Introduction: Who Should Undergo Diagnostics and When

Chordoma is a rare type of bone cancer that grows in the spine or the base of the skull. Because it is so uncommon—affecting only about 1 person in 1 million each year—many people live with symptoms for months or even years before receiving the correct diagnosis. This delay happens partly because the early signs of chordoma can look like everyday health problems that most doctors see regularly, such as persistent back pain, headaches, or neck discomfort.^[1]

Anyone experiencing ongoing symptoms that don’t improve with time or standard treatment should consider seeking diagnostic evaluation. If you notice persistent pain in your lower back, tailbone, or neck that doesn’t go away, numbness or weakness in your arms or legs, or problems with bladder or bowel function, it’s important to talk to your doctor. For tumors at the base of the skull, symptoms might include double vision, blurry vision, headaches, or facial numbness. If you feel a lump you can touch through the skin near your tailbone, this is also a reason to seek medical attention.^[1]

Young adults and children with unexplained symptoms should also be evaluated, even though chordoma most commonly affects people between ages 50 and 80. About 5% of chordoma cases occur in children, and the poorly differentiated type of this cancer is more common in younger people.^[1] Men are about 1.5 times more likely than women to develop chordoma, but it can affect anyone regardless of age, sex, or background.^[1]

Diagnostic Methods for Identifying Chordoma

Getting the right diagnosis for chordoma involves several steps and different types of tests. Because this tumor is rare, and because it can look similar to other conditions on imaging scans, a combination of methods is needed to confirm the diagnosis and understand the full extent of the disease.

Physical Examination and Medical History

The diagnostic process typically begins with a thorough physical exam conducted by a healthcare professional. During this exam, your doctor will ask detailed questions about your symptoms, when they started, how they have changed over time, and your overall health history. The doctor will also perform a physical examination to check for any visible or palpable signs of the tumor, such as a lump near the tailbone, and will assess your neurological function by testing your reflexes, strength, sensation, and coordination.^[8]

Imaging Tests

Imaging tests are the cornerstone of chordoma diagnosis. These tests create detailed pictures of the inside of your body, allowing doctors to see the tumor, understand its size and location, and determine how it might be affecting nearby structures like nerves, blood vessels, and the spinal cord.

Magnetic Resonance Imaging (MRI) is the most important imaging test for diagnosing chordoma. An MRI uses powerful magnets and radio waves to create detailed images of soft tissues in the body. When a chordoma is suspected, you will need an MRI to help doctors make a diagnosis and plan for treatment. MRI scans are particularly good at showing tumors and the tissues around them, including muscles, nerves, and blood vessels. On an MRI, chordomas usually appear as bright spots with darker areas inside them. Doctors often use special types of MRI images, particularly T2-weighted images, to see chordomas most clearly.^[6][17]

Computed Tomography (CT) scans are another key imaging tool. CT scans use X-rays and computer technology to create three-dimensional images of your body. While MRI is better for viewing soft tissues, CT scans excel at showing bone changes. They can reveal holes or weak spots in the bone caused by the tumor, and they can show if the tumor has spread to areas near the skull or neck bones. CT scans can also help doctors see if the tumor has damaged the surrounding bone structure. Sometimes, a special dye called contrast medium is injected into your vein before the scan. This dye appears bright on the images and helps certain areas show up more clearly.^[8][17]

Other imaging tests may be used in specific situations. PET scans (positron emission tomography) can sometimes help doctors see how active the tumor is, though chordomas don’t always show up clearly on these scans.^[17] Regular X-rays may be performed initially but are less useful for diagnosing chordoma because they don’t provide enough detail about soft tissues.

Biopsy: Confirming the Diagnosis

While imaging tests can strongly suggest chordoma, a biopsy is essential to confirm the diagnosis. A biopsy is a procedure in which a small sample of tissue is removed from the tumor and examined under a microscope by a specialist called a pathologist. This is the only way to definitively determine whether the tumor is chordoma and not another condition that might look similar on imaging scans.^[8]

There are two main ways to perform a biopsy for chordoma. A needle biopsy involves inserting a thin needle through the skin and into the tumor to collect tissue samples. This is often done with CT imaging guidance to ensure the needle reaches exactly the right spot. For tumors in the spine or sacrum (the bone at the base of the spine), this needle-through-the-skin approach is preferred because it reduces the risk of spreading tumor cells along the needle’s path. Modern biopsy needles often have a dual-needle design—one needle inside another—which further reduces the chance of tumor cells escaping.^[17]

An open biopsy is performed during surgery, where the doctor makes an incision and removes a piece of tissue directly. This method is less commonly used for chordoma unless the tumor is being removed at the same time. For tumors located at the base of the skull (clival chordomas), biopsies are not always performed before treatment unless radiation therapy is the only planned treatment option.^[17]

The biopsy should always be carefully planned. The path the needle takes through the tissue should be chosen so that, if surgery is later needed, the biopsy tract can be removed along with the tumor. This helps prevent any tumor cells that might have been left behind during the biopsy from causing problems later.^[17]

Pathological Examination and Classification

Once the biopsy sample reaches the laboratory, a pathologist examines it under a microscope to look at the structure and characteristics of the cells. Chordoma cells have a distinctive appearance that helps confirm the diagnosis. The World Health Organization recognizes three main types of chordoma based on how the cells look:

• Classic or conventional chordoma is the most common type, making up 80% to 90% of all cases. Under the microscope, these cells look “bubbly,” similar to soap bubbles floating in a slimy mixture. There’s also a variant called chondroid chordoma, which makes up 5% to 15% of cases and has tissue that looks similar to cartilage.^[1][2]
• Dedifferentiated chordoma is a rarer and more aggressive type, accounting for less than 5% of cases. It appears as a mix of abnormal cells and tends to grow faster and spread to other parts of the body more readily than conventional chordoma.^[1]
• Poorly differentiated chordoma is extremely rare, with fewer than 60 cases recorded in medical literature. This type is identified by the deletion of a gene called SMARCB1 (also known as INI1) and most commonly affects children and young adults.^[1]

In addition to examining the cell structure, the pathologist uses special tests called immunohistochemistry. These tests detect specific proteins in the tumor cells. Chordoma cells typically express two important markers: brachyury (also known as TBXT) and cytokeratin. Finding these proteins helps confirm the diagnosis and distinguish chordoma from other types of tumors that might look similar.^[5]

Additional Diagnostic Considerations

Because chordoma can spread to other parts of the body in 30% to 40% of patients, doctors may order additional imaging tests to check for metastasis (cancer that has spread). The lungs, lymph nodes, other bones, liver, and skin are the most common places where chordoma spreads. Chest CT scans or other imaging may be used to look for any signs of disease beyond the original tumor site.^[1]

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or combinations of treatments for chordoma. Because there are currently no drug therapies approved specifically for chordoma by government agencies like the U.S. Food and Drug Administration or the European Medicines Agency, clinical trials offer an important opportunity for patients to access experimental treatments that might help control their disease.^[10]

To participate in a clinical trial, patients must meet certain criteria. These criteria ensure that the trial can safely test the new treatment and produce meaningful results. The diagnostic tests and standards used to qualify patients for clinical trials are often more detailed than those used for routine diagnosis.

Imaging Requirements for Clinical Trials

Most clinical trials require recent, high-quality imaging studies to confirm the presence, size, and location of the tumor. MRI scans are typically the preferred imaging method. Trial protocols often specify exactly how recent the scans must be—usually within a few weeks or months of enrollment—and may require specific types of MRI sequences or imaging techniques. Some trials may also require baseline PET-CT scans or other specialized imaging to measure the tumor’s activity or metabolism before treatment begins.

These baseline images serve as a reference point. Throughout the trial, patients undergo repeat imaging at set intervals to measure how the tumor responds to the experimental treatment. Doctors compare the new images to the baseline scans to see if the tumor has shrunk, stayed the same size, or grown.

Pathological Confirmation and Molecular Testing

Clinical trials almost always require confirmed pathological diagnosis of chordoma. This means you must have had a biopsy, and the tissue must have been examined by a pathologist who confirmed the diagnosis. Some trials may require that tissue samples be reviewed by a central pathology laboratory affiliated with the trial to ensure consistency in diagnosis across all participants.

Increasingly, clinical trials also require molecular or genetic testing of the tumor tissue. Because scientists have discovered that chordoma involves changes in certain genes and proteins, some experimental treatments target these specific molecular features. For instance, more than 95% of people with chordoma have a genetic variation in the TBXT gene (also called brachyury). Some trials may test for this or other genetic markers, such as changes in the mTOR signaling pathway, PTEN gene, or receptors like PDGFR-beta.^[3][5]

Certain clinical trials specifically target tumors with particular molecular characteristics. For example, trials testing drugs that block PDGFR receptors may only accept patients whose tumors express this protein. Similarly, immunotherapy trials might require testing to see if the tumor expresses certain antigens that the immune therapy targets. Your tumor tissue may need to be sent to a specialized laboratory for these molecular tests.

Disease Stage and Prior Treatment History

Clinical trials often have specific requirements about the stage or extent of your disease. Some trials are only open to patients with advanced or metastatic chordoma—meaning the cancer has spread to other parts of the body—because that’s when experimental treatments are most needed. Other trials may accept patients with newly diagnosed disease or those whose tumor has come back after surgery and radiation.^[10]

Your treatment history also matters. Some trials are designed for patients who have never received drug therapy before (first-line treatment), while others are specifically for patients whose disease did not respond to earlier treatments (second-line or later-line treatment). You may need to provide detailed records of all previous treatments, including surgeries, radiation therapy, and any medications you’ve tried.

General Health and Laboratory Tests

To ensure patient safety, clinical trials typically require blood tests and other laboratory studies to assess your overall health. Common tests include complete blood counts to check your red blood cells, white blood cells, and platelets; tests of liver function and kidney function; and tests to check for infections or other health conditions that might interfere with the experimental treatment.

These tests help doctors determine whether you’re healthy enough to tolerate the treatment being studied. If the experimental drug is known to affect the liver, for example, the trial will require normal liver function tests before you can enroll. Similarly, if the treatment might suppress your immune system, you’ll need adequate white blood cell counts.

Performance Status Assessment

Clinical trials often use standardized scales to measure how well you can carry out daily activities. One common scale is called the performance status, which rates your level of function from fully active to completely unable to care for yourself. Most trials require a certain minimum performance status, meaning you need to be well enough to take care of your basic needs and perhaps do some light work or activities.

This assessment helps ensure that patients enrolled in the trial can safely participate and that any effects of the treatment can be measured against a relatively stable baseline of health.