SMARCA4-Deficient Undifferentiated Tumor: A Rare Malignancy With Distinct Clinicopathological Characteristics

Switch/sucrose non-fermentable-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4-deficient undifferentiated tumor (SMARCA4-dUT) is a rare malignancy due to inactivating mutations in the SMARCA4 gene of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex. These are aggressive malignancies presenting predominantly in male smokers in their fifth and sixth decades of life with nonspecific respiratory symptoms. Most patients have metastatic disease on presentation. The pattern of metastasis is similar to carcinomas, and the most common metastatic sites are lymph nodes, bones, and adrenal glands. Histologically, these tumors can be either entirely sarcomatoid or with mixed features of sarcoma and carcinoma, with extensive necrosis and high mitotic activity. Immunohistochemistry demonstrates negative expression of keratin and claudin-4, and tumor cell nuclei characteristically lack expression of Brahma-related gene-1 (BRG1). No standard treatment guidelines have been established due to the relative rarity of these tumors, and systemic chemoimmunotherapy has demonstrated benefit in some cases. We report two cases of SMARCA4-dUT with their clinical course and management to provide a perspective on the behavior of these tumors in a Western population cohort.