Objective To investigate the clinicopathological features and risk factors of lymph node metastasis of gastrointestinal neuroendocrine neoplasms (GI-NENs).Methods The retrospective case-control study was conducted.The clinicopathological data of 467 patients with GI-NENs who were admitted to the Fourth Hospital of Hebei Medical University from January 2006 to December 2015 were collected.Observation indicators:(1) occurrence sites and pathological classification of GI-NENs;(2) pathological characteristics of surgical specimens of GI-NENs;(3) univariate analysis and multivariate analysis affecting lymph node metastasis of GI-NENs:sex,age,tumor location,tumor diameter,pathological classification,pathological stage and tumor invasive depth.The univariate analysis and multivariate analysis were respectively done using the chi-square test and Logistic regression model.Results (1) Occurrence sites and pathological classification of GI-NENs:of 467 patients with GI-NENs,tumors of 304,15,7,14 and 127 patients were located at stomach,duodenum,small intestine,colon and rectum,respectively.Tumor diameter was 0.3-12.0 cm,with an average diameter of 2.2 cm.Of 467 patients with GI-NENs,G1 and G2 of neuroendocrine tumors (NETs),G3 of neumendocfine carcinomas (NECs) and mixed adenoneuroendocfine carcinomas (MANECs) were respectively detected in 209,64,146 and 48 patients.Lymph node metastasis rate of GI-NENs was 31.48％ (147/467).(2) Pathological characteristics of surgical specimens of GI-NENs:NETs were high-differentiated NENs.Ceils of NETs were solid and nest-,trabeculum-and tubular-shaped,and consisted of small or medium cells,with moderate amount or massive cytoplasms,round or oval nucleus,particle-shaped chromatin,unobvious nucleolus and positive endocrine markers.There were abundant of small blood vessels and surrounding fibrous stroma in peripheral tumor cell nests.NECs were low-differentiated NENs and included small cell carcinoma and large cell NEC.Cells of small cell carcinoma were small round or oval and looked similar to lymphocytes,with few amount cytoplasms,fine granularshaped or hyperchromatic nucleus and common mitosis figures.Cells of large cell NEC were large and greater than 3 lymphocytes,arrayed in organoid-or chrysanthemum-shape,with massive cytoplasms,coarse particle-shaped chromatin,obvious nucleus,clear mitosis figures and large laminar-shaped necrosis.There were different positive expressions of endocrine markers between small cell carcinoma and large cell NEC.MANECs had the characteristics of glandular cavity formation of traditional adenocarcinoma and NENs.Results of immunohistochemical staining in 467 patients showed that Ki-67 of 467 patients was positive;CD56 in 379 of 428 with CD56 test was positive;synaptophysin (Syn) in 416 of 422 with Syn test was positive;cytokeratin (CK) in 354 of 396 with CK test was positive;chromogranin (CgA)in 264 of 388 with CgA test was positive;neuron specific enolase (NSE) in 287 of 346 with NSE test was positive.(3) Univariate analysis and multivariate analysis affecting lymph node metastasis of GI-NENs:results of univariate analysis showed that sex,tumor location,tumor diameter,pathological classification,pathological satge and tumor invasive depth were related factors affecting lymph node metastasis of patients with GI-NENs (X2 =20.654,18.182,26.788,184.709,163.738,195.391,P＜ 0.05).Results of multivariate analysis showed that pathological classification and pathological stage were independent influenced factors affecting lymph node metastasis of patients with GI-NENs (HR =2.129,7.171,95％ confidence interval:1.273-3.561,-2.327-22.098,P＜0.05).Conclusions GI-NENs are mostly located on the stomach and rectum.Results of immunohistochenical staining could help diagnosis of GI-NENs.Pathological classification and pathological stage are independent influenced factors affecting lymph node metastasis of patients with GI-NENs.%目的 探讨胃肠道神经内分泌肿瘤(GI-NENs)的临床病理特征及淋巴结转移危险因素.方法 采用回顾性病例对照研究方法.收集2006年1月至2015年12月河北医科大学第四医院收治的467例GI-NENs患者的临床病理资料.观察指标:(1)GI-NENs的发生部位和病理学分型.(2) GI-NENs手术切除标本的病理学检查特征.(3)影响GI-NENs淋巴结转移的单因素和多因素分析:性别、年龄、肿瘤部位、肿瘤直径、病理学分级、病理学分期、肿瘤浸润深度.单因素分析采用x2检验,多因素分析采用Logistic回归模型分析.结果 (1) GI-NENs的发生部位和病理学分型:467例GI-NENs患者中,肿瘤位于胃304例,十二指肠15例,小肠7例,结肠14例,直肠127例;肿瘤直径为0.3 cm～12.0 cm,平均直径为2.2 cm.467例GI-NENs患者中,G1级神经内分泌瘤(NETs) 209例,G2级NETs 64例,G3级神经内分泌癌(NECs) 146例,混合性腺神经内分泌癌(MANECs) 48例.467例GI-NENs淋巴结转移率为31.48％(147/467).(2)GI-NENs手术切除标本的病理学检查特征:NETs属于高分化NENs,其瘤细胞特征性结构为实性巢状、小梁状或腺管状.细胞为均匀一致的小细胞或中等大小细胞,胞质中等量或丰富;核圆形或卵圆形,染色质颗粒状;核仁不明显;内分泌标记物表达阳性;瘤细胞巢周有丰富的小血管和纤维间质围绕.NECs属于低分化NENs.它包括小细胞癌和大细胞NEC.小细胞癌的细胞似淋巴细胞,小圆形或卵圆形,胞质稀少,核细颗粒状或深染,核分裂象常见.大细胞NEC的细胞体积大,常＞3个淋巴细胞,呈器官样、菊形团样排列,胞质丰富,染色质呈粗颗粒状,核仁明显,核分裂象易见,常伴大片状坏死.两者均不同程度阳性表达内分泌标记物.MANECs同时具有腺腔形成的传统型腺癌和NENs形态特点.467例GI-NENs患者免疫组织化学染色检测结果显示:467例Ki-67阳性;428例行CD56检测,379例阳性;422例行突触泡蛋白检测,416例阳性;396例行细胞角蛋白检测,354例阳性;388例行嗜铬粒蛋白检测,264例阳性;346例行神经元特异性烯醇化酶检测,287例阳性.(3)影响GI-NENs患者淋巴结转移的单因素和多因素分析:单因素分析结果显示:性别、肿瘤部位、肿瘤直径、病理学分级、病理学分期、肿瘤浸润深度是影响GI-NENs患者淋巴结转移的相关因素(X2=20.654,18.182,26.788,184.709,163.738,195.391,P＜0.05).多因素分析结果显示:病理学分级和病理学分期是GI-NENs患者淋巴结转移的独立影响因素(HR=2.129,7.171,95％可信区间:1.273～3.561,-2.327～22.098,P＜0.05).结论 GI-NENs最常见发生部位是胃和直肠.免疫组织化学染色检测有助于GI-NENs的诊断.病理学分级和病理学分期是GI-NENs患者淋巴结转移的独立影响因素.
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