Background
Ependymoma is the third most common brain tumor in children, accounting for approximately 10% of primary CNS neoplasms. It is a neuroepithelial tumor that arises within, or adjacent to, the ependymal lining of the ventricular system or the central canal of the spinal cord. It tends to invade locally, even if histological appearance is benign. Approximately 90% of tumors are intracranial, with as many as 70% occurring in the posterior fossa (see image below). With surgery and radiotherapy, the overall 5-year survival rate is approximately 55%; however, survival rates as high as 80% can be achieved. Individual prognosis mostly depends on age and the extent of resection. The role of chemotherapy for infants and patients with postoperative residual disease is currently under investigation.
MRI showing an ependymoma of the fourth ventricle, compressing the cerebellum and brain stem. Pathophysiology
Ependymomas typically arise from the ependymal lining of the ventricular system, most often the floor, roof, or lateral recesses of the fourth ventricle, as depicted below. The most recent evidence suggests that radial glia cells are the stem cells of origin for this disease. Approximately one third of ependymomas are supratentorial, arising from the surface of the lateral or third ventricles; however, they may be entirely extraventricular. They may also occur in the central canal of the spinal cord and in the filum terminale, although the latter site is uncommon in children.
Sagittal section of an ependymoma of the fourth ventricle. Histologically, ependymoma can be broadly separated into two major subsets, low-grade (cellular) and high-grade (anaplastic). Low-grade ependymoma is well differentiated and lacks mitosis and vascularity. High-grade ependymoma is poorly differentiated and has a high mitotic index, necrosis, calcifications, and endothelial proliferation. Both histological subtypes are locally invasive into adjacent brain. Those in the posterior fossa frequently infiltrate the brain stem, and as many as one third may project through the foramina to involve the medulla and upper spinal cord. Spread via cerebrospinal fluid (CSF) throughout the subarachnoid space is reported, primarily with the higher-grade tumors. Extraneural metastases to liver, lung, or bone are rare. Myxopapillary ependymomas are considered a distinct variant of ependymoma primarily occurring in the region of the cauda equina.
Epidemiology
Frequency
United States
Approximately 140 new cases are reported annually in children younger than 15 years. Ependymoma represents the third most common brain tumor in children, following astrocytoma and medulloblastoma.
International
In the United Kingdom, an estimated 30-35 new pediatric cases are diagnosed annually. More than 300 new pediatric cases per year are reported in Europe.
Mortality/Morbidity
Overall survival rate is approximately 55%. Age and the extent of tumor resection are significant independent predictors of outcome. Five-year survival rate is 25% for infants younger than 1 year, 46% for children aged 1-4 years, and greater than 70% for those older than 5 years. Most patients (as high as 85%) achieve a gross total resection prior to additional therapy because of improved neurosurgical techniques. For those patients in whom complete tumor resection can be achieved, survival rates of 60-80% have been reported following local radiation. In those with partial resection or biopsy only, fewer than 30% respond to currently available best nonsurgical therapy, regardless of age or tumor histology.
Direct distortion and destruction of normal brain tissue by tumor, as well as increased intracranial pressure and surgical trauma, may cause some degree of irreversible neurologic impairment. Also, the volume and location of radiotherapy necessary to treat the tumor may result in cognitive impairment. The expanded use of conformal radiotherapy for localized disease has helped to ameliorate some of these effects.
Radiotherapy to the hypothalamic-pituitary axis may result in deficits of growth hormone, thyroid hormone, gonadotropin, and adrenocorticotropic hormone.
Race
No specific race is predisposed to ependymoma.
Sex
The male-to-female ratio is approximately 1:1.
Age
The mean age at diagnosis is 5-6 years, and 25-40% of cases occur in children younger than 3 years. Spinal cord ependymoma rarely occurs in children younger than 12 years.
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