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in the conus-cauda-filum terminale region) and subependy-
moma, a benign, slowly growing intraventricular lesion with
a very favourable prognosis, WHO grade II ependymoma
andWHO grade III anaplastic ependymoma. Ependymoblas-
tomas are being classified as primitive neuroectodermal
tumours (PNET) and must be distinguished from anaplastic
ependymomas.
2.1.1. Myxopapillary ependymoma (WHO grade I)
This entity is characterised by cuboidal tumour cells, with
GFAP expression and lack of cytokeratin expression, sur-
rounding blood vessels in a mucoid matrix. Mitotic activity
is very low or absent.
2.1.2. Subependymoma (WHO grade I)
Subependymoma has isomorphic nuclei in an abundant
and dense fibrillary matrix with frequent microcysts; mitoses
are very rare or absent.
2.1.3. Ependymoma (WHO grade II)
This neoplasm has moderate cellularity; mitoses are rare
or absent and nuclear morphology is monomorphic. Key
histological features are perivascular pseudorosettes and
ependymal rosettes our histological variants have been
described: cellular ependymoma, which has hypercellularity
and increased mitotic rate, papillary ependymoma, clear cell
ependymoma and tanycytic ependymoma.
2.1.4. Anaplastic ependymoma (WHO grade III)
This tumour is characterised by hypercellularity, cellular
and nuclear pleomorphism, frequent mitosis, pseudopalisad-
ing necrosis and endothelial proliferation. The latter two
criteria do not appear to be independently related to prognosis
Perivascular rosettes are a histological hallmark.
2.2. Immunophenotype
2.2.1. Immunophenotype
Ependymomas typically express GFAP, particularly in
pseudorosettes and in grades I–II lesions, S100 protein and
vimentin In some cases, focal expression of cytok-
eratins has been observed while neuronal antigens are
never observed. The proliferation index is variable and is
higher when anaplastic features are present or the patient is
aged
2.3. Genetic features
2.3.1. Genetic features
Data concerning the cytogenetic features of ependymoma
are sparse. Approximately two thirds of patients exhibit cyto-
genetic abnormalities but no primary deletion is evident.
The most frequent abnormal cytogenetic features consist of
monosomy 22 or in various translocations involving chromo-
some 22, which have been detected in approximately 30%
of cases The absence of a tumour-suppressor gene
located on chromosome 22 has been suggested. Aberrations
involving chromosomes 1, 6, 7, 9, 10, 11, 12, 13, 16, 17,
19 and 20 have been reported less frequently. Ependymomas
are genetically different from astrocytic and oligodendroglial
tumours. No mutations or deletions of the tumour suppres-
sor genes CDKN2A and CDKN2B and no amplification of
CDK4 or CCND1 or EGFR have been described he
p53 gene has only a minor and unclear role in induction of
ependymomas owever, mdm2 gene amplification
has been found in up to 35% of ependymomas he gene
product MDM2 is believed to act as a cellular regulator of
p53-mediated tumour growth. MDM2 immunopositivity was
detected in 96% of specimens, suggesting not only a role of
mdm2 amplification in the tumorigenesis of ependymoma but
also the presence of a mechanism of MDM2 overexpression
other than gene amplification Analyses of mutations of
the NF2 suppressor gene yielded conflicting results
It is likely that NF2 mutations are related to spinal ependymo-
mas only hich constitute a molecular variant, while a
tumour-suppressor gene, independent of the NF2 gene, might
be implicated in the genesis of cerebral ependymomas
The cytogenetic aberrations seem to differ between tumours
from adult and younger patients, and between intracranial
and spinal ependymomas
3. Diagnosis
3.1. Clinical presentation
Clinical presentation is non-specific, and depends on the
size, location and malignancy of the tumour. Anaplastic
ependymomas give rise to signs and symptoms more rapidly.
Intraventricular ependymomas often cause headache, nau-
sea and vomiting, papilloedema, ataxia, and vertigo due
to increased intracranial pressure and hydrocephalus. The
compression of posterior fossa structures leads to visual dis-
turbances, ataxia and hemiparesis, dizziness and neck pain.
Patients with extraventricular supratentorial ependymomas
may show forgetfulness, behavioural changes and lethargy
with signs like seizures and focal neurological deficits. Spinal
cord lesions are typically associated with back pain of long
duration, and motor or sensory deficits of lower and upper
extremities.
3.2. Localisation
Ependymomas are more commonly infratentorial (60%),
particularly in the fourth ventricle, and in 50% of cases can
extend into the subarachnoid space of the cisterna magna
or the cerebello-pontine angle, or involve the medulla and
upper cervical cord he second most common loca-
tion is the spinal cord, followed by the lateral ventricles and
the third ventricle. Approximately one-half of supratentorial
ependymomas are parenchymal and one-half are primarily
intraventricular, arisingmore often (75%) in the lateral ventri-