Information on the following diseases can be found in the Related Disorders section of this report:

• Chondrosarcoma

Symptoms vary with the location of the tumor and from person to person. If the chordoma is located near the top of the spine or the base of the brain, headaches and changes caused by compression of cranial nerves may occur. The symptoms that result from compression of the cranial nerves are called "palsies". Other signs, less frequently encountered, are difficulty in swallowing, facial pain, partial facial paralysis, double vision, loss of hearing and problems with balance (ataxia).

If the chordoma is located at a vertebra of the spine, the symptoms will vary according to the location of the involved vertebra. As more bone becomes involved and degenerates, the symptoms will increase in intensity. Symptoms from spinal chordomas can be subtle and the tumor may take considerable time to be diagnosed. The more frequent signs are lower back pain without distinguishing characteristics and constipation. Other symptoms may include radiating pains in the leg and urinary complaints, such as not being able to control the flow of urine.

Most chordomas arise from remnant cells of the embryonic notochord, the precursor of the vertebrae and discs between the vertebrae. How and why these cells become malignant is not clear. However, there is a rare familial form of the disorder that is genetically transmitted as an autosomal dominant trait. Studies have pinpointed the mutated gene to the long arm of chromosome 7 at Gene Map Locus 7q33.

Chromosomes, which are present in the nucleus of every human cell, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. These consist of 22 pairs of human chromosomes of which each member of a pair looks the same under a microscope and carries the same genes. The pairs are numbered from 1 through 22. The 23rd pair consists of two sex chromosomes. The sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 7q33" refers to band 33 on the long arm of chromosome 7. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Dominant genetic disorders are generally quite rare, because the gene changes that cause them are rare in the population. If a disorder is caused by a dominantly inherited gene change or mutation, this means that only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new gene change (mutation) in the affected individual. This change usually occurs during embryonic development. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Chordomas are more frequently found in males than in females by a factor of about 2:1. Most chordomas are diagnosed in people who are between 50 and 60 years of age but the tumors can occur much earlier and much later. In general, children and females are more likely to have skull base tumors and males are more likely to have sacral tumors.

Chondrosarcomas are the second most frequent primary malignant tumor of bone, representing approximately one-quarter (25%) of all primary bone neoplasms. Chondrosarcomas present with widely varying features and behavior patterns, ranging from slow-growing non-metastasizing lesions to highly aggressive metastasizing cancers. They are classified as central (originating within the marrow hollow of bone) or peripheral. Even more rarely, they may arise as lesions adjacent to the cortex.

Diagnosis
For chordomas located in or near the skull base, imaging techniques such as magnetic resonance imaging (MRI) studies or CT scans are useful to make a tentative diagnosis but microscopic examination of tumor tissue obtained through a biopsy (surgery to obtain a small piece of tumor) or surgery to remove the tumor is essential to make a definitive diagnosis. Chordomas located within or near vertebrae, or the sacrum or coccyx, will usually be seen best using either MRI or CT scans, but diagnosis must be based on examining a piece of tumor tissue removed during surgery under the microscope.

Treatment
Surgery is the primary form of treatment for chordoma with the goal being to remove all visible tumor. This is very difficult to do because of the location of most chordomas. Local recurrence (regrowth of tumor at the site of surgery) after surgical treatment is not uncommon; to prevent this from happening, radiation therapy is often given. The spread of tumor beyond its first location is uncommon, occurring in only about 10±% of cases.

The National Cancer Institute is sponsoring a study of families with two or more relatives with chordoma under a clinical protocol entitled Genetic, Clinical, and Epidemiological Study of Individuals and Families at High Risk of Cancer. Chordoma is only one of many tumors being studied under this protocol. The goal of the study of families with multiple relatives with chordoma is to identify genes that increase risk for chordoma in very rare families. The knowledge that is gained by studying "chordoma genes" should apply to chordomas that occur in the general population.

Among the objectives of the study of chordoma families are to: (1) Evaluate and define the clinical spectrum of familial chordoma; (2) Quantify risks of tumors in family members; (3) Map, clone, and determine function of chordoma tumor susceptibility genes. For further information, interested persons are asked to call the referral nurse at 800-518-8474. The protocol chair for this study is Dr. Margaret Tucker (Tel: 301-496-4375). The principal investigator is Dr. Dilys Parry (Tel: 301-496-4948).

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, go to:
www.centerwatch.com

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Chordoma; CHDM. Entry Number; 215400: Last Edit Date; 3/18/2004.

TEXTBOOKS
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Berkow R, ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:520.

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REVIEW ARTICLES
St. Martin M, Levine SC. Chordomas of the skull base: manifestations and management. Curr Opin Otolaryngol Head Neck Surg. 2003;11:324-27.

Erdem E, Angtuaco EC, Van Hemert R, et al. Comprehensive review of intracranial chordoma. Radiographics. 2003;23:995-1009.

Kay PA, Nascimento AG, Unni KK, et al. Chordoma. Cytomorphologic findings in 14 cases diagnosed with fine needle aspiration. Acta Cytol. 2003;47:202-08.

Dow GR, Robson DK, Jaspan T, et al. Intradural cerebellar chordoma in a child: a case report and review of the literature. Childs Nerv Syst. 2003;19:181-91.

JOURNAL ARTICLES
Casali PG, Messina A, Stacchiotti S, et al. Imatinib mesylate in chordoma. Cancer. 2004 Sep 15 [Epub ahead of print]

Fourney DR, Gokaslan ZL. Current management of sacral chordoma. Neurosurg Focus. 2003;15:E9.

Yamaguchi T, Suzuki S, Ishiiwa H, et al. Intraosseous benign notochordal cell tumors: overlooked precursors of classic chordomas? Histopathology. 2004;44:597-602.

Yamaguchi T, Suzuki S, Ishiiwa H, et al. Benign notochordal cell tumors: A comparative histological study of benign notochordal cell tumors, classic chordomas, and notochordal vestiges of fetal invertebral discs. Am J Surg Path. 2004;28:756-61.

Kurtsoy A, Menku A, Tucer B, et al. Transbasal approaches: surgical details, pitfalls and avoidances. Neurosurg Rev. 2004 Apr 8 [Epub ahead of print]

Pamir MN, Kilic T, Ture U, et al. Multimodality management of 26 skull-base chordomas with 4-year mean follow-up: experience at a single institution. Acta Neurochir (Wien). 2004;146:343-56.

Alvarado R, Gomez J, Morale SG, et al. Neckpain: common complaint uncommon diagnosis—symptomatic clival chordoma. South Med J. 2004;97:83-86.

Boneschi V, Tourlaki A, Parafioriti A, et al. Chordoma cutis. Eur J Dermatol. 2003;23:593-95.

Stark AM, Mehdorn HM. Chondroid Clival Chordoma. N Engl J Med. 2003;349:e10.

McMaster ML, Goldstein AM, Bromley CM, et al. Chordoma: incidence and survival patterns in the United States, 1973-1995. Cancer Causes and Control 2001;12:1-11.

FROM THE INTERNET
Palmer CA. Chordoma. emedicine. Last Updated: October 2, 2001. 8pp.
www.emedicine.com/med/topic2993.htm

Peretti P, Brunel H, Borrione F. Chordoma. emedicine. Last Updated: August 30, 2002. 17pp.
www.emedicine.com/radio/topic169.htm

Parry DM, McMaster ML, Zametkin D. Familial Chordoma. NCI. Division of Cancer Epidemiology and Genetics. November 2003. 4pp.
http://dceg.cancer.gov/chordoma-overview.html