Posterior fossa ependymoma

Posterior fossa ependymomas are the most common type of ependymoma, most commonly occurring in children. They are divided on the basis of DNA-methylation profiling into two groups, A and B. 

Epidemiology

Posterior fossa ependymomas are encountered in all age groups but are usually encountered in children. The epidemiology, however, depends on molecular characteristics ^1,4. 

• posterior fossa group A (PFA) ependymomas

  • primarily in infants and young children

    • <6 years of age: >95% of all posterior fossa ependymomas

    • adolescents: 50%

    • adults: 5-10%

  • somewhat more common in males

• posterior fossa group B (PFB) ependymomas

  • primarily in adolescents and adults

    • <5 years of age: <5% of all posterior fossa ependymomas

    • adolescents: 20-50%

    • adults: 90%

  • somewhat more common in females

Clinical presentation

Initial presentation with signs and symptoms of raised intracranial pressure is common. Other posterior fossa symptoms including ataxia are also encountered ³. Supratentorial ependymomas may also present with seizures or focal neurological deficits ^2,5.

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

Pathology

Ependymomas are glial tumors with ependymal differentiation which tend to arise within or abutting the ventricular system of the brain or central canal of the spinal cord ^1-5. Although for many years ependymomas were believed to be tumors arising from dedifferentiated ependymocytes, it now appears certain that they arise from an undifferentiated glial stem or progenitor cell ^1,6. 

Macroscopic appearance

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

Microscopic appearance

Microscopically, these tumors are characterized 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 ^1,3.

Dystrophic calcification, hemorrhage, myxoid degeneration and even rarely metaplasia (bone or cartilage) are sometimes encountered ¹. 

A number of histological patterns are historically recognized, including papillary ependymoma, clear cell ependymoma, tanycytic ependymoma (usually found in the spinal cord). These are, however, no longer recognized as distinct subtypes ¹. 

Immunohistochemistry

A number of immunohistochemical markers are useful, including ¹:

• 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, tumors can be given a grade of 2 or 3 based on histological features ¹⁸. The term "anaplastic ependymoma" is, however, no longer listed, although remains equivalent to grade 3. 

Radiographic features 

The majority of posterior fossa ependymomas arise from the lateral recess of the fourth ventricle (molecular subgroup: PFA) or midline floor of the fourth ventricle near the obex (molecular subgroup: PFB) ^3-5,8.

Posterior fossa ependymomas are apt to extend through the foramina of Luschka and Magendie, hence the term "plastic ependymoma" or comparsion to a toothpaste. 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 hemorrhage frequently seen. This results in a heterogeneous appearance on all modalities. 

Although intraparenchymal lesions are usually supratentorial, rarely they are found in the cerebellum ⁹, and generally large and variable in appearance, ranging from completely solid, enhancing masses to cysts with a mural nodule, or more heterogeneous masses ³. 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 hemorrhage

MRI

• T1

  • solid portions of ependymoma typically are isointense to hypointense relative to white matter ³

• T2

  • hyperintense to white matter

  • more reliable in differentiating tumor margins than non-contrast T1-weighted images (but less reliable than contrast-enhanced T1)

• T2* (e.g. SWI)

  • foci of blooming from hemorrhage or calcification

• T1 C+ (Gd)

  • enhancement present but heterogeneous

  • enhancement with gadolinium is useful in differentiating tumors from adjacent vasogenic edema and normal brain parenchyma

• DWI/ADC

  • restricted diffusion may be seen in solid components, especially in anaplastic tumor

  • diffusion should be interpreted with caution in masses with significant hemorrhage or calcification

• MRS

  • choline 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 tumors 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 tumors occurring in surgically-challenging locations, making complete resection difficult. 

Poor prognostic factors include a 4^th ventricular location, grade 3 tumors (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% ³. 

Once recurrence has occurred, the prognosis is very poor, with a mortality rate of 90% ³. 

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 may have a significant impact on prognosis ¹⁰:

• PFA: poor

• PFB: 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 usually extend through foramina

  • enhancement often more homogenous, but variable

  • calcification less common

  • lower ADC values

• 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

  • more vividly and homogeneously enhancing

  • lacks adjacent parenchymal edema

  • N.B. choroid plexus carcinoma can be seen in infants, but typically in the lateral ventricles, with heterogeneous signal and brain invasion

• choroid plexus metastasis

  • can appear similar

  • older individuals, usually with a history of malignancy