Ependymoma

Ependymoma is a glial tumor arising from ependymal cells lining the ventricles. This article covers the intracranial form. It makes up 5 to 10% of childhood brain tumors, with a peak at 1 to 5 years, and the posterior fossa holds about two thirds of cases, with the remainder supratentorial.

Molecular groups

• Posterior fossa group A (PFA): infants, loss of H3 K27me3, high recurrence, 5-year survival of 50 to 60%
• Posterior fossa group B (PFB): adolescents and adults, better outcome
• Supratentorial ZFTA (RELA) fusion: aggressive
• Supratentorial YAP1 fusion: favorable

Grade 2 and grade 3 (anaplastic) are recognized, and grading adds less than molecular group. Extent of resection is the strongest modifiable factor. Local recurrence is the dominant pattern (up to 50%), often within 2 to 3 years and sometimes after 10 years. Cerebrospinal fluid dissemination occurs in about 10%. Complications: hydrocephalus, lower cranial nerve palsies from plastic extension through the foramina of Luschka and Magendie, and cognitive effects of radiotherapy.

• Posterior fossa: headache, vomiting, neck stiffness or head tilt, ataxia, and lower cranial nerve signs (dysphagia, hoarseness)
• Supratentorial: seizures, focal weakness and raised pressure
• Infants: irritability, macrocephaly and developmental regression
• Red flags: falling consciousness, apnea, bulbar failure and spinal signs

1. MRI brain and whole spine with gadolinium: a heterogeneous fourth ventricle mass extending into the cerebellopontine angle and cervical canal, with cysts, calcification (visible on CT) and variable enhancement.
2. Postoperative MRI within 72 hours to define residual disease.
3. Lumbar puncture cytology at least 10 days after surgery.
4. Histology with methylation profiling (PFA versus PFB, ZFTA fusion).
5. Germline testing when features are atypical.

Differentials: medulloblastoma, pilocytic astrocytoma, choroid plexus tumor, atypical teratoid rhabdoid tumor.

• Presentation: dexamethasone 0.1 to 0.25 mg/kg IV or orally every 6 hours (maximum 4 mg a dose), and an external ventricular drain or endoscopic third ventriculostomy for hydrocephalus.
• Surgery: maximal safe resection, with a second-look operation if residual tumor is resectable. Complications are lower cranial nerve deficit, cerebellar mutism and hemorrhage.
• Radiotherapy for all grade 2 and 3 tumors in children over 12 to 18 months, starting within 6 weeks of surgery: conformal 54 Gy in 30 fractions of 1.8 Gy to the tumor bed with a 5 mm margin (59.4 Gy for residual disease in older children). Disseminated disease: craniospinal 36 Gy then a boost to 54 Gy.
• Infants: delay radiotherapy with chemotherapy (vincristine 1.5 mg/m2 IV weekly, cyclophosphamide 1.5 g/m2 IV on 2 days with mesna 60% of the dose in divided IV doses, cisplatin 75 mg/m2 IV, etoposide 100 mg/m2 IV on 3 days) in alternating cycles every 3 weeks.
• Chemotherapy has limited benefit in resected disease. Use it for unresectable residual tumor.
• Seizures (supratentorial): levetiracetam 10 mg/kg orally twice daily, increasing to 30 mg/kg twice daily (maximum 3 g a day), with dose reduction in renal impairment.
• Relapse: re-operation and re-irradiation (up to 54 Gy), accounting for the cumulative dose to the brainstem.

Follow-up: MRI brain and spine every 3 months for 3 years, every 6 months to year 5, then annually to year 10. Monitor endocrine, hearing and cognitive function. Counsel on late recurrence.