TP53, NOTCH2, and STK11 Mutations in a Rare Tumor of non-Small Cell Lung Carcinoma with Diffuse Coexpression of TTF1 and p40 in the Same Tumor Cells

Abstract

Introduction. Five cases of non-small cell lung carcinoma (NSCLC) with diffuse coexpression of TTF1 and p40 in the same tumor cells (hereafter referred to as TTF1/P40-NSCLC) have been reported since 2015. It was considered a new entity of NSCLC occurred in aged male smokers with poorly differentiated carcinomas and a similar molecular signature harboring a TP53 mutation. Methods. We report an extremely rare tumor of TTF1/P40-NSCLC. Morphological observation and immunohistochemical examination were performed, clinical and molecular features were summarized, and a review of the relevant literature was provided. Results. The tumor showed a solid growth pattern with patchy necrosis, and glandular and squamous pattern were not obvious. The tumor cells proliferated within the bronchial epithelium. Spreading through air spaces of tumor cells were observed. A peculiar immunohistochemical phenotype of diffuse and strong positivity for TTF1 (8G7G3/1) and p40 in the same tumor cells was detected. Additionally, the tumor cells were positive for KRT7 and KRT20, while negative for PD-L1 (22C3). Negative P53 (null) Immunohistochemistry (IHC) staining indicated mutational status and the Ki67 index was 80%. Molecular investigation was performed using whole exome sequencing, and TP53, NOTCH2, and STK11 mutations were detected. The patient remained alive over a follow-up period of 22 months without tumor recurrence or metastasis. Conclusions. We describe an unusual tumor of TTF1/P40-NSCLC harboring TP53, NOTCH2 and STK11 mutations. These gene mutations may be helpful in providing additional therapeutic possibilities. Our report offers further insight into this rare tumor.