{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:16:21Z","timestamp":1791666981664,"version":"4.3.4"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Clinical Significance: Ganglioneuromas are rare benign tumors of neural crest origin, with gastrointestinal involvement being uncommon and ampullary localization exceptionally rare. Pancreatic neuroendocrine tumors (NETs) are also uncommon neoplasms with variable biological behavior. The coexistence of these two entities is unusual, particularly in the absence of an identifiable hereditary syndrome. Case Presentation: A 38-year-old man presented with hematemesis and multiple episodes of melena over 18 h and was found to have significant anemia with borderline hemodynamic stability. Upper gastrointestinal endoscopy revealed an enlarged, actively bleeding papilla of Vater, and initial hemostasis was achieved with adrenaline injection and endoscopic clipping. However, recurrent massive bleeding developed within 36 h, accompanied by hemodynamic instability. Repeat endoscopy confirmed ongoing hemorrhage, and the patient subsequently underwent emergency pancreaticoduodenectomy. Histopathological examination demonstrated an ampullary ganglioneuroma and an incidental well-differentiated pancreatic neuroendocrine tumor (WHO Grade 2). Surgical margins were negative, and no lymph node metastases were identified. Further evaluation for hereditary endocrine syndromes was unremarkable. The patient remains asymptomatic, with no evidence of recurrence during a 10-year follow-up period. This case highlights the diagnostic and therapeutic challenges associated with rare periampullary tumors. Although ganglioneuromas are typically benign, their anatomical location may result in severe clinical manifestations such as life-threatening bleeding. The coexistence with a pancreatic NET raises questions regarding potential shared pathogenesis, although no genetic syndrome was identified. Limitations of endoscopic management in uncontrolled bleeding and the importance of definitive surgical intervention are emphasized. Conclusions: This case highlights an exceptionally rare coexistence of ampullary ganglioneuroma and pancreatic neuroendocrine tumor presenting with life-threatening gastrointestinal bleeding. Although ganglioneuromas are benign, their anatomical location may result in severe clinical manifestations. Early recognition and decisive surgical management are crucial when endoscopic control fails. Favorable long-term outcomes can be achieved following complete resection.<\/jats:p>","DOI":"10.3390\/diagnostics16121778","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:58:12Z","timestamp":1781053092000},"page":"1778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Life-Threatening Gastrointestinal Bleeding Revealing a Rare Coexistence of Ampullary Ganglioneuroma and Pancreatic Neuroendocrine Tumor: A Case Report"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7198-2628","authenticated-orcid":false,"given":"Francesk","family":"Mulita","sequence":"first","affiliation":[{"name":"Second Department of Surgery, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece"},{"name":"Department of Surgery, Medical School, University of Patras, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kouroupi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios-Ioannis","family":"Verras","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical School, University of Patras, 26504 Patras, Greece"},{"name":"Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7881-7004","authenticated-orcid":false,"given":"Anna-Maria","family":"Mitropoulou","sequence":"additional","affiliation":[{"name":"Second Department of Surgery, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2763-9557","authenticated-orcid":false,"given":"Helen","family":"Bolanaki","sequence":"additional","affiliation":[{"name":"Second Department of Surgery, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8855-6358","authenticated-orcid":false,"given":"Ioannis","family":"Tzimagiorgis","sequence":"additional","affiliation":[{"name":"Second Department of Surgery, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Giatromanolaki","sequence":"additional","affiliation":[{"name":"Department of Pathology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9278-4273","authenticated-orcid":false,"given":"Anastasios J.","family":"Karayiannakis","sequence":"additional","affiliation":[{"name":"Second Department of Surgery, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37730","DOI":"10.18632\/oncotarget.17146","article-title":"Clinical and biological features of neuroblastic tumors: A comparison of neuroblastoma and ganglioneuroblastoma","volume":"8","author":"He","year":"2017","journal-title":"Oncotarget"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1002\/1097-0142(20010515)91:10<1905::AID-CNCR1213>3.0.CO;2-4","article-title":"Metabolic activity and clinical features of primary ganglioneuromas","volume":"91","author":"Geoerger","year":"2001","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1097\/00000478-199403000-00004","article-title":"Ganglioneuromas of the gastrointestinal tract. 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