ReviewofMeningiomaHistopathologyWord格式文档下载.docx
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ReviewofMeningiomaHistopathologyWord格式文档下载.docx
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AbstractandIntroduction
Abstract
Thehistologicalappearanceofameningiomaisanimportantpredictoroftumorbehaviorandisfrequentlyafactorindecisionsconcerningtherapy.TherelationshipbetweenhistologicalfeaturesandprognosisisformalizedingradingschemessuchasthosepublishedbytheWorldHealthOrganization(WHO),mostrecentlyin2007.Althoughthelatesteditionisanimprovementoverpreviousgradingschemes,theWHOschemestillfailstofullyaddressavarietyofimportantissuesregardingtherelationshipbetweenmeningiomahistologicalcharacteristicsandbehavior.Inparticular,routinehistologicalexaminationfailstoidentifythesubsetofGradeItumorsthatbehaveaggressively.Becauseofthis,manyadditionalprognosticmarkersthatrequireimmunohistochemical,cytogenetic,ormoleculartechniquestoevaluateareunderinvestigation.Onlyone,immunohistochemistryfortheproliferationmarker,Ki67(MIB-1),isusedroutinelyandithasonlylimitedutility.Itishopedthatanunderstandingofthegeneticchangesthatunderlietumorprogressionwillimprovehealthcareprofessionals'
abilitytopredictthebehaviorofmeningiomas.
Introduction
Meningiomasareneoplasmsderivedfromarachnoidal(meningothelial)cells.Theselesionscanoccurinpeopleofanyagebutcommonlypresentinmiddleage.Womenaremorelikelytodevelopameningioma,withafemale/maleratioofapproximately2:
1intracraniallyand10:
1inthespine.Mostmeningiomasarebenign("
classic,"
GradeI),well-circumscribed,slow-growing,andcurablebysurgerydependingonlocation.[18]
However,somemeningiomasareclinicallyaggressiveandcanleadtosignificantcomplicationsandevendeath.Many,butnotall,oftheseaggressivetumorsarehistologicalGradeII(atypical)orGradeIII(anaplasticormalignant)tumors.Asof2007,theformerwasreportedtoaccountforbetween4.7and7.2%ofmeningiomas,whereasthelattercomprised1.0to2.8%.[18,30]Theauthorsofsomestudieshavefoundalargerproportion,approximately20%oftheselesions,tohaveaggressivehistologicalfeatures.[32]Interestingly,thefemalepredominanceintheincidenceofmeningiomasdoesnotholdfortheseaggressivetumors.[32]
Twoofthemostimportantfactorsthatdeterminetheprognosisinpatientswithmeningiomasaretheextentoftheresectionandthetumor'
shistologicalgrade.Highergrademeningiomasaremorelikelynottoreceiveagross-totalresection,andevenwhentheydo,theremaystillberecurrence.[7,29]Asanexample,theauthorsofonestudyfoundthatwithin5yearsofresection,12%ofbenignmeningiomasrecurredcomparedwith41%ofGradeIItumors.[32]Onceatumorrecurs,itismorelikelytodosoagain,ultimatelyleadingtoalossoflocalcontrolandrarely,metastasis.[5,8,11]
OneofthemostcommonlyusedclassificationandgradingsystemsformeningiomaswassetforthbytheWHOin2000,andveryrecentlyupdatedin2007.[18,30]Thissystemsummarizesmuchofwhatisknownaboutthefeaturesseenonroutinehistologicalexaminationthatpredictaggressivebehaviorinmeningiomas.The2000versionrepresentedasignificantimprovementoverpreviousgradingschemesandislittlechangedinthe2007version.However,somelimitationsandpitfallsingradingmeningiomasremainandwillbeoutlinedhere.
Becausethelimitsofroutinehistologicalexaminationinpredictingtumorbehaviorhaveperhapsbeenreached,alargenumberofancillarytechniquesareunderevaluation,includingcytogeneticsandtheuseofimmunohistochemicalmarkers.Sofarmostofthesetechniquesremainintheliteratureandhavenotenteredtheroutineworkupforpatientswithmeningiomas.TwoexceptionsincludeimmunohistochemistryfortheproliferationmarkerKi67(MIB-1)andforPR.Neitherofthesemarkershasbeenincorporatedintothe2007WHOgradingschemeformeningiomas,althoughtheirsignificanceiscited.MeasurementofKi67byimmunohistochemistryfortheMIB-1antigenisnotuncommonlyusedasanadditionalwayofevaluatingameningioma'
spotentialforaggressivebehavior.TestingforthepresenceorabsenceofPRsisusedlessoftenbutisofspecialinterestbecausePRantagonistshavebeenusedclinicallytotrytocontrolthegrowthofmeningiomas.
Theissueofmalignantprogressioninmeningiomasatboththegeneticandhistologicallevelsisanareaofactiveresearch.Compellingevidenceforprogressionhasbeendiscoveredatthegeneticlevel,andthelistofgeneticalterationsassociatedwithdifferenttumorgradescontinuestoexpand.Acompletediscussionofthemoleculargeneticsofmeningiomasisbeyondthescopeofthispaper;
however,someofthemoresignificantfindingswillbementioned.
TheWHOClassificationandGradingofMeningiomas
Background:
The1993Version
Inthelate1990sanumberofpublishedgradingsystemsformeningiomaswereinuse.Thismadeitdifficulttocomparedatafromdifferentsources.Furthermore,thedifferentgradingsystemssufferedfromvariousweaknesses,includingvaguenessandsubjectivityofcriteria.[22]
OneofthesegradingsystemswastheWHOclassificationpublishedin1993.[17]Thereweretwocomponentstothisgradingsystem.ThefirstwasaschemebywhichcertainhistologicalfeatureswereassessedtodecideifmeningiomasweretheusualGradeItumorsoriftheywerehighergrade.GradeIImeningiomasweredefinedasthose"
inwhichseveralofthefollowingfeaturesareevident:
frequentmitoses,increasedcellularity,smallcellswithhighnucleus/cytoplasmratiosand/orprominentnucleoli,uninterruptedpatternlessorsheetlikegrowth,andfociofspontaneousorgeographicnecrosis."
Ananaplasticormalignant(GradeIII)meningiomaexhibited"
histologicalfeaturesoffrankmalignancyfarinexcessoftheabnormalitiesnotedinatypicalmeningiomas."
NeededModifications:
TheContributionoftheMayoClinicStudies
Theextremevaguenessandsubjectivityofthecriteriaforatypicalandanaplasticmeningiomasinthisschemeisclear.Howmanyis"
frequent"
?
Howmuchmoreis"
increased"
Exactlyhowmanyis"
several"
InvestigatorsattheMayoClinicpartiallyaddressedtheseproblemsbypublishingtwolargestudieswithtwomaingoals:
clarifyingthesignificanceofbraininvasionanddevelopingobjectivecriteriathatwouldallowreproduciblegradingofmeningiomas.Anumberoftheircriticalfindingswereadoptedinthe2000revisionoftheWHOclassificationofbraintumors.Themeningiomagradingschemerecentlypublishedinthe2007revisionisalmostidenticaltothatproposedbytheMayogroupbasedonthesetwostudies.
DefiningAtypicalMeningiomas
Thefirststudywasaretrospectiveanalysisof581patientswithprimarymeningiomas.[32]Init,theinvestigatorsexaminedthecorrelationbetweennumerousparameters,histologicalandotherwise,andprogression-freesurvival.Indefiningthegradingcriteria,theyincludedonlypatientswithgross-totalresections(463patients).
Thepresenceofmitoticfiguresnumberingfourormoreper10hpfwerehighlypredictiveofrecurrenceandbecameoneofthecriteriaforatypicalmeningioma.Thesecond,independentcriteriontheresearchersfromtheMayoClinicusedwasthepresenceofatleastthreeofthefollowingfourparameters:
"
sheeting"
(Fig.1A),prominentnucleoli(Fig.1B),hypercellularity,andtheformationofsmallcells(Fig.1C).Applyingtheproposedcriteria,81%oftheirmeningiomaswereclassicand15%atypical.Theremaining4%showedbraininvasionandweredealtwithseparately.The5-yearrecurrencerateswere12%forclassictumorsand41%foratypicaltumors.Atypicaltumorswereassociatedwithdecreasedoveralllengthofsurvival;
classicmeningiomaswerenot.
Figure1.
(clickimagetozoom)
PhotomicrographsdemonstratingthreeofthehistologicalcriteriaforatypiaaccordingtotheMayoClinicgradingschemeformeningiomas.A)patternlessarchitectureor"
sheeting;
"
B)prominentnucleoli(arrowindicatesamitoticfigure);
andC)formationofsmallcells.H&
E,originalmagnification×
100(A),×
400(BandC).
PreliminaryFindingsConcerningBrainInvasion
Mostmeningiomashavea"
pushing"
borderwiththebrainanddonotbreachthepia.Ontheotherhand,somemeningiomasexhibitbraininvasioncharacterizedbyanirregularborderbetweenthetumorandbrainwithoutinterveningleptomeninges.Thebrainshowsaglioticresponseandthereisoftenentrapmentofislandsofbrainparenchymawithinthetumor(Fig.2).AtthetimeoftheMayoClinicstudies,braininvasionwasoftenequatedwithmalignancy,irrespectiveoftheotherhistopathologicalfeaturesofthetumor.[32]
Figure2.
Immunohistochemicalstainingforglialfibrillaryacidicproteindemonstratingmeningiomawithbraininvasion.Thebrainparenchymastainspositive(brown)forthisprotein,andthemeningiomastainsnegative(purple),highlightingtheextensiveinterminglingofthetwotissues.Streptavidin–biotin,magnification×
200.
InthefirstMayoClinicstudy,braininvasionwasapowerfulpredictorofshorterrecurrence-freesurvival.[32]Ofbraininvasivetumorsintheirstudy,43%hadclassichistologicalcharacteristicsand57%wereatypical.Therecurrencerateofinvasivetumors,whetherotherwisebenignoratypical,wasnotstatisticallydifferentfromthatofnoninvasiveatypicaltumors.Howeve
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