Transformation of epidermal growth factor receptor mutated lung adenocarcinoma to small-cell carcinoma long after the cessation of tyrosine kinase inhibitor treatment: A case series and literature review

Kenya Miyamoto; Hirokazu Ogino; Takumi Kakimoto; Yugo Matsumura; Keiko Haji; Atsushi Mitsuhashi; Yutaka Morita; Yuki Tsukazaki; Yohei Yabuki; Ryohiko Ozaki; Hiroto Yoneda; Seidai Sato; Masaki Hanibuchi; Yoshimi Bando; Hiroshi Nokihara; Yasuhiko Nishioka

doi:10.1016/j.rmcr.2024.102076

Transformation of epidermal growth factor receptor mutated lung adenocarcinoma to small-cell carcinoma long after the cessation of tyrosine kinase inhibitor treatment: A case series and literature review

Respir Med Case Rep. 2024 Jun 21:51:102076. doi: 10.1016/j.rmcr.2024.102076. eCollection 2024.

Authors

Kenya Miyamoto¹, Hirokazu Ogino¹, Takumi Kakimoto², Yugo Matsumura¹, Keiko Haji¹, Atsushi Mitsuhashi¹, Yutaka Morita¹, Yuki Tsukazaki¹, Yohei Yabuki¹, Ryohiko Ozaki¹, Hiroto Yoneda¹, Seidai Sato¹, Masaki Hanibuchi^{1

3}, Yoshimi Bando², Hiroshi Nokihara^{1

4}, Yasuhiko Nishioka¹

Affiliations

¹ Department of Respiratory Medicine and Rheumatology, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
² Division of Pathology, Tokushima University Hospital, 2-50-1, Kuramoto-cho, Tokushima, 770-8503, Japan.
³ Department of Community Medicine for Respirology, Hematology and Metabolism, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15, Kuramoto-cho, Tokushima, 770-8503, Japan.
⁴ Respiratory Medicine, Center Hospital of the National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjyuku-ku, Tokyo, 162-8655, Japan.

Abstract

Histological transformation to small-cell lung cancer (SCLC) is a well-known mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and almost all patients receive EGFR-TKIs at the time of transformation. We herein report three cases of EGFR-mutated lung adenocarcinoma that transformed into SCLC long after the cessation of EGFR-TKIs. Rapid tumor progression and elevated SCLC marker levels were observed at the time of transformation. Our case highlights the importance of considering SCLC transformation throughout the clinical course. Careful observation of the tumor behavior and SCLC markers should be performed to avoid diagnostic delays.

Keywords: Acquired resistance; Epidermal growth factor receptor; Non-small-cell lung cancer; Small-cell lung cancer transformation; Tyrosine kinase inhibitors.

Publication types

Case Reports