Histopathological subtypes of gastric neuroendocrine cell hyperplasia: a cross-sectional association with hypergastrinemia and coexisting gastric lesions at index endoscopy

Abstract

Gastric neuroendocrine cell hyperplasia (NECH) is a hypergastrinemia-driven spectrum of enterochromaffin-like cell proliferation that may precede or coexist with well-differentiated gastric neuroendocrine tumors (g-NETs). However, the clinical relevance of specific histologic patterns remains unclear. This single-center, retrospective cross-sectional study evaluated the association between NECH subtypes, serum gastrin categories, and coexisting endoscopic and histopathological findings at the index upper gastrointestinal endoscopy in adults with biopsy-proven NECH at Akdeniz University Hospital, Türkiye, between July 1, 2021, and July 1, 2022. Because serum gastrin testing was performed only when clinically indicated, these analyses were restricted to a select subgroup and should be interpreted as exploratory. Of the 605 patients who met the inclusion criteria, 511 with comprehensive data were selected for analysis, and serum gastrin levels were available for 157 individuals. NECH morphology was classified as diffuse, linear, micronodular, adenomatoid, or mixed. The Updated Sydney System was used to grade gastric atrophy and Helicobacter pylori ( H. pylori ) density. The assessed comorbidities included intestinal metaplasia, dysplasia, g-NET, and polyps. The majority of the cohort showed no evidence of gastric atrophy, and H. pylori was detected in 50.9% of cases. Among the 157 patients with documented serum gastrin measurements, levels ≥ 400 pg/mL were associated with a higher prevalence of intestinal metaplasia, dysplasia, and g-NET, as well as an increase in the prevalence of coexisting polyps. No significant association was observed between serum gastrin levels and atrophic gastritis or H. pylori density. Serum gastrin distribution varied by NECH subtype; linear patterns were predominant in patients with normal gastrin levels, whereas adenomatoid or mixed patterns were most frequent in patients with gastrin levels ≥ 400 pg/mL. Subtype-specific g-NET prevalence was 1.4% for diffuse, 0.5% for linear, 1.3% for micronodular, 35.3% for adenomatoid, and 8.5% for mixed, with a full cohort g-NET prevalence of 4.1%. A maximum-likelihood multivariable analysis of the full cohort identified adenomatoid or mixed NECH morphology as being associated with coexisting g-NETs. Given the limitations of this retrospective, single-center, cross-sectional design and the non-systematic assessment of gastrin levels, the observed associations between hypergastrinemia, adenomatoid or mixed NECH, and coexisting gastric lesions are exploratory and do not imply a causal relationship. The full-cohort g-NET prevalence of 4.1% represents a point estimate for this unselected NECH population; however, associations with specific NECH subtypes lacked statistical independence under sparse-event conditions. These findings cannot be generalized to all NECH-positive patients and do not support the development of clinical risk-stratification rules or recommendations for intensified surveillance. Prospective validation using standardized gastrin testing, autoimmune gastritis serology, comprehensive PPI documentation, and longitudinal follow-up is necessary to draw more definitive conclusions.