支气管肺大细胞神经内分泌癌的临床和分子病理特点  

Clinical and molecular pathological features of bronchopulmonary large cell neuroendocrine carcinoma

作　　者：孟宇[1] 练延帮[2] 许跃 董军强[2] 宋敏[1] Meng Yu;Lian Yanbang;Xu Yue;Dong Junqiang;Song Min(Department of Oncology,First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Imaging and Nuclear Ward,Department of Radiology,First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;Department of Pathology,First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院肿瘤科,郑州450052 [2]郑州大学第一附属医院放射科影像与核医学病区,郑州450052 [3]郑州大学第一附属医院病理科,郑州450052

出　　处：《中华医学杂志》2022年第14期1020-1027,共8页National Medical Journal of China

基　　金：河南省医学科技攻关软科学(重点)项目(SBGJ2020002064)。

摘　　要：目的探讨支气管肺大细胞神经内分泌癌(LCNEC)的临床表现、影像和分子病理特征。方法回顾性分析2011—2021年郑州大学第一附属医院216例LCNEC患者的临床资料,分析其临床表现、肿瘤位置及大小、CT影像特征、免疫组化及分子病理特点,并与同期确诊的115例复合型小细胞癌(M-SCLC)对比。结果LCNEC患者中,男190例,女26例,年龄33~85岁,中位年龄65岁。首诊症状以咳嗽[106例(49.1%)]与痰中带血[48例(22.2%)]为主。肿瘤长径中位数4.7 cm,其中结节型55例(25.5%),肿块型161例(74.5%)。CT结果显示,LCNEC病变呈软组织密度,轻度强化的比例低于M-SCLC组(52.3%比74.8%,P<0.001)。相反,LCNEC患者瘤体中出现坏死(87.0%比58.3%,P<0.001)及钙化(26.9%比2.6%,P<0.001)的比例高于M-SCLC组。免疫组化结果显示,LCNEC中的CK阳性率高于M-SCLC(99.0%比90.5%,P<0.05),而TTF-1阳性率低于M-SCLC(51.6%比67.0%,P<0.05)。LCNEC组Ki-67阳性指数在50%~80%间的比例高于M-SCLC组(41.2%比25.2%),而在80%~100%间比例低于M-SCLC(51.9%比72.2%),而两组CD56(91.7%比94.6%,P=0.336)、Syn(83.8%比84.7%,P=0.838)和CgA(54.8%比50.0%,P=0.632)阳性率差异无统计学意义。分子病理检测结果显示,突变频率较高的位点主要位于TP53(54.5%)、RB1(36.4%)、KEAP1(18.2%)、MYC(18.2%)及PTEN(14.3%)等基因,肿瘤突变负荷(TMB)>25个突变/MB的比例为27.3%。结论LCNEC缺乏特异性临床表现,CT影像和M-SCLC有特征性鉴别点,分子病理有一定的突变频谱,确诊仍需要病理联合免疫组化综合判读,与M-SCLC的鉴别主要依靠光镜下细胞大小及核染色质模式。Objective To investigate the clinical manifestations,imaging,pathological and molecular features of bronchopulmonary large-cell neuroendocrine carcinoma(LCNEC).Methods The clinical data of 216 LCNEC patients in the First Affiliated Hospital of Zhengzhou University from 2011 to 2021 were analyzed retrospectively.The clinical manifestations,tumor location and size,characteristics of CT images,immunohistochemical and molecular pathological features were analyzed and compared with 115 cases of mixed small cell carcinoma(M-SCLC)diagnosed in the same period.Results Among the 216 LCNEC patients,there were 190 males and 26 females,with a median age of 65 years.The first symptoms of the patients were mainly cough(106 cases,49.1%)and bloody sputum(48 cases,22.2%).The median tumor length were 4.7cm,including 55 cases of nodular type(25.5%)and 161 cases of mass-forming type(74.5%).CT imaging results showed that LCNEC lesions had soft tissue density,and the proportion of slight enhancement lesions was significantly lower than that in M-SCLC group(52.3%vs 74.8%,P<0.001).In contrast,the proportion of necrosis(87.0%vs 58.3%,P<0.001)and calcification(26.9%vs 2.6%,P<0.001)in LCNEC patients was significantly higher than that in M-SCLC group.Immunohistochemical results showed that the positive rate of CK in LCNEC was significantly higher than that in M-SCLC(99.0%vs 90.5%,P<0.05),while the positive rate of TTF-1 was significantly lower than that in M-SCLC(51.6%vs 67.0%,P<0.05).In LCNEC group,the proportion of patients with Ki-67 positive index between 50% and 80% was significantly higher than that of M-SCLC(41.2%vs 25.2%),while the proportion between 80% and 100% was lower than that of M-SCLC(51.9%vs 72.2%).There was no significant difference in the positive rates of CD56(91.7%vs 94.6%,P=0.336),Syn(83.8%vs 84.7%,P=0.838)and CgA(54.8%vs 50.0%,P=0.632)in both tumor types.Molecular pathology results showed that frequent mutatios were TP53(54.5%),RB1(36.4%),KEAP1(18.2%),MYC(18.2%),and PTEN(14.3%),and the rate of tumor mutation burden whi

关 键 词：神经内分泌瘤 肺癌 大细胞神经内分泌癌 复合型小细胞癌 病理 医学影像 分子病理 

分 类 号：R734.2[医药卫生—肿瘤]