A case of ROS1 ‐rearranged lung adenocarcinoma in a young man with multiple serosal effusions: Diagnostic pitfalls in pericardial fluid cytology

ROS1 ‐rearranged lung adenocarcinoma is a rare subset of non‐small‐cell lung cancer, typically occurring in young never‐smokers. Its occurrence in very young men with a fluid‐dominant presentation is unusual and may lead to diagnostic pitfalls. We herein report a case of ROS1 ‐rearranged lung adenocarcinoma in a never‐smoking man in his early 20s who presented with pericardial, pleural, and peritoneal effusion. The initial cytological assessment of the pericardial fluid, interpreted in the context of the patient's very young age, favored reactive mesothelial proliferation. Clusters with nuclear eccentricity and prominent nucleoli prompted the preparation of a cell block. Hematoxylin and eosin staining revealed cohesive nests, cords of tumor cells, and true gland‐forming tubular structures with scattered mucin‐containing cells. Immunohistochemistry confirmed primary lung adenocarcinoma, and a molecular analysis identified a ROS1 rearrangement. This case underscores the rarity of ROS1 ‐rearranged adenocarcinoma in a very young never‐smoking man, its atypical fluid‐dominant manifestation, particularly pericardial effusion, and the importance of a systematic diagnostic approach that incorporates smear cytology, cell block, immunohistochemistry, and molecular testing, supported by multidisciplinary discussion to avoid a misdiagnosis and guide targeted therapy.