Pediatric Brain Tumors Flashcards
Brain Tumors in Children: Epidemiology
- most common pediatric solid tumor accounting for 18-20% of all childhood cancers
- 2nd most common malignancy after leukemia
- most common in 1st decade of life
- 2,200 cases/year or 3.3 cases per 100,000
- survival to adulthood is 65%
- 2 peaks early childhood + late adulthood (8th decade)
- infratentorial tumors most common in children except in 1st year of life
- male predominance in 1st decade
Brain Tumors Children Histology
- embryonal histology is seen more commonly in 1st decade than in adults
- Medulloblastomas, supratentorial primitive neuroectodermal tumors (PNET) & pineoblastomas occur almost exclusively in children & young adults
- High grade gliomas (glioblastoma multiforme) are rare in the pediatric age group
Most common CNS tumors in Pediatrics?
-Astrocytomas
then PNETs, other gliomas, then ependymomas
Site of Pediatric Brain Tumors
- Supratentorial 30-50%
- Midline 10-15%
- Infratentorial 50-60%
Brain Tumor Distribution & Age
11 yrs Infratentorial (supratentorial) Gliomas, PNET/Medulloblastoma, Germ cell
Pre-disposing factors for Brain Tumors
- Ionizing Radiation
- Other tumors (Kidney, Retinoblastoma)
- Immune Suppression (Wiskott-Aldrich Syndrome, Ataxia-Telangiectasia, Acquired Immunodeficiency)
- Familial Conditions
Origins of Pediatric Brain Tumors
- Most arise from the supporting cells of the brain (glia) and are called “gliomas”
- Others arise from the primitive nerve cells, that are much more common in children than in adults
- A 3rd type of childhood brain tumor arises in the non-neuronal embryonal cells
WHO Classification of Glial Tumors
- Astocytomas
- Oligodendrogliomas
- Ependymal Tumors
- Choroid Plexus Tumors
- Mixed Gliomas
- GBM
WHO Classification of Neuronal Tumors
- Gangliocytoma
- Anaplastic ganglioma
WHO Classification of Primitive Neuro Ectodermal
- PNET
- PNET with differentiation
- Medulloepithelioma
WHO Classification of Pineal Cell Tumors
- Pineocytoma
- Pineoblastoma
Clinical Presentation of Brain Tumor
- Varied
- Location rather than histology
Clinical Manifestations of Pediatric Brain Tumors: Supratentorial
-Localizing Findings: seizures, Hemiparesis
Clinical Manifestations of Pediatric Brain Tumors: Midline (Hypothalamic/Optic, Craniopharynioma, Pineal)
- Endocrinopathies: (Diabetes insipidus, Growth disorders, Dec. vision, Visual field deficits)
- Signs of inc. ICP
Clinical Manifestations of Pediatric Brain Tumors: Infratentorial
-Signs & Symptoms related to inc. intracranial pressure
Clinical Manifestations of Pediatric Brain Tumors: Brain Stem
- Cranial Nerve Deficit: (double vision, slurred speech, swallowing disorders, “crossed-weakness”)
- Occasional Hydrocephalus
Hydrocephalus
- associated with 80% of midline brain tumors
- due to obstruction in ventricular system
- Initial symptoms are early morning intermittent headaches & nausea/vomiting
- most resolve after mass resection, but 15% require placement of shunt or ventriculostomy
- complications include shunt failure, infection or hemmorhage
Ocular Pathology of Tumors
-Proptosis or ptosis
Papilledema
-blurring of optic disc margin with increased ICP
Signs & Symptoms of ICP
Triad: AM headaches, Nausea/Vomiting, Lethargy
- bulging fontanelle, sundowning of eyes, CN 6 palsy, HA/N/V
- 1/3 post. fossa tumor patients will require permanent VP shunts following surgical debulking
- presentation before diagnosis is 4-6 months
Tumor Diagnostic Evaluation
- H&P (neuro exam)
- Diagnostic Imaging (CT, MRI, MRA, MRS)
- Tissue Diagnosis (surgical biopsy, surgical resection, CSF cytology)
- Metastatic evaluation (CSF evaluation, bone scan, bone marrow aspirates)
MRI
- preferred diagnostic study
- easy manipulation of image plane
- avoidance of ionizing radiation
- sensitive to acute, subacute, & chronic blood products
- expensive
- lengthy exam often requiring sedation or anesthesia
CT
- fast
- useful in emergent situations
- less expensive
Low Grade Astrocytoma
- most common childhood brain tumor
- 40% of all CNS tumors
- may be supra or infratentorial
- derived from astrocytes, which are major supportive cells
- astrocytes constitute 40% of CNS cell population & are widely spread throughout the CNS including the optic nerves
Astrocytoma: Grading
- low grade are I & II which are histologically benign
- grade III (anaplastic astrocytoma) & IV are malignant (glioblastoma multiforme)
- high grade gliomas represent 7-11% of all CNS tumors
Low Grade Astrocytoma Treatment
- primarily a surgical disease
- greater than 75% 5 year survival if gross total resection achieved (90% 5 yr survival and >70% 20 year survival
- chemo/radiation options in those with residual tumor or recurrent disease
Juvenile Pilocytic Astrocytoma
- can be in optic pathway
- can be seen with solid & cystic components
- contrast enhancing tumor
- elongated hair-like projections from neoplastic cells
- presence of eosinophillic Rosenthal fibers & hyalinization of blood vessels
Juvenile Pilocytic Astrocytoma
- driven by an oncogenic process activating the MAPK pathway
- KRAS activation, BRAF activation with either duplication of c’s 7 or v600E mutation causes activation of BRAF
- patients with NF1 have loss of inhibitory gene NF1 causing KRAS activation
Pilocytic Astrocytoma Mutations
- BRAF fusion - in cerebellar tumors
- BRAF V600E mutation - extracerebellar regions
- NF1 loss - in optic pathway tumors
Medulloblastoma
- 20% of all CNS tumors (40% of posterior fossa tumors)
- more common in children than adults
- arise in primitive nerve cells
- cerebrum location (primitive neuroectodermal tumor PNET))
- cerebellar location: medulloblastoma
- peak age is 3-4 years
- male to female 1.5:1
Medulloblastoma: Prognostic Factors
- age
- histology
- size at diagnosis
- metastatic spread
- extent of resection
- neurotrophin-3 receptor, TrkC, ErbB2, ErbB-4, C-myc overexpression
Medulloblastoma: Treatment
- malignant WHO grade IV grow rapidly & tend to spread through the CSF
- often infiltrate adjacent brain structures preventing total resection
- surgery with craniospinal radiation
- Adjuvant chemotheraphy beneficial (especially in infants & in desseminated or recurrent disease)
Medulloblastoma: Microscope
- densely cellular, round, oval or angulated “carrot-shaped”
- low vascular density, Homer-Wright rosette = pseudorosettes consisting of tumor cells surrounding a fibrillar area
- hyperchromatic
Medulloblastoma: Pathogenesis
- Wnt pathway - good prognosis
- Shh (PTCH mutation) pathways - good in infants, intermediate in rest
Brainstem Glioma
- 15% of all CNS tumors
- surgery contraindicated
- uniformly fatal in 18-24 months & <10% 5 year survival
- radiation therapy provides temporary improvement
- supportive care
Diffuse Intrinsic Pontine Glioma
-8-10% of all pediatric CNS tumors
-prognosis dismal, median survival from 9-11 months, only 20% past a year
~7 y/o
-symptoms: corticospinal long tract sighs (weakness or hemiparesis), ataxia, CN 6, 7, 8 defects (difficulty w/lateral gaze)
-diagnosis by MRI (engulfs basilar artery by tumor, diffuse extension into pons
-Treatment: not resectable, radiation helps prolong life
Ependymoma
- 9% of all CNS tumors
- highest incidence in 1st 7 yrs of life, 1:1 M:F
- arise from ependymal lining of ventricles or central canal of spinal cord
- Posterior Fossa 60%
- Spinal Cord 10%
Ependymoma Microscope
- Classic (WHO II) exhibits perivascular pseudorosettes of glial tumor cells that are radially arranged around the blood vessels
- also true ependymal rosettes of tumor cells that form a central lumen on their own
Ependymoma action
- 50% of patients are <5yr at presentation
- tumors are locally invasive
- CNS dissemination is 7-10%
- may be low grade or anaplastic
- PNET variant is called ependymoblastoma
- staging should include CSF examination & spinal MRI
Ependymoma Prognostic Factors
- surgical resection
- brain stem involvement
- age
- stage at presentation
Treatment of Brain Tumors
- surgery
- radiation
- chemo
Surgery
- primary treatment modality
- curative alone in only 20% of cases
- goals - established histologic diagnosis reduction in tumor burden
- extent of resection & outcome
- notable exception: diffused brain stem gliomas
Radiation Therapy
- volume & dosage vary according to the histologic diagnosis
- localized treatment unless high likelihood of neuraxis dissemination
- medulloblastoma/PNET
- age & radiation
Radiation & the Developing Brain
- development (axonal growth & synaptogenesis) is most rapid in first 3 years of life
- rate of growth & development slows after age 6
- maturation (degree of myelinization) isn’t complete until puberty
- want to wait till after 3 but 7 is even better
- effects delayed months to years after treatment
- Neuropsychological effects: intellectual impairment, memory deficits, & inability to acquire new knowledge
- Cognitive impairment is most pronounced in kids younger than 4-7
Which is more common: infratentorial or supratentorial?
-infratentorial
