Clinicopathological features and prognostic factors of neuroendocrine neoplasms at different sites in the digestive system
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摘要:
目的 探讨消化系统不同部位神经内分泌肿瘤（neuroendocrine neoplasms，NENs）的临床病理特征及预后因素。 方法 收集天津医科大学肿瘤医院2011年3月至2015年12月收治的284例消化系统NENs，分析比较不同部位NENs临床病理特征的异同，并进行生存分析。 结果 本研究中，消化系统NENs以胰腺部位最多见，其次为结直肠、胃。在胰腺NENs中，以G1（51.8%）和G2（35.8%）型为主，WHO分类与淋巴结转移、周围器官侵犯、神经侵犯有关（均P <0.05），但与患者的总生存无关；有远处转移的胰腺NENs患者总生存期更短（P <0.05）。结直肠NENs以NET G1为主（82.5%），大多经内镜下切除或经肛门直肠肿物切除；神经内分泌癌、有淋巴结转移、有远处转移和进展期患者的总生存期更短（均P <0.05）。与胰腺和结直肠相比，胃NENs中男性患者、年龄> 40岁的患者更多；神经内分泌癌和混合性腺神经内分泌癌比例更高、淋巴结转移和远处转移的比例更高；进展期的患者更多（均P <0.05）。WHO分类和有无淋巴结转移与胃NENs的总生存期有关（均P <0.05）。 结论 消化系统NENs是一组异质性肿瘤，不同部位的肿瘤具有不同的临床病理特征，并与欧美国家存在差异。仍需要大样本多中心研究来了解不同部位消化系统NENs的生物学行为及预后因素。 Abstract:Objective To explore the clinicopathological characteristics and prognostic factors of neuroendocrine neoplasms (NENs) at different sites in the digestive system. Methods The clinicopathological parameters and follow-up data were collected from 284 patients with NENs in the digestive system in Tianjin Medical University Cancer Institute and Hospital from March 2011 to December 2015. The incidence and clinicopathological features were compared between the cases of NENs at different sites and survival analysis was performed. Results In this study, NENs were detected mostly frequently in the pancreas, followed by the colorectum and stomach. In the pancreas, neuroendocrine tumor (NET) G1 (51.8%) and G2 (35.8%) accounted for a large proportion of NENs. World Health Organization (WHO) grades were related to lymph node metastasis, adjacent organ invasion, and nerve invasion (P <0.05 for all) but were not associated with the overall survival time of the patients. The patients with pancreatic NENs with distant metastasis had poor overall survival (P <0.05). Regarding colorectal NENs, most patients had NET G1 (82.5%), and the majority of patients were cured with endoscopic or transanal resection. Patients with NENs, lymph node metastasis, and distant metastasis had poor overall survival (P <0.05 for all). The ratio of male-to-female patients, proportion of patients aged older than 40 years, prevalence of neuroendocrine carcinomas (NECs) and mixed adenoneuroendocrine carcinomas (MANECs), presence of lymph node and distant metastasis, and presence of advanced stage tumors were greater in patients with gastric NENs than in patients with pancreatic and colorectal NENs (P <0.05 for all). WHO grades and lymph node metastasis were associated with the overall survival time of patients with gastric NENs (P <0.05 for both). Conclusions NENs in the digestive system are a group of heterogeneous tumors with different clinicopathological features at different sites. The distribution and clinicopathological features of Chinese patients with NENs in the digestive system are different from those of European and American patients. More multicenter studies with large sample sizes are still needed to understand the biological behaviors and prognostic factors of NENs at different sites in the digestive system. -
Key words:
- neuroendocrine neoplasms /
- stomach /
- intestines /
- pancreas /
- prognosis
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图 1 胃肠胰NENs的病理图像
A：1例直肠NET G1的H&E及免疫组织化学染色图像。肿物呈广基息肉样生长，经肛门内镜下切除。肿物位于黏膜下层，最大径0.8 cm，呈假菊形团样排列，细胞异型性小，核分裂象罕见。免疫组织化学Syn阳性、CgA阳性、Ki-67指数约1%。图像均为×200；B：1例胰腺NET G2的H&E及免疫组织化学染色图像。肿物位于胰体尾，体积4.0 cm×4.0 cm×3.5 cm，累犯脾周软组织，伴有肝转移（单发结节，直径约1 cm）。肿瘤细胞呈脑回状排列，细胞大小较一致，胞质细颗粒状，核染色质粗团块状（椒盐样），核分裂象5个/10高倍镜视野；可见肿瘤细胞围神经侵犯、脉管癌栓及肝转移。▶：神经内分泌瘤；➝：神经；❋：肝实质。免疫组织化学Ki-67指数约为5%。除肝转移H&E图像为×100，其余图像均为×200；C：1例胃NEC的H&E及免疫组织化学染色图像。肿瘤位于贲门，溃疡型，最大径6 cm。肿瘤为大细胞型，由弥漫不规则排列的片状细胞构成，可见地图样坏死，核分裂象>50个/10高倍镜视野。免疫组织化学Syn阳性、CgA阳性（核旁点状着色）、Ki-67指数约85%。除CgA免疫组织化学图像为×400，其余图像均为×200；D：1例胃MANEC的H&E及免疫组织化学染色图像。肿物位于胃体，呈表浅溃疡，体积约2 cm×1 cm。肿瘤位于黏膜内，由腺癌（中分化管状腺癌）和NEC（大细胞型）共同组成，各占50%。免疫组织化学：腺癌Syn阴性、CgA阴性、Ki-67指数约70%；神经内分泌癌Syn阳性、CgA阳性、Ki-67指数约为80%。▶：NEC；➝：腺癌。H&E和Ki-67免疫组织化学图像为×100，Syn和CgA免疫组织化学图像为×200
图 2 284例胃肠胰NENs临床病理参数相关的生存曲线
▶A：NET G1，G2，NEC和MANEC在不同部位所占的比例；B~I：年龄（B），直径（C），部位（D），WHO分类（E），NET G1、G2和NEC、MANEC（F），淋巴结转移（G），远处转移（H）和临床分期（I）等的生存分析
图 3 特定部位NENs的WHO分类与临床病理参数的关系及生存曲线
A：胰腺NETs与NEC/MANEC临床病理参数的比较；B：胰腺NENs远处转移的生存分析；C：结直肠NETs与NEC/MANEC临床病理参数的比较；D~ E：结直肠NENs淋巴结转移（D）和远处转移（E）的生存分析；F：胃NETs和NEC/MANEC临床病理参数的比较；G~H：胃NENs WHO分类（G）和淋巴结转移（H）的生存分析
表 1 263例原发胃肠胰NENs的部位分布及其临床病理特征 n（%）
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