1、 淋巴瘤淋巴瘤 Lymphoma Dr John K.C.CHAN陈国璋陈国璋4th EditionPublished 20/9/2008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
2、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%）(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第二节第二节 淋巴结的免疫结构淋巴结的免疫结构
3、 （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
4、别免疫结构的关键。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）（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。Pre pre B cellPre B cellImmature B cellMature B cellActivated B
5、cellPlasma cellPrecursor cells;antigen non-responsiveVirgin B cells;antigen responsiveGerminal center&post GC cells;antigen encounteredTdTCD20,CD22CD19,PAX5CD79aCD10Bcl-6CD138Cytoplasmic CD22B cells(CD20+,CD10+,BCL-6+)T cells(CD3+);only small numbers of CD20+cells 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
6、熟小淋巴细胞；CD202、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。Marginal zone cells(IgM)Mantle zone cells(IgM+D)Follicle center cells(IgM,IgG,IgA or IgE,not IgD):约约2:12:1，当，当:8-10:18-10:1或或:3:13:1提示轻链限制表达提示轻链限制表达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：CD
7、10+,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。CD20CD79aCD21CD10Bcl-6Dark z
8、oneLight zone BCL-2 Ki67Marginal zone cellsMarginal zone cellsCD20ProthymocyteSubcapsular thymocyteCortical thymocyteMedullary thymocytePeripheral T cellPrecursor cellsMature T cellsCytoplasmicSurfaceCD4CD8CD1CD4,CD8CD3CD2CD7TdTIDCCD3ImmunoblastInfectious mononucleosisCD20CD3 Large cells comprise mi
9、xture of B and T cells-Reactive processCD30+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.KappaLambdaLarge B cells are polytypicT细胞为主时支持良性的依据（细胞为主时支持良
10、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：2.52.5倍小淋巴细胞；常无透明胞质；核形态倍小淋巴细胞；常无透明胞质；核形态较规则，圆形或椭圆形，轻度扭曲或折叠；较规则，圆形或椭圆形，轻度扭曲或折叠；（5）免疫染色）免疫染色:常为常为CD4+为主为主,少为
11、少为CD8+为主为主(AIDS,骨髓移植等骨髓移植等)；一般无一般无CD4-CD8-或或CD4+CD8+表型表型,PanT+（无缺失）；（无缺失）；少见少见ALK,TdT,CD56,T cell receptor等表达等表达 斑驳状斑驳状Autoimmune lymphoproliferative syndrome，ALPS斑驳状斑驳状Reactive large lymphoid cell(immunoblast)Small lymphocytesNuclear size usually does not exceed 2.5 times that of small lymphocyteNu
12、cleus usually round or ovoid,and does not show irregular foldings第三节第三节 淋巴瘤分类淋巴瘤分类 WHO Classification 2008Precursor lymphoblastic lymphoma/leukemia(B or T cell type)Mature B-cell neoplasmsMature T-cell and NK-cell lymphomas Follicular lymphoma B-cell CLL/small lymphocytic lymphoma Lymphoplasmacytic
13、lymphoma Splenic and nodal marginal zone lymphoma%Survival100%0%Years010 Diffuse large B-cell lymphomaMantle cell lymphoma*All peripheral T cell lymphomas(including ALCL&NK cell lymphomas except:Mycosis fungoides)Primary cutaneous anaplastic large cell lymphomaT-cell LGL leukemia%Survival100%0%Years
14、010TreatedUntreated%Survival100%0%Years010Aggressive NHLIndolent NHLParadoxically better outcome in the long run Lymphoblastic lymphoma Burkitt lymphoma%Survival100%0%Years010TreatedUntreatedExtranodal marginal zone B-cell lymphomaof mucosa-associated lymphoid tissue（MALT）typePrimary cutaneousanapla
15、stic large cell lymphomaCD20CD79aB-LBLT-LBL1 major criterion or 3 minor criteria.But confirm by ancillary tests if uncertainMajor criterion fulfilled in 80%of cases of follicular lymphomaJust go on to high magnification to confirm follicle center cell morphologyCentrocytes oftenhave triangularshaped
16、 nucleiReactive folliclesFollicular lymphoma(Bcl-2 immunostaining)Negative 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 lymphomaBcl-2CD20CD10KappaLambdaFL1:Ki67RFH:Ki
17、67FL3:Ki67 Growth pattern of MCLRound nucleiCyclin D1Cyclin D1After Helicobacter eradication therapyCentroblastic/ImmunoblasticMultilobatedPleomorphicCD20CD10Ki67CD3CD21CXCL13SmallMedium-sizedLargeBroad cytologic spectrumSurface CD3Cytoplasmic CD3CD56Frozen tissueParaffin sectionBut immunostaining e
18、ssential for confirming T lineageHallmark cellsCD300510YearsALCL,ALK+*100%50%ALCL,ALK-Lymphocyte predominanceMixed cellularityNodular sclerosisLymphocyte depletionNodular lymphocyte predominant Hodgkin lymphoma(N-LPHL)Classical Hodgkin lymphoma(cHL)Lymphocyte-richMixed cellularityNodular sclerosisLy
19、mphocyte depletionRYE CLASSIFICATIONWHO CLASSIFICATION510YearsOverall survivalN-LPHL defined by immunohistochemistrycHL defined by immunohistochemistryp=0.0071No need to find diagnostic Reed-Sternberg cellsin rendering a diagnosis of Hodgkin lymphoma.Its okay if cells are large enough,with prominent
20、nucleoli and compatible immunophenotype.Reed-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.R-S cells variantsN-LPHL“popcorn”cells“popcorn”cellsCD20
