Myxopapillary Ependymoma

Etiology

Myxopapillary ependymoma arises from the ependymal glia of the filum terminale. No risk factors for the development of this tumor have been described. Extradural myxopapillary ependymomas are thought to arise from the coccygeal medullary vestige or the extradural remnants of the filum terminale.[4]

Epidemiology

Myxopapillary ependymomas account for 1% to 5% of all spinal neoplasms and approximately 13%. In the American population, their incidence was 1.00 per million person-years. The age at onset varies between 30 and 50 years (mean age, 35 years). The most common location of myxopapillary ependymoma is the lumbosacral spine segment, mainly in the conus medullaris and cauda equina regions. Other rare locations include the cerebral ventricles and the brain.[5]

Histopathology

Macroscopy

Grossly, myxopapillary ependymomas are sausage-shaped and often encapsulated. They are reddish to purplish in color and soft in consistency.[6] Mucinous degeneration or hemorrhage may sometimes be seen in these tumors.[7]

Microscopy

Histologically, myxopapillary ependymomas are characterized by a papillary architecture. In the center of the papillae, there are blood vessels that are surrounded by cuboidal to spindled glial cells. The stroma is myxoid and alcian blue–positive.[8] Vascular hyalinization and other degenerative changes are often prominent. Some tumors may show a more compact fascicular pattern with occasional perivascular pseudorosettes with mucin-rich microcysts and occasional perivascular pseudorosettes. Sometimes, the tumor may exhibit rounded to spiculated collagen “balloons.” In these tumors, mitotic figures are usually scarce. Endothelial proliferation and necrosis are absent. Some authors described anaplastic and giant cell variants of myxopapillary ependymomas in isolated case reports.[9]

Immunohistochemistry

An immunohistochemical study is frequently required to distinguish myxopapillary ependymoma from chondrosarcoma or chordoma. The tumor cells are often positive for S-100, GFAP, CD99, and COX-2. However, they are negative for endomysial antibodies.[8]

History and Physical

The clinical presentation of myxopapillary ependymomas is not specific and is similar to that of other intradural tumors located below the spinal cord in the region of the filum terminale.[1] The symptoms related to this tumor are influenced by the size, the presentation site, and the tumor's local extent. An indolent and slow clinical course characterizes myxopapillary ependymomas. Most patients experience symptoms for months to years before diagnosis and have a nonspecific presentation.[10]

Nonspecific Symptoms 

Patients with myxopapillary ependymomas usually complain of radicular and back pain worsening during the night and in the lounging position.[1]

Other Symptoms of Myxopapillary Ependymoma

Patients with myxopapillary ependymoma may complain of motor, sensory, urinary, and gait abnormalities.[1] Among the other symptoms of myxopapillary ependymoma, enlargement of the neural foramina scoliosis, and scalloping of the vertebral body can be distinguished. Sudden exacerbation of the symptoms with leg weakness and sphincter disturbances can occur secondary to hemorrhage.[1]

Evaluation

Magnetic resonance imaging is the best modality for diagnosing myxopapillary ependymoma because of its superior soft-tissue contrast. Other imaging studies include plain radiographs and computed tomography scans. Plain radiographs and computed tomography scans can reveal scalloping of the vertebral bodies secondary to the spinal canal expansion caused by a large myxopapillary ependymoma. Magnetic resonance imaging helps identify the extent of the tumor and its relationship to intraspinal structures. It also allows for visualization of the cauda equina both above and below the tumor and identifies drop metastases in the subarachnoid space. Such information is useful in preoperative surgical planning. Magnetic resonance imaging findings in myxopapillary ependymomas are nonspecific.[4][11] On magnetic resonance imaging, the lesion is iso- to hypointense on T1 and hyperintense on T2. Owing to their mucin content, the signal is hyperintense in myxopapillary ependymoma. Moreover, the tumor is heterogeneous after gadolinium injection. Hemorrhage and cyst formations are common features that contribute to signal inhomogeneity.[11] However, these tumors do contain certain features that help suggest the diagnosis. These features include:

1. An intradural extramedullary thoracolumbar mass
2. The tumor extends to several vertebral levels in the lumbar and sacral canal.
3. It is hypointense to isointense on T1-weighted images.
4. It is hyperintense on T2-weighted images.
5. There is an intense, homogeneous enhancement after the administration of contrast.
6. There is usually a slightly lower intensity region at tumor margin on T2-weighted sequences.
7. Cystic rostral or caudal degeneration exists in 50% of cases.

Treatment / Management

There are no definitive treatment guidelines due to the rarity of myxopapillary ependymomas. The consensus is that surgical excision is the preferred initial treatment modality.[12] Early detection and treatment of patients affected by myxopapillary ependymomas are crucial to achieving optimal patient outcomes. The best treatment modality for myxopapillary ependymoma is complete surgical resection, associated with a complete resolution for most patients.[13][14] Surgery should be performed early to guarantee better postoperative outcomes.[15] Complete resection of this tumor may be hazardous, principally if the tumor involves the conus medullaris or is interlaced with the nerve roots of the cauda equina. Surgeons must be very careful since nerve roots may also penetrate directly through the tumor.[16] In the case of subtotal resection, adjuvant radiotherapy is recommended. However, chemotherapy is used in young children who are more prone to negative side effects from radiation therapy.[15] The efficacy of chemotherapy has not been established in myxopapillary ependymomas, although it has been suggested as a potential treatment to prevent a recurrence.[17] Radical surgery for myxopapillary ependymoma is associated with a favorable outcome in children and adults, as with other spinal cord ependymomas.[18] Long-term survival is better in the case of gross total removal of myxopapillary ependymoma rather than subtotal resection.[1][16](B2)

Differential Diagnosis

The differential diagnoses of filum terminale and small conus myxopapillary ependymomas include:

• Fibrous meningioma: The fibrillary variant of myxopapillary ependymomas may be confused with fibrous meningioma
• Paraganglioma: However, myxopapillary ependymomas are chromogranin-A negative and GFAP positive
• Schwannoma: The fibrillary variant of myxopapillary ependymomas may be confused with schwannoma

The epithelial and papillary variants of myxopapillary meningioma may mimic carcinoma or meningioma.

The differential diagnosis of a large myxopapillary ependymoma that is responsible for sacral destruction includes:

• Aneurysmal bone cyst
• Chondrosarcoma
• Chordoma
• Giant cell tumor
• Metastatic carcinoma: However, myxopapillary ependymomas are devoid of cytological atypia, have a lower Ki-67 LI, and are focally fibrillar

Radiation Oncology

The therapeutic benefits of radiotherapy for myxopapillary ependymomas are still debated owing to the benign and slow-growing nature of the tumor. In 1 study, the authors reported no difference in irradiated versus nonirradiated patients after total or subtotal resection.[16] According to other recent studies, postoperative radiotherapy is beneficial for patients who had subtotal resection of myxopapillary ependymoma and was considered the best treatment option for these patients because of the high risk of long-term recurrence in the case of subtotal resection of the tumor.[19][20][21] Other studies demonstrated that radiotherapy is significantly more beneficial in the case of subtotal resected myxopapillary ependymomas smaller than 6 cm compared to larger tumors (58% versus 92% 5- and 10-year progression-free survival).[22]

Staging

World Health Organization classification:

Recently, the classification of central nervous system tumors has been moving toward a more molecularly oriented classification scheme. In the 2021 WHO classification of central nervous system tumors, ependymal tumors are classified as follows:

• Myxopapillary ependymoma (grade 2)
• Subependymoma (grade 1)
• Classic ependymoma (grade 2)
• RELA fusion-protein positive ependymoma (grade 2 or 3; this is the only molecularly classified ependymoma)
• Anaplastic ependymoma (grade 3)[23]

Prognosis

Currently, neither the histopathology nor the MIB-1 index appears to predict the natural history, likelihood of recurrence, or metastases. Patients should be followed postoperatively with serial magnetic resonance imaging to monitor for tumor recurrence, even if a gross total resection was accomplished, because even then, recurrence rates of 10% to 19% have been reported.[1][16] Despite the good results with surgery, tumor recurrence and dissemination may occur. Local recurrence and metastases have been related to the clinical history of less than 1 year, the extent of resection, atypical histology, and lesions extending into the substance of the spinal cord.[21][24] Myxopapillary ependymomas are considered benign tumors of the central nervous system with long-term survival rates and a tendency for local recurrence. However, an aggressive course has occasionally been described, leading to cerebrospinal fluid dissemination and even systemic metastases.

Despite its well-differentiated appearance, it occasionally shows aggressive behavior. Local progression is common, and systemic metastases have also been described, with the lungs being the organs most commonly affected. Systemic dissemination is more common in cases of a primary extraspinal location.[1] The estimated 10-year overall survival is 92.4%, with a 10-year progression-free survival of 61.2%.[25] Age (<36 vs. ≥36 years), treatment modality (surgery alone vs. surgery and radiotherapy), and extent of surgery are prognostic factors for local control and progression-free survival. The 5-year overall survival rate of patients with myxopapillary ependymoma is excellent and varies from 90% to 100%. Patients who undergo gross total resection of intradural myxopapillary ependymomas have a good prognosis, with a mean survival time of 19 years.[1] Although rarely encountered in children, myxopapillary ependymomas have a more aggressive clinical course with an increased risk of recurrence and dissemination when compared to the adult population. The reason for this more aggressive course in children is unclear.

Complications

Some authors reported that en-bloc removal of encapsulated myxopapillary ependymomas of the filum terminale showed lower dissemination (10%) than myxopapillary ependymomas removed piecemeal (19%).[1] During surgery, the rupture of the capsule of myxopapillary ependymoma may result in cerebrospinal fluid seeding and dissemination.[24] According to the literature, in 30% of the cases, dissemination and treatment failure may occur.[25][24] The factors that increase the risk of recurrence and metastases are the extension of myxopapillary ependymoma into the substance of the spinal cord, a clinical history of less than 1 year, the extent of resection, and atypical tumor histology.[24]