摘要
目的:探讨胰腺神经内分泌肿瘤(pancreatic neuroendocrine neoplasm,PanNEN)的临床病理特征和预后因素。方法:收集2011年1月至2018年12月天津医科大学肿瘤医院收治的胰腺NEN,依据世界卫生组织(WHO)消化系统肿瘤2019版分类进行复核,分析比较不同分类胰腺NEN临床病理特征的异同,并分别进行生存分析。结果:在最终确诊的182例PanNEN中,神经内分泌瘤(neuroendocrine tumor,NET)G1、NET G2、NET G3、神经内分泌癌(neuroendocrine carcinoma,NEC)和混合性神经内分泌-非神经内分泌肿瘤(mixed neuroendocrine-non-neuroendocrine neoplasm,MiNEN)分别为78例(42.9%)、82例(45.1%)、5例(2.7%)、15例(8.2%)和2例(1.1%)。临床病理特征方面,胰腺NEN分级越高,神经/脉管侵犯、淋巴结/远处转移等侵袭性行为越多见,诊断时进展期患者的比例越高(均P<0.05)。NEC的Ki-67指数均值显著高于NET G3(P<0.001),但二者在30%~60%区间有重叠。WHO2019版分类与总体生存(overall survival,OS)和无进展生存(progression-free survival,PFS)显著相关(均P<0.05)。对于NET G1患者,诊断时为进展期是OS和PFS较差的独立预后因素(分别HR=12.472,P=0.002;HR=10.56,P<0.0012)。对于NET G2患者,手术切除是OS较好的独立预后因素(HR=8.217,P=0.001),诊断时即有远处转移是PFS较差的独立预后因素(HR=26.137,P<0.001)。NEN G3的预后主要与Ki-67指数有关,但NET G3和NEC的截断值不同(NET G3:45%,NEC:70%)。结论:胰腺NEN是一组异质性肿瘤,不同WHO分类的胰腺NEN的临床病理特征及预后均不同。胰腺NEN以分化好的NET为主,但是部分NET在诊断时即见转移,术后可以复发/转移。NET G3与NEC的鉴别要点主要是肿瘤分化、细胞增殖活性、p53免疫组织化学染色等分子检测。治疗方面仍无统一标准,尤其对于未明确NET G3或NEC的NEN G3患者,需综合评估分级、分期,并监测疾病进展情况。未来仍需多中心大样本的研究来制定更加全面细致的诊疗标准。
Objective:To identify clinicopathological characteristics and prognostic factors of pancreatic neuroendocrine neoplasms(NENs).Methods:Pancreatic NEN cases treated at the Tianjin Medical University Cancer Institute and Hospital from January 2011 to December 2018 were reviewed and classified according to the 2019 World Health Organization(WHO)Classification.Clinicopathological characteristics were compared among different grades of pancreatic NENs,and survival analysis of all cases and each grade was performed.Results:Among 182 confirmed cases of pancreatic NENs,78(42.9%)had grade one(G1)neuroendocrine tumors(NETs),82(45.1%)had G2 NETs,5(2.7%)had G3 NETs,15(8.2%)had neuroendocrine carcinomas(NECs),and 2(1.1%)had mixed neuroendocrine-non-neuroendocrine neoplasms(MiNEN).Patients with higher-grade pancreatic NENs tended to exhibit aggressive behaviors such as neural or vascular invasion and metastasis to regional lymph nodes or distant tissues.When diagnosed,most patients were in advanced diseases stage(P<0.05 for all).The Ki-67 index in NEC was significantly higher than that in G3 NET(P<0.001);however,their Ki-67 index overlapped in the range from 30%to 60%.Both overall survival(OS)and progression-free survival(PFS)of patients with pancreatic NENs were significantly related to the 2019 WHO classification of the neoplasms(P<0.05 for both).For patients with G1 NET,advanced disease stage at the time of diagnosis was an independent predictor associated with poor OS and PFS[P=0.002,hazard ratio(HR)=12.472;P<0.001,HR=10.562].For patients with G2 NET,surgical resection was an independent predictor for longer OS(P=0.001,HR=8.217)and distant metastases at the time of diagnosis were independent predictors for shorter PFS(P<0.001,HR=26.137).The prognosis of patients with G3 NEN was related to the Ki-67 index;however,cutoff values stratifying G3 NET and NEC differed(G3 NET:45%,NEC:70%).Conclusions:Pancreatic NENs are heterogeneous tumors whose clinicopathological features and prognosis differ.Most pancreatic NENs are well-differentiated NETs,some of which metastasize at the time of diagnosis and can relapse or metastasize after surgery.Differentiation is the most important factor to distinguish G3 NET from NEC;moreover,tumor cell proliferation and molecular monitoring(including immunohistochemical staining of P53)can be useful for differential diagnosis.Currently,there is no standard treatment for these neoplasms,especially G3 NEN that cannot be confirmed as either G3 NET or NEC.Therefore,additional multicenter studies with large sample sizes are needed to formulate a more dedicated criterion for diagnosing and treating pancreatic NENs.
作者
姜雅慧
张靖宜
郭玉虹
罗烨
丁婷婷
孙燕
Yahui Jiang;Jingyi Zhang;Yuhong Guo;Ye Luo;Tingting Ding;SunYan(Department of Pathology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin Key Laboratory of Cancer Prevention and Therapy,Tianjin's Clinical Research Center for Cancer,Tianjin 300060,China)
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2019年第21期1107-1116,共10页
Chinese Journal of Clinical Oncology
基金
国家自然科学基金面上项目(编号:81472263和81871990)资助~~
关键词
胰腺
神经内分泌肿瘤
分类
病理
预后
pancreas
neuroendocrine tumor(NET)
classification
pathology
prognosis