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Cholangiolar pattern and albumin in situ hybridisation enable a diagnosis of intrahepatic cholangiocarcinoma
  1. Diane G Brackett1,
  2. Azfar Neyaz1,
  3. Kshitij Arora1,
  4. Ricard Masia1,
  5. Anthony Mattia1,
  6. Lawerence Zukerberg1,
  7. Joseph Misdraji1,
  8. Lipika Goyal2,
  9. Andrew X Zhu2,
  10. Cristina R Ferrone3,
  11. Omer H Yilmaz1,
  12. Vikram Deshpande1
  1. 1Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
  2. 2Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
  3. 3Depatment of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Vikram Deshpande, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA; vdeshpande{at}


Aims The histological distinction of intrahepatic cholangiocarcinoma (ICC) from metastatic adenocarcinoma remains a challenge. The primary goal was to evaluate the diagnostic value of morphology and albumin expression in the diagnosis of ICC.

Methods We evaluated morphological patterns in 120 ICCs and 677 non-hepatic adenocarcinomas and performed in situ hybridisation (ISH) stain for albumin in the former cohort (retrospective cohort). We also identified 119 samples from primary and metastatic lesions, the validation cohort, in which albumin ISH was performed as part of the diagnostic workup. Targeted sequencing was performed on selected cases. We also mined existing expression profiling data including cases from The Cancer Genome Atlas (TCGA) (41 760 unique samples).

Results In the retrospective cohort, 45% of ICCs and <1% of non-hepatic adenocarcinomas showed a cholangiolar pattern; albumin ISH was positive in 93% of ICCs with significant intratumorous heterogeneity. In the validation cohort, 29% of ICCs showed a cholangiolar pattern and 88% expressed albumin, while all metastatic non-hepatic neoplasms were negative (n=37) (sensitivity 88% and specificity 100%). Targetable genetic alterations (IDH mutations and FGFR2 fusions) were identified in 31% of ICCs (10 of 32). An analysis of the TCGA data validated the specificity of the albumin assay.

Conclusions The cholangiolar pattern and albumin RNA ISH distinguishes ICC from metastatic adenocarcinoma with high specificity. Given the high prevalence of targetable mutations in ICC, albumin RNA ISH is an essential component in the workup of tumours of uncertain origin. A specific diagnosis of ICC could trigger molecular testing and uncover targetable genetic alterations.

  • Intrahepatic cholangiocarcinoma
  • cholangiolar
  • cholangiocellular
  • albumin
  • in situ hybridization

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  • DGB and AN contributed equally.

  • Handling editor Runjan Chetty.

  • Contributors DGB, AN, OHY, CRF and VD were involved in study concept and design and drafting the manuscript. DGB, AN, KA, RM, AM, CRF, and LZ were involved in collection of sample retrieval, laboratory work and data collection. DGB, AN, CRF, VD and JM performed analysis and interpretation of data. LG, AXZ and VD were involved in critical revision of the manuscript for important intellectual content and study supervision.

  • Funding The study was supported by a research grant from Affymetrix, CA, USA. Although this specific study was not supported by Advanced cell diagnostic, the authors institution received support from this institution.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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