Intraaxial Neoplasms - Radiology - Uniformed Services University of ...

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 

USU – Learning to Care for Those in Harm’s Way 

Features of Glioma 

Radiology - http://rad.usuhs.mil 

• 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). 


Pathologic – Radiologic 

Correlation 


Pathology 

Cellularity 

Endothelial proliferation 

and Vascularity 

Necrosis 

Hemorrhage 

Labeling Indices 

Infiltration 

Radiology 

T2 SI, DWI & ADC 

Enhancement, PWI, and 

Permeability Imaging 

Ring Lesion, MRS, DWI 

& ADC 

T1 and T2 SI 

MRS, Th 201 and FDG 

T1 and T2 SI, DTI 

ASTROCYTOMA 

Five Year Survival 

Glioblastoma (IV) 

Anaplastic (III) 

Astrocytoma (I-II) 

Pilocytic 

0 20 40 60 80 100 

Percent Survival 

1

GRADING SYSTEMS 

Sem Rad Onc (1991); 1: 2-9 

Kernohan Berger WHO 1993 

1 Pilocytic,SEGA 

Benign (1) 

Astrocytoma 

2 Astrocytoma 

Benign (2) 

Anaplastic 

3 Anaplastic 

Anaplastic (3) 

Define the Problem: 

• Some Low Grade Enhance 

• Some Low Grade Do Not 

• Some Low Grade => GBM 


Glioblastoma (4) Glioblastoma 4 Glioblastoma 

WHO CORRELATION 

WHO Classification 

• Defines Histologic Subtypes 

• Grades Biologic Potential 

• Allows International Cooperation 

• Ascending scale of Aggression from 1-4 

• Low Grade 

– Long-Term Survival 

– Stable Histology no progression 

Possible 

Cure 

WHO Grading CNS Tumors 

CNS NEOPLASM-GLIAL 

Prognostic Factors 

GRADE 1 JPA SGCA GANG MENING 

GRADE 2 PXA HPC 

GRADE 3 PXA ANAPLASTIC HPC 

Location 

Histology 

Age 

GRADE 4 

GBM 

2

“BENIGN” ASTROCYTOMA 

Normal appearing white matter … few cell bodies 

• Two types: 

– Low grade (“benign”) 

Diffuse (Adults) 

– Low grade “special” 

Circumscribed (Children) 

Diffuse Low Grade Astrocytoma … too many cells ! 


WHO Gr1 - Pilocytic 

Astrocytoma 




Astrocytoma 


Circumscribed Mass: 

Cyst w/Nodule 

Pushing Margin 


Circumscribed Astrocytoma 


Pilocytic 

Astrocytoma 

SEGA 

WHO Grade 1 

Circumscribed 

Astrocytoma 

3

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) 

PILOCYTIC ASTROCYTOMA 

Cystic Cerebellar Astrocytoma 

Juvenile Pilocytic Astrocytoma 

(“PA” or “JPA”) 

• Constellation of findings correlates w/ Histology 


• 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 


Radiology 

• 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% 





4





NOT a true cyst - no lining, just gliosis 



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 Gliomas 

51 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. 


Pilocytic Astrocytoma 


• Variant Appearance 

• Variant Location 

5


Pilocytic Astrocytoma 


Not Always !!! 

A Cyst with mural nodule 



Courtesy of Paul Sherman 



PILOCYTIC ASTROCYTOMA: 

Locations 

• CEREBELLUM 

• Chiasm And Optic Nerve 

• Hypothalmus/thalamus 

• Cerebral Hemisphere 

• Spinal Cord (Intramedullary) 




(Juvenile Pilocytic) 

• Childhood, Young Adults 

• Benign, no mitosis/necrosis 

• Circumscribed - Enhancing 

• Cyst Formation, Mural Nodule 

• Cerebellum and Diencephalon 

(Optic tracts, Hypothalmus) 

6

WHO GRADE I 

• Circumscribed Astrocytoma 

– JPA (Pilocytic) 

– SGCA (Subependymal Giant Cell) 

• Ganglioglioma 

• Meningioma 


Subependymal Giant Cell Astro 



ASTROCYTOMAS 


• “SPECIAL” ASTROCYTOMAS 

– Circumscribed Growth: 

• Pilocytic 

• Subependymal Giant Cell 

• Pleomorphic Xantho-Astrocytoma 


Circumscribed Astrocytoma 


Circumscribed 

Astrocytoma 

PXA 

PXA 

WHO Grade 1 2 3 4 

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 

7


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 

Normal appearing white matter … few cell bodies 

Daddy, 

Where do Glioblastomas 

come from 

Diffuse Astrocytoma … 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 Marked 

Proliferation 

NECROSIS 

Marked 

TRANSITION 

ZONE 

8

Diffuse High Grade Astrocytoma … Cells and Vessels KERNOHAN (KS) 1 2 3 4 





Proliferation 

NECROSIS 

Marked 

TRANSITION 

ZONE 

KERNOHAN (KS) 1 2 3 4 





Proliferation 

NECROSIS 

Marked 

TRANSITION 

ZONE 

ASTROCYTOMA: 

DIFFUSE 

(Fibrillary, protoplasmic, etc.) 

“Adult type” or “Hemispheric” Astrocytoma 

Diffusely infiltrate brain, along WM tracts 

Continuum, from low-grade to high-grade 

Genetic Alterations 17 => 9 => 10 

Many 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 


Astrocyte Mutation 


Diffuse Astrocytoma 


• Normal Astrocyte 

• Neoplastic 

• Anaplastic 

• GBM 

Normal WHO Gr 2 Gr 3 Gr 4 = GBM 

Deletions: 

17 p P53 

22q NF2 

Excess 

production of: 

PDGF 

Deletions: 

13q RB 

19q 

10 

Excess 


CDK4 

Deletions: 

10 PTEN/MMAC1 

9p P16,P15.P14 

Excess 


EGFR 

VEGF 

Genetically Heterogeneous 


WHO GR 4 

WHO GR 3 

WHO GR 2 

Normal 

9


A spectrum of tumors 


Astrocytoma 

Anaplastic Glioblastoma 

Astrocytoma Multiforme 

WHO 2 WHO 3 WHO 4 


Diffuse Astrocytoma 


‘Astrocytoma’ 

Anaplastic Astrocytoma 

Glioblastoma Multiforme 

Dr. Eastwood: 

The Good 

The Bad 

The Ugly 

ASTROCYTOMA 

Radiologic 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.) 


Gr 2 Fibrillary Astrocytoma 


PD 

T2 

10


Gr 2 Fibrillary Astrocytoma 


Gr 2 Astrocytoma: PWI 


T1-non 

T1-gad 


ADC 

PWI-CBV 

Reduced perfusion 



Gliomatosis Cerebri 


Gliomatosis Cerebri: 

Diffuse Astrocytoma – 2 lobes 


T2 

T1-gad 


Spread along White Matter Tracts 





11





CHO 

Cr 

NAA 

{ 




Thickened Genu 

Enlarged Fornix 

Blurring of Gray 

Matter 

Infiltration of peduncle 


Astrocytoma: Microcystic change 



Astrocytoma 




12

MODES OF SPREAD 

SPREAD ALONG TRACTS: 

1. Natural passages 

2. Along surfaces 

3. Along white matter tracts 

• Corona Radiata 

• Peduncles 

• Corpus Callosum 

• Anterior Commisure 

• Arcuate Fibres 

4. Across the meninges 


Astrocytes Track Along WM 


Pontine Astrocytoma 




Pontine Astrocytoma: WHO 2 


WHO 2 … GBM 



Six Weeks Later 

13


Expanded Brain 


Expanded Brain 






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 





14







( WHO 3 ) 


Increased Cellularity, +/- 

minimal vascular changes, no 

necrosis , no hemorrhage 



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 



Astrocytoma Gr4: Angiogenesis 

Necrosis ! 

15






vascularity 


necrosis 




(Gr 4) Glioblastoma: PWI-CBV 



T2 

T1-gad 

Increased perfusion 


Glioblastoma – WHO Grade 4 

GBM 


A solitary, deep, irregular, heterogenous, ringenhancing 

mass with vasogenic edema. 

• 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 

Low NAA – High Choline/Creatine 

16



GBM - Glioblastoma 




Pseudopalisading Necrosis 




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 

17






T2 

T1-gad 

Courtesy of R.D. Zimmerman, NY 


GBM - Multifocal 


Multifocal GBM 




DWI of Glioblastoma (Gr 4) 


Ring Enhancing Mass 


T1-gad 

DWI 


Benign 

•Round 

•Smooth 

•Thin wall 

Malignant 

•Undulating 

•Irregular 

•Thick wall 

Park et al., Neuroradiology 2000;42:716-721 

18



vs. Abscess (toxo) 



DWI: Necrosis vs. PUS 


GBM 

Abscess 


Glioblastomas: Growth/Spread 


Glioblastoma: Ependymal spread 



callosal 

meningeal 

T1-gad 

T1-gad 



GBM – Thicker on Surface 



19


X-Ray Perfusion Imaging 


MR Perfusion Imaging 


Early Draining Veins 


* 

* 

Courtesy of James Provenzale, Duke University 



New Tools for Grading and Staging 


GBM with increased rCBV 


• Radiology 

– Perfusion Imaging 

rCBV and rCBF 

– Diffusion Imaging, 

ADC and DTI 

– Spectroscopy 

– PET/SPECT 

– Monoclonal Ab. 

• Pathology 

– Labeling Index 

– Chromosome Analysis 

– Histochemical 

– Electron Microscopy 

Courtesy Mauricio Castillo, Chapel Hill 


DTI and Tumor Imaging 


Astrocytes Track Along WM 


Loss of Anisotropy 

T2 

DTI 

From: J. Burdette and Neeraj Chepuri, WFU 


Anisotropy: 

Diffusion (ADC) is 

different in 

different 

directions 

20








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 


6/15 

Courtesy of R.D. Zimmerman, NY 

7/22 





21



5 weeks later 




• Some Low Grade Enhance 





Answers 

• Some Low Grade Enhance * 



• Some Low Grade Do Not * 

* These are the Circumscribed Astrocytomas 

The others are the Diffuse Astrocytomas 


WHO Astrocytoma Summary 




Pilocytic 

Astrocytoma 

SEGA 

Circumscribed 

Astrocytoma 

PXA 

PXA 

WHO Grade 1 2 3 4 

Astrocytoma Anaplastic 

Diffuse 

Astrocytoma Glioblastoma 

Multiforme 

Astrocytoma 



Astrocytoma 

WHO 2 

Anaplastic 

Astrocytoma 

WHO 3 

Glioblastoma 

Multiforme 

WHO 4 

22

EUXAPIΣTΩ ! 

Mahalo ! 

Thank You! 

Gracias! Obregado 

Merci Beaucoup 

Danke Shoen 

23

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