Intraaxial Masses - Astrocytoma - Smirniotopoulos (AFIP 2008)

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Intraaxial Masses:Intraaxial Masses:Approach to AstrocytomaApproach to Astrocytoma

James G. Smirniotopoulos, M.D.James G. Smirniotopoulos, M.D.Uniformed Services UniversityUniformed Services University

of the Health Sciencesof the Health SciencesBethesda, MDBethesda, MD

Visit us at: http://Visit us at: http://rad.usuhs.edurad.usuhs.edu

You are Here!*

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

First StepsFirst Steps

Favor NeoplasmFavor Neoplasm–– PrimaryPrimary

SolitarySolitaryDeepDeepLarge lesions +/Large lesions +/-- vasogenic edemavasogenic edema

–– SecondarySecondaryMultipleMultipleSubcorticalSubcorticalSmall lesion Small lesion –– lots of vasogenic edemalots of vasogenic edema

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Primary vs. SecondaryPrimary vs. Secondary

Remember!45 – 55% of

metastasis present as a solitary lesion –

even on MR

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PRIMARY NEOPLASMSPRIMARY NEOPLASMSNeuroectodermalNeuroectodermal

NeuroectodermNeuroectoderm–– Embryologic Neural TubeEmbryologic Neural Tube–– ““NeuroepithelialNeuroepithelial””Broad CategoriesBroad Categories–– Glial Tumors (Gliomas)Glial Tumors (Gliomas)–– Embryonal/Immature (P.N.E.T.Embryonal/Immature (P.N.E.T.’’s)s)–– Neuronal (Neurocytoma)Neuronal (Neurocytoma)–– Mixed (Ganglioglioma)Mixed (Ganglioglioma)

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WHO 1 vs. WHO 4WHO 1 vs. WHO 4

Courtesy of Paul Sherman Courtesy of R.D. Zimmerman

Define the Problem:Define the Problem:

Some Low Grade EnhanceSome Low Grade EnhanceSome Low Grade Do Not Some Low Grade Do Not

Some Low Grade => GBMSome Low Grade => GBMSome Low Grade Do NotSome Low Grade Do Not

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GRADING SYSTEMSGRADING SYSTEMSModified from Modified from SemSem Rad Onc (1991); 1: 2Rad Onc (1991); 1: 2--99

KernohanKernohan BergerBerger WHO 1993WHO 1993--2007 2007 1 Pilocytic,SEGA

Benign (1) Astrocytoma2 Astrocytoma, PXA

Benign (2)Anaplastic 3 Anaplastic, PXA

Anaplastic (3)

Glioblastoma (4) Glioblastoma 4 Glioblastoma

WHO ClassificationWHO Classification

Defines Histologic SubtypesDefines Histologic SubtypesGrades Biologic PotentialGrades Biologic PotentialAllows International CooperationAllows International CooperationAscending scale of Aggression from 1Ascending scale of Aggression from 1--44

WHO CORRELATIONWHO CORRELATION

Low Grade Low Grade –– GradeGrade 11

–– LongLong--Term SurvivalTerm Survival

–– Stable Histology no progressionStable Histology no progression

Possible Surgical Cure

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Cellularity Cellularity ⇑⇑Mitoses Mitoses ⇑⇑Endothelial proliferation Endothelial proliferation ⇑⇑Metabolism Metabolism ⇑⇑

Blood volume Blood volume ⇑⇑Blood flow Blood flow ⇑⇑MTT MTT ⇓⇓

Choline/CreatineCholine/Creatine ⇑⇑MyoInositolMyoInositol ⇓⇓⇑⇑ Lip/Lac and Lip/Lac and ⇓⇓ NAANAA

Incr

easing

Agg

ress

ion

Perfusion Imaging:

CT, MR, Angio

MR Spectroscopy

PET FDG or Th SPECT

⇑⇑ DWI matching ⇓⇓ ADC

Lesion Aggression and GradingLesion Aggression and Grading

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AstrocytomaAstrocytoma

Astrocytoma

WHO 1Circumscribed

EnhancingFluid secreting

WHO 2-3Infiltrating

Water signalMild to Mod. MassNo enhancement

WHO 3-4Infiltratingand Focal

HeterogeneousMass effect

EnhancementNecrosis

MyoInositol ⇑Perfusion ⇓

PWI ⇑Cho/Cr ⇑FDG ⇑

Lac/Lip ⇑

LocationCyst w/ Nodule

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Astrocytoma

WHO 1Circumscribed


WHO 2-3Infiltrating




EnhancementNecrosis



Lac/Lip ⇑

PilocyticSubependymal GC

33

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Astrocytoma

WHO 1Circumscribed


WHO 2-3Infiltrating




EnhancementNecrosis



Lac/Lip ⇑


““BenignBenign”” ASTROCYTOMAASTROCYTOMA

Two typesTwo types––Low grade Low grade ““benignbenign””

Diffuse in AdultsDiffuse in AdultsWHO Grade 2WHO Grade 2

––Low grade Low grade ““specialspecial””Circumscribed in ChildrenCircumscribed in ChildrenWHO Grade 1WHO Grade 1

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Major ConceptMajor Concept

GliomaAstrocyte

Circumscribed Diffuse

PushingMargin

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InfiltratingMargin

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Major ConceptMajor Concept

GliomaAstrocyte

Circumscribed DiffuseWHO 2 - Astrocytoma

WHO 3 – Anaplastic A.

WHO 4 - Glioblastoma

WHO 1Pilocytic

Subependymal Giant Cell

WHO 2-3Pleomorphic Xantho

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What can we What can we DxDx??

Circumscribed AstrocytomaCircumscribed Astrocytoma–– WHO WHO GrGr 1 Pilocytic Astrocytoma1 Pilocytic Astrocytoma–– WHO WHO GrGr 1 Subependymal Giant Cell 1 Subependymal Giant Cell AstroAstro..–– WHO 2,3 WHO 2,3 PleomorphicPleomorphic XanthoastrocytomaXanthoastrocytoma

Diffuse AstrocytomaDiffuse Astrocytoma–– WHO WHO GrGr 2 (2 (““AstrocytomaAstrocytoma””))–– WHO WHO GrGr 3 (3 (““Anaplastic AstrocytomaAnaplastic Astrocytoma””))–– WHO WHO GrGr 4 (4 (““Glioblastoma MultiformeGlioblastoma Multiforme”” -- GBM)GBM)

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Circumscribed AstrocytomaCircumscribed Astrocytoma

WHO Grade 1

Pilocytic

Astrocytoma

SEGA

Circumscribed Astrocytoma

44

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Astrocytoma

WHO 1Circumscribed


WHO 2-3Infiltrating




EnhancementNecrosis



Lac/Lip ⇑

LocationCyst w/ Nodule

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WHO Gr1 WHO Gr1 -- Pilocytic AstrocytomaPilocytic Astrocytoma

Circumscribed Mass:

Fluid-secreting

Cyst w/Nodule

Pushing Margin

ASTROCYTOMA:ASTROCYTOMA:CircumscribedCircumscribed

““SpecialSpecial”” AstrocytomasAstrocytomasAstrocytoma of YoungAstrocytoma of YoungVarious LocationsVarious LocationsWell circumscribed (yet, no capsule)Well circumscribed (yet, no capsule)

Do NOT spread along WMDo NOT spread along WMDo NOT change grade (except PXA)Do NOT change grade (except PXA)

Constellation of findings correlates w/ HistologyConstellation of findings correlates w/ Histology

PILOCYTIC ASTROCYTOMAPILOCYTIC ASTROCYTOMA

Cystic Cerebellar Astrocytoma Cystic Cerebellar Astrocytoma Juvenile Pilocytic AstrocytomaJuvenile Pilocytic Astrocytoma

((““PAPA”” or or ““JPAJPA””))

PILOCYTIC ASTROCYTOMAPILOCYTIC ASTROCYTOMA

Synonyms: Polar Spongioblastoma, Cystic Cerebellar Synonyms: Polar Spongioblastoma, Cystic Cerebellar AstrocytomaAstrocytomaCell of Origin: Astrocyte (biCell of Origin: Astrocyte (bi--polar, hairlike)polar, hairlike)Associations: in Associations: in ON w/ NFON w/ NF--11Incidence: 3Incidence: 3--6% of ALL Cranial, 32% of Child6% of ALL Cranial, 32% of ChildAge: Age: 55--15 (Zulch 315 (Zulch 3--7)7) Sex: Slight F (11/9)Sex: Slight F (11/9)Location: Cerebellum, Chiasm/Hypothal, OpticLocation: Cerebellum, Chiasm/Hypothal, OpticTreatment: Surgery, patienceTreatment: Surgery, patiencePrognosis: Prognosis: 77% at 5 yrs, 75% at 10 yrs, 75% at 15 yrs77% at 5 yrs, 75% at 10 yrs, 75% at 15 yrs

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Pilocytic AstrocytomaPilocytic Astrocytoma

Cyst and Mural NoduleCyst and Mural Nodule–– balanced morphologybalanced morphology

Wall may not enhanceWall may not enhanceCyst fluid has proteinCyst fluid has protein–– Not identical to CSFNot identical to CSF

Nodule low density on CTNodule low density on CT–– may calcify up to 25%may calcify up to 25%

No increase in vascularityNo increase in vascularityWHO Grade 1WHO Grade 1Peak at ~10 yrsPeak at ~10 yrs

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PILOCYTIC ASTROCYTOMAPILOCYTIC ASTROCYTOMARadiologyRadiology

Cerebellum, DiencephalonCerebellum, Diencephalon–– rare in BS or Cerebrumrare in BS or Cerebrum

Majority have significant Majority have significant ““cystcyst””–– ““Cyst and Mural NoduleCyst and Mural Nodule””

part of lining does NOT enhancepart of lining does NOT enhance

–– Nodule may be heterogeneousNodule may be heterogeneous–– Exceptional purely solidExceptional purely solid

Nodule has increased waterNodule has increased waterCalcification in 5Calcification in 5--25%25%

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“Cyst” Nodule

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Pilocytic AstrocytomaPilocytic AstrocytomaCyst and Mural NoduleCyst and Mural Nodule

–– balanced morphologybalanced morphologyWall may not enhanceWall may not enhanceCyst fluid has proteinCyst fluid has protein–– Not identical to CSFNot identical to CSF

Nodule low density on CTNodule low density on CT–– may calcify up to 25%may calcify up to 25%

No increase in vascularityNo increase in vascularityWHO Grade 1WHO Grade 1Peak at ~10 yrsPeak at ~10 yrs

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““CystCyst”” with Nodulewith Nodule

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WHO Gr1 WHO Gr1 –– Pilocytic Pilocytic AstrocytomaAstrocytoma

Circumscribed Mass:

Cyst w/Nodule

Pushing Margin

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PATHOLOGYPATHOLOGYBiphasic patternBiphasic pattern–– dense pilocytic gliadense pilocytic glia–– Rosenthal fibersRosenthal fibers–– loose microcystic areasloose microcystic areasNo necrosisNo necrosisLow gradeLow gradeAbnormal capillariesAbnormal capillaries–– allow enhancementallow enhancement–– fluid productionfluid production

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Variant AppearanceVariant Appearance

Variant LocationVariant Location

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Pilocytic AstrocytomaPilocytic AstrocytomaA Cyst with mural nodule?

Not Always !!!

Neoplasm + thin rim of enhancing

gliosis

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Courtesy of Paul Sherman


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Courtesy of Paul Sherman

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Atypical:

Dense Ca++, No Cyst, No Enhancement


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PILOCYTIC ASTROCYTOMA:PILOCYTIC ASTROCYTOMA:LocationsLocations

CEREBELLUMCEREBELLUM

Chiasm And Optic NerveChiasm And Optic Nerve

Hypothalmus/thalamusHypothalmus/thalamusCerebral HemisphereCerebral HemisphereSpinal Cord (Intramedullary)Spinal Cord (Intramedullary)

Diencephalon

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PILOCYTIC ASTROCYTOMAPILOCYTIC ASTROCYTOMA(Juvenile Pilocytic)(Juvenile Pilocytic)

Childhood, Young AdultsChildhood, Young AdultsBenign, no mitosis/necrosisBenign, no mitosis/necrosisCircumscribed Circumscribed -- EnhancingEnhancingCyst Formation, Mural NoduleCyst Formation, Mural NoduleCerebellum and DiencephalonCerebellum and Diencephalon(Optic tracts, Hypothalmus)(Optic tracts, Hypothalmus)

WHO GRADE 1 TumorsWHO GRADE 1 Tumors

Circumscribed AstrocytomaCircumscribed Astrocytoma–– JPA (Pilocytic)JPA (Pilocytic)–– SGCA (Subependymal Giant Cell)SGCA (Subependymal Giant Cell)

GangliogliomaGangliogliomaMeningiomaMeningioma

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Subependymal Giant Cell AstroSubependymal Giant Cell Astro

85-95% associated with Tuberous Sclerosis

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ASTROCYTOMASASTROCYTOMAS

““SPECIALSPECIAL”” ASTROCYTOMASASTROCYTOMAS–– Circumscribed Growth:Circumscribed Growth:

PilocyticPilocyticSubependymal Giant CellSubependymal Giant CellPleomorphic XanthoPleomorphic Xantho--AstrocytomaAstrocytoma

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Circumscribed AstrocytomaCircumscribed Astrocytoma

WHO Grade 1 2 3 4

PXA PXA

Circumscribed Astrocytoma

PLEOMORPHIC PLEOMORPHIC XANTHOASTROCYTOMAXANTHOASTROCYTOMA

Rare Variant of AstrocytomaRare Variant of AstrocytomaArises from Arises from Subpial AstrocytesSubpial AstrocytesAffects Superficial Cerebral Cortex and Affects Superficial Cerebral Cortex and MeningesMeningesSkull erosion (scalloped excavation)Skull erosion (scalloped excavation)Temporal > Frontal > ParietalTemporal > Frontal > ParietalWHO Grade 2,3WHO Grade 2,350% progress over time50% progress over time

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Pleomorphic XanthoastrocytomaPleomorphic Xanthoastrocytoma

““OrdinaryOrdinary““ AstrocytomasAstrocytomas

Diffuse Infiltration of WM by:Diffuse Infiltration of WM by:–– Fibrillary AstrocytesFibrillary Astrocytes–– Protoplasmic AstrocytesProtoplasmic Astrocytes–– Gemistocytic AstrocytesGemistocytic Astrocytes

WHO 2,3,4 WHO 2,3,4 (NOT 1)(NOT 1)

KS & Mayo Grades 1KS & Mayo Grades 1--44

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AstrocytesAstrocytes GFAP StainGFAP Stain

99

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USU – Learning to Care for Those in Harm’s WayNormal appearing white matter Normal appearing white matter …… few cell bodiesfew cell bodies

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USU – Learning to Care for Those in Harm’s WayDiffuse Grade 2 Astrocytoma Diffuse Grade 2 Astrocytoma …… too many cells !too many cells !

Infiltrating “Margin”

Diffuse Mass

Non-destructive Infiltration

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Astrocytoma

WHO 1Circumscribed


WHO 2-3Infiltrating

Water signalHomogeneous

Mild Mass effectNo enhancement

No Necrosis



EnhancementNecrosis



Lac/Lip ⇑


Daddy,Daddy,Where do GlioblastomasWhere do Glioblastomas

come from?come from?

Progressive Transformation from lower grade diffuse

astrocytoma

- OR -

Arise de novo

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Astrocyte MutationAstrocyte MutationNormal AstrocyteNormal AstrocyteNeoplasticNeoplasticAnaplasticAnaplasticGBMGBM

Deletions:17 p P5322q NF2

Excessproduction of:PDGF

Deletions:13q RB19q 10

Excessproduction of:CDK4

Deletions: 10 PTEN/MMAC19p P16,P15.P14

Excessproduction of:EGFRVEGF

WHO Gr 2 Gr 3 Gr 4 = GBMNormal

Genetically Heterogeneous

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Diffuse AstrocytomaDiffuse 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 PathologyA spectrum of tumors

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Diffuse Astrocytoma Diffuse Astrocytoma …… too many cells !too many cells !

Mild cellular atypia

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Glioblastoma multiforme … too many cells, Atypia, Mitoses, Vessels, and Necrosis!

ASTROCYTOMAASTROCYTOMARadiologic GradingRadiologic Grading

TYPE 1 TYPE 1 -- WHO 2, KS Grade 1WHO 2, KS Grade 1--2, 2, ““BenignBenign””–– HomogeneousHomogeneous–– No Enhancement, No Vasogenic EdemaNo Enhancement, No Vasogenic Edema

TYPE 2 TYPE 2 –– WHO Grade 3, AnaplasticWHO Grade 3, Anaplastic–– Variable Enhancement, EdemaVariable Enhancement, Edema–– 50% enhance 50% enhance -- 50% don50% don’’tt

TYPE 3 TYPE 3 –– WHO Grade 4 GlioblastomaWHO Grade 4 Glioblastoma–– Heterogeneous (Necrosis, Blood)Heterogeneous (Necrosis, Blood)–– Ring Enhancement, EdemaRing Enhancement, Edema

““BENIGNBENIGN”” ASTROCYTOMA:ASTROCYTOMA:WHO 2, KS 1WHO 2, KS 1--2, Mayo 12, Mayo 1

YOUNGER PATIENTYOUNGER PATIENT–– CHILDHOODCHILDHOOD–– Young Adults (20Young Adults (20’’s s -- 4040’’s)s)

NL VESSELS (NO NEOVASCULARITY)NL VESSELS (NO NEOVASCULARITY)–– BBB INTACTBBB INTACT–– NO EDEMANO EDEMA–– NO ENHANCEMENTNO ENHANCEMENT–– NO TUMOR VESSELS NO TUMOR VESSELS

Benign Benign -- DiffuseDiffuse

HOMOGENEOUSHOMOGENEOUS–– NO NECROSISNO NECROSIS–– NO HEMORRHAGENO HEMORRHAGE–– INCREASED WATERINCREASED WATER

DARK and Poorly Demarcated on CTDARK and Poorly Demarcated on CTDark and Sharp on T1WDark and Sharp on T1WBRIGHT and Sharp on T2WBRIGHT and Sharp on T2W

–– MICROCYST >>> MACROCYSTMICROCYST >>> MACROCYST(macrocysts occur in JPA, etc.)(macrocysts occur in JPA, etc.)

1111

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Gr 2 Fibrillary AstrocytomaGr 2 Fibrillary Astrocytoma

T2PD

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T1-gadT1-non

Gr 2 Fibrillary Astrocytoma Gr 2 Fibrillary Astrocytoma

T2

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T1-gadT2

Gliomatosis CerebriGliomatosis Cerebri

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Astrocytoma: Microcystic changeAstrocytoma: Microcystic change

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Gliomatosis Cerebri:Gliomatosis Cerebri:Diffuse Astrocytoma Diffuse Astrocytoma –– 2 lobes2 lobes R

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Spread along White Matter TractsSpread along White Matter Tracts

1212

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Gliomatosis CerebriGliomatosis Cerebri

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CHO

Cr

NAA ?{Gliomatosis CerebriGliomatosis Cerebri

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MRS for the Complete IdiotMRS for the Complete Idiot

4 3 2 1 ppm

Lactate

Lipid

NAA

CR

Cho

MI Glx

Hunter’s Angle

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MRS MRS –– Hypothetical NeoplasmHypothetical Neoplasm

4 3 2 1 ppm

Lactate

LipidNAA

CR

Cho

MI

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Diffuse AstrocytomaDiffuse Astrocytoma

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1313

SPREAD ALONG WM TRACTS:SPREAD ALONG WM TRACTS:

Corona RadiataCorona RadiataPedunclesPedunclesCorpus CallosumCorpus CallosumAnterior Anterior CommissureCommissureArcuate FibresArcuate Fibres

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Pontine AstrocytomaPontine Astrocytoma

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Pontine Astrocytoma: WHO 2Pontine Astrocytoma: WHO 2

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Six Weeks Later

WHO 2 => GBMWHO 2 => GBM

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Expanded BrainExpanded Brain

Tracking Along WM – Uncinate Fasciculus

Anaplastic AstrocytomaAnaplastic Astrocytoma

1414

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Grade 3: Anaplastic AstrocytomaGrade 3: Anaplastic Astrocytoma

Astrocytoma

WHO 1Circumscribed


WHO 2-3Infiltrating



No Necrosis



EnhancementNecrosis



Lac/Lip ⇑


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Anaplastic Astrocytoma: Anaplastic Astrocytoma: Overall CharacteristicsOverall Characteristics

Grade III malignant gliomaGrade III malignant gliomaLess aggressive than GBM, malignant with Less aggressive than GBM, malignant with somewhat better prognosissomewhat better prognosisFrequency: highest in young adults (30 Frequency: highest in young adults (30 –– 40 40 years)years)Recurrence: often as a higherRecurrence: often as a higher--grade gliomagrade gliomaChallenge: difficult to remove completely with Challenge: difficult to remove completely with surgerysurgeryMedian survival: 3 Median survival: 3 –– 4 years4 years

Anaplastic Astrocytoma: Cells, Vessels, but no necrosisAnaplastic Astrocytoma: Cells, Vessels, but no necrosis

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Enhancement – But no necrosis

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Anaplastic AstrocytomaAnaplastic AstrocytomaNo Enhancement – Abnl MRS R

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1515

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Anaplastic AstrocytomaAnaplastic Astrocytoma( WHO 3 )( WHO 3 )

No Enhancement – Clear Mass Effect

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Increased Cellularity, +/Increased Cellularity, +/-- minimal minimal vascular changes, no necrosis , no vascular changes, no necrosis , no

hemorrhagehemorrhage

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Astrocytoma

WHO 1Circumscribed


WHO 2-3Infiltrating



No Necrosis



EnhancementNecrosis



Lac/Lip ⇑


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GlioblastomaGlioblastoma

““MALIGNANTMALIGNANT”” ASTROCYTOMA:ASTROCYTOMA:Older patientOlder patient–– 4040’’s and ups and up–– exceptions (PNET)exceptions (PNET)–– ~ 1/2 arise from previous low grade (2~ 1/2 arise from previous low grade (2--3)3)

Abnormal Vessels (neovascularity)Abnormal Vessels (neovascularity)-- BBB abnormalityBBB abnormality–– vasogenic edemavasogenic edema–– contrast enhancementcontrast enhancement–– irregular vessels, shunting, etc.irregular vessels, shunting, etc.

HETEROGENEOUSHETEROGENEOUS–– hemorrhage (old/new)hemorrhage (old/new)–– tumor necrosistumor necrosis–– tumor itselftumor itself

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Glioblastoma multiformeGlioblastoma multiforme

1616

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Glioblastoma multiformeGlioblastoma multiforme

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Glioblastoma MultiformeGlioblastoma Multiforme

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Glioblastoma Glioblastoma –– WHO Grade 4WHO Grade 4

A solitary, deep, irregular, heterogenous, ring-enhancing mass with vasogenic edema.

Low NAA – High Choline/Creatine

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T1-gad T2

Glioblastoma MultiformeGlioblastoma Multiforme

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(Gr 4) Glioblastoma: PWI(Gr 4) Glioblastoma: PWI--CBVCBV

Increased perfusionIncreased perfusion

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MR Perfusion ImagingMR Perfusion Imaging

Courtesy of James Provenzale, Duke UniversityCourtesy of James Provenzale, Duke University

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CT PerfusionCT Perfusion

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Early Draining Veins mean Short MTT

XX--Ray Perfusion ImagingRay Perfusion Imaging

Hypervascularity means ⇑ rCBV and ⇑ rCBF

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GBM GBM –– Thicker on SurfaceThicker on Surface

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Two Different Two Different GBMGBM’’ss

GBMGBMCenter of Abnl Center of Abnl Density/IntensityDensity/Intensity–– variegated necrosisvariegated necrosis

ENHANCING RIM– hypercellular, fleshy neoplasm– greatest neovascularityCorona of Corona of AbnlAbnl SignalSignal–– ““edematousedematous”” white matterwhite matter–– areas of microscopic neoplastic areas of microscopic neoplastic

infiltrationinfiltration

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GBM GBM -- GlioblastomaGlioblastoma

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Pseudopalisading NecrosisPseudopalisading Necrosis

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Intraaxial Masses - Astrocytoma - Smirniotopoulos (AFIP 2008)

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Transcript of Intraaxial Masses - Astrocytoma - Smirniotopoulos (AFIP 2008)