SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-UT) is a rare malignant tumor characterized by inactivation of the SMARCA4 gene and the presence of undifferentiated or rhabdoid morphology in the tissue. This tumor is highly invasive, typically diagnosed at advanced stages III or IV, and commonly involves thoracic structures, such as the mediastinum and chest wall. Reported cases are limited and treatment guidelines have not yet been established. Here, we present a rare case of surgically treated non-metastatic SMARCA4-UT. The patient presented with blood-tinged sputum, dyspnea, and a history of heavy smoking, and underwent surgery after preoperative evaluation ruled out contraindications. The tumor was successfully removed along with the relevant lymph nodes; analysis determined it to be stage IIB T3N0M0. No recurrence was detected at two months post-surgery. However, four months after surgery, the tumor recurred and invaded the adjacent ribs. The diagnosis, differential diagnosis, and treatment of SMARCA4-deficient undifferentiated lung tumors is considered. The combination of chemotherapy and immunotherapy has shown efficacy, and other treatments such as anti-angiogenic drugs, histone deacetylase inhibitors (HDACi), enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors, and oxidative phosphorylation (OXPHOS) inhibitors may also be beneficial in treating SMARCA4-UT.

Recently, the fifth edition of the WHO classification recognized the thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) as a separate entity from conventional non-small cell lung cancer with SMARCA4 deficiency because of the different clinicopathological characteristics of these two diseases. SMARCA4-UT mainly occurs in young to middle-aged adults and involves a large mass compressing the tissues surrounding the mediastinum and lung parenchyma. Unfortunately, SMARCA4-UT shows a high probability of recurrence after upfront surgery as well as radiotherapy resistance; moreover, chemotherapy has low efficacy. Moreover, given the recent classification of SMARCA4-UT, no data concerning specific clinical trials are currently available. However, several case reports show immunotherapy efficacy in patients with this disease not only in a metastatic setting but also in a neoadjuvant manner, supporting the development of clinical trials. In addition, preclinical data and initial clinical experiences suggest that inhibiting pathways such as CDK4/6, AURKA, ATR, and EZH2 may be a promising therapeutic approach to SMARCA4-UT.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described smoking-related malignancy. The pathogenesis of SMARCA4-UT is the mutational inactivation and loss of expression of a subunit encoding the mammalian switch/sucrose nonfermenting ATPase-dependent chromatin remodeling complex (which can be mobilized using adenosine triphosphate hydrolysis nucleosomes and regulate other cellular processes including development, differentiation, proliferation, and apoptosis), in particular SMARCA4 and SMARCA2. The dynamic activity of this complex plays an important role in regulating the activation and repression of gene expression programs. SMARCA4-UT exhibits morphological features similar to the malignant rhabdoid tumor (MRT), small cell carcinoma of the ovary of the hypercalcemic type (SCCOHT), and INI1-deficient tumor, but SMARCA4-UT differs from SCCOHT and MRT from a genomic perspective. SMARCA4-UT mainly involves the mediastinum and lung parenchyma, and appears as a large infiltrative mass that easily compresses surrounding tissues. At present, chemotherapy is a common treatment, but its efficacy is not clear. Moreover, the inhibitor of the enhancer of zeste homolog 2 showed promising efficacy in some patients with SMARCA4-UT. This study aimed to review the clinical characteristics, diagnosis, treatment, and prognosis of SMARCA4-UT.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is an extremely rare and poor-prognosis malignancy, which has recently been noted as a subtype of lung tumors. We presented a case of SMARCA4-UT in a 50-year-old man with progressively worsening respiratory failure. The tumor was the first reported to involve pulmonary artery, and 90% of tumor cells expressed programmed cell death ligand 1 (PD-L1). High tumor mutational burden (TMB, 23.93/Mb) and mutations in SMARCA4 were detected. It is the first reported case to receive Tislelizumab monotherapy with considerable improvement in clinical condition and no adverse events. As a result of our case, we highlight the importance of recognizing SMARCA4-UT as an individual entity, as well as the efficacy of immune checkpoint inhibitor therapy, particularly in patients with high levels of TMB and PD-L1 expression.