Chordoma

Chordoma is a rare type of bone cancer that grows slowly but can be very difficult to treat because it develops in delicate areas near the spine and skull, close to critical structures like the brain, spinal cord, and major blood vessels.

Table of contents

• What is chordoma?
• Where chordomas occur
• Types of chordoma
• Who gets chordoma
• Symptoms
• Causes and risk factors
• Diagnosis
• Treatment
• Prognosis and recurrence

What is chordoma?

Chordoma is a rare malignant (cancerous) bone tumor that forms in the spine or at the base of the skull. The word malignant means the tumor can spread and is dangerous to health. Chordoma is a type of cancer called a sarcoma, which is a cancer that starts in bones or soft tissues^[1].

These tumors develop from leftover cells that helped form the spine before birth. During early development in the womb, a structure called the notochord helps organize and form tissues, and eventually becomes part of the discs between the bones of the spine. Usually, any leftover notochord cells disappear soon after a baby is born. But sometimes a few cells remain, and very rarely—in about 1 in 1 million people—these leftover cells eventually become cancerous^[2][3].

Chordomas typically grow slowly. However, they are complicated tumors to treat because they grow very close to important structures such as the brainstem, spinal cord, and major nerves and blood vessels^[3][4].

Where chordomas occur

Chordomas can develop at any point along the spine, from the base of the skull down to the tailbone. They most commonly occur in two main locations^[1]:

• About 35% develop at the base of the spine in a bone called the sacrum (the triangular bone at the bottom of the spine between the hip bones)
• About 35% develop where the spine meets the skull, called the skull base. These are often called clival chordomas because they involve a bone called the clivus
• About 30% develop in the moving parts of the spine between the skull and sacrum—most commonly in the neck (cervical spine), followed by the lower back (lumbar spine) and then the mid-back (thoracic spine)

Chordomas account for approximately 20% of primary spinal tumors and about 3% of all bone tumors. They are the most common tumor of the sacrum and cervical spine^[3][4].

Types of chordoma

Medical experts recognize three main types of chordoma based on how the cells look under a microscope^[1][2]:

Classic or conventional chordoma is the most common type, making up 80% to 90% of all cases. Under a microscope, it is made up of a unique type of cell that looks “bubbly,” similar to soap bubbles in a slimy mixture. A variant called chondroid chordoma makes up 5% to 15% of cases and includes tissue that looks similar to cartilage. Chondroid chordoma often forms in the base of the skull^[1][5].

Dedifferentiated chordoma is a rare type, making up less than 5% to just under 10% of cases. It appears as a mix of abnormal cells under a microscope. This type is more aggressive, grows faster, and is more likely to spread to other parts of the body than conventional chordoma^[1][2].

Poorly differentiated chordoma is very rare, with fewer than 60 cases recorded in medical literature. It is characterized by the deletion of a gene called SMARCB1 (also known as INI1). This type most commonly affects children and young adults^[1].

Who gets chordoma

Chordomas can develop in anyone at any age, from infancy to very old age. However, they are most likely to occur in adults aged 40 to 80, with the typical age being the mid-50s. About 5% of cases affect children^[1][4].

Men are approximately 1.5 to 2 times as likely to have a chordoma as women. The disease does not appear to favor any particular ethnicity or geographic region, although it is slightly less common in people of Black African descent^[1][4].

Chordomas are extremely rare. They affect about 1 person for every 1 million people per year. That means about 300 people receive a chordoma diagnosis each year in the United States, and approximately 500 people in the United Kingdom are currently living with the disease^[1][3].

Symptoms

Chordoma usually grows slowly, often without symptoms at first, and then might cause symptoms for years before doctors find it. As the tumor grows, it puts pressure on nearby areas of the spinal cord or brain, and this pressure causes symptoms. The symptoms vary depending on where the tumor is located along the spine^[1][3].

General symptoms of chordoma can include pain, weakness, and numbness in the back, arms, or legs^[1].

When a chordoma develops at the base of the skull, symptoms may include^[1][6]:

• Double vision or blurred vision
• Headaches
• Facial numbness or pain
• Occasionally, problems with facial movement, speech, or swallowing

When a chordoma develops in the neck, it may cause hoarseness of the voice or difficulty swallowing^[6].

When a chordoma develops in the tailbone or lower back, symptoms may include^[1][6]:

• A lump that can be felt through the skin
• Problems with bladder or bowel function
• Low back or tailbone pain
• Numbness or weakness in the legs

Because the symptoms can be similar to other common problems such as back pain, and given that chordoma is so rare, it often takes a long time for a definitive diagnosis to be made. Most general doctors will never meet a patient with chordoma during their career^[6].

Causes and risk factors

Researchers do not know exactly why chordomas form. They believe that changes (called mutations) in a gene called TBXT (also known as brachyury) are likely involved. More than 95% of individuals with chordoma have a single-letter variation in the DNA sequence of this gene, which increases the risk of developing chordoma. However, this variation does not by itself cause chordoma. In fact, a large portion of the general population has this variation, but people who have it are still very unlikely to develop chordoma—the chances are less than 2 in a million^[1][3][4].

There are no known environmental, dietary, or lifestyle risk factors for chordoma^[3].

The vast majority of chordomas occur randomly and are not inherited. However, there are a handful of known cases where multiple members of the same family are affected by chordoma. This is called familial chordoma and is extremely rare, with an estimated rate of 0.4% of all chordomas. In some of these families, an extra copy of the brachyury gene has been found, but there is currently no available test for the presence of extra copies of the gene^[3][5].

Chordomas have been reported at a higher rate in children with a genetic disease called Tuberous Sclerosis Complex (TSC). Changes in either of two genes involved in this condition (TSC1 and TSC2) can cause a predisposition to developing chordoma^[3][5].

Diagnosis

To diagnose chordoma, doctors will perform a physical examination and ask questions about your health history. They will then use imaging tests and take a sample of tissue for laboratory testing^[8].

Imaging tests create pictures of the inside of the body. Chordomas are best seen on MRI scans (magnetic resonance imaging), particularly a type called T2 weighted images. MRI scans are better at showing tumors and the blood vessels and tissues around them. CT scans (computed tomography) are best for seeing bone changes, such as holes or weak spots in the bone. Sometimes a special dye called contrast medium is used during these scans to make certain areas show up better^[8].

Biopsy is a procedure to remove a sample of tissue for testing in a laboratory. A biopsy is essential to confirm whether what is seen on imaging is actually chordoma, because chordoma can look like other conditions that need different treatments. Establishing the correct diagnosis before starting treatment is critical^[8].

For chordomas in the spine and sacrum, the biopsy should be done using a needle inserted through the skin, guided by CT imaging. This approach reduces the risk of spreading tumor cells. The biopsy should be planned so that the tissue along the path the needle takes to the tumor can be removed later with the tumor, if possible. Chordomas at the base of the skull are not usually biopsied beforehand unless radiation is the only planned treatment^[8].

Treatment

Newly diagnosed chordoma is almost always treated with some combination of surgery and radiation. The best treatment for chordoma is to remove it completely in one piece with clean edges (called negative margins), leaving only healthy tissue. This is called en bloc resection. Patients who receive this treatment have the best chance of living disease-free or even being cured^[13].

Surgery

Surgery is the standard and most important treatment for chordoma. The type of surgery depends on where the tumor is located and how big it is^[13][14].

Wide resection (also called en bloc resection or wide excision) removes the bone tumor and a small amount of tissue and bone around it. This is the main surgical method used to treat chordoma^[14].

Curettage is a procedure that uses a spoon-shaped tool with a sharp edge to scrape a tumor out of the bone. After curettage, the surgeon may use a special bone cement that heats up as it hardens to fill the hole left in the bone and destroy any remaining cancer cells. Curettage may be used in areas where a wide resection cannot be done safely, such as in the skull or spine^[14].

Surgery can be difficult because chordomas grow very close to the spinal cord, blood vessels, nerves, and brain. One or more surgeries may be needed. The surgery plan will be based on the location, shape, and size of the tumor^[1][3].

Radiation therapy

Radiation therapy uses high-energy rays or particles to destroy cancer cells. The most important thing to know about radiation for chordoma is that it needs a high dose of radiation to be controlled^[13].

Radiation therapy may be used to^[1][6][14]:

• Destroy any cancer cells left behind after surgery
• Treat chordomas that cannot be removed with surgery

A special type of radiation therapy called proton beam radiation is often used because it can deliver high doses more precisely to the tumor while protecting nearby healthy tissue^[4].

Drug therapy

Drug therapy (also called systemic therapy) uses treatments that spread throughout the body to kill cancer cells wherever they are located. Since surgery and radiation are the recommended treatments for newly diagnosed chordoma, drug therapy is usually only used to treat tumors that can no longer be adequately treated with surgery or radiation, or tumors that have spread to other parts of the body. Drug therapies may also be considered if the tumor is growing rapidly, or if it is the poorly differentiated or dedifferentiated type^[10][13].

Currently, no drug therapies have been approved by government agencies like the U.S. Food and Drug Administration specifically for the treatment of chordoma. However, in some countries, doctors are allowed to prescribe treatments to chordoma patients that have been approved for other cancers. This is called “off-label” use. The most common drugs used include imatinib and other targeted therapies^[10][12][14].

Traditional chemotherapy has not been shown to be very effective for chordoma^[12].

All drug therapies carry the risk of side effects, ranging from mild to severe. These can include low blood counts, hair loss, nausea, fatigue, organ damage, vomiting, diarrhea, liver problems, high blood pressure, and issues with hair, skin, and nails^[10].

Clinical trials

Clinical trials are carefully monitored research studies that test new treatments. They are important options for chordoma patients to consider. It may be possible for patients to receive certain therapies by participating in clinical trials^[10][13].

Prognosis and recurrence

Overall 5-year survival for chordoma is approximately 50%, although this varies depending on the location of the tumor and how completely it can be removed^[4].

Chordomas tend to come back (recur) after treatment, usually in the same place as the first tumor. This is called local recurrence. The tumor comes back in a large percentage of patients even after treatment^[1][3].

In about 30% to 40% of cases, the tumor eventually spreads (metastasizes) to other parts of the body. When chordoma does spread, it most commonly goes to the lungs, nearby lymph nodes, other bones, liver, or skin^[1][3].

Treatment for chordoma that comes back may include one or more of the following: surgery, radiation therapy, cancer drugs, or other specialized treatments^[6].

Patients with chordoma need regular follow-up appointments and monitoring after treatment finishes. You usually have an examination at each appointment, and doctors will ask how you are feeling, whether you have had any symptoms or side effects, and if you are worried about anything. You also have regular MRI scans. How often you have check-ups depends on your individual situation^[6].