Genomic Feature of a Rare Case of Mix Small-Cell and Large-Cell Neuroendocrine Lung Carcinoma: A Case Report

Youcai Zhu; Feng Zhang; Dong Yu; Fang Wang; Manxiang Yin; Liangye Chen; Chun Xiao; Yueyan Huang; Feng Ding

doi:10.3389/fonc.2021.794744

Genomic Feature of a Rare Case of Mix Small-Cell and Large-Cell Neuroendocrine Lung Carcinoma: A Case Report

Front Oncol. 2022 Jan 18:11:794744. doi: 10.3389/fonc.2021.794744. eCollection 2021.

Authors

Youcai Zhu^{1

2}, Feng Zhang³, Dong Yu³, Fang Wang³, Manxiang Yin^{1

2}, Liangye Chen², Chun Xiao², Yueyan Huang⁴, Feng Ding^{3

5}

Affiliations

¹ The Center for Thoracic Diseases, Zhejiang Rongjun Hospital, Jiaxing, China.
² Department of Pathology, The Hospital of Marine Police Corps of the Chinese People's Armed Police Force, Jiaxing, China.
³ Precision Medicine Center, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, China.
⁴ Department of Pharmacy, Jiaxing University Medical College, Jiaxing, China.
⁵ Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing, China.

Abstract

Background: Cases of both of small- (SCLC) and large-cell neuroendocrine lung carcinoma (LCNEC) were rarely reported. Although typical cases are morphologically distinct, the distinction between LCNEC and SCLC is still controversial, with some LCNECs showing close morphologies with SCLC. Here, we reported on a patient who had tumor with a mix of SCLC and LCNEC and uncovered these components' histological and genomic features.

Case presentation: A 59-year-old man was diagnosed with lung cancer and had resection surgery in our hospital. The H&E and immunohistochemistry staining revealed that the tumor had 30%-35% LCNEC and 65%-70% SCLC cells. The whole-exome sequencing (WES) identified no potentially actionable alteration in the tumor sample but found five alterations all with allele frequency over 90%, including TP53 p.R273H, MYH8 p.Q1814K, SLC17A6 p.W505L, PTPN5 p.M40I, and RB1 p.L267X. The genomic results supported that these two different components shared a similar dominant clonal origin. Furthermore, fluorescence in situ hybridization analysis revealed that the LCNECs have a higher copy number of MET than the SCLC component while without notable difference in the copy number of HER2 and TP53. Chemotherapy with pemetrexed and carboplatin was administrated for two cycles after the surgery. Although the chest CT showed remission in the lung, he was diagnosed with bone metastasis in 1 year later. Then, he received chemotherapy with etoposide and carboplatin but had severe side effect, leading to the discontinuation of the regime. Unfortunately, he returned to the local hospital with supportive care and died shortly after.

Conclusion: Based on these observations, we proposed that LCNEC and SCLC components in this patient may have a common clonal origin with dual mutations in TP53 and RB1, while the chromosome instability may cause multiple independent conversion that leads to LCNEC or SCLC morphologies.

Keywords: FISH; MET; case report; genomic feature; large-cell neuroendocrine lung carcinoma (LCNEC); small cell lung cancer (SCLC).

Publication types

Case Reports