1、消化系统消化系统肺其它/未知分布情况百分比分布情况百分比(%)2.0001.003.004.005.006.0001002003004005006005.25年年74 76 78 80 82 84 86 88 90 92 94 96 98 00 02 04所有恶性肿瘤的发病人数所有恶性肿瘤的发病人数神经内分泌治疗的发病人数神经内分泌治疗的发病人数每十万人中的发病人数每十万人中的发病人数过去30年间，NEN的发病率急剧上升(5倍)，这其中部分可能归因于诊断水平的提高来源:美国 SEER数据库.Adapted with permission from Yao JC,et al.J Clin Onc
2、ol.2019:26:3063-3072.65%的晚期NET患者，总生存期不超过5年）前肠前肠 胸腺 食道 肺 胃 胰腺十二指肠中肠中肠 阑尾 回肠 盲肠 升结肠后肠后肠 远端大肠 直肠Consensus Conference on the ENETS Guidelines for the Diagnosis and Treatment of Neuroendocrine Gastrointestinal Tumors Frascati,Italy November,2019，20个国家62名专家Foregut TumorsNovember,2019，18个国家57名专家Midgut and
3、Hindgut Tumors (1)pathology and genetics (11 participants)(2)surgery(10 participants)(3)imaging and radiology(10 participants)(4)medicine and clinical pathology(31 participants)Virchows Arch(2019)449:395401Virchows Arch(2019)451:757762 Rindi,Klppel,Ahlman,Wiedenmann.TNM staging of foregut,midgut and
4、 hindgut(neuro)endocrine tumours:A consensus proposal including a grading system.神经内分泌肿瘤 神经内分泌瘤 神经内分泌癌 消化系统NEN组织学分级 标准 Grade G1 G2G3 Mitotic count(10HPF)a 20 Ki67 labeling index(%)b 2 320 20具体计算方法a.10 HPF(high power field)=2 mm2(40的),at least 50 fields evaluated in areas of highest mitotic density b
5、.MIB1 antibody，%of 5002,000 tumor cells in areas of highest nuclear labeling20304050607080901000010102030405060708090100Ki-67R 2=0.813核分裂像核分裂像/10 HPFStrosberg J,et al.Human Pathology.2009;40:1262-1268.NEN组织学分级注意事项NEN组织学分级注意事项G1G2G3NENde 分级与生存率(%)No.of deaths/total no.(%)2 Years 5 Years 10 Years Grad
6、e 31/158(19.6)1 2/44(4.5)100 95.7 83.7 2 15/85(17.6)88.7 73.4 69.4 3 14/29(48.3)41.6 27.7 ND Pape UF et al.Cancer.2019;113:256-265.050100150200250Time(months)0.00.20.40.60.81.0Cumulative SurvivalG1G2G3G1 vs.G2G1 vs.G3G2 vs.G3P=0.040P0.001P0.001Pape UF et al.Cancer.2019;113:256-265.突触素(Synaptophysin，
7、Syn)广泛表达于NEN的瘤细胞，弥漫阳性，敏感性好高、低分化的NEN均表达 特异性差嗜铬粒蛋白A(Chromogranin A，CgA)特异性好 敏感性差低分化的NEN中可能为阴性 部分大肠和阑尾NEN主要分泌CgB，而大多数市售 商品为CgA抗体，无法检测出CgB Ki67：用MIB-1抗体，标记率最高区，500-2000个细胞低分化NEN高分化NENSynCgA注意事项 a.不推荐使用其它神经内分泌标记物(CD56、PgP9.5、NSE特异性较差)，也不推荐使用PCNAb.阳性只要定位准确即可判断，无需评价阳性强度或 半定量阳性细胞数c.高分化NENSyn与CgA 弥漫、强阳性 低分化N
8、ENSyn弥漫阳性，CgA弱或局灶阳性，甚至阴性CgACgA可选检测项目 多肽激素和生物活性胺 胃泌素、生长抑素、高血糖素、血管活性肠肽、5-羟色胺和组胺等 注意：诊断非功能性NEN时不用瘤，“免疫组化证实有产物”其它标记物 生长抑素受体（SSTR2-奥曲肽、SSTR5等）广谱角蛋白（AE1/AE3）、CK7-CK20(前肠-中后肠)CDX2中后肠 CD34、D2-40脉管癌栓消化系统NEN的TNM分期TNM staging for NEN of the gastric,duodenum/ampulla/proximal jejunum,pancreas;lower jejunum and i
9、leum,appendix,colon and rectum Stage T N M I T1 N0 M0 IIA T2 N0 M0 II B T3 N0 M0 IIIA T4 N0 M0 III B Any T N1 M0 IV Any T Any N M1 the colon and rectum IA，I Bthe appendix TNM staging for NEN of the appendixStage T N M I T1 N0 M0II T2,T3 N0 M0III T4 N0 M0 Any T N1 M0IV Any T Any N M1 GastricTX Primar
10、y tumor cannot be assessedT0 No evidence of primary tumorTis In situ tumor/dysplasia(1 cmT3 Tumor invades subserosaT4 Tumor invades peritoneum or adjacent structures For any T,add(m)for multiple tumors(for all organs)Duodenum/ampulla/proximal jejunumTXT0 T1 T2T3 Tumor invades pancreas or retroperito
11、neumT4 Tumor invades peritoneum or other organsLower jejunum and ileumTX T0T1 T2T3 Tumor invades subserosaT4 Tumor invades peritoneum/other organsColon and rectumTXT0T1 Tumor invades mucosa or submucosa T1A size 2 cmT3 Tumor invades subserosa/pericolic/perirectal fatT4 Tumor directly invades other o
12、rgans/structures and/or perforates visceral peritoneum ENETSAJCCT11cm 侵犯粘膜和粘膜下层T1a:最大径1cmT1b:12cmT2T22cm侵犯粘膜和粘膜下，和/或微小(3mm)侵犯浆膜下/阑尾系膜24cm，或侵犯盲肠T3T32cm，和/或广泛(3mm)侵犯浆膜下/阑尾系膜4cm，或侵犯回肠T4T4侵犯腹膜/其它器官侵犯邻近器官或结构如腹壁或骨骼肌局限于胰腺，2 cm局限于胰腺，24 cm局限于胰腺 4 cm,或侵犯十二指肠/胆管扩散至胰周,但未侵犯大血管壁侵犯邻近器官或大血管壁侵犯大血管壁 ENETSAJCCT1T2T3T4局限于胰腺，2cm局限于胰腺，2cm
