Chondrosarcoma
Chondrosarcoma
Definition
Chondrosarcoma is a malignant tumor that arises from cells that produce cartilage, the rubbery tissue around joints. Therefore, it is a type of sarcoma that is predominantly found in the area around bones.
Description
Sarcomas of the bone are rare and represent about 0.2% of all new cancer cases each year. The two most common forms of bone cancer are osteosarcoma and Ewing's sarcoma . Among the less common are chondrosarcoma, fibrosarcoma , and malignant fibrous histiocytoma , all of which arise from spindle cell neoplasms.
Chondrosarcomas arise from chondroblasts, cells that form cartilage. Cartilage is the matrix found at the tip of the nose and ears. However, cancer that develops from chondroblasts is usually observed on the surface of the pelvis, in the femur of the upper leg, around the shoulder, in the humerus of the upper arm, and in the ribs.
Depending on the type and location of the chondrosarcoma, the tumor can either be high grade and aggressive or low grade and not as invasive. There are two different categories of chondrosarcomas—classic chondrosarcomas and variant chondrosarcomas. Together they have five main types.
Central chondrosarcoma and peripheral chondrosarcoma are both classic chondrosarcomas. Central chondrosarcoma occurs within a bone, and peripheral chondrosarcoma develops on the surface of a bone. Both can develop as a primary tumor or as a secondary tumor to an existing tumor elsewhere in the body. Most, however, are primary tumors. Seventy-six percent of primary chondrosarcomas occur centrally within a bone.
There are three variant chondrosarcomas: clear cell chondrosarcoma, mesenchymal chondrosarcoma, and dedifferentiated chondrosarcoma. Clear cell chondrosarcoma is the most rare form of chondrosarcoma. It is a low grade, slow growing tumor that typically occurs locally in the epiphysis, or end part, of long tubular bones such as the femur and humerus, meaning that it does not normally invade into surrounding soft tissue. As the name implies, cells biopsied from this type of chondrosarcoma appear clear with many large vacuoles.
Mesenchymal chondrosarcoma is another rare variant. However, as opposed to clear cell chondrosarcoma, it is highly malignant and frequently metastasizes, commonly to the lungs, lymph nodes and other bones. This variant has a tendency to develop in flat bones such as vertebra, the pelvis, or the skull, as opposed to long tubular bones. Under a microscope, the cells appear round and contain spindle cell elements and neoplastic cartilage formation.
Dedifferentiated chondrosarcoma is also rare and is the most malignant form of chondrosarcoma. It is characterized by the presence of a mix of low-grade chondrosarcoma and has undergone malignant degeneration, producing a fully malignant soft tissue mass that is no longer identifiable as cartilage. These cancers occur most commonly in the flat bones of individuals over the age of sixty. Despite varied treatments, they are almost always fatal.
Due to the location of chondrosarcoma tumors, the result is often a decrease in the range of motion of limbs, especially tumors occurring on the epiphysis of bones such as those seen in clear cell chondrosarcoma.
Demographics
Although there are exceptions, chondrosarcomas occur mainly in older adults forty to sixty years old and typically occur more in men than in women. Chondrosarcomas are rarely seen in infants and children. Dedifferentiated chondrosarcomas predominantly arise in the elderly over the age of sixty, equally between males and females. Mesenchymal chondrosarcoma develops in the young adult population between the ages of twenty and forty years old, and it is slightly more common in females. Classic chondrosarcomas usually develop in people over the age of forty. However, when they occur in younger age groups, they have a propensity to be highly malignant, capable of metastasis .
Causes and symptoms
As of 2001, there is little known about what causes chondrosarcomas. However, researchers have discovered that chondrosarcomas are sometimes associated with underlying benign bone tumors. They can also result as a side effect from previous radiation therapy for unrelated primary cancer treatment. Individuals with other bone diseases such as Maffucci's syndrome and Ollier's disease are at a higher risk for developing chondrosarcomas.
There are many symptoms associated with the onset of chondrosarcomas. They tend to develop slowly in most cases, except when the cancer is aggressive. The following is a list of the main symptoms that may present:
- pain
- swelling
- firm lump
- broken bone
- impeded normal range of motion
- urinary frequency (seen in pelvic chondrosarcomas)
- urinary obstruction (seen in pelvic chondrosarcomas)
The above symptoms are not always indicators of the presence of chondrosarcoma. Any one of these symptoms could be related to another, less serious condition. A doctor should be seen to diagnose the problem properly.
Diagnosis
In order to diagnose bone cancer, a doctor will take the patient's history and conduct a thorough physical exam. Blood tests will be performed to rule out other conditions and identify cancer markers.
The most revealing initial exam is an x ray . It can show the location, size, and shape of the tumor. If a malignant tumor is present, the x ray will expose a soft tissue mass with ill-defined edges. This procedure takes less than an hour and can be performed in the doctor's office. Depending on the medical facilities, the results can be returned the same day after being interpreted by a physician, and perhaps a consulting oncologist and radiologist.
Once there is evidence of a tumor, one or more of several other procedures may be performed, including CT scans, MRI (magnetic resonance imaging ), angiograms, and biopsy .
Treatment team
If the patient is seeing a primary care provider, the provider may perform the initial diagnostic tests. However, in order to comprehensively diagnose and treat chondrosarcomas, the primary care provider will refer the patient to an orthopaedic oncologist (bone cancer specialist). Radiologists, pathologists and orthopaedic surgeons will also be involved to read x rays, examine tissue samples, and remove the tumor if necessary.
Many other individuals will be involved with the treatment of chondrosarcoma. For example, nurses and dieticians are available to explain side effects of treatment and offer suggestions on eating healthy meals to help fight the side effects. If a limb is totally or partially removed, a physical therapist or vocational therapist will assist the patient in learning how to use a prosthetic limb.
Clinical staging, treatments, and prognosis
After the physician makes the diagnosis, it is important to determine the stage of the cancer. This will help reveal how far the cancer has progressed and how much tissue has been affected.
A new system of staging was adopted in 1980 by the Musculoskeletal Tumor Society. It is based on the fact that differing tissue types associated with the bone behave similarly when cancerous. This classification system uses grade (G), location (T), and lymph node involvement and metastasis (M).
Surgical grade (G) refers to how aggressive the cancer is. For example, G0 represents a benign tumor and G2 represents a highly aggressive tumor. The anatomical location (T) establishes whether or not the tumor is inside the bone (T1) or outside the bone (T2). If metastases are present, then the tumor is classified as M0; and if metastases are not present, the tumor is classified as M1. The following is a list of stages and their indications:
- Stage IA (G1, T1, M0): low grade within the bone, without metastasis
- Stage IB (G1, T2, M0): low grade outside the bone, without metastasis
- Stage IIA (G2, T1, M0): high grade within the bone, without metastasis
- Stage IIB (G2, T2, M0): high grade outside the bone, without metastasis
- Stage IIIA (G1 or G2, T1, M1): inside the bone, with metastasis
- Stage IIIB (G1 or G2, T2, M1): outside the bone, with metastasis
Physicians can employ several courses of treatment to remove chondrosarcomas. The most effective treatment is surgical removal. When performing the surgery, the doctor will remove the tumor and some healthy tissue or bone around it to ensure that the tumor does not recur near the original site. The physician may replace the removed bone with a metal device. In children, the metal device can be lengthened as the child grows, but this will require further surgeries. The fact that most chondrosarcomas tend to be low grade and slow-progressing makes this procedure one that does not necessitate entire limb removal except in extreme cases when the tumor is large.
Even individuals with low-grade chondrosarcoma that have undergone surgery experience a moderate risk of local recurrence. To combat recurrence, chemotherapy (the use of one or more cancer killing drugs) and radiation therapy (the use of high energy rays) have also been used to complement surgery. Employing chemotherapy or radiation therapy individually (without surgery) is much less effective. In fact, chondrosarcomas are generally resistant to chemotherapy alone.
Low stage chondrosarcomas (Stages IA and IB) have greater one and five-year survival rates than the high stages (Stages IIIA and IIIB). High-grade tumors are more aggressive and highly metastatic than lower grade tumors, and therefore they have a lower survival rate. Not only is the grade of the tumor (the estimate of its aggressiveness) important in determining prognosis, but the age of the patient is also crucial. Generally, chondrosarcomas that occur in childhood and infancy have a higher mortality rate than those that occur in adults.
Metastases appear later in the development of chondrosarcomas. The lungs are the sites of primary metastasis. Once metastasis to the lungs has occurred, survival rate decreases.
Coping with cancer treatment
Chemotherapy often results in several side effects, depending on the drug used and the patient's individual tolerance. Patients may have to deal with nausea, vomiting, loss of appetite, and hair loss. Often, chemotherapy and radiation therapy are better handled if the patient is eating well. Nurses and dieticians can aid in choosing healthful foods to incorporate into the patient's diet.
If the chondrosarcoma necessitates limb amputation , the patient will need to learn how to cope with a prosthetic device. Both physical and vocational therapists can help the patient adjust and learn to use prosthetic devices to perform daily activities in new ways.
Clinical trials
Since chondrosarcomas are rare forms of cancer, there is still much to be learned. Clearly, surgery is the most effective treatment. New techniques in cryosurgery are being developed in various institutions across the country.
Chemotherapy trials have shown improved results with more intense regimens. Such drugs that are under study include methotrexate , leucovorin , vincristine , bacillus Calmette-Guérin , doxorubicin , or a combination of two or three of these.
Patients should consult with their physicians or contact the American Cancer Society to learn what procedures are currently in clinical trials . In some cases, insurance companies will not cover clinical trial procedures. Patients should talk with their doctor and insurance company to determine which procedures are covered.
Prevention
Since little is known about what causes chondrosarcomas, there is also little known about how to prevent them. In general, the prevention of cancer can be assisted by avoiding known chemical carcinogens such as alpha-naphthylamine, carbon tetrachloride, and benzene. Another way to avoid developing cancer—especially bone cancer—is to minimize exposure to penetrating radiation such as x rays and radioactive elements. Medical x rays revolutionized the field of medicine and are used to detect and treat many diseases. In most cases, the benefits of medical x rays outweigh the risks.
Special concerns
Cancer treatments, especially surgical amputation, can take a physical and psychological toll on cancer patients and their families. To deal with the psychological impact, many different support groups and psychotherapists are available to help. Some therapists will consider amputation a post-traumatic stress disorder and treat it accordingly. Faith practices are also beneficial for cancer patients in dealing with their condition. Patients should discuss all options with their physician to determine what is available to them.
Once the cancer has been treated, patients should make sure to schedule follow-up appointments with their physicians. Physicians will want to monitor the patient for side effects or possible recurrence that may develop years after treatment.
See Also Tumor staging; Tumor grading; Limb Salvage
Resources
BOOKS
Malawer, Martin M. "Sarcomas of Bone." In Cancer Principles and Practice of Oncology, edited by Vincent T. DeVita, Jr., M.D., et al. New York: Lippincott-Raven Publishers, 1997, pp.1789-852.
Rosen, Gerald, M.D. "Neoplasms of the Bone and Soft Tissue."In Cancer Medicine, edited by Robert C. Bast, Jr., M.D., et al. London: BC Decker, Inc., 2000, pp.1870-95.
PERIODICALS
Lee, Francis, M.D., et al. "Chondrosarcoma of Bone: AnAssessment of Outcome." The Journal of Bone and Joint Surgery (March 1999): 326-38.
Mitchell, A.D., et al. "Experience in the treatment of dedifferentiated chondrosarcoma" The Journal of Bone and Joint Surgery (January 2000): 55-61.
ORGANIZATIONS
American Cancer Society. <http://www.cancer.org>.
National Cancer Institute. <http://cancernet.nci.nih.gov>.
Sally C. McFarlane-Parrott
KEY TERMS
Carcinogen
—An agent that is capable of causing cancer.
Epiphysis
—The end of long tubular bones such as femur in the leg and the humerus in the arm. Initially separated from the main bone by a layer of cartilage that eventually allows the parts to fuse.
Spindle cells
—Spindle-shaped cells typically found in connective tissue.
QUESTIONS TO ASK THE DOCTOR
- What diagnostic procedures are best for the location and type of tumor suspected?
- What treatments are best for the location and type of tumor suspected?
- What kinds of side effects will this course of treatment result?
- Are there support services available?
- What treatments are currently in clinical trials?
- What treatments will my health care insurance cover?
Chondrosarcoma
Chondrosarcoma
Definition
Chondrosarcoma is a malignant tumor that produces a special type of connective tissue called cartilage. Malignant tumors have cells that have the ability to invade and are characterized by uncontrolled growth.
Description
Cartilage is a type of connective tissue that acts as a resistant surface. Cells called chondrocytes produce cartilage. Chondrosarcoma is a malignant growth arising in chondrocytes. There are two types of chondrosarcomas, either primary or secondary. Primary chondrosarcomas arise in areas of previously normal bone that are derived from cartilage. Secondary chondrosarcomas are lesions produced from pre-existing cartilage lesions. The chondrosarcoma tumors either produce enlargement or erosion of the area involved. The lesion is classified further as to where the lesion occurs and the grade of the lesion. It is graded from 1 (low-grade) to 3 (high-grade). This classification states that the higher the grade of the tumor, the higher the increased atypia, or abnormal cell growth.
Two non-cancerous diseases, Maffuci disease and Ollier disease, are similar to chondrosarcoma. Ollier disease, also known as enchondromatosis or dyschondroplasia, is a disorder affecting the growth plates of bone where new bone is deposited. The cartilage laid down is not reabsorbed and masses form near the ends of the long bones such as the thigh bone (femur) and upper arm bone (humerus). Maffucci disease has the same abnormalities as Ollier disease as well as soft tissue destruction including the skin. Patients with Maffucci or Ollier disease should have bone scans every three to five years to monitor potential malignant transformations.
Genetic profile
Anomalies of chromosomes 5, 7, 8, and 18 and structural alterations of chromosomes 1, 12, and 15 are commonly found in patients diagnosed with chondrosarcoma. Interestingly, the gene for the area of normal cartilage production, type II collagen, has been found in the same regions as chondrosarcoma. Studies on the tumor suppressor gene, EXT1, have shown that changes (mutations) of this gene may also be important in the growth of chondrosarcoma.
Demographics
In 2001, an estimated 2,900 new cases of bone and joint cancer will be diagnosed. Primary cancer of bones accounts for less than 0.2% of all cancers. Chondrosarcoma is the second most common primary malignant bone tumor, meaning it did not originate at another site in the body. Osteosarcoma is the first most common.
There are conflicting reports as to how much more frequently men are diagnosed with chondrosarcoma than females. Findings range from twice as many males to only slightly more males than females. Chondrosarcoma occurs in people from the age of 30-70 years old, but it most commonly affects people over the age of 40. No ethnic group is affected more frequently than another.
Signs and symptoms
The signs and symptoms vary due to the type of tumor, but pain is typically the first symptom. If it is a fast growing, high grade form of chondrosarcoma, then the individual may have very severe pain. A low grade, slow growing, tumor usually has pain and swelling in the area of the tumor. If the tumor is located in the pelvis or hip area, the individual may have difficulty with urination or urinary urgency. The patient may also have the sensation of a groin pull if the tumor is in the pelvic area.
Diagnosis
Usually, chondrosarcoma is diagnosed with x ray radiography. X rays can show soft tissue calcification, where the muscles appear to be forming bone. The appearance of a soft tissue mass that has not yet calcified may also be visible. If the chondrosarcoma is secondary to another type of tumor, the chondrosarcoma may start to erode the edges of the other tumor. This is common where an enchondroma, a type of tumor within the bone shaft, is present. In this case, the chondrosarcoma produces areas of lysis, or destruction of the surrounding tissue.
Biopsy is used to determine the grade of the tumor. Grade 1 chondrosarcomas, or low-grade slow growing lesions, have a mild increase of new cell growth. Grade 3 chondrosarcomas are the opposite: they are high-grade, fast growing, and have a dramatic increase in cellular growth. The more radiolucent, or transparent to x rays, the tumor appears, the greater the chance it is a higher grade.
Other imaging tests may also be used. Computed tomography scanning, CT, is an advanced form of x ray that can also produce bone pictures and help determine how much calcification the tumor is producing. Magnetic resonance imaging, MRI, will aid diagnosis since it can differentiate soft tissues such as muscle and fat. MRI will help determine the amount of malignant degeneration of the chondrosarcoma.
Treatment and management
The main course of therapy for chondrosarcoma is surgical removal of the tumor. The amount of surgery depends on the location and the stage of the tumor. Very low-grade tumors may be surgically removed. High-grade chondrosarcomas necessitate more radical operations where normal tissue is also removed due to the possibility of spread. If the tumor is located in an extremity such as an arm or leg, then amputation, or surgical removal of the extremity, may be necessary in order to prevent metastasis, or spread of the cancer. Chemotherapy and radiotherapy may also be used depending on the type of tumor and the area of the body affected, but are usually not effective.
Prognosis
The higher the grade of a chondrosarcoma, the more likely the tumor will spread and thus worsen the prognosis. One study found the five year survival rate of patients with grades 1, 2, and 3 to be 90%, 83%, and 43% respectively. This means that five years after the diagnosis of the tumor, 90 out of 100 people with grade 1 were still alive. On the opposite spectrum, 43 out of 100 patients with grade 3 chondrosarcoma survived five years. Therefore the survival rate is very much dependent on the stage of the tumor and also on its location. Size of the tumor is also an important factor. Tumors greater than 4 in (10 cm) are more likely to become aggressive and spread. When they do spread, or metastasize, they often migrate to the lungs and skeleton.
Resources
BOOKS
Bridge, Julia A., et. al. "Sarcomas of Bone." In Clinical Oncology, 2nd ed. Edited by Martin D. Abeloff et. al. Philadelphia: Churchill Livingstone, 2000.
Levesque, Jerome, et al. A Clinical Guide to Primary Bone Tumors. Baltimore: Williams & Wilkins, 1998.
Rosenberg, Andrew E. "Skeletal System and Soft Tissue Tumors." In Robbins Pathologic Basis of Disease, 5th ed. Edited by Ramzi S. Cotran, Vinay Kumar, Stanley Robbins, and Frederick J. Schoen. Philadelphia: W. B. Saunders Company, 1994.
ORGANIZATIONS
Cancernet. National Cancer Institute, National Institutes of Health. NCI Public Inquiries Office, Building 31, Room 10A03, 31 Center Dr., MSC 2580, Bethesda, MD 20892-2580 USA.
American Cancer Society. Bone Cancer Resource Center. 1599 Clifton Road, NE, Atlanta, GA 30329. (800) 227-2345 or (404) 320-3333. <http://www.cancer.org/>.
WEBSITES
Bone Tumor Organization. <http://www.bonetumor.com/page39.html>.
Jason S. Schliesser, DC
Chondrosarcoma
Chondrosarcoma
Definition
Chondrosarcoma is a malignant tumor that produces a special type of connective tissue called cartilage. Malignant tumors have cells that have the ability to invade and are characterized by uncontrolled growth.
Description
Cartilage is a type of connective tissue that acts as a resistant surface. Cells called chondrocytes produce cartilage. Chondrosarcoma is a malignant growth arising in chondrocytes. There are two types of chondrosarcomas, either primary or secondary. Primary chondrosarcomas arise in areas of previously normal bone that are derived from cartilage. Secondary chondrosarcomas are lesions produced from pre-existing cartilage lesions. The chondrosarcoma tumors either produce enlargement or erosion of the area involved. The lesion is classified further as to where the lesion occurs and the grade of the lesion. It is graded from 1 (low-grade) to 3 (high-grade). This classification states that the higher the grade of the tumor, the higher the increased atypia, or abnormal cell growth.
Two non-cancerous diseases, Maffuci disease and Ollier disease, are similar to chondrosarcoma. Ollier disease, also known as enchondromatosis or dyschondroplasia, is a disorder affecting the growth plates of bone where new bone is deposited. The cartilage laid down is not reabsorbed and masses form near the ends of the long bones such as the thigh bone (femur) and upper arm bone (humerus). Maffucci disease has the same abnormalities as Ollier disease as well as soft tissue destruction including the skin. Patients with Maffucci or Ollier disease should have bone scans every three to five years to monitor potential malignant transformations.
Genetic profile
Anomalies of chromosomes 5, 7, 8, and 18 and structural alterations of chromosomes 1, 12, and 15 are commonly found in patients diagnosed with chondrosarcoma. Interestingly, the gene for the area of normal cartilage production, type II collagen, has been found in the same regions as chondrosarcoma. Studies on the tumor suppressor gene, EXT1, have shown that changes (mutations) of this gene may also be important in the growth of chondrosarcoma.
Demographics
In 2001, an estimated 2,900 new cases of bone and joint cancer were diagnosed. Primary cancer of bones accounts for less than 0.2% of all cancers. Chondrosarcoma is the second most common primary malignant bone tumor, meaning it did not originate at another site in the body. Osteosarcoma is the first most common.
There are conflicting reports as to how much more frequently men are diagnosed with chondrosarcoma than females. Findings range from twice as many males to only slightly more males than females. Chondrosarcoma occurs in people from the age of 30-70 years old, but it most commonly affects people over the age of 40. No ethnic group is affected more frequently than another.
Signs and symptoms
The signs and symptoms vary due to the type of tumor, but pain is typically the first symptom. If it is a fast growing, high grade form of chondrosarcoma, then the individual may have very severe pain. A low grade, slow growing, tumor usually has pain and swelling in the area of the tumor. If the tumor is located in the pelvis or hip area, the individual may have difficulty with urination or urinary urgency. The patient may also have the sensation of a groin pull if the tumor is in the pelvic area.
Diagnosis
Usually, chondrosarcoma is diagnosed with x ray radiography. X rays can show soft tissue calcification, where the muscles appear to be forming bone. The appearance of a soft tissue mass that has not yet calcified may also be visible. If the chondrosarcoma is secondary to another type of tumor, the chondrosarcoma may start to erode the edges of the other tumor. This is common where an enchondroma, a type of tumor within the bone shaft, is present. In this case, the chondrosarcoma produces areas of lysis, or destruction of the surrounding tissue.
Biopsy is used to determine the grade of the tumor. Grade 1 chondrosarcomas, or low-grade slow growing lesions, have a mild increase of new cell growth. Grade 3 chondrosarcomas are the opposite; they are high-grade, fast growing and have a dramatic increase in cellular growth. The more radiolucent or transparent to x rays the tumor appears, the greater the chance it is a higher grade.
Other imaging tests may also be used. Computed tomography scanning, CT, is an advanced form of x ray that can also produce bone pictures and help determine how much calcification the tumor is producing. Magnetic resonance imaging, MRI, will aid diagnosis since it can differentiate soft tissues such as muscle and fat. MRI will help determine the amount of malignant degeneration of the chondrosarcoma.
Treatment and management
The main course of therapy for chondrosarcoma is surgical removal of the tumor. The amount of surgery depends on the location and the stage of the tumor. Very low-grade tumors may be surgically removed. High-grade chondrosarcomas necessitate more radical operations where normal tissue is also removed due to the possibility of spread. If the tumor is located in an extremity such as an arm or leg, then amputation, or surgical removal of the extremity, may be necessary in order to prevent metastasis, or spread of the cancer. Chemotherapy and radiotherapy may also be used depending on the type of tumor and the area of the body affected, but are usually not effective.
Prognosis
The higher the grade of a chondrosarcoma, the more likely the tumor will spread and thus worsen the prognosis. One study found the five year survival rate of patients with grades 1, 2, and 3 to be 90%, 83%, and 43% respectively. This means that five years after the diagnosis of the tumor, 90 out of 100 people with grade 1 were still alive. On the opposite spectrum, 43 out of 100 patients with grade 3 chondrosarcoma survived five years. Therefore the survival rate is very much dependent on the stage of the tumor and also on its location. Size of the tumor is also an important factor. Tumors greater than 4 in (10 cm) are more likely to become aggressive and spread. When they do spread, or metasta-size, they often migrate to the lungs and skeleton.
Resources
BOOKS
Bridge, Julia A., et. al. "Sarcomas of Bone." In Clinical Oncology, 2nd ed. Edited by Martin D. Abeloff et. al. Philadelphia: Churchill Livingstone, 2000.
Levesque, Jerome, et al. A Clinical Guide to Primary Bone Tumors. Baltimore: Williams & Wilkins, 1998.
Rosenberg, Andrew E. "Skeletal System and Soft Tissue Tumors." In Robbins Pathologic Basis of Disease, 5th ed. Edited by Ramzi S. Cotran, Vinay Kumar, Stanley Robbins, and Frederick J. Schoen. Philadelphia: W. B. Saunders Company, 1994.
ORGANIZATIONS
American Cancer Society. Bone Cancer Resource Center. 1599 Clifton Road, NE, Atlanta, GA 30329. (800) 227-2345 or (404) 320-3333. <http://www.cancer.org/>.
Cancernet. National Cancer Institute, National Institutes of Health. NCI Public Inquiries Office, Building 31, Room 10A03, 31 Center Dr., MSC 2580, Bethesda, MD 20892-2580 USA.
WEBSITES
Bone Tumor Organization. <http://www.bonetumor.com/page39.html>.
Jason S. Schliesser, DC