Case record...Intraventricular ependymoma http://yassermetwally.com http://yassermetwally.net

1. CASE OF THE WEEK
PROFESSOR YASSER METWALLY
CLINICAL PICTURE
CLINICAL PICTURE:
A 26 years old male patient presented with manifestations of increased intracranial pressue. (To inspect the patient's full radiological
study, click on the attachment icon (The paper clip icon in the left pane) of the acrobat reader then double click on the attached file) (Click
here to download the attached file)
RADIOLOGICAL FINDINGS
RADIOLOGICAL FINDINGS:
Figure 1. Precontrast CT scan: Intraventricular ependymoma filling the lateral and
third ventricle, the lesion shows extensive perivascular calcification. The tumor is a huge
one, involving both lateral ventricles and causing extensive hydrocephalus.
Figure 2. Postcontrast CT scan: Intraventricular ependymoma filling the lateral and third ventricle, the lesion shows extensive
perivascular calcification (Actually perivenous) and is drained by the deep venous system through the vein of galen. Notice the dense
homogeneous enhancement. Hydrocephalic changes are seen with possible transependymal edema (A). (C is a bone window of B)

2. Figure 3. The tumor has extended to the third ventricle, ? the interhemispheric fissure, and Probably the suprasellar and the
quadrigeminal cistern. CSF seedling is probably the cause of dissemination through the basal cisterns and the bihemispheric fissures.
Figure 4. Angiography shows the extensive tumour hypervascularity that is mainly drained by the deep venous system through the vein of
galen.
The patient's tumor was debulked surgically and histopathological examination revealed an ependymoma of the cellular type with
Perivascular pseudorosettes. The patient was given a course of postoperative radiotherapy (Fig. 5). The patient died 7 month following the
operation.
 Comment
Ependymomas constitute 2% to 6% of all gliomas. Intracranial ependymomas are most common in the first and second decades but are
seen in adults. Of intracranial ependymomas, 30% to 40% occur in the supratentorial compartment. The majority of these supratentorial
ependymomas are parenchymal in location rather than intraventricular, with the reported frequency of a parenchymal origin ranging
from about 56% to 85%. This is because subependymal neural glia may extend into adjacent white matter as a streak or a band, leading to
ependymal cell rests remote from the ventricular lining. This tends to occur particularly where the ventricles are sharply angled.
In the supratentorial compartment, these tumors have a predilection for the frontal and parietal lobes and are usually large at the time of
diagnosis (94% of tumors are larger than 4 cm ). Characteristically they are well defined and homogeneous in appearance, but larger
tumors may undergo cystic degeneration. Hemorrhage is not a characteristic feature.
Microscopically there may be a variable appearance both between different tumors and in different parts of the same tumor. The
pathognomonic histologic feature is the appearance of ependymal rosettes, but these are not frequently seen.

3. Figure 5. Histopathological picture of ependymomas with the characteristic rosettes (The
patient's histopathology)
Rarely malignant or anaplastic ependymomas may occur with rapid growth and recurrence after surgery, although still with a relatively
favorable clinical course compared with other gliomas.
Ependymoblastomas are considered a rare embryonal form of ependymal neoplasm occurring in the supratentorial compartment in
children. These tumors are usually large, frequently invade the leptomeninges, and disseminate through the subarachnoid space. They
have a poor prognosis. Subependymomas are another variant of ependymoma with a significant astroglial component to the tumor,
although microscopically still having characteristic ependymal cellular features. These lesions tend to be intraventricular and multiple,
slow growing, and benign in behavior. They most frequently arise in the fourth ventricle but occur at other sites, including the lateral
ventricles. Large subependymomas may be pedunculated and contain focal areas of cystic degeneration, hemorrhage, and calcification.
These tumors may remain small and asymptomatic, being discovered incidentally on imaging studies or at postmortem. Larger lesions may
produce symptoms secondary to ventricular obstruction and hydrocephalus.
Supratentorial ependymomas are usually large frontoparietal masses. Although dense punctate calcifications are seen in about 50% of CT
scans, overall the tumor is usually hypodense or isodense relative to adjacent brain; intratumoral hemorrhage is not a feature.
Hydrocephalus is frequently seen in infratentorial tumors but is rare in supratentorial lesions. Perifocal edema and cystic change within
the tumor are each seen in about half the cases. The tumor margins may vary from poorly to well defined. There is moderate to marked
enhancement after contrast administration; the pattern is variable, ranging from homogeneous to inhomogeneous or ring enhancing.
MR imaging scanning, with sagittal and coronal images, demonstrates the route of spread of intraventricular ependymomas and
subependymomas well. On Tl-weighted images, the solid components of supratentorial ependymomas are hypointense to isointense and are
hyperintense on T2-weighted images; areas of cystic degeneration usually have similar signal intensities to cerebrospinal fluid. There may,
however, be heterogeneity of signal intensity in solid tumors owing to the presence of blood products (although hemorrhage occurs
infrequently), necrosis, or calcification, which may not be recognized on spin echo images but is identified on gradient echo pulse
sequences. Edema appears as regions of increased signal intensity in adjacent white matter on T2-weighted images. Enhancement is
usually moderate to intense and may vary in its pattern from patchy to homogeneous.
On angiography a number of cases with intraventricular ependymomas have been seen presenting a relatively homogeneous tumor cloud
which tended to persist, although the masses are not sharply circumscribed or lobulated, as occurs with meningiomas.
Early draining veins could be seen in the area of the tumor in some cases. A few mixed intraventricular ependymomas have been observed
presenting increased vascularity and rapid venous drainage by way of branches of the thalamostriate vein. These can usually be identified
as intraventricular because of their location close to the midline in the frontal projection, and in the region of the ventricles in the lateral
projection; at times they have the shape of a lateral ventricle. Some of these intraventricular ependymomas are so vascular that the
possibility of a vascular malformation is suggested . Differentiation from a vascular malformation is possible because even though the
draining veins fill early and are numerous, they do not empty as fast with a glioma as with an arteriovenous malformation.
DIAGNOSIS:
DIAGNOSIS: INTRAVENTRICULAR SUPRATENTORIAL EPENDYMOMA
DISCUSSION
DISCUSSION:
 Intraventricular Ependymoma
Ependymomas are common neoplasms that arise from differentiated ependymal cells that line the cerebral ventricles and the central canal
of the spinal cord (1). They constitute 3%–9% of all neuroepithelial neoplasms, 6%–12% of all pediatric brain tumors, and almost one-
third of all brain tumors in patients younger than 3 years (1).
Ependymomas may manifest at any age, with a documented age range of 1 month to 81 years (1). There is no gender predilection (1). Most
posterior fossa ependymomas arise in children, with a mean age of about 6 years (1). The mean age at presentation is higher for patients
who have a supratentorial ependymoma (18–24 years) (2). Of those ependymomas that occur intraventricularly, 58% originate in the
fourth ventricle, whereas the remaining 42% are located in the lateral and third ventricles (3). Supratentorial ependymomas are more
commonly extraventricular, especially in children (1,2). It is speculated that ependymomas may arise from embryonic rests of ependymal
tissue trapped within the developing cerebral hemispheres (1). Bizarre sites reported for ependymomas include the ovaries, soft tissues,
mediastinum, and sacrococcygeal region (4).
As with other intraventricular masses, clinical signs and symptoms are largely secondary to the effects of increased intracranial pressure

4. and hydrocephalus (1). Because the fourth ventricle is a predominant site for these tumors, some patients may present with cerebellar
ataxia and paresis (1,5). Patients with supratentorial ependymomas tend to present with focal neurologic deficits and seizures (1). In
general, children with ependymomas have a less favorable prognosis than adults, in part from the increased prevalence of a fourth
ventricle location and the predilection of this group for more anaplastic forms of the disease (1).
The 5-year progression-free rate for children overall is about 50% (6), with children younger than 2 years having an especially poor
prognosis (7). The 5-year and 10-year survival rates for adults are 57.1% and 45%, respectively (1). The treatment of choice is gross total
resection, and the degree of resection directly correlates with a better prognosis (8). Patients with supratentorial ependymomas have a
better survival rate than those patients with posterior fossa ependymomas (9). For all types of ependymomas, recurrence is common (2,10).
Postoperative radiation therapy is advocated for partially resected ependymomas (10).
Intraventricular ependymomas are well-circumscribed, grayish-red masses that usually fill the ventricular lumen and occasionally may
extend into the adjacent brain parenchyma (Fig 1) (1). When they arise in the fourth ventricle, these soft pliable tumors originate from the
floor or roof of the ventricle and frequently extend through the foramen of Luschka into the cerebellopontine angle and even the foramen
magnum (Fig 2) (1).
Figure 1. Ependymoma. Photograph of an autopsy specimen sectioned
through the level of the fourth ventricle shows a soft, friable
heterogeneous mass (arrows) within the fourth ventricle. Scattered areas
of hemorrhage are noted.
Figure 2. Ependymoma. Photograph of a brain at autopsy shows
extensive cerebellopontine angle extension (arrows) from a fourth
ventricular ependymoma. Numerous areas of hemorrhage give the mass
a heterogeneous appearance.
At histologic analysis, ependymomas are moderately cellular tumors characterized by rare mitotic figures; perivascular pseudorosettes;
and, less commonly, ependymal rosettes (Fig 3) (1). Accordingly, they are considered World Health Organization (WHO) grade II lesions
(1). Several variant forms are also noted, based on histopathologic features, and include cellular ependymoma, papillary ependymoma,
clear cell ependymoma, tanycytic ependymoma, and anaplastic ependymoma (WHO grade III) (1).

5. Figure 3. Ependymoma. Photomicrograph (original magnification, x100;
hematoxylin-eosin stain) of an ependymoma shows a moderately cellular
matrix composed of glial cells with perivascular rosettes (arrowheads)
and no mitotic figures.
On nonenhanced computed tomographic (CT) images, intraventricular ependymomas are usually isoattenuated, partially calcified masses
(11). The soft-tissue component shows intense enhancement on contrast material–enhanced images (11). The soft-tissue portion of the
tumor is usually hypoattenuated to isoattenuated on nonenhanced CT images (12). Occasionally, intratumoral hemorrhage may produce a
blood-fluid level (2). Calcification, ranging from small punctate foci to large masses, is common (40%–80% of cases) (Fig 4) (2,11).
Contrast enhancement is variable but usually intense within the soft-tissue portions, although it spares the cystlike regions (2,11). In
contrast to most posterior fossa ependymomas, supratentorial ependymomas are usually located in the cerebral parenchyma and
frequently have a cystic appearance on cross-sectional images (2,11,13).
Figure 4. Ependymoma in a 16-month-old child. (a) Axial CT image shows a fourth
ventricular mass that is slightly hyperattenuated compared with the surrounding
cerebellum. Focal calcification (arrow) is noted. (b) Axial T1-weighted magnetic
resonance (MR) image shows the mildly heterogeneous mass, which is slightly
hypointense compared with the cerebellum. (c) On an axial T2-weighted image, the mass
is hyperintense compared with the cerebellum, with no surrounding vasogenic edema.
(d) On a contrast-enhanced axial T1-weighted image, the mass shows intense
heterogeneous enhancement
On MR images, intraventricular ependymomas typically show isointensity compared with gray matter with short repetition time (TR)
pulse sequences and hyperintensity compared with gray matter with long TR pulse sequences. A heterogeneous appearance is typical,
reflecting the calcification, hemorrhage, and cystic changes that are often present (Figs 4–6). As seen on CT images, there is variable
contrast enhancement (2). Supratentorial ependymomas typically show nonspecific hypointensity to isointensity with short TR pulse
sequences and hyperintensity with long TR pulse sequences (2).

6. Figure 5. Malignant ependymoma in a 58-year-old woman with a history of ductal
carcinoma and renal cell carcinoma. (a) Axial CT image shows a heterogeneously
hypoattenuated mass (arrows) adjacent to the right frontal horn of the lateral ventricle.
(b) Axial T1-weighted MR image shows the heterogeneous mass, with cystlike areas
mixed with more hyperintense regions. (c) On an axial T2-weighted MR image, the mass
is predominantly hyperintense with focal regions of more hypointense signal. (d) On a
contrast-enhanced axial T1-weighted MR image, the mass shows intense but
heterogeneous enhancement. At surgery, the mass involved both the lateral ventricle and
the right frontal lobe. Histologic examination revealed ependymoma.
Figure 6. Ependymoma in a 29-year-old adult. (a) Sagittal T1-weighted MR image shows an isointense fourth ventricular mass (arrows)
with inferior extension through the foramen magnum. (b) On an axial T2-weighted MR image, the mass is mildly hyperintense compared
with the cerebellum and extends through the right foramen of Luschka into the cerebellopontine angle. (c) On a contrast-enhanced axial
T1-weighted MR image, the mass shows intense but heterogeneous enhancement.
MR imaging is considered the modality of choice to evaluate these lesions, although CT is superior in the detection of calcification (2).
Postoperative imaging is considered crucial in documenting the presence of postoperative residual disease, which has a substantial negative
impact on survival rates in patients with this tumor (14).
 Intraventricular Subependymoma
In 1945, Scheinker (15) described seven cases of brain tumors arising from the subependymal glial layer surrounding the cerebral
ventricles. These tumors were characterized by expansive growth and lacked an infiltrative pattern at histologic examination. Since that
time, more than 100 similar cases have been reported in the literature. With the exception of a very small number of cases that occurred in
the brain parenchyma, cerebellopontine angle, and spinal cord, the overwhelming majority of these tumors have occurred within the
fourth and lateral ventricles (2,5,15–25). The true incidence of subependymomas is difficult to ascertain because many of the cases
occurred in asymptomatic patients and were detected only incidentally at autopsy. In a review of 1,000 serial necropsies in asymptomatic
patients, Matsumura at al (17) reported the prevalence as 0.4%, compared with a prevalence of 0.7% in 1,000 consecutive craniotomies

7. performed in symptomatic patients. Despite four case reports of subependymomas occurring in siblings, including one set of identical
twins, no genetic susceptibility for the tumor has been proved (19,21,26).
Most subependymomas are smaller than 2 cm in diameter (26). However, symptomatic subependymomas are usually larger, averaging
about 3–5 cm in greatest dimension (5,22). Symptoms most commonly depend on the location and size of the tumor, with intratumoral
hemorrhage being another possible influence (5). The clinical presentation is nonspecific. Most symptomatic patients (80%) present with
symptoms related to hydrocephalus as a consequence of ventricular obstruction (16,26). Less commonly, focal neurologic deficits (27% of
cases), seizures (9%), and subarachnoid hemorrhage (4.5%) have been reported (16).
Males are more commonly affected, and most reported cases (82%) have occurred in patients older than 15 years (16,26). At least half of
the reported cases have occurred in the fourth ventricle, with most of the remainder arising in the lateral ventricle (2,5,15–26). In rare
cases, subependymomas have been recorded arising from the septum pellucidum, the third ventricle, and in the cervical or cervicothoracic
spinal cord (16, 23). Gross total surgical resection is the goal of therapy (16). Even if only partial resection is achieved, postoperative
radiation therapy or chemotherapy is usually not indicated. Recurrence after surgical resection is rare (2,22).
Subependymomas have a white to grayish color and are well circumscribed with a firm texture (16). The tumors grow in a slow deliberate
fashion, are usually avascular, and are attached to the ventricular wall by a narrow pedicle (16). Although the exact histogenesis is still
uncertain, they most likely arise from subependymal glial cells (26). Other possible sites include astrocytes from the subependymal plate,
ependymal cells, and a mixture of ependymal and astrocytic cells (26).
A dense fibrillary matrix interrupted by numerous small cysts and nests of isomorphic nuclei that resemble subependymal glia is typically
seen at histologic examination (Fig 7) (26). Mitotic activity is usually low or absent; thus, subependymomas correspond histologically to
WHO grade I (26). Although most tumors are pure subependymomas, about 10% may manifest as an admixture with an ependymoma
(5,16,26). In addition, other reported combinations include those with melanin, rhabdomyosarcoma, and sarcomatous transformation of
vascular stromal elements (26). The prognosis of a patient with an intraventricular subependymoma is good, with gross surgical resection
being curative (26). A good clinical outcome is less certain when the tumor is mixed with an ependymoma (5).
Figure 7. Subependymoma. Photomicrograph (original magnification,
x40; hematoxylin-eosin stain) of a subependymoma shows scattered
clusters of nuclei (arrowheads) separated by large, acellular regions of
glial processes
The typical CT appearance of a subependymoma is a well-circumscribed, lobulated intraventricular mass that is predominantly
isoattenuated to slightly hypoattenuated compared with the brain parenchyma (Fig 8) (16,22). Hydrocephalus is present in 85% of cases
(16). When hemorrhage is present, the mass may show hyperattenuation compared with the brain parenchyma (17,18). Most (84%) show
at least some enhancement, more likely focal in nature, on contrast-enhanced images (16). Calcification (31.8% of cases) and cystic
degeneration (18%) are common (16,22). Dense calcification is not common (2,16,23). Occasionally, subependymomas may produce
peritumoral edema on cross-sectional images (2,16). Although most are avascular, some may have a blush on angiographic studies from
discrete tumor vascularization (17).

8. Figure 8. Subependymoma in a 53-year-old man. (a) Axial CT image shows a right
frontal horn mass that is predominantly isoattenuated compared with the brain
parenchyma. Curvilinear calcification (arrow) is seen. (b) Axial T1-weighted MR image
shows isointensity within the mass, compared with the white matter. (c) Axial T2-
weighted MR image shows heterogeneous hyperintensity within the mass and no
evidence of periventricular edema. (d) Contrast-enhanced axial T1-weighted MR image
shows scattered heterogeneous enhancement within the mass.
In attempting to differentiate subependymomas from ependymomas with imaging studies alone, Lobato et al (16) noted that
subependymomas tend to be intraventricular, whereas ependymomas tend be paraventricular. They also reported that hyperattenuation
compared with the brain parenchyma, enhancement, calcification, and cyst formation were also more commonly seen in ependymomas
than in subependymomas (16). However, none of these features are sufficiently pronounced to be pathognomonic for either lesion. The
distinctions between these tumors are even less apparent for those that arise in the fourth ventricle (16).
On MR images, subependymomas are generally hypointense compared with white matter with short TR pulse sequences and hyperintense
compared with white matter with long TR pulse sequences (Figs 8 –10) (22–24). Heterogeneity is typical, with cystlike areas interspersed
within the mass (22,24). When hemorrhage is present, characteristic signal intensity representative of hemoglobin by-products is noted
(23). Enhancement is quite variable on contrast-enhanced images (22,23). They may not enhance, enhance minimally, or show intense
enhancement after the intravenous administration of a contrast agent (24). Even when intense enhancement is seen, it is usually
heterogeneous (2,24). Extension of a subependymoma beyond the ventricular margins is rare (23,27). These features may be helpful in
distinguishing subependymomas from ependymomas, since the latter frequently have intense enhancement and extraventricular extension
(24).
Figure 9. Subependymoma in a 70-year-old woman in whom breast
carcinoma had been diagnosed 7 years before. A metastatic lesion to the
chest wall had been found 4 months before she experienced a sudden
onset of weakness and slurred speech that prompted neuroimaging. (a)
Sagittal T1-weighted MR image shows a mass that is isointense
compared with the white matter and that extends inferiorly. A sellar
mass of unknown pathologic characteristics erodes the floor of the sella
turcica. (b) Axial T2-weighted MR image shows a fourth ventricular
mass (arrows) that is slightly hyperintense compared with the white
matter. A metastasis was suspected. (c) Intraoperative photograph shows
the well-circumscribed, firm, glistening mass (arrows) in the inferior
portion of the fourth ventricle. Findings from histologic examination
confirmed subependymoma, not metastatic disease

9. Figure 10. Subependymoma in a 48-year-old man with a history of nausea for several months. Results from a prior abdominal CT study
and endoscopy were negative. After developing new headaches, he presented again for evaluation. (a) Sagittal T1-weighted MR image
shows a soft-tissue mass (arrows) in the inferior portion of the fourth ventricle with extension through the foramen magnum. Note
dilatation of the remaining portions of the ventricular system as a result of the mass. (b) On an axial T2-weighted MR image, the mass
appears heterogeneous, with cystic and soft-tissue components. Note absence of vasogenic edema. (c) Contrast-enhanced sagittal T1-
weighted MR image shows intense heterogeneous enhancement of the mass.
SUMMARY
SUMMARY
 Epidemiology of intracellular ependymoma
Ependymomas are neoplasms derived from the ependymal layer lining the ventricular system and can occur intracranially and in the
spine. Intracranial ependymomas account for 2% to 8% of all primary CNS neoplasms [26], with more than half presenting in the first two
decades of life. In a series of 467 pediatric intracranial neoplasms reviewed by Farwell et al [27], ependymomas made up 9% of all
intracranial tumors, making it the third most common pediatric intracranial tumor. Within the pediatric population, ependymomas favor
young patients, with more than 50% occurring within the first 3 years of life. No consistent gender predilection has been identified.
Intracranial ependymomas can be divided by location into those appearing infratentorially and those appearing supratentorially.
Infratentorial ependymomas make up approximately two thirds of all cases [28], comprise most pediatric cases, and most frequently occur
in the fourth ventricle [40]. Supratentorial ependymomas occur more frequently in older children and adults. In addition to the lateral
ventricles, approximately 50% of supratentorial ependymomas involve the parenchyma [29].
 Macroscopic and microscopic features of intracellular ependymoma
Ependymomas are often sharply demarcated, fleshy, hemorrhagic, soft, and sometimes rubbery masses. Rare examples are heavily
calcified, giving the tumor a gritty texture. Intraventricular examples of ependymomas are often lobulated and display a discrete interface
with surrounding brain. Some tumors may exhibit a delicate overlying ependymal layer that gives them a shiny texture.
Ependymomas are glial neoplasms composed of a monomorphous proliferation of neoplastic cells with typical “perivascular
pseudorosettes” (see Fig. 1C, D). Some ependymomas are predominantly glial in appearance and may not have distinct perivascular
pseudorosettes, whereas others may be predominantly epithelial. The latter may present as a tumor with oval to round nuclei, discrete
cytoplasmic borders, frank papillary structures, and well-formed fibrovascular cores. Other tumors may show “true ependymal rosettes”
distinguished by their well-defined lumina and cells forming pseudoglandular structures. Most ependymomas show a substantial number
of nuclear grooves that can be identified in intraoperative smears and help with the rapid interpretation of frozen sections [30]. This
feature, however, needs to be interpreted in the context of other histologic findings, because many other tumors, such as meningiomas and
other gliomas, can exhibit nuclear grooves. The tumor nuclei are uniform, round to oval, and often feature a distinct nucleolus.
Clear cell change in ependymoma is a rare but significant finding [31]. Intraventricular ependymomas may exhibit focal or predominant
clear cell change. When clear cell change is predominant, the hematoxylin-eosin appearance of an oligodendroglioma is recapitulated. It is
likely that many tumors previously reported as intraventricular oligodendroglioma are examples of clear cell ependymoma [21]. Clear cell
ependymomas are usually higher grade and exhibit increased mitotic activity and vascular proliferation. The so-called “tanycytic
ependymoma” is remarkably similar to a pilocytic astrocytoma. This highly fibrillary tumor has moderate cell density, spindled cells, and
a fascicular architecture. It has also been described as a “piloid tumor with ependymal nuclei” [32]. The tanycytic ependymoma often lacks
nuclear pleomorphism or aggressive features, such as mitoses or vascular proliferation. Perivascular pseudorosettes are rudimentary and
sometimes absent.

10. Ependymomas are commonly calcified and rarely exhibit cartilaginous and osseous metaplasia. Rare ependymomas contain cytoplasmic
eosinophilic granules, clear vacuoles, lipid, or melanin [33,34].
The current WHO classification defines grade II ependymomas as tumors with mild cellular pleomorphism, pseudorosettes, or true
ependymal rosettes. The tumors can have occasional mitotic figures and necrosis without pseudopalisading. Occasional foci of
hypercellularity and increased mitoses are allowed. “Anaplastic,” “high-grade,” or grade III ependymomas have moderate to high
cellularity, increased mitotic figures, and vascular proliferation. Necrosis is often present, either in the form of geographic necrosis or,
rarely, in the pseudopalisading form. Perivascular pseudorosettes or occasional true ependymal rosettes can be found in most high-grade
ependymomas. There is controversy around whether focal “atypia” or “anaplasia” should elevate a lesion to grade III “anaplastic
ependymoma.” Some require atypia and anaplasia to predominate in the tumor tissue, whereas others report a less favorable prognosis
even for tumors with focal anaplastic features.
 Immunohistochemical features of intracellular ependymoma
Ependymomas are variably positive for GFAP, which highlights the fibrillary processes around vessels. Tumors are diffusely positive for
vimentin and stain less avidly with S-100 protein and neurospecific enolase (NSE). Positive staining for epithelial markers, such as EMA
and cytokeratins, has been reported in most posterior fossa and spinal cord ependymomas [35]. Rare tumor cells, true rosettes, and
occasional papillary structures are EMA-positive.
Studies suggest that high Ki-67/MIB-1 and p53 protein positivity might be reliable indicators of high-grade ependymomas [36]. Even
though there seems to be a positive correlation between high-grade features and the Ki-67/MIB-1 index [37], none of the
immunohistochemical variables significantly correlate with tumor grade. Conversely, Ki-67/MIB-1 and p53 were reported to correlate
with patient survival [39]. Currently, there is no clear evidence for the utility of these markers in determination of tumor grade or
behavior.
 Ultrastructural features of intracellular ependymoma
The acellular zones around pseudorosettes are composed of large numbers of closely packed, filament-rich, cytoplasmic processes.
Microlumina are often present, even though they may not be observed by light microscopy [40]. These microlumina contain slender
curving microvilli and a variable number of cilia. Bordering cells are connected by unusually long tight junctions. This triad (cilia,
intracytoplasmic intermediate filaments, and cell junctions) makes up the typical ultrastructural components. The epithelioid cells found in
ependymomas and true rosettes are characterized by intracellular lumina, cilia, and microvilli. Clear cell ependymomas reveal densely
packed polyhedral cells with clear cytoplasm and well-developed intercellular junctions. Abundant hyaloplasmic lipid vacuoles can also
contribute to the clear appearance of the tumor cells [41].
 Molecular and genetic features of intracellular ependymoma
There is a body of evidence suggesting the presence of a tumor suppressor gene on the long arm of chromosome 22 that plays a role in the
pathogenesis of ependymomas [42]. In one study, the most frequent copy number abnormality in ependymomas was 22q loss, followed by
gain of chromosome 9 and occasional loss of 6q, 3p, 10q, and 15q [41]. A heterozygous mutation in the MEN1 gene has also been reported
in ependymomas [42].
 Pathologic differential diagnosis of intracellular ependymoma
Formulation of the differential diagnosis for ependymoma is dependent on the location of the lesion. In the posterior fossa,
medulloblastoma needs to be considered first in the differential diagnosis, although its architecture is more reminiscent of a small blue
round cell tumor than that of a glioma. Pilocytic astrocytoma of the cerebellum or brain stem is a second possibility but can be easily
excluded when classic features of pilocytic astrocytomas, such as Rosenthal fibers, eosinophilic granular bodies, and a fairly paucicellular
appearance, are present. Infiltrating astrocytomas or the so-called “brain stem gliomas” may have an exophytic quality and may resemble
ependymoma. They are easily distinguished by their invasive quality, lack of epithelial features or pseudorosettes, and marked nuclear
pleomorphism.
Supratentorial intraventricular ependymomas need to be distinguished from subependymomas. Such distinction is often subjective and
may not always translate into a significant change in clinical outcome. Nevertheless, based on the overall clinical behavior of ependymomas
and the likelihood of supratentorial examples being higher grade, one is compelled to make the distinction. The distinction is usually not
difficult, and the differential diagnosis is confounded by limited tissue sample size. A second yet more important differential diagnosis is
oligodendroglioma, which can easily be confused with clear cell ependymoma. Clear cell ependymomas are noninfiltrating, solid, and
distinct from the surrounding brain. Purely intraventricular neoplasms are not likely to be oligodendrogliomas, but when a question exists,
immunohistochemistry and electron microscopy readily settle the issue. Another diagnostic consideration is the central neurocytoma. The
central neurocytoma is a highly cellular neoplasm that may show perivascular pseudorosettes. The cells appear more neurocytic, and the
fibrillar areas resemble neuropil. The tumor strongly reacts with synaptophysin and only weakly (if at all) with GFAP. Electron
microscopy can distinguish the two entities. Papillary ependymomas may resemble CPP. The overall immunohistochemical profile and
ultrastructural features can be used to separate the two entities.
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REFERENCES
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