胃肠结外淋巴瘤-刘艳艳PMA课件.ppt

1、声明本幻灯片代表个人观点。处方请参考国家食品药品监督管理总局批准的药物说明书。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 EXTRANOD

2、AL LYMPHOMA STUDY GROUP 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%Non Hodgkins Lymphoma Classification Project.Blood 1997;89:3909-18Frequency%G Gastric I IntestinNodal sit

3、e1.4%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%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 comple

4、te blood counts basic biochemical studies(renal and liver function,LDH and 2MG,serum protein immunofixation)HIV,HCV and HBV serology CT of the chest,abdomen and pelvis-GASTRIC:Gastroduodenal endoscopy with multiple biopsies taken from each region of the stomach,duodenum,gastro-esophageal junction an

5、d from any abnormal-appearing site;H.pylori status must be evaluated in gastric L.-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.-LARGE INTESTINE:colonoscopy

6、Recommended bone marrow aspirate and biopsy If clinically indicated,head&neck MRI studies and other imaging are to be realizedAuto-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

7、相关MALT LymphomasSite Infectious agents-Stomach Helicobacter pylori-Intestin Campylobacter jejuni-Ocular adnexa Chlamydia psittaci-skin Borrelia burgdorferi Hepatitis C VirusMicrobial pathogens1.2.+Splenic MZLIsaacson P,Wright DH.Cancer 1983HELICOBACTER PYLORI in STOMACHMZL:associated with a chronic

8、antigenic stimulationchronic Ag stimulation -chronic inflammationINFECTIONAUTOANTIGENAcquisition of MALTAg-dependantMALT lymphomaAg-independantMALT lymphomaEpithelium of extranodal sitesMALT CONCEPTMALT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

9、MALT Lymphoma+additional factors:host,environment,geneticHPNFKBt(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 Lymphom

10、a+additional factors:host,environment,geneticHPNFKBt(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

11、;18)Hussel,Lancet 1993;Wootherspoon,Lancet 1993;Wndisch,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,200119C

12、TEUS 95 2-19 0Ruskone-Formestraux,200124CT+EUS 79 2-18 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 patie

13、nts抗生素治疗后的缓解期抗生素治疗后的缓解期Normal stomachChronic gastric 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.Treatm

14、entNber of eradicationResponseTo lymphomaTime to CR(mo)1234567891067/M65/F60/M56/F44/M74/F35/M34/F75/M73/FAntrumAntrumCorpusAntrumAntrumCorpusAntrumCorpusAntrumCorpusIEIIE2IEIEIEIIE1IEIIE2IIE1IIE12111112211CRCRCRCRCRResidual MALTCRCRCRCR1222221432JC Delchier et al.IELSG 2011 Biomarkers associated wi

15、th antigen dependanceRT in localized gastric MALT lymphomaAuthor n RT dose(Gy)FFPSchechter,19981728-43100%at 2 yrTsang,2001 920-30100%at 5 yrYahalom,20025130 median89%at 4 yr Hitchcock,2002 934 median78%(100%local)Goda JS,2010 25 25-30 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 IVCyclophos

16、phamide or Chlorambucil for 8-24 mos.100%ORR(75%CR)5-year EFS:50%5-year 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 Celi

17、ac 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

18、to detect the Hp.-dependant gastric DLBCL Standard R-CHOPGI DLBCL LymphomaNodalExtranodalGastro-intestinalNon Gastro-intestinalGastric:B-cellMALTDLBCLH.PyloriIntestinal:T-cell Celiac diseaseTestisBrainT/NK nasal TypeEATL肠病型小肠肠病型小肠T细胞淋巴瘤细胞淋巴瘤(EATL)通常有谷蛋白敏感性肠病既往史通常有谷蛋白敏感性肠病既往史 腹腔疾病患者腹腔疾病患者:Relative ri

19、sk of EATL x 50-100 临床表现临床表现:多发空肠溃疡多发空肠溃疡 Extension:GI tract:estomac,colon Extra-intestinal:blood,skin,lungEATLEATL 粘膜内粘膜内T淋巴细胞增殖淋巴细胞增殖 Phenotype T CD3+CD4-CD8-/+TCR-CD103+Phenotype T cytotoxic TIA1+granzyme B+Granzyme BCD103组织学表现组织学表现治疗治疗 不含谷蛋白膳食不含谷蛋白膳食 No good chemotherapy OS poor 1 year=35%5 years=20%EATL结论结论 结外淋巴瘤具有独特的临床病理特征结外淋巴瘤具有独特的临床病理特征 胃肠道淋巴瘤最常见胃肠道淋巴瘤最常见 多数与慢性抗原刺激相关多数与慢性抗原刺激相关 治疗应采取个体化治疗应采取个体化