Non-small cell lung carcinomas, not otherwise specified (NSCLC-NOS) with a specific signature including high-grade hepatoid/clear cell morphology, negative lung panel mutational analysis, negative TTF-1/Napsin A staining can be reported as a morphologic variant of an aggressive carcinoma with loss of one of the subunits of the SWI/SNF-chromatin complex. However, this entity is often underdiagnosed, and the specific percentages of each subunit affected remain unclear. In this study, we used immunomarkers for common major (BRG1 and BRM) and minor subunits (ARID1B, ARID1B, and ARID2) in suspicious cases in a retrospective method. Our study revealed that 90% (62 out of 69 cases) of the cases exhibiting the abovementioned signature showed loss of one of the common SWI/SNF complex subunits, with BRG1 and ARID1B being the most lost subunits. We suggest that the combination of hepatoid or clear cell cytomorphology, negative TTF1/Napsin A, and negative lung panel mutational analysis should trigger immunohistochemical examination of SWI subunits expression. The uniqueness of this study lies in the large number of cases, with their specimens obtained via cytopathological methods and immunostained with all five common SWI markers. This study contributes to the familiarity and awareness of pathologists and oncologists by highlighting the importance of cytomorphology and immunohistochemical profile of SWI/SNF-deficient NSCLC-NOS, facilitating earlier diagnosis, and may ultimately lead to more specific and novel therapeutic targets.
Keywords: ARID1B; BRG1; NSCLC; SMARCA4 fine needle aspiration (FNA); SWI/SNF complex; cytopathology.
© 2026 The Author(s). Diagnostic Cytopathology published by Wiley Periodicals LLC.