Ependymomas are a common type of glioma formed from ependymal (glial) cells, which line the passageways of the central nervous system (CNS). The CNS is responsible for all sensory and motor functions in the body, and is composed of the brain and spinal cord.
The brain is a complex organ that is responsible for controlling all functions of the body. It has five main portions: the cerebrum, cerebellum, brainstem, pituitary gland, and hypothalamus. The cerebrum is the biggest part of the brain, and consists of the frontal, parietal, temporal, and occipital lobes. This part of the brain is responsible for voluntary movement, intelligence, and memory. The cerebellum is a small part of the brain located at the back of the head, and regulates posture and balance. The brainstem is a small, stalk-like structure towards the bottom of the brain that connects the brain to the spinal cord. It regulates many vital bodily processes, such as swallowing, breathing, and heart rate. The pituitary gland is a pea sized organ located behind the eyes, and is responsible for the production and secretion of hormones in the body. The hypothalamus is located deep within the brain, and has many important functions, such as producing and secreting different hormones, regulating temperature, and controlling appetite.
The spinal cord is a long, thin, tubular structure that extends down from the brainstem to the lower back. It is made of nerve tissue, and is surrounded by the bones of the spine (vertebrae). The spinal cord is responsible for transmitting nerve signals from the brain to the body, and vice versa. It has motor functions (such as voluntary movement), sensory functions (such as pressure, touch, temperature, and pain), and autonomous functions (such as regulating digestion, heart rate, and blood pressure).
In children, an ependymoma is most commonly found in the cerebellum portion of the brain, which is responsible for voluntary movements such as walking, balance, coordination and speech. In adults, an ependymoma is more likely to be found in the spinal cord and may cause weakness in the portion of the body controlled by the nerves affecting the tumour.
Ependymomas are mostly diagnosed in young children and are more prevalent in males, however, they can develop in anyone at any age.
Types of Ependymomas
There are several types of ependymomas, which can be categorised by their location within the CNS, as well as their cellular appearance under the microscope.
Ependymoma Subtypes Based on Location
Ependymomas can be classified by their location within the CNS.
Posterior Fossa/Infratentorial Ependymoma
Posterior fossa ependymomas, also referred to as infratentorial ependymomas, are the most common subtype of ependymoma found in the posterior fossa, a small area in the skull near the cerebellum and brainstem. They can be classified into three primary categories (posterior fossa groups A and B, and subependymomas) based on cellular appearance.
The aggressiveness and prognosis of ependymomas found in the posterior fossa vary based on the subtype diagnosed and cellular appearance.
Supratentorial Ependymoma
Supratentorial ependymomas are a less common subtype of ependymoma most commonly found within the cerebral hemispheres. They can be classified into four primary categories (ZTFA fusion-positive, YAP1-MAMLD1 fusion, supratentorial ependymomas without ZFTA or YAP1 fusion, and subependymomas) based on cellular appearance.
The aggressiveness and prognosis of ependymomas found in the supratentorial region vary based on the subtype diagnosed and cellular appearance.
Spinal Ependymoma
Spinal ependymomas are a common type of spinal tumour that develop from glial cells in the spinal cord. Unlike other types of ependymoma, this disease tends to occur in patients between the ages of 30-40, and are generally more common in males. Spinal ependymomas can be classified into four primary categories (subependymoma, myxopapillary, MYCN-amplified, and not otherwise specified).
Ependymoma Subtypes Based on Cellular Appearance
In addition to their location, ependymomas can also be categorised based on their cellular appearance.
Posterior Fossa Group A (PFA) Ependymoma
Posterior fossa group A (PFA) ependymomas are a relatively common subtype of posterior fossa ependymomas that generally occur in infants and children under six years old. It is characterised by increased DNA-methylation, which is a specific process that changes a person’s DNA sequence, and is slightly more common in males. PFA ependymoma is often aggressive, and may not have as good of a prognosis as other ependymoma subtypes.
Posterior Fossa Group B (PFB) Ependymoma
Posterior fossa group B (PFB) ependymomas are a relatively common subtype of posterior fossa ependymomas that generally occur in adolescents and adults. It is also characterised by increased DNA-methylation, however it is not as high as PFA ependymomas. Unlike most ependymoma subtypes, PFB ependymomas are slightly more common in females. This subtype generally carries more favourable prognosis than PFA ependymomas.
Supratentorial Ependymoma ZFTA Fusion-Positive
Supratentorial ependymomas that are ZFTA fusion-positive are a common type of supratentorial ependymoma that occurs when the ZFTA (zinc finger translocation associated) gene fuses together with another gene, most commonly the RELA (REL-associated) gene. Both ZFTA and RELA are responsible for coding proteins, so changes in these genes (including a fusion of the two) often results in altered DNA and potentially adverse health conditions.
Supratentorial ependymomas ZTFA fusion-positive are slightly more common in males, and tends to affect older children around the age of nine. This subtype is often aggressive, and may not have as good of a prognosis as other types of ependymoma.
Supratentorial Ependymoma YAP1 Fusion
Supratentorial ependymomas with a YAP1 fusion are a rare type of supratentorial ependymoma that occurs when the YAP1 (Yes1 Associated Transcriptional Regulator) fuses together with another gene, most commonly the MAMLD1 (mastermind like domain containing 1 gene). Both YAP1 and MAMLD1 are responsible for coding proteins, so changes in these genes (including a fusion of the two) often results in altered DNA and potentially adverse health conditions.
Supratentorial ependymomas YAP1 fusion are slightly more common in females, and tend to affect infants under the age of three. This subtype generally carries a more favourable prognosis than supratentorial ependymoma ZFTA fusion positive.
Supratentorial Ependymoma – Not Otherwise Specified (NOS)
Supratentorial ependymomas not otherwise specified (NOS) occur when the ZFTA and YAP1 fusions are absent. These tumours are very rare, and have limited data available on their aggressiveness and prognosis.
Myxopapillary Ependymoma
Myxopapillary ependymomas are a type of spinal ependymoma that most commonly develop in the lumbosacral portion of the spine. They are most commonly found in patients between the ages of 35-39, and are slightly more common in males. While these tumours can be aggressive, they often have a good prognosis.
Spinal Ependymoma – Not Otherwise Specified (NOS)
Spinal ependymomas not otherwise specified (NOS) are the most common subtype of spinal ependymomas, and are generally found in the centre of the spinal cord. This subtype is generally diagnosed between the ages of 30-40, and are most commonly diagnosed in males. While these tumours can be aggressive, they often have a good prognosis.
Spinal Ependymoma – MYCN-amplified
Spinal ependymomas MYCN-amplified are a newly recognised spinal tumour that is caused by an amplification of the MYCN gene. MYCN is responsible for coding proteins, so changes in these genes often results in altered DNA and potentially adverse health conditions. It most commonly affects young adults, and are often aggressive. Because of how rare these tumours are, there has been limited research done into the prognosis of this disease.
Subependymoma
Subependymomas are a rare type of ependymoma that can develop in the posterior fossa, supratentorial region and the spinal cord. They are most commonly found in people between 50 and 60, and are slightly more common in males. These tumours are often slow-growing, non-aggressive, and often have a good prognosis.
Treatment
When cancers are detected, they are staged and graded based on size, metastasis (whether the cancer has spread to other parts of the body), and how the cancer cells look under the microscope. Staging and grading helps your doctors determine the best treatment for you. However, brain cancers are rarely staged, as they rarely spread to other parts of the body. Instead, they are generally graded.
Ependymomas are generally graded by subtype:
- Grade I (low-grade) tumours: cancer cells present as slightly abnormal and are usually slow growing.
- Grade II (intermediate-grade) tumours: cancer cells present as abnormal and grow faster than grade-I tumours.
- Grade III (high grade) tumours: cancer cells present as very abnormal and grow quickly.
Your doctor may also recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. They will then discuss the most appropriate treatment option for you.
Treatment is dependent on several factors, including location, age, stage of disease and overall health.
Treatment options for ependymomas may include:
- Surgery to remove as much of the tumour as possible.
- Radiation therapy.
- Chemotherapy.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
Risk factors
Because of how rare ependymomas are, there isn’t a lot of information surrounding the risk factors of this disease. However, a potential link has been identified between the condition neurofibromatosis type 2 (NF2), and the development of ependymomas.
Early symptoms
The symptoms in people with ependymomas will vary depending on the tumour stage and location. Some of the common symptoms of ependymomas in the brain are:
- Hydrocephalus (fluid build-up in the brain), which carries its own set of symptoms:
- Headaches.
- Nausea and/or vomiting.
- Difficulties with eye movement.
- Difficulties with balance.
- Difficulties with walking.
- Dizziness.
- Difficulties with vision, such as increased blurriness.
- Walking difficulties.
- Difficulties controlling eye movement.
- Neck pain.
- Delayed or regressed developmental milestones.
- Seizures.
Some of the common symptoms of ependymomas in the spine are:
- Back pain.
- Numbness and weakness in limbs or trunk.
- Difficulties with urinating and bowel movements.
Not everyone with the symptoms above will have cancer but see your general practitioner (GP) if you are concerned.
Diagnosis/diagnosing
If your doctor suspects you have an ependymoma, they will order a variety of tests to confirm the diagnosis and refer you to a specialist for treatment.
Neurological exam
A neurological examination assesses sensory and motor functions, and can generally be done in your GPs office. The doctor may check your vision, hearing, balance, coordination, strength and reflexes, depending on the signs and symptoms you have described. Any problem that is detected in this exam can help determine which portion of the CNS needs further investigation.
Imaging & blood tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), x-ray, and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis. Additionally, a blood test may be taken to assess your overall health and help guide treatment decisions.
Lumbar puncture
A lumbar puncture, or spinal tap, involves inserting a needle between two vertebrae in the lower spine and extracting a sample of cerebral spinal fluid (CSF) for analysis. A local anaesthetic or sedative is given prior to the procedure. Your doctor will discuss any risks and possible complications with you prior to the procedure.
Biopsy
Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. This can be done by either a punch biopsy, a fine needle aspiration, and/or a lymph node biopsy. The samples are then analysed for cancer cells.
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor will be able to give you a general idea based on stage, rate/depth of tumour growth, susceptibility to treatment, age, overall fitness and medical history. Generally, early-stage ependymomas have good prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis is not as good and there is a higher risk of cancer recurrence.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.