122 malignant gliomas anaplastic astrocytoma gb gliosarcoma

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Chapter 122 Malignant Gliomas : Anaplastic Astrocytoma Glioblastoma Multiforme Gliosarcoma Youmans,Neurological surgery 15/12/2015

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Chapter 122 Malignant Gliomas : Anaplastic AstrocytomaGlioblastoma MultiformeGliosarcomaYoumans,Neurological surgery15/12/2015

OutlineEpidemiologyClinical manifestationHistopathologyNeuroimaging studiesManagement

Epidemiology : Anaplastic Astrocytoma (WHO grade III)Glioblastoma Multiforme(WHO grade IV)Most common primary brain tumor in adultsMedian age : AAs 40 yrs, GBM 53 yrsGBM is more common in men, with a male-to-female ratio of 1.5:1

Epidemiology : Gliosarcoma2% and 8% of cases of GBM (WHO grade IV)Clinical findings and prognosis are similar in gliosarcoma and GBMMean age of 53 Yrs(40-60 Years)Male-to-female ratio of 1.8 : 1May also occur in children

Clinical manifestation : Anaplastic Astrocytoma Glioblastoma MultiformeCerebral hemispheresCan arise from low-grade astrocytoma (WHO grade II)AAs can progress to GBM and recur locally,often at the margins of the tumor resectionSymptoms and signs are nonspecific in patients with GBMraised intracranial pressureextraocular palsies, objective papilledema, pupil abnormalities, or decreased level of consciousness

Clinical manifestation : Anaplastic Astrocytoma Glioblastoma MultiformeProminent in the morning and improve over the course of the dayProgressive headaches are a hallmark of the symptomatology of these tumorsSeizure

Clinical manifestation : GliosarcomaMost common : Temporal lobe, also occur in parietal, frontal, occipital lobesMultifocal display of cerebral and cerebellar gliosarcomasCan spread into the cerebrospinal fluid pathways and invade the ventricles, cranial nerves, leptomeninges, and spinal cordTendency toward peripheral brain localization and dural attachment

Clinical manifestation : GliosarcomaMetastasis much more frequently than glioblastomaMost common symptoms : headache, hemiparesis, nausea, seizures, and personality changeMost common signs : focal weakness, visual field defects, papilledema, and dysphasia

Clinical manifestation : Gliosarcoma

Histopathology : Anaplastic Astrocytoma Glioblastoma MultiformeMorphology is the gold standard Pilocytic astrocytoma (WHO grade I)Low-grade astrocytoma (WHO grade II)nuclear atypia, no mitosisAnaplastic Astrocytoma (WHO grade III)mitotic activity and nuclear atypiaGlioblastoma Multiforme (WHO grade IV)nuclear atypia, mitoses, and endothelial proliferation or necrosis

Atypia pleomorphism10


Histopathology : Anaplastic Astrocytoma Glioblastoma MultiformeMIB-1 /Ki-67 labeling index increases proportionally with tumor gradeAA (WHO grade III) : 5-10%GBM (WHO grade IV) : 10-20%

Primary glioblastomasSecondary glioblastomas

> 50 yearsyounger patients as low-grade astrocytoma or AA and then transform over a period of several years into glioblastomaMutation or amplification of EGFRoverexpression of platelet-derived growth factor receptor (PDGFR)

loss of heterozygosity of chromosome 10q loss of heterozygosity of chromosome 10qdeletion of the phosphatase and tensin homologue on chromosome 10 (PTEN)mutations in the TP53 tumor suppressor gene

deletion of chromosome p16.abnormalities in the p16 mutation of isocitrate dehydrogenase 1 (IDH1)

Molecular biology

-epidermal growth factor (EGF) receptror -TP53 P53 2 1) 2) 2 -LOH allel heterozygosity


Histopathology : GliosarcomasCharacterized by a biphasic tissue pattern with glial and mesenchymal componentGlial portion : astrocytes with nuclear atypia and mitotic figuresSarcomatous region : neoplastic mesenchymal cells with associated reticulin formationGlial fibrillary acidic protein (GFAP) immunostaining : distinguishing between gliosarcoma and other tumors such as glioblastoma or pure sarcoma


Histopathology : GliosarcomasVimentin : marker for mesenchymal cells, occurs mostly in sarcomatous areas with scarce staining in glial regionsGrosstough, well-circumscribed lobular mass often attached to the dura and at surgery may resemble a meningiomacontain areas of necrosisThe sarcomatous component of these tumors is firm and well circumscribed

Neuroimaging studies : Anaplastic Astrocytoma Glioblastoma MultiformeMRIT1 : irregular hyposignal with various degrees of contrast enhancementRing-like enhancement surrounding irregularly shaped areas : suggests glioblastomaHowever, AAs can appear as nonenhancing tumors, and even glioblastomas may initially be manifested as a nonenhancing lesions, especially in older patients

Neuroimaging studies : Anaplastic Astrocytoma Glioblastoma MultiformefMRIlocations of functionally eloquent cortex, such as the motor cortex, Brocas area, Wernickes area, and the visual cortexPseudoprogression : increased enhancement reflects a transient increase in vessel permeability that is a result of radiotherapyMagnetic resonance spectroscopy(MRS) : differentiate tumors from stroke, old trauma, radionecrosis, infection, and multiple sclerosis

Neuroimaging studies : Anaplastic Astrocytoma Glioblastoma MultiformeFluorodeoxyglucose positron emission tomography (FDG-PET)effective in demonstrating hypermetabolism in high-grade tumorsdistinguishing tumor or tumor recurrence from radionecrosis

Neuroimaging studies : GliosarcomasMRIT1 : well demarcated hyperdense mass with heterogeneous or irregular ring enhancementT2 : isosignal with surrounding edemaIntraaxial superficial with a dural baseVasogenic edemaCentral hypodensity, as a result of necrosis, is less common in gliosarcomas

Management : General Medical ManagementSeizureSelecting antiepileptic drugs to prevent drug interactions(phenytoin,carbamazepine)Prefer levetiracetamAAN : advises against the routine use of antiepileptic drugs in patients who have never had a seizureVenous thromboembolismanticoagulation therapyLMWH may be more effective and safer than warfarin

American academy of neurology21

Management : General Medical ManagementPeritumoral edemaCorticosteroid(dexamethasone)Side effect : Cushings syndrome, corticosteroid myopathy, Pneumocystis jiroveci pneumonitisNew therapy : corticotropin releasing factor, bevacizumab (VEGF monoclonal antibody), VEGF receptor inhibitorsFatigueMethylphenidate for abuliaDonepezil and memantine may reduce memory loss

Donepezil Rx Alzheimer disaseMethylphendinate : stimulate sympathetic systemAbulia lack of will power22

Management : SurgeryGoalobtain a tissue diagnosisdecrease the mass effectreduce the tumor burden

Retrospective study24

ManagementRadiation TherapyChemotherapy

Carmustine-loaded biodegradable polymersRCTImprove survival : 23 weeks to 31 weeks after revision resectionSurgery time to death : 58 weeks vs 39 weeks placeboMedian survival time : 13.8 months vs 11.6 months placebo

ManagementRadiation TherapyChemotherapy

Most effective treatment

ResectionCarmustine-loaded biodegradable wafers TemodarRadiation therapy

20 Months

Tenodar Temozolamide26

ManagementRadiation TherapyChemotherapyO6-Methylguanine-DNA methyltransferase (MGMT)Repair enzyme that contributes to resistance of tumors to alkylating agents such as carmustine or Temodar

Management : GliosarcomaSurgeryfirm, well demarcated, and vascularcan be excised to achieve gross macroscopic clearanceChemotherapyRadiotherapyAll patientIncrease survival 8-15 wks

Patient outcome and survivalMedian survival is less than 2 yearsAnaplastic glioma : 2-5 yearsAge and KPS score are the most significant prognostic factors

Gliosarcoma : 6 - 14.8 months