淋巴组织肿瘤[行业经验]

淋巴瘤淋巴瘤 Lymphoma 基础医学院病理学系基础医学院病理学系同济医院病理研究所同济医院病理研究所 敖启林敖启林1 1沐风书苑沐风书苑i iDr John K.C.CHAN陈国璋陈国璋2 2沐风书苑沐风书苑i i4th EditionPublished 20/9/20083 3沐风书苑沐风书苑i i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%）4 4沐风书苑沐风书苑i i(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5 5沐风书苑沐风书苑i i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。6 6沐风书苑沐风书苑i i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7 7沐风书苑沐风书苑i i（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。8 8沐风书苑沐风书苑i i9 9沐风书苑沐风书苑i i1010沐风书苑沐风书苑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;antigen encounteredTdTCD20,CD22CD19,PAX5CD79aCD10Bcl-6CD138Cytoplasmic CD221111沐风书苑沐风书苑i iImmunoarchitecture of normal lymph nodeB cells(CD20+,CD10+,BCL-6+)T cells(CD3+);only small numbers of CD20+cells1212沐风书苑沐风书苑i i1313沐风书苑沐风书苑i i 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；1414沐风书苑沐风书苑i iCD202、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。1515沐风书苑沐风书苑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):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1616沐风书苑沐风书苑i i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。1717沐风书苑沐风书苑i iCD201818沐风书苑沐风书苑i iCD79a1919沐风书苑沐风书苑i i2020沐风书苑沐风书苑i i2121沐风书苑沐风书苑i i2222沐风书苑沐风书苑i iCD212323沐风书苑沐风书苑i iCD10Bcl-62424沐风书苑沐风书苑i i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。2525沐风书苑沐风书苑i i2626沐风书苑沐风书苑i i2727沐风书苑沐风书苑i iDark zoneLight zone2828沐风书苑沐风书苑i i BCL-2 Ki672929沐风书苑沐风书苑i iMarginal zone cells3030沐风书苑沐风书苑i iCD203131沐风书苑沐风书苑i i（三）（三）T淋巴细胞分布：副皮质区淋巴细胞分布：副皮质区(paracortex)T 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););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;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；3232沐风书苑沐风书苑i i3333沐风书苑沐风书苑i i3434沐风书苑沐风书苑i iProthymocyteSubcapsular thymocyteCortical thymocyteMedullary thymocytePeripheral T cellPrecursor cellsMature T cellsCytoplasmicSurfaceCD4CD8CD1CD4,CD8CD3CD2CD7TdT3535沐风书苑沐风书苑i i3636沐风书苑沐风书苑i iIDC3737沐风书苑沐风书苑i iCD33838沐风书苑沐风书苑i i副皮质区增生副皮质区增生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；HEVHEV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；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。3939沐风书苑沐风书苑i i4040沐风书苑沐风书苑i i4141沐风书苑沐风书苑i iImmunoblastInfectious mononucleosis4242沐风书苑沐风书苑i iCD20CD3 Large cells comprise mixture of B and T cells-Reactive process4343沐风书苑沐风书苑i iCD30+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.4444沐风书苑沐风书苑i iKappaLambdaLarge B cells are polytypic4545沐风书苑沐风书苑i iT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 BLeukemia(ALL):B TUntreated:rapidly fatalAggressive therapy:good survivalCannot predict lineage from morphologyDefining marker:TdT+，CD997878沐风书苑沐风书苑i i7979沐风书苑沐风书苑i i8080沐风书苑沐风书苑i iCD20CD79aB-LBL8181沐风书苑沐风书苑i iT-LBL8282沐风书苑沐风书苑i i滤泡性淋巴瘤滤泡性淋巴瘤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 germinal 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,testis)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)translocation)8383沐风书苑沐风书苑i iFollicular lymphoma vsreactive follicular hyperplasiaMajor criterionClosely packed follicles throughout,with scanty interfollicular tissues8484沐风书苑沐风书苑i i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 morphology8585沐风书苑沐风书苑i i8686沐风书苑沐风书苑i i8787沐风书苑沐风书苑i iCentrocytes oftenhave triangularshaped nuclei8888沐风书苑沐风书苑i i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In the remaining 20%of cases(non-crowded follicles),a combination of minor criteria(3)have to be considered,and supplemented by ancillary studies as required8989沐风书苑沐风书苑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 mantlesFollicles 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 interfollicular tissuesInvasion of walls of blood vesselsInvasion of walls of blood vessels9090沐风书苑沐风书苑i i9191沐风书苑沐风书苑i i9292沐风书苑沐风书苑i i9393沐风书苑沐风书苑i i9494沐风书苑沐风书苑i iFollicular lymphoma vs RFH:ancillary techniquesImmunostaining 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 lymphomalymphoma9595沐风书苑沐风书苑i iReactive follicles9696沐风书苑沐风书苑i iFollicular lymphoma(Bcl-2 immunostaining)9797沐风书苑沐风书苑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 tests to confirmor refute a diagnosis offollicular lymphoma9898沐风书苑沐风书苑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 cells)II(mixed small and large cells)85%85%III(predominantly large cells)III(predominantly large cells)75%75%9999沐风书苑沐风书苑i i100100沐风书苑沐风书苑i iBcl-2101101沐风书苑沐风书苑i iLook 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 Look for vascular invasion n nMany CD10+cells in the walls of perinodal Many CD10+cells in the walls of perinodal blood vesselsblood vessels102102沐风书苑沐风书苑i iCD20103103沐风书苑沐风书苑i iCD10104104沐风书苑沐风书苑i i105105沐风书苑沐风书苑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 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 inconclusiveinconclusiveMolecular 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 FISH106106沐风书苑沐风书苑i iKappaLambda107107沐风书苑沐风书苑i iFL1:Ki67RFH:Ki67108108沐风书苑沐风书苑i iFL3:Ki67109109沐风书苑沐风书苑i i套细胞淋巴瘤套细胞淋巴瘤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 lymphoid 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 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沐风书苑沐风书苑i i Growth pattern of MCL111111沐风书苑沐风书苑i i112112沐风书苑沐风书苑i i113113沐风书苑沐风书苑i i114114沐风书苑沐风书苑i iRound nuclei115115沐风书苑沐风书苑i iMantle 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沐风书苑沐风书苑i iCyclin D1117117沐风书苑沐风书苑i i 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)Specialized 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,stomachstomachSimilar organization as lymph node:B-cell follicles,T-cell zonesLymphoid cells acquire homing properties118118沐风书苑沐风书苑i i119119沐风书苑沐风书苑i iLOW GRADE B CELL LOW GRADE B CELL MALTMALT LYMPHOMA LYMPHOMA(extranodal marginal zone B-cell lymphoma)(extranodal marginal 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沐风书苑沐风书苑i iHistologic features of 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沐风书苑沐风书苑i i122122沐风书苑沐风书苑i i123123沐风书苑沐风书苑i i124124沐风书苑沐风书苑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 lesionn nexclusion of other low grade B-cell exclusion of other low grade B-cell lymphomaslymphomas125125沐风书苑沐风书苑i iAfter Helicobacter eradication therapy126126沐风书苑沐风书苑i i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）Commonest nodal B-cell lymphomaA heterogeneous entityFinal common pathway for high grade transformation of low grade B-cell lymphomas127127沐风书苑沐风书苑i iCentroblastic/Immunoblastic128128沐风书苑沐风书苑i i129129沐风书苑沐风书苑i iMultilobatedPleomorphic130130沐风书苑沐风书苑i iBURKITT LYMPHOMAThree 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)African cases can also be AIDS-related!African cases can also be AIDS-related!131131沐风书苑沐风书苑i iBurkitt 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沐风书苑沐风书苑i i133133沐风书苑沐风书苑i i134134沐风书苑沐风书苑i iBurkitt lymphoma:ImmunogeneticsProbably corresponds to IgM+blasts in germinal 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沐风书苑沐风书苑i iCD20CD10136136沐风书苑沐风书苑i iKi67137137沐风书苑沐风书苑i i外周外周T T和和NKNK细胞淋巴瘤细胞淋巴瘤PERIPHERAL T AND NK CELL LYMPHOMASUncommon;80%)(80%)149149沐风书苑沐风书苑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 cells150150沐风书苑沐风书苑i i151151沐风书苑沐风书苑i i152152沐风书苑沐风书苑i iSmallMedium-sizedLargeBroad cytologic spectrum153153沐风书苑沐风书苑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 CD56-,requires EBER+and cytotoxic granules+for diagnosis154154沐风书苑沐风书苑i iSurface CD3Cytoplasmic CD3CD56Frozen tissueParaffin section155155沐风书苑沐风书苑i iPERIPHERAL 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A wastebasket categoryVariable clinical manifestationsUsually high stage disease(nodal/extranodal)May have eosinophiliaAggressive;relapse commonThe extranodal cases often express a cytotoxic cell phenotype156156沐风书苑沐风书苑i iPeripheral T-cell lymphoma:Morphologic clues for recognitionPredominant paracortical involvementProminent high endothelial venulesSpectrum of cells sizes and shapesIrregular nuclear contoursClear cellsMany admixed epithelioid histiocytes and eosinophilsBut immunostaining essential for confirming T lineage157157沐风书苑沐风书苑i i158158沐风书苑沐风书苑i i159159沐风书苑沐风书苑i iANAPLASTIC 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Tends to occur in children 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 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沐风书苑沐风书苑i iHallmark cells161161沐风书苑沐风书苑i iALK translocation(or expression)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 cellnLymphohistiocyticLymphohistiocyticnHypocellularHypocellular162162沐风书苑沐风书苑i i163163沐风书苑沐风书苑i iCD30164164沐风书苑沐风书苑i i Overall survivalPrimary systemic form of ALCL0510YearsALCL,ALK+*100%50%ALCL,ALK-165165沐风书苑沐风书苑i i 霍奇金淋巴瘤霍奇金淋巴瘤 HODGKIN LYMPHOMAHODGKIN LYMPHOMA166166沐风书苑沐风书苑i iLymphocyte predominanceMixed cellularityNodular sclerosisLymphocyte depletionNodular lymphocyte predominant Hodgkin lymphoma(N-LPHL)Classical Hodgkin lymphoma(cHL)Lymphocyte-richMixed cellularityNodular sclerosisLymphocyte depletionRYE CLASSIFICATIONWHO CLASSIFICATION167167沐风书苑沐风书苑i i510YearsOverall survivalN-LPHL defined by immunohistochemistrycHL defined by immunohistochemistryp=0.0071168168沐风书苑沐风书苑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 169169沐风书苑沐风书苑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 prominentnucleoli and compatible immunophenotype.170170沐风书苑沐风书苑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沐风书苑沐风书苑i iDiagnostic Reed-Sternberg cellDiagnostic Reed-Sternberg cell172172沐风书苑沐风书苑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 and neutrophilsEosinophils and neutrophilsn nFibroblastsFibroblasts173173沐风书苑沐风书苑i iClassical Hodgkin lymphoma经典型霍奇金淋巴瘤经典型霍奇金淋巴瘤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 mixture of lymphocytes,plasma cells,histiocytes and eosinophils,except lymphocyte-rich classical Hodgkin lymphoma174174沐风书苑沐风书苑i i175175沐风书苑沐风书苑i iR-S cells variants176176沐风书苑沐风书苑i ilacunar cellslacunar cells177177沐风书苑沐风书苑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