neuro - intraaxial neoplasms - smirniotopoulos (rsna 2005)
DESCRIPTION
Neuro - Intraaxial Neoplasms - Smirniotopoulos (RSNA 2005)TRANSCRIPT
11
The WHO 2000 Astrocytoma Classification
James G. Smirniotopoulos, M.D.Uniformed Services University
of the Health SciencesBethesda, MD
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Features of Glioma• Site of Origin• Character of lesion
– Signal intensity (MR)– Attenuation (CT)– Blood-brain-barrier (Gd or I)– Chemistry (MRS)– Metabolism (Th 201, FDG-PET)– Vascularity (PWI)
• Mode of Spread– DTI
Traditional Tumor Grading
• PATHOLOGIST– LOW GRADE– HIGH GRADE
• RADIOLOGIST– NON-ENHANCING– ENHANCING
• NEUROSURGEON– “SUCKABLE”– “NON-SUCKABLE”
Kernohan-Sayre (AFIP)Grading System:
• GRADE I- “BENIGN” or “Low-Grade”• GRADE II - “ “• GRADE III - ANAPLASTIC
– cellular atypia, etc.• GRADE IV- MALIGNANT
– NECROSIS, Vascularity, Mitoses– GLIOBLASTOMA MULTIFORME
• NOTE: Numerous modifications exist, most into three grades, e.g..: Low Grade (Benign), Anaplastic, and GBM (w/ NECROSIS).
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Correlation
T2 SI, DWI & ADCCellularity
T1 and T2 SI, DTIInfiltration
MRS, Th 201 and FDGLabeling Indices
T1 and T2 SIHemorrhage
Ring Lesion, MRS, DWI & ADC
Necrosis
Enhancement, PWI, and Permeability Imaging
Endothelial proliferation and Vascularity
RadiologyPathology
ASTROCYTOMAFive Year Survival
0 20 40 60 80 100
Percent Survival
Glioblastoma (IV)
Anaplastic (III)
Astrocytoma (I-II)
Pilocytic
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GRADING SYSTEMSSem Rad Onc (1991); 1: 2-9
Kernohan Berger WHO 1993 1 Pilocytic,SEGA
Benign (1) Astrocytoma2 Astrocytoma
Benign (2)Anaplastic 3 Anaplastic
Anaplastic (3)
Glioblastoma (4) Glioblastoma 4 Glioblastoma
Define the Problem:
• Some Low Grade Enhance• Some Low Grade Do Not
• Some Low Grade => GBM• Some Low Grade Do Not
WHO Classification
• Defines Histologic Subtypes• Grades Biologic Potential• Allows International Cooperation• Ascending scale of Aggression from 1-4
WHO CORRELATION
• Low Grade
– Long-Term Survival
– Stable Histology no progression
Possible Cure
WHO Grading CNS Tumors
GRADE 1 JPA SGCA GANG MENING
GRADE 2 PXA HPC
GRADE 3 PXA ANAPLASTIC HPC
GRADE 4 GBM
CNS NEOPLASM-GLIALPrognostic Factors
Location Age
Histology
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“BENIGN” ASTROCYTOMA
• Two types:– Low grade (“benign”)
Diffuse (Adults)– Low grade “special”
Circumscribed (Children)
Normal appearing white matter Normal appearing white matter …… few cell bodiesfew cell bodies
Diffuse Low Grade Astrocytoma Diffuse Low Grade Astrocytoma …… too many cells !too many cells !
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WHO Gr1 - Pilocytic Astrocytoma
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WHO Gr1 - Pilocytic Astrocytoma
Circumscribed Mass:
Cyst w/Nodule
Pushing Margin
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Circumscribed Astrocytoma
WHO Grade 1
Pilocytic
Astrocytoma
SEGA
Circumscribed Astrocytoma
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ASTROCYTOMA:Circumscribed
• “Special” Astrocytomas• Astrocytoma of Young• Various Locations• Well circumscribed (yet, no capsule)
• Do NOT spread along WM• Do NOT change grade (except PXA)
• Constellation of findings correlates w/ Histology
PILOCYTIC ASTROCYTOMA
Cystic Cerebellar Astrocytoma Juvenile Pilocytic Astrocytoma
(“PA” or “JPA”)
PILOCYTIC ASTROCYTOMA
• Synonyms: Polar Spongioblastoma, Cystic Cerebellar Astrocytoma
• Cell of Origin: Astrocyte (bi-polar, hairlike)• Associations: in ON w/ NF-1• Incidence: 3-6% of ALL Cranial, 32% of Child• Age: 5-15 (Zulch 3-7) Sex: Slight F (11/9)• Location: Cerebellum, Chiasm/Hypothal, Optic• Treatment: Surgery, patience• Prognosis: 77% at 5 yrs, 75% at 10 yrs, 75% at 15 yrs
PILOCYTIC ASTROCYTOMARadiology
• Cerebellum, Diencephalon– rare in BS or Cerebrum
• Majority have significant “cyst”– “Cyst and Mural Nodule”
• part of lining does NOT enhance– Nodule may be heterogeneous– Exceptional purely solid
• Nodule NOT hyperdense• Calcification in 5-25%
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NOT a true cyst - no lining, just gliosis
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WHO Gr1 - Pilocytic Astrocytoma
Circumscribed Mass:
Cyst w/Nodule
Pushing Margin
PATHOLOGY• Biphasic pattern
– dense pilocytic glia– Rosenthal fibers– loose microcystic areas
• No necrosis• Low grade• Abnormal capillaries
– allow enhancement– fluid production
Grading Problems in Gliomas51 Pilocytic (WHO Gr. 1)
KERNOHAN MAYO-ST.ANNE
1 26% 1 2%
2 69% 2 55%
3 6% 3 35%
4 0% 4 8%
By conventional “feature counting” most pilocytic astrocytomas were overgraded.
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Pilocytic Astrocytoma
• Variant Appearance
• Variant Location
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Pilocytic AstrocytomaA Cyst with mural nodule?
Not Always !!!
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Courtesy of Paul Sherman
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USU – Learning to Care for Those in Harm’s WayPILOCYTIC ASTROCYTOMA:
Locations
• CEREBELLUM
• Chiasm And Optic Nerve
• Hypothalmus/thalamus• Cerebral Hemisphere• Spinal Cord (Intramedullary)
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PILOCYTIC ASTROCYTOMA(Juvenile Pilocytic)
• Childhood, Young Adults• Benign, no mitosis/necrosis• Circumscribed - Enhancing• Cyst Formation, Mural Nodule• Cerebellum and Diencephalon
(Optic tracts, Hypothalmus)
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WHO GRADE I
• Circumscribed Astrocytoma– JPA (Pilocytic)– SGCA (Subependymal Giant Cell)
• Ganglioglioma• Meningioma
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Subependymal Giant Cell Astro
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ASTROCYTOMAS
• “SPECIAL” ASTROCYTOMAS– Circumscribed Growth:
• Pilocytic•Subependymal Giant Cell• Pleomorphic Xantho-Astrocytoma
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Circumscribed Astrocytoma
WHO Grade 1 2 3 4
PXA PXA
Circumscribed Astrocytoma
PLEOMORPHIC XANTHOASTROCYTOMA
• Rare Variant of Astrocytoma• Arises from Subpial Astrocytes• Affects Superficial Cerebral Cortex and
Meninges• Skull erosion (scalloped excavation)• Temporal > Frontal > Parietal• WHO Grade 2,3• 50% progress over time
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ASTROCYTOMAS
• “Ordinary” Astrocytoma• Diffuse Infiltration of WM by:
– Fibrillary Astrocytes– Protoplasmic Astrocytes– Gemistocytic Astrocytes
• WHO 2,3,4 (NOT 1)
• KS & Mayo Grades 1-4
Daddy,Where do Glioblastomas
come from?
Normal appearing white matter Normal appearing white matter …… few cell bodiesfew cell bodies
Diffuse Astrocytoma Diffuse Astrocytoma …… too many cells !too many cells ! KERNOHAN (KS) 1 2 3 4
ANAPLASIA 0 Min >1/2 Marked
CELLULARITY Mild Mild Inc Marked
MITOSIS 0 0 Plus Marked
ENDOTHELIAL 0 Min Min MarkedProliferation
NECROSIS Marked
TRANSITION <== Broad Sharp ==>ZONE
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Diffuse High Grade Astrocytoma Diffuse High Grade Astrocytoma …… Cells and Vessels Cells and Vessels KERNOHAN (KS) 1 2 3 4
ANAPLASIA 0 Min >1/2 Marked
CELLULARITY Mild Mild Inc Marked
MITOSIS 0 0 Plus Marked
ENDOTHELIAL 0 Min Min MarkedProliferation
NECROSIS Marked
TRANSITION <== Broad Sharp ==>ZONE
KERNOHAN (KS) 1 2 3 4
ANAPLASIA 0 Min >1/2 Marked
CELLULARITY Mild Mild Inc Marked
MITOSIS 0 0 Plus Marked
ENDOTHELIAL 0 Min Min MarkedProliferation
NECROSIS Marked
TRANSITION <== Broad Sharp ==>ZONE
ASTROCYTOMA:DIFFUSE
(Fibrillary, protoplasmic, etc.)
“Adult type” or “Hemispheric” AstrocytomaDiffusely infiltrate brain, along WM tractsContinuum, from low-grade to high-gradeGenetic Alterations 17 => 9 => 10Many Progress in Histology over time, changing from
WHO Gr. 2 => Gr. 3 => Gr. 4 (GBM)Imaging tends to correlate with histology, especially at
the ends of spectrum
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Astrocyte Mutation
• Normal Astrocyte• Neoplastic• Anaplastic• GBM
Deletions:17 p P5322q NF2
Excess production of:PDGF
Deletions:13q RB19q 10
Excess production of:CDK4
Deletions: 10 PTEN/MMAC19p P16,P15.P14
Excess production of:EGFRVEGF
WHO Gr 2 Gr 3 Gr 4 = GBMNormal
Genetically Heterogeneous
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Diffuse Astrocytoma
WHO GR 2
WHO GR 3
WHO GR 4
Normal
1010
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WHO 4WHO 3WHO 2
AstrocytomaAnaplastic
Astrocytoma
Glioblastoma
Multiforme
A spectrum of tumors
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Dr. Eastwood:
The Good
The Bad
The Ugly
Diffuse Astrocytoma
‘Astrocytoma’
Anaplastic Astrocytoma
Glioblastoma Multiforme
ASTROCYTOMARadiologic Grading
• TYPE 1 - WHO 2, KS Grade 1-2, “Benign”– Homogeneous– No Enhancement, No Vasogenic Edema
• TYPE 2 – WHO Grade 3, Anaplastic– Variable Enhancement, Edema– 50% enhance - 50% don’t
• TYPE 3 – WHO Grade 4 Glioblastoma– Heterogeneous (Necrosis, Blood)– Ring Enhancement, Edema
“BENIGN” ASTROCYTOMA:WHO 2, KS 1-2, Mayo 1
• YOUNGER PATIENT– CHILDHOOD– Young Adults (20’s - 40’s)
• NL VESSELS (NO NEOVASCULARITY)– BBB INTACT– NO EDEMA– NO ENHANCEMENT– NO TUMOR VESSELS
Benign - Diffuse
• HOMOGENEOUS– NO NECROSIS– NO HEMORRHAGE– INCREASED WATER
• DARK and Poorly Demarcated on CT• Dark and Sharp on T1W• BRIGHT and Sharp on T2W
– MICROCYST >>> MACROCYST(macrocysts occur in JPA, etc.)
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Gr 2 Fibrillary Astrocytoma
T2PD
1111
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Gr 2 Fibrillary Astrocytoma
T1-gadT1-non
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Gr 2 Astrocytoma: PWI
Reduced perfusionReduced perfusionADCADC PWIPWI--CBVCBV
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T1-gadT2
Gliomatosis Cerebri
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Gliomatosis Cerebri:Diffuse Astrocytoma – 2 lobes
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Spread along White Matter Tracts
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Gliomatosis Cerebri
1212
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CHO
Cr
NAA ?
Gliomatosis Cerebri
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Thickened Genu
Enlarged Fornix
Blurring of Gray Matter
Infiltration of peduncle
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Astrocytoma: Microcystic change
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Astrocytoma
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MODES OF SPREAD
1. Natural passages
2. Along surfaces
3. Along white matter tracts
4. Across the meninges
SPREAD ALONG TRACTS:
• Corona Radiata• Peduncles• Corpus Callosum• Anterior Commisure• Arcuate Fibres
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Astrocytes Track Along WM
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Pontine Astrocytoma
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Pontine Astrocytoma: WHO 2
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Six Weeks Later
WHO 2 … GBM
1414
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Expanded Brain
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Expanded Brain
Anaplastic Astrocytoma Rad
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Anaplastic Astrocytoma: Overall Characteristics
• Grade III malignant glioma• Less aggressive than GBM, malignant with somewhat
better prognosis• Frequency: highest in young adults (30 – 40 years)• Recurrence: often as a higher-grade glioma• Challenge: difficult to remove completely with surgery• Median survival: 3 – 4 years
Anaplastic AstrocytomaAnaplastic Astrocytoma
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Anaplastic Astrocytoma
1515
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Anaplastic Astrocytoma
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Anaplastic Astrocytoma( WHO 3 )
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Increased Cellularity, +/-minimal vascular changes, no necrosis , no hemorrhage
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GBM - Glioblastoma
“MALIGNANT” ASTROCYTOMA:• Older patient
– 40’s and up– exceptions (PNET)– ~ 1/2 arise from previous low grade (2-3)
• Abnormal Vessels (neovascularity)- BBB abnormality– vasogenic edema– contrast enhancement– irregular vessels, shunting, etc.
• HETEROGENEOUS– hemorrhage (old/new)– tumor necrosis– tumor itself
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Astrocytoma Gr4:
Necrosis !
Angiogenesis
1616
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Glioblastoma Multiforme Rad
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Glioblastoma Multiforme
vascularity
necrosis
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T1-gadT2
Glioblastoma Multiforme
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(Gr 4) Glioblastoma: PWI-CBV
Increased perfusionIncreased perfusion
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Glioblastoma – WHO Grade 4
A solitary, deep, irregular, heterogenous, ring-enhancing mass with vasogenic edema.
Low NAA – High Choline/Creatine
GBM
• Center of Abnl Density/Intensity– variegated necrosis
• ENHANCING RIM– hypercellular, fleshy neoplasm– greatest neovascularity
• Corona of Abnl Density/Intensity– “edematous” white matter– areas of microscopic neoplastic infiltration
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GBM - Glioblastoma
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Pseudopalisading Necrosis
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Ring Lesion and Infiltration GLIOBLASTOMA MULTIFORME(Surrounding Zone of Infiltration)
• GBM arose from a preexisting low grade– surrounding lower grade neoplasm– may also transform over time
• GBM arose de novo– sends cells to invade the brain
1818
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T1-gadT2
Glioblastoma Multiforme
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Courtesy of R.D. Zimmerman, NY
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GBM - Multifocal
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Multifocal GBM
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DWI of Glioblastoma (Gr 4)
Park et al., Neuroradiology 2000;42:716-721
DWIDWIT1T1--gadgad
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Ring Enhancing Mass
•Round
•Smooth
•Thin wall
•Undulating
•Irregular
•Thick wall
Benign Malignant
1919
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Glioblastoma Multiformevs. Abscess (toxo) R
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DWI: Necrosis vs. PUS
GBM Abscess
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meningealcallosal
Glioblastomas: Growth/Spread
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T1-gadT1-gad
Glioblastoma: Ependymal spread
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GBM – Thicker on Surface
2020
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Early Draining Veins
X-Ray Perfusion Imaging
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MR Perfusion Imaging
Courtesy of James Provenzale, Duke UniversityCourtesy of James Provenzale, Duke University
****
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GBM with increased rCBV
Courtesy Mauricio Castillo, Chapel Hill
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New Tools for Grading and Staging• Radiology
– Perfusion Imaging rCBV and rCBF
– Diffusion Imaging, ADC and DTI
– Spectroscopy– PET/SPECT– Monoclonal Ab.
• Pathology– Labeling Index– Chromosome Analysis– Histochemical– Electron Microscopy
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DTI
Loss of Anisotropy
DTI and Tumor Imaging
T2From: J. Burdette and Neeraj Chepuri, WFU
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Astrocytes Track Along WM
Anisotropy:Diffusion (ADC) is different in different directions
2121
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Glioblastoma Multiforme
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Glioblastoma Multiforme
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Two Port Radiotherapy• Bad News
– Can’t define full extent of tumor by any current test
• Good News– 90% of tumor
recurrence within 2cm of enhancing rim
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USU – Learning to Care for Those in Harm’s Way
6/15
7/22Courtesy of R.D. Zimmerman, NY
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hs.m
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hs.m
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USU – Learning to Care for Those in Harm’s Way
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Rad
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rad
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hs.m
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USU – Learning to Care for Those in Harm’s Way
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USU – Learning to Care for Those in Harm’s Way
5 weeks later
Define the Problem:
• Some Low Grade Enhance• Some Low Grade Do Not
• Some Low Grade => GBM• Some Low Grade Do Not
Define the Problem:Answers
• Some Low Grade Enhance *• Some Low Grade Do Not
• Some Low Grade => GBM• Some Low Grade Do Not *
* These are the Circumscribed AstrocytomasThe others are the Diffuse Astrocytomas
Rad
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hs.m
ilUSU – Learning to Care for Those in Harm’s Way
WHO Astrocytoma Summary
Astrocytoma Anaplastic
AstrocytomaGlioblastoma
Multiforme
WHO Grade 1 2 3 4
PXA PXA
Pilocytic
Astrocytoma
SEGA
Circumscribed Astrocytoma
Diffuse
AstrocytomaA spectrum of tumors
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USU – Learning to Care for Those in Harm’s Way
WHO 4WHO 3WHO 2
AstrocytomaAnaplastic
Astrocytoma
Glioblastoma
Multiforme
A spectrum of tumors
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EUXAPIΣTΩ !Mahalo !
Gracias! ObregadoMerci Beaucoup
Danke Shoen
Thank You!