7例肺腺癌转化小细胞癌患者的临床病理特征分析

Analysis of clinicopathological features of seven patients with lung adenocarcinoma translating to small cell lung cancer

目的:分析总结肺腺癌转化为小细胞癌的临床病理特征.方法:回顾性分析2014年1月至2018年12月7例于河北医科大学第四医院确诊为肺腺癌转化为小细胞肺癌(small cell lung cancer,SCLC)患者的临床、病理及随访资料.结果:随访截至2020年6月1日.肺腺癌发生小细胞癌转化的中位时间为31个月,转化前应用酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)的中位时间为14个月.3例患者的转化部位与原发部位相同.7例患者转化前神经元特异性烯醇化酶(neuron-specific enolase,NSE)水平均升高,病情进展部位多为多个部位,肺、骨、脑、胸膜及淋巴结常见.7例患者转化后的免疫组织化学指标显示TTF1均为阳性,而Napsin A均为阴性,Syn、CD56、AE1/AE3均为阳性,Ki67均为高表达,PD-L1均不表达转化后基因检测显示,6例患者仍保持原有EGFR基因突变类型.转化后治疗主要为以化疗为主的综合治疗,中位无进展生存期为6个月,5例患者死亡,中位生存时间为10个月.结论:肺腺癌一旦发生小细胞癌转化,疾病进展迅速,生存期短.肺腺癌EGFR E19突变及接受靶向治疗的患者发生小细胞癌转化的几率较大,首诊至转化的时间多>2年,转化前病情常呈多部位进展且NSE升高,转化后患者仍保持原有EGFR基因突变型.

Objective:To analyze the clinicopathological features of small cell lung cancer transformed from lung adenocarcinoma.Methods:We retrospectively analyzed the clinical and pathological characteristics and follow-up data of seven patients who had been diagnosed with small cell lung cancer transformed from lung adenocarcinoma following treatment from January 2014 to December 2018 at the Fourth Hospital of Hebei Medical University.Results:The latest follow-up had been performed on June 1,2020.The median time of small cell lung cancer transformation from lung adenocarcinoma following treatment was 31 months;the median time of tyrosine kinase inhibitor(TKI)application before transformation is 14 months.Three patients had transformation at the same site as the original.Seven patients had higher levels of neuron-specific enolase(NSE)before transformation.Before the transformation,disease progression mostly occurred at multiple sites,and the lung,bone,brain,pleura,and lymph nodes were commonly affected.In all cases,immunohistochemical indicators after transformation showed that thyriod transcription factor-1(TTF-1)was positive;Napsin A was negative;Syn,CD56,and AE1/AE3 were positive;Ki67 expression was high;and PD-L1 expression was negative.Genetic testing after transformation showed that six patients had maintained the original mutant EGFR gene.Treatments after transformation were mainly comprehensive,based on chemotherapy.The median progression-free survival time after transformation was 6 months,and median survival time after transformation for five patients who died was 10 months.Conclusions:Once lung adenocarcinoma undergoes transformation to small cell lung cancer,the disease progresses rapidly,and survival time is short.Patients with lung adenocarcinoma due to EGFR E19 mutation who undergo EGFR-TKI therapy are more prone to small cell lung cancer transformation,and the time to transformation generally exceeds 2 years.The sites of disease progression before transformation are often multiple,and NSE is increased.After transformation,patients generally maintain the original EGFR mutation.