Overview Flashcards
What is the most common primary malignant brain tumor in adults?
GBM is the most common (80%) primary malignant brain tumor in adults
What is the incidence of GBM in the US?
Incidence: 3 to 4 cases per 100,000
10,000 cases/year in the United States
What is median age at diagnosis for GBM? Male to female ratio?
Median age at diagnosis is 64 and the male-to-female ratio is approximately 1.5:1
How does GBM infiltrate?
Diffusely infiltrative tumor that grows along white matter tracts
Most common location in brain for GBM? Why?
75% are supratentorial (31% temporal, 24% parietal, 23% frontal, 16% occipital), <20% multifocal, 2% to 7% multicentric, 10% present with positive CSF cytology; Location is dependent on amount of white matter
What is the cell of origin for GBM?
Cell of origin is the supporting glial cells of CNS
Name the distinct types of GBM according to WHO? Name other rare variants
The World Health Organization 2016 update now defines three distinct types: Glioblastoma IDH-wild-type; Glioblastoma IDH mutant; Glioblastoma NOS
Other rare variants include giant cell glioblastoma, gliosarcoma, or epithelioid glioblastoma
According to WHO pathologic grading, what is required for grade IV glioma diagnosis? What is the MEAN criteria?
Diagnosis of a WHO grade IV glioma requires the pathognomonic finding of “pseudopalisading” necrosis OR at least three of MEAN criteria
High Mitotic índex, Endothelial proliferation, Nuclear Atypia, Necrosis
What is the purpose of MGMT gene? What chromosome is it found?
O6-methylguanine-DNA methyltransferase is located on chromosome 10q26.
Its purpose is to repair alkylation of guanine at the O-6 position
What is the result of MGMT gene methylation? Why is this important?
When the promoter undergoes epigenetic silencing by methylation, the gene is downregulated and repair of alkylated guanine decreases
MGMT methylation results in a better response to TMZ treatment (Hegi study)
What percentage of GBM have IDH1 mutations? What are they associated with?
Associated with increased age and secondary tumors that developed from previous low-grade gliomas.
IDH1 mutation is an independent positive prognostic factor (MS 27.4 mos for IDH1-mutated vs. 14 mos for IDH1-wild-type)
What is EGFRv3 variant? What is it a predictor for?
In-frame deletion of exons 2 to 7 of the EGFR gene affecting 801 base pairs
An independent predictor of a poor prognosis with standard chemoRT
In GBM, BRAF V600E mutation is associated with which type of GBMs?
Seen commonly in giant cell, epithelioid glioblastomas, and lower grade gliomas
What is ATRX? Mutations are most commonly seen in which tumors?
Alpha-thalassemia/mental retardation syndrome x-linked gene (ATRX) is a gene that is involved in chromatin regulation.
A mutation in ATRX is frequently seen in pts with grade II/III astrocytomas as well as pts with secondary GBM
Common clinical presentations of GBM?
Headache, cognitive changes, seizure, motor weakness, nausea/vomiting, visual loss, sensory loss, language disturbance, dysphagia, papilledema, gait disturbance, intracranial bleed
MRI imaging findings of GBM?
Heterogeneous enhancement, central necrosis, surrounding edema; T1 hypointense and T2 edema hyperintense
What is the RPA classification for GBM?
