肺肠型腺癌患者临床病理特征分析

Clinicopathological Characteristics of Patients with Pulmonary Enteric Adenocarcinoma

目的总结并探讨肺肠型腺癌(PEAC)患者的临床病理特点,提高临床医生对该疾病的认识。方法回顾性选取2015年8月至2020年12月在郑州大学第一附属医院经病理诊断为PEAC的24例患者,并对其临床特征、实验室资料、影像学表现、病理特征、治疗方法进行分析。结果24例PEAC患者中男9例(37.5%),女15例(62.5%);年龄23~83(63.12±13.56)岁;多以咳嗽(37.5%)、咯血(12.5%)、胸闷(8.3%)为主要症状,6例(25.0%)患者无明显症状;肿瘤标志物检测显示神经元特异性烯醇化酶(NSE)、癌胚抗原(CEA)、糖类抗原19-9(CA19-9)、CA153有不同水平的升高,分别为2例(8.3%)、16例(66.7%)、16例(66.7%)、12例(50.0%);影像学无特异性表现,多表现为单一结节样病灶,右肺15例(62.5%),左肺6例(25.0%),有3例(12.5%)表现为双肺多发结节;发生脑转移7例(7/18),骨转移10例(10/18);肿瘤细胞不同程度表达NapsinA(2/11)、甲状腺转录因子1(TTF1)(4/23)、细胞角蛋白7(CK7)(17/19)、尾型同源盒转录因子2(CDX2)(11/17)、Villin(15/16)、CK20(16/22);基因检测发现Kirsten鼠肉瘤基因(KRAS)突变10例(41.7%),表皮生长因子受体(EGFR)突变2例(8.4%),未发现间变性淋巴瘤激酶(ALK)基因突变信号;15例(62.5%)接受含铂双药治疗,4例(16.7%)接受手术切除并术后化疗,1例(4.2%)口服靶向药物治疗。结论PEAC是一种特殊类型的肺腺癌,难以与经典型肺腺癌及肺转移性结直肠癌相鉴别,详细病史、组织病理学异质性、CK7联合肠源性免疫标志物(CDX2、Villin、CK20)阳性以及KRAS基因突变率高是该疾病诊断的要点,在治疗上目前与肺腺癌的治疗方案保持一致。

Objective To summarize and discuss the clinicopathological characteristics of patients with pulmonary enteric adenocarcinoma(PEAC)and improve clinicians’awareness of the disease.Methods A total of 24 patients who were pathologically diagnosed as PEAC in the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2020 were retrospectively enrolled,and the clinical features,laboratory tests,imaging manifestations,pathological features and treatment plans were analyzed.Results There were 9 males(37.5%)and 15 females(62.5%)in 24 patients with PEAC,and the age ranged from 23 to 83(63.12±13.56)years.Cough(37.5%),hemoptysis(12.5%)and chest tightness(8.3%)were the main symptoms,and 6 patients(25.0%)had no obvious symptoms.The levels of neuron-specific enolase(NSE),carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9)and CA153 were increased in the detection of tumor markers,which were 2 cases(8.3%),16 cases(66.7%),16 cases(66.7%),12 cases(50.0%),respectively.There were no specific imaging findings,most of them were single nodular lesions,15 cases(62.5%)of the right lung,6 cases(25.0%)of the left lung and 3 cases(12.5%)showed multiple nodules in both lungs.Brain metastasis occurred in 7 cases(7/18)and bone metastasis occurred in 10 cases(10/18).Tumor cells expressed NapsinA(2/11),thyroid transcription factor 1(TTF1)(4/23),cytokeratin 7(CK7)(17/19),caudal type homeobox transcription factor 2(CDX2)(11/17),Villin(15/16)and CK20(16/22)with different degrees.Gene detection showed that Kirsten rat sarcoma viral oncogene(KRAS)mutation occured in 10 cases(41.7%),epidermal growth factor receptor(EGFR)mutation occured in 2 cases(8.4%),and no anaplastic lymphoma kinase(ALK)gene mutation signal was found.15 cases(62.5%)received platinum containing dual drug therapy,4 cases(16.7%)received surgical resection and postoperative chemotherapy,and 1 case(4.2%)received oral targeted drug therapy.Conclusion PEAC is a special type of lung adenocarcinoma,which is difficult to distinguish from classical lung adenocarcinoma and pulmonary metastatic colorectal cancer.Detailed medical history,histopathological heterogeneity,positive CK7 combined intestinal derived immune markers(CDX2,Villin,CK20)and high mutation rate of KRAS gene are the key points of the diagnosis of the disease.At present,it is consistent with the treatment scheme of lung adenocarcinoma.