Brainstem glioma part 1

BRAINSTEM GLIOMAS
Dr NAJEEB C A
PART ONE

• By definition, BSGs are tumors that arise
within the anatomic structures that make
up the brainstem (m i d b r a i n , t h e p o n s ,
o r t h e m e d u l l a o b l o n g a t a )
• This definition excludes patients with
tumors originating in the t h a l a m u s and
h y p o t h a l a m u s or lesions originating
in the c e r e b e l l u m , c e r e b e l l a r
p e d u n c l e s , or u p p e r c e r v i c a l
s p i n a l c o r d

<1980
• Because of its difficult
accessand
functional
importance, in the
past, the brainstem was
seldom
exploredby
neurosurgeons, with its injury
often conducive to deep coma
• For many years, a tumor
growing inside the brainstem
was considered
malignantin itself and
managed empirically as a
homogeneous
• B a i l e y et al (1939) - ‘BSG are a
hopeless problem for treatment’
• D a n d y (1962) - ‘ There is little
indication for attempting any
enucleation of the tumor in this
region
• M a t s o n (1969) - Regardless of
specific histology, brainstem
gliomas must be classified as
malignant tumors since their
location in itself renders them
inoperable
• B a k e r (1964) - published a
series of pts with ‘subependymal
gliomas’
• Pool (1968) - First
reported case of
surgical resection of
BST located in the area

>1980
• Gradual advancement in
mi cr osur gi cal
techni ques , sophisticated
imaging technology, most importantly
availability of MRI
• Identification of subcategor ies
of tumors which appear to have low -
gr ade pathologies and offer a better
prognosis
• D i f f e r e n t s e r i e s o n B S G s i n c e

• Location
• Focality
• Growth
• Imaging
• DIBG & Non
diffuse (Focal) BG
• F o c a l
- <50% of the axial
brainstem
diameter
• D i f f u s e
- Poorly
demarcated

• MIDBRAIN (7 - 8%)
- Almost always low-grade
pilocytic astrocytomas
(WHO I & II)
- Good prognosis
• PONS (80 %)
- Usually High grade
astrocytomas (WHO III &
IV)
- Dismal prognosis
• MEDULLA (10 - 15%)
- Usually low grade pilocytic
astrocytomas (WHO I & II)
- Good to fair prognosis
Brainstem gliomas – A clinicopathological study of 45 cases with p53
immunohistochemistry
Badhe Prerna B, Chauhan Pritika P, Mehta Nishaki K
Departments of Pathology, Seth G. S. Medical College and KEM Hospital,

Classification Schemes for Brain
Stem Tumors
Author Method Used to
Create System
Classification System
Epstein CT Intrinsic
Diffuse
Focal
Cervicomedullary
Exophytic
Anterolateral into CP angle
Posterolateral and into brachium pontis
Disseminated
Positive cytology
Positive myelography
Epstein
and
McCleary
CT, MRI, and
surgical
observation
Diffuse
Focal
Cervicomedullary

Stem Tumors
Author Method Used
to
Create System
Stroink
etal
CT Group I
dorsal exophytic glioma
Group IIa
intrinsic brainstem tumors - Hypodense, no
enhancement
Group IIb
intrinsic brainstem tumors - Hyperdense,
contrast enhancing exophytic
Group III
focal cystic tumor with contrast
enhancement

Stem TumorsAuthor Method Used
to
Create System
Barkovi
ch
MRI 1. Location (midbrain, pons,
medulla)
2. Focality (diffuse or focal)
3. Direction and extent of
tumor growth
4. Degree of brainstem
enlargement
5. Exophytic growth
6. Hemorrhage or necrosis
7. Evidence of hydrocephalus
Albrigh MRI 1. Focal (midbrain, pons,

Stem Tumors
Author Method Used to
Create System
Fischbein
et al
MRI 1. Midbrain
Diffuse
Focal
Tectal
2. Pons
Diffuse
Focal
3. Medulla
Diffuse
Focal
4. Dorsal exophytic
Choux et al CT and MRI Type I—diffuse
Type II—intrinsic, focal
Type III—exophytic, focal
Type IV—cervicomedullary

Epstein & Farmer Classification
1. DIPG (80%)
2. Focal Tumors (5%)
a) Tectal tumors
b) Pontine tumors
c) Midbrain tumors
3. Dorsal exophytic tumors(10 -15%)
4. Tumors of the cervicomedullary junction
(CMJ) 5 -10%
• Thalamic tumors - considered some authors
• CMJ tumors - considered by most to be a subgroup of BSGs, although some
clinicians believe that they are the most cephalic extension of cervical
intramedullary spinal cord tumors

Ref : Brainstem gliomas – A clinicopathological study of
45 cases with p53 Immunohistochemistry
Badhe Prerna B, Chauhan Pritika P, Mehta Nishaki ;
Departments of Pathology, Seth G. S. Medical College
and KEM Hospital, Parel, Mumbai, India
• 10 - 20% - primary pediatric
brain tumors (1 . 5 % - 2 . 5 %
adults)
• 25% - posterior fossa tumors
• Incidence – 150 - 300 / year
• Mean age - 6.5 - 9 yrs;
Rare<3 yrs
• No predilection gender or race
• No outstanding genetic
inheritance
• No sufficient data - Geographic
propensity
• No specific risk factors -
Environmental or infectious
• DPGs - most commonly seen BSGs
in the pediatric population and
represent approximately 60% to 75% of
these tumors

SIGNS AND SYMPTOMS
• Typically, a combination of cranial nerve
dysfunction and long-tract signs is
considered suggestive of a brainstem lesion

• Clinical behavior and presentation highly variable –
Depends on location, growth pattern, age etc
• Symptom evolution reflects aggressiveness
• Insidious course , Gradual evolution = LOW-GRADE
TUMORS
• Shorter and more abrupt onset = HIGHER GRADE TUMORS
• NONDIFFUSE GLIOMAS
- Low grade lesions ; slow growth
- Insidious onset and may not be readily appreciated
• Careful history
• DIPG
• High grade
- Short prodrome of symptoms
- 1-2 months or shorter

• Pattern of symptoms reflects the extent of the tumor
• DIPG
- Multiple and bilateral cranial neuropathies
- Long tract signs and ataxia
- Hydrocephalus uncommon initially
- Isolated cranial neuropathies
- Signs and symptoms of increased intracranial
pressure, and ataxia
- Hemiparesis – Rare

• Cranial neuropathies are common in most
tumors of the brainstem
- Simultaneous involvement of multiple
cranial nerves = DIPG
- Focal lesions - Limited cranial nerve
involvement
• Upper brainstem - Oculomotor deficits
• Pons – VI, VII
• Lower brainstem - Lower cranial nerve
involvement (Changes in voice, dysphagia and/or
aspiration pneumonias)

• Long tract signs (motor dysfunction and
hyperreflexia) - Diffusely growing tumors / Focal
tumors of CMJ
Long tract signs - Conspicuously absent with
dorsal exophytic gliomas
• Ataxia - Loss of proprioceptive sensation, CN VIII
involvement and/or invasion of cerebellar
peduncles, Frequent in DIPG
• Obstructive hydrocephalus – Usually first
sign in focal tectal gliomas (compression of
cerebral aqueduct); In dorsal exophytic gliomas
(Grow dorsally into 4th ventricle)
• Failure to thrive - Infants (CMJ - swallowing
difficulties)

Diffuse Pontine Glioma
• Classic triad
1. Cerebellar dysfunction - 87%
2. Multiple lower cranial nerve palsies - 77%
3. Motor paresis and sensory changes (long-tract involvement) – 53%
• Diagnosis on a clinical basis alone
• The extent and duration of symptoms – Less than expected
• Relatively short, 94% - Less than 6 months
• Duration of symptoms
- Predictor of outcome
- Better outcome  6 months or longer
- Worse outcome  1 month or less

Diffuse Pontine Glioma
• Most commonly affect VI, VII, IX, and X, and most have diplopia
• Isolated cranial nerve palsy of longer duration (VII) - Better outcome
and longer survival
• Other clinical signs
Cerebellar peduncles – Ataxia (truncal or appendicular)
Long tracts/cerebral peduncles – Hemiparesis, rarely sensory changes
• Obstruction of the fourth
ventricle is rare!
• Hydrocephalus – 20%
• But frequent at the time of tumor progression

Tectal Glioma
• Hydrocephalus (aqueductal
stenosis)
• Classic Parinaud syndrome is
not common
• Most have had a long standing history of headaches
and on occasion “clumsiness” or ataxia
• Oculomotor palsy – rare
• Macrocephaly
• Rapidly progressive symptoms - Atypical or more
aggressive tectal gliomas (tend to occur in younger patients)

Focal Tumors
• Anywhere in brainstem
• Symptoms reflect the involved anatomic structures
• MIDBRAIN lesions
1. Hydrocephalus
2. Focal neurological deficits
• PONTINE lesions
1. Isolated facial palsies
2. Long-tract signs
3. Hearing loss
• MEDULLA OBLONGATA
1. Lower cranial nerves palsies
2. Respiratory difficulties (including apnea)
3. Recurrent upper respiratory tract infections and pneumonia, and
swallowing difficulties with aspiration of food and saliva
4. In infants
- Failur e to thr iv e
- Gag r eflex affec ted
- Tongue as y mmetr y.

Exophytic Tumors
• Difference - only BSG originating from
subependymal glia in the floor of
the fourth ventricle and growing
posteriorly, thereby filling the fourth ventricle
• Only ~ 10% of tumor mass growth occurs
in the brainstem - spared for a long time,
very gradually progressive symptoms
• Careful history - initial symptoms >1 year
• Hydrocephalus – 4th ventricle obstruction not
uncommon
- Intractable vomiting and failure to thrive in infants
- headaches, vomiting, and ataxia in older children
• Papilledema and torticollis - ICP & chronic
tonsillar herniation

Cervicomedullary Tumors
• Two clinical syndromes , depending on location of these
tumors at the junction between the medulla and cervical
spinal cord
1. Tumors arising in the medulla
 Lower cranial nerve dysfunction Failure to
thrive, dysphagia, dysarthria and dysphonia, chronic upper
respiratory tract infections and aspiration, and sleep apnea
2. Tumors arising in the cervical spinal cord
• Neck pain, torticollis, and sensorimotor deficits in limbs or
cervical myelopathy with weakness and spasticity
 Cranial nerve palsies are not typically encountered
• Hydrocephalus - Obstruction the fourth ventricle outlets
• The average duration of symptoms is 2.1 years (slowly
progressive and low-grade nature)

Cervicomedullary Tumors
• Similar to intramedullary spinal cord gliomas
• MRI – Delineates rostral and caudal pole; Identify syrinx
or cysts.
• Majority = Benign low grade astrocytomas
• Almost no infiltrative capacity and as a
consequence their growth is limited rostrally by
the decussating white matter tracts of the
corticospinal tract and medial lemniscus
which act as a barrier for further rostral growth
• Medullary tumors - Confined by the decussating fibers
and expand within the medulla, pushing the motor tracts
and nuclei peripherally
• Only high grade tumors with an infiltrative capacity grow
rostrally

BRAIN STEM GLIOMAS
Oguz <;ataltepe. M.D ..*. Ahmet <;olak.M.D..*.
Tunc;alp Ozgen. M.D..**. Aykut Erbengi. M.D..**.
Department of Neurosurgery. Faculty of Medicine.
Hacettepe University
Adult Brainstem Gliomas
GERMAN REYES-BOTERO,a,d,e,f KARIMA
MOKHTARI,b,d,e,f NADINE MARTIN-
DUVERNEUIL,c JEAN-YVES

• Gait disturbances. headache and
motor weakness were the most
common symptoms
• The most common finding was
cranial nerve involvement (90.3 %)
• Sixth and seventh nerve
involvement were the most
common; occurring in over 69 % of
cases.
• Nystagmus, evidence of cerebellar
disorders and pyramidal tract signs
were frequent manifestations
• Distinct from other tumour in that
they do not cause raised
intracranial pressure early in the
course of the disease despite all
these neurological signs
• Midbrain gliomas of the tectum
behave as very low-grade
lesions
• Focal tumors of the tectum
(te cta l glioma s ) begin to
cause significant neurological
symptoms when they enlarge
and compress the aqueduct of
Sylvius thereby producing
ob str uctive
hy d r oce p halus
• T e gme nta l tumor s can
present with
hy d r oce p halus and
oculomotor p a r e sis
with or without associated
long -tra ct find ings

CT
• Screening tool
- Tumor
- Hydrocephalus, or both
• Cannot delineate the exact location and
extent

DPG
1. Diffuse enlargement
of pons(diffuse pontine
hypertrophy)
2. Posterior
displacement of the
fourth ventricle
3. Hydrocephalus (rare)
4. Contrast enhanced images –
Nonhomogeneous
enhancement patterns and

• Focal tumors in the midbrain
and tectum
- Missed on CT
- False negative diagnosis
- Late onset aqueductal
stenosis
• Calcifications – Rare;
Implies an atypical BSG
• Single-Photon Emission CT
using thallium 201 –
Accumulation of the
radioactive tracer in the
tumor, which is 90% specific
for a BSG (Not correlated
with tumor grade,
enhancement patterns of
other contrast media, or

Magnetic Resonance Imaging
Preferred method

DPG
• T1
- Hypo to Isointense
- Diffuse enlargement of pons with
indistinct margins
- Underestimate true extent
• T2
- Best appreciated
- Hyperintense
• Characteristically engulf the basilar
artery ventrally
• Contrast enhancement – Variable
- Nonhomogeneous inside or around
the tumor or may be absent altogether
in 1/3
- Limited prognostic value
- Indicative of malignant degeneration
• Dissemination along the CSF
pathways
- 15%
DPG
A - Sagittal T1, showing diffuse enlargement of the pons
B - Sagittal T2
C – Axial FLAIR showing tumor engulfing the basilar
artery ventrally
D - T1 contrast demonstrating irregular enhancement
within the tumor

Tectal
tumors
- Infiltrating lesions in
tectal plate
- Poorly delineated
and rarely enhance
- Hypointense on T1
bright on T2
- Size > 2 cm and
enhancement
- Worse outcome
- Suggest an
atypical tectal tumor
Tectal glioma
A - Sagittal T2 (expansion and
hydrocephalus)
B – Axial FLAIR showing infiltrative
lesion

Focal lesions
• Better circumscribed
• No edema
• Cystic or solid
• Size and characteristics -
similar on T1 and T2
(because of relative lack of
infiltration and edema) 
Isointense
• Enhancement – Variable
(Brightly enhancing if
juvenile pilocytic
astrocytoma)
• Occupy <50% of a
brainstem region
(designation “focal”)
• Most common - Midbrain
and medulla
Focal pontine juvenile pilocytic astrocytoma
A - Axial T1 contrast  Well-circumscribed
tumor with cysts
B - Sagittal T1 a focal lesion in the pons
C and D - Axial and sagittal T1 contrast
showing complete resection (5 years)

Dorsal exophytic
tumors
• Usually NOT well
delineated from brainstem
& Well demarcated
outside
• Frequently extends to 4th
Ventricle
• Variable enhancement
• Follow the imaging
characteristics of
infiltrating gliomas
- T1 hypo
- T2 hyper
• Grow laterally & ventrally
into the brainstem = HGG
• Growing dorsally into the
Dorsal exophytic and cervicomedullary junction (CMJ)
tumors
A & B – Sagittal and axial T1 contrast of a dorsal
exophytic tumor
C - Axial T1 of CMJ tumor demonstrating a rim of
normal tissue around the tumor
D - T1 contrast showing irregular enhancement
within the tumor

Cervicomedullary glioma with dorsal exophytic
component
A, Post-contrast sagittal MRI demonstrates
enhancing mass
B, Post-contrast axial MRI
- Similar in appearance to
infiltrating gliomas
- Evidence of growth in
the medulla and cervical
spinal cord
- Epicenter  Foramen
magnum area
- Large exophytic
component
- Obstructing 4th V
outlet
- Located in CP angle,
causing compression
and distortion of lower
CMJ tumors

MR Spectroscopy
• Limited - Technical difficulties
Small size of anatomical structures
& Proximity of bone and fatty tissue
of the skull base
• Changes observed using MRS
appear similar to those observed in
supratentorial gliomas
• In the pediatric population, MRS has
been shown to detect progression
(decrease in NAA, elevation of Cho,
and decrease in the NAA/Cho and
Cr/Cho ratios) before radiological or
clinical deterioration
• Retrospective study,
9 adult patients with
brainstem gliomas
(histologically
confirmed in 4
cases) evaluated
with single-voxel
MRS before
treatment
- All = Elevation in the
Cho/NAA ratio from
1.08 to 3.32 (normal
is 0.6–0.8)
- 8 = Elevation in the
Cho/creatine ratio
(range 1.89 –1.01)
- 3 = Elevation in the
lactate signal
• The creatine/NAA
ratio was abnormal
in all patients
because of the loss
of the NAA signal

MRI
• MR spectroscopy
- Helpful in distinguishing them from the benign
diffuse pontine enlargements (NF1, Acute
demyelinating encephalomyelitis etc)
• Lesions associated with NF1
- Multifocal
- Frequently extend into the cerebellar
peduncles
- Show contrast enhancement

- Differentiate b/w low-grade and high-
grade lesions
- Evaluate response to treatment
- Determine the degree of malignancy
in paediatric population
FluoroDeoxyGlucose PET

DIFFUSION TENSOR IMAGING &
WHITE MATTER FIBER
TRACTOGRAPHY
• Differentiate diffuse
brainstem gliomas
(deflected fibers) from
demyelinating disease
(lack of distortion)
• The relationship of sensory
and motor tracts to brain
stem tumors has been
investigated in pediatric
patients
• With further studies and
evolution of this technique for
use in the brain stem, DTI
may play a role in assisting
the treatment planning for
brain stem lesions in adults

Diffuse lesions
• Fibrillary infiltrating gliomas
but the histologic grade can vary
considerably
- low grade (37%)
- anaplastic (56%), and
- Glioblastoma (5%)
• The true incidences are not known
because of the low biopsy and
resection rate of these tumors
with a BSG
• Other pathologies
- Pilocytic astrocytoma
- Infantile ganglioglioma
- Ganglioglioma and gangliocytoma
- Primitive neuroectodermal tumor
- Germinoma and non
germinomatous germ cell tumors
- Atypical teratoid-rhabdoid tumor
- Vascular anomalies
cavernous or arteriovenous
malformations
- Hemangioblastomas
- Lesions associated with NF1
- Tuberculomas or other infectious
process
- Abscesses
- Focal inflammatory and
demyelinating lesions
- Metastatic tumors
- Demyelinating processes
- Hematomas
- Infarction
- Lymphoma
- Lipoma
- Acoustic neuroma

• Little is known about
the pathobiology
- Low rate of biopsy and
resection
• NF1
- Intrinsic lesions in
brainstem that at least
radiographically
resemble diffuse
BSGs but follow a
more benign course
- Focal lesions –
indolent

• Brainstem gliomas are typically astrocytomas
• FOCAL, DORSAL EXOPHYTIC AND CERVICOMEDULLARY
GLIOMAS
- Are usually PILOCYTIC astrocytoma (WHO grade I) and
FIBRILLARY astrocytoma (WHO grade II)
- Other low-grade gliomas with indolent growth such as ganglioglioma are
also seen
• DIPGs
- Majority = ANAPLASTIC astrocytoma (WHO grade III) and
GLIOBLASTOMA MULTIFORME (WHO grade IV) : 70-90%
- Remainder = fibrillary astrocytoma (WHO grade II)
• Later stage - Invasion of adjacent levels of the brainstem and
cerebellar peduncles
• Autopsy - Majority of DIPGs are high-grade and more than 50% have
disseminated within the neuraxis
• Growth of low-grade gliomas typically respect fiber tracts and
pial borders
• In contrast, high-grade gliomas grow and expand without
respecting anatomic boundaries of these surrounding tissues

• Tectal gliomas – Majority cause hydrocephalus
• Dorsal exophytic gliomas
- Arise from subependymal glial tissue
- > 90% = Pilocytic astrocytomas that grow along the path of least resistance
- Most extends into 4th ventricle rather than infiltrating the brainstem
ventrally
- Tumors that extend laterally and/or ventrally into the brainstem
are usually more aggressive and of higher grade on pathological
examination
• Cervicomedullary gliomas
- Arise from lower medulla or upper cervical spinal cord
- Most = Low-grade astrocytomas, but gangliogliomas and ependymomas are
also seen
- Tumors with epicenters in the upper cervical cord grow dorsally into the
cisterna magna
- Those with epicenters in the lower medulla grow centrifugally as focal
nodules
- Growth is usually confined rostrally by the white matter of the corticospinal tract and
medial lemniscus

LOW-GRADE OLIGOASTROCYTOMA in a 19-year-old man presenting a progressive cerebellar syndrome and dysphagia.
Upper panel: (A, B): Evocative radiologic pattern in magnetic resonance showing a diffuse intrinsic brainstem hypointense
lesion without contrast enhancement as seen in T1 sequences and T2-Fluid Attenuation Inversion Recovery (FLAIR)
(C): Magnetic resonance spectroscopy showing only a mild increase of the choline/N-acetyl aspartate ratio without
lipids/lactates peaks modification (white arrow)
Lower panel: (D, E): Histologic sample obtained after biopsy showing a low-grade glioma with an astrocytic component and
oligodendroglial differentiation
(F): Immunohistochemistry showing a low MIB-1 proliferation index.
GERMAN REYES-BOTERO,a,d,e,f KARIMA MOKHTARI,b,d,e,f NADINE MARTIN-DUVERNEUIL,c JEAN-YVES DELATTRE,a,d,e,f FLORENCE LAIGLE-
DONADEYa,d,e,f aService de Neurologie 2-Division Mazarin, bService de Neuropathologie, and cService de Neuroradiologie Groupe Hospitalier Pitie´-
Salpeˆtrie`re, APHP, Paris, France; dUniversite´ Pierre et Marie Curie-Paris 6, Centre de Recherche de l’Institut du Cerveau et de la Moelle epiniere,

facial paresthesia.
Upper panel: (A): Magnetic resonance image showing a hyperintensity in T2 sequences involving the pons.
(B): T1-weighted sequence showing a contrast-enhanced pontine tumor with “ringlike” pattern. (C): Magnetic
resonance spectroscopy showing an increase in Cho peak and notable reduction in Naa (Cho/Naa 3.5)
Lower panel: (D, E): Histologic sample obtained after biopsy showing a microvascular proliferation (black
arrow) and diffuse expression of glial fibrillary acidic protein. (F): Immunohistochemistry showing a high MIB-1
proliferation index.
GERMAN REYES-BOTERO,a,d,e,f KARIMA MOKHTARI,b,d,e,f NADINE MARTIN-DUVERNEUIL,c JEAN-YVES DELATTRE,a,d,e,f FLORENCE LAIGLE-DONADEYa,d,e,f
aService de Neurologie 2-Division Mazarin, bService de Neuropathologie, and cService de Neuroradiologie Groupe Hospitalier Pitie´-Salpeˆtrie`re, APHP, Paris,
France; dUniversite´ Pierre et Marie Curie-Paris 6, Centre de Recherche de l’Institut du Cerveau et de la Moelle epiniere, UMR_S975, Faculte´ deme´decine site Pitie´-

Fibrillary Astrocytoma
• Most common
• Grading is difficult - issue of sampling and relative rarity of specimens
• Predominantly composed of fibrillary
neoplastic astrocytes with nuclear atypia
• Mitotic activity (Ki-67/MIB-1 labeling index) is usually < 4%
• Necrosis and microvascular proliferation - can be present
• Molecular characterization
- commonly shows TP53 mutations (>60%), not a predictor of
outcome
- loss of heterozygosity of 22q (1/3)
• The cytogenetic abnormalities of diffuse BSGs resemble those of adult malignant
gliomas
- TP53 mutations
- Mutated epidermal growth factor receptor
genes

Pilocytic Astrocytoma
• Cytogenetic analysis - Normal karyotype in
majority
• Focal brainstem lesion
- most often pilocytic astrocytomas
- pathologically do not show any difference

Pilocytic Astrocytoma
• Pilocytic astrocytomas with NF1 - genetically
distinct
- loss of normal NF1 expression
- Ras activation, and
- hyperactivation of the mTOR (mammalian
target of rapamycin) pathway
• Less aggressive than non-NF1 lesions
• Difference from diffuse fibrillary astrocytomas
- altered and increased activation of immune response genes
- higher content of proliferating Microglia

Ganglioglioma and Gangliocytoma
• Chromosomal abnormalities - 1/3
• gain of chromosome 7 - most common
alteration
• 3 patients had adverse outcomes when
chromosomal abnormalities were present
• Anaplastic changes and high MIB-1 and
TP53 labeling indices - more aggressive
behavior

Atypical Teratoid/Rhabdoid Tumor
• First described in 1985, common in the
infratentorial compartment and brainstem
in children younger than 6 years
• Mutation or loss of the INI1 locus on
22q11- typical chromosomal abnormality
of ATRT
• Age > 3 years at diagnosis - Longer
survival (more aggressive therapies)

TREATMENT
Dorsal exophytic gliomas are the most amenable to surgical
resection in brainstem gliomas.

• DBSG - Will not benefit from surgical
intervention
• Focal BSG - Amenable to surgical
resection
• Dorsal midbrain tumors (tectal gliomas)
- Indolent and stable clinically and radiographically for
many years
- Initially managed in a nonoperative manner with
serial imaging
- Surgery is performed in cases of tumor progression on
MRI
- Obstructive hydrocephalus  ETV

Surgical anatomy - Dorsal
aspect
• Floor of IV ventricle
- Rhomboid
- Pons- rostral 2/3rd
- Medulla- caudal 1/3rd

Surgical anatomy - Dorsal
aspect
• Three parts
- Superior / pontine
- Intermediate /
junctional
- Inferior / Medullary
part

DPG
• Fatal  6 to 24 ms after diagnosis / treatment & 3 to 6 m
after local progression
• Median survival - 10 months, 13% survive 3 years
• Systemic metastasis – rare
• Leptomeningeal disease - 30% of patients after relapse
• low rate of surgical intervention
- Poor outcomes
- Characteristic radiographic appearance on MRI
- Past surgical morbidity
• This is in contrast to focal, exophytic, and cervicomedullary tumors, which are
amenable to surgical resection

Biopsy
• Limited role
- Prognosis is not related to its histologic grade
- Management is mostly independent of the histology of the tumor
Biopsy not indicated when imaging features are
characteristic of DPG
 Indication for biopsy
• Atypical features (prognosis and outcome not significantly affected)
• Some of the focal or exophytic lesions
 Techniques
- Open biopsy
- Stereotactic biopsy (either frameless or fixed)
• Stereotactic biopsy
- 6% to 11% morbidity rate
- Transient and permanent morbidity rates- 5.6% and 1.4%

• Since 1970s
• 5% to 12% of all brain
biopsies
• Not used widely in the
pediatric population
(characteristic MRI -
sufficient to diagnose
DBSG)
• Reported rate of
complications = 2.5% -
7.7% (published series)
• Adults - contrast-
enhancing brain stem
lesions ?? -
Radiographic Diagnosis
incorrect in 10%-25%
(over 20 yrs age )
• Heterogeneity - Difficult to
make a diagnosis on the
basis of imaging alone
• Indicated in many adult
brain stem lesions that
- Enhance with contrast
- Diagnosis of the lesion is

• Image guidance - CT or MRI
• Approaches - Depending on the location
1. TRANSFRONTAL - Frequently requires traversing the
lateral ventricle and is limited to midline regions of the
pons and medulla by the tentorial incisura
2. TRANSTENTORIAL - Not used routinely; places vital
vasculature and cranial nerves at risk; cause pain with
tentorial puncture; crosses the pia two additional times
above and below the tentorium
3. TRANSCEREBELLAR - Lesions in the lower midbrain, pons,
middle cerebellar peduncle, and rostral medulla;
intubation and GA generally required (patient
positioning); Discomfort associated with muscle dissection
prior to placement of the twist drill hole

• An alternative
CONTRALATERAL,
TRANSFRONTAL,
EXTRAVENTRICULAR
APPROACH using a
Leksell stereotactic
frame system
described for reaching
lesions in the lateral
pons and middle
cerebellar peduncle
• The needle’s trajectory
crosses only one pial
surface and avoids the
ventricle and
tentorium
• In a reported series of six patients,
diagnostic samples were obtained
in all patients and there was no
surgical morbidity
Illustration depicting the
contralateral, transfrontal,
extraventricular approach to an
infratentorial lesion with the aid
of a Leksell stereotactic frame
system

Diffuse glioma is an infiltrative,
highly aggressive lesion which
is always malignant regardless
of the histology at the time of
biopsy, associated with a very
poor prognosis, MR
appearance is reliable → No
role of biopsy for these lesions
(Epstein,McCleary,1986)
No role of open
surgery/stereotactic
biopsy in diffuse
tumor because of
typical MRI
characteristics and
clinical presentation (
Isamat, 1999)
Risks of biopsy far
outweigh the
remote possibility
of diagnosing
something other
than a glioma
Majority of focal, dorsally
exophytic and cervicomedullary
BSG are benign and resectable
by direct surgery with low
morbidity and good outcome
New york symposium on
Brainstem surgery, 1996 ;
Epstein, Constantini ,Hoffman, A
Bricolo
• Reserved to
-When the diagnosis is uncertain, to rule out inflammatory pathology like
TB
-Focal intrinsic endophytic lesion - well limited masses within the brainstem
surrounded by neural tissue and therefore do not reach the surface

Surgery
• Role in the management of all BSGs but DPG
• Location requires careful planning
preoperatively to minimize surgical morbidity
• Preoperative CSF diversion - Not necessary in
majority
- Exceptions  Tectal tumors (hydrocephalus -
initial & frequently sole symptom)
- No need for biopsy of tectal tumors, and the
treatment recommended for hydrocephalus is
endoscopic third ventriculostomy

• Adjuncts to surgery -
Essential in focal tumors
- Laser treatment (Nd-YAG
laser)
- Intraoperative monitoring
- Ultrasound and navigation
• Brain stem auditory,
somatosensory, and
motor-evoked potentials
- Monitor their
corresponding pathways
- Does not help to prevent
the injury (functional
mapping is not taking
place)

FUNCTIONAL MAPPING
- Responses from muscles innervated by cranial nerves VII, IX, X, and
XII
- Stimulates the floor of the fourth ventricle with a hand-held monopolar
probe
- Tip of the probe = Round & 0.75 mm
- Muscle action potentials (EMG) - Orbicularis oculi and oris
muscles (CN VII), posterior pharyngeal wall (CN IX, X), and
tongue muscles (CN XII)
- Muscle relaxant  X
- Threshold intensity = 0.2 Ma (hematoma) - 2.0 mA (tumors)
- Moving the stimulation probe every 1 mm
• No impulses  Technical problems / cranial nerve motor nuclei is
ventral to the pathology
• If ventral - Repeated stimulation through the lesion

Focal
• Intraoperative navigation
with a frameless system
(MRI) & operating
microscope = Essential
• Approached in the most
direct path, sometimes
guided by bulging or a
small area of
discoloration that is
visible through the pia
• Intraoperative ultrasound
- Ascertaining amount
resected
- Localization for
placement of catheters
in the cystic components
• Intracystic catheters
have been implanted for
- Repeated aspiration of
tumor-related cysts
- Deliver therapeutic
agents (radioactive
sources,
chemotherapeutic
agents)

Focal
• Surgical risk - Related to the anatomy and type
- Cystic and pilocytic tumors - Less morbidity
- Solid or infiltrating fibrillary astrocytomas – More
• Goals of the surgery - Clearly thought out and
discussed with the patient and family (benefits and
complications)
• M E D U L L A
- Need for tracheostomy and feeding gastrostomy (
considerable recovery potential in children)
• P O N S A N D M I D B R A I N
- Permanent eye movement problems
- Injury to the long tracts

Exophytic
• Midline posterior fossa craniotomy
• No indication to split the vermis
• Elevation of the cerebellar tonsils via a telovelar approach will allow
access to the tumor
• Two types - Warrant different surgical approaches
1. TRUE EXOPHYTIC TUMORS
- Grow primarily outside the brainstem
- Only a very small component that is infiltrating the brainstem
- Floor of the fourth ventricle is identified first and then the tumor is
removed in a stepwise fashion that avoids pursuit of the tumor into
the brainstem itself
2. INTRINSIC BRAINSTEM TUMOR WITH A LARGE EXOPHYTIC
COMPONENT
- Approached by removing the exophytic component capping the
intrinsic component
- It opens a broad pathway into the intrinsic tumor component, which
can be removed by internal debulking and careful dissection at the
margins

Cervicomedullary
• Resectable - Infiltration into the medulla
and the cervical spinal cord limit the
extent of resection
• Early surgery - Avoid the late neurological
deficits
• Approached via a midline posterior fossa
craniotomy and possibly a cervical
laminotomy
• Often arises from the floor of the fourth
ventricle, no exophytic component 
myelotomy or opening through the floor
of the fourth ventricle

Anesthesia for brainstem
surgery
• Multimodal
monitoring – SpO2
& ETCO2
monitoring, CVP
line, arterial line,
trans-esophageal
echocardiography,
etc.

Surgical Techniques
• Precise movements & good intraoperative
judgment
• An optimally functioning surgical
microscope
• Intrinsic tumors
- Incision in the surface of the brain stem;
require a thorough understanding of the
anatomy
- Many tumors can be accessed where it is
closest to the surface (Not always the rule)
- Incision small and less than 1 cm
- Tumors in the vicinity of the corticospinal
tracts in the cerebral peduncles, fourth
ventricular floor – M a p p i n g

Surgical Techniques
• Dorsal pontine tumors approached through the
fourth ventricular floor can be entered through
the
- median sulcus above the facial colliculus
- suprafacial, infrafacial, and area acoustica
• Tectal mesencephalic
- Supracollicular, infracollicular, and lateral
mesencephalic sulcus
• Medullary and cervicomedullary tumors
- Longitudinal myelotomies in the posterior
median fissure below the obex, posterior
intermediate sulcus, and posterior lateral sulcus

Tumour decompression
• Consistency determines the method of
extirpation (piecemeal fashion= solid / Suction &
aspiration= soft)
• Frozen section determines amount of extirpation
• Conventional suction technique frequently causes
brainstem dysfunction manifested by bradycardia
& arrhythmia
• CUSA causes movement of adjacent structures
only within 1mm of vibrating tip, allowing for
extensive and quick dissection adjacent to or
within the substance of brainstem
• Cyst - Aspiration / Debulking early
• Tumor resection should be stopped when an
interface between the two cannot be visualized

Surgical technique-
Focal tumour
• Use of plated
bayonet(very small
plates at the tip) as
‘microretractor’
• CUSA at a low setting
• Careful identification
of white matter
interface
• Minimal manipulation
of adjacent normal
tissue

Surgical technique-
Cervicomedullary tumor
• Suboccipital craniotomy
+ osteoplastic
laminotomy
• Expose both rostral and
caudal extent of the
tumor
• USG guidance to know
extent of tumor prior to
opening the dura -
entire tumor should be
within the confines of
the operative exposure

Surgical technique- Cervicomedullary tumor
• The rostral end of a benign
cervicomedullary tumor
invariably expands
posteriorly at the obex
• Tumor is, in fact,
displacing the medulla
rostrally rather than
extending into it
• This explains why these
tumor present with cervical
myelopathy rather than
LCN dysfunction
• Conceptually, these tumor
should be regarded as ‘
intramedullary spinal cord
tumors’
• Tumor is approached from
within its center

Surgical technique-
• Midline myelotomy
- ‘True’ midline to be
identified
- Identify DREZ bilaterally
• If tumor is solid-cystic,
myelotomy to be placed
first at tumor –cyst
junction and cyst is
removed prior to tumor
excision
• If tumor is non-cystic,
myelotomy where tumor
is most voluminous &
closest to the pial surface

Surgical technique-
• Myelotomy to be
terminated 1 cm
proximal to the caudal
pole of the tumor →
tumor is least
voluminous here,
removed by gradual
upward dissection
• At the rostral pole,
tumor invariably subpial
and bulging posteriorly
at the obex

Surgical technique-
Cervicomedullary tumour
• USG to guide the extent of tumor excision-
to confirm bulk of tumor is removed
• Don’t chase small questionable fragments
• If deterioration of SSEP/MEP during the
procedure, interrupt the dissection and
move to another area

Peri-operative care
• Perioperative steroids( methylprednisolone)
• Elective ventilation for at least 48 hours
• Mechanical ventilation till recovery of
ventilation & normal cough reflex
• LCN paresis - NG/feeding gastrostomy
• V,VII nv paresis - temporary tarsorrhaphy
• Good nursing care
• Physiotherapy
• Post-op brainstem injury mostly reversible if
surgical technique is proper

Adjuvant Therapy
• Corticosteroids - Earlier improvement in symptoms than with
other interventions
• RT
- Standard of care for DIPG
- Not recommended as an early treatment for nondiffuse brainstem
gliomas if pathology shows a low-grade glioma
- Usually used in patients with high-grade pathology, upon clinical and
imaging evidence of progression, or late in the disease course
• Stereotactic radiosurgery is also used in nondiffuse
brainstem gliomas
• Chemotherapy
- Limited use in the management of brainstem gliomas
- Mainly used for high-grade pathology or at late stage of the disease

DIPG
• Established role in the management of BSG
• Standard treatment of DIPG - Alone or in
combination with chemotherapy(before, during, or
after completion of RT)
• The standard of care for DIPG is involved field
external beam radiation therapy, typically
delivered at 1.8Gy/fraction for 30-33 fractions
• Most DIPGs responded well to radiation with often
dramatic improvement in the scan and clinically
• However 90% died by 2 years and less than 2%
survived on long term follow-up
• Median survival only 9 to 10 months
Even with Direct RT + CT <10% will survive 2 years

Focal gliomas
• Conventional RT - Limited efficacy
• High-grade tumors
- After recovery from surgery
- When surgery is not indicated
• Low-grade tumors may be observed and treated only if there is
subsequent tumor progressio
• Implantation of iodine-129 (I-129) or iodine-125 (I-125) seeds has
been used in some patients with acceptable tumor control
• I-125 is an alternative to resection, external beam radiation
therapy and chemotherapy in children with progressively
symptomatic low-grade gliomas in deep and eloquent areas
where high postoperative morbidity would be expected with
open surgery
• Stereotactic radiosurgery has been used as an alternative
means for managing focal brainstem gliomas
• Its use has been reported in patients with progressive tumor
growth or worsening neurological deficits.

Dorsal exophytic gliomas
• Inoperable tumors
• Recurrent disease not amenable to re-
resection
• Treatment primarily consists of
conventional external beam radiation
therapy with 30-33 daily fractions of
1.8Gy/fraction
• Use of stereotactic radiation therapy
and radiosurgery has also been
examined in small cohorts

Cervicomedullary gliomas
• Surgery is typically the initial treatment
modality
• RT reserved for
- Advanced diseases
- Recurrent diseases not amenable to
surgical resection
• Conventional fractionated external beam
radiation given at 1.8Gy/fraction for 30-33
fractions
• Stereotactic radiation therapy and
radiosurgery has also been examined in
small cohorts

Radiation Therapy
ADULT DIFFUSE INTRINSIC LOW-GRADE BRAINSTEM GLIOMA
• Standard treatment ; can improve or stabilize patients for
years
• Conventional median dose = 50–55 Gy (Fractions of 1.8–2
Gy)
• Clinical improvement occurs in the majority
• Reports of Substantial discrepancy between the clinical and
radiological response
• 48 adult patients (including 46% of intrinsic diffuse gliomas),
radiotherapy
- Improved clinical status in 61%
- Partial radiological response (a decrease of 50% in the T2
hyperintensity in the greatest axial cross-sectional area) was noted in
only 19%
• Specific criteria to evaluate tumor response to treatment
in brainstem gliomas could be different than the criteria
used for supratentorial glioma
• The optimal time of treatment remains unknown
• Some patients may have mild symptoms during extended
periods without any treatment - Radiotherapy may

Radiation Therapy
ENHANCING MALIGNANT BRAINSTEM
GLIOMAS
• Malignant brainstem gliomas are highly
resistant to treatment by radiotherapy
• Only 13% (2 out of 15 patients) showed
clinical and radiological improvement
• Gamma knife radiosurgery has been
reported in some cases of high-grade
brainstem gliomas, but the published
data are limited and preliminary

• FOCAL TECTAL BRAINSTEM
GLIOMAS – No role
• Associated with longer
median survival
(exceeding 10 years)
following
ventriculoperitoneal
shunting and in some cases
focal radiotherapy
• EXOPHYTIC
BRAINSTEM
GLIOMAS –
No role
Hamilton MG, Lauryssen C, Hagen N. Focal
midbrain glioma: long term survival in a cohort of 16
patients and the implications for management.
Can J Neurol Sci 1996;23:204 –207
Bowers DC, Georgiades C, Aronson LJ et al. Tectal
gliomas: natural history of an indolent lesion in
pediatric patients
Pediatr Neurosurg 2000;32:24–29.

Radiation Therapy
• Chemotherapy before RT - No survival
benefit
• Temozolomide after RT - Efficacious for
high-grade gliomas, but did not alter the
poor prognosis associated with newly
diagnosed DPG in children
• Dose escalation and hyperfractionation -
Not shown evidence of dose-dependent
improvement of the 2-year survival rate
(3% to 21%) and of median survival (9 to 13
months)

Role of GKRS
• 20 patients
• 10-18 Gy
• Median follow up- 78 months
• Tumor disappeared in 4 pts,
decreased in size in 12 pts
• Minimal peri & post-
procedural morbidity
• Currently, there is no role
for stereotactic
radiosurgery in the
management of DPG
• Stereotactic RT, either
fractionated or single
dose, can be very
effective for the treatment
of
 Recurrent or residual
low-grade focal or
infiltrative tumors that are
unresectable or have
failed chemotherapy
Yen CP, Sheehan J, Steiner
M, Patterson G, Steiner L.
Gamma knife surgery for
focal brainstem gliomas.
J Neurosurg. 2007
Jan;106(1):8-17.

DIPG
• Various chemotherapeutic
regimens have been
studied either alone or in
combination with
radiation therapy
• Up to date, no
chemotherapeutic agent,
either alone or in
combination, or in
conjunction with radiation
therapy, has altered the
natural history of DIPG
• Many patients are
enrolled in clinical trials of
new agents or previously
used agents in previously
untested combinations
• Response rates – up to 15%
to 20%
• No survival benefit
• Various regimen -
cyclophosphamide,
carboplatin, cisplatin,
etoposide, and thiotepa,
some in combination with
blood-brain barrier
disrupting agents
• Metronomic therapy
- Continuous low-dose
chemotherapy
- Block mechanisms
stimulating the growth of
new blood vessels needed
to feed the tumor
- Promising results in the
management of gliomas
(no significant effect on
DPG)

 Other BSGs - follows the same principles
as for gliomas in other locations in the
central nervous system

FOCAL GLIOMAS
• Role not been well evaluated
• In general, for tumors that total or
subtotal resection has been performed on
and subsequently progress, chemotherapy
may be considered with or without
radiation therapy
• In children younger than 3 years old,
chemotherapy may be used alone in
attempts to delay the need for radiation
therapy

DORSAL EXOPHYTIC
GLIOMAS
• No proven efficacy
CERVICOMEDULLARY
GLIOMAS
• No role

• Cytotoxic chemotherapy, including the newest
agent temozolomide is not effective and the
recently introduced targeted therapies with
imatinib mesylate, gefitinib, erlotinib, and
antiangiogenic therapy did not produce better
results
• Multitargeted therapy with antineoplastons
A10 and AS2-1 (ANP), currently in clinical trials,
has produced encouraging results in newly
diagnosed DBSG
• New strategies employing multitargeted
approach may offer better results in the future.

Combination Therapy
• A Pediatric Oncology Group study
- No significant difference between hyperfractionated irradiation
with 78 and 54 Gy in conventional one-per-day fractions
combined with cisplatin
- Combining hyperfractionation with interferon beta therapy had
a more benign side effect profile but failed to change survival
• Combinations with radiosensitizers
- No combination has demonstrated more benefit than RT has
alone
• An aggressive therapy scheme
- Toxic in a series of 11 patients
- Long-term objective good outcomes in more than 50% of
patients with histologically confirmed DPG and dorsal
exophytic BSGs

PROGNOSIS AND
OUTCOMES
• Two radiographic features provide the most useful prognostic
information : epicenter of the tumor and diffuseness
• 5-year survival rate
- Focal tumors - 75% and 65% (midbrain and medulla
respectively)
- DPG – 18%
- Focal tumors - 70%
- Diffuse tumors - 22%
- Other studies - lower 3-year survival rates of 10%
• Preoperative symptoms such as upper respiratory tract
infections, pneumonia, and voice alterations were associated
with postoperative ventilator dependency
• Preoperative swallowing difficulties - correlated closely with
the need for a feeding gastrostomy postoperatively

SUMMARY
The DIPG “ranks first
amongst pediatric brain
tumors with a poor
prognosis.”J. Neurosurgery
Peds 3:257-258, 2009

• MIDBRAIN (7 - 8%)
- Almost always low-grade pilocytic astrocytomas (WHO I & II)
- Good prognosis
• PONS (80 %)
- Usually High grade astrocytomas (WHO III & IV)
- Dismal prognosis
• MEDULLA (10 - 15%)
- Usually low grade pilocytic astrocytomas (WHO I & II)
- Good to fair prognosis

• FOCAL, DORSAL EXOPHYTIC AND
CERVICOMEDULLARY GLIOMAS
- Are usually PILOCYTIC astrocytoma
(WHO grade I) and FIBRILLARY
astrocytoma (WHO grade II)
• DIPGs
- Majority = ANAPLASTIC astrocytoma
(WHO grade III) and GLIOBLASTOMA
MULTIFORME (WHO grade IV) : 70-90%
- Remainder = fibrillary astrocytoma (WHO
grade II)
• Growth of low-grade gliomas typically
respect fiber tracts and pial borders

• Symptom evolution reflects aggressiveness
• Low-grade tumors - Insidious course over several
months of gradual symptom progression
• Shorter and more abrupt onset = Higher grade
tumors
• Pattern of symptoms reflects the extent of the
tumor
• DIPG
- Multiple and bilateral cranial neuropathies
- Long tract signs and ataxia
- Hydrocephalus uncommon
- Isolated cranial neuropathies
- Signs and symptoms of increased intracranial
pressure, and ataxia

Tumors arising in the medulla
Lower cranial nerve dysfunction
Failure to thrive, dysphagia, dysarthria
and dysphonia, chronic upper respiratory
tract infections and aspiration, and sleep
apnea
2. Tumors arising in the cervical spinal cord
• Neck pain, torticollis, and sensorimotor
deficits in limbs or cervical myelopathy
myelopathy with weakness and spasticity
Cranial nerve palsies are not typically
encountered

• Long tract signs (motor dysfunction
and hyperreflexia) - Diffusely growing
tumors / Focal tumors of CMJ
Long tract signs - Conspicuously
absent with dorsal exophytic gliomas
• Obstructive hydrocephalus –
Usually first sign in focal tectal gliomas
(compression of cerebral aqueduct)

• Mutation of P53, a tumor suppressor
gene
• Amplification of mutated EGFR gene
• Trisomy 1q, deletion of chr 19
• NF 1  More indolent course

CONCLUSION
• MRI and PET : Commonly used, it does not
accurately replace histological diagnosis
• DIPG – RT + CT
• For BSG with NF1 , no treatments are
recommended unless there is rapid tumor
growth and symptomatic worsening in the
patient’s condition (Pollack et al, 1996; Guillamo
et al, 2001)
• Therapy for focal, dorsal exophytic and
cervicomedullary tumors is similar to other
types of primary brain tumors (Freeman and
Farmer, 1998)

CONCLUSION
• The determination of frequency of
histopathologic types is not accurate, since
only approximately 25% of these patients
have a biopsy
• Autopsy results confirm that the majority
are high-grade gliomas, usually anaplastic
astrocytomas (AA) (Freeman and Farmer,
1998)
• Glioblastoma multiforme (GBM) and low-
grade, or grade 2 astrocytoma, occur in
lesser frequency

CONCLUSION
• Stereotactic biopsy : Since the pathology diagnosis
is difficult to obtain, dangerous and misleading,
diagnosis based on MRI is the standard of care
(Freeman and Farmer, 1998)
• Reserved to many adult brain stem lesions that
- Enhance with contrast & When the diagnosis is
uncertain, to rule out inflammatory pathology like
TB
- Focal intrinsic endophytic lesion - Well limited
masses within the brainstem surrounded by neural
tissue and therefore do not reach the surface

• Dorsally exophytic tumor
- Likely to be benign
- Radical excision
- Do not enter brainstem
• Cervicomedullary tumor
- Likely to be benign
- Radical excision
• Cystic tumor
- Radical excision
• Focal pontine tumor - Radical excision if tumor
is close to the surface

• Uncommon  1%–2% of intracranial gliomas
• Heterogeneous group
• Low grade phenotype predominates(80%)- Better
prognosis
• Longer survival
• Adult diffuse intrinsic brainstem gliomas are low-grade
tumors at the onset in contrast with those in children
where a similar nonenhancing MRI aspect often
indicates a high-grade glioma associated with rapidly
progressive clinical impairment and shorter survival
• Histological proof necessary in many contrast-enhanced
focal brainstem lesions - Wide variety of DD’s
• Diffuse intrinsic low-grade BSG - Conventional
radiotherapy (the median survival is 5 years)
• Malignant BSG - Radiotherapy
• Combined radiotherapy and chemotherapy
(temozolomide or other agents) - Not been thoroughly
evaluated in adults

• A biopsy is rarely performed in typical
intrinsic diffuse glioma in adults
• When it is performed, a low-grade
histology (grade II glioma) is found in up to
80% of cases, whereas in children a grade
IV glioma is the most frequent phenotype
reported in 50%–60% of cases
• This feature probably accounts for the
better prognosis of the adult form

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