eMedicine Specialties > Oncology > Carcinomas of the Central and Peripheral Nervous System

Ependymoma

Author: Jeffrey N Bruce, MD, Edgar M Housepian Professor of Neurological Surgery Research, Professor of Neurological Surgery, Director of Brain Tumor Tissue Bank, Director of Bartoli Brain Tumor Laboratory, Department of Neurosurgery, Columbia University College of Physicians and Surgeons
Coauthor(s): David J Fusco, MD, Columbia University College of Physicians and Surgeons; Neil A Feldstein, MD, Director of Pediatric Neurosurgery, Department of Neurosurgery, Babies and Children's Hospital of New York, Assistant Professor, Departments of Clinical Neurosurgery and Pediatrics, Columbia-Presbyterian Medical Center, Columbia University; Benjamin Kennedy,, Columbia University College of Physicians and Surgeons
Contributor Information and Disclosures

Updated: Jan 26, 2009

Introduction

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.

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.²

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 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.^3,4

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.⁵ 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,⁶ a recurring breakpoint at band 11q13,⁷ abnormal karyotypes with frequent involvement of chromosome 6 and/or 16,⁸ 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).^{9,10,11,12,13}

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.

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.¹⁴

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.¹⁵ 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 Americans16

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.

Clinical

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; most patients have symptoms from 3-6 months.

• For children with masses in the fourth ventricle, a history of progressive lethargy, headache, nausea, and vomiting may be experienced secondary to increased intracranial pressure from obstructive hydrocephalus. As the tumor extends along the floor of the fourth ventricle, it may cause multiple cranial-nerve palsies (primarily VI-X), as well as cerebellar dysfunction.
• For those children who present prior to closure of cranial sutures, enlarging head circumference secondary to obstructive hydrocephalus also may be part of the clinical history.
• Supratentorial ependymomas may be associated with increased intracranial pressure manifested as headache, nausea, vomiting, and cognitive impairment. Headaches can vary in intensity and quality and are frequently more severe in the early morning or upon first awakening.
• Changes in personality, mood, and concentration can be early indicators or may be the only abnormalities observed. Seizures are a presenting symptom in 20% of patients, and focal neurologic deficits may also be prominent.
• Spinal ependymomas are usually associated with a history of progressive neurologic deficit related to involvement of ascending or descending nerve tracts, exiting peripheral nerves, and pain that correlates with the level of the lesion.
• Dissemination of the tumor through the cerebrospinal fluid (CSF) is observed in fewer than 10% of patients at diagnosis when ependymoblastomas are excluded. The incidence is higher with infratentorial ependymomas than with supratentorial tumors (9% vs 1.6%).

Physical

• Intracranial ependymoma
  • Neurologic symptoms and signs affecting patients with intracranial ependymoma can be either general or focal, and they reflect the location of the tumor.
  • At the time of diagnosis, the most common signs of infratentorial ependymomas include papilledema and ataxia. Nystagmus is present in 40-50% of patients at the time of diagnosis.
  • Supratentorial lesions often present with hemiparesis, sensory loss, visual loss, aphasia, and cognitive impairment.
• Cervical/thoracic ependymoma
  • Patients with spinal tumors in the upper segments of the cervical cord can present with pain or paresthesia in the occipital or cervical region, stiffness of the neck, and weakness and wasting of neck muscles.
  • Below the lesion, a spastic tetraplegia or hemiplegia and weakness of the ventrolateral region may occur.
  • Cutaneous sensation may be affected below the lesion with concurrent involvement of the descending trigeminal nucleus.
  • When considering radicular symptoms associated with cervical tumors, note that nerve roots in the cervical region exit above the pedicle of the like-numbered vertebra. Anatomically, the cervical nerve root exits in close relation to the undersurface of the pedicle through the neural foramen.
  • Characteristic findings associated with various cervical and upper thoracic levels are outlined as follows:
    • C4 (paralysis of the diaphragm)
    • C5 (atrophic paralysis of the deltoid, biceps, supinator longus, rhomboid, and spinate muscles): The upper arms hang limp at the side. The sensory level extends to the outer surface of the arm. The biceps and supinator reflexes are lost.
    • C6 (paralysis of triceps and wrist extensors): The forearm is held semiflexed, and a partial wrist drop is present. The triceps reflex is lost. Sensory impairment extends to a line running down the middle of the arm slightly to the radial side.
    • C7 (paralysis of the flexors of the wrist and of the flexors and extensors of the fingers): Efforts to close the hands result in extension of the wrist and slight flexion of the fingers (ie, preacher's hand). The sensory level is similar to that of the sixth cervical segment but slightly more to the ulnar side of the arm.
    • C8 (atrophic paralysis of the small muscles of the hand with resulting clawhand [main-en-griffe]): Horner syndrome, unilateral or bilateral, results from lesions at this level and is characterized by the triad of ptosis, small pupil (ie, miosis), and loss of sweating on the face. Sensory loss extends to the inner aspect of the arm and involves the fourth and fifth fingers and the ulnar aspect of the middle finger.
    • T1: Lesions rarely cause motor symptoms because this nerve root provides little functional innervation of the small hand muscles. Other signs of cervical tumors include nystagmus, especially with tumors in the upper segment. This condition is presumably caused by damage to the descending portion of the median longitudinal fasciculus. Horner syndrome may be found with intramedullary lesions in any portion of the cervical cord if the descending sympathetic pathways are affected.
• Thoracic ependymoma
  • Unlike the cervical or lumbar region of the cord where motor dysfunction is easily discernible, tumors in the thoracic region are localized more by the sensory examination.
  • Determining the location of lesions in the upper half of the thoracic cord by testing the strength of intercostal muscles is difficult.
  • The Beevor sign, in which the umbilicus moves upward when the supine patient attempts to flex the head on the chest against resistance, can be used to localize lesions below T10.
  • Abdominal skin reflexes usually are absent below the lesion.
• Lumbar ependymoma
  • The location of a lumbar lesion can be deduced easily from the patient's root level of sensory loss and associated motor weakness.
  • Radicular pain and weakness are associated with nerve root compression. In the lumbar region, the nerve root exits below and in close proximity to the pedicle of its like-numbered vertebra with the intervertebral disc space situated well below the pedicle.
  • Tumors that compress only the first and second lumbar segments cause loss of the cremasteric reflexes. The abdominal reflexes are preserved, while knee and ankle jerks are increased.
  • If the tumor affects the third and fourth segments of the lumbar cord and does not involve the roots of the cauda equina, weakness of the quadriceps, loss of the patellar reflexes, and hyperactive Achilles reflexes occur. More commonly, lesions at this level also involve the cauda equina with resulting flaccid paralysis of the legs as well as loss of knee and ankle reflexes.
  • If the spinal cord and cauda equina are affected concurrently, spastic paralysis of one leg with increased ankle reflexes ipsilaterally and flaccid paralysis with loss of reflexes contralaterally may occur.
• Myxopapillary ependymoma of the conus and cauda equina
  • The presenting symptom of tumors that involve the conus or cauda equina is pain in the back, rectal area, or both lower legs, often leading to a misdiagnosis of sciatica. Although the two regions are related anatomically, several clinical features can serve to distinguish lesions of the conus from those of the cauda equina.
  • Spontaneous pain is rarely associated with conus lesions, whereas it is usually the most prominent symptom in patients who have cauda equina lesions. The pain of a cauda equina lesion is severe and radicular in nature, involving the perineum, thighs, and legs, often asymmetrically. The pain of a conus lesion is usually bilateral and symmetric. Symmetric saddle anesthesia and dissociation mark the sensory deficit of a conus lesion secondary to the compromise of crossing fibers. Patients with sensory deficits attributable to cauda equina lesions do not have dissociation and often present with unilateral or asymmetric findings. Motor dysfunction is symmetric for conus lesions and asymmetric for cauda equina lesions. Autonomic dysfunction, such as bladder dysfunction and impotence, is typically an early sign in patients with conus medullaris lesions, whereas it is a late finding in patients with cauda equina lesions.
  • Patients with spinal tumors in the conus and cauda equina can have a combination of symptoms. As the tumor grows, flaccid paralysis of the legs, atrophy of the leg muscles, and foot drop may occur. Fasciculations may be observed in the atrophied muscles. Sensory loss may affect the perianal or saddle area as well as the remaining sacral and lumbar dermatomes. This loss may be slight, or it may be so severe that a trophic ulcer develops over the lumbosacral region, buttocks, hips, or heels. Signs of raised intracranial pressure may be observed with ependymomas of this region if the cerebrospinal fluid (CSF) protein content is high.

Causes

• Ependymomas have no known environmental cause.
• 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. 
• Intramedullary ependymomas have been associated with neurofibromatosis type I.

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