BRAIN TUMOURS

Brain tumor It is defined as any intracranial tumor caursed by abnormal and uncontrolled cell division, normally either - in the brain itself (neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells), lymphatic tissue, blood vessels), - in the cranial nerves (myelin-producing Schwann cells), - in the brain envelopes (meninges), skull, pituitary and pineal gland, - or metastatic tumors

Brain tumor

Primary (true) brain tumors are commonly located in the - posterior cranial fossa in children - anterior 2/3 of the cerebral hemispheres in adults, although they can affect any part of the brain.

AETIOLOGY

PRIMARY - sporadic

Environmentsl risk factor Smoking Diet Occupation Mobile phone No causative link proven

Immunosupression -

Linked with Genetic abnormalities -

Genetic LinkingDisease Mutation Protein Tumour

Neurofibromatosis Type 1

Chromosone 17

Nourofibromin

AstrocytomaNeurofibroma

Neurofibromatosis Type 2

Chromosone 22

Schwannomin Acoustic neuroma

Meningioma

Li-Fraumeni’sSyndrome

Chromosone 17

P 53 Astrocytoma

Basal cell naevus syndrome

PTCH gene Medulloblastoma

Familial Adenomatous

Polyposis Syndrome

APC gene Medulloblastoma

WHO CLASSIFICATION

Neuroepithelial Tumor

GliomaAstrocytomasOligodendrogliomasEpendymomaChoroid Plexus Tumor

Pineal Tumor

Neuronal Tumor GangliogliomaGangliocytomaNeuroblastoma

Medulloblastoma

Nerve Sheath Tumor Vestibular Schwanoma

Meningeal Tumor Meningioma

Pituitary Tumor

Germ Cell Tumor Germinoma

Lymphomas Teratoma

Tumor Like MalformationCraniopharyngiomaEpidermoid TumorDermoid TumorColloid Cyst

Metastatic Tumor

Contiguous extension from regional Tumor ( Glomus Tumor )

GLIOMA Arises from glial cellsThe most common site of gliomas is the brain

ClassificationClassified - by cell type, - by grade, - by location.

By cell type

Glial Cells Glial Tumour

Astrocytes Astrocytomas

Oligodendrocytes Oligodendrogliomas

Ependymal cells Ependymomas

Different types of glia Mixed gliomas (oligoastrocytomas)

By grade

Grade Differentiation Type Prognosis

Low-grade well-differentiated

(not anaplastic)

benign better

High-grade

undifferentiated (anaplastic)

malignant worse

HISTOLOGICAL CRITERIA

Cellularity

Nuclear pleomorphism

Mitoses

Vascular proliferation

Necrosis

By locationType Location Site Age

Supratentorial above the tentorium in the cerebrum mostly in adults (70%)

Infratentorial below the tentorium in the cerebellum mostly in children (70%)

GLIOMA

WHO CLASSIFICATION

Astrocytomas

Oligodendrogliomas

Ependymoma

Choroid Plexus Tumor

GRADING

GRADE I Pilocytic Astrocytoma

GRADE II Diffuse Astrocytoma

GRADE III Anaplastic Astrocytoma

GRADE IV Glioblastoma Multiforme

SymptomsDepends on which part of the central nervous system

is affected

Drop metastases: not metastasize by the bloodstream but they can spread via the cerebrospinal fluid and cause "drop metastases" to the spinal cord

Affected organ Symptoms

brain glioma increased intracranial pressureheadaches, nausea, vomiting, seizures,

cranial nerve disorders optic nerve glioma visual loss

Spinal cord gliomas pain, weakness, numbness in the extremities

PathologyHigh-grade gliomas highly-vascular tumorstendency to infiltrateextensive areas of necrosis and hypoxiabreakdown of the blood-brain barrieralmost always recur even after complete surgical excision

Low-grade gliomas grow slowlyover many yearsfollowed without treatment unless they grow and cause symptoms

Treatmentdepends on - location, - cell type - grade of malignancy

combined approach - Surgery - Radiation therapy external beam radiation stereotactic approach using radiosurgery Spinal cord tumors - surgery + radiation - Chemotherapy Temozolomide able to cross the blood-brain barrier

PrognosisGliomas cannot be cured

High-grade gliomas Poor prognosis50% - 1 year after diagnosis25% - 2 years after diagnosisanaplastic astrocytoma survive about three yearsGlioblastoma multiforme has a worse prognosis

Senator Kennedy passed away from the malignant glioma tumor on August 25, 2009 at his home in Hyannis Port, Massachusetts

PROGNOSIS

Histological grade

Cell type

Tumor size

Patient’s factor

ASTROCYTOMA

Astrocytomas originate in star-shaped brain cells called astrocytesmost common primary CNS malignancy75% of neuroepithelial tumors

low grade - < 6 % of Intracranial tumorsgrade (IV) - 20 % of Intracranial tumors - survival 3 - 12 months

ASTROCYTOMAClassificatio

nTumour Grade

I Pilocytic astrocytoma I Low

I A Pilomyxoid astrocytoma II Low

II Subependymal giant cell astrocytoma

I Low

III Pleomorphic xantho astrocytoma II Low

IV Diffuse astrocytoma II Low

V Anaplastic astrocytoma III High

VI Glioblastoma IV High

VI A Giant cell glioblastoma IV High

VI B Gliosarcoma IV High

VII Gliomatosis cerebri III High

Glioblastoma multiforme

standard name - “Glioblastoma”- most common - most aggressive - 52% of all parenchymal brain tumor- 20% of all intracranial tumorsClassified - Giant cell glioblastoma - Gliosarcoma

Glioblastoma multiformeCauses

Sporadic , without any genetic predispositionNo links - smoking,diet, cellular phones, electromagnetic fieldsSex: male Age: over 50 years old Ethnicity: Caucasians, Latinos, Asians Linked - low-grade astrocytoma (brain tumor) - genetic disorder Neurofibromatosis, Tuberous sclerosis, Von Hippel-Lindau disease, Li-Fraumeni syndrome, Turcot syndrome - cytomegalovirus. - ionizing radiation - polyvinyl chloride

Glioblastoma multiforme

Symptomsdepends highly on the location asymptomatic conditionseizure, nausea and vomiting, headache, and hemiparesisprogressive memory, personality, or neurological deficit due to temporal and frontal lobe involvement

DiagnosisMRI ring-enhancing lesionsDefinitive diagnosis of a suspected GBM on CT or MRI stereotactic biopsy or craniotomy with tumor resection

Glioblastoma multiforme

Sagittal MRI with contrast glioblastoma

WHO grade IV in a 15-year-old boy

Glioblastoma multiformePathogenesispresence of small areas of necrotizing tissue that is surrounded by anaplastic cells (pseudopalisading necrosis)differentiates Grade 3 astrocytomas presence of hyperplastic blood vesselssecondary GBM degeneration of lower grade gliomas more common in younger patientsIn the cerebral white matter, grow quicklyextend into the meninges or ventricular wall high protein content in the (CSF) (> 100 mg/dL)About 50% of GBM > one lobe of a hemisphere or are bilateralclassic infiltration across the corpus callosum butterfly (bilateral) gliomaMass effect - tumor and edema compress the ventricles and cause hydrocephalus

Glioblastoma multiforme

Treatment very difficultThe tumor cells are very resistant to chemotherapy and other conventional therapies The brain is susceptible to damage due to therapy The brain has a very limited capacity to repair itself Many drugs cannot cross the blood brain barrier to act on the tumor

Symptomatic therapyAnticonvulsantsCorticosteroids - reduce peritumoral edema

Glioblastoma multiformePalliative therapyto improve quality of life to achieve a longer survival time

Surgery1011 cells reduced to 109 cellsThe greater the extent of tumor removal, the longer the survival time

to take a section for a pathological diagnosis to remove some of the symptoms of a large mass pressing against the brain to remove disease before secondary resistance to radiotherapy and chemotherapy to prolong survival

Glioblastoma multiforme

Radiotherapyradiotherapy after surgery reduce the tumor size to 107 cellsA total radiation dose of 60–65 Gy - optimal

Chemotherapystandard of care for glioblastoma is chemotherapy during and after radiotherapychemotherapy after surgery and radiotherapy reduce the tumor size to 106 cellsTemozolomide during radiotherapy for six months post radiotherapy

Glioblastoma multiformePrognosis

Median survival time from the time of diagnosis without any treatment - 3 months

glioblastoma multiforme prognosis depends on - Karnofsky Performance Score (KPS) - age of the patient - treatment

Oligodendrogliomaa type of glioma that are believed to originate from the oligodendrocytes of the brain or from a glial precursor cell.

derives from the Greek roots 'oligo' meaning “ few” 'dendro' meaning “trees”

They occur primarily in adults (9.4% of all primary brain ) in children (4% of all primary brain tumors)The average age at diagnosis is 35 years

etiology of oligodendrogliomas is unknownlinked - viral cause - irradiation of pituitary adenoma

Symptoms

first symptom - seizure frontal lobe - affecting personalityHeadaches combined with increased intracranial pressureDepending on the location of the tumor, any neurological deficit

(CT) or (MRI) scan is necessary to characterize the anatomy of this tumor (size, location, heter/homogeneity)

final diagnosis of this tumor, relies on histopathologic examination (biopsy examination).

Microscopic Appearance

characteristic fried egg-like cells, with clear cytoplasm and well-defined cell borders. H&E stain.

composed of cells with small to slightly enlarged round nucleiwith dark, compact nuclei and a small amount of eosinophilic cytoplasm

Micrograph of an oligodendroglioma showing the characteristic branching, small, chicken wire-like blood vessels and fried egg-like cells, with clear cytoplasm and well-defined cell borders. H&E stain.

Oligodendroglioma

Incurableslowly growing with prolonged survivalmedian survival times -11.6 years for grade II -3.5 years for grade IIIvery high (almost uniform) rate of recurrence gradually increase in grade over time

Tumour

Grading

Oligodendroglioma II

Anaplastic oligodendroglioma III

TREATMENTChemotherapy - Temozolomidestandard dosing schedule 5 consecutive days of daily dosing during 28 day cycles

SurgeryBecause of their diffusely infiltrating nature, oligodendrogliomas cannot be completely resected not curable by surgical excisionSurgery may be followed up by chemotherapy, radiationStereotactic surgery small tumors that have been diagnosed early

Ependymomaa tumor that arises from the ependyma, a tissue of the central nervous systemlocation in children - intracranial in adults - spinal common intracrania location - fourth ventricle can occur in - pelvic cavitySyringomyelia can be caused by an ependymonaEpendymomas are also seen with Neurofibromatosis Type II5% of adult intracranial gliomas10% of childhood tumors of (CNS)peak at age 5 years and then again at age 35About 85% of ependymomas benign myxopapillary ependymoma (MPE)usually arise from the floor of the fourth ventricle

Symptomsby obstructing the flow of cerebrospinal fluid headache, nausea and vomiting hydrocephalusOther symptoms loss of appetite, difficulty sleeping, temporary inability to distinguish colors, uncontrollable twitching, seeing vertical or horizontal lines when in bright light, temporary memory loss

Ependymoma

TUMOUR GRADE

Subependymoma I

Myxopapillary ependymoma I

Ependymoma II

Anaplastic ependymoma III

TREATMENTwell-differentiated ependymomas radiation therapy onlyother ependymomas total surgical removal is the preferred treatment cannot be totally removed - require radiation therapymalignant (anaplastic) varieties of this tumor malignant ependymoma Ependymoblastoma - treated similarly to medulloblastoma combination of radiation therapy and chemotherapyin infants and children younger than 5 years of age, may spread through the cerebrospinal fluid usually require radiation therapy

Subependymomaa variant of the ependymomaarise in the fourth ventricle in the septum pellucidum cervical spinal cordover 40 years of age men > women

subependymal giant-cell astrocytoma, (giant-cell glioma) is typically associated with tuberous sclerosis but can occur independent of that condition Arising in the walls of the lateral ventricles over the basal ganglia - cause obstruction well-encapsulated tumor generally has a very benign course

Extraspinal ependymoma (EEP)

also known as extradural ependymoma, may be an unusual form of teratoma or may be confused with a sacrococcygeal teratoma

Choroid plexus Tumours

Tumour Grade

Choroid plexus papilloma I

Atypical choroid plexus papilloma II

Choroid plexus carcinoma III

Choroid plexus papilloma

rare, slow-growing, histologically benign intracranial tumor commonly located in the ventricular system of the choroid plexus obstruct the cerebrospinal fluid flow

causing increased intracranial pressure

Pathophysiology

neuroectodermal in origin similar in structure to a normal choroid plexusmay be created by epithelial cells of choroid plexus

Frequency and age affected0.4-0.6% of all intracranial neoplasmsmost commonly affects young children under the age of 5 mean patient age of 5.2 years

Signs and symptoms

Signs of increased intracranial pressure - 91% common symptoms - vomiting, homonymous visual field defects and headache

Surgical treatmentbenign tumors usually cured by surgery malignant progression has been rarely reported

Pineal tumoursarise from specialized cells of pineal gland -PineocytesPineocytoma - also known as a pinealocytoma - benign, slowly-growing tumor - low grade tumor - well-differentiated - areas of neutropil + tumor cells with small round nuclei - no mitoses or necrosisPineoblastoma - high grade tumor - densely packed small cells - necrosis and mitoses - spread through CSF - more common in children - may occur inRetinoblastoma patients

Pineal tumours

TUMOUR GRADE

Pineocytoma I

Pineal parenchymal tumour of intermediate differentiation

II – III

Pineoblastoma IV

Papillary tumour of the pineal region II – III

Pineal glandreddish-gray size of a pea (8 mm)shaped like a tiny pine conepineal body, epiphysis cerebri, epiphysis or the "third eye“

located - just retro-dorsal to the superior colliculus - behind and beneath the stria medullaris, - between the laterally positioned thalamic bodies. part of the epithalamus.located near to the center of the brain, between the two hemispheres, tucked in a groove where the two rounded thalamic bodies joinmidline structure, often seen in plain skull X-rays, (often calcified )produces melatonin, a hormone that affects the modulation of wake/sleep patterns and photoperiodic (seasonal) functions

.

Ganglioglioma

tumour that arises from ganglion cells in CNStemporal lobe can occur anywhere in the brain, or in the spinal cordoften associated with seizures

second most common cause of spinal cord tumors in childrenmature ganglion cells clustered with neoplastic glial cells

Dysplastic Cerebellar Ganglioglioma (Lhermitte-Duclos disease)

Neuronal and mixed neuronal-glial tumours

Tumour Grade

Gangliocytoma I

Ganglioglioma I

Anaplastic ganglioglioma II

Desmoplastic infantile astrocytoma and ganglioglioma I

Dysembryoplastic neuroepithelial tumour I

Central neurocytoma II

Extraventricular neurocytoma II

Cerebellar liponeurocytoma II

Paraganglioma of the spinal cord I

Papillary glioneuronal tumour I

Rosette-forming glioneuronal tumour of the fourth ventricle I

Neuroblastoma

microscopic view of a typical neuroblastoma with rosette formation

Neuroblastoma

most common extracranial solid cancer in childhood most common cancer in infancy50 % of neuroblastoma children < 2 years old

neuroendocrine tumor, arising from any neural crest element of the sympathetic nervous system

most frequently originates in one of the adrenal glands but can also develop in nerve tissues in the neck, chest, abdomen, or pelvis

Neuroblastoma

one of the few human malignancies known to demonstrate spontaneous regression from an undifferentiated state to a completely benign cellular appearance

three risk categories: - low - intermediate - high riskLow-risk disease is most common in infants highly curable with observation only or surgeryhigh-risk disease is difficult to cure even with the most intensive multi-modal therapies available

Etiology

not well understoodlinked to geneticsFamilial neuroblastoma very rare germline mutations in the anaplastic lymphoma kinase (ALK) gene

Epidemiology6-10% of all childhood cancers15% of cancer deaths in children

annual mortality rate 10 per million in 0 – 4 year old age group 4 per million in 4 – 9 year old age group

highest incidence - first year of life

some cases are congenital

10% > 5 years of age < 2% > 18 years of age

MILESTONESYear Name Findings

1864 German physician Rudolf Virchow

abdominal tumor in a child as a "glioma"

1891 German pathologist Felix Marchand

characteristics of tumors from the sympathetic nervous system and the adrenal medulla

1901 William Pepper distinctive presentation of stage 4S in infants (liver but no bone metastases)

1910 James Homer Wright the tumor to originate from primitive neural cells, named it neuroblastoma

circular clumps of cells in bone marrow samples which are now termed"Homer-Wright pseudorosettes"

German physician Rudolf Virchow

the first to describe an abdominal tumor in a child as a "glioma"

ClassificationInternational Neuroblastoma Staging System

STAGE TUMOUR

1 Localized tumor confined to the area of origin

2 A Unilateral tumor with incomplete gross resection; identifiable ipsilateral and contralateral lymph node negative for tumor

2 B Unilateral tumor with complete or incomplete gross resection; with ipsilateral lymph node positive for tumor; identifiable contralateral lymph node negative for tumor

3 Tumor infiltrating across midline with or without regional lymph node involvement; or unilateral tumor with contralateral lymph node involvement; or midline tumor with bilateral lymph node involvement

4 Dissemination of tumor to distant lymph nodes, bone marrow, bone, liver, or other organs except as defined by Stage 4S

4 S Age <1 year old with localized primary tumor as defined in Stage 1 or 2, with dissemination limited to liver, skin, or bone marrow (less than 10 percent of nucleated bone marrow cells are tumors)

International Neuroblastoma Risk Group Staging System (INRGSS)

STAGE GRADE

L 1 Localized disease without image-defined risk factors

L 2 Localized disease with image-defined risk factors

M Metastatic disease

M s Metastatic disease "special" where MS is equivalent to stage 4S

Signs and symptoms

Fatigue, loss of appetite, fever, and joint paindepend on primary tumor locations and metastases if present50 to 60% cases - present with metastasesA tumor in the abdomen, may cause swollen belly and constipation.A tumor in the chest may cause breathing problems.A tumors pressing on the spinal cord may cause weakness and thus an inability to stand, crawl, or walk.Bone lesions in the legs and hips may cause pain and limping.A tumor in the bones around the eyes or orbits may cause distinct bruising and swelling

Neuroblastomaoften spreads to other parts of the body before any symptoms are apparent50 - 60% - present with metastasesmost common location of primary tumor - adrenal glands 40% of localized tumors 60% of cases of widespread diseasecan also develop anywhere along the SNS chain

Site Percentage

neck 1%

chest 19%

abdomen 30% non-adrenal

pelvis 1%

no primary tumor

characteristic presentations Disease % of

casesPresentation

tumor spinal cord compression 5% transverse myelopathy

tumor vasoactive intestinal peptide secretion

4% treatment-resistant diarrhea

cervical tumor 2.4% Horner's syndrome

suspected paraneoplastic cause 1.3% opsoclonus myoclonus syndrome and ataxia

catecholamine secretion or renal artery compression

1.3% hypertension

Diagnosisusually confirmed by a surgical pathologistclinical presentation, microscopic findings, other laboratory tests

Serologyurine or bloodelevated levels of catecholamines or its metabolites - dopamine, - homovanillic acid (HVA), - vanillylmandelic acid (VMA)90% of cases of neuroblastoma

ImagingmIBG scan (meta-iodobenzylguanidine)mIBG-avid90 to 95% of all neuroblastomas

MechanismmIBG is taken up by sympathetic neurons functioning analog of neurotransmitter norepinephrineWhen it is radio-ionated with I-131 or I-123 (radioactive iodine isotopes) very good radiopharmaceutical for diagnosis and monitoring of response to treatment for this diseasehalf-life of I-123 - 13 hours, preferred isotope for imaging sensitivity and quality.half-life of I-131 - 8 days higher doses is an effective therapy as targeted radiation against relapsed and refractory neuroblastoma

Histology

microscopic view of stroma-rich ganglioneuroblastoma

tumor cells are typically described as small, round and blue, and rosette patterns (Homer-Wright pseudo-rosettes)

Neuroblastoma

one of the peripheral neuroblastic tumors (pNTs) wide pattern of differentiation benign ganglioneuroma stroma-rich ganglioneuroblastoma highly malignant neuroblastomaimportant prognostic factor with - age and - mitosis-karyorrhexis index (MKI)pathology classification systemInternational Neuroblastoma Pathology Committee (INPC, also called Shimada system) - Favorable - Unfavorable

ScreeningUrine catecholamine level can be elevated in pre-clinical neuroblastoma1980s - Japan, Canada, and Germany asymptomatic infants at three weeks, six months, 1 year

homovanillic acid and vanilmandelic acid 1984 - Japan six-month olds

Screening was halted 2004 - Canada and Germany - no reduction in deaths due to neuroblastoma, - increase in diagnoses that would have disappeared without treatment, unnecessary surgery and chemotherapy.

Treatmentlocalized lesion - generally curable

long-term survival for children with advanced disease > 18 months of age is poor despite aggressive multimodal therapy - intensive chemotherapy - surgery - radiation therapy - stem cell transplant - differentiation agent isotretinoin also called 13-cis-retinoic acid - immunotherapy with anti-GD2 monoclonal antibody therapy

Treatment options - different according to different risk categories low, intermediate, and high risk diseaseRisk assesment - age of the patient - extent of disease spread - microscopic appearance - genetic features - DNA ploidy and N-myc oncogene amplification (N-myc regulates microRNAs)

Risk % Treatment options Cure rates

low 37% observed without any treatment at all or cured with surgery alone

90%

intermediate 18% surgery and chemotherapy 70-90%

high 45% intensive chemotherapy, surgery, radiation therapy, bone marrow / Hematopoietic stem cell transplantation biological-based therapy with 13-cis-retinoic acid (isotretinoin or Accutane) antibody therapy (cytokines GM-CSF and IL-2)

30%

Chemotherapy agents

platinum compounds cisplatin, carboplatin

alkylating agents cyclophosphamide, ifosfamide, melphalan

topoisomerase II inhibitor etoposide

anthracycline antibiotics doxorubicin

vinca alkaloids vincristine

topoisomerase I inhibitors topotecan and irinotecan (recurrent disease)

Medulloblastoma

highly malignant primary brain tumor originates in the cerebellum or posterior fossafamily of cranial primitive neuroectodermal tumors (PNET)Infratentorialinfratentorial PNETmost common PNET originating in the brain

All PNET tumors of the brain are invasive and rapidly growing tumors unlike most brain tumors spread through CSF metastasize to different locations in brain and spine

IncidenceBrain tumors second most common malignancy < 20 years of ageMedulloblastoma in children most common malignant brain tumor 14.5% in adults 2% of CNS malignancies

higher in males (62%) than females (38%)more prevalent in younger children Diagnostic age % of medulloblastoma Age Group

40% 0 - 5

31% 5 - 9

18.3% 10 - 14

12.7% 15 - 19

Pathogenesisusually form in the fourth ventricle, between the brainstem and the cerebellumexact cell of origin "medulloblast“ may be arised from cerebellar "stem cells" prevented from dividing and differentiating of normal cell types

highly characteristic of medulloblastoma perivascular pseudorosette and Homer-Wright rosette formation seen in up to half of the cases

Molecular genetics loss of genetic information on the distal part of chromosome 17, distal to the p53 geneneoplastic transformation of the undifferentiated cerebellar cells

may be associated with - Gorlin syndrome - Turcot syndrome - JC virus, the virus that causes multifocal leukoencephalopathy.

Clinical manifestation1 to 5 months before diagnosis increased intracranial pressure blockage of the fourth ventriclelistless,repeated episodes of vomitingmorning headachedevelop - stumbling gait - frequent falls - diplopia - papilledema - sixth cranial nerve palsy - positional dizziness - nystagmus - facial sensory loss or motor weakness Late - decerebrate attacks

Extraneural metastases to the rest of the body is rare - only after craniotomy

DiagnosisMRIdistinctive on T1 and T2-weighted MRI - with heterogeneous enhancement - typical location - adjacent to and - extension into the fourth ventricle

Histologicallysolidpink-gray in colorwell circumscribedvery cellularmany mitoseslittle cytoplasmhas tendency to form clusters and rosettes

Treatmentmaximal resection of the tumorto increase the disease-free survival - radiation to the entire neuraxis - chemotherapyIncreased ICP - corticosteroids or - ventriculoperitoneal shunt

Prognosiscombination therapy 5 year survival in > 80% of casesbetter prognosis presence of desmoplastic features - connective tissue formation poor prognosis - less than 3 years old - inadequate degree of resection - any CSF, spinal, supratentorial or systemic spread

Embryonal tumoursTomour Grade

Medulloblastoma IV

CNS primitive neuroectodermal tumour (PNET) IV

Atypical teratoid / rhabdoid tumour IV

SchwannomaNeurilemmomabenign nerve sheath tumor composed of Schwann cells which normally produce the insulating myelin sheath covering peripheral nervesvery homogeneous tumorsconsisting only of Schwann cellstumor cells always stay on the outside of the nervebut the tumor itself may either push the nerve against a bony structure thereby possibly causing damagerelatively slow growingmostly benign < 1% become malignantdegenerating into a form of cancer known as neurofibrosarcomacan arise from a genetic disorder called neurofibromatosiscan be removed surgically but can then recur

Tumours of the cranial and paraspinal nerves

Tumour Grade

Schwannoma I

Neurofibroma I

Perineurioma I , II , III

Malignant peripheral nerve sheath tumour (MPNST) II , III , IV

Meningeal tumoursWHO classification

Tumour Grade

Meningioma I

Atypical meningioma II

Anaplastic / malignant meningioma III

Haemangiopericytoma II

Anaplastic haemangiopericytoma III

Haemangioblastoma I

Meningiomasecond most common primary tumor of the central nervous system arising from the arachnoid "cap" cells of the arachnoid villi in the meninges

usually - benign - can be malignant

Causesmost - sporadic some - familialrisk factor - radiation to the scalp genetic mutations - inactivation mutations in the neurofibromatosis 2 gene (merlin) on chromosome 22q

Signs and symptomsSmall tumors (e.g., < 2.0 cm) - usually incidental findings at autopsy - without having caused symptoms

Larger tumors - symptoms depending on the size and location

Increased ICP eventually occurs but is less frequent than in gliomas

Location being overlied Presentation

cerebrum Focal seizures

parasagittal frontoparietal region Progressive spastic weakness in legs and incontinence

Sylvian tumors myriad motor, sensory, aphasic, and seizure symptoms depending on the location

Mechanismarise from arachnoidal cells most of which are near the vicinity of the venous sinuses (site of greatest prevalence for meningioma formation)

most frequently attached to the dura over the superior parasagittal surface of frontal and parietal lobes along the sphenoid ridge, in the olfactory grooves, the sylvian region, superior cerebellum along the falx cerebri, cerebellopontine angle, and the spinal cord

Tumour - gray, well-circumscribed, and space occupies dome-shaped, with the base lying on the dura

Cells - relatively uniform, (histologically) with a tendency to encircle one another - forming whorls and psammoma bodies (laminated calcific concretions) - have a tendency to calcify and are highly vascularized

Diagnosisvisualized with - contrast CT - MRI with gadolinium - arteriography lumbar puncture protein is usually elevated

A contrast enhanced CT scan of the braindemonstrating the appearance of a Meningioma

Classification of meningiomasbased upon the WHO classification system

majority of meningiomas are benign some - malignant

Type Grade %

Benign I 90% meningothelial, fibrous, transitional, psammomatous, angioblastic

Atypical II 7% choroid, clear cell, atypical

Anaplastic/malignant III 2% papillary, rhabdoid, anaplastic

Tumour type Mean overall survival Mean relapse free survival

Atypical 11.9 years 11.5 years

Anaplastic/malignant 3.3 years 2.7 years

Treatment

Observation

Observation with close imaging follow-up can be used in select cases if a meningioma is small and asymptomatic

Observation is not recommended in tumors that are already causing symptoms

Conventional chemotherapy likely not effective

Surgical resectioncan usually be surgically resected with permanent cure if the tumor is - superficial on the dural surface - and easily accessible

Transarterial embolization standard preoperative procedure in the preoperative management

If invasion of the adjacent bone occurs total removal is nearly impossible

Malignant transformation is rare

probability of tumor recurrence estimated - by the tumor's WHO Grade and - by the extent of surgery by the Simpson Criteria

Tumour recurrence estimationSimpson Criteria

Simpson Grade Completeness of Resection 10-year Recurrence

I complete removal including resection of underlying bone and associated dura

9%

II complete removal + coagulation of dural attachment

19%

III complete removal w/o resection of dura or coagulation

29%

IV subtotal resection 40%

Radiation therapy

Gamma Knife radiosurgery small tumors located away from critical structures

fractionated external beam radiation primary treatment for tumors that are surgically unresectable

inoperable for medical reasons

INDICATIONS FOR POST- OPERATIVE RADIATION

WHO GRADE TUMOUR RESECTIONS

Grade I subtotal (incomplete)

Grade II Complete or incomplete

Grade III Complete or incomplete

PITUITARY TUMOUR

10 – 50 % of all cranial tumourMajority - benignMetastasis - may occur especially in elderly

One type of sellar region tumourDifferential diagnosis of sellar region mass - craniopharyngioma - meniongioma - aneurysm - Rathke’s cleft cyst

Clinical features

Mass effect - bitemporal hemianopia - pressure on optic chiasma - cranial nerve III, IV, VI disorderEndocrine disturbance

TUMOUR PRESENTATIONS

Prolactinoma GalactorrhoeaAmenorrhoea (P’,2’)

ACTH – producing tumour Cushing syndrome

GH – secreting tumour Acromegalygigantism

Clinical syndrome for secretory pituitary tumor

Type of adenoma

Secretion

Staining Pathology %

corticotrophic

(ACTH) (POMC)

basophilic Cushing's disease 15 %

somatotrophic

(GH) acidophilic Acromegaly(gigantism)

20 %

thyrotrophi (TSH) basophilic hyperthyroidism 1 %

gonadotrophic

(LH) (FSH)

basophilic 1- 2 %

lactrotrophic /

prolactinomas

prolactin

acidophilic galactorrhea, hypogonadism, amenorrhea,infertility,impote

nce

40 %

null cell α subunit

synaptophysin

20 %

Tumours of the sellar regionTumour Grade

Craniopharyngioma I

Granular cell tumour of the neurohypophysis I

Pituicytoma I

Spindle cell oncocytoma of the adenohypophysis I

Pituitary apoplexy

Hemorrhagic infarction of pituitary tumourPresentations - sudden onset of - headache - visual loss - opthalmoplegia - altered concious levelSudden onset of headache & meningism similar to SAHManagement - preoperative resuscitation - urgent decompression

InvestigationFormal visual field & acuity testImaging - MRI scanof pituitary regionBaseline assesment of pituitary function - prolactin - fasting serum - urinary cortisol - Growth hormopne - Insulin like growth factor 1 - Folicular stimulating hormone - Leutinizing hormone - Thyroid function

Investigation

Essential assesment - endocrine status - ACTH cortisol axis - Cortisol deficiency must be corrected (pre- op) - Diagnosis of ACTH secreting tumour is difficult - Petrosal sinus sampling - Dexamethasone supression test

- Prolactin - high Prolactin level - Prolactinoma - preclude the need for surgery (Pituitary stalk compression - moderately elevate prolactin level)

ManagementAIM - to alleviate mass effect - restore or replace endocrine function - prevent recurrenceClose co-operation of - Neurosurgeon - Endocrinologist

Prolactinoma - initial treatment - medically - Dopamine agonist - Cabergoline - BromocryptineGrowth hormone secreting tumour - medically - Somatostatin analogues - Octreotide - Dopamine agonist

Surgical treatmentTranssphenoidal Surgery - operating microscope - endoscope assistedLarge tumour with suprssellar extension - CraniotomyTranssphenoidal Surgery Complication

- pituitary stalk manipulation - Diabetes insipidusDetermination of surgical success (transient)

Complication Percentage

CSF leakage 3 %

Visual deterioration 1 %

Major vessel injury 1 %

Pan hypo pituitarism 1 %

Normalisation of endocrine dysfunction

Lack & Recurrence Vs condition being treated

Size of tumor

Metastatic brain tumorA metastatic brain tumor is brain cancer that has spread from another part of the bodyCausesMany tumor or cancer types can spread to the brainmost common lung cancer, 40 % breast cancer, 10 – 30 % melanoma, 5 – 15 % kidney cancer, bladder cancer, certain sarcomas, testicular and germ cell tumors, and a number of others 15 %Some types of cancers only spread to the brain infrequently - colon cancer, very rarely - prostate cancerunknown primary (CUP) origin Infrequently, a tumor can spread to the brain, yet the original site or location of the tumor is unknown 10 - 30% of adult cancers

INCIDENCEmore common than primary brain tumorsabout one-fourth of all cancers that metastasize 10 - 30% of adult cancers

81 % - diagnosed after their primary cancer has been diagnosed and treated35 % - have not been previously diagnosed

Lung, colon and renal cancers - 80 % of metastatic brain tumors in menBreast, lung, colon and melanoma cancers - 80 % of metastatic brain tumors in women

incidence increased over time - advances in neuroimaging procedures - improvements in treatment of primary tumour and systemic diseasemedian survival - approximately one month without any treatment two months with corticosteroids three to six months with cranial irradiation

CHARACTERISTICS OF METASTATIC BRAIN TUMORS

in the - cerebrum (80%), - cerebellum (13-16%) - brain stem (3%)

usually solid and spherical in shape with well-defined margins, center is often soft and filled with dead cells zone of active tumor cells ( ringlike structure on the scan )

commonly grow in the junction of white and grey matter (most blood vessels)

50% of the time multiple tumors

usually accompanied by widespread edema

exact diagnosis - biopsy sometimes recommended to eliminate the chance of misdiagnosis

Exams and Testsexamination - neurologic changes specific to the location of the tumor - Signs of increased ICP - Some -no symptoms until they are very large. Then, rapid decline in neurologic functionInvestigationCT scan or MRI of the brain confirm the diagnosis identify the location of the tumor. MRI - better Cerebral angiography show a space-occupying mass which may or may not be highly vascular (filled with blood vessels).chest x-ray, mammogram, CT scans of the chest, abdomen, and pelvis, and other tests are performed to look for the original site of the tumor.EEG may reveal abnormalities.Histology - specimen from the tumor during surgery or CT scan-guided biopsy is used to confirm the exact type of tumor If the primary tumor can be located outside of the brain, primary tumor is usually biopsied rather than the brain tumor.lumbar puncture - to test the cerebral spinal fluid.

Treatmentdepends on - size and type of the tumor - initial site of the tumor - general health of the persongoals of treatment - relief of symptoms - improved functioning - comfort

Radiation - whole brain is often used - especially > one tumor

external irradiation - total dose of 3000 cGy to the entire brain - 300 cGy portions five days a week, for two weeks - followed by a booster dose of 900 cGy to the tumor - often follows brain surgery standard treatment - whole brain radiotherapy (WBRT)

Surgery - a single lesion and when there is no cancer elsewhere in the body - some - completely removed - deep or that infiltrate brain tissue - debulked (reduce tumor size) - reduce pressure and relieve symptoms in cases when the tumor cannot be removedKarnofsky Performance Scale 100 Normal; no complaints; no evidence of disease 90 Able to carry on normal activity; minor signs or symptoms of disease 80 Normal activity with effort; some signs or symptoms of disease 70 Cares for self; unable to carry on normal activity or to do active work 60 Requires occasional assistance but is able to care for most of needs > 60 or 70, surgery could be considered, if other factors are favorable

Chemotherapy - not as helpful as surgery or radiation for many types of cancer. - does not pass the blood brain barrier - metastatic from breast cancer cyclophosphamide, 5-FU, and methotrexate. Tamoxifen

Medications for some symptoms of a brain tumor Corticosteroids such as dexamethasone to reduce brain swellingOsmotic diuretics such as urea or mannitol to reduce brain swellingAnticonvulsants such as phenytoin to reduce seizuresPain medicationAntacids or antihistamines to control stress ulcers

multiple metastases (widespread cancer) treatment - relief of pain and other symptomsComfort measures, safety measures, physical therapy, occupational therapy -to improve the patient's quality of life. Legal advice may be helpful in forming advanced directives, such as power of attorney, in cases where continued physical or intellectual decline is likely

Brain tumors in infants and childrenMost common solid tumor in childrensecond most common tumour (haematological dis orders)20 per cent of childhood malignancies2—5 cases per 100 000male preponderance of 1.2:1

Brain tumors in infants and children

Neonates - neuroectodermal origin - mostly in supratentorial

tumor types - teratoma - primitive neuroectodermal tumor - high grade astrocytoma - choroid plexus papilloma / carcinoma

Children < 2 years - mostly in infratentirial

tumor types - medulloblastoma - Ependymoma about 70% of brain tumors - Pilocystic astrocytoma

Germ cell tumors, including teratoma 3% of pediatric primary brain tumors

Brain tumors in infants and children

survival rate in children - approximately 60% - varies with - type of cancer - age of onset: younger patients have higher mortality

brain-stem glioma in four year old MRI sagittal, without contrast

Focal neurologic signs

perceptual or behavioral impairments which are caused by lesions in a particular area of the central nervous system.disease process is focal rather than diffuseFocal disease processes include tumors or infarctions; Diffuse disease processes include meningitis or encephalitis

Frontal lobe signsusually involve the motor system, and may include many special types of deficit, depending on which part of the frontal lobe is affectedunsteadiness in walking muscular rigidity, resistance to passive movements of the limbs (hypertonia) paralysis of a limb (monoparesis) or a larger area on one side of the body (hemiparesis) paralysis head and eye movements inability to express oneself linguistically, described as an expressive aphasia (Broca's aphasia) focal seizures which can spread to adjacent areas (Jacksonian seizure) grand mal or tonic-clonic seizure

Frontal lobe signs changes in personality disinhibition, inappropriate jocularity, rage without provocation; loss of initiative and concern, apathy, akinetic mutism, general retardation "frontal release" signs, i.e. reappearance of primitive reflexes snout reflex, the grasp reflex, palmar-mental reflex unilateral loss of smell (anosmia)

Parietal lobe signsusually involve somatic sensationimpairment of tactile sensation impairment of proprioception, i.e. postural sensation and sensation of passive movement sensory and visual neglect syndromes, i.e. inability to pay attention to things in certain parts of the person's sensory or spatial environment. This can be as extreme as denial of a limb. loss of ability to read, write or calculate (dyslexia, dysgraphia, dyscalculia) loss of ability to find a defined place (geographical agnosia) loss of ability to identify objects based on touch (astereognosia)

Temporal lobe signs

usually involve auditory sensation and memorydeafness without damage to the structures of the ear, described as cortical deafness tinnitus, auditory hallucinations loss of ability to comprehend music or language, described as a sensory aphasia (Wernicke's aphasia) amnesia, memory loss (affecting either long- or short-term memory or both) other memory disturbances such as deja vu complex, multimodal hallucinations

complex partial seizures (temporal lobe epilepsy)

Occipital lobe signsusually involve visual sensationtotal loss of vision (cortical blindness) loss of vision with denial of the loss (Anton's syndrome) loss of vision on one side of the visual field of both eyes (homonymous hemianopsia) visual agnosias, i.e. inability to recognize familiar objects, colors, or faces visual illusions such as micropsia (objects appear smaller) and macropsia (objects appear larger) visual hallucinations, displaying elementary forms, such as zig-zags and flashes, in one half of the visual field only for each eye. (In contrast, temporal lobe visual hallucinations display complex forms, and fill the entire visual field.)

Cerebellar signsinvolve balance and coordinationunsteady and clumsy motion of the limbs or torso (ataxia) inability to coordinate fine motor activities (intention tremor) e.g. "past-pointing" (pointing beyond the finger in the finger-nose test) inability to perform rapid alternating movements (dysdiadochokinesis), e.g. inability to rapidly flip the hands involuntary left-right eye movements (nystagmus)

Brainstem signs

specific sensory and motor abnormalities depending on which fiber tracts and cranial nerve nuclei are affected

Spinal cord signs

generally involve unilateral paralysis with contralateral loss of pain sensation

Stereotactic surgery

The first stereotactic frame is attributed to Horsley and Clarkprinciple of stereotaxy is that described by Descartes;any point in space can be identified in relation to three planes running perpendicular to each other

frame-based stereotaxy

a device is fixed to the head, so that the co-ordinates of any point within the confines of the frame itself or an imaginary extension of it can be accurately localised. This requires CT or MRI to be per formed after the frame has been applied to the head, so that the position of the region of interest can be related to the frame used not only for tumour biopsy but also for localising cranio tomies for minimally invasive excision of tumoursfor catheter placement, for drug or isotope delivery or cyst drainage

frameless stereotaxy

An extension of the stereotactic process is to obtain a preoperative scan without the use of a frame and then use a mathematical algorithm to correlate with the surface markings of the skull at the time of surgeryless clumsy and time consuming