GLIOMA

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Glioma is a general term used to describe any

tumor that arises from the supportive (gluey)
tissue of the brain. This tissue, called glia, helps
to keep the neurons in place and functioning well.

GLIOMAS

Astrocytic tumors
Pilocytic astrocytoma
Pituicytoma (**)
Pilomyxoid astrocytoma (**)
Subependymal giant cell astrocytoma
Pleomorphic xanthoastrocytoma
Diffuse astrocytoma
Fibrillary astrocytoma
Gemistocytic astrocytoma
Protoplasmic astrocytoma
Anaplastic astrocytoma
Glioblastoma
- Giant cell glioblastoma
- Gliosarcoma
Gliomatosis cerebri

grad
e

II

III

IV

nd

*
*

*
*
*
*
*
*
*

*
*
*

Oligodendroglial tumors
Oligodendroglioma
Anaplastic oligodendroglioma
Oligoastrocytic tumors
Oligoastrocytoma
Anaplastic oligoastrocytoma
Ependymal tumors
Subependymom
Myxopapillary ependymoma
Ependymoma
- Cellular
- Papillary
- Clear Cell
- Tanycytic
Anaplastic ependymoma
nd = not defined

grad
e

II

III

IV

*
*

Etiology
>70% of all primary brain tumors.
The most common (65%) and most malignant
type is glioblastoma.
With the exception of pilocytic astrocytomas, the
prognosis of glioma patients is still poor. Less
than 3% of glioblastoma patients are still alive at
5 years after diagnosis, higher age being the
most significant predictor of poor outcome.

Population-based data of incidence rates, age and sex, and survival of patients with gliomas. From:
Ohgaki H and Kleihues P. Epidemiology and etiology of gliomas. Acta Neuropathol 2005, 109: 93-108

Epidemiology
Epidemiologic factors including specific
occupational exposures, environmental
carcinogens, foods containing N-nitroso
compounds, electromagnetic fields, etc. have
been associated to only a small proportion of
gliomas.
The only two firmly established factors of
primary brain tumors are the exposure to high
doses of ionizing radiation and inherited
mutations of highly penetrant genes associated
with rare syndromes

Inherited mutations in members of families at increased risk of glioma. From Epidemiology and
molecular pathology of glioma. Schwartzbaum JA, Fisher JL, Aldape KD and Wrensch M. Nat Clinical
Practice Neurology 2006, 9:494-503.

Astrocytic tumour

Pilocytic astrocytoma
Pilocytic astrocytomas correspond to WHO grade I.
A relatively circumscribed, slowly growing, often cystic
astrocytoma occurring in children and young adults.
Approximately 56% of all gliomas with an overall
incidence of 0.37 per 100 000 persons per year.
The most common glioma in children, in whom the
majority arise in the cerebellum.

Localization
Optic nerve
Optic chiasm/hypothalamus
Thalamus and basal ganglia
Cerebral hemispheres
Cerebellum
Brain stem
Spinal cord (in children represent about 11% of spinal
tumours)

Signs and symptoms

Macrocephaly
Headache
Endocrinopathy
Increased intracranial pressure
Seizures
Visual loss
Hypothalamic/pituitary dysfunction

Macroscopy
Soft, grey and rather discrete
Cyst formation (intra or paratumoura)
Syrinx formation can extend over many segments (in
spinal cord )
Contain calcium or haemosiderin deposits
(chronic lesions)
Collar-like
Primary diffuse
leptomeningeal pilocytic
astrocytoma is a rarity

Histologically characterized by a biphasic pattern with

varying proportions of compacted bipolar cells
associated with Rosenthal fibers and loose-textured
multipolar cells associated with microcysts and
eosinophilic granular bodies/hyaline droplets.

Compacted piloid cells with

Rosenthal fibers and loose
textured
multipolar cells with microcysts

A biphasic, compact and spongy

pattern

Biphasic (cystic and solid) pilocytic

astrocytoma with numerous Rosenthal
fibers.

Pilocytic astrocytoma. H&E

stain demonstrates numerous
Rosenthal fibers (arrow).

Pilocytic astrocytoma. H&E

stain reveals eosinophilic
granular bodies (arrow).

Pilocytic astrocytoma.
Granular eosinophilic bodies.

Vascular wickerwork pattern

typically encountered in
cerebellar lesions

Tumour vessels with extensive

hyalinization.

Pilomyxoid astrocytoma
Corresponds to a WHO grade II neoplasm.
Prominent mucoid matrix and angiocentric
arrangement of monomorphous, bipolar tumour cells,
typically without Rosenthal fibers or eosinophilic
granular bodies/ hyaline droplets.
Presents in the very young (median 10 months), but
can occur in older children, rare in adults.
Male / female : roughly equal.

Localization
The hypothalamic/chiasmatic region is the most
common location.
The thalamus
Cerebellum
Brain stem
Temporal lobe
Spinal cord

Macroscopy

Solid, gelatinous mass

In at least some parts
the tumours may
infiltrate parenchyma,
a clear surgical plane
may not be identified.

Histopathology
Markedly mucoid matrix
Monomorphous bipolar cells,
and a predominantly
angiocentric cell
arrangement.
Compact, rather solid
architecture, but some are
infiltrative.
Monomorphous, intermediate
size, bipolar
Cells may be also aligned
along the long axis of vessels.
Pilomyxoid astrocytoma. H&E stain
demonstrates small piloid cells in a
mucopolysaccharide matrix

Tumours typically show a

monomorphous population of
cells in a homogeneouslymyxoid
background.

Pilomyxoid astrocytomas lack Ro

senthal fibers, and the tumor c
ells usually cluster around blo
od

The vascularity is often

prominent with the aboveThe prominent feature of pilomyxoid
mentioned angiocentric
astrocytoma is the angiocentric
arrangement of tumour cells,
arrangement of tumour cells
but florid vascular proliferation is
rare

Tumours are typically diffusely and strongly positive

for GFAP.

Pleomorphic xanthoastrocytoma
Corresponds to a WHO grade II neoplasm
Typically encountered in children and young adults,
with superficial location in the cerebral hemispheres
and involvement of the meninges.
Expressing GFAP and often surrounded by a reticulin
network as well as eosinophilic granular bodies.

Localization
Involving the meninges and cerebrum.
Ninetyeight percent occur supratentorially, in particular
the temporal lobe.
Cases involving the cerebellum and spinal cord are also
on record.
Two children with primary pleomorphic
xanthoastrocytoma of the retina were reported.

Clinical features
Fairly long history of seizures
Symptoms reflect the sites of involvement
CT and MRI scans usually outline the tumour mass
and/or its cyst.

Macroscopy
Attached to the meninges.
Accompanied by a cyst, sometimes forming a mural
nodule within the cyst wall.
Invasion of the dura, predominantly exophytic growth,
multicentricity, leptomeningeal dissemination.

Histopathology
Well established
Pleomorphic refers to the variable histological
appearance of the tumour, in which spindly elements
are intermingled with mono- or multinucleated giant
astrocytes, the nuclei of which show great variation in
size and staining. Intranuclear inclusions are frequent.

A leptomeningeal PXA, sharply

Granular bodies, intensely
delineated
eosinophilic or pale, are almost a
from the underlying cerebral cortexconstant finding

PXA. Cellular atypia and granular

eosinophilic bodies.

PXA. Lipidized tumor

cells.

Tumour cells showing nuclear and

cytoplasmic pleomorphism and
xanthomatous change

Pleomorphic
xanthoastrocytoma.
Xanthic cells, expressed as
vacuolization of the neoplastic
cells, are shown

Mature ganglion cell

and lymphocytic infiltrates in a PXA

Immunohistochemistry
GFAP and S-100 protein
Synaptophysin, neurofilament, class III -tubulin and
MAP2
CD34 is frequently expressed in pleomorphic
xanthoastrocytoma cells.

GFAP expression in large

pleomorphic and
xanthomatous cells

Synaptophysin immunostaining in
PXA cells

Diffuse astrocytoma
Corresponds to a WHO grade II neoplasm
Diffuse astrocytoma
- Fibrillary astrocytoma
- Gemistocytic astrocytoma
- Protoplasmic astrocytoma
Represents 1015% of all astrocytic brain tumours,
approximately 1.4 new cases / 1 million population a
year

Localization
Located in any region of the CNS
Most commonly develops supratentorially in the frontal
and temporal cerebral lobes of both children and adults
(one third of cases each).
The brain stem and spinal cord
Uncommon in the cerebellum.

Clinical features
Seizures
Speech difficulties,
Changes in sensation, vision
Motor change may have been present earlier.
Changes in behaviour

Macroscopy
Local mass lesions.
Indistinct boundaries.
Smaller or larger cysts, granular areas and zones of
firmness or softening.
Single, large cyst filled
with clear fluid.
Single, large
smoothwalled cysts.
Focal calcification.

diffuse astrocytoma; enlargement of

thalamus; infiltration of adjacent white
matter; doesn't destroy brain tissue, just

Histopathology
Well differentiated fibrillary or gemistocytic neoplastic
astrocytes on the background of a loosely structured,
often microcystic tumour matrix.
Cellularity is moderately increased and occasional
nuclear atypia.
Contains astrocytes that are increased in number and
also usually in size.

Fibrillary astrocytoma
This most frequent histological variant of astrocytoma.
Nuclear atypia is a diagnostic criterion but mitotic
activity, necrosis and microvascular proliferation are
absent.
Nuclear atypia is a histological hallmark distinguishing
tumour cells from normal and reactive astrocytes.

A fibrillary astrocytoma infiltrating

gray matter.
Note the neurons with large nuclei
and prominent nucleoli in the left
upper and center fields of the figure

A moderately cellular tumour

composed of
uniform fibrillary astrocytic cells with
microcystic stroma

Cellular lesion with a sworling fibrillary appearance to many

of the cells. Note variation in nuclear shape and size. The
background has a somewhat vacuolated appearance,
looking like neuropil.

Extensive microcyst formation

Cytoplasm and processes showing GFAP

immunoreactivity

Low MIB-1 labelling index.

Gemistocytic astrocytoma
Conspicuous, though variable, fraction of gemistocytic
neoplastic astrocytes.
More than approximately 20% of all tumour cells.
Plump, glassy, eosinophilic cell bodies of angular shape.
Stout, randomly oriented processes,
forming a coarse fibrillary network.

Gemistocytic astrocytoma. The

tumor cells are similar to certain
reactive astrocytes

Tumour cells have a large

eosinophilic cytoplasm with nuclei
displaced to the periphery.

Characteristic feature of
perivascular lymphocytic
infiltrate

Strong, consistent GFAP expression.

p53 accumulation is marked in nuclei of small and

gemistocytic tumour cells.

Protoplasmic astrocytoma
Composed of neoplastic astrocytes showing a small cell body
with a few flaccid processes with a low content of glial
filaments and scant GFAP expression.
Cellularity is low and mitotic activity absent.
Mucoid degeneration and microcyst formation are common
and characteristic features.
Nuclei are uniformly round
to oval.

Protoplasmic astrocytoma
showing extensive mucoid
degeneration.

Anaplastic astrocytoma
Corresponds to WHO grade III.
Diffusely infiltrating, malignant astrocytoma
Primarily affects adults.
May arise from diffuse astrocytoma WHO grade II or de
novo.
Inherent tendency to undergo progression to
glioblastoma.

Clinical features
Similar to those of patients with diffuse astrocytoma
WHO grade II.
Increasing neurological deficits, seizures and signs of
intracranial pressure.
Shorter course, present without clinical evidence of a
preceding astrocytoma WHO grade II.

Localization
Corresponds to that of other diffuse infiltrating
astrocytomas, with a preference for the cerebral
hemispheres.

Macroscopy
Macroscopic cysts are uncommon.
Areas of granularity, opacity and soft consistency.
Discernible tumour mass with a more clear distinction
from surrounding structures than is the case in diffuse
astrocytomas WHO grade II

Histopathology
Diffusely infiltrating astrocytoma with increased cellularity
as compared to the grade II equivalent.
Distinct nuclear atypia and mitotic activity.
Microvascular proliferation (multilayered vessels) and
necrosis are absent.

Hypercellularity and hyperchromatic, irregular "naked nuclei"

appearing within a fibrillary background.
Several mitotic figures are evident

GFAP immunoreactivity.

Several tumour cells show immunoreactivity for the

proliferation marker MIB-1, including a cell in
mitosis

Glioblastoma
Variants correspond to WHO grade IV.
The most frequent primary brain tumour.
The most malignant neoplasm with predominant
astrocytic differentiation.
Manifest rapidly de novo.
Invasive nature, cannot be completely resected.
Older age as the most significant adverse prognostic
factor.

Localization
Subcortical white matter of the cerebral hemispheres.
Fronto-temporal.
Infiltration often extends into the adjacent cortex and
through the corpus callosum into the contralateral
hemisphere.
Brain stem (infrequent and often affects children)

Clinical features
The disease is usually short (less than 3 months in
more than 50% of cases)
Signs of raised intracranial pressure.
Seizure. (1/3 patients)
Non-specific neurological symptoms : headache,
personality changes.

Macroscopy
The tumours are often surprisingly large and may
occupy much of a lobe.
The lesion is usually unilateral, but can be bilaterally
symmetrical in the brain stem and corpus callosum.
Variable colour with peripheral greyish tumour masses
and central areas of yellowish necrosis from myelin
breakdown.

Glioblastoma and its variants

correspond to WHO grade IV.
Spread and metastasis
Mechanisms of invasion
Multifocal glioblastomas
Primary and secondary glioblastoma

Histopathology
Tissue patterns
Secondary structures
Epithelial structures
Cellular composition
Small cell glioblastoma.
Glioblastoma with oligodendroglioma component.
Multinucleated giant cells
Gemistocytes
Granular cells
Lipidized cells
Perivascular lymphocytes
Metaplasia
Microvascular proliferation

Glioblastoma with high degree of

anaplasia

Cellular anaplasia in large cell

glioblastoma.

Extreme anaplasia in giant cell

glioblastoma.

Adenoid GBM with formation of

glandular structures

Oligodendroglial component in
a GBM

Microvascular proliferation in a
glioblastoma with formation of a
multilayered 'glomeruloid tuft'

Focal squamous cell metaplasia in a glioblastoma

characterized by

Giant cell glioblastoma consists of An atypical mitotic figure in a

cells with variable size and shape giant cell.

A very large multinucleated giant cell.

The cells seen in

bear some
resemblance to
neurons, but
immunoreactivity
for GFAP confirms
their astrocytic
nature

Small cell glioblastoma with

very high MIB-1 labelling index.

Glioblastoma with (A) overexpression of EGFR in the plasma

membrane of tumour cells and (B) nuclear accumulation of
p53 protein in tumour cells but not endothelial cells.

Reticulin stain showing a 'garland' of proliferated

glioma vessels

Marked cytokeratin expression.

Most but not all tumour cells express GFAP

Marked stromal reaction (Bodian silver stain)

Tumour shows a high labelling index with MIB-1

antibody.

Gliosarcoma
Corresponds histologically to WHO grade IV.
characterized by a biphasic tissue pattern with
alternating areas displaying glial and mesenchymal
differentiation.
Gliosarcoma constitutes approximately 2% of all
glioblastoma.
Preferential manifestation between ages 40 and 60,
rare cases in children.
Males are more frequently affected.

Localization
Usually located in the cerebral hemispheres.
Temporal.
Frontal.
Parietal.
Occipital lobes.
Posterior fossa and the spinal cord (rarely).

Clinical features
Symptoms of short duration
Reflect the location of the tumour
Increased intracranial pressure
Associated with prior irradiation
The radiological features are similar to those of
glioblastoma.

Macroscopy
Gross appearance of a firm
Well-circumscribed mass that can be mistaken for a
metastasis or, when attached to the dura, for a
meningioma
Lesions less rich in connective tissue

Histopathology
Biphasic tissue pattern
Malignant transformation : nuclear atypia, mitotic
activity, necrosis ...
Malignant fibrous histiocytoma
Mesenchymal differentiation : the formation of
cartilage, bone, osteoid-chondral tissue, smooth and
striated muscles, lipomatous features.

Gliosarcoma.
(a) Elongated cells are
arranged in fascicles;
mitotic figures are readily
found in these
sarcomatoid neoplasms
which also contain foci of
astrocytic cells.

(b) Cells with astrocytic

features are
immunoreactive for
GFAP, whereas the
spindle-shaped cells

Gliosarcoma. The gliomatous component shows

strong GFAP expression and may be geographically
separated from

Gliosarcoma. Intermingled with the

sarcomatous tumourcells

A biphasic tissue pattern denoting reticulin-rich

sarcomatous and reticulin-free gliomatous
elements.

Gliomatosis cerebri
Corresponds to WHO grade III in a majority of cases.
Most commonly displays an astrocytic phenotype.
(oligodendroglioma and mixed oligoastrocytoma can
also present)
Coined by Nevin in 1938, describe the extensive
involvement of large areas of the brain by glial cells in
the absence of a mass lesion.

Localization
No anatomic site of the brain has been excluded. The
most commonly involved areas,
The cerebral hemispheres (76%), the mesencephalon
(52%), the pons (52%), the thalamus (43%), the basal
ganglia (34%), the cerebellum (29%), the medulla
oblongata (13%), the hypothalamus, the optic nerves
and chiasm, and the spinal cord (each at 9%)

Clinical features
Depending on the cerebral areas infiltrated.
Changes in mental status : dementia, lethargy,
seizures, headache, pyramidal symptoms, cranial nerve
dysfunction
Signs and symptoms of increased intracranial pressure,
spinocerebellar deficits, sensory deficits, paraesthesia,
visual disturbances.

Macroscopy
Swollen and firm
Blurred distinction between grey and white

Histopathology
A proliferation of small glial cells with elongated,
fusiform nuclei.
Obviously astrocytic, and gemistocytic form, classical
morphologic features of oligodendroglioma have also
been described.
Signs of demyelination, but neurons and axons are
intact .

Histological features of gliomatosis

cerebri. A Diffuse infiltration of the
corpus callosum with elongated
tumour cells.

Gliomatosis cerebri. Poorly

differentiated glial cells infiltrate the
brain and crowd around blood vessels
and neurons.

Histologically, it showsatypical glial

cells (usually Grade II or III)
diffusely infiltratingthroughout the
involved lobes

Higher magnification from the

previous case showing
occasionalatypical glial cellswith
mildly enlarged hyperchromatic
nucleidiffusely infiltrating

Immunohistochemistry
GFAP and S-100 protein immunostaining results are variable;
in many cases, tumour cells exhibit strong positivity for both
markers, whereas in others a majority of tumour cells are
non-reactive.

Figure 3: Immunohistochemistry of tumour cells showing

GFAP positivity, Ki 67 labelling index-40%

Oligodendroglial tumours
Oligodendroglioma
Anaplastic oligodendroglioma

Oligodendroglioma
Constitute 7-10% of primary intracranial neoplasma.
Occur with equal incidence in males and females
Are uncommon in childhood
Occur most frequently in patients aged 30- 50 years

Oligodendroglioma
Occur most often in the frontal lobe
Most often present with epilepsy
Are probabyly more chemossensitive and radiosensitive and
more prone to hemorrhage
Abnormal genetic chromosomes 1p and 19q

Oligodendroglioma
Have a variety of macroscopic appearance
Difficult to locate in resection specimens
Distortion of the normal cortical gray and white matter interface
Discoloration of tissue provide clues to their location.

Oligodendroglioma

- White matter in
the frontal lobe
- Expands the gyri
- Distorting the
lateral ventricles

Oligodendroglioma

- Composed of uniform cells

-The round nuclei and ill-defined cytoplasm

Oligodendroglioma

A relatively circumscribed border to what is generally an

infiltrating neoplasm may be observed in white matter

Oligodendroglioma

Dystrophic calcification is a common feature

Oligodendroglioma

A network of delicate bifurcating capillaries is typical

Oligodendroglioma

May show rhythmic nuclear palisading

DIFFERENTIAL DIAGNOSIS OF
OLIGODENDROGLIOMA
Non- neoplasm condition: demyelination (small round
nuclei and clear cytoplasm)
Diffuse astrocytoma
- Nuclei more pleomorphism
- Do not have the network of branching capillaries and
cells with perinuclear halos

Oligodendroglioma
Immunohistochemistry:
- Positive: GFAP, S100, MAP2 (strong)
- Negative: EMA

Anaplastic oligodendroglioma
Endothelial hypertrophy
Complex microvascular proliferation
Conspicuous mitotic activity joined
In some cases, by necrosis and often accompanied by dense
cellularity and obvious nuclear atypism.

Anaplastic oligodendroglioma

Oligoastrocytic tumours
The only mixed gliomas broadly recognized by both
neuropathologists and the WHO are those manifesting
astrocytic and oligodendroglial features.
Oligoastrocytoma
Anaplastic oligoastrocytoma

Epidemiology & Clinical presentation

Common
Constitute approximately 35% of oligodendroglial
neoplasms, with the WHO grade II tumors accounting
for about 20% of neoplasms
The peak manifestation is during the 3rdand
4thdecades
OAs most commonly present with either partial or
generalised seizures, headaches, and personality
changes.

 These tumors can be

found anywhere within
the cerebral
hemispheres of the
brain
Oligoastrocytomas arise
primarily in the cerebral
hemispheres, with the
frontal lobes being most
frequently affected,
followed by the
temporal lobes.

Oligoastrocytoma
Contain tumor cell populations that manifest both oligodendroglial and astroglial phenotypes.
Show a mild degree of pleomorphism and few mitotic gures.
Endothelial proliferation and necrosis are absent.

Anaplastic Oligoastrocytoma
Increased cellularity, nuclear atypia, and high mitotic
activity, microvascular proliferation

Immunohistochemistry
GFAP

Mixed oligoastrocytoma (GFAP x40). Certain areas of the tumour are

rich in GFAP-positive astrocytes while other zones exhibit the typical
appearance of an oligodendroglioma and contain GFAP-negative cells
(plus several rare included astrocytes).

Ependymal tumours
Subependymoma
Myxopapillary ependymoma
Ependymoma
Cellular
Papillary
Clear cell
Tanycytic

Anaplastic ependymoma

Ependymomas
< 59% of primary CNS neoplasms
Varies with patient age and presenting location
A majority of intracranial examples arise in childhood,
intramedullary variants more commonly afflict adults.
10% of intracranial neoplasms in the pediatric population
Up to 30% of those encountered in children under 3 years of
age.
At least two-thirds of these childhood tumors are situated
within the fourth ventricle with increased intracranial pressure
secondary to obstructive hydro- cephalus

 Principal clinical manifestations include

Pain localized to the neck or back

Numbness
Paresthesias of the distal extremities
Atrophy of hand musculature
Gait disturbances.

 In the fourth ventricle, ependymomas are typically solid or

papillary masses arising from the floor of the ventricle.

 In the intraspinal tumors, the sharp demarcation

sometimes makes total removal feasible.

Ependymoma
Typified by a dense meshwork of fibrillary
cytoplasmic, stromal blood vessels in formations
known as perivascular pseudorosettes

Cellular Ependymoma
Cells with a high nuclear-cytoplasmic ratio.
Few pseudorosettes are present.

Papillary Ependymoma

Microphotograph shows
papillary structures lined by
single and multiple layers of
monomorphic cuboidal tumor

Tumors in which neoplastic

ependymal cells assume a columnar
configuration and are supported by
fibrovascular cores

Clear Cell Ependymoma

Clear cell ependymomasare frequentlysupratentorial and
cysticand are characterized by large nuclei and clear
cytoplasm. The cytoplasmic features create someresemblance
to oligodendrogliomas.
However, unlike oligodendrogliomas, they are sharply
demarcated.

Tanycytic Ependymoma

Tanycytic ependymoma. Note the

spindled morphology and vague
perivascular pseudorosettes. This
example contains scattered cells with
striking nuclear atypia.

The tanycytic ependymoma frequently

takes on an astrocytic appearance with
fibrillar cytoplasm that streams by vessels
rather than orienting towards them.

Myxopapillary Ependymoma
Contain papillary elements in a myxoid background, admixed with
ependymoma-like cells.
Cuboidal cells, sometimes with clear cytoplasm, are arranged around
papillary cores containing connective tissue and blood vessels. The
myxoid areas contain neutral and acidic mucopolysaccharides.

Anaplastic Ependymoma
The diagnosis ofanaplastic ependymoma (WHO Grade
III)requireshypercellularity, cytologic atypia, increased
mitotic activity, andmicrovascular proliferation. The image
shows highly anaplastic tumor cells arranged around a vessel
creating a pseudorosette.

Subependymoma
Account for <10% of ependymomas.
Are generally found in the fourth and lateral ventricles.
Mainly occur in adult patients.
Present with hydrocephalus or may be asymptomatic,
being found at autopsy.

Subependymoma

The body of the right lateral

ventricle is filled by a nodular
mass of firm, white tissue.

Bilateral Subependymoma

Characteristic microscopic appearance, with clusters of ependymal

appearing nuclei scattered in a dense, fine, glial fibrillar background

Immunohistochemistry

Ependymoma

Glial fibrillary acidic protein (GFAP)

immunoreactivity is usually most
intense in the perivascular structures of
ependymomas

It is important to note that ependymomas show variable immunoreactivity for

EMA and cytokeratins.
However, the ependymal nature of the tumors is readily confirmed by the
nuclear chromatin pattern and the fibrillary character of cytoplasmic processes,
highlighted by GFAP and vimentin immunoreactivity.

Tanycytic ependymoma. Glial fibrillary

acidic protein (GFAP) immunoreactivity
highlights the intense fibrillary nature of
the tumors cells

Papillary ependymoma:
Microphotograph shows GFAP
immunoreactivity predominantly in the
pseudorosettes (GFAP 400).

Anaplastic Ependymoma

S100 staining showing diffuse

nuclear and cytoplasmic positivity

Immunohistochemistry with a Ki-67 antibody

typically shows a high labeling index in areas
with a high nuclear:cytoplasmic ratio.

DIFFERENTIAL DIAGNOSIS OF
EPENDYMOMA
Astrocytoma, oligodendroglioma, medulloblastoma,
central neurocytoma, microcystic/papillary meningioma
The presence of perivascular anuclear zones (pseudorosettes) with fine
fibrillary GFAP-positive processes is the key to differentiating
ependymomas from these neoplasms

Astroblastoma
Papillary tumor of the pineal region
This tumor often expresses cytokeratins (unlike ependymoma), but
only sparse GFAP.

Paraganglioma of the filum terminale, schwannoma

Paragangliomas can be distinguished by their immunoreactivity for
chromogranin and synaptophysin, and an arrangement of cells in
nests or cords surrounded by reticulin.
Schwannomas can be distinguished by their dense pericellular
reaction for reticulin.

Glial tumors of uncertain origin

Astroblastoma
Angiocentric glioma
Chordoid glioma of the third ventricle

Astroblastoma
Rare neoplasm (<3% primary brain gliomas)
Occurs in the cerebral hemispheres of young adults and
teenage children (median age 11 years, range 1-58 years)
Sensitive radiotherapy

Astroblastoma
Usually a solid uniform mass of firm
Slightly mucoid tissue
Cyst formation can occur

Astroblastoma
Characterized microscopically by two particular features:
Astroblastomatous rosettes
A focal hyalinization of its vascular network

Astroblastomatous rosettes

- Characterized by a corona of short fibrillary

processes from perivascular tumor cells
- Tumor cells in astroblastomas tend to have a high
nuclear cytoplasm ratio and monomorphic nuclei

A focal hyalinization of its vascular network

Astroblastoma
Differential diagnosis
- Ependymoma: more fibrillar, nuclei smaller
Immunohistochemistry: + (GFAP, vimentin, S100), -(CK,
synatophysin)

Angiocentric glioma
Who grade 1 tumor of children and young adults (2 to 70 years,
mean 17 years)
History of intractable epilepsy
Occurs in the superficical cerebral cortex
With features of infiltrating astrocytoma and ependymoma.
Relationship to ependymoma is unclear

Angiocentric glioma
Macroscopically, expand and distort involved brain
Microscopically
Consist of uniform cells with oval or spindle-shape nuclei.
Cytoplasmic are poorly defined, though some cells appear epithelioid
Necrosis and angiogenesis are absent
Dystrophic calcification is rare
Mitotic figures are very rare

Angiocentric glioma

At low power perivascular and infilltrative

tumor cell patterns can discerned, as can
aggregates of subpial cells

Angiocentric glioma

Spindled profile sheath and colar cerebrocortical

blood vessels in this typical example

Angiocentric glioma
Differential diagnosis
- Astroblastoma: discrete borders, epithelioid cells,
vascular sclerosis
- Astrocytoma infiltrating: no pseudorosettes or
subpial palisading
- Ependymoma: enhancing, discrete borders
Immunohistochemistry: + EMA, + GFAP

Chordoid glioma of the third ventricle

This rare neoplasm occurs in third ventricle of adult patients
Presents with obstructive hydrocephalus
Usually middle age women (63%, median age 4 years)

Chordoid glioma of the third ventricle

The mucoid nature of this generally solid neoplasm

Chordoid glioma of the third ventricle

Cords of tumor, focal microvasculation and

lymphoplasmacytic infiltrate

Chordoid glioma of the third ventricle

A vague trabecular arrangement of moderately uniform cells is

evident, along with microvacuolation and a myxoid background

Chordoid glioma of the third ventricle

A mixture of epithelioid cells and cells with fibrillary

cytoplasmic processes is present.
Note the plasma cells and the russell bodies

Chordoid glioma of the third ventricle

Cytoplasmic borders are apparent in this population

of epithelioid cells

Chordoid glioma of the third ventricle

Immunohistochemistry:
- Positive: GFAP, vimentin, CD34, EMA+CK (focal)
- Negative: NSE, desmin, p53

Chordoid glioma of the third ventricle

Differential diagnosis
- Chordoid meningioma: whorls, psammoma bodies, nuclear
pseudoinclusions, - GFAP
- Chordoma: infitrates bone, physaliphorous cells, -GFAP

Pilocytic Astrocytoma
Bipolar cells
Rosenthal fibers
Eosinophilic granular
bodies/
hyaline droplets

PXA
Pleomorphism
significant cellular and
nuclear pleomorphism
Xantho cells
vacuolated tumor cells
containing lipid droplets

Diffuse Astrocytoma
Mild atypia, particularly
nuclear pleomorphism and
hyperchromasia

Fibrillary
Protoplasmic
Gemistocytic

Anaplastic
Astrocytoma
Densely cellular moderate
Nuclear pleomorphism
Increased mitotic activity

Glioblastoma
High cellularity, admixtures of
Gemistocytes,
Fibrillary astrocytes,
Small cells,
Multinucleated giant cells.
Cellular and nuclearanaplasiawhich is the basis of the designation
"multiforme",
Mitoses
Microvascularproliferation, andnecrosis.

Oligodendroglioma
Uniform, round central nuclei
Clear halo

Anaplastic Oligodendroglioma

Cellularity
Atypia
Mitotic
Microvascular proliferation
Necrosis

Oligoastrocytoma
2 phenotypes
Oligodendroglial cells
Astrocytes

Anaplastic
Oligoastrocytoma
Nuclear
atypia/pleomorphism
High cellularity
High mitotic activity

Astroblastoma
Astroblastomatous rosettes
Vascular hyalinization

Ependymoma
Perivascular pseudorosettes
Cellular
Papillary
Clear cell
Tanycytic
Myxopapillary
Anaplastic

W.H.O GRADING
Atypia

AMEN
Mitosis

Necrosis

Endothelial
proliferation

Grade 1tumors do not meet any of the criteria.

Grade 2tumors meet one criterion, usually nuclear
atypia.
Grade 3tumors meet two criteria, usually nuclear
atypia and mitosis.
Grade 4tumors meet three or four of the criteria.