BRAIN TUMORS Flashcards
most common solid malignancy in children and most common malignancy overall in kids
solid: CNS, overall: leukemia with CNS next
gender distribution in CNS tumors
M >F
name the gene abnormality and CNS leison: neurofibromatosis type 1
NF1, LGG (optic glioma, brainstem)
name the gene abnormality and CNS leison: Neurofibromatosis type 2
NF2, bilateral acoustic schwannomas, meningiomas, and ependymomas
name the gene abnormality and CNS leison Tuberous Sclerosis
TSC1 and TSC2, subependymal giant cell astrocytoma (SEGA)
name the gene abnormality and CNS leison: Li Fraumeni
TP53, malignant glioma, choroid plexus carcinoma
name the gene abnormality and CNS leison Gorlins (nevoid basal cell carcinoma syndrome)
PTCH, medulloblastoma
name the gene abnormality and CNS leison (familial adenomatous polyposis aka Gardners or Turcots)
APC, medulloblastoma, malignant glioma
name the gene abnormality and CNS leison rhabdoid tumor predisposition syndrome
SMARCB1 and SMARCB4 (aka INI-1), AT/RT
name the gene abnormality and CNS leison retinoblastoma (gremlin)
RB1, trilateral retinoblastoma aka unilateral or bilateral + pineoblastoma
name 3 key other findings in NF1
cafe au last spots, lisch nodules, axillary freckling
increased risk of what besides CNS tumors in NF2
cataracts, seizures
increased risk of what in tuberous sclerosis (Besides CNS lesions)
skin and renal growths
key risks in Li Fraumeni
numerous cancers at younger ages- breast, sarcoma, adrenal cortical carcinoma
key other tumor in gorlins
basal cell carcinoma
other key things to know about rhabdoid tumor predisposition syndrome
rhqbdoid renal tumors, schwannomatosis, usually less than 1 year at diagnosis
when is pineoblastoma often dx in trilateral rB
after RB but before age 5
what fraction of peds brain tumors are infratentorial
2/3
describe symptoms of a tumor int his location: frontal lobe
personal8ty, brocas (decreased motor speech), seizures
what are symptoms in temporal leison
seizures, poor memory, language comprehension (wernickes)
symptoms if tumor in parietal lobe
decreased sense of touch/pain, poor spatial and visual perception, poor interpretation of language
occipital lobe tumor symptoms
vision
where is the brain tumor if there is autonomic dysfunciton
brainstem or hypothalamus
where is the tumor if consciousness and weakness and motor control with sleep abnormalities
thalamus
what is the most common pediatric CNS tumor and how many of peds brain tumors are this
LGG_ 30%
how to make diagnosis of LGG
biopsy or resection with goal of CR. EXCEPTION- NF1 if classic appearance in optic pathway
What staging is needed for most LGG and what is 1 exception
generally none. if pilomyxoid astrocytoma, increased risk of mets
treatment for SEGA
historically surgery, now Mtor inhibitors like everolimus
Diagnostic criteria for NF1 if a kid does not have a parent with NF1 (7)
2 or more of the following; - 6 or more cafe o last, axillary OR inguinal freckles, 2 or more neurofibromas of any time, 1 plexiform neurofibroma, optic pathway glioma, 2 or more iris lunch nodule OR 2 or more choroidal abnormalities, key osseous leison, heterozygous NF1 variant n 50% of apparently normal cells
how many criteria are needed t dx NF1 f there’s a kid whose parent has the dx
1 or more
what % of pts with NF1 will develop LGG
15-20
treatment strategy in NF1 LGG
often dont do anything unless in optic pathway with visual acuity decline or other Neuro symptom. then step 1) chemo
what treatment is avoided in NF1
radiotherapy and alkylators- high risk of secondary malignancy
most common LGG histology
pilocytic astrocytoma
describe path of pilocytic astrocytoma
Rosenthal fibers (corkscrew shape, eosinophilic on H and E), low to moderate cellularity with + GFAP
most common molecular abnormality in LGG
MAPk abberations
non NF1 LGG treatment approach
attempt total resection. then chemo (1 carbo/VCR, 2 Vinblastine, 3 is combo). Radiation works but avoid- developmental
recently accepted new standard of care for kids 1 year and older with BRAF V600E mutant LGG
dabrafenib/trametinib
define diencephalic syndrome
usually tumor in diencephalon aka hypothalamus an thalamus, usually from LGG. FTT, emaciation, abnormal eye issues, vomiting, hydrocephalus . Would be indication to treat with chemo
who is at risk of HG
previous chemo or radiation exposure and patients with the following two syndromes: Li Fraumeni OR FAP
diagnosis of HGG and excpetion
biopsy/resection EXCEPT DIPG
staging for HGG
spine MRI, do NOT need LP
histology of HGGT
HIGHLy cellular, lots of mitosis, vascular proliferation, pseudopalisading necrosis, USUALly gap +
genetic finding in most DIPG
histone mutation (H3 K27M)
classic triad of DIPG
- Cranial nerve symptom, 2. long-tract signs, 3. ataxia
only known beneficial therapy for DIPG
radiation
mean survival of DIPG
10-12 months, all dead by 2 years
most common malignant brain tumor of childhood
medulloblastoma
where is medulloblastoma located
posterior fossa (cerebellum)
M:F ratio in medullo
1.7 to 1
increase risk of medulloblastoma in who
Gorlins syndrome (aka nevoid basal carcinoma syndrome) DUE TO PTCH gene mutation in SHH pathway. ALSO in FAP (aka Gardners and turbots due to APC)
diagnosis of medulloa
resection (both diagnostic and prognostic), you need LP and spine MRI- usually mets exist
when to do staging for medulloa
before surgery or 10-14 days after
histology of medulloblastoma
highly cellular, synaptophysin positive
4 major molecular subgroups of medullo
- WNT, 2. SHH, 3. Group 3, 4. group 4
which subgroup of medullo has best prognosis
WNT, early 90-100%
what subtype of medullo is usually infants
SHH
worst prognostic subgroup of medullo
group 3
what type of medullo do patients with goblins get
SHH
3 key risk factors for medullo that make you High risk
- Resection– high risk if >1.5cm cubed of residual tumor (otherwise standard). 2. M Staging- any mets are high risk. 3. histology- bad is anaplastic/large cell
standard risk 5 year OS medulloblastoma
75-90%
third most common pediatric CNS tumor
ependymoma
who has increased risk of ependymoma
NF2
staging: ependymoma
must include full spine MRI and LP
where is ependymoma and general term youll see on rads report
usually in cerebellum, “patchy heterogenous enhancement”
pathology of ependymoma histology
perivascular pseudo rosettes, monomorphic cells with oval nuclei
treatment approach ependymoma
maximum resection. if localized, then radiation. chemotherapy has unclear benefit and only used if under 1 year
ependymomas outcome
5 year OS is 50-60% but actually keeps declining after that. Long term survival is more like 30%, generally recurs
2 circulating tumor markers you can see in CNS germ cell tumors
AFP and beta HCG
2 major categories of germ cell CNS tumors
- Germinoma. Does NOT secrete. better outcome. 2 non-germinomatous germ cell tumor (SECRETES_ worse outcome)
where are germ cell tumors more common in the world
Japan and asian countries (up to 15%, more like 2-3% in US)
imaging of germ cell tumor
heterogenous and enhancing mass in 1 of the following locations- 1. suprasellar pituitary OR pineal (could be both- doublet or bifocal)w
what is parinauds sydnrome
cluster of eye abnormalities in movement and pupil dysfunction, can be from pineal tumor
what type of germ cell tumor has elevated beta HCG
choriocarcinoma
hat type of germ cell tumor has elevated AFP
yolk sac tumor
how to diagnose CNS germ cell tumor
if imaging is in pineal gland and suprasellar region and AFP or bHCG Is very high, that is good enough. otherwise, biopsys
staging CNS germ cell tumor
spine MRI and LP
three tumors that need full staging
ependymoma, medullo, germ cell tumor
treatment approach for germinoma
either neoadjuvant chemo then response based XRT OR XRT alone
treatment approach NGGCT
neoadjuvant then XRT
Prognosis germinoma
excellent more than 90%
associate schwannomatosis with this
ATRT and rhabdoit umor predisposition syndrome
where are choroid plexus tumors usually located
lateral ventricles
presenting symptoms in craniopharyngioma and location
headache, emesis, visual field cut, endocrinopathies. most common in suprasellar- pituitary
long term effects of CNS radiation and timeline
second brain tumor- HGG and meningioma. Usually 7-10 years. risk is less tan 5%
long term toxicity of MTX
leukoencephalopathy
long term toxicity of cisplat
oto toi, renal
long term cyclophosphamide tox
renal, infertility
time frame for secondary malignant brain tumor
7-10 yrs
2 common types of secondary brain tumors
meningioma and HGG
2 syndromes with risks for LGG
NF1 and TS (for SEGA)
3 big risks for HGG
Li fraumemi, hx CNS radiation, FAP
2 syndromes with risks for medullo
Nevoid basal cell carcinoma, FAP
syndrome with risk for ependymoma
NF2
