Objective: To investigate the clinicopathological features, molecular pathology characteristics, and prognosis of non-small cell lung carcinoma (NSCLC) exhibiting co-expression of p40 and thyroid transcription factor1 (TTF1). Methods: Clinical and pathological data of six NSCLC cases with co-expression of p40 and TTF1 diagnosed at the First People's Hospital of Xiaoshan District, Hangzhou, China from January 2016 to December 2023 were collected. Relevant literature was also reviewed. Results: NSCLC with co-expression of p40 and TTF1 commonly occurred in male smokers and had been in stage Ⅲ-Ⅳ when diagnosis. Microscopic examination revealed that the tumor cells were arranged in solid nests and sheets with marked atypia and visible mitotic figures. There was no prominent evidence of keratinization or glandular formation. The tumor cells diffusely co-expressed p40 and TTF1, exhibiting a dual immunophenotype characteristic of both squamous cell carcinoma and adenocarcinoma. Molecular testing of four NSCLC co-expressing p40 and TTF1 revealed the presence of common EGFR mutations, as well as mutations of NRAS (mutation rate of 2.09%), EML4-ALK (mutation rate of 24.77%), and PIK3CA (exon 10 c.1658 G>C p.S553T, mutation rate of 4.32%). All six tumors were poorly differentiated, highly invasive, and associated with poor prognosis. Four of the six patients experienced widespread metastasis and died within 7 to 30 months after the diagnosis or initial treatment. Conclusions: NSCLC with co-expression of p40 and TTF1 exhibits distinct clinicopathological features, immunophenotypes, molecular alterations, and clinical outcomes, characterized by rapid progression and poor prognosis. Pathologists should be vigilant in recognizing this entity to avoid misdiagnosis and missed diagnosis.
目的： 探讨p40和甲状腺转录因子1（thyroid transcription factor 1，TTF1）共表达的非小细胞肺癌临床病理学、分子病理和预后等特征。 方法： 收集2016年1月至2023年12月杭州市萧山区第一人民医院诊断的6例p40和TTF1共表达的非小细胞肺癌，总结其临床病理资料，并回顾相关文献。 结果： 共表达p40和TTF1的非小细胞肺癌常见于吸烟男性，确诊时已处于Ⅲ~Ⅳ期。镜下观察：细胞呈实性巢片状分布，异型性明显，核分裂象可见，无明显角化和腺样结构证据。肿瘤分化差，肿瘤细胞弥漫p40和TTF1共表达，具有鳞状细胞癌与腺癌的双向免疫表型。本组中4例p40和TTF1共表达非小细胞肺癌患者分子检测结果，除了常见的表皮生长因子受体（EGFR）基因突变，还检测出NRAS基因突变（突变比例2.09%）、EML4与ALK发生融合基因变异（变异比例24.77%），PIK3CA基因突变（外显子10 c.1658 G>C p.S553t，突变比例4.32%）。另外这6例肿瘤均为低分化癌，易侵袭，预后较差。其中4例患者于确诊或治疗后7~30个月出现肿瘤全身扩散死亡。 结论： p40和TTF1共表达的非小细胞肺癌，具有独特的临床病理特征、免疫表型、分子改变和临床预后，病程进展快、患者预后差。病理医师应提高对其认识，避免误诊及漏诊。.