Pediatric Brain Tumors (7) Flashcards
What is the 2nd most common malignancy overall in childhood?
Brain tumors–> 2nd in incidence to leukemia, but are the most common solid tumor in children
What is the most common malignancy overall in childhood?
Leukemia
What is the most common anatomical site for brain tumors in children?
70% occur below the tentorium cerebelli (infratentorial) –> so in cerebellum and brainstem
*except in 1st year of life
What three types of brain malignancies occur almost exclusively in children?
- Medulloblastoma
- Supratentorial primitive neuroectodermal tumors (PNET)
- Pineoblastomas
In a child less than 1 year of age with a supratentorial mass, what are three possible tumors? (supratentorial is the MC location for this particular age group)
- Gliomas
- Teratoma
- PNET
(maybe could be choroid plexus tumor)
In age 1-11, what are three types of tumors that are more likely (these have much higher incidence of infratentorial)?
- Medulloblastoma
- Ependymoma
- Brain stem Glioma
Other than Hx of radiation, Polycystic Kidney dz, and RB, what are two conditions that can predispose to brain tumors in childhood?
- Wiskott-Aldrich syndrome
2. Ataxia-Telangectasia
Where do most tumors in the CNS arise from in children?
From glial cells (gliomas) just like adults
*Children do more commonly have tumors arising from primitive nerve cells however
What general kinds of symptoms will be seen due to a tumor in the supratentorial location?
Localized neuro findings–> seizures, hemiparesis, etc
What general kinds of findings will be seen in pt with a tumor in the midline?
Endocrinopathies also hydrocephalus in 80%
What general issues will a tumor in the infratentorial space cause?
Signs/ symptoms of increased intracranial pressure (papilledema, headache, vomiting, lethargy; esp. HA and or vomiting that is worse in the AM after waking up)–> due to compression of 4th ventricle
What are two SIGNS that may be present in a child presenting with increased ICP?
- Bulging fontanelle
- “Sundowning” of eyes
*also CN 6 palsy; presentation before Dx is usually 4-6 months
What is the preferred imaging modality for detecting brain tumors?
MRI
What deficits in general will be caused by masses in the brainstem?
Cranial nerve deficits also “crossed weakness” deficits (upper motor neuron paralysis of arm and leg contralateral to lesion and lower motor neuron paralysis involving cranial nerve motor function ipsilateral to the lesion)
What is the most common specific brain tumor in children?
Pilocytic (low-grade) astrocytoma
*high grade astrocytomas are also fairly common in peds, but less than the low grade (7-11% are high grade)
What is the characteristic microscopic path finding dor a astrocytoma (low-grade)? What are they positive for?
Rosenthal fibers–> hair-like basophilic projections; cells are GFAP+
*hyalinization of blood vessels is a common feature as well
What location in the brain are most astrocytomas found in in the pediatric population?
Posterior fossa (+/- optic nerve involvment)
What location in the brain are astrocytomas commonly BRAF fusion gene positive?
Cerebellar tumors
What location in the brain are astrocytomas with BRAF v600e mutations commonly found?
Extracerebellar tumors
What mutation is involved often when there is optic pathway involvement in an astrocytoma?
NF1–> is a inhibitory gene for KRAS, so loss equals unchecked KRAS activation = increased nuclear transcription
What is the gross appearance of an astrocytoma?
Cystic lesions
What is the best treatment for an astrocytoma?
Is primarily a surgical disease; chemo/radiation are options in those with residual tumor or recurrent disease.
Is prognosis good for pediatric astrocytomas?
Very; over 90% 5 year survival with pilocytic (grade 1) astrocytomas and over 70% 20 year survival
Which oncogenic pathway is activated in pilocytic astrocytomas?
MAPK pathway–> leads to increased nuclear transcription
How do BRAF mutations cause astrocytoma neoplasms?
BRAF mutations all activate RAF (downstream of KRAS) = net result is increased activation of MAPK pathway (of which KRAS is the first intracell mediator, then RAF–>MEK–>ERK–> nuclear transcription)
What highly malignant CNS tumor from primitive nerve cells accounts for 20% of all CNS tumors and is more common in children than adults?
Medulloblastoma–> peak age is 3-4 years; affects males very slightly more
Where are medulloblastomas very commonly found?
In the cerebellum (in 3-4 year old children)
What is the histological appearance of medulloblastoma?
Densely cellular; carrot-shaped small blue cells with Homer-Wright rosettes (psuedorosetts consisting of tumor cells surrounding a fibrillar area)
What two molecular pathways are involved in meduloblastomas?
Wnt and sonic hedgehog pathways
What is the gross appearance of medulloblastomas?
Solid tumor, usually in the midline of the cerebellum
What are 5 prognostic factors for meduloblastomas?
- Age of patient
- Histology
- Size at diagnosis
- Metastatic spread
- C-myc overexpression (bad)
What two molecular subtypes of meduloblastoma have a good prognosis?
- Wnt (classic histology)
- SHH
*meduloblastomas are very sensitive to radiation
What type of CNS tumor is commonly found in the third ventricle and has a bad prognosis?
Ependymoma–> can cause hydrocephalus
What is a common benign childhood CNS tumor?
Craniopharyngioma
What embryonic structure are Craniopharyngiomas derived from? Common symptom?
Rathke’s pouch–> may cause bitemporal hemianopnia
Craniopharyngioma is the most common childhood tumor to be found in what anatomical location?
Supratentorial
In what type of astrocytoma subtype is surgery contraindicated?
Brainstem glioma–> horrible prognosis; iniformly fatal in 18-24 months; radiation can be used for temporary improvement
What characteristic feature on MRI is seen with a brainstem glioma, more specifically Diffuse Intrinsic Pontine Glioma?
Engulfment of the basilar artery–> visualization of this on MRI confirms the Dx
What age is the median age of onset for diffuse intrinsic pontine glioma?
7 years
What are the three classic symptoms of diffuse intrinsic pontine glioma?
- Corticospinal long tract signs (weakness or hemiparesis)
- Ataxia
- CN 6, 7, 8 deficits (especially difficulty with lateral gaze)
When is the highest incidence of ependymoma?
First seven years of life; 50% are less than 5 years at presentation
Staging for ependymoma should include what two investigations?
- CSF examination
2. spinal MRI
What 4 factors are involved in determining prognosis for ependymoma?
- Surgical resection
- Brainstem involvement
- Age
- Stage at presentation
Surgery alone is curative what % of time in pediatric CNS tumors?
20%. but reduces tumor burden and can allow for biopsy ans subsequent histological diagnosis
What determines the volume and dosage of radiation given in CNS tumors?
Histologic Dx
What age do oncologists try to wait before beginning any kind of radiation therapy to the brain? What age is better than that?
3 years–> axonal growth and synaptogenesis is most rapid in the first three years
If possible, wait until age 7; rate of growth and development slows after age 6
When is myelinization of CNS complete?
Not until puberty
What 3 deficits can occur as the result of starting radiation too young?
- intellectual impairment
- memory deficits
- inability to acquire new knowledge
Overall, CNS tumors have ___% cure rates
65%
