Thoracic SMARCA4-deficient undifferentiated tumor: diagnostic characteristics, molecular insights, and treatment approaches

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a newly defined disease entity characterized by aggressive clinical behavior, diagnostic complexity, and poor prognosis. Given its rarity and heterogeneous histological presentation, establishing a definitive diagnosis can be challenging and relies heavily on comprehensive molecular and immunohistochemical evaluation. Here, illustrating the challenges highlighted by a real-world case, we describe the diagnostic pathway leading to SMARCA4-UT identification and discuss the differential diagnosis of thoracic tumors, relevant molecular evaluations, the molecular basis of SMARCA4-UT, and treatment implications. Recognition of this recently described entity is crucial, as an accurate diagnosis—as demonstrated by our case—can guide effective therapy and facilitate enrollment in targeted clinical trials.