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1、 淋巴瘤淋巴瘤 Lymphoma 基礎(chǔ)醫(yī)學(xué)院病理學(xué)系基礎(chǔ)醫(yī)學(xué)院病理學(xué)系同濟醫(yī)院病理研究所同濟醫(yī)院病理研究所 敖啟林敖啟林1 1沐風(fēng)書苑沐風(fēng)書苑i iDr John K.C.CHAN陳國璋陳國璋2 2沐風(fēng)書苑沐風(fēng)書苑i i4th EditionPublished 20/9/20083 3沐風(fēng)書苑沐風(fēng)書苑i i第一節(jié)第一節(jié) 概述概述一、定義一、定義 “來源于來源于”成熟淋巴細(xì)胞及其前體細(xì)胞（淋巴母細(xì)胞）的惡性成熟淋巴細(xì)胞及其前體細(xì)胞（淋巴母細(xì)胞）的惡性腫瘤，分為非霍奇金腫瘤，分為非霍奇金/白血病和霍奇金淋巴瘤兩大類。白血病和霍奇金淋巴瘤兩大類。二、分類二、分類（一）（一）非霍奇金淋巴瘤非霍奇金淋巴

2、瘤(NHL)(NHL)：包括：包括B B，T T和和NKNK細(xì)胞（細(xì)胞（70%70%）1 1、前體細(xì)胞前體細(xì)胞：B/T/NKB/T/NK前體細(xì)胞（淋巴母細(xì)胞）淋巴瘤（前體細(xì)胞（淋巴母細(xì)胞）淋巴瘤（2%2%）2 2、成熟細(xì)胞成熟細(xì)胞：成熟細(xì)胞淋巴瘤（：成熟細(xì)胞淋巴瘤（68%68%）B B細(xì)胞（細(xì)胞（54%54%）T T細(xì)胞（細(xì)胞（12%12%）NK/TNK/T或或NKNK細(xì)胞（細(xì)胞（2%2%）4 4沐風(fēng)書苑沐風(fēng)書苑i i(二二)霍奇金淋巴瘤霍奇金淋巴瘤(HL):特殊類型成熟特殊類型成熟B細(xì)胞淋巴瘤細(xì)胞淋巴瘤(30%)結(jié)節(jié)性淋巴細(xì)胞為主型結(jié)節(jié)性淋巴細(xì)胞為主型（1.5%1.5%）經(jīng)典型經(jīng)典型(28.

3、5%)(28.5%)(缺陷性缺陷性B B細(xì)胞細(xì)胞)結(jié)節(jié)硬化型結(jié)節(jié)硬化型 淋巴細(xì)胞豐富型淋巴細(xì)胞豐富型 混合細(xì)胞型混合細(xì)胞型 淋巴細(xì)胞消減型淋巴細(xì)胞消減型5 5沐風(fēng)書苑沐風(fēng)書苑i i第二節(jié)第二節(jié) 淋巴結(jié)的免疫結(jié)構(gòu)淋巴結(jié)的免疫結(jié)構(gòu) （immunoarchitecture）一、概念：一、概念：通過免疫組織化學(xué)染色顯示淋巴結(jié)的結(jié)通過免疫組織化學(xué)染色顯示淋巴結(jié)的結(jié)構(gòu)特征。包括腫瘤性或非腫瘤性細(xì)胞的成分（淋巴構(gòu)特征。包括腫瘤性或非腫瘤性細(xì)胞的成分（淋巴細(xì)胞細(xì)胞,輔助性非淋巴細(xì)胞輔助性非淋巴細(xì)胞,淋巴竇淋巴竇,血管血管,網(wǎng)狀纖維等）、網(wǎng)狀纖維等）、數(shù)量、分布方式等特征。通過對比，掌握正常和異數(shù)量、分布方式等

4、特征。通過對比，掌握正常和異常免疫結(jié)構(gòu)，對淋巴結(jié)病變進(jìn)行診斷和鑒別診斷。常免疫結(jié)構(gòu)，對淋巴結(jié)病變進(jìn)行診斷和鑒別診斷。高質(zhì)量的組織學(xué)切片高質(zhì)量的組織學(xué)切片和和合理的免疫標(biāo)記物合理的免疫標(biāo)記物的選擇是的選擇是識別免疫結(jié)構(gòu)的關(guān)鍵。識別免疫結(jié)構(gòu)的關(guān)鍵。6 6沐風(fēng)書苑沐風(fēng)書苑i i二、淋巴結(jié)的正常免疫結(jié)構(gòu)二、淋巴結(jié)的正常免疫結(jié)構(gòu)（一）淋巴結(jié)結(jié)構(gòu)（一）淋巴結(jié)結(jié)構(gòu):皮質(zhì)皮質(zhì),髓質(zhì)髓質(zhì),竇竇,被膜和纖維小梁被膜和纖維小梁7 7沐風(fēng)書苑沐風(fēng)書苑i i（二）（二）B淋巴細(xì)胞分布：淋巴細(xì)胞分布：1.1.主要在主要在淺皮質(zhì)區(qū)淺皮質(zhì)區(qū)的初級和次級濾泡，髓索和副的初級和次級濾泡，髓索和副皮質(zhì)區(qū)也含一定量皮質(zhì)區(qū)也含一定量B

5、細(xì)胞細(xì)胞;2.2.B細(xì)胞分化過程中的形態(tài)和免疫學(xué)特征成為非霍細(xì)胞分化過程中的形態(tài)和免疫學(xué)特征成為非霍奇金奇金B(yǎng)細(xì)胞淋巴瘤分類的基礎(chǔ)。細(xì)胞淋巴瘤分類的基礎(chǔ)。8 8沐風(fēng)書苑沐風(fēng)書苑i i9 9沐風(fēng)書苑沐風(fēng)書苑i i1010沐風(fēng)書苑沐風(fēng)書苑i iPre pre B cellPre B cellImmature B cellMature B cellActivated B cellPlasma cellPrecursor cells;antigen non-responsiveVirgin B cells;antigen responsiveGerminal center&post GC cells;

6、antigen encounteredTdTCD20,CD22CD19,PAX5CD79aCD10Bcl-6CD138Cytoplasmic CD221111沐風(fēng)書苑沐風(fēng)書苑i iImmunoarchitecture of normal lymph nodeB cells(CD20+,CD10+,BCL-6+)T cells(CD3+);only small numbers of CD20+cells1212沐風(fēng)書苑沐風(fēng)書苑i i1313沐風(fēng)書苑沐風(fēng)書苑i i 1、初級濾泡：、初級濾泡：處女型處女型B細(xì)胞和成熟小淋巴細(xì)胞；細(xì)胞和成熟小淋巴細(xì)胞；1414沐風(fēng)書苑沐風(fēng)書苑i iCD202、次級濾泡

7、：、次級濾泡：由生發(fā)中心、套區(qū)和邊緣區(qū)構(gòu)成。由生發(fā)中心、套區(qū)和邊緣區(qū)構(gòu)成。1515沐風(fēng)書苑沐風(fēng)書苑i iOrganization of secondary lymphoid follicleOrganization of secondary lymphoid follicle Marginal zone cells(IgM)Mantle zone cells(IgM+D)Follicle center cells(IgM,IgG,IgA or IgE,not IgD):約約2:1，當(dāng)，當(dāng):8-10:1或或:3:1提示輕鏈限制表達(dá)提示輕鏈限制表達(dá)1616沐風(fēng)書苑沐風(fēng)書苑i i次級濾泡次級濾泡生發(fā)

8、中心、套區(qū)和邊緣區(qū)免疫標(biāo)記：生發(fā)中心、套區(qū)和邊緣區(qū)免疫標(biāo)記：（1）生發(fā)中心生發(fā)中心(Germinal Center,GC)：1）中心細(xì)胞和中心母細(xì)胞：中心細(xì)胞和中心母細(xì)胞：CD10+,BCL-6+,Bcl-2-,2）濾泡樹突細(xì)胞濾泡樹突細(xì)胞(Follicular dendritic cells,FDC):CD21+,CD23+,CD35+3）T細(xì)胞：細(xì)胞：CD4+,CD10+,CXCL13/PD-1+,少量少量CD57+4）可染體巨噬細(xì)胞可染體巨噬細(xì)胞：CD68+,lysozyme+,CD11c+（2）套區(qū)套區(qū):處女型處女型B細(xì)胞和記憶細(xì)胞細(xì)胞和記憶細(xì)胞,表達(dá)表達(dá)IgM,IgD（3）邊緣區(qū)：邊

9、緣區(qū)：無特殊標(biāo)記，絕大多數(shù)次級濾泡難以鑒別，無特殊標(biāo)記，絕大多數(shù)次級濾泡難以鑒別，腹腔腹腔 淋巴結(jié)淋巴結(jié)易識別。易識別。1717沐風(fēng)書苑沐風(fēng)書苑i iCD201818沐風(fēng)書苑沐風(fēng)書苑i iCD79a1919沐風(fēng)書苑沐風(fēng)書苑i i2020沐風(fēng)書苑沐風(fēng)書苑i i2121沐風(fēng)書苑沐風(fēng)書苑i i2222沐風(fēng)書苑沐風(fēng)書苑i iCD212323沐風(fēng)書苑沐風(fēng)書苑i iCD10Bcl-62424沐風(fēng)書苑沐風(fēng)書苑i i反應(yīng)性濾泡增生的特點反應(yīng)性濾泡增生的特點n n對對對對T T細(xì)胞依賴性抗原的反應(yīng)細(xì)胞依賴性抗原的反應(yīng)細(xì)胞依賴性抗原的反應(yīng)細(xì)胞依賴性抗原的反應(yīng)n n濾泡增多，大小、形態(tài)不等，可彌漫分布，主濾泡增多，

10、大小、形態(tài)不等，可彌漫分布，主濾泡增多，大小、形態(tài)不等，可彌漫分布，主濾泡增多，大小、形態(tài)不等，可彌漫分布，主要位于皮質(zhì)區(qū)，無要位于皮質(zhì)區(qū)，無要位于皮質(zhì)區(qū)，無要位于皮質(zhì)區(qū)，無背靠背背靠背背靠背背靠背現(xiàn)象。現(xiàn)象?，F(xiàn)象?，F(xiàn)象。n n典型生發(fā)中心具有極性典型生發(fā)中心具有極性典型生發(fā)中心具有極性典型生發(fā)中心具有極性(PolarityPolarity):):明區(qū)和暗區(qū)，明區(qū)和暗區(qū)，明區(qū)和暗區(qū)，明區(qū)和暗區(qū)，套區(qū)明顯，扁桃體組織更易識別；套區(qū)明顯，扁桃體組織更易識別；套區(qū)明顯，扁桃體組織更易識別；套區(qū)明顯，扁桃體組織更易識別；n n星天現(xiàn)象，中心細(xì)胞和中心母細(xì)胞混雜，星天現(xiàn)象，中心細(xì)胞和中心母細(xì)胞混雜，星天

11、現(xiàn)象，中心細(xì)胞和中心母細(xì)胞混雜，星天現(xiàn)象，中心細(xì)胞和中心母細(xì)胞混雜，n n免疫染色：免疫染色：免疫染色：免疫染色：生發(fā)中心細(xì)胞生發(fā)中心細(xì)胞生發(fā)中心細(xì)胞生發(fā)中心細(xì)胞BCL-2-BCL-2-，ki-67ki-67指數(shù)指數(shù)指數(shù)指數(shù)較高。較高。較高。較高。n n濾泡間區(qū)一般無濾泡間區(qū)一般無濾泡間區(qū)一般無濾泡間區(qū)一般無B B細(xì)胞彌漫陽性，細(xì)胞彌漫陽性，細(xì)胞彌漫陽性，細(xì)胞彌漫陽性，B B細(xì)胞細(xì)胞細(xì)胞細(xì)胞CD43CD43和和和和CD5CD5陰性。陰性。陰性。陰性。2525沐風(fēng)書苑沐風(fēng)書苑i i2626沐風(fēng)書苑沐風(fēng)書苑i i2727沐風(fēng)書苑沐風(fēng)書苑i iDark zoneLight zone2828沐風(fēng)書苑沐

12、風(fēng)書苑i i BCL-2 Ki672929沐風(fēng)書苑沐風(fēng)書苑i iMarginal zone cells3030沐風(fēng)書苑沐風(fēng)書苑i iCD203131沐風(fēng)書苑沐風(fēng)書苑i i（三）（三）T淋巴細(xì)胞分布：副皮質(zhì)區(qū)淋巴細(xì)胞分布：副皮質(zhì)區(qū)(paracortex)T T淋巴細(xì)胞為主淋巴細(xì)胞為主 (CD4CD8):(CD4CD8):主為小淋巴細(xì)胞，主為小淋巴細(xì)胞，偶爾出現(xiàn)大細(xì)胞偶爾出現(xiàn)大細(xì)胞 (可以是活化的可以是活化的B B細(xì)胞細(xì)胞););含有含有高內(nèi)皮靜脈高內(nèi)皮靜脈 (High endothelial venules,High endothelial venules,HEVHEV):):):):血液淋巴細(xì)

13、胞入淋巴結(jié)的通道血液淋巴細(xì)胞入淋巴結(jié)的通道;含有含有指狀樹突細(xì)胞指狀樹突細(xì)胞(interdigitating dendritic interdigitating dendritic cells,cells,IDCIDC):S100+):S100+的專職抗原遞呈細(xì)胞；的專職抗原遞呈細(xì)胞；3232沐風(fēng)書苑沐風(fēng)書苑i i3333沐風(fēng)書苑沐風(fēng)書苑i i3434沐風(fēng)書苑沐風(fēng)書苑i iProthymocyteSubcapsular thymocyteCortical thymocyteMedullary thymocytePeripheral T cellPrecursor cellsMature T c

14、ellsCytoplasmicSurfaceCD4CD8CD1CD4,CD8CD3CD2CD7TdT3535沐風(fēng)書苑沐風(fēng)書苑i i3636沐風(fēng)書苑沐風(fēng)書苑i iIDC3737沐風(fēng)書苑沐風(fēng)書苑i iCD33838沐風(fēng)書苑沐風(fēng)書苑i i副皮質(zhì)區(qū)增生副皮質(zhì)區(qū)增生常見病因常見病因常見病因常見病因:病毒感染病毒感染病毒感染病毒感染,接種疫苗，藥物，自身免接種疫苗，藥物，自身免接種疫苗，藥物，自身免接種疫苗，藥物，自身免疫疾病疫疾病疫疾病疫疾病,皮病性淋巴結(jié)炎，腫瘤轉(zhuǎn)移等皮病性淋巴結(jié)炎，腫瘤轉(zhuǎn)移等皮病性淋巴結(jié)炎，腫瘤轉(zhuǎn)移等皮病性淋巴結(jié)炎，腫瘤轉(zhuǎn)移等形態(tài)特征：形態(tài)特征：形態(tài)特征：形態(tài)特征：副皮質(zhì)擴大，可形成

15、結(jié)節(jié)；副皮質(zhì)擴大，可形成結(jié)節(jié)；副皮質(zhì)擴大，可形成結(jié)節(jié)；副皮質(zhì)擴大，可形成結(jié)節(jié)；HEVHEV增生；增生；增生；增生；混合小淋巴細(xì)胞和轉(zhuǎn)化淋巴細(xì)胞，混合小淋巴細(xì)胞和轉(zhuǎn)化淋巴細(xì)胞，混合小淋巴細(xì)胞和轉(zhuǎn)化淋巴細(xì)胞，混合小淋巴細(xì)胞和轉(zhuǎn)化淋巴細(xì)胞，漿細(xì)胞，樹突細(xì)胞，嗜酸性粒細(xì)胞等；漿細(xì)胞，樹突細(xì)胞，嗜酸性粒細(xì)胞等；漿細(xì)胞，樹突細(xì)胞，嗜酸性粒細(xì)胞等；漿細(xì)胞，樹突細(xì)胞，嗜酸性粒細(xì)胞等；免疫染色：主為免疫染色：主為免疫染色：主為免疫染色：主為T T細(xì)胞，或細(xì)胞，或細(xì)胞，或細(xì)胞，或T/BT/B細(xì)胞混合細(xì)胞混合細(xì)胞混合細(xì)胞混合,一般一般一般一般無無無無B B細(xì)胞為主彌漫分布。細(xì)胞為主彌漫分布。細(xì)胞為主彌漫分布。細(xì)胞為

16、主彌漫分布。3939沐風(fēng)書苑沐風(fēng)書苑i i4040沐風(fēng)書苑沐風(fēng)書苑i i4141沐風(fēng)書苑沐風(fēng)書苑i iImmunoblastInfectious mononucleosis4242沐風(fēng)書苑沐風(fēng)書苑i iCD20CD3 Large cells comprise mixture of B and T cells-Reactive process4343沐風(fēng)書苑沐風(fēng)書苑i iCD30+cells are scattered and staining is weak or moderate,which indicates the heterogeneity of the large cell popu

17、lation.CD30 staining is diffusely strong positive,which indicates the monoclone entity.4444沐風(fēng)書苑沐風(fēng)書苑i iKappaLambdaLarge B cells are polytypic4545沐風(fēng)書苑沐風(fēng)書苑i iT細(xì)胞為主時支持良性的依據(jù)（細(xì)胞為主時支持良性的依據(jù)（謹(jǐn)慎！謹(jǐn)慎！）：）：（1）結(jié)構(gòu)不同程度保留：淋巴竇和皮質(zhì)淋巴濾泡；結(jié)構(gòu)不同程度保留：淋巴竇和皮質(zhì)淋巴濾泡；（2 2）大細(xì)胞群體分布不規(guī)則或呈地圖樣，不形成膨脹性團塊；）大細(xì)胞群體分布不規(guī)則或呈地圖樣，不形成膨脹性團塊；（3 3）無浸潤現(xiàn)

18、象：上皮）無浸潤現(xiàn)象：上皮,脂肪脂肪,血管血管,神經(jīng)神經(jīng),纖維間質(zhì)中單行排列；纖維間質(zhì)中單行排列；（4 4）細(xì)胞無明顯異型：）細(xì)胞無明顯異型：2.5 BLeukemia(ALL):B TUntreated:rapidly fatalAggressive therapy:good survivalCannot predict lineage from morphologyDefining marker:TdT+，CD997878沐風(fēng)書苑沐風(fēng)書苑i i7979沐風(fēng)書苑沐風(fēng)書苑i i8080沐風(fēng)書苑沐風(fēng)書苑i iCD20CD79aB-LBL8181沐風(fēng)書苑沐風(fēng)書苑i iT-LBL8282沐風(fēng)書苑沐風(fēng)

19、書苑i i濾泡性淋巴瘤濾泡性淋巴瘤FOLLICULAR LYMPHOMAFOLLICULAR LYMPHOMAUsually involving lymph nodesUsually involving lymph nodesHigh-stage disease at presentationHigh-stage disease at presentationPathology:Recapitulates the organization and Pathology:Recapitulates the organization and cytology of the normal germin

20、al centerscytology of the normal germinal centersKey immunophenotype:Key immunophenotype:B marker+,CD10+,B marker+,CD10+,Bcl6+,Bcl6+,Bcl2+Bcl2+Follicular lymphoma involving some Follicular lymphoma involving some extranodal sites(such as skin,duodenum,testis)extranodal sites(such as skin,duodenum,te

21、stis)show distinctive clinical and biologic featuresshow distinctive clinical and biologic featuresGeneticsGenetics:Ig gene rearrangement:Ig gene rearrangement;t(14;18)(q32;q21)t(14;18)(q32;q21)bcl-2 gene rearrangementbcl-2 gene rearrangement (due to (due to BCL2/IGHBCL2/IGH translocation)translocat

22、ion)8383沐風(fēng)書苑沐風(fēng)書苑i iFollicular lymphoma vsreactive follicular hyperplasiaMajor criterionClosely packed follicles throughout,with scanty interfollicular tissues8484沐風(fēng)書苑沐風(fēng)書苑i i濾泡性淋巴瘤主要診斷標(biāo)準(zhǔn)示意圖濾泡性淋巴瘤主要診斷標(biāo)準(zhǔn)示意圖 Major criterion fulfilled in 80%of cases of follicular lymphomaJust go on to high magnification

23、to confirm follicle center cell morphology8585沐風(fēng)書苑沐風(fēng)書苑i i8686沐風(fēng)書苑沐風(fēng)書苑i i8787沐風(fēng)書苑沐風(fēng)書苑i iCentrocytes oftenhave triangularshaped nuclei8888沐風(fēng)書苑沐風(fēng)書苑i i濾泡性淋巴瘤的次要診斷標(biāo)準(zhǔn)濾泡性淋巴瘤的次要診斷標(biāo)準(zhǔn)In the remaining 20%of cases(non-crowded follicles),a combination of minor criteria(3)have to be considered,and supplemented by

24、 ancillary studies as required8989沐風(fēng)書苑沐風(fēng)書苑i iMinor criteria No tingible-body macrophagesNo tingible-body macrophagesCellular monotony:centrocyte predominanceCellular monotony:centrocyte predominanceNo cellular polarisationNo cellular polarisationAbsent or incomplete mantlesAbsent or incomplete mantl

25、esFollicles in perinodal tissuesFollicles in perinodal tissuesDysplastic follicular center cells,e.g.signet ring Dysplastic follicular center cells,e.g.signet ring cells,frequent cytoplasmic globulescells,frequent cytoplasmic globulesAtypical cells in interfollicular tissuesAtypical cells in interfo

26、llicular tissuesInvasion of walls of blood vesselsInvasion of walls of blood vessels9090沐風(fēng)書苑沐風(fēng)書苑i i9191沐風(fēng)書苑沐風(fēng)書苑i i9292沐風(fēng)書苑沐風(fēng)書苑i i9393沐風(fēng)書苑沐風(fēng)書苑i i9494沐風(fēng)書苑沐風(fēng)書苑i iFollicular lymphoma vs RFH:ancillary techniquesImmunostaining for bcl-2n nMost useful immunostainMost useful immunostainn nNormal:Both T and

27、B cells positive except Normal:Both T and B cells positive except follicle center cellsfollicle center cellsn nLook for positive staining of cells in follicle Look for positive staining of cells in follicle centerscenters:positive staining supports diagnosis of:positive staining supports diagnosis o

28、f lymphomalymphoma9595沐風(fēng)書苑沐風(fēng)書苑i iReactive follicles9696沐風(fēng)書苑沐風(fēng)書苑i iFollicular lymphoma(Bcl-2 immunostaining)9797沐風(fēng)書苑沐風(fēng)書苑i iCommon misconceptions in hematopathologyNegative bcl-2 stain rules out follicular lymphomaThe truth:It does not.20-25%offollicular lymphoma cases are negative.Pursue with other t

29、ests to confirmor refute a diagnosis offollicular lymphoma9898沐風(fēng)書苑沐風(fēng)書苑i iBcl-2 staining infollicular lymphomaGradeGrade(Cytologic composition)(Cytologic composition)Bcl-2 Bcl-2 immunoreactivityimmunoreactivityI(predominantly small cells)I(predominantly small cells)100%100%II(mixed small and large ce

30、lls)II(mixed small and large cells)85%85%III(predominantly large cells)III(predominantly large cells)75%75%9999沐風(fēng)書苑沐風(fēng)書苑i i100100沐風(fēng)書苑沐風(fēng)書苑i iBcl-2101101沐風(fēng)書苑沐風(fēng)書苑i iLook for evidence interfollicular invasionn nDensely packed CD20+or CD79+B-cells Densely packed CD20+or CD79+B-cells between follicles is i

31、ndicative of interfollicular between follicles is indicative of interfollicular invasioninvasionn nPresence of a significant number of CD10+Presence of a significant number of CD10+lymphoid cells(not neutrophils,which are also lymphoid cells(not neutrophils,which are also CD10+)between follicles als

32、o indicates CD10+)between follicles also indicates interfollicular invasion interfollicular invasion Look for vascular invasion n nMany CD10+cells in the walls of perinodal Many CD10+cells in the walls of perinodal blood vesselsblood vessels102102沐風(fēng)書苑沐風(fēng)書苑i iCD20103103沐風(fēng)書苑沐風(fēng)書苑i iCD10104104沐風(fēng)書苑沐風(fēng)書苑i i

33、105105沐風(fēng)書苑沐風(fēng)書苑i iLook for monoclonality or low proliferation indexn nImmunostain for Ig to look for light chain Immunostain for Ig to look for light chain restrictionrestrictionn nDemonstrated by Ki67,a low Ki67 index favors Demonstrated by Ki67,a low Ki67 index favors diagnosis of follicular lympho

34、ma over RFH(mean diagnosis of follicular lymphoma over RFH(mean index 15.6%vs 64.9%);a high Ki67 index is index 15.6%vs 64.9%);a high Ki67 index is inconclusiveinconclusiveMolecular analysisn nIg gene rearrangement by Southern blot or PCR Ig gene rearrangement by Southern blot or PCR(Note that PCR m

35、ay have false negative results)(Note that PCR may have false negative results)n nDetection of Detection of BCL2BCL2 gene rearrangement by gene rearrangement by Southern blot,PCR or FISHSouthern blot,PCR or FISH106106沐風(fēng)書苑沐風(fēng)書苑i iKappaLambda107107沐風(fēng)書苑沐風(fēng)書苑i iFL1:Ki67RFH:Ki67108108沐風(fēng)書苑沐風(fēng)書苑i iFL3:Ki671091

36、09沐風(fēng)書苑沐風(fēng)書苑i i套細(xì)胞淋巴瘤套細(xì)胞淋巴瘤Mantle cell lymphoma:morphologyMantle cell lymphoma:morphologyDiffuseDiffuse,vaguely nodularvaguely nodular,or,or mantle zone mantle zone patternpatternBroad cytologic spectrumBroad cytologic spectrumn nClassic typeClassic type:small lymphoid cells with irregular to:small ly

37、mphoid cells with irregular to round nucleiround nuclein nBlastoid variantBlastoid variant(lymphoblasts,but TdT-)(lymphoblasts,but TdT-)n nPleomorphic variantPleomorphic variantOften with solitary epithelioid histiocytesOften with solitary epithelioid histiocytesInterspersed naked nuclei(follicular

38、dendritic Interspersed naked nuclei(follicular dendritic cells)cells)Genetics:Ig gene rearrangementGenetics:Ig gene rearrangement t(11,14)(q13;q32)t(11,14)(q13;q32)110110沐風(fēng)書苑沐風(fēng)書苑i i Growth pattern of MCL111111沐風(fēng)書苑沐風(fēng)書苑i i112112沐風(fēng)書苑沐風(fēng)書苑i i113113沐風(fēng)書苑沐風(fēng)書苑i i114114沐風(fēng)書苑沐風(fēng)書苑i iRound nuclei115115沐風(fēng)書苑沐風(fēng)書苑i i

39、Mantle cell lymphoma:biologic markersB marker+,CD5+,CD10-,CD23-,IgM+,IgD+Key defining feature:Cyclin D1+due to t(11;14)(q13;q32)or cryptic translocation116116沐風(fēng)書苑沐風(fēng)書苑i iCyclin D1117117沐風(fēng)書苑沐風(fēng)書苑i i 粘膜相關(guān)淋巴組織粘膜相關(guān)淋巴組織 Mucosa-Associated Lymphoid Tissue(MALT)Mucosa-Associated Lymphoid Tissue(MALT)Specializ

40、ed secondary lymphoid compartments of mucosal tissuesn nNatural,e.g.,Waldeyers ring,small intestine,Natural,e.g.,Waldeyers ring,small intestine,lunglungn nAcquired in autoimmune disease/inflammation Acquired in autoimmune disease/inflammation e.g.,thyroid,salivary gland,lacrimal gland,e.g.,thyroid,s

41、alivary gland,lacrimal gland,stomachstomachSimilar organization as lymph node:B-cell follicles,T-cell zonesLymphoid cells acquire homing properties118118沐風(fēng)書苑沐風(fēng)書苑i i119119沐風(fēng)書苑沐風(fēng)書苑i iLOW GRADE B CELL LOW GRADE B CELL MALTMALT LYMPHOMA LYMPHOMA(extranodal marginal zone B-cell lymphoma)(extranodal margi

42、nal zone B-cell lymphoma)Usually localized at presentation(66-79%)Recurrence at other MALT sites(“homing”)Many can be treated by locoregional therapy or eradication of antigen-stimulation sourceComplete remission rate=72%5-year overall survival=74%(Gastric:90%)120120沐風(fēng)書苑沐風(fēng)書苑i iHistologic features of

43、 low grade Histologic features of low grade MALT lymphomaMALT lymphomaSmall/medium-sized cells(lymphocytes,centrocyte-like,monocytoid B cells)Patterns:diffuse,interfollicular,marginal zoneLymphoepithelial lesionsPlasma cells are commonReactive lymphoid follicles+/-colonization121121沐風(fēng)書苑沐風(fēng)書苑i i122122

44、沐風(fēng)書苑沐風(fēng)書苑i i123123沐風(fēng)書苑沐風(fēng)書苑i i124124沐風(fēng)書苑沐風(fēng)書苑i iLow grade MALT lymphoma:Low grade MALT lymphoma:ImmunophenotypeImmunophenotypeA neoplasm of post-germinal center B cellsPan B+,CD10-,CD5-,Cyclin D1-,CD23-Key features:n nsite of involvementsite of involvementn nlymphoepithelial lesionlymphoepithelial lesi

45、onn nexclusion of other low grade B-cell exclusion of other low grade B-cell lymphomaslymphomas125125沐風(fēng)書苑沐風(fēng)書苑i iAfter Helicobacter eradication therapy126126沐風(fēng)書苑沐風(fēng)書苑i i彌漫性大彌漫性大B B細(xì)胞淋巴瘤細(xì)胞淋巴瘤DIFFUSE LARGE B CELL DIFFUSE LARGE B CELL LYMPHOMALYMPHOMA（DLBCLDLBCL）Commonest nodal B-cell lymphomaA heterogen

46、eous entityFinal common pathway for high grade transformation of low grade B-cell lymphomas127127沐風(fēng)書苑沐風(fēng)書苑i iCentroblastic/Immunoblastic128128沐風(fēng)書苑沐風(fēng)書苑i i129129沐風(fēng)書苑沐風(fēng)書苑i iMultilobatedPleomorphic130130沐風(fēng)書苑沐風(fēng)書苑i iBURKITT LYMPHOMAThree different forms:Three different forms:n nEndemicEndemic(Equatorial Af

47、rica;strong association (Equatorial Africa;strong association with EBV 90%;commonly affecting jaws,with EBV 90%;commonly affecting jaws,gonads,kidneys)gonads,kidneys)n nSporadicSporadic(EBV association only 15%;(EBV association only 15%;commonly involving terminal ileum and commonly involving termin

48、al ileum and Waldeyers ring)Waldeyers ring)n nAIDS-relatedAIDS-related(EBV association 30%;(EBV association 30%;commonly involving lymphonode and bone commonly involving lymphonode and bone marrow)marrow)African cases can also be AIDS-related!African cases can also be AIDS-related!131131沐風(fēng)書苑沐風(fēng)書苑i iB

49、urkitt lymphomat(8;14)(q24;q32)or variants,with translocation between c-myc and Ig geneMostly a disease of young patientsHighly aggressive,but potentially curable by chemotherapy132132沐風(fēng)書苑沐風(fēng)書苑i i133133沐風(fēng)書苑沐風(fēng)書苑i i134134沐風(fēng)書苑沐風(fēng)書苑i iBurkitt lymphoma:ImmunogeneticsProbably corresponds to IgM+blasts in ge

50、rminal centerPan-B+,CD10+,Bcl-6+,Bcl-2-Key features:n nC-MYCC-MYC translocation translocation n nmedium-sized cellsmedium-sized cellsn nhigh Ki67 indexhigh Ki67 index：100%100%n ngerminal center cell phenotypegerminal center cell phenotype135135沐風(fēng)書苑沐風(fēng)書苑i iCD20CD10136136沐風(fēng)書苑沐風(fēng)書苑i iKi67137137沐風(fēng)書苑沐風(fēng)書苑i

51、i外周外周T T和和NKNK細(xì)胞淋巴瘤細(xì)胞淋巴瘤PERIPHERAL T AND NK CELL LYMPHOMASUncommon;80%)(80%)149149沐風(fēng)書苑沐風(fēng)書苑i iExtranodal NK/T cell lymphoma:PathologyNecrosis(apoptosis)common Angioinvasion common(not invariably seen)Broad cytologic spectrum:small,medium-sized or large cells,or mixedMay have many admixed inflammatory

52、 cells150150沐風(fēng)書苑沐風(fēng)書苑i i151151沐風(fēng)書苑沐風(fēng)書苑i i152152沐風(fēng)書苑沐風(fēng)書苑i iSmallMedium-sizedLargeBroad cytologic spectrum153153沐風(fēng)書苑沐風(fēng)書苑i iExtranodal NK/T cell lymphoma:immunophenotypeCD2+.sCD3-,cCD3e+,CD56+Cytotoxic granules perforin,granzyme B,TIA-1 positiveCD4,CD5,CD7,CD8:usually negativeKey features:CD56+,EBER+If

53、CD56-,requires EBER+and cytotoxic granules+for diagnosis154154沐風(fēng)書苑沐風(fēng)書苑i iSurface CD3Cytoplasmic CD3CD56Frozen tissueParaffin section155155沐風(fēng)書苑沐風(fēng)書苑i iPERIPHERAL T CELL LYMPHOMA UNSPECIFIED外周外周T T細(xì)胞淋巴瘤，非特殊型細(xì)胞淋巴瘤，非特殊型A wastebasket categoryVariable clinical manifestationsUsually high stage disease(nodal

54、/extranodal)May have eosinophiliaAggressive;relapse commonThe extranodal cases often express a cytotoxic cell phenotype156156沐風(fēng)書苑沐風(fēng)書苑i iPeripheral T-cell lymphoma:Morphologic clues for recognitionPredominant paracortical involvementProminent high endothelial venulesSpectrum of cells sizes and shapes

55、Irregular nuclear contoursClear cellsMany admixed epithelioid histiocytes and eosinophilsBut immunostaining essential for confirming T lineage157157沐風(fēng)書苑沐風(fēng)書苑i i158158沐風(fēng)書苑沐風(fēng)書苑i i159159沐風(fēng)書苑沐風(fēng)書苑i iANAPLASTIC LARGE CELL LYMPHOMA,primary systemic form間變性大細(xì)胞淋巴瘤，原發(fā)系統(tǒng)性間變性大細(xì)胞淋巴瘤，原發(fā)系統(tǒng)性Tends to occur in childre

56、n and young Tends to occur in children and young adultsadultsNodal or extranodal presentation(which Nodal or extranodal presentation(which may include skin,soft tissue,bone,G.I.may include skin,soft tissue,bone,G.I.tract)tract)Immunophenotype:Immunophenotype:n nCD30+;CD30+;EMA usually+EMA usually+n

57、nT-lineage markers+/-(T or null cell)T-lineage markers+/-(T or null cell)n nA proportion of cases express A proportion of cases express ALKALK due to due to translocation involving translocation involving ALKALK gene gene160160沐風(fēng)書苑沐風(fēng)書苑i iHallmark cells161161沐風(fēng)書苑沐風(fēng)書苑i iALK translocation(or expression

58、)has helped to define a homogeneous subgroup of ALCLThis can be easily detected by immunostaining for ALK-permitting re-definition of the morphologic spectrum of ALCL:nClassical typeClassical typenMonomorphicMonomorphicnSmall cellSmall cellnLymphohistiocyticLymphohistiocyticnHypocellularHypocellular

59、162162沐風(fēng)書苑沐風(fēng)書苑i i163163沐風(fēng)書苑沐風(fēng)書苑i iCD30164164沐風(fēng)書苑沐風(fēng)書苑i i Overall survivalPrimary systemic form of ALCL0510YearsALCL,ALK+*100%50%ALCL,ALK-165165沐風(fēng)書苑沐風(fēng)書苑i i 霍奇金淋巴瘤霍奇金淋巴瘤 HODGKIN LYMPHOMAHODGKIN LYMPHOMA166166沐風(fēng)書苑沐風(fēng)書苑i iLymphocyte predominanceMixed cellularityNodular sclerosisLymphocyte depletionNodular

60、 lymphocyte predominant Hodgkin lymphoma(N-LPHL)Classical Hodgkin lymphoma(cHL)Lymphocyte-richMixed cellularityNodular sclerosisLymphocyte depletionRYE CLASSIFICATIONWHO CLASSIFICATION167167沐風(fēng)書苑沐風(fēng)書苑i i510YearsOverall survivalN-LPHL defined by immunohistochemistrycHL defined by immunohistochemistryp=

61、0.0071168168沐風(fēng)書苑沐風(fēng)書苑i iA lymphoma characterized by:n npresence of presence of Reed-Sternberg cellsReed-Sternberg cells and their and their variantsvariants confirmed by confirmed by mmunohistochemistryn nin an appropriate in an appropriate reactive cellular reactive cellular environment environment

62、169169沐風(fēng)書苑沐風(fēng)書苑i iReed-Sternberg cells and variantsDiagnostic Reed-Sternberg cellsMononuclear Hodgkin cellLacunar cellL&H cellPleomorphic Reed-Sternberg cellKi67+100%No need to find diagnostic Reed-Sternberg cellsin rendering a diagnosis of Hodgkin lymphoma.Its okay if cells are large enough,with pro

63、minentnucleoli and compatible immunophenotype.170170沐風(fēng)書苑沐風(fēng)書苑i iReed-Sternberg cells and variantsSmall lymphocytesNuclear size of most neoplastic cells usually exceeds 3 times that of small lymphocyteSince the R-S cells are so large,they often“stand out”fromthe background cells.171171沐風(fēng)書苑沐風(fēng)書苑i iDiagn

64、ostic Reed-Sternberg cellDiagnostic Reed-Sternberg cell172172沐風(fēng)書苑沐風(fēng)書苑i iAppropriate cellular environmentDepending on the specific subtype of Hodgkin lymphoma,presence or absence of the following:n nSmall lymphocytesSmall lymphocytesn nHistiocytesHistiocytesn nPlasma cellsPlasma cellsn nEosinophils a

65、nd neutrophilsEosinophils and neutrophilsn nFibroblastsFibroblasts173173沐風(fēng)書苑沐風(fēng)書苑i iClassical Hodgkin lymphoma經(jīng)典型霍奇金淋巴瘤經(jīng)典型霍奇金淋巴瘤Large neoplastic cells(R-S cells and variants,e.g.mononuclear,lacunar cells):most,or at least some have large eosinophilic inclusion-like nucleoliBackground often rich in a

66、mixture of lymphocytes,plasma cells,histiocytes and eosinophils,except lymphocyte-rich classical Hodgkin lymphoma174174沐風(fēng)書苑沐風(fēng)書苑i i175175沐風(fēng)書苑沐風(fēng)書苑i iR-S cells variants176176沐風(fēng)書苑沐風(fēng)書苑i ilacunar cellslacunar cells177177沐風(fēng)書苑沐風(fēng)書苑i iClassical Hodgkin lymphoma:ImmunophenotypeLarge cells(“crippled”B cells):n nCD30+CD30+n nCD15 commonly+CD15 commonly+n nCD20 CD20 or heterogeneous+or heterogeneous+n nCD79 CD79 or focally+or focally+n nPAX5+PAX5+n nOct.2,Bob.1:both negative or positive Oct.2,Bob.1:both negat