Chordoma

What is Chordoma?

Chordoma is an extremely rare type of bone cancer that develops from remnants of the notochord, a structure present during early fetal development. These slow-growing tumors typically occur at the base of the skull or in the sacrum (lower spine), where they can invade surrounding tissues and cause significant neurological problems. Chordoma affects approximately one person per million annually, making it one of the rarest cancers. While the tumors grow slowly, they are locally aggressive and notoriously difficult to treat due to their location near critical structures like the brain and spinal cord.

Key statistics

Symptoms

Common symptoms include: headaches, neck pain, lower back pain, numbness, weakness, bowel or bladder dysfunction, visual changes, hearing problems, difficulty swallowing.

Symptoms depend heavily on tumor location. Skull-base chordomas often cause persistent headaches that worsen over time, double vision, hearing loss, facial numbness, difficulty swallowing, and voice changes. Patients may experience nasal congestion or nosebleeds if the tumor extends into nasal passages.

Sacral chordomas typically present with lower back pain that radiates to the hips or legs, often mistaken initially for disc problems or sciatica. As tumors grow, patients may develop bowel or bladder incontinence, sexual dysfunction, numbness in the saddle area (buttocks and inner thighs), and weakness in the legs. A palpable mass may be felt during rectal examination.

Submit Your Paper

Spinal chordomas can cause neck or back pain, arm or leg weakness, numbness, and in severe cases, paralysis. Early symptoms are often subtle and progress slowly, leading to delays in diagnosis that can span months or years.

Causes and risk factors

Chordoma is primarily a sporadic cancer, meaning it occurs randomly without clear hereditary patterns. The key genetic factor involves the brachyury gene (TBXT), which is overexpressed in virtually all chordomas. This gene normally plays a crucial role in notochord development during embryonic growth but becomes inappropriately activated in chordoma cells.

Most cases arise from genetic duplications of the brachyury gene region on chromosome 6. While the vast majority of chordomas are sporadic, rare familial cases have been reported, suggesting possible inherited susceptibility in some families.

Risk factors include age (most common in adults over 40), male gender, and possibly prior radiation exposure, though this link is not definitively established. Unlike many cancers, there are no known environmental, lifestyle, or infectious causes of chordoma.

Prevention

Currently, there are no evidence-based methods for preventing chordoma, as the genetic changes that cause these tumors appear to occur randomly during a person’s lifetime. Since most cases are sporadic rather than inherited, routine genetic screening is not recommended for the general population.

For the rare families with multiple affected members, genetic counseling may be beneficial to discuss potential risks and surveillance options. However, no specific screening protocols exist even for high-risk individuals due to the tumor’s rarity and unpredictable development.

Research into the brachyury gene and notochord development may eventually lead to prevention strategies, but these remain investigational.

Complications

Without treatment, chordomas continue to grow and invade surrounding structures, leading to progressive neurological deterioration. Skull-base tumors can compress the brainstem, causing life-threatening respiratory or cardiac problems, severe swallowing difficulties, and complete cranial nerve dysfunction.

Sacral chordomas can result in permanent bowel and bladder incontinence, sexual dysfunction, and lower extremity paralysis. The slow growth pattern means symptoms worsen gradually, but eventual compression of vital structures can be fatal.

Even with treatment, complications include surgical risks near critical structures, radiation-induced damage to surrounding healthy tissue, tumor recurrence (common due to difficult complete removal), and chronic pain requiring long-term management.

Diagnosis

Diagnosing chordoma requires a combination of clinical evaluation, advanced imaging, and tissue confirmation. The diagnostic journey is often lengthy due to the tumor’s rarity and non-specific early symptoms.

Imaging studies are crucial and typically include magnetic resonance imaging (MRI) to define tumor extent and relationship to surrounding structures, and computed tomography (CT) to evaluate bone destruction. These show characteristic features including a lobulated mass with internal septations and bone destruction.

Biopsy provides definitive diagnosis through histopathological examination. Tissue samples show characteristic physaliferous cells (bubble-like cells) and positive immunostaining for brachyury protein, which is virtually pathognomonic for chordoma.

Genetic testing may reveal brachyury gene amplification, supporting the diagnosis. Additional immunohistochemical markers include cytokeratins and epithelial membrane antigen (EMA).

Differential diagnosis includes chondrosarcoma, metastatic adenocarcinoma, and other rare bone tumors, making expert pathological review essential.

Treatment

Treatment requires a multidisciplinary approach involving neurosurgeons, orthopedic oncologists, radiation oncologists, and medical oncologists experienced with rare tumors.

Surgery remains the primary treatment, with the goal of complete tumor removal (en bloc resection) while preserving neurological function. This often requires complex approaches and may involve multiple specialists. Complete removal significantly improves outcomes but is frequently impossible due to tumor location.

Radiation therapy is typically used after surgery, particularly for incomplete resections. High-dose precision techniques like proton beam therapy or stereotactic radiosurgery are preferred to minimize damage to surrounding healthy tissue.

Systemic therapy options include targeted agents such as imatinib for tumors expressing platelet-derived growth factor receptors, and afatinib for EGFR-expressing tumors. Clinical trials are investigating novel agents including brachyury-targeted immunotherapies.

Emerging treatments include immunotherapy approaches targeting the brachyury protein and combination therapies aimed at tumor-specific vulnerabilities.

Prognosis

Prognosis varies significantly based on tumor location, completeness of surgical resection, and patient age. Overall 5-year survival rates range from 65-70%, but this varies considerably by site and treatment completeness.

Skull-base chordomas generally have better survival rates than sacral tumors, partly due to earlier detection when they cause neurological symptoms. Complete surgical resection dramatically improves outcomes, with some patients achieving long-term disease-free survival.

However, local recurrence remains common, occurring in 15-40% of patients even after aggressive treatment. Metastasis is relatively uncommon but can occur to lungs, liver, bone, and lymph nodes, particularly in recurrent disease.

Quality of life outcomes depend heavily on neurological preservation during treatment and successful management of tumor-related symptoms.

Quality of life

Living with chordoma requires ongoing adaptation to physical limitations and treatment effects. Many patients experience chronic pain requiring multimodal pain management including medications, physical therapy, and sometimes interventional procedures.

Physical function may be permanently altered, particularly for sacral chordoma patients who may require mobility aids, bowel and bladder management programs, and adaptive equipment for daily activities.

Emotional support is crucial given the cancer diagnosis, treatment complexity, and potential for permanent disability. Many patients benefit from counseling, support groups, and connection with other chordoma patients through advocacy organizations.

Work and activities may require modification based on neurological deficits and treatment schedules. Occupational therapy can help optimize function and independence.

Regular monitoring with imaging studies and clinic visits becomes a lifelong routine, which can cause anxiety but is essential for detecting recurrence early.

Pregnancy and fertility

Chordoma during pregnancy presents complex management challenges requiring multidisciplinary care. Treatment decisions must balance maternal health with fetal safety, often requiring delayed treatment until after delivery if the tumor is slow-growing.

Fertility may be affected by sacral chordomas that damage reproductive organs or nerves, and by treatments including radiation therapy to the pelvis. Fertility preservation options should be discussed before treatment when appropriate.

Pregnancy is generally possible after chordoma treatment, but requires high-risk obstetric care and coordination with oncology teams. Genetic counseling may be recommended for the rare familial cases, though most chordomas are sporadic.

Children

Pediatric chordoma is extremely rare but tends to be more aggressive than adult forms. Children more commonly develop skull-base tumors, which can cause rapid neurological deterioration.

Treatment principles are similar to adults but require specialized pediatric expertise to minimize effects on developing structures. Proton beam radiation is particularly important in children to reduce long-term complications.

Long-term follow-up is crucial to monitor for treatment effects on growth and development, cognitive function, and hormone production, particularly after skull-base radiation.

When to see a doctor

Seek immediate medical attention for sudden severe headaches, rapid vision changes, difficulty breathing or swallowing, sudden bowel or bladder incontinence, or new weakness or numbness in arms or legs.

Schedule routine evaluation for persistent headaches that worsen over weeks or months, chronic lower back pain that doesn’t improve with standard treatments, gradual onset of bowel or bladder dysfunction, or progressive numbness or weakness.

Given the rarity of chordoma, initial evaluation by primary care physicians is appropriate, with referral to specialists if concerning features persist or worsen despite standard treatment.

Regional context

Specific prevalence data for chordoma in the Caucasus region (Georgia, Armenia, Azerbaijan) and Eastern Mediterranean are limited due to the tumor’s extreme rarity. The overall incidence rate of 1 per million annually likely applies globally, but regional cancer registries may not have sufficient cases to establish precise local rates.

Healthcare systems in these regions may benefit from establishing referral networks to centers with chordoma expertise, given the specialized knowledge required for optimal management. We invite medical professionals from these regions to contribute their experiences and data to the Georgian Medical Journal to better understand regional patterns and challenges in chordoma care.

Research and clinical trials

Current research focuses on several promising areas including brachyury-targeted immunotherapies, novel drug combinations targeting chordoma-specific pathways, and improved surgical techniques using advanced imaging guidance.

Recent breakthroughs include development of brachyury vaccines and CAR-T cell therapies specifically designed for chordoma. Combination approaches using immunotherapy with targeted agents are showing promise in early trials.

Active clinical trials are investigating agents such as nivolumab (anti-PD1), brachyury-targeted vaccines, and novel small molecule inhibitors. Patients should discuss clinical trial eligibility with their oncology team and can search for current trials at ClinicalTrials.gov using the search term “chordoma.”

The Chordoma Foundation actively supports research initiatives and maintains updated information about available trials and emerging treatments.

Frequently asked questions

Is chordoma hereditary?

The vast majority of chordomas are sporadic, occurring randomly without family history. Rare familial cases have been reported, but hereditary chordoma accounts for less than 5% of all cases.

Can chordoma be cured?

Complete cure is possible with total surgical removal, but this is often technically impossible due to tumor location. Many patients achieve long-term disease control with aggressive treatment combining surgery and radiation.

How fast does chordoma grow?

Chordomas are typically slow-growing tumors, often developing over months to years. However, growth rates can vary, and some tumors may have periods of more rapid expansion.

What is the difference between chordoma and chondrosarcoma?

While both are rare bone tumors that can occur in similar locations, chordoma arises from notochord remnants and shows brachyury protein expression, while chondrosarcoma develops from cartilage cells and has different genetic markers.

Should I get a second opinion?

Yes, given chordoma’s rarity, seeking evaluation at a specialized center with chordoma experience is strongly recommended. The Chordoma Foundation maintains a list of expert centers worldwide.

Support and resources

• Chordoma Foundation: chordomafoundation.org – Primary patient advocacy organization with comprehensive resources
• National Organization for Rare Disorders (NORD): rarediseases.org
• Orphanet: orpha.net – European database of rare diseases
• EURORDIS: eurordis.org – European rare disease patient organization
• ClinicalTrials.gov: clinicaltrials.gov – Database of clinical trials
• Sarcoma Foundation of America: curesarcoma.org

Related conditions

• Chondrosarcoma – Another rare bone cancer that can occur in similar locations
• Craniopharyngioma – Brain tumor that can present similarly to skull-base chordoma
• Sacral insufficiency fracture – Can mimic sacral chordoma symptoms
• Schwannoma – Nerve tumor that may present with similar neurological symptoms
• Metastatic bone disease – Must be differentiated from primary chordoma

Sources: Orphanet (orpha.net), OMIM, GeneReviews (NCBI), WHO ICD-11, relevant guidelines. Informational only; not medical advice. CC BY 4.0.

Licensed under CC BY 4.0. Free to share with attribution to GMJ News.

Sources: Orphanet (orpha.net), OMIM, GeneReviews (NCBI), WHO ICD-11, EULAR/ACR guidelines. Schema.org MedicalCondition structured data included.