w w w . j c o l . o r g . b r
Journal
of
Coloproctology
Original
Article
Interobserver
variability
in
histological
diagnosis
of
serrated
colorectal
polyps
Rosimeri
Kuhl
Svoboda
Baldin
a,∗,
Raul
Alberto
Anselmi
Júnior
b,
Marina
Azevedo
b,
Ana
Paula
Martins
Sebastião
a,c,
Mário
Montemor
d,
Luiz
Fernando
Tullio
e,
Luiz
Felipe
de
Paula
Soares
e,
Lúcia
de
Noronha
a,baUniversidadeFederaldoParaná(UFPR),Curitiba,PR,Brazil
bPontifíciaUniversidadeCatólicadoParaná(PUCPR),Curitiba,PR,Brazil cUniversidadePositivo,Curitiba,PR,Brazil
dUniversidadeEstadualdePontaGrossa,PontaGrossa,PR,Brazil eServiceofEndoscopy,HospitalSantaCruz,Curitiba,PR,Brazil
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Articlehistory:
Received31March2015 Accepted8June2015
Availableonline2October2015
Keywords: Colon Polyps Serrated
a
b
s
t
r
a
c
t
Objectives: Tocomparetheinterobservervariabilityinthediagnosticofserratedand non-serrated adenomatouslesionsandhyperplasticpolyps ofcolonbetweentwogroupsof pathologists.
Methods:310colorectalpolypswerestudied,withhistologicaldiagnosesestablishedbya groupofpathologistscomprisingthreegeneralpathologistsforinitialdiagnosis,andtwo gastrointestinalpathologistsforexpertdiagnosis.
Results:High interobservervariability wasobservedinthediagnosisofserrated polyps, when comparingtheinitial diagnosiswiththeexpert diagnosis(kappa=0.102).For the majorityofbothtraditionalserratedadenomasandsessileserratedadenomas(27/31),a diagnosisofhyperplasticpolypswasestablishedattheinitialdiagnosis.
Conclusions: Pooragreementwasobservedinthediagnosisofserratedpolypsbetweenthe twogroupsofpathologists.Theaccuracyinthediagnosisoftheselesionsisessentialfor thepreventionofcolorectalcancer.
©2015SociedadeBrasileiradeColoproctologia.PublishedbyElsevierEditoraLtda.All rightsreserved.
Variabilidade
interobservador
no
diagnóstico
histológico
de
pólipos
colorretais
serrilhados
Palavras-chave: Cólon Pólipos Serrilhado
r
e
s
u
m
o
Objetivo:Comparar a variabilidade interobservador dos diagnósticosdas lesões adeno-matosasserrilhadasenãoserrilhadasepóliposhiperplásicosdocólonentredoiscomitê depatologistas.
∗ Correspondingauthor.
E-mails:rosimeribaldin@gmail.com,rksbaldin@ufpr.br(R.K.S.Baldin). http://dx.doi.org/10.1016/j.jcol.2015.06.008
Métodos: Foramestudados310póliposcolorretais,diagnosticadoshistologicamenteporum comitêdepatologia,compostoportrêspatologistasgeraisparaodiagnósticoinicialepor doispatologistasgastrointestinaisparaodiagnósticodosespecialistas.
Resultados: Houvealta variabilidadeinterobservador no diagnóstico dospólipos serril-hados, ao seremcomparadosodiagnósticoinicial comodiagnósticodos especialistas (kappa=0,102).Amaioriadaslesõesadenomatosasserrilhadassésseisetradicionais(27/31) foidiagnosticadapelodiagnósticoinicialcomopóliposhiperplásicos.
Conclusões: Houvebaixaconcordâncianodiagnósticodospóliposserrilhadoscolorretais entreosdoiscomitêsdepatologistas.Aacuráciadessesdiagnósticoséfundamentalparaa prevenc¸ãodocarcinomacolorretal.
©2015SociedadeBrasileiradeColoproctologia.PublicadoporElsevierEditoraLtda. Todososdireitosreservados.
Introduction
Serratedpolyps(SP),whichrepresent20%ofcolorectalpolyps, maybeprecursorsof15–20%ofcolorectalcancers.1
ThehistologicaldiagnosisofSPhasbeenimprovedsince 1990,fromthenewconceptsofLongacreandFenoglio-Preiser untilthepresentday,beingnaturalthatdifficultiesarisedue tochangeswhichhadoccurred;however,thelackof preci-sionjeopardizesthepatientfollow-upand undervaluesthe method.2
Thecurrentclassificationandnomenclatureofcolorectal SPrecommendedbytheWorldHealthOrganization3
subdi-videcolorectalserratedpolyps(SP)intothreegroups:
• Hyperplasticpolyps(HP)
• Adenomas/sessileserratedpolyps(A/SSP)
- Withcytologicaldysplasia - Withoutcytologicaldysplasia
• Traditionalserratedadenomas(TSA)
Atfirst,hyperplasticpolyps(HP),consideredasbenign con-ditions,didnotrequire follow-up.Usuallytheendoscopists didnotbothertocarryoutresectionofminorHP-likeinjuries, thankstotheabsenceoftheriskofmalignancy.Butcurrently, inthefaceoftheknownriskofmalignanttransformationof adenomas/serratedsessilepolyps(A/SSP),especiallythosein therightcolonandinthefaceofdifficultiesof differentiat-ingbetweencolorectalSPthroughcolonoscopy,removaland histologicalexaminationoftheselesionsaremandatory.4–6
Unknown factorslead tochangesin thelocation ofthe cryptalproliferativezone,aswellasincrypts’ anchoringin theselesions,withvariantsofhistologicalappearance.7What
primarilyallowsustodistinguishbetweenthedifferent cat-egoriesofpolypsaresomearchitecturalchangesresultingof theseproliferativeabnormalities.
Accordingtosomeauthors,8avariationoccursatthe
loca-tionoftheproliferativezone,whichusuallyislocatedinthe lowerthirdofcrypts,andthematurecellsarepushedtoward theintestinallumen.
InHPpatients,theproliferativezoneismaintainedinthe lowerportionofthecrypt,occupyingmorethanhalfofthe lengthofthecrypt.Cellscontinuetomaturetowardthe sur-face;butduetoalateapoptosis,thesecellstendtopileup, formingserratedstructures.
InA/PSS,theproliferativezonemovestowardthelateral aspectofthecrypt.Thisallowsthatmaturecellsmoveboth toward the intestinal lumen and to the base ofthe crypt, whichbecomesenlargedanddistorted,becausethe muscu-larismucosaeblocksthecryptalgrowth.
Incasesoftraditionalserratedadenoma(TSA),the proli-ferativezoneislocatedinsmallectopiccryptsthatdevelop atthesideoftheoriginalcrypt.Thesemini-cryptsdevelopa complexpatternofgrowth.
Objective
Tocomparetheinterobservervariabilityofdiagnosesoflarge bowelserratedandnon-serratedadenomatouspolypsandof HP,inparticularintheSPgroup(HP,A/PSSandTSA)between twogroupsofpathologists.
Methods
ThecaseswereselectedfromfilesofreportsfromtheService ofPathologyofHospitalSantaCruz,Curitiba-Pr.Histological slidesfromcollectedpolypsbycolonoscopyduring2008and stainedwithhematoxylin–eosin(H&E)wereused.
This projectwas approved bythe Ethics Committeefor ResearchinHumanBeingsofHC-UFPR,accordingtothetasks setoutinResolutionCNS466/2012andinOperationalNorm No.001/2013ofCNSunderopinionNo.820,432.
Wecollectedclinicaldata,including patientage,gender, polyplocationinthecolon(right,leftorsigmoid),presenceof singleormultiplepolyps,associationwithcancer,polypsize atendoscopy,polypappearance(sessileorpedunculated), ini-tialpathologicaldiagnosis(bytheDepartmentofPathologyof HospitalSantaCruz,composedofthreegeneralpathologists) andexpertdiagnosis(twogastrointestinalpathologists).
Inclusioncriteria(eligiblecases):
- polyps collected by colonoscopyprocedure performed in patientsattheServiceofEndoscopy,SantaCruzHospital, in2008.
- serratedandnon-serratedadenomatouscolorectalpolyps andHP.
310 slides (polyps) 507 slides (polyps)
452 tests included 407 excluded (there
were no polyps)
859 colorectal exams
197 slides excluded (insufficient material,
with artifacts, etc.)
Fig.1–Sequentialflowchartofcollectionofcasesof colorectalpolyps.
- absenceofinflammatorypolyps.
- absenceofdiagnosticdisagreementamonggeneral pathol-ogists.
- absenceofdiagnosticdisagreementamonggastrointestinal pathologists.
Thesequenceofcollectionofcasesfromthebeginningtill attainingthestudy“n”canbeseeninFig.1.
Areinterpretationoftheslideswascarriedoutbytwo doc-torswithgastrointestinalpathologyspecializationblindedfor thediagnosisinitiallyestablishedbygeneralpathologists.
For statistical evaluation, SP were divided into two groups: the first composed by HP and the second by ser-ratedadenomatouslesions(SAL)comprisingA/PSSandTSA, sincetheselastconditionsclearlydemonstratepotentialfor malignancy.9
Statisticalanalysis
Toevaluatetheagreementbetweendiagnosesofpaired eval-uators, Cohen’s Kappa coefficient was estimated.10 For a
comparisonoftheevaluatorsregardingthelikelihoodof diag-nosis,thebinomialtestwasconsidered.p-Values<0.05were consideredstatisticallysignificant.
Table1–Clinicalandendoscopicdataofcolorectal polypsinthisstudy.
Polyps,total(n) 310 Totalnumberof
patients(orof colonoscopy procedures)
240
Ageofpolypcarriers Minimum19years Maximum91years Median60years
Gender 129women
181men Aspectofthepolyp 281sessile(90.6%)
29withpedicle(9.4%) Localization 135ontherightside(rightand
transversecolon)
175ontheleftside(leftcolon andsigmoid)
Singleormultiple 113singlepolyps 197multiplepolyps
Size 2–30mm
>10mm(22%) 6–9mm(11%) 4–5mm(43%) 2–3mm(24%)
Results
310 casesof colorectal polypsfrom a total of240 patients (somewithmorethanonepolyp)wereconsideredeligiblefor thestudy.Ofthetotalnumberofcases,129polypsinwomen and181inmenwereobserved.Themedianagewas60years, rangingfrom19to91yearsofage.
Astotheendoscopicformofthepolyp,29polyps(9.4%) wereclassifiedbytheendoscopistaspedicledpolyps,and281 (90.6%)assessilepolyps.Endoscopically,thepolypsizeranged from2to30mminitslargestdiameter,withameanof6.5mm perpolyp,withthefollowingdistribution:polyps≥10mm,22% ofcases;6–9mm,11%;4–5mm,43%;and2–3mm,24%.Polyps <2mmwerenotremoved.
As for the location in the colon, 135 polyps were located on the right (ascending and transverse colon) and 175 on the left (descending and sigmoid colon). At endoscopy,113singlepolypsand 197multiplepolypswere found. Thirteen casesof polyp-associated carcinoma were diagnosed.
Table1showspartiallytheresultofdatatabulationof clin-icalandendoscopicdataobtained.
Table2showshowwasthedistributionofdiagnosesbythe pathologycommittee(initialdiagnosis)andby gastrointesti-nalpathologists(expertdiagnosis).
Serratedpolyps
The31SALdiagnosedbygastrointestinal pathologistswere previouslydistributedbythepathologycommitteeasfollows: 27HP(87.1%of31polyps),1TA-LGD(3.2%of31polyps)and3 SAL(9.7%of31polyps).
Table2–Histologicaldiagnosisof310colorectalpolyps inthisstudy,establishedbyagroupofpathologyandby expertsingastrointestinalpathology.
InitialDx(group) ExpertDx
HP 87(28.1%) 46(14.8%)
SAL 3(0.9%) 31(10%)
TA-LGD 172(55.5%) 142(45.8%)
TA-HGD 9(2.9%) 5(1.6%)
TVA-LGD 22(7.1%) 46(14.8%)
TVA-HGD 16(5.2%) 4(1.3%)
VA-LGD 0(0%) 25(8.1%)
VA-HGD 1(0.3%) 11(3.5%)
HP,hyperplastic polyp; SAL,serratedadenomatous lesion (ade-noma/sessile serratedpolypandtraditional serratedadenoma); TA-LGD,tubularadenomawithlow-gradedysplasia;TA-HGD, tubu-laradenomawithhigh-gradedysplasia;TVA-LGD,tubule-villous adenomawithlow-gradedysplasia;TVA-HGD,tubule-villous ade-nomawithhigh-gradedysplasia;VA-LGD,villousadenomawith low-gradedysplasia; VA-HGD,villousadenoma with high-grade dysplasia;initialDx(group),initialdiagnosismadebythepathology committee;expertDx,diagnosismadebytwoexpertpathologists ingastrointestinalpathology;SALvalueswerehighlighted.
Evaluationofagreementbetweeninitialandexpert diagnoses
We tested the null hypothesis of non-correlation between initialdiagnosticevaluationsandofthediagnosis ofexpert pathologistsversusanalternative hypothesis ofagreement. Table3presentstheresultsobtainedinthestudy.
TheCohen’skappacoefficientwasestimatedat0.102.The statisticaltestresultsindicatednon-rejectionoftheabsence ofanagreementhypothesisbetweenthetwogroupsof evalu-ators(p=0.151).Thus,ourstudydoesnotrejectthehypothesis thatthenon-agreementhasbeenaproductofchance.
Additionally,wetestedanullhypothesisfortheprobability thatadiagnosis ofSALisequalforbothgroups of evalua-torsversusanalternativehypothesisofdifferentprobabilities.
0 5 10 15 20 25 30
27 1
3
Dx Initial
LASs
AT-DBG
PH
n.º of cases
Fig.2–Initialdiagnosisof31casesofserratedcolorectal polypsevaluatedbygastrointestinalpathologistsasbeing serratedadenomatouslesions.InitialDx,diagnosticofthe pathologygroup;SALS,serratedadenomatouslesions (adenoma/sessileserratedpolypandtraditionalserrated adenoma);TA-LGD,tubularadenomawithlow-grade dysplasia;HP,hyperplasticpolyp.
Table3–ConcordanceofdiagnosticofSALbetweenthe initialdiagnosisandthatofexperts.
ExpertDx InitialDx Total
SAL OtherDx
SAL 2(0.65%) 29(9.35%) 31(10%)
OtherDx 1(0.32%) 278(89.68%) 279(90%) Total 3(0.97%) 307(99.03%) 310(100%)
Dx,diagnosis;SAL,serratedadenomatouslesion.
The test results indicated rejection of the null hypothesis (p<0.001).Thus,thereisevidencethattheexpertgroup diag-nosishasahigherprobabilityofobtainingaclassificationof SAL(10%ofsamplecases)incomparisonwiththeinitial diag-nosis(0.97%ofsamplecases).
Discussion
Therecognitionoftheexistenceofaserratedcarcinogenesis pathwaymakesitimportanttostandardizethehistological diagnosisofSP,asthefollow-upinpatientswithapolypwill dependonitshistologicclassification.1
Todescribetheagreementbetweenobservers,weusedthe statisticindexkappa(k),whichusesmathematicalcoefficients to adjust the agreement to chance. In this index, a value closeto0indicatesanagreementsimilartothatwhichwould be expectedbychance.k values <0.21,0.21–0.40,0.41–0.60, 0.61–0.80and>0.80representpoor,weak,moderate,strong, andverystronginterobserveragreement,respectively.11
Inareviewof20histologicalsectionsofcolorectalpolyps performed for 20 randomlychosen general pathologists, a correctdiagnosisofadenomawasidentifiedin94%ofthe read-ings;ontheotherhand,foracorrectdiagnosisofcaseswith high-gradedysplasia,only47%ofthereadingswerecorrect. HPwascorrectlydiagnosedin75%ofcases.Theauthorsofthat reviewconcludedfortheoccurrenceofdiscrepancymainlyin thediagnosisofhigh-gradedysplasia.12
From the colonic SPgroup, agreater interobserver vari-abilityisexpected,asthisisarelativelynewconceptamong pathologists,andwhichhasbeenperfectedovertime.Inthis study,theagreementofadiagnosisofserratedpolypsbetween thepathologycommittee(initialdiagnosis)andexpert pathol-ogistsresultedinakappavalue=0.102(poor),showingavery lowcorrelationbetweenthesetwogroups.AdiagnosisofLSA wasestablishedin0.97%ofcasesbythecommittee(first diag-nosis)and in10%ofcasesbygastrointestinal pathologists, showingthatthelatterweremorelikelytoestablisha diagno-sisofSALversusgeneralpathologists.
In 2009, investigators carried out an assessment of 40 proximal colonicpolyps(size≥5mm)removed in2001and
originallyinterpretedasHPbygeneralpathologistsat Indi-ana University, and later revised by three gastrointestinal pathologists.13 In this review, A/PSS diagnoses were
interobserver variation (little agreement on the diagnosis) amongpathologists,similartothevarietyfoundinourstudy: from 31 SALdiagnosed bygastrointestinal pathologists, 27 (87.1%)wereinitiallyclassifiedasHPbythepathology com-mittee.
Otherresearchers14evaluated60casesofpolypsdiagnosed
by4gastrointestinalpathologists,withclassificationof colo-rectalpolypsin5categories:serratedadenoma,hyperplastic polyp,conventional adenoma, mixed polyp,and other ser-ratedpolyps.Acompleteconcordanceoccurredonlyin40% ofcases.Thekvalueforobserverswas0.49.Thekvaluefor thediagnosisofserratedadenomaversusallotherpolypswas 0.38.Theauthorsconcludedthatgastrointestinalpathologists achievedamoderateagreementinthediagnosisof colorec-talserratedpolyps,withweakagreementinthediagnosisof serratedadenomas.
Someauthors1 appliedan onlinequestionnaire with20
colorectal polyps, containing 3 images of each lesion, to 168pathologists, inorder totest the diagnostic variability, especiallyindistinguishingthetwoprecursorlesionsofthe serratedpathwayforcolorectalcancer,TSAandA/PSS, com-paredtoHPandtubular-villousadenomas(TVA).Thecorrect responsesforA/PSS (54%)andTSA(44%)were significantly lowerthanthoseresponsesforTVA(90%)andHP(80%).The authorsmentionthatTSAcouldbeconfusedwithTVAinthose casesinwhichtheserratedarchitecturewaslesspronounced, andinthefaceofaprominentnuclearpseudo-stratification andhyperchromasia.
Some considerations can be proposed with respect to the growing curve of diagnoses of A/PSS by the pathol-ogy committee in relation to that of gastrointestinal pathologists:
- Thediagnosisestablishedbythecommitteewascarriedout earlier(2008),andtheexpertdiagnosiswasmorerecently established(2013)andthereforemoreupdated.
- Thegreaterexperienceanddeeperunderstandingofcriteria forthediagnosisofserratedpolypsamonggastrointestinal pathologists.
Therefore,wecanconcludethat,betweenthetwogroups studied,theinterobservervariabilityinthediagnosisof colo-rectalserratedpolypswashigh,possiblyduetodifferencesin thedatesofdiagnoses,suspicionlevel,andabetterknowledge ofmorphologicalcharacteristics bygastrointestinal pathol-ogists. The relevance of this issue is important, because the follow-updepends solelyon thehistological diagnosis. Increasingthe qualityofpreventionofcolorectalcancer in the community can be achieved with a more consistent
diagnosisofthesepolyps.Thevalueofthisstudyisthesense ofself-criticismthatboostedtheirauthors.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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