DiseaseofHematopoieticandLymphoidSystems

(淋巴造血系統疾病)HematopoieticandLymphoidSystemsBonemarrowLymphnodesThymusSpleenBonemarrow+Redcells,platelets,granulocytes,andmononuclearcellsinperipheralblood

MyeloidtissueThymus+lymphnodes+spleen

LymphoidtissueHematopoieticandLymphoidSystemsThymusspleenlymphnodeStructureofnormallymphnodesCD20CD3DisordersofthehematopoieticandlymphoidsystemsencompassawiderangeofdiseasesTraditionallysortedintodisordersthatprimarilyaffectredcells,whitecells,orthehemostaticsystem,whichincludesplateletsandclottingfactors.Themostcommonredcelldisordersleadtoanemia,astateofredcelldeficiency.Whitecelldisordersaremostoftencausedbyexcessproliferation,whichusuallyhasaneoplasticbasis.TumorsofHematopoieticandLymphoidSystems1.Thetumorsariseinmyeloidtissue(bonemarrow):AcuteMyeloidLeukemiaChronicMyeloidLeukemiaMyelodysplasticsyndromes2.Thetumorsariseinlymphoidtissue: (1)LymphoidLeukemia (2)Lymphoma:Hodgkinlymphoma andnon-HodgkinlymphomaInbothbenignandmalignanthematolymphoiddisorders,asingleunderlyingabnormalitycanresultindiverse,systemicmanifestations.ClassificationofLymphoidNeoplasms1994年：Non-Hodgkinlymphoma1.PrecursorB-andT-celltumors2.PeripheralB-andT-celltumorsHodgkinlymphomaWHO分類的原則定義每一個獨立類型的淋巴瘤應具有（組織病理學、免疫表型、分子遺傳學和臨床）一組特點能被病理醫師識別與臨床相關2008年WHO淋巴瘤新分類

一、前驅腫瘤（PRECURSORNEOPLASMS）1、母細胞性漿細胞樣樹狀突細胞腫瘤（Blasticplasmacytoiddendriticcellneoplasma),以前稱為母細胞性NK細胞淋巴瘤。2、譜系未定的急性白血病（AcuteLeukemiasofambiguouslineage)－急性未分化白血?。èCAcuteundifferentiatedleukemia，AUL)－混合表型急性白血病，有/無重現性遺傳學異常（–Mixedphenotypeacuteleukemia，MPAL)(+/-recurrentgeneticabnormalities)二、前驅淋巴性腫瘤（PRECURSORLYMPHOIDNEOPLASMS）1、B淋巴母細胞白血病/淋巴瘤，非特殊類型【BLymphoblasticLeukemia/Lymphoma,nototherwisespecified】2、B淋巴母細胞白血病/淋巴瘤伴重現性遺傳學異常【Blymphoblasticleukemia/lymphomawithrecurrentgeneticabnormalities】－B淋巴母細胞白血病/淋巴瘤伴t(9:22)(q34;q11.2);BCR/ABL【B-lymphoblasticleukemia/lymphomawitht(9:22)(q34;q11.2);BCR/ABL】－B淋巴母細胞白血病/淋巴瘤伴t(v;11q23);MLLrearranged，【Blymphoblasticleukemia/lymphomawitht(v;11q23);MLLrearranged】－B淋巴母細胞白血病/淋巴瘤伴t(v;11q23);MLLrearranged(ETV6-RUNX1)，【Blymphoblasticleukemia/lymphomawitht(v;11q23);MLLrearranged(ETV6-RUNX1)】－B淋巴母細胞白血病/淋巴瘤伴超二倍體【Blymphoblasticleukemia/lymphomawithhyperdiploidy】－B淋巴母細胞白血病/淋巴瘤伴低二倍體【Blymphoblasticleukemia/lymphomawithhypodiploidy(HypodiploidALL)】－B淋巴母細胞白血病/淋巴瘤伴t(5;14)(q31;q32)(IL3-IGH)，【Blymphoblasticleukemia/lymphomawitht(5;14)(q31;q32)(IL3-IGH)】－B淋巴母細胞白血病/淋巴瘤伴t(1;19)(q23；p13.3);(E2A-PBX1;TCF3/PBX1)，【Blymphoblasticleukemia/lymphomawitht(1;19)(q23；p13.3);(E2A-PBX1;TCF3/PBX1)】2008年WHO淋巴瘤新分類

3、T-淋巴母細胞白血病/淋巴瘤【T-lymphoblasticleukemia/lymphoma】三、成熟B細胞淋巴瘤1、慢性淋巴細胞性白血病/小淋巴細胞性淋巴瘤2、B-前淋巴細胞性白血病3、脾邊緣帶淋巴瘤4、毛細胞白血病5、脾淋巴瘤/白血病，不能分類6、淋巴漿細胞淋巴瘤7、重鏈病8、漿細胞骨髓瘤/漿細胞瘤9、結外粘膜相關淋巴組織邊緣帶B細胞淋巴瘤（MALT淋巴瘤）10、原發皮膚濾泡中心淋巴瘤11、濾泡性淋巴瘤－胃腸道濾泡性淋巴瘤－兒童濾泡性淋巴瘤－“原位”濾泡性淋巴瘤12、結內邊緣帶B細胞淋巴瘤13、套細胞淋巴瘤2008年WHO淋巴瘤新分類

14、彌漫大B細胞淋巴瘤－彌漫大B細胞淋巴瘤，非特殊類型

T細胞/組織細胞豐富的大B細胞淋巴瘤老年人EBV陽性的彌漫大B細胞淋巴瘤慢性炎癥相關的彌漫大B細胞淋巴瘤－膿胸相關淋巴瘤－慢性骨髓炎相關淋巴瘤－植入物相關淋巴瘤原發中樞神經彌漫大B細胞淋巴瘤－淋巴瘤樣肉芽腫－原發縱膈（胸腺）大B細胞淋巴瘤－血管內大B細胞淋巴瘤－原發皮膚大B細胞淋巴瘤，腿型－漿母細胞性淋巴瘤－原發滲漏性淋巴瘤－ALK陽性彌漫大B細胞淋巴瘤－起源于HHV8陽性的多中心Castleman病的大B細胞淋巴瘤15、伯基特淋巴瘤16、介于彌漫大B細胞淋巴瘤和伯基特淋巴瘤之間的不能分類的B細胞淋巴瘤17、介于彌漫大B細胞淋巴瘤和經典霍奇金淋巴瘤之間的不能分類的B細胞淋巴瘤四、成熟T/NK細胞淋巴瘤1、T前淋巴細胞白血病2、T大顆粒淋巴細胞白血病2008年WHO淋巴瘤新分類

3、慢性NK細胞淋巴增殖性疾患4、侵襲性NK細胞白血病5、成人T細胞白血病/淋巴瘤6、EBV相關的克隆性淋巴組織增殖性疾患（兒童）－兒童系統性EBV陽性T細胞增殖性疾?。ㄅc慢性活動性EBV感染相關）－種痘水皰病樣淋巴瘤7、結外NK/T細胞淋巴瘤，鼻型8、腸病相關T細胞淋巴瘤9、肝脾T細胞淋巴瘤10、皮下脂膜炎樣T細胞淋巴瘤11、蕈樣霉菌病12、賽塞里綜合征13、原發皮膚間變性大細胞淋巴瘤14、原發皮膚侵襲性嗜表皮CD8陽性細胞毒性T淋巴瘤15、原發皮膚gamma/deltaT細胞淋巴瘤16、原發皮膚小/中CD4陽性T細胞淋巴瘤17、外周T細胞淋巴瘤，非特殊類型18、血管免疫母細胞T細胞淋巴瘤19、ALK陽性間變性大細胞淋巴瘤20、ALK陰性間變性大細胞淋巴瘤五、霍奇金淋巴瘤1、結節性淋巴細胞為主淋巴瘤2、經典霍奇金淋巴瘤－結節硬化型－淋巴豐富型－混合細胞型－淋巴細胞消減型WHO新分類的特點分類依據：組織病理學、免疫表型、遺傳學特征、臨床表現和過程強調獨特的臨床病理、免疫學表型和遺傳學表現明確了淋巴瘤和淋巴細胞白血病的關系廢棄了對淋巴瘤的惡性程度的分級，根據淋巴瘤的全身程度和臨床進展情況引進了惰性、侵襲性和高度侵襲性淋巴瘤的概念淋巴瘤的病理診斷臨床實踐指南強調，對于所有的淋巴瘤患者，準確的病理學診斷是最重要的；病理診斷是治療淋巴瘤和判斷預后的基礎；為了保證病理學診斷和分型的準確，指南建議所有的病人都應當作淋巴結切除活檢，保證有足夠的組織進行組織學、免疫組化、分子生物學和流式細胞術檢查。淋巴瘤的病理診斷：淋巴結粗針穿刺活檢對于淋巴瘤初診病例，不推薦粗針穿刺活檢（corebiopsy）粗針穿刺活檢的應用是淋巴瘤初篩的一種方法用于淋巴瘤分期全身情況差，不能承受手術的患者不愿意手術的患者淋巴瘤的病理診斷“四結合原則”臨床特點（病史、體征、實驗室檢查等）組織病理學形態（HE）免疫表型（免疫組化、流式細胞術）分子生物學特征（FISH、PCR、基因重排等）惡性淋巴瘤的病理診斷惡性淋巴瘤的組織病理學特點（HE）淋巴結或淋巴組織結構破壞細胞大小、形態一致小淋巴細胞背景上散在大細胞血管侵犯淋巴結被膜外脂肪組織浸潤其他惡性淋巴瘤的病理診斷輔助診斷技術的應用免疫組化區別反應性病變和淋巴瘤確定細胞來源，區別淋巴瘤和其它非淋巴瘤性腫瘤淋巴瘤的分類淋巴瘤的預后指導淋巴瘤的治療分子病理學技術原位雜交：NK/T細胞淋巴瘤、血管免疫母細胞性T淋巴瘤、霍奇金淋巴瘤、Burkitt淋巴瘤等Ig基因及TCR基因重排：BIOMED-2方法、毛細血管電泳法、FISH淋巴瘤類型分子遺傳學標記檢測套細胞淋巴瘤的IgH/CycinD1融合基因：PCR、FISH惡性淋巴瘤的病理診斷免疫組化標記物B細胞標記物：CD20、CD19、PAX-5T細胞標記物：CD3、CD2、CD7濾泡樹突狀細胞（FDC）標記物：CD21、CD35單克隆性標記物：Lamda、Kappa淋巴瘤類型標記物淋巴母細胞淋巴瘤：CD34、CD99、CD10、TDT套細胞淋巴瘤：CD5、CyclinD1間變大細胞淋巴瘤：EMA、CD30、ALK小淋巴細胞淋巴瘤/白血?。篊D5、CD23NK/T細胞淋巴瘤：CD56、TIA-1、GrB髓系標記物：MPOHodgkinLymphomaOccurringpredominantlyinyoungpersons,characterizedas:1.Itarisesalmostinvariablyinasingle nodeorachainofnodes.2.Presenceofdistinctiveneoplasticgiant cellscalledRead-Sternberg(RS)cells.3.MostofthemariseinB-lymphocyte4.Witharelativelygoodprognosis.

HodgkinLymphomaClassification1.NodularlymphocytepredominantHodgkinLymphoma(NLPHL)2.ClassicalHodgkinLymphoma（CHL）－nodularsclerosis－mixedcellularity

－lymphocyterich

－lymphocytedepletionReed-Sternberg(RS)cell:"classic"RScellscellswithtwomirror-imagenucleiornuclearlobescommoninmixed-cellularitysubtype,uncommoninnodularsclerosissubtype,rarelymphocyte-predominancesubtype"classic"RScellsCD30+CD15+variantoftheRScell:“lacunarcell”“陷窩細胞”

cytoplasmoftenretracts：cellslyinginemptyspacesexpressCD15andCD30單核細胞“lacunarcell”“陷窩細胞”LP細胞（L&Hvariant）oftheRScell:"popcorncell”

singlemultilobatednucleuswithmultiplesmallnucleoli多形性R-S細胞NodularlymphocytepredominantHodgkinLymphoma(NLPHL)Comprisingabout5%ofHodgkinlymphomaLP(L&Hvariant)oftheRScell:"popcorncell”NLPHL

NodularlymphocytepredominantHodgkinLymphoma(NLPHL)Comprisingabout5%ofHodgkinlymphomaLP(L&Hvariant)oftheRScell:"popcorncell”CD15-，CD30-，CD20+，CD79+(differentfromRScells)CD20EMAClassicalHodgkinLymphoma－nodularsclerosis（NSHL）ThemostcommonformEquallyfrequentinmenandwomenMostofthepatientsareadolescentsoryoungadultsTheoverallprognosisisexcellentThepresenceofaparticularvariantoftheRScell,thelacunarcell:expressCD15andCD30,donotexpressB-andT-cell-specificantigensThepresenceofcollagenbandsthatdividethelymphoidtissueintocircumscribednodulesNSCHL低倍鏡觀NodularsclerosisHLNSCHL中倍鏡觀NSCHL高倍鏡觀陷窩細胞ClassicalHodgkinLymphoma－mixedcellularity（MCHL）ThemostcommonformofHodgkinlymphomainpatientsolderthantheageof50AmalepredominanceClassicRScellsCellularinfiltrate:smalllymphocyteseosinophilsplasmacellsbenignhistiocytesMixedcellularityHLClassicalHodgkinLymphoma－lymphocytedepleted（LDHL）5%ofHLThenumberofcellsdecreases,andwithheavydepositionofcollagenfibersVerylargenumberofdiagnosticRScellsamongatypicalmononuclearcellsPoorprognosisLDCHL—彌漫纖維化型低倍鏡觀LDCHL—彌漫纖維化型中倍鏡觀LDCHL—網狀細胞型中倍鏡觀LDCHL—網狀細胞型高倍鏡觀ClassicalHodgkinLymphoma－lymphocyterich（LRHL）RScellsscatteredBackgroundislargelycomposedofsmalllymphocytesDifferentialdiagnosisiswithNLPHD:immunohistochemicalfeaturesofRScellsRScells:CD15+,CD30+A：HE染色，B：CD20，C：CD21，D：CD20LymphocyterichHLThestagingofHodgkinlymphomaisimportance:theclinicalcourse,choiceoftherapy,andprognosisAcuteLymphoblasticLeukemia/Lymphoma(ALL)

Introduction(1)ItistypicalPre-BorPre-Tcellmalignanttumors.Thereareoftenoverlapbetweentheseleukemiaandlymphoma.T,orBcellderivingisdifficulttobedistinguishedfromeachotherbasedonthemorphology,whileitiseasytobedistinguishedbyimunohistochemistry.(2)itisthemostcommoncancerinchildren.(3)Morethan85%ariseinB-cell.Pathogenesis1.Thecancercellscannotmaturetofunctionalcells.2.Asblastsaccumulateinthemarrow,theysuppressnormalhematopoieticstemcells.Pathologicchanges1.ThecancerarisinginB-celloftenemergesas acuteleukemia.Itcharacteristically extensivelyinvolvesbonemarrowand peripheralblood.

2.ThecancerarisinginT-celloftenemergesas lymphoma.Itcharacteristicallyinvolves lymphnodesatfirst.

OVERLAP3.BothareTdTpositive,T-(CD3,CD7)orB-cell(PAX-5)derivingbasedonimmunohistochemistry.Lymphoblasticleukemia/lymphomaPrognosisMostpatientscanbereleasedcompletelyafterthechemotherapy.Children2to10yearsofagehavethebestprognosisMorethan2/3patientscanbecured.PeripheralLymphoidCellTumors1.

Smalllymphocyticlymphoma/chroniclymphocyticleukimia:SLL/CLLThesearevirtuallyidenticaltumorsthatdifferonlyintheextentofperipheralbloodinvolvement.Ittypicallyaffectspersonsolderthanage50years.Themediansurvivalis4~6years.Lymphnodes,thebonemarrow,spleen,andliverareinvolvedinalmostallcasesWBC（30-100）×109/L>95%fromBcellsThepredominantcellsarecompact,small,restinglymphocyteswithdark-stainingroundnuclei,scantycytoplasm,andlittlevariationinsize,small,mature-lookinglymphocytesB-Smalllymphocyticlymphoma/chroniclymphocyticleukimia形態特點

小淋巴細胞

增殖中心（區）免疫表型surfaceIgMDweakCD19,20,79a +CD5 +CD23 +CD10,CyclinD1 -遺傳學特征trisomy1213qin25%

克隆性IgHIgL50%自體突變臨床特點

常有白血病

成人,50歲以上

惰性CD23CD5ClinicalFeaturesCLL/SLLisoftenasymptomaticatpresentationThemostcommonsymptomsarenonspecificandincludeeasyfatigue,weightloss,andanorexia（厭食）Lymphadenopathyandhepatosplenomegalyarepresentin50%to60%ofcasesPeripheralLymphoidCellTumors2.FollicularLymphoma:

Occurringpredominantlyinolderpersons.Characterizedbyanodularorfolliculararchitecture.Itisthesecondmostcommonlymphomainadults.BCL-2overexpressionisthemolecularbasisoftumorigenesis.“centrocyte-like”“centroblast-like”CD20pan-B-cellmarkers:CD19andCD20,CD10,BCL6CD10BCL-2+:differentfromReactiveHyperplasiaBCL-2BCL-2ClinicalFeaturesusuallypresentsaspainlesslymphadenopathybonemarrowalmostalwayscontainslymphomaatthetimeofdiagnosis.Thenaturalhistoryisprolonged(mediansurvival,7-9years),inactive.noteasilycurable,mayberelatedinparttotheelevatedlevelsofBCL2,whichmayprotecttumorcellsfromtheeffectsofchemotherapeuticagents.about40%ofpatientsprogressestoadiffuselargeB-celllymphomaPeripheralLymphoidCellTumors3.DiffuseLargeB-cellLymphoma:

Itisthemostcommonlymphomainadults(50%)Itoccurmainlyinoldpersons(60years)ThefeaturesincludeaB-cellphenotype,adiffusegrowthpattern,andahigheraggressiveclinicalhistory.3-4timesthesizeofnormallymphocytespan-B-cellantigens,suchasCD19andCD20.ManyalsoexpresssurfaceIgMand/orIgGCD20CD79ClinicalFeaturesaggressivetumorsthatarerapidlyfatalifuntreated;completeremissioncanbeachievedin60%to80%ofthepatientscanariseatanyage;constitute15%ofchildhoodlymphomasarapidlyenlarging,oftensymptomaticmass

PeripheralLymphoidCellTumors4.

BurkittLymphoma:BurkittlymphomaisendemicinsomepartsofAfricaandsporadicinotherareas.Histologically,theyareidentical,althoughthereareclinicalandvirologicdifferences.Itmaybethefastestgrowinghumanneoplasm,however,withveryaggressivechemotherapy,themajorityofpatientscanbecured.Thetumorcellsareuniformandintermediateinsizeandhaveroundorovalnucleicontainingtwotofiveprominentnucleoli"starrysky"pattern--benignmacrophagesB-celltumorsexpresssurfaceIgM,κorλlightchain,thepan-B-cellmarkersCD19andCD20,andCD10highmitoticrateClinicalFeaturesBoththeendemicandnonendemicformsaffectmainlychildrenandyoungadultsusuallyarisesatextranodalsitesahigh-gradetumorthatisamongthefastestgrowinghumanneoplasmsveryaggressivechemotherapyregimens,themajorityofpatientscanbecuredPeripheralLymphoidCellTumors5.MultipleMyeloma/PlasmaCellDyscrasias:Itisaclonalproliferationofneoplasticplasmcellinthebonemarrowthatisusuallyassociatedwithmultifocallyticlesionsthroughouttheskeletalsystem.MultiplemyelomapresentsmostoftenasmultifocaldestructivebonelesionsthroughouttheskeletalsystemAlthoughanybonecanbeaffected:vertebralcolumn,66%Bonemarrowaspirate:Normalmarrowcellsarelargelyreplacedbyplasmacells,includingatypicalformswithmultiplenuclei,prominentnucleoli,andcytoplasmicdropletscontainingimmunoglobulin.ClinicalFeaturesThepeakageofincidenceofmultiplemyelomaisbetween50and60yearsBonepain,resultingfrominfiltrationbyneoplasticplasmacells,isextremelycommonhypercalcemia:focalbonedestructionanddiffuseresorptionRecurrentinfectionsRenalinsufficiencyoccurs50%ofpatients:thetoxiceffectsofBence-JonesproteinsoncellsliningthetubulesPeripheralLymphoidCellTumors

6.PeripheralTcelltumors:

includingmycosisfungoides,peripheraT-celllymphoma.mycosisfungoidesCD20CD3Bcells:CD20+Tcells:CD3+SummaryoftheMoreCommonLymphoidNeoplasmsSummaryoftheMoreCommonLymphoidNeoplasmsMyeloidblasts(糼稚細胞）makeupmorethan20%ofthecellsinthemarrowMyeloidLeukemiaMyeloidneoplasmsarisefromstemcellsthatnormallygiverisetotheformedelementsoftheblood:granulocytes,redcells,andplatelets.AcutemyelogenousleukemiaperipheralbloodChronicmyelogenousleukemia

Acutemyelogenous