Ependymoma

Ependymomas represent a relatively 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. 

Ependymomal tumours can occur anywhere within the neuraxis, but distribution and molecular characteristics are fairly site-dependent, divided into three groups depending on the anatomical compartment in which they are found ^11,13,15:

• posterior fossa (60%)
• supratentorial (30%)
• spinal cord (10%)

In addition to subependymomas, that can be encountered in all three compartments, the molecular characteristics of tumours, with different epidemiology and prognosis, are site-specific and form the basis of the current WHO classification ^11,13:

• posterior fossa
  • posterior fossa A
  • posterior fossa B
  • subependymoma
• supratentorial ependymoma
  • RELA ZFTA (C11oft95)  fusion-positive
  • YAP1-MAMLD1 fusion
  • subependymoma
• spinal cord/canal
  • spinal cord ependymoma
  • myxopapillary ependymoma
  • spinal subependymoma (rare)

The remainder of this article concerns itself with posterior fossa ependymomas. The other entities are discussed separately (see above). 

Epidemiology

Although there is no overall recognised gender predilection when all ependymomas are treated as a group ³, each subgroup does have different gender and age predilection ¹³.

PFA tumours (see below) are more common in males (M:F = 2:1) and are usually encountered in infants and young children. In contrast, PFB tumours have no gender predilection and are found in older children and adults ^13,15.

Associations

• neurofibromatosis type 2 (NF2)

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, the presentation will be hyper-acute. 

Pathology

Ependymomas are glial tumours with ependymal differentiation which tend to arise within or abutting the ventricular system of the brain or central canal of the spinal cord ^7,11. Although for many years ependymomas were believed to be tumours arising from dedifferentiated ependymocytes, it now appears fairly certain that in fact, they arise from radial glial stem cells ^9-11. 

Posterior fossa ependymomas are divided into two groups, posterior fossa A and B subtypes that vary in the degree of methylation and global levels of histone H3 K27-trimethylation ¹⁵. 

Macroscopic appearance

Macroscopically, ependymomas tend to be well defined lobulated grey or tan-coloured soft and frond-like tumours which are moderately cellular. They may have focal areas of calcification. 

Microscopic appearance

Microscopically, these tumours are characterised by well-differentiated cells. Characteristic features include ependymal rosettes, which are uncommon but pathognomonic and perivascular pseudorosettes which are far more common and seen in most ependymomas ^8,11.

Dystrophic calcification, haemorrhage, myxoid degeneration and even rarely metaplasia (bone or cartilage) are sometimes encountered ¹¹. 

A number of histological patterns are historically recognised, including papillary ependymoma, clear cell ependymoma, tanycytic ependymoma (usually found in the spinal cord). These are no longer recognised as distinct subtypes, however ¹⁸. 

Immunohistochemistry

A number of immunohistochemical markers are useful, including ^11,12:

• glial fibrillary acid protein (GFAP)
  • almost always positive in the cytoplasmic process around the perivascular pseudorosettes
  • variable elsewhere
• epithelial membrane antigen (EMA)
  • positive in the luminal surface of the ependymal rosettes
  • positive dot or ring-like perinuclear intracytoplasmic structure (intracytoplasmic microrosette)
• S100: positive
• vimentin: positive
• OLIG2: negative

Grading

Ependymoma grading is controversial and probably not as important as molecular features ¹⁸. Nonetheless, tumours can be given a grade of 2 or 3 based on histological features ¹⁸. 

Radiographic features 

The majority of all intracranial ependymomas (60%) are located in the posterior fossa (infratentorial), usually arising from the lateral recess of the fourth ventricle (molecular subgroup: posterior fossa A) and midline inferior floor of the fourth ventricle near the obex (molecular subgroup: posterior fossa B) ^5-7,13.

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 a heterogeneous appearance on all modalities. 

Although intraparenchymal lesions are usually supratentorial, rarely they are found in the cerebellum ¹⁶, and generally large and variable in appearance, ranging from completely solid, enhancing masses to cysts with a mural nodule, or more heterogeneous masses ⁷. They are believed to arise from the trapping of embryonic rests of ependymal tissue in the developing brain parenchyma ⁵.

CT

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

MRI

• T1
  • solid portions of ependymoma typically are isointense to hypointense relative to white matter ⁷
• T2
  • hyperintense 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
  • choline peak elevation according to the cellularity of tumour
  • 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 may 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 a 4^th ventricular location, grade 3 tumours (previously known as anaplastic) and incomplete resection. As such, children have a worse prognosis (both 4^th 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, the prognosis is very poor, with a mortality rate of 90% ⁷. 

Rarely extraneural metastases may occur, reported sites include: lymph nodes, mediastinum, lungs, pleura, diaphragmatic muscle, retroperitoneum, liver and bone ¹⁴.

Molecular subgroup prognosis

The molecular subgroup has a have a significant impact on prognosis ¹³:

• posterior fossa A: poor
• posterior fossa B: good

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
  • usually not enhancing
• 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 the 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 tumour