Objective: To investigate the clinicopathologic features and genetic profile of large cell lung carcinoma (LCC) redefined by new classification. Methods: Basing on 2015 WHO classification criteria in redefining large cell lung carcinoma, the expression of specific markers (TTF1, Napsin A, p40, CK5/6, CK, vimentin and ZEB1) was detected by immunohistochemistry and D-PAS staining in 303 surgically-removed lung specimens previously diagnosed as large cell lung carcinoma. The clinicopathologic and genetic characteristics (including EGFR, KRAS, BRAF, ALK and ROS1 gene mutation) were analyzed. Results: Based on the new definition of LCC, 116 cases (116/303, 38.3%) of LCC formerly diagnosed were reclassified as solid adenocarcinoma, 49 cases (49/303, 16.2%) as squamous cell carcinoma, 6 cases (6/303, 2.0%) as adenosquamous carcinoma, 22 cases (22/303, 7.3%) as spindle cell carcinoma and only 110 cases (110/303, 36.3%) as large cell carcinoma. Redefined LCCs were characterized as middle-age (range 40-80), male (102/110, 92.7%) and smoking patients (64/110, 58.2%) with intermediate-advanced stage. Among 110 cases, 9 cases with EGFR mutation and 10 cases with KRAS mutation and 1 case with ALK fusion were found. No BRAF and ROS1 alterations were identified. Conclusions: According to the new classification, LCCs formerly diagnosed are mostly reclassified as adenocarcinoma and non-keratinizing squamous cell carcinoma. The newly defined LCC may significantly benefit from clinical therapy.
目的： 探讨新定义下的肺大细胞癌临床病理特征及基因突变情况。 方法： 以2015版WHO肺癌新分类的大细胞肺癌诊断标准，采用免疫组织化学[甲状腺转录因子1、Napsin A、p40、细胞角蛋白(CK)5/6、广谱CK、波形蛋白和ZEB1]和消化过碘酸雪夫(D－PAS)染色的方法，对以往诊断的303例大细胞肺癌(手术切除标本)进行回顾性分析，并对符合新定义标准的大细胞肺癌进行基因突变检测，包括表皮生长因子受体(EGFR)、KRAS、BRAF、间变性淋巴瘤激酶(ALK)、ROS1基因。 结果： 按新的诊断标准，经对免疫组织化学及D－PAS染色结果分析，原303例大细胞肺癌中，实性型腺癌116例(116/303，38.3%)，非角化型鳞癌49例(49/303，16.2%)，梭形细胞癌22例(22/303，7.3%)，腺鳞癌6例(6/303，2.0%)，符合新定义的大细胞癌只有110例(110/303，36.3%)。临床病理特征显示大细胞癌好发于中老年(年龄范围40～80岁)、男性(102/110，92.7%)、吸烟(64/110，58.2%)的中晚期患者。对110例符合新标准的大细胞癌进行基因检测，发现9例EGFR基因突变、10例KRAS基因突变和1例ALK基因融合，而BRAF、ROS1均为野生型。 结论： 按新的诊断标准，以往诊断的大细胞肺癌实则绝大多数为腺癌和非角化型鳞癌，新的诊断标准有利于临床治疗方案的确定。.
Keywords: Carcinoma, large cell; DNA mutational analysis; Diagnosis, differential; Immunohistochemistry; Lung neoplasms.