NORD gratefully acknowledges Justin M. M. Cates, MD, PhD, Professor of Pathology, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, for assistance in the preparation of this report.
A chordoma is a rare tumor that develops in the bones of the skull and the spine. These tumors arise from the remnants of the notochord, a flexible, rod-like structure that provides support to the developing embryo. During fetal development, the notochord is replaced by the bones of the spine. Notochordal cells that persist within the spinal column may give rise to chordoma. Chordomas are slow growing tumors that cause destruction of the surrounding bone and eventually extend into the surrounding soft tissue. Sometimes chordoma spreads through the bloodstream (metastasizes) to other organs, such as the lungs, lymph nodes, liver or other bones. Although chordoma can develop at any point during life, it most commonly occurs in older adults. The symptoms associated with a chordoma depend upon the size and location of the tumor. Almost all cases of chordoma occur randomly for no apparent reason. In extremely rare cases, chordomas may develop in multiple members of the same family as a result of certain genetic risk factors (familial chordoma).
Chordomas may be classified as a type of sarcoma. Sarcoma is a general term for a group of cancers that can affect bone or connective tissue – the tissues that connect, support and surround various structures and organs in the body. Although chordomas are primary bone tumors, they are sometimes classified as central nervous system tumors when they occur near the skull base.
A chordoma can develop anywhere along the spine from the base of the skull to the tailbone (coccyx). The most common locations for a chordoma are at the triangular bone near the base of the spine (sacrum), the coccyx, and the clivus, which is a bone in the base of the skull. The clivus is located in front of the brainstem and behind the back of the throat.
Symptoms vary from one person to another and depend in part upon the location and size of the tumor. Chordomas located in the lower spine may be associated with lower back pain and tenderness, pain the legs, weakness and numbness in the lower back or legs, and abnormalities affecting the bladder and intestines including loss of bladder control (urinary incontinence) and/or loss of bowel control. In some cases, a mass may be felt (palpable) over the small of the back.
Chordomas of the skull base (cranial chordomas) can be associated with double vision (diplopia), headaches, and/or facial pain. Paralysis (palsy) of certain facial nerves can also occur, resulting in swallowing difficulties, speech and voice abnormalities, and abnormal eye movements.
In some cases, an intracranial chordoma can block the flow of cerebrospinal fluid (CSF), causing CSF to accumulate in the skull and putting pressure on the brain (hydrocephalus). Hydrocephalus can cause several symptoms that differ based upon age. In infants, it can cause bulging at the soft spots on the skull, an increase in head circumference, and downward casting of the eyes (sunsetting). In older children, it can cause nausea, vomiting, sleepiness, double vision, rapid eye movements and difficulties with balance. In adults, it can also cause headaches, changes in personality, and difficulty focusing the eyes.
Chordomas in the area immediately below the skull (cervical spine) can cause neck pain, hoarseness, difficulty swallowing (dysphagia), and, less often, bleeding from the voice box (laryngeal bleeding).
The underlying causes of chordoma are unknown. Most cases arise spontaneously and are not due to an inherited genetic change. A prevailing theory is that acquired genetic abnormalities or mutations result in cancerous growth of notochordal remnants. These genetic abnormalities may arise spontaneously for unknown reasons or, more rarely, be inherited.
Both non-familial and familial chordomas have been linked to the T gene located on the long arm of chromosome 6 (6q27). This gene creates (encodes) a protein known as transcription factor T or brachyury homologue. This protein is important in the development of the notochord and is highly expressed in the chordoma cells.
Most individuals with a sporadic chordoma have a single nucleotide polymorphism (SNP) in the T gene. SNPs are the most common genetic variation in humans and occur frequently in a person’s DNA. Most SNPs have no effect on a person’s health. The SNP in the T gene has been identified in over 80% patients with sporadic chordoma (compared to around 50% of people without chordoma), and therefore is believed to convey a predisposition to developing chordoma. However, since this SNP is common in the general population and most people who have it do not develop chordoma additional factors are thought to be necessary for the development of chordoma.
Researchers have also learned that many familial chordomas are due to a specific chromosomal abnormality known as a duplication, in which three copies of the T gene are present instead of two. This extra copy of the T gene seems to be associated with a strong genetic predisposition to developing a chordoma.
Abnormalities on chromosome 7 have been studied as potential cause of familial and non-familial chordoma. Multiple additional complex chromosomal abnormalities (involving chromosomes 1p, 3, 4, 9p, 9q, 10, and 13) have been identified in some tumors as well. Whether these various abnormalities play a role in the development of a chordoma in specific cases is unknown. Further research is necessary to determine the complex mechanisms responsible for the development of a chordoma.
Chordomas can affect individuals of any age, including young children, but most often are diagnosed in individuals between 40-75 years of age (the average age at diagnosis is 55 years). Collectively, chordomas affect males more often than females by a ratio of approximately 2:1. However, skull base tumors have an equal (1:1) gender distribution. Children are more likely to have skull base tumors. Chordomas account for approximately 1-4% of all malignant bone tumors and around 20% of primary tumors of the spinal column. The incidence of chordoma is estimated to be approximately 1 per 1,000,000 people. About 300 new cases of chordoma are diagnosed in the United States each year. Some reports state that these tumors are more common in individuals of European ancestry.
The symptoms of chordoma are not specific. Therefore the diagnosis is based on characteristic radiologic pathologic findings.
Clinical Testing and Workup
Plain x-rays (radiography) or other specialized imaging techniques may be used to diagnose a chordoma. Such specialized imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI). During CT scanning, a computer uses x-rays to create cross-sectional images of the body. An MRI uses magnetic fields and radio waves to produce cross-sectional images. These imaging techniques may be used to detect the presence of a tumor and can evaluate the size, location, and local extension of the tumor, which help surgeons plan any surgical procedures that may be indicated for treatment.
A core needle or incisional biopsy is necessary to confirm a diagnosis of chordoma. During this procedure, a physician inserts a needle through the skin and into the tumor to obtain a small sample of cells. In some cases, a surgical procedure is necessary to procure enough tissue for diagnosis. A pathologist examines the tissue sample under a microscope to determine the specific type of tumor present.
Treatment usually requires the coordinated effort of a team of specialists. Physicians who specialize in the diagnosing and treatment of cancer (oncologists), physicians who specialize in using ionizing radiation to treat cancer (radiation oncologists), neurosurgeons, physicians who specialize in the diagnosis and treatment of the musculoskeletal system (orthopedic surgeons), and other healthcare professionals need to systematically and comprehensively plan an affected person’s treatment.
Specific therapeutic procedures and interventions may vary depending upon numerous factors such as disease stage, tumor size and location, specific tumor subtype, the presence or absence of certain symptoms, and the age and general physical health of the patient. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team together with the patient. Thorough discussions of the potential benefits and risks of specific therapies, including possible side effects are helpful in allowing the patient to make an informed decision regarding his or her preferred therapy.
Treatment for chordoma usually involves surgery to remove as much as the tumor as possible while preserving neurological function and quality of life. Because these tumors are located near the brain or in the spinal cord, surgical removal may be difficult and the surgeon may not be able to remove the entire tumor despite multiple operations. Removing the entire tumor through surgery in one piece (total en bloc resection) is possible for only approximately 50% of sacral chordomas. The percentage is even lower in chordomas of the spine and skull base. Clival chordomas can rarely be removed through en bloc resection, and often require other advanced neurosurgical techniques.
Radiation therapy is often used in conjunction with surgery to treat a chordoma and lower the risk of recurrence. Unfortunately, chordomas are generally resistant to radiation therapy and high doses of radiation are often necessary.
A chordoma may recur despite successful treatment with surgery and radiation. Recurrence is common and may require additional surgical and/or radiation therapy.
Referral to a specialized cancer center with physicians who have experience in diagnosing, treating, and managing chordoma patients is strongly recommended.
Chemotherapy and targeted drug therapies are being investigated as potential therapies for individuals with chordoma. Newer radiation therapy techniques designed to better protect and preserve surrounding, healthy tissue are also being investigated. More research is necessary to determine the long-term safety and effectiveness of investigational therapies.
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