1 The WHO 2000 Astrocytoma Classification James G. Smirniotopoulos, M.D. Uniformed Services University of the Health Sciences Bethesda, MD Visit us at: http://rad.usuhs.mil Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way 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). Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way Pathologic – Radiologic Correlation T2 SI, DWI & ADC Cellularity T1 and T2 SI, DTI Infiltration MRS, Th 201 and FDG Labeling Indices T1 and T2 SI Hemorrhage Ring Lesion, MRS, DWI & ADC Necrosis Enhancement, PWI, and Permeability Imaging Endothelial proliferation and Vascularity Radiology Pathology ASTROCYTOMA Five Year Survival 0 20 40 60 80 100 Percent Survival Glioblastoma (IV) Anaplastic (III) Astrocytoma (I-II) Pilocytic
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11
The WHO 2000 Astrocytoma Classification
James G. Smirniotopoulos, M.D.Uniformed Services University
of the Health SciencesBethesda, MD
Visit us at: http://rad.usuhs.mil
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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
• 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:
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
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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.)
• 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
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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
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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)