Pulmonary Large Cell Carcinoma with Neuroendocrine Morphology Shows Genetic Similarity to Large Cell Neuroendocrine Carcinoma

Overview

Journal Diagn Pathol

Publisher Biomed Central

Specialty Pathology

Date 2022 Feb 11

PMID 35144629

Authors

Zuoyu Liang

Weiya Wang

Qianrong Hu

Ping Zhou

Ying Zhang

Yuan Tang

Qian Wu

Yiyun Fu

Xue Li

Yang Shao

Lili Jiang

Affiliations

Soon will be listed here.

Abstract

Background: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade malignant pulmonary neuroendocrine tumour. The distinction of pulmonary large cell carcinoma (LCC) and LCNEC is based on the presence of neuroendocrine morphology and the expression of at least one neuroendocrine marker in at least 10% of tumour cells in the latter. According to the current classification, LCC with neuroendocrine morphology and without neuroendocrine marker expression is classified as LCC. This subgroup we have named LCNEC-null and aimed to analyze its characteristics.

Methods: 31 surgical samples resected in West China Hospital of Sichuan University between 2017 to 2021 were collected, including 7 traditional LCCs, 11 LCNEC-nulls and 13 LCNECs. Each case was conducted to immunohistochemistry and 425-panel-NGS.

Results: Compared to other LCCs, detailed analysis of LCNEC-nulls revealed biological features similar to those of LCNECs, especially for immunohistochemistry and molecular analysis: 1. diffusive, coarse granular and high expression of Pan-CK; 2. rare PD-L1 expression; 3. High rate of p53 expression and Rb deficiency 4. abundant genetic alterations are similar to LCNEC. All characteristics above deviated from traditional LCC, indicating they have the same origin as LCNEC. Furthermore, LCNEC could be genetically divided into two subtypes when we reclassified LCNEC-null as LCNEC, and the mutational type and prognosis differed significantly.

Conclusions: We consider that LCNEC-null should be reclassified as LCNEC based on analysis above. In addition, two genetic types of LCNEC with different prognosis also indicate two mechanism of tumour formation.

Citing Articles

Right Upper Lobe Large Cell Neuroendocrine Carcinoma with Atypical Carcinoid Features: Case Report.

Lee Y, Rodrigs R, Wallace W, Wightman S Case Rep Oncol. 2024; 17(1):1042-1049.

PMID: 39474548 PMC: 11521487. DOI: 10.1159/000540889.

Complete Favorable Response after Second-Line Immunotherapy in Stage IV Non-Small Lung Cancer with Visceral Metastases and Operated Brain Metastasis.

Rahnea-Nita R, Rebegea L, Toma R, Nechifor A, Constantin G, Rahnea-Nita G J Pers Med. 2024; 14(7).

PMID: 39064008 PMC: 11278410. DOI: 10.3390/jpm14070754.

Primary lung adenocarcinoma with breast metastasis harboring the EML4‑ALK fusion: A case report.

Zhang W, Zhang Y, Zhou L, Tan N, Bai Y, Xing S Oncol Lett. 2024; 27(6):276.

PMID: 38690101 PMC: 11058636. DOI: 10.3892/ol.2024.14409.

Characterization of two transcriptomic subtypes of marker-null large cell carcinoma of the lung suggests different origin and potential new therapeutic perspectives.

Simbolo M, Centonze G, Gkountakos A, Monti V, Maisonneuve P, Golovco S Virchows Arch. 2024; 484(5):777-788.

PMID: 38168015 PMC: 11106141. DOI: 10.1007/s00428-023-03721-4.

LCMR1 Promotes Large-Cell Lung Cancer Proliferation and Metastasis by Downregulating HLA-Encoding Genes.

Liu L, Li C, Wu Z, Li Y, Yu H, Li T Cancers (Basel). 2023; 15(22).

PMID: 38001705 PMC: 10670470. DOI: 10.3390/cancers15225445.

References

Zhou Z, Zhu L, Niu X, Shen S, Zhao Y, Zhang J . Comparison of genomic landscapes of large cell neuroendocrine carcinoma, small cell lung carcinoma, and large cell carcinoma. Thorac Cancer. 2019; 10(4):839-847. PMC: 6449265. DOI: 10.1111/1759-7714.13011. View

Liu R, Liu J, Shi T, Li X, Ren D, Chen G . Clinicopathological and genetic characteristics of pulmonary large cell carcinoma under 2015 WHO classification: a pilot study. Oncotarget. 2017; 8(59):100754-100763. PMC: 5725061. DOI: 10.18632/oncotarget.21736. View

Chan A, Chau S, Tong J, Chow C, Kwan J, Chung L . The Landscape of Actionable Molecular Alterations in Immunomarker-Defined Large-Cell Carcinoma of the Lung. J Thorac Oncol. 2019; 14(7):1213-1222. DOI: 10.1016/j.jtho.2019.03.021. View

Lee K, Lee Y, Oh S, Jin K, Goo J . Large cell neuroendocrine carcinoma of the lung: CT and FDG PET findings. Eur J Radiol. 2015; 84(11):2332-8. DOI: 10.1016/j.ejrad.2015.07.033. View

Bi Y, Qu Y, Liang Z, Liu Z, Zhang H, Liang X . Clinicopathological analysis of Large Cell Lung Carcinomas definitely diagnosed according to the New World Health Organization Criteria. Pathol Res Pract. 2018; 214(4):555-559. DOI: 10.1016/j.prp.2018.02.006. View

Sakre N, Wildey G, Behtaj M, Kresak A, Yang M, Fu P . RICTOR amplification identifies a subgroup in small cell lung cancer and predicts response to drugs targeting mTOR. Oncotarget. 2016; 8(4):5992-6002. PMC: 5351607. DOI: 10.18632/oncotarget.13362. View

Simbolo M, Mafficini A, Sikora K, Fassan M, Barbi S, Corbo V . Lung neuroendocrine tumours: deep sequencing of the four World Health Organization histotypes reveals chromatin-remodelling genes as major players and a prognostic role for TERT, RB1, MEN1 and KMT2D. J Pathol. 2016; 241(4):488-500. PMC: 5324596. DOI: 10.1002/path.4853. View

Rekhtman N, Travis W . Large No More: The Journey of Pulmonary Large Cell Carcinoma from Common to Rare Entity. J Thorac Oncol. 2019; 14(7):1125-1127. DOI: 10.1016/j.jtho.2019.04.014. View

Miyoshi T, Umemura S, Matsumura Y, Mimaki S, Tada S, Makinoshima H . Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung. Clin Cancer Res. 2016; 23(3):757-765. DOI: 10.1158/1078-0432.CCR-16-0355. View

10.

Peng W, Sano T, Oyama T, Kawashima O, Nakajima T . Large cell neuroendocrine carcinoma of the lung: a comparison with large cell carcinoma with neuroendocrine morphology and small cell carcinoma. Lung Cancer. 2005; 47(2):225-33. DOI: 10.1016/j.lungcan.2004.06.018. View

11.

Copin M . [Large cell carcinoma, lymphoepithelioma-like carcinoma, NUT carcinoma]. Ann Pathol. 2016; 36(1):24-33. DOI: 10.1016/j.annpat.2015.11.006. View

12.

Rekhtman N, Tafe L, Chaft J, Wang L, Arcila M, Colanta A . Distinct profile of driver mutations and clinical features in immunomarker-defined subsets of pulmonary large-cell carcinoma. Mod Pathol. 2012; 26(4):511-22. PMC: 3594043. DOI: 10.1038/modpathol.2012.195. View

13.

Karlsson A, Brunnstrom H, Micke P, Veerla S, Mattsson J, La Fleur L . Gene Expression Profiling of Large Cell Lung Cancer Links Transcriptional Phenotypes to the New Histological WHO 2015 Classification. J Thorac Oncol. 2017; 12(8):1257-1267. DOI: 10.1016/j.jtho.2017.05.008. View

14.

Driver B, Portier B, Mody D, Deavers M, Bernicker E, Kim M . Next-Generation Sequencing of a Cohort of Pulmonary Large Cell Carcinomas Reclassified by World Health Organization 2015 Criteria. Arch Pathol Lab Med. 2015; 140(4):312-7. DOI: 10.5858/arpa.2015-0361-OA. View

15.

Umemura S, Mimaki S, Makinoshima H, Tada S, Ishii G, Ohmatsu H . Therapeutic priority of the PI3K/AKT/mTOR pathway in small cell lung cancers as revealed by a comprehensive genomic analysis. J Thorac Oncol. 2014; 9(9):1324-31. PMC: 4154841. DOI: 10.1097/JTO.0000000000000250. View

16.

Karlsson A, Brunnstrom H, Lindquist K, Jirstrom K, Jonsson M, Rosengren F . Mutational and gene fusion analyses of primary large cell and large cell neuroendocrine lung cancer. Oncotarget. 2015; 6(26):22028-37. PMC: 4673143. DOI: 10.18632/oncotarget.4314. View

17.

Iyoda A, Hiroshima K, Toyozaki T, Haga Y, Fujisawa T, Ohwada H . Clinical characterization of pulmonary large cell neuroendocrine carcinoma and large cell carcinoma with neuroendocrine morphology. Cancer. 2001; 91(11):1992-2000. DOI: 10.1002/1097-0142(20010601)91:11<1992::aid-cncr1224>3.0.co;2-5. View

18.

Rekhtman N, Pietanza M, Hellmann M, Naidoo J, Arora A, Won H . Next-Generation Sequencing of Pulmonary Large Cell Neuroendocrine Carcinoma Reveals Small Cell Carcinoma-like and Non-Small Cell Carcinoma-like Subsets. Clin Cancer Res. 2016; 22(14):3618-29. PMC: 4995776. DOI: 10.1158/1078-0432.CCR-15-2946. View

19.

Jung K, Lee K, Han J, Kwon O, Kim J, Shim Y . Large cell neuroendocrine carcinoma of the lung: clinical, CT, and pathologic findings in 11 patients. J Thorac Imaging. 2001; 16(3):156-62. DOI: 10.1097/00005382-200107000-00003. View

20.

Pelosi G, Fabbri A, Papotti M, Rossi G, Cavazza A, Righi L . Dissecting Pulmonary Large-Cell Carcinoma by Targeted Next Generation Sequencing of Several Cancer Genes Pushes Genotypic-Phenotypic Correlations to Emerge. J Thorac Oncol. 2015; 10(11):1560-9. DOI: 10.1097/JTO.0000000000000658. View