All that is small is not a small cell carcinoma: Thoracic SMARCA4 undifferentiated tumors masquerading as SCLC

Abstract Small cell lung carcinoma (SCLC) cell lines have been widely utilized as a preclinical model of this highly aggressive disease. However, since their creation decades ago, novel tumor entities have been defined that may clinicopathologically mimic SCLC, which notably includes thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Multi-omic reassessment of the presumed SCLC cell lines with high YAP1 expression reveals that nearly all of these tumors represent unsuspected SMARCA4-UT.