GLIAL AND GLIO- NEURONAL TUMORS Arie Perry, M.D. School of Medicine DISCLOSURES (Arie Perry, MD) • I have no financial relationships to disclose. - and - • I will not discuss off label use or investigational use in my presentation School of Medicine NEUROPATHOLOGY AND REAL ESTATE • Location • Location • Location • Patient Age • Neuroimaging
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GLIAL AND GLIO- NEURONAL TUMORS - Pathology€¦ · GLIAL AND GLIO-NEURONAL TUMORS Arie Perry, M.D. School of Medicine DISCLOSURES (Arie Perry, MD) • I have no financial relationships
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GLIAL AND GLIO-NEURONAL TUMORS
Arie Perry, M.D.
School of Medicine
DISCLOSURES (Arie Perry, MD)
• I have no financial relationships to disclose.
- and -
• I will not discuss off label use or investigational use in my presentation
School of Medicine
NEUROPATHOLOGY AND REAL ESTATE
• Location
• Location
• Location
• Patient Age
• Neuroimaging
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GLIOMAS
• Astrocytomas (A)
• Oligodendrogliomas (O)
• Mixed oligoastrocytomas (MOA)?
• Ependymomas
• Diffuse glioma = A, O, or MOA
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GLIOMA GRADING: WHO 2016
• Grade I = Benign
• Grade II = Low-grade
• Grade III = “Anaplastic”
• Grade IV = High-grade malignant, e.g. “GBM”
Distribution of Malignant Primary Brain and CNS Tumors by CBTRUS Histology Groupings and Histology (N = 117,023), CBTRUS Statistical Report: NPCR and SEER, 2008-2012.
Quinn T. Ostrom et al. Neuro Oncol 2015;17:iv1-iv62
• Average age 30-40 years• Corticotropism / seizures common• Cerebral, especially frontal lobe• Slow progression• Survival ~10-20 years for oligo (grade
II); 5-10 years for anaplastic oligo (grade III): microvascular proliferation, high mitotic index, and/or necrosis
OLIGODENDROGLIOMA, IDHm and 1p19q-codel (WHO GRADE II or III)
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OLIGODENDROGLIOMA
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N
N
N
OLIGODENDROGLIOMA, WHO GRADE II
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OLIGODENDROGLIOMA
GFAP
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ANAPLASTIC OLIGODENDROGLIOMA
SYN
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1p321q42
19p1319q13
Oligodendroglioma, IDH-mutant and 1p/19q-codeleted (WHO 2016)
IDH1
PreneoplasticCell
IDHm
TP53mATRXm
IDHmTERTm
1p19q‐codel
IDHwtEGFR‐ampTERTm
9p (CDKN2A/B) LOH
PIK3CAm?
Astro, IDHm
AA, IDHm
GBM, IDHm
Oligo, IDHm, 1p19q‐codel
AO, IDHm, 1p19q‐codel
GBM, IDHwt
Diffuse midlineglioma, H3‐K27Mm
PIK3R1/PIK3CAm
CICmFUBP1m
4q LOH?
Note: no oligoastro!
(H3 G34R/V)
PILOCYTIC ASTROCYTOMA
PILOCYTIC ASTROCYTOMA
Nat Genet 45: 927-932, 2013
MAPKpathway
BRAFKIAA1549
PILOMYXOID ASTROCYTOMA, WHO?
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Komotar et al. Neurosurgery 54:72, 2004
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LONG-TERM EPILEPSY ASSOCIATED TUMORS (LEAT)
• Glioneuronal– Ganglioglioma (GG), WHO I
– Dysembryoplastic neuroepithelial tumor (DNET), WHO I
– Others: mixed GG/DNET, PGNT, EVN
• Gliomas– Pleomorphic xanthoastrocytoma (PXA), WHO II/III
– Diffuse LGGs, WHO II
– Pilocytic astrocytoma, WHO I
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GANGLIOGLIOMA (WHO I)
• Most common LEAT
• Children/young adults
• Temporal lobe
• Benign/surgically curable
• Anaplasia rare: definition?– WHO grade III (grade II eliminated in 2007)
• BRAF-V600E in up to half
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GANGLIOGLIOMA (WHO I)
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GANGLIOGLIOMA (WHO I)
SYN NFP
Neu-N
CD34
BRAF V600E
Ganglioglioma
ANA GG, WHO GRADE III
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DNET (WHO I)
• LEAT of children/young adults
• Temporal lobe
• Benign/surgically curable
• Tumor vs. hamartoma
• Simple, complex, ‘non-specific’ variants
• BRAF-V600E: 0-50%; FGFR1-alt: 58%?, IDHwt, no 1p19q-codeletion
GFAP
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PXA, WHO II-III
PXA, WHO GRADE II
PXA, WHO GRADE II
PXA, WHO GRADE II
Reticulin
PXA, WHO GRADE II
GFAP
PXA, WHO GRADE II
SYN NFP
PXA, WHO GRADE II
CD34
PXA, WHO GRADE II
PXA c ANA transformation, WHO GRADE III
Ki-67
PXA c ANA transformation, WHO GRADE III
BRAF-V600E
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EPENDYMOMA (WHO GRADE I, II, III)
• Kids: 4th ventricle, supratentorial
• Adults: spinal cord
• Prognostic Variables
– Extent of resection / location
– Patient age (poor if <2 years old)
– Histologic grade?
• Subependymoma or MPE, WHO grade I
• Ependymoma, WHO grade II
• Anaplastic ependymoma, WHO grade III
– Molecular subgroups
Subependymoma, WHO GRADE I
MPE, WHO GRADE I
TrichromePAS
MPE, WHO GRADE I
NFP
Ependymoma, WHO GRADE II
Ependymoma, WHO GRADE II
Ependymoma, WHO GRADE II
GFAP
EMA CD99
Tanycytic ependymoma
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EPENDYMOMA: PROGNOSIS
Tihan T, et al., Mod Pathol 2008: 21, 165–177
Pajtler et al., 2015, Cancer Cell 27, 728–743
Clear cell ependymoma
Clear cell ependymoma
L1CAM
Clear cell (RELA fusion+) ependymoma
UCSF 500 NGS
H3K27me3
PF-A Ependymoma PF-B Ependymoma
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Neuropathology CD Recording
• Neuropathology songs
• Common disorders
• 2nd Year medical students
• Memorization aid
• Fun way to learn!
www.neuropathsongs.comiTunes or amazon.com
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O----ligodendroglio-oh-oh-ma, diffuse cerebral tumor of adultsInvading cortex, causing epilepsy; on imaging, often you are calcifiedAnd although, you tend to progress over time, for long periods your fineYou're famous for your rounded nuclei, Clear haloes look like honeycombs or fried eggsWith branching chicken wire capillaries, and perineuronal satellitosis
O----ligodendroglio-oh-oh-ma, genetically, you are quite uniqueWith 1p and 19q deletions, from translocation with loss of one derivativeRepresents a genetically favorable set, when FISH criteria are met
Anaplastic cases grow more rapidly, assigned a W.H.O. grade IIIWith microvascular proliferation, or increased mitotic activityO----ligodendroglio-oh-oh-ma
OligodendrogliomaMusic to Ave Maria by F. Schubert, Lyrics by Arie Perry, MD