Unit2_CNS Tumors Flashcards
(82 cards)
1
Q
What WHO histological type grade is the worst Px?
A
Grade IV (4)
2
Q
Astrocytoma, oligodendroglioma, ependymoma, ganglioma are known as ____1____, and are derived from the ____2____.
A
- GLIOMAS
2. NEUROECTODERM
3
Q
Tumors of low proliferative potential, possibility of cure with surgical resection alone describe what WHO grade of tumors?
A
Grade 1
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.
5
Q
Where are Pilocytic Astrocytoma located?
A
Location: Cerebellum, optic nerves/chiasm, and hypothalamic region
Children often have tumors in posterior fossa.
6
Q
How do you Tx Pilocytic Astrocytoma?
A
surgical excision alone (some locations require other therapy as well)
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
8
Q
What are the genetics ~w/ Pilocytic Astrocytoma?
A
BRAF-KIAA fusion → Constitutive activation of BRAF gene = FAVORABLE feature in slow growing tumors
9
Q
Pilocytic Astrocytoma is WHO grade?
A
Grade 1
10
Q
Ganglioglioma is WHO grade?
A
Grade 1
11
Q
What is the location of Ganglioglioma?
A
usually in the Temporal lobe.
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.
13
Q
Can Ganglioglioma have BRAF mut?
A
YES!
14
Q
Choroid plexus papilloma is WHO grade ?
A
Grade 1
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
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
17
Q
Choroid plexus papilloma can produce _____1_____ by ____2____ CSF flow.
A
- HYDROCEPHALUS
- BLOCKING CSF
Produce HYDROCEPHALUS by BLOCKING CSF flow (not by CSF overproduction)
18
Q
Choroid plexus papilloma have ___1___ mitotic rate, mild ____2____
A
- low
2. nuclear atypia
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
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
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.
22
Q
Where is the location of Diffuse Astrocytoma?
A
white matter of cerebral hemisphere
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
24
Q
What genetics are ~w/ Diffuse Astrocytoma?
A
IDH1/2 mutation + no LOH 1p, 19q + p53/ATRX mutation
25
Main difference between anaplastic astrocytoma and Diffused Astrocytoma?
Diffused Astrocytoma has an ABSENCE of:
- necrosis
- mitotic activity
- microvascular proliferation
26
Can Diffuse Astrocytoma be surgically resected?
NO! WHO grade 2
27
What WHO grade is Oligodendroglioma?
WHO grade 2.
- Common Glioma
- Mostly Adults
- Infiltrative, no clear borders, cannot be surgically resected
- Better overall prognosis that diffuse astrocytoma
28
What is the appearance of Oligodendroglioma?
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
29
Where are Oligodendroglioma located?
Cerebral Hemisphere.
White matter of cerebral hemisphere but quickly spread to overlying cortex → seizures
30
What Genetics are ~W/ Oligodendroglioma?
IDH1/2 mutation + LOH 1p, 19q + no p53/ATRX mutation.
Can be diagnostic in differentiating oligodendroglioma or anaplastic oligodendroglioma from an astrocytoma
31
Oligodendroglioma has an overall ________ prognosis that diffuse astrocytoma.
Oligodendroglioma has an overall BETTER prognosis that diffuse astrocytoma.
32
What WHO grade is Ependymoma?
Ependymoma = WHO grade 2
33
Where are Ependymoma located?
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
What is the Appearance of Ependymoma?
Gross:
Microscopic:
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
Ependymoma in children is located in the 4th ventricle this produces → ?
Children → 4th ventricle → HYDROCEPHALUS.
Less favorable diagnosis
36
Ependymoma in adults is located in the spinal cord, this produces → ?
Adults → Spinal cord
| Typically well demarcated, full excision may be possible
37
What are the WHO grade 1 Tumors?
1. Pilocytic Astrocytoma
2. Ganglioglioma
3. Choroid Plexus Papilloma
38
What are the WHO grade 2 Tumors?
1. Diffuse Astrocytoma
2. Oligodendroglioma
3. Ependyoma
39
What are the WHO grade 3 Tumors?
1. Anaplastic Astrocytoma
2. Anaplastic Oligodendroma
3. Anaplastic Ependymoma
40
What are the WHO grade 4 Tumors?
1. Glioblastoma (aka astrocytoma)
| 2. Medulloblastoma
41
Extrinsic Brain Tumors are meningeal & mesenchymal tumors and includes?
1. Meningomas
2. Hemangiopericytomas
3. Schwannomas
42
Histological evidence of malignancy (nuclear atypia, high mitotic activity) describes what WHO grade of tumors?
WHO grade 3
43
What is the overall Tx for grade 3 tumors?
Tx: adjuvant radiation and/or chemo
44
What is Anaplastic Astrocytoma and what is it's WHO grade?
Anaplastic Astrocytoma = WHO grade 3.
Common glioma, progression from diffuse astrocytoma
45
What is the appearance of Anaplastic Astrocytoma?
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
What is the major difference between Anaplastic Astrocytoma and Diffuse Astrocytoma?
Anaplastic Astrocytoma has an Increased mitotic rate = big difference between diffuse/anaplastic astrocytoma.
47
What is Anaplastic Oligodendroglioma and what is it's WHO grade?
Anaplastic Oligodendroglioma = WHO grade 3
48
What is the appearance of Anaplastic Oligodendroglioma?
DOES show enhancement on preop imaging studies.
Round, uniform nucleus, scant cytoplasm, “fried egg” appearance, microvascular proliferation present.
49
What is Anaplastic ependymoma and what is it's WHO grade?
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
cytologically malignant, mitotically active, necrosis prone neoplasms describes what WHO grade tumor?
WHO grade 4 = Rapid disease, often fatal.
51
What WHO grade is Glioblastoma?
Glioblastoma = Grade 4.
Most common and most malignant glioma.
Most occur in 50s and 60s
Not surgically curable, debulking only
52
What are the genetics ~w/ Glioblastoma?
EGFR typical mutation (diagnostic) in high grade GBM.
53
What is the appearance of Glioblastoma?
Hemorrhagic, necrotic, multifocal.
Deceptively well demarcated, but microscopically infiltrative.
54
Can you surgically resect a Glioblastoma?
NO. Debunking only!
55
What is the criteria for GBM? How many do you need to be considered a GBM?
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
Giloblastoma typically arise ______ (“primary GBM”).
But if diagnosis with lower grade astrocytoma first → “____2____” (via IDH+ pathway)*
1. de novo
| 2. secondary GBM
57
What is the most malignant glioma?
Glioblastoma: (aka astrocytoma) (Grade 4)
58
What is WHO grade is Medulloblastoma?
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
Medulloblastoma presents with Sx of:
- Increased ICP → headache, vomiting, papilledema.
| - Disturbances of gait, nystagmus, and dysmetria (cerebellum).
60
What is the appearance of Medulloblastoma?
Patternless sheets of small embryonal cells with scant cytoplasm (“small blue cells”), minimal differentiation
61
"small blue cells" are ~w/ ?
Medulloblastoma
62
What tumor is a Malignant embryonal tumor of cerebellum (primitive neuroectodermal tumor)?
Medulloblastoma
63
What are the extrinsic brain tumors? (3)
- Meningiomas
- Hemangiopericytoma
- Schwannomas
64
What are Meningiomas?
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
What are Hemangiopericytomas?
Hemangiopericytoma: meningeal-based tumor.
- Less favorable prognosis than meningioma, high recurrence rate.
- Accumulates more mutations as grade increases.
66
What are Schwannomas?
Schwannomas: (aka neurofibromas)
- Benign, can rarely degenerate into malignant form (neurofibrosarcoma)
- Slow growing
67
Most brain tumors are ____1____ and of ____2____ etiology
1. SPORADIC
| 2. UNKNOWN
68
Where do brain tumors typically met from?
Typically mets from breast, lung, kidney, melanoma, and GI tract cancer
69
What are IDH1 and IDH2?
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
What is the difference of gliosis in peds v. adults?
Both look similar, but have different genetics markers.
71
Pilocytic astrocytoma: BRAF-KIAA fusion → Constitutive activation of BRAF gene = FAVORABLE feature in slow growing tumors
NO IDH MUTATION
Pilocytic astrocytoma: BRAF-KIAA fusion → Constitutive activation of BRAF gene = FAVORABLE feature in slow growing tumors
NO IDH MUTATION
72
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
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
What are the tumors that tend to spread throughout the CSF?
Tumors that tend to spread via CSF:
- Medulloblastoma
- Anaplastic Ependyoma
74
1p and 19q codeletions are the established genetic markers of ______________ tumors.
Oligodendroglial tumors
75
You have a 1p and 19q codeletion that leads to Oligodendroglial, how do you progress to Anaplastic Oligodendroglia?
by losing either 9p or 10q
76
- 10q loss.
- PTEN mut.
- EGFR amplification.
- CDKN2A/B del.
Leads to what tumor?
GBM; Glioblastoma multiforme
77
EGRF amplification is done by ____1____.
EGFRvIII testing is done by _____2_____
1. FISH
| 2. rtPCR
78
50% of what tumor has a EGFR amp. containing EGFRvIII?
GBM.
EGFR amp of EGFRvIII in neoplastic ASTROCYTES is Dx for high-grade GBM.
79
What is a utility of IDH1/2 mut. ?
can be used to figure out:
- Neoplastic vs. non-neoplastic
- Primary CNS vs. non-CNS tumors
- Marker of Astrocytic and Oligodendroglial tumors.
80
What mutation is present in 60-80% of WHO grade II and grade III gliomas (Asteocytic and oligodendroglial)
IDH1 mut.
81
What tumor does NOT have a IDH1 mutation?
Pilocytic Astrocytoma
82
______ antibody is 100% specific for WHO grade 2 and 3 tumors?
IDH1 antibodies
