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Ependymomas represent a relatively broad group of glial tumors 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 pediatric brain tumors and up to 33% of brain tumors occurring in those less than 3 years of age.
Ependymomal tumors 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 tumors, 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
- supratentorial ependymoma
- spinal cord/canal
The remainder of this article concerns itself with posterior fossa ependymomas. The other entities are discussed separately (see above).
Although there is no overall recognized gender predilection when all ependymomas are treated as a group 3, each subgroup does have different gender and age predilection 13.
PFA tumors (see below) are more common in males (M:F = 2:1) and are usually encountered in infants and young children. In contrast, PFB tumors have no gender predilection and are found in older children and adults 13,15.
Clinical presentation can vary according to location. Initial presentation with signs and symptoms of raised intracranial pressure is common, particularly with tumors 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 hemorrhage, the presentation will be hyper-acute.
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 7,11. Although for many years ependymomas were believed to be tumors 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.
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.
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 8,11.
Dystrophic calcification, hemorrhage, myxoid degeneration and even rarely metaplasia (bone or cartilage) are sometimes encountered 11.
A number of histological patterns are historically recognized, including papillary ependymoma, clear cell ependymoma, tanycytic ependymoma (usually found in the spinal cord). These are no longer recognized as distinct subtypes, however 18.
A number of immunohistochemical markers are useful, including 11,12:
- glial fibrillary acid protein (GFAP)
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
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 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 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 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.
- coarse calcification is common (50%)
- cystic areas (50%)
- solid component iso- to hypodense
- heterogeneous enhancement
- variable hemorrhage
- solid portions of ependymoma typically are isointense to hypointense relative to white matter 7
- 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 tumor from adjacent vasogenic edema and normal brain parenchyma
- 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
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 4th ventricular location, grade 3 tumors (previously known as anaplastic) 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, 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
General imaging differential considerations include:
- similar demographic, especially if around the 4th ventricle
- arises from vermis
- less 'plastic', does not tend to extend through foramina
- enhancement more homogenous
- calcification less common
- 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 edema
- 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
- difficult to distinguish from intraparenchymal supratentorial ependymoma
- usually older patients
- epicenter usually in the white matter
- usually arises from/in contact with septum pellucidum
- less vivid enhancement
- atypical teratoid/rhabdoid tumor
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