CNS neoplasms Flashcards
Gliomas are classified based off of what?
• Their resemblance to normal, non-neoplastic glial cells
What are the common gliomas and their WHO grade by definition?
• Pilocytic astrocytoma ○ Grade I • Diffuse astrocytoma ○ Grade II • Anaplastic astrocytoma ○ Grade III • Oligodendroglioma ○ Grade II • Anaplastic oligodendroglioma ○ Grade III • Glioblastoma ○ Grade IV
What makes a grade I glioma “not so bad”?
- Well demarcated
- Generally do not upgrade over time
- Can be surgically-excised if in an anatomically favorable location
- Treated with surgery alone
- Usually doesn’t require adjuvant therapies like radiation/chemo
What are the characteristics of pilocytic astrocytoma?
• Most common CNS neoplasm of childhood
• found also in young adults
• Cerebellum, optic pathway, hypothalamus, thalamus, spinal cord, temporal lobe
• WHO grade I, does not progress to higher grades (usually)
• Different genetic origins in different anatomical sites
• Histopathology
○ Bipolar neoplastic cells with elongated hairlike processes in parallel bundels
○ Rosenthal fibers, eosinophilic granular bodies
○ May be vascular with calcifications
in what population would you expect a pilocytic astrocytoma to be found?
- Most common CNS neoplasm of childhood
* found also in young adults
What is the histopathology of a pilocytic astrocytoma?
• Histopathology
○ Bipolar neoplastic cells with elongated hairlike processes in parallel bundels
○ Rosenthal fibers, eosinophilic granular bodies
○ May be vascular with calcifications
When you see pilocytic astrocytoma, what genetic underpinnings must you think of?
- BRAF:KIAA fusion
- BRAF fusion
- The grade I pilocytic astrocytomas by definition have the BRAF fusion
What does the BRAF gene product do?
- Mitogen-activated protein kinase
- MAPK
- In the RAS/RAF/MEK/ERK pathway
- Key in cell proliferation, survival, differentiation and apoptosis
- Ends up making cyclin D1
What makes the BRAF:KIAA fusion such an advantage for the tumor cell?
- Don’t know what KIAA does alone but fusion leads to ablation of BRAF N-terminal domain
- Renders BRAF constitutively active and leads to oncogene-induced senescence (OIS)
- Favorable feature in a slowly growing tumor
What’s up with diffuse astrocytoma?
• Mean age 30s-40s
• WHO grade II, may progress to higher grade
• Cerebral hemispheres, rarely posterior fossa
• Histopathology
○ Discohesive monotonous cellular infiltrate in patternless array
○ Fibrillary, protoplasmic, gemistocytic subtypes
○ Occasional microcystic change
○ Rare mitoses, two or more on small stereotactic biopsies = WHO grade III
○ No microvascular proliferation or necrosis
○ Ki67/MIB1 less than 4%
§ Marker of cell cycle
○ Often nuclear p53 IHC+
§ This is unlike oligodendrogliomas
What is the histopathology of diffuse astrocytoma?
• Histopathology
○ Discohesive monotonous cellular infiltrate in patternless array
○ Fibrillary, protoplasmic, gemistocytic subtypes
○ Occasional microcystic change
○ Rare mitoses, two or more on small stereotactic biopsies = WHO grade III
○ No microvascular proliferation or necrosis
○ Ki67/MIB1 less than 4%
§ Marker of cell cycle
○ Often nuclear p53 IHC+
§ This is unlike oligodendrogliomas
What are the important IHC markers in diffuse astrocytoma?
○ Ki67/MIB1 less than 4%
§ Marker of cell cycle
○ Often nuclear p53 IHC+
§ This is unlike oligodendrogliomas
What makes diffuse astrocytoma a difficult tumor to treat surgically?
- Microcysts and ill-defined borders
- Surgeon can’t tell where the tumor starts and stops
- Radiologist can’t tell…you can’t operate on this lesion
What’s up with anaplastic astrocytoma?
• Mean age is 45 years
• WHO grade III
• Cerebral hemispheres in adults
• Histopathology
○ Higher cellularity, increased nuclear pleomorphism, hyperchromasia, mitoses compared to WHO grade II astrocytomas
○ No necrosis or microvascular proliferation
○ Ki-67/MIB1 higher than WHO grade II, 5-15%
○ MOST IMPORTANT USE OF MIB1 is in distinguishing WHO grade II astrocytoma from WHO grade III anaplastic astrocytoma
What is the MOST IMPORTANT USE OF MIB1?
○ MOST IMPORTANT USE OF MIB1 is in distinguishing WHO grade II astrocytoma from WHO grade III anaplastic astrocytoma
- less than 4% for grade II
- 5-15% for grade III
In terms of IDH, what do each of the tumors we discussed have?
- All pilocytic astrocytomas are IDH wildtype
- All oligodendrogliomas are IDH mutant AND show 1p/19q deletion
- Diffuse astrocytoma, anaplastic astrocytoma, GBM today SEPARATED into/DEFINED BY IDH mutant and IDH wildtype status
- GBM - glioblastoma multiformans
What is IDH?
• IDH - isocitrate dehydrogenase
• Absolutely essential to know that this is a CNS neoplasm diagnostic marker and it defines certain tumors
*normal function is protection against oxidative damage
If there is a problem in IDH, what is the result?
• IDH mutation can lead to too little alpha-ketoglutarate, which is protective against oxidative damage
• If there is too little alpha-ketoglutarate there is a release of HIF1
○ Hypoxia inducible factor
• Leads to angiogenesis really, and promotes the tumor invasion, survival and angiogenesis
What is the utility of the IDH1/2 mutations?
• Determining if the lesion is neoplastic vs. non-neoplastic
• Primary CNS tumor vs. non-CNS tumor (metastasis)
○ Remember that metastatic brain lesions are more common than primary
• Marker of astrocytic and oligodendroglial tumors
What is the IDH1 mutation important for?
- Diffuse astrocytomas, anaplastic astrocytomas, GBMs today DEFINED by IDH-mutant or wildtype status
- All adult oligodendrogliomas defined by presence of LOH 1p,19q AND IDH mutation (either IDH1 or 2)
- 90% of IDH1 mutations are at position R132H
Where do you find IDH2 mutations?
• These are less common and mostly are found in oligodendroglial tumors
