New Approaches to Pediatric Brain Tumors

Report
CASE
PRESENTATION
By
Dr. Ayman S.Iskander
History
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Name : Aziza Ahmed Mohmed Makaran .
Age : 4 years- 10 months .
Sex : Female .
Nationality : Somali
Complaint:
Repeated vomiting , colic 3 days duration
?? Hx of fever (not documented)
Condition started 3 days prior to her admission by vomiting ,
colic mainly in epigastric region.
Unclear history of fever, headache.
Child was product of C.S. with normal neonatal history.
No history of contact to sick person .
No history of previous admission.
No history of head trauma.
No history suggestive of food poisoning .
No history of drug intake.
EXAMINATION
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Vital signs :
Temp. : 37 c
HR : 120/m
RR : 30/m
O2 SAT : 97%
Bl P 110/70
Patient did not look well, but conscious
Chest , Heart clinically free
ENT :free
Abdomen : soft ,lax with some epigastric tenderness .
Genitalia : normal female genitalia
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CNS : slighitly drowsy ,coscious .
no signs of meningial irritation .
no hyper or hypotonia, normal DTR
reflexes .
pupil : round, regular and reactive
Apparent convergent squint .
Gait : she is bed ridden, very irritable and
refusing to move
Fundus : Bilateral papiledema and retinal
hemorrhage .
Progress in Hospital
 Brought to Emergency Dept on 17-09-1012 at afternoon with
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vomiting, colic 3 days , giving IVF for 2 hours but still tired,
vomiting colic not improved .
Admitted to the hospital at 09:00 pm
To continue IVF , I V. Zantac
At 7 am of next day after 8 hrs from admission she had severe
attack of vomiting ,??convulsion in sort of staring look ,without
tonic or clonic components.
Vital sign was o2 sat 98% , HR :60/min ,
Bp : 131/78 , and drowsy .
CT brain urgently requested and done .
An Uregent CT brain
FINDINGS
" Well defined hyper-dense spherical-shaped lesion in the cerebellar vermis,
floor of the 4th ventricle, showing enhancement in the post-contrast images.
This lesion has central calcification and areas of necrosis, and demonstrates
mass effect in terms of compressing the 4th ventricle with mild dilatation of the
distal ventricular system.
" The cerebral cortical hemispheres demonstrate normal gyri with preserved
grey/white matter differentiation.
" Normal attenuation and configuration of the basal ganglia, internal and external
capsules.
" Normal attenuation of the peri-ventricular white matter and centrum semi-oval.
" No midline shift.
" Normal calvarium bones.
CONCLUSION
" Well defined hyper-attenuated lesion in the cerebellar vermis with central
areas of calcification and necrosis associated with mild hydrocephalus. The
patient age and CT features are suggestive of Medulloblastoma.
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Then neurosurgeon contacted and he adviced
to send the case to Neurosurgery Dept, Ibin
Sina Hospital and patient admitted their same
morning.
BRAIN TUMORS
IN
PEDIATRICS
Cancer in Children <15 years old:
Major Histologic Subtypes
11%
5%
32%
6%
7%
8%
11%
20%
Leukemia
CNS tumors
Lymphomas
Neuroblastoma
Sarcomas
Wilms tumor
Bone tumors
Misc
Pediatric Brain Tumors
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Second most common malignancy of childhood
(~20% of all childhood cancers)
Leading Cause of Cancer Death in Children
Incidence in developed countries is 32.7-34.9
cases per million
Classification of brain tumors
in
pediatrics
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Intracranial neoplasms
Primary
 Secondary
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Metastatic
 Local invasion
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Tumors of the spinal cord
Primary brain tumors
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Primary brain tumors are rare
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2.5% of all cancer deaths
Second most common type of tumor in children
There are over 100 different brain tumors
Most common types
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Astrocytomas
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Medulloblastomas
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Grades I-IV
primitive neuroectodermal tumor-PNET
Meningiomas
Pituitary adenomas
Clinical presentation
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Clinical symptoms depend upon:
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Age, location, and type of tumor and grade
Symptoms may include:
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Increased intracranial pressure
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secondary to obstruction of CSF at aqueduct
hydrocephalus (infants), headache, papilledema, vomiting
seizures
focal neurological deficits
hormonal changes (pituitary adenoma)
visual changes (diplopia, field defects)
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Pituitary adenoma - pressure on optic chiasm
Medulloblastoma
the most common malignant brain tumor
in children, accounting for 10-20% of
primary CNS neoplasms and approximately
40% of all posterior fossa tumors. It is a
highly invasive embryonal neuroepithelial
tumor that arises in the cerebellum and has a
tendency to disseminate throughout the CNS
early in its course
Epidemiology
Posterior fossa tumors are more
common in children than the adults.
Between 54% and 70% of all
childhood brain tumors originate in the
posterior fossa.
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Peak age of incidence is 5-7 years
Approximately 300 new cases in the US/year ~
5/1 million children
2:1 Male predominence
75% diagnosed <15 years of age
No associated environmental factors known
Clinical presentation
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Although 70-90% of patients with
medulloblastomas present with a history of
headaches, emesis, and lethargy, these symptoms
are generally intermittent and subtle. Duration of
symptoms for 3 months or more before diagnosis is
common.
Increased intracranial pressure (ICP)
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Early symptoms are secondary to increased ICP.
The classic triad consists of morning headaches,
vomiting, and lethargy.
Cushing triad (ie, hypertension , bradycardia,
and hypoventilation), an uncommon finding in
children with increased intracranial pressure, usually
indicates impending herniation.
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Initial signs of increased ICP are usually
subacute, nonspecific, and nonlocalizing.
School-aged children may complain of vague
intermittent headaches and fatigue.
Infants may present with irritability, anorexia,
and developmental delay.
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Cerebellar dysfunction
With increasing tumor size and invasion into the surrounding
brain tissue, more characteristic symptoms appear. One
symptom is progressively worsening ataxia involving the lower
extremities
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Brain stem deficits
Tumor infiltration of the brain stem or increased ICP may result
in diplopia and multiple other cranial nerve findings, such as
facial weakness, tinnitus, hearing loss, head tilt, and stiff neck.
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Metastatic disease Uncommon
Causes
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Environmental
Epidemiological studies investigating parental
occupational exposures, environmental
exposures and maternal nutritional intake have
not proven a direct link
Familial and heritable disease
Medulloblastoma is associated with recessively
inherited Turcot and ataxia-telangiectasia syndromes.
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Genetic associations
The most frequent cytogenetic abnormality in
sporadic medulloblastoma is an isochromosome
17q [i(17q)]. Of tumors analyzed, 40-50% have a
deletion of the short arm of chromosome 17, implicating
the presence of a tumor suppressor gene that
maps to 17p, which is distinct from
the p53 gene. Alternatively, a gene on 17q may
be related to transformation because of
increased copy number.
Current Risk Stratification
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Average Risk
Age > 3 years
M0 at diagnosis
Less than 1.5cm3 of
residual tumor on
post-operative MRI
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High Risk
Age < 3 years
M1-M4 stage at
diagnosis
Treatment
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Surgery: Goal is for gross total resection of the
primary mass
Radiation: Craniospinal with a posterior fossa
boost: Currently trying to safely reduce dose and
field
Chemotherapy: Platinum based regimens.
(Allows for lower dose radiation in M0 patients
Prognosis according to Risk
Group
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< 3 years of age at diagnosis: <30 % chance of
cure
>3 years with localized disease: 80% chance of
cure (goal= decrease toxicity)
>3 years with metastatic disease: ~ 50% chance
of cure (increase cure)
Sisters having fun together: Life
after brain tumor treatment
References
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Giangaspero F, Eberhart CG, Haapasalo H, Pietsch T, Wiestler OD, et al.
(2007) Medulloblastoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee
WK, eds. WHO classification of tumours of the central nervous system.
Lyon: IARC .Press. pp 132–140.
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Hui AB, Takano H, Lo KW, Kuo WL, Lam CN, et al. (2005) Identification of
a novel homozygous deletion region at 6q23.1 in medulloblastomas using
high resolution array comparative genomic hybridization analysis. Clin
Cancer Res. 4716–4707 :11
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Rutkowski S, von Bueren A, von Hoff K, Hartmann W, Shalaby T, et al.
(2007) Prognostic relevance of clinical and biological risk factors in childhood
medulloblastoma: results of patients treated in the prospective multicenter
trial HIT’91. Clin Cancer Res 13: 2651–2657.
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Lamont JM, McManamy CS, Pearson AD, Clifford SC, Ellison DW (2004)
Combined histopathological and molecular cytogenetic stratification of
medulloblastoma patients. Clin Cancer Res 10: 5482–5493.
Di C, Liao S, Adamson DC, Parrett TJ, Broderick DK, et al. (2005)
Identification of OTX2 as a medulloblastoma oncogene whose product can
be targeted by all-trans retinoic acid. Cancer Res 65: 919–924.
28. de Haas T, Oussoren E, Grajkowska W, Perek-Polnik M, Popovic M, et
al. (2006) OTX1 and OTX2 expression correlates with the clinicopathologic
classification of medulloblastomas. J Neuropathol Exp Neurol 65: 1–11.

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