CNS Tumors

Question 1

What are the four molecular subtypes of glioblastoma multiforme?

Answer 1

1. Classic subtype
2. Proneural
3. Neural
4. Mesenchymal

Question 2

Which has a better prognosis, a mutant form of Isocitrate Dehydrogenase or a wild type Isocitrate Dehydrogenase?

Answer 2

The mutant form has a better prognosis

Question 3

What is the WHO grade of Gliomatosis cerebri?

Answer 3

WHO grade III/IV. Although it is just a diffuse glioma, it is extensive.

Question 4

What gene is involve in Pilocytic astrocytoma that is often used in targeted therapy?

Answer 4

BRAF

Question 5

What syndrome/ condition is often associated with Pilocytic astrocytoma?

Answer 5

Neurofibromatosis type 1 (Von Recklinghausen Disease)

Question 6

A 5- year old male presented with seizure. There is a mass in the temporal lobe on imaging. Biopsy shows bizarre astrocytes filled with lipids but with absence of necrosis and mitotic activity. Diagnosis? WHO grade?

Answer 6

Pleomorphic Xanthoastrocytoma, WHO grade II

Question 7

Brainstem gliomas mostly have this type of amino acid mutation.

Answer 7

Lysine to methionine mutation at position 27.

Question 8

What is the most common genetic abnormality in oligodendrogliomas?

Answer 8

Mutation in isocitrate dehydrogenase genes (IDH1 and IDH2) and co-deletion of 1p and 19q. Tumors with these mutations have better prognosis than without and they are more responsive to chemotherapy and radiation.

Question 9

What is the WHO grade for oligodendrogliomas?

Answer 9

WHO grade II

Question 10

What is the most common location of ependymoma?

Answer 10

In young adults (first 2 decades): fourth ventricle.

In older adults: Spinal cord - particularly associated with Neurofibromatosis type 2.

Question 11

What are the four molecular subtypes of Medulloblastoma?

Answer 11

1. WNT type (Classic) - older children, best prognosis
2. Sonic Hedgehog/MYCN (Nodular desmoplastic)
3. Group 3/MYCN (Classic or large cell histology) - worst
   prognosis.
4. i117q alteration (Classic or large cell histology).

Question 12

What is the WHO grade of Medulloblastoma?

Answer 12

WHO grade IV

Question 13

2 year-old female with tumor in the posterior fossa. Biopsy shows epithelial, mesenchymal, neuronal and glial components with some rhabdoid cells. What is the molecular hallmark of this tumor?

Answer 13

Atypical Teratoid/ Rhabdoid tumor - hallmark is chromosome 22 mutation (>90%).
Immunostaining: Loss of nuclear staining for INI1.
WHO grade IV (highly aggressive)

Question 14

Majority of CNS lymphomas are of what cell origin?

Answer 14

B- cell origin. Diffuse Large B-cell is the most common histologic group.

Question 15

What special stain will be helpful to determine if lymphoma is primary to the CNS?

Answer 15

Reticulin stain - demonstrating “hooping” - characteristic of primary CNS lymphoma.

Question 16

Most common genetic abnormality in Meningioma?

Answer 16

loss of chromosome 22, long arm. 22q.

Associated with Neurofibromatosis type 2 (merlin gene mutation)

Question 17

What are the meningioma subtypes that are WHO grade II?

Answer 17

WHO grade II - Clear cell, Atypical, Choroid (CAC-2)

4 or more mitoses/10HPF

Question 18

What are the meningioma subtypes that are WHO grade III?

Answer 18

WHO grade III - Rhabdoid, Anaplastic, Papillary (RAP-3)

>20 mitoses/10HPF

Question 19

What specific meningioma subtype has a unique mutation in the TRAF7 and KLF4? Clue: PAS-positive.

Answer 19

Secretory subtype - WHO grade I.

They are also CEA positive.

Question 20

What are the most common tumors metastasizing to the brain - give at least 5.

Answer 20

Skin (melanoma), breast, lung, kidney, GIT

Choriocarcinoma - high likelihood to metastasize in the brain as well.

Question 21

Cowden syndrome is also known as _?

Answer 21

Dysplastic gangliogliocytoma of the Cerebellum or Lhermitte-Duclos disease.
PTEN mutation

Question 22

Turcot syndrome mutation?

Answer 22

Mutations in APC or mismatch repair.
Colonic polyposis + Medulloblastomas/Astrocytomas
2/3: Medulloblastoma and FAP
1/3: Glioblastoma and Lynch/HNPCC

Question 23

Gorlin syndrome mutation?

Answer 23

Mutation in the PTCH gene –> upregulation of sonic hedgehog signaling pathway.
BCC + Medulloblastoma etc.

Question 24

Tuberous sclerosis mutation?

Answer 24

mutation in TSC1 gene - hamartin protein
mutation in TSC2 gene - tuberin protein
mTOR - responsible for voluminous amounts of cytoplasm
Therapy: mTOR inhibitors.

Question 25

Tuberous sclerosis brain tumor?

Answer 25

subependymal giant cell astrocytoma (SEGA); cortical tubers and subependymal nodules.
+ Renal angiomyolipoma, Retinal glial hamartomas, cardiac Rhabdomyomas. (3R’s)
+ shagreen patches and ash-leaf patches.

Question 26

Autosomal Dominant disease associated with hemangioblastomas of the CNS + renal cell ca + pheochromocytoma.

Answer 26

Von Hippel- Lindau Disease. VHL- tumor suppressor gene in chromosome 3.
Hemangioblastoma most commonly in the cerebellum and retina.

Question 27

What immunostaining will favor a chordoma versus a chordoid meningioma?
A. EMA (+), CK (+), S100 (+), Brachyury (+)
B. EMA (-), CK (-), S100 (-), Brachyury (-)
C. EMA (+), CK (-), S100 (-), Brachyury (-)
D. EMA (-), CK (-), S100 (+), Brachyury (-)

Answer 27

A.