Multiple faces of pulmonary large cell neuroendocrine carcinoma: update with a focus on practical approach to diagnosis

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive malignancy that is strongly linked to smoking and notoriously difficult to diagnose and treat. Recent molecular data reveal that it represents a biologically heterogeneous group of tumors, characterized by morphologic and genomic diversity that straddles small cell and non-small cell lung carcinomas (NSCLCs), and in a minority of cases atypical carcinoids. This review provides an update on recent molecular and clinical developments in LCNEC with the main focus on practical approach to pathologic diagnosis using illustrative examples of the main differential diagnostic considerations.