Beyond the Obvious: Spectrum of Neuroendocrine Proliferation and Tumors in the Biliary Tree - A Case Series

Abstract

Abstract Introduction/Objective Neuroendocrine tumors (NETs) in the biliary system are extremely uncommon and often pose a diagnostic challenge due to their non-specific presentation and radiological features. While typically NETs form mass lesions causing biliary obstruction, to the best of our knowledge, microscopic neuroendocrine cell proliferation without mass formation has not been formally reported in the literature. This study aims to describe the clinicopathological features of a series of NETs/neuroendocrine cell proliferation involving the biliary tree. Methods/Case Report Surgical resections of NETs/neuroendocrine cell proliferation affecting the extrahepatic bile ducts and gallbladder were identified from the electronic pathology databases of five institutions between January 2010 and May 2023. The clinical data was obtained through chart review, and histologic findings were reviewed by a gastrointestinal pathologist at each institution. Results (if a Case Study enter NA) The study involved six patients with a mean age of 66 years (range: 58-75 years, males:3, females:3). The patients presented with abdominal pain or biliary obstruction. Pathologic examination revealed that three cases showed visible mass-forming lesions (1.6-2.4 cm) in the gallbladder or common bile duct, diagnosed as well-differentiated NETs. The remaining three cases had no grossly visible masses but showed incidental microscopic neuroendocrine cell proliferation/NETs (either in cystic duct or common bile duct) ranging from 0.2-0.4 cm, all associated with biliary lithiasis. All patients recovered after surgical resection without metastasis or recurrence, except for one patient who died a month after surgery due to an unrelated cause (multisystem organ failure). Conclusion This study highlights the spectrum of neuroendocrine proliferation in the biliary tree, ranging from microscopic incidental findings to grossly visible mass-forming NETs, which may result in variable clinical management and outcomes. Notably, incidental neuroendocrine proliferations were found to be associated with biliary lithiasis in all 3 cases, raising a possibility of a potential neuroendocrine metaplastic pathogenesis, which should be explored more via additional studies.