Overall, although preliminary, our data suggest that supra-carcinoids could be diagnosed based on a combination of morphological features (carcinoid-like morphology, useful for the differential diagnosis with LCNEC/SCLC) and the high expression of a panel of immune checkpoint (IC) genes (LCNEC/SCLC-like molecular features, useful for the differential diagnosis with other carcinoids); the levels of IC genes, such as PD-L1, VISTA, and LAG3, could also be used to drive the therapeutic decision for patients harbouring a tumour belonging to this subset of very aggressive carcinoids. Here, VSIR is linked to large cell neuroendocrine carcinoma.