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CASEREPORTOpenAccessIsolatedgranulocyticsarcomaofthepancreas:AtrickydiagnosticforprimarypancreaticextramedullaryacutemyeloidleukemiaMathieuMessager1,3,DavidAmielh1,CarolineChevallier1,2,3andChristopheMariette1,2,3*AbstractWereporttwoclinicalcasesofprimarygranulocyticsarcomaofthepancreasthatwerediagnosedonthesurgicalspecimen.
Atypicalclinicalandmorphologicalpresentationsmayhaveleadtopretherapeuticbiopsiesofthepancreaticmassinordertoindicateprimarychemotherapy.
Literaturereviewofthisrareclinicalpresentationmayhelpphysicianstoanticipatediagnosticandtherapeuticstrategies.
Keywords:Granulocyticsarcoma,Chloroma,Myeloidtumor,Pancreas.
BackgroundGranulocyticsarcoma(GS)isanextramedullarysolidtumormasscomposedofimmaturemyeloidcells[1].
GSisararemanifestationofacutemyeloidleukemia(AML)usuallyarisingduringorafterthecourseofthedisease,inupto8%ofpatientsinautopsystudies[2].
Occasionally,itcanbethefirstandtheonlymanifesta-tionofAML,leadingtodiagnosticchallenges.
WereporttwoexceptionalcasesofisolatedpancreaticGStofocusphysicians'attentiontospecificdiagnosticandtherapeuticstrategiesforasolidpancreaticmass.
CasespresentationThefirstpatientwasa45-year-oldwoman,withoutsignifi-cantcomorbidity,whowasreferredtoourinstitutionforsurgery.
Epigastricpainwithjaundicebeganonemonthpreviouslywithoutperformancestatusalteration.
Standardbloodexamsexhibitedcholestasis(alkalinephosphatases3.
8N,gama-glutamyltranspeptidases37N)andhyperamy-lasemia(1.
9N)withnormalvaluesofhemoglobin,whitebloodcells,platelets,carbohydrateantigen19-9(CA19-9)andcarcinoembryonicantigen(CEA).
Abdominalcom-putedtomodensitometry(CTscan),magneticresonanceimaging(MRI)andendoscopicultrasonography(EUS)ofthepancreasallidentifiedthedistensionofboththecommonbileduct(15mm)andtheWirsungduct(6mm),abovea28*20mmirregular,hypoechoicandhypodensemassofthepancreatichead,withoutanylymphnodeorvascularinvasionordistantsecondarylesiondetected.
Basedonthesymptoms,asuspecteddiagnosisofpancrea-ticadenocarcinomaandaresectablemass,itwasdeter-minedtoproceedwithprimarysurgerywithoutobtainingpreoperativesamplebiopsies.
Curativewhipplepancreati-coduodenectomywithregionallymphadenectomywasper-formedwithnospecificperoperativediscoveryanduneventfulpostoperativecourse.
HistologicalexaminationofthesurgicalspecimenrevealedapancreaticGSbasedonthepresenceofcellsofmyeloidlineagewithpositiveimmunostainingforCD43myeloid-associatedantigen(Figure1A),whereasimmunostainingsforothermyeloidmarkers(CD31,CD34,CD38,CD45,CD99,CD117),B-cellmarkers(CD20,CD79a),T-cellmarkers(CD3,CD4),com-muneB-andT-cellmarkers(CD30)andmyeloperoxidase(MPO)werenegative.
Sixweekslater,diffuserelapseoccurredwiththeappearanceofleftcervicalandmultiplethoraciclymphnodes.
Aftercervicalbiopsy,histologicalanalysisconfirmedrecurrencewiththesameimmunostain-ingprofile.
Braintomodensitometryandbonemarrowbiopsywerenormal.
Cisplatin-cytarabin-dexametha-sone-basedchemotherapywasadministeredquickly,butthepatientdiedduetodiseasedisseminationonemonthlater.
Thesecondpatientwasa19-year-oldwoman,withoutsignificantcomorbidityoranyalcoholconsumption,*Correspondence:christophe.
mariette@chru-lille.
fr1DepartmentofDigestiveandOncologicalSurgery,CentreRégionaletUniversitairedeLille,PlacedeVerdun,59037Lillecedex,FranceFulllistofauthorinformationisavailableattheendofthearticleMessageretal.
WorldJournalofSurgicalOncology2012,10:13http://www.
wjso.
com/content/10/1/13WORLDJOURNALOFSURGICALONCOLOGY2012Messageretal;licenseeBioMedCentralLtd.
ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense(http://creativecommons.
org/licenses/by/2.
0),whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.
AMPOCD34CD43BFigure1Fixed,paraffin-embeddedtissuesectionsofi)pancreaticinvasion(A,casen°1,magnificationat*100)ofmediumsizedcells,withCD43positiveexpressionsigningmyeloidlineage,insetshowscontiguouslymphnodewithhighCD43expression(internalpositivecontrolofmyeloidlineage);andofii)omentuminvasion(B,casen°2,hematoxylinandeosinstaining,magnificationat*400)bymyeloid-likecells,somewithmitoticactivity(arrowhead),surroundingfatcells(arrow),insertsshowmyeloperoxydase(MPO),CD43,andCD34expression(arrowheadshowinginternalpositivecontrolwithvessel).
Messageretal.
WorldJournalofSurgicalOncology2012,10:13http://www.
wjso.
com/content/10/1/13Page2of5whopresentedatourinstitutionforepigastricpainscombinedwithhyperamylasemia(1.
7N)andhyperlipa-semia(7.
8N).
Hemogram,hepaticenzymes,C-reactiveprotein,CEAandCa19.
9valueswerenormal.
TheabdominalCTscanshoweda9-mmWirsungductdila-tion(Figure2A)withinthe30-mmmassofthepancrea-tichead(Figure2B,C),thetumoralorinflammatorynatureofwhichwasuncertain.
Afterconventionalmedi-caltreatmentforpancreatitis,thesymptomsdisap-peared,allowinghospitaldischargewithadditionalmorphologicaloutpatientexamsscheduled.
Duetoearlyrecurrentepigastricpainepisodes,combinedwithhyperli-pasemia,shewasre-admitted.
EUSrevealedan11-mmceliaclymphnodewitha9-mmWirsungductdilationandnoclearpancreaticmass,whereaspancreaticMRIidentifiedamoderatelylowsignalintensityonT1-weightedimages,middle-highsignalintensityonT2-weightedimages,andminimalenhancementonpost-gadoliniumimages,consistentwiththediagnosisofhypo-vascularsolidtissues.
NormalpentetreotidescintigraphyandthechromograninAvalueruledoutthediagnosisofneuroendocrinetumor.
Duetotheabsenceofacleardiag-nosis,persistentsymptomsandthediscordancebetweentheexamsthathadbeenperformed,thedecisionwasmadetoproceedwithasurgicalexploration,revealingdif-fuseperitonealcarcinomatosiscombinedwithanunre-sectableandinflammatory30-mmpancreaticmass.
HistologicalanalysisofthepancreaticmassandperitonealbiopsiesrevealedextramedullarmyeloidtumoralcellswithimmunohistochemistrypositiveforMPO,CD43,andCD34(Figure1B),aswellasCD117andCD45,andnega-tiveforCD79a,CD3,CD2,CD4,CD8andCD68,leadingtothediagnosisofpancreaticGS.
ThebrainCTscanandbonemarrowbiopsywerenormal.
Aninductioncytara-bin-basedchemotherapywasbegunquickly,leadingtoacompletemorphologicalresponseafterthreeconsolidationcycles.
Eightmonthslater,leftinguinallymphnoderecur-rencewasdiagnosed.
Second-lineamsacrine-cytarabin-basedchemotherapyachievedapartialmorphologicalresponse.
Duetotumoralprogressionfourmonthslater,third-lineclofarabine-basedchemotherapywasadminis-teredwithanoptimalresponsethatallowedbonemarrowtransplantationtwomonthslater.
DiffuseperitonealandhepaticrecurrencewasdiagnosedbasedonPETscanningsixmonthslater,leadingtopalliation.
DiscussionGS,alsocalledchloroma,referstotheinfrequentgreencolorobservedasaresultofmyeloperoxydaseactioninneoplasticcells[3].
GSusuallyoccurssimultaneouslyorfollowstheonsetofAMLin3-10%ofpatients[1,4].
Rarely,GSisthefirstmanifestationofAML.
GSmayalsobethefirstsignoftransformationintoAMLinpatientswithmyeloproliferativedisordersormyelodysplasicsyn-drome[3].
Othercommonsitesoforiginaresofttissues,lymphnodes,skinandbones[5],withabdominaloriginbeingveryrare.
EvenifGSincidenceisincreasingduetoprolongedleukemicremissionofAML,pancreaticGScaseshaverarelybeenreportedintheliterature.
Toourknowledge,10caseshavebeenpublished(Table1)[4,6-13],onlyfourofwhich,inadditiontothetworeportedinthepresentpaper,wereisolatedpancreaticGSwithoutbonemarrowinvolvement[6,7,12,13].
Comparingwithotherpublishedcases(Table1),thisworkistoourknowledge,thefirsttodescribetwoisolatedpancreaticGStreatedinasinglecenter,withdifferenttherapeuticstrate-gies,includingasurgicalapproach.
Wealsoprovidedacompletefollow-upforeachcase,criticallyanalyzedthetherapeuticstrategiesandhighlightedthewanderingdiag-nosis.
Regardingotherdigestivelocations,GSofthesmallintestine,colonandliverhavebeendescribed,thosesitua-tionsbeingextremelyrare[14,15].
GScanoccurinpatientsofallageswithafocusonmalepatients(male:femaleratio1.
2:1)duringthelastdecadesoflife(medianageis56years,range:1month-89years)[7,16].
EveniftheoverallprognosisofAMLisfavorable,theassociationwithGSmakesworsenstheprognosisbecauseonly24%ofpatientswithGSwillbealive2yearsaftertheinitialdiagnosis,withanoverallmediansurvivalof7to20months[3,17].
ACBACBFigure2Abdominalcomputedtomodensitometry,withinjectionofcontrastproduct,portalsequence.
Axial(A)projectionshowingWirsungdilatation(arrowhead).
Axial(B)andfrontal(C)projectionsshowinglowdensitypancreaticmass(arrowheads),casen°2.
Messageretal.
WorldJournalofSurgicalOncology2012,10:13http://www.
wjso.
com/content/10/1/13Page3of5Clinicalbehaviorandresponsetotherapywerenotinfluencedbyanyofthefollowingfactors:age,sex,ana-tomicsite,denovopresentation,histotype,phenotypeorcytogeneticfindings[18].
ItremainsuncertainwhatconstitutesthebesttreatmentinGS-associatedAMLpatients[12].
However,high-dosechemotherapyandstemcelltransplantationmaybenefitthesepatients,whereasradiationtherapyorsurgicalresectionhavebeenfoundtobelesseffective[12].
TheseobservationsshowthatcliniciansshouldthinkaboutpancreaticGSwhenthepancreaticmassdevelopsduringorafterAML.
However,inthecasesreportedhereinwhichGSwasthefirstandtheonlymanifesta-tionofAML,diagnosisischallenging.
Becausesurgeryisnotrequiredandmayprobablyworsentheprognosisduetothedelayedadministrationofinductionche-motherapy,alleffortsshouldbemadetoobtainprether-apeuticbiopsiesforapancreaticmass,especiallyifallofthebiologicalandmorphologicalexamresultsarenottypicalandinagreement.
ThenegativevalueofCA19.
9aswellastheyoungageofourpatientsmayhavebeenwarningsthatindicatethevalueofEUScytologicalexaminationfordetectingdifferentialdiagnosesofpan-creaticadenocarcinoma.
ApositivediagnosisofGSissometimeschallengingandrequiresexpertpathologists.
Histologicalobserva-tionrevealsmyeloblats,promyelocytesandsometimesneutrophils.
ThedefinitivediagnosisofGSrequirespositiveimmunostainingforatleastoneofthemyeloid-associatedantigens(indecreasingfrequency:CD68,MPO,CD43,CD45,CD117,CD99,CD33,CD34,CD13)associatedwithnegativeimmunostainingforthelym-phoidlineages(CD3forT-cellsandCD20forB-cells)[1,12].
MajordifferentialdiagnosesareHodgkinlym-phoma,Burkittlymphoma,large-celllymphoma,andsmallroundcelltumours.
WhenahistologicaldiagnosisofGSismade,bonemarrowsamplingismandatorytoassesstheabsenceofAML.
TheriskofmetachronousAMLoccurrenceinnon-leukemicpatientswithGSisveryhigh,withamediandelayof5months;mostpatientswilldevelopAMLwithin1year[7,12].
Therefore,earlyintensive(induc-tion/intensification)chemotherapysimilartothatusedtotreatAMLshouldbeadministered,eveninGSpatientswhodidnotpresentAMLuponinitialdiagno-sis[3].
ConclusionsTheauthorsdescribedtwocasesofisolatedgranulocyticsarcomaofthepancreas.
Theexperienceofthesecaseshighlightedthedifficultiesofcorrectdiagnosisandcare.
Toconclude,pretherapeuticbiopsiesshouldbethecor-nerstoneforthediagnosisofapancreaticmasswithaty-picalclinicalpresentation.
ConsentWritteninformedconsentwasobtainedfromthepatientforpublicationofthiscasereportandtheaccompanyingimages.
Forthepatientwhodied,consentwassoughtfromthenextofkinofthepatient.
Table1Clinicalcharacteristics,treatmentandoutcomesofliteraturereportsofpancreaticgranulocyticsarcomasAuthor/YearofreportSexAgeConcomitantAMLTreatmentResponse/StatusKingetal.
/1987F/36NoRadiotherapy+CT(Daunorubicin,Cytarabine,Thioguanine)CRMoreauetal.
/1996M/32NoDuodenopancreatectomy+CT(Idarubin,Cytarabine)CRafter2yearsfollow-upMarcosetal.
/1997F/37YesNoneDiedafterinitialMRIRavandi-Kashanietal.
/1999M/31YesCT(Idarubicin,Cytarabine,All-transretinoicacid)CR,(follow-upunknown)F/61YesCT(Idarubicin,Cytarabine,Lisofylline)Recurrence,diedServin-Abadetal.
/2003M/64InremissionCT(Unknownregimen)CR,diedofstrokeBrecciaetal.
/2003F/42YesCT(Cytosine,Arabinoside,Idarubicin)+BMallogarftCRat49monthsfromgraftSchferetal.
/2008F/75YesCT(Etoposide,Cytarabine,reduceddoseMitoxantrone)Recurrence(7months),diedRong/2010M/40NoDuodenopancreatectomy+CT(Cytarabinebasedregimen)CR,(follow-upunknown)Lietal.
/2011F/48NoDistalpancreatectomy+splenectomy,patientrefusedadjuvantCTRecurrence(2months),died3monthsaftersurgeryOurstudy/2011F/45NoCTafterduodenopancreatectomy(Cisplatin,Aracytine,Dexamethasone)Earlyrecurrence,diedF/19NoCT(Aracytinebasedregimen)Recurrence(8months),aliveafterBMtransplantation(22monthsfollow-up)AML:AcuteMyeloidLeukemia;M:Man;F:Female;CT:Chemotherapy;CR:CompleteResponse;BM:BoneMarrowMessageretal.
WorldJournalofSurgicalOncology2012,10:13http://www.
wjso.
com/content/10/1/13Page4of5AcknowledgementsTheauthorsthankDr.
ClaireDelattreandDr.
MarionClassefromtheDepartmentofPathology,UniversityHospitalofLille,fortheirhelpincollectingandreviewingthehistologicaldata.
Authordetails1DepartmentofDigestiveandOncologicalSurgery,CentreRégionaletUniversitairedeLille,PlacedeVerdun,59037Lillecedex,France.
2UniversitéLilleNorddeFrance,PlacedeVerdun,59045,Lillecedex,France.
3Inserm,UMR837,Team5Mucins,epithelialdifferentiationandcarcinogenesisJPARC,RuePolonovski,59045Lillecedex,France.
Authors'contributionsDr.
DAandDr.
CCcontributedtodatacollection.
Dr.
MMandPr.
CMcontributedtowritingthemanuscript.
CompetinginterestsTheauthorsdeclarethattheyhavenocompetinginterests.
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doi:10.
1186/1477-7819-10-13Citethisarticleas:Messageretal.
:Isolatedgranulocyticsarcomaofthepancreas:Atrickydiagnosticforprimarypancreaticextramedullaryacutemyeloidleukemia.
WorldJournalofSurgicalOncology201210:13.
SubmityournextmanuscripttoBioMedCentralandtakefulladvantageof:ConvenientonlinesubmissionThoroughpeerreviewNospaceconstraintsorcolorgurechargesImmediatepublicationonacceptanceInclusioninPubMed,CAS,ScopusandGoogleScholarResearchwhichisfreelyavailableforredistributionSubmityourmanuscriptatwww.
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