Neuroendocrine pathology of the stomach: the Parma contribution

The current knowledge on gastric neuroendocrine pathology essentially developed in the last four decades. The historical evolution of the concepts and of the relevant clinical implications is described from the perspective of a group actively participating in this research domain. The histamine-producing enterochromaffin-like (ECL) cells have been recognized as the leading cell type involved in the most significant alterations of gastric neuroendocrine cells. The trophic stimulus exerted by circulating gastrin has been demonstrated to have a crucial role on proliferative changes of ECL cells through a sequence of hyperplasia-dysplasia-neoplasia described by Solcia et al. (Digestion 41:185-200,1988). The development of ECL cell tumors in rats treated with toxicological doses of inhibitors of gastric acid secretion prompted appropriate anatomoclinical investigations proving the lack of tumor risk in humans when therapeutic dosages of the drugs are used. Moving from the comprehensive concept of gastric carcinoid, different types of neuroendocrine tumors have been identified in the stomach with substantial variations in prognosis and treatment options. In general, ECL cell tumors developed in hypergastrinemic conditions were found to behave better than those originating outside the setting of hormonal stimulation. Pathological features highly predictive of patient survival have been described. The genetic changes involved in tumor development and progression have revealed substantial overlapping with those of neuroendocrine tumors of other foregut derivatives (i.e., pancreas, duodenum, lung) delineating a family of neuroendocrine tumors genetically distinct from those of the distal parts of the digestive system.