Neuroendocrine proliferations of the stomach: a pragmatic approach for the perplexed pathologist

The classifications of neuroendocrine proliferations that lead from enterochromaffin-like cell hyperplasia to neuroendocrine tumors in the stomach are complicated and relatively inaccessible to nonspecialists. Consequently, these lesions tend to remain widely underdiagnosed until they progress to easily recognizable neuroendocrine tumors. This review provides simple, yet rigorous guidelines on how to recognize, classify, and diagnose the neuroendocrine proliferations found in the stomach, emphasizing the most common background in which they arise, atrophic gastritis. After a succinct outline of the types and distribution of the neuroendocrine cells in the normal gastric mucosa we discuss the most common situations in which the pathologist needs to think about gastric neuroendocrine cells. In general practice gastric biopsy specimens are often numerically and topographically inadequate for the evaluation of atrophic gastritis; therefore, we have included an algorithm to address specifically the steps that should be taken when confronted with suboptimal sampling. Finally, we illustrate the suggested diagnostic process with 4 cases that are fairly representative of the type of situations encountered in everyday practice. The pathologist who follows our simple steps will be better aware of this neglected area of gastric pathology and will learn to suspect, recognize, and accurately diagnose the most common abnormalities of the neuroendocrine system in the stomach.