病理學(xué)英文版教學(xué)課件：The Disease of Hematopoietic and Lymphoid Systems

TheDiseaseofHematopoieticandLymphoidSystemsHematopoieticandLymphoidSystemsMyeloidtissueBonemarrowRBC,platelets,granulocytes,monocytesLymphoidtissuelymphnodesthymusspleenDisorders

encompassawiderangeofdiseases,involvingitsanyorgansortissues.RBC:usuallyanemiaWBC:overgrowth,usuallymalignantcommonandlethal

NeoplasticproliferationsofwhitecellsBedefinedbrieflyasfollows:Myeloidneoplasms

髓樣組織腫瘤Lymphoidneoplasms淋巴樣組織腫瘤HistiocytosisMan-madeclassificationThedistinctioninsomecasesmaybeblurred.MyeloidneoplasmsArisewithinhematopoieticstemcellsThreegeneralcategories:Acutemyelogenousleukemia(AML急性髓性白血病)

Chronicmyeloproliferativedisorders

（慢性骨髓增生性疾病）Chronicmyelogenousleukemia慢性髓性白血病Polycythemiavera真性紅細(xì)胞增生癥Myeloidmetaplasiawithmyelofibrosis伴骨髓纖維化的髓樣增生Essentialthrombocythemia真性血小板增生癥Myelodysplasticsyndromes（骨髓增生異常綜合癥）Myeloidneoplasms:CD13,CD14,CD15,CD648types:FABclassificationM1~8Lymphoidneoplasms

AgroupofentitiesthatvarywidelyintermsoftheirclinicalpresentationandbehaviorClassificationschemethatreliesonacombinationofclinical,morphologic,phenotypicandgenotypicfeaturestherelationshipbetweenlymphomaandlymphocyticleukemiaCertainimportantrelevantprinciplesmost:BCelloriginneoplasmsareoftencomposedofcellsthatarrestatspecificstagesⅠA.PrecursorB-cellneoplasmsⅠB.PeripheralB-cellneoplasmsⅡA.PrecursorT-cellneoplasmsⅡB.PeripheralT-/NK-cellneoplasmsⅢ.HodgkinlymphomaLymphoidneoplasmsNHLⅠA.PrecursorB-cellneoplasms

1.PrecursorB-cellleukemia/lymphomaⅡA.PrecursorT-cellneoplasms

1.PrecursorT-cellleukemia/lymphomapre-B-lymphoblastictumor:firstleukemialymphomapre-T-lymphoblastictumor:mediastinalmassesinvolvedthethymusleukemia

Bothtumorsusuallyhavetheclinicalappearanceofanacutelymphoblasticleukemia(ALL)

Commonfeaturesofacuteleukemias

ALL+AMLClinicalfeatures1.

Abruptstormyonset—within3months2.SymptomsrelatedtodepressionofnormalmarrowfunctionPathophysiology

Blockindifferentiationblastsaccumulateinmarrownormalhematopoieticstemcells

AnemiafatigueMatureleukocytes

infectionThromobocytopeniableedingClinicalfeatures3.Bonepainandtenderness4.Generalizedlymphadenopathysplenomegaly,andhepatomegaly

MorecommoninALL5.Centralnervoussystemmanifestations

Headache,vomiting,andnervepalsieschildren＞adults,ALL＞AMLCommonfeaturesofacuteleukemiasLaboratoryfindingsAnemiaPlateletcountisusuallydepressedWBCcountisvariablyelevated Muchmoreimportant:blastsinthecirculatingbloodandthebonemarrowCommonfeaturesofacuteleukemiasClinicaltreatment

ChemotherapyBonemarrowstemcell(MSCs)transplantation

CommonfeaturesofacuteleukemiasDifferentfeaturesbetweenAMLandALLMorphologycoarseandclumpedchromatin1-2nucleoliAMLALLAgeadults;medianage:50yrsPeroxidase+Finechromatin;3-5nucleoli,morecytoplasmcontaininggranules,AuerrodsPre-B(85%):children,4years;Pre-T(15%):adolescentmales,

15-20yearsPAS+histochemistryClinicalfeaturesAsdescribedpreviouslyimmunophenotypingCD13,CD14,CD15,CD64TdT(95%+)B:CD19T:CD2AMLALLKaryotypicchangesPre-B:Hyperdiploidyt(12;21);

PhprognosisGood:2-10yrs,pre-BDevastatingdiseaseM2:t(8;21)M3:t(15;17)維甲酸治療M4:inv(16)/del(16)Age

25-60yearsPeakincidence:40-50yearsClinicalfeatures

1.Onsetisslow;2.nonspecificinitialsymptoms

Easyfatigability,weakness,andweightloss3.ExtremesplenomegalyinfarctpainsChronicmyelogenousleukemia,CMLPathologychangesLeukocytecount↑↑andbonemarrowishypercellular

Predominantly:neutrophilsandmyelocytesBasophilsandeosinophils

myeloblasts＜10%SpleeninfarctsacuteonsetleftupperquadrantpainChronicmyelogenousleukemia,CMLChronicmyelogenousleukemia,CMLKaryotypicchanges

Ph(Philadelphia)chromosome:t(9;22)(q34;q11)c-abl-berfusiongenes/P210protein:increased,dysregulatedtyrosinekinaseactivityPrognosisSlowprogressionwithouttreatment,mediansurvivalis3yearsBonemarrowtransplantationSTI-571:theexcitingconceptofdesignerdrugsthatspecificallytargetoncoproteinsⅠB.PeripheralB-cellneoplasmsSmalllymphocyticlymphoma/chroniclymphocyticleukimia(慢性淋巴細(xì)胞性白血病/小淋巴細(xì)胞性淋巴瘤）B-cellprolymphocytecleukemiaB細(xì)胞性前淋巴細(xì)胞白血病Lymphoplasmacyticlymphoma淋巴細(xì)胞、槳細(xì)胞性淋巴瘤Mantlecelllymphoma套細(xì)胞性淋巴瘤FollicularLymphoma濾泡性淋巴瘤Extranodalmarginalzonelymphoma(MALTlymphoma)

節(jié)外邊緣帶淋巴瘤7.Splenicmarginalzonelymphoma脾邊緣帶淋巴瘤8.Nodalmarginalzonelymphoma淋巴結(jié)邊緣帶淋巴瘤9.Hairycellleukemia毛細(xì)胞性白血病10.

Plasmacytoma/plasmacellmyeloma漿細(xì)胞瘤/骨髓瘤11.DiffuseLargeB-cellLymphoma彌漫性大細(xì)胞性淋巴瘤12.BurkittLymphoma伯基特淋巴瘤PeripheralLymphoidCellTumorsSmalllymphocyticlymphoma/chroniclymphocyticleukimiaAge

＞50yearsClinicalfeatures

1.

Oftenasymptomaticornonspecific(easyfatigability,weightloss,andanorexia)2.Hypogammaglobulinemiasusceptibilitytobacterialinfections3.Generalizedlymphadenopathy,splenohepatomegaly4.TotalleukocytecountLymphnodes,thebonemarrow,spleen,liverMorphologyLowpower:sheetsoftumorcellsdiffuselyeffaceinvolvedlymphnodesSmalllymphocyticlymphoma/chroniclymphocyticleukimiaMorphologyPredominantcellscompact,small,dark-stainingroundnuclei,Scantycytoplasm,andlittlevariationinsizeProliferationcenters--PseudofolliclefociofmitoticallyactiveprolymphocytesSmalllymphocyticlymphoma/chroniclymphocyticleukimiaImmunophenotyping:matureB

cells

Pan-B-cellmarkers:CD19,CD20,SIgPrognosisthecourseandprognosisareextremelyvariableThemediansurvivalis4~6years.

Totransformtomoreaggressivetumors,suchasdiffuselargeB-celllymphoma:lessthan1yearSmalllymphocyticlymphoma/chroniclymphocyticleukimiaAge

Olderpersons(rarelybeforeage20years)Clinicalcharacteristics

Painlesslymphadenopathy,frequentlygeneralized

MorphologylymphnodesareeffacedbyanodularorfolliculararchitectureFollicularLymphomaMorphologyPredominantneoplasticcells---centrocyte,CC1.slightlargerthanrestinglymphocytes2.CoarseandcondensedchromatinprominentindentationsandlinearinfoldingsNucleoliareindistinctOthercells---Centroblast,CB1.3-4timesthesizeofrestinglymphocytes2.VesicularchromatinseveralnucleolimodestamountsofcytoplasmFollicularLymphomaImmunophenotypingPan-B-cellmarkers:CD19,CD20,BCL2BCL214:IgHgene;18:BCL2geneTranslocationt(14,18)Bcl-2proteinantiapoptoticeffectPrognosisIndolentcourse,mediansurvival,7to9yearsnoteasilycurable40%ofpatientsprogresstoadiffuselargeB-celllymphomadiffuselargeB-celllymphomaAge

Mostimportanttypeoflymphomainadultsapproximatelly50%ofalladultNHLsMorphologyitsnucleiislargeandvarible(3-4timesthesizeofrestinglymphocytes)ImmunophenotypePan-B-cellmarker:CD19,CD20Subtypes: epstein-Barrvirus(EBV)associatedacquiredimmunodeficiencysyndromeandiatrogenicimmunosuppressionhumanherpestype8(HHV-8)infectionsararegroup

mediastinallargeB-celllymphomausuallyinyoungadultsapredilectionforspreadtoabdominalvisceraandCNSdiffuselargeB-celllymphomaKaryotype30%t(14;18)BCL2arrangement1/33q27BCL6arrangementPrognosisAggressive,RapidlyfatalifuntreatedWithintensivecombinationchemotherapy,completeremissioncanbeachievedin60%-80%ofthepatientsBurkittLymphomaAge

ChildrenoryoungadultsendemicinsomepartsofAfricaandsporadicinotherareas.CommonsitesAfrica:Maxilla(上頜骨）ormandible（下顎骨）

otherareas:abdominal(bowel,retroperitoneum,ovaries)PathogenesisCorrelatedwithEBVinfectionMorphologyStarrysky:macrophageswithingestednucleardebrisMonotonousroundorovalnucleicontaining2-5prominentnucleoli

ActivemitosisImmunophenotypeSIgM,pan-B-cellmarkers:CD19,CD10Karyotype

t(8;14)etalTranslocationsinvolvingMYCgene8MYC14IgHor2、22К，λPrognosisItmaybethefastestgrowinghumanneoplasm,however,withveryaggressivechemotherapy,themajorityofpatientscanbecured.BurkittLymphomaⅢ.HodgkinLymphoma10%~20%,TomasHodgkinItwasseparatedfromNHLsforseveralreasonsItarisesalmostinvariablyinasinglenodeorachainofnodesdistinctiveneoplasticgiantcellscalledRead-Sternberg(RS)cellsmixedwithavariableinfiltrateofreactiveinflammatorycells.Systemicmanifestations,suchasfeverWitharelativelygoodprognosis.RScellsAbundantcytoplasm,d=15to45umMultilobatenucleusormultinucleatewithlarge,round,prominentnucleoliMirror-imagenucleiⅢ.HodgkinLymphomaVariantofRScellsMononuclearvariantsLacunarcellAlargefoldedorhyperlobatenucleuswithmultiplesmallnucleoliAbundant,pale-stainingcytoplasmⅢ.HodgkinLymphomaVariantofRScells3.Lymphocyticandhistocyticvariants,(L&HcellorPopcorncell)

havetwisted,multilobatenuclei,resemblingpopcornkernelsⅢ.HodgkinLymphoma1.NodularlymphocytepredominantHodgkinlymphomaCD45+;CD15,CD30–2.ClassicalHodgkinlymphoma

CD45-;CD15,CD30+HodgkinlymphomaNodularlymphocytepredominantHodgkinlymphomaMorphology

L&Hcells:nodularordiffuseMany