淋巴组织肿瘤-课件

淋巴瘤淋巴瘤 Lymphoma 淋巴瘤1 1Dr John K.C.CHAN陈国璋陈国璋Dr John K.C.CHAN2 24th EditionPublished 20/9/20084th Edition3 3第一节第一节 概述概述一、定义一、定义 “来源于来源于”成熟淋巴细胞及其前体细胞（淋巴母细胞）的恶性成熟淋巴细胞及其前体细胞（淋巴母细胞）的恶性肿瘤，分为非霍奇金肿瘤，分为非霍奇金/白血病和霍奇金淋巴瘤两大类。白血病和霍奇金淋巴瘤两大类。二、分类二、分类（一）（一）非霍奇金淋巴瘤非霍奇金淋巴瘤(NHL)(NHL)：包括：包括B B，T T和和NKNK细胞（细胞（70%70%）1 1、前体细胞前体细胞：B/T/NKB/T/NK前体细胞（淋巴母细胞）淋巴瘤（前体细胞（淋巴母细胞）淋巴瘤（2%2%）2 2、成熟细胞成熟细胞：成熟细胞淋巴瘤（：成熟细胞淋巴瘤（68%68%）B B细胞（细胞（54%54%）T T细胞（细胞（12%12%）NK/TNK/T或或NKNK细胞（细胞（2%2%）第一节 概述4 4(二二)霍奇金淋巴瘤霍奇金淋巴瘤(HL):特殊类型成熟特殊类型成熟B细胞淋巴瘤细胞淋巴瘤(30%)结节性淋巴细胞为主型结节性淋巴细胞为主型（1.5%1.5%）经典型经典型(28.5%)(28.5%)(缺陷性缺陷性B B细胞细胞)结节硬化型结节硬化型 淋巴细胞丰富型淋巴细胞丰富型 混合细胞型混合细胞型 淋巴细胞消减型淋巴细胞消减型(二)霍奇金淋巴瘤(HL):特殊类型成熟B细胞淋巴瘤(30%5 5第二节第二节 淋巴结的免疫结构淋巴结的免疫结构 （immunoarchitecture）一、概念：一、概念：通过免疫组织化学染色显示淋巴结的结通过免疫组织化学染色显示淋巴结的结构特征。包括肿瘤性或非肿瘤性细胞的成分（淋巴构特征。包括肿瘤性或非肿瘤性细胞的成分（淋巴细胞细胞,辅助性非淋巴细胞辅助性非淋巴细胞,淋巴窦淋巴窦,血管血管,网状纤维等）、网状纤维等）、数量、分布方式等特征。通过对比，掌握正常和异数量、分布方式等特征。通过对比，掌握正常和异常免疫结构，对淋巴结病变进行诊断和鉴别诊断。常免疫结构，对淋巴结病变进行诊断和鉴别诊断。高质量的组织学切片高质量的组织学切片和和合理的免疫标记物合理的免疫标记物的选择是的选择是识别免疫结构的关键。识别免疫结构的关键。第二节 淋巴结的免疫结构 （immunoarc6 6二、淋巴结的正常免疫结构二、淋巴结的正常免疫结构（一）淋巴结结构（一）淋巴结结构:皮质皮质,髓质髓质,窦窦,被膜和纤维小梁被膜和纤维小梁二、淋巴结的正常免疫结构7 7（二）（二）B淋巴细胞分布：淋巴细胞分布：1.1.主要在主要在浅皮质区浅皮质区的初级和次级滤泡，髓索和副的初级和次级滤泡，髓索和副皮质区也含一定量皮质区也含一定量B细胞细胞;2.2.B细胞分化过程中的形态和免疫学特征成为非霍细胞分化过程中的形态和免疫学特征成为非霍奇金奇金B细胞淋巴瘤分类的基础。细胞淋巴瘤分类的基础。（二）B淋巴细胞分布：8 8淋巴组织肿瘤-课件9 9淋巴组织肿瘤-课件1010Pre pre B cellPre B cellImmature B cellMature B cellActivated B cellPlasma cellPrecursor cells;antigen non-responsiveVirgin B cells;antigen responsiveGerminal center&post GC cells;antigen encounteredTdTCD20,CD22CD19,PAX5CD79aCD10Bcl-6CD138Cytoplasmic CD22Pre pre B cellPre B cellImmatu1111Immunoarchitecture of normal lymph nodeB cells(CD20+,CD10+,BCL-6+)T cells(CD3+);only small numbers of CD20+cellsImmunoarchitecture of normal l1212淋巴组织肿瘤-课件1313 1、初级滤泡：、初级滤泡：处女型处女型B细胞和成熟小淋巴细胞；细胞和成熟小淋巴细胞；淋巴组织肿瘤-课件1414CD202、次级滤泡：、次级滤泡：由生发中心、套区和边缘区构成。由生发中心、套区和边缘区构成。CD202、次级滤泡：由生发中心、套区和边缘区构成。1515Organization 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):约约2:1，当，当:8-10:1或或:3:1提示轻链限制表达提示轻链限制表达Organization of secondary lym1616次级滤泡次级滤泡生发中心、套区和边缘区免疫标记：生发中心、套区和边缘区免疫标记：（1）生发中心生发中心(Germinal Center,GC)：1）中心细胞和中心母细胞：中心细胞和中心母细胞：CD10+,BCL-6+,Bcl-2-,2）滤泡树突细胞滤泡树突细胞(Follicular dendritic cells,FDC):CD21+,CD23+,CD35+3）T细胞：细胞：CD4+,CD10+,CXCL13/PD-1+,少量少量CD57+4）可染体巨噬细胞可染体巨噬细胞：CD68+,lysozyme+,CD11c+（2）套区套区:处女型处女型B细胞和记忆细胞细胞和记忆细胞,表达表达IgM,IgD（3）边缘区：边缘区：无特殊标记，绝大多数次级滤泡难以鉴别，无特殊标记，绝大多数次级滤泡难以鉴别，腹腔腹腔 淋巴结淋巴结易识别。易识别。次级滤泡生发中心、套区和边缘区免疫标记：1717CD20CD201818CD79aCD79a1919淋巴组织肿瘤-课件2020淋巴组织肿瘤-课件2121淋巴组织肿瘤-课件2222CD21CD212323CD10Bcl-6CD10Bcl-62424l反应性滤泡增生的特点反应性滤泡增生的特点n n对对对对T T细胞依赖性抗原的反应细胞依赖性抗原的反应细胞依赖性抗原的反应细胞依赖性抗原的反应n n滤泡增多，大小、形态不等，可弥漫分布，主滤泡增多，大小、形态不等，可弥漫分布，主滤泡增多，大小、形态不等，可弥漫分布，主滤泡增多，大小、形态不等，可弥漫分布，主要位于皮质区，无要位于皮质区，无要位于皮质区，无要位于皮质区，无背靠背背靠背背靠背背靠背现象。现象。现象。现象。n n典型生发中心具有极性典型生发中心具有极性典型生发中心具有极性典型生发中心具有极性(PolarityPolarity):):明区和暗区，明区和暗区，明区和暗区，明区和暗区，套区明显，扁桃体组织更易识别；套区明显，扁桃体组织更易识别；套区明显，扁桃体组织更易识别；套区明显，扁桃体组织更易识别；n n星天现象，中心细胞和中心母细胞混杂，星天现象，中心细胞和中心母细胞混杂，星天现象，中心细胞和中心母细胞混杂，星天现象，中心细胞和中心母细胞混杂，n n免疫染色：免疫染色：免疫染色：免疫染色：生发中心细胞生发中心细胞生发中心细胞生发中心细胞BCL-2-BCL-2-，ki-67ki-67指数指数指数指数较高。较高。较高。较高。n n滤泡间区一般无滤泡间区一般无滤泡间区一般无滤泡间区一般无B B细胞弥漫阳性，细胞弥漫阳性，细胞弥漫阳性，细胞弥漫阳性，B B细胞细胞细胞细胞CD43CD43和和和和CD5CD5阴性。阴性。阴性。阴性。反应性滤泡增生的特点2525淋巴组织肿瘤-课件2626淋巴组织肿瘤-课件2727Dark zoneLight zoneDark zoneLight zone2828 BCL-2 Ki67 BCL-2 Ki672929Marginal zone cellsMarginal zone cells3030CD20CD203131（三）（三）T淋巴细胞分布：副皮质区淋巴细胞分布：副皮质区(paracortex)(paracortex)lT T淋巴细胞为主淋巴细胞为主(CD4CD8):(CD4CD8):主为小淋巴细胞，主为小淋巴细胞，偶尔出现大细胞偶尔出现大细胞(可以是活化的可以是活化的B B细胞细胞););l含有含有高内皮静脉高内皮静脉(High endothelial venules,High endothelial venules,HEVHEV):):):):血液淋巴细胞入淋巴结的通道血液淋巴细胞入淋巴结的通道;l含有含有指状树突细胞指状树突细胞(interdigitating dendritic interdigitating dendritic cells,cells,IDCIDC):S100+):S100+的专职抗原递呈细胞；的专职抗原递呈细胞；（三）T淋巴细胞分布：副皮质区(paracortex)T淋巴3232淋巴组织肿瘤-课件3333淋巴组织肿瘤-课件3434ProthymocyteSubcapsular thymocyteCortical thymocyteMedullary thymocytePeripheral T cellPrecursor cellsMature T cellsCytoplasmicSurfaceCD4CD8CD1CD4,CD8CD3CD2CD7TdTProthymocyteSubcapsular thymoc3535淋巴组织肿瘤-课件3636IDCIDC3737CD3CD33838副皮质区增生副皮质区增生l常见病因常见病因常见病因常见病因:病毒感染病毒感染病毒感染病毒感染,接种疫苗，药物，自身免接种疫苗，药物，自身免接种疫苗，药物，自身免接种疫苗，药物，自身免疫疾病疫疾病疫疾病疫疾病,皮病性淋巴结炎，肿瘤转移等皮病性淋巴结炎，肿瘤转移等皮病性淋巴结炎，肿瘤转移等皮病性淋巴结炎，肿瘤转移等l形态特征：形态特征：形态特征：形态特征：副皮质扩大，可形成结节；副皮质扩大，可形成结节；副皮质扩大，可形成结节；副皮质扩大，可形成结节；HEV HEV增生；增生；增生；增生；混合小淋巴细胞和转化淋巴细胞，混合小淋巴细胞和转化淋巴细胞，混合小淋巴细胞和转化淋巴细胞，混合小淋巴细胞和转化淋巴细胞，浆细胞，树突细胞，嗜酸性粒细胞等；浆细胞，树突细胞，嗜酸性粒细胞等；浆细胞，树突细胞，嗜酸性粒细胞等；浆细胞，树突细胞，嗜酸性粒细胞等；l免疫染色：主为免疫染色：主为免疫染色：主为免疫染色：主为T T细胞，或细胞，或细胞，或细胞，或T/BT/B细胞混合细胞混合细胞混合细胞混合,一般一般一般一般无无无无B B细胞为主弥漫分布。细胞为主弥漫分布。细胞为主弥漫分布。细胞为主弥漫分布。副皮质区增生常见病因:病毒感染,接种疫苗，药物，自身免疫3939淋巴组织肿瘤-课件4040淋巴组织肿瘤-课件4141ImmunoblastInfectious mononucleosisImmunoblastInfectious mononucl4242CD20CD3 Large cells comprise mixture of B and T cells-Reactive processCD20CD3 Large cells compris4343CD30+cells are scattered and staining is weak or moderate,which indicates the heterogeneity of the large cell population.CD30 staining is diffusely strong positive,which indicates the monoclone entity.CD30+cells are scattered and 4444KappaLambdaLarge B cells are polytypicKappaLambdaLarge B cells are p4545T细胞为主时支持良性的依据（细胞为主时支持良性的依据（谨慎！谨慎！）：）：（1）结构不同程度保留：淋巴窦和皮质淋巴滤泡；结构不同程度保留：淋巴窦和皮质淋巴滤泡；（2 2）大细胞群体分布不规则或呈地图样，不形成膨胀性团块；）大细胞群体分布不规则或呈地图样，不形成膨胀性团块；（3 3）无浸润现象：上皮）无浸润现象：上皮,脂肪脂肪,血管血管,神经神经,纤维间质中单行排列；纤维间质中单行排列；（4 4）细胞无明显异型：）细胞无明显异型：2.5 BlLeukemia(ALL):B TlUntreated:rapidly fatallAggressive therapy:good survivallCannot predict lineage from morphologylDefining marker:TdT+，CD99 淋巴母细胞淋巴瘤Rapidly growing7878淋巴组织肿瘤-课件7979淋巴组织肿瘤-课件8080CD20CD79aB-LBLCD20CD79aB-LBL8181T-LBLT-LBL8282滤泡性淋巴瘤滤泡性淋巴瘤FOLLICULAR LYMPHOMAFOLLICULAR LYMPHOMAl lUsually involving lymph nodesUsually involving lymph nodesl lHigh-stage disease at presentationHigh-stage disease at presentationl lPathology:Recapitulates the organization and Pathology:Recapitulates the organization and cytology of the normal germinal centerscytology of the normal germinal centersl lKey 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,testis)show distinctive clinical and biologic featuresshow distinctive clinical and biologic featuresl lGeneticsGenetics: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)translocation)滤泡性淋巴瘤FOLLICULAR LYMPHOMAUsua8383Follicular lymphoma vsreactive follicular hyperplasiaMajor criterionlClosely packed follicles throughout,with scanty interfollicular tissuesFollicular lymphoma vsreactiv8484滤泡性淋巴瘤主要诊断标准示意图滤泡性淋巴瘤主要诊断标准示意图 Major criterion fulfilled in 80%of cases of follicular lymphomaJust go on to high magnification to confirm follicle center cell morphology滤泡性淋巴瘤主要诊断标准示意图 Major criterio8585淋巴组织肿瘤-课件8686淋巴组织肿瘤-课件8787Centrocytes oftenhave triangularshaped nucleiCentrocytes often8888滤泡性淋巴瘤的次要诊断标准滤泡性淋巴瘤的次要诊断标准lIn the remaining 20%of cases(non-crowded follicles),a combination of minor criteria(3)have to be considered,and supplemented by ancillary studies as required滤泡性淋巴瘤的次要诊断标准In the remaining 8989Minor criteria l lNo tingible-body macrophagesNo tingible-body macrophagesl lCellular monotony:centrocyte predominanceCellular monotony:centrocyte predominancel lNo cellular polarisationNo cellular polarisationl lAbsent or incomplete mantlesAbsent or incomplete mantlesl lFollicles in perinodal tissuesFollicles in perinodal tissuesl lDysplastic follicular center cells,e.g.signet ring Dysplastic follicular center cells,e.g.signet ring cells,frequent cytoplasmic globulescells,frequent cytoplasmic globulesl lAtypical cells in interfollicular tissuesAtypical cells in interfollicular tissuesl lInvasion of walls of blood vesselsInvasion of walls of blood vesselsMinor criteria 9090淋巴组织肿瘤-课件9191淋巴组织肿瘤-课件9292淋巴组织肿瘤-课件9393淋巴组织肿瘤-课件9494Follicular lymphoma vs RFH:ancillary techniqueslImmunostaining for bcl-2n nMost useful immunostainMost useful immunostainn nNormal:Both T and 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 of lymphomalymphomaFollicular lymphoma vs RFH:an9595Reactive folliclesReactive follicles9696Follicular lymphoma(Bcl-2 immunostaining)Follicular lymphoma(Bcl-2 imm9797Common misconceptions in hematopathologyNegative bcl-2 stain rules out follicular lymphomaThe truth:It does not.20-25%offollicular lymphoma cases are negative.Pursue with other tests to confirmor refute a diagnosis offollicular lymphomaCommon misconceptions in hemat9898Bcl-2 staining infollicular lymphomaBcl-2 staining infollicular l9999淋巴组织肿瘤-课件100100Bcl-2Bcl-2101101lLook for evidence interfollicular invasionn nDensely packed CD20+or CD79+B-cells Densely packed CD20+or CD79+B-cells between follicles is indicative 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 also indicates CD10+)between follicles also indicates interfollicular invasion interfollicular invasion lLook for vascular invasion n nMany CD10+cells in the walls of perinodal Many CD10+cells in the walls of perinodal blood vesselsblood vesselsLook for evidence interfollicu102102CD20CD20103103CD10CD10104104淋巴组织肿瘤-课件105105lLook 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 lymphoma 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 inconclusiveinconclusivelMolecular analysisn nIg gene rearrangement by Southern blot or PCR Ig gene rearrangement by Southern blot or PCR(Note that PCR may 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 FISHLook for monoclonality or low 106106KappaLambdaKappaLambda107107FL1:Ki67RFH:Ki67FL1:Ki67RFH:Ki67108108FL3:Ki67FL3:Ki67109109套细胞淋巴瘤套细胞淋巴瘤Mantle cell lymphoma:morphologyMantle cell lymphoma:morphologylDiffuseDiffuse,vaguely nodularvaguely nodular,or,or mantle zone mantle zone patternpatternlBroad cytologic spectrumBroad cytologic spectrumn nClassic typeClassic type:small lymphoid cells with irregular to:small lymphoid cells with irregular to round nucleiround nuclein nBlastoid variantBlastoid variant(lymphoblasts,but TdT-)(lymphoblasts,but TdT-)n nPleomorphic variantPleomorphic variantlOften with solitary epithelioid histiocytesOften with solitary epithelioid histiocyteslInterspersed naked nuclei(follicular dendritic Interspersed naked nuclei(follicular dendritic cells)cells)lGenetics:Ig gene rearrangementGenetics:Ig gene rearrangement t(11,14)(q13;q32)t(11,14)(q13;q32)套细胞淋巴瘤Mantle cell lymphoma:m110110 Growth pattern of MCL Growth pattern of MCL111111淋巴组织肿瘤-课件112112淋巴组织肿瘤-课件113113淋巴组织肿瘤-课件114114Round nucleiRound nuclei115115Mantle cell lymphoma:biologic markerslB marker+,CD5+,CD10-,CD23-,IgM+,IgD+lKey defining feature:Cyclin D1+due to t(11;14)(q13;q32)or cryptic translocationMantle cell lymphoma:biologi116116Cyclin D1Cyclin D1117117 粘膜相关淋巴组织粘膜相关淋巴组织 Mucosa-Associated Lymphoid Tissue(MALT)Mucosa-Associated Lymphoid Tissue(MALT)lSpecialized 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,salivary gland,lacrimal gland,stomachstomachlSimilar organization as lymph node:B-cell follicles,T-cell zoneslLymphoid cells acquire homing properties 粘膜相关淋巴组织 118118淋巴组织肿瘤-课件119119LOW GRADE B CELL LOW GRADE B CELL MALTMALT LYMPHOMA LYMPHOMA(extranodal marginal zone B-cell lymphoma)(extranodal marginal zone B-cell lymphoma)lUsually localized at presentation(66-79%)lRecurrence at other MALT sites(“homing”)lMany can be treated by locoregional therapy or eradication of antigen-stimulation sourcelComplete remission rate=72%l5-year overall survival=74%(Gastric:90%)LOW GRADE B CELL MALT LYMPHOMA120120Histologic features of low grade Histologic features of low grade MALT lymphomaMALT lymphomalSmall/medium-sized cells(lymphocytes,centrocyte-like,monocytoid B cells)lPatterns:diffuse,interfollicular,marginal zonelLymphoepithelial lesionslPlasma cells are commonlReactive lymphoid follicles+/-colonizationHistologic features of low gra121121淋巴组织肿瘤-课件122122淋巴组织肿瘤-课件123123淋巴组织肿瘤-课件124124Low grade MALT lymphoma:Low grade MALT lymphoma:ImmunophenotypeImmunophenotypelA neoplasm of post-germinal center B cellslPan B+,CD10-,CD5-,Cyclin D1-,CD23-lKey features:n nsite of involvementsite of involvementn nlymphoepithelial lesionlymphoepithelial lesionn nexclusion of other low grade B-cell exclusion of other low grade B-cell lymphomaslymphomasLow grade MALT lymphoma:Immun125125After Helicobacter eradication therapyAfter Helicobacter eradication126126弥漫性大弥漫性大B B细胞淋巴瘤细胞淋巴瘤DIFFUSE LARGE B CELL DIFFUSE LARGE B CELL LYMPHOMALYMPHOMA（DLBCLDLBCL）lCommonest nodal B-cell lymphomalA heterogeneous entitylFinal common pathway for high grade transformation of low grade B-cell lymphomas弥漫性大B细胞淋巴瘤DIFFUSE LARGE B CEL127127Centroblastic/ImmunoblasticCentroblastic/Immunoblastic128128淋巴组织肿瘤-课件129129MultilobatedPleomorphicMultilobatedPleomorphic130130BURKITT LYMPHOMAlThree different forms:Three different forms:n nEndemicEndemic(Equatorial Africa;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 terminal 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)lAfrican cases can also be AIDS-related!African cases can also be AIDS-related!BURKITT LYMPHOMAThree differen131131Burkitt lymphomalt(8;14)(q24;q32)or variants,with translocation between c-myc and Ig genelMostly a disease of young patientslHighly aggressive,but potentially curable by chemotherapyBurkitt lymphomat(8;14)(q24;q132132淋巴组织肿瘤-课件133133淋巴组织肿瘤-课件134134Burkitt lymphoma:ImmunogeneticslProbably corresponds to IgM+blasts in germinal centerlPan-B+,CD10+,Bcl-6+,Bcl-2-lKey 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 phenotypeBurkitt lymphoma:Immunogeneti135135CD20CD10CD20CD10136136Ki67Ki67137137外周外周T T和和NKNK细胞淋巴瘤细胞淋巴瘤PERIPHERAL T AND NK CELL LYMPHOMASlUncommon;80%)(80%)Extranodal NK/T cell lymphomaN149149Extranodal NK/T cell lymphoma:PathologylNecrosis(apoptosis)common lAngioinvasion common(not invariably seen)lBroad cytologic spectrum:small,medium-sized or large cells,or mixedlMay have many admixed inflammatory cellsExtranodal NK/T cell lymphoma:150150淋巴组织肿瘤-课件151151淋巴组织肿瘤-课件152152SmallMedium-sizedLargeBroad cytologic spectrumSmallMedium-sizedLargeBroad cy153153Extranodal NK/T cell lymphoma:immunophenotypelCD2+.sCD3-,cCD3e+,CD56+lCytotoxic granules perforin,granzyme B,TIA-1 positivelCD4,CD5,CD7,CD8:usually negativelKey features:CD56+,EBER+lIf CD56-,requires EBER+and cytotoxic granules+for diagnosisExtranodal NK/T cell lymphoma:154154Surface CD3Cytoplasmic CD3CD56Frozen tissueParaffin sectionSurface CD3Cytoplasmic CD3CD5155155PERIPHERAL T CELL LYMPHOMA UNSPECIFIED外周外周T T细胞淋巴瘤，非特殊型细胞淋巴瘤，非特殊型lA wastebasket categorylVariable clinical manifestationslUsually high stage disease(nodal/extranodal)lMay have eosinophilialAggressive;relapse commonlThe extranodal cases often express a cytotoxic cell phenotypePERIPHERAL T CELL LYMPHOMA UNS156156Peripheral T-cell lymphoma:Morphologic clues for recognitionlPredominant paracortical involvementlProminent high endothelial venuleslSpectrum of cells sizes and shapeslIrregular nuclear contourslClear cellslMany admixed epithelioid histiocytes and eosinophilsBut immunostaining essential for confirming T lineagePeripheral T-cell lymphoma:Mo157157淋巴组织肿瘤-课件158158淋巴组织肿瘤-课件159159ANAPLASTIC LARGE CELL LYMPHOMA,primary systemic form间变性大细胞淋巴瘤，原发系统性间变性大细胞淋巴瘤，原发系统性lTends to occur in children and young Tends to occur in children and young adultsadultslNodal 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)lImmunophenotype:Immunophenotype:n nCD30+;CD30+;EMA usually+EMA usually+n 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 geneANAPLASTIC LARGE CELL LYMPHOMA160160Hallmark cellsHallmark cells161161lALK translocation(or expression)has helped to define a homogeneous subgroup of ALCLlThis can be easily detected by immunostaining for ALK-permitting re-definition of the morphologic spectrum of ALCL:n nClassical typeClassical typen nMonomorphicMonomorphicn nSmall cellSmall celln nLymphohistiocyticLymphohistiocyticn nHypocellularHypocellularALK translocation(or expressi162162淋巴组织肿瘤-课件163163CD30CD30164164 Overall survivalPrimary systemic form of ALCL0510YearsALCL,ALK+*100%50%ALCL,ALK-Overall survivalPrimary syst165165 霍奇金淋巴瘤霍奇金淋巴瘤 HODGKIN LYMPHOMAHODGKIN LYMPHOMA 霍奇金淋巴瘤 HODGKIN LY166166Lymphocyte predominanceMixed cellularityNodular sclerosisLymphocyte depletionNodular lymphocyte predominant Hodgkin lymphoma(N-LPHL)Classical Hodgkin lymphoma(cHL)Lymphocyte-richMixed cellularityNodular sclerosisLymphocyte depletionRYE CLASSIFICATIONWHO CLASSIFICATIONLymphocyte predominanceMixed c167167510YearsOverall survivalN-LPHL defined by immunohistochemistrycHL defined by immunohistochemistryp=0.0071510YearsOverall survivalN-LPHL168168lA lymphoma characterized by:n npresence of presence of Reed-Sternberg cellsReed-Sternberg cells and their and their variantsvariants confirmed by confirmed by mmunohistochemistrymmunohistochemistryn nin an appropriate in an appropriate reactive cellular reactive cellular environment environment A lymphoma characterized by:169169Reed-Sternberg cells and variantslDiagnostic Reed-Sternberg cellslMononuclear Hodgkin celllLacunar celllL&H celllPleomorphic Reed-Sternberg celllKi67+100%No need to find diagnostic Reed-Sternberg cellsin rendering a diagnosis of Hodgkin lymphoma.Its okay if cells are large enough,with prominentnucleoli and compatible immunophenotype.Reed-Sternberg cells and varia170170Reed-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.Reed-Sternberg cells and varia171171Diagnostic Reed-Sternberg cellDiagnostic Reed-Sternberg cellDiagnostic Reed-Sternberg cell172172Appropriate cellular environmentlDepending on the specific subtype of Hodgkin lymphoma,presence or absence of the following:n nSmall lymphocytesSmall lymphocytesn nHistiocytesHistiocytesn nPlasma cellsPlasma cellsn nEosinophils and neutrophilsEosinophils and neutrophilsn nFibroblastsFibroblastsAppropriate cellular environme173173Classical Hodgkin lymphoma经典型霍奇金淋巴瘤经典型霍奇金淋巴瘤lLa