Spectra of well-differentiated neuroendocrine lesions in the extrahepatic biliary system: a case series

Yongjun Liu; Ashwini K Esnakula; Shilpa Jain; Jingmei Lin; Nicole Panarelli; Sergey Pyatibrat; Dipti M Karamchandani

doi:10.1111/his.15316

Spectra of well-differentiated neuroendocrine lesions in the extrahepatic biliary system: a case series

Histopathology. 2024 Sep 12. doi: 10.1111/his.15316. Online ahead of print.

Authors

Yongjun Liu¹, Ashwini K Esnakula², Shilpa Jain³, Jingmei Lin⁴, Nicole Panarelli⁵, Sergey Pyatibrat⁶, Dipti M Karamchandani⁷

Affiliations

¹ Department of Laboratory Medicine and Pathology, University of Washington Medical Center, Seattle, WA, USA.
² Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
³ Department of Pathology, Baylor College of Medicine, Houston, TX, USA.
⁴ Department of Pathology and Laboratory Medicine, School of Medicine, Indiana University, Indianapolis, IN, USA.
⁵ Department of Pathology, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY, USA.
⁶ Department of Pathology and Laboratory Medicine, Royal Columbian Hospital, University of British Columbia, New Westminster, BC, Canada.
⁷ Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA.

PMID: 39267205
DOI: 10.1111/his.15316

Abstract

Aims: Neuroendocrine tumours (NETs) occurring in the extrahepatic biliary system are exceedingly rare. While NETs typically manifest as mass lesions, the occurrence of microscopic neuroendocrine cell proliferation without a distinct mass remains undocumented at this location. This study aims to characterise the clinicopathological features of a series of well-differentiated neuroendocrine lesions involving the extrahepatic biliary tree, including mass forming NETs and microscopic non-mass-forming neuroendocrine cell proliferation, designated neuroendocrine cell micronests (NCMs).

Methods and results: Surgical resections of NETs/NCMs involving the extrahepatic bile ducts and gallbladder were identified from electronic pathology databases among seven institutions spanning from January 2011 to September 2023. Clinical and histological findings were recorded. Ten patients (four female, six male: age range = 34-75 years) were included in the study. Histopathological examination revealed visible mass-forming lesions in four cases (1.6-14.0 cm in size), identified in the gallbladder (n = two) or extrahepatic bile duct (n = two), all diagnosed as well-differentiated NETs. The remaining six cases revealed incidental non-mass-forming NCMs in either the cystic duct (n = two), common bile duct (n = three) or gallbladder (n = one), ranging from < 0.1 to 0.4 cm; four were associated with biliary lithiasis. No evidence of metastasis or recurrence was seen in the follow-up period (range = 0.1-11.2 years).

Conclusions: This study highlights the spectrum of extrahepatic biliary well-differentiated neuroendocrine lesions, ranging from incidental microscopic NCMs to grossly apparent mass-forming NETs, potentially requiring different clinical management. Noteworthy is the frequent association of incidental microscopic neuroendocrine cell proliferations with biliary lithiasis, indicating a potential neuroendocrine metaplastic pathogenesis that merits further exploration.

Keywords: extra hepatic biliary system; neuroendocrine proliferation; neuroendocrine tumour.