breast fine needle aspiration cytology practices and commonly perceived diagnostic significance of...

24/08/2015 Breastfineneedleaspirationcytologypracticesandcommonlyperceiveddiagnosticsignificanceofcytologicalfeatures:ApanIndiasurvey

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3480767/?report=printable 1/13

JCytol.2012JulSep29(3):183189.doi:10.4103/09709371.101168

PMCID:PMC3480767

Breastfineneedleaspirationcytologypracticesandcommonlyperceiveddiagnosticsignificanceofcytologicalfeatures:ApanIndiasurveyHrushikeshTukaramGarud, DebdootSheet, ManjunathaMahadevappa, JyotirmoyChatterjee, AjoyKumarRay,andArindamGhosh

SchoolofMedicalScienceandTechnology,IndianInstituteofTechnologyKharagpur,Kharagpur,IndiaVideoSignalProcessing,TexasInstruments(India)Pvt.Ltd.,Bangalore,IndiaDepartmentofElectronicsandElectricalCommunicationEngineering,IndianInstituteofTechnology,Kharagpur,IndiaBengalEngineeringandScienceUniversity,Shibpur,Howrah,IndiaDepartmentofPathologySubDivisionalHospital,Kharagpur,India

Addressforcorrespondence:Mr.HrushikeshGarud,SchoolofMedicalScienceandTechnology,IndianInstituteofTechnologyKharagpur,Kharagpur721302,India.Email:[email protected]

Copyright:JournalofCytology

ThisisanopenaccessarticledistributedunderthetermsoftheCreativeCommonsAttributionNoncommercialShareAlike3.0Unported,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.

Abstract

Background:

Methodicalandmeticulousunderstandingofclinicopathologicalproceduresanddecisionmakingprocessofcancerdiagnosisandidentificationofaspectsthatarewellsuitedforcomputeraidedanalysisarefirststepstowarddevelopmentofassistivecomputationaltoolforanalysisofbreastfineneedleaspirationcytology(FNAC)slides.

Aims:

ToidentifyvariablesinpracticeofFNACasusedfordiagnosisofbreastlesionsandcommonlyperceiveddiagnosticsignificanceofcytologicalfeaturesfordiagnosisofbenignormalignantconditionofbreastlesions.

MaterialsandMethods:

AnIndiawidequestionnairebasedsurveyofcytopathologists/pathologistsbreastFNACreportingpracticesandtheiropinionondiagnosticsignificanceofcytologicalfeaturesindiagnosisofbenignormalignantnatureofbreastlesionwereconducted.

Results:

Fiftyoneexpertsworkingwithvariousmedicaleducationinstitutes(~52%ofparticipants),oncologicaltertiarycarecenters(~28%)andprimarycarecenters/privatediagnosticpathologylaboratories(~20%)spreadover13statesofIndiahaveparticipatedinthesurvey.Constantsandvariablesobservedinclinicocytopathologicalpracticesandcombinedopinionoftheparticipantsondiagnosticsignificanceofcytologicalfeaturesarepresentedhere.

Conclusions:

1,2 1 1 1 3,45

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Thereexistanalogousaswellasvariedcomponentsinclinicopathologicalproceduresanddiagnosticinterpretationbyindividuals.TheseconstantsandvariablesinthepracticeofbreastFNACshouldbeconsidered,whendrawingupspecificationsforanassistivecomputationaltoolforanalysisofbreastFNACslides.TheestimateforcommonlyperceivedsignificanceofcytologicalfeaturesobtainedthroughthisstudywillhelpintheirselectionforcomputeraidedanalysisofbreastFNACslidesandfurtherinselectionofcorrespondingfeaturequantificationtechniques.

Keywords:Breast,clinicalpractices,FNAC,survey

Introduction

Fineneedleaspirationcytology(FNAC)isapartoftripleassessmentofbreastlesionsandhasbeenrecognizedasthemostcosteffectiveprocedurewithshortestturnaroundtime.[1]IncurrentpracticeofbreastFNAC,diagnosisisbasedonsubjectiveassessmentofmicroscopicappearanceoftheaspirates,therefore,difficultiesinmaintainingconsistencyandreproducibilityinfindingsareinevitable.Moreover,thereexistsanoverlapincytologicalfeaturesofbenignandmalignantlesionswhichmayleadtoequivocaldiagnosis.[2]Whenusingfivereportingcategoriesforbreastcytology(i.e.,C1inadequateC2benignC3atypicalC4suspiciousandC5malignant),[3]atypicalandsuspiciousfindingsindicateequivocaldiagnosiswhereintissuebiopsyisnecessaryfordefinitediagnosis.Thesefindingscombinedtogetherhavereportedratesof6.920%,[2]whereas,AlKaisai[4]foundthatthetruegrayzoneinbreastcytologyis2%ofallcases.Thusthereisascopetoreducetherateofequivocaldiagnosis.

Alsothereexistsdifferentialpreferenceforclinicocytopathologicalproceduresanddiscordanceamongexpertcytopathologists/pathologistsinmorphometricdiagnosis.Pathologistseitherdonotusethesamecriteriafordiagnosisorapplythesamecriteriadifferentlyfromoneanother.[5]Alternativelyithasbeenobservedthatgloballycytopathologists/pathologistsseethesamebutlocallytheyseedifferentthings.[6]

Toovercometheinherentlimitationspresentedbysubjectiveevaluationofcytologicalsmearsandimprovethereliabilityofdiagnosis,itisimportanttodevelopanduseassistivecomputationaltoolsforbreastcancerdiagnosisthatoperateonobjectivefeaturesandquantitativemeasures.Inliterature,manysuchcomputationaltoolsforbreastcancerdiagnosiscanbefoundwithmostofthemconcentratingonclassificationofFNACslidesasbenignormalignantandsomefocusingonstagingofmalignancy.[7]Whendesigninganddevelopingsuchcomputationalaiditisnecessarytounderstandpracticesandperceptionsoftheexpertstoidentifyaspectssuitableforcomputeraidedanalysis.Thiswillalsohelpdefineusercentricfunctionalityaspectsofthesystem.InthisregardanationwidequestionnairebasedsurveytitledPracticeofFNACasascreeningtoolinclinicalmanagementofsymptomaticpatientsofbreastcancerwasconducted.Thefindingsofthesurveyarereportedhere.

MaterialsandMethods

Surveydesign

Thesurveywasdesignedwithprimarygoalsto

Identifycommonpracticesandvariablesinclinicocyopathotologicalproceduresofaspiration,sampleprocessingandvisualassessmentusingmicroscopeinreportingofbreastFNAC.ThiswillhelpdefineusercentricfunctionalityaspectsofthesystemIdentifycommonlyperceiveddiagnosticsignificanceofcytologicalfeaturesfordiagnosisofbenignormalignantconditionofbreastlesions.Thiswillhelpdevelopbetterpatternrecognitionalgorithms.

Tocomplementthesegoals,thequestionnaireforpathologistcomprisedoftwoparts.Firstpartofthequestionnaireincludedquestionsonclinicocytopathologicalproceduressuchassamplecollectionand



Needlesize

Imageguidanceforaspiration

processingtechniquesused,typeofstainsusedandadditionalinvestigationsperformedroutinelyinbreastFNAC.

Inthesecondpartofthequestionnaire,participantswereaskedtospecifytheimportanceleveltheyattachtoeachcytologicalfeatureduringdiagnosisofbenignormalignantconditions.Foreachcytologicalfeature,theparticipantshadtoselectoneofthefivepredefinedlinguisticsignificancelevelsi)Notsignificant(0),ii)Slightlysignificant(1),iii)Moderatelysignificant(2),iv)Significant(3)andv)Mostsignificant(4).Numericalvaluesinthebracketsrepresentcorrespondingnumericalvaluesusedtocombineindividualopinionsandfindcommonperception.Simultaneously,participantsalsohadtospecifythemicroscopeobjectivemagnificationtheypreferablyusewhileassessingconditionofcytologicalfeatures.ParticipantswerealsorequestedtoprovidedetailsabouttheirreportingexperienceandpersonalconfidencelevelonFNACasascreeningtoolinmanagementofsymptomaticpatientsofbreastcancer.HelpofscholarlytextsinclinicalpathologysuchasManualandAtlasofFineNeedleAspirationCytology,[8]FineNeedleAspirationCytology:DiagnosticPrinciplesandDilemmas,[2]Cytology:DiagnosticPrinciplesandClinicalCorrelates[9]andTextbookofPathology[10]wastakenwhilepreparingthequestionnaire.

Targetexperts

ParticipationinthesurveywasvoluntaryandquestionnairebookletcarriedStatementofPurposewhichapprisedparticipantsaboutpurposeofthesurvey.Hundredquestionnairesweresenttotheheadsofthepathology/cytologydepartmentsatrenownedmedicaleducationandresearchinstitutes,oncologicaltertiarycarecentresandprimarycarecentres/privatediagnosticpathologylaboratories(total50institutes).Theheadofthedepartments(institutes)wererequestedtodistributethequestionnaireswithintheirinstitutestotheconcernedcytology/pathologyexpertstheyfeltcouldbestprovidetherepresentativeinformation.

ResultsoftheSurvey

Responses

Currentlywehavereceivedresponsesfrom51cytopathologists/pathologistsfromrenownedmedicaleducationinstitutes(52%oftheresponsesreceived),oncologicaltertiarycarecentres(28%)andprimarycarecentres/privatediagnosticpathologylaboratories(20%)spreadover13statesofIndia(Assam,AndhraPradesh,Bihar,Chandigarh,Karnataka,MadhyaPradesh,Maharashtra,Punjab,NewDelhi,Orissa,Rajasthan,TamilNaduandWestBengal).Individualreportingexperiencesoftheparticipantsareintherangeof241yearswithaveragereportingexperienceof17years.

Herefindingsofthesurveyarereportedintwoparts.PartIpresentsfindingsofthesurveyrelatedtobreastFNACprocedures,whichincludetissuesamplecollection,processing,stainingtechniquesandimmunocytochemicalinvestigationsusedbycytopathologists/pathologists.PartIIpresentsfindingsoncommonlyperceivedsignificancelevelofthecytologicalcriteriaindiagnosisofbenignormalignantconditionofbreastlesions.

PartI:TheconstantsandvariablesinbreastFNACpractices

Mostoftheparticipantsofthesurveyusedifferentsizesoftheneedlesforaspirationvaryingfromcasetocase,withmostofthemusingfinerneedles(>22G).Approximately62%oftheparticipantsofthissurveyuse23Gneedle,while39%oftheparticipantsprefer22Gneedles[Table1].

Imageguidanceduringaspirationofbreastlesionsishelpfulforexactlocalizationofthelump.Overall74%percentoftheparticipantsuseimageguidanceforaspiration.However,imageguidancemightnotbenecessaryforaspirationofobviousandpalpableorsuperficialanddefinitelesions,whichisevident,as62%oftheparticipantshavereportedusingitonlysometimes(notfor



everyaspirationperformed[Table2]).

Seventyninepercentoftheparticipantsusingimageguidancepreferultrasound.Availability,easeofuse,costofownershipandoperation,andrealtimeinterventioncapabilitiesseemtoinfluencechoiceoftheimagingmodalityforguidedaspiration.TheusagedatafordifferentimagingmodalitiesisreportedinTable3.

FixationandstainingmethodsusedforprimarydiagnosisfromFNAC

Mostnumberofparticipantsofthesurveyreportusingbothwetfixationandairdryingfixationtechniquesinslidepreparation[Table4],whereasthreestainingmethodsareroutinelyusedinbreastprimarycytodiagnosis,namelyRomanowsky,hematoxylinandeosin(HandE)andPapanicolaou(Pap).However,everycytopathologist/pathologistseemstofavorthemethodthatwasusedinhis/hertraininginstitute.Mostoftheparticipantcytopathogists/pathologists,inthissurvey,usemorethanoneslidepreparedfromtheaspirateofasinglelump.Useofbothwetfixedandairdriedslidesforeachaspirateisdoneby66%oftheparticipants[Table5].Ithasalsobeenobservedthattheuseofonlyairdryingfixationduringslidepreparationismorecommonamongsttheparticipantsfromprimarycarecenters/privatepathologylaboratoriesascomparedtoparticipantsfrommedicaleducationinstitutesortertiarycarecenters.

Additionalstainingmethods

Inadditiontoroutinestainingcombinations,moretypesofstainingtechniques[Table6]areusedby20%oftheparticipants.Sixtypercentoftheparticipantsusingadditionalstainsarefrommedicaleducationinstitutesandremainingfromprimaryortertiarycarecenters.Stainsusedforconfirmationofmucinouscarcinoma,arethemostcommonlyusedadditionalstains.

Immunocytochemicalinvestigations

Immunocytochemicalinvestigationsareperformedby27%oftheparticipantsofthissurvey71%oftheparticipantsperformingimmunocytochemicalinvestigationsarefromtertiarycarecentersandrest29%fromeducationalinstitutions.Noneoftheparticipantsfromprimarycarecenters/privatepathologylaboratoriesperformimmunocytochemicalinvestigations.Almost87%oftheparticipantsfromtertiarycarecenterspracticeimmunocytochemistry,ascomparedto15%fromeducationalinstitutes.Prognosticinvestigationssuchascheckforestrogenprogesterone(ER/PR)receptorstatusandhumanepidermalgrowthfactorreceptor2(HER2/neuorcerbB2)statusarethemostcommonlyusedimmunocytochemicalinvestigationspracticedby24%and14%oftheoverallparticipants,respectively.Useoftumormarkerssuchascytokeratin(CK),vimentin(VIM),neuronspecificenolase(NSE),prostatespecificantigen(PSA),cathepsinD(CATHD),leukocytecommonantigen(LCA)andp53hasalsobeenreportedbytheparticipants.TheusagedatafordifferentimmunocytochemicalinvestigationsinbreastFNACisgiveninTable7.

PartII:Commonlyperceiveddiagnosticsignificanceofthecytologicalcriteria

Thisworkhasbeeninitiatedwiththebeliefthatcommonlyperceiveddiagnosticsignificanceofacytologicalcriterionrepresentsitsrealabilityindiscriminatingbenignandmalignantconditionofabreastlump.ParticipantspercentageopinionisgiveninFigure1.Inordertocombineindividualopinionsandfindcommonperceptionoftheparticipantsmeanshifttechnique[11]hasbeenused.Whencombiningavailableindividualopinionsthreeexperimentswereperformed.Numericalfindingsoftheseexperimentsarepresented[Table8].

Infirstexperiment,opinionsofalltheparticipantswerecombinedtocomputeoverallmeansignificancescore(commonlyperceivedsignificance)forthefeatures.Also,thecoefficientofvariationaboutthemeanwascomputedtoestimatethevariabilityinopinion[Figure2].Thefeaturesareorderedinnonincreasing



fashionofoverallmeansignificancescores.

FromoverallmeansignificancescoresitcanbeobservedthatNuclearchromatinistheonlymostsignificantfeaturenatureofbackground,andvolumeandcolorofcytoplasmareinmoderatelysignificantcategory,whereas,allothercytologicalfeaturesbelongtothesignificantcategory.FromFigures1and2itcanalsobeobservedthatthereexistsaconsiderabledegreeofconcordanceamongtheparticipantsaboutdiagnosticsignificanceofmostofthecytologicalcriteria.Onlyinthecaseoffourcriteria,namelysizeandshapeofaggregates,natureofbackground,numberofnucleoli,andvolumeandcolorofcytoplasmparticipantsexhibitrelativelyhigherdegreeofdisagreementwithcoefficientofvariation[12]ofmorethan0.3.

Insecondexperiment,theresponsesweredividedinthreegroupsasfromprimarycarecenters/privatepathologylabs,medicaleducationinstitutionsandtertiarycarecenteres,andgroupwisecollectivesignificancescorewerecomputed[Figure3].Theoverallmeansignificancescoreshavealsobeenplottedforcomparativeevaluation.Perceivedsignificanceplotsshowhighdegreeofdisparityamongthreehierarchicallevelsofhealthcaredelivery,withcollectiveopinionoftheparticipantsfrommedicaleducationinstitutionscloselyfollowingthetrendsoftheoverallmeanopinion.Thecollectiveopinionoftheparticipantsfromprimarycarecentres/privatepathologylabsshowshighdynamismanddivergencefromtheoverallmeanopinion.

Inexperimentthree,variationsinperceptionofexpertsaccordingtotheirreportingexperiencewasstudied.Theresponsesweredividedinthreegroupsaccordingtothereportingexperienceinyears,asbelow5years,morethan5yearsbutlessthanaveragereportingexperience(17years)andmorethanaverageexperiencegroupwisecollectivesignificancescorewerecomputed.Perceivedsignificancescoreshavebeenplottedalongwithoverallmeansignificancescores[Figure4].Thisfigureshowsconvergingtrendinperceivedsignificancelevelswithincreasingexperience,alsodifferenceofopinionwiththeoverallopiniondecreaseswithincreasingreportingexperience.

Discussion

Amongthecytopathologist/pathologistsconcurrenceisseenonthetypeofneedlesandimageguidancetobeusedforaspirationofbreastlumps.Interestinglymorethanhalfoftheparticipantsreportofsometimesusingimageguidanceforaspirationtheyotherwiseperformfreehandprocedures.Thismightbeattributedtoapossiblereflectionofthescenariowherelatepresentationofthediseasewithobviousandpalpablelumpsiscommon.Also,whenchoosingtheimagingmodalityforguidedaspiration,availability,easeofuse,costofownershipandoperation,andrealtimeinterventioncapabilityofthemodalitiesseemtoinfluencethedecision.

Thefindingsalsoindicatehighestdegreeofvariationinpracticeofspreadingandstainingtechniquesusedforprimarydiagnosis.Althoughmostofthesurveyedrespondentsagreeonusemorethanoneslidespreparedfromtheaspirateofasinglelumpacytopathologist/pathologistmostlyfavorthestainingmethodthatwasusedathis/hertraininginstitute.Itisalsoseenthatnomorethan25%participantsusesamestaincombinations.Additionaldiagnostic/prognosticinvestigationslikespecialstainingandimmunocytochemicalinvestigationsshowhighdegreeofdivergenceamongdifferenthealthcaredeliverylevels.Theseinvestigationsarenotperformedbyanyoftheparticipantsfromtheprimarycarecentres/privatepathologylabsonlyparticipantsfrommedicaleducationinstitutesandtertiarycarecentersreportofperformingthem.Additionalstainingtechniquesarepredominantlyusedbymedicaleducationinstituteswhileimmunocytochemicalinvestigationsaremostlyperformedattertiarycarecentres.

OverallperceptiononthesignificancelevelofthecytologicalfeaturesindiagnosticinterpretationofbreastFNACslidescanbeconsideredtorepresenttheactualdiscriminationabilityofthefeature.Thecollective



opinionshowsdisparityfromonelevelofhealthcaredeliverymodeltotheother.Fromthefindingsofthesurveyitcanbeenobservedthatnuclearfeatureslikenuclearchromatin,prominenceofnuclei,nuclearmembrane,mitoticfigureareconsideredmoresignificantbyparticipantsfrommedicaleducationinstitutesandtertiarycarecentersnuclearfeaturesandgrosscytoarchitecturalpatternssuchassizeandshapeofaggregates,cohesivenessofclustersandpresenceofbarenucleiarefavoredbyparticipantsfromprimarycarecentersothercytologicalfeaturesviz.,myoepthelialcellpopulation,nuclearcytoplasmicratioandcellularpleomorphismarepreferredequallybyalltheparticipants.Alsoasobservedearlier,theperceptionaboutthefeaturesshowsconvergingtrendwithincreasingexperience.Theperceivedsignificancevarieswidelyamongthedifferentexperiencegroupsforfeaturessuchascohesivenessofepithelialcells,numberofnucleoli,natureofbackground,andvolumeandcolorofcytoplasmwhereastheperceivedsignificanceoffeaturesnuclearcytoplasmicratio,mitosis,bimodalpatternofaggregates,nuclearshapeandnuclearsizeisalmostsimilarforallexperiencegroups.

Conclusions

FromthenationwidesurveyonpracticeofFNACasascreening/diagnostictoolinbreastcancerdiagnosis,ithasbeenobservedthatthereexistanalogousaswellasvariedcomponentsinclinicopathologicalproceduresanddiagnosticinterpretationbyindividuals.TheseconstantsandvariablesinpracticeofFNACforbreastcancerscreening/diagnosisshouldbeconsidered,whendrawingupspecificationsforanassistivecomputationaltoolforanalysisofbreastFNACslides.Suchacomputationaltoolusingobjectivefeatureswillensureprovisionofrelevant,appropriateandaccurateassistanceindiagnosticinterpretationanditssubsequentbroadacceptability.TheestimateforcommonlyperceivedsignificanceofcytologicalfeaturesobtainedthroughthisstudywillhelpinselectionofcytologicalfeaturesandselectionofcorrespondingobjectivefeaturequantificationtechniquestobeusedinanalysisofbreastFNACslides.

Acknowledgments

Wearegratefulofalltheinstitutesandindividualswhokindlyrespondedtoourcallandparticipatedinthissurvey.WearealsothankfultooursponsorsTexasInstruments,AuthoritiesatSMST,IITKharagpurandallthosewhodirectlyorindirectlysupportedusinthisactivity.

FootnotesSourceofSupport:Nil

ConflictofInterest:Nonedeclared.

References

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FiguresandTables

Table1

UsagedatafordifferentneedlesizesinbreastFNACaspiration

Table2

Usagedataforimageguidanceforaspirationofbreastlumps

Table3



Usagedataofimagingmodalitiesforguidanceduringbreastlumpaspiration

Table4

UsagedatafortissuefixationtechniquesinbreastFNACslidepreparationforprimarydiagnosis

Table5

StainingmethodsusedinbreastFNACslidepreparationforprimarydiagnosis

Table6

UsagedataforadditionalstainingtechniquesinbreastFNAC



Table7

Immunocytochemicalinvestigations

Figure1

Participantspercentageopinion

Table8



Commonlyperceivedsignificanceofthecytologicalcriterion

Figure2



Overallopinionandtheextentofvariationamongparticipants

Figure3



Perceivedsignificanceofcytologicalfeaturesatdifferenthierarchicallevelsofthehealthcaredelivery

Figure4



Perceivedsignificanceofcytologicalfeaturesandeffectofexperienceonit

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