Chordoma is a rare bone cancer that develops along the spine or at the base of the skull, growing slowly but posing significant treatment challenges due to its location near critical structures like the spinal cord and brain.
Epidemiology
Chordoma is an exceptionally uncommon form of cancer. Approximately one person for every one million people per year receives a chordoma diagnosis. This means that in the United States, roughly 300 individuals are diagnosed with this disease each year. While this number may seem small, for those affected and their families, understanding this disease becomes crucial.[1]
These tumors account for about three percent of all bone tumors and approximately twenty percent of primary tumors that originate in the spine. Despite representing such a small fraction of bone cancers overall, chordomas are actually the most common tumor type found in the sacrum (the triangular bone at the base of the spine) and the cervical spine in the neck region.[3][4]
The disease does not discriminate by geography, ethnicity, or sexual orientation, though certain demographic patterns have been observed. Chordomas most commonly affect adults between the ages of 40 and 60, with the peak incidence occurring in people in their mid-50s. However, this does not mean younger individuals are immune. About five percent of all chordoma cases occur in children, making it even rarer in younger populations.[1][4]
Men are more likely to develop chordoma than women, with males affected approximately 1.5 to 2 times more frequently. Interestingly, the disease appears to be less common in individuals of Black African descent compared to other populations. At any given time, approximately eight people per million in the general population are living with chordoma, which translates to an estimated 500 people currently managing this disease in the United Kingdom.[1][20]
Causes
The exact reason why chordomas develop remains largely unknown to researchers, but the origins of these tumors can be traced back to early human development. During the formation of a baby in the womb, a structure called the notochord plays an important role. The notochord is a rod-like structure made of cells that helps signal other tissues to organize and develop properly. As the baby continues to grow, the notochord normally disappears, with its remnants becoming the soft, gel-like centers of spinal discs known as the nucleus pulposus.[2][4]
However, in some rare cases, small groups of notochord cells do not disappear after birth. These leftover cells remain dormant in the bones of the spine or skull. In approximately one in one million people, these persistent notochord cells eventually transform into cancerous cells, forming a chordoma. This transformation can happen many years or even decades after birth, which helps explain why most chordomas appear in middle-aged and older adults.[2][3]
Researchers have identified genetic factors that may contribute to chordoma development. More than 95 percent of people with chordoma have a specific variation in the DNA sequence of a gene called brachyury, also known as TBXT. This variation, called a single nucleotide polymorphism or SNP, increases the risk of developing chordoma. However, having this genetic variation does not guarantee someone will develop the disease. In fact, a large portion of the general population carries this SNP, but the vast majority of these individuals will never develop chordoma. The actual risk remains incredibly small, at less than two in a million.[1][3]
Other genes and biological pathways have been implicated in chordoma formation. These include the mTOR signaling pathway, the PTEN gene, and platelet-derived growth factor receptor beta (PDGFR-beta). Scientists continue to study these genetic markers to better understand how chordomas form and to potentially develop more effective treatments.[4][5]
Risk Factors
Unlike many other cancers, there are no known environmental, dietary, or lifestyle risk factors that increase the chance of developing chordoma. A person cannot prevent chordoma through changes in diet, exercise, or by avoiding certain exposures. This makes the disease particularly challenging because there are no clear preventable causes that individuals can control.[3]
The most significant risk factor for chordoma is age. While the disease can occur at any point in life, from infancy through old age, it is most commonly diagnosed in adults between 40 and 80 years old. Gender also plays a role, with men having a higher likelihood of developing chordoma compared to women.[1][4]
Genetic factors represent another area of risk. The vast majority of chordoma cases occur randomly, without any family history of the disease. This is called sporadic chordoma. However, in extremely rare instances, multiple members of the same family may develop chordoma. This is known as familial chordoma and indicates a strong genetic predisposition that can be inherited. Scientists have discovered that some families with familial chordoma carry an extra copy of the brachyury gene, though currently no widely available test exists to detect these extra copies.[3][5]
There is also a possible link between chordoma and a genetic condition called Tuberous Sclerosis Complex (TSC). Children with TSC have been reported to develop chordoma at higher rates than the general population. Changes in either of two genes involved in TSC—TSC1 and TSC2—can create a predisposition to developing chordoma. This connection remains an area of ongoing research.[3][5]
Symptoms
Chordoma typically grows very slowly, which means symptoms often develop gradually over months or even years before a diagnosis is made. Because the symptoms can mimic more common conditions like routine back pain or headaches, many people experience significant delays before chordoma is identified. Given how rare the disease is, most general practitioners will never encounter a patient with chordoma during their entire career, which can contribute to diagnostic delays.[6][20]
The specific symptoms a person experiences depend largely on where the tumor is located along the spine or skull. As the chordoma grows, it begins to press against nearby structures, including the spinal cord, brain, nerves, and blood vessels. This pressure is what causes the symptoms.[1]
General symptoms that can occur regardless of location include pain, weakness, and numbness in the back, arms, or legs. These symptoms may start mildly and worsen gradually over time. Some people notice a progressive loss of energy or experience unexplained weight loss.[1][15]
When a chordoma develops at the base of the skull, often in a bone called the clivus, it can cause distinctive symptoms. These may include double vision, where a person sees two images of a single object, or blurred vision. Persistent headaches are common. Some individuals experience numbness or pain in the face, or difficulty with speech and swallowing. Changes in throat function can also occur as the tumor presses on nerves that control these areas.[1][6][17]
Chordomas that form in the neck, specifically in the cervical spine, may cause hoarseness in the voice or make swallowing difficult. People might notice changes in their voice quality or feel as though food is not moving properly down the throat.[6]
For chordomas that develop in the lower spine, particularly in the sacrum or coccyx (tailbone), symptoms often center around the lower back and pelvis. Low back pain or tailbone pain is very common and may be persistent. Some people can feel a lump or mass under the skin in the tailbone area. Problems with bladder or bowel function may develop as the tumor affects the nerves that control these organs. This can manifest as difficulty passing urine or changes in bowel habits. Weakness in the legs, numbness, or tingling sensations may also occur.[1][6][17]
Many young patients have reported that their initial symptoms were dismissed by primary care physicians, who attributed them to stress, eating disorders, or other more common conditions. This underscores the importance of persistent advocacy when symptoms continue or worsen, especially if they include unusual combinations like balance problems, changes in handwriting or grip strength, and progressive fatigue.[15]
Prevention
Currently, there are no known methods to prevent chordoma. Because the disease arises from leftover cells present from before birth, and because there are no identified environmental or lifestyle risk factors, standard prevention strategies that work for other cancers do not apply to chordoma. Individuals cannot reduce their risk through dietary changes, exercise, avoiding certain substances, or other behavioral modifications.[3]
There are no screening programs available for chordoma in the general population. Screening tests like mammograms for breast cancer or colonoscopies for colorectal cancer have not been developed for chordoma, primarily because the disease is so rare that widespread screening would not be practical or cost-effective.[3]
For the very small number of families with familial chordoma—where multiple family members have been affected—a different approach may be considered. In these cases, genetic counseling can be valuable. Family members may be monitored over time through periodic imaging studies to detect any tumors at the earliest possible stage. Early detection, while not prevention, could potentially lead to treatment before the tumor grows large enough to cause symptoms or become more difficult to remove.[3]
Researchers continue to study the genetic and molecular factors involved in chordoma development. Understanding exactly why notochord cells transform into cancer cells may one day lead to preventive strategies, but such approaches remain in the realm of future research rather than current medical practice.[4]
Pathophysiology
Understanding how chordoma affects the body requires looking at what happens at both the cellular and structural level. At its core, chordoma is a tumor that arises from cells that should have disappeared during fetal development. These persistent notochordal cells retain some of their original characteristics but undergo cancerous transformation, beginning to grow and divide in an uncontrolled manner.[4][5]
Chordomas are classified as low-grade, slow-growing tumors, but they behave in a malignant, or cancerous, manner. They belong to a family of cancers called sarcomas, which are cancers that develop in bones or soft connective tissues. While chordomas typically grow slowly compared to many other cancers, they are locally invasive, meaning they aggressively invade the tissues immediately surrounding them.[4][11]
The tumors most commonly develop in three locations along the spine. About 35 percent form in the sacrum at the base of the spine. Another 35 percent develop where the spine meets the skull, in an area called the skull base, often involving the clivus bone. The remaining 30 percent occur in the vertebrae of the mobile spine, most frequently in the second cervical vertebra in the neck, followed by the lumbar spine in the lower back, and then the thoracic spine in the mid-back.[1][4]
At the microscopic level, doctors recognize three main types of chordoma based on how the cells appear under a microscope. The most common type, called classic or conventional chordoma, makes up 80 to 90 percent of cases. These cells have a distinctive “bubbly” appearance, sitting in a slimy substance that resembles soap bubbles. A variant called chondroid chordoma accounts for five to fifteen percent of cases and contains tissue that looks similar to cartilage.[1][2]
A more aggressive form called dedifferentiated chordoma represents less than five percent of cases. These tumors appear as a mix of different abnormal cell types and grow faster than conventional chordomas. They are also more likely to spread to other parts of the body. The rarest type, poorly differentiated chordoma, is characterized by the loss of a gene called SMARCB1 or INI1, and fewer than 60 cases have been documented in medical literature. This type most commonly affects children and young adults.[1][2]
Several molecular pathways are disrupted in chordoma cells. The mTOR signaling pathway, which normally helps regulate cell growth and metabolism, becomes hyperactive in chordoma. Studies have shown that in sacral chordomas, specific markers of mTOR activity are present in the vast majority of cases. The PTEN gene, which normally acts as a tumor suppressor, is often partially or completely deficient in chordoma cells, allowing unchecked growth.[5]
Chordomas also frequently express certain growth factor receptors on their cell surfaces. These include platelet-derived growth factor receptor-beta (PDGFR-beta), which appears in virtually all cases, and epidermal growth factor receptor (EGFR), found in about two-thirds of chordomas. These receptors can receive signals that promote tumor growth, which is why some targeted therapies aim to block these pathways.[5]
Genetic changes are also common. The CDKN2A and CDKN2B genes, which are located on chromosome 9 and help regulate the cell cycle, are frequently deleted in chordoma cells. This deletion removes an important brake on cell division, allowing tumor cells to multiply more readily.[5]
One of the most challenging aspects of chordoma from a pathophysiological standpoint is its location. Because these tumors grow along the spine and skull base, they develop in very close proximity to critical structures. The spinal cord, brainstem, major blood vessels, and important nerves all lie near where chordomas typically form. As the tumor grows, it doesn’t just press against these structures—it can actually infiltrate and invade them. This makes complete surgical removal extremely difficult without causing damage to these vital tissues.[1][3]
Chordomas have a strong tendency to recur after treatment, usually in the same location as the original tumor. This happens because achieving completely clear surgical margins—removing the entire tumor plus a rim of healthy tissue—is often impossible given the proximity to the spinal cord or brain. Even tiny clusters of cancer cells left behind can eventually grow into a new tumor.[1][3]
In 30 to 40 percent of patients, chordoma eventually spreads to distant parts of the body, a process called metastasis. When this happens, the most common sites are the lungs, nearby lymph nodes, other bones, the liver, and occasionally the skin. Metastatic spread significantly complicates treatment and affects long-term outcomes.[1][3]
