Primaryreferences

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AmericanJournalofClinicalPathology(AJCP),August1975toFebruary2006

AmericanJournalofSurgicalPathology(AJSP),March1977toFebruary2006

ArchivesofPathologyandLabMedicine(Archives),January1976toFebruary2006

HumanPathology(HumPath),March1970toFebruary2006

ModernPathology(ModPath),January1988toFebruary2006

Rosai,J:Ackerman’sSurgicalPathology(9thEd);Mosby,2004

Sternberg,S:DiagnosticSurgicalPathology(4thEd);LippincottWilliams&Wilkins,2004UniversityofPittsburghMedicalCenterCaseReports,cases1-462

CDMarkerwebsites:http://www.hlda8.org/CD1toCD339.htm,http://ca.expasy.org/cgi-bin/lists?cdlist.txt,ProteinReviewsOntheWeb,http://www.ebioscience.com/ebioscience/whatsnew/humancdchart.htm

Imagesneeded

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Wewelcomeyourcontributionsofdigitalimages,whichwewillpostintheappropriatesectionofthischapter,andwhichhelppathologistsworldwide.

Tocontribute,emailyourdigitalimages(GIForJPG,anysize)toDr.Pernickatinfo@PathologyOutlines.com.Wewilllistyournameasacontributorunlessyouwanttobeanonymous.Clickhereformoreinformation

ImagesareparticularlyneededfortheseCDmarkers:

CD11a,CD11b,CD11c,CD13,CD15s,CD16a,Cd16b,CD17-CD19,CD22,CD24-CD29,CD32-CD33,CD35-CD42,CD45RB,CD45RC,CD46-CD48,CD49a-f

Background

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CD:clusterdesignationorclusterofdifferentiation

Nomenclatureproposedin1982atFirstInternationalWorkshopandConferenceonHumanLeukocyteDifferentiationAntigens(HLDA);workshopsnowcalledHumanCellDifferentiationMolecules

Classificationsystemformonoclonalantibodiesgeneratedbylaboratoriesworldwideagainstcellsurfacemoleculesonleukocytesinitially,nowalsoantigensfromothercelltypes

Datacollatedandanalyzedbyclusteranalysisbasedonpatternofbindingtoleukocytesorothercelltypes

Mustbeatleasttwomonoclonalantibodiesforeachantigen

“w"indicatestheCDisnotwellcharacterizedorisrepresentedbyonlyonemonoclonalantibody

Interpretationshouldbebasedoncellulardistributionofstaining(i.e.membranous,cytoplasmic,nuclear),proportionofpositivelystainedcells,stainingintensityandcutofflevels

Usedinimmunohistochemistryandflowcytometry

References:JImmunol1994;152:1,BullWorldHealthOrgan1997;75:385,JImmunolMethods2003;275:1-8,Blood2005;106:3123

CD1

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Familyofnon-polymorphicMHCclassI-likeglycoproteinsonsurfaceofvariousantigen-presentingcells

Memberofimmunoglobulinsuperfamily

Has5differentsubsets(CD1a-CD1e),allnoncovalentlyassociatedwithbeta2microglobulin,allon#1q22-23(nonMHClinked)

ThedifferentCD1formsbindtodifferenttypesoflipidantigenbasedondifferencesintheirantigenbindinggrooves(NatRevImmunol2005;5:387)

CellularinfectionwithliveMycobacteriatuberculosisorexposuretomycobacterialcellwallproductsconvertsCD1negativemyeloidprecursorsintocompetentCD1+antigenpresentingcells(JImmunol2005;175:1758);pollenlipidsarealsorecognizedasantigensbyTcellsviaCD1dependentpathway(JExpMed2005;202:295);maygenerateinflammatorycomponentinatheroscleroticlesions(AmJPathol1999;155:775)

InhibitionofCD1expressionmaybeamechanismofimmunesystemevasionbymetastaticmelanoma(AmJPath2004;165:1853),Leishmaniadonovani(InfectImmun2004;72:589),andsomeMycobacterialinfections

Function:involvedinpresentationofautologousandbacteriallipidantigenstoTcells;mayalsomediatethymicTcelldevelopment

Uses:diagnosisofLangerhanscellhistiocytosis

Positivestaining(normal):corticalthymocytes(70%),activatedTcells,Langerhanscells,interdigitatingdendriticcells

Positivestaining(disease):Langerhanscellhistiocytosis,preTALLwithcorticalthymocytephenotype;indolentTcelllymphoblasticproliferations(AJSP1999;23:977;AJSP2001;25:411),thymoma(JpnJThoracCardiovascSurg2003;51:481)

Negativestaining:matureperipheralTcells,peripheralTcelllymphomas

CD1a

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AlsocalledLeu6

Onchromosome1q22-23(notMHClinked)

Tcellsurfaceantigenimportantindendriticcellpresentationofglycolipidsandlipopeptideantigens

MayactivateintrathyroidalTcellsinHashimoto’sthyroiditisandGrave’sdisease(JImmunol2005;174:3773)

Interpretation:membranousstaining

Uses:diagnosisofLangerhanscellhistiocytosisandexclusionofotherentitiesthatareCD1anegative

Positivestaining(normal):corticalthymocytes,Langerhanscells(Langerin+,CD86+),immaturedendriticcells(Langerin-,CD86-,HLA-DRlow,CD40-low)

Positivestaining(disease):Langerhanscellhistiocytosis(fairlyspecific),myeloidleukemias,mycosisfungoides(variable),almostallcutaneousTcelllymphomas,T-ALL(age28-60years,AJCP2002;117:252),dendriticcellsindermis/epidermisofbenigninflammatoryskindisordersincludingpseudolymphomatousfolliculitis(AJSP1999;23:1313),spongioticdermatitisandlichenplanus(ArchDermatolRes2002;294:297),psoriasis(JCutanPathol1995;22:223);Barrett’smetaplasiaofesophagus(BrJCancer2005;92:888),monocytesinmostsicklecellanemiapatients(HumImmunol2004;65:1370)

Negativestaining:normalBcells,dendriticcellsinmostcutaneousBcelllymphomas(AJCP2001;116:72),histiocyticlymphoma/sarcoma,histiocytoma,folliculardendriticcells,folliculardendriticcelltumor,interdigitatingdendriticcells(variable,AJSP1998;22:1048,AJCP2001;115:589),interdigitatingdendriticcellsarcoma,dendriticcellneurofibroma,juvenilexanthogranuloma,sinushistiocytosiswithmassivelymphadenopathy,Erdheim-Chesterdisease

References:AJSP2001;25:630(Langerhanscellhistiocytosis),JClinInvest2004;113:701(Langerhanscells),OMIM188370

CD1b

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Onchromosome1q22-23(notMHClinked);noncovalentlyassociatedwithbeta2microglobulin

Canpresenttoantigenpresentingcellsasetofglycolipidspecieswithbroadrangeofvariationinlengthofacylchains(JImmunol2004;172:2382),includingthosefrompathogenicMycobacteriatuberculosisandMycobacterialepraetocytotoxicTcells

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):corticalthymocytes,Langerhanscells(weakerstainingthanCD1a),myeloiddendriticcells,brainpyramidalcells,subpopulationofBcells

Positivestaining(disease):dendriticcellsinmycosisfungoides(JCutanPathol1995;22:223);myeloidleukemias,someBandTcellmalignancies,monocytesofmostsicklecellanemiapatients(HumImmunol2004;65:1370)

Negativestaining:normalBcells

References:OMIM188360

CD1c

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Onchromosome1q22-23(notMHClinked);noncovalentlyassociatedwithbeta2microglobulin

ActivatedbyphospholipidantigenproducedbyMycobacteriatuberculosisandM.bovisBacille-Calmette-Guerin(JExpMed2004;200:1559,Nature2000;404:884);assistswithpresentationoflipidantigens

MayactivateintrathyroidalTcellsinHashimoto’sthyroiditisandGrave’sdisease(JImmunol2005;174:3773);maypromoteautoantibodiesinsystemiclupuserythematosus(JImmunol2000;165:5338)

B-CLLcellsdownregulateCD1cgenes,whichmaymediateevasionofimmuneresponse(Leukemia2002;16:2429)

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):corticalthymocytes,Langerhanscells(weakerthanCD1a),immaturemyeloiddendriticcells,subsetofnormalperipheralBcells,activatedTcells

Positivestaining(disease):dendriticcellsinmycosisfungoides(JCutanPathol1995;22:223);myeloidleukemiasandsomeBandTcellmalignancies,monocytesofmostsicklecellanemiapatients(HumImmunol2004;65:1370)

Negativestaining:manynormalBcells

References:OMIM188340

CD1d

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Onchromosome1q22-23(notMHClinked)

NKTcellsaredefinedasCD1ddependentTcellsthatcarryaninvariantTCRalpha-chainandproducehighlevelsofcytokines

CD1disexpressedinNKTcellsactiveinautoimmunediabetes,tumorrejectionandsomemicrobialinfections

Mayprotectagainstlipidantigen-richinfectiousmicrobesonhumanscalp(JClinPathol2005;58:1278)

B-CLLcellsdownregulateCD1dgenes,whichmaymediateevasionofimmuneresponse(Leukemia2002;16:2429)

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):dendriticcells,intestinalepithelialcells,Bcellsubset,NKTcellsubset(ImmunolLett2005;100:42,JImmunol2005;175:4416),lowlevelsinthymusandmonocytes

Positivestaining(disease):someBandTcellmalignancies;keratinocytesinpsoriasis

References:OMIM188410

CD1e

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Onchromosome1q22-23(notMHClinked);noncovalentlyassociatedwithbeta2microglobulin

Processesmycobacterialantigen(insteadofpresentingantigendirectly),andhelpsexpandrepertoireofglycolipidTcellantigenstooptimizetheimmuneresponse(Science2005;310:1321);presentmentisdonebyCD1b

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):dendriticcells

References:OMIM188411

CD2

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AlsocalledErosettereceptor(anti-CD2antibodiesinhibitformationofrosetteswithsheeperythrocytes),LFA2(leukocytefunctionantigen),T11

At1p13.1;memberofimmunoglobulinsuperfamily

EarlyTcellmarker

Functions:(a)bindsCD58(LFA3)onantigen-presentingcells,whichenablesTcellstorespondtolowerconcentrationsofantigen(JExpMed1999;190:1383);(b)inducescostimulatorysignalsinTcells(c)inducesTcellcytokineproduction;(d)mediatesadhesionbetweenTcellsandantigenpresentingcells;(e)regulatesTandNK-mediatedcytolysis;(f)inhibitsapoptosisofactivatedperipheralTcells;(g)regulatesTcellanergy

Uses:Tcellmarker(althoughCD3ismorecommon),markerofsystemicmastocytosis

Interpretation:membranousstaining

Positivestaining(normal):thymocytes(95%),matureperipheralTcells(almostall),NKcells(80-90%),thymicBcells(50%)

Positivestaining(disease):T-ALL,otherTcelllymphoma/leukemia,indolentsystemicmastocytosis(HumPath2001;32:545),variableacutemyeloidlymphoma-M0,rarelypyothoraxassociatedBcelllymphoma(AJSP2002;26:724,UnivPittsburghcasereport),rarelyReed-Sternberg/Hodgkin’scells(ModPath2005;18:1542),rarelymyeloma(ModPath1990;3:302),rarelymyeloidleukemia

Negativestaining:Bcells,nonhematopoieticneoplasms(AJCP2003;120:64),mastcellsinnon-mastocytosisdisorders

CD2R

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CD2epitopepresentonactivatedTcells,unmaskedbyconformationalchangeofCD2glycoproteinduringactivation

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):activatedTcells

Positivestaining(disease):bloodandsynovialfluidTcellsinrheumatoidarthritis;peripheralbloodTcellsinjuvenilerheumatoidarthritis,SLE,ankylosingspondylitisandLymedisease(ScandJImmunol1991;34:351)

CD3

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AlsocalledOKT3

Memberofimmunoglobulinsuperfamilyon11q23

Complexofdelta,epsilon,gamma,zetaandetachainsofintegralmembraneglycoproteinsthatassociateswithTcellantigenreceptor(TCR),andisrequiredforTCRcellsurfaceexpressionandsignaltransduction

TCR-CD3complexconsistsofeitherTCRalpha/betaorTCRgamma/deltaheterodimerscoexpressedatthecellsurfacewithCD3

CD3deltaandepsilondefectscauseautosomalrecessiveseverecombinedimmunodeficiency(noTcells,normalBcells,normalNKcells,OMIM608971,CurrOpinAllergyClinImmunol2004;4:479)

CD3zetainteractswithHIVNefprotein(JExpMed1999;189:1489)

Uses:mostspecificTcellantibody;diminishedexpressioninTcellcutaneouslymphoma(AJCP2000;114:467),althoughanotherstudyfindsCD8:CD3ratio<25%inepidermalcomponentoflymphocyticinfiltrateinthesetumors(ModPath2003;16:857);treatmentwithanti-CD3antibodiesmayrestoreself-toleranceinautoimmunediseases(CurrOpinImmunol2005;17:632,AnnNYAcadSci2004;1037:1)

Interpretation:cytoplasmicexpressionatearlyTcelldifferentiation,thenmembranousexpression

Positivestaining(normal):thymocytes,peripheralTcells,NKcells(CD3epsilon,cytoplasmicin56%,notmembranous);alsoPurkinjecellsofcerebellum;note:nonspecificcytoplasmicstainingmaybepresentinplasmacellsandmacrophages

Positivestaining(disease):80%ofTcelllymphomas,NKlymphoma(cytoplasmic,notmembranous),lymphomatoidgranulomatosis,lymphomatoidpapulosis;variableinprimaryeffusionlymphomaandpyothoraxassociatedlymphoma

Negativestaining:mostBcelllymphomas,NKlargegranularlymphocyteleukemia,Reed-SternbergcellsarenegativeinHodgkin’slymphomabutmaybesurroundedbyCD3epsilon+rosettes,smallcellcarcinoma,melanoma,granulocyticsarcoma,post-transplantlymphoproliferativedisorders

References:OMIM186790(CD3delta),OMIM186830(CD3epsilon),OMIM186740(CD3gamma),OMIM186780(CD3zeta);AJCP2005;124:199(adultTcellleukemia/lymphoma),AJSP2001;25:1413(achalasiainesophagectomyspecimens)

CD4

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AlsocalledOKT4

At#12pter-p12

Nonpolymorphousglycoproteinsbelongingtoimmunoglobulinsuperfamily

ExpressedonsurfaceofThelpercells;servesascoreceptorinMHCclassII-restrictedantigeninducedTcellactivation

CD4+CD25+Tcellsmaintainperipheraltoleranceandpreventautoimmunity(CurrTopMicrobiolImmunol2005;293:115)

ServesasHIVreceptoronTcells,macrophages,brain

DownregulatedbyHIVNefproteinduringAIDSprogression(JVirol2003;77:11536,JBiolChem2003;278:33912)

NormallyCD4>CD8;inHIVpatients,CD4/CD8ratioisinverted(i.e.CD4<CD8)andpatientsareatriskforopportunisticinfections

HomologoustoCD223

Uses:classifylymphomasandinflammatoryconditions;serumlevelsaremarkerofHIVdiseaseprogressionandresponsetotherapy(CD4+cellsarekilledbyHIV);serumlevelsalsoincreasedbytransientstress(AJCP2002;117:819)

Positivestaining(normal):thymocytes(80-90%),Thelpercells,macrophages,Langerhanscells,dendriticcells,granulocytes

Positivestaining(disease):manypost-thymicTcellleukemia/lymphomas,indolentTcelllymphoblasticproliferation,pityriasislichenoides,CD4+CD56+hematodermicmalignancies(blasticNKlymphoma),histiocyticlymphoma/sarcoma,acutemyeloidleukemia(AJCP1995;104:204),somepyothoraxassociatedlymphomas,cutaneouslymphomatoidgranulomatosis(AJSP2001;25:1111),lymphomatoidpapulosis(variable),floridantiviralinflammatoryresponse(ModPath2003;16:166)

Negativestaining:NKcells,Tcelllymphomawithcytotoxicphenotype,hepatosplenicalpha/betaandgamma/deltalymphoma,enteropathyassociatedTcelllymphoma,Bcelllymphoma(usually),Hodgkin’slymphoma(usually),nonhematopoieticneoplasms

References:Cell1985;42:93(earlyarticle),OMIM186940

CD5

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Belongstoancientscavengerreceptorsuperfamily;at11q13

CD5+Bcells,whichmayarisefromB-1cells(subsetofBcells)produce“generalistantibodies”-polyreactivelowaffinity"natural"antibodiestoexogenousantigens(tetanustoxoid,lipopolysaccharide)aswellasautoreactiveantibodies(ImmunolLett1993;38:159)

Firstlineofdefenseagainstantigens;havealowactivationthreshold;aretheonlylineofdefenseforthosewhocannotproducespecificantibody

Produceantibodiesusinggermline(nonmutated)configurationofgenesegments,usuallyIgM

CD5productioniselevatedinrheumatoidarthritis(27-52%ofcirculatingBcellsvs.20%normal)

CD5mayserveasadualreceptor,givingeitherstimulatoryorinhibitorysignalsdependingbothonthecelltypeandthedevelopmentstage

Keyregulatorofimmunetolerance;abnormalitiesmayproduceautoimmunity(ImmunolRes2002;26:255)

BindstoCD72

PolymorphisminCD5promoterassociatedwithsusceptibilitytomantlecelllymphomaandCLL(AJCP2005;123:646)

Uses:markerforCLL,mantlecelllymphoma,Tcells(normalandmalignant),thymiccarcinoma

Positivestaining(normal):thymocytes,almostallTcells,Bcellsofmantlezoneofspleenandlymphnodes(12%ofBcellsinperipheralblood,AJCP2004;121:368),Bcellsinperitonealandpleuralcavities

Infetus,mostBcellsinspleenandcordbloodareCD5positive

Positivestaining(disease):BcellCLL/SLL,mantlecelllymphoma(80-90%),diffuselargeBcelllymphoma(10%-usuallyaggressive),aggressivevariantoffollicularlymphoma(rare,AJCP2005;124:182),mostTcellmalignancies,NK/Tcelllymphoma(variable),prolymphocyticleukemia,atypicalthymoma(some),thymiccarcinoma(almostall),CASTLE(thyroidtumor)

Negativestaining:enteropathyassociatedTcelllymphoma,hepatosplenicalpha-betaandgamma-deltaTcelllymphomas,Tcelllargegranularlymphocyticlymphoma,mostBcelllymphomasotherthanmantlecellorCLL(althoughthererarelyareCD5+variantforms),Reed-SternbergcellsinHodgkin’slymphoma

References:OMIM153340

CD6

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Belongstoancientscavengerreceptorsuperfamily;at#11q13

Adhesionmoleculemediatingthebindingofdevelopingthymocyteswiththymicepithelialcells

AntibodiestoCD6areusedtodepleteTcellsfrombonemarrowtransplantstopreventgraftversushostdisease(JClinOncol2001;19:1152,IntJHematol1999;69:27)

BindstoCD166(ALCAM);essentialforstableTcell-antigenpresentingcellcontactandforTcellproliferation(Blood2005Dec13;[Epubaheadofprint])

Uses:seeaboveforbonemarrowtransplants

Positivestaining(normal):lowlevelsonimmature(cortical)thymocytes,highlevelsonmature(medullary)thymocytes;alsomatureTcells,Bcellsubset(B1acells),CNScells

References:OMIM186720

CD7

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Memberofimmunoglobulinsuperfamilyat17q25.2-25.3

HascostimulatoryactivityforTcells(ImmunolRes2001;24:31)

MembraneexpressionearlyduringTcelldevelopment,beforeTCRrearrangement;persistsuntilterminalstagesofTcelldevelopment

PlaysimportantroleinTcell-Bcellinteractioninearlylymphoiddevelopment

Downregulatedininfectiousmononucleosis(AJCP2003;120:49)

LossofCD7expressionandalteredcellularglycosylationmaycontributetoapoptosisresistanceofmalignantTcellsinmycosisfungoides(ModPath2003;16:543)

Uses:maybeusefulinidentifyingmycosisfungoides

Positivestaining(normal):thymocytes,matureTcells(85%),NKcells(majority),monocytes,pluripotenthematopoieticprogenitorcells,earlymyeloidcells,pre-Bcells

Positivestaining(disease):T-ALL(verygoodmarker)andothermalignantimmatureTcells,NK,lymphomas,rarelyBcelllymphomas(AJCP2001;115:396),AML(some),chronicmyelogenousleukemia,Down’ssyndromeassociatedtransientmyeloproliferativedisorderandAML(AJCP2001;116:204),lymphocyterichthymoma(AJCP2004;121:268),pancreaticductalcarcinoma,cholangiocarcinomaandepithelioidsarcoma(AJCP2003;120:64);

Negativeexpression:matureBcells,granulocytes,BcellALL,mycosisfungoides,adultTcellleukemia/lymphoma,Reed-SternbergcellsinHodgkin’slymphoma(ModPath2005;18:1542)

References:OMIM186820

CD8

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AlsocalledTcellsuppressor/cytotoxiccells,OKT8

Cellsurfaceglycoprotein,memberofimmunoglobulinsuperfamily;at2p12

Heterodimerofanalphaandabetachainlinkedbytwodisulfidebonds;heterodimeronthymocytesandhomodimeronperipheralbloodTcells

MHCclassIrestrictedreceptor;bindstononpolymorphicregionofclassImolecules;mayincreaseavidityofinteractionsbetweencytotoxicTcellandtargetcellduringantigen-specificactivation

Cankilltargetcellsbyrecognizingpeptide-MHCcomplexesonthemorbysecretingcytokinescapableofsignalingthroughdeathreceptorsontargetcellsurface

CD8alphacellspromotesurvivalanddifferentiationofactivatedTcellsintomemoryCD8+Tcells,whichmaybecomeclonal(butnotmalignant)intheelderly(ImmunolRev2005;205:170)

Contributetoinitiation,progressionandregulationofautoimmuneresponses(CurrOpinImmunol2005;17:624)

Associatedwithlymphoepithelioma-likecarcinomaoflung(AJSP2002;26:715);lowCD8:CD3ratioinepidermotrophiccomponentoflymphoidinfiltrateissuggestiveofmycosisfungoides(ModPath2003;16:857)

Uses:cytotoxicTcellmarker

Positivestaining(normal):corticalthymocytes(70-80%),Tcells(25-35%ofmatureperipheralTcells,mostlycytotoxicTcells);NKcells(30%,whicharealsoCD3negative)

Positivestaining(disease):epidermotrophiclymphocytesinmycosisfungoides(AJSP2002;26:450),subcutaneouspanniculitis-likeTcelllymphoma,indolentTcelllymphoblasticproliferation,sinusliningcellsinsplenichemartoma,heterotopicovariansplenoma,NK/Tcelllymphoma(variable),somepost-thymicTcelllymphomas,rarelymantlecelllymphoma(AJCP1998;109:689),rarelyCLL(AJCP1994;102:212,Archives2000;124:1361),Tcellinfiltratein30%ofcasesofnodularregenerativehyperplasiaofliver(HumPath2004;35:1241)

Negativestains:adultTcellleukemia/lymphoma,littoralcellhemangiomaofspleen

References:ModPath2002;15:1131;OMIM186910(alphachain),OMIM186730(betachain)

CD9

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Alsocalledmotilityrelatedprotein1(MRP1)

Memberoftransmembrane4superfamily(tetraspaninfamily);at12p13

Inhibitscellmotility;alsomediatescelldevelopment,activation,growthandadhesion

Triggersplateletactivationandaggregation,supportsmyotubemaintenanceandpromotesmusclecellfusion

Antibodiesareusedtopurgebonemarrowpriortoperipheralstemcellbonemarrowtransplant

Expressiondownregulatedinvarioustumors(otherthanbrain),whichmaypromotetumordissemination(CancerRes2005;65:2617)

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):preBcells,Bcellsubset,activatedTcells,plasmacells,macrophages,platelets,eosinophils,basophils,megakaryocytes,brain,cardiacmuscle,GIsystem,kidney(glomeruli,tubulesandcollectiveducts),liver,lymphaticepithelium,ovariansurfaceepithelium,peripheralnerve,skin,spleen,thyroid,tonsil,vascularendothelialcells-variesbystudy

Positivestaining(disease):pre-BALL,AML-M3,astrocytoma(JHistochemCytochem2002;50:1195),ovariansurfacecarcinoma(90%ofpapillaryserousandendometrioid,HumPath2004;35:1014),ovariancorticalinclusioncysts,renalcarcinoma(allpapillaryandchromophobe,50%ofclearcell,HumPath2001;32:1071),renaloncocytoma,lymphangioma;alsojuvenilenasopharyngealangiofibroma,angiosarcomaandKaposi’ssarcoma(ModPath2003;16:1028)

Negativestaining:redbloodcells,renalcollectingductcarcinomas(almostall)

CD10

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AlsocalledCommonAcuteLymphoblasticLeukemiaAntigen(CALLA),neutralendopeptidase24.11,neprilysin,enkephalinase

90-110kDacellmembranemetallopeptidase,characteristicmarkeroffollicularcentercellsandfollicularlymphoma,butalsowidelydistributedinnormaltissueandneoplasms;alsolocalizedtobrushborderinsmallbowelmucosa

At3q21-27;inactivatesbioactivepeptides,includingbombesin

Uses:

Acutelymphoblasticleukemia(ALL):oneofthefirstmarkerstoidentifyleukemiccellsinchildren(henceitsname)

AngioimmunoblasticTcelllymphoma:tumorcellsareCD10+atnodalandextranodalsitesotherthanbonemarrow(AJSP2004;28:54,HumPath2005;36:784)versusCD10-forotherTcelllymphomas;butbenignTcellsmaybeCD10+(ModPath2003;16:879)

Breast:markerofmyoepithelialcells(ModPath2002;15:397)

Burkitt’slymphoma:confirmdiagnosis

Diffuselargecelllymphoma:markerforgerminalcenterphenotype(alsobcl6),whichhaslongersurvivalinsomestudies(ModPath2005;18:1113,Archives2002;126:956-primaryintestinaltumors);butnotothers(AJCP2001;116:183-CD10+bcl2+havelowerremissionrates,VirchowsArch2004;445:545-nodifferenceinsurvival)

Ectopicprostate:confirmdiagnosisinuterusandvagina(AJSP2006;30:209)

Endometrialstromaltumors:consistentlyCD10+vs.CD10-smoothmuscletumors(ModPath2001;14:465),althoughleiomyomaandhighgradeleiomyosarcomamaybeCD10+(ModPath2002;15:923)

Endometriosis:helpfulinidentifyingareasofendometriosisifsparseglandulartissue(Archives2003;127:1003)

Follicularlymphoma:CD10+mayconfirmdiagnosis(AJCP2002;117:291);CD10+andbcl6+patientshavemorefavorableprognosis(AJCP2004;121:34),butseeAJCP2001;115:582;highgradefollicularlymphomasandinterfollicularinfiltratesmaybeCD10-(AJCP2001;115:862)

Gynecologictumors:mesonephricremnantsandtumorsareCD10+;CD10differentiatesmetastaticrenalcellcarcinoma(CD10+,AJSP2003;27:178)fromprimaryclearcellcarcinoma(CD10-);CD10isnotusefulindifferentiatingmuscleinvasiveendometrialadenocarcinoma(CD10+desmoplasticstroma)fromendometrialadenocarcinomainvadingadenomysosis(CD10+stroma,ModPath2003;16:22)

Hemangioblastoma:CD10-,CD10differentiatesfrommetastaticrenalcellcarcinoma(CD10+,ModPath2005;18:788)

Hepatocellularcarcinomavs.nonhepatocellularcarcinomas:52-68%sensitiveand>95%specificwithcanalicularpattern(AJSP2001;25:1297,AJSP2002;26:978),althoughanotherstudyrecommendsHepatocyte,MOC31,andpCEAbutnotCD10(ModPath2002;15:1279)

Microvillousinclusiondisease:strongCD10+cytoplasmicstainingvs.linearbrushborderstaininginnormals(AJSP2002;26:902)

Pancreas:solidandpseudopapillarytumorisCD10+(AJSP2000;24:1361)

Aberrantexpressioninlymphoma:describedinmantlecelllymphoma(AJCP2004;122:122),marginalzonelymphoma(JClinPathol1999;52:849),otherlymphomaswithCD5coexpression(AJCP2003;119:218,Archives2001;125:951)

Positivestaining(normal):hematopoieticcells-pre-Bcells,pre-Tcells,follicularcenter(germinalcenter)cells,granulocytes,Tcells(some);othercells-adrenalcortex,brain,choroidplexus,corticalthymocytes,endometrialstroma,endothelialcells,fibroblasts,genitourinary(male)epithelium,hepatocytes,kidneymicrovilli,liver,mesonephricremnants,myoepithelialcells(breast,ModPath2002;15:397,JClinPathol2004;57:625),ovary,placenta(cytotrophoblast,intermediatetrophoblast,syncytiotrophoblast),prostatebasalandsecretorycells,smallintestine(linearbrushborderstaining),wolffian(butnotmullerian)typeepithelium

Positivestaining(disease):leukemia/lymphoma-preBALL(75%),preTALL(63%,Archives2000;124:704);angioimmunoblasticTcell,Burkitt’s,CMLinblastcrisis(90%),diffuselargeBcell(variable),follicularcentercell(70%),hairycellleukemia(10%,AJCP2003;120:228),myeloma(some),plasmablastic(variable),primarycutaneousdiffuselargeBcell(variable),primarymediastinalBcell(32%,AJSP2001;25:1277);other-breastcancerassociatedstroma,breastmetaplasticcarcinoma,choriocarcinoma,coloniccarcinomaandhighgradedysplasiaassociatedstroma(HumPath2002;33:806),dermatofibroma,dermatofibrosarcoma,endometrialadenocarcinoma(mayalsobepresentindesmoplasticstroma,AJSP2003;27:786),endometrialadenomyosis,endometrialstromaltumors,Ewing’ssarcoma,gastriccarcinomaassociatedstroma(JpnJClinOncol2005;35:245),glioma,hepatocellularcarcinoma(canalicularpatternsimilartopolyclonalCEA,AmJPathol2001;159:1415),malignantfibroushistiocytoma,malignantmixedmulleriantumors,mediastinalgermcelltumors,melanoma(40%,associatedwithtumorprogression,ModPath2004;17:1251),mesonephrictumors(AJSP2001;25:1540),microvillousinclusiondisease(strongcytoplasmicstaining),mullerianadenosarcoma,pancreaticadenocarcinoma(50%),pancreaticsolid-pseudopapillarytumor,placentalsitetrophoblastictumor,prostatecarcinoma(someGleasonpattern4and5cases),renalcellcarcinoma(mostclearcell,variablepapillary,“aggressive”chromophobesubtypes,AJSP2000;24:203,ModPath2005;18:535,ModPath2004;17:1455),renalcellsarcoma,rhabdomyosarcoma(60%)andothersarcomas,schwannoma(45%),tumorofwolffianoriginofbroadligamentandovary,urothelialcarcinoma(54%),uterinecellularleiomyoma(50%),uterineleiomyosarcomaandotheruterinesarcomas,yolksactumor

Negativestaining:leukemia/lymphomas-AML,Burkitt’s-like,CLL,EBV+lymphoproliferativedisorders,lymphoplasmacytic,mantlecell,marginalzone,pyothoraxassociated;other-myeloidanderythroidprecursors,clearcellcarcinomasoffemalegenitaltract,prostateadenocarcinoma(allGleasonpatterns2and3,some4and5),highgradePINandprostaticbasalcellhyperplasia(HumPath2003;34:450),CNShemangioblastoma

References:OMIM120520;AJCP2005;124:371-inurothelialneoplasms,moreintensestaininginhighgradevs.lowgradelesions),AJCP2000;113:374-staininginnonhematopoietictumors),AdvAnatPathol2004;11:310-expressioninfemalegenitaltracttumors)

CD11

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CD11a,11band11callhavesamebetachain(CD18);perhapsalsoCD11dsinceitishomologoustotheothers

Membersofintegrinreceptorfamily;heterodimersofnoncovalentlyassociatedalphaandbetasubunits

Deficiency(leukocyteadhesiondeficiency)isarare,inheriteddisorder,causingrecurrentseverebacterialinfectionsearlyinlife,possiblyfatal(OMIM116920,HematolOncolClinNorthAm1988;2:13)

CD11a

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AlsocalledintegrinalphaL,LFA-1alphachain(incomplexwithCD18)

At16p11-13.1

AnalphaintegrinchainthatbindstoCD18andmediatesleukocyteadhesiontoendothelium,leukocytetraffickingthroughactivatedendothelium,lymphocyteblastogenesis,lymphocyte-endothelialcelladhesion,lymphocyterecirculationthroughlymphnodes;alsobindingtounopsonizedbacteria(e.g.E.coli)andfungi(e.g.Histoplasmacapsulatum),cytotoxicTcellmediatedkillingandantibodydependentkillingbyneutrophilsandmonocytes

WithCD18,bindstoICAM1(CD54),ICAM2(CD102),ICAM3(CD50)andICAM4(CD242)

Markerofdifferentiationinacutepromyelocyticleukemia

Uses:anti-CD11aantibodytherapy(efalizumab)improvesmoderate/severeplaquepsoriasis(JCutanMedSurg2003;7:198,ArchDermatol2002;138:591)

Positivestaining(normal):allleukocytes

Negativestaining:platelets,variousintermediateandhighgradelymphomas

References:OMIM153370

CD11b

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AlsocalledintegrinalphaM,Mac-1

At16p11-13.1

MediatesadhesiontosubstratesbyopsonizationwithiC3bandsubsequentphagocytosis,neutrophilaggregation,chemotaxis

Ligandsincludefibrinogen,FactorX,ICAM1,iC3b,Saccharomycescerevisiae,Staphylococcusepidermidis,Histoplasmacapsulatum,

HistoplasmacapsulatumcausesdecreasedcellsurfaceCD11bexpressionandanantiapoptoticstateonleukocytes(ScandJImmunol2002;56:392)

Uses:commonmyeloidmarkerandnaturalkillercellantigen;differentiatesrecoveryfromacuteagranulocytosis(CD11b+,CD117-)fromacutepromyelocyticleukemia(CD11b-,CD117+,AJCP2002;118:31);differentiatesDown’ssyndromepatientswithAML(usuallyCD13+,CD11b+)fromtransientmyeloproliferativedisorder(usuallyCD13-,CD11b-,AJCP2001;116:204),documentsmaturationoftumorcellsinacutepromyelocyticleukemiapatientsreceivingall-transretinoicacidtherapy(cellsbecomeCD11b+,CD16+,Archives2003;127:e4)orarsenictrioxide(CD11b+,CD33+,ModPath2000;13:954)

Positivestaining(normal):folliculardendriticcells,myeloidcellsbeginningwithpromyelocytes,granulocytes,macrophages,NKcells,someB/Tcells

Positivestaining(disease):AML-M1,M2andM3(35-70%),M4andM5(80-90%,AJCP1997;107:283);hairycellleukemia(virtuallyall),variouslymphomas,sinushistiocytosiswithmassivelymphadenopathy(HumPath1992;23:647)

Negativestaining:Gaucher’scells(AJCP2004;122:359)

References:OMIM120980

CD11c

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AlsocalledintegrinalphaX,CR4,LeuM5

At16p11-13.1

Clearsopsonizedparticlesandimmunecomplexes;alsobindstofibrinogenandisinvolvedinadhesionofmonocytesandneutrophilstoendothelium

Memberofbeta2familyofintegrinreceptors

Uses:histiocyticmarker,NKcellmarker,diagnosisofhairycellleukemia(withothermarkers)

Prognosticvalue:associatedwithgoodprognosisinB-CLL

Positivestaining(normal):50%ofactivatedCD4/CD8+Tcells;granulocytes,lymphocytes,macrophages,NKcells

Positivestaining(disease):AML-M4andM5(50%);hairycellleukemia(classicandvariant,virtuallyallcases,AJCP1991;96:100),lymphoplasmacyticlymphoma(81%,AJCP2005;124:414),SLL(AJCP1998;110:582),spleniclymphomawithvillouslymphocytes(AJCP1988;90:250),Langerhanscellhistiocytosis,sinushistiocytosiswithmassivelymphadenopathy(HumPath1992;23:647,HumPath1989;20:711),psoriaticskinlesions(ProcNatlAcadSciUSA2005;102:19057),somefollicularlymphomas

Negativestaining:mantlecelllymphoma,AML-M3(AJCP1998;109:211),splenicandnon-splenicmarginalzonelymphoma(AJCP1996;105:277)

References:OMIM151510

CD11d

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AlsocalledintegrinalphaD

At16p11.2

ReceptorforICAM3andVCAM1

Mayplayaroleinclearinglipoproteinsfromplaquesandphagocytosis

Monoclonalanti-CD11dantibodymayhaveaneuroprotectiveeffectinspinalcordinjury(JNeuroimmunol2004;156:42)

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):myeloidandmonocyticcells;peripheralbloodleukocytes,splenicredpulpmacrophages

Positivestaining(disease):macrophagefoamcellswithinatheroscleroticplaques

References:OMIM602453

CDW12

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Mayhavebeendeleted-minimalinformationispresentasofFebruary2006

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):granulocytes,monocytes,NKcells,platelets

Negativestaining:basophils,bonemarrowprecursors,AML

CD13

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AlsocalledAminopeptidaseN(APN)

Myeloidantigen,althoughCD33ismorespecific

Peptidecleavingenzymeofbrushbordermembranesofsmallintestine,renalproximaltubulesandplacenta

AlsopresentonCNSsynapticmembranes

Receptorforonestrainofhumancoronavirusthatcausesmanyupperrespiratorytractinfections;servesanimportantfunctionforearlyCMVinfection

Defectsappeartocausevariousleukemias/lymphomas

CD13autoantibodiesarestronglyassociatedwithchronicgraftversushostdiseaseafterbonemarrowtransplantation

Uses:(a)differentiateDown’ssyndromepatientswithAML(usuallyCD13+,CD11b+)fromtransientmyeloproliferativedisorder(usuallyCD13-,CD11b-,AJCP2001;116:204)

(b)myeloidmarkertodifferentiateAMLM0fromALL(AJCP2002;117:380)

(c)maybemarkerinchronicmyelomonocyticleukemiaifpartiallossinmaturemastcells(AJCP2004;122:865)

Positivestaining(normal):macrophages,myelomonocytes,interdigitatingdendriticcells,immaturemastcells,granulocytes(most,butlowlevelsintermbabies,ModPath1993;6:414),largegranularlymphocytes(some),fibroblasts,osteoclasts,perineuriumofperipheralnerves,centralnervoussystemsynapses,endothelialcells,placenta,renalproximaltubules,prostatesecretorycells,smallintestine,bileductcanaliculi,

Positivestaining(disease):AMLM1-M5(75-95%),M6(usually),CML(90%),CMLinblasttransformation(ModPathol1998;11:1211),neoplasticmastcells(AJSP2003;27:1013),anaplasticlargecelllymphoma(AJCP2003;119:205[47%],Archives2000;124:1804[casereport],AJCP2003;120:617[leukemic]),chronicBcelllymphoproliferativedisorders(Archives1995;119:53),preBALL(7-10%),preTALL(rare),CLL/SLL(rare,AJCP2003;119:824)

Negativestaining:prostateadenocarcinoma(AmJPathol2004;165:1543)

CD14

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Alsocalledlipopolysaccharide(LPS)receptor,monocytedifferentiationantigen

Patternrecognitionreceptorthatdetectsantigenicmoleculesonthesurfaceofbacteria(lipoteichoicacidongrampositive,LPSongramnegative),myobacteria(glycolipids),fungi(mannans),aspartoftheinnateimmunesystem

Adaptiveimmunesystem,bycontrast,referstolymphocytesrecognizingmicroorganismproteinsviaTcellreceptorsandantibodies

SolubleformofCD14issecretedbyliverandmonocytes;inlowconcentrationsitconfersLPSresponsivenesstocellswhichareotherwiseCD14negative

MacrophageswithamultiproteincomplexofCD14,MD-2andTLR4bindtoLPS,causingmacrophageactivationandreleaseofcytokines;overstimulationmaycausetoxicshocksyndrome

DetectionoflipopolysaccharideinducesIL-12production(mediatedbyCD14),producinginterferongamma,whichsteersimmunesystemawayfromallergydrivenThelper2phenotype,associatedwithIgEproduction

Mutationscanpreventadequateinflammatoryresponsetoinfection,leadingtosystemicinfections

Alsoinvolvedintheclearanceofapoptoticcells

EarlypromonocytesexpressMY4epitope;maturemonocytesexpressMO2epitope;neoplasticmonocytesalsooftenexpressMY4butnotMO2(AJCP2005;124:930)

Uses:identifymaturemonocytes/macrophages

Positivestaining(normal):macrophages/monocytes(90%),granulocytes-weak(30%),Langerhanscells;dendriticcells,Bcells

Positivestaining(disease):B-CLL(90%),follicularcentercelllymphoma(80%),diffuselargeBcelllymphoma(40%);AML-M4/M5(50-90%)

Negativestaining:myeloidprogenitors,AMLM0-M2(usually),M3,M6,M7;sinusoidalhistiocyteswithphagocyticproperties(erythrophagocytosis,anthracosis,tingiblebodymacrophages,HumPath2006;37:68),Gauchersmacrophages(HumPath1992;23:1410),mostepithelialandendothelialcells

References:OMIM158120

CD15

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AlsoknownasLeuM1,LewisX,3-fucosyl-N-acetyl-lactosamine

SynthesisisdirectedbyFUT9(OMIM104230)inlymphoidcellsandmaturegranulocytesandbyFUT4(OMIM606865)inpromyelocytesandmonocytes

Associatedwithmultipotentneuralstemcellsinmice(Glia2006;53:277)

Acarbohydrateadhesionmolecule(notaprotein)thatmediatesphagocytosisandchemotaxis

Interpretation:membranous,diffusecytoplasmicorGolgistaininginHodgkin’slymphoma

Uses:confirmdiagnosisofHodgkin’slymphoma(Reed-SternbergcellsareCD15+),helpdifferentiatebetweenHodgkin’slymphoma(CD15+)andanaplasticlargecelllymphoma(usuallyCD15-),helpdifferentiatebetweenadenocarcinoma(CD15+)andmesothelioma(CD15-),granulocytemarker

Casereports:CD15+pre-BALL(Archives2001;125:1227)

Positivestaining(normal):neutrophilsandeosinophils;activatedBandTcells(includinginfectiousmononucleosis);proximalconvolutedtubulesofkidney;normalsmallintestinalPanethcells(JClinPathol1996;49:474);variablemonocytes

Positivestaining(disease):Reed-Sternbergcells(classicHodgkin’slymphomaandfollicularHodgkin’slymphoma,AJCP2002;117:29),15%ofperipheralTcelllymphoma(AJSP2003;27:1513,IntJOncol2003;22:319),50%ofcarcinomas,5%ofBcelllymphomas(someB-CLLandpre-preBALL,AJCP2002;117:380.Archives2001;125:1227),someAML,occasionallyanaplasticlargecelllymphoma(AJCP2003;119:205,Archives1992;116:1192,butusuallynegative,AJSP2006;30:223)

Negativestaining:non-activatedlymphocytes,basophils,platelets,erythroidcells;L&HcellsinHodgkin’slymphoma,diffuselargeBcelllymphoma,granulocyticsarcoma(AJCP1994;102:55),systemicmastocytosis(HumPathol2001;32:545),pleuralepithelialmesothelioma(usually,HumPath2001;32:529),hairycellleukemia,malignantmeningioma(ModPath2006;19:417),malignanthistiocytes,Langerhanscellhistiocytosis

References:qualitycontrolforCD15

CD15s

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AlsoknownassialylLewisX

Mediatesleukocyterolling(ProcNatlAcadSciUSA1997;94:3172)

Ligand(receptor)forCD62PandCD62E

Mayplayaroleinclusterformationinlymphoidfollicles(ImmunolLett2001;79:181)

Hasborderlineprognosticsignificanceincolorectalcancer(Oncology2003;65:52;JSurgRes2002;103:68)

Expressedathighlevelsonperipherallymphocytesafterrenaltransplantrejection(Transplantation2000;69:59)

Expressionisstronglycorrelatedwithsusceptibilitytohumangranulocyticehrlichiosis(JClinInvest1999;103:407)

DeficiencycausesRambam-Hasharonsyndrome(#266265),atypeofleukocyteadhesiondeficiency(Emedicine)

Uses:nosignificantclinicalusebypathologistsforpathologists,butseeabove

Positivestaining(normal):granulocytes,macrophages

Positivestaining(disease):cirrhosis,metastaticcarcinoma,fibrolamellarandotherhepatocellularcarcinoma(Archives1992;116:643).CD4+CD56+neoplasia(LeukLymphoma2003;44:281),Sezarysyndrome(JAmAcadDermatol2001;44:456)

Negativestaining:normalhepatocytes

CD15u

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AlsoknownassulfatedCD15

Adhesionprotein

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):neutrophils,basophils,maturegranulocytes,monocytes,NKcellsandTlymphocytes;expressiononlymphocytesisvariabledependingontheantibodiesusedfordetection;alsoimmaturebonemarrowcellsandonendothelialcellsofhighendothelium(HEV)ofperipherallymphnodes

Positivestaining(disease):myelomonocyticleukemiacells,adenocarcinoma

CD16a

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AlsoknownasFcgammareceptorIIIA,lowaffinityimmunoglobulingammaFcregionreceptorIII-A

ReceptorfortheFcportionofIgG;bindsvariousIgGmolecules,includingrheumatoidfactor

Mediatesantibodydependentcytotoxicityofforeigncells,phagocytosisandotherantibody-dependentresponses;alsoplateletsatellitism(AJCP1995;103:740)

Affinitytoligandisregulatedbyglycosylation(Immunology2003;110:335)

CD14+CD16+monocyteshaveincreasedcapacitytoproduceproinflammatorycytokinessuchasTNF-alpha,andareelevatedinvariousinflammatorydiseases,includingcoronaryarterydisease(ThrombHaemost2004;92:419)

Polymorphismsinfluence:(a)theseveritybutnottheincidenceofIgAnephropathyinJapanesepatients(NephrolDialTransplant2005;20:2439);(b)pathogenesisofcoronaryarterydisease(Atherosclerosis2005;180:277),(c)clinicalresponsetorituximab(CancerRes2004;64:4664)

IftargetcellhasclassIMHC,thenNKcellskillercellinhibitoryreceptor(KIR)inhibitscytolysis

Note:preincubationwithCD16/CD32antibodiesiscommonlyusedtopreventnonspecificbinding

Uses:NKcellandmacrophagemarker;tosubtypeleukemia/lymphoma

Positivestaining(normal):NKcells(10-20%),granulocytes,macrophages,Tcells(reactive),immaturethymocytes,placentaltrophoblast

Positivestaining(disease):NKproliferativedisorders,Tcelllargegranularlymphocyteleukemia,hepatosplenicgamma-deltaTcelllymphoma

References:OMIM146740

CD16b

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AlsoknownasFcgammareceptorIIIB,lowaffinityimmunoglobulingammaFcregionreceptorIII-B

HighlyhomologoustoCD16a

ThemostcommonreceptorfortheFcdomainofIgGonleukocytes

TheonlyFcreceptorlinkedtotheplasmamembranebyaGPI(glycosylphosphatidylinositol)anchor

Bearsallotypesthatdefinethehumanneutrophilantigen-1(HNA-1andNA)systeminvolvedinmajorpost-transfusionalreactions(TissueAntigens2004;64:119)

Lowcopynumberisassociatedwithglomerulonephritisinsystemiclupuserythematosus(Nature2006;439:851)

CD16+eosinophilsareupregulatedinallergicconditions(JAllergyClinImmunol2002;109:463)

Affinitytoligandisregulatedbyglycosylation(Immunology2003;110:335)

Uses:nosignificantclinicalusebypathologists

Positivestaining:neutrophils

CD17/CDw17

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Alsoknownaslactosylceramide

[Note:“CD17”isalsoatypeofmutationinbeta-thalassemia,unrelatedtoCDmarkers]

AglycosphingolipidthatactsasalipidsecondmessengerinmediatingTNF-alpha,plateletderivedgrowthfactorandoxidizedLDL-inducedphenotypicchangesincellsofthevascularwall

Themostabundantglycosphingolipidinneutrophils

Elevatedlevelsarepresentinplasmaofpatientswithfamilialhypercholesterolemiaandplaqueintimaofaortainpatientswhodiedofcardiovasculardisease(ProcNatlAcadSciUSA2004;101:6490)

Rapidlyandextensivelydown-modulatedonactivatedgranulocytes

Bindstobacteriaandmayfunctioninphagocytosis

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):granulocytes,macrophages/monocytes,platelets,basophils,CD19+Bcells,tonsillardendriticcells

References:JImmunol1989;142:2784

CD18

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Formsthebeta2chainofCD11a-c(leukocyteadhesionmolecule)

GeneisdesignatedITGB2(integrinbeta2)

CombineswithalphaLchaintoformtheintegrinLFA-1;combineswiththealphaMchaintoformtheintegrinMac-1(macrophageantigen1,complementreceptor3)

Importantforadhesionandsignalinginthehematopoieticsystem(seeCD11a-cabove);alsoforphagocytosis(JImmunol2002;169:2003)

CD11b/CD18isreceptorforBordetellapertussisadhesinfilamentoushemagglutinin(FHA)andfortheadenylatecyclasetoxin(ACT),whichblocksneutrophilfunction(InfectImmun2005;73:7317,JExpMed2001;193:1035)

CD11b/CD18inducesneutrophilicresponseleadingtokillingofSteptococcuspyogenes(EurJImmunol2005;35:1472)

GroupAStreptococciM5proteinblocksbacterialassociationwithCD11b/CD18,whichpreventsingestionofbacteria(JImmunol2004;172:3798)

LeukocyteAdhesionDeficiency(LAD-1)iscausedbyCD18defectcodingforcommonB2subunit;patientssufferfromrecurrentinfections

Uses:nosignificantclinicalusebypathologists

Positivestaining:neutrophils,macrophages,monocytes,NKcells

References:OMIM600065

CD19

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CoreceptorwithCD21

EarliestBcellantigeninfetaltissue

RegulatesBcelldevelopment,activationanddifferentiation(JImmunol2003;171:5921)

Maydefineintrinsicandantigenreceptor-inducedsignalingthresholdscriticalforclonalexpansionoftheBcellpoolandhumoralimmunity(CurrDirAutoimmun2005;8:55)

MorecommoninplasmacellsinsteroidresistantulcerativecolitisthanCrohn’sdisease(VirchowsArch2006Jan25:1[Epubaheadofprint]);presenceofCD19+cellsinintestinalmucosamaypredictlongremissionafterinfliximab(anti-TNFalpha)therapyinCrohn’sdisease(Hepatogastroenterology2005;52:1128)

Uses:diagnosisofBcellsandBcelldisorders;maybemoresensitivethanCD20todetectBcellacuteleukemias(ZhongguoShiYanXueYeXueZaZhi2005;13:943),todifferentiatefollicularlymphoma(dimmerCD19inCD10+Bcellsbyflowcytometry)fromreactivehyperplasia(AJCP2005;124:576)

Positivestaining(normal):PreBcells,Bcells(consideredapanBcellantigen);firstBcellantigenafterHLA-DR,folliculardendriticcells

Positivestaining(disease):Bcelllymphomasandleukemiasbutoftenweak/negativeinfollicularlymphomaordiffuselargeBcelllymphoma(Histopathology2006;48:239,CytometryBClinCytom2005;63:28),occasionalmyeloidleukemias(AML-AJCP1998;109:211;AML-M0-AJCP2001;115:876;CMLblastphase-AJCP2004;121:836),occasionalanaplasticlargecelllymphomabyflowcytometry(AJCP2003;119:205)

Negativestaining:plasmacells,myeloma(AJCP2004;121:482),mostTcelllymphomas,oftenL&HcellsinlymphocytepredominantHodgkin’slymphoma,oftenpost-transplantBcelllymphoproliferativedisorder

References:OMIM107265

CD20

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AlsocalledL26,membranespanning4domains(MS4A1)

33kdphosphoproteinwith3hydrophobicregionsthattraversethecellmembrane,creatingastructuresimilartoanionchannelthatallowsfortheinfluxofcalciumrequiredforcellactivation

InitiallyexpressedonBcellsafterCD19/CD10expressionandbeforeCD21/CD22andsurfaceimmunoglobulinexpression;retainedonmatureBcellsuntilplasmacelldevelopment

DeliversearlysignalinBcellactivation,allowingrestingBcellstorespondtolaterantigens

CloselyrelatedtoFMC7,whichrecognizesaCD20epitope(Leukemia2003;17:1384),particularlyifthereisstrongCD20expression(AJCP2003;120:754)

Rituximabisachimericmurine-humananti-CD20antibodyusedtotreatBcelllymphomas;treatmentmaycauseselectionofCD20negative(butCD79a+)tumorsubclones(AJSP2005;29:1399)

Rituximabisalsousedtotreatautoimmunedisorders(ClinImmunol2005;117:207),TTP/HUS(ActaCytol2005;19:423),ABOincompatibletransplantation(TransplantProc2005;37:1205)andtransplantrejection(ClinTransplant2005;19:137)

AntiCD20-antibodyattachedtoradioisotopesisalsousedtotreatBcelllymphomas(ClinExpMed2006;6:1)

Casereports:CD20+Tcelllymphomas(AmJHematol2002;71:331,AJCP1994;102:483,ModPath2001;14:105,ModPath2000;13:1244);rarelystainsnucleoliofmalignantTcells(ActaCytol2005;49:365),butseeJClinPathol2004;57:442

Uses:commonlyusedmarkerforBcells

Positivestaining(normal):mostBcells(consideredapanBcellantigen),alsofolliculardendriticcells

Positivestaining(disease):90%ofBcelllymphomas;alsoB-CLL,hairycellleukemia,spindlecellthymomas(AJSP1992;16:988),40%ofpreBALL/LBL;80%ofnodularlymphocytepredominantHodgkin’slymphoma,20%ofclassicHodgkin’slymphoma(maybeanadverseprognosticfactor,BrJHaematol2004;125:701);dimlyexpressedinTcells(benignandneoplastic,particularlyinbonemarrow,AJCP1996;106:78,AJCP1994;102:483),somemyelomas(ModPath2004;17:1217,Blood2003;102:1070)

Negativestaining:non-hematopoieticcells,mostTcells,plasmacells,mastocytosis

Note:stainingdoesnotworkwellwithBouin’sfixative

Flowcytometry:brighterexpressioninfollicularlymphomasthannormalBcells(AJCP2005;124:576)

References:OMIM112210,JBiolChem2004;279:19893(presenceinlipidrafts)

CD21

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AlsocalledCR2,C3dreceptor,EBVreceptor

BindstoEpsteinBarrvirus(EBV)andHHV8(JVirol2005;79:4651),breakdownproductsofcomplementcomponentC3(C3d),CD23(playsaroleinIgEsynthesis)andpossiblygammainterferon

FolliculardendriticcellsproduceadifferentisoformofCD21thanBcells(JExpMed1997;185:165)

CD21,CD23andCD35aredendriticcellmarkers

Hodgkin’slymphomademonstratesdisruptionoffolliculardendriticcell-germinalcellclusters(evaluatedbyCD21andCD23)

Note:althoughCD21isthereceptorforEBV,itisnotnecessarilyexpressedinEBV+tumors

Showsvariabilityinflowcytometryexpressionbetweenspecimensfromsamepatient(AJCP2002;117:615)

Uses:diagnosefolliculardendriticcellsarcomas(AJSP1996;20:944);assessfolliculardendriticcellmeshworkinfrastructure(AJCP2005;124:182,AJSP2001;25:388),distinguishcutaneousornodalmantlecelllymphomafromfollicularlymphoma(AJSP2001;25:732,IntJSurgPathol2005;13:73),distinguishspleniclittoralcellangioma(CD21+liningcells)fromsplenichamartomas(CD21-,AJSP1997;21:827),confirmthatatypicalcellshavefolliculardendriticorigininfineneedleaspiratesofhyaline-vascularCastleman’sdisease(DiagnCytopathol2000;22:230)

Positivestaining(normal):matureBcells(particularlymarginalandmantlecells),folliculardendriticcells,pharyngealandcervicalepithelialcells,somethymocytes,someTcells

Positivestaining(tumors):folliculardendriticcellsarcoma(AJSP2004;28:988,AJSP2001;25:721),hairycellleukemia,Bcelllymphomas(particularlymantleandmarginalzone),hyalinevascularvariantofCastlemansdisease(AJSP2002;26:662),spleniclittoralcellangiomas(liningcellsareCD21+,AJSP1997;21:827),someT-ALL

Negativestaining:dendriticcellneurofibromawithpseudorosettes(AJSP2001;25:587),interdigitatingdendriticcellsarcoma(AJCP2001;115:589),histiocyticsarcoma(AJSP2004;28:1133),inflammatoryfibroidpolypsofGItract(AJSP2004;28:107),splenichamartomas,plasmacells

References:AJSP2001;25:721,ModPath2002;15:50,OMIM120650

CD22

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AlsocalledBlymphocytecelladhesionmolecule(BL-CAM)

InhibitsBcellreceptorsignalingviaalpha2,6sialicacidligandbindingactivity;alsohaspropertiesofalectinwithadhesionproperties(JExpMed2002;195:1207)

MaylocalizeBcellsinlymphoidtissues;bindsCD45

Showsvariabilityinflowcytometryexpressionbetweenspecimensfromsamepatient(AJCP2002;117:615)

CMC-544isaCD22-targetedcytotoxicimmunoconjugatecurrentlybeingevaluatedinB-celllymphomapatients(ClinCancerRes2004;10:8620);alsoepratuzumab(ClinCancerRes2004;10:5327)

Uses:panBcellmarker;diagnosisofhairycellleukemia;aberrantCD22expressionisusefultodetectmonoclonalBcellsadmixedwithbenignpolyclonalBcellsinB-CLL(usuallyCD22negative,AJCP2005;123:826)

Positivestaining(normal):Bcells(consideredapanBcellantigen)

Positivestaining(disease):hairycellleukemia;preBALL;otherBcellleukemias/lymphomas(variable,AJCP2002;117:615)

Negativestaining:plasmacells

References:OMIM107266

CD23

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AlsoknownaslowaffinityIgEreceptor,FcfragmentofIgEreceptor,FCER

AtypeClectinthatcanbesecreted

Afterphysiologicgerminalcelldevelopment,thefolliculardendriticcellmeshworkexpandsandfolliculardendriticcellsinthelightzoneofthegerminalcenterbecomeCD23positive

CD23actsasaBcellgrowthandactivationfactor,promotingdifferentiationintoplasmacells

RegulatesIgEsynthesisthroughCD21andIgEbinding(JExpMed2005;202:751),andmediatesIgErelatedimmuneresponses(ClinRevAllergyImmunol2005;29:61)

Showsvariabilityinflowcytometryexpressionbetweenspecimensfromsamepatient(AJCP2002;117:615)

CD21,CD23andCD35aredendriticcellmarkers

HighexpressiononBcellsinperipheralbloodisassociatedwithbullouspemphigoid(JDermatolSci2004;35:53)

CD23antibodiesmaydecreaseadherenceofPlasmodiumfalciparum-infectederythrocytes(CellMicrobiol2004;6:839)

Mantlecelllymphoma:usuallyCD23negative,butrarely/oftenhasCD23presentwithdimintensitybyflowcytometry,AJCP2003;120:760/AJCP2001;116:893;CD23+mantlecellcaseshavehighcyclinD1levels,AJCP2002;117:237);rarelyhasCD23+cellsinperipheralblood(AJCP2002;118:758)

Uses:differentiateSLL/CLL(CD23+)vs.mantlecelllymphomaorMALTlymphoma(CD23-);Bcellmarker,particularlyforSLL/CLL,mediastinallargeBcelllymphomaandlymphoplasmacyticlymphoma;distinguishnodalmantlecelllymphomafromfollicularlymphomabyidentifyingadisruptedfolliculardendriticcellpattern(IntJSurgPathol2005;13:73),mayidentifyprognosticallyfavorablecasesofdiffuselargeBcelllymphoma(ClinCancerRes2003;9:722),highsolubleCD23isassociatedwithaggressivediseaseandpoorerprognosisinCLL(LeukLymphoma2002;43:549,ClinLabHaematol2006;28:30)

Positivestaining(normal):activatedmatureBcellsexpressingIgMorIgD(particularlymantlecells),activatedmonocytes/macrophages,Tcellsubsets,platelets,eosinophils,Langerhanscells,folliculardendriticcells,intestinalepithelium(encodesIgEreceptor,Gastroenterology2005;129:928)

Positivestaining(disease):B-cellCLL/SLL(almostallcases;highlevels,LeukRes2002;26:809;atypicalcasesmayhavehigherlevels,AJCP2001;116:655);folliculardendriticcelltumors(includinginflammatorypseudotumortype-AJSP2001;25:721),mediastinallargeBcelllymphoma(70%,Histopathology2004;45:619),lymphoplasmacyticlymphoma(61%,usuallydimintensitybyflowcytometry,AJCP2005;124:414,ClinLymphoma2005;5:246),hairycellleukemia(17%,AJCP2006;125:251),diffuselargeBcelllymphoma(16%),

Negativestaining:otherBcelllymphomasincludingBurkitt’slymphoma,Burkitt-likelymphoma(AJSP2005;29:1652),follicularlymphoma,mantlecelllymphoma,marginalzonelymphoma(AJSP1999;23:59,ModPath1998;11:967);alsomostTcelllymphomas,inflammatoryfibroidpolypsofthegastrointestinaltract(althoughofdendriticcellorigin,AJSP2004;28:107),folliculardendriticcelltumor,interdigitatingdendriticcelltumor

References:OMIM151445,HumPath1999;30:648(earlystudy)

CD24

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Alsocalledheatstableantigenhomologue(HAS)

Aglycosylphosphatidylinositolanchorprotein(alsoCD14,CD16,CD48,CD55,CD58,CD59,CD67andCD73)withmucin-likeadhesionproperties

PromotesantigendependentproliferationofBcells

AligandofP-selectinontumorcellsthatisassociatedwithinvitroinvasiveness(TumourBiol2002;23:139,CancerRes2005;65:10783)andpoorerprognosisincarcinoma(seeUsesbelow)

Alsopreventsdifferentiationintoplasmacells,andmodifiesriskforprogressioninmultiplesclerosis(ProcNatlAcadSciUSA2003;100:15041)

RelativelyspecificandsensitiveforAMLM4/M5vs.AMLM1/M2(AJCP1994;101:296)

HigherlevelsbyRT-PCRinprostaticcarcinomavs.nodularhyperplasia(BMCUrol2006;6:7)

Uses:strongexpressionisapoorprognosticfactorincolorectalcarcinoma(ClinCancerRes2005;11:6574),nonsmallcelllungcarcinoma(BrJCancer2003;88:231),ovariancancer(AmJPathol2002;161:1215),intrahepaticcholangiocarcinoma(CancerLett2006;235:34)

Positivestaining(normal):allBcells,granulocytes,kidneycells,epithelialcells,nucleuspulposusofintervertebraldiscs,fallopiantube,muscle(ProcNatlAcadSciUSA2006;103:6374),someneurons

Positivestaining(disease):carcinomas,mostpre-BALL/lymphoblasticlymphoma,virtuallyallBcelllymphomas,chordoma(BiochemBiophysResCommun2005;338:1890),varioussolidcarcinomas(PatholResPract2005;201:479),Wilm’stumor(HumPathol1990;21:536)

Negativestaining:Tcells,monocytes,redbloodcells,platelets,plasmacells,ovarianepithelium,multiplemyeloma,chondrosarcoma

References:OMIM600074

CD25

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AlsocalledIL-2receptoralphachain,TAG;existsinatleast3forms

Consideredtobeanactivationantigen(alsoCD30)

CD4+CD25+cellsareregulatoryTcellsthat(a)suppresstheactivationofself-reactiveTcellsandpreventautoimmunity(diagram),(b)maypreventcytotoxicTcellsfromkillingtumorcells(JHepatol2006Mar9;[Epubaheadofprint],ZhongguoShiYanXueYeXueZaZhi2006;14:119),and(c)suppressimmunecellsreactivetohostantigensandpreventgraftversushostdisease(SeminCancerBiol2006;16:150)

CD4+CD25+cellsalsosuppressNKcells(ProcNatlAcadSciUSA2006;103;5460,JImmunol2006;176:1582),andmayactdirectlyonBcells(Blood2006Jan17[Epubaheadofprint])

Showsvariabilityinflowcytometryexpressionbetweenspecimensfromsamepatient(AJCP2002;117:615)

CoexpressionwithCD134onmemoryTcellsisamarkerfortype1diabetesassociatedTcellimmunity(Diabetes2006;55:50)

Highlevelsbyflowcytometryareassociatedwithadvancedstageinesophagealandgastriccancer(CancerImmunolImmunother200523;1)

Anti-CD25antibodyisclinicallyusefulintreatingfulminatingulcerativecolitisinchildren(JPediatrGastroenterolNutr2006;42:245)andinsequentialtherapyinrenaltransplantswithriskofdelayedgraftfunction(TransplantProc2005;37:3736)

Uses:highCD25expressionisassociatedwithadvancedcutaneousTcelllymphomaandwithclinicalresponsetodenileukindiftitoxtherapy,arecombinantfusionproteinofdiphtheriatoxinandIL-2,whichbindstoCD25(JInvestDermatol2006;126:575)

Positivestaining:activatedBandTcells,macrophages;somethymocytes,somemyeloidprecursorsandsomeoligodendocytes

Positivestaining(disease):hairycellleukemia(most,AJCP2006;125:251),anaplasticlargecelllymphoma(AJCP2003;119:205),mostBcellneoplasms,adultTcellleukemia/lymphoma,Reed-Sternberg-likecellsinperipheralTcelllymphoma(AJSP2003;27:1513),mostHodgkin’slymphomas,neuroblastoma,somemastocytosis(AJSP2004;28:1319),idiopathicretroperitonealfibrosis(AJSP1993;17:482),someAML

Negativestaining:non-neoplasticmastcells(AJCP2004;122:560),marginalzoneBcelllymphoma(AJCP1996;105:277),Tcelllargegranularleukemia/lymphoma(AJSP2005;29:935),often/usuallyvarianthairycellleukemia(AJCP2005;123:132)

References:OMIM147730

CD26

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Alsocalleddipeptidyl-peptidaseIV,DDPIV,adenosinedeaminasecomplexingprotein2

CostimulatorymoleculeinTcellactivationandproliferation;alsoregulatesvariouschemokinesandcytokines

Cleavesamino-terminaldipeptides;playsaroleincellspreadingandmigration

Eithersolubleinplasmaoroncellsurface

HIV1TaTproteinbindstoCD26andinhibitsitsactivity(ProcNatlAcadSciUSA1994;91:6594)

AcutekidneytransplantrejectionisassociatedwithincreasedserumCD26activity,andCD26inhibitionreducesacuteandacceleratedrejection(AdvExpMedBiol2003;524:133)

Reducedexpressioninmelanoma,endometrial(AmJObstetGynecol2003;188:670)andprostaticcarcinomabutincreasedexpressioninthyroidcarcinoma(DiagnCytopathol2002;26:366,AJCP1991;96:306);functionsasatumorsuppressorinnonsmallcelllungcarcinoma(IntJCancer2004;109:855)

BlastocystimplantationmayoccurbybindingofendometrialCD26toembryonalfibronectin(MolHumReprod2006Apr18[Epubaheadofprint])

HighCD4+CD26+Tcellcountsmayidentifymultiplesclerosispatientsathighriskfordevelopinganattackduringinterferontreatment(MultScler2005;11:641)

Uses:absenceofCD26stainingonperipheralbloodCD4+TcellsbyflowcytometryisusefultodiagnoseTcelllymphoma(AJCP2001;115:885,ClinExpDermatol2005;30:702);normallyCD26inactivatescutaneousSDF-1whichbindstoCXCR4inSezarycells(Blood2006;107:1108)

Positivestaining(normal):activatedTandBcells,NKcells,macrophages,endothelialcells,fibroblasts,mesothelialcells(Oncology2002;63:158)

epithelium-endometrium,hepatocytes,lung,prostate,renalproximaltubularcells,smallintestine

other-cytotrophoblastandextravilloustrophoblast(JClinEndocrinolMetab2002;87:4287),biliarycanaliculae,splenicsinusliningcells,maturethymocytes

Positivestaining(disease):esophagealadenocarcinoma(2/3ofBarrett’sassociated,alsoBarrett’smetaplasia,HumPath1999;30:1291),prostatecarcinoma,thyroidanaplasticcarcinoma(reducedexpressioninundifferentiatedvs.differentiatedareas(AJCP2006;125:399),Wilm’stumor(HumPath1990;21:536)

Negative/dimstaining:normalthyroidgland,Tcellsinperipheralbloodofmycosisfungoides/cutaneousTcelllymphoma(40%,BMCClinPathol2002;2:5)

References:OMIM102720

CD27

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Alsocalledtumornecrosisfactorreceptorsuperfamilymember7

BindstoCD70

MarkerofTcellactivation;alsoregulatesBcellactivationandimmunoglobulinsynthesis

Uses:helpdifferentiatememory-typeCD8+Tcells(CD27+)fromeffector-typeCD8+Tcells(importantagainstpathogens,CD27-);memoryBcells(CD27+)fromnaïveBcells(CD27-)

Positivestaining(normal):Tcells,memoryBcells,NKcells,plasmacells,medullarythymocytes

Positivestaining(disease):myelomas(64%,BrJHaematol2006;132:168)

Negativestaining:hairycellleukemia(Haematologica2005;90:266)

References:OMIM186711

CD28

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Tcellsrequire2signalsforfullactivation-thefirstbybindingoftheantigen/MHCcomplexonantigenpresentingcelltotheTcellreceptor;thesecondisdeliveredbytheinteractionofCD28withitsligandsCD80(B7-1)orCD86(B7-2),foundonactivatedBcells,andiscalledacostimulationsignal(diagramof2signals)

However,“superantagonistic”anti-CD28antibodies,awaitingclinicaltrialsforautoimmunediseases,activatematureTcellswithonlyonesignal(AnnRheumDis2005;64Suppl4:iv91)

ThecostimulatorysignalinducesTcellactivationandsurvival,interleukin-2production,T-helpertype2developmentandclonalexpansion

CD28isaconstitutive,highabundance,lowaffinityreceptor;itsbindingalsoincreasesexpressionofCTLA4(CD152),astructurallyrelatedcellsurfacereceptoronTcellswhichhasthesameligandsbutoppositeeffects(JClinImmunol2002;22:1,CurrPharmDes2006;12:149);CTLA4competeswithCD28forthesameligands(diagram)

ImbalanceinCTLA-4/CD28expressionatthematernal-fetalinterfacemayconfersusceptibilitytounexplainedpregnancyloss(IntJGynaecolObstet2006;93:123)

CD8+,CD28+Tcells:antigenspecificcytotoxicTcells(classIrestricted)(90%ofCD8+Tcells)

CD8+,CD28-Tcells:suppressorTcells;increasedinvariousinfectiousdiseasesandautoimmunediseasesandassociatedwithagingLossofTcellCD28expressionisassociatedwithaging,andfrequencyofCD28(null)Tcellspredictsimmuneincompetenceinelderly;theseTcellsarefunctionallyactiveandlong-lived,buthaveno/limitedproliferativecapacity(ImmunolRev2005;205:158)

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):CD4+Tcells(95%),CD8+Tcells(50%);activatedBcells,plasmacells(some)

Positivestaining(disease):myeloma(95%)

References:OMIM186760,Blood2005;105:13

CD29

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AlsocalledplateletGPIIa,integrinbeta-1(ITGB1),fibronectinreceptorbetasubunit,VLA(CD49)betachain

CommonbetasubunitofintegrinsVLA1toVLA6,whicharealsocomposedofalphasubunitsalpha1toalpha6(CD49a-f)

Involvedinlymphocyteandendothelialadhesion;importantforlymphocytetraffickingandtransvascularmigration

Promotesorinhibitsapoptosis,dependingontheligandsandapoptoticinsults(CancerRes2003;63:8302)

Effectsoftracrolimus(FK506)maybeduetoearlyinhibitoryeffectsofCD29(ClinExpRheumatol2004;22:197)

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):fibroblasts,platelets,Tcells,monocytes,granulocytes(low),mastcells,endothelialcells,myoepithelium;alsootherdiversecelltypes

Positivestaining(disease):bileductepitheliuminalcoholicliverdisease(16%,Archives1999;123:411),breastmetaplasticcarcinoma(90%,AJSP2005;29:347),breastsarcomasNOSthatareCD10+(some,AJSP2006;30:450),CD5+diffuselargeBcelllymphoma(CD29mRNApresentinlymphomacells,associatedwithhighserumLDH,IntJOncol2005;27:1241),myelomasinbonemarrow(BrJHaematol2002;119:70)

Negativestaining:intravascularlymphomatosis(HumPath2000;31:220)

References:OMIM135630

CD30

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AlsoknownasKi-1,Ber-H2

Memberoftumornecrosisfactorfamilyofcellsurfacereceptors;alsoalymphocyteactivationantigen

Overexpressioncausesconstitutiveexpressionofnuclearfactor-KB,whichisconsideredthemolecularbasisforaberrantgrowthandcytokineexpressionthatcausesHodgkin’slymphoma(AmJPathol2003;163:633)

LigandisCD153

MayalsobeinvolvedineliminationofautoreactiveTcellsinthymus

Inrenaltransplants,highserumsolubleCD30levelsingraftrecipientspredictsacuteandchronicrejectionandgraftloss(AmJTransplant2005;5:1922,TransplantProc2005;37:1776,Transplantation2005;79:1154)

AntiCD30antibodiesarepossibletreatmentforrefractoryHodgkin’slymphoma(JClinOncol2005;23:4669)

Interpretation:membranousandGolgitypestaining;doesn’tworkwellwithprolongedformalinfixationorwithB5fixation

Uses:confirmdiagnosisofanaplasticlargecelllymphoma,classicHodgkin’slymphoma,embryonalcarcinoma;otherlymphomadiagnosis

Positivestaining(normal):granulocytes,plasmacells(some,AJCP1989;91:18),activatedB,TandNKcells,monocytes,decidua(AmJPathol1994;145:276)

Positivestaining(disease):lymphoma-anaplasticlargecelllymphoma(systemicorprimarycutaneous,90%),classicHodgkin’slymphoma(Reed-Sternbergcells),alsoReed-Sternberglikecellsinfollicularlymphoma(AJCP2004;122:858,Archives2001;125:1036),primarymediastinallargeBcelllymphoma(usuallyfocal,AmJPathol2003;162:243),peripheralT-celllymphoma(occasional,AJSP2003;27:1513),sprueassociatedlymphoma,Lennert’slymphoma(occasional),primaryeffusionlymphoma(AJCP1996;105:221),primarycutaneousCD30+lymphoma,lymphomatoidpapulosis(Blood2002;100:578),granulocyticsarcoma(JClinPathol1996;49:762),diffuselargecelllymphoma(variable,usuallyfocal,AJSP2002;26:1458),plasmablasticlymphoma(Archives2004;128:581)andplasmacellneoplasms(some),eosinophilrichCD30+lymphoproliferativedisorderoforalmucosa(AJCP2004;121:43),sinonasalNK/Tcelllymphomawithlargecellmorphology(focal,AJSP2000;24:1511),nasalNK/TcelllymphomainChinesepatients(HumPath2006;37:54)

other-embryonalcarcinomaoftestis(100%,butvariableintensity,AJSP2004;28:935),yolksactumors(24%,HumPath1998;29:737),seminoma(6%,AJCP2000;113:583),rarelymesothelioma(Archives2000;124:1077),lymphocytesinfectedwithHIV,HTLV-1,EBV,HHV8,hepatitisB,herpes(AJSP2006;30:50);alsonon-neoplasticinflammatorycutaneousinfiltrates(AJSP2003;27:912)

Negativestaining:nodularlymphocytepredominantHodgkin’slymphoma(AJCP2003;119:192),Tcellprolymphocyticleukemia(AJSP2005;29:935),adultTcellleukemia/lymphoma,pre-BALL,interdigitatingdendriticcellsarcoma(AJCP2001;115:589),folliculardendriticcelltumor,histiocyticsarcoma(AJSP2004;28:1133),reticulohistiocytoma(AJSP2006;30:521),Kikuchi’sdisease/necrotizinglymphadenitis(AJSP1999;23:1040),extramedullarymyeloidtumors(AJSP1993;17:1011),systemicmastocytosis(HumPath2001;32:545),melanoma,lymphoepithelioma-likecarcinoma

References:OMIM153243,JClinPathol2002;55:162(Hodg,kin’slymphoma)

CD30v

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VariantformofCD30whichretainsonlythecytoplasmicdomain

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):alveolarmacrophages

Positivestaining(disease):myeloidandlymphoidmalignancies

Negativestaining:bonemarrow

References:AmJPathol1999;155:2029

CD31

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Alsoknownasplateletendothelialcelladhesionmolecule,PECAM-1

Belongstoimmunoglobulinsuperfamily;ligandisCD38

Celladhesionmoleculethatplaysakeyroleinleukocytetraffickingacrossendothelium(Blood2003;101:2816);alsoangiogenesisandremovalofagedneutrophilsfrombody

Maymediatesignal-transductionpathwayregulatingcapacitationinspermatozoa(JCellSci2005;118:4865)

MayactasaminorhistocompatibilityantigeninHLA-identicalstemcelltransplantation(BoneMarrowTransplant2005;36:151)

Interpretation:membranousstain(notcytoplasmic);endotheliumisapositiveinternalcontrol;don’tconfuseCD31+macrophages(granular,membranousexpression)withavasculartumor(AJSP2001;25:1167)

Uses:confirmsvascularoriginoftumors,highlightvesselsandidentify/confirmvascularinvasion(JClinPathol2003;56:786,Archives2005;129:354);CD31isthemostsensitiveandspecificendothelialmarkerinparaffinsections;stainssmallandlargevessels

Positivestaining(normal):endothelialcells(atcelljunctions)includingglomeruli,alveolarwallcapillaries,hepatic,lymphaticandsplenicsinuses(JHistochemCytochem2006;54:385),platelets,megakaryocytes(Archives2002;126:618),monocytes,macrophages,Kupffercells,osteoclasts,granulocytes,T/NKcells,plasmacells(extramedullary-strong;bonemarrow-focal,JClinPathol1997;50:490),fibroblasts,brownfat(Archives2006;130:480),trophoblast(MolHumReprod1998;4:357),spermatozoa

Positivestaining(disease):vascularlesions-benignvascularproliferations(AJSP2002;26:328)andbloodvesselsintumors(usually);angiosarcoma;hemangioendothelioma(AJSP2003;27:48,AJSP2004;28:559);hemangioma;intravascularpapillaryendothelialhyperplasia(HumPath1996;27:986),Kaposi’ssarcoma;littoralcellangiomaofspleen;lymphangioendothelioma(AJSP2000;24:1047);lymphangioma(ModPath1999;12:569,HumPath2005;36:426);papillaryendovascularangioendothelioma(AJSP1999;23:1004),sclerosingangiomatoidnodulartransformationofspleen(AJSP2004;28:1268),splenichamartoma

other-breastDCIS-highgrade(JPathol2001;194:254);epithelioidsarcoma(focalin7%,HumPath1999;30:934,VirchowsArch2003;443:93,butproximaltypeisnegative,AJSP1997;21:130),Ewing’ssarcoma/PNET(focalin5%,ApplImmunohistochemMolMorphol2000;8:19),granulocyticsarcoma(25%,AJCP1994;102:55),hibernoma,histiocytesingranulomas,Langerhanscellhistiocytosisandsinushistiocytosiswithmassivelymphadenopathy(Archives2003;127:341);histiocyticsarcoma(AJSP2004;28:1133);intimalsarcomaoflargesystemicvessels(AJSP2005;29:1184);juvenilexanthogranuloma;lymphoblasticlymphoma(ApplImmunohistochemMolMorphol2000;8:19),plasmacytomas(50%);rareincarcinomaandmesothelioma(AJCP1998;110:374)

Negativestaining:normal-Bcells,epidermalLangerhanscells,vascularadventitialfibroblasticcells;disease-adenomatoidtumor,gastrointestinalstromaltumor,giantcellfibroblastoma,lipomatoushemangiopericytoma(HumPath2000;31:1108),mesothelialcyst(AJSP1997;21:334),nonvascularsofttissuetumors,mycobacterialpseudotumor(AJSP1999;23:656),myeloma,myxoma,peripheralTcelllymphoma,pseudoangiomatousstromalhyperplasiaofbreast;sclerosinghemangiomaoflung(Archives2001;125:1335),solitaryfibroustumor(HumPath1995;26:440)

References:OMIM173445

CD32

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AlsocalledFcgammaRII;subtypedasFcgammaRIIa,RIIbandRIIc

Lowaffinityreceptoronwhitebloodcells(seebelow)thatbindstotheFcregionofIgGimmunecomplexestoremoveforeignantigens

AllelesR131andH131differintheirabilitytobindIgG2(H131providesoptimalbindingifhomozygous)

Polymorphismsaffectsincidenceorseverityofsomediseases,includingantiphospholipidsyndrome(ArthritisRheum2003;48:1930),IgAnephropathy(NephrolDialTransplant2005;20:2439),malaria(AmJTropMedHyg2003;69:565),myastheniagravis(JNeuroimmunol2003;144:143),peripheralatherosclerosis(ThrombHaemost2004;92:1273),rheumaticfever(ClinBiochem2004;37:925)andsystemiclupuserythematosus(ArthritisRheum2002;46:1563)

SpecificCD16andCD32allelesareassociatedwithresponseoffollicularlymphomatorituximab(JClinOncol2003;21:3940)

Indendriticcells,CD32aisconsideredanactivatingisoformandCD32baninhibitoryisoform;thebalancebetweenthesereceptorsestablishesathresholdofactivationandenablesimmunecomplexestomediateopposingeffectsondendriticcellmaturationandfunction(JClinInvest2005;115:2914)

PreincubationwithCD16/CD32antibodiesiscommonlyusedtopreventnonspecificbinding

Uses:nosignificantclinicalusebypathologists

Positivestaining:monocytes,macrophages,Bcells,NKcells,granulocytes,eosinophils,basophils,platelets,plasmacells(some)

Positivestaining(disease):follicularlymphoma

Negativestaining:Tcells(usually,Immunology1997;90:109)

References:OMIM146790

CD33

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Glycosylatedtransmembraneproteinofsialicacid-bindingimmunoglobulin-likelactic(siglec)family

Maymediatecell-to-celladhesion;actsasreceptorthatinhibitstheproliferationofnormalandleukemicmyeloidcells

Classicmyeloidantigen(alsoCD13)

Anti-CD33antibody,gemtuzumabozogamicin,isusedtotreatAML(BioDrugs2006;20:137,Cancer2005;104:1442)

Moreintenseinbonemarrowvs.peripheralblood;intensityalsovariesbetweenleukemias(AJCP2002;118:560)

Uses:distinguishmyeloidandlymphoidleukemia;identifymonocytesbyflowcytometry;negativeselectionforstemcells

Positivestaining(normal):progenitorandothermyeloidcells(decreasingexpressionwithmaturation,AmJPathol2001;158:1473);granulocytes(lowlevelexpression),mostmonocyticcells,mastcells(AmJPathol1996;149:1493),NKcells,Tcells(some,JLeukocBiol2006;79:46),epidermalLangerhanscells(variable),circulatingperipheraldendriticcells(variable)

Positivestaining(disease):AMLM0(almostall,AJCP2001;115:876),M1-M5(75-85%),M6,M7(variable),CML(90%);myeloid/granulocyticsarcoma(JClinPathol2005;58:325),transientmyeloproliferativedisorder(AJCP2001;116:204),CD4+CD56+acuteleukemias(Blood2005;105:1256)andlineagenegativemalignancies(weakin44%,AJSP2005;29:1274),myelomaandplasmacytoma(occasionalreports),aberrantexpressioninanaplasticlargecelllymphoma(AJCP2003;119:205),Burkitt’slymphoma(JClinPathol1993;46:778),SLL/CLL(AJCP2003;119:824)orT-ALL(AJCP2000;113:823)

Negativestaining:pluripotentstemcells,Bcells,dendriticcells(tonsil,AmJPathol2001;159:285);mostBandTcelllymphoma,usuallyblasticNKlymphoma;notexpressedoutsidehematopoieticsystem

References:OMIM159590

CD34

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Intercellularadhesionproteinandcellsurfaceglycoprotein;ligandisCD62L(L-selectin)

Maymediateattachmentofstemcellstobonemarrowextracellularmatrixordirectlytostromalcells,althoughspecificfunctionisunknown

CD34+stromalcellsarecalleddendriticinterstitialcells

Definesadulthematopoieticstemcells;canalsodifferentiateintoneuralcells(ExpNeurol2006;197:399)

Note:countingCD34+mononuclearcellsmayoverestimatemyeloidblastsinbonemarrowsmearsduetoCD34+hematogonesandCD34+megakaryocytes(Archives2002;126:823)

InAML,detectionofCD34+cellsbyflowcytometryandimmunohistochemistryarecomparable(Archives2001;125:1063)

Stainingrepresentspresenceofprotein,notcrossreactivity,despitewiderangeoftissuesthatareCD34+(AmJPathol2000;156:21)

CD34stainingofperitumoralstroma:positive:gastricadenocarcinoma-diffusetypeinvadingmuscularispropria(JClinPathol2001;54:846);negative:breastcarcinoma(JClinPathol2003;56:271),colorectaladenocarcinoma(JClinPathol2000;53:626),gastricadenocarcinoma-intestinaltypeanddiffusetypeconfinedtosubmucosa(JClinPathol2004;57:183)

Interpretation:membranousstain;endotheliumactsasapositiveinternalcontrol

CD34Uses:(a)distinguishDFSPandKaposi’ssarcoma(CD34+)orepithelioidsarcoma(oftenCD34+)fromdematofibroma(CD34-);(b)distinguishsolitaryfibroustumor(CD34+)fromdesmoplasticmesothelioma(CD34-,HumPath1995;26:428);(c)distinguishhemangiopericytoma(CD34+)fromendometrialstromalsarcoma(CD34-,ModPath2005;18:40);(d)distinguishvascularinvasionfromdisplacedepithelium(JClinPathol2002;55:780);(e)differentiatelymphocyterichthymoma(CD34+cells)fromT-ALL(usuallyCD34-,AJCP2004;121:268);(f)quantifyandpurifylymphohematopoieticstemcell/progenitorcellsforresearchandforclinicalbonemarrowtransplantation(FoliaHistochemCytobiol2006;44:53,EurJHaematol2006;76:160,BreastCancer2005;12:178);(g)identifyblastsinhypoplasticmarrowstodistinguishacuteleukemiaandmyelodysplasticsyndrome(blastspresent)fromaplasticanemia(noblasts/lowmarrowCD34+cells,Leukemia2006;20:458);(h)determinevascularizationoftumorsordiseaseprocesses(SaudiMedJ2006;27:154);(i)poorprognosticfactorinnewlydiagnosedAML(Neoplasma2005;52:402),(j)maysupportdiagnosisofessentialthrombocythemia;(k)possiblyconfirmdiagnosisofchronicintestinalpseudo-obstruction(AJSP2003;27:228)

Highmicrovesseldensity(usingCD34):associatedwithpoorerprognosisinesophagealsquamouscellcarcinoma(JClinPathol2001;54:940),poorsurvivalinnonsmallcelllungcancer(JClinPathol2004;57:591),PSArecurrence(AJCP2000;113:555)

CD34Positivestaining(normal):dendriticinterstitialcells,dermaldendrocytes,endometrialstroma,endoneurium(ModPath2003;16:293),fibroblastsinbreast,hairendothelialcellsofbloodvessels[includesalveolarwallcapillaries,glomeruliandperiportalhepaticsinusoidsbutnotsplenicsinusoids,JHistochemCytochem2006;54:385],endothelialcellsofsomelymphatics,fibrocytes,hematopoieticprogenitorcells(pluripotentanderythroid-,lymphoid-andmonomyeloidcommittedcells),folliclecells,interstitialcellsofCajal(20%,AmJPathol2000;156:1157),lymphocyte(BandT)precursors,neuralstemcellsinCNS(ExpNeurol2006;197:399),perivascularstroma,umbilicalcordblood(JClinPathol2001;54:428),vascularadventitialfibroblasticcellsinstomach

CD34Positivestaining(disease):preB-ALL(75%,AJCP2004;121:512),alveolarsoftpartsarcoma,AML(40-60%,Archives2003;127:42)butnotM3,AML-M0(almostall,AJCP2001;115:876,particularlyadults,AJCP2000;113:193),AML-M7(most),AMLwitht(6;9)(AJCP2004;122:348),analskintags,angioblastoma(tuftedangioma,JClinPathol2005;58:214),angiomyofibroblastoma(variable,Archives2000;124:1679,HumPath1997;28:1046),angiosarcoma(70%,AJSP1998;22:683),atypicalfibroushistiocytomaofskin(focalin10%,AJSP2002;26:35),benignepithelioidperipheralnervesheathtumor(fibroblastsareCD34+,AJSP2005;29:39),bloodvesselsintumors,calcifyingfibrouspseudotumor(IntJSurgPathol2002;10:189),cellularangiofibroma(60%,AJSP2004;28:1426),cellulardigitalfibroma(JCutanPathol2005;32:413),chordoidglioma(focal,AJSP2002;26:1330),congenital/infantilefibrosarcoma,cysticpanfolliculoma-surroundingfibroticstromaisCD34+(Archives2006;130:389),dendriticfibromyxolipoma,dendriticinterstitialcellsatmarginofsalivaryglandtumors(Archives2001;125:232),dermaldendrocytoma(AmJDermatopathol2002;24:50),dermatofibrosarcomaprotuberans(BrJDermatol1992;127:79,AJSP2003;27:27),epithelioidhemangioendothelioma(AJCP1991;96:25),epithelioidsarcoma(50%,HumPath1999;30:934,AJSP1997;21:130),fibroadenoma(breast),ganglioglioma,glioneuralhamartoma,gastriccarcinoma-diffusetype-vascularadventitialfibroblasticcells(JClinPathol2004;57:970),gastrointestinalstromaltumor(50-80%,AJSP2005;29:52),giantcellangiofibroma(AJSP2000;24:971),giantcellfibroblastoma(AJSP2003;27:27),glomustumor/glomangioma(variable,JCutanPathol1993;20:15,TohokuJExpMed1997;182:241),granulocyticsarcoma(47%,Archives2001;125:1448),hamartomatoustumorsofchronicdrugresistantepilepsy,hemangioblastoma,hemangioma(variable,AJSP1999;23:97),hemangiopericytoma(50-100%,includingmeningeal,AJSP1999;23:1201,HumPath1998;29:636),hepatocellularcarcinoma,inflammatoryfibrouspolypsofstomach/GItract(HumPath2002;33:307,AJSP2004;28:107),juxtaglomerularcelltumor(AJCP2001;116:854,maybefocal,AJSP2004;28:1098),kaposiformhemangioendothelioma(AJSP2004;28:559),Kaposi’ssarcoma(90%,stronganddiffuseinspindlecells),Kaposi’ssarcoma-likepyogenicgranuloma(JClinPathol2002;55:619),lipomatoustumors(benignandmalignant,AJSP1997;21:195),liposarcoma(myxoid,pleomorphic,welldifferentiated,AJSP2002;26:601),lymphangioma(50%,HumPath2005;36:426),lymphangioendothelioma,malignantfibroushistiocytoma,malignantperipheralnervesheathtumors(lowgradestronger/morefrequentthanhighgrade,AJSP2003;27:1337),meningioma(some,AJSP2002;26:125),metanephricadenosarcomaofkidney(stromaonly,AJSP2001;25:1451),metanephricstromaltumorofkidney(patchy,AJSP2000;24:917),microcysticadnexalcarcinoma(AJSP2001;25:464),mucosalepithelioidnervesheathtumors(AJSP2005;29:1310),myelodysplasticsyndrome(myeloidblasts),myofibroblastoma(breast,cervicovaginal,softtissue,AJSP2001;25:1022),myxoidMFH(38%,JClinPathol2003;56:666),neurofibroma(AJCP2000;114:123),nuchalfibroma,papillarythyroidcarcinoma,paratesticularleiomyosarcoma(30%),periductalstromalsarcomaofbreast(AJSP2003;27:343),perineurioma(variable,AJSP2005;29:859),phyllodestumorofbreast(morecommonifbenign,JSurgRes2000;94:84),pleomorphichyalinizingangiectatictumor(Archives2000;124:423),pseudoangiomatousstromalhyperplasiaofbreast(JClinPathol1998;51:204,AJSP1995;19:270),reactiveangioendotheliomatosisofskin,schwannoma(AntoniBareas,AJCP2000;114:123),sclerosingangiomatoidnodulartransformationofspleen(capillaries,AJSP2004;28:1268),sclerosinghemangiomaoflung,sclerosingliposarcoma(spindleandatypicalcells),solitaryfibroustumor(AJSP1994;18:992,HumPath1995;26:440,expressionmaybelostwithmalignanttransformation,Archives2004;128:460),solitaryscleroticfibromaofskin(JCutanPathol2003;30:631),spindlecelllipoma,stromalsarcomaofprostate,superficialacralfibromyxoma(HumPath2001;32:704),thymoma(ectopichamartomatousvariant;otherwiseweak(AJSP2005;29:1208),transientmyeloproliferativedisorderblasts(AJCP2001;116:204),tumorlymphaticendothelialcells(AmJPathol2006;168:1045),vaginalmixedtumor/spindlecellepithelioma(ModPath2004;17:1243),vulvarfibroma-prepubertal(AJSP2004;28:1601)

CD34Negativestaining:normalhepaticsinusoidsandbonemarrowmasscells;adenomatoidtumor(AJSP2003;27:969),AML-M3,angiofibroma(cellular)ofvulva,angiomyxofibromatoustumor(AJSP2006;30:545),benignfibroushistiocytoma,benignvascularproliferationsinirradiatedskin(AJSP2002;26:328),carcinoma,chondromyxoidfibroma,epithelioidsarcoma-likehemangioendothelioma(AJSP2003;27:48),Ewing’ssarcoma/PNET,fibroblasticpolypofcolon(maybeweak/focal,AJSP2004;28:374),fibromatosis(JClinPathol2004;57:1119,AJSP2002;26:1296),folliculardendriticcellsarcoma,gliosarcoma(Archives1997;121:129),histiocyticsarcoma(AJSP2004;28:1133),inflammatorymyofibroblastictumor,interdigitatingdendriticcellsarcoma(AJSP2002;26:530),leiomyoma(usually,AJSP2001;25:1355)andvascularleiomyoma(JClinPathol2002;55:395),leiomyosarcoma(usually),littoralcellangiomaofspleen(AJSP1997;21:827),melanoma(rarelyCD34+,JCutanPathol2005;32:685),mesothelialcyst(AJSP1997;21:334),myofibrosarcomaofbreast,PEComa(AJSP2005;29:1558),plexiformxanthomatoustumor(AJSP2002;26:1302),synovialsarcoma(focalin6%ofmonophasictumors,AJSP2002;26:1434),thymoma

References:OMIM142230,Archives2002;126:1189(GISTandsolitaryfibroustumor)

CD35

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Alsocallederythrocytecomplementreceptor1(CR1),C3bandC4breceptor

BindsimmunecomplexescoatedwithC3borC4bandmediatestheirtransporttoandremovalbythefixedphagocytesystemsofthespleenandliver

CofactorforspecificproteolyticcleavageofC3bandC4bbyplasmaserineproteasefactorI,whichlimitscomplementactivationandproducesligandsforothercomplementreceptors

TheKnops,McCoy,Swain-Langley,andYorkbloodgroupantigensarelocatedonCD35(moreinformation)

CD21,CD23andCD35aredendriticcellmarkers

ReducedexpressionbyPCRingallbladdercarcinoma(WorldJGastroenterol2004;10:3480)andinredbloodcellsinsevereacuterespiratorysyndrome(ClinExpImmunol2005;139:112),mesangiocapillaryglomerulonephritis,preeclampsia(AmJReprodImmunol2005;54:352),systemiclupuserythematosis(ArthritisRheum2004;50:3596)

Actsasamalariaresistancegene,anddeficienciesofCR1areprotective(ProcNatlAcadSciUSA2004;101:272)

Aspecificgenotypeisassociatedwithsarcoidosisinfemales(AmJRespirCellMolBiol2002;27:17)

Uses:diagnosefolliculardendriticcellsarcomas(AJSP1996;20:944);confirmpresenceoffolliculardendriticcellmeshworkinprogressivetransformationofgerminalcenters(JClinPathol2002;55:162)andlackofmeshworkinsplenicTcellrichBcelllymphoma(AJSP2003;27:903)

Positivestaining:granulocytes,monocytes,macrophages(some),Bcells,Tcells(10%),NKcellsubset,erythrocytes,folliculardendriticcells,eosinophils,glomerularpodocytes(AJCP1993;99:257),someastrocytes

Positivestaining(tumors):folliculardendriticcellsarcoma(AJSP1998;22:1048,AJSP2001;25:721,ModPath2002;15:50),Hodgkin’slymphoma(Reed-Sternbergcellsin5%,AJSP1999;23:363),inflammatoryGIfibroidpolyps(focalinstromalcells,AJSP2004;28:107),mantlecelllymphoma,marginalzonelymphoma

Negativestaining:fibroblasticreticulumcelltumor,histiocyticsarcoma(AJSP2004;28:1133),inflammatorymyofibroblastictumor(AJSP1998;22:412),interdigitatingdendriticcelltumor(AJSP1999;23:1141)

Reference:OMIM120620

CD36

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AlsoknownasplateletGPIVorGPIIIb,fattyacidtranslocase(FAT);givesrisetoNakaantigen

Associatedwithplateletdisorders:receptorforthrombospondin;actsascelladhesionmoleculeinplateletadhesionandaggregation,platelet-monocyteandplatelet-tumorcellinteractions

CD36isoantibodymaycauseposttransfusionpurpuraandplatelettransfusionrefractoriness(Transfusion1995;35:777);maycauselifethreateninghypotensionandthrombocytopenia(Transfusion2005;45:803)

DefectscauseplateletglycoproteinIVdeficiency(MIM:608404)

Hydropsfetalismaybecausedbyanti-CD36antibody(ThrombHaemost2006;95:267)

Associatedwithatherosclerosis:scavengerreceptorforoxidizedLDL(Atherosclerosis2006;184:15)andshedphotoreceptoroutersegments;alsotransportslongchainfattyacids

Upregulatedinfamilialcombinedhyperlipidemia(FASEBJ2005;19:2063)

CD36deficiencyassociatedwithhyperlipidemia,insulinresistanceandmildhypertension(MolCellBiochem2006May3;[Epubaheadofprint]);deficiencymorecommoninAsiansandAfricans

Maybetastereceptorforfattyacids(JClinInvest2005;115:2965)

Associatedwithmalaria:siteofcytoadherenceofPlasmodiumfalciparuminfectederythrocytestomicrovascularendothelialcells

CD36deficiencyisfrequentinsub-SaharanAfrica,Asia,andisassociatedsurprisinglywithsusceptibilitytoseverecerebralmalaria

AssociatedwithAlzheimer’sdisease:maymediatebindingtofibrillarbeta-amyloid;presentinmicrogliaandendotheliuminAlzheimer’sdisease;lowlevelsonperipheralbloodleukocytesinAlzheimerpatients(NeurobiolAging2006Mar21;[Epubaheadofprint])

Associatedwithmacrophagephagocytosis:diagram

Uses:

Positivestaining(normal):platelets,monocytes,macrophages,endothelialcells,earlyerythroidcells,megakaryocytes;alsoadiposetissue,breastepithelialcells,cardiacmuscle,Sertolicellsoftestis(elderlymen,hypospermatogenesis,HumPath2004;35:34),skeletalmuscle,spleniccells

Positivestaining(disease):Alzheimer’sdisease(microglial,endothelialcells,AmJPathol2002;160:101),AMLM4-M7,cervicalLSIL(HumPath1994;25:73),CML(60%,ModPath1998;11:1211),Gauchercells(AJCP2004;122:359),myxoidliposarcoma(AJCP1995;103:20),plasmacytoidTcelllymphoma(casereport,AJCP1990;93:822),transientmyeloproliferativedisorderinDown’ssyndrome(AJCP2001;116:204)

Negativestaining:AMLM0-M2(usually),AML-M3(AJCP1998;109:211)

References:OMIM173510

CD37

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Belongstotetraspaninfamily(membershave4hydrophobicdomains)

RegulatesTcellproliferation(JImmunol2004;172:2953)

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):Bcells,Tcells(low),neutrophils(low),monocytes(low),macrophages,dendriticcells

Positivestaining(disease):mostBcelllymphomas(Leukemia1994;8:1864),someTcelllymphomas

Negativestaining:NKcells,platelets,erythrocytes,plasmacellneoplasms,preB-ALL(orlow)

References:OMIM151523

CD38

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Multifunctionalenzyme;ligandisCD31

Functions:(a)synthesizescyclicADP-ribose,asecondmessengerforglucoseinducedinsulinsecretion;(b)positiveandnegativeregulatorofcellactivationandproliferation,dependingonthecellularenvironment;(c)involvedinadhesionbetweenhumanlymphocytesandendothelialcells;(d)consideredanactivationmarker;(e)maycausephysiologicdeathofTcellprecursorsinhumanthymus(IntImmunol2003;15:1105)

IncreasedTcellexpressioninHIV+patients(JAcquirImmuneDeficSyndr2005;38:373);CD8+CD38+TcellsinHIV+patientsmaybemorepronetoapoptosis,hinderingtheirusualanti-viralrole(ProcNatlAcadSciUSA2004;101:2464)

Presenceon30%ormoreB-CLLcellsbyflowcytometryisassociatedwithpoorprognosis(Leukemia2005;19:750);maybeduetodirectsignalingroleinthesecells(Blood2003;102:2146)

BimodalantigenexpressioniscommonbyflowcytometryinCLL,buthasnoprognosticimportance(AJCP2005;123:818)

Medianfluorescenceintensity(MFI)ofCD38expressiononmemory(CD45RO)CD8TcellscorrelateswithRNAviralload(JAcquirImmuneDeficSyndr2006;41:416)

AutoimmunereactionagainstCD38isassociatedwithnewly-diagnosedtype1diabetes(JPediatrEndocrinolMetab2005;18:1417)

Uses:identifyplasmacellsandplasmablasticdifferentiation,diagnosisofmyeloma,prognosisforCLLpatients(seeabove)

Positivestaining(normal):plasmacells(strong),committedhematopoieticprogenitorcells,NKcells,BandTcells,monocytes,erythroidandmyeloidprecursors;neurons(brain-BrainRes1995;697:235andperivascularautonomicnerveterminals-Neuroscience2006Mar29;[Epubaheadofprint]),pancreaticislets,smallintestinallacteals(VirchowsArch2002;441:605),thymocytes

Positivestaining(disease):

Hematopoieticneoplasms-pre-TALL(AJSP1992;16:1075),AML-t(6;9)subtype(100%,AJCP2004;122:348),CLL/SLL(classic-47%[AJSP2002;26:624],only9%ofatypicalCLL[AJCP2001;116:655],83%oftransformedCLL[AJCP2001;115:385]),diffuselargeBcelllymphoma(some),follicularlymphoma(AmJPathol2003;162:105),lymphoplasmacyticlymphoma(48%,AJCP2005;124:414),myeloma,plasmablasticlymphoma(AJSP2004;28:736),plasmacellneoplasms,primaryeffusionlymphoma(AJCP1996;105:221),transientmyeloproliferativedisorderinDown’ssyndrome(AJCP2001;116:204)

Other-acuteinfectiousmononucleosis(AJCP2003;120:49),Kikuchi’s(plasmacytoidmonocytes,AJCP1989;92:42),neuroblastoma,prostateadenocarcinoma(lessintensethannormalprostate,AmJPathol2004;165:1543)

Negativestaining:mastcells,primitivepleuripotentstemcells(ordim),splenicmarginalzonelymphoma(AJCP1996;105:277)

References:OMIM107270,NatureMedicine2002;8:336

CD39

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Alsocallednucleosidetriphosphatediphosphohydrolase(NTPDase-1)

Plasmamembrane-boundenzymethathydrolyzesextracellularATPandADPtoAMP(Platelets2005;16:159),andactsasimportantinhibitorofplateletactivationbyblockingplateletaggregationresponsestoADP;mayhaveatherapeuticanti-thromboticeffect(SeminThrombHemost2005;31:234)

Itsbiochemicalactivityislostatsitesofacutevascularinjury,suchasinischemiareperfusionandimmunegraftrejection(BloodCellsMolDis2006;36:217)

Alsoregulatesvascularandimmunecelladhesionandsignalingeventspivotalininflammation(BiochemJ2006;396:23)

IncreasedexpressioninlymphocytesofHIV+patients(BiochimBiophysActa2005;1746:129)

Presenceincoronaryatheromatousplaquemaypreventacutecoronarysyndromes(AmJCardiol2005;95:632)

Uses:nosignificantclinicalusebypathologists

Positivestaining(normal):Bcells,cytotoxicTcells(EurJImmunol1992;22:2681),NKcells,monocytes,macrophages,endothelialcells,Langerhanscells(JInvestDermatol2005;125:482),vascularsmoothmuscle,pancreas(JHistochemCytochem2002;50:549),placenta(EurJHistochem2004;48:253)

References:OMIM601752,NatureMedicine2002;8:336

CD40

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AlsocalledTNFreceptorsuperfamilymember5;ligandisCD40L(CD154)

Playsacentralroleinregulatingcell-mediatedimmunityandantibodymediatedimmunity

AlsomediatesTcelldependentimmunoglobulinclassswitching,memorycelldevelopmentandgerminalcenterformation

Cardiovasculardisease:(a)maymediateinflammatorycomponentofatherogenesis;(b)variationofCD40geneisassociatedwithcoronaryarterycalcificationindiabetes(AmHeartJ2006;151:706);(c)CD40/CD40Lsignalingcontributestoinflammatoryandprothrombogenicresponsesandbraininfarctioninducedbymiddlecerebralarteryocclusionandreperfusion(Circulation2005;111:1690)andtoacutecerebralischemia(Stroke2003;34:1412);(d)CD40mediatedplateletactivationmayplayaroleinthrombosis,inflammationandatherosclerosis(CircRes2003;92:1041)

Autoimmunedisease:contributestocartilaginousdegradationinrheumatoidarthritis(JRheumatol2004;31:1506)

Otherimmunedisorders:(a)mutationsmaycausehyperIgMdiseasetype3(OMIM606843)withopportunisticinfectionsduetoinabilityofBcellstoundergotypeswitchingandtodefectiveTcellmediatedimmunity(Blood2003;102:4099);(b)maybeimportantpathwayofinductionofSteven-Johnsonsyndrome(BrJDermatol2006;154:319)

Uses:nosignificantclinicalusebypathologists

Prognosticvalueintumors:expressionin>50%ofcellsmayhavepoorprognosticvalueinadultsofttissuesarcomas(ClinCancerRes2004;10:2824),CD40+diffuselargeBcelllymphomasareassociatedwithfavorablesurvival(ClinCancerRes2003;9:722)

Positivestaining(normal):Bcells,monocytes,macrophages,platelets,dendriticcells,endothelialcells,fibroblasts,keratinocytes,Langerhanscells(inoralmucosa),nevuscells,pancreaticisletcells(Diabetologia2005;48:268),prostaticacini,otherepithelialcells

Positivestaining(disease):Kaposi’ssarcoma(AmJPathol1996;148:1387),melanoma(AmJPathol1996;149:1953),Reed-Sternbergcells(70%,AmJPathol1994;144:21),mostBcelllymphomas(70%ofdiffuselargeBcelllymphoma),B-ALL(some)

carcinoma:renalcell(CellImmunol2005;235:145),squamouscellcarcinomaoforalmucosa(JOralPatholMed2006;35:268),thyroid(Thyroid2005;15:105)

Negativestaining:plasmacells,Gauchercells,prostaticadenocarcinoma(OncolRep2004;12:679)

References:OMIM109535

CD41

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AlsocalledplateletGPIIb

Geneencodesintegrinalphachain2b,whichundergoespost-translationalcleavagetoyielddisulfidelinkedlightandheavychains,thatjoinwithintegrinbeta3toformafibronectinreceptorexpressedinplatelets,whichiscrucialforplateletaggregation

Alsoareceptorforfibrinogen,vonWillebrandfactorandvitronectin

DownregulatedbyfactorXIIIandcalpain(JBiolChem2004;279:30697)

MutationscauseGlanzmannthrombasthenia(OMIM273800),withatendencytobleedforprolongedperiodsfollowinginjury

Uses:identifyplateletsormegakaryocytes(markerisspecific);isolateplatelets(CytometryA2005;65:84);confirmdiagnosisofAML-M7,diagnoseGlanzmannthrombasthenia

Positivestaining(normal):platelets,megakaryocytes,hematopoieticprogenitorcells(erythroid,myeloid,megakaryocytes,BrJHaematol1999;105:1044,Development2002;129:2003)

Positivestaining(disease):AMLM7,blastsintransientmyeloproliferativedisorder(AJCP2001;116:204),mastcells(ExpHematol2005;33:403)

Negativestaining:AMLM0toM6

References:OMIM607759;JClinInvest2005;115:3363(structureandfunction),ArteriosclerThrombVascBiol2003;23:945(functionandantagonism)

CD42a

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AlsocalledplateletglycoproteinGPIXandGP9

CD42a-dcomplexisreceptorforvonWillebrandfactorandthrombin

Thiscomplexmediatesadhesionofplateletstosubendothelialmatricesthatareexposedindamagedendotheliumandamplifiesplateletresponsetothrombin

ActualbindingsiteofvWfandthrombinisonCD42b

AbsenceofCD42complex(mutationsinCD42a-c)causesBernard-Souliersyndrome(giantplateletsyndrome,OMIM231200),ableedingdisorderwiththrombocytopenia,prolongedbleedingtimeandgiantplatelets

Positivestaining(normal):plateletsandmegakaryocytes

Negativestaining:redbloodcells,Tcells

References:OMIM173515

CD42b

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AlsocalledplateletGPIbalpha,glycoproteinIb-alpha

CD42a-dcomplex(alsocalledglycoproteinIb-IX-Vreceptor)isthesurfaceplateletreceptorforvonWillebrandfactoronendothelium(particularlyCD42b);endothelialdamageexposesvWF,whichbindstoplateletsveryquicklydespitehighshearpressures;thisleadstoplateletactivation,thenachangeintheGpIIbIIIareceptor,whichallowsbindingtosurfaceboundfibrinogenandfreefibrinogen;thisleadstoplateletcrosslinkingandaggregation

GPIbalpha(CD42b)andGPIbbeta(CD42c)formmainpartofVWFreceptor

CD42balsobindstothrombospondin-1,aglycoproteininarterioscleroticplaques,causingthrombusformationindependentofvonWillebrandfactor(FASEBJ2003;17:1490)

CD42bmutationscauseBernard-Soulierdisease(giantplateletsyndrome,OMIM231200);alsoplatelettypevonWillebranddisease,whichisknownaspseudo-vonWillebranddisease(OMIM177820)

ReducedlevelsareassociatedwithbleedingdisordersinAMLpatients(SaudiMedJ2005;26:1095)

AspirininducessheddingofCD42dandCD42bfromplatelets(JBiolChem2005;280:39716)

Microbiology:(a)virulencefactorofStreptococcussanguis,anoralbacteriacausinginfectiveendocarditis,isabilitytoadheretoplatelets(andplatelet-fibrinvegetations)viaCD42b(BrJHaematol2005;129:101);(b)somestrainsofH.pyloriinduceplateletactivationmediatedbyH.pylori-boundvWFinteractingwithCD42b/GPIb;theseplatelet-H.pyloriinteractionsmaypromotepepticulcerdiseaseandH.pylori-associatedcardiovasculardisease(Gastroenterology2003;124:1846)

Toxicology:TVMA,asnakevenom,inducesplateletaggregationviaCD42b/GPIb(Toxicon2004;44:649butseeXenotransplantation2004;11:203-oppositeeffect);AlboluxinisanothersnakevenomwithplateletaggregatingpropertiesviaCD42b(ThrombHaemost2002;87:692),asisBilinexin(ThrombHaemost2001;86:1277)

Casereports:Bernard-Soulierdiseasevariant(Archives2005;129:e214)

Uses:diagnosisofAML-M7;distinguishAML-M7(CD42b+)fromacutemyelosiswithmyelofibrosis(CD42bnegusually,ModPath2005;18:603);markerofmegakaryocytes

Positivestaining(normal):platelets,megakaryocytesandmegakaryoblasts

Positivestaining(disease):blastsintransientmyeloproliferativedisorder

References:OMIM606672

CD42c

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AlsocalledplateletGPIbbeta,glycoproteinIb-beta

PartoftheGPIb-V-IXcomplexthatservesasvonWillebrandfactorreceptor

GPIbalpha(CD42b)andGPIbbeta(CD42c)formmainpartofVWFreceptor

CD42calsoamplifiestheplateletresponsetothrombinduringplateletactivationwherethrombinisinvolved

MutationsareassociatedwithBernard-Souliersyndrome(OMIM231200,IntJHematol2002;76:319)

ReducedlevelsareassociatedwithbleedingdisordersinAMLpatients(SaudiMedJ2005;26:1095)

Casereports:mutationinBernard-Souliersyndromepatient(JThrombHaemost2006;4:217)

Positivestaining(normal):plateletsandmegakaryocytes

References:OMIM138720,ThrombHaemost2001;86:1238

CD42d

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AlsocalledplateletGPV

AspirininducessheddingofCD42dandCD42bfromplatelets(JBiolChem2005;280:39716)

CD42disthepredominanttargetantigeningold-inducedautoimmunethrombocytopenia(Blood2002;100:344)

DeficiencydoesNOTappeartocauseBernard-Souliersyndrome(Blood1999;94:4112)

Positivestaining(normal):plateletsandmegakaryocytes

References:OMIM173511

CD43

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Alsocalledleukosialin,sialophorin

Appearstobeimportantforimmunefunctionandmaybepartofaphysiologicligand-receptorcomplexinvolvedinT-cellactivation

ServesasaligandforE-selectinonTcellsandmayregulateTcelltrafficking(Blood2006;107:1421,JImmunol2005;175:8042)

DefectiveexpressioninTcellsofmaleswithWiskott-Aldrichsyndrome(OMIM301000)

Uses:panTcellmarker,diagnosisofgranulocyticsarcoma(JClinPathol2005;58:211),classifyTcellandlowgradeBcelllymphomasubtype,differentiatepulmonaryMALTlymphoma(CD20+CD43+)fromlymphoidhyperplasia(CD43neg,AJSP2002;26:76)

Positivestaining(normal):mostTcells,activatedBcells,Bcellsinterminalileum(ApplImmunohistochemMolMorphol2005;13:138),plasmacells(ScandJImmunol.1991Feb;33(2):211-8.),NKcells,granulocytes,monocytes,megakaryocytes,erythroidcells,hematogones(BrJHaematol2005;128:820),Langerhanscells,brain,thymocytes,somemacrophages,platelets(weak)

Positivestaining(disease):T/NKcelllymphomas-anaplasticlargecell(variable),blasticNK,hepatosplenicgamma-deltaTcell,lymphoplasmacytic(variable),NK/Tcell-nasaltype(96%,HumPath2004;35:86),peripheralTcell,subcutaneouspanniculitis-like,CD4+CD56+lineagenegativemalignancies(AJSP2005;29:1274)

Bcelllymphomas-ALL(most),Burkitt’s(almostall),Burkitt’s-like(almostall,AJSP2005;29:1652),lymphoblastic(variable),mantlecell(100%,AJCP2003;119:218),marginalzone(variable),nodalmarginalzone(variable,AJSP2003;27:762),plasmablastic,SLL/CLL(AJCP1999;112:319)

other-AML,granulocyticsarcoma,hemangioma,Langerhanscellhistiocytosis,mastcelldisease(AJSP2000;24:703),plasmacytoma;earlycolonicadenoma(OncolRep2004;11:327)

Negativestaining:colonicepithelium,follicularlymphoma,Hodgkin’slymphoma,lymphoepithelioma-likethymiccarcinoma,primaryeffusionlymphoma,splenicmarginalzonelymphoma

References:OMIM182160

CD44

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AlsocalledCD44s(standardisoform)orCD44H,whichlacksallalternativeexons;allreferencesbelowaretostandardisoformunlessstatedotherwise

Familyofcellsurfaceglycoproteinswithnumerousisoformsandposttranslationalmodificationsinvolvingglycosylation(CD44v6iscommonvariant)generatedbyalternatesplicingofmRNA

Importantinepithelialcelladhesion(cell-cellandcell-matrix)tohyaluronateinbasementmembranes,andmaintainingpolarorientationofcells;thisprocessmaycontributetotissueremodelingandmaystimulatecellproliferationandmigration

CD44alsobindslaminin,collagen,fibronectin,osteopontinandmatrixmetalloproteinases

AlsoconsideredamarkerofactivatedBcells

Involvedinleukocyteattachmentandrollingonendothelialcells,homingtoperipherallymphoidorgans(bybindingtomucosaladdressin,aproteinpresentonhighendothelialcellsofPeyer’spatchesandlymphnodes),andleukocytechemotaxisandaggregation

CD44splicingvariantsmightmediateinvasionoftrophoblastintomaternaltissueinearlypregnancy(EurJObstetGynecolReprodBiol2006Feb25;[Epubaheadofprint])