Chen Xiting, He Wenyuan, Yang Ning, Xiong Lijuan, Wang Haoqiang, Liu Peng, Xie Bo, Zhou Juan
Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Department of Pathology, General Hospital of Southern Theater Command, Guangzhou 510010, China.
Zhongguo Fei Ai Za Zhi. 2025 Jul 20;28(7):558-566. doi: 10.3779/j.issn.1009-3419.2025.101.12.
Non-small cell lung cancer (NSCLC), as the predominant histological subtype of lung cancer, accounts for approximately 85% of all lung cancer cases. In recent years, immune checkpoint inhibitors (ICIs), represented by programmed death 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors, have achieved breakthrough advancements in patients with driver gene-negative NSCLC. They have been established as a key component of first-line treatment regimens and have significantly improved clinical outcomes. However, limited clinical evidence has emerged showing the phenomenon of histological transformation from NSCLC to small cell lung cancer (SCLC) in patients experiencing disease progression after ICIs monotherapy or combination therapy. Systematic research data on the clinical characteristics, molecular biological basis, and subsequent treatment strategies for such transformation events are currently lacking. This article reports a case of SCLC transformation occurring in a patient with KRAS-mutated lung adenocarcinoma after 16 months of ICIs combination therapy and provides a systematic review of 22 similar published cases. The study demonstrates that small cell transformation is a critical mechanism of immunotherapy resistance, and transformed patients exhibit poor prognosis. The research emphasizes the importance of dynamic monitoring of neuron-specific enolase (NSE) and standardized repeat biopsies during treatment, providing a basis for clinical practice. This aids in enhancing the recognition and management capabilities for this rare histological transformation, ultimately improving patient outcomes.
非小细胞肺癌（NSCLC）作为肺癌的主要组织学亚型，约占所有肺癌病例的85%。近年来，以程序性死亡1/程序性死亡配体1（PD-1/PD-L1）抑制剂为代表的免疫检查点抑制剂（ICIs）在驱动基因阴性的NSCLC患者中取得了突破性进展。它们已成为一线治疗方案的关键组成部分，并显著改善了临床结局。然而，有限的临床证据显示，在接受ICIs单药治疗或联合治疗后疾病进展的患者中，存在NSCLC向小细胞肺癌（SCLC）组织学转化的现象。目前缺乏关于此类转化事件的临床特征、分子生物学基础及后续治疗策略的系统性研究数据。本文报告了1例KRAS突变型肺腺癌患者在接受16个月ICIs联合治疗后发生SCLC转化的病例，并对22例类似的已发表病例进行了系统性综述。该研究表明，小细胞转化是免疫治疗耐药的关键机制，转化患者预后较差。该研究强调了在治疗期间动态监测神经元特异性烯醇化酶（NSE）和标准化重复活检的重要性，为临床实践提供了依据。这有助于提高对这种罕见组织学转化的识别和管理能力，最终改善患者预后。
