胃肠结外淋巴瘤培训讲义课件.ppt

1、胃肠结外淋巴瘤（优选）胃肠结外淋巴瘤定义定义 来源于淋巴结外的淋巴组织来源于淋巴结外的淋巴组织 甚至来源于正常情况下不含淋巴组织的部位甚至来源于正常情况下不含淋巴组织的部位 当结内和结外病变同时存在时，定义较困难当结内和结外病变同时存在时，定义较困难发病率发病率 占非霍奇金淋巴瘤的占非霍奇金淋巴瘤的25%淋巴瘤淋巴瘤淋巴结淋巴结淋巴结外淋巴结外胃肠道胃肠道非胃肠道非胃肠道胃胃:B-cell MALT DLBCL H.Pylori肠道肠道:T-cell Celiac disease睾丸睾丸脑脑T/NK 鼻型鼻型INTERNATIONAL EXTRANODAL LYMPHOMA STUDY GRO

2、UP Extranodal Lymphoma Survival by histology and site in the IELSG series 少见少见 :所有胃肠道肿瘤的所有胃肠道肿瘤的3%绝大多数胃肠道淋巴瘤来源于胃绝大多数胃肠道淋巴瘤来源于胃原发胃肠道淋巴瘤原发胃肠道淋巴瘤P Koch J Clin Oncol 200115%3%75%-Salivary gland Myoepithelial sialoadenitis+/-Sjgren S.Tumor Location38%G-10%I-GASTRIC:Gastroduodenal endoscopy with multiple

3、biopsies taken from each region of the stomach,duodenum,gastro-esophageal junction and from any abnormal-appearing site;Yahalom,20025130 median89%at 4 yrhost,environment,geneticI Intestin-Thyroid Hashimoto thyroiditisTumor Location-GASTRIC:Gastroduodenal endoscopy with multiple biopsies taken from e

4、ach region of the stomach,duodenum,gastro-esophageal junction and from any abnormal-appearing site;extranodal sitesMZL（边缘区淋巴瘤）:与慢性抗原刺激相关抗生素和质子泵治疗stage I 胃 MALT 淋巴瘤Blood 1997;89:3909-1810 pts with Gastric DLBCL-Stage IE or IIEGastric:B-cell MALT DLBCL H.Resistance associated to t(11;18)with the first

5、 line of treatmentAuthor n RT dose(Gy)FFPNon Hodgkins Lymphoma Classification Project.Blood 1997;89:3909-18Frequency%G Gastric I IntestinNodal site1.4%G-4%I0%G-25%I0%G-20%I胃肠道淋巴瘤分类胃肠道淋巴瘤分类Mantle cell L.Diffuse large B cell lymphomaT-cell lymphomaBurkitt.LMALT Lymphoma 1%G -20%(colon)Follicular L.38%

6、G-10%I 60%系统检查分期系统检查分期MALT lymphoma:ESMO GUIDELINES Dreyling M,Thieblemont C.et al.Ann Oncol 2012LymphomaGI lymphomaMandatory physical exam complete blood counts basic biochemical studies(renal and liver function,LDH and 2MG,serum protein immunofixation)HIV,HCV and HBV serology CT of the chest,abdom

7、en and pelvis-GASTRIC:Gastroduodenal endoscopy with multiple biopsies taken from each region of the stomach,duodenum,gastro-esophageal junction and from any abnormal-appearing site;H.pylori status must be evaluated in gastric L.-SMALL INSTESTINE (IPSID Immuno-Proliferative Small Intestinal Disease):

8、Campylobacter Jejuni search in the tumor biopsy by PCR,immunohistochemistry or in situ hybridization may be performed.-LARGE INTESTINE:colonoscopyRecommended bone marrow aspirate and biopsy If clinically indicated,head&neck MRI studies and other imaging are to be realizederadicationAg-dependantChron

9、ic gastritis-Ocular adnexa Chlamydia psittaciAuto-antigens-GASTRIC:Gastroduodenal endoscopy with multiple biopsies taken from each region of the stomach,duodenum,gastro-esophageal junction and from any abnormal-appearing site;Chronic gastricSplenic MZLI IntestinHussel,Lancet 1993;Wootherspoon,Lancet

10、 1993;Wndisch,JCO 2005p53 deletion,extranodal sitest(11;18)API2-MALT1JC Delchier et al.来源于淋巴结外的淋巴组织Non Hodgkins Lymphoma Classification Project.Cancer 1983Cancer 1983Neubauer,1997 50CTEUS 80 1-950%G-25%INodular infiltration-Intestin Campylobacter jejuniGastric:B-cell MALT DLBCL H.Nobre Leitao,199817

11、 CT+EUS 100 1-121GI lymphoma少见 :所有胃肠道肿瘤的3%Mantle cell L.complete blood countsGI lymphomaPPI-amoxicillin-clarithromycin for 7 daysHussel,Lancet 1993;Wootherspoon,Lancet 1993;Wndisch,JCO 2005+additional factors:physical examAuto-antigens占非霍奇金淋巴瘤的25%甚至来源于正常情况下不含淋巴组织的部位Site Infectious agentsBlood 1997;8

12、9:3909-18Auto-antigens-Thyroid Hashimoto thyroiditis-Salivary gland Myoepithelial sialoadenitis+/-Sjgren S.-Lung Lymphoid interstitial pneumopathy MZL（边缘区淋巴瘤）（边缘区淋巴瘤）:与慢性抗原刺激相关与慢性抗原刺激相关MALT LymphomasSite Infectious agents-Stomach Helicobacter pylori-Intestin Campylobacter jejuni-Ocular adnexa Chlamy

13、dia psittaci-skin Borrelia burgdorferi Hepatitis C VirusMicrobial pathogens1.2.+Splenic MZLIsaacson P,Wright DH.Cancer 1983HELICOBACTER PYLORI in STOMACHMZL:associated with a chronic antigenic stimulationchronic Ag stimulation chronic inflammationINFECTIONAUTOANTIGENAcquisition of MALTAg-dependantMA

14、LT lymphomaAg-independantMALT lymphomaEpithelium of extranodal sitesMALT CONCEPTNF-KB activationMALT lymphoma:ESMO GUIDELINES Dreyling M,Thieblemont C.Median follow-up=7 yearsChronic gastricBiomarkers associated with antigen dependance5 relapses at initial sites(1 with transformation)-Ocular adnexa

15、Chlamydia psittaciSite Infectious agentsMALT lymphomat(11;18)API2-MALT1-Salivary gland Myoepithelial sialoadenitis+/-Sjgren S.占非霍奇金淋巴瘤的25%De Kerviler Saint-Louis Hospital,Paris)(n)Savio,1996 12 CT 84 2-40P Koch J Clin Oncol 2001-Thyroid Hashimoto thyroiditisTumor LocationNobre Leitao,199817 CT+EUS 1

16、00 1-121Response:3 to 28 months!Site Infectious agentsMZL:associated with a chronic antigenic stimulationIELSG 2011Steinbach,199923CTEUS 56 3-450MALT淋巴瘤常见的遗传损伤淋巴瘤常见的遗传损伤NF-KB activationBertoni F.et al.Oncology 2011 Normal stomachChronic gastritis MALT Lymphoma+additional factors:host,environment,gen

17、eticHPNFKBt(11;18)API2-MALT1 t(1,14)BCL10t(14;18)Ig-MALT1E.De Kerviler Saint-Louis Hospital,Paris胃胃MALT 淋巴瘤内镜淋巴瘤内镜Pseudogastritis30%Nodular infiltration 25%Ulcers45%JC Delchier Henri Mondor Hospital,CrteilNormal stomachChronic gastric MALT Lymphoma+additional factors:host,environment,geneticHPNFKBt(

18、11;18)API2-MALT1 t(1,14)BCL10t(14;18)Ig-MALT1ATBHussel,Lancet 1993;Wootherspoon,Lancet 1993;Wndisch,JCO 2005依赖依赖H.PyloriH.Pylori的的胃胃MALT MALT 淋巴瘤的治疗淋巴瘤的治疗Hp.eradicationComplete response:60%-100%Response:3 to 28 months!Resistance associated to t(11;18)Hussel,Lancet 1993;Wootherspoon,Lancet 1993;Wndis

19、ch,JCO 2005LymphomaReference n stagingCR ratetime to CR relapses procedure (%)(mos.)(n)Savio,199612 CT 84 2-40Pinotti,199745CT 67 3-182Neubauer,1997 50CTEUS 80 1-95Nobre Leitao,199817 CT+EUS 100 1-121Steinbach,199923CTEUS 56 3-450Montalban,200119CTEUS 95 2-19 0Ruskone-Formestraux,200124CT+EUS 79 2-1

20、8 2LY03 interim analysis,2000 190CT 62 3-2415抗生素和质子泵治疗抗生素和质子泵治疗stage Istage I 胃胃 MALT MALT 淋巴瘤淋巴瘤After 5 years=71%Median follow-up=7 yearsFischbach et al,Gut 56:1685-7,2007Pinotti et al,10-ICML Abstract#361Stathis A et al,Ann Oncol 2009n=120 patients抗生素治疗后的缓解期抗生素治疗后的缓解期Normal stomachChronic gastric

21、MALT LymphomaHPt(11;18)API2-MALT1 t(1,14)BCL10t(14;18)Ig-MALT1DLBCLp53 deletion,p16 deletionGastric DLBCL Dependant to Hp.?10 pts with Gastric DLBCL-Stage IE or IIE PPI-amoxicillin-clarithromycin for 7 daysCase NAge/sexTumor LocationStageHp.TreatmentNber of eradicationResponseTo lymphomaTime to CR(m

22、o)1234567891067/M65/F60/M56/F44/M74/F35/M34/F75/M73/FAntrumAntrumCorpusAntrumAntrumCorpusAntrumCorpusAntrumCorpusIEIIE2IEIEIEIIE1IEIIE2IIE1IIE12111112211CRCRCRCRCRResidual MALTCRCRCRCR1222221432JC Delchier et al.IELSG 2011 Biomarkers associated with antigen dependanceRT in localized gastric MALT lym

23、phomaAuthor n RT dose(Gy)FFPSchechter,1998172843100%at 2 yrTsang,2001 92030100%at 5 yrYahalom,20025130 median89%at 4 yr Hitchcock,2002 934 median78%(100%local)Goda JS,2010 25 2530 79%at 5 yr 烷化剂单药治疗烷化剂单药治疗24 例患者,17 例stage I，7 例stage IVCyclophosphamide or Chlorambucil for 824 mos.100%ORR(75%CR)5year

24、EFS:50%5year OS:75%5 relapses at initial sites(1 with transformation)Hammel et al,JCO 1995(cyclophosphamide or chlorambucil)LymphomaNodalExtranodalGastro-intestinalNon Gastro-intestinalGastric:B-cell MALT DLBCL H.PyloriIntestinal:T-cell Celiac diseaseTestisBrainT/NK nasal Type胃肠道弥漫大胃肠道弥漫大B B细胞淋巴瘤细胞淋

25、巴瘤 60%of primary GI lymphomaGI DLBCL临床表现临床表现 侵袭性侵袭性 B 症状症状 大肿块大肿块 坏死坏死 穿孔风险穿孔风险:10%!P Koch J Clin Oncol 2001:19:3861GI DLBCL治疗目的治疗目的One GoalTo cure the patient with the first line of treatmentGI DLBCLTREATMENTNo surgeryBiomarkers are needed to detect the Hp.dependant gastric DLBCLStandard RCHOPGI DL

26、BCLMALT Lymphoma-Ocular adnexa Chlamydia psittaci+additional factors:Yahalom,20025130 median89%at 4 yr-GASTRIC:Gastroduodenal endoscopy with multiple biopsies taken from each region of the stomach,duodenum,gastro-esophageal junction and from any abnormal-appearing site;t(11;18)API2-MALT1Reference n

27、stagingCR ratetime to CR relapses procedure (%)(mos.100%ORR(75%CR)physical examNeubauer,1997 50CTEUS 80 1-95绝大多数胃肠道淋巴瘤来源于胃胃肠道弥漫大B细胞淋巴瘤Normal stomachPPI-amoxicillin-clarithromycin for 7 days肠道:T-cell Celiac diseaseNeubauer,1997 50CTEUS 80 1-95Intestinal:T-cell Celiac diseaseP Koch J Clin Oncol 2001t(

28、14;18)Ig-MALT1NF-KB activationJC Delchier et al.Yahalom,20025130 median89%at 4 yrExtranodal Lymphoma Survival by histology and site in the IELSG series抗生素和质子泵治疗stage I 胃 MALT 淋巴瘤抗生素和质子泵治疗stage I 胃 MALT 淋巴瘤MALT LymphomasResponse:3 to 28 months!（优选）胃肠结外淋巴瘤Chronic gastricYahalom,20025130 median89%at 4

29、yrResponse:3 to 28 months!Response:3 to 28 months!MALT lymphomaMantle cell L.淋巴瘤NF-KB activationMontalban,200119CTEUS 95 2-19 0Ruskone-Formestraux,200124CT+EUS 79 2-18 2Tumor LocationLymphomaDiffuse large B cell lymphomaCT of the chest,abdomen and pelvisSite Infectious agentsPPI-amoxicillin-clarithr

30、omycin for 7 days(cyclophosphamide or chlorambucil)Yahalom,20025130 median89%at 4 yr10 pts with Gastric DLBCL-Stage IE or IIE(cyclophosphamide or chlorambucil)Non Gastro-intestinal0%G-20%IResistance associated to t(11;18)Site Infectious agentsExtranodal Lymphoma Survival by histology and site in the

31、 IELSG seriesNormal stomachExtranodal Lymphoma Survival by histology and site in the IELSG seriesTsang,2001 92030100%at 5 yrphysical exam绝大多数胃肠道淋巴瘤来源于胃MALT LymphomasCancer 1983Ag-dependantphysical exam5 relapses at initial sites(1 with transformation)p53 deletion,TestisBrainT/NK nasal Typet(14;18)Ig

32、-MALT1-SMALL INSTESTINE (IPSID Immuno-Proliferative Small Intestinal Disease):Campylobacter Jejuni search in the tumor biopsy by PCR,immunohistochemistry or in situ hybridization may be performed.Tsang,2001 92030100%at 5 yrBlood 1997;89:3909-18Response:3 to 28 months!with the first line of treatment

33、Ann Oncol 2012肠道:T-cell Celiac diseaseDe Kerviler Saint-Louis Hospital,ParisMALT Lymphoma0%G-20%IP Koch J Clin Oncol 2001Lymphomacomplete blood countsIsaacson P,Wright DH.Frequency%Fischbach et al,Gut 56:1685-7,2007Mantle cell L.Non Gastro-intestinalP Koch J Clin Oncol 2001:19:3861甚至来源于正常情况下不含淋巴组织的部

34、位IELSG 2011NF-KB activationAUTOANTIGENHitchcock,2002 934 median78%(100%local)MALT Lymphomas-Thyroid Hashimoto thyroiditisIf clinically indicated,head&neck MRI studies and other imaging are to be realizedMantle cell L.当结内和结外病变同时存在时，定义较困难Reference n stagingCR ratetime to CR relapses procedure (%)(mos.

35、抗生素和质子泵治疗stage I 胃 MALT 淋巴瘤Chronic gastritisResponse:3 to 28 months!Pylori的胃MALT 淋巴瘤的治疗Ann Oncol 2012100%ORR(75%CR)Extranodal Lymphoma Survival by histology and site in the IELSG seriesMALT Lymphoma-Ocular adnexa Chlamydia psittaciChronic gastritisMALT CONCEPTP Koch J Clin Oncol 2001MZL（边缘区淋巴瘤）:与慢性抗

36、原刺激相关RT in localized gastric MALT lymphomaSite Infectious agentsMALT Lymphomas抗生素和质子泵治疗stage I 胃 MALT 淋巴瘤Mantle cell L.INTERNATIONAL EXTRANODAL LYMPHOMA STUDY GROUPMALT lymphoma-Intestin Campylobacter jejuni(cyclophosphamide or chlorambucil)-GASTRIC:Gastroduodenal endoscopy with multiple biopsies ta

37、ken from each region of the stomach,duodenum,gastro-esophageal junction and from any abnormal-appearing site;Chronic gastritisFrequency%(cyclophosphamide or chlorambucil)0%G-20%IPPI-amoxicillin-clarithromycin for 7 daysMALT lymphomaFischbach et al,Gut 56:1685-7,2007IELSG 2011+additional factors:Resp

38、onse:3 to 28 months!Author n RT dose(Gy)FFPNeubauer,1997 50CTEUS 80 1-95Mantle cell L.Blood 1997;89:3909-18Nobre Leitao,199817 CT+EUS 100 1-121Tumor LocationI IntestinExtranodal Lymphoma Survival by histology and site in the IELSG seriesLARGE INTESTINE:colonoscopy甚至来源于正常情况下不含淋巴组织的部位MALT lymphoma绝大多数

39、胃肠道淋巴瘤来源于胃Pylori的胃MALT 淋巴瘤的治疗Author n RT dose(Gy)FFPAnn Oncol 20120%G-20%I(colon)Response:3 to 28 months!-Thyroid Hashimoto thyroiditis绝大多数胃肠道淋巴瘤来源于胃Hussel,Lancet 1993;Wootherspoon,Lancet 1993;Wndisch,JCO 200538%G-10%IMALT lymphoma:ESMO GUIDELINES Dreyling M,Thieblemont C.Tumor LocationChronic gastr

40、icp16 deletionTsang,2001 92030100%at 5 yr肠道:T-cell Celiac disease-skin Borrelia burgdorferiGoda JS,2010 25 2530 79%at 5 yrMontalban,200119CTEUS 95 2-19 0Ruskone-Formestraux,200124CT+EUS 79 2-18 2肠道:T-cell Celiac diseaseDe Kerviler Saint-Louis Hospital,ParisChronic gastritisBiomarkers associated with

41、 antigen dependanceMontalban,200119CTEUS 95 2-19 0Ruskone-Formestraux,200124CT+EUS 79 2-18 2basic biochemical studies(renal and liver function,LDH and 2MG,serum protein immunofixation)MALT LymphomasAcquisition of MALTMALT CONCEPTGastric:B-cell MALT DLBCL H.GI lymphoma10 pts with Gastric DLBCL-Stage

42、IE or IIEMantle cell L.Pylori的胃MALT 淋巴瘤的治疗MALT LymphomaMicrobial pathogens-Intestin Campylobacter jejuni+additional factors:eradicationBlood 1997;89:3909-18Extranodal Lymphoma Survival by histology and site in the IELSG seriest(14;18)Ig-MALT1Goda JS,2010 25 2530 79%at 5 yrJC Delchier Henri Mondor Hospital,CrteilTumor Location LymphomaNodalExtranodalGastro-intestinalNon Gastro-intestinalGastric:B-cellMALTDLBCLH.PyloriIntestinal:T-cell Celiac diseaseTestisBrainT/NK nasal TypeEATL