Neuropathology 2 Flashcards

1
Q

Identify the main classifications of tumors.

A
  • Benign versus malignant

* Malignant: primary versus metastatic

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2
Q

Why is the word benign inadequate when talking of benign brain tumors ?

A

Because although they are benign in terms of cell biology and invasive potential, their clinical features are NOT benign (i.e. may cause compression of the brain, or raised ICP)

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3
Q

Are most malignant brain cancers primary or secondary ?

A

Most malignant brain cancers are metastases (but often late in the disease when the patient presents with this, so may not become a driving clinical problem, e.g. because patient already dying from primary cancer)

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4
Q

Identify a primary cancer causing brain metastasis where the metastasis may actually occur early.
Identify a primary cancer causing brain metastasis where the metastasis occurs very late.

A

Breast cancer

Gastric and colorectal cancer can metastasise in very late stage disease (i.e. not clinically significant)

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5
Q

Identify non-metastatic/indirect effects of brain neoplasia.

A

E.g. tumor in pituitary can result in release of prolactin, and therefore milk-secreting phenotype

Paraneoplastic Syndromes with Endocrine Function:
Malignant tumors may produce diverse peptide hormones whose secretion is not under normal regulatory control.

1) Cushing’s Syndrome: secretion of ACTH by a tumor leads to features of Cushing syndrome
2) Inappropriate Anti-diuresis: Production of ADH by a tumor may cause sodium and water retention to such an extent that it is manifested as water intoxication

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6
Q

Identify commonest primary sites of tumor spreading to brain.

A
(main ones)
• Breast
• Melanoma
• Lung
• Kidney

(minor ones)
• Gut
• Haematopoietic

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7
Q

Which types of breast cancers can metastasise into the brain ?

A

HER2 negative, GFR positive or negative, estrogen receptor positive or negative

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8
Q

How does renal cancer spread to the brain ?

A

NOT via lymphatics, but grows along renal vein, into IVC

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9
Q

Identify types of haemoatopoietic tumors which can spread to the brain.

A
  • Leukaemia (if treat systematically, sometimes relapse of leukaemia can occur in the CNS, because BBB means the CNS becomes protected immunological site for residual cancer stem cells to reside)
  • Lymphoma
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10
Q

Identify the main clinical effects of metastatic brain tumors.

A

• Nil (cerebral metastases may not give symptoms initially)

• Space occupying lesion
– Raised intracranial pressure
– Headache
– Fits
– Drowsiness
– Behavioural change
– More specific changes (depending on area of brain affected, e.g. sight disturbances, personality changes if frontal, speech changes)

• Haemorrhage (some patients may present with stroke as a result of hemorrhage, but hemorrhage commonly results from treatment of metastasis)

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11
Q

Identify the main types of lung cancers which may metastasise into brain. Why does the type of primary tumor matter ?

A
  • Especially small cell undifferentiated (because primary neuroendocrine type origin, used to being migratory type cell)
  • Squamous
  • Adeno

The type matters for treatment

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12
Q

Identify the main features of breast cancer which metastasises into the brain.

A

Tends to be high grade breast cancer (tends to metastasise more)

Not limited to one subtype (which subtype will determine treatment)

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13
Q

To what extent is the molecular pathology of the tumor in the brain similar to that of the primary (in the case of secondary brain tumors) ?

A

Molecular pathology of tumor in brain, similar to primary but can get further genetic change (e.g. from melanoma, see black, nodular tumor mass in the brain)

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14
Q

Describe the findings of a brain metastasis arising from a melanoma, on imaging.

A

Density oedema around it, as it compresses and damages adjacent tissue

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15
Q

Identify the main treatment options for secondary brain cancer.

A
  • Chemotherapy (tumor may have damaged BBB anyway so many chemo drugs will be able to access brain)
  • Beam therapy (form of radiation, at very high doses but targeted to avoid damaging adjacent tissue)
  • Biological targeting (for tumors with known particular mutation which can be targeted)
  • Surgery (can be contemplated)
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16
Q

What is the main risk of treatment for secondary brain cancer ?

A

Risks of haemorrhage: if result in necrosis of tumor (which we aim for), may damage blood vessels so get secondary haemorrhage. This can result in expansion, osmosis of fluid into blood area, surrounding compression of brain, and raised ICP.

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17
Q

Identify the main intracranial constituents which can give rise to primary brain tumors.

A
• Linings – arachnoid
membrane
• Pituitary
• Peripheral nerve elements (e.g. VIII cranial nerve)
• Neurons
• Astrocytes
• Microglia
• Oligodendroglia
• Choroid plexus
• Ependyma
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18
Q

Identify the main primary brain tumors, both benign and malignant.

A
  • Intracranial primary (pretty much benign) neoplasm is mengioma
  • Primary neoplasms on the malignant spectrum are gliomas
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19
Q

What proportion of primary tumors do mengiomas make up ? Gliomas ?

A

Meningiomas: 1/3
Gliomas: 2/3

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20
Q

Identify an example of intracranial peripheral nerve tumor. What proportion of primary brain tumors does this account for ? What

A

Acoustic Schwannoma (acoustic neuroma) <10%

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21
Q

Which cells do gliomas arise from? Are they benign or malignant ?

A

Astrocytes, microglia, oligodendroglial cells

ALL MALIGNANT (but low grade have little malignant potential, whereas high grade high). Invasive.

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22
Q

To what extent do brain tumors metastasise ?

A

They typically do not (except one arising in cerebellum)

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23
Q

Are meningiomas benign or malignant ?

A

Said to be benign but not entirely true: non-invasive but have recognised genetic and molecular changes that occur

24
Q

Describe the main anatomical and clinical features of meningiomas.

A
  • Anatomical: Arise at site of arachnoid, on surface of the brain. Grossly, well demarcated.
  • Clinical: Typically can expand causing compression of brain, atrophy, raised ICP. Can also erode through skull. Present and grow slowly (may present with nothing or small gradual changes like headaches, fits, drowsiness, visual disturbances, changes in personality if frontal etc.) so may present late.
  • Can recur
25
Q

What are the main causes of meningioma ?

A
  • Sporadic (commonest)
  • Post-irradiation (e.g. if leukemia as a child)
  • Part of NF2 (genetic syndrome)
26
Q

What is the treatment of choice for meningiomas ?

A

Surgical removal (radiation may excite tumor)

27
Q

Describe the histological features of meningiomas.

A
  • Low mitotic activity
  • No invasion
  • Not much necrosis
28
Q

Describe the main anatomical and clinical features of gliomas.

A

-Anatomical: white shadow occupying large part of the brain, NOT well demarcated (difficult to tell where brain starts and tumor ends)

29
Q

To what extent can surgery be used for gliomas ?

A

Resecting gliomas surgically can be problematic, due to their poorly demarcated nature.

30
Q

Identify the main types of gliomas.

A
  • Oligodendroglioma (low grade potential as benign as gliomas get, fairly localised but still possibly poor demarcation, can be removed surgically)
  • Astrocytomas (rapidly growing, associated with secondary haemorrhage, raised ICP, very poor demarcation)
  • Ependymoma
  • Choroid plexus tumours
  • Medulloblastoma and PNET
31
Q

Describe astrocyte grading. What is the point of grading ?

A
  • I Localised (easier to resect)
  • II Diffuse
  • III Anaplastic (no differentiation) astrocytoma
  • IV Glioblastoma multiforme

Grading informs
prognosis and treatment (higher grade = more invasive, higher spread, poorer demarcation, more difficult to remove)

32
Q

Define multiforme.

A

Variable and heterogenous

33
Q

Describe histology of oligodendroglioma.

A

Small regular cells
Many blood vessels around
No necrosis
No mitotic activity

Refer to slide 19

34
Q

Describe histology of anaplastic astrocytoma.

A
  • Nuclei vary in size and shape
  • Mitotic figures, some of which are abnormal

Refer to slide 20

35
Q

Describe histology of Glioblastoma multiforme (grade IV astrocytoma).

A
  • Lots of cells including dead cells
  • Necrosis
  • Blood vessels present
  • Haemorrhage

Refer to slide 21

36
Q

Which groups of patients tend to be affected by astrocytoma ?

A

Young adults or young middle aged adults

37
Q

Which groups of patients tend to be affected by medullobastoma ? Where in the brain does it occur ? What are its main clinical features ?

A

Children

Typically occurs in cerebellum

Raised ICP + problems with coordination, ataxia

38
Q

What is the function of molecular genetic testing ?

A

Subtyping by molecular pathology can aid diagnosis, prognosis (some mutations confer better prognosis) and prediction (of correct treatment to give, i.e. different targeted therapies such as GF inhibitors or changes in gene methylation, will work for different mutations)

39
Q

Identify examples of peripheral nerve tumors.

A
  • Neuroblastoma, ganglioneuroma (from neural cells)
  • Schwannoma or neurofibroma
  • Cranial Nerve VIII: acoustic nerve
40
Q

Which groups of patients tend to be affected by neuroblastoma ?

A

Children

41
Q

What is the cause of Schwannomas ? of Neurofibromas ?

A

Usually spontaneous (no family history) for both

42
Q

Describe anatomical, and clinical features of Schwannomas.

A
  • Anatomical: arise from Schwann cells, typically within nerve. Single entity that expands.
  • Clinical: compresses nerve, causes pain and may cause loss of function
43
Q

How are Schwannomas treated ?

A

Typically surgical removal (if affects major nerve trunk do NOT resect whole trunk but possible if minor nerve)

44
Q

Describe anatomical, and clinical features of neurofibromas.

A
  • Anatomical: contains both fibroblast cells, and possibly Schwann cells. Arises from nerve sheath, but more primitive stem cell form. Grows between nerve fibers, so mix of cell types.
  • Clinical: Benign but
45
Q

How are Neurofibromas treated ?

A

CANNOT excise just them, because integrated with nerve.

If within small nerve, can resect nerve. If major nerve trunk, more problematic.

46
Q

Describe the pattern of inheritance of Neurofirbomatosis 1. Is it always inherited ?

A

Autosomal dominant
BUT
50% of cases involves spontaneous mutation

47
Q

Describe anatomical and clinical features of neurofibromatosis type 1.

A

Anatomical: Multiple neurofibromas, with cafe au lait spots.
Clinical: Due to development of tumors, some can be visceral and cause problems, other can be intracerebral and cause fits etc.

48
Q

Identify a genetic syndrome which can cause brain tumors.

A

Neurofibromatosis 2

49
Q

Describe treatment for Neurofibromatosis type 1?

A

Surgery not an option if hundreds, or thousands of neurofibromas, potentially including visceral ones (often the case).

50
Q

What tumors may arise in Neurofibromatosis 2 ?

A

• Neurofibromas

• MISME (other name for it): Multiple Inherited Schwannomas
Meningiomas and Ependymomas

• Possible bilateral acoustic Schwannoma

51
Q

What genetic defect is responsible for Neurofibromatosis type 2 ? Is this the same as the gene responsible for type 1 ?

A

• Merlin protein (coded by NF2 gene)

different to genetic defect in type 1 (Neurofibromin protein, coded by NF1 gene)

52
Q

Identify a clinical feature of bilateral acoustic Schwannoma.

A

Deafness

53
Q

What are the main causes of neurofibromatosis type 2 ?

A

Typically inherited (but can be spontaneous)

54
Q

Identify a possible complication of Neurofibromatosis ?

A

Sarcoma (malignancy)

55
Q

Identify possible clinical features of NF type 2.

A

Due to development of tumors, some can be visceral and cause problems, other can be intracerebral and cause deafness, fits.