Ependymoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Associate Editor(s)-in-Chief: Ahmad Al Maradni, M.D. [3]

Overview

On gross pathology, a well-encapsulated tumor arises from the floor of the fourth ventricle, situated in the lower back portion of the brain is a characteristic finding of ependymoma. On microscopic histopathological analysis, perivascular pseudorosettes are characteristic findings of ependymoma. Development of ependymoma is the result of multiple genetic mutations (ERBB2, ERBB4, MMP2, MMP14, NOTCH1, and MEN1).

Pathology

• Ependymomas represent a relatively broad group of glial tumours which share common origin from differentiated ependymal cells lining 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.
• Ependymomas can occur anywhere, but certain location are typical. Common locations include:

• Floor of the fourth ventricle (common location in children)
• Spinal cord ependymoma
• Myxopapillary ependymoma (conus medullaris)
• Supratentorial ependymoma

• The subependymomas, variant of the ependymoma, arise in the fourth ventricle but may occur in the septum pellucidum and the cervical spinal cord.

Gross Pathology

• Ependymomas are well-encapsulated tumors and usually arise from the floor of the fourth ventricle, situated in the lower back portion of the brain.

• 

  Fourth ventricle ependymomas frequently extend out of the ventricle into the subarachnoid space.

Microscopic Pathology

• Ependymomas are composed of cells with regular, round to oval nuclei. There is a variably dense fibrillary background.
• Tumor cells may form gland-like round or elongated structures that resemble the embryologic ependymal canal, with long, delicate processes extending into the lumen; more frequently present are perivascular pseudorosettes in which tumor cells are arranged around vessels with an intervening zone consisting of thin ependymal processes directed toward the wall of the vessel.
• Ependymal rosettes are rare but pathognomonic feature.

• 

  Micrograph of an ependymoma. H&E stain show pseudoressettes pattern of ependymal cells.

• 

  True ependymal rosette consisting of tumor cells arranged around well-defined lumens forming gland-like structures.<ref name=radiopaedia> Image courtesy of Dr Dharam RamnaniRadiopaedia (original file

• 

  Higher magnification of one of the true ependymal rosettes showing a collar of cells around a central lumen forming a gland-like structure.

Associated Conditions

The subependymal giant-cell astrocytoma, also called giant-cell glioma, is typically associated with tuberous sclerosis but can occur independently.

Genetics

• Posterior fossa ependymoma can be divided into the following two groups based on distinctive patterns of gene expression.

• One expression-defined group occurs primarily in young children and is characterized by a largely balanced genomic profile with an increased occurrence of chromosome 1q and proteins such as tenascin C and epidermal growth factor receptor.
• The second expression-defined group occurs primarily in older children and adults and is characterized by a numerous cytogenetic abnormalities involving the whole chromosome or chromosomal arms.
• Genes involved in ependymoma formation and progression are:

• ERBB2
• ERBB4
• Human telomerase reverse transcriptase TERT
• KIT receptor tyrosine kinase and phospho-KIT receptor expression is associated with tumor progression
• MMP2 and MMP14 appear to also play a role in tumor growth and progression in intracranial cases.
• NOTCH1 mutations have been found in approximately 8% of pediatric ependymomas
• MEN1 mutations are occasionally found in pediatric ependymomas.
• TPR and CHIBBY, have been identified in pediatric ependymomas.
• S100A6 and S100A4 on chromosome 1q have also been found to correspond to supratentorial tumor development and tumors occurring before the age of 3 years old.