Youmans Neurological Surgery

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

2. Outline
• Epidemiology
• Clinical manifestation
• Histopathology
• Neuroimaging studies
• Management

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

4. Epidemiology : Gliosarcoma
• 2% and 8% of cases of GBM (WHO grade IV)
• Clinical findings and prognosis are similar in
gliosarcoma and GBM
• Mean age of 53 Yrs(40-60 Years)
• Male-to-female ratio of 1.8 : 1
• May also occur in children

5. Clinical manifestation :
Anaplastic Astrocytoma
Glioblastoma Multiforme
• Cerebral hemispheres
• Can arise from low-grade astrocytoma (WHO grade II)
• AAs can progress to GBM and recur locally,often at
the margins of the tumor resection
• Symptoms and signs are nonspecific in patients
with GBM
– raised intracranial pressure
– extraocular palsies, objective papilledema, pupil
abnormalities, or decreased level of consciousness

6. Clinical manifestation :
Anaplastic Astrocytoma
Glioblastoma Multiforme
• Prominent in the morning and improve over the
course of the day
• Progressive headaches are a hallmark of the
symptomatology of these tumors
• Seizure

7. Clinical manifestation :
Gliosarcoma
• Most common : Temporal lobe, also occur in
parietal, frontal, occipital lobes
• Multifocal display of cerebral and cerebellar
gliosarcomas
• Can spread into the cerebrospinal fluid pathways
and invade the ventricles, cranial nerves,
leptomeninges, and spinal cord
• Tendency toward peripheral brain localization and
dural attachment

8. Clinical manifestation :
Gliosarcoma
• Metastasis much more frequently than glioblastoma
• Most common symptoms : headache, hemiparesis,
nausea, seizures, and personality change
• Most common signs : focal weakness, visual field
defects, papilledema, and dysphasia

9. Clinical manifestation :
Gliosarcoma

10. Histopathology :
Anaplastic Astrocytoma
Glioblastoma Multiforme
• Morphology is the “gold standard”
– Pilocytic astrocytoma (WHO grade I)
– Low-grade astrocytoma (WHO grade II)
• nuclear atypia, no mitosis
– Anaplastic Astrocytoma (WHO grade III)
• mitotic activity and nuclear atypia
– Glioblastoma Multiforme (WHO grade IV)
• nuclear atypia, mitoses, and endothelial
proliferation or necrosis

13. Histopathology :
Anaplastic Astrocytoma
Glioblastoma Multiforme
• MIB-1 /Ki-67 labeling index increases proportionally
with tumor grade
– AA (WHO grade III) : 5-10%
– GBM (WHO grade IV) : 10-20%

14. Primary glioblastomas Secondary glioblastomas
> 50 years younger patients as low-grade astrocytoma or
AA and then transform over a period of several
years into glioblastoma
Mutation or amplification of EGFR overexpression of platelet-derived growth
factor receptor (PDGFR)
loss of heterozygosity of chromosome 10q loss of heterozygosity of chromosome 10q
deletion 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

15. Histopathology :
Gliosarcomas
• Characterized by a biphasic tissue pattern with
glial and mesenchymal component
• Glial portion : astrocytes with nuclear atypia and
mitotic figures
• Sarcomatous region : neoplastic mesenchymal cells
with associated reticulin formation
• Glial fibrillary acidic protein (GFAP) immunostaining
: distinguishing between gliosarcoma and other
tumors such as glioblastoma or pure sarcoma

16. Histopathology :
Gliosarcomas
• Vimentin : marker for mesenchymal cells, occurs
mostly in sarcomatous areas with scarce staining in
glial regions
• Gross
– tough, well-circumscribed lobular mass often attached to
the dura and at surgery may resemble a meningioma
– contain areas of necrosis
– The sarcomatous component of these tumors is firm and
well circumscribed

17. Neuroimaging studies :
Anaplastic Astrocytoma
Glioblastoma Multiforme
• MRI
– T1 : irregular hyposignal with various degrees of
contrast enhancement
– Ring-like enhancement surrounding irregularly
shaped areas : suggests glioblastoma
– However, AAs can appear as nonenhancing
tumors, and even glioblastomas may initially be
manifested as a nonenhancing lesions, especially
in older patients

18. Neuroimaging studies :
Anaplastic Astrocytoma
Glioblastoma Multiforme
• fMRI
– locations of functionally eloquent cortex, such as
the motor cortex, Broca’s area, Wernicke’s
area, and the visual cortex
• Pseudoprogression : increased enhancement
reflects a transient increase in vessel permeability
that is a result of radiotherapy
• Magnetic resonance spectroscopy(MRS) :
differentiate tumors from stroke, old trauma,
radionecrosis, infection, and multiple sclerosis

19. Neuroimaging studies :
Anaplastic Astrocytoma
Glioblastoma Multiforme
• Fluorodeoxyglucose positron emission tomography
(FDG-PET)
– effective in demonstrating hypermetabolism in high-
grade tumors
– distinguishing tumor or tumor recurrence from
radionecrosis

20. Neuroimaging studies :
Gliosarcomas
• MRI
– T1 : well demarcated hyperdense mass with
heterogeneous or irregular ring enhancement
– T2 : isosignal with surrounding edema
– Intraaxial superficial with a dural base
– Vasogenic edema
– Central hypodensity, as a result of necrosis, is less
common in gliosarcomas

21. Management : General Medical Management
• Seizure
– Selecting antiepileptic drugs to prevent drug
interactions(phenytoin,carbamazepine)
– Prefer levetiracetam
– AAN : advises against the routine use of antiepileptic
drugs in patients who have never had a seizure
• Venous thromboembolism
– anticoagulation therapy
– LMWH may be more effective and safer than warfarin

22. Management : General Medical Management
• Peritumoral edema
– Corticosteroid(dexamethasone)
– Side effect : Cushing’s syndrome, corticosteroid
myopathy, Pneumocystis jiroveci pneumonitis
– New therapy : corticotropin releasing factor,
bevacizumab (VEGF monoclonal antibody),
VEGF receptor inhibitors
• Fatigue
– Methylphenidate for abulia
– Donepezil and memantine may reduce memory loss

23. Management : Surgery
• Goal
– obtain a tissue diagnosis
– decrease the mass effect
– reduce the tumor burden

25. Management
Radiation Therapy
Chemotherapy
• Carmustine-loaded biodegradable polymers
• RCT
• Improve survival : 23 weeks to 31 weeks after revision resection
• Surgery time to death : 58 weeks vs 39 weeks placebo
• Median survival time : 13.8 months vs 11.6 months placebo

26. Management
Radiation Therapy
Chemotherapy
• Most effective treatment
• Resection
• Carmustine-loaded
biodegradable wafers
• Temodar
• Radiation therapy
• 20 Months

27. Management
Radiation Therapy
Chemotherapy
• O6-Methylguanine-DNA methyltransferase
(MGMT)
• Repair enzyme that contributes to resistance of
tumors to alkylating agents such as carmustine
or Temodar

28. Management : Gliosarcoma
• Surgery
– firm, well demarcated, and vascular
– can be excised to achieve gross macroscopic
clearance
• Chemotherapy
• Radiotherapy
• All patient
• Increase survival 8-15 wks

29. Patient outcome and survival
• Median survival is less than 2 years
• Anaplastic glioma : 2-5 years
• Age and KPS score are the most significant
prognostic factors
• Gliosarcoma : 6 - 14.8 months