Liu H S, Zhang Y J, Huang B, Ge H Y, Cai L B, Chen M M
Department of Pathology, the First People's Hospital of Xiaoshan District, Hangzhou 311200, China.
Department of Pathology, the Second People's Hospital of Xiaoshan District, Hangzhou 311241, China.
Zhonghua Bing Li Xue Za Zhi. 2024 Nov 8;53(11):1111-1116. doi: 10.3760/cma.j.cn112151-20240513-00312.
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). 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. 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. 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.
探讨p40与甲状腺转录因子1（TTF1）共表达的非小细胞肺癌（NSCLC）的临床病理特征、分子病理学特征及预后。收集了2016年1月至2023年12月在中国杭州萧山区第一人民医院诊断的6例p40与TTF1共表达的NSCLC患者的临床和病理资料。同时回顾了相关文献。p40与TTF1共表达的NSCLC常见于男性吸烟者，诊断时多为Ⅲ-Ⅳ期。显微镜检查显示，肿瘤细胞呈实性巢状和片状排列，异型性明显，可见核分裂象。未见明显的角化或腺管形成证据。肿瘤细胞弥漫性共表达p40和TTF1，表现出鳞状细胞癌和腺癌的双重免疫表型特征。对4例p40与TTF1共表达的NSCLC进行分子检测，发现存在常见的表皮生长因子受体（EGFR）突变，以及NRAS突变（突变率为2.09%）、棘皮动物微管相关蛋白样4-间变淋巴瘤激酶（EML4-ALK）突变（突变率为24.77%）和磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（PIK3CA）突变（外显子10 c.1658 G>C p.S553T，突变率为4.32%）。所有6例肿瘤均为低分化，侵袭性强，预后差。6例患者中有4例发生广泛转移，在诊断或初始治疗后7至30个月内死亡。p40与TTF1共表达的NSCLC具有独特的临床病理特征、免疫表型、分子改变和临床结局，其特点是进展迅速，预后不良。病理学家应警惕识别这一实体，以避免误诊和漏诊。
