Gastric neuroendocrine neoplasms (g-NENs) include heterogeneous entities with distinct etiological, biological and clinical profiles. Type 1 g-NENs are classically associated with autoimmune chronic atrophic gastritis, whereas type 3 lesions behave more aggressively with higher metastatic potential. Long-term European real-world data remain limited. This study aimed to describe the epidemiology, autoimmune background, treatment strategies and outcomes of g-NENs diagnosed over 15 years at a high-volume Italian tertiary center, and to compare risk factors for recurrence and metastatic spread.

We performed a retrospective observational cohort study including all consecutive patients diagnosed with g-NENs at the Gastroenterology Unit, Santa Maria della Misericordia Hospital, Udine (Italy) between 2010 and 2025. Clinical, biochemical, endoscopic, histological and therapeutic data were retrieved from electronic records. Variables included demographics, autoimmune markers (APCA), presence of autoimmune atrophic gastritis (AAG), tumor location, size, Ki-67, grading, treatment modality, recurrence, lymph-node involvement and distant metastasis. Statistical analyses included chi-square/Fisher’s exact test, Mann–Whitney U test and odds ratios with 95% confidence intervals.

Thirty patients were included (66.7% male; mean age 68.8±11.3 years). Autoimmune disorders were present in 54.2%, AAG in 36.7% and APCA positivity in 36.7%. Strong associations emerged between type 1 g-NENs and AAG (10/11 with AAG; p<0.001; OR 10.0) as well as APCA positivity (10/11 APCA+; p=0.002; OR 28.0). Half of the cohort had type 1 g-NENs (n=15) and half type 3 (n=15). Type 1 patients were significantly younger than type 3 (64.7±10.6 vs 72.9±10.5 years; p=0.019).Overall, 63.6% of tumors were G1, 22.7% G2 and 13.6% G3/NEC. Mean lesion size was 12.7±8.4 mm (median 10 mm). Lymph-node metastases occurred in 3/30 patients (10%), and distant metastasis in 1 patient (3.3%), exclusively in tumors with very high Ki-67 (90–100%; p=0.024) and larger size (p=0.018).Treatment consisted of endoscopic resection in 55.6% and surgery in 29.6%; type 1 lesions showed a non-significant trend toward less surgery (p=0.678). Local recurrence occurred in 3/29 patients (10.3%), all intragastric and manageable endoscopically. No tumor-related deaths were observed during available follow-up.

This long-term experience confirms the distinct biological behaviors of gastric NENs, with indolent type 1 lesions linked to autoimmunity and more aggressive type 3 tumors associated with high proliferative index and metastatic risk. The strong link between AAG/APCA positivity and type 1 g-NEN supports the role of autoimmune biomarkers in diagnostic classification. Endoscopic therapy was effective and safe in most low-risk lesions, while high-grade or large type 3 tumors required surgical management. Recurrence was infrequent and locally manageable.These findings align with current ENETS guidance and highlight the need for structured long-term endoscopic surveillance in AAG-associated type 1 NENs, and for early multidisciplinary evaluation in type 3 disease. Prospective multicenter studies with standardized follow-up intervals are warranted to refine prognostic stratification and optimize treatment pathways.