OfficialreprintfromUpToDate

www.uptodate.com2015UpToDate

Ampullarycarcinoma:Epidemiology,clinicalmanifestations,diagnosisandstaging
Author
JohnAMartin,MD

SectionEditor
DeputyEditors
DouglasAHowell,MD,FASGE,FACG
AnneCTravis,MD,MSc,FACG,AGAF
DianeMFSavarese,MD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Mar2015.|Thistopiclastupdated:Jan06,2015.
INTRODUCTIONPeriampullarytumorsareneoplasmsthatariseinthevicinityoftheampullaofVater.They
canoriginatefromthepancreas,duodenum,distalcommonbileduct(CBD),orthestructuresoftheampullary
(ampullaofVater)complex.TheampullaofVaterisformedbytheduodenalaspectofthesphincterofOddi
muscle,whichsurroundstheconfluenceofthedistalCBDandmainpancreaticductaswellasthepapillaof
Vater,amucosalpapillarymoundatthedistalinsertionoftheseductsonthemedialwalloftheduodenum(figure
1).Ampullarycarcinomasaredefinedasthosethatarisewithintheampullarycomplex,distaltothebifurcationof
thedistalcommonbileductandthepancreaticduct(figure2).
Thepapillaisanipplelikestructureonthemedialaspectofthesecondportionoftheduodenumbestvisualized
withasideviewingendoscope.Thedistalbileandventralpancreaticductstraversetheduodenalwallinthis
locationandopenintotheduodenallumenthroughthesmallmucosalelevationofthepapillaofVater.
Theepidemiology,clinicalfeatures,diagnosis,andstagingofampullarycarcinomawillbereviewedhere.
Treatmentofampullarycancersandtheapproachtothepatientwithampullaryadenomaispresentedseparately.
(See"Ampullarycarcinoma:Treatmentandprognosis"and"Clinicalmanifestationsanddiagnosisofampullary
adenomas"and"Treatmentofampullaryadenomas".)
EPIDEMIOLOGYANDBIOLOGICBEHAVIORNeoplastictransformationoftheintestinalmucosaoccurs
morecommonlyneartheampullathanatanyothersiteinthesmallintestine.Despitethis,primaryampullary
tumorsarerare,withanincidenceofapproximatelyfourtosixcasespermillionpopulation[14].Theyaccountfor
only6percentoflesionsthatariseintheperiampullaryregion[5],butareresponsiblefor20percentofalltumor
relatedobstructionsofthecommonbileduct[6].Thereissomeevidencethattheincidencehasincreasedover
thelast30years[3].
Bothbenignandmalignantampullarytumorscanoccursporadicallyorinthesettingofageneticsyndrome.The
incidenceofampullarytumorsisincreased200to300foldamongpatientswithhereditarypolyposissyndromes,
suchasfamilialadenomatouspolyposis(FAP)andhereditarynonpolyposiscolorectalcancer(HNPCC)compared
withthegeneralpopulation[79].Surveillanceendoscopyisparticularlyimportanttodetectearlyampullarylesions
inpatientswithFAPgiventhehighincidenceofcoexistingpremalignantduodenaladenomatouspolyps.Upto90
percentofpatientswithFAPdevelopadenomasintheuppergastrointestinaltract[10].(See"Familial
adenomatouspolyposis:Screeningandmanagementofpatientsandfamilies".)
Theaverageageatdiagnosisofsporadicampullarycarcinomasis60to70yearsold[8,1113].Incontrast,
patientswhoseampullarycarcinomasariseinthesettingofaninheritedpolyposissyndromeusuallypresentatan
earlierage,dueinparttoendoscopicscreeningandsurveillanceprograms.
BiologicbehaviorSeverallinesofevidencesuggestthatthebiologyofprimaryampullaryadenomasand
carcinomasismoreanalogoustointestinalratherthanpancreaticobiliaryneoplasms:
Thehistologyofprimaryampullaryneoplasmsmoreoftenresemblesthatofadenomasandadenocarcinomas
ofintestinaloriginratherthanpancreaticobiliaryorigin.Inonestudyof170ampullarycarcinomas,themost
commonhistologicsubtypewasintestinal(47percent),followedbypancreatobiliary(24percent),poorly
differentiatedadenocarcinomas(13percent),intestinalmucinous(8percent),andinvasivepapillary(5

percent)[14].
Ampullarycarcinomasarethoughttoarisefromampullaryadenomas,apremalignantprecursorlesion
displayingtheadenomacarcinomasequenceobservedincolorectalneoplasia.Moreover,patientswithFAP
haveasignificantlyincreasedincidenceofbothampullaryandcolorectalcancersrelativetothegeneral
population,suggestingthatthemechanismofampullaryandcolorectalcarcinogenesismaybesimilar[15].
Krasmutationsareanearlyeventinampullarycarcinogenesis,withanincidence(37percent)thatissimilar
tothatincoloncancer(upto50percent)[16].(See"Moleculargeneticsofcolorectalcancer",sectionon
'Oncogenes'.)
Expressionprofilingofcyclooxygenase2(COX2)byampullarycarcinomasismoreconsistentwitha
neoplasmofintestinaloriginthanpancreaticobiliaryorigin.HighCOX2expressionhasbeendetectedin78
percentofampullarycarcinomas[17].Ofampullarycarcinomasclassifiedashavinganintestinalorigin,95
percenthadhighCOX2expression,whereasonly50percentoflesionswithapancreaticobiliaryorigin
demonstratedhighCOX2expression.
Trueampullarycancershaveabetterprognosisthanperiampullarymalignanciesofpancreatic[1820]or
extrahepaticbiliary[21]origin.Resectabilityratesarehigher(over90percentinsomecontemporaryseries),
andfiveyearsurvivalratesareapproximately30to50percent,eveninpatientswithlymphnode
involvement.Incontrast,fewerthan10percentofpatientswithcompletelyresectednodepositivepancreatic
cancerarealiveattwoyears.(See"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerand
prognosis"and"Ampullarycarcinoma:Treatmentandprognosis".)
SubdividingadenocarcinomasoftheampullaofVateraccordingtohistologicsubtypeandimmunohistochemical
stainingpatternintodistinctsubsetswithdifferingbiologicbehaviorhasprognosticimportance.Inaretrospective
studyof208patientstreatedforampullaryadenocarcinomainSydney,Australia,thosewithahistomolecular
pancreaticobiliaryphenotype(CDXnegative,MUC1positive)hadasignificantlyworseoutcomethandidthose
withanintestinalphenotype(CDXpositive,MUC1negative),withmediansurvivalof16versus116months[22].
Whenhistomolecularphenotypewascombinedwiththelymphnodestatus,threesubsetsofampullary
adenocarcinomasemergedwithsignificantlydifferentsurvivaloutcomes:
Patientswithanodenegative,nonpancreaticobiliaryhistomolecularphenotypetumorhadanexcellent
prognosis(fiveyearsurvival88percent).
Patientswithanodepositivepancreaticobiliaryphenotypehadapoorprognosis(fiveyearsurvival20
percent).
Theremainingpatients(nodepositivenonpancreaticobiliaryphenotype,nodenegativepancreaticobiliary
phenotype)hadanintermediateprognosis(fiveyearsurvival47percent).
Theresultswerecomparableintwoadditionalindependentcohortsof90patientsfromGlasgow,Scotland,and46
fromVerona,Italy.
Identificationofprognosticallyrelevantsubgroupshasalsobeenachievedbyuseofgeneexpressionprofilingin
conjunctionwithimmunohistochemicalstainingforcytokeratins7and20[23].However,moleculartechniques
suchasthesearenotyetreadyforclinicalapplication.(See"Overviewofgeneexpressionprofiling,proteomics,
andmicroRNAprofilinginclinicaloncology".)
Whetherandhowthisinformationcouldbeusedtoindividualizetreatmentdecisions,particularlyaboutadjuvant
therapy,isunclear.Theimpactofadjuvanttherapyonoutcomesaccordingtohistomolecularphenotypecouldnot
beaddressedinthestudydescribedabovesinceonlyaminorityofpatients(64of208)inallthreecohorts
receivedadjuvantchemotherapy,anditwasnotrandomlyassigned[22].Prospectivestudyoftreatmentselection
baseduponhistomolecularphenotypeisneededbeforeconclusionscanbedrawn.Atpresent,adjuvanttherapy
recommendationsforpatientswithampullarycancerfollowguidelinesestablishedforpancreaticcancer,rather

thanintestinalcancer.(See"Ampullarycarcinoma:Treatmentandprognosis",sectionon'Adjuvanttherapy'.)
CLINICALMANIFESTATIONSAswithampullaryadenomas,themostcommonpresentingsymptomof
ampullarycarcinomaisobstructivejaundice(80percent)causedbycompressionofthedistalbileductbythe
tumor[11,24].(See"Clinicalmanifestationsanddiagnosisofampullaryadenomas".)
Ampullarycancersarenotusuallysuspectedasacauseofobstructivejaundicebecauseoftheirlowerincidence
relativetootherperiampullarymalignancies.Additionalsymptomsmayincludediarrheaduetofatmalabsorption
(steatorrhea),mildweightloss,andfatigue.
Uptoonethirdofpatientshavechronic,frequentlyoccultgastrointestinalbloodlosswithanassociatedmicrocytic
anemiaorhemepositivestools.Patientsoccasionallypresentwithfrankbleedingduetosloughingofthetumor,a
conditionexacerbatedbytheuseofantiplateletagentssuchasaspirinandclopidogrel.Inonereport,nonspecific
symptomsincludeabdominalpain(45percent),fever(45percent),mildnausea,anddyspepsia[25].Largelesions
mayproducegastricoutletobstructionassociatedwithseverenauseaandvomiting.
DIAGNOSISANDSTAGINGThediagnosisofanampullarycarcinomaisestablishedbyacombinationof
endoscopic,radiologic,andhistologicfeatures.Accuratestagingisessentialforplanningsurgicaltreatment.
TNMstagingsystemThemostcommonlyusedstagingsystemisthetumornodemetastasis(TNM)system
ofthecombinedAJCC(AmericanJointCommitteeonCancer)/UICC(InternationalUnionAgainstCancer)(table
1)[26].
Intheabsenceofmetastases,theprognosisofanampullarycarcinomadependsprimarilyupontwofactors:the
degreeoflocaltumorinvasion,asreflectedbytheTstage,andthepresenceoflymphaticspread,asreflectedby
theNstage.
DiagnosticevaluationThediagnosticevaluationofajaundicedpatientwithasuspectedmalignantbileduct
obstructionisdesignedtoeliminatebenigntumorsorgallstonesfromthedifferential,andtoestablishtheextentof
tumorinvasionandspread.Althoughadvancedendoscopictechniquescanhelptodifferentiateampullary
adenomasfromcarcinomas,itmaybedifficulttocompletelyexcludeacarcinomawithoutcompleteresectionof
thelesion.Ampullaryadenomashavethepotentialtoundergomalignanttransformation,andanoccultfocusof
carcinomamaybepresentwithinapredominantlybenignadenoma.(See"Clinicalmanifestationsanddiagnosisof
ampullaryadenomas".)
Atransabdominalultrasound(US)isareasonablefirsttestinpatientspresentingwithobstructivejaundice,butit
willgenerallynotshowthetumor.Helicalcomputedtomography(CT)scanningshouldbeobtainedtovisualizethe
pancreasandsurroundingstructures.Althoughitsspatialresolutionisinadequatetodeterminethedegreeoflocal
tumorinvasion,itisthemostusefultesttoexcludethepresenceofdistantmetastases.(See'Transabdominal
ultrasonography'belowand'AbdominalCT'below.)
Endoscopicretrogradecholangiopancreatography(ERCP)isthesinglemostusefulendoscopicstudyfor
diagnosingampullarycarcinomabecauseitpermitsidentificationofthetumor,biopsy,anddecompression,if
needed.Whileendoscopicultrasonography(EUS)isassensitiveasERCPandsuperiortoCTandtransabdominal
USfordetectingsmallampullarytumors,itistypicallynotrequiredfordiagnosis.Itmayhavearolein
preoperativestagingbutmayresultinoverstaging.Asaresult,wedonotroutinelyemployEUSforthediagnosis
andstagingofampullarycarcinoma.(See'ERCP(endoscopicretrogradecholangiopancreatography)'belowand
'Endoscopicultrasonography(EUS)'below.)
Differentiatingaprimaryampullarycarcinomafromothermorecommonperiampullarymalignancies(arisinginthe
pancreas,duodenum,orbileduct)ischallenging.Althoughthedistinctionmaybeevidentafterradiographicand
endoscopicevaluation,itmaynotbepossibletodeterminethetissueoriginofamalignantperiampullaryneoplasm
untilresectionandhistopathologicevaluationoftheentiresurgicalspecimeniscompleted[27].Thisisparticularly
trueifthelesionislargeandobstructstheduodenallumen.Fromasurgicalstandpoint,thedistinctionbetween
ampullaryandperiampullarycancersisnotessentialpreoperativelysincethetreatmentisthesameforboth

lesions.However,theoncologicimplicationsandprognosisoftheampullaryandperiampullarytumorsare
substantiallydifferent.(See"Overviewofsurgeryinthetreatmentofexocrinepancreaticcancerandprognosis"
and"Diagnosisandstagingofsmallbowelneoplasms",sectionon'Adenocarcinoma'and"Treatmentoflocalized
cholangiocarcinoma:Adjuvantandneoadjuvanttherapyandprognosis",sectionon'Distalcholangiocarcinoma'.)
TransabdominalultrasonographyTransabdominalultrasonography(US)shouldbethefirstimagingstudy
orderedforpatientswithjaundice,sinceUScanidentifyintrahepaticandextrahepaticbileductdilatationand
gallstones.However,overlyingbowelgasfrequentlyobscuresthedistalbileduct,ampulla,andpancreas.Inone
study,only10of127ampullarymassesweredetectedbyultrasound[28].Theoverallaccuracywas15percent,
accordingtoonestudy[29].Asaresult,abdominalCTshouldbeorderedasthenextdiagnosticprocedureifUS
doesnotdemonstrategallstonesoranobviouspancreaticheadmassinajaundicedpatient.
AbdominalCTCTismoresensitivethanUSforevaluatingtheperiampullaryregion(image1).A"pancreatic
massprotocol"CTshouldbeordered.Specifically,patientsshouldreceivewaterastheoral"contrastagent"(to
distendtheduodenumandimprovevisualizationoftheduodenallumenandadjacentpancreas),andIVcontrastis
injectedasabolustopermitbotharterialandvenousphaseimaging.Imagesareacquiredat1.0to2.5mm
intervalstoimprovethesensitivityofpancreaticimaging.(See"Clinicalmanifestations,diagnosis,andstagingof
exocrinepancreaticcancer",sectionon'Imagingstudies'.)
AlthoughhelicalCTcandetectmassesobstructingthedistalcommonbileduct(CBD),itssensitivityusuallydoes
notpermitthevisualizationofsmallampullaryneoplasmswithintheduodenallumen[30].Inonereport,theoverall
accuracywasonly20percent[29].Furthermore,CTbyitselfisinadequateforstagingampullarycancersbecause
itlacksthespatialresolutiontodeterminethedegreeoflocaltumorinvasionintotheduodenalwall,adjacent
pancreas,orthepresenceofmajorvascularinvolvement[31].Ontheotherhand,CTisgenerallythemostuseful
studytoevaluateforthepresenceofdistantmetastaticdiseasewhichmostfrequentlyinvolvestheregionallymph
nodes,liver,peritoneum,lungs,andbone.
ERCP(endoscopicretrogradecholangiopancreatography)Inajaundicedpatientwithsuspectedmalignant
bileductobstruction,ERCPisthepreferredinitialendoscopicstudysinceitpermitssimultaneousendoscopic
visualizationoftheampulla,cholangiographyofthepancreaticandbileducts,biopsyfromthepapillaand
ampullarysegmentoftheCBDorpancreaticduct,andplacementofastentforbiliarydecompression,if
necessaryandtechnicallyfeasible.However,ERCPcannotdeterminetheextentoflocaltumorinvasionofan
ampullarycarcinomaintotheadjacentduodenumorpancreaticparenchyma,informationthatisessentialfor
preoperativestagingandsurgicalplanning.
Mostampullarycancersareobviousendoscopically(image2).Ifanexophyticampullarytumorisidentifiedthat
hastheappearanceofanadenoma,malignancyshouldbestronglysuspectedifthemassisulceratedorover3
cminsize.However,becausethefalsenegativerateofendoscopicbiopsyisashighas50percent,anegative
resultisinsufficienttoexcludethepresenceofmalignancyinanampullarylesion[3237].Theoverallaccuracyof
diagnosiswithERCPinonereportwas88percent(p>0.05)[38].
Attemptstoenhancetheaccuracyofendoscopicbiopsyincludetheacquisitionoftissueatleast48hours
followingsphincterotomy[39,40],theperformanceofmultiplebiopsies[41],andtheuseofpolymerasechain
reaction(PCR)orimmunohistochemicalstainingtodetectp53(atumorsuppressorgenethatisfrequentlylostin
periampullaryneoplasms)orKrasgenemutations[16,4246].Noneofthesemethodsareusedroutinelyincurrent
clinicalpractice.
MRCPandpercutaneoustranshepaticcholangiographyAmpullaryobstructioncanalsobeevaluatedby
magneticresonancecholangiopancreatography(MRCP)orpercutaneoustranshepaticcholangiography(PTC)in
patientswithcontraindicationstoERCP(eg,thosewhohaveundergonegastricsurgery,suchasaRouxenY
gastrojejunostomy,withresultantanatomythatmaymakeendoscopicaccessoftheduodenumtechnically
challengingorimpossible,evenwithdeepenteroscopytechniques).However,neitheroftheseimagingmodalities
permitsdirectluminalvisualizationofthepapillaryaspectoftheampulla,nordotheyprovideaccessfortissue
acquisitionviadirectforcepsbiopsy.

MRCPisanoninvasivemethodofimagingthepancreaticobiliarytreeviamagneticresonanceimaging.Some
authorsrecommendthisapproachinplaceofERCPinpatientswhowillnottolerateinvasiveproceduresorin
whomalargetumoroccludestheorificeofthepancreaticobiliaryducts,thuspreventingcannulationandduct
opacificationatthetimeofERCP.Ampullarycarcinomasappearasmasses(fillingdefects)protrudingintothe
duodenallumen,withcharacteristicdelayedenhancementandhyperintensityondiffusionweightedimaging
[47,48].InonereporttheoverallaccuracyofdiagnosiswithMRCPwas76percent[38].(See"Magnetic
resonancecholangiopancreatography".)
Incontrast,PTCisaninvasiveprocedureduringwhichthebiliarytreeisaccessedpercutaneouslyusinganeedle
insertedthroughtheparenchymaoftheliverintoanintrahepaticbileduct,thencontrastopacifiedunder
fluoroscopy.PTCismostcommonlyperformedwhenthebiliarytreeisdilatedandERCPhasfailedtocannulate
oradequatelydemonstratethebiliaryanatomy.PTCprovidesnotonlycholangiographybutalsotheopportunityfor
brushcytology(althoughnotforcepsbiopsyforhistology)ofradiographicstrictures,althoughampullarylesions
thatdonotextendintothedistalCBDmaynotbeamenabletotissueacquisitionviathisroute.Anotherlimitation
ofPTCisthatitcannotdirectlyvisualizeampullarylesions,duodenaltumoringrowth,orinvolvementofthe
pancreaticduct.(See"Percutaneoustranshepaticcholangiography".)
Endoscopicultrasonography(EUS)Endoscopicultrasonography(EUS)isassensitiveasERCPand
superiortoCTandtransabdominalUSfordetectingsmallampullarytumors,thoughitistypicallynotrequiredfor
diagnosis[29,47,4957].Itmayhavearoleinpreoperativestagingtolookfortumorextensionandtodeterminethe
depthoftumorinvasion,butitmayresultinoverstaging.Asaresult,wedonotroutinelyemployEUSforthe
diagnosisandstagingofampullarycarcinoma.
BecausebiliaryandpancreaticsphincterotomyandstentplacementcannotbeperformedusingEUSequipment,
patientswhorequiretherapeuticinterventionmustalsoundergoanERCP,whichcanoftenbeperformed
concomitantly.
RoleindiagnosisMostcancersareclearlyseenendoscopically,andampullectomywillprovidetissuefor
histologicdiagnosis,soEUSisgenerallynotrequiredfordiagnosis.Inaddition,EUSwillnotbehelpfulfor
identifyingfociofcarcinomawithinotherwisebenignlesions.EUSmaybeindicatedfortheoccasionalbiopsy
negativeampullarylesionthathasequivocalendoscopicfeaturesofmalignancy.(See"Treatmentofampullary
adenomas",sectionon'Endoscopicampullectomy'.)
IfmalignancyissuspectedinapatientundergoingEUS,fineneedleaspiration(FNA)oftheampulla,papilla,and
surroundingdeeperstructuresincludinglocallymphnodescanbeobtainedduringtheprocedure.However,a
negativeresultdoesnotexcludethepresenceofamalignantfocuswithinanadenoma.(See"Endoscopic
ultrasoundguidedfineneedleaspirationbiopsyinthegastrointestinaltract".)
Inonereport,theoverallaccuracyofEUSguidedfineneedleaspirationbiopsy(FNAB)forprimarymassesofthe
ampullaryregionwas89percent,withasensitivityof82percentandaspecificityof100percent[58].
RoleinstagingEUSisthemostaccuratemodalityavailabletoassessthetumor(T)stageofampullary
tumors,whichiscriticalforplanningsurgicalintervention.MultipleseriesconsistentlydocumentprimaryTstaging
accuraciesof70to90percent[7,49,51,54,5965].However,EUSstagingmethodstendtooverestimatethedepth
oftumorinvasionandresultingTstage,whichcouldleadtoinappropriatetreatment[6].Accuracymaybe
decreasedinthepresenceofanendobiliarystent[53].EUSislesshelpfulfornodal(N)staging.
EUSiscapableofobtainingimagesofthedistalbiliaryandpancreaticducts,permittingassessmentoflocal
intraductaltumorextension.EUSalsoaccuratelydemonstratesthedepthoftumorpenetrationintotheduodenum
bydemonstratingobliterationoftheinterfacebetweenthetumorandthemuscularispropriaoftheduodenum(a
featurethatupstagesthetumortoT2).Tumorextensionintothepancreasisassessedbythedepthofinvasion
(<2cmsignifyingT3,and>2cmorcontiguousspreadtoadjacentorganssignifyingT4disease)(image3).
EUSislessaccurateforNstagingthanitisforTstaging.Ampullarycancersdrainintotwolymphnodebasins:

theretroduodenopancreaticchainandthesuperiormesentericchain.Onestudyreportedasensitivityand
specificityof67and96percent,respectively,forEUSdetectionofnodalmetastaseswhenabnormalnodeswere
seen(definedasthoseoveronecentimeterindiameterandlocatedintheabovetwopositions)[65].Another
seriesfoundsensitivityandspecificityratesof69and38percent,respectively,whenallvisualizedlymphnodes
presentaroundtheduodenopancreaticblockwerepresumedtobemetastatic,regardlessofsizeorposition[64].
However,othershavereportedsensitivityratesaslowas21percentfordetectionofnodalmetastasesbyEUS
[66].
EUSguidedFNAofsuspiciouslymphnodesmayfurtherincreasetheaccuracyofnodalstaging.Thistopicis
discussedindetailelsewhere.(See"Endoscopicultrasoundguidedfineneedleaspirationbiopsyinthe
gastrointestinaltract",sectionon'Pancreaticmasses'.)
IntraductalultrasonographyThetechnicalevolutionofEUShasledtothedevelopmentofsmallcaliber
intraductalultrasound(IDUS)miniprobes(approximately2mm),whichcanbepassedthroughstandard
endoscopesdirectlyintothebileorpancreaticduct.Thesmallcaliber,flexibility,andexcellentimagequality
producedbythesecathetersmakesthemusefulforevaluatingavarietyofbiliaryandpancreaticdisorders.IDUS
accuratelyvisualizestheanatomyofthepapillaandistheonlyprocedurethatreliablydifferentiatesthesphincter
ofOddimusclefromtheremainderofthepapilla.Asaresult,IDUScanbeusefulfordiagnosingandassessing
thesizeandextentofpapillarytumors.Inastudyof40patientswithampullarycarcinoma,IDUSwasmore
accuratethanEUSforTstagingandevaluatingductalinvasion[67].(See"Intraductalultrasoundofthe
pancreaticobiliaryductalsystem".)
MagnificationendoscopywithnarrowbandimagingNarrowbandimagingusesopticalfilterstoenhance
visualizationofmicrovesselsandmucosalsurfacearchitectureingastrointestinaldiseases.Thetechnique
demonstratesabnormalvesselsassociatedwithhighgradedysplasiaonthesurfaceofhighgradeadenomasand
adenocarcinomas.Abnormalvesselshavenotbeenidentifiedonthesurfaceofbenignampullaryadenomaswith
hyperplasticorinflammatoryhistology.Preliminarystudieshavesuggestedapotentialroleforevaluationof
ampullarylesions[68].
LiverbiochemicaltestsBloodchemistriescannotestablishthediagnosisofampullarycarcinoma,butmay
reflectthepresenceofcholestasiswhenanampullaryneoplasmresultsinpartialorcompletebiliaryobstruction.
Patientsgenerallyhaveacholestaticpatternofliverbiochemicaltestabnormalities,althoughaminotransferases
mayalsobeelevated[25].Theprothrombintimemaybeelevatedduetoimpairedabsorptionoffatsoluble
vitaminsincludingvitaminK[69].
SerumtumormarkersSerumtumormarkersarenotspecificforampullarycarcinomasandhavelimited
diagnosticapplication.Nevertheless,someampullarycancersareassociatedwithincreasedserumlevelsof
carbohydrateantigenCA199and/orcarcinoembryonicantigen[19,70],andserialassayofthesetumormarkers
maybeusefulforposttreatmentfollowup.(See"Ampullarycarcinoma:Treatmentandprognosis",sectionon
'Posttreatmentsurveillance'.)
SUMMARYANDRECOMMENDATIONSPatientswithampullarycancermostcommonlypresentwith
jaundice(80percent)causedbyobstructionofthedistalbileductbytumor.Diagnosisandstagingareachievedby
acombinationofendoscopic,radiologic,andhistologicfeatures(algorithm1).Therearetwomajorconsiderations:
identificationofthetumor,anddistinctionfromanampullaryadenomaortumorarisingfromoutsideoftheampulla
(mainlypancreaticcarcinomaoradistalcholangiocarcinoma).
Atransabdominalultrasound(US)isareasonablefirsttestinpatientspresentingwithobstructivejaundice,
butitwillgenerallynotshowthetumor.Helicalcomputedtomography(CT)scanningshouldbeobtainedto
visualizethepancreasandsurroundingstructures.Althoughitsspatialresolutionisinadequatetodetermine
thedegreeoflocaltumorinvasion,itisthemostusefultesttoexcludethepresenceofdistantmetastases.
(See'Transabdominalultrasonography'aboveand'AbdominalCT'above.)
Endoscopicretrogradecholangiopancreatography(ERCP)isthesinglemostusefulendoscopicstudysinceit

permitsidentificationofthetumor,biopsy,anddecompression,ifneeded.Whileendoscopicultrasonography
(EUS)isassensitiveasERCPandsuperiortoCTandtransabdominalUSfordetectingsmallampullary
tumors,itistypicallynotrequiredfordiagnosis.Itmayhavearoleinpreoperativestagingbutmayresultin
overstaging.Asaresult,wedonotroutinelyemployEUSforthediagnosisandstagingofampullary
carcinoma.(See'ERCP(endoscopicretrogradecholangiopancreatography)'aboveand'Endoscopic
ultrasonography(EUS)'above.)
ACKNOWLEDGMENTTheauthorsandUpToDatewouldliketothankDr.A.JamesMoser,whocontributed
toearlierversionsofthistopicreview.
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
Topic655Version11.0

GRAPHICS
SphincterofOddiinrelationtotheampullaofVater

DiagramoftheanatomyofthesphincterofOddiandampullaofVater.The
musclefibersofthesphincterofOddisurroundtheintraduodenalsegmentof
thecommonbileductandtheampullaofVater.Acircularaggregateofmuscle
fibers,knownasthesphinctercholedochus(orsphincterofBoyden),keeps
resistancetobileflowhigh,andtherebypermitsfillingofthegallbladderduring
fastingandpreventsretrograderefluxofduodenalcontentsintothebiliarytree.
Aseparatestructure,calledthesphincterpancreaticus,encirclesthedistal
pancreaticduct.Themusclefibersofthesphincterpancreaticusareinterlocked
withthoseofthesphinctercholedochusinafigureeightpattern.
Graphic78786Version3.0

Locationsampullarytumors

Graphic53240Version1.0

TNMstagingforampullarycarcinoma
Primarytumor(T)
TX

Primarytumorcannotbeassessed

T0

Noevidenceofprimarytumor

Tis

Carcinomainsitu

T1

TumorlimitedtotheampullaofVaterorsphincterofOddi

T2

Tumorinvadesduodenalwall

T3

Tumorinvadespancreas

T4

Tumorinvadesperipancreaticsofttissuesorotheradjacentorgansorstructuresother
thanpancreas

Regionallymphnodes(N)
NX

Regionallymphnodescannotbeassessed

N0

Noregionallymphnodemetastasis

N1

Regionallymphnodemetastasis

Distantmetastasis(M)
M0

Nodistantmetastasis

M1

Distantmetastasis

Anatomicstage/prognosticgroups
Stage0

Tis

N0

M0

Stage

T1

N0

M0

Stage
IB

T2

N0

M0

Stage

T3

N0

M0

T1

N1

M0

T2

N1

M0

T3

N1

M0

T4

AnyN

M0

AnyT

AnyN

M1

IA

IIA
Stage
IIB

Stage
III
Stage
IV

Note:cTNMistheclinicalclassification,pTNMisthepathologicclassification.
UsedwiththepermissionoftheAmericanJointCommitteeonCancer(AJCC),Chicago,Illinois.The
originalsourceforthismaterialistheAJCCCancerStagingManual,SeventhEdition(2010)publishedby
SpringerNewYork,Inc.

Graphic77606Version9.0

Ampullarycarcinoma

SpiralabdominalCTscanshowingasmallampullarymass(arrow)in
a74yearoldwomanwithoccultgastrointestinalbloodloss.Notethat
thepancreaticheadappearsuninvolved.
CourtesyofAJamesMoser,MD.
Graphic63759Version2.0

Ampullarycancerendoscopy

Endoscopicviewofanampullarycarcinoma.Notethenodular
appearanceofthetumor.
CourtesyofDavidCarrLocke,MD.
Graphic70689Version2.0

Ampullarycarcinoma

EndoonographicimageobtainedduringEUSshowinginvasionofan
ampullarylesionintothepancreatichead(T3).Thetumorclearly
penetratesthemuscularispropria.
CourtesyofAJamesMoser,MD.
Graphic72481Version2.0

Ampullarycarcinomaalgorithm

Graphic51015Version1.0