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ALK-rearrangement neuroendocrine carcinoma of the lung: a comprehensive study of a rare case series and review of literature

Authors Zheng Q, Zheng M, Jin Y, Shen X, Shan L, Shen L, Sun Y, Chen H, Li Y

Received 24 April 2018

Accepted for publication 13 June 2018

Published 17 August 2018 Volume 2018:11 Pages 4991—4998


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava

Qiang Zheng,1,2,* Mingjia Zheng,1,2,* Yan Jin,1,2 Xuxia Shen,1,2 Ling Shan,1,2 Lei Shen,1,2 Yihua Sun,2,3 Haiquan Chen,2,3 Yuan Li1,2

1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; 2Department of Oncology, Shanghai Medical College of Fudan University, Shanghai, China; 3Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China

*These authors contributed equally to this work

Abstract: Driver mutations involving tyrosine kinase receptors play crucial roles in the oncogenesis of lung adenocarcinoma. However, receptor tyrosine kinase mutations are extremely rare events in primary pulmonary neuroendocrine carcinoma (NEC), which is a molecular heterogeneous entity. In this study, we examined 4 cases of NEC with anaplastic lymphoma kinase (ALK) rearrangement between 2008 and 2018 at our hospital. We comprehensively analyzed the carcinomas’ clinicopathological features, genetic alterations, and response to ALK inhibitor. One case of atypical carcinoid tumor and 1 case of large cell NEC (LCNEC) achieved response to ALK inhibitor (crizotinib) treatment. One case of combined LCNEC with adenocarcinoma harboring KLC1-ALK (K9:A20) fusion genes was confirmed by NGS of both components, while only the LCNEC component presented RB1 mutation. Notably, tumor cells of different components exhibited different ALK-positive signal patterns by fluorescence in situ hybridization, which revealed isolated 3' signals in the adenocarcinoma component but split signals in the LCNEC. As the largest case series study, our findings suggested that preliminary screening for ALK rearrangement should also be considered in atypical carcinoid and high-grade NEC. Patients with ALK rearrangement-positive NEC would benefit from ALK inhibitor intervention.

Keywords: anaplastic lymphoma kinase, driver mutation, neuroendocrine carcinoma, tumor evolution

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