6 cns tumors

7/29/2019 6 CNS Tumors

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Central nervous system tumors


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Anatomy

Central nervous system


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Anatomy


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Anatomy

CNS=brain+spinal cordBrain=

1) Supratentorial part:

-cerebral hemispheres

-diencephalon (1. thalamus, 2. hypothalamus, 3.epithalamus, 4. prethalamus or subthalamus and 5.pretectum)

2) Infratentorial part:

-brainstem-cerebellum


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Cerebrospinal fluid

Between pia mater on one side and the

arachnoid and dura mater on the other side

Produced by the choroid plexuses from the

ventricles and reabsorbed by the arachnoid

granulations


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Epidemiology

90% of brain tumors=metastases from other

tumors

Only 10% of brain tumors=primary brain

tumors

This represents about 3% from all cancers

In adults 2/3 of primary brain tumors aresupratentorial, whereas in children, 2/3 of

brain tumors are infratentorial.


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Neurofibromatosis type 1 (NF1): - schwannomas, meningiomas, and certain types ofgliomas, as well as neurofibromas (benign tumors of peripheral nerves). Changes in the NF1gene cause this disorder.

Neurofibromatosis type 2 (NF2): much less common than NF1; is associated with vestibular

schwannomas (acoustic neuromas) and, in some patients, meningiomas or spinal cordependymomas. Changes in the NF2 gene are responsible.

Tuberous sclerosis: -subependymal giant cell astrocytomas (low-grade astrocytomas thatdevelop beneath the ependymal cells of the ventricles), in addition to benign tumors of theskin, heart, or kidneys. It is caused by changes in either the TSC1 or the TSC2 gene.

Von Hippel-Lindau disease: -inherited tendency to develop hemangioblastomas (bloodvessel tumors) of the cerebellum or retina as well as tumors of the kidney, adrenal glands,

and pancreas. It is caused by changes in the VHL gene. Li-Fraumeni syndrome: -at higher risk for developing gliomas, along with certain other types

of cancer. It is caused by changes in the p53 gene.

Other inherited conditions, including Gorlin syndrome, Turcot syndrome, and Cowdensyndrome are also linked with increased risks of certain types of brain and spinal cordtumors.

Other families may have genetic disorders that are not well recognized or that may even be

unique to a particular family.

I. Genetic risk factors


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II. Environmental risk factors

1. Ionizing radiation is the only unequivocal risk

factor that has been identified for glial andmeningeal neoplasms.

Irradiation of the cranium, even at low doses,

can increase the incidence ofmeningiomas by afactor of 10 and the incidence ofglial tumors by a

factor of 3 to 7,

latency period of 10-20+ years after exposure


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2. Lack of proper exercise and obesity during teen years

3. Taller people have brain tumors more frequentlyBoth of the data comes form the NIH-AARP Diet and Health Study (~500 000

subjects)

Those who reported doing substantial amounts of light, moderate and vigorous

exercise between the ages 15 and 18 were 36% less likely to develop a glioma

than those who were sedentary. Activities included walking, aerobics, biking,

swimming, running, heavy housework or gardening.

Who were obese during their teen years had a three to 4 times greater risk ofdeveloping glioma than those of a normal weight.

It could be that obesity increases the risk of brain cancer, or if could be that

some underlying condition increases both the risk of obesity and brain cancer

Each 10 centimeter increase in height meant a nearly 20% increase in risk of

developing glioma.


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4. Cell phone use-microwaves

Some of the strongest evidence supporting a link between brain tumors and

cell phone use comes from a series of Swedish studies, led by Dr. Hardell

Overall.

The researchers found that risk increased with the number of cumulative hours of

use, higher radiated power, and length of cell phone use.

Younger users had a higher risk. In fact, the highest risk was among people who

were younger than 20 years at the time of first use.

(Int J Oncol. 2006;28:509-518; Int Arch Occup Environ Health. 2006;79:630-639;

Arch Environ Health. 2004;59:132-137; Pathophysiology. 2009;16:113-122).

A meta-analysis that incorporated 11 long-term epidemiologic studies in this

field also reported a link between cell phone use and brain tumors. Using a cell

phone for 10 years or longer was positively associated with the development ofan ipsilateral brain tumor; in fact, it doubled the risk

(Surg Neurol. 2009;72:205-214)


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5. Presence of allergy decreases the risk risk

of glioma

-2007 study: relative risks (RRs) ofglioma comparingpeople with a history of an atopic condition with

people with no history of atopy were 0.61 for

allergy, 0.68 for asthma, and 0.69 for eczema.

-no relation between meningioma and allergy

6. Impaired immune system (AIDS) =>

increased risk of developing lymphoma of

the brain or spinal cord


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Histological subtypes of CNS tumorsCellular origin Histological subtypes Frequency

Age of diagnosis

Treatment % survival

1 yr/ 5 yrs

Astrocytes High grade

astrocitomas :

-Glioblastoma

multiforme (grade IV)

-Anaplastic astrocytoma

(grade III)Low grade

astrocitomas:

-Low grade astrocytoma

(grade II)

-Pylocyitic astrocitoma

(grade I)

Most frequent

malignant

primary brain

tumors in adults;

60 years

Rare tumors50 years

Rare tumors

30-40 years

Excision

RT

Chemotherapy

Excision +/- RT

Excision

45%

< 5% !!!

60%

< 10 %

80%

60%

>90%

Oligodendrocytes Anaplastic

oligodendrogliomas

(grade III)

Oligodendrogliomas

(grade II)

Rare tumors

50 years

Excision

RT

Chemotherapy

50%

30%

85%

60%


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Histological subtypes of CNS tumors (2)Cellular origin Histological subtypes Frequency

Age of

diagnosis

Treatment Prognostic

% survival

1 yr/ 5 yrs

Cerebellar cells Medulloblastoma Most frequentprimary

malignant

brain tumors in

children

(3/4 in children)

Excision

+/-Cranio-spinal

RT

+/-Chemotherapy

80%/50%

Ependimocytes Ependimoma Rare tumors Excision

+/-RT

55/45%

Hypophyseal cells Hypophyseal tumors

-benign/malignant

-secreting/non-

secreting

Rare tumors;

adults

Stereotactic

radiosurgery/

Gamma-knife

>95%

Meningeal cells Beningn or malignant

meningiomas

Frequent

tumors;

age around 40

yrs;

female

predominance

excision +/-

adjuvant RT

>90% for

benign tu.


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Glioblastoma multiforme (grade IV)

The worst prognosis

Despite its apparent demarcation on enhanced

scans, the lesion may diffusely infiltrate into the

brain, crossing the corpus callosum in 50-75% of

cases.


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Physiopathology Effect on normal neural tissue:

1. Invasion2. Compression

Edema

Necrosis

Intracranial hypertension

Hydrocephalus

The evolution of the disease can be:

-slow-months, years (grade I, II)

-fast-weeks, months (grades III,IV)


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Dissemination routes

Leptomeningeal dissemination: NHL,

medulloblastoma, ependimoblastoma.

Distant metastases: rare; might be present in

medulloblastoma

There are no lymphatics in the CNS=>no

lymph node metastases!!!


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Symptoms

Headache

Signs of intracranial hypertension (nausea,

vomiting, somnolence)

Epileptic seizure

Focal neurological signs depending on the

localization of the tumor


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Cerebellar symptoms

Most commonly found in children, the tumorinvolves the cerebellar vermis and causes gait ataxia

more readily than unilateral symptoms.

Adults more commonly harbor the desmoplastic

variant of medulloblastoma, which arises in the

cerebellar hemisphere. These patients often have

symptoms of ipsilateral dysmetria (undershoot or overshoot ofintended position with the hand, arm, leg, or eye)


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Leptomeningeal dissemination

Presenting symptoms rarely are related to

dissemination of tumor in the CSF.

Patients can complain of severe weakness from

tumor compression of the spinal cord or nerve

roots (eg, radiculopathy).


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Diagnostic work-up (1)

MRI with gadolinium

contrast of the skull

Search for an other primary which can give a

CNS metastasis

General laboratory work-up, performance index

Tumor biopsy/excision


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Diagnostic work-up (2) Lumbar puncture for NHL, medulloblastoma,

ependimoblastoma Ophthalmoscopy

- optic disc=where the nerves of the eye converge to pass

to the brain.

Normally: clearly-defined, pale concave disc, but if the

pressure in the CSF is raised, the disc may bulge

forwards into the cavity of the eye = papilledema

Campimetry

Search for distant metastases (medulloblastoma)

T t t


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Treatment

High grade gliomas:

maximum safe resection

adjuvant radiotherapy and chemotherapy

with temozolomide

younger pacients have better prognosis

Low grade gliomas, meningiomas:

Resection

+/- adjuvant radiotherapy

Hypophyseal tumors:

Stereotactic radiosurgery/

Gamma-knife


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Contouring on fused CT/MRI image


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k f


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Gamma-knife


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Proton therapy


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Side effects of RT

ACUTE:

edema

Increased intracranial pressure

CHRONIC:

Necrosis of brain tissue

In children: decreased IQ

Adults: decreased mental functions


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Questions What is the most frequent primary brain

tumor in adults? And in children? What CNS tumors disseminate through de

CSF?

Enumerate some negative prognosticfactors for CNS tumors. (Answer: older age,

high grade histology (III, IV), larger residual

tumor, lower performance index). What is the treatment sequence for high

grade gliomas?

6 cns tumors

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