CNS Tumors

Epidemiology

The annual incidence

10 to 17 per 100,000 for intracranial tumors and
1 to 2 per 100,000 for intraspinal tumors;
to are primary tumors, and the rest are

metastatic.
Tumors of the CNS account for 20% of all
cancers of childhood.
2nd most frequent malignancy in
childhood and adolescence
Location
Childhood--infratentorial
Adults--supratentorial

Unique characteristics CNS tumors

Distinction between benign and malignant lesions

is less evident

The pattern of growth of low-grade lesions (low mitotic rate,

cellular uniformity, and slow growth) may still include
infiltration of large regions of the brain, thereby leading to
serious clinical deficits and poor prognosis.

The anatomic site of the neoplasm can have lethal

consequences irrespective of histologic classification;

Difficult to resect
The pattern of spread of primary CNS neoplasms
differs from that of other tumors.
Highly malignant gliomas rarely metastasize outside the
CNS,
The subarachnoid space does provide a pathway for spread
so that seeding along the brain and spinal cord can occur.

Four major classes of brain tumors :-

1 - Gliomas
2 - Neuronal tumors
3 - Poorly differentiated
neoplasms
4 - Meningiomas

Neurons

Gangliocytoma

Glia

Astrocyte

Astrocytoma
Grade I

II

III

Oligodendrocyte

Oligodendroglioma

Ependyma

Ependymoma

IV / Glioblastoma multiforme

Embryonal cells

Medulloblastoma

Leptomeninx (arachnoid) Meningioma

Others: lymphoma, mesenchymal tumors (angioma), metastasis
11/15/16

nuclear atypia, mitoses, endothelial cell proliferation, and necrosis G I G IV

G-I

G-III

G-II

G-IV

Gliomas
Gliomas-- derived from glial cells,
include

astrocytomas,
oligodendrogliomas,
ependymomas.

and

Astrocytoma
categories of tumors
fibrillary astrocytoma,
glioblastoma,
pilocytic astrocytoma, and

Fibrillary Astrocytoma
80% of adult primary brain tumors.
Age 4th -6th decades.
Common location- cerebral hemispheres.
signs and symptoms
seizures,
headaches, and
focal neurologic deficits related to the anatomic

site of involvement.

Classification
Based on the degree of histologic

differentiation that correlates well with

clinical course and outcome and
tretment response
Well differentiated Atrocytoma,
anaplastic astrocytoma, and
glioblastoma multiforme

For well-differentiated astrocytomas, -- Sx

static or progress only slowly during a

number of years
mean survival of more than 5 years.
with the appearance of anaplastic
features-- more rapid clinical
deterioration.
Many patients present with glioblastoma
from the start,
Independent of the initial lesion, the
prognosis for patients with glioblastoma is
very poor.
With proper treatment -- mean survival of
only 8 to 10 months;

Morphology
The macroscopic appearance
poorly defined,
gray,
infiltrative tumor that expands and distorts the invaded
brain.
Distant Infiltration
Consistency-- firm, or soft and gelatinous; cystic

degeneration may be seen.

In glioblastoma,-- variation in the gross appearance
Some areas -- firm and white,
Others -- soft and yellow (the result of tissue necrosis),

and
others show regions of cystic degeneration and
hemorrhage.

Microscopically
Well-differentiated fibrillary astrocytomas are

characterized by
mild to moderate increase in the number of glial

cell nuclei,
some variability in nuclear pleomorphism, and
an intervening feltwork of fine, GFAP-positive
astrocytic cell processes that give the background
a fibrillary appearance.

The transition between neoplastic and normal

tissue is indistinct, and tumor cells can be seen

infiltrating normal tissue at some distance from
the main lesion.

Anaplastic astrocytomas
more densely cellular and
have greater nuclear pleomorphism;
increased mitoses are often observed.
Glioblastoma,
histologic features of anaplastic astrocytoma +
necrosis and vascular or endothelial cell

proliferation
pseudo-palisading nuclei.

High-grade astrocytomas have abnormal

vessels that are "leaky" and will show

contrast enhancement with imaging studies.

Explanation of the above figure

Glioblastoma. Areas of necrosis (arrows) are

a characteristic feature of this neoplasm, and

are usually surrounded by the nuclei of small
malignant cells. The neoplastic cell population
is pleomorphic, and also includes
multinucleate cells. Vascular endothelial
proliferation is another characteristic
histological feature.

Explanation of the above figure

Figure 23-22 Astrocytomas. A, Low-grade

astrocytoma is seen as expanded white

matter of the left cerebral hemisphere and
thickened corpus callosum and fornices. B,
Glioblastoma appearing as a necrotic,
hemorrhagic, infiltrating mass. C,
Glioblastoma is a densely cellular tumor with
necrosis and pseudo-palisading of tumor cell
nuclei.

Pilocytic Astrocytoma
relatively benign tumors,
Cystic consistency,
Age -- in children and young adults
Location-- in the cerebellum

may also appear in the floor and walls of the third

ventricle, the optic nerves, and occasionally the cerebral
hemispheres.

Symptoms difficulty to coordinate

movements, Sn and Sx of hydrocephalus, Visual

compliant,
Tumors that extend into the hypothalamic

region from the optic tract can have a more

difficult clinical course because of location.

Morphology
Macroscopic
cystic, with a mural nodule in the wall of the cyst;
if solid,--usually well circumscribed.

Microscopic
Composed of areas with bipolar cells with long,

thin "hairlike" processes that are GFAP positive;

Rosenthal fibers, eosinophilic granular bodies,
and microcysts are often present.
Necrosis and mitoses are absent.
Narrow range of infiltration
Increase in the number of blood vessels with
vascular cell proliferation,
Genetics p53 change is rare.

Explanation of the above figure

The fibers are found in astrocytic processes and are

thought to be clumped intermediate filamentproteins.

Their components includeglial fibrillary acidic protein.
Its presence is associated with eitherpilocytic
astrocytoma
Rosenthal fiberis a thick, elongated, worm-like or
"corkscrew" eosinophilic (pink) bundle that is found on
H&E stainingof the brain in the presence of long
standinggliosis, occasional tumors, and some
metabolic disorders.

Oligodendroglioma
constitute about 5% to 15% of gliomas
most common in 4th and 5th decades.
Patients may have had several years of neurologic

complaints, (seizures).
Location --mostly in the cerebral hemispheres, with a
predilection for white matter.
has a better prognosis than astrocytomas.

With optimal treatment (S,R,C) average survival is 5

to 10 years.
Patients with anaplastic oligodendroglioma have a
worse prognosis.
The most common genetic findings are loss of -1p and 19q;
tumors with just those specific changes have a consistent

and long-lasting response to chemotherapy and

radiation.

Morphology
Macroscopic

are well-circumscribed tumors

form gelatinous, gray masses, and
may show cysts, focal hemorrhage, and calcification.

Microscopic
the tumor is composed of sheets of regular cells with
Spherical nuclei (similar to normal oligodendrocytes)
surrounded by a clear halo of cytoplasm.
The tumor typically contains a delicate network of

anastomosing capillaries.
Calcification, present in as many as 90% of these
tumors, ranges from microscopic foci to massive
depositions.
Low Mitotic activity

Oligodendrogliomas are considered to be WHO grade

II/IV lesions

With increasing cell density, nuclear anaplasia, increased

mitotic activity and necrosis, the tumor becomes higher
grade (anaplastic oligodendrogliomaWHO III).

Explanation of the above figure

Other gliomas. A, In oligodendroglioma tumor

cells have round nuclei, often with a

cytoplasmic halo. Blood vessels in the
background are thin and can form an
interlacing pattern. B, Microscopic appearance
of ependymoma.

Ependymoma

Arise next to the ependyma-lined ventricular

system, including the central canal of the

spinal cord.
In the first two decades of life--fourth ventricle

(5% to 10% of the primary brain tumors)

In adults--spinal cord

Tumors in this site are particularly frequent in the setting of

neurofibromatosis type 2.

CSF dissemination is a common occurrence.

The clinical outcome for completely resected

supratentorial and spinal ependymomas is

better than for those in the posterior fossa.

Morphology
In the fourth ventricle, ependymomas

are typically solid or papillary masses

extending from the floor of the ventricle.
better demarcated than astrocytomas,
proximity to the vital pontine and
medullary nuclei usually makes complete
extirpation impossible.
Intraspinal tumors-- total removal feasible.
These tumors are composed of cells
with
regular, round to oval nuclei with abundant

granular chromatin.

Tumor cells may form gland-like round or

elongated structures (rosettes, canals),

with long, delicate processes extending into a
lumen;
more frequently present are perivascular
pseudo-rosettes in which tumor cells are
arranged around vessels with thin
ependymal processes directed toward the wall
of the vessel.
Most are WHO II
Anaplastic ependymomas(WHO III) show
increased cell density,
high mitotic rates,
necrosis. and
less evident ependymal differentiation.

Expalnation of the figure

Ependymoma: ventricular obstruction.

The ependymoma (E) arising from the lining of

the fourth ventricle has almost totally
obstructed the CSF pathway and produced
obstructive hydrocephalus. This results in
characteristic clinical features that are
common presenting symptoms for this group
of neoplasms.

Microscopic appearance of
ependymoma

Neuronal Tumors

Central neurocytoma
low-grade
Found within and adjacent to the ventricular
system (3rd and 4th ),
Xed by evenly spaced, round, uniform nuclei
and often islands of neuropil.
Gangliogliomas
Mixture of glial elements (looking like a low-grade

astrocytoma) and mature-appearing neurons.

Glial component occasionally becomes frankly
anaplastic, and the disease then progresses
rapidly.
Often present with seizures.
Location Temporal lobe

Poorly Differentiated Neoplasms

Neuroectodermal in origin but express

few if any of the phenotypic markers

of mature cells of the nervous system.
The most common is the
medulloblastoma, accounting for 20%
of pediatric brain tumors.

Medulloblastoma

Common children
Found exclusively in the cerebellum.
Neuronal and glial markers may be expressed, but

the tumor is often largely undifferentiated.

Highly malignant with Poor prognosis;

Exquisitely radiosensitive.
With total excision and radiation, the 5-year

survival rate may be as high as 75%.

Morphology

Macroscopic morphology
Location--In children -in the midline of the

cerebellum;
--In adults -- lateral tumors.
Well circumscribed, gray, and friable, and
may extending to the leptomeninges or
occlude csf flow.
Microscopic morphology
Extremely cellular, with sheets of anaplastic
("small blue") cells.
Tumor cells are small, with little cytoplasm
and hyperchromatic nuclei; mitoses are
abundant.
The tumor has the potential to express neuronal

Sagittal section of brain showing medulloblastoma

destroying the superior midline cerebellum.

The cells contain hyperchromatic, mitotically active nuclei and

very little cytoplasm.
Occasional rosette-like structures are also present in this case.

Primary Central Nervous System Lymphoma

Acounts for 2% of extranodal lymphomas and

1% of intracranial tumors.
It is the most common CNS neoplasm in
immunosuppressed individuals.
Nearly all driven by Epstein-Barr virus.
In nonimmunosuppressed populations the
age spectrum is relatively wide, with the
incidence increasing after 60 years of age;
Most of these tumors are diffuse large B-cell
lymphomas.
Primary brain lymphoma is an aggressive
disease with relatively poor response to
chemotherapy as compared with peripheral
lymphomas.

Individuals with primary brain lymphoma often

have multiple sites of tumor within the

brain parenchyma;
nodal, bone marrow, or extranodal involvement
outside of the CNS is a rare and late
complication.
Conversely, lymphoma arising outside the
CNS rarely involves the brain parenchyma;
when it does occur, there is usually tumor within
the CSF and around intradural nerve roots.

Morphology
Lesions often involve deep gray structures, as

well as white matter and cortex.

Periventricular spread is common.
relatively well defined as compared with glial
neoplasms but are not as discrete as metastases.
extensive areas of central necrosis.
The tumors are nearly always high grade, most
commonly large-cell lymphomas,
infiltrate the parenchyma of the brain and
accumulate around blood vessels.

Meningiomas

benign tumors of adults, usually attached to

the dura, and arising from the meningothelial cell

of the arachnoid.
Lcation-- external surfaces of the brain
within

the ventricular system, where they arise

from the stromal arachnoid cells

When a person has multiple meningiomas,

especially in association with eighth nerve

schwannomas or glial tumors, a possible
diagnosis of neurofibromatosis type 2 (NF2)
should be considered.

About half of meningiomas not

associated with NF2 still have

mutations in the NF2 gene on the long
arm of chromosome 22 (22q).
The overall prognosis inluenced by
the size and location of the

lesion,
surgical accessibility,
and histologic grade

Morphology
Meningiomas grow as well-defined dural-

based masses that compress underlying

brain but are easily separated from it.
Extension into the overlying bone may be
present.
The surface of the mass is usually encapsulated
with thin, fibrous tissue and may have a
bosselated or polypoid appearance.
There are many different histologic patterns
found in
syncytial, named for the whorled clusters of cells

that sit in tight groups without visible cell membranes;

fibroblastic, with elongated cells and

abundant collagen deposition between

them;
transitional, which shares features
of the syncytial and fibroblastic
types;
psammomatous, with numerous
psammoma bodies;
secretory, with PAS-positive
intracytoplasmic droplets and
intracellular lumina by electron
microscopy; and
microcystic, with a loose, spongy

Meningioma with a whorled pattern of

cell growth and psammoma bodies.

the tendency of the usual meningioma to push against, rather than

infiltrate, adjacent normal brain. Many meningiomas contain
compact clusters, or whorls, of cells, like those present in this lesion.

Eplanation of the figure

As noted previously, meningiomas are

neoplastic proliferations of meningiothelial cells.

In many cases, accordingly, the cells of
meningiomas contain bland, relatively uniform
nuclei and prominent nuclear pseudoinclusions
reminiscent of those seen in non-neoplastic
meningothelial cells. An amazingly wide variety
of histological patterns may be encountered in
these tumors, however, most of which have no
prognostic significance.

Atypical meningiomas-WHO II
lesions with a higher rate of recurrence,
more aggressive local growth, and
a possible need for therapy in addition to surgery are recognized by several histologic features including a
higher mitotic rate.
Anaplastic (malignant)WHO III meningiomas are

highly aggressive tumors that resemble a high-grade

sarcoma, although there is usually some histologic
evidence that indicates a meningothelial cell origin.
The presence of brain invasion is associated with

increased risk of recurrence.

but may produce clinical manifestations by

compression of the adjacent brain. This neoplasm
has the lobulated surface characteristic of
meningiomas, and is sharply demarcated from the
cerebrum.

Metastatic Tumors

Account for a quarter to half of intracranial tumors.

The five most common primary sites are
lung,
breast,
skin (melanoma),
kidney, and
gastrointestinal tract,

Accounting for about 80% of all metastases.

In the brain, metastases form sharply demarcated

masses, often at the gray matter-white matter

junction, usually surrounded by a zone of edema.
The boundary between tumor and brain parenchyma is
well defined microscopically as well, with surrounding
reactive gliosis.

Metastatic melanoma. Metastatic lesions are distinguished grossly from

most primary CNS tumors by their multicentricity and well-demarcated
margins. The dark pigment in the tumor nodules in this case is
characteristic of most malignant melanomas.

paraneoplastic syndromes may involve

the peripheral and central nervous systems.

Commonly associated with small-cell
carcinoma of the lung.
There are several manifestations of
paraneoplastic syndromes; some
characteristic patterns include:
Subacute cerebellar degeneration

resulting in ataxia, with destruction of

Purkinje cells, gliosis, and a mild
inflammatory infiltrate

Limbic encephalitis causing a subacute

dementia, with perivascular inflammatory cuffs,

microglial nodules, some neuronal loss, and
gliosis, all centered in the medial temporal
lobe
Subacute sensory neuropathy leading to
altered pain sensation, with loss of sensory
neurons from dorsal root ganglia, in association
with inflammation.

Neoplasms of the Peripheral Nervous

System
These tumors arise from cells of the

peripheral nerve, including

Schwann cells,
Perineurial cells, and
Fibroblasts.
Many express Schwann cell
characteristics, including the presence
of S-100 antigen as well as the
potential for melanocytic
differentiation.

Schwannoma
benign tumors
Sx are due to local compression of the involved nerve,

or to compression of adjacent structures (brain

stem or spinal cord).
often intracranial (cerebellopontine angle), where
they are attached to the vestibular branch of the
eighth nerve
present with tinnitus and hearing loss, and the
tumor is often referred to as an acoustic neuroma,
although it is more accurately called a vestibular
schwannoma.
Sensory nerves are preferentially involved, including
branches of the trigeminal nerve and dorsal roots.
When extradural, schwannomas -- large nerve trunks,
Sporadic schwannomas are associated with
mutations in the NF2 gene on chromosome 22.

Morphology
Schwannomas -- well-circumscribed

encapsulated masses that are attached to

the nerve but can be separated from it.
Tumors form firm, gray masses but may also

have areas of cystic and xanthomatous

change.

On microscopic examination, tumors show

a mixture of two growth patterns .

In the Antoni A pattern
elongated cells with cytoplasmic processes are
arranged in fascicles( Bundle) in areas of
moderate to high cellularity
with little stromal matrix;
the "nuclear-free zones" of processes that lie
between the regions of nuclear palisading are termed
Verocay bodies.

In the Antoni B pattern of growth

less densely cellular with a loose meshwork
of cells along with
microcysts and myxoid changes.
In both areas, the cytology of the

individual cells is similar, with

elongated

cell cytoplasm and

regular oval nuclei.
Because the lesion displaces the nerve

of origin as it grows, axons are largely

excluded from the tumor.
These tumors are usually uniformly
immunoreactive for S-100 protein.