Diagnosis of thoracic SMARCA4-deficient undifferentiated tumor in cytology.

Abstract

Although alterations in SMARCA4-deficient occur in non-small cell lung carcinoma (SD-NSCLC), thoracic SMARCA4-deficient undifferentiated tumor (TSDUT) is recognized as a distinct entity in the 2021 World Health Organization Classification of Thoracic Tumors because of unique morphologic, immunophenotypic and molecular features, and worse survival compared with SD-NSCLC. Cytologic diagnosis of TSDUT is clinically important because of its aggressive behavior and because it is often diagnosed by fine-needle aspiration because TSDUTs are usually unresectable at presentation. Here, we identify cytologic features that can be used for recognition of TSDUT and distinction from SD-NSCLC. Cytomorphologic features were investigated in cytology specimens from patients with TSDUT (n=11) and compared with a control group of patients with SD-NSCLC (n=20). The presence of classic rhabdoid morphology, at least focally, was entirely specific for TSDUT (n=6, 55%) compared with SD-NSCLC (n=0) in this study. TSDUT more frequently showed tumor necrosis (n=11, 100% vs. n=8, 40%; p=.001), dominant single-cell pattern on aspirate smears or touch preparation slides (n=8 [of 9], 80% vs. n=3, 15%; p=.010), nuclear molding (n=5, 45% vs. n=1, 5%; p=.013), and indistinct cell borders (n=11, 100% vs. n=5, 25%; P<.001) compared with SD-NSCLC, respectively. Cytomorphologic features occurring more frequently in TSDUT include tumor necrosis, dominant single-cell pattern, nuclear molding indistinct cell borders, and focal rhabdoid cells. Presence of these features in a cytology specimen of an undifferentiated tumor, particularly in a patient with a thoracic mass, should raise suspicion for TSDUT and prompt appropriate ancillary workup.