What is chordoma?

Chordoma: A Rare and Locally Invasive Bone Tumor

Chordoma is a rare bone tumor that develops from persistent notochordal elements, characterized by its locally invasive nature, typically low-grade malignancy, and predilection for the sacrum (50%), skull base (30%), and mobile spine (20%).

Definition and Origin

Chordoma is a rare primary bone malignancy with an incidence of approximately 0.1 per 100,000 people per year 1. These tumors arise specifically from remnants of the embryonic notochord that persist into adulthood. The diagnostic hallmark of chordoma is nuclear expression of the transcription factor brachyury, which is involved in notochord differentiation 1.

Epidemiology and Classification

• Median age at diagnosis is 60 years, though skull base presentations can affect younger populations, including children and adolescents 1
• Slightly more common in males
• The World Health Organization (WHO) classification divides chordoma into three subtypes:
  • Conventional chordoma (most common) - locally invasive and typically low-grade
  • Dedifferentiated chordoma (less than 5% of cases) - more aggressive behavior
  • Poorly differentiated chordoma (PDC) - rare, aggressive subtype 1

Anatomical Distribution

• Sacrum: 50% of cases
• Skull base/clivus: 30% of cases
• Mobile spine: 20% of cases
• Extraskeletal cases are extremely rare 1

Clinical Behavior and Prognosis

Chordomas are characterized by:

• Slow growth but locally aggressive and destructive behavior 2
• High rates of local recurrence, even after optimal treatment
• Metastatic potential of approximately 30-40%, with metastases typically occurring late in the disease course and usually after local recurrence 1
• Common metastatic sites include lung, liver, bone, subcutaneous tissues, lymph nodes, and other locations 1
• Prognosis is more related to local aggressiveness than to metastases 1
• Long-term survival projections do not plateau, even after optimal local therapy 1

Diagnosis

• MRI is the best modality for local staging 1
• CT scan should be used in cases of diagnostic doubt 1
• Preoperative core-needle biopsy is recommended for most locations, with the biopsy track needing to be included in the surgical resection 1
• For skull base chordoma, preoperative biopsy may not be recommended if the tumor cannot be reached easily or safely 1, 3
• Immunohistochemistry for brachyury is strongly recommended to confirm diagnosis 1
• Chordoma should be differentiated from benign notochordal cell tumors, which are believed to be chordoma precursors 1

Treatment Approaches

Due to the rarity and complexity of chordoma, management should be carried out at specialized centers with multidisciplinary teams 1, 3:

Surgery

• En bloc R0 resection (complete removal with negative margins) is the standard treatment when feasible and if sequelae are acceptable to the patient 1, 3
• For skull base and upper cervical tract chordoma, complete R0 resection is rarely achievable, and R1 (microscopic positive margin) should be the goal of surgery 1, 3
• For sacral chordoma, surgery should definitely be offered as first choice for lesions arising from S4 and below, but should be carefully considered for tumors originating above S3 due to significant neurological sequelae 1

Radiation Therapy

• Adjuvant radiation therapy should always be considered for skull base and cervical spine chordomas 1
• Particle therapy (high-dose protons or carbon ions) provides better local control and survival compared to conventional radiation 1, 3
• High doses (at least 74 GyE) are required due to the relative radiation resistance of chordomas 3

Systemic Therapy

• Conventional chemotherapy is generally ineffective for chordoma 4
• Targeted therapies such as imatinib or sorafenib may be considered for advanced or recurrent disease 3, 4

Management Challenges and Complications

• Local recurrence has extremely poor survival rates and local control is rarely achievable 1, 3
• Recurrence-free survival rates at 5 and 10 years range from 47-76% and 32-71%, respectively, depending on tumor location 1
• Regular follow-up imaging with MRI is essential to detect recurrence 3

Clinical Pearls and Pitfalls

• Pitfall: Delayed diagnosis due to slow growth and insidious onset, leading to lower survival rates 2
• Pitfall: Inadequate surgical margins, which significantly increase recurrence risk
• Pearl: Treatment at specialized centers with multidisciplinary expertise improves outcomes 1, 3
• Pearl: Brachyury immunohistochemistry is essential for accurate diagnosis 1

Chordoma management requires a highly specialized approach with careful consideration of tumor location, extent of resection possibilities, and adjuvant therapy options to maximize patient outcomes and quality of life.