Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 26, 2021; 9(18): 4617-4626
Published online Jun 26, 2021. doi: 10.12998/wjcc.v9.i18.4617
Histological transformation of non-small cell lung cancer: Clinical analysis of nine cases
Cai-Bao Jin, Ling Yang
Cai-Bao Jin, Ling Yang, Department of Thoracic Oncology, Hubei Cancer Hospital, Wuhan 430000, Hubei Province, China
Author contributions: Jin CB performed the research and wrote the paper; Yang L supervised the report.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Hubei Cancer Hospital.
Informed consent statement: Written informed consent was waived.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ling Yang, MD, Chief Doctor, Department of Thoracic Oncology, Hubei Cancer Hospital, No. 116 Zhuodaoquan South Road, Wuhan 430000, Hubei Province, China. 348711624@qq.com
Received: January 26, 2021
Peer-review started: January 26, 2021
First decision: February 25, 2021
Revised: March 11, 2021
Accepted: April 12, 2021
Article in press: April 12, 2021
Published online: June 26, 2021
Abstract
BACKGROUND

Histological transformation is one of the numerous mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Given its rarity, the underlying transformational mechanisms, clinical features, and therapeutic prognoses are only studied through limited case reports.

AIM

To analyze the clinical characteristics and underlying mechanisms in non-small cell lung cancer (SCLC) patients with histological transformation after treatment with EGFR-TKIs.

METHODS

We retrospectively investigated nine patients diagnosed with non-SCLC transforming to SCLC, large-cell neuroendocrine carcinoma (LCNEC), or squamous cell carcinoma on re-biopsy after first- or third-generation EGFR-TKIs.

RESULTS

The median age of nine patients was 60 years. Among them, six patients had the EGFR 19del mutation, one had the L858R mutation, and one had wild-type EGFR. The level of plasma NSE was measured in six patients with SCLC or LCNEC transformation when transformation occurred, and five patients had elevated plasma NSE levels. All patients received standard chemotherapy after transformation with the exception of one patient who received chemotherapy and anlotinib.

CONCLUSION

Tumor re-biopsy should be performed routinely when EGFR-TKI therapy fails in lung cancer patients to avoid ignoring histological transformation and to select a subsequent therapeutic strategy. The transformed tumor retained the original EGFR mutation, indicating that histological transformation represents an evolution from the initial tumor.

Keywords: Histological transformation, Epidermal growth factor receptor tyrosine kinase inhibitors, Non-small cell lung cancer, Tumor re-biopsy, Epidermal growth factor receptor mutation

Core Tip: We retrospectively diagnosed nine cases of non-small cell lung cancer (SCLC) transforming to SCLC, large-cell neuroendocrine carcinoma, or squamous cell carcinoma on re-biopsy after epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Tumor re-biopsy should be performed routinely when EGFR-TKI therapy fails in lung cancer patients to avoid ignoring histological transformation and to select a subsequent therapeutic strategy. The plasma pro-gastrin-releasing peptide and NSE levels could be valuable and significant biomarkers to predict histological transformation. The transformed tumor retained the original EGFR mutation, which indicates that histological transformation represents an evolution from the initial tumor.