A rare case of non-small cell lung carcinoma with diffuse coexpression of TTF1 and p40 in the same tumour cells

Background: Three cases of non-small cell lung carcinoma (NSCLC) with diffuse co-expression of TTF1 and p40 in the same tumour cells have been reported since 2015, which may be an underrecognized new entity of the lung. All of the cases were aged male smoking patients, with poorly differentiated carcinomas, and a similar molecular signature harboring TP53 mutation. Case Presentation: A 75-year-old man who underwent lung cancer surgery was diagnosed as NSCLC with diffuse co-expression of TTF1 and p40 in the same tumour cells. Microscopically, the tumor showed solid growth pattern with patchy necrosis. Neither glandular nor squamous pattern were found. The carcinoma cells were round or polygonal shaped with obvious nucleoli and numerous mitoses. In some areas, the carcinoma cells proliferated within the bronchial epithelium. Spread through air spaces (STAS) and visceral pleura invasion can be observed. Immunohistochemistry(IHC) showed intense diffuse positivity for both TTF-1(8G7G3/1) and p40 in the same tumor cells. Tumor cells were positive for p63, CK7, CK20, E-cadherin, GPC-3, Oct3/4, focally positive for CK5/6, Vimentin, EGFR, and negative for NapsinA, CDX-2, SATB2, chromogranin, synaptophysin and PD-L1(22C3). Negative P53 IHC staining indicated mutational status and Ki-67 index was 80%. Molecular investigation was performed by Whole Exome Sequencing, and TP53 , Notch2 and STK11 mutations were detected. The patient remained alive over a follow-up period of 21 months and was free of tumour recurrence or metastasis. Conclusions: : NSCLC with diffuse co-expression of TTF-1 and p40 in the same tumor cells may be a new unique entity. Expression of both “adenocarcinoma” and “squamous” markers may be an implication for classification and clinical therapy. Our case offers further insight into this rare tumor.