Rapidly Progressive Pericardial Metastasis in SMARCA4-Deficient Non–Small Cell Lung Cancer: Implicating the SWI/SNF-YAP-EMT Axis

Background SMARCA4-deficient non–small cell lung cancer (SMARCA4-dNSCLC) is a rare and aggressive subtype with rapid progression and poor prognosis. Patterns of pericardial invasion and their biological mechanisms remain insufficiently characterized. Case Presentation A 46-year-old man presented with a mediastinal mass that enlarged from 4.9 cm to 7.1 cm over nine months. Despite relatively gradual enlargement of the primary lesion, the clinical course was abruptly dominated by diffuse pericardial involvement. Serial imaging demonstrated circumferential, infiltrative pericardial thickening with an armor-like configration, leading to restrictive cardiac physiology and fatal hemodynamic compromise. Cytological and immunohistochemical revealed malignant epithelial cells with TTF-1 (-), p40 (-), CK7 (+), and MOC31 (+), accompanied by markedly elevated proliferative index of Ki-67. Heterogeneous loss of SMARCA4/BRG1 confirmed the diagnosis of SMARCA4-dNSCLC. Conclusions This case illustrates a pericardial, non-linear progression pattern in SMARCA4-dNSCLC. Early recognition of SMARCA4 deficiency through SMARCA4/BRG1 immunohistochemistry is essential, as such aggressive kinetics may warrant early systemic evaluation. This case supports a hypothesis that SMARCA4 deficiency sensitizes cells to YAP-driven EMT program, while cardicac-derived mechanical strech provides a permissive microenvironment, synergistically contributing to the aggressive, armor-like pericardial thickening in this malignancy.