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Brain tumour information



Informations regarding Brain Tumour for doctors

Introduction


  • Brain tumours are a group of heterogeneous tumour with different presentation, histology, treatment options and prognosis.
  • Glial tumors are most common brain tumor of adult.
  • ‘Gliomas’, as called loosely are a group of tumor of glial cell origin and include a group of tumours with different treatment and prognosis.
  • Glial cells are supporting cells to neuron and have mitogenic potential.
  • Different glial cells produce different glial cell tumours; Astrocyte?astrocytoma, Oligodendrocytes?oligodendrocytoma,
  • Ependymal cells?ependymoma.
  • Depending upon pathologic findings these tumors are graded.
  • Treatment and prognosis of glial cell tumours depends upon grade

Tata Memorial Hospital Neuro-Oncology data 2006



Incidence:

Brain tumors are considered rare tumours. But, it is the most common solid tumor of childhood. Recently we have analyzed the Neuro-Oncology registration data of 2006. Tata Memorial Hospital is a tertiary referral hospital and patients are referred from different parts of India. Thus, TMH neuro-oncology registration data provides important informations regarding brain tumour in India.


TMH Neuro-Oncology registration data 2006:

TMH Neuro-oncology data 2006

Total No. of cases

656

Male

402 (61.3%)

Female

254 (38.7%)


TMH Neuro-Oncology registration data 2006:

Age distribution

Age

No. of patient

below 6 yr

41

7-15 yr

74

16-30 yr

132

31-50 yr

236

51-70 yr

134

above 70 yr

13

Etiology



Few proven etiologic risk factors

Clearest risk factor is presence of a hereditary tumor syndrome .

Most common genetic syndromes are neurofibromatoses.

Incidence -
  • NF-1 : 1 in 3000
  • NF-2 : 1 in 35000

Hereditary Syndromes:

Syndrome

Brain Tumor

Genetics

Neurofibromatosis 1

Glioma, sarcoma

NF1 on 17q12 ; AD

Neurofibromatosis 1

Schwannoma, meningioma

NF2 on 22q12 ; AD

VHL

Haemangioblastoma

VHL on 3p25-26 ; AD

Cowden

Gangliocytoma

PTEN/MMAC1 on 10q23 ; AD

Turcot

Glioblastoma, Medulloblastoma

5q21 ; AD

Tuberous sclerosis

Subependydoma

TSC1 on 9q ; TSC2 on 16p

Li Fraumeni

PNET

TP53 on 17p13 ; AD

Basal Naevus

Medulloblastoma

PTCH on 9q31 ; AD


Other Risk Factors:

1. Environmental and occupational risk factors : (The Radiation Epidemiology Branch of the NCI)

  • No association between the development of brain tumours and cellular telephone use.
  • History of allergies or autoimmune diseases was protective.
  • No increased risk with previous polio vaccination ( e.g. simian virus 40 contamination)

2. Radiation: Proven to be a causative factor in 1) Astrocytoma 2) Meningioma – benign / malignant 3) Sarcoma 4) Nerve sheath tumors.

Classification



Depending upon the origin classification done.

CNS tumours are divided into tumours derived from :

  • glial cells
  • neuronal cells
  • cells that surround or insulate the CNS
  • cells that form specialized anatomic structures.

Pathological Classification:

Astrocytic Tumour –

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Astrocytoma

  • Anaplastic Astrocytoma
  • Glioblastoma
  • Pilocytic
  • Pleomorphic xantoastrocytoma
  • Subependymal giant cell astrocytoma

Oligodendroglial Tumour

  • Oligodendroglioma
  • Anaplastic Oligodendroglioma

Ependymal Tumour

  • Ependymoma
  • Anaplastic
  • Myxopapillary Ependymoma
  • Subependymoma


Mixed Glial Tumour –

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Choroid plexus Tumour –

  • Papilloma
  • Carcinoma

Neuroepithelial Tumour –

  • Astroblastoma
  • Polar spongioblastoma
  • Gliomatosis cerebri

Neuronal & mixed neuronal-glial Tumour –

  • Gangliocytoma
  • Ganglioglioma
  • Anaplastic Ganglioglioma
  • Dysembryoplastic


Pineal Tumour –

  • Pineocytoma
  • Pineoblastoma

Embryonal Tumour –

  • Medulloepithelioma
  • Neuroblastoma
  • PNET
  • Medulloblastoma

Tumour of cranial & spinal Nr.

  • Schwanoma
  • Neurofibroma
  • Meningioma
  • Hemangiopericytoma
  • Germ cell tumor
  • Pituitary adenoma & carcinoma
  • Craniopharyngioma
  • Metastatic

Clinical Features



Intracranial tumors produce three kinds of symptoms:

a) General symptoms - related to intracranial pressure (ICP)

  • Headache: brain itself is not pain sensitive, tumour headache arise from stretching of dura-matter and intracranial vessels
  • Nausea & vomiting
  • Seizures

b) False localizing signs- sixth cranial nerve palsy, headache. It does not depend only on site of lesion, but on other factors like rapidity of growth of tumour, duration of disease.

c) Local symptoms- specific to the tumour's location.

1) Frontal lobe syndrome:

  • Anterior frontal tumours : changes in personality, loss of initiative, and abulia.
  • Posterior frontal lobe tumours: contra-lateral weakness, with expressive aphasia.
  • Bifrontal disease :impairment of memory, lability of mood, urinary incontinence, and frank dementia.

2) Temporal lobe syndromes: severe memory impairment, homonymous superior quadrantanopsia, auditory hallucinations, abnormal behavior and fluent (Wernicke's-like) aphasia.

3) Parietal lobe tumours: affect sensory and perceptual functions more than motor modalities. Stereoagnosis, hemianesthesia, poor proprioception, homonymous inferior quadrantanopsia,

  • Non-dominant parietal lobe tumors: contralateral neglect, anosognosia and apraxia for self-dressing.
  • Dominant parietal lobe tumors : alexia, dysgraphia, and apraxia.

4) Occipital lobe tumours: contra-lateral homonymous hemianopsia; complex visual aberrations affecting perception of color, object size, or location.

  • Bilateral occipital disease - cortical blindness.

5) Classic corpus callosum disconnection syndromes :rare disorder

  • Interruption of the anterior part of the corpus callosum- failure of the left hand to carry out spoken commands.
  • Lesions in the posterior corpus callosum - inability to read or name colours.

6) Thalamic tumours:both local effects and obstructive hydrocephalus.

  • Basal ganglia involvement: "Thalamic" pain disorders or motor syndromes.

7) Brainstem disease :

  • ‘Long tract sign, cranial nerve palsies, ataxia with less than 2 month disease duration’.
  • Pontine astrocytoma (glioma)- cranial nerve VI and VII palsies. Also, hemiplegia, unilateral limb ataxia, ataxia of gait, paraplegia, hemisensory syndromes, gaze disorders, and hiccups.
  • Midbrain
  • Tectal involvement : Parinaud's syndrome,
  • Peduncular lesions: contralateral motor impairment,obstruction of the aqueduct causes hydrocephalus.
  • Medulla - fulminant course with cranial nerve palsy of VII, IX, and X. dysphagia, dysarthria, respiratory distress.

8) Cerebellar tumours : localizing presentations.

  • Midline lesions- truncal and gait ataxia,
  • Lateral hemispheric lesions : unilateral appendicular ataxia,abnormal head position, bilateral VI cranial nerve palsies

Cerebral Herniation -

Herniation syndromes with respiratory arrest and death or paraplegia or quadriplegia. Typess:-

  • Subfalcine
  • Transtentorial
  • Tonsillar

Imaging



Imaging used for-
  • 1. Differential diagnosis based on imaging characteristics and anatomic site;
  • 2. Precise anatomic localization for surgical or radiotherapeutic planning;
  • 3. Measurement of residual tumor size after surgery, radiation or chemotherapy;
  • 4. Detection of late effects of therapy.

Facts -
  • MRI and CT - major neuro-imaging techniques used.
  • For most tumors, gadolinium-enhanced MRI is the modality of choice because of higher sensitivity to pathologic alterations in brain tissue and superior anatomic resolution.
  • Tumors are contrast enhancing when the BBB is disrupted. Contrast-enhancement provides information regarding high or low grade malignancies.
  • Most low-grade gliomas (except-pilocytic astrocytomas) do not enhance on CT or MRI scan.
  • Almost all enhancing lesions are high grade.

Newer MRI techniques-

Can provide additional information, They are -

  • 1. Magnetic resonance spectroscopy (MRS)- images the regional distribution of chemicals associated with tumor metabolism. This can distinguish tumor cells from necrosis or treatment effect.
  • 2. Dynamic contrast-enhanced MRI- by quantization of the uptake of gadolinium contrast agent into the lesion, can distinguish the slow rate of uptake of radiation injury from the rapid rate of uptake seen in malignant tumors
  • 3. Diffusion-perfusion MRI - cause restricted water diffusion in the brain to help differentiate malignant tumor from radiation effect.
  • 4. Functional MRI - exploits small, localized changes in blood flow that occur in the brain during neurologic activity to image language, sensory, and motor areas directly. This enables better protection of normal brain function during a resection.

Immuno-cytochemistry


In few clinical situations, histopathology is not enough to provide a definite diagnosis. In those cases immuno-chemistry may help to come to a definite diagnosis.


EMA

CK

S-100

CEA

LCA

VIMENTIN

GFAP

Glioma

-

+

+

-

-

+

+

Primary CNS Lymphoma

-

-

-

-

+

+/-

-

Metastasis

+

+

+/-

+/-

-

+/-

-

Meningioma

+

+/-

+/-

+/-

-

+

-

Medulloblastoma

-

-

+/-

-

-

+/-

+/-

Choroid plexus tumour

+/-

+/-

+

+/-

-

+

+/-

Schwannoma

+/-

-

+

-

-

+

+/-

Staging & Grading




Staging of Glial cell tumors-

There is no clinical classification for brain tumour used in day to day practice. There is a proposed AJCC system based on ‘GTM classification’ (G, grade; T, tumor size; M, metastasis).


In GTM system following rules are followed -

T stage is divided into supra-tentorial and infra-tentorial.

Separated into five staging group;

  • 1) Clinical- diagnostic
  • 2) Surgical- evaluative
  • 3) Post-Surgical – pathologic
  • 4) Retreatment
  • 5) Autopsy.

Grading is the most important prognostic tool. It is divided according to –

  • 1) G1 is well differentiated.
  • 2) G2 is moderately differentiated.
  • 3) G3 is poorly differentiated.
  • 4) G4 is features of pleomorphism and necrosis.

Grading of glial tumors :

As there is no effective staging system for brain tumours, the histology and grade of the disease are the most important factors that determine the prognosis and treatment decision.Grading of Astrocytoma: Depends on -

  • 1) Nuclear Atypia
  • 2) Mitosis
  • 3) Endothelial Proliferation
  • 4) Necrosis

GRADE I – None of the features

GRADE II – Only 1 feature – Low Grade Glioma (LGG)

GRADE III – 2 features –Anaplastic Astrocytoma (AA)

GRADE IV – >=3 features – Glioblastoma Multiforme(GBM)

Natural History of Astrocytomas




Description of glial cell tumours –

Features :

Children and young adult :
  • Commonest solid tumour (20%)
  • Usually infra-tentorial
  • Pilocytic Astrocytoma – most common
  • Usually manifests early with increase in Intra-cranial pressure and prognosis is better than adult.

Adults and elderly:
  • Astrocytomas are the commonest
  • Glioblastoma Multiforme comprises 40%.
  • Usually Supra-tentorial and presents late.

Natural History :

Pilocytic astrocytoma
  • More common in young & children
  • Usually presents as posterior fossa tumour
  • Slow growing tumor.
  • Tumor usually localized and well delineated.
  • Do not progress to higher grade.
  • H/P - ‘rosenthal fibre’ ++
  • P53 gene - not inactivated.

Diffuse (oligodendrocytic) astrocytoma -
  • Occur at any age, but usually occur in young adult
  • Arises from cerebral hemisphere
  • Relatively slow growing
  • Subgrouped – a) fibrillary, b) protoplasmic c) gemistocytic.
  • These subgroups have prognostic implication. Gemistocytic variety is more aggressive.
  • May progress to higher grade with time.

Anaplastic astrocytoma -
  • Occur in middle age
  • Diffusely infiltrating astrocytic tumour.
  • Rapidly growing tumour. Produce symptoms early and rapidly progressive disease.
  • H/P- Diffuse endothelial proliferation. But no necrosis.
  • Progression to Glioblastoma occurs with time.

Glioblastoma (grade –IV)-
  • Occur at any age. But more in elderly ( >60 yr)
  • Poorly differentiated astrocytic tumor. Rapidly progressive fatal disease.
  • Occur in cerebral hemisphere
  • H/P- Necrosis always seen. Also microvascular proliferation seen. Multinucleated giant cell – hallmark of Glioblastoma.
  • Profuse Peritumoral oedema seen.
  • Cross corpus callosum some times involved; called ‘ butter-fly’ tumor.

Prognostication



Prognostic index (PI):

Prognostic Factors

Category.

Score



Age

below 44

0

45-59

6

above 60

12



WHO PS

0-1

0

2

4

3-4

8



Extent of surgery

CR

0

PR

4

Biopsy

8



H/O Fits

Below 3

0

Above 3

5

None

10


Sum of scores = PI

Low PI = better prognosis


Oligodendroglioma



Oligodendroglioma :
  • Diffuse infiltrating glial tumour
  • Arise from oligodendrocytes.
  • Slow growing.
  • LOH 1p - associated with marked chemo-sensitivity.

Imaging used for-
  • More in frontal / parietal region.
  • Hyper dense lesion.
  • Enhance with contrast
  • Calcification+>50%

Natural history:
  • Slow growing
  • Unclear if endothelial proliferation / necrosis – determine prognosis
  • Usually not graded according to astrocytomas

Ependymoma



Ependymoma :
  • Arise from ependymal cells of ventricles & central canal of cord.
  • More in young children
  • Usually in post. Cranial fossa.

Natural history :
  • Slow growing
  • Peri-vascular rosette formation.
  • Spread via CSF in 10% cases.
  • May be high/low grade depending on pleomorphism.

Imaging :
  • Posterior cranial fossa tumour
  • Calcification ++
  • Contrast enhancement +
  • Sign of hydrocephalous

Prognosis



Prognosis of brain tumour depends upon the histology of tumour and grade of tumour.


Astrocytic Tumours –

Grade

Prognosis

Pilocytic

Complete Remission – 80-90%

Diffuse

Median Survival – 5-8 year

Anaplastic

Median Survival – 2-4 year

Glioblastoma

Median Survival – 10-12 month


Oligodendroglioma –

Grade II : 30-80% 5 yr Survival


Epenymoma –

5 yr survival - low grade: 30-50%

Supportive Treatment



Principles of Supportive treatment :

Supportive treatment has a significant role in brain tumour.

Agents used in supportive management of brain tumour -

Corticosteroids –
  • Dexamethasone
  • Solumedrol

Anticonvulsants –
  • Phenetoin
  • Valproic acid
  • Phenobarbitone
  • Carbapamazipine

Anti-coagulants / IVC filter

Description of agents - Corticosteroid :

Acts by :
  • 1) Anti-oedema effect – by reducing capillary permeability.
  • 2) Tumorcidal effect – by increasing apoptosis.
  • 3) Dexamethasone used with minimal dosage (4-8 mg/d).Max. dose = 100mg /day

Dexamethasone is used in brain tumor for following reasons -
  • 1. Crosses Blood Brain Barrier
  • 2. Little mineralo-corticoid activity
  • 3. Lower probability of infection
  • 4. Lower cognitive dysfunction
    • Symptoms improve by 24-72 hr.
    • Headache responds better than focal-deficit.
    • But, imaging need >7 day for to show response

Side-effects –
  • 1. Fluid retention , wt gain
  • 2. Myopathy, gastritis , hyperglycemia
  • 3. Infection (pneumocystis carinii )
  • 4. Co-trimoxazole prophylaxis used to prevent infection

Indications :
  • 1. Symptomatic brain metastasis
  • 2. During Radiotherapy, if volume of treatment is large.
  • 3. Post surgery – usually < 4 week.
  • 4. Sign of increased intracranial tension.


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