SMAD4 and large cell neuroendocrine carcinoma: Using the pancreas as example, since this was the presumed primary in one of our cases, poorly differentiated pancreatic neuroendocrine carcinomas may show features of small cell carcinoma or large cell neuroendocrine carcinoma [11] and differ from well-differentiated pancreatic NETs in their biology with more frequent inactivation of SMAD4, RB1 and TP53 and no loss of function of ATRX and DAXX [21–23].