Ependymoma is a rare tumor that arises within the central nervous system (CNS), which encompasses the brain and spinal cord. It is classified as a primary CNS tumor. Although it can affect individuals of any age, ependymoma represents a significant portion of brain tumors diagnosed in children, while also occurring in adults.
Origin and Characteristics
The tumor develops from ependymal cells, which are specialized glial cells that line the fluid-filled spaces of the CNS. These spaces include the four ventricles of the brain and the central canal that runs through the spinal cord.
In children, ependymomas most frequently form in the posterior fossa, the lower back part of the brain near the brainstem and cerebellum. Adult cases, by contrast, are more commonly found in the spinal cord, often in the cervical or lumbosacral regions. Ependymomas are generally slow-growing, but their behavior varies significantly, with some subtypes exhibiting aggressive growth patterns.
The proximity of these tumors to delicate nerve tissue means that even slow growth can cause serious neurological issues. When they arise in the ventricles, they may obstruct the flow of cerebrospinal fluid (CSF), leading to fluid accumulation and pressure buildup. Ependymomas rarely spread outside the CNS, but tumor cells can sometimes travel through the CSF to seed other areas of the brain or spine.
Grading and Subtypes
Ependymomas are classified using the World Health Organization (WHO) grading system, which provides an indication of the tumor’s expected biological behavior. This system assigns a grade from I to III, with a lower number corresponding to a slower-growing tumor. Grade I tumors, such as subependymoma and myxopapillary ependymoma, are considered the slowest-growing and have the most favorable outlook.
The most common form is the Grade II ependymoma, often referred to as classic ependymoma, which is intermediate in its growth rate. Grade III, historically called anaplastic ependymoma, is characterized by features like increased cell division and rapid, aggressive growth. The grade assigned by a neuropathologist is based on the tumor’s appearance under a microscope, assessing features like cell density and the presence of necrosis.
Modern diagnostics incorporate location-based and molecular classification for greater precision. The major anatomical subtypes include supratentorial (ST-EPN), posterior fossa (PF-EPN), and spinal ependymoma (SP-EPN). Supratentorial tumors are often subclassified based on gene fusions, such as ZFTA-fusion positive or YAP1-fusion positive, which carry different implications for patient outlook. Posterior fossa tumors are divided into Group A (PFA) and Group B (PFB), with PFA generally associated with a less favorable outcome than PFB.
Symptoms and Diagnostic Tools
The clinical presentation of an ependymoma depends entirely on its location within the central nervous system. When a tumor develops in the brain, symptoms are often related to increased intracranial pressure caused by the blockage of cerebrospinal fluid flow. This can manifest as persistent headaches, which are often worse in the morning, along with nausea and vomiting.
If the tumor is located in the posterior fossa, it may affect the cerebellum, leading to problems with coordination, balance, and gait instability. Intracranial tumors can also trigger seizures or cause specific neurological deficits, such as changes in vision or personality. Because these symptoms can be non-specific, there is often a delay in diagnosis, particularly in young children who cannot articulate their discomfort.
Spinal ependymomas typically present with localized pain, weakness, or sensory changes in the limbs, torso, or neck, depending on the segment of the spinal cord affected. For example, a tumor in the lower spinal cord may cause back pain that radiates to the legs, along with difficulty walking or bladder and bowel dysfunction. These symptoms often progress slowly, mimicking more common back issues initially.
Diagnosis begins with detailed imaging, primarily using magnetic resonance imaging (MRI) of the brain and spine, which provides high-resolution pictures of the tumor’s size and exact location. A computed tomography (CT) scan may also be used to identify calcification within the tumor. A definitive diagnosis, however, requires a tissue sample obtained through a biopsy or surgical removal.
The tissue sample is examined by a neuropathologist to determine the tumor’s grade and histological subtype. Modern diagnostic protocols also include molecular testing to identify specific genetic alterations, such as the ZFTA fusion or MYCN amplification, which are now recognized as distinct disease entities. In some cases, a lumbar puncture (spinal tap) may be performed to check the cerebrospinal fluid for the presence of tumor cells, indicating potential spread within the CNS.
Primary Treatment Modalities
The cornerstone of ependymoma treatment is maximal safe surgical resection, aiming to remove the tumor without causing new neurological deficits. A complete surgical removal is the single most important factor associated with a positive long-term outcome. The feasibility of achieving a complete resection is heavily dependent on the tumor’s location and its adherence to surrounding structures.
Following surgery, adjuvant therapy is often administered, with radiation therapy being the standard next step. Radiation is typically delivered to the tumor bed to eliminate any microscopic residual disease, especially when a complete removal was not possible. For higher-grade tumors (Grade III) or those with molecular features indicating a higher risk of recurrence, radiation may be recommended even after a gross total resection.
The use of chemotherapy is less common for ependymomas compared to other brain tumors, as the tumors are generally not highly responsive to these agents. It is sometimes employed in specific situations, such as in very young children to delay radiation until the developing brain is less vulnerable to its effects. Chemotherapy may also be considered for tumors that recur after initial treatment or those that have spread through the cerebrospinal fluid.