10 06 2014 Brain Tumors

Question 1

What are the two major diffuse gliomas

Answer 1

1. Astrocytes –> Astrocytoma (includes glioblastoma)

2. Oligodendrocytes –> Oligodendroglioma

Question 2

Astrocytoma

1. 3 types
2. Histology
3. Cause?

Answer 2

1. well defined astocytoma (grade II)
   Histology: tumor cell cytoplasm + for glial fibrillary acidic protein (GFAP)
   - IDH1 or IDH2 (isocitrate dehydrogenase)
2. Anaplastic astrocytoma (grade II-III)- Malignant
   Histology: Pale cells , Endothelial hyperplasia, increase in mitotic index (6 or more mitotically active cells in 10 high power fields)
3. Glioblastoma Multiforme Grade IV - MALIGNANT
   -most common primary brain tumor in adults
   - P53, P13K, Rb tumor supressor, IDH1, IDH2
   *characteristically crosses the corpus calloused
   Histology: pseudopalsading + Endothelial proliferation

Question 3

Oligodendroglioma

1. Malignant or Benign?
2. how common?
3. Where is the tumor located?
4. how does it present?
5. Histology

Answer 3

Malignant -- oligodendrocytes
-relatively rare
- usually seen 4th-5th decade
-calcified tumor in white matter -- frontal lobe
-presents with seizures
Histology: fried egg appearance

Question 4

Identify the two major types of childhood brain tumors (general)

Answer 4

1. Pilocytic Astrocytoma– Benign

2. Medulloblastoma – Malignant

Question 5

Pilocytic Astrocytoma

1. cell of origin
2. where is cancer?
3. benign or malignant
4. Histology?
5. how does it present?
6. Cause?

Answer 5

Astrocytes
Cerebellum ( posterior fossa)
Benign: good prognosis
Histology: + GFAP; Rosenthal fibers (cork-screw)

-appears as a cystic lesion with a mural nodule. May affect optic pathways

Caused by BRAF mutations

Question 6

Medulloblastoma

1. cell of origin
2. where is cancer?
3. benign or malignant
4. Histology?
5. how does it present?
6. Cause?

Answer 6

1. Granular cells in cerebellum
2. Cerebellum (neuroectodermal)
3. Malignant
4. Homer-Wright rosettes: solid, blue colored cells
5. can compress the 4th ventricle –> hydrocephalus. Also has Drop metastasis (to spinal cord)

Question 7

What are the 4 major adult intracranial tumors? (just name)

Answer 7

1. Glioblastoma Multiforme ( #1)
2. Meningioma
3. Schwannoma
4. Oligodendroglioma (relatively rare)

Question 8

Meningioma

1. how common
2. malignant or benign
3. Origin? (cells?)
4. How does it present?

Answer 8

2nd most common primary brain tumor

• benign, resectable - mostly in females
• arachnoid cells (surface of the brain) BUT DOES NOT INVADE THE CORTEX
• may have a dural tail = compression-> seizures

Question 9

Schwannoma

1. how common
2. malignant or benign
3. Origin? (cells?)
4. How does it present?

Answer 9

3rd most common primary brain tumor.
Benign, resectable
Schwann cells around Cn VIII
- often asymptomatic or may present with seizures, loss of hearing/ tinnitus

Question 10

What are paraneoplastic syndromes?

Name the 4 and quickly what they do?

Answer 10

direct or localized effects due to metastasis
* patient may form antibody to tumors

1. Subacute Cerebellar degeneration = clinical ataxia
   
   • cerebellar purkinje cells are destroyed
2. Limbic encephalitis = dementia and severe memory loss over time
   
   • -chronic inflammation of medial temporal lobe.
3. Subacute Sensory neuropathy – altered pain sensation ( DRG)
4. Syndrome of rapid onset psychosis, catatonia, epilepsy, and coma
   
   • ovarian teratoma
   • antibodies against NMDA receptors

Question 11

Tuberous Sclerosis (TSC)

Answer 11

Autosomal Dominant mutations = cancer
- Hamartomas and benign neoplasms of the brain and other tissues
TSC1 or TSC2 gene mutations
- form a dimer that negatively regulates mTOR1
- high mTOR 1 = increase cell growth

Question 12

Von Hippel-Lindau Disease

Answer 12

VHL tumor suppressor gene mutated
encodes ubiquitin-complex protein that targets HIF. Mutation = no ubiquitination

high HIF –> HIGH VEGF = Angiogenesis

Question 13

What are the two cancers (benign) peripheral nerve sheath tumors

Answer 13

• Schwannoma

- Meningiomas

Question 14

Neurofibromas
(background)

1. malignant or benign
2. Origin
3. NF1 mutations and types (2)
4. NF2

Answer 14

benign

• arise from schwann cells (peripheral nerve)
• NF1 mutations – autosomal dominant

1. dermal - no evidence of turning malignant – superficial
2. Plexiform– multiple nerves/bundles can cause pain, disfigurement, neurological and other clinical deficits.
   10% become malignant

NF2 non-malignant – Multiple Inherited Schwannomas, Meningiomas, Ependymomas (MISME)
- CN8 = auditory-vestibular issues

Question 15

Malignant peripheral nerve sheath tumors (MPNST)

Answer 15

Malignant neurofibromatosis

• Autosomal Dominant
• sarcomas that originate in Schwann cells (any nerve)
• since it is from multiple cell lines, the appearance varies

Question 16

Corticotroph Cell Adenomas

Answer 16

(pituitary adenomas)
ACTH and other POMC-derived peptides
1. hypercortisolism = Cushing’s
2. ACtH: release of corticosteroids from adrenal gland = Cortisol

Question 17

Somatotroph Cell adenomas

Answer 17

GH

- Giantism (children) or Acromegaly (adults)

Question 18

Thyrotroph

Answer 18

TSH overproduction
= Hyperthyroidism : accelerated metabolism = weight loss, rapid/irregular heart beat, sweating, nervousness/irritability.

Question 19

Ependymoma

1. origin?
2. where is the tumor usually located?
3. When is it seen?

Answer 19

Childhood cancer – 2 decades of life

• Epmendymal cells – line the ventricle
• 4th ventricle = hydrocephalus

Histology: perivascular pseudorosettes; Rod-shaped blepharoplasts (basal ciliary bodies round near nucleus)

Question 20

Craniopharyngioma

1. Malignant or benign?
2. origin?
3. where is the tumor usually located?
4. effects of tumor placement?

Answer 20

1. Benign
2. Epithelial remnant of Rathke’s pouch
3. SUPRATENTORIAL mass in CHILD!!
4. optic chiasm compression - bitemporal hemianopsia