Journal
VIRCHOWS ARCHIV
Volume 478, Issue 1, Pages 5-19Publisher
SPRINGER
DOI: 10.1007/s00428-020-03015-z
Keywords
Neuroendocrine; Lung; Carcinoma; Carcinoid; Typical; Atypical; Large cell; Small cell; Classification; Stem cell; Progression; Differentiation; Gene; Molecular; Signature
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Funding
- Universita degli Studi di Milano
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The discussion in the article revolves around the morphological and molecular classification of lung neuroendocrine neoplasms, focusing on supervised and unsupervised approaches. It emphasizes the strengths and weaknesses of the current classification of lung NENs and provides an alternative outlook based on biological data.
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.
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