PathologyUnknownCase:

April2016KyleMuir

MS4PathologyElecAve

ClinicalHistoryA71yohealthymalepresentedwithprogressivefaAgueandwasfoundtobepancytopenic.BonemarrowbiopsywasconsistentwithmyelodysplasAcsyndrome.HereceivedaCMV-BMTandwasadmiNed5weekspost-transplantwithvomiAnganddiarrhea.

EGDFindings(Stomach/Duodenum)

Erythema,edema,erosions.

MicroscopicFindings

GASTRICMUCOSA

DUODENALMUCOSA

MicroscopicDescripAon

GastricandduodenalmucosawithepithelialapoptosisanddropoutwithoutsignificantinflammatorycellinfiltraAon.

Whatisthediagnosis?

A.  IschemiaB.  InfecAousgastroenteriAsC.  GraX-versus-hostdiseaseD.  Autoimmuneenteropathy

Answer

C.GraX-versus-hostdisease

ClinicalQuesAon

•  WhichofthefollowingeAologiescanmostcloselyresemblethepathologyofthiscondiAon?

a.  CMVreacAvaAonb.  AcutecoliAsc.  C.DifficileinfecAond.  Ischemicbowel

Answer

a.  CMVreacHvaHonCMVinfecAonoftheGItractcanpresentwithawidevarietyofpathologicfeaturesincludingthetypicalGVHDfindingsofcryptdropoutandepithelialapoptosis.Therefore,itiscrucialtolookforinclusions(unfortunatelycanberareorevenabsentinthesecases)andperformappropriateIHCtesAngifthereisanydoubt.

OverallPathologicImpression

•  FurtherIHCtesAngwasnegaAveforCMV,herpesandadenovirus.

•  OverallpathologyconsistentwithadiagnosisofgraX-versus-hostdisease(GVHD).

AcuteGVHDClinicalStaging

ClinicalStage Skin Liver—Bilirubin,μmol/L(mg/dL) Gut

1 Rash<25%bodysurface 34–51(2–3) Diarrhea500–1000

mL/d

2 Rash25–50%bodysurface 51–103(3–6) Diarrhea1000–

1500mL/d

3 Generalizederythroderma 103–257(6–15) Diarrhea>1500mL/

d

4 DesquamaAonandbullae >257(>15) Ileus

OverallClinicalGrade SkinStage LiverStage GutStage

I 1–2 0 0

II 1–3 1 1

III 1–3 2–3 2–3

IV 2–4 2–4 2–4

•  MostcommonlyaffectedorgansinacuteGVHDareskin,liverandGItract.•  BelowistheclinicalgradingschemeforacuteGVHD

AcuteGVHDoftheGItract•  DefiniHon:aNackbyengraXedhematopoieAccellsonhostGIAssuesinfirst

100dayspost-transplant•  DiagnosAcCriteria(GradeI-IV)

–  IncreasedcryptapoptosisprogressingtocryptdestrucAonandmucosalnecrosisinhighergrades

•  PotenHalPiNalls–  ConsiderinfecAonifpresenceofacuteorchronicinflammaAonor

neutrophilicabscesses/ulceraAon.AlsokeepinmindthepossibilityofadiminishedinflammatorycellresponseintheseimmunocompromisedpaAents.

–  UseIHCtocheckforCMV/herpes–  BevigilantasinfecAoncanoXencoexistwithGVHDandhasaprofound

impactonmanagement

Grade1=isolatedapoptoAcepithelialcells,withoutcryptlossGrade2=individualcryptlossGrade3=conAguousareaofmulAplecryptlossGrade4=extensivecryptdropoutwithdenudaAonofepithelium.

References•  HeymerB.ClinicalanddiagnosAcpathologyofgraXversushostdisease.

SpringerVerlag,2002.•  ShulmanHMetal.HistopathologicdiagnosisofchronicgraX-versus-host

disease:NaAonalInsAtutesofHealthConsensusDevelopmentProjectonCriteriaforClinicalTrialsinChronicGraX-versus-HostDisease:II.PathologyWorkingGroupReport.BiolBloodMarrowTransplant.2006Jan;12(1):31-47.

•  Kambham,Neeraja.SurgicalPathologyCriteria.AcuteGra*versusHostDisease(GVHD)ofGastrointes6nalTract.StanfordSchoolofMedicine,9May2007.Web.15Feb.2016.<hNp://surgpathcriteria.stanford.edu/transplant/giacutegvhd/printable.html>.

•  LernerKG,KaoGF,StorbR,etal.HistopathologyofgraX-vs-hostreacAon(GvHR)inhumanrecipientsofmarrowfromHL-A-matchedsiblingdonors.TransplantProc1974;6:367–371.

•  ModernPathology(2011)24,117–125;doi:10.1038/modpathol.2010.163;publishedonline15October2010