Ependymoma

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 (commonest location in children)
• spinal cord ependymoma: discussed separately 
• myxopapillary ependymoma (conus medullaris): discussed separately
• supratentorial ependymoma

The remainder of this article concerns itself with intracranial ependymomas. 

Epidemiology

There is no recognised gender predilection ³. Although they can occur at any age, the posterior fossa tumours tend to present more commonly in the paediatric age group (mean age at diagnosis is 6 years of age), with a smaller second peak for supratentorial tumours around the 3^rd decade ⁷. 

Clinical presentation

Clinical presentation can vary according to location. Initial presentation with signs and symptoms of raised intracranial pressure is common, particularly with tumours in the fourth ventricle. Other posterior fossa symptoms including ataxia are also encountered ⁷. Supratentorial ependymomas may also present with seizures or focal neurological deficits ^2,5.

In the infrequent scenario of haemorrhage, presentation will be hyper-acute. 

Associations

• neurofibromatosis type 2 (NF2)

Pathology

Ependymomas are glial tumours with ependymal differentiation ⁷. They tend to be well defined lobulated soft and frond like tumours which are moderately cellular. Ependymal rosettes are rare but pathognomonic feature. Peri-vascular pseudorosettes are more common and seen in most of ependymomas ⁸.

Although for many years ependymomas were believed to be tumours arising from dedifferentiated ependymal cells that line the ventricles of the brain and central canal of the spinal cord, it now appears fairly certain that in fact they arise from radial glial stem cells ^9-10. 

Markers

• GFAP: ~50% positive

Classification

Ependymomas can occurare WHO grade II tumours, with more histologically aggressive tumours denoted WHO III (anaplastic ependymoma) although the reliability of histological features in both malignantgrading these tumours, and benign formsthe prognostic significance is somewhat controversial, and recently there has been a shift towards molecular markers to subdivide ependymomas ¹¹. 

In the current (2016 update) WHO classification of CNS tumours the following entities are accepted as belonging to the ependymoma family of tumours ¹¹:

• WHO grade I
  • subependymoma  (discussed separately)
  • myxopapillary ependymoma  (discussed separately)
• WHO grade II
  • ependymoma - 9391/3
    • cellularpapillary ependymoma
    • papillary ependymoma
    • clear cell ependymoma
    • tanycytic ependymoma
    • RELA fusion-positive (new entity in 2016 update)  
• WHO grade III
  • anaplastic ependymoma
  • features include
    • increased cellularity and increased mitotic activity
    • microvascular proliferation
    • necrosis

Radiographic features 

The majority of intracranial ependymomas (60%) are located in the posterior fossa (infratentorial), usually arising from the floor of the fourth ventricle ^5-7. This is especially true in children. The remainder (40%) are located supratentorially and up to half of these are intraparenchymal ⁷. 

Posterior fossa ependymomas are apt to extend through the foramina of Luschka and Magendie, hence the term plastic ependymoma. This is a characteristic feature and can be seen on both CT and MRI. 

Ependymomas are typically heterogeneous masses with areas of necrosis, calcification, cystic change and haemorrhage frequently seen. This results in heterogeneous appearance on all modalities. 

Intraparenchymal lesions (usually supratentorial) are usually large and also variable in appearance, ranging from completely solid enhancing masses, to cysts with a mural nodule or more heterogeneous masses ⁷. These are believed to be due to trapping of embryonic rests of ependymal tissue in the developing cerebral paranchyma ⁵.

CT

Brain

• coarse calcification is common (50%) 
• cystic areas (50%) 
• solid component iso to hypodense
• heterogeneous enhancement 
• variable haemorrhage

MRI

Brain

• T1
  • solid portions of ependymoma typically are isointense to hypointense relative to white matter ⁷
• T2
  • hyper intense to white matter
  • more reliable in differentiating tumour margins than non-contrast T1-weighted images (but less reliable than contrast enhanced T1)
• T2* (e.g. SWI)
  • foci of blooming from haemorrhage or calcification
• T1 C+ (Gd)
  • enhancement present but heterogeneous
  • enhancement with gadolinium is useful in differentiating tumour from adjacent vasogenic oedema and normal brain parenchyma
• DWI/ADC
  • restricted diffusion may be seen in solid components especially in anaplastic tumour
  • diffusion should be interpreted with caution in masses with significant haemorrhage or calcification
• MRS
  • Cho peak elevation according to the cellularity of tumor
  • NAA peak reduction
  • elevated Cho/Cr ratio
  • lipid and lactate rise when degeneration occurs

Although it is uncommon when compared to tumours like medulloblastomas, careful examination of the entire neuraxis is required to assess for the presence of CSF seeding. 

Treatment and prognosis

A total or partial resection could be attempted +/- irradiation.

Prognosis is however relatively poor which is mainly due to tumours occurring in surgically challenging locations making complete resection difficult. 

Poor prognostic factors include location in the 4th ventricle, anaplastic variant and incomplete resection. As such children have a worse prognosis (both 4th ventricular location and anaplastic variant are more common in children). Overall the 5-year survival rate in children ranges from 50 to 75% ⁷. 

Once recurrence has occurred prognosis is very poor, with a mortality rate of 90% ⁷. 

Differential diagnosis

General imaging differential considerations include:

• medulloblastoma 
  • similar demographic especially if around the 4^th ventricle
  • arises from vermis
  • less 'plastic', does not tend to extend through foramina
  • enhancement more homogenous
  • calcification less common
• subependymoma
  • tends to occur in older individuals
• choroid plexus papilloma
  • in children usually in the trigone of the lateral ventricles
  • in adults usually in the fourth ventricle (i.e opposite to ependymoma)
  • more vividly and homogeneously enhancing
  • lacks adjacent parenchymal oedema
  • NB choroid plexus carcinoma can be heterogeneous and invade brain
• choroid plexus metastasis
  • can appear similar
  • older individuals, usually with a history of malignancy
• glioblastoma
  • difficult to distinguish from intraparenchymal supratentorial ependymoma
  • usually older patients
  • epicentre usually in the white matter
• central neurocytoma
  • usually arises from/in contact with septum pellucidum
  • less vivid enhancement
• atypical teratoid/rhabdoid tumor