P40及TTF-1共表达非小细胞肺癌7例临床病理分析

Clinicopathological analysis of 7 cases of non-small cell lung cancer with co-expression of P40 and TTF-1

目的:P40及甲状腺转录因子1(thyroid transcription factor-1,TTF-1)被广泛应用于肺鳞状细胞癌和肺腺癌的鉴别诊断,两者共表达的非小细胞肺癌(non-small cell lung cancer,NSCLC)病例则极为罕见。本研究旨在探讨P40及TTF-1共表达NSCLC的临床及病理学特点。方法:收集山东大学附属威海市立医院2019年5月至2023年9月确诊的7例P40及TTF-1共表达NSCLC患者,分析其临床及病理学特点,采用基因检测及免疫组织化学染色检测相关指标表达情况,并随访患者。结果:7例患者均为男性,年龄57~80(中位数71)岁,除1例外其余6例均有吸烟史;6例患者肿瘤为外周型,1例为中央型;肿物长径为2.0~8.5(中位数5.8)cm。5例患者出现肿瘤转移。2例病死患者第1次确诊至死亡的时间间隔分别为12和55个月。HE染色示肿瘤分化差,肿瘤细胞排列紧密,呈片状、巢团样分布,可见坏死及炎细胞浸润,肿瘤细胞大小不一,形态多样,细胞质多呈嗜酸性,细胞核大,形状不规则,核仁易见。免疫组织化学染色可见P40、TTF-1、P63、细胞角蛋白(cytokeratin,CK)7、CK5/6广泛阳性表达,而天冬氨酸肽酶A(Napsin A)基本上为阴性表达。基因检测除1例为TP53突变外,其余无突变。结论:P40及TTF-1共表达NSCLC是一种罕见的亚型,其发病率低,但恶性程度高,好发于有吸烟史的老年人,大部分病例发现时即偏向晚期,病理结果显示其为既不属于腺癌也不属于鳞状细胞癌的低分化肿瘤。

Objective:P40 and thyroid transcription factor-1(TTF-1)are widely used in the differential diagnosis of lung squamous cell carcinoma and lung adenocarcinoma.However,co-expression of both markers in non-small cell lung cancer(NSCLC)cases is extremely rare.This study aims to investigate the clinical and pathological characteristics of NSCLC with co-expression of P40 and TTF-1.Methods:Seven cases of NSCLC with co-expression of P40 and TTF-1 diagnosed from May 2019 to September 2023 at Weihai Municipal Hospital affiliated to Shandong University were collected.Clinical and pathological characteristics were analyzed.Gene detection and immunohistochemical testing of relevant markers were performed,and patient follow-up was conducted.Results:All 7 patients were male,aged 57 to 80(median 71)years.Except for one patient,all others had a history of smoking.Six patients had peripheral tumors and one had a central type,with tumor sizes ranging from 2.0 to 8.5(median 5.8)cm.Five patients had tumor metastasis.The two deceased patients survived for 12 and 55 months from initial diagnosis to death,respectively.The tumors showed poor differentiation,dense arrangement of tumor cells with patchy and nest-like distribution,and inflammatory cell infiltration by HE staining.Tumor cells varied in size and shape,with eosinophilic cytoplasm and irregularly shaped nuclei with visible nucleoli.Immunohistochemical staining showed widespread positive for P40,TTF-1,P63,cytokeratin(CK)7,and CK5/6,while Napsin A was mostly negative.Gene testing revealed TP53 mutation in one case and no mutations in the others.Conclusion:Co-expression of P40 and TTF-1 in NSCLC is a rare subtype with low incidence but high malignancy,predominantly affecting elderly individuals with a history of smoking.Most cases are diagnosed at an advanced stage,and pathological results show poorly differentiated tumors that do not belong to adenocarcinoma or squamous cell carcinoma.