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Background: The association of intravenous prostacyclin therapy, essential for improving prognosis and survival in pulmonary arterial hypertension (PAH), with gastric epithelial neoplasms is uncertain. This study aimed to analyze the clinicopathologic features of gastric neoplasms in patients with PAH undergoing continuous intravenous prostacyclin therapy. Methods: We screened the registry of patients with pulmonary hypertension who visited the NHO Okayama Medical Center. Of the patients with PAH managed between January 2003 and December 2022, those who underwent esophagogastroduodenoscopy (EGD) were assessed for gastric neoplasms. Their clinical, endoscopic, and histopathological data were reviewed. Results: Among the 186 patients with PAH, 56 underwent EGD, revealing 4 patients (aged 37–50 years) with gastric epithelial neoplastic lesions. All four patients received continuous intravenous prostacyclin therapy for a median of 151 months. Of the 98 patients who received prostacyclin, 28 patients underwent EGD; the incidence of gastric epithelial neoplasms was 4.1% (4/98) and the endoscopic detection rate was 14.3% (4/28). All patients had multiple tumors against a background of hypertrophic gastropathy (histologically being foveolar epithelial hyperplasia), with shared features of distal location, elevated morphology, and absent submucosal invasion. However, lymph node metastasis was observed in one lesion. By immunohistochemistry, the tumors exhibited gastric-predominant mucus phenotype and were managed by surgical or endoscopic resection without recurrence. Conclusions: The consistent clinicopathologic features of these cases suggest an association between continuous intravenous prostacyclin therapy and the development of hypertrophic gastropathy with potential progression to gastric epithelial neoplasia. Further prospective clinical trials are warranted to ensure safer prostacyclin use. Full article