胃肠结外淋巴瘤刘艳艳PMA PPT课件.ppt

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1、原发胃肠结外淋巴瘤诊疗进展原发胃肠结外淋巴瘤诊疗进展刘艳艳刘艳艳河南省肿瘤医院淋巴综合内科河南省肿瘤医院淋巴综合内科P-MAR-2015.06-046 Valid Until 2017.06专业资料，仅供医药卫生专业人士使用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%淋巴瘤淋巴瘤淋巴淋巴结淋巴淋

2、巴结外外胃胃肠道道非胃非胃肠道道胃胃:B-cell MALT DLBCL H.Pylori肠道道:T-cell Celiac disease睾丸睾丸脑T/NK 鼻型鼻型INTERNATIONALEXTRANODALLYMPHOMASTUDYGROUPExtranodal 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 H

3、odgkins 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%G-10%I 60%系统检查分期系统检查分期MALT lymphoma:ESMO GUIDE

4、LINES 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,abdomen and pelvis-GASTRIC:Gastroduodenal endoscopy

5、 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):Campylobacter Jejuni search in the tumor biops

6、y 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 realizedAuto-antigens-Thyroid Hashimoto thyroiditis-Salivary gland Myoepithelial s

7、ialoadenitis+/-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 Chlamydia psittaci-skin Borrelia burgdorferi Hepatitis C VirusMicrobial pathogens1.2.+Spl

8、enic MZLIsaacson P,Wright DH.Cancer 1983HELICOBACTER PYLORI in STOMACHMZL:associated with a chronic antigenic stimulationchronic Ag stimulation -chronic inflammationINFECTIONAUTOANTIGENAcquisition of MALTAg-dependantMALT lymphomaAg-independantMALT lymphomaEpithelium of extranodal sitesMALT CONCEPTMA

9、LT淋巴瘤常淋巴瘤常见的的遗传损伤NF-KB activationBertoni F.et al.Oncology 2011 Normal stomachChronic gastritis 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

10、 25%Ulcers45%JC Delchier Henri Mondor Hospital,CrteilNormal stomachChronic gastric MALT Lymphoma+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

11、治疗Hp.eradicationComplete response:60%-100%Response:3 to 28 months!Resistance associated to t(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 50C

12、TEUS 80 1-95Nobre Leitao,199817 CT+EUS 100 1-121Steinbach,199923CTEUS 56 3-450Montalban,200119CTEUS 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 a

13、l,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 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-Sta

14、ge IE or IIE PPI-amoxicillin-clarithromycin for 7 daysCase NAge/sexTumor LocationStageHp.TreatmentNber of eradicationResponseTo lymphomaTime to CR(mo)1234567891067/M65/F60/M56/F44/M74/F35/M34/F75/M73/FAntrumAntrumCorpusAntrumAntrumCorpusAntrumCorpusAntrumCorpusIEIIE2IEIEIEIIE1IEIIE2IIE1IIE1211111221

15、1CRCRCRCRCRResidual MALTCRCRCRCR1222221432JC Delchier et al.IELSG 2011 Biomarkers associated with antigen dependanceRT in localized gastric MALT lymphomaAuthor n RT dose(Gy)FFPSchechter,19981728-43100%at 2 yrTsang,2001 920-30100%at 5 yr Yahalom,20025130 median89%at 4 yr Hitchcock,2002 934 median78%(

16、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 IVCyclophosphamide 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)LymphomaNodalExtranod

17、alGastro-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

18、 patient with the first line of treatmentGI DLBCLTREATMENTNo surgeryBiomarkers are needed to detect the Hp.-dependant gastric DLBCLStandard R-CHOPGI DLBCL LymphomaNodalExtranodalGastro-intestinalNon Gastro-intestinalGastric:B-cellMALTDLBCLH.PyloriIntestinal:T-cell Celiac diseaseTestisBrainT/NK nasal

19、 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 risk 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,colonExtra-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 chemotherapyOS poor1 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