They are predominantly intraventricular and account for 1%-3% of all primary brain tumors.

In children, they constitute 10% of intracranial tumors and are third in frequency after astrocytoma and medulloblastoma.

Some authors have found a predominance in the first two years of life.  However, congenital ependymomas are very rare and they are often malignant, and in most cases, located above the tentorium.

A second incidence peak is found between the third and fifth decade.    

Pathology:

Since Bailey and Cushing’s in 1926, a lot of classification and grading systems were proposed.

WHO classifies ependymomas as follows:

          Ependymoma (grade II) - Cellular, Papillary, Clear cell, and Tanycytic

          Anaplastic ependymoma (grade III)

          Myxopapillary ependymoma (grade I)

          Subependymoma (grade I)

Ependymoblastomas, are rare and malignant, with distinct ependymal differentiation, and included in the group of embryonal tumors.

Intracranial lesions are 1) Ependymomas, 2) Anaplastic  ependymomas, and 3) Subependymomas.

Myxopapillary ependymomas are almost exclusively located in the region of the cauda equina and originate from the filum terminale.

Ependymomas are thought to arise from the ependymal epithelium of the ventricles and central canal.  In children, posterior fossa is the most common site, whereas it is equally distributed through out the CNS in adults. Floor of the fourth ventricle is the most common intraventricular location, followed by the lateral and third ventricles. Tumors which originate at the floor of the fourth ventricle may grow through the foramen of Magnendie into the cisterna magna and furthermore, through the foramen magnum into the upper cervical spinal canal as far down as the level of C5.  Ependymomas which arise from the medullary velum at the lateral recess may extend through the foramina of Luschka into the cerebellopontine cisterns.

Histologically, there is perivascular pseudorosettes and true ependymal rosettes. These are seen as rosette like arrangements of cells with ependymal differentiation. Electron microscopy reveals these vascular elements surrounded by an acellular zone. Presence of pleomorphism, increased cell density, and mitosis suggest anaplasia.

There are numerous variants including common cellular, papillary and clear cell and the uncommon tanycytic, a fibrillar variant. They are not of clinical relevance. 

Ependymomas are characteristically GFAP positive by immunohistochemistry.

Familial cases have been identified, but the cause of most cases remains unknown. Cytogenic analysis has characterized the loss of chromosome 22q as the most common genetic abnormality. As more than 50% of them have lost or altered chromosome 22q sequences, the possibility exists that a tumor suppressor gene important in ependymomas is located on this chromosome.

Clinical presentation:

Intraventricular ones present with features of hydrocephalus. Cranial neuropathy can occur in 25% of cases, due to compression or invasion of the floor of the fourth ventricle. Spinal seeding is suspected in the presence of backache and radicular symptoms.

Hemispheric ones usually with seizures and neurological deficit.

Spinal cord tumors present with signs and symptoms of an intramedullary lesion.

Imaging:

Radiologically, the CT reveals an iso to hypodense enhancing peri/intra ventricular lesion with different degrees of calcifications, necrotic and cystic changes. It is iso to hypodense on T1 and hyperdense on T2 MRI images. Hemorrhage is reported in 10% of cases. A tumor-vermis cleavage plane in a posterior fossa tumor that is isodense on CT is highly suggestive of ependymoma.

Management:

Surgical excision and post operative irrradiation have been the mainstay of treatment.

Uncontrolled studies suggest that total surgical resection offers long term remission. Second stage surgery, if needed, has been recommended to to achieve total excision. Recent advances in surgical tools, intraoperative imaging, and electrophysiological monitoring have greatly helped the surgeon in his goal of total excision.

Regardless of location, craniospinal radiation is advocated both for cases with evidence of spinal seeding and for high grade ones. In the absence of spinal seeding, some consider spinal radiation less useful.

Most surgeons add cervical radiation in all infratentorial cases, although not supported by controlled studies.

Ependymomas are traditionally considered to be one of the most radiosensitive brain tumors. Furthermore, low grade ependymomas represent the most radioresponsive tumors within the glioma group.  Although the need for postoperative high-dose radiation therapy to achieve local tumor control is generally agreed upon, there remains a controversy as to the extent of irradiation.  Recent studies of postoperative radiation therapy did not reveal an improvement  in survival by additional prophylactic spinal irradiation. Thus, local control remains the main therapeutic challenge in the treatment of intracranial ependymomas.

Recommended doses are 50-60Gy for the primary tumor, 45-60Gy for whole brain irradiation and 30-40Gy for the spine.  Children should receive 80% of adult doses. A few study groups use interstitial irradiation for the treatment of ependymomas.

However, the role of radiotherapy in low grade cases where total tumor resection has been achieved remains unanswered.

Ependymomas have been reported to be relatively less responsive to chemotherapy.  Responses have been documented to nitrosoureas and vincristine.  However, despite a variety of protocols, improvement of progression free interval by chemotherapy in addition to surgery and radiotherapy has not yet been established. 

Currently, the indication for adjuvant chemotherapy is mostly restricted to recurrences of anaplastic ependymomas in childhood.

Use of stem cells to enhance the effectiveness of chemotherapy is being studied.

Genetherapy and immunotherapy are under trial.

Prognosis:

The prognosis has improved recently. With complete excision, 5 year survival rates of 37% to 69%.

The prognosis is poorer in the very young, in recurrences and in anaplastic variants. The main cause of death in ependymomas patients is recurrence at the primary tumor site. Median survival time after diagnosis of spinal seeding is 6 months.

Infratentorial and anaplastic ependymomas metastasize most frequently. 

Nearly two thirds of spinal metastases previously reported originated from an anaplastic infratentorial ependymoma.

According to autopsy data, spinal seeding can be expected in 25% of cases subsequent to surgery of the primary tumor. 

Extraneural metastasis is rare; they are usually from the supratentorial ones, and carry worse prognosis..

SUBEPENDYMOMA:

They are also called subependymal giant cell astrocytoma (SEGA).

These are thought to be derived from glial elements of the subependymal tissues found just beneath the ependymal epithelial tissues found just beneath the ependymal epithelial layer. They are slow growing, intraventricular tumors whose diagnosis is most commonly made in adults, particularly in older men.

Familial occurrences has been described.  Subependymomas are most often asymptomatic and incidentally found at autopsy.

They can be supratentorial (27%), infratentorial (71%),or cervicothoracic(2%). Lateral ventricles is the most common site, with obstruction at foramen munro and resultant hydrocephalus.