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Myxopapillary Ependymoma


Myxopapillary Ependymoma

Article Author:
Faten Limaiem
Article Editor:
Joe M Das
Updated:
10/16/2020 6:17:02 PM
For CME on this topic:
Myxopapillary Ependymoma CME
PubMed Link:
Myxopapillary Ependymoma

Introduction

Initially described by Kernohan in 1932, myxopapillary ependymoma is a distinct subtype of spinal cord ependymomas that has a predilection for the lumbosacral region.[1] It represents 13% of all spinal ependymomas and accounts for 90% of all tumors in the conus medullaris.[2][3] Myxopapillary ependymoma is a benign and slow-growing neoplasm that has been histologically classified as grade I, according to the World Health Organization (WHO) classification.

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% of all spinal ependymomas. 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]

Pathophysiology

 

 

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 be sometimes 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. In some cases, 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 in isolated case reports anaplastic and giant cell variants of myxopapillary ependymomas.[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, COX-2. However, they are negative for endomysial antibody (EMA).[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 site of presentation, and the local extent of the tumor. Myxopapillary ependymomas are characterized by an indolent and slow clinical course. The majority of the 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 a motor, sensory, urinary, and gait abnormalities.[1] Among the other symptoms of myxopapillary ependymoma, we can distinguish enlargement of the neural foramina scoliosis and scalloping of the vertebral body. Sudden exacerbation of the symptoms with leg weakness and sphincter disturbances can occur secondary to hemorrhage.[1]

Evaluation

The best imaging modality for the diagnosis of myxopapillary ependymoma is magnetic resonance imaging (MRI) because of its superior soft-tissue contrast. Other imaging studies include plain radiograph and computed tomography (CT) scan.

Plain radiograph and computed tomography (CT) scan

Plain radiograph and CT scan can reveal scalloping of the vertebral bodies secondary to the expansion of the spinal canal caused by the presence of a large myxopapillary ependymoma.

Magnetic resonance imaging (MRI)

Magnetic resonance imaging is helpful in identifying 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 will identify 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 for 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 will be an intense, homogeneous enhancement after administration of contrast.
  6. There will usually be a region of slightly lower intensity at tumor margin on T2-weighted sequences.
  7. Cystic rostral or caudal degeneration exists in 50% of cases.

Treatment / Management

Owing to the rarity of myxopapillary ependymomas, there are no definitive treatment guidelines. 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, which is associated with a complete resolution for the majority of patients.[13][14] Surgery should be performed early so as 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 both 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]

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 one 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 as the best treatment option for these patients because of the high risk of long-term recurrence in case of subtotal resection of the tumor.[19][20][21]

Other studies demonstrated that radiotherapy is significantly more beneficial in the case of subtotally 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 is moving toward a more molecularly oriented classification scheme.

In the 2016 WHO classification of central nervous system tumors, ependymal tumors are classified as follows:

  • Myxopapillary ependymoma (grade I)
  • Subependymoma (grade I)
  • Classic ependymoma (grade II)
  • RELA fusion-protein positive ependymoma (grade II or III, this is the only molecularly classified ependymoma)
  • Anaplastic ependymoma (grade III)[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 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-years overall survival has been reported to be 92.4%[25] 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 a lower proportion of 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 literature, in 30% of the cases, dissemination and treatment failure may occur.[25][24] 

Local recurrence and metastases

The factors that increase the risk of recurrence and metastases are the extension of myxopapillary ependymoma into the substance the spinal cord, a clinical history of less than one year, the extent of resection, and atypical histology of the tumor.[24]

Consultations

  • Neurosurgeon
  • Neurologist
  • Radiotherapist
  • Radiologist
  • Pathologist

Deterrence and Patient Education

Patients should consult with a neurologist when they suffer from radicular pain and back pain. The interprofessional team should ensure that the patients are well informed about myxopapillary ependymoma. Patients should be informed about educational websites so as to help them better understand this benign neoplasm, its prognosis, and its treatment. Patient education plays a very important role in the deterrence of the processes that can cause a myxopapillary ependymoma. Specialty-trained nurses often play a crucial role.

Pearls and Other Issues

Although myxopapillary ependymomas are classified as benign tumors, dissemination, and local recurrence pose a major challenge in their clinical treatment.

Therefore, a close follow-up of the patients with myxopapillary ependymoma is mandatory in order to detect local recurrent or spread of the tumor.

Enhancing Healthcare Team Outcomes

Management of myxopapillary ependymoma needs an interprofessional approach involving a team that consists of a neurosurgeon, neurologist, radiotherapist, radiologist, and pathologist. The primary clinicians should refer patients with any neurological deficits to a neurologist or a neurosurgeon for further workup. All health professionals must coordinate their actions to enhance the management of patients with myxopapillary ependymoma. Coordination begins with proper communication between clinicians, nurses, and pharmacists. 

The optimal treatment of myxopapillary ependymoma relies on surgical removal of the tumor. The interprofessional team should perform an exhaustive preoperative workup to minimize postoperative complications of surgery.


References

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