Hermans BCM, Sanduleanu S, Derks JL, et al. - This study was intended to assess if molecular subtypes of large cell neuroendocrine carcinoma (LCNEC), i.e. small cell lung carcinoma (SCLC)-like (with pRb loss) vs. non-small cell lung carcinoma (NSCLC)-like (with pRb expression), can be discerned by imaging based on imaging interpretation, semantic features, and/or a radiomics signature, designed to tell SCLC from NSCLC. Data were collected from 48 SCLC and 76 NSCLC scans and validated on an external set of 58 SCLC and 40 NSCLC scans. Researchers applied the signature on scans of 28 SCLC-like and 8 NSCLC-like LCNEC patients. It was indicated that LCNEC seems to have radiological features of both SCLC and NSCLC, regardless of pRb loss, compatible with the SCLC-like subtype. The results of this study exhibit that imaging interpretation, semantic characteristics and the radiomics signature designed to tell the difference between SCLC and NSCLC were unable to separate molecular LCNEC subtypes, which highlights that LCNEC is a unique disease.