高级别胃肠胰神经内分泌肿瘤-NET G3的临床病理特征分析

Clinicopathologic features of high-grade G3 gastroenteropancreatic neuroendocrine tumors

目的:分析高级别胃肠胰神经内分泌肿瘤(high-grade G3 gastroenteropancreatic neuroendocrine tumors,GEP NET G3)的临床病理特征及生存预后影响因素。方法:回顾性分析2012年9月至2019年7月间北京大学肿瘤医院收治的86例GEP NET G3,收集临床病理及随访资料,采用单因素Log-rank检验和多因素Cox回归模型进行预后影响因素分析。结果:86例GEP NET G3的原发肿瘤部位包括胰腺(40例)、胃肠(37例)以及原发肿瘤不明(9例)。镜检肿瘤均分化良好,呈器官样、巢状生长,局灶可见假腺样、细条索样或缎带样结构。免疫组织化学分析显示,肿瘤的Ki-67指数范围为21%~60%,中位值为30%,生长抑素受体2(somatostatin receptor type 2,SSTR2)的阳性率为83.9%(26/31),在检测病例中没有发现微卫星不稳定和P53异常表达(分别为0/24、0/11)。生存分析表明,获得随访的76例患者,27例患者死亡,中位生存时间为48.6(26.6~70.6)个月,确诊时有无远处转移和能否进行根治性手术切除对患者的总生存影响差异有统计学意义(P<0.05),但患者的年龄、性别、原发肿瘤部位、确诊时血清神经元特异性烯醇化酶(neuron specific enolase,NSE)水平以及Ki-67指数对患者的总生存影响无显著差异(P>0.05)。多因素分析显示,确诊时有远处转移是影响患者生存的独立危险因素(P=0.01;HR=7.33,95%CI:1.56~34.10)。结论:GEP NET G3的确诊依赖于组织病理学和免疫组织化学检测,易发生远处转移是其临床特点和主要的预后影响因素。

Objective:To analyze the clinicopathological features and prognostic factors of high-grade G3 gastroenteropancreatic neuroendocrine tumors(GEP NETs).Methods:A retrospective analysis was conducted on 86 patients diagnosed with G3 GEP NET and treated at our hospital from September 2012 to July 2019.All clinical and pathological data were summarized.The univariate log-rank test and multivariate Cox regression model were used to analyze the prognostic factors.Results:Among the 86 patients with G3 GEP NET,the primary tumor sites were the pancreas,the gastrointestinal tract,and unidentified in 40,37,and 9 patients,respectively.Microscopically,the tumors were well-differentiated and showed an organoid or a nest-like growth pattern,with focal pseudo-adenoid,fine cord,or ribbon-like structures.Immunohistochemical analysis showed that the Ki67 index ranged from 21%to 60%,with a median value of 30%.The positive expression rate of SSTR2 was 83.9%(26/31),and no microsatellite instability or abnormal expression of p53 was found in the detected cases(0/24 and 0/11,respectively).Follow-up was attended by 76 patients,of whom 27(35.5%)died during the period.The median survival time was 48.6 months(95%confidence interval[CI]:26.6-70.6 months).Univariate analysis showed that radical resection and distant metastasis could significantly influence the overall survival(P<0.05),but there were no significant differences in age,sex,primary site,serum NSE(neuron specific enolase,NSE)level or Ki67 index(P>0.05).Multivariate analysis showed that distant metastasis at diagnosis was an independent risk factor for the patients'overall survival(P=0.01,hazards ratio=7.33,95%CI:1.56-34.10).Conclusion:The diagnosis of G3 GEP NET depends on histopathological morphology and immunohistochemistry.Distant metastasis is a major clinical feature and prognostic factor.