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1、 淋巴瘤淋巴瘤 Lymphoma 基礎醫(yī)學院病理學系基礎醫(yī)學院病理學系同濟醫(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沐風書苑沐風書苑i iDr John K.C.CHAN陳國璋陳國璋2 2沐風書苑沐風書苑i i4th EditionPublished 20/9/20083 3沐風書苑沐風書苑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”成熟淋巴細胞及其前體細胞（淋巴母細胞）的惡性成熟淋巴細胞及其前體細胞（淋巴母細胞）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細胞（細胞（70%70%）1 1、前體細胞前體細胞：B/T/NKB/T/NK前體細胞（淋巴母細胞）淋巴瘤（前體細胞（淋巴母細胞）淋巴瘤（2%2%）2 2、成熟細胞成熟細胞：成熟細胞淋巴瘤（：成熟細胞淋巴瘤（68%68%）B B細胞（細胞（54%54%）T T細胞（細胞（12%12%）NK/TNK/T或或NKNK細胞（細胞（2%2%）4 4沐風書苑沐風書苑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細胞淋巴瘤細胞淋巴瘤(30%)結節(jié)性淋巴細胞為主型結節(jié)性淋巴細胞為主型（1.5%1.5%）經典型經典型(28.

3、5%)(28.5%)(缺陷性缺陷性B B細胞細胞)結節(jié)硬化型結節(jié)硬化型 淋巴細胞豐富型淋巴細胞豐富型 混合細胞型混合細胞型 淋巴細胞消減型淋巴細胞消減型5 5沐風書苑沐風書苑i i第二節(jié)第二節(jié) 淋巴結的免疫結構淋巴結的免疫結構 （immunoarchitecture）一、概念：一、概念：通過免疫組織化學染色顯示淋巴結的結通過免疫組織化學染色顯示淋巴結的結構特征。包括腫瘤性或非腫瘤性細胞的成分（淋巴構特征。包括腫瘤性或非腫瘤性細胞的成分（淋巴細胞細胞,輔助性非淋巴細胞輔助性非淋巴細胞,淋巴竇淋巴竇,血管血管,網狀纖維等）、網狀纖維等）、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構，對淋巴結病變進行診斷和鑒別診斷。常免疫結構，對淋巴結病變進行診斷和鑒別診斷。高質量的組織學切片高質量的組織學切片和和合理的免疫標記物合理的免疫標記物的選擇是的選擇是識別免疫結構的關鍵。識別免疫結構的關鍵。6 6沐風書苑沐風書苑i i二、淋巴結的正常免疫結構二、淋巴結的正常免疫結構（一）淋巴結結構（一）淋巴結結構:皮質皮質,髓質髓質,竇竇,被膜和纖維小梁被膜和纖維小梁7 7沐風書苑沐風書苑i i（二）（二）B淋巴細胞分布：淋巴細胞分布：1.1.主要在主要在淺皮質區(qū)淺皮質區(qū)的初級和次級濾泡，髓索和副的初級和次級濾泡，髓索和副皮質區(qū)也含一定量皮質區(qū)也含一定量B

5、細胞細胞;2.2.B細胞分化過程中的形態(tài)和免疫學特征成為非霍細胞分化過程中的形態(tài)和免疫學特征成為非霍奇金奇金B(yǎng)細胞淋巴瘤分類的基礎。細胞淋巴瘤分類的基礎。8 8沐風書苑沐風書苑i i9 9沐風書苑沐風書苑i i1010沐風書苑沐風書苑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沐風書苑沐風書苑i iImmunoarchitecture of normal lymph nodeB cells(CD20+,CD10+,BCL-6+)T cells(CD3+);only small numbers of CD20+cells1212沐風書苑沐風書苑i i1313沐風書苑沐風書苑i i 1、初級濾泡：、初級濾泡：處女型處女型B細胞和成熟小淋巴細胞；細胞和成熟小淋巴細胞；1414沐風書苑沐風書苑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)構成。由生發(fā)中心、套區(qū)和邊緣區(qū)構成。1515沐風書苑沐風書苑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，當:8-10:1或或:3:1提示輕鏈限制表達提示輕鏈限制表達1616沐風書苑沐風書苑i i次級濾泡次級濾泡生發(fā)

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

9、緣區(qū)：無特殊標記，絕大多數(shù)次級濾泡難以鑒別，無特殊標記，絕大多數(shù)次級濾泡難以鑒別，腹腔腹腔 淋巴結淋巴結易識別。易識別。1717沐風書苑沐風書苑i iCD201818沐風書苑沐風書苑i iCD79a1919沐風書苑沐風書苑i i2020沐風書苑沐風書苑i i2121沐風書苑沐風書苑i i2222沐風書苑沐風書苑i iCD212323沐風書苑沐風書苑i iCD10Bcl-62424沐風書苑沐風書苑i i反應性濾泡增生的特點反應性濾泡增生的特點n n對對對對T T細胞依賴性抗原的反應細胞依賴性抗原的反應細胞依賴性抗原的反應細胞依賴性抗原的反應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，主要位于皮質區(qū)，無要位于皮質區(qū)，無要位于皮質區(qū)，無要位于皮質區(qū)，無背靠背背靠背背靠背背靠背現(xiàn)象?，F(xiàn)象。現(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，中心細胞和中心母細胞混雜，星天現(xiàn)象，中心細胞和中心母細胞混雜，星天

11、現(xiàn)象，中心細胞和中心母細胞混雜，星天現(xiàn)象，中心細胞和中心母細胞混雜，n n免疫染色：免疫染色：免疫染色：免疫染色：生發(fā)中心細胞生發(fā)中心細胞生發(fā)中心細胞生發(fā)中心細胞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細胞彌漫陽性，細胞彌漫陽性，細胞彌漫陽性，細胞彌漫陽性，B B細胞細胞細胞細胞CD43CD43和和和和CD5CD5陰性。陰性。陰性。陰性。2525沐風書苑沐風書苑i i2626沐風書苑沐風書苑i i2727沐風書苑沐風書苑i iDark zoneLight zone2828沐風書苑沐

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

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

14、ellsCytoplasmicSurfaceCD4CD8CD1CD4,CD8CD3CD2CD7TdT3535沐風書苑沐風書苑i i3636沐風書苑沐風書苑i iIDC3737沐風書苑沐風書苑i iCD33838沐風書苑沐風書苑i i副皮質區(qū)增生副皮質區(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,皮病性淋巴結炎，腫瘤轉移等皮病性淋巴結炎，腫瘤轉移等皮病性淋巴結炎，腫瘤轉移等皮病性淋巴結炎，腫瘤轉移等形態(tài)特征：形態(tài)特征：形態(tài)特征：形態(tài)特征：副皮質擴大，可形成

15、結節(jié)；副皮質擴大，可形成結節(jié)；副皮質擴大，可形成結節(jié)；副皮質擴大，可形成結節(jié)；HEVHEV增生；增生；增生；增生；混合小淋巴細胞和轉化淋巴細胞，混合小淋巴細胞和轉化淋巴細胞，混合小淋巴細胞和轉化淋巴細胞，混合小淋巴細胞和轉化淋巴細胞，漿細胞，樹突細胞，嗜酸性粒細胞等；漿細胞，樹突細胞，嗜酸性粒細胞等；漿細胞，樹突細胞，嗜酸性粒細胞等；漿細胞，樹突細胞，嗜酸性粒細胞等；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細胞，或細胞，或細胞，或細胞，或T/BT/B細胞混合細胞混合細胞混合細胞混合,一般一般一般一般無無無無B B細胞為主彌漫分布。細胞為主彌漫分布。細胞為主彌漫分布。細胞為

16、主彌漫分布。3939沐風書苑沐風書苑i i4040沐風書苑沐風書苑i i4141沐風書苑沐風書苑i iImmunoblastInfectious mononucleosis4242沐風書苑沐風書苑i iCD20CD3 Large cells comprise mixture of B and T cells-Reactive process4343沐風書苑沐風書苑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沐風書苑沐風書苑i iKappaLambdaLarge B cells are polytypic4545沐風書苑沐風書苑i iT細胞為主時支持良性的依據(jù)（細胞為主時支持良性的依據(jù)（謹慎！謹慎?。海海?）結構不同程度保留：淋巴竇和皮質淋巴濾泡；結構不同程度保留：淋巴竇和皮質淋巴濾泡；（2 2）大細胞群體分布不規(guī)則或呈地圖樣，不形成膨脹性團塊；）大細胞群體分布不規(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,神經神經,纖維間質中單行排列；纖維間質中單行排列；（4 4）細胞無明顯異型：）細胞無明顯異型：2.5 BLeukemia(ALL):B TUntreated:rapidly fatalAggressive therapy:good survivalCannot predict lineage from morphologyDefining marker:TdT+，CD997878沐風書苑沐風書苑i i7979沐風書苑沐風書苑i i8080沐風書苑沐風書苑i iCD20CD79aB-LBL8181沐風書苑沐風書苑i iT-LBL8282沐風書苑沐風

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沐風書苑沐風書苑i iFollicular lymphoma vsreactive follicular hyperplasiaMajor criterionClosely packed follicles throughout,with scanty interfollicular tissues8484沐風書苑沐風書苑i i濾泡性淋巴瘤主要診斷標準示意圖濾泡性淋巴瘤主要診斷標準示意圖 Major criterion fulfilled in 80%of cases of follicular lymphomaJust go on to high magnification

23、to confirm follicle center cell morphology8585沐風書苑沐風書苑i i8686沐風書苑沐風書苑i i8787沐風書苑沐風書苑i iCentrocytes oftenhave triangularshaped nuclei8888沐風書苑沐風書苑i i濾泡性淋巴瘤的次要診斷標準濾泡性淋巴瘤的次要診斷標準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沐風書苑沐風書苑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沐風書苑沐風書苑i i9191沐風書苑沐風書苑i i9292沐風書苑沐風書苑i i9393沐風書苑沐風書苑i i9494沐風書苑沐風書苑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沐風書苑沐風書苑i iReactive follicles9696沐風書苑沐風書苑i iFollicular lymphoma(Bcl-2 immunostaining)9797沐風書苑沐風書苑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沐風書苑沐風書苑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沐風書苑沐風書苑i i100100沐風書苑沐風書苑i iBcl-2101101沐風書苑沐風書苑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沐風書苑沐風書苑i iCD20103103沐風書苑沐風書苑i iCD10104104沐風書苑沐風書苑i i

33、105105沐風書苑沐風書苑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沐風書苑沐風書苑i iKappaLambda107107沐風書苑沐風書苑i iFL1:Ki67RFH:Ki67108108沐風書苑沐風書苑i iFL3:Ki671091

36、09沐風書苑沐風書苑i i套細胞淋巴瘤套細胞淋巴瘤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沐風書苑沐風書苑i i Growth pattern of MCL111111沐風書苑沐風書苑i i112112沐風書苑沐風書苑i i113113沐風書苑沐風書苑i i114114沐風書苑沐風書苑i iRound nuclei115115沐風書苑沐風書苑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沐風書苑沐風書苑i iCyclin D1117117沐風書苑沐風書苑i i 粘膜相關淋巴組織粘膜相關淋巴組織 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沐風書苑沐風書苑i i119119沐風書苑沐風書苑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沐風書苑沐風書苑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沐風書苑沐風書苑i i122122

44、沐風書苑沐風書苑i i123123沐風書苑沐風書苑i i124124沐風書苑沐風書苑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沐風書苑沐風書苑i iAfter Helicobacter eradication therapy126126沐風書苑沐風書苑i i彌漫性大彌漫性大B B細胞淋巴瘤細胞淋巴瘤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沐風書苑沐風書苑i iCentroblastic/Immunoblastic128128沐風書苑沐風書苑i i129129沐風書苑沐風書苑i iMultilobatedPleomorphic130130沐風書苑沐風書苑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沐風書苑沐風書苑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沐風書苑沐風書苑i i133133沐風書苑沐風書苑i i134134沐風書苑沐風書苑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沐風書苑沐風書苑i iCD20CD10136136沐風書苑沐風書苑i iKi67137137沐風書苑沐風書苑i

51、i外周外周T T和和NKNK細胞淋巴瘤細胞淋巴瘤PERIPHERAL T AND NK CELL LYMPHOMASUncommon;80%)(80%)149149沐風書苑沐風書苑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沐風書苑沐風書苑i i151151沐風書苑沐風書苑i i152152沐風書苑沐風書苑i iSmallMedium-sizedLargeBroad cytologic spectrum153153沐風書苑沐風書苑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沐風書苑沐風書苑i iSurface CD3Cytoplasmic CD3CD56Frozen tissueParaffin section155155沐風書苑沐風書苑i iPERIPHERAL T CELL LYMPHOMA UNSPECIFIED外周外周T T細胞淋巴瘤，非特殊型細胞淋巴瘤，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沐風書苑沐風書苑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沐風書苑沐風書苑i i158158沐風書苑沐風書苑i i159159沐風書苑沐風書苑i iANAPLASTIC LARGE CELL LYMPHOMA,primary systemic form間變性大細胞淋巴瘤，原發(fā)系統(tǒng)性間變性大細胞淋巴瘤，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沐風書苑沐風書苑i iHallmark cells161161沐風書苑沐風書苑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沐風書苑沐風書苑i i163163沐風書苑沐風書苑i iCD30164164沐風書苑沐風書苑i i Overall survivalPrimary systemic form of ALCL0510YearsALCL,ALK+*100%50%ALCL,ALK-165165沐風書苑沐風書苑i i 霍奇金淋巴瘤霍奇金淋巴瘤 HODGKIN LYMPHOMAHODGKIN LYMPHOMA166166沐風書苑沐風書苑i iLymphocyte predominanceMixed cellularityNodular sclerosisLymphocyte depletionNodular

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

61、0.0071168168沐風書苑沐風書苑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沐風書苑沐風書苑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沐風書苑沐風書苑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沐風書苑沐風書苑i iDiagn

64、ostic Reed-Sternberg cellDiagnostic Reed-Sternberg cell172172沐風書苑沐風書苑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沐風書苑沐風書苑i iClassical Hodgkin lymphoma經典型霍奇金淋巴瘤經典型霍奇金淋巴瘤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沐風書苑沐風書苑i i175175沐風書苑沐風書苑i iR-S cells variants176176沐風書苑沐風書苑i ilacunar cellslacunar cells177177沐風書苑沐風書苑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