Clinicopathological characteristics and prognostic factors of gastric neuroendocrine neoplasms: an analysis of 117 cases
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摘要:
目的 探讨胃神经内分泌肿瘤（neuroendocrine neoplasm，NEN）的临床病理特征和预后因素。 方法 收集天津医科大学肿瘤医院2011年3月至2017年12月收治的胃NEN病例，依据WHO（2010年版）分类复核，分析不同分类胃NEN临床病理特征，并进行生存分析。 结果 在117例胃NEN中，神经内分泌瘤（neuroendocrine tumor，NET）G1、NET G2、神经内分泌癌（neuroendocrine car? cinoma，NEC）和混合性腺神经内分泌癌（mixed adenoneuroendocrine carcinoma，MANEC）分别为13例（11.1%）、6例（5.1%）、57例（48.7%）和41例（35.1%）。胃NET G1/G2以多发肿物为主，肿物直径小，浸润深度浅，淋巴结和远处转移少见，确诊时分期较早；治疗方式包括胃镜黏膜下剥离术和根治性手术；大多数胃NET G1/G2包含NET的前驱病变；患者的预后较好。胃NEC和MANEC以单发肿物为主，肿物直径大，浸润深度深，淋巴结和远处转移多见，确诊时多为进展期；全部患者行手术切除，且大部分进行了辅助治疗。胃NEC以大细胞型和分化差为主，胃MANEC的神经内分泌和腺癌成分组成形式多样；胃NEC和MANEC患者的预后均较差，但影响两者无进展生存期和总体生存期的预后因素不同。 结论 胃NEN是一组异质性肿瘤，不同分类的胃NEN具有不同的临床病理特征，并且预后也存在差异。需要多中心大样本研究来完善胃NEN的分类，并探索预后相关因素。 Abstract:Objective To explore the clinicopathological characteristics and prognostic factors of gastric neuroendocrine neoplasm (NEN). Methods Clinicopathological parameters and follow-up data collected from 117 patients with gastric NEN at Tianjin Medical University Cancer Institute and Hospital from March 2011 to December 2017 were reviewed, classified, and graded according to World Health Organization (WHO) 2010 classification. Clinicopathological characteristics of different types and grades of gastric NEN were compared and survival analysis was performed. Results Among the 117 cases confirmed as gastric NEN, this entire cohort comprised 13 cases (11.1%) of neuroendocrine tumor (NET) G1, 6 cases (5.1%) of NET G2, 57 cases (48.7%) of neuroendocrine carcinoma (NEC), and 41 cases (35.1%) of mixed adenoneuroendocrine carcinoma (MANEC). Gastric NET G1 and G2 typically consisted of multiple small tumors with shallow invasion and infrequent lymphatic and distant metastases at early stages at the time of diagnosis. The treatment of patients with gastric NET included endoscopic submucosal dissection and radical surgical resection. Precursor neuroendocrine lesions were detected in most cases. The patients with gastric NET G1 and G2 had a good prognosis. Gastric NEC and MANEC mostly consisted of single large tumors with deep infiltration, and common lymphatic and distant metastases at advanced stages when the diagnoses were confirmed. All the patients with gastric NEC and MANEC underwent surgical resection, and most received adjuvant therapy. Histopathological changes of gastric NEC were characterized by large cells and poorly differentiated tumors, while gastric MANEC had various forms of neuroendocrine and adenocarcinoma components. The prognosis of patients with gastric NEC and MANEC was poor for both; however, the predictors of progression-free survival and overall survival were different between gastric NEC and MANEC. Conclusions Gastric NEN are a group of heterogeneous tumors with different clinicopathological features and prognosis. More multicenter studies with large sample sizes are still needed to improve the classification of gastric NEN and explore the prognostic factors. -
Key words:
- stomach /
- neuroendocrine neoplasm (NEN) /
- classification /
- pathology /
- prognosis
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图 2 胃NET G1/G2的典型组织病理学图像
A~C：1例胃NET G1的H&E及免疫组织化学染色图像（200×），依次为H&E、Syn（+）、Ki-67（<1%+）；D~E：1例胃NET G1伴随NET前驱病变的组织学图像（200×），依次为H&E和Syn（+），箭头提示神经内分泌细胞微结节样增生；F~H：1例胃NET G2的H&E及免疫组织化学染色图像（200×），依次为H&E、CgA（+）、Ki-67（5%+）；I：1例胃NET G2淋巴结转移的H&E图像（200×），箭头指示转移性NET
图 3 胃NEC的典型组织病理学图像
A~D：1例大细胞型NEC的H&E及免疫组织化学染色图像（200×），依次为H&E、Syn（+）、CgA（+）、Ki-67（70%+）；E~H：1例小细胞型NEC的H&E及免疫组织化学染色图像（200×），依次为H&E、Syn（+）、CgA（+）、Ki-67（90%+）；I~L：1例分化好且Ki-67<55%的NEC的H&E及免疫组织化学染色图像（200×），依次为H&E、Syn（+）、CgA（-）、Ki-67（40%+），本例符合新近提出的“高增殖活性的NET G3”
图 4 57例胃NEC患者的单因素生存分析
A~D：与患者PFS相关的单因素生存曲线图，依次为肿瘤个数、肿瘤细胞类型、有无远处转移和分期；E~ I：与患者OS相关的单因素生存曲线图，依次为肿瘤个数、肿瘤细胞类型、有无远处转移、分期和随访期间复发/转移
图 5 胃MANEC的典型组织病理学图像
A~C：1例“碰撞型”MANEC的H&E（40×）及免疫组织化学染色（100×）图像，依次为H&E（神经内分泌癌与腺癌两种成分相邻但不交叉，有分界）、Syn（NEC成分+，AC成分-）、CK8/18（两种成分均+）。箭头指示NEC成分（大细胞型），星指示AC成分（中分化管状腺癌）；D~F：1例“组合型” MANEC的H&E（200×）及免疫组织化学染色（400×）图像，依次为H&E（神经内分泌癌与腺癌两种成分交叉混合，无明显分界）、Syn（NEC成分+，AC成分-）、CK8/18（两种成分均+）。箭头指示NEC成分（大细胞型），星指示AC成分（印戒细胞癌）；G~I：1例“双泌型”MANEC的H&E（200×）、免疫组织化学染色（200×）及PAS特殊染色（200×）图像，依次为H&E（肿瘤细胞同时分泌黏液与表达神经内分泌标记物）、Syn（+）、PAS（+）
图 6 41例胃MANEC患者的单因素生存分析
▶A~E：与患者PFS有关的单因素生存曲线图，依次为肿物直径、有无淋巴结转移、有无远处转移、分期和肿瘤成分组成形式；F~K：与患者OS有关的单因素生存曲线图，依次为有无淋巴结转移、有无远处转移、分期、肿瘤成分组成形式、淋巴结转移成分和随访期间复发/转移
表 1 117例胃NEN的WHO 2010分类及其临床病理特征n（%）
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