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1、 淋巴瘤淋巴瘤 Lymphoma 1 1Dr John K.C.CHAN陈国璋陈国璋2 24th EditionPublished 20/9/20083 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）的恶性肿瘤，分为非霍奇金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/ /白血病和霍白血病和霍奇金淋巴瘤两大类。奇金淋巴瘤两大类。二、分类二、分类（一）非霍奇金淋巴瘤（一）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
2、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：成熟细胞淋巴瘤（、成熟细胞：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(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
3、减型淋巴细胞消减型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：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一、概念：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（淋巴细胞成分（淋巴细胞,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）、数量、分布方式等特征。网状纤维等）、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。高质量的组织通过对比，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。高质量的组织学切片和合理的免
4、疫标记物的选择是识别免疫结构的关键。学切片和合理的免疫标记物的选择是识别免疫结构的关键。6 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7 7（二）（二）B淋巴细胞分布：淋巴细胞分布： 1.1.主要在浅皮质区的初级和次级滤泡，髓索和副主要在浅皮质区的初级和次级滤泡，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 89 91010Pre pre B c
5、ellPre 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 CD221111Immunoarchitecture of normal lymph nodeImmuno
6、architecture of normal lymph nodeB cells (CD20+,CD10+,BCL-6+)T cells (CD3+); only small numbers of CD20+ cells12121313 1、初级滤泡：处女型、初级滤泡：处女型B细胞和成熟小淋巴细胞；细胞和成熟小淋巴细胞； 1414CD202、次级滤泡：由生发中心、套区和边缘区构成。、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 folli
7、cle 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次级滤泡生发中心、套区和边缘区免疫标记：次级滤泡生发中心、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 de
8、ndritic 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：无特殊标记，绝大多数次级滤泡难以鉴别，腹腔）边缘区：无特殊标记，绝大多数次级滤泡难以鉴别，腹腔 淋巴结易识别。淋巴结易识别。1717CD201818CD79a1919202021212222CD212323CD10Bcl-62424反应性滤泡增
9、生的特点反应性滤泡增生的特点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，主要位于皮质区，无滤泡增多，大小、形态不等，可弥漫分布，主要位于皮质区，无滤泡增多，大小、形态不等，可弥漫分布，主要位于皮质区，无滤泡增多，大小、形态不等，可弥漫分布，主要位于皮质区，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(Polarity):(Polarity):明区和暗区，套区明显，扁
10、桃体组织更易识别；明区和暗区，套区明显，扁桃体组织更易识别；明区和暗区，套区明显，扁桃体组织更易识别；明区和暗区，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：生发中心细胞免疫染色：生发中心细胞免疫染色：生发中心细胞免疫染色：生发中心细胞BCL-2-BCL-2-，ki-67ki-67指数较高。指数较高。指数较高。指数较高。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
11、 B细胞细胞细胞细胞CD43CD43和和和和CD5CD5阴性。阴性。阴性。阴性。252526262727Dark zoneLight zone2828 BCL-2 Ki672929Marginal zone cells3030CD203131（三）（三）（三）（三）T T淋巴细胞分布：副皮质区淋巴细胞分布：副皮质区淋巴细胞分布：副皮质区淋巴细胞分布：副皮质区(paracortex)(paracortex)T T T T淋巴细胞为主淋巴细胞为主淋巴细胞为主淋巴细胞为主 (CD4CD8): (CD4CD8): (CD4CD8): (CD4CD8): 主为小淋巴细胞，偶尔出现大细胞主为小淋巴细胞，偶
12、尔出现大细胞主为小淋巴细胞，偶尔出现大细胞主为小淋巴细胞，偶尔出现大细胞 ( ( ( (可以是活化的可以是活化的可以是活化的可以是活化的B B B B细胞细胞细胞细胞););););含有高内皮静脉含有高内皮静脉含有高内皮静脉含有高内皮静脉 ( ( ( (High endothelial venules,HEVHigh endothelial venules,HEV):):):): 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; ; ; ;含有指状树突细胞含有指状树突细胞含有指状树突细胞含有指状树突细胞( ( ( (interdigit
13、ating dendritic cells,IDCinterdigitating dendritic cells,IDC): S100+ ): S100+ ): S100+ ): S100+ 的专职抗原递呈细胞；的专职抗原递呈细胞；的专职抗原递呈细胞；的专职抗原递呈细胞；323233333434ProthymocyteSubcapsular thymocyteCortical thymocyteMedullary thymocytePeripheral T cellPrecursor cellsMature T cellsCytoplasmicSurfaceCD4CD8CD1CD4, CD8C
14、D3CD2CD7TdT35353636IDC3737CD33838副皮质区增生副皮质区增生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，自身免疫疾病接种疫苗，药物，自身免疫疾病接种疫苗，药物，自身免疫疾病接种疫苗，药物，自身免疫疾病, , 皮病性淋巴结炎，肿瘤转皮病性淋巴结炎，肿瘤转皮病性淋巴结炎，肿瘤转皮病性淋巴结炎，肿瘤转移等移等移等移等形态特征：副皮质扩大，可形成结节；形态特征：副皮质扩大，可形成结节；形态特征：副皮质扩大，可形成结节；形态特征：副皮质扩大，可形成结节； HEVHEV增生；增生；增生；增生； 混合小
15、淋巴细胞和转化淋巴细胞，浆细胞，树突细胞，嗜酸性粒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；等；等；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, ,一般无一般无一般无一般无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。393940404141ImmunoblastInfectious mononucleosis4242C
16、D20CD3 Large cells comprise mixture of B and T cells-Reactive process4343CD30+ 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. 4444KappaLambdaLarge B
17、 cells are polytypic4545T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 BLymphoma: T BLeukemia (ALL): B TLeukemia (ALL):
18、 B TUntreated: rapidly fatalUntreated: rapidly fatalAggressive therapy: good survivalAggressive therapy: good survivalCannot predict lineage from morphologyCannot predict lineage from morphologyDefining marker: TdT+Defining marker: TdT+，CD99CD99787879798080CD20CD79aB-LBL8181T-LBL8282滤泡性淋巴瘤滤泡性淋巴瘤滤泡性淋
19、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 cytology of the normal Pathology: Recapitulates the organization and cytology of t
20、he normal germinal centersgerminal centersKey immunophenotype: B marker+, CD10+, Bcl6+, Bcl2+ Follicular Key immunophenotype: B marker+, CD10+, Bcl6+, Bcl2+ Follicular lymphoma involving some extranodal sites (such as skin, duodenum, lymphoma involving some extranodal sites (such as skin, duodenum,
21、testis) show distinctive clinical and biologic featurestestis) show distinctive clinical and biologic featuresGenetics:Ig gene rearrangement;Genetics:Ig gene rearrangement; t(14;18)(q32;q21) t(14;18)(q32;q21) bcl-2 gene rearrangement bcl-2 gene rearrangement (due to (due to BCL2/IGHBCL2/IGH transloc
22、ation) translocation)8383Follicular lymphoma vsFollicular lymphoma vsreactive follicular hyperplasiareactive follicular hyperplasiaMajor criterionMajor criterionClosely packed follicles throughout, with scanty interfollicular tissuesClosely packed follicles throughout, with scanty interfollicular ti
23、ssues8484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 morphology858586868787Centrocytes oftenhave triangularshaped nuclei8888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滤泡性淋
24、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 In the remaining 20% of cases (non-crowded follicles), a combination of minor criteria (criteria ( 3 3) have to be considered, and supplemented by ancillary studies as ) have to be considered, and sup
25、plemented by ancillary studies as requiredrequired8989Minor criteriaMinor criteria No tingible-body macrophagesNo tingible-body macrophagesCellular monotony: centrocyte predominanceCellular monotony: centrocyte predominanceNo cellular polarisationNo cellular polarisationAbsent or incomplete mantlesA
26、bsent or incomplete mantlesFollicles in perinodal tissuesFollicles in perinodal tissuesDysplastic follicular center cells, e.g. signet ring cells, frequent cytoplasmic Dysplastic follicular center cells, e.g. signet ring cells, frequent cytoplasmic globulesglobulesAtypical cells in interfollicular t
27、issuesAtypical cells in interfollicular tissuesInvasion of walls of blood vesselsInvasion of walls of blood vessels90909191929293939494Follicular lymphoma vs RFH: ancillary techniquesFollicular lymphoma vs RFH: ancillary techniquesImmunostaining for Immunostaining for bcl-2bcl-2n nMost useful immuno
28、stainMost useful immunostainn nNormal: Both T and B cells positive except follicle center cellsNormal: Both T and B cells positive except follicle center cellsn nLook for positive staining of cells in follicle centers: positive staining supports Look for positive staining of cells in follicle center
29、s: positive staining supports diagnosis of lymphomadiagnosis of lymphoma9595Reactive follicles9696Follicular lymphoma (Bcl-2 immunostaining) 9797Common misconceptions in hematopathologyCommon misconceptions in hematopathologyNegative bcl-2 stain rules out follicular lymphomaThe truth: It does not. 2
30、0-25% offollicular lymphoma cases are negative.Pursue with other tests to confirmor refute a diagnosis offollicular lymphoma9898Bcl-2 staining inBcl-2 staining infollicular lymphomafollicular lymphomaGradeGrade(Cytologic composition)(Cytologic composition)Bcl-2 immunoreactivityBcl-2 immunoreactivity
31、I (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%9999100100Bcl-2101101Look for evidence interfollicular invasionLook for evidence interfollicular
32、 invasionn nDensely packed CD20+ or CD79+ B-cells between follicles is indicative of Densely packed CD20+ or CD79+ B-cells between follicles is indicative of interfollicular invasioninterfollicular invasionn nPresence of a significant number of CD10+ lymphoid cells (not neutrophils, which Presence o
33、f a significant number of CD10+ lymphoid cells (not neutrophils, which are also CD10+) between follicles also indicates interfollicular invasion are also CD10+) between follicles also indicates interfollicular invasion Look for vascular invasionLook for vascular invasion n nMany CD10+ cells in the w
34、alls of perinodal blood vesselsMany CD10+ cells in the walls of perinodal blood vessels102102CD20103103CD10104104105105Look for monoclonality or low proliferation indexLook for monoclonality or low proliferation indexn nImmunostain for Ig to look for light chain restrictionImmunostain for Ig to look
35、 for light chain restrictionn nDemonstrated by Ki67, a low Ki67 index favors diagnosis of follicular lymphoma over Demonstrated by Ki67, a low Ki67 index favors diagnosis of follicular lymphoma over RFH (mean index 15.6% vs 64.9%); a high Ki67 index is inconclusiveRFH (mean index 15.6% vs 64.9%); a
36、high Ki67 index is inconclusiveMolecular analysisMolecular analysisn nIg gene rearrangement by Southern blot or PCR (Note that PCR may have false Ig gene rearrangement by Southern blot or PCR (Note that PCR may have false negative results)negative results)n nDetection of Detection of BCL2BCL2 gene r
37、earrangement by Southern blot, PCR or FISH gene rearrangement by Southern blot, PCR or FISH106106KappaLambda107107FL1: Ki67RFH: Ki67108108FL3: Ki67109109套细胞淋巴瘤套细胞淋巴瘤套细胞淋巴瘤套细胞淋巴瘤Mantle cell lymphoma: morphologyMantle cell lymphoma: morphologyDiffuse, vaguely nodular, or mantle zone patternDiffuse, va
38、guely nodular, or mantle zone patternBroad cytologic spectrumBroad cytologic spectrumn nClassic type: small lymphoid cells with irregular to round nucleiClassic type: small lymphoid cells with irregular to round nuclein nBlastoid variant ( lymphoblasts, but TdT-)Blastoid variant ( lymphoblasts, but
39、TdT-)n nPleomorphic variantPleomorphic variantOften with solitary epithelioid histiocytesOften with solitary epithelioid histiocytesInterspersed naked nuclei (follicular dendritic cells)Interspersed naked nuclei (follicular dendritic cells)Genetics: Ig gene rearrangementGenetics: Ig gene rearrangeme
40、nt t(11,14) (q13;q32) t(11,14) (q13;q32) 110110 Growth pattern of MCL111111112112113113114114Round nuclei115115Mantle cell lymphoma: Mantle cell lymphoma: biologic markersbiologic markersB marker+, B marker+, CD5+,CD5+, CD10-, CD23-, IgM+, CD10-, CD23-, IgM+, IgD+IgD+Key defining feature: Key defini
41、ng feature: Cyclin D1+Cyclin D1+ due to t(11;14) (q13;q32) due to t(11;14) (q13;q32) or cryptic translocationor cryptic translocation116116Cyclin D1117117 粘膜相关淋巴组织粘膜相关淋巴组织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 com
42、partments of mucosal tissuesSpecialized secondary lymphoid compartments of mucosal tissuesn nNatural, e.g., Waldeyers ring, small intestine, lungNatural, e.g., Waldeyers ring, small intestine, lungn nAcquired in autoimmune disease/inflammation e.g., thyroid, salivary gland, Acquired in autoimmune di
43、sease/inflammation e.g., thyroid, salivary gland, lacrimal gland, stomachlacrimal gland, stomachSimilar organization as lymph node: B-cell follicles, T-cell zonesSimilar organization as lymph node: B-cell follicles, T-cell zonesLymphoid cells acquire homing propertiesLymphoid cells acquire homing pr
44、operties118118119119LOW GRADE B CELL MALT LYMPHOMA (extranodal marginal zone B-cell LOW GRADE B CELL MALT LYMPHOMA (extranodal marginal zone B-cell lymphoma)lymphoma)Usually localized at presentation (66-79%) Usually localized at presentation (66-79%) Recurrence at other MALT sites (“homing”)Recurre
45、nce at other MALT sites (“homing”)Many can be treated by locoregional therapy or eradication of antigen-stimulation Many can be treated by locoregional therapy or eradication of antigen-stimulation sourcesourceComplete remission rate = 72%Complete remission rate = 72%5-year overall survival = 74% (G
46、astric: 90%)5-year overall survival = 74% (Gastric: 90%)120120Histologic features of low grade Histologic features of low grade MALT lymphomaMALT lymphomaSmall/medium-sized cells (lymphocytes, centrocyte-like, monocytoid B cells)Small/medium-sized cells (lymphocytes, centrocyte-like, monocytoid B ce
47、lls)Patterns: diffuse, interfollicular, marginal zonePatterns: diffuse, interfollicular, marginal zoneLymphoepithelial lesionsLymphoepithelial lesionsPlasma cells are commonPlasma cells are commonReactive lymphoid follicles +/- colonizationReactive lymphoid follicles +/- colonization1211211221221231
48、23124124Low grade MALT lymphoma: ImmunophenotypeLow grade MALT lymphoma: ImmunophenotypeA neoplasm of post-germinal center B cellsA neoplasm of post-germinal center B cellsPan B+, CD10-, CD5-, Cyclin D1-, CD23 -Pan B+, CD10-, CD5-, Cyclin D1-, CD23 -Key features: Key features: n nsite of involvement
49、site of involvementn nlymphoepithelial lesionlymphoepithelial lesionn nexclusion of other low grade B-cell lymphomasexclusion of other low grade B-cell lymphomas125125After Helicobacter eradication therapy126126弥漫性大弥漫性大弥漫性大弥漫性大B B B B细胞淋巴瘤细胞淋巴瘤细胞淋巴瘤细胞淋巴瘤DIFFUSE LARGE B CELL LYMPHOMADIFFUSE LARGE B C
50、ELL LYMPHOMA（DLBCLDLBCL）Commonest nodal B-cell lymphomaCommonest nodal B-cell lymphomaA heterogeneous entityA heterogeneous entityFinal common pathway for high grade transformation of low grade B-cell lymphomasFinal common pathway for high grade transformation of low grade B-cell lymphomas127127Cent
51、roblastic/Immunoblastic128128129129MultilobatedPleomorphic130130BURKITT LYMPHOMABURKITT LYMPHOMAThree different forms:Three different forms:n nEndemic (Equatorial Africa; strong association with EBV 90%; Endemic (Equatorial Africa; strong association with EBV 90%; commonly affecting jaws, gonads, ki
52、dneys)commonly affecting jaws, gonads, kidneys)n nSporadic (EBV association only 15%; commonly involving terminal Sporadic (EBV association only 15%; commonly involving terminal ileum and Waldeyers ring)ileum and Waldeyers ring)n nAIDS-related (EBV association 30%; commonly involving AIDS-related (E
53、BV association 30%; commonly involving lymphonode and bone marrow)lymphonode and bone marrow)African cases can also be AIDS-related!African cases can also be AIDS-related!131131Burkitt lymphomaBurkitt lymphomat(8;14) (q24;q32) or variants, with translocation between t(8;14) (q24;q32) or variants, wi
54、th translocation between c-mycc-myc and and IgIg gene geneMostly a disease of young patientsMostly a disease of young patientsHighly aggressive, but potentially curable by chemotherapyHighly aggressive, but potentially curable by chemotherapy132132133133134134Burkitt lymphoma: ImmunogeneticsBurkitt
55、lymphoma: ImmunogeneticsProbably corresponds to IgM+ blasts in germinal centerProbably corresponds to IgM+ blasts in germinal centerPan-B+, CD10+, Bcl-6+, Bcl-2-Pan-B+, CD10+, Bcl-6+, Bcl-2-Key features:Key features:n nC-MYCC-MYC translocation translocation n nmedium-sized cellsmedium-sized cellsn n
56、high Ki67 indexhigh Ki67 index：100%100%n ngerminal center cell phenotypegerminal center cell phenotype135135CD20CD10136136Ki67137137外周外周外周外周T T T T和和和和NKNKNKNK细胞淋巴瘤细胞淋巴瘤细胞淋巴瘤细胞淋巴瘤PERIPHERAL T AND NK CELL LYMPHOMASPERIPHERAL T AND NK CELL LYMPHOMASUncommon; 10% of all non-Hodgkins lymphomas in Caucas
57、ians, but 15-20% in Uncommon; 80%)within 1-2 years (80%)149149Extranodal NK/T cell lymphoma: PathologyExtranodal NK/T cell lymphoma: PathologyNecrosis (apoptosis) common Necrosis (apoptosis) common Angioinvasion common (not invariably seen)Angioinvasion common (not invariably seen)Broad cytologic sp
58、ectrum: small, medium-sized or large cells, or mixedBroad cytologic spectrum: small, medium-sized or large cells, or mixedMay have many admixed inflammatory cellsMay have many admixed inflammatory cells150150151151152152SmallMedium-sizedLargeBroad cytologic spectrum153153Extranodal NK/T cell lymphom
59、a:Extranodal NK/T cell lymphoma:immunophenotypeimmunophenotypeCD2+. CD2+. sCD3-sCD3-, cCD3, cCD3e e+, CD56+ +, CD56+ Cytotoxic granules perforin, granzyme B, TIA-1 positiveCytotoxic granules perforin, granzyme B, TIA-1 positiveCD4, CD5, CD7, CD8: usually negativeCD4, CD5, CD7, CD8: usually negativeK
60、ey features: CD56+, EBER+Key features: CD56+, EBER+If CD56-, requires EBER+ and cytotoxic granules+ for diagnosisIf CD56-, requires EBER+ and cytotoxic granules+ for diagnosis154154Surface CD3Cytoplasmic CD3CD56Frozen tissueParaffin section155155PERIPHERAL T CELL LYMPHOMA UNSPECIFIEDPERIPHERAL T CEL
61、L LYMPHOMA UNSPECIFIED外周外周外周外周T T T T细胞淋巴瘤，非特殊型细胞淋巴瘤，非特殊型细胞淋巴瘤，非特殊型细胞淋巴瘤，非特殊型A wastebasket categoryA wastebasket categoryVariable clinical manifestationsVariable clinical manifestationsUsually high stage disease (nodal/extranodal)Usually high stage disease (nodal/extranodal)May have eosinophiliaMay
62、have eosinophiliaAggressive; relapse commonAggressive; relapse commonThe extranodal cases often express a cytotoxic cell phenotypeThe extranodal cases often express a cytotoxic cell phenotype156156Peripheral T-cell lymphoma:Peripheral T-cell lymphoma:Morphologic clues for recognitionMorphologic clue
63、s for recognitionPredominant paracortical involvementPredominant paracortical involvementProminent high endothelial venulesProminent high endothelial venulesSpectrum of cells sizes and shapesSpectrum of cells sizes and shapesIrregular nuclear contoursIrregular nuclear contoursClear cellsClear cellsM
64、any admixed epithelioid histiocytes and eosinophilsMany admixed epithelioid histiocytes and eosinophilsBut immunostaining essential for confirming T lineage157157158158159159ANAPLASTIC LARGE CELL LYMPHOMA, primary systemic formANAPLASTIC 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
65、胞淋巴瘤，原发系统性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 adultsTends to occur in children and young adults Nodal or extranodal presentation (which may include skin, soft tissue, bone, Nodal or extranodal presentation (which may include skin, soft tissue, bone, G.I. tract)G.I. tr
66、act) Immunophenotype:Immunophenotype:n nCD30+; EMA usually +CD30+; EMA usually +n nT-lineage markers +/- (T or null cell)T-lineage markers +/- (T or null cell)n nA proportion of cases express ALK due to translocation involving A proportion of cases express ALK due to translocation involving ALKALK g
67、enegene160160Hallmark cells161161ALKALK translocation translocation (or expression) has helped to define a homogeneous subgroup (or expression) has helped to define a homogeneous subgroup of ALCLof ALCLThis can be easily detected by immunostaining for ALK - permitting re-definition of This can be ea
68、sily detected by immunostaining for ALK - permitting re-definition of the morphologic spectrum of ALCL:the morphologic spectrum of ALCL:n nClassical typeClassical typen nMonomorphicMonomorphicn nSmall cellSmall celln nLymphohistiocyticLymphohistiocyticn nHypocellularHypocellular162162163163CD3016416
69、4 Overall survivalOverall survivalPrimary systemic form of ALCLPrimary systemic form of ALCL0510YearsALCL, ALK+*100%50%ALCL, ALK-165165 霍奇金淋巴瘤霍奇金淋巴瘤霍奇金淋巴瘤霍奇金淋巴瘤 HODGKIN LYMPHOMAHODGKIN LYMPHOMA166166Lymphocyte predominanceMixed cellularityNodular sclerosisLymphocyte depletionNodular lymphocyte predo
70、minant Hodgkin lymphoma (N-LPHL)Classical Hodgkin lymphoma(cHL)Lymphocyte-richMixed cellularityNodular sclerosisLymphocyte depletionRYE CLASSIFICATIONWHO CLASSIFICATION167167510YearsOverall survivalN-LPHL defined by immunohistochemistrycHL defined by immunohistochemistryp = 0.0071168168A lymphoma ch
71、aracterized by:A lymphoma characterized by:n npresence of Reed-Sternberg cells and their variants confirmed by presence of Reed-Sternberg cells and their variants confirmed by mmunohistochemistrymmunohistochemistryn nin an appropriate reactive cellular environment in an appropriate reactive cellular
72、 environment 169169Reed-Sternberg cells and variantsReed-Sternberg cells and variantsDiagnostic Reed-Sternberg cellsDiagnostic Reed-Sternberg cellsMononuclear Hodgkin cellMononuclear Hodgkin cellLacunar cellLacunar cellL&H cellL&H cellPleomorphic Reed-Sternberg cellPleomorphic Reed-Sternberg cellKi6
73、7+Ki67+100%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.170170Reed-Sternberg cells and variantsSmall lymphocytesNuclear size of most neoplastic cells usually e
74、xceeds 3 times that of small lymphocyteSince the R-S cells are so large,they often “stand out” fromthe background cells.171171Diagnostic Reed-Sternberg cellDiagnostic Reed-Sternberg cell172172Appropriate cellular environmentAppropriate cellular environmentDepending on the specific subtype of Hodgkin
75、 lymphoma, presence or absence of Depending on the specific subtype of Hodgkin lymphoma, presence or absence of the following:the following:n nSmall lymphocytesSmall lymphocytesn nHistiocytesHistiocytesn nPlasma cellsPlasma cellsn nEosinophils and neutrophilsEosinophils and neutrophilsn nFibroblasts
76、Fibroblasts173173Classical Hodgkin lymphomaClassical Hodgkin lymphoma经典型霍奇金淋巴瘤经典型霍奇金淋巴瘤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): Large neoplastic cells (R-S cells and variants, e.g. mononuclear, lacunar cells): most, or at least some have lar
77、ge eosinophilic inclusion-like nucleolimost, or at least some have large eosinophilic inclusion-like nucleoliBackground often rich in a mixture of lymphocytes, plasma cells, histiocytes and Background often rich in a mixture of lymphocytes, plasma cells, histiocytes and eosinophils, except lymphocyt
78、e-rich classical Hodgkin lymphomaeosinophils, except lymphocyte-rich classical Hodgkin lymphoma174174175175R-S cells variants176176lacunar cellslacunar cells177177Classical Hodgkin lymphoma: ImmunophenotypeClassical Hodgkin lymphoma: ImmunophenotypeLarge cells (Large cells (“ “crippledcrippled” ” B
79、cells): 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 for one markerOct.2, Bob.1: both negative or positive for one markern nEMA -EMA -Backgrou
80、nd lymphocytes:Background lymphocytes:n nMostly CD3+ T cells, CD4+ CD8+Mostly CD3+ T cells, CD4+ CD8+178178179179180180Nodular lymphocyte predominant Nodular lymphocyte predominant Hodgkin lymphoma(Hodgkin lymphoma(N-LPHL)N-LPHL)Basis of diagnosis is recognition of a focal nodular component:Basis of
81、 diagnosis is recognition of a focal nodular component:n nMorphologically (i.e. focal nodules), orMorphologically (i.e. focal nodules), orn nBy immunohistochemical staining (nodular aggregates of large CD20+ By immunohistochemical staining (nodular aggregates of large CD20+ cells(CD30-,CD15-) +/- CD20+ small B cells)cells(CD30-,CD15-) +/- CD20+ small B cells)181181N-LPHL 182182“popcorn” cells183183“popcorn” cells184184CD20185185186186
