Thymus neuroendocrine tumors with CTNNB1 gene mutations, disarrayed ß-catenin expression, and dual intra-tumor Ki-67 labeling index compartmentalization challenge the concept of secondary high-grade neuroendocrine tumor: a paradigm shift.

Détails

ID Serval
serval:BIB_8CDCE54EEE72
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Thymus neuroendocrine tumors with CTNNB1 gene mutations, disarrayed ß-catenin expression, and dual intra-tumor Ki-67 labeling index compartmentalization challenge the concept of secondary high-grade neuroendocrine tumor: a paradigm shift.
Périodique
Virchows Archiv
Auteur(s)
Fabbri A., Cossa M., Sonzogni A., Bidoli P., Canova S., Cortinovis D., Abbate M.I., Calabrese F., Nannini N., Lunardi F., Rossi G., La Rosa S., Capella C., Tamborini E., Perrone F., Busico A., Capone I., Valeri B., Pastorino U., Albini A., Pelosi G.
ISSN
1432-2307 (Electronic)
ISSN-L
0945-6317
Statut éditorial
Publié
Date de publication
07/2017
Peer-reviewed
Oui
Volume
471
Numéro
1
Pages
31-47
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
We herein report an uncommon association of intimately admixed atypical carcinoid (AC) and large cell neuroendocrine (NE) carcinoma (LCNEC) of the thymus, occurring in two 20- and 39-year-old Caucasian males. Both tumors were treated by maximal thymectomy. The younger patient presented with a synchronous lesion and died of disease after 9 months, while the other patient was associated with a recurrent ectopic adrenocorticotropic hormone Cushing's syndrome and is alive with disease at the 2-year follow-up. MEN1 syndrome was excluded in either case. Immunohistochemically, disarrayed cytoplasmic and nuclear ß-catenin expression was seen alongside an intra-tumor Ki-67 antigen labeling index (LI) ranging from 2 to 80% in the younger patient's tumor and from 3 to 45% in the other. Both exhibited upregulated cyclin D1 and retinoblastoma, while vimentin was overexpressed in the recurrent LCNEC only. Next-generation sequencing revealed CTNNB1, TP53, and JAK3 mutations in the synchronous tumor and CTNNB1 mutation alone in the metachronous tumor (the latter with the same mutation as the first tumor of 17 years prior). None of the 23 T-NET controls exhibited this hallmarking triple alteration (p = 0.003). These findings suggested that LCNEC components developed from pre-existing CTNNB1-mutated AC upon loss-of-function TP53 and gain-of-function JAK3 mutations in one case and an epithelial-mesenchymal transition upon vimentin overexpression in the other case. Both tumors maintained intact cyclin D1-retinoblastoma machinery. Our report challenges the concept of secondary LCNEC as an entity that develops from pre-existing AC as a result of tumor progression, suggesting a paradigm shift to the current pathogenesis of NET.

Mots-clé
Atypical carcinoid, Immunohistochemistry, Large cell neuroendocrine carcinoma, Next-generation sequencing, Thymus, ß-catenin
Pubmed
Web of science
Création de la notice
02/05/2017 7:44
Dernière modification de la notice
20/08/2019 14:51
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