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Neuro Week 5 > ICL 10.13: CNS Tumors > Flashcards

ICL 10.13: CNS Tumors Flashcards

1
Q

what are the most common tumors in children?

A

brain tumors

this is because kids don’t get other tumors like lung cancer, and kidney cancer etc.

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2
Q

what are the most common locations of brain tumors in kids vs. adults?

A

adults = 70% supratentorial

kids = 70% infratentorial

that’s because the top 2-3 tumors in kids happen in the cerebellum

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3
Q

what’s the difference in brain infiltration between primary malignant tumors vs. metastatic malignant tumors?

A
  1. primary malignant tumors of astrocyte, oligodendrocytes, or ependymal cells infiltrate the brain because they’re used to that environment
  2. metastatic malignant tumors in the brain from like lung cancer do not! they don’t like the brain because there’s no collagen, etc. so they cling together as a solid mass. as a consequence, surgeons can usually easily remove brain mets!
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4
Q

what does the clinical course of a brain neoplasm depend on?

A

the anatomical location!!

there’s different presentations based on if it’s in the brainstem vs. motor cortex vs. speech

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5
Q

do primary brain tumors metastasize outside the CNS?

A

no!!

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6
Q

what things can cause brain tumors?

A
  1. radiation
  2. immunosuppression
  3. genetic syndromes

other etiologic factors like cell phones are unproven

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7
Q

which genetic syndromes can cause brain tumors?

A
  1. neurofibromatosis
  2. tuberous sclerosis (astrocytomas)
  3. Von-Hippel Lindau (hemangioblastomas)
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8
Q

what is the clinical presentation of a brain tumor?

A
  1. headache (not specific)
  2. new onset seizure (most common presenting symptom)
  3. mental or personality changes (not specific)
  4. symptoms of increased ICP like nausea, vomiting, drowsiness, blurred or double vision
  5. possible focal neurological deficits dependent on location
  6. possible swollen optic nerve = papilledema
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9
Q

what does a cyst indicate?

A

usually a benign tumor

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10
Q

what does a brain tumor with adjacent edema indicate?

A

edema suggests rapid growth

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11
Q

what is enhancement? what does it suggest?

A

contrast dye is injected that won’t cross the BBB

so if you inject enhancement and the lesion lights up, it means it’s damaging the BBB and this indicates malignancy

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12
Q

what are the 4 classifications of tumors?

A

tumors are classified by what cell they’re made of:

  1. gliomas
    ex. astrocytoma, ependymoma, oligodendroglioma
  2. neuronal
    ex. ganglion cell tumors (usually benign)
  3. primitive
    ex. medulloblastoma (in the cerebellum of kids)
  4. other
    ex. meningioma, hemangioblastoma, lymphoma, metastatic tumors
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13
Q

which brain tumors have a preference for kids?

A
  1. poorly differentiated tumors (not just the brain, throughout the body too)
  2. medulloblastoma*
  3. pilocytic astrocytoma*
  4. dysembryoplastic neuroepithelial tumor
  5. ependymoma*
  6. ganglion cell tumors
  7. oligodendroglioma

all 3 of the * are the most common and they’re usually in the cerebellum which is what accounts for most pediatric brain tumors being infratentorial

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14
Q

which brain tumors have a preference for adults?

A
  1. astrocytoma
  2. schwannoma
  3. central neurocytoma
  4. meningioma
  5. glioblastoma (high grade astrocytoma)
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15
Q

which brain tumors have a preference for elderly?

A
  1. lymphoma

2. glioblastoma (high grade astrocytoma)

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16
Q

which patient population are lymphomas most common in?

A

usually seen in immunocompromised patients so this is why brain lymphomas are usually in the elderly but if you’ve got AIDs or organ transplant, you could get a brain lymphoma

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17
Q

what are the most common spinal cord tumors?

A

OF CORD:
1. astrocytoma

  1. ependymoma

OF NERVE ROOTS:
1. meningioma

  1. schwannoma

nerve root tumors are more common

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18
Q

which neural tumors are benign?

A
  1. pilocytic astrocytoma
  2. meningioma
  3. ganglion cell tumors
  4. dysembryoplastic NE tumor
  5. central neurocytoma
  6. schwannoma
  7. neurofibroma

schwannomma and neurofibroma are seen in peripheral nerves, not the CNS

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19
Q

which neural tumors are low grade?

A
  1. astrocytoma
  2. oligodendroglioma
  3. ependymoma
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20
Q

which neural tumors are high grade?

A
  1. glioblastoma
  2. CNS lymphoma
  3. medulloblastoma
  4. primitive NE tumor
  5. malignant peripheral nerve sheath tumor
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21
Q

what are the different grades of astrocytomas?

A

WHO grade I = benign

malignant:
WHO grade II = astrocytoma

WHO grade III = anaplastic astrocytoma

WHO grade IV = glioblastoma

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22
Q

what are fibrillary/diffuse astrocytomas?

A
  1. low grade astrocytoma
  2. anaplastic astrocytoma
  3. glioblastoma

so they are malignant WHO grade II-IV astrocytomas

they collectively account for 80% of adult, primary, intraparenchymal brain tumors (so mets, kids and meninges are out)

low grade astrocytomas may progress to higher grade over time

symptoms are critically dependent on anatomic site

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23
Q

what is the average survival length of a fibrillary astrocytoma?

A

they usually effect 30-60 year olds with higher grades at older ages

low grade astrocytoma = 5 year survival

glioblastoma = 8-10 months

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24
Q

what are the gross changes seen in the brain with a low grade astrocytoma?

A
  1. destruction of the hippocampus and temporal horn

it’s destroying normal architecture

  1. subtle mass effect –> sylvian fissure is pushed up and so are the putamen and globes pallidus

tumor will appear grey even though it’s in the middle of what should be white matter

you can tell it’s low grade because it’s all homogeneous, it all looks like grey matter, there’s no hemorrhage or necrosis, and it got really big without effecting the midline which tells you it was growing pretty slowly

slide 15

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25
Q

what are the microscopic changes in the brain with a low grade astrocytoma?

A

too many astrocytes and too much pleomorphism (lots of variation in how the cells appear)

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26
Q

what is an anaplastic astrocytoma?

A

WHO grade III malignant astrocytoma

it’s intermediate grade with intermediate prognosis

Anaplastic astrocytomas generally receive post-operative therapy, unlike low grade astrocytoma

pathology shows greater cellularity and nuclear pleomorphism than a low grade astrocytoma plus mitotic activity

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27
Q

what is a glioblastoma?

A

WHO grade IV malignant astrocytoma = highest grade

key features:
1. tumor necrosis due to the tumor outgrowing its blood supply

  1. proliferating balls of small blood vessels responding to VEGF secreted by ischemic tumor cells
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28
Q

what are the 2 ways you can get a glioblastoma?

A
  1. dedifferentiation of lower grade astrocytoma into a glioblastoma (more common in younger patients)
  2. de novo (more common in older patients)

these two tumors are different molecularly

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29
Q

what are the histological features of glioblastoma?

A
  1. greater cellularity of astrocytes
  2. tons of nuclear pleomorphism
  3. mitotic activity (cells look like they’re trying to divide; reflects growth of tumor)
  4. tumor necrosis = no blue staining nuclei; the tumor looks white because the tumor cells are dying due to tumor outgrowing its blood supply – you see a ton of cells around this ischemic area and it’s cells trying to run away from the ischemia = pseudopalisading
  5. microvascular proliferation = proliferating balls of small blood vessels from VEGF secreted by ischemic tumor cells

glioblastoma is a bunch of different colors and it doesn’t all look like a uniform tumor, it looks horrible

slide 19

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30
Q

how do glioblastomas spread?

A

malignant brain tumors vs. metastatic brain tumors love to infiltrate in the brain, particularly white matter tracts

the corpus collosum is the major white matter tract in the brain and what a glioblastoma does is crawl across to the other hemisphere = “butterfly tumor”(basically diagnostic of a glioblastoma)

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31
Q

which astrocytomas are considered benign?

A
  1. pilocytic astrocytoma
  2. pleomorphic xanthoastrocytoma
  3. subependymal giant cell astrocytoma of tuberous sclerosis
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32
Q

what is a pilocytic astrocytoma?

A

WHO grade I astrocytomas that is benign

usually seen in children and usually in the cerebellum in the midline – can also occur in the hypothalamus, optic nerve and brainstem

also usually has a cyst! the cyst is what usually causes the problems too because it outgrows the tumor

so a midline, cerebellar mass with a cyst in a kid, it’s basically 100% a pilocytic astrocytoma

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33
Q

what are the 2 key histological features of a pilocytic astrocytoma?

A
  1. alternating biphasic growth pattern of fibrillar and loose areas
  2. Rosenthal fibers
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34
Q

what is a pleomorphic xanthoastrocytoma?

A

WHO grade I astrocytomas that is benign

superficial, circumscribed, cerebral tumor of children and young adults

*striking tumor cell pleomorphism with giant cells may falsely suggest a high grade tumor (slide 27)

usually also has a cyst that is the cause of the problems because it gets so big

35
Q

what is a subependymal giant cell astrocytoma?

A

WHO grade I astrocytomas that is benign

it’s only seen in patients with tuberous sclerosis

36
Q

what is an ependymoma?

A

tumor involving ependymal cells which is seen in both children and adults

slow growing, malignant and clinical features depend on the location

they tend to grow in the ventricles (duh, the ependymal cells line ventricles) and a consequence is that pieces of the tumor can break off and float through the CSF = seeding of the subarachnoid space in aggressive tumors

poor prognosis; average survival is 4 years

37
Q

where can you find ependymomas?

A
  1. kids and young adults: primarily in the 4th ventricle –> close proximity to the pons and medulla makes a complete resection really difficult
  2. adults: primarily an intraspinal glioma –> easier to ressect
38
Q

what are the histological changes seen with an ependymoma?

A

cells are arranged around vessels with thin ependymal processes directed towards vessels –> they create a ribbon appearance

the tumor cells have long thin tails which go down and attach to the blood vessels so that’s why you get this clear pink halo of tails surrounding the blood vessels with no blue nuclei

slide 31

39
Q

what would you see in an electron microscopy of an ependymoma?

A
  1. tiny lumens filled with microvilli
  2. long serpentine cell junctions

now it looks like an adenocarcinoma as expected!

slide 32

40
Q

what are oligodendrogliomas?

A

slow growing tumors of oligodendrocytes that comprise 5-15% of gliomas

they have a predilection for white matter (duh that’s where all the oligodendrocytes are)

tumors occur in the 4th-5th decade of life and the prognosis is relatively good (:

41
Q

what are the histological changes seen in an oligodendroglioma?

A
  1. fried egg appearance = blue tumor cell surrounded by a halo of white
  2. delicate branching vessels = “chicken wire”
  3. microcalcifications
42
Q

what are neuronal tumors?

A

neurons are mature post-mitotic cells and after embryogenesis they usually don’t divide so you wouldn’t expect them to make tumors

so usually if you have a tumor made of neurons it’s probably something that’s been sitting there since embryogenesis so it’s more of a malformation than a tumor

usually benign

43
Q

what are the 3 important types of neuronal tumors?

A

neuronal tumors:
1. ganglion cell tumor

  1. central neurocytoma
  2. dysembryoplastic neuroepithelial tumor
44
Q

what is a ganglion cell tumor?

A

a type of neuronal tumor that is general benign – usually only found when someone has a seizure

large, mature neurons may be the only feature = gangliocytoma

or may occur with a glial component = ganglioglioma

slide 39

45
Q

what is a central neurocytoma?

A

a type of neuronal tumor that is general benign

it can be a calcified intra or periventricular mass

it’s composed of uniform small neurons that aren’t growing

this mass is usually in the middle of the brain around the area of the germinal matrix so they’re basically left over cells in the germinal matrix that never made it to the cortex

slide 40

46
Q

what is a dysembryoplastic neuroepithelial tumor?

A

a type of neuronal tumor that is general benign and seen in kids

patients will present with seizures

47
Q

what are the histological findings of a dysembryoplastic neuroepithelial tumor?

A

multiple cortical nodules show diverse histological patterns

a key pattern is normal neurons that “float” in a mucinous matrix between vessels lined by small round cells (“specific glioneuronal component”)

when you see a floating neuron, you hit de net, get it? DNET?

slide 42

48
Q

which types of tumors are ventricular tumors?

A
  1. choroid plexus papilloma

2. colloid cyst of the 3rd ventricle

49
Q

what is a choroid plexus papilloma?

A

a ventricular tumor

they’re usually just masses that block CSF and then the surgeon will go in and take it out

can sometimes rarely cause hydrocephalus in children due to a choiroid plexus papilloma that is overproducing CSF

50
Q

what is a colloid cyst of the 3rd ventricle?

A

a ventricular tumor that has a “ball valve” effect with intermittent hydrocephalus

patients will have intermittent headache, loss of consciousness, etc. –> can cause sudden death

slide 46

51
Q

which types of tumors are classified as poorly differentiated tumors?

A

all of these are tumors of childhood!!

they are all known as primitive neuroectodermal tumors = PNETs

  1. medulloblastoma (in the cerebellum)
  2. neuroblastoma (in the cerebral hemispheres)
  3. pineoblastoma
  4. retinoblastoma
52
Q

what is a medulloblastoma?

A

a type of poorly differentiated tumor that is the most common malignant brain tumor of children (pilocytic tumor is benign)

it’s a solid tumor arising from the cerebellar vermis – primitive cells with *high nuclear to cytoplasmic ratios

highly malignant, but sensitive to radiation and chemotherapy: 5-year survival is ~75%

53
Q

how does a medulloblastoma spread?

A

it disseminates through the CSF pathways and metastases to other parts of the CNS (never outside the CNS)

they often go to the bottom of the spinal cord to the cauda equina due to gravity = “drop metastases”

54
Q

what are primary brain lymphomas?

A

a disease of the elderly and immunocompromised –> it’s the most common CNS neoplasm in immunosuppressed individuals including AIDS

tumors are mostly made of B-cell, large cells

lymphomas have a preference for periventricular areas –> tumors collect in perivascular spaces –> damage to vessel walls leads to “hooping” seen in reticulin stain

slide 51

55
Q

what is a meningioma?

A

benign tumors derived from arachnoid cells

common locations = convexity, skull base, spinal cord nerve roots

56
Q

what are the gross anatomical changes seen with a meningioma?

A

meningiomas do not invade the brain!!! it’s outside the brain because it’s made from the meninges!!

it just looks like a ball inserted into the middle of the brain (slide 53)

however, they may invade the overlying skull –> but invasion of bone does not make it malignant!!! it’s only malignant if it invades the brain which isn’t common

57
Q

what are the histological findings seen in a meningioma?

A

Most meningiomas are “transitional” types with whorls of spindled cells wrapped around more polygonal cells

whorls are characteristic!

slide 55

58
Q

what is a hemangioblastoma?

A

a benign, highly vascular tumor of adults – most common in the cerebellum

often cystic but cell of origin is unknown (tumors that make cysts are usually benign)

may produce erythropoietin, causing erythrocytosis = increased Hct levels

multiple hemangioblastomas are seen in von Hippel-Lindau syndrome

59
Q

what are the gross and microscopic changes seen with a hemangioblastoma?

A

gross anatomy shows a red tumor in the cerebellum from all the blood vessels

microscopically, the tumor cells have foamy cytoplasm, and fill the spaces between small blood vessels

slide 57

60
Q

what are the most common origins of brain mets?

A
  1. lung
  2. breast
  3. skin
  4. kidney
  5. GI

these are also the most common tumors overall

61
Q

where are brain mets most commonly found?

A

the gray-white junction in territory of MCA

it’s because these things arise as tumor emboli –> anything arriving from the blood comes through the cortex to the white matter; the white matter needs less oxygen so the blood vessels there get smaller so anything coming to the brain will get stuck at this grey-white matter junction where the blood vessels get smaller

62
Q

what do brain mets look like in an MRI or gross anatomy?

A

mets are generally sharply demarcated (except melanoma because they come from the neural crest) and multiple, with adjacent edema

even on histology, you can see a straight line between the met and the brain tissue!

they don’t invade because they aren’t in an environment that they like (except melanoma, that invades)

63
Q

what are paraneoplastic syndromes?

A

if you have a tumor in the body that has some antigens that resemble antigens of the brain then when the body makes antibodies against them, your own antibodies will attack your brain too

signs and symptoms of paraneoplastic syndromes of the nervous system often begin even before a cancer is diagnosed!

they can involve the central or peripheral nervous system

64
Q

what type of cancer most often causes paraneopalstic syndrome?

A

small cell carcinoma of the lung

65
Q

what are the types of paraneoplastic syndromes?

A
  1. Lambert-Eaton myasthenic syndrome
  2. Stiff-man syndrome
  3. Retinal degeneration
  4. Limbic and brain stem encephalitis
  5. Subacute cerebellar degeneration
  6. Subacute sensory neuropathy
66
Q

which tumors are tumors of nerve roots and peripheral nerves?

A
  1. meningioma (because meninges go all the way down the spinal cord)
  2. schwannoma

CN 8, spinal nerve roots, peripheral nerves

  1. neurofibroma

spinal roots (rare), peripheral nerves

67
Q

which cranial nerve is most often effected by schwannomas?

A

CN 8

this is an acoustic neuroma!!! it’s Schwann cells growing on the auditory nerve!!

68
Q

what’s the difference between a schwanomma and neurofibroma?

A

these are both benign tumors of peripheral nerves

SCHWANNOMA
1. made of schwann cells

  1. adjacent to nerve
  2. encapsulated
  3. easily resettable without nerve damage
  4. anybody can get a schwannoma

NEUROFIBROMA
1. made of intramural fibroblasts

  1. infiltrates nerve
  2. not encapsulated
  3. not resectable without sacrificing nerve
  4. almost nobody gets neurofibromas unless they have neurofibromatosis
69
Q

what does a Schwannomma look like histologically?

A

palisading of tumor cells in the Antoni A areas can be striking – looks like jelly fish tentacles

there are dense, spindly Antoni type A areas and looser Antoni type B areas; there are no nerve fibers within the tumor

slide 66

70
Q

what does a neurofibroma look like histologically?

A

The involved nerve shows normal nerve fibers (dense, pink) separated by infiltrating tumor (lighter areas)

looks like streaks of pink in-between lighter pink

slide 67

71
Q

i say whorls, you say….

A

meningioma

think meningiomas wrap around the brain

72
Q

i say fried-egg cells, chicken-wire vasculature, you say…

A

oligodendroglioma

73
Q

i say pseudopalisading you say…..

A

glioblastoma

74
Q

i say true palisading, you say….

A

schwannoma

75
Q

i say perivascular pseudorosettes you say…

A

ependymoma

76
Q

what are the 4 familial tumor syndromes?

A
  1. neurofibromatosis = von Recklinghausen disease
  2. tuberous sclerosis
  3. spurge-weber disease
  4. von hippel-lindae disease

these people have mutations that causes them to have multiple brain or peripheral tumors

77
Q

what is neurofibromatosis?

A

aka von Recklinghausen disease

it’s a familial tumor syndrome: a genetic disorder characterized by the development of multiple (benign) tumors of nerves and skin (neurofibromas) and areas of abnormal skin color

it’s dominant inheritance

there is neurofibromatosis type 1 and 2 –> type 1 has lesions all over the body on peripheral nerves while type 2 has tumors in the head

78
Q

what are the characteristics of neurofibromatosis type 1?

A

NF1:
1. multiple peripheral nerve neurofibromas

like nodules literally all over the body; very disfiguring and hopeless to try and remove them unless one of them is growing because then you worry it’s malignant

  1. pigmented nodules (Lisch) in iris
  2. cafe-au-lait spots (melanosis) in skin
  3. lephantiasis: increased connective tissue
  4. increased incidence of malignant tumors
79
Q

what are the characteristics of neurofibromatosis type 2?

A

NF2:
bilateral schwannomas of 8th cranial nerve

increased incidence of meningiomas and gliomas

80
Q

what is tuberous sclerosis?

A

it’s a familial tumor syndrome with dominant inheritance that causes congenital cognitive disability

there are benign neural-glial hamartomas in the brain and eye –> they can be in the gyri or down in the subependymal cells of the ventricles or they can be retinal

it kind of appears like acne on the face, near the nails, etc. = facial angiofibromas

81
Q

what does the gross anatomy of tuberous sclerosis look like?

A
  1. giant, dimpled gyrus that is hardened

2. cortex is white white the grey matter is white; it’s reverse!

82
Q

what is von hippel-lindau disease?

A

it’s a familial tumor syndrome with dominant inheritance

it causes multiple hemangioblastomas in the cerebellum, retina, and spinal cord

there’s also erythrocytosis due to erythropoietin production

so it’s a hereditary condition associated with tumors arising in multiple organs –include hemangioblastomas, which are blood vessel tumors of the brain, spinal cord, and eye. The eye tumors are also called retinal angiomas

83
Q

what are the systemic findings of von hippie-lindau disease?

A
  1. cysts in pancreas and kidneys
  2. renal cell carcinoma –> this is why you get increased EPO production!
  3. pheochromocytoma of adrenal

Neuro Week 5 (11 decks)

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