Gastric neuroendocrine tumors: a comprehensive analysis of clinicopathological characteristics and survival outcomes from a reference center.

Abstract

Background: Gastric neuroendocrine tumors (gNETs) are uncommon neoplasms arising from enterochromaffin-like cells, representing a distinct subset of gastric malignancies, with challenging clinical management.

Aims: To analyse the classification, treatment indication, and survival of patients diagnosed with gNETs.

Methods: We retrospectively analyzed patients diagnosed with gNETs between 2009 and 2025 at a high-volume tertiary center in Brazil. Clinical, pathological, and treatment data were reviewed, and tumors were classified according to World Health Organization and clinicopathological criteria into Types I, II, and III.

Results: Of the 75 patients included, 53 (70.7%) were classified as Type I, 5 (6.7%) as Type II, and 17 (22.6%) as Type III. Treatment included surgery in 25 patients (33.3%) and endoscopic resection in 50 (66.7%). Type I tumors predominated in females (p<0.001), were frequently multifocal (p<0.001), associated with higher body mass index (p=0.002), and were mainly managed endoscopically (p=0.008). Type II tumors were rare and associated with multiple endocrine neoplasia Type 1, while Type III tumors were predominantly male, larger, high-grade (G3), and frequently metastatic, requiring surgical resection and palliative therapy. Among the 25 surgically treated patients, most were men (52%) and included 12 patients (48.0%) with Type I, 3 (12.0%) with Type II, and 10 (40.0%) with Type III tumors. Survival analysis showed significantly worse outcomes for Type III and G3 tumors. Multivariable analysis identified advanced age (hazards ratio 4.11; 95% confidence interval (95%CI): 1.14-14.80; p=0.030) and tumor, lymph node, metastasis (TNM) stage III/IV (HR 5.42; 95%CI: 1.26-23.26; p=0.023) as independent predictors of poorer survival.

Conclusions: gNETs exhibit heterogeneous clinical behavior, with Type I tumors predominating in the Brazilian population. Tumor type, grade, and TNM stage are critical determinants of prognosis and should guide individualized treatment strategies.

Central message: The stomach is the most frequent site of gastrointestinal neuroendocrine neoplasms (NENs), with an annual incidence of approximately 0.4 per 1,00,000 individuals. According to the most recent World Health Organization Classification of Tumors of the Digestive System, NENs are divided into three major categories: gastric neuroendocrine tumors, which are the most common, well-differentiated, and have any grade; neuroendocrine carcinomas, which are poorly differentiated and high-grade; and mixed neuroendocrine-non-neuroendocrine neoplasms, which are aggressive and harbor multiple molecular alterations. These neoplasms originate from enterochromaffin-like cells of the gastric mucosa.

Perspectives: Gastric neuroendocrine tumors (gNETs) are uncommon and heterogeneous, and require individualized management. In this largest Brazilian cohort, Type I gNET predominated, showing indolent behavior and favorable outcomes with endoscopic treatment. Type II tumors were rare and invariably linked to multiple endocrine neoplasia type 1, while Type III tumors presented aggressive features, advanced stage, and poor survival. Prognosis was strongly determined by tumor, lymph node, metastasis stage, highlighting the importance of accurate staging and histopathological evaluation.