Histological Transformation from Non-small Cell Lung Cancer to Small Cell Lung Cancer Induced by Immune Checkpoint Inhibitor Therapy: A Case Report and Literature Review.
10.3779/j.issn.1009-3419.2025.101.12
- Author:
Xiting CHEN
1
;
Wenyuan HE
2
;
Ning YANG
3
;
Lijuan XIONG
1
;
Haoqiang WANG
3
;
Peng LIU
3
;
Bo XIE
3
;
Juan ZHOU
3
Author Information
1. Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
2. Department of Pathology, General Hospital of Southern Theater Command, Guangzhou 510010, China.
3. Department of Oncology, General Hospital of Southern Theater Command, Guangzhou 510010, China.
- Publication Type:English Abstract
- Keywords:
Histological transformation;
Immune checkpoint inhibitors;
Lung neoplasms
- MeSH:
Humans;
Immune Checkpoint Inhibitors/therapeutic use*;
Lung Neoplasms/immunology*;
Carcinoma, Non-Small-Cell Lung/immunology*;
Small Cell Lung Carcinoma/genetics*;
Male;
Middle Aged;
Female
- From:
Chinese Journal of Lung Cancer
2025;28(7):558-566
- CountryChina
- Language:Chinese
-
Abstract:
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.
