Chordoma: Causes, Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Chordoma is a rare, slow-growing but locally destructive and potentially lethal malignant bone tumor arising from notochordal remnants — vestigial cells of the embryonic notochord (the precursor to the spinal column) that persist in adults within axial skeletal structures. It occurs in three anatomical sites: the sacrococcygeal region (approximately 50%), the clivus at the base of the skull (approximately 35%), and the mobile cervical, thoracic, or lumbar spine (approximately 15%). Annual incidence is approximately 1 per million, making it among the rarest bone tumors. Despite its slow growth rate and generally bland histological appearance, chordoma behaves as a malignant tumor with high local recurrence rates (40-60%), occasional distant metastases (most often to lung, bone, and soft tissue), and progressive neurological destruction unless treated aggressively with en bloc resection and high-dose particle beam radiotherapy. Brachyury (T gene transcription factor) is the defining molecular marker, expressed in over 90% of chordomas and absent from other bone tumors.

Most chordomas arise sporadically without an identified hereditary predisposition. Germline duplication of the brachyury (T gene) locus on chromosome 6q27 is an established hereditary risk factor for familial chordoma: families carrying this duplication show markedly increased chordoma risk across generations, though penetrance is incomplete. Brachyury drives notochordal cell identity and is ectopically expressed in chordoma cells, promoting epithelial-mesenchymal transition and invasiveness. PDGFRB amplification is found in approximately 50% of chordomas, providing a rationale for imatinib therapy. CDKN2A deletion and TP53 mutations contribute to aggressive behavior in a subset. Males are affected approximately twice as often as females. Prior therapeutic radiation exposure and benign notochordal cell tumor (BNCT) — a precursor lesion — may predispose to chordoma development in rare cases. The median age at diagnosis is 58 years for sacrococcygeal chordoma and 55 years for clival chordoma.

Sacrococcygeal chordoma: deep, dull, non-specific lower back and buttock pain that is persistent and not relieved by rest or NSAIDs — often present for years before diagnosis; bowel and bladder dysfunction (difficulty urinating, urinary retention, constipation, fecal incontinence) from compression of sacral nerve roots; a large presacral or gluteal mass palpable per rectum or through the skin. Clival chordoma: headache, diplopia from sixth cranial nerve (abducens) palsy causing lateral gaze restriction, and other cranial nerve palsies (III, IV, VII, IX-XII) — all from compression along the skull base; nasal obstruction. Mobile spine chordoma: radiculopathy, myelopathy, and local pain at the affected level. Symptoms progress insidiously over months to years — the average time from symptom onset to diagnosis for sacrococcygeal chordoma exceeds 2 years due to non-specific presentation.

MRI of the primary site with gadolinium contrast is the definitive imaging modality: chordomas appear as lobulated, heterogeneous masses with characteristic T2 hyperintensity (mucoid matrix) and moderate heterogeneous enhancement. CT of the primary site characterizes bone destruction, matrix calcification, and guides surgical planning. Core needle biopsy confirms histopathology — chordoma is characterized by physaliphorous cells (large vacuolated cells with bubbly cytoplasm) and strongly positive brachyury IHC and S100 protein; negative for SMA, desmin, and epithelial markers. Staging: CT thorax, abdomen, and pelvis to assess distant metastases (present at diagnosis in approximately 10-20% of cases). PET-CT may identify additional sites. TNM staging by AJCC 8th edition bone tumor staging. Bone scintigraphy for detection of skip metastases within the spine.

En bloc surgical resection achieving wide (R0) negative margins is the primary treatment and the most important predictor of local recurrence and overall survival. Sacral chordoma: en bloc sacrectomy — the extent of sacral sacrifice determines functional outcome; preservation of S1-S3 unilaterally enables ambulatory function and partial continence. Clival chordoma: endoscopic endonasal or transcranial skull base approaches to achieve maximal safe resection — complete resection is rarely achievable due to brainstem and carotid proximity. High-dose proton beam radiotherapy (74 GyE in 37 fractions) or carbon ion radiotherapy: essential adjuvant treatment after subtotal resection and as definitive treatment for unresectable disease — provides superior local control compared to conventional photon radiation due to the Bragg peak dose distribution. Stereotactic radiosurgery (Cyberknife, Gamma Knife) for small residual clival disease. Systemic therapy: imatinib mesylate 800 mg daily for PDGFRB-expressing recurrent chordoma (modest activity: partial response in approximately 15%); erlotinib for EGFR-expressing tumors. Immune checkpoint inhibitor trials (pembrolizumab, ipilimumab) ongoing.

Prognosis for chordoma reflects its locally destructive behavior and high recurrence rate despite slow growth. Overall 5-year OS is approximately 67-80% and 10-year OS approximately 40-54%, with most patients ultimately succumbing to progressive local recurrence or distant metastases rather than rapidly aggressive tumor growth. Local recurrence is the dominant problem, occurring in 40-60% of patients even after wide-margin resection and substantially worsening prognosis with each successive recurrence. En bloc R0 (margin-negative) resection combined with high-dose proton beam radiotherapy (74 GyE) provides the best local control: 5-year local control rates of approximately 70-80% at specialized centers, compared to 30-40% with conventional photon radiotherapy alone. Five-year OS by primary site: sacral chordoma approximately 65-70%; clival chordoma approximately 70-75%; mobile spine chordoma approximately 55-65%. Distant metastases — most commonly to lung, bone, and soft tissue — occur in approximately 30-40% of patients over time, often years to decades after initial treatment. Dedifferentiated chordoma, representing malignant transformation of classic chordoma, carries a median OS of less than 12 months. Complete surgical resection at initial presentation is the most critical prognostic determinant; subtotal resection markedly increases recurrence risk and reduces long-term survival. Other prognostic factors include tumor size at diagnosis, duration of symptoms before surgery, histological variant, and CDKN2A deletion status. Long-term follow-up includes MRI of the primary site every 6-12 months for 5 years then annually, CT thorax every 1-2 years for metastatic surveillance, and bladder and bowel function assessment for sacral chordoma patients to monitor for progressive sacral nerve injury.

No environmental or lifestyle risk factors for sporadic chordoma are established, making primary prevention impossible for most cases. For families with identified germline brachyury (T gene) duplication — detectable through genetic testing — genetic counseling enables family members to understand their elevated risk. Affected family members may benefit from surveillance imaging (whole-spine and skull-base MRI) to detect chordoma at the earliest, smallest, and most surgically accessible stage, though formal screening protocols remain to be established given the rarity of familial chordoma. Individuals incidentally found to have a benign notochordal cell tumor (BNCT) — an asymptomatic MRI finding of T2-hyperintense notochordal foci within the spine — should be monitored with interval MRI, as rare malignant transformation to chordoma is documented. Treatment at a specialized center with dedicated orthopedic oncology and particle beam radiotherapy expertise achieves substantially better local control than treatment at non-specialized institutions.

Because chordoma symptoms are non-specific and insidious, delays in diagnosis are common. Seek medical evaluation and consider dedicated MRI of the sacrum, clivus, or spine for: persistent lower back or buttock pain lasting more than 3-4 months that is not explained by lumbar disc disease or musculoskeletal causes; new bowel or bladder dysfunction in association with back pain (urgency, retention, or incontinence); a new presacral mass found incidentally on imaging performed for another reason; persistent headache with double vision or other cranial nerve symptoms (especially in adults aged 40-70); or any palpable midline mass over the sacrum or coccyx. When chordoma is suspected or confirmed, the patient should be referred urgently to a multidisciplinary center with experience in both complex axial skeleton surgery and particle beam radiotherapy — these two institutions rarely coincide at the same site, requiring coordination between surgical and radiotherapy teams.