Factors associated with type 1 gastric neuroendocrine tumor occurrence in autoimmune atrophic gastritis: insights from a real-world cohort.

BACKGROUND

Autoimmune gastritis (AIG) is characterized by chronic inflammation and represents a key step in the multistage precancerous process of the stomach. Patients with AIG are at increased risk of developing type I gastric neuroendocrine tumors (T1gNETs), but clinical and histological associated factors still remain incompletely defined.

AIM: To evaluate the occurrence of T1gNETs in our AIG patients cohort and to identify clinical, biochemical, and histological factors associated with tumor development.

METHODS

Retrospective analysis of histologically confirmed AIG followed at Humanitas Research Hospital (from January 2020 to February 2025). Clinical, biochemical, and histological variables were extracted from a dedicated database. Associations between T1gNETs incidence and risk factors (smoking, BMI, gastrin,chromogranin- CgA levels, histology, clinical presentation) were tested using chi-square, Spearman and Mann-Whitney tests, with bootstrap-derived confidence intervals for effect sizes.

RESULTS

Among 175 AIG patients, 28 (16%) were diagnosed with T1gNETs. ECL cell hyperplasia emerged as the strongest histological factor associated with T1gNETs (82.1 vs 55.8; p= 0.0109, OR = 3.65). Conversely, dyspeptic symptoms showed a significant inverse correlation with tumor occurrence (21.4% vs 43.5%; p=0.035, OR = 0.35), suggesting that T1gNETs often develop in asymptomatic patients. No significant predictive value was found for smoking, alcohol, BMI, severe hypergastrinemia/CgA (>3x ULN) levels or degree of corpus atrophy, although a trend was observed for corpus metaplasia.

CONCLUSIONS

Patients with AIG face significantly elevated occurrence of T1gNETs compared with the general population, with percentage being in line with recent studies. ECL hyperplasia was found as a factor associated with NET development, according to literature, confirming that the chronic stimulation of a cell with the ability to proliferate, results in tumors formation. Most patients with T1gNETs were asymptomatic and no correlation was found with smoking, alcohol and BMI. As a future perspective, these findings, even though preliminary, may help in the risk stratification of patients for more personalized endoscopic surveillance protocols, but further data are warranted to better standardize their use.