CNS Tumors Flashcards
What are the four molecular subtypes of glioblastoma multiforme?
- Classic subtype
- Proneural
- Neural
- Mesenchymal
Which has a better prognosis, a mutant form of Isocitrate Dehydrogenase or a wild type Isocitrate Dehydrogenase?
The mutant form has a better prognosis
What is the WHO grade of Gliomatosis cerebri?
WHO grade III/IV. Although it is just a diffuse glioma, it is extensive.
What gene is involve in Pilocytic astrocytoma that is often used in targeted therapy?
BRAF
What syndrome/ condition is often associated with Pilocytic astrocytoma?
Neurofibromatosis type 1 (Von Recklinghausen Disease)
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?
Pleomorphic Xanthoastrocytoma, WHO grade II
Brainstem gliomas mostly have this type of amino acid mutation.
Lysine to methionine mutation at position 27.
What is the most common genetic abnormality in oligodendrogliomas?
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.
What is the WHO grade for oligodendrogliomas?
WHO grade II
What is the most common location of ependymoma?
In young adults (first 2 decades): fourth ventricle.
In older adults: Spinal cord - particularly associated with Neurofibromatosis type 2.
What are the four molecular subtypes of Medulloblastoma?
- WNT type (Classic) - older children, best prognosis
- Sonic Hedgehog/MYCN (Nodular desmoplastic)
- Group 3/MYCN (Classic or large cell histology) - worst
prognosis. - i117q alteration (Classic or large cell histology).
What is the WHO grade of Medulloblastoma?
WHO grade IV
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?
Atypical Teratoid/ Rhabdoid tumor - hallmark is chromosome 22 mutation (>90%).
Immunostaining: Loss of nuclear staining for INI1.
WHO grade IV (highly aggressive)
Majority of CNS lymphomas are of what cell origin?
B- cell origin. Diffuse Large B-cell is the most common histologic group.
What special stain will be helpful to determine if lymphoma is primary to the CNS?
Reticulin stain - demonstrating “hooping” - characteristic of primary CNS lymphoma.
Most common genetic abnormality in Meningioma?
loss of chromosome 22, long arm. 22q.
Associated with Neurofibromatosis type 2 (merlin gene mutation)
What are the meningioma subtypes that are WHO grade II?
WHO grade II - Clear cell, Atypical, Choroid (CAC-2)
4 or more mitoses/10HPF
What are the meningioma subtypes that are WHO grade III?
WHO grade III - Rhabdoid, Anaplastic, Papillary (RAP-3)
>20 mitoses/10HPF
What specific meningioma subtype has a unique mutation in the TRAF7 and KLF4? Clue: PAS-positive.
Secretory subtype - WHO grade I.
They are also CEA positive.
What are the most common tumors metastasizing to the brain - give at least 5.
Skin (melanoma), breast, lung, kidney, GIT
Choriocarcinoma - high likelihood to metastasize in the brain as well.
Cowden syndrome is also known as _?
Dysplastic gangliogliocytoma of the Cerebellum or Lhermitte-Duclos disease.
PTEN mutation
Turcot syndrome mutation?
Mutations in APC or mismatch repair.
Colonic polyposis + Medulloblastomas/Astrocytomas
2/3: Medulloblastoma and FAP
1/3: Glioblastoma and Lynch/HNPCC
Gorlin syndrome mutation?
Mutation in the PTCH gene –> upregulation of sonic hedgehog signaling pathway.
BCC + Medulloblastoma etc.
Tuberous sclerosis mutation?
mutation in TSC1 gene - hamartin protein
mutation in TSC2 gene - tuberin protein
mTOR - responsible for voluminous amounts of cytoplasm
Therapy: mTOR inhibitors.
Tuberous sclerosis brain tumor?
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.
Autosomal Dominant disease associated with hemangioblastomas of the CNS + renal cell ca + pheochromocytoma.
Von Hippel- Lindau Disease. VHL- tumor suppressor gene in chromosome 3.
Hemangioblastoma most commonly in the cerebellum and retina.
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 (-)
A.
