PRIMITIVE NEUROECTODERMAL

TUMORS
 Incidence
• More common in children
• Posterior fossa/ medulloblastomas- most
common malignant brain tumors in
children
• Constitute approx 20% of childhood brain
tumors and 30% of all posterior fossa
tumors
• 1% of adult tumors
• Median age of diagnosis- 9y.o.
• 1.4-1.8 times more common in males than
females
• Syndromes with increased familial incidence
of PNET:
• 1.turcot’s syndrome
• 2. Gorlin’ s syndrome
• Supratentorial PNET-may be seen with
retinoblastoma termed as pinealoblastoma

• Pathology
• Approx 50% of medulloblastoma has neuronal
or glial differentiation
• Homer wright peudorosettes found in 40% of
medulloblastoma
 Highly cellular medulloblastoma with
Homer wright pseudorosettes scanty cytoplasm
 Pathology

• Astrocytic differentiation is seen in >50% of

tumors, (+) GFAP
• Gross: soft, friable, purplish tumors located in
proximity to the 4th ventricle
• An isochromosome of the long arm of 17q is
seen in up to 66% of medulloblastoma—
related to tumor progression
 CLINICAL EVALUATION
• Children with medulloblastoma present with
s/sx of increased ICP
• Other symptoms: unsteady gait, ataxia,
decreased coordination
• In very children: macrocephaly, loss of
milestones, irritability & vomiting
• Many have evidence of hydrocephalus
• Diplopia is secondary to CN VI palsy
• Severity of hydrocephalus may result to loss of
VA & blindness
• Radiographic evaluation:
• CT- hyperdense & homogenously enhancing, with
smaller areas of calcification
• MRI- isointense or hypointense ion T1-weighted
images.hyperintense in T2. intensely enhancing
in gad
• 10-15% of medulloblastoma do not enhance
with contrast in MRI
• Treatment
• Hydrocephalus- placement of EVD or
ventriculostomy at the time of surgery
• Dexamethasone given preop
• Preoperative shunting before removal of the
tumor is discouraged to avoid upward herniation
• In the postoperative period the level of EVD is
gradually increased to allow normal CSF
pathways to resume absorption
• not to wean from EVD when: s/sx increased
ICP; CSF leakage from the wound;
development of pseudomeningocele
• The need for postoperative shunting has been
correlated with: younger patients, large
ventricles, longstanding ventriculostomy &
large tumors
• Tumor removal:
• 24-48 hrs.Preop corticosteroid decrease
peritumoral edema
• AED are not needed for PNET
• Preop EVD placement is generally reserved for
moribund state & hydrocephalus is so severe
• Adequate venous access & arterial pressure
monitoring are important
• Angulated concorde position for tumors in
posterior fossa
• Dura is usually opened in Y-shaped fashion.
• Special attention to the circulator sinus &
occipital sinus
• Medulloblastoma of 4th ventricle generally
involve the vermis & occasionally invade
bainstem
• Protecting the floor of 4th ventricle before
splitting the tonsils & resecting a portion of
inferior 4th ventricle
• Dissection between the vermis & tonsils may
adequate exposure
• Debulking of the tumor can allow the surgeon
to bring the edges of the tumor
• Gross total resection of the tumor is the goal
 Complications
• 15-40% of medulloblastomas invade the floor
of the 4th ventricle or brainstem—may limit
the total resection of the tumor
• Sever deficits preoperativele have greatest
introp risk
• Postop morbidity-50% of patients: transient or
permanent deficits, hemiparesis, nausea &
vomiting
• Posterior fossa syndrome AKA cerebellar
mutism in 15%-20%—a post op complication
of resection of medulloblastoma
• Characterized by: mutism, abulia, high-pitched
cry, oral motor apraxia, drooling & ataxia
• Associated with edema of the
dentorubrothalamic tract, splitting of the
inferior vermis
 OUTCOME:
• With residual tumor of <1.5cc correlated with
improved outcome
• Gross total resection without adjuvant
therapy, tumors tend to recur locally &
disseminate through CSF
• Doubling in survival rates in patients who
received radiation treatment 50%-70% with
5400 to 5800cGy
• Cognitive deficits are associated with
craniospinal irradiation esp in patients
younger than 3 y.o
• Children younger than 3y.o with malignant are
treated with cyclophosphamide +vincristine
followed by cisplatin +etoposide----40%
progression free survival
• Supratentorial PNET are staged and treated
the same as posterior fossa PNET &
medulloblastoma
• 2 factors correlating survival in
medulloblastoma: 1. age at diagnosis 2.
evidence of spread
• Recurrence of medulloblastoma after initial
treatment is usually incurable
PINEAL TUMORS
• Most pineal masses originate infratentorially
& expand into the posterior 3rd ventricle
• Malignant tumors of glial origin can inavde
into midbrain & thalamus
 Pathology

• 4 main categories of pineal tumors:

• 1.germ cell tumors
• 2. pineal parenchymal cell tumors
• 3. glial cell tumors
• 4. cysts/miscellaneous tumors
• Miscellaneous tumors: meningioma,
hemangioblastoma, choroid plexus
papiplloma, metastatic tumor, chemotectoma,
adenocarcinoma, lymphoma
• Vascular lesions: cavernous malformation,
arteriovenous malformation, vein of galen
malformation
 Clinical features
• Symptoms:
• 1. s/sx of increase ICP from obstructive
hydrocephalus
• 2. direct brainstem & cerebellar compression
• 3. endocrine dysfunction
• Headache- most common symptom
associated with increase ICP
• Direct compression of the midbrain at the
superior colliculus can cause disorders of
EOM-Parinaud’s syndrome(upward gaze palsy,
convergence or retraction nystagmus, light-
near pupillary dissociation)
• Sylvian aqueduct syndrome-paresis in
downward gaze or horizontal gaze
• Collier’s sign- lid retraction (due to dorsal
midbrain compression or infiltration) diplopia
and head tilt
• Ataxia & dysmetria-- Interference with
cerebellar efferent pathways of the superior
cerebellar peduncles
• DI- occurs with germinoma spreading along the
floor of 3rd ventricle
• Precocious pseudopuberty- hypothalamic-
gonadal axis is not mature—limited in males
with chorioCA or germinoma producing beta
HCG
 diagnostic
• MRI with gad- principal diagnostic test for
pineal tumors
• Reveals the degree of hydrocephalus, tumor
size, vascularity, homogeneity and anatomic
relationships with surrounding structures
• Tumor markers- CSF alpha feto protein
and beta human chorionic gonadrotropin

• Tumor markers are useful for monitoring

response to adjuvant therapy or early
signs of recurrence
• CSF cytology ocassionally reveals
malignant cells but is rarely diagnostic
• Presence of malignant cell markers tissue
tissue diagnosis is unnecessary—
chemotherapy and RT should proceed
• Stereotactic biopsy-for patients with
known primary systemic tumors, multiple
lesions or medical conditions that make
open resection dangerous and
radiographic evidence of brainstem
invasion
 treatment
• Management of hydrocephalus:
• Mildly symptomatic patients—ventricular
drain placed at the time of surgical
resection
• More advance symptoms– ct-guided
stereotactic ETV to allow gradual
reduction of ICP
• Open resection- ability to obtain larger
amounts of tissue & extensive tissue
sampling---esp for tumors where
heterogeneity and mixed cell population
are common
• Tumor burden is reduced
• 1/3 of tumors that are benign resection
is usually complete & curative
 Surgery
• Stereotactic procedure
• 2 possible approaches:
1. Precoronal entry point– reaching the
tumor throught the
anterolaterosuperior approach
2. Posterolaterosuperior approach near
the parieto-occipital junction
• Patient positioning
1. Sitting position-preferred for the
infratentorial-supracerebellar approach
2. Lateral position—for the occipital-
transtentorial approach the head should be
positioned with the patient’s nose rotated 30
deg toward the floor
• More desirable variation of lateral position is
the three-quarter prone position—suitable for
more posterior approaches such as the
occipital-transtentorial
• Operative approaches
I.Supratentorial approaches- transcallosal-
interhemispheric, occipital-
transtentorial, transcortical-
transventricular
II. Infratentorial-supracerebellar approach
• Location of most pineal tumors
infratentorially and midline gives the
infratentorial-supracerebellar approach
several advantage
• The approach is less favorable if the
tumor has a significant supratentorial or
lateral extension
 Complication
• Immediate postop- impairment of extraocular
movements particularly limited up-gaze and
convergence
• More sever morbidity can be a sequela of
overzealous brainstem manipulation
• Most devastating complications is hemorrhage
into an incompletely resected tumor bed
 Surgical outcome
• The impact of surgery on long-term
outcome depends on the tumor’s
histology and responsiveness to adjuvant
therapy
• Benign tumors with complete surgical
removal, excellent long-term follow-up---
probable cure
 Postoperative work-up

• postopMRI with Gad should be done

within 72hours of the surgery
• Tumor markers should be measured
postop for detecting early recurrence or
for monitoring treatment response
 Adjuvant therapy
• Radiation therapy
Malignant germ cell or pineal cell tumors-
recommended dose 5500cGy given in 180 cGy
daily fractions with 4000cGy to the ventricular
system & additional 1500cGy to the tumor
bed
• RT may be withheld for the rare histologically
benign pineocytoma or ependymoma that has
been completely resected

• Chemotherapy
• Beneficial for patients with
nongerminomatous malignant germ cell
tumors
• Regimen of cisplatin or carboplatin with
etoposide is among the most widely used
EPENDYMOMA
• Neoplasms arising from ependymal cells
lining the ventricles and central canal of
the spinal cord
• 4 most prevalent locations:
1.supratentorial
2.infratentorial 3.spinal 4. conus-
cauda-filum
• Behavior:
1.Resistance to drugs and radiotherapy
2. Propensity to recur 10-20 years after the
initial resection
3.Marked inconsistencies between their
histology and prognosis
4. Infants & children are affected without
obviuos risk factors
 Epidemiology

• Incidence rate for children-3/100,000

children younger than 15 yrs
• Male-to-female ratio in children is about
14:1
• The rate of new cases peaks at about age
4 years
 Diagnosis
• S/sx of increased ICP: frequent HA that
are worst in the morning (assoc with
nausea, vomittng, ataxia, lethargy,
irritability & decline in school or wok
performance)
• Papilledema; nystagmus; changes in
vision
GRADE NAME COMMON LOCATION
Myxopapillary Spine, 4th ventricle, lateral
ventricle
Subependymoma
Papillary CP angle
cellular 4th ventricle and midline area
Clear cell 4th ventrice and midline area
anaplastic Cerebral hemisphere
Ependymoblastoma several
 Diagnostic surgical pathology

• Characteristic
features: rosette
pattern of cells
formed by a ring
of polygonal cells
surrounding a
central cavity
• Malignant cells are generally characterized by
significant mitotic activity, nuclear
polymorphism & variation in the shape of the
membrane
• Parameters for prognosis:
1.Number of mitosis
2. Labeling indexes of proliferation markers
3. Cell density
• Imaging
CT non-contrast- lesionis isodense to cerebral
cortex. Low density necrotic areas are also
seen
Highly suggestive of ependymoma-presence of
desmoplastic development & a tumor-vermis
cleavage plane in a posterior fossa that
isodense
• MRI- T1 weighted images- hypointense
to isointense with gray matter.
• T2 weighted images-isointense to
hyperintense
 TReatment
• Surgical resection offers long-term
remission in about half of the newly
diagnosed patients
• Radical surgery alone may be sufficient
for infants and adults with low-grade
tumors
• Second look surgery may be useful in
dealing with residual tumors
• Aggressive efforts at local control and
surgery in eloquent areas such as the
brainstem can lead to significant
morbidity
• In addition to preoperative deficits new
or increased postsurgical cranial nerve
palsies worsening ataxia and bulbar
dysfunction occurred in 10-19 children
• Postoperative deficits arising from aggressive
surgery in 11 infants with CP angle tumors
resolved at a median follow-up of 37 months
HEMNGIOBLASTOMAS OF THE
CNS
 EPIDEMIOLOGY AND GENETICS
• Account for 2% of intracranial tumors
• 10% of posterior fossa tumors
• Constitute 2%-3% of all intramedullary
spinal cord tumors
• 25% are associated with VHL disease
• Sporadic hemangioblastomas typically
present at 40-50 years of age
• Patients with VHL present in their 20s to 30s
• Absolute ratio of men to women varies from
1.3:1 to 2:1
 CLINICAL PRESENTATION
• sporadic hemangioblastomas
predominantly occur in the cerebellum
but VHL associated hemangioblastomas
occur in the cerebellum brainstem or
spinal cord with multiple hemngiomas in
various sites.
• Slowly growing masses associated with cysts
in the cerebellum or a syrinx in the brainstem
or spinal cord
• In the posterior fossa cause impaired
cerebrospinal flow because of compression of
the 4th ventricle
• S/SX:
• Headache-subocciptal region worse in the
morning
• Lhermitte’s sign neck stiffness due to
compression of the brainstem as ot passes
through the foramen magnum
• Vomiting is common due to obstructive
hydrocephalus
• Vertigo-for tumors located in the
brainstem or middle cerebellar peduncle
adjacent to the vestibular nuclei
• Unstable gait-tumors in the cerebellum
or pons
• Cerebellar hemispheric lesions cause
limb ataxia, dysmetria and intention
tremor
• Spinal pain and spasticity, weakness, sensory
changes, hyperactive reflexes, impaired
urination
 DIAGNOSTIC STUDIES
• MRI with contrast is the dx of choice
• T1 weighted images appears as contrast
enhancing nodule with an associated sharply
demarcated non-enhancing smooth cyst
• Without contrast in T1-weighted images
nodule is hypointense to isointense
• On T2 its hyperinstense
 Conventional angiography
• Can demonstrate the location of dominant
feeding arteries.
• It shows the highly vascular tumor nodule
with an avascular cyst
 TREATMENT
• Surgery with complete excision
• Tumors in the cerebellum are best approach with
the patient in the prone position through a
suboccipital craniotomy or craniectomy
• Brainstem hemangiblastoma resection is not
recommeded
• Tumors located dorsally in the spinal cordwide
laminectomy with resection of the medial portion
of the facets provides adequate exposure
• Ventrally located tumors are best approached
using a posterolateral trajectory with
laminectomy facetectomy, resection of the
pedicle & gentle rolling of the spinal cord
 RADIATION THERAPY
• External beam radiation can be used to
control incompletely resected solid
lesions or multiple lesion in the patients
VHL disease
• SRS provide greater benefit for VHL
disease with recurrent disease or
multiple tumors in the brainstem and
spinal cord