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CNS Patho > Sheet 7 > Flashcards

Sheet 7 Flashcards

1
Q

CNS tumors are divided into:

A

1) Primary

2) Secondary (Metastatic)

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2
Q

Primary tumors may arise from:

A

1) The cells of the coverings
2) The brain cells
3) Other CNS cell populations

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3
Q

Primary tumors account for about -% of CNS tumors.

A

50-75%

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4
Q

Secondary tumors account for about -% of CNS tumors.

A

25-50%

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5
Q

What are the characteristic features of CNS tumors?

A

1) No premalignant or in situ stages
2) Metastasis is rare
3) The prognosis is highly affected by:
a) Growth pattern
b) Location
c) Age
4) Radio imaging

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6
Q

What can influence the patient’s outcome independent of histologic type or grade?

A

The anatomic site of the neoplasm

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7
Q

The histologic grading of CNS tumors is based on 4 criteria:

A

1) Presence of atypia
2) Mitotic count
3) The presence or absence of microvascular proliferation
4) Necrosis

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8
Q

What is microvascular proliferation?

A

The presence of abnormal vessels (irregular in shape, lined by at least two layers of endothelial cells and sometimes these cells are mitotically active).

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9
Q

CNS tumors are classified into 4 types:

A

1) Grade 1 lesions (benign)
2) Grade 2 lesions (low grade)
3) Grade 3 lesions (anaplastic)
4) Grade 4 lesions (high grade)

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10
Q

What are the characteristics of Grade 1 lesions?

A

1) Low proliferative activity

2) Can be cured after surgical resection alone

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11
Q

What are some examples of Grade 1 lesions?

A

1) Pilocytic astrocytoma (PA)
2) Subependymal giant cell astrocytoma (SEGA)
3) Choroid plexus papilloma
4) Myxopapillary ependymoma

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12
Q

What are the characteristics of Grade 2 lesions?

A

1) Low proliferative activity
2) Usually infiltrative and often recur
3) Some grade II entities tend to progress to higher grades of malignancy

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13
Q

What are some examples of Grade 2 lesions?

A

1) Diffuse astrocytoma
2) Oligodendroglioma
3) Neurocytoma
4) Some types of ependymoma

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14
Q

What are the characteristics of Grade 3 lesions?

A

1) Clear histological evidence of malignancy (nuclear atypia and higher
proliferative activity = mitosis)
2) In most settings, patients receive radiation and/or chemotherapy

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15
Q

What are some examples of Grade 3 lesions?

A

1) Anaplastic astrocytoma

2) Anaplastic oligodendroglioma

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16
Q

What are the characteristics of Grade 4 lesions?

A

1) Cytologically malignant
2) Mitotically active
3) Rapid proliferation
4) Necrosis-prone
5) Associated with rapid pre- and postoperative disease evolution and fatal
outcome

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17
Q

What are some examples of Grade 4 lesions?

A

1) Glioblastoma
2) Medulloblastoma
3) Pineoblastoma
4) Most embryonal neoplasms

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18
Q

Pediatric CNS tumors make up about _% of all pediatric tumors.

A

20%

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19
Q

Childhood CNS tumors differ from those in adults in:

A

1) Location

2) Histological type

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20
Q

Where are pediatric CNS tumors most commonly found?

A

2/3 infratentorial in kids (posterior fossa):

1) Cerebellum
2) Brain stem
3) 4th ventricle

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21
Q

Where are adult CNS tumors most commonly found?

A

2/3 supratentorial in adults (cerebral hemispheres above tentorium)

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22
Q

What histological tumor types are most commonly found in pediatrics?

A

1) Medulloblastoma
2) Pilocytic astrocytoma
3) Ependymoma

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23
Q

What histological tumor types are most commonly found in adults?

A

1) Glioblastoma
2) Metastases
3) Meningiomas
4) Diffuse gliomas constitute most gliomas in adults (including diffuse astrocytomas and oligodendrogliomas).

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24
Q

The 2016 WHO classification implemented:

A

The combined phenotypicgenotypic diagnostics based on tumor genetic profile and histologic
features (integrated diagnoses).

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25
Q

The 2016 WHO classification helped with what?

A

1) Improving treatment protocols

2) Predicting prognosis

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26
Q

What are the genetic alterations in Gliomas?

A

1) Mutations in isocitrate dehydrogenase (IDH) genes
2) Co-deletion of 1p (short arm of chromosome 1) and 19q (long arm of chromosome 19) chromosomal segments
3) Mutations in the promoter for telomerase
4) Other genetic alterations

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27
Q

Mutations in isocitrate dehydrogenase (IDH) genes are observed in which tumors?

A

Astrocytomas and oligodendrogliomas in IDH1 or IDH2 genes

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28
Q

Mutations in isocitrate dehydrogenase (IDH) genes can be detected by which stains and molecular studies?

A

1) IDH1-R132H immune stain
2) IDH2 doesn’t have an immune stain
3) IDH sequencing for IDH1 codon 132 and IDH2 codon 172

29
Q

Mutations in isocitrate dehydrogenase (IDH) genes leads to:

A

Increased production of 2-hydroxyglutarate = interferes with the activity of several enzymes that regulate gene expression = maintaining the cells in stem cell-like physiological states = self- renewal and tumorigenesis.

30
Q

In which tumors are Co-deletions of 1p (short arm of chromosome 1) and 19q (long arm of chromosome 19) chromosomal segments found?

A

Oligodendrogliomas

31
Q

What do mutations in the promoter for telomerase do?

A

Immortalize tumor cells

32
Q

In which tumors are mutations in the promoter for telomerase found?

A

Glioblastomas

33
Q

What do other genetic alterations include?

A

Mutations that lead to overexpression of the EGF receptor and other receptor tyrosine kinases or disable p53 or RB.

34
Q

What are gliomas?

A

Tumors of brain parenchyma, classified according to morphologic similarities to the glial cells

35
Q

Which cells are the most common cells and outnumber the neurons?

A

Astrocytes

36
Q

What do astrocytes look like histologically?

A

1) Round nucleus with many cell processes

2) If you stain the cell with GFAB = star shape with cell body and processes lightened by brown stain = GFAB positive

37
Q

What do oligodendrocytes look like histologically?

A

Regular rounded nucleus with perinuclear halos (artifactual clear areas)

38
Q

What do ependymal cells look like histologically?

A

It’s like epithelial cells, cuboidal to columnar lining the ventricular system and the central canal.

39
Q

Astrocytomas are classified according to:

A

Their infiltrative potential

40
Q

What are the 2 major categories of astrocytomas?

A

1) Diffuse (infiltrating) astrocytoma = you can’t draw a line between the
normal brain parenchyma and the neoplastic area.
2) Circumscribed astrocytic gliomas

41
Q

What are some examples of circumscribed astrocytic gliomas?

A

1) PA
2) SEGA
3) Pleomorphic xanthoastrocytoma (PXA).

42
Q

Diffuse (infiltrating) astrocytomas make up about _% of adult gliomas.

A

80%

43
Q

At what age are diffuse (infiltrating) astrocytomas diagnosed?

A

40–60-year olds

44
Q

Where are diffuse (infiltrating) astrocytomas found?

A

Cerebral hemispheres

45
Q

How do diffuse (infiltrating) astrocytomas clinically present?

A

1) Seizures
2) Headaches
3) Focal neurologic deficits related to the anatomic
site of involvement

46
Q

What is the outcome of diffuse (infiltrating) astrocytomas?

A

Static or progressive.
(If the patient shows rapid clinical deterioration, it can be correlated with the appearance of higher-grade component and more rapid tumor growth).

47
Q

On the basis of histologic features astrocytomas are stratified into three groups:

A

1) Diffuse astrocytoma (grade 2)
2) Anaplastic astrocytoma (grade 3)
3) Glioblastoma (grade 4)

48
Q

What is the mean survival of diffuse astrocytoma (grade 2)?

A

> 5 years

49
Q

What is the mean survival of anaplastic astrocytoma (grade 3)?

A

2-3 years

50
Q

What is the mean survival of glioblastoma (grade 4)?

A

15 months

51
Q

The prognosis of astrocytomas gets poorer as:

A

The grade increases

52
Q

Which one does not exist:

A) Grade 1 diffuse astrocytoma
B) Grade 2 diffuse astrocytoma
C) Grade 3 diffuse astrocytoma
D) Grade 4 diffuse astrocytoma

A

A) Grade 1 diffuse astrocytoma

53
Q

What are the characteristics of diffuse astrocytomas (grade 2)?

A

1) Mild to moderate increase in the number of glial cells
2) Fibrillary background made of fine astrocytic cell processes
3) Variable nuclear pleomorphism, however not prominent atypia.
4) Hyper chromatic nuclei and may be elongated
5) Mitotic activity is generally absent
6) NO necrosis
7) NO microvascular proliferation
8) It is common to have microcyst formation

54
Q

What are the histological characteristics of diffuse astrocytomas (grade 2)?

A

1) The cell body and the process are GFAB positive.
2) Low proliferative activity = mitotic figures are usually absent
3) Ki67 stain (proliferative marker)= Shows just 2 nuclei that are dark brown.

55
Q

What are the characteristics of anaplastic astrocytomas (grade 3)?

A

1) More cellular
2) Greater nuclear pleomorphism
3) Mitotic figures are present
4) NO necrosis
5) NO microvascular proliferation

56
Q

What are the characteristics of glioblastomas (grade 4)?

A

Lesions can start as Glioblastoma from the beginning (primary) or progress from a previous grade 2 or 3 tumors to grade 4 (secondary).

57
Q

What is the prognosis for glioblastomas (grade 4)?

A

Very poor even with treatment (resection, radiotherapy, and

chemotherapy)

58
Q

What are the macroscopic characteristics of a glioblastoma (grade 4)?

A

1) Variation in the gross appearance of the tumor from region to region is characteristic (was called glioblastoma multiforme).
2) Some areas are firm and white, others are soft and yellow (due to tissue necrosis), and others show regions of cystic degeneration and hemorrhage.
3) It shows multiple pictures depend on where you are looking from

59
Q

What are the microscopic characteristics of a glioblastoma (grade 4)?

A

1) Cellular tumor with nuclear pleomorphism as in
anaplastic astrocytoma with either:
a) Necrosis: irregular zones of necrosis surrounded
by dense accumulations of tumor cells (Palisading
necrosis).
OR
b) Microvascular proliferation

60
Q

What are the characteristics of Pilocytic Astrocytoma?

A

1) Relatively benign
2) Slow growing tumors
3) Can be treated by resection

61
Q

At what age does Pilocytic Astrocytoma present?

A

Children and young adults

62
Q

Where are Pilocytic Astrocytomas found?

A

Cerebellum> 3rd ventricle > optic pathways> spinal cord> cerebral hemispheres

63
Q

What is the molecular profile of Pilocytic Astrocytomas?

A

Activating mutations or translocations involving the gene encoding the BRAF, which result in activation of the MAPK signaling
pathway.

64
Q

What differentiates Pilocytic Astrocytomas from low-grade diffuse gliomas?

A

Pilocytic Astrocytomas do not have mutations in IDH1 and IDH2

65
Q

How do Pilocytic Astrocytomas appear microscopically?

A

1) Bipolar cells with long, thin GFAP positive “hairlike” processes
2) Rosenthal fibers
3) Eosinophilic granular bodies
4) microcysts are often present
5) necrosis and mitoses are rare
6) Well circumscribed, cystic with a mural nodule in the wall of the cyst or solid
7) Formed by large radiolucent area which represents the cystic
cavity, so the tumor has a cystic cavity with a solid area.
8) Lesion (infratentorial tumor) usually within the
midline.

66
Q

What are Rosenthal fibers?

A

Rounded or elongated, homogenous, and brightly eosinophilic structures within the astrocytic processes

67
Q

What are Rosenthal fibers made of?

A

Clumped intermediate filament proteins, primarily glial fibrillar acidic protein (GFAP +VE)

68
Q

In which diseases are Rosenthal fibers found?

A

Physiologic (gliosis) or Pathologic (PA) and
Alexander disease , so it is not diagnostic or
exclusive for pilocytic astrocytoma

69
Q

What are eosinophilic granular bodies?

A

Rounded hyaline droplets in

cytoplasm of astrocytes seen in PA and ganglion-cell tumors

CNS Patho (8 decks)

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