Rare Etiologies of Upper Gastrointestinal Bleeding: A Narrative Review

Rare presentations are surprising and may disturb the day-to-day routine of a medical unit; however, they are expected (not as individual entities, but as a group of "uncommon causes"). While reviewing the literature in relation to three clinical cases of upper gastrointestinal bleeding (UGIB) encountered in our institution-gastric metastases of breast cancer (GMB), pyloric gland adenoma, and gastrointestinal stromal tumor (GIST)-we identified seven and 29 case reports for the first two entities, and over 100 publications addressing GIST. This prompted a shift in focus from novel reporting to diagnostic contextualization. We found it difficult to obtain an overview of the spectrum of UGIB etiologies, as most publications refer to a few individual entities or to a subgroup of rare causes. The narrative review we conducted arose from this particular research methodology. Based on a broad literature search, UGIB etiologies were organized in five categories (lesions of the mucosa, neoplasms, vascular causes, bleeding predisposition, and external sources of bleeding). In the management of patients with UGIB, the underlying etiology deviates from the classic peptic ulcer disease/esophageal varices dyad in approximately half of the cases. This underscores the need for heightened clinical vigilance, particularly in complex scenarios, where endoscopic findings, imaging results, and histopathological interpretations may be unexpected or prone to misinterpretation. As an illustration, we conducted two systematic reviews of case reports of bleeding GMB and PGA. Our findings support a proactive diagnostic and research mindset and advocate for improved awareness of uncommon UGIB etiologies.