Spinal Cord Ependymomas in Adults: Grades, Diagnosis, Treatment, and Short-Term & Long-Term Prognosis
Mimoun Azizi *1, Dr. Med. Franklin Famdie Simo 2, Ibrahim Krenawi *3
*Correspondence to: Ibrahim Krenawi, Consultant Neurologist, Ain Al Khaleej Hospital, Al Ain, UAE.
Copyright
© 2026 Ibrahim Krenawi, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 24 August 2026
Published: 01 September 2026
DOI: https://doi.org/10.5281/zenodo.22242006
The most widespread primary intramedullary spinal cord tumor in adults is spinal cord ependymoma, which causes about 60-70 percent of all intramedullary gliomas. The tumors originate in ependymal cells that line the central canal of the spinal cord and exist on a wide histological and molecular spectrum, each with a different biological behavior, treatment implications, and a prognostic outcome according to the World Health Organization (WHO).
This review article presents an evidence-based overview of the spinal cord ependymomas in the adult population, including the tumor classification and grading based on the most recent classification of WHO CNS Tumor Classification of spinal cord tumors (2021), a clinical presentation, advanced diagnostic measures including neuroimaging with MRI and molecular biomarker profiling, and current treatment regimens, including maximal safe surgical resection Moreover, both short-term surgical and perioperative outcomes and long-term survival, recurrence patterns, and quality of life factors are critically analyzed in this article.
This review aims to be a consolidated, clinically useful resource in the management of adult patients with spinal cord ependymomas and to provide easy-to-use, evidence-based information to patients and their caregivers struggling with this diagnosis.
Keywords: Spinal cord ependymoma, intramedullary tumor of the spinal cord, WHO classification, ependymoma treatment, spinal cord tumor prognosis, myxopapillary ependymoma, anaplastic ependymoma, spinal MRI, gross total resection, spinal cord oncology.
Introduction
What Are Ependymomas?
Ependymomas are benign tumors of the primary central nervous system (CNS) that originate in ependymal cells, special cells in the brain that are made of glial cells that line the ventricular system and the central canal in the spinal cord. These cells are important in the production, circulation, and maintenance of cerebrospinal fluid (CSF). It is possible to have neoplastic transformation of ependymal cells, resulting in tumors along the entire neuraxis, including the cerebral ventricles up to the filum terminale.
Ependymomas are the most frequent primary intramedullary tumor of the spinal cord in adults [1]. In contrast to pediatric ependymomas, which occur mostly intracranially, adult spinal ependymomas are generally indolent in nature - although clinical behavior differs significantly based on tumor grade, location, and molecular subtype. The most common is the cervical cord, then the thoracic cord, and lastly the conus medullaris/filum terminale area [2], [3].
Epidemiology & Incidence
About 60 to 70% of all intramedullary spinal cord gliomas in adults are spinal ependymomas with a yearly incidence of 0.27 per 100,000 individuals [4]. They are most prevalent in adults between the ages of 30 and 60 years, with the Grade II tumors having a slight male bias. Grade I Myxopapillary ependymomas are predominantly common in young adult males and occur nearly exclusively in the conus/filum terminale area. Grade III anaplastic ependymomas are rare but have a much worse prognosis and are more likely to appear in older adults [5], [6].
There is no geographic or ethnic clustering that is significant, and this implies that environmental factors have a small role to play. Nonetheless, there is a strong genetic correlation with Neurofibromatosis Type 2 (NF2) - an autosomal dominant disorder with mutations in the NF2 tumor suppressor gene in chromosome 22 - that greatly increases lifetime risk and predisposes patients to multifocal spinal ependymomas at earlier ages [7]. The infrequency of these tumors and lack of large randomized controlled trials highlight the clinical importance of a meticulous review of articles in informing best-practice diagnosis and management in this emerging area.
Classification & WHO Grading of Spinal Cord Ependymomas
The most recent 5th Edition of the World Health Organization (WHO) Classification of CNS Tumors classifies spinal cord ependymomas, with the most recent 5th Edition of the classification representing a paradigm shift (adding molecular and genetic parameters and integrating them with traditional histology to create more accurate and clinically meaningful integrated diagnoses) [8]. The most important molecular changes, NF2 mutations and MYCN amplification, have independent diagnostic and prognostic significance, and the field is now squarely in the era of precision medicine [9].
Three WHO grades are recognized, each representing a distinct clinicopathological entity:
The laziest subtype, MPE, occurs nearly exclusively due to the conus medullaris, cauda equina, and filum terminale. Histologically, the tumor cells are arranged in a papillary pattern around hyalinized fibrovascular cores in an excessive myxoid stroma and have low mitotic activity. The recurrent chromosome 22q loss and MYBL1 fusions are also molecularly revealed to be the distinguishing features [10].
Although the Grade I designation implies low recurrence risk, MPE has a non-negligible recurrence risk - especially after subtotal resection, which carries 20-40% local recurrence rates. Although rare, the spread of CSF has been reported - a non-characteristic trait of Grade I tumor - which has led certain authorities to suggest adjuvant radiotherapy in case of incomplete resection.
Grade II ependymomas are the most frequent clinical form in adults, developing mostly in the cervical cord, followed by the thoracic cord [11]. These are real intramedullary tumors which develop out of ependymal cell which covers the central canal, and are usually seen as centrally positioned, well-demeanoured lesions, often accompanied by rostral/caudal syringomyelia on MRI.
The perivascular pseudorosette -the tumor cells are radially oriented around blood vessels with a nuclear fibrillary interspersed zones- is the histological characteristic. The true ependymal rosettes are less common and are very specific. NF2 mutations are detected in 40-60 percent of the cases, which are the basis of the SP-NF2 molecular subgroup category that is included in the 2021 WHO classification.
The clinically important characteristic of Grade II tumors is that they have a predilection to create a surgical cleavage plane with cord parenchyma surrounding them, allowing gross total resection (GTR) in 50-70% of cases in the most specialized institutions, the chief determinant of long-term outcome.
The least frequent yet most aggressive subtype, Grade III anaplastic ependymoma, most typically affects the cervical and thoracic cord and is typified by poorly defined, diffuse growth, which greatly complicates surgical excision. Grade III histological characteristics, such as increased mitotic activity (>4/10 HPF), microvascular proliferation, pseudopalisading necrosis, and prominent nuclear pleomorphism, distinguish it from Grade II disease.
The molecularly defined SP-MYCN subgroup, characterized by MYCN proto-oncogene amplification on chromosome 2p24, represents the most aggressive molecular entity within this grade, demonstrating rapid progression and poor survival despite multimodal treatment.
Clinical Presentation & Symptoms of Spinal Cord Ependymomas
The clinical presentation of spinal cord ependymomas is highly variable, determined primarily by tumor location, size, and rate of growth. Due to their typically slow-growing nature, symptoms develop insidiously over months to years, with a diagnostic delay averaging 2–4 years from symptom onset — underscoring the need for high clinical suspicion in adults with progressive, unexplained neurological symptoms.
Pain is the most common presenting symptom, affecting 60–80% of patients, typically described as deep, axial, and worse at night — a feature that distinguishes neoplastic from mechanical spinal pain [12]. As the tumor enlarges, progressive sensory disturbances, motor weakness, sphincter dysfunction, and sexual dysfunction emerge. In rare cases involving Grade III tumors or intratumoral hemorrhage, acute neurological deterioration may occur, constituting a neurosurgical emergency.
Diagnosis of Spinal Cord Ependymomas
The diagnosis of spinal cord ependymoma requires the integration of clinical evaluation, advanced neuroimaging, histopathological examination, and increasing molecular profiling. No single modality is sufficient in isolation [13]. A complete and accurate diagnosis depends on the synthesis of findings across all these domains, ideally within a multidisciplinary neuro-oncology team setting.
Neuroimaging — MRI as the Gold Standard
Magnetic Resonance Imaging (MRI) of the spine with and without gadolinium contrast is the cornerstone of spinal ependymoma diagnosis and the single most informative investigation available. MRI provides unparalleled soft tissue resolution, allowing precise tumor localization, delineation of tumor extent, assessment of cord compression, and identification of associated findings that collectively point toward the diagnosis [14].
Characteristic MRI Features: On T1-weighted sequences, spinal ependymomas typically appear as isointense to hypointense intramedullary lesions relative to normal cord parenchyma. On T2-weighted sequences, they are characteristically hyperintense, often with well-defined margins that reflect the tumor's tendency to expand the cord symmetrically around the central canal. Following gadolinium administration, most Grade II and Grade III ependymomas demonstrate vivid, homogeneous contrast enhancement, reflecting disruption of the blood-spinal cord barrier within the tumor.
Several MRI findings are particularly suggestive of ependymoma and help distinguish it from other intramedullary tumors such as astrocytoma:
For myxopapillary Grade I ependymomas of the filum terminale, MRI demonstrates a sausage-shaped, well-encapsulated, intensely enhancing intradural extramedullary mass in the lumbosacral canal, often with characteristic T1 hyperintensity reflecting mucinous content.
Whole-spine MRI is mandatory in all patients with confirmed or suspected spinal ependymoma to evaluate for drop metastases — CSF-disseminated tumor nodules along the leptomeninges — which occur in approximately 5–15% of cases, most commonly with myxopapillary and anaplastic subtypes. Brain MRI with gadolinium should also be obtained to exclude intracranial ependymoma or leptomeningeal spread to the posterior fossa [17].
CSF Analysis
Lumbar puncture with cerebrospinal fluid (CSF) analysis plays a supplementary but valuable role in the diagnostic workup of spinal ependymomas. CSF cytology may reveal malignant cells in cases with leptomeningeal dissemination, though sensitivity is limited — a negative cytology does not exclude CSF spread [18]. Elevated CSF protein is a non-specific but commonly observed finding, reflecting blood-spinal cord barrier disruption. CSF analysis should be performed after MRI to avoid the risk of neurological deterioration from lumbar puncture in the setting of significant cord compression or elevated intraspinal pressure.
Emerging research is investigating the utility of liquid biopsy — detection of circulating tumor DNA (ctDNA) or tumor-derived extracellular vesicles in CSF — as a non-invasive molecular diagnostic tool for spinal ependymomas. While still investigational, early results are promising and may eventually complement or partially replace tissue biopsy in select clinical scenarios.
Histopathology & Tissue Diagnosis
Definitive diagnosis of spinal ependymoma requires histopathological examination of tumor tissue obtained at surgical resection or, in rare cases where upfront surgery is not feasible, stereotactic biopsy. Neuropathological assessment remains the diagnostic gold standard, providing information on tumor grade, mitotic activity, presence of necrosis, and vascular proliferation that directly informs treatment planning [19], [20].
Key histopathological features evaluated include the presence of perivascular pseudorosettes — the hallmark of ependymoma — true ependymal rosettes, mitotic index, Ki-67 proliferation labeling index, nuclear pleomorphism, microvascular proliferation, and pseudopalisading necrosis. Immunohistochemical staining for GFAP (glial fibrillary acidic protein), EMA (epithelial membrane antigen), and S100 protein supports the ependymal lineage of the tumor. EMA positivity in a dot-like or ring-like cytoplasmic pattern is particularly characteristic of ependymoma and helps distinguish it from other glial tumors.
Molecular Diagnostics & Biomarkers
In alignment with the 2021 WHO CNS Tumor Classification, molecular testing is now an integral component of spinal ependymoma diagnosis at specialized centers. Recommended molecular analyses include:
The integration of molecular findings with histology produces an integrated diagnosis — the current standard of care in neuro-oncology — that provides more accurate risk stratification and guides individualized treatment planning than histology alone.
Treatment of Spinal Cord Ependymomas
Management of spinal cord ependymomas requires a multimodal, individualized approach guided by tumor grade, location, extent of resection, molecular subtype, and the patient's neurological status. Treatment decisions are best made within a multidisciplinary neuro-oncology team comprising neurosurgeons, radiation oncologists, medical oncologists, and neuropathologists [22], [23].
Surgical Resection — The Primary Treatment
Surgery remains the cornerstone of treatment for spinal cord ependymomas. The primary surgical goal is gross total resection (GTR) — complete removal of the tumor — which is the single most important determinant of long-term outcome across all grades.
Grade II ependymomas frequently develop a natural cleavage plane between the tumor and the surrounding cord, enabling GTR in 50–70% of cases at experienced neurosurgical centers. Intraoperative adjuncts, including intraoperative neurophysiological monitoring (IONM) combining motor evoked potentials (MEPs) and somatosensory evoked potentials (SSEPs) are now standard practice, allowing real-time detection of neurological compromise and guiding the safe extent of resection. Intraoperative ultrasound and intraoperative MRI further aid tumor localization and resection completeness assessment [24].
Myxopapillary Grade I ependymomas, while technically extramedullary, can be adherent to cauda equina nerve roots, making en bloc resection challenging. Piecemeal resection associated with significantly higher recurrence rates should be avoided whenever possible. For Grade III anaplastic ependymomas, the infiltrative nature of the tumor frequently precludes GTR, and maximal safe resection is pursued to reduce tumor burden while preserving neurological function.
Radiation Therapy
The role of adjuvant radiotherapy in spinal ependymomas is grade- and resection-dependent.
Following GTR of Grade II ependymoma, observation with surveillance MRI is the accepted standard, with radiotherapy reserved for recurrence. Following subtotal resection (STR) of Grade II tumors, adjuvant focal radiotherapy to the tumor bed is recommended, with doses typically ranging from 45–54 Gy delivered in conventional fractionation [25]. This approach has been shown to significantly improve progression-free survival in incompletely resected tumors.
For Grade III anaplastic ependymomas, adjuvant radiotherapy is strongly recommended regardless of resection extent, given the high risk of local recurrence and CSF dissemination. Craniospinal irradiation (CSI) an irradiation of the entire neuraxis is considered in cases with documented or high-risk leptomeningeal spread, though its use must be carefully weighed against the significant toxicity profile, particularly in adults of reproductive age.
For myxopapillary Grade I ependymomas, adjuvant radiotherapy following GTR is generally not recommended [26]. However, following STR particularly in cases with evidence of CSF seeding focal radiotherapy or CSI may be considered on an individualized basis.
Stereotactic radiosurgery (SRS) and proton beam therapy represent emerging radiotherapy modalities that offer the potential for highly conformal dose delivery with reduced radiation exposure to surrounding normal cord tissue, though evidence specific to spinal ependymomas remains limited.
Chemotherapy
The role of chemotherapy in spinal cord ependymomas remains limited and largely investigational. Unlike intracranial ependymomas in pediatric patients where chemotherapy plays a more established role, adult spinal ependymomas have not demonstrated consistent sensitivity to standard cytotoxic agents in clinical trials.
Chemotherapy is currently considered primarily in the setting of recurrent or refractory disease where further surgery and radiotherapy are not feasible [27]. Agents that have been investigated include temozolomide, carboplatin, cisplatin, etoposide, and bevacizumab (an anti-VEGF monoclonal antibody). Response rates with these agents are generally modest, and no regimen has demonstrated sufficient efficacy to establish a standard-of-care role.
The identification of recurrent molecular alterations particularly NF2/merlin loss and MYCN amplification has stimulated interest in targeted therapeutic approaches. Preclinical studies have explored inhibitors of the Hippo/YAP pathway, mTOR inhibitors, and CDK inhibitors as potential targeted agents, but clinical translation remains in early phases.
Enrollment of eligible patients in clinical trials investigating novel targeted and immunotherapeutic strategies is strongly encouraged at the time of recurrence.
Surveillance & Follow-Up
Following treatment, all patients require long-term radiological surveillance with periodic MRI of the spine and brain, where indicated. Recommended surveillance intervals vary by institution and tumor grade, but a common protocol involves MRI every 3–6 months for the first 2 years, followed by annual imaging thereafter [28]. Given the potential for late recurrence particularly in myxopapillary ependymomas — lifelong surveillance is warranted in most patients.
Short-Term Prognosis & Post-Surgical Outcomes
The short-term prognosis of spinal cord ependymomas is primarily determined by surgical outcomes, perioperative complications, and the patient's preoperative neurological status [29]. A well-established principle in spinal ependymoma surgery is that preoperative neurological function is the strongest predictor of postoperative neurological recovery, patients with mild or moderate deficits preoperatively consistently achieve better functional outcomes than those presenting with severe or long-standing neurological compromise.
Post-Surgical Neurological Outcomes
Following GTR of Grade II spinal ependymoma, the majority of patients experience either neurological stability or improvement in the early postoperative period. Large surgical series report neurological improvement or stability in approximately 70–85% of patients following GTR, with the remainder experiencing transient or permanent worsening. Transient neurological deterioration including increased weakness, sensory disturbance, or sphincter dysfunction is relatively common in the immediate postoperative period, often reflecting cord edema or manipulation rather than permanent injury, and frequently resolves within weeks to months with rehabilitation.
Permanent neurological worsening following surgery occurs in approximately 10–20% of cases and is more likely in the setting of subtotal resection attempts in firmly adherent or extensively infiltrative tumors, particularly in the cervical cord, where the neural structures are most densely packed [31]. The use of intraoperative neurophysiological monitoring has significantly reduced the rate of permanent postoperative deficits in experienced centers.
Perioperative Complications
Beyond neurological outcomes, patients undergoing spinal cord ependymoma resection face a range of perioperative complications that contribute to short-term morbidity:
Long-Term Prognosis
Long-term outcomes in spinal cord ependymomas are strongly influenced by tumor grade, extent of surgical resection, molecular subtype, and the use of adjuvant therapy [32]. Overall, spinal ependymomas carry a considerably more favorable long-term prognosis than intracranial high-grade gliomas, reflecting their predominantly low-grade biology and the feasibility of curative surgical resection in a significant proportion of patients.
Survival Rates by Grade
Grade I — Myxopapillary Ependymoma: Following GTR, myxopapillary ependymomas are associated with excellent long-term survival, with 10-year overall survival rates exceeding 85–90% in most reported series. However, local recurrence remains a clinically significant concern particularly following STR with recurrence rates of 20–40% at 10 years reported in incompletely resected tumors [33]. Late recurrences beyond 10 years are well documented, underscoring the necessity of lifelong surveillance. CSF dissemination, while uncommon, worsens prognosis considerably when present.
Grade II — Classic Ependymoma: Grade II spinal ependymomas treated with GTR demonstrate favorable long-term outcomes, with reported 5-year overall survival rates of 80–95% and 10-year survival rates of 70–85% in large institutional series. Extent of resection exerts the most powerful influence on recurrence-free survival — GTR is associated with 5-year progression-free survival (PFS) rates of 70–80%, compared to 40–55% following STR. Adjuvant radiotherapy following STR partially mitigates this survival disadvantage, improving local control rates in incompletely resected tumors.
Grade III — Anaplastic Ependymoma: Anaplastic spinal ependymomas carry a significantly worse long-term prognosis. Reported 5-year overall survival rates range from 30–60%, with wide variation reflecting tumor heterogeneity, treatment differences across institutions, and the small patient numbers in most published series. Tumors harboring MYCN amplification — the SP-MYCN molecular subtype — demonstrate particularly aggressive behavior, with median overall survival often below 2 years despite aggressive multimodal treatment. High rates of local recurrence and CSF dissemination characterize the natural history of Grade III tumors.
Recurrence Patterns & Management
Tumor recurrence represents the most significant long-term challenge in spinal ependymoma management. Recurrence may be local at the original tumor site or disseminated, involving leptomeningeal spread along the neuraxis. Local recurrence is more common and occurs at a median of 3–5 years following initial treatment in Grade II tumors, though late recurrences beyond 10 years are well documented, particularly for myxopapillary ependymomas.
Management of recurrent spinal ependymoma depends on prior treatment, recurrence pattern, and patient performance status. Repeat surgical resection is the preferred approach for accessible local recurrences in patients who have not previously received radiotherapy to the site [34]. Salvage radiotherapy or re-irradiation in previously irradiated patients may be considered with careful attention to cumulative spinal cord dose tolerance. Systemic chemotherapy or enrollment in clinical trials investigating targeted agents remains the primary option for patients with disseminated recurrence or those exhausting local treatment options.
Quality of Life Outcomes
Beyond survival statistics, quality of life (QoL) represents a critical dimension of long-term prognosis that is increasingly recognized as an essential outcome measure in spinal ependymoma management [35]. Neurological deficits including motor weakness, sensory disturbance, chronic pain, sphincter dysfunction, and sexual dysfunction can persist long after treatment and significantly impact daily functioning, psychological well-being, and social participation.
Studies evaluating long-term QoL in spinal ependymoma survivors consistently demonstrate that functional independence and return to premorbid activity levels are achievable in the majority of patients treated with GTR and a favorable neurological status at presentation [36]. However, a subset of patients particularly those with high cervical tumors, incomplete resections, or Grade III disease experience permanent neurological disability that necessitates ongoing rehabilitation, assistive devices, and psychosocial support.
Structured neurorehabilitation incorporating physiotherapy, occupational therapy, bladder and bowel management programs, and psychological counseling — plays an essential role in optimizing functional recovery and QoL in the long-term survivorship phase. Multidisciplinary survivorship clinics, where available, provide a coordinated framework for addressing the complex physical and psychosocial needs of spinal ependymoma survivors.
Conclusion
Spinal cord ependymomas represent a clinically and biologically diverse group of primary intramedullary tumors that constitute the most common spinal cord glioma in the adult population. Their management demands a sophisticated, multidisciplinary approach informed by an integrated understanding of tumor grade, anatomical location, molecular subtype, and individual patient factors.
The 2021 WHO CNS Tumor Classification has significantly advanced our diagnostic framework, moving beyond purely histology-based grading toward molecularly integrated diagnoses that more accurately reflect tumor biology and predict clinical behavior. The recognition of distinct molecular subgroups particularly the SP-NF2 subgroup with its relatively favorable prognosis and the aggressive SP-MYCN subgroup has important implications for risk stratification, treatment planning, and the development of future targeted therapies.
Surgical resection remains the cornerstone of treatment, with gross total resection representing the single most powerful determinant of long-term outcome across all tumor grades. Advances in intraoperative neurophysiological monitoring, intraoperative imaging, and microsurgical technique have progressively improved the safety and completeness of resection at specialized neurosurgical centers. Adjuvant radiotherapy plays an established role in incompletely resected Grade II tumors and all Grade III tumors, while the role of chemotherapy remains largely investigational and confined to recurrent or refractory disease.
Long-term prognosis varies considerably by grade — from the excellent survival rates associated with completely resected Grade I myxopapillary ependymomas to the poor outcomes of MYCN-amplified Grade III tumors. Regardless of grade, the potential for late recurrence mandates lifelong radiological surveillance in all patients. Quality of life considerations, including neurological rehabilitation and psychosocial support, must be integral components of the long-term survivorship care plan.
Looking ahead, the field of spinal ependymoma research is advancing on several promising fronts. Liquid biopsy technologies, genome-wide methylation profiling, and next-generation molecular diagnostics are poised to further refine diagnosis and risk stratification. Preclinical and early-phase clinical investigations targeting the Hippo/YAP pathway, mTOR signaling, and MYCN-driven transcriptional programs offer hope for more effective systemic therapies in recurrent and high-grade disease. Collaborative, multi-institutional research efforts essential given the rarity of this tumor will be critical in translating these biological insights into meaningful clinical advances for patients.
In summary, while significant progress has been made in understanding and treating spinal cord ependymomas, continued investment in molecular research, prospective clinical trials, and multidisciplinary care models remains essential to improving outcomes and quality of life for adult patients living with this challenging diagnosis.
References