Neuroendocrine tumors of unknown primary: a case report and review of tumors with gastroenteropancreatic features.

BACKGROUND: Neuroendocrine tumors (NETs) are a complex group of tumors that arise from cells of the nervous and endocrine systems. They occur predominantly in the digestive or respiratory tracts, with those occurring along the gastrointestinal tract and pancreas classified as gastroenteropancreatic NETs. While certain features may suggest a gastroenteropancreatic origin, definitive localization of the primary site remains elusive in a substantial number of metastatic cases. These cases, referred to as NETs of unknown primary origin, can pose significant diagnostic, therapeutic, and prognostic implications. Here, we present a case of a NET of unknown primary, with features suggestive of gastroenteropancreatic origin, alongside a focused literature review highlighting key clinical features, diagnostic approaches, and therapeutic strategies to increase awareness of this challenging entity. CASE DESCRIPTION: A 19-year-old male with a history of celiac disease and gastroesophageal reflux disease (GERD) was found to have a grade 2 metastatic well-differentiated NET involving the perigastric region and the liver. On pre-operative workup, extensive imaging, and surgical exploration of the abdomen, no primary tumor was identified. The patient underwent cytoreductive surgery and was started on lanreotide injections with no definite evidence of disease recurrence or progression on imaging after a post-operative follow-up of 6 months. Ultimately, it remains unclear what the primary source of the neuroendocrine malignancy was in this patient despite endoscopic interventions, imaging modalities, and an array of histopathological tests. CONCLUSIONS: NETs of unknown primary, in particular those with gastroenteropancreatic features, remain poorly characterized in the literature, with no standardized diagnostic or management framework. In this case report, we present the case of a young male with metastatic NET of unknown primary, as well as highlight the features, mechanisms, workup, and management of such tumors. By presenting this case, we hope to emphasize the diagnostic complexity of these NETs with unknown primary and why careful consideration of undetectable lesions, atypical tumor origins, or spontaneous regression must be integrated into clinical decision-making and prognostic assessment.