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,CASEREPORT,Transmissionofbreastcancerbyasinglemultiorgandonorto4transplantrecipients,2,LiteraturesSource,Americanjournaloftransplantation,YvetteA.H.Matser1|MattyL.Terpstra2|SilvioNadalin3|GeorgeD.Nossent4|JandeBoer5|BarbaraC.vanBemmel6|SusannevanEeden7|KlemensBudde8|SusanneBrakemeier8|FrederikeJ.Bemelman2,Author,IF:6.493,3,1、INTRODUCTION,Thiscasereportdescribesthetransmissionofbreastcancerfromasingleorgandonorto4recipientsmanyyearsafterdonation.Atthetimeofdonation,itwasunknownthatthedonorsufferedfromamalignancy.,2、CASEREPORT,The53-year-olddonorinthiscasehadnorelevantmedicalhistoryanddonatedherkidneys,lungs,liver.Theother4recipientsdevelopeddonor-derivedbreastcancer(provenbyDNAmicrosatellite)within16monthsto6yearsaftertransplantation.Unfortunately,thedouble-lungrecipient,left-kidneyrecipient,andliverrecipientdiedduetothedonor-derivedbreastcancer.Theright-kidneyrecipientremainsalive.Afterthediagnosisofbreastcancerinthetransplantedkidney,thepatientunderwenttransplantnephrectomy,hisimmunosuppressionwasstopped,chemotherapywasinitiated,andheachievedcompleteremissiondespitewidelymetastasizeddisease.,5,FIGURE11,6,、Double-lungrecipient,Thelungswereallocatedtoa42-year-oldfemalewhosufferedfromend-stagelungdiseaseduetosarcoidosiswithremittingpneumothoraces.InAugust2008(16monthsaftertransplantation),thepatientwasadmittedtothehospitalbecauseoftransplantdysfunction.AchestX-rayshowedmediastinallymphadenopathy.Amediastinallymphnodebiopsyshowedestrogenreceptorandprogesterone-receptorpositive(ER+,PR+)adenocarcinoma.TheFES-PETscanrevealedabnormalitiesinthelungsandbones.Thepatientsimmunosuppressionwasreduced.InSeptember,aCTscanshowedlesionsintheliverandbonesthatwerecompatiblewithmetastases.Sixmonthslater,shepresentedwithincreasingthoracicpain,hypercalcemia,andrenalinsufficiency.InAugust2009,palliativecarewasstarted,andafterafewdays,thepatientpassedaway.Extensiveresearchwith5independentDNAmicrosatellitemarkersrevealedthatthisbreastcancerwasdonorderived.,7,、Left-kidneyrecipien,Theleft-kidneyrecipientwasa62-year-oldfemale.SheunderwentapostmortemdonorkidneytransplantationinApril2007underhighlyurgentstatusbecauseofanimminentlackofvascularaccess,whichwaslimitingdialysisoptions.WhenEurotransplantreportedthedeathofthelungrecipientin2010duetodonor-derivedmetastaticbreastcancer,thesituationwasdiscussedwiththepatient.Itseemedthatremovalofthetransplantwasnotanoptionbecauseofalackofaccess.ACTscanofthetransplantedkidneywasperformed,whichmajorpathology.Prophylacticantihormonaltreatmentwasconsidered.However,becausetherewerenodataintheliteraturesupportingthistreatment,itwasfinallydecidednottostartantihormonaldrugs.Fiveyearslater,thepatientpresentedwithhypercalcemia,weightloss,andmalaise.ACTscanoftheabdomenshowedmultiplelesionsintheliver.AliverbiopsyrevealedER+,PR+adenocarcinoma,whichappearedtohavespreadtothekidney,liver,bone.,、Liverrecipient,Thelivergraftwasallocatedtoa59-year-oldfemalerecipientsufferingfromdecompensatedprimarybiliarycirrhosis.Fouryearslater(in2011),atumorwasdetectedinsegmentVIIIofthelivergraftandhistologicallyproventobedonor-derivedmetastasizedER+breastcancer.Aretransplantationwasimmediatelyproposedtotherecipient,whichsherefused.Shefeltwellandwasafraidofpotentialpostoperativecomplicationsshehadexperiencedin2007afterthelivertransplantation.Shedecidedtoundergoanablativeprocedurebymeansofextracorporealprotonradiationatanothercenter,andtherewereradiologicalsignsofcompleteresponse.Afteralong-termstabledisease,in2014(7yearsafterthetransplant),thepatientdevelopedextrahepatictumorprogressionthatwasmainlylocalizedatthehilarregion.Sherefusedanyfurtheroncologicaltreatmentanddiedafewmonthslaterduetodiffusetumorprogression.,9,、Right-kidneyrecipient,A32-year-oldmalereceivedtherightkidney.Afterhewasinformedofthetransmissionofbreastcancertothelungrecipientin2010,regulartumorscreeninginvestigationswereperformed,includingachestX-rayandultrasoundoftheabdomen.Inaddition,aCTscanofthechestwasperformedinJanuary2011.Allofthefindingswereunremarkable.InJuly2011,thepatientdevelopedmassiveproteinuria(3g/d),andantibody-mediatedrejectionwassuspectedduetoweakHLA-classIIantibodies.AbiopsyshowedwidespreadinvasionoftherenalallograftbyER+,PR+adenocarcinoma,whichappearedtobehumanepidermalgrowthfactorreceptor2positive.ACTscanofthetransplantedkidneyrevealedseveralfocalhypodenseareasandaheterogeneouscortex.,10,4、DISCUSSION,Itsnotthefirsttimethatacancerhasmetastasizedbetweenanorgandonorandanorganrecipient,buttheoddsofthathappeningareverylow,somewherebetween1in10,000and5in10,000,andinthiscase,itsthefirsttimeadonorhastransferredcancercellstofourreceptors.Whywouldapersonwhoshowsnosignsofcancerinfectorganrecipientsafteranorgantransplant?Whydopatientswithdifferentorganshavethesamekindofcancer?Atpresent,theresearchershaveonlysomespeculationaboutthecause,thedefinitivereasonisunknown.Onehypothesisisthatdonorbreastcancerhasmetastasizedormetastasizedineverytransplantorgan,andpreviousstudieshaveshownthatcirculatingtumorcellswerefoundinthefirststageofbreastcancer.Recipientsoforgantransplantsrequirelong-termuseofimmunosuppressants,whichallowcancercellsinorgansthatdonotnormallydevelop.Anotherpossiblereasonisthatischemia-reperfusioninjuryassociatedwithorgantransplantation