Abstract
BACKGROUND: SMARCA4 and SMARCA2, mutually exclusive catalytic ATPase subunits of human mammalian Switch/Sucrose-Nonfermentable chromatin remodeling enzymes, function as tumor suppressor genes. SMARCA4-deficient adenocarcinoma (SMARCA4-dADC) is a relatively rare subtype of TTF1/P40-negative non-small cell lung cancer. The concurrent presentation of SMARCA4-dADC and poorly differentiated adenocarcinoma with SMARCA2 (also known as BRM) loss in separate lobes of the same patient is even less common. This report describes such a case involving the simultaneous occurrence of these two tumor types in distinct locations within the lungs. CASE PRESENTATION: A 68-year-old male presented with a three-week history of vague pain in the right side of the chest, with no obvious trigger. Imaging revealed solid masses in the upper and lower lobes of the right lung with bilateral enlarged cervical lymph nodes. So, both of these masses underwent wedge resection. Histopathological examination confirmed that the lower lobe tumor was SMARCA4-dADC, while the upper lobe tumor was diagnosed as poorly differentiated adenocarcinoma. Although histologically similar, both exhibiting predominantly solid sheets and complex glandular structures, the two tumors displayed distinct immunohistochemical and molecular profiles. The lower lobe mass showed complete loss of BRG1 protein expression and partial loss of BRM. Immunohistochemical analysis revealed negative expression of TTF1, Napsin A, SALL4, CD34, and SOX2, and positive expression of CK7, pan-Cytokeratin (CK-pan), and HepPar-1. Molecular analysis identified mutations in SMARCA4, KRAS, and STK11. Conversely, the upper lobe mass retained BRG1 expression but showed complete loss of BRM protein expression, and negative expression of SALL4, CD34, and HepPar-1, positive expression of CK7, CK-pan, TTF1, Napsin A, and SOX2. A KRAS mutation was also detected in this tumor. CONCLUSION: The simultaneous occurrence of SMARCA4-dADC and conventional adenocarcinoma in different locations within the same patient is exceedingly rare. However, the distinct immunophenotypic and molecular characteristics of SMARCA4-dADC differentiate it as a unique entity from conventional adenocarcinoma. We recommend including SMARCA4 in the marker panel used to evaluate TTF1-negative adenocarcinomas of potential or uncertain pulmonary origin. This report underscores the diagnostic challenge of concurrent SMARCA4-dADC and poorly differentiated adenocarcinoma, proposing a standardized immunohistochemical workflow to guide therapeutic decisions.