Chordoma

Introduction

Chordoma is a rare, slow-growing malignant tumor that originates from remnants of the notochord – that embryonic structure that helps shape our spine early in development. Though “slow” sounds reassuring, chordomas can quietly invade bone and nearby tissue over months or years, causing pain, neurological issues, or difficulty swallowing (for skull-base lesions). Affecting roughly one in a million people annually, these tumors can have a profound impact on daily life. In the sections below, we’ll explore symptoms, causes, diagnosis, treatment options, and long-term outlook for chordoma, helping you understand this uncommon but important condition.

Definition and Classification

Definition: Chordoma is a malignant neoplasm deriving from notochordal remnants along the axial skeleton, typically found at the sacrum, clivus (base of skull), or mobile spine. It is locally aggressive, with a propensity for bone invasion and recurrence.

Classification:

• Based on location:
  • Sacral chordoma (≈50% of cases)
  • Skull base (clival) chordoma (≈35%)
  • Mobile spine chordoma (≈15%)
• Histologic subtypes:
  • Conventional chordoma (most common)
  • Chondroid chordoma (has cartilage-like features, slightly better prognosis)
  • Poorly differentiated chordoma (rare, more aggressive, often SMARCB1-deficient)

Chordomas primarily affect the axial skeleton and are considered malignant but with indolent behavior compared to other bone cancers. While they rarely metastasize early, local invasion and recurrence are major clinical challenges.

Causes and Risk Factors

Chordomas arise from vestigial notochordal cells that persist along the spine after birth. These cells, usually quiescent, can transform malignantly through mechanisms not fully understood. Below are key contributing factors and risks:

• Genetic alterations:
  • Chromosomal abnormalities such as losses on 1p, 3p, and 9p
  • SMARCB1 (INI1) tumor suppressor gene deficiency in poorly differentiated chordomas
• Developmental factors: Persistence of notochordal remnants along the craniocervical junction, mobile spine or sacrum is the fundamental prerequisite. Why these cells turn malignant remains partly a mystery.
• Age and sex: Most common in adults between 40–70 years; slight male predominance (1.6:1).
• Environmental influences: There’s scant evidence of radiation or chemicals directly causing chordomas; unlike thyroid cancer, no clear link to environmental carcinogens.
• Non-modifiable vs. modifiable risks:
  • Non-modifiable: age, genetics, embryologic remnants
  • Modifiable: none established – lifestyle changes can’t prevent chordoma onset

In short, chordomas don’t result from smoking, diet, or sun exposure. Their roots lie deep in developmental biology and rare genetic hits that awaken silent notochord cells.

Pathophysiology (Mechanisms of Disease)

Chordoma pathophysiology centers on malignant transformation of notochordal remnants. In healthy embryos, the notochord serves as an early scaffold for the developing spine and then mostly disappears, leaving only nucleus pulposus cells in intervertebral discs. When some notochord cells persist along the axial skeleton, they may eventually accumulate genetic mutations, leading to neoplastic changes.

• Cellular origin: Notochordal cells express brachyury (T gene), a transcription factor critical for notochord development; chordoma cells often show high brachyury expression, serving as both a diagnostic marker and potential therapeutic target.
• Tumor microenvironment: Chordoma tissue tends to have a myxoid (gelatinous) matrix, rich in mucopolysaccharides, allowing the tumor to expand like a slowly inflating balloon, eroding adjacent bone and nerve roots.
• Local invasion: These tumors produce metalloproteinases and other enzymes that degrade extracellular matrix, facilitating bone lysis and soft tissue infiltration. That’s why patients might first notice sacral pain or cranial nerve deficits rather than a palpable mass.
• Angiogenesis: Moderate neovascularization supports slow but steady tumor growth. Unlike highly vascular glioblastomas, chordomas rely on a modest blood supply, contributing to their indolent pace.
• Recurrence mechanisms: Even with surgical resection, microscopic remnants along bone margins can regrow, leading to local relapse in 30–50% of cases within 5 years if radiation isn’t added.

Overall, chordoma development is a complex interplay of embryologic origin, genetic hits, and invasive biology, producing a tumor that’s weirdly persistent but not explosively fast.

Symptoms and Clinical Presentation

Because chordomas grow slowly, patients often experience vague symptoms for months to years before diagnosis. Presentation varies heavily with tumor location.

• Sacral chordoma:
  • Chronic lower back or buttock pain (often misdiagnosed as sciatica or degenerative disc disease)
  • Urogenital complaints: urinary incontinence, constipation, sexual dysfunction if sacral nerves are involved
  • Palpable mass in rare cases of large tumor bulging into pelvis
• Clival (skull-base) chordoma:
  • Headaches, often retro-orbital or occipital and persistent
  • Cranial nerve palsies: double vision (VI nerve), facial numbness (V nerve), swallowing difficulties if lower cranial nerves are hit
  • Hearing changes or tinnitus (rare)
• Mobile spine chordoma:
  • Localized mid-back or neck pain, sometimes radiating along dermatomes
  • Myelopathic signs with spinal cord compression: limb weakness, gait instability, hyperreflexia
  • Possible sensory deficits or bladder/bowel changes in advanced cases

Early symptoms are insidious—think “nagging backache” or “persistent headache” that doesn’t improve with rest. People sometimes get diagnosed years later after imaging for unrelated issues reveals the culprit.
Warning signs that call for urgent evaluation include sudden neurological deficits (e.g., acute limb weakness, bladder retention) or severe bone pain at night unrelieved by NSAIDs. Don’t brush these off.

Diagnosis and Medical Evaluation

Diagnosing chordoma usually involves a mix of imaging, biopsy, and specialized pathology:

• Clinical assessment: Comprehensive history (pain patterns, neurological changes) and physical exam focusing on neurological deficits, cranial nerve function, and sphincter tone.
• Imaging studies:
  • MRI (gold standard): reveals a lobulated, T2-bright mass with bone destruction and soft tissue extension; identifies involvement of nerves or dura
  • CT scan: better visualizes bony erosion and calcifications; aids in surgical planning
  • PET-CT: occasionally used to assess metabolic activity and detect distant metastases
• Biopsy: Image-guided core needle biopsy or surgical biopsy to obtain tissue. Pathology shows physaliphorous (bubble-bearing) cells in a mucinous stroma, and brachyury immunostain confirms diagnosis.
• Differential diagnosis:
  • Chondrosarcoma (especially at skull base)
  • Metastatic carcinoma (e.g., from prostate or breast)
  • Benign notochordal cell tumor (a very rare, non-cancerous cousin)
  • Giant cell tumor of bone
• Multidisciplinary review: Neuroradiology, neurosurgery or orthopedic oncology, pathology, and radiation oncology discuss findings to finalize the plan.

Getting to a chordoma diagnosis can be a bit of a winding road – think referrals to spine centers, cancer centers, and maybe a second opinion on that “unusual sarcoma.”

Which Doctor Should You See for Chordoma?

If you suspect chordoma due to persistent back pain with neurological features, a sudden cranial nerve deficit, or imaging shows an odd lesion on your spine or skull base, here’s who to consult:

• Primary care provider (PCP): First stop for assessment, ordering initial imaging, and referral coordination.
• Neurosurgeon or orthopedic spine surgeon: Experts in spinal tumors and skull-base lesions; they often perform biopsies and resections.
• Radiation oncologist: For postoperative radiotherapy (e.g., proton beam therapy) to reduce recurrence risk.
• Medical oncologist: Though chordomas are relatively chemo-resistant, clinical trials and targeted therapies (e.g., tyrosine kinase inhibitors) may be offered.

Online consultations and telemedicine can be very helpful early on – you can share your MRI scans and pathology reports for a remote second opinion, ask questions you forgot at your in-person visit, or clarify complex treatment steps. Yet, remember that nothing replaces a hands-on neurological exam if you’ve got gait problems or numbness. In emergencies—such as sudden paralysis, severe intractable pain, or acute cranial nerve loss—head straight to the ER or call your neurosurgeon urgently.

Treatment Options and Management

Managing chordoma demands a multidisciplinary approach, combining surgery, radiation, and sometimes systemic therapies:

• Surgery:
  • En bloc resection with wide margins where possible offers the best control; achieving negative margins in the sacrum may require sacrificing nerve roots (balancing function vs cure).
  • Skull-base chordomas often need complex neurosurgical and ENT collaboration to reach deep clival tumors.
• Radiation therapy:
  • Proton beam or carbon ion therapy preferred due to precise dose delivery, sparing surrounding brain or spinal cord.
  • Conventional photon radiotherapy is an option when particle therapy is unavailable, though with slightly higher toxicity.
• Targeted/systemic therapies:
  • Imatinib or other tyrosine kinase inhibitors for tumors expressing PDGFR or EGFR; modest responses observed.
  • Clinical trials of brachyury vaccines, immunotherapy, and novel molecular agents ongoing.
• Supportive care:
  • Pain management: NSAIDs, opioids, neuropathic agents
  • Rehabilitation: physical therapy for strength and gait training, occupational therapy for ADLs
  • Psychosocial support: counseling for emotional distress, support groups

Long-term surveillance with MRI every 6–12 months is crucial to spot recurrences early.

Prognosis and Possible Complications

Chordoma prognosis depends on location, surgical margins, and patient age. Key points include:

• 5-year overall survival: Approximately 70%–80% with complete resection and adjuvant radiation.
• Local recurrence: Occurs in up to 50% of cases without adequate margins; even with ideal treatment, 20%–30% may recur within 5 years.
• Distant metastases: Seen in 10%–20%, typically to lung, liver, or bones; more common in poorly differentiated subtype.
• Complications:
  • Sacral resection: bowel/bladder dysfunction, sexual dysfunction
  • Skull-base surgery: cerebrospinal fluid leaks, cranial nerve deficits, meningitis risk
  • Radiation effects: fibrosis, myelopathy, secondary malignancies decades later (rare)

Factors linked to better outcomes: complete tumor removal, use of particle therapy, younger patient age, and conventional (vs poorly differentiated) histology. Unfortunately, chordomas often recur, so lifelong follow-up is the norm.

Prevention and Risk Reduction

Given its embryologic origin, chordoma can’t be truly prevented through lifestyle changes. However, strategies to reduce disease impact and catch tumors earlier include:

• Awareness of red flags: Chronic back pain unresponsive to standard therapy, neurological changes (numbness, weakness), or cranial nerve symptoms prompt timely imaging.
• Genetic counseling: For families with rare hereditary cancer syndromes involving SMARCB1, though most cases of chordoma are sporadic.
• Regular medical check-ups: While no screening exists for chordoma, people with prior spine irradiation (e.g., for childhood cancers) should report new bone pain quickly.
• Optimized surgical planning: Referral to high-volume tertiary centers reduces incomplete resections and complications.
• Radiation techniques: Using proton/carbon ion therapy reduces damage to healthy tissue, lowering long-term toxicity.

Overall, the goal is not prevention of tumor origin (impossible) but early detection and optimal treatment to limit recurrence and preserve function.

Myths and Realities

Because chordoma is so rare, misinformation can flourish. Let’s debunk a few myths:

• Myth: “It’s just a benign bone cyst.”

  Reality: Chordoma is malignant and locally invasive; benign notochordal cell tumors are a separate, harmless entity identified incidentally.

• Myth: “Chemotherapy cures chordoma.”

  Reality: Traditional chemo has minimal effect. Current systemic options are limited to targeted agents and clinical trials.

• Myth: “If the surgeon says it’s removed, you’re done.”

  Reality: Even with gross total resection, microscopic cells can linger. Adjuvant radiation and lifelong imaging follow-up are key.

• Myth: “Chordoma only affects old people.”

  Reality: While peak incidence is in middle age, chordomas can occur from childhood through the elderly.

• Myth: “Eating organic will prevent recurrence.”

  Reality: No diet has been proven to stop microscopic chordoma cells. Healthy eating aids overall recovery but won’t replace medical therapy.

By separating hype from hard facts, patients and caregivers can make informed decisions and avoid wasted time on unproven “cures.”

Conclusion

Chordoma is a rare but formidable tumor arising from notochord remnants along the axial skeleton. Its slow growth belies the potential for serious neurological deficits, local bone destruction, and challenging recurrences. Key points to remember:

• Early recognition of persistent pain and new neurological signs is critical.
• A multidisciplinary approach—combining skilled surgery, precision radiation, and supportive care—offers the best outcomes.
• Lifelong surveillance is essential due to high rates of local relapse.

While no lifestyle tweak can prevent chordoma, prompt evaluation and treatment at specialized centers greatly improve prognosis. If you or a loved one faces this diagnosis, lean on qualified neurosurgeons, radiation oncologists, and supportive teams to navigate each step. And above all, don’t hesitate to seek professional advice early—timely medical care is your strongest ally.

Frequently Asked Questions (FAQ)

• 1. What is chordoma?

  A malignant tumor from embryonic notochord remnants along the spine or skull base.

• 2. How common is chordoma?

  About one new case per million people annually—very rare.

• 3. What are early symptoms?

  Chronic back or head pain, numbness, or weakness in limbs; often mistaken for musculoskeletal issues.

• 4. How is chordoma diagnosed?

  MRI and CT imaging, followed by a biopsy confirming physaliphorous cells and brachyury positivity.

• 5. Which specialists treat chordoma?

  Neurosurgeons or orthopedic oncologists for surgery, radiation oncologists for particle therapy, plus medical oncologists for trials.

• 6. Can chordoma be cured?

  Complete resection plus radiation offers best chance; however, recurrence rates remain significant.

• 7. Is chemotherapy effective?

  Standard chemo has limited benefit; targeted agents (imatinib) and clinical trials are explored.

• 8. What is the role of proton therapy?

  Proton beam allows precise radiation delivery, sparing healthy tissue and reducing side effects.

• 9. Can chordoma metastasize?

  Yes, in about 10%–20% of patients, often to lung, liver, or bones, usually in advanced or poorly differentiated cases.

• 10. How often should I get follow-up scans?

  Typically MRI every 6–12 months, sometimes more frequently if high recurrence risk.

• 11. Are there genetic tests for chordoma risk?

  No routine test; most cases are sporadic. Rare hereditary syndromes involving SMARCB1 exist.

• 12. What complications can arise from surgery?

  Sacral resections risk bowel/bladder issues; skull-base surgery risks CSF leak and cranial nerve deficits.

• 13. Can telemedicine help my chordoma care?

  Yes—for second opinions, discussing scan results, clarifying treatment plans—but urgent in-person exams remain crucial.

• 14. What lifestyle changes aid recovery?

  Healthy diet, gentle exercise, pain management, and psychosocial support improve quality of life but won’t replace therapy.

• 15. When should I seek emergency care?

  Sudden limb weakness, loss of bladder control, or acute severe headaches warrant immediate ER evaluation.