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NS_BTRAN > Unit2_CNS Tumors > Flashcards

Unit2_CNS Tumors Flashcards

1
Q

What WHO histological type grade is the worst Px?

A

Grade IV (4)

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2
Q

Astrocytoma, oligodendroglioma, ependymoma, ganglioma are known as ____1____, and are derived from the ____2____.

A
  1. GLIOMAS

2. NEUROECTODERM

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3
Q

Tumors of low proliferative potential, possibility of cure with surgical resection alone describe what WHO grade of tumors?

A

Grade 1

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4
Q

Pilocytic Astrocytoma: ?

A

Most common glioma seen in childhood.

Well circumscribed, non-infiltrative, minimal tendency to undergo malignant upgrading.

Location: Cerebellum, optic nerves/chiasm, and hypothalamic region
Children often have tumors in posterior fossa.

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5
Q

Where are Pilocytic Astrocytoma located?

A

Location: Cerebellum, optic nerves/chiasm, and hypothalamic region
Children often have tumors in posterior fossa.

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6
Q

How do you Tx Pilocytic Astrocytoma?

A

surgical excision alone (some locations require other therapy as well)

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7
Q

What is the appearance of Pilocytic Astrocytoma?

A
  • Grossly = cystic
  • Microscopic = hair-like “piloid” astrocytes and Rosenthal fibers (eosinophilic intracytoplasmic glial filaments)
    May have vascular calcifications
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8
Q

What are the genetics ~w/ Pilocytic Astrocytoma?

A

BRAF-KIAA fusion → Constitutive activation of BRAF gene = FAVORABLE feature in slow growing tumors

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9
Q

Pilocytic Astrocytoma is WHO grade?

A

Grade 1

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10
Q

Ganglioglioma is WHO grade?

A

Grade 1

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11
Q

What is the location of Ganglioglioma?

A

usually in the Temporal lobe.

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12
Q

What is the appearance of Ganglioglioma?

Gross:

Microscopic:

A

Ganglioglioma are well demarcated.

Appearance:
- Grossly = cystic, more likely to be calcified

  • Microscopic = increased number of jumbled, cytologically abnormal neurons mixed into a low grade glial background.
    Microcysts with mucin.
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13
Q

Can Ganglioglioma have BRAF mut?

A

YES!

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14
Q

Choroid plexus papilloma is WHO grade ?

A

Grade 1

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15
Q

What is the location of Choroid plexus papilloma?

A

Location: intraventricular, closely mimic choroid plexus but more “papillary formations”, more abundant/crowded cells covering surface.

Children → Lateral ventricles
Adults → 4th ventricle

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16
Q

In children, Choroid plexus papilloma are located in ______?

In ADULTS, Choroid plexus papilloma are located in ______?

A

Children → Lateral ventricles

Adults → 4th ventricle

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17
Q

Choroid plexus papilloma can produce _____1_____ by ____2____ CSF flow.

A
  1. HYDROCEPHALUS
  2. BLOCKING CSF

Produce HYDROCEPHALUS by BLOCKING CSF flow (not by CSF overproduction)

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18
Q

Choroid plexus papilloma have ___1___ mitotic rate, mild ____2____

A
  1. low

2. nuclear atypia

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19
Q

infiltrative, low proliferative level, but often recur describe a CNS tumor of what WHO grade?

A

WHO grade 2.

Tend to progress to higher grade
TX: watchful waiting or external beam cranial irradiation

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20
Q

What is the general Tx of WHO grade 2 CNS tumors?

A

WHO GRADE 2:

TX: watchful waiting or external beam cranial irradiation

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21
Q

What WHO grade is Diffuse Astrocytoma?

A

WHO grade 2

  • Common glioma.
  • Occur in young adults, Age = 30s-50s
  • Potential to progress in grade
  • Infiltrative, no borders, cannot be surgically resected, only debulked.
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22
Q

Where is the location of Diffuse Astrocytoma?

A

white matter of cerebral hemisphere

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23
Q

What is the appearance of Diffuse Astrocytoma?

A
  • Mild hypercellularity
  • Mild nuclear pleomorphism
  • Irregular distribution of tumor astrocytes
  • Variations in nuclear features and cytoplasmic content.
  • Absence of necrosis, mitotic activity, and microvascular proliferation
    - Main difference between anaplastic astrocytoma
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24
Q

What genetics are ~w/ Diffuse Astrocytoma?

A

IDH1/2 mutation + no LOH 1p, 19q + p53/ATRX mutation

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25
Q

Main difference between anaplastic astrocytoma and Diffused Astrocytoma?

A

Diffused Astrocytoma has an ABSENCE of:

  • necrosis
  • mitotic activity
  • microvascular proliferation
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26
Q

Can Diffuse Astrocytoma be surgically resected?

A

NO! WHO grade 2

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27
Q

What WHO grade is Oligodendroglioma?

A

WHO grade 2.

  • Common Glioma
  • Mostly Adults
  • Infiltrative, no clear borders, cannot be surgically resected
  • Better overall prognosis that diffuse astrocytoma
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28
Q

What is the appearance of Oligodendroglioma?

A

a. Calcified significantly
b. Vascular (“Chicken wire”) vascular pattern)
c. Round monotonous nuclei, equal spacing, minimal cytoplasm–“Fried egg” appearance.
d. Minimal/absent mitotic activity

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29
Q

Where are Oligodendroglioma located?

A

Cerebral Hemisphere.

White matter of cerebral hemisphere but quickly spread to overlying cortex → seizures

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30
Q

What Genetics are ~W/ Oligodendroglioma?

A

IDH1/2 mutation + LOH 1p, 19q + no p53/ATRX mutation.

Can be diagnostic in differentiating oligodendroglioma or anaplastic oligodendroglioma from an astrocytoma

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31
Q

Oligodendroglioma has an overall ________ prognosis that diffuse astrocytoma.

A

Oligodendroglioma has an overall BETTER prognosis that diffuse astrocytoma.

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32
Q

What WHO grade is Ependymoma?

A

Ependymoma = WHO grade 2

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33
Q

Where are Ependymoma located?

A

mostly, but not always in ventricles

Children → 4th ventricle → HYDROCEPHALUS
Less favorable diagnosis

Adults → Spinal cord
Typically well demarcated, full excision may be possible

34
Q

What is the Appearance of Ependymoma?

Gross:

Microscopic:

A

Gross: Calcified, masses protrude up from 4th ventricle as exophytic masses

Microscopic: ependymal differentiation, mild-moderate cell density, few mitotic figures. Minimal necrosis or microvascular proliferation.

35
Q

Ependymoma in children is located in the 4th ventricle this produces → ?

A

Children → 4th ventricle → HYDROCEPHALUS.

Less favorable diagnosis

36
Q

Ependymoma in adults is located in the spinal cord, this produces → ?

A

Adults → Spinal cord

Typically well demarcated, full excision may be possible

37
Q

What are the WHO grade 1 Tumors?

A
  1. Pilocytic Astrocytoma
  2. Ganglioglioma
  3. Choroid Plexus Papilloma
38
Q

What are the WHO grade 2 Tumors?

A
  1. Diffuse Astrocytoma
  2. Oligodendroglioma
  3. Ependyoma
39
Q

What are the WHO grade 3 Tumors?

A
  1. Anaplastic Astrocytoma
  2. Anaplastic Oligodendroma
  3. Anaplastic Ependymoma
40
Q

What are the WHO grade 4 Tumors?

A
  1. Glioblastoma (aka astrocytoma)

2. Medulloblastoma

41
Q

Extrinsic Brain Tumors are meningeal & mesenchymal tumors and includes?

A
  1. Meningomas
  2. Hemangiopericytomas
  3. Schwannomas
42
Q

Histological evidence of malignancy (nuclear atypia, high mitotic activity) describes what WHO grade of tumors?

A

WHO grade 3

43
Q

What is the overall Tx for grade 3 tumors?

A

Tx: adjuvant radiation and/or chemo

44
Q

What is Anaplastic Astrocytoma and what is it’s WHO grade?

A

Anaplastic Astrocytoma = WHO grade 3.

Common glioma, progression from diffuse astrocytoma

45
Q

What is the appearance of Anaplastic Astrocytoma?

A

Lack enhancement or necrosis on preop imaging studies

Microscopic: increased mitotic rate

  • MIB-1+ nuclear labeling → important, used to look at cells undergoing mitosis.
  • DOES NOT show necrosis or microvascular proliferation.
  • Crowded tumor cells, nuclear hyperchromatism, and variation in cell shape and size.
46
Q

What is the major difference between Anaplastic Astrocytoma and Diffuse Astrocytoma?

A

Anaplastic Astrocytoma has an Increased mitotic rate = big difference between diffuse/anaplastic astrocytoma.

47
Q

What is Anaplastic Oligodendroglioma and what is it’s WHO grade?

A

Anaplastic Oligodendroglioma = WHO grade 3

48
Q

What is the appearance of Anaplastic Oligodendroglioma?

A

DOES show enhancement on preop imaging studies.

Round, uniform nucleus, scant cytoplasm, “fried egg” appearance, microvascular proliferation present.

49
Q

What is Anaplastic ependymoma and what is it’s WHO grade?

A

Anaplastic ependymoma = WHO grade 3.

Progression from Ependymoma (WHO-2)

a. Higher mitotic activity
b. Typically in childhood and in 4th ventricle
c. Histological criteria not very indicative of prognosis.
d. Can recur in distant sites due to CSF dissemination

50
Q

cytologically malignant, mitotically active, necrosis prone neoplasms describes what WHO grade tumor?

A

WHO grade 4 = Rapid disease, often fatal.

51
Q

What WHO grade is Glioblastoma?

A

Glioblastoma = Grade 4.

Most common and most malignant glioma.

Most occur in 50s and 60s
Not surgically curable, debulking only

52
Q

What are the genetics ~w/ Glioblastoma?

A

EGFR typical mutation (diagnostic) in high grade GBM.

53
Q

What is the appearance of Glioblastoma?

A

Hemorrhagic, necrotic, multifocal.

Deceptively well demarcated, but microscopically infiltrative.

54
Q

Can you surgically resect a Glioblastoma?

A

NO. Debunking only!

55
Q

What is the criteria for GBM? How many do you need to be considered a GBM?

A

Need 3 out of 4.

1) Nuclear abnormalities (nuclear atypia, hyperchromatism, variation in nuclear size and shape).
2) Mitotic activity.
3) Microvascular .proliferation.
4) Necrosis.

56
Q

Giloblastoma typically arise ______ (“primary GBM”).

But if diagnosis with lower grade astrocytoma first → “____2____” (via IDH+ pathway)*

A
  1. de novo

2. secondary GBM

57
Q

What is the most malignant glioma?

A

Glioblastoma: (aka astrocytoma) (Grade 4)

58
Q

What is WHO grade is Medulloblastoma?

A

Medulloblastoma = WHO grade 4.
- Malignant embryonal tumor of cerebellum (primitive neuroectodermal tumor)

  • Usually in children (3-8 years old) - most common malignant brain tumor in children
  • Spreads throughout CSF pathways; Outcome is better if it has not spread in CSF
59
Q

Medulloblastoma presents with Sx of:

A
  • Increased ICP → headache, vomiting, papilledema.

- Disturbances of gait, nystagmus, and dysmetria (cerebellum).

60
Q

What is the appearance of Medulloblastoma?

A

Patternless sheets of small embryonal cells with scant cytoplasm (“small blue cells”), minimal differentiation

61
Q

“small blue cells” are ~w/ ?

A

Medulloblastoma

62
Q

What tumor is a Malignant embryonal tumor of cerebellum (primitive neuroectodermal tumor)?

A

Medulloblastoma

63
Q

What are the extrinsic brain tumors? (3)

A
  • Meningiomas
  • Hemangiopericytoma
  • Schwannomas
64
Q

What are Meningiomas?

A

Meningiomas:

  • Typically grade I, but can be life-threatening if in a location difficult to resect from.
  • Peak incidence is WOMEN IN THEIR 50’S
  • Arise from arachnoid “cap” cell within arachnoid villus.
  • May penetrate dura, occlude venous sinuses, invade bone, and cause hyperostosis.
65
Q

What are Hemangiopericytomas?

A

Hemangiopericytoma: meningeal-based tumor.

  • Less favorable prognosis than meningioma, high recurrence rate.
  • Accumulates more mutations as grade increases.
66
Q

What are Schwannomas?

A

Schwannomas: (aka neurofibromas)

  • Benign, can rarely degenerate into malignant form (neurofibrosarcoma)
  • Slow growing
67
Q

Most brain tumors are ____1____ and of ____2____ etiology

A
  1. SPORADIC

2. UNKNOWN

68
Q

Where do brain tumors typically met from?

A

Typically mets from breast, lung, kidney, melanoma, and GI tract cancer

69
Q

What are IDH1 and IDH2?

A

IDH1 and IDH2: isoforms of enzyme Isocitrate dehydrogenase.

  • Frequently mutated in gliomas.
  • IDH1 → mutated in 70-80% of grade II and III astrocytomas, oligodendrogliomas, oligoastrocytomas, and secondary (but not primary) glioblastomas.

NOT present in pilocytic astrocytomas
Mutation → make tumor cells less viable, increase susceptibility to oxidative damage.

Better prognosis with IDH mutation.

70
Q

What is the difference of gliosis in peds v. adults?

A

Both look similar, but have different genetics markers.

71
Q

Pilocytic astrocytoma: BRAF-KIAA fusion → Constitutive activation of BRAF gene = FAVORABLE feature in slow growing tumors
NO IDH MUTATION

A

Pilocytic astrocytoma: BRAF-KIAA fusion → Constitutive activation of BRAF gene = FAVORABLE feature in slow growing tumors
NO IDH MUTATION

72
Q

Adult:
All adult oligodendrogliomas defined by presence of LOH 1p19q AND IDH mutation (either IDH1 or IDH2)
LOH1p19q → unbalanced translocation, fusion → fusion protein
Common in oligodendrogliomas
Prognostic, diagnostic, and predictive

A

Adult:
All adult oligodendrogliomas defined by presence of LOH 1p19q AND IDH mutation (either IDH1 or IDH2)
LOH1p19q → unbalanced translocation, fusion → fusion protein
Common in oligodendrogliomas
Prognostic, diagnostic, and predictive

73
Q

What are the tumors that tend to spread throughout the CSF?

A

Tumors that tend to spread via CSF:

  • Medulloblastoma
  • Anaplastic Ependyoma
74
Q

1p and 19q codeletions are the established genetic markers of ______________ tumors.

A

Oligodendroglial tumors

75
Q

You have a 1p and 19q codeletion that leads to Oligodendroglial, how do you progress to Anaplastic Oligodendroglia?

A

by losing either 9p or 10q

76
Q
  • 10q loss.
  • PTEN mut.
  • EGFR amplification.
  • CDKN2A/B del.

Leads to what tumor?

A

GBM; Glioblastoma multiforme

77
Q

EGRF amplification is done by ____1____.

EGFRvIII testing is done by _____2_____

A
  1. FISH

2. rtPCR

78
Q

50% of what tumor has a EGFR amp. containing EGFRvIII?

A

GBM.

EGFR amp of EGFRvIII in neoplastic ASTROCYTES is Dx for high-grade GBM.

79
Q

What is a utility of IDH1/2 mut. ?

A

can be used to figure out:

  • Neoplastic vs. non-neoplastic
  • Primary CNS vs. non-CNS tumors
  • Marker of Astrocytic and Oligodendroglial tumors.
80
Q

What mutation is present in 60-80% of WHO grade II and grade III gliomas (Asteocytic and oligodendroglial)

81
Q

What tumor does NOT have a IDH1 mutation?

A

Pilocytic Astrocytoma

82
Q

______ antibody is 100% specific for WHO grade 2 and 3 tumors?

A

IDH1 antibodies

NS_BTRAN (21 decks)

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