9/16 Brain Tumors - Davidson Flashcards
WHO grading system
predicts clinical behavior based on pathohisto features of a tumor
I: curable with complete surgical resection
II: complete surgical resection might not be curative (7-10yr life expectancy)
III: not surgically curable (3-7yr LE)
IV: not surgically curable; chemo/rad tx can extend life, but response is short-lived. kills quickly (12-18mo)
glioma
tumor arising from glia
three types:
- astrocytomas (from astrocytes)
- oligodendrogliomas (from oligodendrocytes)
- ependymomas (from ependymal cells)
pilocytic astrocytoma
usually grade I → potentially curable with surgery
usually arises in children
low grade, minimally infiltrative astrocytoma
often suprasellar, cerebellar
MRI: cyst with mural nodule
- elongated cells with “hairlike” processes
- Rosenthal fibers: thick, deeply eosinophilic processes
diffuse astrocytoma
WHO grade II, III, IV
- II ~3rd decade
- III ~4th, 5th decades
- IV ~6th decade
irregular, elongated, crowded nuclei
fibrillary background
GFAP + (gliofibrillary acidic protein)
infiltrate normal brain → makes surgical resection difficult
glioblastoma
what differentiates grade III and grade IV?
WHO grade IV
- microvascular proliferation
- palisading necrosis
malignant, poorly differentiated tumor of glial cells
genetics: freq amplification of receptor Tyr kinases (EGFR, MET, PDGFR)
radiologic pic: cerebral rim/rim-enhancing lesion
gross anatomy: butterfly lesion
MGMT
what happens when promoter is…
- hypomethylated
- hypermethylated
O6-methylguanine-DNA methyltransferase
- converts O6-methylguanine (naturally occuring mutagenic lesion) → guanine
- crucial for DNA repair and genomic stability
- also removes lethal DNA adduct formed by rxn with temozolomide (commonly used anti-glioma chemotx)
promoter hypomethylated
- MGMT transcribed/translated
- MGMT can remove temozolomide bound to tumor cell DNA → GOOD FOR TUMOR!
promoter hypermethylated
- minimal MGMT transcription/translation
- MGMT not made → can’t remove temozolomide from DNA → TUMOR CELLS DIE
oligodendroglioma
- neoplasm of oligodendroglial cells
- WHO grade II, III (anaplastic oligo.)
- usually in cerebral hemispheres
- often hemorrhagic
- genetics: codeletion of 1p, 19q
- “fried egg” nuclei
- chickenwire vasculature
- calcifications
ependymoma
tumor of ependymal cells
WHO grade II or III (anaplastic ependymoma)
can occur wherever ependymal cells present
- typically in 4th ventricle (kids; v aggressive)or spinal cord (low grade, surgically tx)
characteristic histo: perivascular pseudorosettes
pituitary adenoma
low grade neuroendocrine tumor
most common: null-cell adenoma
most common hormone-producing adenoma: prolactinoma
sx:
- hemianopsia
- hormone overproduction
- prolactin: amenorrhea, galactorrhea
- GH: acromegaly
- ACTH: Cushing’s disease
craniopharyngioma
tumor in very young children
derived from remnants of Rathke pouch
histo features:
- squamous epithelium
- “wet keratin”
- cholesterol clefts
tumor predisposition syndromes
mutant gene picked up by either:
- familiar inheritance
- de novo mutation
- mutation in egg or sperm that made zygote
- mutation v early in devpt
tumorigenesis almost universally involves loss of other, wt copy of gene
neurofibromatosis type 1
neurofibromin (NF1 gene pdt) negatively regulates Ras oncoprotein
tumors:
- neurofibromas
- cafe au lait spots
- optic gliomas
- pheochromocytomas
- malignant peripheral nerve sheath tumor
neurofibromatosis type 2 (NF2)
NF2 gene (chr22) encodes Merlin (links pro-prolif signals at membrane with underlying actin cytoskeleton)
CNS tumors
- Schwannoma: bilateral vestibular schwannoma is the hallmark
- vestibular nerve is most common site of sporadic schwannoma
- meningioma
- ependymoma
most tumors are surgically tx-able, but recurrence or number can be a cause of M&M
Schwannoma
tumor of Schwann cells
WHO grade I
almost 100% have bi-allelic inactivation of NF2!
sx caused by compression of involved nerve
- vestibular n. sx: tinnitus, deafness
histo: bland spindle-shaped cells with…
- rod-like nuclei
- hypercellular areas (Antoni A), hypocellular areas (Antoni B)
- Verocay bodies (nuclei lining up together)
meningioma
dural-based tumor of meningothelial cells
classic MRI sign: “dural tail”
WHO grade I (atypical)-II-III (malignant)
genetics: 50% have NF2 mutation
numerous histologies, mostly commonly with:
- whorls
- psammomatous calcification
medulloblastoma
pediatric tumor
WHO grade IV
- malignant tumor of primitive neurons, located in posterior/cerebellar fossa
- mostly affects young children
- synaptophysic positive (unlike normal neurons)
v densely cellular
