgery, University of Minnesota Cancer Center, KWRISF Board member and was originally in the Journal of the American Academy of Orthopaedic Surgeons, October 2004. For the the full article, including figures, click here.


Description

This is a cancerous (malignant) tumor. It usually begins growing initially in a bone. Occasionally, it also begins in the soft tissues (extraosseous Ewing’s sarcoma). Doctors don’t know the exact cell of origin. Recently, doctors have defined the disease to include a family of tumors. This includes the Ewing’s sarcoma of bone or soft tissue, primitive neuroectodermal tumor (PNET), and Askin tumor of chest wall.  Sometimes these tumors are called small blue cell (round cell) tumors. They are named for the way they look under a microscope.  

Compared with other cancers, all malignant bone tumors are rare. Among malignant bone tumors in children and young adults, Ewing’s sarcoma is the second most common. It occurs in 1.7 per million to 2.7 per million children who are younger than 15 years old. There is no known cause.

First a doctor uses imaging studies to diagnose a bone tumor. These include X-rays  and MRI (magnetic resonance imaging), CT (computed tomography) and bone scans. The doctor confirms the diagnosis by taking a piece of tissue to look at under a microscope (biopsy). This may be done in an operating room or X-ray department.

Then, special tests can help the doctor diagnose Ewing’s sarcoma. The hallmark is an abnormality in the cell’s chromosomes. Genetic material is mismatched. Chromosomes #11 and #22 are affected.

More tests (blood tests, lung CT scan, bone scan, and bone marrow biopsy) are needed to show the extent of disease. This process is known as “staging”.  Tests can show if cancer has spread to other sites. This can include the lungs or bone marrow. The part of the body where the first tumor develops is called the “primary” site. Any parts of the body where it spreads are called “metastatic” sites.


Risk Factors/Prevention

There are no known risk factors for developing Ewing’s sarcoma. There is no known genetic link. There is no means of prevention either. The tumor does not develop as a result of any dietary, social or behavioral habits. Parents of affected children should know that there is nothing they could have done to prevent the tumor.


Symptoms

There is usually pain and/or swelling at the affected site. But the tumor may be present for many months before it becomes large enough to cause pain and swelling. Injuries are not a known cause—but injury may draw attention to a tumor. A bone weakened by disease may break after a minor injury. Ewing’s sarcoma usually affects the long bones. These include the thighbone (femur), shinbone (tibia) and upper arm (humerus) bone. The bones of the pelvis may also be affected.

 
Treatment Options

Doctors in many specialties help treat Ewing’s sarcoma. These include orthopaedic surgical oncologists, pediatric or adult medical oncologists, radiation oncologists, pathologists and radiologists. Most patients are treated at major hospital institutions or cancer centers. The main treatments are:

  • Chemotherapy. This is used to kill the primary tumor and any unknown microscopic spread.
  • Surgery. This is used to remove the primary tumor, and occasionally metastatic lesions. If necessary, surgery can also rebuild the limb or body part.
  • Radiation.This is used to lower the chance of the primary tumor coming back (recurring) or may be used instead of surgery at sites where surgery is too risky or complicated.

Ewing’s sarcoma is usually diagnosed as a primary bone tumor without evidence of spread elsewhere. Even if tests to do not show spread, the treatment strategy assumes that a very small amount of spread (micrometastatic disease) has already happened.

 

Chemotherapy

Chemotherapy uses multiple medications.  The most common agents are vincristine (Oncovin®), dactinomycin (actinomycin D®), cyclophosphamide (cytoxan®), and doxorubicin (adriamycin®). Recent evidence shows the addition of ifosfamide (Ifex®) and etoposide (VePesid®, VP-16) helps.  The chemotherapy is given through an indwelling central venous catheter. This is placed just before treatment is started. Chemotherapy is done in cycles. It uses combinations of the various drugs. The time between cycles lets the blood cell count recover. This includes white blood cells and platelets. The drugs depress them. The patient will lose their hair. Various medications can lessen other side effects. These include nausea, mouth sores and fevers.

It generally takes close to one year to finish all the cycles of chemotherapy, with surgery and/or radiation. A doctor will look at the effect of chemotherapy. He or she will evaluate the number of cells killed in the tumor after it has been removed. This happens following several cycles of chemotherapy that may shrink the tumor, (figures 2 and 3). Many advances in chemotherapy have been made through knowledge gained by placing patients in clinical trials. Your doctor can tell you more. A physician may request permission to enroll a patient in a specific clinical trial.


Surgery

Both surgery and radiation are effective treatments for the primary tumor. Many surgeons remove the tumor when doing so will not cause a major loss of function of the body part involved. Many doctors use radiation treatment only when a tumor cannot be removed completely or without the patient losing function.

The surgeon can reconstruct the bone, joint or soft tissue site. He or she may use use bone grafts, artificial joints, or a combination. The goal is to restore the body part so the patient can do their normal everyday activities. Strenuous or athletic activities are likely to cause too much stress or wear on the reconstruction. 

Some patients may need more operations to keep the limb functioning for the rest of their life. Reconstruction of a bone in a growing child is a special challenge. As the child grows, multiple procedures are needed to lengthen the reconstructed bone.  Surgery and/or radiation can be done either before or during chemotherapy. Most centers will halt the chemotherapy sessions sometime during the first half of the treatments to complete the surgery/radiation. Chemotherapy is restarted once the wound site has healed enough. This is usually about 2 weeks to 3 weeks after surgery.

Depending on the site involved, the patient may need to limit weight bearing on the limb.  Ongoing rehabilitation with physical therapy is needed to optimize function.

In many cases, doctors can avoid amputation by surgically removing the primary tumor. Rebuilding the bone and joints is then needed. It’s important to consider the risks and complications associated with the surgery. Infections, problems with prosthesis and wound healing are the most frequent concerns.

 

Radiation

When radiation treatment is used, daily treatments are given over the course of many weeks.  While the discomfort of surgery may be avoided, there are risks, however, associated with the radiation including:

  • skin damage
  • muscle scarring and loss of joint flexibility
  • damage to nearby organs
  • loss of bone growth in growing children
  • secondary cancers caused by radiation
  • chronic swelling of an extremity
  • slow wound healing


Recently, more doctors are using surgery to remove the tumors when possible. Most physicians work as a team to tailor their recommendations of surgery and/or radiation to a patient’s specific situation.


Treatment outcome and success

The outcome for patients with Ewing’s sarcoma has improved a lot. This is thanks to improvements in chemotherapy, diagnostic imaging and reconstructive techniques. In general, two-thirds of patients without any demonstrable spread will survive at least five years after diagnosis with standard treatment. When tumors come back, it usually happens within the first few years after treatment. The absence of known spread is the most important factor in favor of being more likely to survive.  Other factors include having excellent response to chemotherapy, primary tumors in the extremities instead of pelvis, and complete removal of the tumor.



Fibrosarcoma

This type of bone cancer is also most commonly found in adults, particularly during middle age. A typical site is the thigh bone. Fibrosarcoma cancers arise in the fibroblast-type cells (any cell from which connective tissue is developed) in the body. These cells form scars as well as perform other important connective functions. This sarcoma contains much connective tissue.


Malignant fibrous histiocytoma

This is a very rare type of bone cancer that occurs in adults. It is usually found in the arms and legs, especially around the knee joint.


Osteosarcoma (also called osteogenic sarcoma)


Note: This section is used with permission from the author, Edward Y. Cheng, M.D., Mairs Family Professor, Department of Orthopaedic Surgery, University of Minnesota Cancer Center, KWRISF Board member and is based on an article entitled: Osteosarcoma, “An unusual cancer arising in the bone”. The full article, including figures can be found in the internet edition of this Notebook at www.reininsarcoma.org.



Introduction to Osteosarcoma

Most cancers in the bone have spread (metastasized) to the bone from another area in the body (the “primary” site, e.g., lung, breast, kidney) or are related to a cancerous tumor of blood cells (e.g, myeloma).  On rare occasion, however, a cancer can begin in the bone itself from cancerous cells that make bone tissue.  A malignant tumor that forms bone tissue from the cancerous cells is called an osteosarcoma.  Although cancers that begin in the bone (primary bone cancer) are much less common that those that metastasize to the bone, among the primary bone cancers, osteosarcoma is the most common type.


Epidemiology and anatomic site

Osteosarcoma is a rare tumor and only about 2000 new cases are diagnosed in the USA per year and this comprises < 1% of all new cancer cases in the USA annually.  The vast majority of these tumors develop in patients with bones that are growing rapidly, namely adolescents or young adults.  However, a smaller concentration of osteosarcomas also affects the elderly age group, in part due to another disease, Paget’s disease, that occurs in the elderly and may turn into an osteosarcoma.  The higher prevalence of osteosarcoma in the young age group is intuitive if one thinks of cancer as an error in cellular growth resulting in uncontrolled growth.  During the pubertal growth spurt, a higher number of bone cells are multiplying and it is more likely that an error in the cellular duplicating machinery might occur at that time.

Just as osteosarcomas tend to occur in the rapidly growing adolescent, the tumors tend to occur in those bony sites growing most rapidly, namely the distal femur (figure 1), proximal tibia, and proximal humerus.  Tumors may also start growing in the spinal column or the pelvis.  Obviously, depending upon the extent of the tumor, these anatomic sites are much more difficult to operate upon completely eradicate the mass.

 

The different types of osteosarcoma

There are many different types of osteosarcoma that are quite different in natural history and their potential for lethal growth (table 1).  By far the most common osteosarcoma is the so called classical or conventional high grade central type which accounts for 90% of all osteosarcomas.  The “grade” is a term used to indicate the level of aggressive growth and potential for metastasis, usually based upon the appearance of the tumor under microscopic analysis.  Several other unusual high grade types are the telangiectatic, small cell and secondary (associated with another pre-existing disease such as Paget’s disease or prior radiation exposure) type.  There are low grade types of osteosarcoma too.  They include the surface or juxtacortical low grade osteosarcoma (also known by the names parosteal or periosteal osteosarcoma), and low grade central osteosarcoma.  For the most part, a simplified way to view osteosarcoma for purposes of treatment and management is into 2 groups: high grade and low grade.  Most, but not all, tumors arising from the central or medullary portion of the bone are high grade while most, but not all, tumors arising from the surface of the bone are low grade.

  

World Health Organization Classification of Osteosarcoma

A. Conventional central (medullary)
  1. Chondroblastic
  2. fibroblastic
  3. osteoblastic  
B. Telangiectatic
C. Small cell
D. Low grade central
E. Secondary
F. Surface
  1. Parosteal
  2. Periosteal
G. High grade surface
table 1

 

What is the cause of osteosarcoma and why does one have this rare cancer?

Osteosarcoma in most instances is not due to any previous behavioral, dietary, environmental, or genetic factor.  It is a random event and there is no predisposing factor or decision that a patient, parent or other family member could have made that would have any bearing on developing the tumor.  No patient or parent should believe that they somehow contributed to one’s having the tumor.  In some very rare cases, there is a genetic link to the disease (see below).

 

Is it genetic and do immediate family members need to be concerned about having the tumor too?

There are 2 instances in which there is a known genetic link for osteosarcoma.  An eye tumor known as retinoblastoma is associated with a mutation of a gene that also is associated with osteosarcoma.  In a second situation, a syndrome known as the Li-Fraumeni syndrome is characterized by an osteosarcoma occurring in one family member and a higher presence of breast cancer and other types of sarcomas in other family members.  Again a gene mutation is associated with this syndrome.  For this reason, any family history of cancers should be mentioned to a treating physician.

 

Signs or symptoms suggestive of the tumor and establishing the diagnosis

There are no particular signs or symptoms the herald the onset of this cancer.  Although patients usually will have pain and subsequent swelling of a body part, some patients do not have pain and only notice the swelling.  An injury may direct attention to a particular body part but usually the tumor precedes the injury.  If the tumor has eroded enough bone to reduce its structural integrity, a fracture may occur with only a slight amount of force applied to the bone.  A fracture greatly compromises treatment and therefore any patient experiencing pain with weight bearing (lower extremities) or lifting (upper extremities) should notify their physician immediately so that appropriate steps can be taken to minimize the risk for a fracture.  The tumor’s presence is seen on xrays most commonly and xrays are the best screening tool for this tumor.  Additional complementary information is gained from magnetic resonance imaging scansw which define the extent of the tumor and its relationship to surrounding anatomic structures much more clearly, a so called anatomic “map”.  Other tests that might be performed on newly diagnosed patients are bone scans, positron emission tomography (PET) scans, and various blood tests looking at how active the body is at making or remodeling bone tissue.

 

Once a tumor is suspected based upon imaging tests, a tissue sampling (biopsy) is necessary before embarking upon treatment plans.  The appearance of the tumor cells under the microscope is characteristic in most cases but other tests can help establish the diagnosis by ruling out other types of tumors.  Some of these other tumors’ microscopic appearance may resemble osteosarcoma so diagnosing this tumor is greatly facilitated by also viewing the imaging studies.  Having experts in the disciplines pathology, radiology and orthopaedic surgery working together as a team is the optimal means making accurate diagnoses.

 

Treatment of osteosarcoma

In the USA, and also in many other developed countries, most patients are enrolled upon various clinical trials or protocols established by national experts in osteosarcoma.  Nearly all major cancer centers work together participating in cooperative groups which gather these experts together frequently to design modify and implement these protocols.  This improves the rate of and ability of gaining meaningful information about the chances for success or level of effectiveness of a treatment plan. 

For classical, high grade, conventional osteosarcoma (and other high grade types), most major cancer centers will recommend treatment consisting of systemic multiagent chemotherapy initially for several months, followed by surgical excision with limb reconstruction or amputation, as appropriate.  Chemotherapy then resumes as soon as the surgical incision has healed sufficiently, usually around 2 weeks post-operatively, and usually continues for many more months.  The chemotherapy is given in cycles with various drugs during each cycle.  The blood cell counts drop due to the chemotherapy but recover to an adequate level in between each cycle.  The most commonly used drugs effective against osteosarcoma are adriamycin, ifosfamide, cis-platin, methotrexate, and vincristine, The response to the chemotherapy is closely observed using various tests and scans.  Frequently patients wonder why chemotherapy is given first before surgical removal of the tumor as one might think the tumor should be removed immediately.  However, giving chemotherapy prior to surgery theoretically stops the growth of microscopic deposits of tumor cells elsewhere in the body that are undetectable despite the most powerful scanners and if the chemotherapy shrinks the tumor, the surgery is greatly facilitated.  Clinical studies have not shown any drop in a treatment’s success when chemotherapy is given prior to tumor excision. 

For surface osteosarcoma (and other low grade types), chemotherapy is generally not advisable and instead surgical excision is performed with reconstruction of the remaining extremity after bone or joint loss using various types of bone grafts, prosthetic implants, or a combination of the two.  In general, radiation is not considered an effective treatment against an osteosarcoma in the usual doses given to patients.

 

Does removal of the tumor require an amputation?

Decades ago, amputations were much more commonly needed as a means of eradicating the main tumor.  Presently, however, most extremities are preserved after removing the tumor and reconstructing the remaining limb.  The tumor removal involves resecting the tumor with a layer of normal tissue surrounding it (wide local excision) so that the wound is not exposed or contaminated with tumor cells as it is gradually taken out.  To the extent possible, the nerve and major blood vessels will be preserved as long as it does not compromise an adequate tumor removal.  Reconstruction of the joint defect is done with specialized artificial joint prostheses (figure 3).  Bone is reconstructed with either a structural bone graft or a prosthetic implant.  Soft tissue and muscle function restoration, at times, requires tendon reattachment.   Major arteries can successfully be reconstructed using either autogenous vein grafts or a tube made of gortex® material.  The goal of limb salvage surgery and reconstruction is primarily complete removal of the tumor and secondarily reconstruction to achieve as normal function as possible (figure 4-5). 

Some unusually challenging situations are patients with lower extremity tumors who have yet to go through their growth spurt.  In this situation, the growing limb can either be reconstructed with an expanding type of prosthesis, the opposite limb can be shortened slightly, or an unusual surgery removing the tumor and knee but using the healthy lower ankle to function as a knee by rotating the remaining limb 180 degrees and transporting the ankle to the knee level (Van Ness rotationplasty) can be performed.

 

How effective are the treatments for osteosarcoma and what is the prognosis?

The likelihood of being alive and completely free of all osteosarcoma cancer cells 5 years after diagnosis of an osteosarcoma that hasn’t metastasized is in the range of 65-75% for nearly all major cancer centers.  The response to the chemotherapy is one of the most important predictive factors of outcome.  This response can be assessed by using xrays and scans but the more important analysis is the percentage of tumor cells killed by the chemotherapy as judged by the appearance microscopically. 

The functional outcome of treatment depends heavily upon where within the bone the tumor began and what structures must be sacrificed in order to completely remove the tumor.  Most types of reconstructions with limb salvage procedures will allow a gait independent of any aids but strenuous athletic activity is discouraged.  Any type of reconstruction will have a limited durability and lifespan.  Device failure through loosening, breakage, infection or fracture of the bone around the implant may result in a series of operations being done during the course of a patient’s lifetime. 

 

Summary

Osteosarcoma is a rare and challenging cancer to treat considering the multiple different types of this cancer and the functional consequences of partially losing a major bone or joint.  Fortunately, a multidisciplinary team approach, along with biological, surgical and technological advances has resulted in the majority of patients surviving their cancer and the majority of limbs being preserved.