Peadiatric Brain Tumour

Wong Ann ChengMD (UKM) MRCPCH (UK)

Normal Anatomy of Brain (MRI)

• Supratentorial compartment:– Cerebral hemispheres– Basal ganglia– Thalamic nuclei– Lateral ventricles– Hypothalamus– Corpus callosum

• Infratentorial compartment:– Cerebellum– Brain stem (MB/P/MO)– 4th ventricle

Sagittal

Axial

Epidemiology

• 2nd most common pediatric malignancy– 2.4-4.1 cases / 100000 children– About 2000 new cases / year

• Leading cause of cancer death

• More common in males (M:F = 1.29)

• Children 1-11years old– Majority arises infratentorially

Cancer research UK

Epidemiology

• Classified by histology

• Medulloblastoma most common malignant brain tumour

• Low grade astrocytoma most common benign brain tumour

Table :   Relative Incidence of Common Brain Tumors in Children

Diagnosis Relative Frequency Peak Age Group (years)

Astrocytoma   -Supratentorial   -Infratentorial

35%22%13%

2-10>62-10

Malignant glioma (anaplastic astrocytoma and glioblastoma multiforme)

8% <1, >6

Brain stem glioma 8% 3-9

Oligodendroglioma 2% <6

Medulloblastoma 20% 1-10

Ependymoma   -Supratentorial   -Infratentorial

8%5%3%

 >61-5

Craniopharyngioma 7% 8-14

Pineal region and germ cell tumors

4% <2, >6

Choroid plexus tumors 2% <1

Others: ganglioglioma, meningioma, neuroblastoma, primitive embryonal tumors

<2% each  

Etiology

• Largely unknown• Certain inherited familial syndromes associated

with predisposition to brain tumours• Other predisposing factors include certain

immunodeficiencies and exposure to ionizing radiation

• Other environmental exposure e.g parental occupation, diet, magnetic field inconclusive

Inherited familial syndromeInherited Familial Syndrome Brain Tumour

Neurofibromatosis type 1 Optic pathway glioma, astrocytoma

Neurofibromatosis type 2 Acoustic neuroma, meningioma, ependymoma

Tuberous sclerosis Subependymal giant cell tumour, ependymoma

Li-Fraumeni Astrocytoma, medulloblastoma

Nevoid basal cell carcinoma medulloblastoma

Turcot Medulloblastoma, astrocytoma

Von Hippel Landau haemangioblastoma

Clinical presentation

• Dictated by location rather than histology• Generalized sx caused by increased ICP, usu

results frm CSF obstruction or SOL within fixed skull

• Likely to occur with tumours in posterior fossa, pineal, suprasellar or tectal region

• Sx include headache (esp morning), nausea, vomiting, and fatigue

• Neurological findings include decreased upward gaze, 6th CN palsy, and papiloedema

• Macrocephaly, FTT, and developmental delay common in infants

Clinical presentationTumour location Localizing symptoms

Cerebral hemisphere Seizures

Hemiparesis

Visual field deficits

Change behaviour/ school performance

Suprasellar region Visual field deficit

Endocrinopathy

Weight gain

Pineal region Parinaud’s syndrome

-impaired upward gaze

-convergence nystagmus

-Light near dissociation

Cerebellum Ataxia

Dysmetria

Brain stem CN deficits

Long tract signs

Spinal cord Back pain

Extremity weakness

Sensory dysfunction

Bowel/ bladder dysfunction

Diagnostic test• Neuroimaging

– CT• Useful as quick screen• Hydrocephalus, blood, calcification

– MRI• Gold standard• Post-op scan within 24-48 hrs of resection

– MR spectrometry– PET

• CSF cytology• Tumour markers

– AFP and β-hCG– For germ cell tumour

• Bone marrow aspirate or biopsy

Differential diagnosisLocation Differential diagnosis

Cerebral hemisphere Glioma

Ependymoma

PNET

Suprasellar region Craniopharyngioma

Glioma

Germ cell tumour

Pituitary adenoma

Pineal region Germ cell tumour

Glioma

Pineoblastoma

Cerebellum Pilocystic astrocytoma

Medulloblastoma

Ependymoma

Brain stem Glioma

Spinal cord Astrocytoma

Ependymoma

Treatment modalities

• Surgical resection

• Radiation therapy

• Chemotherapy

Late effects of treatment

• Neurocognitive (age and dose related)

• Endocrinopathies

• Radiation necrosis

• Stroke

• Hearing loss

• Secondary tumours– Meningioma, glioma, sarcoma– leukaemia

Infant brain tumours

• 20% paediatric brain tumours

• Age < 1 year old: more likely supratentorial

• Presentation:– Macrocephaly– FTT– Lethargy– Vomiting– Development delayed or

loss of milestones

• Tumour types– PNET– Low grade glioma– Ependymoma– Malignant glioma– Atypical teratoid/ rhabdoid

tumour– Choroid plexus tumour

Infant brain tumours• Treatment

– Radiotherapy• Assoc with significant

long term toxicity (neurocognitive, endocrine,..)

– Chemotherapy• Initially designed to delay

radiotherapy• Has resulted in cures in

some patients in whom radiotherapy was deferred

• 3-5 years PFS: 23-30%

• Future directions– Dose intensification of

therapy• High dose radiotherapy with

stem cell rescue

– Intrathecal chemotherapy– New agents– Focused radiotherapy

• To limit toxicity to normal brain

Medulloblastoma

• Most common CNS malignancy in childhood• Medulloblastoma = posterior fossa PNET

– 20% primary CNS tumour– 40% posterior fossa tumour– 72% of PNETs– Mean age of presentation: 3-4 years– More common in males (M:F = 2:1)

• Very invasive– CNS manifestation in 11-43% at presentation– Extraneural spread rare (BM, LN, liver, lung)

Usually midline Hypointense T1Isointense T2Enhancing

Propensity to disseminateImaging of the spineLumbar puncture for CSF

PNET/MB Prognostic factors (High-risk features)

• Residual tumour (>1.5 cm2)• Patient age (<3 years old)• Location (supratentorial)• Metastasis (+)• Molecular markers

– 17p deletion– C-myc amplification– Increased HER2/HER4 coexpression– Low TrkC

PNET/MB staging

Standard risk High risk

Age >= 3 years < 3 years

Location Cerebellum Supratentorial

Residual tumour < 1.5 cm2 >= 1.5 cm2

Metastases no yes

PNET/MB therapy

• Surgery• Radiotherapy

– Local: 5400- 5940 cGy– Craniospinal:

• High risk: 3600 cGy• Standard risk: 2340 cGy

• Chemotherapy (active agents)– Vincristine, lomustine, cisplatin, etoposide,

cyclophosphamide

With current therapy approaches, 3-5 year progression free survival

• Standard risk medulloblastoma 86% 3 yr PFS

• High risk medulloblastoma 67% 5 yr PFS

• Infant with PNET/MB 30% 5 yr PFS

• Pineal PNETs 61% 3 yr PFS

• Non-pineal supratentorial PNETs 33% 3 yr PFS

PNET/MB new directions

• High risks – Goal: improve survival– Radiation enhancers– Chemotherapy dose intensification

• Standard risks– Goal: reduce toxicity, maintain efficacy– Reduce craniospinal dose to 1800 cGy– Limit radiation boost field

Ependymoma

• 8-10% of childhood brain tumours

• Most occur in children <7 years

• 60% infratentorial

• 2-5% dissemination at diagnosis

MRIHypointense T1Hyperintense T2Strongly enhancing

Often have necrosis, haemorrhage, calcificationheterogenous

Ependymoma prognostic factors (high risks features)

• Extent of resection– Complete: 50-70% 5yr PFS– Incomplete: 0-30% 5yr PFS

• Histology (anaplastic)

• Metastases (+)

• Age (<3 years)

• Location (infratentorial)

Ependymoma therapy

• Surgery- aggressive resection• Radiation

– Focal: 5400-5940 cGy– Craniospinal: if metastatic disease

• Chemotherapy– Several active agents– Minimal impact on survival– Used in recent trials to shrink tumour

• Observation – May be feasible for supratentorial well-differentiated

tumours

Glioma-astrocytoma grading

Grade Histology

Low grade

(benign)

I

II

Pilocytic astrocytoma

Fibrillary astrocytoma

High grade

(malignant)

III

IV

Anaplastic astrocytoma

Glioblastoma multiforme

Low grade glioma

• Most common paediatric brain tumour• Locations

– Cerebellum– Cerebral hemisphere– Deep midline structures– Optic pathway/ hypothalamus

• MRI– Hypointense T1, hypeintense T2– Pilocytic: well circumcribed, cystic component,

enhancing mural nodule– Fibrillary: little enhancement

Posterior fossa low grade glioma

• Histology– 80-85% pilocystic astrocytoma

• Treatment– Surgery primary therapy

• Complete resection: 100% 10 yr survival• Subtotal resection: 35-65% 5 yr survival

• Management of residual tumour– Observation– Re-resection– Radiotherapy

• STR + XRT: 70-92% 5 yr survival

Optic pathway/ hypothalamic glioma

• 5% of paediatric tumour

• 2/3 diagnosed before age of 5 y.o

• 70% assoc with NF1

• 15% kids with NF1 have OP/HG

• Diagnosis often by MRI alone (esp if NF1)

• Most are fibrillary astrocytomas, although pilocystic astrocytomas are common as well

Optic nerve tumour

OP/HG treatment

• Surgery not often pursue because of likelihood of further compromise in vision

• Observation– Justification: tumor and vision may stay stable for years– Serial MRI and ophthalmology exams

• Radiotherapy– 53-88% PFS – Assoc with significant toxicity

• Chemotherapy– Attempt to delay or eliminate need for radiation– Vincristine/ carboplatin: 78% 5yr survival– TPCV: 68% 3 yr survival

Supratentorial malignant glioma

• 11% paediatric brain tumour• MRI

– Heterogenous (necrosis and haemorrhage)– Enhancing

• Staging – Consider spinal imaging and cytology

• Molecular alteration– P53 pathway abnormalities– EGFR overexpression

Brainstem glioma

• 10-20% peadiatric brain tumour

• Median age diagnosis 6.5 years

• Types:– Diffuse intrinsic– Dorsally exophytic– Cervicomedullary– Focal midbrain

Diffuse intrinsic BSG

• 80% of brain stem tumour

• Most arise in the pons

• Presentation– CN deficits (usu VI and VII)– Hemiparesis– 10% with hydrocephalus

• Pathology- high grade glioma

Hypodense T1Hyperdense T2Little enhancement

Prognostic factors unfavourable

• Short duration of symptoms at diagnosis

• CN deficits at diagnosis

• Pontine location

• Age < 2 years old

Assoc with NF1 confers survival advantage

Treatment –diffuse intrinsic BSG

• Surgery– No role– Biopsy rarely needed

• DXT– 54-55.8 Gy– Prolongs survival– Neurologic improvement

• Chemotherapy– Nothing useful so far

• Survival– Median 9-13 months– 2 year survival <20%

Germ cell tumours• 3-5% of paediatric brain tumours in US, 15-18%

in Asia• Peak age incidence 10-15 years• Location: 2/3 pineal, 1/3 suprasellar• Pathology:

– Germinoma (60%)– NGGCT

• Mature and immature teratoma• Yolk sac tumour• Choriocarcinoma• Embryonal carcinoma• Mixed GCTs

Germ cell treatment

Mature teratoma

- Resection alone

Germinoma•Radiotherapy- 90% 5 year survival- Ventricular volume with tumour bed boost- CSI for disseminated dis•Chemotherapy

- Explored to reduce radiation dose and field

Malignant NGGCT•Radiotherapy- CSI + involved field boost- 20-56% 3 year survival•Chemotherapy

- no standard approach

- has improved survival to

74% in 4 years

Craniopharyngioma

•6-9% of paediatric brain tumours•Over 50% of suprasellar tumours•Peak incidence 6-10 yrs•Benign histology

MRI-Heterogenous with cystic, solid, calcified component-Hyperintense on T2, enhancing

Work Up-Hormone testing-Ophthalmologic evaluation (acuity and fields)

Treatment- craniopharyngioma

• Surgery– Primary modality– Complete resection improved PFS

• Radiotherapy– Subtotal resection + radiation

• survival similar with complete resection

• Prognosis– 60-80% 5yr PFS– 95% 5 yr OS

• Multidisciplinary follow up– Neuro-oncology, ophthalmology, endocrinology

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