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.

Frequency:

• In the US: Frequency of ependymomas is similar to that in other parts of the world.

• Internationally: Intracranial ependymomas represent 6-9% of primary CNS neoplasms and account for 30% of primary CNS neoplasms in children younger than 3 years. They 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, most of which are of a myxopapillary subtype. Intramedullary ependymomas have been associated with neurofibromatosis type I. Intracranial tumors are seen more often in children, particularly in the infratentorial compartment.

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.

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