CytologyCytology of of PleuralPleural FluidFluid as a as a
DiagnosticDiagnostic ChallengeChallenge
Paavo Paavo PääkköPääkkö, MD, , MD, PhDPhD
ChiefChief PhysicianPhysician and and HeadHead of the of the DepartmentDepartment
DepartmentDepartment of of PathologyPathology,,
Oulu Oulu UniversityUniversity HospitalHospital, Finland, Finland
Oulu University Hospital
General General overviewoverview of of cytologycytology of of
pleuralpleural effusionseffusions
!! ExfoliativeExfoliative cytologicalcytological examinationexamination of of pleuralpleural effusionseffusionscommon common methodmethod for for determiningdetermining whetherwhether effusioneffusion is isbenignbenign oror malignantmalignant
!! EffusionsEffusions subdividedsubdivided into into transudatestransudates and and exudatesexudatesdependingdepending on the on the proteinprotein contentcontent
!! TransudatesTransudates resultresult fromfrom alterationsalterations in in hydrostatichydrostatic ororoncoticoncotic pressurepressure, , oftenoften duedue to to systemicsystemic factorsfactors, , e.ge.g..congestivecongestive heartheart failurefailure
!! ExudatesExudates resultresult fromfrom pathologicalpathological processesprocesses localizedlocalizedto the to the serosalserosal membranesmembranes => => higherhigher proteinprotein contentcontentand and cellularitycellularity increasedincreased comparedcompared to to transudatestransudates, , e.ge.g..infectionsinfections
UtilityUtility and and limitationslimitations of of cytologycytology of of
pleuralpleural effusionseffusions
!! CellsCells exfoliatedexfoliated into into effusioneffusion fluidfluid cancan bebe examinedexamined as as
cytologycytology smearssmears, , liquid-basedliquid-based preparationspreparations, , cytospincytospin
preparationspreparations, , oror cellcell blocksblocks
!! MostMost of the of the exudatesexudates benignbenign
!! The The absenceabsence of of malignantmalignant cellscells doesdoes notnot rulerule out out
malignancymalignancy
!! OnlyOnly 30-40 % of 30-40 % of malignantmalignant mesotheliomasmesotheliomas, and 60-70, and 60-70
% of % of cancerscancers metastaticmetastatic to the to the pleurapleura diagnoseddiagnosed byby
exfoliativeexfoliative cytologycytology
CytologyCytology vs. vs. histologyhistology
!! ExfoliativeExfoliative cytologycytology hashas of of limitedlimited usefulnessusefulness in indiagnosingdiagnosing malignantmalignant mesotheliomamesothelioma
!! BenignBenign reactivereactive mesothelialmesothelial cellscells maymay havehave featuresfeatures thatthatmimicmimic malignancymalignancy, and , and malignantmalignant mesotheliomasmesotheliomas maymaybebe cytologicallycytologically blandbland
!! WithoutWithout evidenceevidence of of invasioninvasion of of underlyingunderlying tissuestissues,,diagnosisdiagnosis of of mesotheliomamesothelioma on on cytologiccytologic groundsgrounds maybemaybedifficultdifficult
!! SarcomatousSarcomatous mesotheliomasmesotheliomas typicallytypically dodo notnot shedshed cellscellsinto into effusioneffusion
CytologicalCytological featuresfeatures of of malignancymalignancy
!! CancerCancer cellscells as as individualindividual cellscells, , sheetssheets of of cohesivecohesive cellscells,,
and and three-dimensionalthree-dimensional sphericalspherical clustersclusters, , calledcalled morulaemorulae
!! PapillaryPapillary oror acinaracinar structuresstructures
!! UsuallyUsually the the numbernumber of of malignantmalignant cellscells highhigh, , rarelyrarely a a fewfew
!! PresencePresence of of psammomapsammoma bodiesbodies
!! EnlargedEnlarged cellscells withwith enlargedenlarged nucleinuclei, , coarsecoarse chromatinchromatin,,
prominentprominent nucleolinucleoli
!! MitosesMitoses, , atypicalatypical mitosesmitoses, and , and necroticnecrotic debrisdebris
ReactiveReactive atypiaatypia of of mesothelialmesothelial cellscells
!! BenignBenign mesothelialmesothelial cellscells exfoliateexfoliate easilyeasily and and
displaydisplay a a spectrumspectrum of of reactivereactive changeschanges fromfrom
minimalminimal reactivereactive changechange to to highlyhighly atypicalatypical
reactivereactive changechange, , mimickingmimicking malignancymalignancy
!! ReactiveReactive mesothelialmesothelial cellscells shedshed as as invidualinvidual cellscells,,
in in clustersclusters oror sheetssheets, , withwith adjacentadjacent cellscells
separatedseparated fromfrom oneone anotheranother byby spacesspaces referredreferred
to as to as ””windowswindows””
CytologicalCytological featuresfeatures of of reactivereactive
mesothelialmesothelial cellscells
!! NucleiNuclei roundround oror ovaloval withwith distictdistict nuclearnuclear membranesmembranes,,
chromatinchromatin vesicularvesicular oror finelyfinely granulargranular, and , and cytoplasmcytoplasm
adundantadundant and and darkly-staineddarkly-stained
!! PeripheralPeripheral cytoplasmcytoplasm stainsstains darkerdarker thanthan centralcentral
cytoplasmcytoplasm, and , and microvillimicrovilli aroundaround the the peripheryperiphery resultresult in in
fuzzyfuzzy rimrim oror borderborder
!! BinucleationBinucleation oror multinucleationmultinucleation frequentfrequent
!! CytoplasmicCytoplasmic vacuolesvacuoles maymay compresscompress the the nucleusnucleus,,
suggestingsuggesting the the signetsignet ringring cellscells of of adenocarcinomaadenocarcinoma
ReactiveReactive mesothelialmesothelial cellscells
CytologicalCytological featuresfeatures of of malignantmalignant
mesotheliomamesothelioma
!! MalignantMalignant mesotheliomasmesotheliomas causecause <1 % of <1 % of
malignantmalignant pleuralpleural effusionseffusions, and , and onlyonly epithelialepithelial
malignantmalignant mesotheliomasmesotheliomas likelylikely exfoliateexfoliate cellscells
into into effusioneffusion fluidsfluids
!! MalignantMalignant mesotheliomamesothelioma cellscells lacklack the the significantsignificant
degreedegree of of cytologicalcytological pleomorphismpleomorphism
!! CellsCells arrangedarranged in in sheetssheets, , clustersclusters, , morulaemorulae oror
papillarypapillary structuresstructures
HintsHints for for correctcorrect interpretationinterpretation
!! AtypicalAtypical reactivereactive mesothelialmesothelial cellscells blendblend withwith cellscells withwith lesserlesserdegreesdegrees of of reactivereactive atypiaatypia withinwithin a a benignbenign effusioneffusion, , givinggiving the theimpression of impression of oneone populationpopulation of of cellscells
!! In In casescases of of malignancymalignancy, , reactivereactive mesothelialmesothelial cellscells and and malignantmalignantcellscells oftenoften appearappear as as twotwo separateseparate and and distinctdistinct populationpopulation of of cellscells
!! ItIt is is necessarynecessary to to firstfirst determinedetermine ifif cellscells in a in a fluidfluid areare trulytrulymalignantmalignant beforebefore secondarilysecondarily determiningdetermining the the typetype of of malignancymalignancy
!! ImmunohistochemicalImmunohistochemical confirmationconfirmation thatthat atypicalatypical cellscells arearemesothelialmesothelial in in originorigin doesdoes notnot help to help to distinguishdistinguish betweenbetweenreactivereactive mesothelialmesothelial cellcell proliferationproliferation and and mesotheliomamesothelioma
Case 1Case 1
!! 60-year 60-year oldold manman
!! ExposedExposed to to asbestosasbestos
!! HydrothoraxHydrothorax and and pleuralpleural plaquesplaques
!! CytologicalCytological specimenspecimen takentaken fromfrom pleuralpleural cavitycavity
Calretinin
CK 5/6
CK7
EMA
ConclusionConclusion fromfrom Case 1 Case 1
!! StrongStrong suspicionsuspicion for for malignancymalignancy, , fittingfitting ratherrather
for for malignantmalignant mesotheliomamesothelioma thanthan metastaticmetastatic
adenocarcinomaadenocarcinoma
!! The The diagnosisdiagnosis of of malignantmalignant mesotheliomamesothelioma waswas
laterlater confirmedconfirmed byby histologicalhistological samplesample
Calretinin
WT1
EMA
Case 2Case 2
!! 76-year 76-year oldold malemale
!! SuspicionSuspicion for for lunglung malignancymalignancy
!! HydrothoraxHydrothorax
!! An An aspirationaspiration fromfrom leftleft pleuralpleural cavitycavity performedperformed,,
and and cytologicalcytological analysesanalyses requestedrequested
TTF-1
CK 7
CK 5/6
EMA
E-Cadherin
Calretinin
ConclusionConclusion fromfrom Case 2 Case 2
!! StrongStrong suspicionsuspicion for a for a metastaticmetastatic carcinomacarcinoma
!! TTF-1 TTF-1 positivitypositivity suggestssuggests for for pulmonarypulmonary originorigin
of the of the carcinomacarcinoma
Case 3Case 3
!! 76-year 76-year oldold femalefemale
!! BreastBreast carcinomacarcinoma operatedoperated 6 6 yearsyears agoago
!! FluidFluid in the in the pleuralpleural cavitycavity and and bothboth lungslungs
containcontain tumourtumour infiltrationsinfiltrations
!! PleuralPleural cytologycytology requestedrequested
PAN-CK
CK 5/6 Estrogen receptor
ConnclusionConnclusion fromfrom Case 3 Case 3
!! StrongStrong suspicionsuspicion for a for a metastaticmetastatic carcinomacarcinoma
!! EstrogenEstrogen receptor-positivityreceptor-positivity suggestssuggests for a for a
metastaticmetastatic breastbreast carcinomacarcinoma
Case 4Case 4
!! 76-year 76-year oldold malemale
!! LaryngealLaryngeal squamoussquamous cellcell carcinomacarcinoma operatedoperated
19931993
!! COPDCOPD
!! Heavy Heavy smokersmoker
!! AbundantAbundant fluidfluid in the in the leftleft pleuralpleural cavitycavity
CK 7 CK 7
CK 5/6
TTF-1
Calretinin
ConclusionConclusion fromfrom Case 4 Case 4
!! MildMild suspicionsuspicion for a for a malignancymalignancy, , originorigin of of whichwhich
possiblypossibly in the in the lungslungs
!! In In additionaddition, the , the cellcell populationpopulation containedcontained
atypicalatypical mesothelialmesothelial cellcell proliferationproliferation
SummarySummary and and conclusionsconclusions
!! MostMost of the of the exudatesexudates benignbenign
!! The The absenceabsence of of malignantmalignant cellscells doesdoes notnot rulerule out outmalignancymalignancy
!! MalignantMalignant mesotheliomasmesotheliomas causecause <1 % of <1 % of malignantmalignantpleuralpleural effusionseffusions, and , and onlyonly epithelialepithelial malignantmalignantmesotheliomasmesotheliomas likelylikely exfoliateexfoliate cellscells into into effusioneffusion fluidsfluids
!! ItIt is is necessarynecessary to to firstfirst determinedetermine ifif cellscells in a in a fluidfluid arearetrulytruly malignantmalignant beforebefore secondarilysecondarily determiningdetermining the the typetypeof of malignancymalignancy
!! ImmunohistochemistryImmunohistochemistry of of histologicalhistological sectionssections fromfrom a acellcell blockblock maymay help to help to determinedetermine the the typetype of of malignancymalignancy
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