CASE REPORT article
Front. Oncol.
Sec. Thoracic Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1538548
This article is part of the Research TopicAdvancements in Understanding and Treating Pulmonary Neuroendocrine TumorsView all articles
Three cases of lung large cell neuroendocrine carcinoma with clinicopathological features of SMARCA4 (BRG1) deficiency
Provisionally accepted
- 1Department of Pathology, Weihai Municipal Hospital, Weihai, Shandong, China
- 2Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 3Department of Pathology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, China
- 4Boao International Hospital, Hainan, China
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Objective To investigate the clinicopathological characteristics, differential diagnosis and potential therapeutic targets of SMARCA4-deficient large cell neuroendocrine carcinoma (SD-LCNEC) in the lung. Methods We analyzed the clinicopathological features of 3 cases of SD-LCNEC and reviewed relevant literature. Differential diagnoses were conducted using a panel of immunohistochemical antibodies. Results The patients, aged 57 to 73 years, had tumors located in the right upper lobe, left hilum, and left upper lobe of the lung, respectively. All patients presented with lung masses. The tumors exhibited neuroendocrine carcinoma morphology, characterized by large tumor cells (nuclear diameter >3 lymphocytes), frequent mitoses, and prominent nucleoli. Tumor cells tested negative for SMARCA4 but were positive for Chromogranin-A(CgA), Synaptophysin (SYN), Insm-1, TTF-1 (partial), and Ki67 (90%). They were also negative for NapsinA, P63, P40, CK5/6, CK7, and NUT. Postoperative follow-up revealed one death, one case of Progressive Disease (PD), and one case of Stable Disease (SD). Conclusion SD-DLCNEC is a rare and clinically aggressive carcinoma, often presenting with lymph node metastasis at the initial stage. Its morphology is similar to LCNEC; however, immunohistochemical staining indicates the absence of SMARCA4 and a reduction in neuroendocrine markers and TTF-1. There is no standardized treatment, but SMARCA4 may serve as a potential therapeutic target. Accurate identification of the molecular subtype of SD-LCNEC is crucial.
Keywords: Lung Neoplasms, SMARCA4-deficient, Large cell neuroendocrine carcinoma, Immunohistochemistry, differential diagnosis
Received: 03 Dec 2024; Accepted: 10 Jun 2025.
Copyright: © 2025 Zou, Jia, Wang, Fei, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoyan Chen, Department of Pathology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, China
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