Ependymoma

Original Editor - George Prudden

Top Contributors - Shaimaa Eldib, Lucinda hampton, George Prudden, Kim Jackson, Vidya Acharya and Rewan Elsayed Elkanafany

Introduction

Ependymomas represent a broad group of glial tumours most often arising from the lining of the ventricles of the brain or the central canal of the spinal cord. They account for ~5% of all neuroepithelial neoplasms, ~10% of all paediatric brain tumours and up to 33% of brain tumours occurring in those less than 3 years of age.

Unlike other kinds of cancer, ependymomas usually don’t spread to other parts of the body, but can spread to more than one area of the brain or spine. In children, these tumors are likely to come back after treatment.

They can be divided into three groups depending on the anatomical compartment in which they are found:

1. Posterior fossa (60%)
2. Supratentorial (30%) ie above the tentorium cerebelli
3. Spinal cord (10%)

Central nervous system

Clinically Relevant Anatomy

Glial cells

Glial cells are a cell type that are found between nerve cells that share a general function of holding the CNS together. There are more glial cells than nerve cells and thereby constitute half of the total volume of the CNS. The four types of glial cells are: oligodenrocytes, microglia, epndymal cells and astrocytes.

Ventricals

Ventricals and the central canal of the spinal cord are fluid-filled spaces within the CNS that contain cerebrospinal fluid. Both are common locations for tumours.

Tentorium Cerebelli

Tentorium Cerebelli is an extension of the dura matter that separates the cerebellum from the inferior aspect of the occipital lobes. Tumour below the tentorium are called infratentorial and those above are called supratentorial.

Pathological Process:

Ependymomas are traditionally thought to arise from oncogenetic events that transform normal ependymal cells into tumor phenotypes. The precise nature and order of these genetic events are unknown.

Incidence

Children:

• The 3rd most common pediatric CNS tumour.
• It represents around 6% to 12% of children brain tumor and 2% of all childhood cancer.
• The prognosis for pediatric ependymomas remains relatively poor when compared with other brain tumors in children,despite advances in neurosurgery, neuroimaging techniques, and postoperative adjuvant therapy.
• The 5-year survival rate ranges from 39% to 64%.

Adults:

• the most common primary glial neoplasm of spinal cord representing 50%–60% of all intramedullary cord neoplasms.
• Most commonly occur in the spinal cord
• Ependymomas are believed to be slow-growing tumors and exhibit benign pathology behavior.

Clinical Presentation

Brain tumor symptoms include:

• Headache or pressure in the head
• Nausea or vomiting
• Blurred vision
• Weakness or numbness and tingling

Spinal cord symptoms include:

• Back pain
• Weakness in the arms or legs
• Numbness or tingling in the arms, legs or trunk
• Problems going to the bathroom or controlling bowel or bladder function

Diagnostic Procedures

The diagnosis and disease staging is performed by craniospinal MRI. Tumor classification is achieved by histological and molecular diagnostic assessment of tissue specimens according to the World Health Organization (WHO) classification 2016. 

If the MRI confirms a primary tumour, patients normally do not need other imaging tests of the blood because ependymoma tumours do not tend to spread outside of the CNS. MRI scans provide a baseline so as to measure disease progression as well as identifying areas that have been affected.

Tumours are classified and graded according to their appearance when viewed through the microscope follow the collection of cells from biopsy.A recent molecular classification has distinguished 9 subgroups of ependymal tumors that appear to reflect more precisely than histology alone the biological, clinical, and histopathological heterogeneity across the major anatomical compartments, age groups, and tumor grades[null .]Each of the 9 molecular subgroups is characterized by distinct DNA methylation profiles and associated genetic alterations.

World Health Organization (WHO) Classification of Tumors of the Nervous System:

Myxopapillary ependymoma (WHO grade I)

This entity is characterised by cuboidal tumour cells, with GFAP expression and lack of cytokeratin expression, surrounding blood vessels in a mucoid matrix. Mitotic activity is very low or absent.

Subependymoma (WHO grade I)

Subependymoma has isomorphic nuclei in an abundant and dense fibrillary matrix with frequent microcysts; mitoses are very rare or absent.

Ependymoma (WHO grade II)

This neoplasm has moderate cellularity; mitoses are rare or absent and nuclear morphology is monomorphic. Key histological features are perivascular pseudorosettes and ependymal rosettes. Four histological variants have been described: cellular ependymoma, which has hypercellularity and increased mitotic rate, papillary ependymoma, clear cell ependymoma and tanycytic ependymoma.

Anaplastic ependymoma (WHO grade III)

This tumour is characterised by hypercellularity, cellular and nuclear pleomorphism, frequent mitosis, pseudopalisading necrosis and endothelial proliferation. The latter two criteria do not appear to be independently related to prognosis. Perivascular rosettes are a histological hallmark.

Management

Many factors impact decisions about the treatment of ependymoma including the tumor location and grade, and the age of the person. Children and adults tolerate treatments differently, for that reason treatment for adults and treatment for pediatric patients may be very different.

Surgery

When possible, removing the tumour from the brain or spinal cord is a priority as SCI associated with spinal tumor is often managed surgically. A secondary goal of surgery is obtaining a biopsy of cancerous cells for diagnosis.

Radiation Treatment

External beam radiation treatment is commonly used to treat ependymoma. Beams of X-rays, gamma rays or protons are aimed at the area of head or spine where the tumour is located. The treatment aims to kill cancer cell and shrink tumours. The treatments last several weeks.

There are several methods of delivering radiation treatment:

• Conformal radiotherapy
• Intensity-modulated radiotherapy (IMRT)
• Proton beam radiotherapy
• Stereotactic radiosurgery (SRS)

Chemotherapy

Chemotherapy is drug treatment for cancers or tumors. There are many types of drugs used to treat cancer. Traditionally cytotoxic agents designed to kill growing tumor cells are used.

These agents often have side effects such as hair loss, nausea and vomiting and can cause a decrease in blood counts.

Differential Diagnosis

• Astrocytoma
• Choroid Plexus Papilloma
• Glioblastoma Multiforme
• Tumors of the Conus and Cauda Equina
• Vascular Surgery for Arteriovenous Malformations

Key Evidence

• 
  The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.
• Biology and management of ependymomas,
• Ependymoma.
• Neurofibromatosis type 2 service delivery in England.
• Interdisciplinary management of hemicorporectomy after spinal cord injury.

Spinal ependymoma in an adult patient	Anaplastic ependymoma in an adult patient from the axial view	Pediatric ependymoma image – fourth ventricular ependymoma (T1 weighted with contrast)