|Tamara P. Miller, MD|
|The Children's Hospital of Philadelphia|
Brain tumors are the second most common tumor in children and account for 20% of all pediatric cancers. Ependymoma is the third most common type of pediatric brain tumor, accounting for approximately 8-10% of brain tumors in children. Ependymomas are more common in children who are younger than 3, with 25-40% of ependymomas being diagnosed in this age group.
Ependymomas are tumors that come from an abnormal growth of glial cells. A glial cell are a type of brain cells that surround the neurons. The neurons conduct electrical impulses to transmit information. Glial cells support and insulate the neurons. Ependymomas specifically come from the cells that line the ventricles, which are the fluid-filled cavities in the brain, and the canal that holds the spinal cord. The most common place where ependymomas occur in children is in the posterior fossa around the fourth ventricle. The posterior fossa is the lower part of the brain in the back. Ependymomas can also occur in the supratentorial brain, which is the part of the brain above the cerebellum, or in the spinal cord. Most ependymomas are only in the primary site where they form. However, up to 5-10% of ependymomas spread to other parts of the brain or the spine (metastases). Ependymomas can occasionally spread to other areas, outside of the brain or spine, but this is very rare.
Who gets ependymomas, and how?
Ependymomas are rare tumors. While they are never common, they are more likely to occur in younger children. It is not known why some children develop these brain tumors.
What are the signs and symptoms of an ependymoma?
When ependymomas grow, they press on and displace the normal parts of the brain. The signs and symptoms of an ependymoma depend on where the tumor is located in the brain. The most common signs of an ependymoma are headache and vomiting.
Ependymomas are often found along the lining of the ventricles. The ventricles are the spaces in the brain where cerebrospinal fluid (CSF) flows and moves around the brain. Ependymomas may grow into the ventricles and block the flow of CSF. When the flow of CSF is blocked, the CSF can back up and make the ventricles above the blockage get larger. This is called obstructive hydrocephalus. Many children have obstructive hydrocephalus when they are diagnosed with an ependymoma, and the symptoms that they experience are related to the hydrocephalus. When the fluid takes up more space than it should, the brain has less space within the skull – this can cause headaches or severe vomiting. Children may also have double or blurry vision, or hold their heads in a "tilted" position due to the increased pressure from the blocked fluid. A child may also have cranial neuropathies, which include problems with hearing, speech articulation, or swallowing. Children may also be clumsier, lose their balance easily, or be unsteady when walking.
When ependymomas are located along the spinal cord, children may have pain or weakness in their arms or legs. Children may appear to have scoliosis as well.
How are ependymomas diagnosed?
Ependymomas are diagnosed using imaging, such a Computed Tomography (CT) scan or Magnetic Resonance Imaging (MRI). If a child is seen in the emergency room he or she might first have a CT scan. CT scans use x-rays to take a series of pictures of the brain from different angles. A child may have dye injected into a vein before the CT scan is performed. CT scans are very quick. Usually children will not need to take medication to make them sleepy before having a CT scan. If the CT scan shows a possible tumor, a child will have an MRI to confirm the diagnosis.
MRI scans give the best pictures to diagnose an ependymoma. MRI scans uses magnets to take detailed pictures of the brain from multiple angles. A chemical called gadolinium is injected into the vein before the MRI is performed to help certain parts of the brain light up (enhance) to help with the diagnosis. MRI scans take several hours and the child needs to lie completely still for the entire time. Therefore children will sometimes receive medications to make them sleepy in order to not move during the MRI scan. On MRI the ependymoma will light up. The tumor is usually seen along the ventricles and may extend through the holes between the ventricles (foramen). There may also be evidence of obstructive hydrocephalus on MRI due to blockage of flow of CSF by the tumor.
While most ependymomas are localized, these tumors can occasionally spread to other parts of the brain or spine. Children who have ependymomas will usually have an MRI of the spine to make sure there is no tumor along the spine. Children will typically also need a lumbar puncture (spinal tap) to look for tumor cells in the spinal fluid. A lumbar puncture is when a small needle is inserted into the lower back to get a sample of the spinal fluid. A specially trained doctor called a pathologist will look at the cells from the CSF, under a microscope, to see if the tumor has spread.
While ependymomas usually appear a certain way on MRI scans, the diagnosis cannot be officially made until a biopsy or surgical removal of the tumor is performed. A biopsy is when a surgeon takes a small piece of tissue from the tumor. A pathologist will look at the tumor cells under a microscope to determine what type of tumor it is.
How are ependymomas staged?
Ependymomas are classified by World Health Organization (WHO) grading. The grading is determined based on how the tumor cells appear under the microscope, ranging from grade I, which looks most like normal cells, to grade III, which appear very abnormal.
There are four major types of ependymoma:
The grading of the tumor affects what type of treatment is needed.
How are ependymomas treated?
Pediatric oncologists, who are doctors that specialize in treating cancer in children, work with each patient to develop an individualized plan to treat his or her tumor. Pediatric oncologists use information learned from years of research trials that have been performed to try to discover more about the best ways to treat cancer in children. The main options for treating ependymomas include surgery, radiation and chemotherapy.
The primary treatment for ependymoma is surgical resection of the tumor. This will be performed by a neurosurgeon, who is a surgeon specialized in doing brain surgery. The goal of surgery is to completely remove the tumor, which is called gross total resection. Studies have shown that children who have a gross total resection have better long-term outcomes. After the surgery a child will have a post-operative CT or MRI scan to look for residual tumor. Patients may need more than one surgery to remove the tumor if there appears to be left over tumor after the first surgery. Sometimes the whole tumor cannot be removed because doing so would cause too much harm to the normal brain structures.
Although some patients can be treated with surgery alone, most patients will receive radiation therapy, after surgical resection, to the area where the tumor was located. Radiation therapy uses x-rays or high-energy particles that are directed at a tumor to kill abnormal cells. There are two types of radiation therapy that can be used: photon radiotherapy and proton radiotherapy. Photon radiotherapy is the traditional form of radiation therapy and has been available for much longer. In this therapy, x-rays are aimed at the tumor, enter the body, travel through the tumor, and then exit through the other side of the body. This means that the tissues on either side of the tumor receive radiation, in addition to the tumor itself. When proton therapy is used, protons enter the body and are at their peak dose at the site of the tumor. This means that they do not give as much radiation to the tissues on either side of the tumor. Only some cancer centers are able to use proton therapy currently, but it can be a good option for treating brain tumors in children.
Children will receive high doses of radiation to the area of the original ependymoma. If the MRI of the spine or lumbar puncture shows that the tumor spread to other areas, a patient will also need radiation to the spine as well. If the tumor was in the infratentorial brain, which is the lower part of the brain near the middle of the back of the head and includes the cerebellum and the brainstem, radiation therapy is needed even if the whole tumor was removed to improve the chance of survival. If the tumor is in the supratentorial brain, which is the part of the brain above the cerebellum, then sometimes the child does not need radiation if there was a gross total resection. Some infants can be cured with surgery and chemotherapy alone in order to avoid radiation therapy exposure to their very young brains. Sometimes doctors will try to wait as long as possible to use radiation to treat ependymomas in children less than 3 years of age due to the long-term side effects of radiation therapy on the developing brain.
Some children with ependymomas will also receive chemotherapy. Chemotherapy is medication taken through a vein or by mouth to treat cancer. The addition of chemotherapy is more common in children with high-grade tumors and in children whose tumor could not be surgically removed. Sometimes chemotherapy is given to shrink the tumor prior to surgery and make it easier to remove. There are clinical trials that are currently going on to determine the best chemotherapy treatment schedule. Children may receive a combination of vincristine, cisplatin, carboplatin, cyclophosphamide, etoposide or CCNU.
What is the prognosis of a child with an ependymoma?
The biggest factor related to prognosis for children with ependymomas is if the whole tumor can be removed. If a patient has a gross total resection and receives radiation therapy, the prognosis is good with current five-year survival rates estimated at 65-80%. If the whole tumor could not be removed, the five-year survival rate is approximately 20-30%. The prognosis is worse for children who have metastatic disease at diagnosis and for children with anaplastic ependymomas. Children who had an ependymoma will be monitored closely with MRI imaging for many years to evaluate for a recurrence of their tumor.
What happens if the tumor comes back?
If a child has a recurrence of his or her ependymoma, the best approach is to surgically remove the recurrent tumor, if possible. The most common place for an ependymoma to recur is at the primary tumor site. Recurrent disease is sometimes not curable, but a combination of surgery, chemotherapy and/or radiation therapy may help a child have fewer symptoms and improve quality of life.
References & Further Reading
Fleming AJ, Chi SN. Brain Tumors in Children. Current Problems in Pediatrics and Adolescent Health Care. 2012, 42:80-103.
Gajjar A, Packer RJ, Foreman NK, Cohen K, Haas-Kogen D, Merchant TE. Children's Oncology Group's 2013 Blueprint for Research: Central Nervous System Tumors. Pediatric Blood and Cancer. 2012. 60: 1022-1026.
Hastings, C. The Children's Hospital Oakland Hematology/Oncology Handbook. Mosby. 2002.
Kim JH, Huang Y, Griffin AS, Rajappa P, Greenfield JP. Ependymoma in Children: Molecular Considerations and Therapeutic Insights. Clinical and Translational Oncology. April 2013. Epub ahead of print.
Pediatric Brain Tumor Consortium: research organization devoted to the study of tumor biology and new therapies for primary CNS tumors of childhood.