Successful Treatment With Neoadjuvant Chemo-Immunotherapy for Thoracic SMARCA4-Deficient Undifferentiated Tumor: A Patient Report and Literature Review

BackgroundThoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rare neoplastic entity classified in the 2021 World Health Organization Classification of Thoracic Tumors. Due to its rarity, challenges remain in achieving accurate diagnosis, determining optimal therapeutic strategies, and assessing prognosis.Patient PresentationAn elderly heavy smoker was admitted due to the rapid growth of a solid tumor in the right lower lobe. Histopathological examination revealed undifferentiated, epithelioid morphology. Immunohistochemistry demonstrated diffuse positivity for SOX2, alongside loss of expression of brahma-related gene 1 (BRG1) and brahma (BRM). Next-generation sequencing identified a nonsense mutation in <i>SMARCA4</i> (c.2196T > G, p.Y732Ter), with wild-type status for <i>SMARCA2</i>. The tumor was staged as T1N2M0 (stage IIIA), exhibiting a programmed death-ligand 1 tumor proportion score of 2%, a tumor mutational burden of 16.3 mutations per megabase (Mb), and microsatellite stability. The patient received neoadjuvant chemo-immunotherapy followed by right lower lobectomy, resulting in a complete pathological response with ypT0N0Mx status. Subsequently, 5 cycles of adjuvant chemo-immunotherapy were administered. Throughout a 38-month follow-up period, neither computed tomography imaging nor minimal residual disease assessments indicated evidence of recurrence or metastasis.ConclusionThe diagnosis of SMARCA4-UT requires the co-loss of BRG1 and BRM expression, characteristic histological features, and the exclusion of other SMARCA4-deficient thoracic malignancies. This tumor exhibits aggressive clinical behavior, limited availability of targeted therapeutic options, and only modest responses to conventional chemotherapy. The present report underscores the potential efficacy of immune checkpoint inhibitors as a viable treatment modality for SMARCA4-UT.