Pediatric Brain Tumor Flashcards
What is the most common pediatric solid tumor? Accounts for how much of childhood cancers?
Brain tumors
18-20%
What are the peak ages for CNS tumors?
Early childhood and late adulthood
What is the gender predominance in the first decade of life?
Male
What location of CNS tumors is the most common in children? Except when?
Infratentorial tumors
1st year of life
What type of CNS tumors are more likely to occur in children and young adulthood? Older adulthood?
Medulloblastomas, supratentorial primitive nueroectodermal tumors (PNET) and pineoblastomas;
GBMs
What is most common type of CNS tumors in pediatric populations?
Astrocytomas followed by PNETs, other gliomas then ependynomas
What the anatomic sites and percent of incidence for pediatric CNS tumors?
Supratentorial [30-50%]
Midline [10-15%]
Infratentorial [50-60%]
Location of infratentorial tumors?
75% in cerebellum & 4th ventricles
Tumors of Posterior Fossa?
Medulloblastoma
Astrocytoma
Brainstem glioma
Ependynoma
Suprasellar Tumors?
Chiasmal gliomas
Craniopharyngiomas
Hemispheric tumors?
Low-grade astrocytoma
High-grade astrocytoma
What location of CNS tumors do you think of in patients < 1 year? Type?
Supratentorial; Gliomas, Teratomas, PNETs, Choriod Plexus
What location of CNS tumors do you think of in patients 1 - 11 year? Type?
Infratentorial > supratentorial; Medulloblastoma, Ependymoma, Brainstem gliomas
What location of CNS tumors do you think of in patients > 11 year? Type?
Infratentorial = Supratentorial; Gliomas, PNET/Medulloblastoma, Germ cell
Pre-disposing factors for CNS tumors in children?
Ionizing radiation
Other tumors (i.e. Kidney, retinoblastoma)
Immune suppression (i.e. Wiskott-Aldrich Syndrome, Ataxia - telangiectasia, AIDs)
Famial conditions
Neurofibromatosis I - tumor type? Cytogenetic features?
Optic gliomas, meningiomas, ependymomas; 17q11.2 allelic loss
Neurofibromatosis II - tumor type? Cytogenetic features?
Bilateral vestibular schwannomas; 22q deletions/ NF2 gene mutations
Tuberous sclerosis - tumor type? Cytogenetic features?
Subependymal giant cell tumors; TS gene map to 9q/16p
Von Hippel-Lindau disease - tumor type? Cytogenetic features?
Hemangioblastomas; VHL gene on 3p25
Turcot syndrome - tumor type? Cytogenetic features?
Medulloblastomas, glioblastoma multiforme; Germline mutation in APC gene or mismatch repair genes hMLh1 & hPMS2
Cowden - tumor type? Cytogenetic features?
Dysplastic ganliocytoma of the cerebellum;
Loss-of-function in PTEN –> hyperactivity of mTOR pathway
Li-Fraumeni - tumor type? Cytogenetic features?
Multiple brain tumor types but commly astrocytoma and medulloblastoma; p53 mutation
Nevoid basal cell carcinoma/Gorlin syndrome - tumor type? Cytogenetic features?
Medulloblastoma; Mutations in PTCH
Most pediatric brain tumors arise from what?
Glia of the brain
Where else can pediatric brain tumors arise from?
Primitive nerve cells
Non-neuronal embryonal cells
Clinical presentation the Ped CNS tumor depends on what?
Location rather than histology
What is the clinical presentation of those pts with supratentorial tumors?
Localizing findings
Seizures
Hemiparesis
What is the clinical presentation of those pts with midline tumors?
Endocrinopathies Diabetes insipidus Growth disorders decreased vision Visual field deficits Signs of increased ICP
What is the clinical presentation of those pts with infratentorial tumors?
Signs/Symptoms related to increased intracranial pressure
What is the clinical presentation of those pts with brain stem tumors?
Cranial nerve deficit: Double vision, slurred speech, swallowing disorders, “Crossed-weakness”
Occasional hydrocephalus
What is hydrocephalus associated with?
Midline brain tumors
What causes hydrocephalus?
Obstruction in the ventricular system
Initial symptoms of hydrocephalus?
Early morning intermittent headaches and nausea/vomiting
Classic triad of signs/symptoms of ICP?
AM headches, nausea & vomiting, and lethargy
If a patient presents with what, do you need immediate intervention?
Sun-downing eyes —> increased ICP
Most common childhood brain tumor?
Low grade Astorcytoma
Location of low grade astrocytoma?
May be either supra or infratentorial
Astrocytomas are derived from?
Astrocytes
Histo of juvenile pilocytic astrocytomas?
elongated hair-like projections (pilocytic) and presence of eosiophillic Rosenthal fibers and hyalinization of blood vessels
What is the process behind juvenile Pilocytic astrocytomas?
Activation of the MAPK pathway
How is the MAPK pathway activated in JPA?
KRAS or BRAF activation
KRAS is activated by what?
Pts with neurofibromatosis type 1 lose the inhibitory gene NF1 which leads to activation of KRAS
BRAF can be activated through what?
v600E mutation
BRAF fusion JPAs are typically found where?
Cerebellar tumors
BRAF v600E mutation JPAs are typically found where?
extracerebellar regions
NF1 loss JPAs are typically found where?
Optic pathway
From where do medulloblastomas arise?
Primitive nerve cells
What is a medulloblastoma found in cerebrum locations called?
Primitive neuroectodermal tumor (PNET)
What is a medulloblastoma found in cerebellar locations called?
Medulloblastoma
Peak age of medulloblastoma?
3-4 years
Male:Female ratio of medulloblastoma?
1.5:5
Growth speed of medulloblastoma?
Rapidly and tend to spread through the CSF
Histo of medulloblastoma?
Densely cellular, Round, oval or angulated (‘carrot-shaped’), Low vascular density, Homer-Wright rosette.
Hyperchromatic
What are Homer-Wright rosettes?
Pseudorosettes consisting of tumor cells surrounding a fibrillar area
Two most common pathways involved in medulloblastomas?
Shh and Wnt pathways
Describe the inactive Wnt pathway?
Frizzled receptors are inactive and b-catenin is phosphyorylated and bound in a protein complex, which is targeted for proteosomal degradation
Describe the active Wnt pathway?
Frizzled receptors are active and b-catenin complex is disrupted allowing translocation to the nucleus where it is a transcriptional activator.
Describe the inactive Shh pathway?
Ptch receptors inhibit Smoothened receptors preventing Smoothened relocating to the cilium. Some Smoothened receptors undergo endocytosis and are incorporated by endosomes. SuFu binds Gli2 and Gli3, downstream effectors in the cytoplasm and primary cilium. Gli2 is also targeted for degradation through the proteosomal pathway
Describe the active Shh pathway?
Ptch does not suppress Smoothened, which relocates to the cilium with the aid of Kif7. SuFu no longer binds to Gli2 and Gli3, so Gli2 relocates to the nucleus and is a transcriptional activator. Gli3 is a repressor.
What is contraindicated in brainstem glioma?
Surgery
Symptoms of diffuse intrinsic pontine glioma?
Corticospinal long tract signs (weakness or hemiparesis), ataxia, and CN 6,7,8 deficits
MRI characteristics of diffuse intrinsic pontine glioma on MRI?
Engulfs basilar artery by tumor, diffuse extension into pons
From what do ependymoma arise?
Ependymal lining of ventricles or central canal of spinal cord
Sites of ependymoma?
Posterior fossa 60%
Spinal Cord 10%
Histo of ependymoma?
Perivascular pseudorosettes of glial tumor cells that are radially arranged around the blood vessels and true ependymal rosettes of tumor cells that form a central lumen on their own
When is development(axonal growth and synaptogenesis) most rapid?
< 3 yrs
When does growth and development slow?
> 6 yrs
When is maturation (degree of myelinization) complete?
Puberty
Neuropsychological effects of radiation on the developing brain?
Intellectual impairment, memory deficits, and inability to acquire new knowledge
When is cognitive impairment due to radiation therapy most pronounced?
< 4 - 7 yrs of age
