胃腸結(jié)外淋巴瘤

1、,原發(fā)胃腸結(jié)外淋巴瘤診療進展,劉艷艷河南省腫瘤醫(yī)院淋巴綜合內(nèi)科,P-MAR-2015.06-046 Valid Until 2017.06,專業(yè)資料，僅供醫(yī)藥衛(wèi)生專業(yè)人士使用,聲明,本幻燈片代表個人觀點。處方請參考國家食品藥品監(jiān)督管理總局批準(zhǔn)的藥物說明書。,,定義,來源于淋巴結(jié)外的淋巴組織 甚至來源于正常情況下不含淋巴組織的部位 當(dāng)結(jié)內(nèi)和結(jié)外病變同時存在時，定義較困難,,發(fā)病率,占非霍奇金淋巴瘤的25%,,,淋巴瘤,淋巴結(jié),淋巴結(jié)

2、外,胃腸道,非胃腸道,胃 : B-cell MALT DLBCL H. Pylori,腸道 : T-cell Celiac disease,睪丸腦T/NK 鼻型,,,,,,,,,INTERNATIONAL EXTRANODAL LYMPHOMA STUDY GROUP,Extranodal Lymphoma Survival by histology and site

3、in the IELSG series,少見 : 所有胃腸道腫瘤的3%絕大多數(shù)胃腸道淋巴瘤來源于胃,原發(fā)胃腸道淋巴瘤,,P Koch J Clin Oncol 2001,,15%,,3%,,75%,Non Hodgkin’s Lymphoma Classification Project. Blood 1997;89:3909-18,Frequency %G Gastric I IntestinNodal site,1

4、.4%G - 4%I,0%G - 25%I,0%G - 20%I,,胃腸道淋巴瘤分類,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%,系統(tǒng)檢查分期,MALT lymphoma : ESM

5、O GUIDELINES Dreyling M, Thieblemont C. et al. Ann Oncol 2012,,,Auto-antigens,- Thyroid Hashimoto thyroiditis - Salivary gland Myoepithelial sialoadenitis +/ - Sjögren S. - - Lung

6、 Lymphoid interstitial pneumopathy,MZL（邊緣區(qū)淋巴瘤）: 與慢性抗原刺激相關(guān),,MALT Lymphomas,Site Infectious agents- Stomach Helicobacter pylori - Intestin

7、 Campylobacter jejuni- Ocular adnexa Chlamydia psittaci- skin Borrelia burgdorferi,Hepatitis C Virus,Microbial pathogens,1.,2.,+,,,,,Splenic MZL,,,,Isaacson P, Wright DH

8、. Cancer 1983,,,HELICOBACTER PYLORI in STOMACH,MZL: associated with a chronic antigenic stimulation,,chronic Ag stimulation -> chronic inflammation,MALT CONCEPT,MALT淋巴瘤常見的遺傳損傷,,,NF-KB activation,Bertoni F. et al.

9、Oncology 2011,Normal stomach,Chronic gastritis MALT Lymphoma,+ additional factors: host, environment, genetic,,HP,NFKB,,t(11;18) API2-MALT1 t(1,14) BCL10t(14;18) Ig-MALT1,,,E. De Kerviler – Saint-Louis Hospital,

10、 Paris,胃MALT 淋巴瘤內(nèi)鏡,Pseudogastritis30%,Nodular infiltration 25%,Ulcers45%,JC Delchier – Henri Mondor Hospital, Créteil,Normal stomach,Chronic gastric MALT Lymphoma,+ additional factors: host, environment,

11、 genetic,,HP,NFKB,,t(11;18) API2-MALT1 t(1,14) BCL10t(14;18) Ig-MALT1,,,,ATB,Hussel, Lancet 1993; Wootherspoon, Lancet 1993; Wündisch, JCO 2005,依賴H. Pylori的胃MALT 淋巴瘤的治療,Hp. eradication,Complete response: 60% - 100

12、%Response: 3 to 28 months ! Resistance associated to t(11;18),Hussel, Lancet 1993; Wootherspoon, Lancet 1993; Wündisch, JCO 2005,Lymphoma,,Reference n stagingCR ratetime to CR relapses procedure (%

13、) (mos.) (n) Savio, 199612 CT 84 2-40Pinotti, 199745CT 67 3-182Neubauer, 1997 50CT±EUS 80 1-95Nobre Leitao, 199817 CT+EUS 100 1-121Steinbach,

14、 199923CT±EUS 56 3-450Montalban, 200119CT±EUS 95 2-19 0Ruskone-Formestraux, 200124CT+EUS 79 2-18 2LY03 interim analysis, 2000 190CT 62 3-2415,,抗生素和質(zhì)子泵治療stage

15、I 胃 MALT 淋巴瘤,,,After 5 years = 71%,Median follow-up = 7 years,Fischbach et al, Gut 56:1685-7, 2007Pinotti et al, 10-ICML Abstract # 361Stathis A et al, Ann Oncol 2009,n = 120 patients,,抗生素治療后的緩解期,Normal stomach,Chroni

16、c gastric MALT Lymphoma,,HP,t(11;18) API2-MALT1 t(1,14) BCL10t(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-c

17、larithromycin for 7 days,JC Delchier et al. IELSG 2011,Biomarkers associated with antigen dependance,RT in localized gastric MALT lymphoma,Author n RT dose (Gy) FFPSchechter, 19981728-43100% at 2 yrTsan

18、g, 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,,,,烷化劑單藥治療,24 例患者, 1

19、7 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 ch

20、lorambucil),,,Lymphoma,Nodal,Extranodal,Gastro-intestinal,Non Gastro-intestinal,Gastric : B-cell MALT DLBCL H. Pylori,Intestinal : T-cell Celiac disease,TestisBrainT/NK nasal Type,,,,,,,,,胃腸道彌漫大B細

21、胞淋巴瘤,60% of primary GI lymphoma,,,,GI DLBCL,臨床表現(xiàn),侵襲性B 癥狀大腫塊壞死穿孔風(fēng)險: 10%!,,P Koch J Clin Oncol 2001:19:3861,GI DLBCL,治療目的,One Goal,,To cure the patient with the first line of treatment,GI DLBCL,TREATMENT,No surgeryBi

22、omarkers are needed to detect the Hp. - dependant gastric DLBCLStandard R-CHOP,,GI DLBCL,,,Lymphoma,Nodal,Extranodal,Gastro-intestinal,Non Gastro-intestinal,Gastric : B-cellMALTDLBCLH. Pylori,Intestinal : T-cell

23、Celiac disease,TestisBrainT/NK nasal Type,,,,,,,,EATL,腸病型小腸T細胞淋巴瘤(EATL),通常有谷蛋白敏感性腸病既往史腹腔疾病患者: Relative risk of EATL x 50-100 臨床表現(xiàn): 多發(fā)空腸潰瘍Extension:GI tract : estomac, colonExtra-intestinal : blood, skin, lung,EA

24、TL,EATL,粘膜內(nèi)T淋巴細胞增殖Phenotype T CD3+CD4- CD8-/+ TCR- CD103+Phenotype T cytotoxic TIA1+ granzyme B+,Granzyme B,CD103,組織學(xué)表現(xiàn),治療,不含谷蛋白膳食No good chemotherapyOS poor1 year = 35% 5 years = 20%,EATL,結(jié)論,結(jié)外淋巴瘤具有獨特的臨床病理特征胃腸道