Feng Xiaoyue, Jie Ruixia, Peng Fang, Lei Huan, Dai Xiaomin
Department of Pathology, Zhejiang Hospital, 12 Lingyin road, Xihu District, Hangzhou, Zhejiang, China.
BMC Pulm Med. 2025 Aug 26;25(1):406. doi: 10.1186/s12890-025-03891-8.
The SWI/SNF (Switch/Sucrose Non-fermentable) chromatin remodeling complex plays a critical role in regulating cellular transcription, and its dysfunction has been associated with the development of aggressive lung adenocarcinoma. The SWI/SNF complex comprises a variety of potential subunit combinations, including the ATP-dependent catalytic subunits SMARCA4 and SMARCA2. Notably, SMARCA4 deletions are observed in approximately 5-10% of lung adenocarcinomas. Conversely, SMARCA2-deficient and SMARCA4-preserved lung adenocarcinoma are relatively rare.
A 52-year-old woman presented with the complaints of persistent cough and dyspnea lasting for one week. Chest computed tomography demonstrated an irregularly shaped mass in the dorsal segment of the left lower lobe, accompanied with left pleural effusion and atelectasis. Cytological examination and cell block analysis revealed markedly atypical epithelial tumor cells exhibiting poor cohesion and rhabdoid morphological features. Immunocytochemical staining demonstrated positivity for Claudin4, TTF-1 and SMARCA4, while SMARCA2 expression was absent. Following these results, the pathological diagnosis was poorly differentiated lung adenocarcinoma with isolated SMARCA2 deficiency. Subsequently, next-generation sequencing (NGS) analysis identified a non-frameshift deletion in exon 19 of the EGFR gene. Based on these findings, target therapy with osimertinib was initiated, and the patient remained clinical stability for a duration of seven months following the initial presentation.
The understanding of isolated SMARCA2-deficient lung adenocarcinoma remains limited, and no cases of this subtype diagnosed via cytology have been reported in the literature. The preparation of cell blocks combined with appropriate immunocytochemical staining represents a valuable and reliable diagnostic approach.
SWI/SNF（开关/蔗糖非发酵）染色质重塑复合体在调节细胞转录中起关键作用，其功能障碍与侵袭性肺腺癌的发生有关。SWI/SNF复合体包含多种潜在的亚基组合，包括ATP依赖性催化亚基SMARCA4和SMARCA2。值得注意的是，在约5%-10%的肺腺癌中观察到SMARCA4缺失。相反，SMARCA2缺陷且SMARCA4保留的肺腺癌相对罕见。
一名52岁女性因持续咳嗽和呼吸困难一周前来就诊。胸部计算机断层扫描显示左肺下叶背段有一不规则形肿块，伴有左侧胸腔积液和肺不张。细胞学检查和细胞块分析显示明显非典型上皮肿瘤细胞，细胞间黏附性差，呈横纹肌样形态特征。免疫细胞化学染色显示Claudin4、TTF-1和SMARCA4呈阳性，而SMARCA2表达缺失。根据这些结果，病理诊断为孤立性SMARCA2缺陷的低分化肺腺癌。随后，下一代测序（NGS）分析在EGFR基因第19外显子中发现一个非移码缺失。基于这些发现，开始使用奥希替尼进行靶向治疗，患者在初次就诊后临床稳定了七个月。
对孤立性SMARCA2缺陷肺腺癌的认识仍然有限，文献中尚未报道通过细胞学诊断的该亚型病例。制备细胞块并结合适当的免疫细胞化学染色是一种有价值且可靠的诊断方法。
