Ependymoma

Updated: Apr 14, 2015
  • Author: Jeffrey N Bruce, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Overview

Practice Essentials

Ependymomas are glial tumors that arise from ependymal cells within the CNS (see the image below).

CT scan without contrast. Fourth ventricle ependym CT scan without contrast. Fourth ventricle ependymoma.

The World Health Organization (WHO) divides them into 4 types on the basis of histologic appearance:

  • WHO grade I: Myxopapillary ependymoma, subependymoma
  • WHO grade II: Ependymoma (with cellular, papillary, and clear cell variants)
  • WHO grade III: Anaplastic ependymoma

Signs and symptoms

The clinical history associated with ependymomas varies according to the age of the patient and the location of the lesion. Reported symptoms may include the following:

  • Masses in the fourth ventricle: Progressive lethargy, headache, nausea, and vomiting; multiple cranial-nerve palsies (primarily VI-X), as well as cerebellar dysfunction
  • In children who present before closure of cranial sutures, enlarging head circumference secondary to obstructive hydrocephalus
  • Supratentorial ependymomas: Increased intracranial pressure manifested as headache, nausea, vomiting, and cognitive impairment
  • Changes in personality, mood, and concentration; seizures; focal neurologic deficits
  • Spinal ependymomas: Progressive neurologic deficit

Physical findings with intracranial ependymomas may include the following:

  • General or focal neurologic signs reflecting the location of the tumor
  • Infratentorial ependymomas: Papilledema ataxia; nystagmus
  • Supratentorial ependymomas: Hemiparesis, sensory loss, visual loss, aphasia, and cognitive impairment

Physical findings with cervical or thoracic ependymomas may include the following:

  • Spinal tumors in the upper cervical cord: Occipital or cervical pain or paresthesia, neck stiffness, and weakness and wasting of neck muscles
  • Spastic tetraplegia or hemiplegia and weakness ventrolaterally below the lesion
  • Altered cutaneous sensation below the lesion
  • Characteristic findings associated with specific cervical and upper thoracic levels (eg, C4, C5, C6, C7, C8, T1)

Physical findings with thoracic ependymomas may include the following:

  • These tumors are localized more by the sensory (as opposed to motor) examination
  • Localizing upper thoracic lesions by testing intercostal muscle strength is difficult
  • Beevor sign localizes lesions below T10
  • Abdominal skin reflexes usually are absent below the lesion

Physical findings with lumbar ependymomas may include the following:

  • These lesions are localized from the root level of sensory loss and motor weakness
  • Nerve root compression: Radicular pain and weakness
  • Lesions compressing only the first and second lumbar segments: Lost cremasteric reflexes, preserved abdominal reflexes, and increased knee and ankle jerks
  • Lesions affecting the third and fourth lumbar segments: If the roots of the cauda equina are not affected, weakness of the quadriceps, loss of the patellar reflexes, and hyperactive Achilles reflexes may be present; if they are affected, flaccid paralysis of the legs and loss of knee and ankle reflexes may occur
  • Lesions affecting spinal cord and cauda equina concurrently: Spastic paralysis of one leg with increased ankle reflexes ipsilaterally may occur, as well as flaccid paralysis with loss of reflexes contralaterally

Physical findings with myxopapillary ependymomas of the conus and cauda equina may include the following:

  • Presenting symptom is pain in the back, rectal area, or both lower legs
  • Spontaneous pain is rare with conus lesions but prominent with cauda equina lesions
  • Motor dysfunction is symmetric for conus lesions and asymmetric for cauda equina lesions
  • Autonomic dysfunction is typically an early sign with conus lesions but a late finding with cauda equina lesions

See Clinical Presentation for more detail.

Diagnosis

No laboratory studies are helpful in making the diagnosis of ependymoma. On CT and MRI, e pendymomas have some characteristic features that help narrow the differential diagnosis, including the following:

  • Intracranial ependymoma: Typically isodense on unenhanced CT, with minimal to moderate enhancement on contrast administration; on precontrast and postcontrast MRI, usually hypointense to isointense on T1-weighted images and hyperintense (compared with gray matter) on T2-weighted images
  • Spinal ependymoma: Most intramedullary tumors are isointense or slightly hypointense to the surrounding spinal cord on T1-weighted images; most tumors are hyperintense to the spinal cord on T2-weighted images

Other diagnostic modalities that may be helpful include the following:

See Workup for more detail.

Management

Medical management of ependymomas includes the following [1, 2] :

  • Adjuvant therapy (ie, conventional radiation therapy, radiosurgery, chemotherapy)
  • Steroids for treatment of peritumoral edema
  • Anticonvulsants in patients with supratentorial ependymoma

The National Comprehensive Cancer Network (NCCN) suggests the following for adults:

  • After gross total resection (GTR) of an intracranial WHO grade II ependymoma, limited field fractionated external beam radiotherapy (LFFEBRT) can be considered
  • Postoperative LFFEBRT is recommended for WHO grade II ependymoma when subtotal resection is noted on postoperative MRI and for grade III anaplastic ependymoma regardless of extent of resection [3] ; if postoperative spinal MRI or LP findings are positive, craniospinal radiation therapy is indicated regardless of grade or extent of resection
  • For recurrent ependymoma, if a patient has not received radiation therapy, such therapy should be administered; if a patient has received radiation therapy, then chemotherapy, radiation therapy, or supportive care should be considered [4]

In terms of surgical care, a GTR is optimal. Approaches include the following:

  • Children with posterior fossa lesions: Midline suboccipital approach; hydrocephalus can be managed with a perioperative external ventricular drain, ventriculoperitoneal shunt, or, more rarely, third ventriculostomy
  • Intramedullary tumors: Standard laminectomy with the patient prone; laminoplasty is performed in children but does not guarantee long-term stability
  • Filum terminale ependymoma: Gross total en bloc resection whenever possible

See Treatment and Medication for more detail.

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Background

Ependymomas are glial tumors that arise from ependymal cells within the central nervous system (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.

See the image below.

Gross surgical specimen of a fourth ventricle epen Gross surgical specimen of a fourth ventricle ependymoma.

Intracranial ependymomas present as intraventricular masses with frequent extension into the subarachnoid space, [5] 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. [6]

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. [7, 8, 9, 10]

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Pathophysiology

Ependymomas are traditionally thought to 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. Some evidence now suggests that radial glia may be the cells of origin. [11, 12]

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. [13] 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, [14] a recurring breakpoint at band 11q13, [15] abnormal karyotypes with frequent involvement of chromosome 6 and/or 16, [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). [17, 18, 19, 20, 21, 22]

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.

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Epidemiology

Frequency

United States

Frequency of ependymomas is similar to that in other parts of the world.

International

Intracranial ependymomas represent 6-9% of primary CNS neoplasms and account for 30% of primary CNS neoplasms in children younger than 3 years. [23]

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. [24] Stratification based on age reveals 5-year survival rates of 76% in adults and 14% in children.

Race

Grade II and III ependymoma are more common in black Americans than white Americans. [25]

Sex

The incidence of ependymoma is approximately equal in males and females.

Age

Ependymomas generally present in young children with a mean age of diagnosis of 4 years, yet 25-40% of patients are younger than 2 years. Spinal ependymomas are most common in patients aged 15-40 years, most of which are of a myxopapillary subtype. Intracranial tumors are seen more often in children, particularly in the infratentorial compartment.

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