Most high-grade neuroendocrine tumours of the lung are likely to secondarily develop from pre-existing carcinoids: innovative findings skipping the current pathogenesis paradigm

Giuseppe Pelosi, Fabrizio Bianchi, Elisa Dama, Michele Simbolo, Andrea Mafficini, Angelica Sonzogni, Sara Pilotto, Sergio Harari, Mauro Papotti, Marco Volante, Gabriella Fontanini, Luca Mastracci, Adriana Albini, Emilio Bria, Fiorella Calabrese, Aldo Scarpa

Research output: Contribution to journalArticle

Abstract

Among lung neuroendocrine tumours (Lung-NETs), typical carcinoid (TC) and atypical carcinoid (AC) are considered separate entities as opposed to large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC). By means of two-way clustering analysis of previously reported next-generation sequencing data on 148 surgically resected Lung-NETs, six histology-independent clusters (C1 → C6) accounting for 68% of tumours were identified. Low-grade Lung-NETs were likely to evolve into high-grade tumours following two smoke-related paths. Tumour composition of the first path (C5 → C1 → C6) was coherent with the hypothesis of an evolution of TC to LCNEC, even with a conversion of SCLC-featuring tumours to LCNEC. The second path (C4 → C2–C3) had a tumour composition supporting the evolution of AC to SCLC-featuring tumours. The relevant Ki-67 labelling index varied accordingly, with median values being 5%, 9% and 50% in the cluster sequence C5 → C1 → C6, 12% in cluster C4 and 50–60% in cluster C2–C3. This proof-of-concept study suggests an innovative view on the progression of pre-existing TC or AC to high-grade NE carcinomas in most Lung-NET instances.

Original languageEnglish
Pages (from-to)567-577
Number of pages11
JournalVirchows Archiv
Volume472
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

Keywords

  • Cluster analysis
  • Lung
  • Neuroendocrine
  • Transition
  • Tumours

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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