Gastric Neuroendocrine Neoplasia

Abstract

The enterochromaffin-like (ECL) cell is the best-characterized neuroendocrine cell in the gastric mucosa and constitutes one type of at least seven different neuroendocrine cell types (approximately 1%–2% of total mucosal cells) that comprise the fundic mucosa. The ECL cell, however, is the predominant endocrine cell population of the gastric fundus and accounts for approximately 35%–65% of the gastric endocrine cell mass (Figure 7.1). The ECL cell is a pivotal regulator of acid secretion via a mechanism that involves its activation by circulating gastrin produced by antral G cells. Activation of the ECL CCK2R elicits the release of histamine which acts in a paracrine manner to initiate parietal cell secretion of protons into the gastric lumen (Figure 7.2). Low acid states engendered by acid suppression or loss of parietal cell mass (atrophic or autoimmune gastritis) results in diminution of acid secretion, elevated luminal pH, activation of antral G cells, hypergastrinemia, and endoscopic and histopathologic evidence of ECL cell hyperplasia and neoplasia variously recognized under the terminology of gastric neuroendocrine tumors (NETs) or gastric carcinoids. The latter term should be discarded as archaic and confusing because it embraces at least three different tumor types and does not indicate the specific cell type or malignant phenotype of the lesion. Gastric NETs have, in recent times, become the subject of substantial clinical and investigative interest. This reflects global concerns regarding the consequences of prolonged hypochlorhydria, longstanding hypergastrinemia (increased use of acid-suppressive pharmacotherapeutic agents), as well as the proposed putative relationship between gastric adenocarcinoma and gastric NETs. These tumors were previously considered rare lesions, overall representing less than 2% of all gastrointestinal NETs and less than 1% of all gastric neoplasms. The misconception of rarity is redundant because current cancer databases indicate that gastric NETs are increasing in incidence/prevalence and that the current figures are closer to 5%. Whether this represents increased clinical awareness, more accurate pathologic identification, or more thorough endoscopic surveillance is debatable, but nevertheless, provides a far larger group of patients whose disease requires