January 16, 2007


Synonyms and related keywords: cellular ependymoma, papillary ependymoma, clear cell ependymoma, anaplastic ependymoma, myxopapillary ependymoma, subependymoma, glial tumor, ependymal cell


Background: Ependymomas are glial tumors that arise from ependymal cells within the CNS. They were first described by Bailey in 1924. The World Health Organization (WHO) classification scheme for these tumors includes 4 divisions based on histologic appearance: WHO grade I, myxopapillary ependymoma and subependymoma; WHO grade II, ependymoma (with cellular, papillary, and clear cell variants); WHO grade III, anaplastic ependymoma. Myxopapillary ependymomas are considered a biologically and morphologically distinct variant of ependymoma, occurring almost exclusively in the region of the cauda equina and behaving in a more benign fashion than grade II ependymoma. Subependymomas are uncommon lesions that share the benign features of myxopapillary ependymomas. Ependymoblastomas are now considered a primitive neuroectodermal tumor (PNET) and are distinct from ependymoma.

Intracranial ependymomas present as intraventricular masses with frequent extension into the subarachnoid space, while spinal ependymomas present as intramedullary masses arising from the central canal or exophytic masses at the conus and cauda equina.

The anatomic distinction between intracranial and spinal locations has an epidemiologic and clinical correlate. In children, approximately 90% of ependymomas are intracranial, with the majority of these usually arising from the roof of the fourth ventricle (infratentorial). In adults and adolescents, 75% of ependymomas arise within the spinal canal, with a significant minority occurring intracranially in the supratentorial compartment.

Treatment of patients with ependymomas depends upon neurosurgical intervention to facilitate definitive diagnosis and to decrease tumor burden. Postoperative adjuvant therapy can include brain or spine radiation, chemotherapy, and radiosurgery.

Pathophysiology: Ependymomas arise from oncogenetic events that transform normal ependymal cells into tumor phenotypes. The precise nature and order of these genetic events are unknown; however, significant progress has been made toward delineating mutations that segregate with various tumor phenotypes.

In 1988, Dal Chin and colleagues described cytogenetic studies on a supratentorial ependymoma from a 3-year-old girl that showed a t(10;11;15)(p12.2;q13.1;p12) and loss of one X chromosome. This relatively simple karyotypic change was not observed in the analysis of 4 ependymomas published 1 year later. In 1 of the 4 ependymomas studied, translocations involving chromosomes 9, 17, and 22 were observed together with loss of the normal chromosome 17. A second ependymoma had many chromosomal alterations that included a translocation between chromosomes 1 and 2 and rearrangements involving chromosome 17. Consistent genetic alterations were not detected in the remaining 2 cases.

These initial studies underscore the molecular heterogeneity that can exist among histologically identical tumors. Subsequent studies have identified more consistent genetic defects as follows: a loss of loci on chromosome 22, a mutation of p53 in malignant ependymoma, a recurring breakpoint at band 11q13, abnormal karyotypes with frequent involvement of chromosome 6 and/or 16, and NF2 mutations. Clustering of ependymomas has been reported in some families, with segregation analysis in one family suggesting the presence of an ependymoma tumor suppressor gene in the region of the chromosome 22 locus loss (22pter-22q11.2).

The ultimate goal of genetic studies is to demonstrate a causal relationship between specific mutations and tumor progression. Current efforts in the field are directed toward identifying another tumor suppressor gene on chromosome 22.


Mortality/Morbidity: Depending on the patient population, the reported 10-year overall survival rate for ependymoma can vary from 45-55%. The current 5-year survival rate for patients with intracranial ependymomas is approximately 50%, when rates from children and adults are combined. Stratification based on age reveals 5-year survival rates of 76% in adults and 14% in children.

Sex: The incidence of ependymoma is approximately equal between males and females.


History: The clinical history associated with ependymomas varies depending upon the age of the patient and the location of the lesion. The duration of symptoms prior to diagnosis usually varies from 1-36 months, with the majority of patients having symptoms from 3-6 months.



  • As noted earlier in Pathophysiology, a number of genetic mutations have been associated with ependymomas. However, a causal relationship between these mutations and tumor progression has not yet been determined.


Arteriovenous Malformations
Choroid Plexus Papilloma
Glioblastoma Multiforme
Tumors of the Conus and Cauda Equina

Other Problems to be Considered:

Intracranial (posterior fossa)

Cerebral neuroblastoma
Choroid plexus papilloma

Intracranial (supratentorial)

Central neurocytoma
Microcystic meningioma
Glioblastoma multiforme

Spinal (intramedullary)

Metastatic tumor

Spinal (exophytic/extramedullary)

Paraganglioma of the filum terminale

Other considerations

Arteriovenous malformations
Cavernous malformation


Lab Studies:

Imaging Studies:

    • Spinal ependymoma: In general, most intramedullary tumors are isointense or slightly hypointense to the surrounding spinal cord on T1-weighted images. Often, only subtle spinal cord enlargement is evident. T2-weighted images are more sensitive because most tumors are hyperintense to the spinal cord on these pulse sequences. T2 studies are not particularly specific and may not distinguish the solid tumor from polar cysts. Nearly all intramedullary neoplasms enhance on T1-weighted contrast examinations. Ependymomas usually demonstrate uniform contrast enhancement and are located symmetrically within the spinal cord. Polar cysts are identified in the majority of cases, particularly in the setting of cervical or cervicothoracic tumors. Heterogeneous enhancement from intratumoral cysts or necrosis also can be observed.

      In some cases, contrast enhancement of a cystic ependymoma may be minimal. In these cases, distinguishing these tumors from intramedullary astrocytomas is difficult.

Other Tests:

  • Electroencephalography (EEG) performed on a patient with a supratentorial ependymoma may show generalized, diffuse slowing and/or epileptogenic spikes over the area of the tumor. However, no findings on EEG are specific for ependymoma.


  • Lumbar puncture (LP) generally is contraindicated in the setting of a brain tumor because of the risk of transtentorial herniation secondary to increased intracranial pressure. CSF studies do not aid significantly in the diagnosis of ependymomas, with the possible exception of determining leptomeningeal spread in children with posterior fossa tumors. Yet even in this case, spinal MRI performed with and without contrast enhancement is a more optimal study for such a determination. In the case of spinal ependymoma, CSF obtained from LP may show elevated protein levels.
Histologic Findings: Ependymoma (WHO grade II) pathology includes cellular, papillary, and clear cell variants, as well as anaplastic ependymomas (WHO grade III), myxopapillary ependymomas (WHO grade I), and subependymomas (WHO grade I) . Histologically, ependymomas are characterized by ependymal pseudorosettes with glial fibrillary acidic protein (GFAP)–positive processes tapering toward blood vessels. Myxopapillary ependymomas are located at the cauda equina and conus, while subependymoma and anaplastic ependymomas are described at intramedullary locations.

A variety of histologic ependymoma subtypes may be encountered. The cellular ependymoma is the most common, but epithelial, tanycytic (fibrillar), subependymoma, myxopapillary, or mixed examples also occur. Histologic differentiation from astrocytoma may be difficult, but the presence of perivascular pseudorosettes or true rosettes establishes the diagnosis. Most spinal ependymomas are histologically benign, although necrosis and intratumoral hemorrhage are frequent. Although unencapsulated, these glial-derived tumors are usually well circumscribed and do not infiltrate adjacent spinal cord tissue. Recent attempts to correlate the expression of MIB-1 antigen with malignancy of ependymomas have been confounded by tumor heterogeneity. Myxopapillary ependymoma histology consists of a papillary arrangement of cuboidal or columnar tumor cells surrounding a vascularized core of hyalinized and poorly cellular connective tissue.

Staging: No conventional staging criteria exist for intracranial or spinal ependymomas. Postoperative MRI is recommended within 48 hours of tumor resection to assess presence of residual tumor and to facilitate adjuvant treatment planning. In the case of children with ependymomas of the fourth ventricle, a surveillance spinal MRI often is recommended to rule out seeding.


Medical Care: Medical management of patients with ependymomas includes adjuvant therapy (ie, conventional radiation therapy, radiosurgery, chemotherapy), steroids for treatment of peritumoral edema, and anticonvulsants in patients with supratentorial ependymoma.

Surgical Care: The extent of tumor resection is the most important prognostic factor associated with long-term survival for patients with nonmalignant forms of ependymoma, regardless of location. Thus, a gross total resection (GTR) is optimal.


Diet: No restrictions of diet are required for patients with ependymomas.

Activity: No universal restrictions on activity are required for patients with ependymomas.


No specific medications exist to treat ependymomas; however, supratentorial ependymomas require medical treatment. For seizures, patients usually are started on phenytoin (Dilantin) or carbamazepine (Tegretol). Vasogenic cerebral edema is treated with corticosteroids (eg, dexamethasone), generally in combination with an anti-ulcer agent. Corticosteroids also are effective to treat edema associated with intramedullary tumors in the preoperative and postoperative settings.

Drug Category: Anticonvulsants -- These agents are used to treat and to prevent seizures.

Drug Name
Phenytoin (Dilantin) -- Blocks sodium channels and prevents repetitive firing of action potentials. Effective anticonvulsant and first-line agent in treating partial and generalized tonic-clonic seizures.
Adult DoseLoading dose: 15 mg/kg or 1000 mg/kg IV over 4 h divided bid/tid
Maintenance dose: 5 mg/kg/d or 300 mg PO/IV qd or divided tid; adjust based on serum levels
Pediatric DoseLoading dose: 15 mg/kg PO/IV
Maintenance dose: 5 mg/kg/d PO/IV qd or divided tid
ContraindicationsDocumented hypersensitivity; sinoatrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome
InteractionsAmiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, isoniazid, and valproic acid may increase toxicity; barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate may decrease effects; may decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, oral contraceptives, and valproic acid
Pregnancy D - Unsafe in pregnancy
PrecautionsRapid IV infusion may result in death from cardiac arrest, marked by QRS widening
Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if skin rash appears, and do not resume use if rash is exfoliative, bullous, or purpuric; caution in acute intermittent porphyria and diabetes (may elevate blood glucose); discontinue use if hepatic dysfunction occurs; follow for signs of toxicity including nystagmus, diplopia, and ataxia (may necessitate lowering dose)
Drug Name
Carbamazepine (Tegretol) -- Like phenytoin, interacts with sodium channels and blocks repetitive neuronal firing. First-line agent to treat partial seizures and may be used for tonic-clonic seizures as well. Extended release form available, which is administered bid. Serum drug levels should be monitored (ideal range is 4-8 mcg/mL).
Adult Dose200-600 mg PO tid/qid
Pediatric Dose15-25 mg/kg/d PO divided tid/qid
ContraindicationsDocumented hypersensitivity; history of bone marrow depression; MAOIs within last 14 d
InteractionsDanazol within 30 days may increase serum levels significantly (avoid whenever possible); do not coadminister with MAOIs; cimetidine may increase toxicity, especially if taken in first 4 wk of therapy; may decrease primidone, valproic acid, and phenobarbital levels (coadministration may increase carbamazepine levels)
Pregnancy D - Unsafe in pregnancy
PrecautionsCaution with increased intraocular pressure; obtain CBC counts and serum iron at baseline prior to treatment, during first 2 mo, and yearly or every other year thereafter; can cause drowsiness, dizziness, and blurred vision; caution while driving or performing other tasks requiring alertness
Drug Category: Corticosteroids -- These agents reduce peritumoral edema, frequently leading to symptomatic and objective improvement.
Drug Name
Dexamethasone (Decadron) -- Postulated mechanisms of action in brain tumors include reduction in vascular permeability, cytotoxic effects on tumors, inhibition of tumor formation, and decreased CSF production.
Adult Dose16 mg/d PO/IV divided q6h; taper to minimum effective dose or discontinue
Pediatric Dose0.5 mg/kg/d PO/IV divided q6h
ContraindicationsDocumented hypersensitivity; active bacterial or fungal infection
InteractionsBarbiturates, phenytoin, and rifampin decrease effects; decreases effects of salicylates and vaccines used for immunization
Pregnancy C - Safety for use during pregnancy has not been established.
PrecautionsIncreases risk of multiple complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use; severe stress may necessitate extra dosing


Further Inpatient Care:

Further Outpatient Care:

In/Out Patient Meds:




  • As noted in Mortality/Morbidity, intracranial ependymoma has an overall 5-year survival rate of approximately 50%, but the survival rate is significantly less for children with posterior fossa tumors.

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