Standard therapy‑resistant small cell lung cancer showing dynamic transition of neuroendocrine fate during the cancer trajectory: A case report

Ito,Fumimaro; Sato,Takashi; Emoto,Katsura; Kaizuka,Nobuki; Yagi,Kazuma; Watanabe,Rinako; Hashiguchi,Mizuha Haraguchi; Ninomiya,Hironori; Ikematsu,Yuki; Tanaka,Kentaro; Domoto,Hideharu; Shiomi,Tetsuya

doi:10.3892/mco.2021.2423

Standard therapy‑resistant small cell lung cancer showing dynamic transition of neuroendocrine fate during the cancer trajectory: A case report

Authors:
- Fumimaro Ito
- Takashi Sato
- Katsura Emoto
- Nobuki Kaizuka
- Kazuma Yagi
- Rinako Watanabe
- Mizuha Haraguchi Hashiguchi
- Hironori Ninomiya
- Yuki Ikematsu
- Kentaro Tanaka
- Hideharu Domoto
- Tetsuya Shiomi
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Affiliations: Department of Medicine, Keiyu Hospital, Yokohama, Kanagawa 220‑8521, Japan, Division of Diagnostic Pathology, Keio University School of Medicine, Tokyo 160‑8582, Japan, Division of Pathology, Cancer Institute, Tokyo 135‑0063, Japan, Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812‑8582, Japan, Department of Pathology, Keiyu Hospital, Yokohama, Kanagawa 220‑8521, Japan
Published online on: October 20, 2021 https://doi.org/10.3892/mco.2021.2423
Article Number: 261

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Abstract

While small cell lung cancer (SCLC) has been treated as a single disease historically, recent studies have suggested that SCLC can be classified into molecular subtypes based on the expression of lineage transcription factors such as achaete‑scute homolog 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), POU domain class 2 transcription factor 3 (POU2F3) and transcriptional coactivator YAP1 (YAP1). These transcription factor‑based subtypes may be specifically targeted in therapy, and recent studies have suggested that the SCLC subtypes represent different stages of dynamic evolution of SCLC rather than independent diseases. Nevertheless, evidence of shift in neuroendocrine differentiation during SCLC evolution has been lacking in the clinical setting. In the present study, a 60‑year‑old male was diagnosed with extensive SCLC. The tumor responded not to the standard SCLC regimen of carboplatin, etoposide and atezolizumab, but to the non‑SCLC regimen of carboplatin, nab‑paclitaxel and pembrolizumab. The patient succumbed 5 months after the initial diagnosis and a pathological autopsy was performed. The tumor was originally negative for all four transcription factors, ASCL1, NEUROD1, POU2F3 and YAP1, in the biopsy specimens at diagnosis. Loss of synaptophysin expression and emergence of Myc proto‑oncogene protein and YAP1 expression was recorded in the autopsy specimens, suggesting the transition to a decreased neuroendocrine fate during the disease trajectory. This case provides clinical evidence of dynamic transition of neuroendocrine fate during SCLC evolution. In light of SCLC heterogeneity and plasticity, development of precision medicine is required.

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