Morphologic and molecular classification of lung neuroendocrine neoplasms
Jasna Metović, Marco Barella, Fabrizio Bianchi, Paul Hofman, Véronique Hofman, Myriam Remmelink, Izidor Kern, Lina Carvalho, Linda Pattini, Angelica Sonzogni, Giulia Veronesi, Sergio Harari, Fabien Forest, Mauro Papotti, Giuseppe Pelosi
Abstract
Neuroendocrine neoplasms (NENs) of the lung encompass neuroendocrine tumors (NETs) composed of typical (TC) and atypical (AC) carcinoids and full-fledged carcinomas (NECs) inclusive of large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC). NETs and NECs are thought to represent distinct and separate lesions with neither molecular overlap nor common developmental continuum. Two perspectives were addressed regarding the morphologic and molecular classification of lung NENs: (i) a supervised approach by browsing the traditional classification, the relevant gene alterations, and their clinical implications; and (ii) an unsupervised approach, by reappraising neoplasms according to risk factors and natural history of disease to construct an interpretation model relied on biological data. We herein emphasize lights and shadows of the current classification of lung NENs and provide an alternative outlook on these tumors focused on what we currently know about the biological determinants and the natural history of disease.