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Ependymomas are glial neoplasms originating from ependymal cells that line the cerebral ventricles and the central canal of the spinal cord. Representing approximately 2% to 3% of adult primary central nervous system tumors and up to 10% of pediatric brain tumors, ependymomas exhibit diverse anatomical and molecular profiles. Pediatric cases typically develop in the posterior fossa, whereas adult lesions more frequently are located within the spinal cord. The 2021 World Health Organization classification introduced molecular subgroups that refine the prognostic assessment and guide management decisions. Diagnosis integrates neuroimaging, histopathologic analysis, and molecular testing to distinguish tumor subtypes. Standard management involves maximal safe resection, often followed by adjuvant radiotherapy, while chemotherapy remains reserved for specific cases. Long-term surveillance is essential due to the risks of recurrence and treatment-related morbidity, highlighting the need for a coordinated multidisciplinary team follow-up approach. Through participation in this educational activity, clinicians will improve their ability to recognize ependymoma subtypes, interpret molecular and imaging findings, and integrate evidence-based strategies for diagnosis and management. This course enhances clinician competence in surgical planning, radiotherapeutic decision-making, and risk-adapted postoperative surveillance. Emphasis on interprofessional collaboration among neurosurgeons, neuro-oncologists, pathologists, radiation oncologists, radiologists, and rehabilitation medicine specialists promotes comprehensive, patient-centered care. By fostering communication across disciplines, clinicians improve diagnostic precision, reduce treatment variability, and support long-term functional and neurocognitive recovery in individuals affected by ependymoma. Objectives: Create individualized, multimodal management plans that integrate surgery, radiation therapy, and supportive therapies to improve functional recovery and quality of life. Differentiate ependymomas from other glial and embryonal tumors through radiologic, molecular, and immunohistochemical analysis. Determine appropriate criteria for maximal safe surgical resection, balancing oncologic control with preservation of neurological function.

Create individualized, multimodal management plans that integrate surgery, radiation therapy, and supportive therapies to improve functional recovery and quality of life. Differentiate ependymomas from other glial and embryonal tumors through radiologic, molecular, and immunohistochemical analysis. Determine appropriate criteria for maximal safe surgical resection, balancing oncologic control with preservation of neurological function. Coordinate among interprofessional team members to improve outcomes for patients affected by ependymoma. Access free multiple choice questions on this topic.

Ependymomas are glial tumors originating from ependymal cells that line the ventricular system of the brain and the central canal of the spinal cord. They account for approximately 2% to 3% of all primary central nervous system (CNS) tumors in adults and up to 10% in children, making them one of the more common pediatric brain tumors after medulloblastoma and juvenile pilocytic astrocytoma.[1] These tumors demonstrate a wide anatomic distribution: approximately two-thirds occur intracranially in children, most often in the posterior fossa; in adults, most cases are located in the spinal cord.[2] The 2016 and 2021 World Health Organization (WHO) classifications of CNS tumors have reshaped ependymoma classification, emphasizing histopathological features and molecular subgroups with distinct prognostic and therapeutic implications. For instance, posterior fossa ependymomas are now stratified into 2 groups: posterior fossa group A (PFA) and posterior fossa group B (PFB), which demonstrate markedly different biological behaviors and survival outcomes.[2][3] Similarly, supratentorial ependymomas often harbor ZFTA (formerly RELA) fusions or YAP1 fusions, each defining a molecularly distinct disease entity.[3] Clinically, ependymomas present with symptoms related to mass effect, hydrocephalus, or focal neurological deficits, depending on their location. The mainstay of treatment remains maximal safe resection, often followed by adjuvant radiotherapy, usually in cases of incomplete surgical resection. The role of chemotherapy remains limited, although investigational protocols are being studied.[4][5] Despite advances in surgery, imaging, and molecular classification, ependymomas remain challenging tumors with a significant risk of recurrence and variable prognosis across age groups and molecular subtypes. Ongoing research into targeted therapies and molecular diagnostics is expected to refine treatment strategies further and improve outcomes.

The etiology of ependymoma (EPN) is multifactorial and remains incompletely understood. Historically, these tumors were thought to arise from residual embryonic ependymal cells lining the ventricular system and central canal of the spinal cord. Contemporary molecular studies suggest that their origin is more complex, involving disruptions in neural stem cell populations and specific genetic alterations that promote tumorigenesis.[3][6] Evidence from animal models and human molecular profiling suggests that ependymomas may originate from radial glia-like stem cells in specific CNS regions. These progenitor cells possess the ability for self-renewal and multipotency, making them susceptible to oncogenic transformation when critical regulatory pathways are disrupted.[7] Most notably, the anatomic and molecular heterogeneity of ependymomas suggests that tumors originating in different CNS compartments arise from distinct precursor cell populations. Molecular profiling has identified several distinct genetic alterations that define ependymoma subgroups.[8] Subgroups of Ependymoma Posterior fossa (PF): PF-EPN-SE (subependymoma) PF-EPN-B (group B) is more common in older children and adults, with a better prognosis PF-EPN-A (group A) typically found in infants and young children, with a poor prognosis PF-A tumors often exhibit epigenetic dysregulation, including widespread DNA hypermethylation, but lack recurrent coding mutations [3][8][9] Supratentorial (ST): ST-EPN-SE (subependymoma) ST-EPN-YAP1 (YAP1 fusions) is associated with a more favorable prognosis and occurs predominantly in young children [10] ST-EPN-ZFTA (formerly RELA fusions) activate nuclear factor (NF) kappa-light-chain-enhancer of activated B cells signaling and defining an aggressive subgroup[11] Spinal ependymomas: SP-EPN-MPE (myxopapillary) SP-EPN-SE (subependymoma) SP-EPN Spinal ependymomas are often associated with NF2 gene inactivation, consistent with the known link between neurofibromatosis type 2 and spinal ependymomas.[2][6] Unlike other brain tumors, such as gliomas, environmental risk factors for ependymomas are not well established. There have been no clear associations with prior radiation treatment, toxins, or infectious agents.

Ependymomas are uncommon primary CNS tumors that represent approximately 1.6% of all CNS tumors across all age groups and approximately 6% to 12% of pediatric intracranial neoplasms.[1] The annual incidence of ependymomas is estimated at 0.3 to 0.4 per 100,000 population in the United States, with slight variations by geography and registry.[1] Their distribution, age of onset, and anatomical predilection differ significantly between children and adults. Children often present with intracranial ependymomas, of which approximately two-thirds are in the posterior fossa.[1] Adults tend to develop spinal cord ependymomas, most often in the cervical and cervicothoracic regions.[4] There are no strong racial or ethnic predilections. However, there may be a slightly higher incidence of ependymomas among white populations compared with black or asian populations.[1]

Ependymomas are glial tumors that exhibit a range of morphological features, which historically have determined their classification. The 2021 WHO classification of CNS tumors incorporates molecular alterations into the diagnostic criteria. The histological evaluation provides critical diagnostic, grading, and prognostic information.[2] Ependymomas typically display a moderately cellular, well-demarcated growth pattern, characterized by two hallmark microscopic features. The most characteristic finding is perivascular pseudorosettes, in which tumor cells are arranged radially around blood vessels, with tapered processes extending toward the vessel wall, separated by an intervening zone of fibrillary processes.[12] The other hallmark finding is true ependymal rosettes, which are less common than pseudorosettes but pathognomonic when present. True ependymal rosettes consist of tumor cells arranged around a central lumen, resembling the embryonic ependymal canal. Other features include round to oval nuclei with salt-and-pepper chromatin, perinuclear clearing, and occasional calcifications. While the 2021 WHO classification primarily relies on genetic profiling, specific ependymoma subtypes warrant a separate mention. Subependymomas are WHO grade 1 tumors characterized by low cellularity with clusters of bland nuclei in a gliofibrillary matrix. These tumors are often found in adults within the lateral or fourth ventricles. Myxopapillary ependymomas are characterized by papillary structures with tumor cells arranged around connective tissue cores in a myxoid background. These tumors commonly arise in adults near the conus medullaris and cauda equina. Immunohistochemical staining aids in diagnosis: Glial fibrillary acidic protein (GFAP): Often positive, it reflects glial cell origin. Epithelial membrane antigen (EMA): This characteristically shows dotlike or ringlike paranuclear positivity. L1 cell adhesion molecule (L1CAM): It is strongly expressed in ZFTA-fusion–positive supratentorial ependymomas and serves as a surrogate marker for molecular testing.[11] Ki-67 (MIB-1) index: This is useful for assessing proliferative activity, with higher indices correlating with more aggressive clinical behavior. Histone 3 lysine 27 trimethylation (H3K27me3): Immunohistochemistry is a useful biomarker for posterior fossa group A ependymomas.[13][14][15][16]

Ependymomas present differently depending on their location within the CNS. The more common posterior fossa tumors tend to present with signs and symptoms of increased intracranial pressure due to obstructive hydrocephalus. In infants, hydrocephalus may present with macrocephaly, a tense or bulging anterior fontanelle, and diastatic cranial sutures. In older children, hydrocephalus can present with headache, nausea, vomiting, and lethargy. Posterior fossa tumors can lead to mass effect on the cerebellum and brainstem, resulting in ataxia, dysmetria, nystagmus, and long-tract signs. Cranial neuropathies can result from direct brainstem compression or from compression of the nerves themselves, as ependymomas have a predilection to extend through the foramen of Luschka into the cerebellopontine angle.[4] Supratentorial tumors often present with seizures, focal neurological deficits, or progressive headaches. Hydrocephalus can develop if these tumors grow within the lateral ventricles and obstruct the foramen of Monro. Spinal ependymomas tend to present with gradually progressive symptoms such as pain, motor and sensory deficits, and autonomic dysfunction. Pain may be localized to the spine or may be radicular in nature. Upper motor neuron signs, such as hyperreflexia and clonus, are frequently present. Because myxopapillary ependymomas occur near the conus and cauda equina, patients may present with features of a cauda equina syndrome, such as saddle anesthesia, radicular pain, and bladder sphincter dysfunction leading to urinary incontinence.

Diagnosing ependymomas requires a multimodal approach that integrates clinical presentation, neuroimaging, and molecular diagnostics. Given their diverse anatomical distribution and overlapping clinical features with other CNS tumors, accurate diagnosis is critical for directing management and determining prognosis. Patients often present acutely to the emergency department with new-onset focal neurological deficits or signs and symptoms of hydrocephalus, with computed tomography often being the first diagnostic imaging test obtained. Intracranial ependymomas are often isodense to slightly hyperdense, and calcifications and cystic components are common. Magnetic resonance imaging is the gold standard for imaging intracranial and spinal masses. Posterior fossa ependymomas tend to arise near or from the floor of the fourth ventricle, often extending through the foramina of Luschka or Magendie into the cerebellopontine angle cistern. Supratentorial tumors are usually periventricular and more likely to have cystic components. These tumors are isointense to hypointense on T1-weighted images and hyperintense on T2-weighted images. A blooming artifact is commonly seen on susceptibility-weighted images due to hemorrhage or calcifications. Contrast enhancement is commonly heterogeneous. Study results comparing the imaging features of posterior fossa subtypes revealed significant differences in intratumor calcifications, invasion of the posterior fossa foramina, and more pronounced hydrocephalus in group A tumors compared with group B.[17] Other studies use machine learning algorithms to aid in the identification of radiomic signatures preoperatively.[18] Spinal ependymomas are intradural, intramedullary tumors that expand the spinal cord and are more often located in the central portion, whereas astrocytomas occupy the cord asymmetrically. One suggestive finding of spinal ependymomas is the cap sign, a hypointense rim on T2-weighted images, typically seen at the tumor poles and due to hemorrhage. Peritumoral edema is present in up to 60% of cases.[19] In patients with a suspected ependymoma, an MRI of the brain and entire spinal axis is indicated to evaluate for leptomeningeal disease. Lumbar puncture for CSF cytology is important for staging and evaluating disseminated disease, and it is typically performed 10 to 14 days after surgical resection of the primary tumor.[20][21]

Management of ependymomas requires a multimodal strategy, integrating surgical resection, radiotherapy, and in select cases, systemic chemotherapy.[22] Treatment is tailored to the tumor location, molecular subtype, patient age, and the extent of surgical resection. The primary goal is maximal safe surgical resection, as this is the most important prognostic factor, followed by adjuvant therapies, where indicated. Surgical resection can sometimes be technically challenging when posterior fossa tumors extend laterally into the cerebellopontine angle. These cases may require a staged approach in which the bulk of the tumor is removed via a standard suboccipital approach, with more lateral extensions removed via a retrosigmoid or far-lateral approach.[23][24][25] Because these tumors often encase the lower cranial nerves, neuromonitoring is essential. Postoperative imaging should be obtained within 24 to 48 hours to assess for residual tumor and establish a pretreatment baseline.[26] Adjuvant focal radiation therapy is recommended after subtotal resection of WHO grade 2 or 3 intracranial ependymoma and is commonly administered after gross total resection in high-risk settings (eg, younger age, unfavorable molecular subgroup). Usually, radiation therapy is delivered using traditional conformal radiation techniques; however, proton beam therapy and stereotactic radiosurgery have also been used.[5][27][28][29][30] For spinal disease, postoperative radiation therapy is usually administered if resection is incomplete.[4] Most centers prescribe a dose of 54.0 to 59.4 Gy in 1.8-Gy daily fractions for intracranial ependymomas.[4][5][31][32] In cases of disseminated disease, craniospinal irradiation is indicated, typically with a dose of 36 Gy, followed by a boost to the tumor bed.[4]

Adjuvant focal radiation therapy is recommended after subtotal resection of WHO grade 2 or 3 intracranial ependymoma and is commonly administered after gross total resection in high-risk settings (eg, younger age, unfavorable molecular subgroup). Usually, radiation therapy is delivered using traditional conformal radiation techniques; however, proton beam therapy and stereotactic radiosurgery have also been used.[5][27][28][29][30] For spinal disease, postoperative radiation therapy is usually administered if resection is incomplete.[4] Most centers prescribe a dose of 54.0 to 59.4 Gy in 1.8-Gy daily fractions for intracranial ependymomas.[4][5][31][32] In cases of disseminated disease, craniospinal irradiation is indicated, typically with a dose of 36 Gy, followed by a boost to the tumor bed.[4] Tumor recurrence can occur locally or disseminate throughout the craniospinal axis. Posterior fossa ependymomas tend to recur locally, whereas supratentorial ependymomas tend to be disseminated at relapse.[33] Tumor recurrence is typically treated with repeat surgical resection with or without radiotherapy, with the goal of surgery being a gross total resection.[34][35] Results from a multicenter study reported an improved 5-year overall survival (OS) rate of 48.7% for patients undergoing gross total resection compared with 5.3% for those undergoing near-total resection. Although no improvement in OS was observed in the cohort undergoing gross total resection and radiotherapy, radiotherapy was advantageous in the near-total resection cohort.[36] Reirradiation with craniospinal irradiation is a safe treatment option for patients with locally recurrent disease, yielding improved outcomes compared with focal reirradiation.[37] Results from another study reported that irradiation at first relapse delayed progression; however, it was not associated with prolonged OS.[38]

The differential diagnosis for tumors in the posterior fossa includes pilocytic astrocytoma, medulloblastoma, atypical teratoid tumor, rhabdoid tumor, and choroid plexus tumors. For supratentorial tumors, the differential diagnosis consists of glial tumors, choroid plexus carcinoma or papilloma, and embryonal tumors.[39] Spinal ependymomas must be distinguished from spinal astrocytomas.

The prognosis for ependymomas is heterogeneous and determined by a combination of factors, including patient age, tumor location, and molecular subgroup. The extent of surgical resection for intracranial ependymomas has been the most reliable and consistent independent prognostic factor.[40][41] Final results from the International Society for Pediatric Oncology Ependymoma I trial showed a 5-year and 10-year OS of 69.3% and 60.5%, respectively. This trial also compared gross total resection with postoperative radiotherapy versus subtotal resection with vincristine, etoposide, and cyclophosphamide before radiotherapy. The subgroup with gross total resection had a significantly improved event-free survival compared with the subtotal resection group (69.1% vs 33.8%) and a nonsignificant improvement in OS of 21.8%.[42] Similar findings were reported in a French cohort, with a 10-year OS of 68.2%.[43] Recurrence is a common feature, particularly for intracranial tumors, with local recurrence predominating while distal leptomeningeal dissemination is less frequent. Posterior fossa tumors in young children tend to have worse outcomes than spinal ependymomas in adults. By molecular subgroup, posterior fossa group A tumors have a much higher recurrence risk than group B tumors and are associated with a poorer prognosis.[36][44] Regarding supratentorial tumors, ZFTA-fusion–positive tumors tend to have worse outcomes than YAP1-fusion–positive tumors.[45] Other negative prognostic factors include tumors with 1q gain, loss of cyclin-dependent kinase inhibitor 2A (CDKN2A), and loss of 6q, often independent of 1q gain.[46] At tumor recurrence, the extent of disseminated disease and the extent of resection are important prognostic factors.[45]

The clinical course of ependymomas is often complicated by sequelae related to the tumor itself, the neurological morbidity of surgery, and the toxicities of adjuvant radiotherapy or chemotherapy. Complications can be divided into disease-related, treatment-related, and long-term survivorship complications, with particular consideration for pediatric patients, in whom therapy carries lifelong neurocognitive and endocrine consequences. Disease-related complications include hydrocephalus, neurological deficits, and tumor recurrence.[47] Treatment-related complications include hemorrhage or brainstem injury during posterior fossa resection. A well-known complication of posterior fossa surgery is cerebellar mutism (posterior fossa syndrome), which presents with speech arrest, emotional lability, and hypotonia.[48][49] For spinal ependymomas, spinal instability may result from multilevel laminectomies necessitating a spinal fusion procedure. Radiation-related complications include neurocognitive decline, endocrinopathies, radiation necrosis, and secondary malignancies.[50]

Patients should receive counseling regarding prognosis and treatment options. Patients with CNS tumors at the end of life may benefit from palliative care consultation. Family members and patients benefit from early and anticipatory counseling, as well as comfort measures when appropriate.[51][52]

Optimal care for patients with ependymomas relies on an interprofessional framework that integrates role-specific skills, team strategy, ethical responsibilities, clear communication, and coordinated care to advance patient-centered outcomes, safety, and performance. Clinicians (neurosurgeons, neuro-oncologists, radiation oncologists, neuroradiologists, neuropathologists) provide evidence-based diagnosis and treatment planning, employ maximal safe resection with neuromonitoring, align adjuvant therapy with molecular subgroup data, and provide timely palliative care. Nurses conduct continuous neurologic assessment, maintain device and wound safety, educate patients and their families, and use standardized handoffs. Pharmacists reconcile medications, prevent drug interactions, optimize medication dosing and supportive-care protocols, and monitor cumulative toxicity. Rehabilitation and allied health professionals initiate early mobilization, balance, and speech therapies, and provide cognitive screening and support for reintegration into school or work.