Cytomorphologic features of SMARCA4‐deficient non–small cell lung carcinoma and correlation with immunohistochemical and molecular features

Abstract

BACKGROUND: SMARCA4/BRG1-deficient tumors and those that have loss of SMARCA/BRG1 have been described as various aggressive carcinomas and sarcomas, including a subset of non-small cell lung carcinoma (NSCLC). Cytomorphologic features of NSCLCs are yet to be described. The objective of this study was to evaluate the cytomorphologic features, immunohistochemical profile, and molecular profile of SMARCA4/BRG1-deficient NSCLC (SMARCA4-dNSCLC). METHODS:The authors retrospectively searched for cases with SMARCA4/BRG1 functional loss alterations, which were identified in molecular studies and further confirmed by immunocytochemistry, and they reviewed the cytomorphologic features. Tumors with BRG1 loss were also stained with an extensive antibody panel. Molecular profiling and clinical information of the identified cases were scrutinized. RESULTS: In total, 12 cytopathology cases from different anatomic sites were included. All cases showed variable expression of cytokeratin irrespective of type. One-half of cases had glandular features, followed by squamoid features, and poorly differentiated features. The most common cytologic features included sheets or papillary architecture, round or oval cell shapes, nuclear enlargement, moderate-to-marked pleomorphism, and coarse chromatin. Two cases with poorly differentiated cytomorphology had a predominance of single cells, scant cytoplasm, and macronucleoli. Variable expression of epithelial markers was noted in all cases. TP53 was the most frequently co-mutated gene in SMARCA4-dNSLCs. CONCLUSIONS: This study demonstrates that SMARCA4-dNSCLCs can have a wide spectrum of cytomorphologic features, ranging from a relatively well differentiated adenocarcinoma to a poorly differentiated/undifferentiated carcinoma, with the majority of cases exhibiting some high-grade features, such as mitosis, apoptosis, necrosis, and marked pleomorphism.

Diagnosis of thoracic SMARCA4‐deficient undifferentiated tumor in cytology

“…This finding is consistent with the findings of our study because dominant single‐cell pattern was significantly more frequent in cytology specimens of TSDUT, but we did observe a dominant single‐cell pattern in a minority of SD‐NSCLC cases. Furthermore, Sun et al 24 . reported dominant single‐cell pattern in two cases of SD‐NSCLC, further highlighting that this feature is not exclusive to TSDUT.…”

“…Furthermore, Sun et al 24 reported dominant single-cell pattern in two cases of SD-NSCLC, further highlighting that this feature is not exclusive to TSDUT.…”

Efficacy of immune checkpoint inhibitors in SMARCA4-deficient and TP53 mutant undifferentiated lung cancer

“…Although as a novel disease entity, undifferentiated NSCLC with SMARCA4-deficient/TP53 mutations has already been deemed to be highly aggressive disease, rarely response to current treatment schedules, and extremely poor prognosis. [14][15][16] A retrospective research by Massachusetts General Hospital was performed to assess the clinical features of patients with tumors harboring SMARCA4/BRG1-inactivating mutations. They have detected SMARCA4 genomic alterations in 9% (n = 117 of 1422) and 11% (n = 3188 of 27,281) of NSCLC in the institutional and foundation medicine data sets, respectively.…”

SMARCA4-deficient non-small cell lung cancer: a case description and literature analysis

“…Several case reports and studies have reported the clinicopathologic features of SMARCA4 -dNSCLC ( 1 , 3 , 14 ). SMARCA4 -dNSCLC is a heterogenous group in terms of cytomorphology, ranging from a relatively well-differentiated adenocarcinoma pattern or squamous differentiation to an undifferentiated morphology ( 1 , 3 , 15 ).…”

“…There is limited information available regarding the imaging characteristics of SMARCA4 -dNSCLC. Moreover, patients with SMARCA4 -dNSCLC respond poorly to conventional therapeutic approaches, further complicating treatment ( 2 , 3 ). Here, we present a case of a 52-year-old male with SMARCA4 -dNSCLC and a review of the relevant literature.…”