Introduction: Inactivating mutations of the SMARCA4 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4) gene and/or loss of the BRG1 (brahma-related gene 1) protein defines SMARCA4-deficient thoracic sarcoma (SMARCA4-dTS), an aggressive neoplasm with a usually fatal outcome. Similar SMARCA4 mutations/BRG1 loss is also seen in a subset of non-small cell lung carcinomas (NSCLCs; SMARCA4-dNSCLCs) that lack alterations in currently targetable oncogenic drivers, that is, EGFR, ALK, and ROS1. There is limited knowledge on the cytomorphological features of these SMARCA4-deficient thoracic neoplasms. Methods: We retrospectively analysed the cytology of 2 cases each of SMARCA4-dNSCLC and SMARCA4-dTS to understand their cytomorphological overlap, if any, and identify features that would prompt testing for BRG1 loss. Results: All 4 patients were males presenting with advanced disease, with a mean age of 41.5 years (SMARCA4-dTS) and 58.5 years (SMARCA4-dNSCLC) at presentation. The cytology of the 2 SMARCA4-dTSs was strikingly similar, showing predominantly singly dispersed rhabdoid phenotype tumour cells with perinuclear cytoplasmic condensations in an inflammatory or necrotic background. The cytology raised suspicion for a wide range of differentials, including melanoma, high-grade lymphoma, germ cell tumour, undifferentiated carcinoma, and undifferentiated sarcoma. SMARCA4-dNSCLCs, on the other hand, were recognizable as poorly differentiated (adeno)carcinomas and were easily distinguished from SMARCA4-dTSs, with both cases showing cohesive clusters of frequently large tumour cells with abundant pale cytoplasm. Conclusion: A diagnosis of SMARCA4-dTS is possible on cytology with appropriate ancillary testing and a high index of suspicion. The cytology of SMARCA4-dNSCLCs does not overlap with SMARCA4-dTS; rather, it resembles that of any poorly differentiated (adeno)carcinoma in the limited numbers analysed in this study.
Acta Cytologica

中文翻译：

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SMARCA4缺陷胸腔肿瘤的细胞学：SMARCA4缺陷非小细胞肺癌和SMARCA4缺陷胸腔肉瘤的比较分析。

简介： SMARCA4（SWI / SNF相关，基质相关，肌动蛋白依赖的染色质调节剂，亚家族A，成员4）基因的失活突变和/或BRG1（梵天相关基因1）蛋白的丢失定义了SMARCA4-胸肉瘤（SMARCA4-dTS）缺乏症，一种侵袭性肿瘤，通常具有致命的后果。在非小细胞肺癌（NSCLCs; SMARCA4-dNSCLCs）的子集中也观察到类似的SMARCA4突变/ BRG1丢失，这些子集在当前可靶向的致癌驱动因子，即EGFR， ALK和ROS 1中缺乏变化。这些SMARCA4缺陷胸腔肿瘤的细胞形态学特征。方法：我们回顾性分析了SMARCA4-dNSCLC和SMARCA4-dTS各自2例的细胞学，以了解它们的细胞形态学重叠（如有），并确定可提示检测BRG1缺失的特征。结果：所有4例患者均为男性，患有晚期疾病，平均年龄为41.5岁（SMARCA4-dTS）和58.5岁（SMARCA4-dNSCLC）。2个SMARCA4-dTSs的细胞学非常相似，显示出主要分布在炎性或坏死背景下的单个横纹状表型肿瘤细胞，并伴有核周细胞质缩合。细胞学检查结果令人怀疑存在多种差异，包括黑色素瘤，高级淋巴瘤，生殖细胞肿瘤，未分化癌和未分化肉瘤。另一方面，SMARCA4-dNSCLCs可以识别为低分化（腺）癌，很容易与SMARCA4-dTSs区别开来，这两种情况均显示了具有大量苍白细胞质的常见大型肿瘤细胞的凝聚簇。结论：通过适当的辅助检查和很高的怀疑指数，可以在细胞学上诊断SMARCA4-dTS。SMARCA4-dNSCLCs的细胞学与SMARCA4-dTS不重叠；相反，它与本研究中分析的有限数量的任何低分化（腺）癌相似。
细胞学学报