Sood Ridhi, Tandon Arshi, Khatoon Warisa, Vasanthraman Jayashimman, Nambirajan Aruna, Mohan Anant, Malik Prabhat Singh, Jain Deepali
Department of Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India.
AIIMS, New Delhi, India.
J Clin Pathol. 2025 May 25;78(6):370-380. doi: 10.1136/jcp-2024-209619.
This study was undertaken to compare and expand the clinicopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumour (SMARCA4-dUT) and switch/sucrose non-fermentable-deficient non-small cell lung carcinomas (SWI/SNF-dNSCLC) and to address cases with intermediate features.
The pathology department archive was searched for all primary mediastinal, pleural and lung-based malignancies that showed aberrant expression of two SWI/SNF proteins the Brahma (BRM) aka and/or (Brahma-related gene 1 (BRG1) aka . Patient demographics, treatment and clinical outcomes were collected from records and telephonic interviews. Differences in histopathological features and immunohistochemical stains were analysed. Cases with characteristics intermediate between both tumour entities were sequenced to advance our understanding of their biology and to assign them a more accurate classification.
We identified 50 tumours with SMARCA4 and/or SMARCA2 deficiencies, including 23 (46%) SMARCA4-dUT, 18 (36%) SMARCA4-dNSCLC and 2 (4%) SMARCA2-dNSCLC. Dyscohesive or undifferentiated cellular morphology versus frank gland formation along with keratin, claudin-4 and expression of >1 stem cell marker helped classify the SWI/SNF deficient tumours as SMARCA4-dUT or SWI/SNF-dNSCLC (p<0.05). Seven (14%) cases with BRG1 deficiency displayed 'intermediate' features of both SMARCA4-dNSCLC and SMARCA4-dUT and had the shortest overall survival. The smoking-related gene signature was observed on sequencing in all four cases examined.
Tumours with intermediate features between SMARCA4-dUT and SWI/SNF-dNSCLC exist and portend an equally poor prognoses. Immunostains, including keratin, claudin-4, TTF1, HepPar1, stem cell markers, along with BRG1 and BRM testing, are essential adjuncts to morphology, while molecular studies can offer supplementary evidence in challenging cases.
本研究旨在比较并扩展SMARCA4缺陷型胸部分化未明肿瘤（SMARCA4-dUT）和开关/蔗糖非发酵缺陷型非小细胞肺癌（SWI/SNF-dNSCLC）的临床病理特征，并处理具有中间特征的病例。
在病理科档案中搜索所有显示两种SWI/SNF蛋白（即Brahma（BRM）又名 和/或Brahma相关基因1（BRG1）又名 ）异常表达的原发性纵隔、胸膜和肺源性恶性肿瘤。从记录和电话访谈中收集患者的人口统计学资料、治疗情况和临床结局。分析组织病理学特征和免疫组化染色的差异。对具有两种肿瘤实体中间特征的病例进行测序，以增进我们对其生物学特性的了解，并为其赋予更准确的分类。
我们鉴定出50例具有SMARCA4和/或SMARCA2缺陷的肿瘤，其中包括23例（46%）SMARCA4-dUT、18例（36%）SMARCA4-dNSCLC和2例（4%）SMARCA2-dNSCLC。与紧密黏附或未分化的细胞形态相对的是明显的腺体形成，同时伴有角蛋白、claudin-4以及>1种干细胞标志物的表达，这有助于将SWI/SNF缺陷型肿瘤分类为SMARCA4-dUT或SWI/SNF-dNSCLC（p<0.05）。7例（14%）具有BRG1缺陷的病例表现出SMARCA4-dNSCLC和SMARCA4-dUT的“中间”特征，且总生存期最短。在所检测的4例病例的测序中均观察到与吸烟相关的基因特征。
存在具有介于SMARCA4-dUT和SWI/SNF-dNSCLC之间中间特征 的肿瘤，且预后同样较差。包括角蛋白、claudin-4、TTF1、HepPar1、干细胞标志物以及BRG1和BRM检测在内的免疫组化染色是形态学诊断的重要辅助手段，而分子研究可为疑难病例提供补充证据。
