Chordoma

Chordoma is a rare, locally aggressive malignant tumor derived from notochordal remnants. Incidence is about 0.08 per 100,000 people a year, with a peak at 50 to 60 years and a male to female ratio of about 2 to 1. Sites are the sacrococcygeal region (about 50%), the skull base at the clivus (about 35%) and the mobile spine (about 15%).

Features: expression of brachyury (TBXT), which is diagnostic, and duplication of TBXT in familial cases. Tuberous sclerosis is also associated. Subtypes are conventional, chondroid (better prognosis) and dedifferentiated (poor prognosis).

Natural history is slow growth with a high local recurrence rate (30 to 60%) after incomplete resection. Metastases (lung, bone, liver, soft tissue) occur in 20 to 40%, usually late. Median survival is 6 to 7 years, and 5-year survival is about 70 to 80%. Complications: bowel and bladder dysfunction, cranial neuropathies, brainstem compression and tract seeding after intralesional biopsy.

• Sacral: persistent low back and sacral pain, constipation, urinary or fecal incontinence, a firm presacral mass on rectal examination
• Clivus: headache, diplopia from sixth nerve palsy, other cranial neuropathies, nasal obstruction
• Mobile spine: localized pain, radiculopathy and myelopathy
• Red flags: rapidly growing mass, cord compression, brainstem signs, new neurological deficit

1. MRI with gadolinium: a lobulated mass, markedly hyperintense on T2, with septa and variable enhancement, destroying bone and extending into soft tissue.
2. CT: bone destruction with intratumoral calcification (higher in the sacrum).
3. Biopsy by a core needle through the planned surgical tract, so the tract can be excised, ideally after review by the surgical team. Histology: physaliferous cells in a myxoid matrix, brachyury, cytokeratin and S100 positive.
4. Staging: CT chest, and whole-spine MRI.

Differentials: chondrosarcoma (brachyury negative), giant cell tumor, metastasis, plasmacytoma, ecchordosis physaliphora (benign notochordal rest), lymphoma.

• En bloc resection with wide margins is the strongest determinant of control. Sacral tumors: sacrectomy with preservation of at least bilateral S2 roots where possible (bladder and bowel function is largely preserved if S2 to S4 roots stay), with spinopelvic reconstruction for resections above S3 and plastic closure with a flap. Skull base: endoscopic endonasal or open approach with maximal safe resection.
• Prophylaxis: cefazolin 2 g IV before incision (3 g if over 120 kg) and repeated every 4 hours, and enoxaparin 40 mg SC daily. Sacral wound complications occur in 30 to 50%.
• Radiotherapy: proton or carbon ion beam after incomplete resection or for unresectable tumors, 70 to 74 Gy (RBE) in 1.8 to 2 Gy fractions (up to 76 Gy for skull base tumors, limited by the brainstem and optic apparatus). High-dose photon therapy 74 to 78 Gy by intensity-modulated technique is an alternative. Local control is about 70 to 80% at 5 years.
• Systemic therapy for advanced disease: imatinib 400 mg orally once daily (increase to 400 mg twice daily at progression), monitoring blood count and liver tests every 2 weeks for the first month, with edema, nausea and rash as common effects. Erlotinib 150 mg orally once daily or sirolimus are alternatives. Chemotherapy is ineffective except for the dedifferentiated type.
• Metastatic disease: resection of isolated lung metastases and palliative radiotherapy for painful bone lesions.

Follow-up: MRI every 6 months for 2 years, then yearly for life, with chest CT yearly. Counsel on late recurrence and bowel and bladder function.