BreastBreastCytopathologyCytopathology--TechniquesTechniques--MorphologyMorphology

JerzyJerzy KlijanienkoKlijanienko MDMD

Institut Curie, Paris, FranceInstitut Curie, Paris, France

HistoryHistory of FNAof FNA

19261926 Martin, Martin, Ellis Ellis ((MemorialMemorial Hospital)Hospital)19541954 CardozoCardozo (Pays Bas)(Pays Bas)19541954 ZajicekZajicek ((KarolinskaKarolinska))19541954 ZajdelaZajdela (Institut Curie)(Institut Curie)19721972 Rilke (Milan)Rilke (Milan)19801980 USA, CanadaUSA, Canada

Avantages for Avantages for thethe patientpatient

SimpleSimpleNo No anaesthesiaanaesthesiaCan Can bebe repeatedrepeatedNot time Not time consumingconsuming

Avantages for Avantages for thethe clinicianclinician 11

AmbulatoryAmbulatoryCan Can bebe performedperformed duringduring pregnancypregnancyImmediateImmediate resultsresultsCan Can bebe therapeutictherapeutic ((cystcyst, , abcessabcess))Multiple localisationsMultiple localisationsN (+) or N (N (+) or N (--))

Avantages for Avantages for thethe clinicianclinician 22

Can Can identifyidentify a a recurrencerecurrenceCan Can identifyidentify nonnon--palpable palpable lesionslesionsCan Can identifyidentify metastasismetastasis ((liverliver, distant , distant organsorgans))Can Can determinedetermine proliferationproliferation indexindexCan Can identifyidentify malignancymalignancy for palliative for palliative treatmenttreatmentProcedure explanationProcedure explanation to patient to patient isis easyeasyHospitalHospital occupation occupation cancan bebe plannedplanned

Avantages for Avantages for thethe laboratorylaboratory

MGG MGG andand DQ, DQ, fastfast stainingstainingSimple Simple materialmaterialLowLow costcostPossibilityPossibility of FCM, of FCM, BacteriologyBacteriology, HR, HRLymphomaLymphoma, , SarcomaSarcoma

ComplicationsComplications

Distant Distant disseminationdissemination: : nevernever observedobservedLocal Local disseminationdissemination: : nevernever observedobservedHematomaHematoma: 40: 40--50% of cases50% of casesPneumothoraxPneumothorax: 1 in 28 000 cases: 1 in 28 000 casesInfectionInfection: 3 in 200 000 cases: 3 in 200 000 cases

ResultsResults (1)(1)

ExactExact: M/M, B/B, S/S: M/M, B/B, S/SSuspiciousSuspicious: S/M, S/B: S/M, S/BFalseFalse negativenegative: B/M: B/MFalseFalse positivepositive: M/B: M/BNon Non significantsignificant: NS/M, NS/B, NS/S: NS/M, NS/B, NS/S

ResultsResults (2)(2)

((excludingexcluding NS)NS)

SensitivitySensitivity = VM / VM+FB x 100= VM / VM+FB x 100

SpecificitySpecificity = VB / VB+FM x 100= VB / VB+FM x 100

MalignantMalignant TumorsTumors

93.293.26.16.16.66.683.783.7173721737220002000CurieCurie

96964455909076276219931993SneigeSneige

97973399828299099019811981BriffodBriffod

9696443388881745174519751975ZajdelaZajdela

929288151577771068106819701970ZajicekZajicek

SensibilitySensibility(%)(%)

FBFB(%)(%)

SuspSusp(%)(%)

ExactExact(%)(%)

# # CasesCases

YrYrAuthorsAuthors

BenignBenign TumorsTumors

0.20.2

0.40.4

0.30.3

0.10.1

FPFP(%)(%)

99.799.73.83.889.289.29662966220012001KlijanienkoKlijanienko

92926678781449144919871987FessiaFessia

95954489891027102719751975ZajdelaZajdela

93937793931009100919701970ZajicekZajicek

SpecificitySpecificity(%)(%)

SuspSusp(%)(%)

ExactExact(%)(%)

# # CasesCases

YrYrAuthorsAuthors

FalseFalse--positivepositive

0.020.02 % in % in ourour seriesseriesAdenofibromaAdenofibromaDuctalDuctal ectasiaectasiaSclerosingSclerosing adenosisadenosisPapillomasPapillomas

WhyWhy are are thethe resultsresults differentdifferentbetweenbetween studiesstudies??

InterpretationInterpretation-- numbernumber of of pathologistspathologists-- competencecompetence-- numbernumber of FNA of FNA perper daydayUnsatisfactoryUnsatisfactory samplessamples-- multiple localisationsmultiple localisations-- tumor tumor fibrosisfibrosis

How to How to improveimprove

9999868681819595248248PowlesPowles

1001008080868680.880.89494HermasenHermasen

98.998.994.294.294.294.288.488.4223223BriffodBriffod

98.898.887.187.188.788.792.192.113001300CornillotCornillot

All All threethree(%)(%)

FNAFNA(%)(%)

RadioRadio(%)(%)

ClinicalClinical(%)(%)

# # CasesCases

AuthorsAuthors

TechniquesTechniques

SampleSample (1)(1)

MaterialMaterial23 G 23 G needlesneedlesSlidesSlidesDisinfectantDisinfectant andand bandagesbandagesMicroscope + Microscope + DiffDiff--QuikQuik

SampleSample (2)(2)

Clinical Clinical impressionimpression, tissue , tissue resistanceresistanceand and smearingsmearing modality modality are the are the THREETHREEimportant criteria to provide a high important criteria to provide a high quality FNAquality FNA

The procedure should be simple and The procedure should be simple and reproducible reproducible

SampleSample (3)(3)

ErrorsErrorsSlow or violent Slow or violent needleneedle introductionintroductionTooToo long or long or numerousnumerous needleneedle passespassesUse of Use of pistolpistolBandagingBandaging tootoo quicklyquickly cancan cause cause ulteriorulteriorhematoma hematoma

QualityQuality control (1)control (1)

ClinicalClinical impressionimpressionRound, mobile: Round, mobile: cystscysts, FA, , FA, mucinousmucinousRound Round withwith marginsmargins: FA, : FA, phyllodesphyllodes tumortumorPoorlyPoorly delimiteddelimited: : mastopathiamastopathia, , lobularlobular cacaFixedFixed +/+/-- fossette: fossette: carcinomascarcinomasproximityproximity to to scarsscars: fat : fat necrosisnecrosis, , recurrencerecurrence

QualityQuality control (2)control (2)

Tissue Tissue resistanceresistance

No No resistanceresistance: : cystscysts, FA, fat , FA, fat necrosisnecrosisFibrousFibrous: : mastopathiamastopathia, FA, , FA, lobularlobular cacaHeterogenousHeterogenous: : mastopathiamastopathia, , carcinomascarcinomas, , necrosisnecrosis

QualityQuality control (3)control (3)

SmearSmear macroscopymacroscopyColorColor

White, White, pinkpink: : galactophotiritisgalactophotiritis, , cystscysts, FA, , FA, mucinousmucinousGray: Gray: carcinomacarcinomaAdipousAdipous: fat : fat necrosisnecrosis, , lipomalipoma, NS, NS

CellularityCellularitywetwet samplesample, , ovaloval, , centeredcentered on on slideslideDiffDiff--QuikQuik

NonNon--palpable palpable lesionslesions (1)(1)

No No microcalcificationsmicrocalcificationsUS image (FNA) > 2mm < 8mmUS image (FNA) > 2mm < 8mmFNA plus CNB > 8mmFNA plus CNB > 8mmMultiple Multiple lesionslesionsRadioRadio-- suspicioussuspicious lesionslesions (ACR 3(ACR 3--4)4)WellWell--trainedtrained staffstaff

NonNon--palpable palpable lesionslesions (2)(2)

MaterialMaterialUS 7US 7--10 MHz10 MHzStandard FNA Standard FNA materialmaterialNeedleNeedle attachedattached to syringe: aspirationto syringe: aspiration

NonNon--palpable palpable lesionslesions techniquetechnique

The The shortestshortest waywayOptimal Optimal cutaneouscutaneous point point AngularAngular insertioninsertionVertical insertionVertical insertionAspirationAspirationVisualizedVisualized on on screenscreen duringduring aspiration aspiration PossibilityPossibility of of completioncompletion by USby US--CNBCNB

CytologyCytology analysisanalysisClinicalClinical datadata: age, size, site, tumor : age, size, site, tumor kineticskinetics, , clinicsclinics, , radiologyradiology, N, M, , N, M, previousprevious treatmenttreatmentFNA componentsFNA components:: cellularitycellularity, , distribution, distribution, cohesivenesscohesiveness, , chromatinchromatin, , stroma, stroma, necrosisnecrosis, , secretionssecretionsSimple report, one Simple report, one diagnosisdiagnosis

Cell Cell blocbloc

ER

PR

cerbB2

ReferencesReferences for for diagnosisdiagnosis of of breastbreast lesionslesionsInstitut Curie, ParisInstitut Curie, Paris

20082008

# patients# patients

29.229.256561767176720012001

29.529.556.356.31252125219991999

31.931.956561130113019971997

31.831.855.755.71161116119891989

36.336.355.855.898298219851985

41.241.255.955.994194119811981

DiameterDiameter((meanmean))

Age Age ((meanmean))

##

Diagnostic Diagnostic circumstancescircumstances

61%61%33%33%19991999

61%61%33%33%19971997

60%60%33%33%19931993

68%68%23%23%19891989

74%74%6%6%19851985

71%71%4%4%19811981

PalpationPalpationMammographyMammography

Stage Stage atat diagnosis diagnosis 11

Stage Stage atat diagnosis diagnosis 22

8%8%38%38%40%40%14%14%19991999

8%8%40%40%42%42%10%10%19971997

8%8%41%41%44%44%7%7%19931993

11%11%48%48%36%36%5%5%19891989

16%16%60%60%21%21%3%3%19851985

23%23%61%61%14%14%2%2%19811981

IIIIIIIIIIII00

Initial Initial surgicalsurgical treatment treatment

62%62%1999:1999:

60%60%1997:1997:

52%52%1993:1993:

41%41%1989:1989:

30%30%1985:1985:

19%19%1981:1981:

DiagnosisDiagnosis

AnamnesisAnamnesisClinicalClinical examinationexaminationRadiologyRadiology

MammographyMammographyUSUSCTCT--scanscan andand IRM (if IRM (if necessarynecessary))

PathologyPathology reportreport

But But alsoalso ……..

FCM for DNA ploidy FCM for DNA ploidy andand SPhaseSPhaseKiKi--67, c67, c--erbB2, p53, erbB2, p53, ……..HR HR usingusing ICCICCMicrobiologyMicrobiologyFCM for FCM for lymphomalymphoma membrane markersmembrane markersCellCell andand tissue tissue banks banks –– molecular molecular profileprofile

PathologyPathology reportreport

To To obtainobtain thethe diagnosisdiagnosis in in orderorder to to informinform thethe patient about patient about treatmenttreatmentmodalitiesmodalitiesTo To indicateindicate SentinelSentinel LNLNTo To avoidavoid successive interventionssuccessive interventionsTo know To know prognosticprognostic parametersparameters andand to to predictpredict prognosisprognosis(HR, (HR, SPhSPh, MI, EE grade, cerbB2, E+), MI, EE grade, cerbB2, E+)

BreastBreast lesionslesions

Mammotome

MicrocalcificationsACR 4ACR 5

Cytoponction

Suspect < 7mm

Microbiopsie+/- Cytoponction

Suspect > 7mm

Nodule échographiqueSuspect

CytoponctionMicrobiopsie

Nodule échographiqueIndéterminé

Lésion non palpable

DRILL-BIOPSIE, 11G

MICRO-BIOPSIE AU PISTOLET 22mm, 14G

FNA vs CNB FNA vs CNB vsvs SurgicalSurgical SpecimenSpecimen

31 mm31 mm9.2%9.2%2.8%2.8%88%88%

MeanMean sizesizeFNA:MFNA:MMB:BMB:BSS:MSS:M

FNA:BFNA:BMB:MMB:MSS:MSS:M

FNA:MFNA:MMB:MMB:MSS:MSS:M

The drawbacksThe drawbacks

The The procedureprocedure maymay bebe painfulpainfulImpossible to Impossible to samplesample MCAMCAInfiltration Infiltration featuresfeatures are are seenseen in in onlyonly90% of 90% of carcinomascarcinomasProcedureProcedure needsneeds wellwell--trainedtrained staffstaff

MorphologyMorphology

HistologyHistology((BenignBenign tumorstumors))

specificspecific andand nonnon--specificspecificInflammationInflammation

Double compositionDouble compositionFibroadenomaFibroadenoma

TumorTumor vs hyperplasiavs hyperplasiaPapillomaPapilloma

i.e. i.e. oncocytic metapl oncocytic metapl MetaplasiaMetaplasia

PathologicalPathological dilatationdilatationCystCyst

IncreasedIncreased numbernumberHyperplasiaHyperplasia

IncreasedIncreased numbernumberAdenosisAdenosis

HistologyHistology ((MalignantMalignant tumors)tumors)

NON INFILTRATIVENON INFILTRATIVEDuctalDuctal in situin situLobularLobular in situin situ

INFILTRATIVEINFILTRATIVEDuctalDuctalDIC DIC withwith in situ in situ predpred..LobularLobularMucinousMucinousMedullaryMedullaryPapillaryPapillaryTubularTubularAd Ad CysticCystic CaCaApocrineApocrineMetaplasticMetaplasticPaget Paget diseasediseaseOthersOthers: MM, : MM, LymphLymph, , SarcSarc

BreastBreast PathologyPathologyin FNAin FNA

-- BenignBenign-- MalignantMalignant

InflammatoryInflammatory cytologycytology

Acute inflammationAcute inflammationChronicChronic inflammationinflammationNonNon--specificspecific granulomagranulomaForeignForeign body body granulomagranulomaTBC/TBC/sarcoidosissarcoidosisFat Fat necrosisnecrosis

Acute InflammationAcute Inflammation

Purulent collectionPurulent collectionPainfulPainful FNAFNAFeverFever+/+/-- DermatitisDermatitisMalignantMalignant clinicalclinical aspectaspectMicrobiologyMicrobiologyNo CNBNo CNB

GranulomasGranulomas

TBC or TBC or SarcoidosisSarcoidosisMicrobiologyMicrobiology ((liquidliquid, PCR, , PCR, smearssmears))

ForeignForeign body body granulomagranulomaFrequentFrequent postpost--surgicalsurgical complicationcomplication

HaematomaHaematomaSebaceousSebaceous cystcyst

Fat Fat necrosisnecrosis

DifferentDifferent chronologychronology::Initial:Initial: lipophageslipophagesAdvancesAdvances:: fibroblasticfibroblastic reparationreparation

May May bebe a a problemproblem of of diagnosisdiagnosisPossibilityPossibility of FP !!of FP !!

BenignBenign TumorsTumors (1)(1)CystsCysts

DifferentDifferent typestypesApocrineApocrine metaplasiametaplasia«« OldOld »» cystcystPossibilityPossibility of of atypicalatypical cellscells

DifferentialDifferential diagnosisdiagnosisApocrineApocrine carcinoma carcinoma PapillomaPapillomaPapillaryPapillary carcinomacarcinoma

BenignBenign TumorsTumors (2)(2)BreastBreast dystrophiadystrophia

BreastBreast dystrophiadystrophiaBenignBenign cytologycytologyVariableVariableCysticCystic backgroundbackgroundNo No atypiaatypiaClinicallyClinically benignbenign50% of patients50% of patients

BenignBenign TumorsTumors (3)(3)EpithelialEpithelial hyperplasiahyperplasia

EpithelialEpithelial hyperplasiahyperplasiasimplesimpleatypicalatypical

BenignBenign TumorsTumors (5)(5)AtypicalAtypical hyperplasiahyperplasia

AtypicalAtypical hyperplasiahyperplasia33--D clustersD clustersIrregularIrregular nucleinucleiBenignBenign//AtypicalAtypical FNA FNA morphologymorphology

BenignBenign TumorsTumors (6)(6)FIBROADENOMAFIBROADENOMA

UsuallyUsually 2020--35 35 yrsyrsMultiple in 20% of casesMultiple in 20% of casesCharacteristicCharacteristic cytologycytology

EpithelialEpithelial cellscellsNakedNaked nucleinucleiConnective fragmentsConnective fragmentsMucinMucin (+/(+/--))DigitiformDigitiform clusters (+/clusters (+/--))

BenignBenign TumorsTumors (7)(7)PHYLLODES PHYLLODES TumorTumor

RareRareLarge sizeLarge size«« malignantmalignant »» or or «« benignbenign»» behaviourbehaviourFNA: pseudoFNA: pseudo--FAFA

AbundantAbundant connective fragmentsconnective fragments«« normalnormal »» epithelialepithelial cellscellsSomeSome C/N C/N atypiaatypiaMitoses +/Mitoses +/--

BENIGN TUMORS (8)BENIGN TUMORS (8)DUCTAL ECTASIA, PAPILLOMADUCTAL ECTASIA, PAPILLOMA

DuctalDuctal ectasiaectasiaPossibilityPossibility of of nipplenipple retractionretractionPseudoPseudo--cysticcystic morphologymorphologyCentral Central localizationlocalization

PapillomaPapillomaCysticCystic backgroundbackgroundPapillaryPapillary clustersclustersVascularVascular structuresstructuresMacrophagesMacrophagesMyoepithelialMyoepithelial cellscells

PossibilityPossibility of FP !!!!of FP !!!!

BENIGN TUMORS (9)BENIGN TUMORS (9)RARE CONDITIONSRARE CONDITIONS

LipomaLipomaGranularGranular cellcell tumortumorIntramammaryIntramammary LymphLymph NodeNodeGynecomastiaGynecomastia

MALIGNANT TUMORS (1)MALIGNANT TUMORS (1)DUCTAL CARCINOMADUCTAL CARCINOMA

-- 8080--85%85%-- PolymorphousPolymorphous cellscells

-- GlandularGlandular structures.structures.-- IsolatedIsolated cellscells withwith preservedpreserved cytoplasmcytoplasm-- IrregularIrregular nucleinuclei-- HugeHuge nucleinuclei-- NecrosisNecrosis-- Mitoses +/Mitoses +/--

MALIGNANT TUMORS (2)MALIGNANT TUMORS (2)LOBULAR CARCINOMALOBULAR CARCINOMA

5%5%Variable Variable cellularitycellularityMonomorphicMonomorphic nucleinucleiIsolatedIsolated cellscellsSmall clustersSmall clustersCellsCells in in indianindian filefileDiscreteDiscrete C/N C/N atypiaatypiaConnective tissueConnective tissue

MALIGNANT TUMORS (3)MALIGNANT TUMORS (3)MUCINOUS CARCINOMAMUCINOUS CARCINOMA

2%2%Mixed variantsMixed variantsCharacteristicCharacteristic mucinmucinInconspiciousInconspicious C/N C/N atypiaatypiaDifferentialDifferential diagnosisdiagnosis::

FibroadenomaFibroadenomaDuctalDuctal ectasiaectasia

MALIGNANT TUMORS (4)MALIGNANT TUMORS (4)MEDULLARY CARCINOMAMEDULLARY CARCINOMA

Round Round –– clinicallyclinically benignbenignVariable size of Variable size of cellscellsHugeHuge nucleolinucleoliLymphocytesLymphocytesPlasma Plasma cellscells +/+/--DifferentialDifferential diagnosisdiagnosis::

InflammatoryInflammatory carcinomacarcinoma

MALIGNANT TUMORS (5) MALIGNANT TUMORS (5) PAPILLARY CARCINOMAPAPILLARY CARCINOMA

Rare (2%)Rare (2%)MalignantMalignant cellscells in in papillarypapillary clustersclustersIsolatedIsolated cellscells andand nakednaked nucleinucleiCysticCystic backgroundbackgroundNecroticNecrotic backgroundbackgroundDifferentialDifferential diagnosisdiagnosis::

PapillomaPapilloma ((atypiaatypia!)!)CysticCystic carcinomacarcinoma

Actine smooth

MALIGNANT TUMORS (6)MALIGNANT TUMORS (6)TUBULAR CARCINOMATUBULAR CARCINOMA

Super grade ISuper grade ITubularTubular clustersclustersDifferentialDifferential diagnosisdiagnosis::

AtypicalAtypical hyperplasiahyperplasiaFibroadenomaFibroadenomaPossibilityPossibility of of falsefalse--negativenegative

MALIGNANT TUMORS (7)MALIGNANT TUMORS (7)ADENOID CYSTIC CARCINOMAADENOID CYSTIC CARCINOMA

0.1%0.1%CharacteristicCharacteristic smearssmearsRound Round cellscells, , «« fingerfinger--likelike »»EosinophilicEosinophilic fragmentsfragmentsDifferentialDifferential diagnosisdiagnosis::

MetaplasticMetaplastic carcinomacarcinoma

MALIGNANT TUMORS (8)MALIGNANT TUMORS (8)APOCRINE CARCINOMAAPOCRINE CARCINOMA

1%1%ApocrineApocrine cellscells ((benignbenign +/+/-- morphologymorphology))Important C/N Important C/N atypiaatypiaNecrosisNecrosisDifferentialDifferential diagnosisdiagnosis::

ComedocarcinomaComedocarcinomaCystsCysts withwith dystrophicdystrophic cellscells

MALIGNANT TUMORS (9)MALIGNANT TUMORS (9)METAPLASTIC METAPLASTIC CARCINOMACARCINOMA

SCCSCCSpindleSpindle cellcell carcinomacarcinomaChondroidChondroid, , osseousosseousMixedMixed

MALIGNANT TUMORS (10)MALIGNANT TUMORS (10)SpecificSpecific variantsvariants

Neuroendocrine Neuroendocrine carcinomacarcinomaPagetPaget’’s s diseasediseaseGiantGiant cellcell carcinomacarcinoma11°° SarcomaSarcomaSarcomasSarcomas afterafter RTRTLymphomasLymphomasMetastasesMetastases

IsIs itit possible to possible to distinguishdistinguish????????

InfiltrativeInfiltrative

Not Not infiltrativeinfiltrative

REFERENCESREFERENCESZajdelaZajdela A, A, VielhVielh P, Di Bonito L. Manuel et Atlas P, Di Bonito L. Manuel et Atlas

de Cytologie Mammaire. de Cytologie Mammaire. PiccinPiccin 19951995

Cytopathologie Mammaire par Cytopathologie Mammaire par MonctionMonction. Marsan . Marsan C coordination, C coordination, DieboldDiebold J J editeurediteur, Elsevier 2001, Elsevier 2001

KlijanienkoKlijanienko J et al. J et al. CriticalCritical clinicopathologicclinicopathologicanalysisanalysis of 23 cases of fineof 23 cases of fine--needleneedle breastbreastsamplingsampling initiallyinitially recordedrecorded as as falsefalse--positive. The positive. The 4444--year year experienceexperience of of thethe Institut Curie. Cancer Institut Curie. Cancer 93: 13293: 132--139, 2001139, 2001

CasesCases

FN

Sa

LMS

ThankThank youyou !!!!!!!!!!!!!!!!

WouawWouaw

NowNow itit isis finishedfinished !!