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The WHO 2000 Astrocytoma Classification

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The WHO 2000 Astrocytoma Classification The WHO 2000 Astrocytoma Classification Document Transcript

  • USU – Learning to Care for Those in Harm’s Way Features of Glioma The WHO 2000 Astrocytoma Radiology - http://rad.usuhs.mil Classification • Site of Origin • Character of lesion – Signal intensity (MR) – Attenuation (CT) James G. Smirniotopoulos, M.D. – Blood-brain-barrier (Gd or I) Uniformed Services University – Chemistry (MRS) – Metabolism (Th 201, FDG-PET) of the Health Sciences – Vascularity (PWI) Bethesda, MD • Mode of Spread – DTI Visit us at: http://rad.usuhs.mil Kernohan-Sayre (AFIP) Traditional Tumor Grading Grading System: • PATHOLOGIST • GRADE I- “BENIGN” or “Low-Grade” – LOW GRADE • GRADE II - “ “ – HIGH GRADE • GRADE III - ANAPLASTIC • RADIOLOGIST – cellular atypia, etc. – NON-ENHANCING • GRADE IV- MALIGNANT – ENHANCING – NECROSIS, Vascularity, Mitoses • NEUROSURGEON – GLIOBLASTOMA MULTIFORME – “SUCKABLE” – “NON-SUCKABLE” • NOTE: Numerous modifications exist, most into three grades, e.g..: Low Grade (Benign), Anaplastic, and GBM (w/ NECROSIS). USU – Learning to Care for Those in Harm’s Way Pathologic – Radiologic ASTROCYTOMA Correlation Five Year Survival Pathology RadiologyRadiology - http://rad.usuhs.mil Cellularity T2 SI, DWI & ADC Glioblastoma (IV) Endothelial proliferation Enhancement, PWI, and Anaplastic (III) and Vascularity Permeability Imaging Necrosis Ring Lesion, MRS, DWI Astrocytoma (I-II) & ADC Hemorrhage T1 and T2 SI Pilocytic Labeling Indices MRS, Th 201 and FDG 0 20 40 60 80 100 Infiltration T1 and T2 SI, DTI Percent Survival 1
  • GRADING SYSTEMS Define the Problem: Sem Rad Onc (1991); 1: 2-9 • Some Low Grade EnhanceKernohan Berger WHO 1993 1 Pilocytic,SEGA • Some Low Grade Do NotBenign (1) Astrocytoma 2 AstrocytomaBenign (2) Anaplastic 3 Anaplastic • Some Low Grade => GBMAnaplastic (3) • Some Low Grade Do NotGlioblastoma (4) Glioblastoma 4 Glioblastoma WHO CORRELATION WHO Classification • Low Grade • Defines Histologic Subtypes • Grades Biologic Potential – Long-Term Survival • Allows International Cooperation Possible • Ascending scale of Aggression from 1-4 Cure – Stable Histology no progression WHO Grading CNS Tumors CNS NEOPLASM-GLIAL Prognostic FactorsGRADE 1 JPA SGCA GANG MENING Location AgeGRADE 2 PXA HPCGRADE 3 PXA ANAPLASTIC HPC HistologyGRADE 4 GBM 2
  • Normal appearing white matter … few cell bodies “BENIGN” ASTROCYTOMA • Two types: – Low grade (“benign”) Diffuse (Adults) – Low grade “special” Circumscribed (Children) USU – Learning to Care for Those in Harm’s Way Diffuse Low Grade Astrocytoma … too many cells ! WHO Gr1 - Pilocytic Astrocytoma Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way WHO Gr1 - Pilocytic Circumscribed Astrocytoma AstrocytomaRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Pilocytic Circumscribed Astrocytoma Astrocytoma SEGA Pushing Margin WHO Grade 1 Circumscribed Mass: Cyst w/Nodule 3
  • ASTROCYTOMA: Circumscribed • “Special” Astrocytomas PILOCYTIC ASTROCYTOMA • Astrocytoma of Young • Various Locations • Well circumscribed (yet, no capsule) Cystic Cerebellar Astrocytoma Juvenile Pilocytic Astrocytoma • Do NOT spread along WM (“PA” or “JPA”) • Do NOT change grade (except PXA) • Constellation of findings correlates w/ Histology PILOCYTIC ASTROCYTOMA PILOCYTIC ASTROCYTOMA Radiology • Synonyms: Polar Spongioblastoma, Cystic Cerebellar • Cerebellum, Diencephalon Astrocytoma • Cell of Origin: Astrocyte (bi-polar, hairlike) – rare in BS or Cerebrum • Associations: in ON w/ NF-1 • Majority have significant “cyst” • Incidence: 3-6% of ALL Cranial, 32% of Child – “Cyst and Mural Nodule” • Age: 5-15 (Zulch 3-7) Sex: Slight F (11/9) • Location: Cerebellum, Chiasm/Hypothal, Optic • part of lining does NOT enhance • Treatment: Surgery, patience – Nodule may be heterogeneous • Prognosis: 77% at 5 yrs, 75% at 10 yrs, 75% at 15 yrs – Exceptional purely solid • Nodule NOT hyperdense • Calcification in 5-25% USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s WayRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil 4
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s WayRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil NOT a true cyst - no lining, just gliosis USU – Learning to Care for Those in Harm’s Way WHO Gr1 - Pilocytic PATHOLOGY Astrocytoma • Biphasic patternRadiology - http://rad.usuhs.mil – dense pilocytic glia – Rosenthal fibers – loose microcystic areas • No necrosis Pushing Margin • Low grade • Abnormal capillaries Circumscribed Mass: – allow enhancement Cyst w/Nodule – fluid production USU – Learning to Care for Those in Harm’s Way Grading Problems in Gliomas Pilocytic Astrocytoma 51 Pilocytic (WHO Gr. 1) Radiology - http://rad.usuhs.mil KERNOHAN MAYO-ST.ANNE • Variant Appearance 1 26% 1 2% • Variant Location 2 69% 2 55% 3 6% 3 35% 4 0% 4 8% By conventional “feature counting” most pilocytic astrocytomas were overgraded. 5
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Pilocytic Astrocytoma A Cyst with mural nodule?Radiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Not Always !!! Courtesy of Paul Sherman USU – Learning to Care for Those in Harm’s Way PILOCYTIC ASTROCYTOMA: LocationsRadiology - http://rad.usuhs.mil • CEREBELLUM • Chiasm And Optic Nerve • Hypothalmus/thalamus • Cerebral Hemisphere • Spinal Cord (Intramedullary) USU – Learning to Care for Those in Harm’s Way PILOCYTIC ASTROCYTOMA (Juvenile Pilocytic)Radiology - http://rad.usuhs.mil • Childhood, Young Adults • Benign, no mitosis/necrosis • Circumscribed - Enhancing • Cyst Formation, Mural Nodule • Cerebellum and Diencephalon (Optic tracts, Hypothalmus) 6
  • USU – Learning to Care for Those in Harm’s Way WHO GRADE I Subependymal Giant Cell Astro Radiology - http://rad.usuhs.mil • Circumscribed Astrocytoma – JPA (Pilocytic) – SGCA (Subependymal Giant Cell) • Ganglioglioma • Meningioma USU – Learning to Care for Those in Harm’s Way ASTROCYTOMASRadiology - http://rad.usuhs.mil • “SPECIAL” ASTROCYTOMAS – Circumscribed Growth: • Pilocytic • Subependymal Giant Cell • Pleomorphic Xantho-Astrocytoma USU – Learning to Care for Those in Harm’s Way PLEOMORPHIC Circumscribed Astrocytoma XANTHOASTROCYTOMARadiology - http://rad.usuhs.mil Circumscribed • Rare Variant of Astrocytoma Astrocytoma • Arises from Subpial Astrocytes PXA PXA • Affects Superficial Cerebral Cortex and Meninges WHO Grade 1 2 3 4 • Skull erosion (scalloped excavation) • Temporal > Frontal > Parietal • WHO Grade 2,3 • 50% progress over time 7
  • USU – Learning to Care for Those in Harm’s Way ASTROCYTOMASRadiology - http://rad.usuhs.mil • “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 <== Broad Sharp ==> ZONE 8
  • Diffuse High Grade Astrocytoma … 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 Marked Proliferation NECROSIS Marked TRANSITION <== Broad Sharp ==> ZONE KERNOHAN (KS) 1 2 3 4 ASTROCYTOMA: ANAPLASIA 0 Min >1/2 Marked DIFFUSE (Fibrillary, protoplasmic, etc.) CELLULARITY Mild Mild Inc Marked “Adult type” or “Hemispheric” Astrocytoma MITOSIS 0 0 Plus Marked Diffusely infiltrate brain, along WM tracts ENDOTHELIAL 0 Min Min Marked Continuum, from low-grade to high-grade Proliferation Genetic Alterations 17 => 9 => 10 Many Progress in Histology over time, changing from NECROSIS Marked WHO Gr. 2 => Gr. 3 => Gr. 4 (GBM) Imaging tends to correlate with histology, especially at TRANSITION <== Broad Sharp ==> the ends of spectrum ZONE USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Astrocyte Mutation Diffuse AstrocytomaRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil • Normal Astrocyte WHO GR 4 • Neoplastic Genetically Heterogeneous • Anaplastic WHO GR 3 • GBM Normal WHO Gr 2 Gr 3 Gr 4 = GBM WHO GR 2 Deletions: Deletions: Deletions: 17 p P53 13q RB 10 PTEN/MMAC1 Normal 22q NF2 19q 9p P16,P15.P14 10 Excess Excess Excess production of: production of: production of: PDGF CDK4 EGFR VEGF 9
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way A spectrum of tumors Diffuse Astrocytoma ‘Astrocytoma’Radiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Anaplastic Astrocytoma Glioblastoma Multiforme Anaplastic Glioblastoma Astrocytoma Astrocytoma Multiforme Dr. Eastwood: WHO 2 WHO 3 WHO 4 The Good The Bad The Ugly ASTROCYTOMA “BENIGN” ASTROCYTOMA: Radiologic Grading WHO 2, KS 1-2, Mayo 1 • TYPE 1 - WHO 2, KS Grade 1-2, “Benign” • YOUNGER PATIENT – Homogeneous – No Enhancement, No Vasogenic Edema – CHILDHOOD – Young Adults (20’s - 40’s) • TYPE 2 – WHO Grade 3, Anaplastic – Variable Enhancement, Edema • NL VESSELS (NO NEOVASCULARITY) – 50% enhance - 50% don’t – BBB INTACT – NO EDEMA • TYPE 3 – WHO Grade 4 Glioblastoma – NO ENHANCEMENT – Heterogeneous (Necrosis, Blood) – NO TUMOR VESSELS – Ring Enhancement, Edema USU – Learning to Care for Those in Harm’s Way Gr 2 Fibrillary Astrocytoma Benign - Diffuse Radiology - http://rad.usuhs.mil • 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.) PD T2 10
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Gr 2 Fibrillary Astrocytoma Gr 2 Astrocytoma: PWIRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil ADC PWI-CBV PWI- T1-non T1-gad Reduced perfusion USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Gliomatosis Cerebri Gliomatosis Cerebri: Diffuse Astrocytoma – 2 lobesRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil T2 T1-gad USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Spread along White Matter Tracts Gliomatosis CerebriRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil 11
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Gliomatosis CerebriRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil CHO Cr NAA ? { USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Astrocytoma: Microcystic change Thickened GenuRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Enlarged Fornix Blurring of Gray Matter Infiltration of peduncle USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way AstrocytomaRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil 12
  • MODES OF SPREAD SPREAD ALONG TRACTS: 1. Natural passages • Corona Radiata • Peduncles 2. Along surfaces • Corpus Callosum • Anterior Commisure 3. Along white matter tracts • Arcuate Fibres 4. Across the meninges USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Astrocytes Track Along WM Pontine AstrocytomaRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Pontine Astrocytoma: WHO 2 WHO 2 … GBMRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Six Weeks Later 13
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Expanded Brain Expanded BrainRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way Anaplastic Astrocytoma: Anaplastic Astrocytoma Overall Characteristics Radiology - http://rad.usuhs.mil • 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 USU – Learning to Care for Those in Harm’s Way Anaplastic Astrocytoma Anaplastic Astrocytoma Radiology - http://rad.usuhs.mil 14
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Anaplastic Astrocytoma Anaplastic Astrocytoma ( WHO 3 )Radiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Increased Cellularity, +/- GBM - Glioblastoma minimal vascular changes, noRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil necrosis , no hemorrhage “MALIGNANT” ASTROCYTOMA: USU – Learning to Care for Those in Harm’s Way • Older patient Astrocytoma Gr4: Angiogenesis – 40’s and up Radiology - http://rad.usuhs.mil – exceptions (PNET) – ~ 1/2 arise from previous low grade (2-3) • Abnormal Vessels (neovascularity) - BBB abnormality – vasogenic edema Necrosis ! – contrast enhancement – irregular vessels, shunting, etc. • HETEROGENEOUS – hemorrhage (old/new) – tumor necrosis – tumor itself 15
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Glioblastoma Multiforme Glioblastoma MultiformeRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil vascularity necrosis USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Glioblastoma Multiforme (Gr 4) Glioblastoma: PWI-CBVRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil T2 T1-gad Increased perfusion USU – Learning to Care for Those in Harm’s Way Glioblastoma – WHO Grade 4 GBMRadiology - http://rad.usuhs.mil • Center of Abnl Density/Intensity – variegated necrosis • ENHANCING RIM – hypercellular, fleshy neoplasm – greatest neovascularity • Corona of Abnl Density/Intensity A solitary, deep, irregular, heterogenous, ring- – “edematous” white matter enhancing mass with vasogenic edema. – areas of microscopic neoplastic infiltration Low NAA – High Choline/Creatine 16
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way GBM - GlioblastomaRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Pseudopalisading NecrosisRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil GLIOBLASTOMA MULTIFORME Ring Lesion and Infiltration (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
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Glioblastoma MultiformeRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Courtesy of R.D. Zimmerman, NY T2 T1-gad USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way GBM - Multifocal Multifocal GBMRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way DWI of Glioblastoma (Gr 4) Ring Enhancing MassRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Benign Malignant •Round •Undulating •Smooth •Irregular T1-gad T1- DWI •Thin wall •Thick wall Park et al., Neuroradiology 2000;42:716-721 18
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Glioblastoma Multiforme DWI: Necrosis vs. PUS vs. Abscess (toxo)Radiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil GBM Abscess USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Glioblastomas: Growth/Spread Glioblastoma: Ependymal spreadRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil callosal meningeal T1-gad T1-gad USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way GBM – Thicker on SurfaceRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil 19
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way X-Ray Perfusion Imaging MR Perfusion ImagingRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil * * Early Draining Veins Courtesy of James Provenzale, Duke University USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way New Tools for Grading and Staging • Radiology • PathologyRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil – Perfusion Imaging – Labeling Index rCBV and rCBF – Chromosome Analysis – Diffusion Imaging, – Histochemical ADC and DTI – Electron Microscopy – Spectroscopy – PET/SPECT – Monoclonal Ab. GBM with increased rCBV Courtesy Mauricio Castillo, Chapel Hill USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way DTI and Tumor Imaging Astrocytes Track Along WMRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Loss of Anisotropy Anisotropy: Diffusion (ADC) is different in T2 DTI different From: J. Burdette and Neeraj Chepuri, WFU directions 20
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Glioblastoma Multiforme Glioblastoma MultiformeRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way Two Port RadiotherapyRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil • Bad News – Can’t define full extent of tumor by any current test 6/15 • Good News – 90% of tumor recurrence within 2cm of enhancing rim Courtesy of R.D. Zimmerman, NY 7/22 USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s WayRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil 21
  • USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way 5 weeks laterRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Define the Problem: Define the Problem: Answers • Some Low Grade Enhance • Some Low Grade Enhance * • Some Low Grade Do Not • Some Low Grade Do Not • Some Low Grade => GBM • Some Low Grade => GBM • Some Low Grade Do Not * • Some Low Grade Do Not * These are the Circumscribed Astrocytomas The others are the Diffuse Astrocytomas USU – Learning to Care for Those in Harm’s Way USU – Learning to Care for Those in Harm’s Way WHO Astrocytoma Summary A spectrum of tumorsRadiology - http://rad.usuhs.mil Radiology - http://rad.usuhs.mil Pilocytic Circumscribed Astrocytoma Astrocytoma SEGA PXA PXA Anaplastic Glioblastoma Astrocytoma WHO Grade 1 2 3 4 Astrocytoma Multiforme WHO 2 WHO 3 WHO 4 Astrocytoma Anaplastic Glioblastoma Diffuse Astrocytoma Multiforme Astrocytoma A spectrum of tumors 22
  • EUXAPIΣTΩ ! Mahalo ! Thank You!Gracias! Obregado Merci Beaucoup Danke Shoen 23