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29-09-2023 | Carcinoid Tumor | Original Article

Clinical impact of mixed pulmonary carcinoma and carcinoid: the driver from their mono-clonal origin

Authors: Paolo Graziano, Paola Parente, Flavia Centra, Massimo Milione, Giovanni Centonze, Marco Volante, Alberto Cavazza, Diego Urbano, Giuseppe Di Maggio, Teresa Balsamo, Concetta Di Micco, Giulio Rossi, Antonio Rossi, Lucia Anna Muscarella

Published in: Virchows Archiv | Issue 1/2024

Abstract

The combination of neuroendocrine/non neuroendocrine lung tumors (CNNELT) mentioned in the last edition of the World Health Organization (WHO) of Thoracic Tumors refers to small cell carcinoma (SCLC) or large cell neuroendocrine carcinoma (LCNEC) mixed with any other non-small cell lung carcinoma (NSCLC). Typical Carcinoid (TC)/Atypical Carcinoid (AC) combined with NSCLC is not included among this category. However, case reports of TC/AC combined with NSCLC have been described. We previously reported 2 cases of lung adenocarcinoma (LUA) mixed with carcinoid sharing mutations in both components supporting the hypothesis of a clonal origin. We extended our analysis to other four cases of mixed NSCLC-carcinoid by performing targeted-DNA and RNA-based NGS analysis in both primary and their paired lymph nodes metastasis. In all cases, LUA and AC components shared at least 1 common mutation (KRAS driver mutation p.Gly12Val in cases 1 and 3, AKAP13-RET fusion in case 2, and missense KRAS driver mutation p.Gly12Ala in case 4, reinforcing the hypothesis of a clonal origin. Moreover, the same mutation was detected in the metastasis constituted only by AC (cases 2 and 4). Although it is a rare malignancy in the lung, mixed LUA and TC/AC could be included among the histotypes for which a deep molecular characterization of both components is needed to identify the presence of potential druggable genetic alterations.

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Travis WD, Beasley M, Cree I et al (2021) Lung neuroendocrine neoplasms. In: WHO classification of tumors Editorial Board (ed) Thoracic Tumours. Lyon. IARC Press

Rindi G, Mete O, Uccella S et al (2022) Overview of the 2022 WHO classification of neuroendocrine neoplasms. Endocr Pathol 33(1):115–154. https://doi.org/10.1007/s12022-022-09708-2CrossRefPubMed

La Rosa S, Simbolo M, Franzi F et al (2018) Combined adenocarcinoma-atypical carcinoid of the lung. Targeted next-generation sequencing (NGS) suggests a monoclonal origin of the two components. Diagn Histopath 24:3,120–3,123. https://doi.org/10.1016/j.mpdhp.2018.02.002CrossRef

Parente P, Rossi A, Sparaneo A et al (2021) Mixed pulmonary adenocarcinoma and atypical carcinoid: a report of two cases of a non-codified entity with biological profile. Front Mol Biosci 3(8):784876. https://doi.org/10.3389/fmolb.2021.784876CrossRef

Metovic J, Barella M, Bianchi F et al (2021) Morphologic and molecular classification of lung neuroendocrine neoplasms. Virchows Arch 478(1):5–19. https://doi.org/10.1007/s00428-020-03015-zCrossRefPubMedPubMedCentral

Miyanaga A, Masuda M, Motoi N et al (2020) Whole-exome and RNA sequencing of pulmonary carcinoid reveals chromosomal rearrangements associated with recurrence. Lung Cancer 145:85–94. https://doi.org/10.1016/j.lungcan.2020.03.027CrossRefPubMed

Derks JL, Rijnsburger N, Hermans BCM et al (2021) Clinical-pathologic challenges in the classification of pulmonary neuroendocrine neoplasms and targets on the horizon for future clinical practice. J Thorac Oncol 16(10):1632–1646. https://doi.org/10.1016/j.jtho.2021.05.020CrossRefPubMed

Alcala N, Leblay N, Gabriel AAG et al (2019) Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids. Nat Commun 10(1):3407. https://doi.org/10.1038/s41467-019-11276-9CrossRefPubMedPubMedCentral

Cavazza A, Toffanetti R, Ferrari G et al (2001) Combined neoplasia of the lung: description of a case of adenocarcinoma mixed with typical carcinoid. Pathologica 93(3):216–220PubMed

10.

Olofson AM, Tafe LJ (2018) A case of a primary lung cancer comprised of adenocarcinoma and atypical carcinoid tumor with both components harboring BRAF p.V600E mutation. Exp Mol Pathol 104:26–28. https://doi.org/10.1016/j.yexmp.2017.12.004CrossRefPubMed

11.

Okazaki M, Sano Y, Soga Y et al (2015) Combined atypical carcinoid tumour and squamous cell carcinoma of the lung. Intern Med 54:1385–1388. https://doi.org/10.2169/internalmedicine.54.3846CrossRefPubMed

12.

Owens CL, Fraire AE (2011) Combined carcinoid tumor and squamous cell carcinoma of lung: expanding the spectrum of combined tumors of lung. Int J Surg Pathol 19:273–275. https://doi.org/10.1177/1066896910397883CrossRefPubMed

13.

Inoue C, Konosu-Fukaya S, Murakami K et al (2022) Coexistence of carcinoid tumor and adenocarcinoma of the lung; morphological, immunohistochemical and genetic analyses, a case report. Diagn Pathol 17(1):25CrossRefPubMedPubMedCentral

14.

Nagamatsu Y, Iwasaki Y, Omura H et al (2012) A case of resected synchronous multiple primary lung cancer comprising adenocarcinoma and carcinoid (cancer-in-cancer). Gen Thorac Cardiovasc Surg 60(8):518–521. https://doi.org/10.1007/s11748-012-0029-zCrossRefPubMed

15.

Abbi KKS, Hameed MK, Jiang Y et al (2014) Pulmonary collision tumor consisting of adenocarcinoma and typical carcinoid-a case report and review of literature. Am J Ther 21(6):e234–e238. https://doi.org/10.1097/MJT.0b013e318293b0b0CrossRefPubMed

16.

Sen F, Borczuk AC (1998) Combined carcinoid tumor of the lung: a combination of carcinoid and adenocarcinoma. Lung Cancer 21(1):53–58. https://doi.org/10.1016/S0169-5002(98)00042-7CrossRefPubMed

17.

Lloyd RV, Osamura RY, Klöppel G et al (2017) WHO classification of tumours of endocrine organs. IARC, Lyon

18.

Klimstra DS, Klöppel G, La Rosa S et al (2019) WHO classification of tumours of digestive system tumours, 5th edn. IARC, Lyon

19.

La Rosa S, Sessa F, Uccella S (2016) Mixed neuroendocrine-nonneuroendocrine neoplasms (MiNENs): unifying the concept of a heterogeneous group of neoplasms. Endocr Pathol 27(4):284–311. https://doi.org/10.1007/s12022-016-9432-9CrossRefPubMed

20.

Acker F, Stratmann J, Aspacher L et al (2021) KRAS Mutations in squamous cell carcinomas of the lung. Front Oncol 11:788084CrossRefPubMedPubMedCentral

21.

Philpott C, Tovell H, Frayling IM et al (2017) The NF1 somatic mutational landscape in sporadic human cancers. Hum Genomics 11:13. https://doi.org/10.1186/s40246-017-0109-3CrossRefPubMedPubMedCentral

22.

Swarts DRA, Ramaekers FCS, Speel EJM (1826) Molecular and cellular biology of neuroendocrine lung tumors: evidence for separate biological entities. Biochim Biophys Acta - Rev Cancer 2012:255–271. https://doi.org/10.1016/j.bbcan.2012.05.001CrossRef

23.

Vogt A, Schmid S, Heinimann K et al (2017) Multiple primary tumours: challenges and approaches, a review. ESMO Open 2(2):1–11. https://doi.org/10.1136/esmoopen-2017-000172CrossRef

Title: Clinical impact of mixed pulmonary carcinoma and carcinoid: the driver from their mono-clonal origin
Authors: Paolo Graziano
Paola Parente
Flavia Centra
Massimo Milione
Giovanni Centonze
Marco Volante
Alberto Cavazza
Diego Urbano
Giuseppe Di Maggio
Teresa Balsamo
Concetta Di Micco
Giulio Rossi
Antonio Rossi
Lucia Anna Muscarella
Publication date: 29-09-2023
Publisher: Springer Berlin Heidelberg
Keywords: Carcinoid Tumor
NSCLC
NSCLC
Metastasis
Published in: Virchows Archiv / Issue 1/2024
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-023-03663-x

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Clinical impact of mixed pulmonary carcinoma and carcinoid: the driver from their mono-clonal origin

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