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Pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: Napsin A expression and genomic alterations

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive malignancy, which was recently found to comprise three major genomic subsets: small cell carcinoma-like, non-small cell carcinoma (predominantly adenocarcinoma)-like and carcinoid-like. To further characterize adenocarcinom...

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Autores principales: Rekhtman, Natasha, Pietanza, Catherine M., Sabari, Joshua, Montecalvo, Joseph, Wang, Hangjun, Habeeb, Omar, Kadota, Kyuichi, Adusumilli, Prasad, Rudin, Charles M., Ladanyi, Marc, Travis, William D., Joubert, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937126/
https://www.ncbi.nlm.nih.gov/pubmed/28884744
http://dx.doi.org/10.1038/modpathol.2017.110
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author Rekhtman, Natasha
Pietanza, Catherine M.
Sabari, Joshua
Montecalvo, Joseph
Wang, Hangjun
Habeeb, Omar
Kadota, Kyuichi
Adusumilli, Prasad
Rudin, Charles M.
Ladanyi, Marc
Travis, William D.
Joubert, Philippe
author_facet Rekhtman, Natasha
Pietanza, Catherine M.
Sabari, Joshua
Montecalvo, Joseph
Wang, Hangjun
Habeeb, Omar
Kadota, Kyuichi
Adusumilli, Prasad
Rudin, Charles M.
Ladanyi, Marc
Travis, William D.
Joubert, Philippe
author_sort Rekhtman, Natasha
collection PubMed
description Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive malignancy, which was recently found to comprise three major genomic subsets: small cell carcinoma-like, non-small cell carcinoma (predominantly adenocarcinoma)-like and carcinoid-like. To further characterize adenocarcinoma-like subset, here we analyzed the expression of exocrine marker napsin A, along with TTF-1, in a large series of LCNECs (n=112), and performed detailed clinicopathologic and genomic analysis of napsin A-positive cases. For comparison, we analyzed napsin A expression in other lung neuroendocrine neoplasms (177 carcinoids, 37 small cell carcinomas) and lung adenocarcinomas (n=60). We found that napsin A was expressed in 15% of LCNEC (17/112), whereas all carcinoids and small cell carcinomas were consistently negative. Napsin A reactivity in LCNEC was focal in 12/17 cases, and weak or moderate in intensity in all cases, which was significantly lower in the extent and intensity than seen in adenocarcinomas (p<0.0001). The combination of TTF-1-diffuse/napsin A-negative or focal was typical of LCNEC but was rare in adenocarcinoma, and could thus serve as a helpful diagnostic clue. The diagnosis of napsin A-positive LCNECs was confirmed by classic morphology, diffuse labeling for at least one neuroendocrine marker, most consistently synaptophysin, and the lack of distinct adenocarcinoma component. Genomic analysis of 14 napsin A-positive LCNECs revealed the presence of mutations typical of lung adenocarcinoma (KRAS and/or STK11) in 11 cases. In conclusion, LCNECs are unique among lung neuroendocrine neoplasms in that some of these tumors exhibit low-level expression of exocrine marker napsin A, and harbor genomic alterations typical of adenocarcinoma. Despite the apparent close biological relationship, designation of adeno-like LCNEC as a separate entity from adenocarcinoma is supported by their distinctive morphology, typically diffuse expression of neuroendocrine marker(s) and aggressive behavior. Further studies are warranted to assess the clinical utility and optimal method of identifying adenocarcinoma-like and other subsets of LCNEC in routine practice.
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spelling pubmed-59371262018-05-07 Pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: Napsin A expression and genomic alterations Rekhtman, Natasha Pietanza, Catherine M. Sabari, Joshua Montecalvo, Joseph Wang, Hangjun Habeeb, Omar Kadota, Kyuichi Adusumilli, Prasad Rudin, Charles M. Ladanyi, Marc Travis, William D. Joubert, Philippe Mod Pathol Article Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a highly aggressive malignancy, which was recently found to comprise three major genomic subsets: small cell carcinoma-like, non-small cell carcinoma (predominantly adenocarcinoma)-like and carcinoid-like. To further characterize adenocarcinoma-like subset, here we analyzed the expression of exocrine marker napsin A, along with TTF-1, in a large series of LCNECs (n=112), and performed detailed clinicopathologic and genomic analysis of napsin A-positive cases. For comparison, we analyzed napsin A expression in other lung neuroendocrine neoplasms (177 carcinoids, 37 small cell carcinomas) and lung adenocarcinomas (n=60). We found that napsin A was expressed in 15% of LCNEC (17/112), whereas all carcinoids and small cell carcinomas were consistently negative. Napsin A reactivity in LCNEC was focal in 12/17 cases, and weak or moderate in intensity in all cases, which was significantly lower in the extent and intensity than seen in adenocarcinomas (p<0.0001). The combination of TTF-1-diffuse/napsin A-negative or focal was typical of LCNEC but was rare in adenocarcinoma, and could thus serve as a helpful diagnostic clue. The diagnosis of napsin A-positive LCNECs was confirmed by classic morphology, diffuse labeling for at least one neuroendocrine marker, most consistently synaptophysin, and the lack of distinct adenocarcinoma component. Genomic analysis of 14 napsin A-positive LCNECs revealed the presence of mutations typical of lung adenocarcinoma (KRAS and/or STK11) in 11 cases. In conclusion, LCNECs are unique among lung neuroendocrine neoplasms in that some of these tumors exhibit low-level expression of exocrine marker napsin A, and harbor genomic alterations typical of adenocarcinoma. Despite the apparent close biological relationship, designation of adeno-like LCNEC as a separate entity from adenocarcinoma is supported by their distinctive morphology, typically diffuse expression of neuroendocrine marker(s) and aggressive behavior. Further studies are warranted to assess the clinical utility and optimal method of identifying adenocarcinoma-like and other subsets of LCNEC in routine practice. 2017-09-08 2018-01 /pmc/articles/PMC5937126/ /pubmed/28884744 http://dx.doi.org/10.1038/modpathol.2017.110 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Rekhtman, Natasha
Pietanza, Catherine M.
Sabari, Joshua
Montecalvo, Joseph
Wang, Hangjun
Habeeb, Omar
Kadota, Kyuichi
Adusumilli, Prasad
Rudin, Charles M.
Ladanyi, Marc
Travis, William D.
Joubert, Philippe
Pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: Napsin A expression and genomic alterations
title Pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: Napsin A expression and genomic alterations
title_full Pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: Napsin A expression and genomic alterations
title_fullStr Pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: Napsin A expression and genomic alterations
title_full_unstemmed Pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: Napsin A expression and genomic alterations
title_short Pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: Napsin A expression and genomic alterations
title_sort pulmonary large cell neuroendocrine carcinoma with adenocarcinoma-like features: napsin a expression and genomic alterations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5937126/
https://www.ncbi.nlm.nih.gov/pubmed/28884744
http://dx.doi.org/10.1038/modpathol.2017.110
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