About clival chordoma

What is clival chordoma?

Chordomas are very rare primary bone tumors that can arise at almost any point along the axis of the spine from the base of the skull to the sacrum and coccyx (tailbone). The incidence of chordoma in the general U.S. population is about 8 per 10,000,000 people. They occur somewhat more often in males than females and, for unknown reasons, are rare in African Americans. Under the microscope, chordoma cells appear to be benign, but because of their location, invasive nature, and recurrence rate, the tumors are considered to be malignant. They arise from cellular remnants of the primitive notochord, which is present in the early embryo. In normal mammalian development, the notochord and substances produced by it are involved in forming the tissues that give rise to vertebrae. Normally, the tissues derived from the notochord disappear after the vertebral bodies have begun forming. However, in a small percentage of people, some tissues from the notochord do not disappear. Rarely, these leftover tissues give rise to chordomas.

About one-third of chordomas are found in the region around the clivus. The clivus is a bone in the base of the skull. It is located in front of the brainstem and behind the back of the throat (nasopharynx). Chordomas occur with equal frequency in the skull base, the vertebrae and the sacrococcygeal area towards the bottom of the spine.

Symptoms of the presence of chordomas vary with their location and size. Most chordomas occur randomly among the population (sporadic). However, some people develop this tumor as a result of a mutation inherited as an autosomal dominant trait.

What are the symptoms for clival chordoma?

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).

What are the causes for clival chordoma?

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.

What are the treatments for clival chordoma?

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.

What are the risk factors for clival chordoma?

Spinal cord tumors are more common in people who have:

  • Neurofibromatosis 2. In this hereditary disorder, benign tumors develop on or near the nerves related to hearing. This may lead to progressive hearing loss in one or both ears. Some people with neurofibromatosis 2 also develop spinal canal tumors.
  • Von Hippel-Lindau disease. This rare, multisystem disorder is associated with blood vessel tumors (hemangioblastomas) in the brain, retina and spinal cord and with other types of tumors in the kidneys or adrenal glands.

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