9/16 Brain Tumors - Davidson Flashcards Preview

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Flashcards in 9/16 Brain Tumors - Davidson Deck (19):
1

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)

2

glioma

tumor arising from glia

three types:

  1. astrocytomas (from astrocytes)
  2. oligodendrogliomas (from oligodendrocytes)
  3. ependymomas (from ependymal cells)

3

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

 

1. elongated cells with "hairlike" processes

2. Rosenthal fibers: thick, deeply eosinophilic processes

4

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

5

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

6

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

7

oligodendroglioma

  • neoplasm of oligodendroglial cells
  • WHO grade II, III (anaplastic oligo.)
  • usually in cerebral hemispheres
  • often hemorrhagic
  • genetics: codeletion of 1p, 19q

 

1. "fried egg" nuclei

2. chickenwire vasculature

3. calcifications

8

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

9

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

10

craniopharyngioma

tumor in very young children

derived from remnants of Rathke pouch

histo features:

  • squamous epithelium
  • "wet keratin"
  • cholesterol clefts

11

tumor predisposition syndromes

mutant gene picked up by either:

1. familiar inheritance

2. 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

12

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

 

13

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

14

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)

15

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

16

tuberous sclerosis complex (TSC)

CNS lesions:

  • cortical tubers
  • **SEGA** : subependymal giant cell astrocytoma
    • most common in lateral ventricles

other organs

  • renal agiomyolipomas
  • pulmo lympangioleimyomatosis
  • dermal angiofibroma

genetics: mutation in TSC1 or TSC2

  • protein pdt regulates mTOR protein (kinase involved in reg of energy, metabolism, mRNA transl)

17

Von Hippel Lindau (VHL)

lesions:

  • **hemangioblastoma** (WHO grade I)
    • usually cerebellum (also spine, brainstem, retina)
    • histo: foamy stromal cells, dense capillary network
  • renal cell carcinoma
  • pheochromocytoma
  • retinal angiomas
  • skin, organ hemangiomas

 

genetics: mutation in VHL (chr3) → constitutive activation of HIF → overprod of angiogenic growth factors

18

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

19

metastasis to CNS

 

features

what cancers?

most common source of brain tumors

  • typical location: gray-white jx
  • usually well-circumscribed, unlike astrocytomas

usual suspects for primary cancers (*most common to metastasize to brain):

  • lung 
  • *breast
  • *melanoma
  • colon
  • *renal

 

 

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