Albumin expression distinguishes bile duct adenomas from metastatic adenocarcinoma

Histopathology. 2016 Sep;69(3):423-30. doi: 10.1111/his.12942. Epub 2016 Apr 27.

Abstract

Aims: Bile duct adenomas may be difficult to distinguish from metastatic carcinomas, particularly well-differentiated pancreatic ductal adenocarcinoma. Prior studies have evaluated the utility of various immunohistochemical markers, although these markers are notable for low sensitivity and/or specificity. The aim of this study was to investigate the utility of albumin and BRAFV600E expression in distinguishing between metastatic pancreatic adenocarcinoma and bile duct adenoma.

Methods and results: We studied 26 bile duct adenomas, three bile duct hamartomas, and 158 pancreatic ductal adenocarcinomas. Branched-chain in-situ hybridization (bISH) for albumin was performed; bISH is based on the branched DNA technology, wherein signal amplification is achieved via a series of sequential steps. Additionally, BRAFV600E immunohistochemistry (IHC) was performed on a subset of cases. Twenty-three of 25 (92%) bile duct adenomas were positive for albumin; 18 (72%) showed diffuse staining, and five showed focal staining (20%), including two challenging examples. Two bile duct hamartomas also stained positively. All pancreatic adenocarcinomas were negative for albumin. Seven of 16 (44%) bile duct adenomas and five of 106 (5%) pancreatic ductal adenocarcinomas were positive for BRAFV600E by IHC. The sensitivity and specificity of expression of albumin, as detected by bISH, for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 92% and 100%, respectively; the sensitivity and specificity of BRAFV600E IHC for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 43.8% and 95.3%, respectively.

Conclusions: Diagnostically challenging examples of bile duct adenoma may be distinguished from metastatic pancreatic adenocarcinoma by the use of albumin bISH.

Keywords: BRAF; albumin; bile duct adenoma; in-situ hybridization.

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenoma, Bile Duct / diagnosis*
  • Adult
  • Aged
  • Albumins / analysis
  • Albumins / biosynthesis*
  • Bile Duct Neoplasms / diagnosis*
  • Bile Ducts, Intrahepatic / pathology
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Diagnosis, Differential
  • Female
  • Humans
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / diagnosis
  • Proto-Oncogene Proteins B-raf / biosynthesis
  • Retrospective Studies
  • Sensitivity and Specificity
  • Tissue Array Analysis

Substances

  • Albumins
  • Biomarkers, Tumor
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf