胃肠结外淋巴瘤课件

原发胃肠结外淋巴瘤诊疗进展 刘艳艳 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 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 当结内和结外病变同时存在时，定义较困难 发病率 占非霍奇金淋巴瘤的25% 淋巴瘤 淋巴结结 淋巴结结外 胃肠肠道非胃肠肠道 胃 : B-cell MALT DLBCL H. Pylori 肠肠道 : T-cell Celiac disease 睾丸 脑脑 T/NK 鼻型 INTERNATIONAL EXTRANODAL LYMPHOMA STUDY GROUP Extranodal Lymphoma Survival by histology and site in the IELSG series 少见 : 所有胃肠道肿瘤的3% 绝大多数胃肠道淋巴瘤来源于胃 原发胃肠道淋巴瘤 P Koch J Clin Oncol 2001 15% 3% 75% Non Hodgkins Lymphoma Classification Project. Blood 1997;89:3909-18 Frequency % G Gastric I Intestin Nodal site 1.4%G - 4%I 0%G - 25%I 0%G - 20%I 胃肠道淋巴瘤分类 Mantle cell L. Diffuse large B cell lymphoma T-cell lymphoma Burkitt. L MALT Lymphoma 1%G - 20% (colon) Follicular L. 38%G - 10%I 60% 系统检查分期 MALT lymphoma : ESMO GUIDELINES Dreyling M, Thieblemont C. et al. Ann Oncol 2012 LymphomaGI lymphoma Mandatory 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 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 biopsy by PCR, immunohistochemistry or in situ hybridization may be performed. - LARGE INTESTINE : colonoscopy Recommended bone marrow aspirate and biopsy If clinically indicated, head 18) API2-MALT1 t(1,14) BCL10 t(14;18) Ig-MALT1 E. De Kerviler Saint-Louis Hospital, Paris 胃MALT 淋巴瘤内镜 Pseudogastritis 30% Nodular infiltration 25% Ulcers 45% JC Delchier Henri Mondor Hospital, Crteil Normal stomach Chronic gastric MALT Lymphoma + additional factors: host, environment, genetic HP NFKB t(11;18) API2-MALT1 t(1,14) BCL10 t(14;18) Ig-MALT1 ATB Hussel, Lancet 1993; Wootherspoon, Lancet 1993; Wndisch, JCO 2005 依赖H. Pylori的胃MALT 淋巴瘤的治疗 Hp. eradication Complete response: 60% - 100% Response: 3 to 28 months ! Resistance associated to t(11;18) Hussel, Lancet 1993; Wootherspoon, Lancet 1993; Wndisch, JCO 2005 Lymphoma Reference n stagingCR ratetime to CR relapses procedure (%) (mos.) (n) Savio, 199612 CT 84 2-40 Pinotti, 199745CT 67 3-182 Neubauer, 1997 50CTEUS 80 1-95 Nobre Leitao, 199817 CT+EUS 100 1-121 Steinbach, 199923CTEUS 56 3-450 Montalban, 200119CTEUS 95 2-19 0 Ruskone-Formestraux, 200124CT+EUS 79 2-18 2 LY03 interim analysis, 2000 190CT 62 3-2415 抗生素和质子泵治疗stage I 胃 MALT 淋巴瘤 After 5 years = 71% Median follow-up = 7 years Fischbach et al, Gut 56:1685-7, 2007 Pinotti et al, 10-ICML Abstract # 361 Stathis A et al, Ann Oncol 2009 n = 120 patients 抗生素治疗后的缓解期 Normal stomach Chronic gastric MALT Lymphoma HP t(11;18) API2-MALT1 t(1,14) BCL10 t(14;18) Ig-MALT1 DLBCL p53 deletion, p16 deletion Gastric DLBCL Dependant to Hp. ? 10 pts with Gastric DLBCL - Stage IE or IIE PPI-amoxicillin-clarithromycin for 7 days Case N Age /sex Tumor Location StageHp. Treatment Nber of eradication Response To lymphoma Time to CR (mo) 1 2 3 4 5 6 7 8 9 10 67/M 65/F 60/M 56/F 44/M 74/F 35/M 34/F 75/M 73/F Antrum Antrum Corpus Antrum Antrum Corpus Antrum Corpus Antrum Corpus IE IIE2 IE IE IE IIE1 IE IIE2 IIE1 IIE1 2 1 1 1 1 1 2 2 1 1 CR CR CR CR CR Residual MALT CR CR CR CR 1 2 2 2 2 2 1 4 3 2 JC Delchier et al. IELSG 2011 Biomarkers associated with antigen dependance RT in localized gastric MALT lymphoma Author n RT dose (Gy) FFP Schechter, 19981728-43100% at 2 yr Tsang, 2001 920-30100% at 5 yr Yahalom, 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 24 例患者, 17 例stage I ，7 例stage IV Cyclophosphamide 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) Lymphoma Nodal Extranodal Gastro-intestinalNon Gastro-intestinal Gastric : B-cell MALT DLBCL H. Pylori Intestinal : T-cell Celiac disease Testis Brain T/NK nasal Type 胃肠道弥漫大B细胞淋巴瘤 60% of primary GI lymphoma GI DLBCL 临床表现 侵袭性 B 症状 大肿块 坏死 穿孔风险: 10%! P Koch J Clin Oncol 2001:19:3861 GI DLBCL 治疗目的 One Goal To cure the patient with the first line of treatment GI DLBCL TREATMENT No surgery Biomarkers are needed to detect the Hp. - dependant gastric DLBCL Standard R-CHOP GI DLBCL Lymphoma Nodal Extranodal Gastro-intestinalNon Gastro-intestinal Gastric : B-cell MALT DLBCL H. Pylori Intestinal : T-cell Celiac disease Testis Brain T/NK nasal Type EATL 肠病型小肠T细胞淋巴瘤(EATL) 通常有谷蛋白敏感性肠病既往史 腹腔疾病患者: Relative risk of EATL x 50-100 临床表现: 多发空肠溃疡 Extension: GI tract : estomac, colon Extra-intestinal : blood, skin