Abstract

Intradural extramedullary anaplastic ependymomas in the cauda equina are extremely rare. The latent period from the beginning of symptoms until diagnosis is notably shorter compared to other ependymoma subtypes. In some cases, severe neurological deficit may develop rapidly due to intratumoral hemorrhage.

We present the case of a 36-year-old male who experienced sudden numbness in his legs, followed by an inability to move his feet. In the following days, independent walking became impossible, and he stopped urinating. At the time of admission, bilateral hypesthesia was observed across the area of L4, L5, and sacral nerve root distribution, along with clinical signs indicative of cauda equina syndrome. Enhanced magnetic resonance imaging showed the presence of an intradural extramedullary mass occupying the spinal canal in the L3–S1 segment. Intraoperatively, an intradural tumor was identified between the roots of the cauda equina, with signs of intratumoral hemorrhage. The tumor was dissected free from the uninvolved surrounding nerve roots using a microsurgical technique. Following the sectioning of the filum terminale at the tumor attachment site, total tumor removal was achieved. In the postoperative period, a reduction of preoperative symptoms was noted. The patient underwent postoperative radiotherapy. The two-year follow-up demonstrated mild hypesthesia in the L5 and S1 dermatomes, reduction of the weakened plantar and dorsiflexion of the feet, and persistent bladder control impairment. Postoperative MRI revealed no evidence of recurrence.

Anaplastic ependymomas require adjuvant radiation therapy, even after total resection and systemic neuroimaging screening for recurrence or metastases. Early detection and operative treatment aiming at gross-total removal provide patients with an improved quality of life and prolonged survival.

clinical characteristics, spinal anaplastic ependymoma, treatment

Ependymomas are neuroepithelial tumors of the central nervous system (CNS) that arise from ependymal cells that line the ventricles, plexus choroideus, central canal of the spinal cord, and filum terminale.^[1] They are the most common type of tumors in children and adolescents and the most common intramedullary lesions in adult patients.^[1]

Spinal anaplastic ependymoma (SAE) is an extremely rare tumor. SAE corresponds to grade III according to the 2016 World Health Organization (WHO) classification and encompasses 2.2%–7.3% of all spinal cord ependymomas.‌^[2,3] The latest classification from 2021 of CNS tumors recategorized ependymal tumors based on histopathological and molecular characteristics and location.^[4] A small group of spinal ependymomas is defined by MYCN amplification. Spinal ependymomas associated with MYCN amplification are more aggressive, with a higher rate of recurrence and metastatic potential, as well as reduced progression-free survival and overall survival rates.^[5] This type of tumor was usually classified as a grade III anaplastic ependymoma in the previous 2016 WHO classification.^[6]

In this case report, we present a rare case of spinal anaplastic ependymoma (grade III) in the cauda equina, and we discuss the clinical presentation, diagnostic and therapeutic modalities, and also the treatment outcome.

We describe the case of a 36-year-old man who has been complaining of moderate low back pain for a number of months and does not have any comorbid conditions. Within a week, he developed numbness and weakness in the distal parts of the legs. Gradually, independent walking became impossible, and the patient stopped urinating. Upon admission to the clinic, the neurological examination revealed cauda equina syndrome with hypesthesia in the bilateral L4–S1 nerve root dermatomes and the perineal area, along with bilateral foot weakness and urinary retention. An emergency non-contrast computed tomography (CT) scan revealed a disc protrusion at the L5–S1 level that did not match the clinical symptoms (Fig. 1A, B) . Initially, MRI was unavailable due to technical limitations, and CT-assisted myelography was conducted. It showed a complete obstruction at the level of the L3 vertebral body, with a round formation measuring 12 mm in diameter and a density of 64 HU, with proximal stop of the contrast material penetration at the level of the L3 vertebra (Fig. 1C, D) . MRI with contrast enhancement the next day demonstrated an intradural extramedullary formation occupying the spinal canal in the L3–S1 segment. (Fig. 2) .

Figure 1.

A, B. Preoperative native CT scan reveals a disc protrusion at the L5–S1 level (white arrow); C, D. CT-assisted myelography: C. Sagittal reconstruction shows filling defect with stop of the contrast material at L3 level and intratumoral air (black arrow); D. Axial projection showing the presence of intradural tumor (black arrow).

Figure 2.

Preoperative MRI. A. Sagittal T1 projection visualizes a discretely lobulated intradural extramedullary formation with relative signal isointensity; B. Sagittal projection T2—presence of heterointense components from probable intratumoral hemorrhage and absence of cystic areas; C. Sagittal view with gadolinium enhancement—heterointense signal amplification; D. Axial T1 contrast-enhanced MRI of the lesion (arrow).

The patient was considered a surgical candidate based on the clinical presentation and imaging data. Considering the anticipated extensive multilevel laminectomy and to avoid future spinal instability, a navigated posterior pedicular fixation from L3 to S1 was first performed. After laminectomy at the L3–L4–L5 levels and partially at the S1 vertebra. The dura was found to be tense with a marked bluish discoloration. After midline durotomy, hemorrhagic-xanthochromic CSF was evacuated. After cutting the arachnoid, an intradural tumor formation was found between the roots of the cauda equina with signs of recent intratumoral hemorrhage. Using microsurgical technique, the tumor was carefully dissected free from the surrounding nerve roots, which were not invaded. The tumor was firmly attached to the filum terminale, which necessitated its transection in close vicinity to the tumor attachment zone. Gross total removal was achieved. The histological examination revealed evidence of anaplastic ependymoma—Grade III (Fig. 3) . The postoperative period was uneventful, with a reduction of preoperative symptoms. Early postoperative CT confirmed accurate screw placement (Fig. 4) .

Figure 3.

Anaplastic ependymoma of the filum terminale. Proliferation of densely packed atypical cells with large hyperchromatic nuclei and ependymal rosettes (H&E staining, magnification ×100).

Figure 4.

Postoperative CT scan showing the performed laminectomy and posterior pedicle screw fixation.

Given the malignant nature of the tumor, the patient underwent adjuvant radiotherapy, both to the local area and the entire neuroaxis. At the follow-up examination two years after the surgical treatment, the patient had residual mild hypesthesia across the L5 and S1 dermatomes, reduced motor deficit in the feet, and persistent disturbance of urinary control. He was able to walk unassisted. A follow-up MRI showed adhesions with dislocation and clustering of the nerve roots without evidence of recurrence (Fig. 5).

Figure 5.

Two-year follow-up MRI—presence of adhesions and clustering of the nerve roots of the cauda equina, with no evidence of recurrence.

The incidence of SAE is low and ranges from 1% to 7.4% of all spinal ependymomas.^[3,6] SAEs are usually located intramedullary and rarely are intradural extramedullary.^[7] In their systematic review, Wu et al. found 57 cases of primary SAEs and reported an additional 38 cases.^[8] Out of all 95 cases reported by Wu et al., 49 (51.6%) were men, the average age of patients was 31.5 years (2–67 years), and only 26 (27.4%) cases were localized intradurally extramedullary in the lumbar region, without specifying whether they originated from the conus medullaris or the cauda equina.^[8] The age and sex of our patient were similar to the data found in the literature.

Wu et al. mentioned that younger age was a significant critical factor negatively affecting the prognosis of the disease. In their study, patients under 25 years had both worse neurological status before and after treatment and a greater tendency to disease progression.^[8]

The typical localization of SAE is mainly in the cervical and thoracic regions, while the location in the lumbar region at the level of the conus medullaris is extremely rare.‌^[7,8] SAEs are slow-growing tumors, with the average length of the tumor covering 3 segments (1–9), which also resembles our case.^[6]

Although in 80%–83% of cases, ependymal cells covering the filum terminale give rise to myxopapillary ependymomas, both our case and that of Montoya et al. show that those cells can also lead to the development of SAE.^[7]

The symptoms and type of neurological deficit depend on the location of the ependymoma, its size, and degree of malignancy. Local pain is the most common clinical symptom in all subtypes of spinal ependymomas, followed by sensory disturbances, motor weakness, and sphincter disturbances.^[3] The period from the onset of complaints to the diagnosis of the disease in SAE is shorter compared to other ependymomas (on average 6 months versus 19–32 months).^[3] In some cases, a clinical presentation with marked neurological deficit may develop in a few days as a result of intratumoral hemorrhage.^[9] This is unequivocally confirmed also by our case, in which the cauda equina syndrome developed over several days as a result of intratumoral hemorrhage we confirmed intraoperatively.

The clinical presentation of ependymomas localized in the cauda equina is nonspecific, showing no significant difference from other intradural extramedullary tumors that arise in the cauda equina and filum terminale, as well as from the clinical features caused by lumbar disc herniation, lumbar spinal stenosis, and other conditions.^[7] Delaying the accurate diagnosis allows the tumor to increase in size, which can complicate its total removal, leading to recurrence and subarachnoid dissemination. Computed tomography (CT) has little diagnostic value except in cases with areas of calcification and is, therefore, an alternative only when MRI is contraindicated or unavailable.^[10] CT-assisted myelography is able to detect proximal or distal “stops” of the contrast filling but is unable to demonstrate the real extension and dimensions of the tumor, a fact also confirmed by our case.

MRI with gadolinium enhancement is the diagnostic method of choice for detection of spinal ependymomas. In relation to the spinal cord, SAEs are usually well-defined tumors that are iso- or hypointense in T1 and iso- or moderately heterogeneously hyperintense in T2, with contrast accumulation inside the tumor of varying degrees.^[11] The heterogeneity of MRI images can be related to the presence of cystic formations, hemorrhage, necrosis, and/or the presence of calcifications.^[10]

Treatment modalities for spinal cord ependymomas include surgical resection, radiotherapy, and, in specific cases, chemotherapy.^[12] Radical resection has been found to improve and prolong progression-free survival.^[12] Total resection rates of intraspinal ependymomas range from 11% to 89% in published series.^[8] In contrast to infiltrative spinal gliomas, intraspinal ependymomas are usually well demarcated from the surrounding neural structures, allowing for total microsurgical resection, also noted by us.^[13] Intradural extramedullary ependymomas are often encapsulated, which facilitates radical resection.^[14] In cases where infiltration of the surrounding nervous structures is detected, its total resection cannot be achieved, and postoperative adjuvant radiotherapy should be mandatory.^[12] The median progression-free survival was 48 months for patients treated with subtotal resection alone and 96 months for patients who also underwent postoperative radiotherapy.^[12] According to Lin et al., radiotherapy improves the quality of life of patients with intraspinal ependymomas by reducing the local recurrences and leptomeningeal metastases.^[15]

Chemotherapy is indicated for patients with recurrent ependymomas that are no longer suitable for local treatment (surgery and radiotherapy). Temozolomide is usually used in adult patients.^[12]

Spinal ependymomas are associated with a favorable outcome, with progression-free survival of 70%–90% and overall survival of 90%–100%, respectively, over a 5–10 year period.^[16] SAEs are characterized by early metastases, rapid progression upon recurrence, leptomeningeal spreading, and poor response to multimodal treatment.^[17] Swanson et al. report a high recurrence rate of 75%-100% in cases with SAEs, with an average progression-free interval of 17 months.^[5] The extent of resection was reported to be a key prognostic factor in most studies, as patients with total resection experience more favorable progression-free periods.^[18]

The outcome of SAE treatment depends on early diagnosis and the severity of the preoperative neurologic status. Tumor progression remains a major concern in the clinical course of SAE. In cases of SAE, adjuvant radiation therapy and systemic neuroimaging screening for recurrence or metastases are crucial for the treatment strategies. Although these aggressive tumors have a poor prognosis, early diagnosis and timely surgical intervention can provide patients with an improved quality of life and extend survival time.

Ethical statement

• The authors declared that no clinical trials were used in the present study.
• The authors declared that no experiments on humans or human tissues were performed for the present study.
• Written informed consent covering the use of anonymized clinical data and images for scientific publication was obtained from the patient upon hospital admission.
• The authors declared that no experiments on animals were performed for the present study.
• The authors declared that no commercially available immortalized human and animal cell lines were used in the present study.

Conflict of interest

The authors have declared that no competing interests exist.

Artificial Intelligence (AI) use

The authors accept full responsibility for the content of the manuscript, including the disclosure of any use of AI. No AI tools were used in the preparation of this manuscript.

Funding

No funding was reported.

Author contributions

All authors have contributed equally.

Author ORCIDs

Ivo Kehayov https://orcid.org/0000-0001-5799-1739

Daniel Markov https://orcid.org/0000-0003-4015-3514

Data availability

All of the data that support the findings of this study are available in the main text.