Tumor of CNS and Peripheral Nerve(Dr.betty)

7/30/2019 Tumor of CNS and Peripheral Nerve(Dr.betty)

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PATHOLOGY & GENETICS

TUMOURS OF THE NERVOUS SYSTEM

Bethy Suryawathy, dr.,SpPA.,PhD


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Tumors of the CNS

General

General - Statistics vary widelyPrimary tumors of the CNS is 9% of all neoplasms.

Gliomas (50%), followed by Meningiomas (15%), andacoustic nerve Schwannomas (5-10%). Of all

intracranial tumors, approximately 30% are metastatic.

Relative to site and age

70% of primary intracranial tumors in adults aresupratentorial.

70% of primary intracranial tumors in children areinfratentorial


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The most common primary malignantintracerebral tumor inadults is the glioblastoma

multiforme; in children is the medulloblastoma.

PATHOPHYSIOLOGY

Symptoms and Signs Produced by Brain Tumors

orTumor Mass Effect

In general, the signs & symptoms are due

primarily to the tumor Size and Location. Theseeffects are expressed in two ways:


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1. Compression: example - meningioma's compress theadjacent brain

2. Infiltration: examples - low grade astrocytoma. In thesecases, the tumor infiltrates and pushs apart importantneural structures, and thus these structures fail tofunction properly.

Surrounding Edema

Metastatic tumors create most of their mass effects on

the adjacent brain by inducing cerebral edema Consequences: Hemiation of cerebral and brain stem

structures.


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METASTATIC TUMORS

Mode of metastatic extension is usually via the

blood stream to:

1. Bone

Vertebral body

Often metastasize to epidural space (top of column)

with compression of spinal cord.

Result of compression: paraplegia, failure of boweland bladder control


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2. Leptomeninges

Growth of carcinoma cells within leptomeninges =Carcinomatous Meningitis.

3. Brain

Brain metastases can involve the cerebrum, cerebellum,

or uncommonly, the brain stem. Typically, they are at thejunction of the cortex and white matter. 80% are from thelung, breast, melanoma, kidney and Gl tract.

Metastases are discrete, and may be multiple.

Most important effect - surrounding edema, withsubsequent swelling of white matter. This sometimesresponds to steroids or hyperosmolar urea.


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TUMORS OF MENINGES

Meningioma

A tumor of arachnoid cells, especially those within

the arachnoidal villi. The most common sites reflect

the areas where these villi are most numerous (e.g.

parasagittal area, falx cerebri, sphenoidal ridge, and

olfactory groove).

Age 45-60. Sex: F/M 1.5/1. These are wellcircumscribed benign tumors which are attached to

and frequently invade the dura.


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They cause symptoms by compression of theadjacent brain or by invasion of the skull, which

commonly shows a reactive hyperostosis. There

are various histologic types.Microscopically : most have meningothelial

whorls (resembling arachnoidal villi) with

laminated calcifications called psammoma bodies.


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PRIMARY NEUROEPITHELIAL

TUMORS

Neuroglial Tumors (Gliomas)

Astrocytomas, anaplastic astrocytomas, and

glioblastoma multiforme together account forapproximately 80% of primary brain tumors in adults.

Low grade astrocytomas may progress to the anaplastic

variant, which in turn may progress to glioblastoma

multiforme. These tumors occur primarily in the

cerebral hemispheres.


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A. Astrocytoma

1. Fibrillary: Astrocytes abundant fibrillary processes

2. Gemistocytic: Large cells with eccentric nuclei and

swollen, glassy, eosinophilic cytoplasm

3. Pilocytic extremely low grade tumors, which tend

to occur in children, and generally are found in the

cerebellum or regron of the 3rd ventricle.


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Glial fibrillary Acidic Protein (GFAP) is ahistologic aid in confirming the astrocytic

origin of these neoplasms. The cytoplasm of

astrocytes contains glial filamentscomprised of GFAP. The protein has been

isolated and antibodies have been prepared

against it and used to identify the protein in

tumor cells.


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B. Glioblastoma Multiforme

Most arise from pre-existing AnaplasticAstrocytomas.

They produce VEGF AND FDGF factors which

encourages blood vessel growth with strikingendothelial hyperplasia resulting in formation of

glomeruloid and angiomatoid structures.

Local ischemia causes the diagnostic "stellate" foci

of necrosis, which are surrounded by palisadedtumor cells, (pseudopalisading necrosis)


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C. Ependymoma Ependymomas are derived from ependymal cells,

which line all ventricles.

In the first two decades, they constitute 5 -10% ofbrain tumors, and are found typically in the 4th

ventricle where they form solid/papillary masses

projecting from the floor of the ventricle. They

often cause obstruction of the 4th ventricle with

obstructive hydrocephalus. The prognosis is poor

because their location prevents complete removal.


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D. Oligodendroglioma These tumors arise in the cerebral hemispheres

of adults, where they appear as well-

circumscribed gelatinous grey masses. There

are sheets of monotonous cells with uniform

central nuclei, surrounded by a clear halo of

cytoplasm. These resemble a "fried-egg".


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E. Meduloblastoma A primitive, undifferentiated embryonal tumor

derived from neuroepithelial stem cells.

They are the most commom primary intracranialtumor of childhood and account for 25% of all

primary brain tumors in the first 2 decades. They

typically arise in the cerebellum usually in the

midline vermis in young children.


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PRIMARY CEREBRAL

LYMPHOMA

Systemic lymphomas/leukemias can secondarily

involve the brain - typically the meninges. Patients in

the late late stages of AIDS frequently developprimary lymphomas of the CNS. Sporadic cerebral

lymphoma (unasssociated with HIV) typically affects

older adults. Typically, the tumor is deep-seated and

periventricular in distribution (masses, ant. horns oflateral ventricle), may be nodular or diffuse, and

multiple masses are commom.


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Microscopically, these are always

large cell lymphomas which

typically infiltrate and expand the

walls of blood vessels. These have

a poor prognosis with a mean

survival of 18 months. Dramatic

but temporary shrinkage of the

mass follows administration of

corticosteroids.


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TUMORS OF PERIPHERAL

NERVES

Schwannoma

Antoni A PatternAntoni B Pattern

*Neurofibroma

Neurofibromatosis type 1 (Von Recklinghausensdisease)


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Differentiated astrocytes or precursor cells

Low grade astrocytoma

P53 Mutation (>65%)

PDGF-A, PDGFR-a

Overexpression ( ~ 60%)

LOH 19q (~ 50%)

RB alteration (~25%)

Anaplastic astrocytoma

Secondary glioblastoma

LOH 10q

PTEN mutation (5%)

DCC loss of expression (~50%)PDGFR-a amplification (


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Oligodendrocyte or precursor cells

Oligodendroglioma WHO Grade II

Anaplastic Oligodendroglioma WHO Grade III

EGFRPDGF/PDGFR

overexpression

LOH 1pLOH 19q

LOH 4q

CDK4, EGFR, MYC

Amplification (rare)

VEGF overexpression

CDKN2A deletion

CDKN2C mut./del.

LOH 9p and 10q

Fig.2 Flowchart showing molecular alterations identified in oligodendrogliomas and

Anaplastic oligodendrogliomas


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Arachnoidal cells

Meningioma, WHO grade I

Atypical meningioma, WHO grade II

Anaplastic (malignant) meningioma, WHO grade III

NF2 gene mutation / chromosome

22q lost? Other loci

Loses of 1q, 6q, 10q,14q and 18q

Gains of 1q, 9q 12q, 15q, 17q and 20q

Loses of 6q, 9p,10 and 14q

17q amplification

Rare mutation: TP53, PTEN

Rare deletion: CDKN2A

Fig. 3 Genetic changes associated with meningioma progression


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Tumor of CNS and Peripheral Nerve(Dr.betty)