Intraductal Implantation of Biliary Neoplasms: A Potential Cause of "Multifocal" Tumors

Am J Surg Pathol. 2024 Nov 1;48(11):1464-1471. doi: 10.1097/PAS.0000000000002279. Epub 2024 Jul 1.

Abstract

Multiple biliary tumors rarely develop in patients without underlying chronic hepatobiliary disease. Those lesions are regarded as multifocal neoplasms if there is no interconnecting dysplasia. This study aimed to determine whether 2 separate tumors in the biliary tract represent true multifocal independent tumorigenesis or intraluminal implantation of a single neoplasm. Two separate biliary tumors without intervening dysplasia were identified in 9 cases: biliary intraductal papillary neoplasm (IPNB; n=5) and extrahepatic cholangiocarcinoma (n=4). The 2 tumors were histologically similar in all cases. In 5 metachronous cases, the second tumor developed 2 to 13 years after the complete resection of the first tumor. In 4 synchronous cases, 2 separate neoplasms were identified in a surgical specimen. The metachronous presentation was more common in IPNB cases, whereas the synchronous development was more frequent in cholangiocarcinoma cases. The second tumors in 4 metachronous cases (4/5; 80%) and smaller lesions in all synchronous cases (4/4; 100%) were located in a lower part of the biliary. Immunophenotypes of cytokeratins and mucin core proteins were almost identical between the 2 lesions. Next-generation sequencing also confirmed that the 2 neoplasms shared gene mutations involving KRAS , GNAS , APC , BRAF , CTNNB1 , SMAD4 , TP53 , or ARID1A in all cases. In conclusion, multiple biliary tumors without underlying chronic biliary disease are most likely due to intraductal implantation of a single neoplasm. Thick mucinous bile in IPNB and increasing use of trans-ampullary biliary interventions may contribute to this unique form of tumor extension.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms* / genetics
  • Bile Duct Neoplasms* / pathology
  • Bile Duct Neoplasms* / surgery
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Cholangiocarcinoma* / genetics
  • Cholangiocarcinoma* / pathology
  • Cholangiocarcinoma* / surgery
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation
  • Neoplasms, Multiple Primary / genetics
  • Neoplasms, Multiple Primary / pathology
  • Neoplasms, Multiple Primary / surgery
  • Neoplasms, Second Primary / genetics
  • Neoplasms, Second Primary / pathology

Substances

  • Biomarkers, Tumor