Format

Send to

Choose Destination
Diagn Pathol. 2016 Mar 9;11:27. doi: 10.1186/s13000-016-0475-5.

Hepatocellular adenoma classification: a comparative evaluation of immunohistochemistry and targeted mutational analysis.

Author information

1
Department of Pathology and Cell Biology, Columbia University Medical Center, 630 W 168th Street, VC14-238, New York, NY, 10032, USA. bethmargolskee@gmail.com.
2
Department of Pathology, Scripps Clinic, La Jolla, CA, USA. fbao03@gmail.com.
3
Department of Pathology and Cell Biology, Columbia University Medical Center, 630 W 168th Street, VC14-238, New York, NY, 10032, USA. ak3304@cumc.columbia.edu.
4
Department of Pathology, Mayo Clinic, Rochester, MN, USA. Moreira.roger@mayo.edu.
5
Department of Pathology and Cell Biology, Columbia University Medical Center, 630 W 168th Street, VC14-238, New York, NY, 10032, USA. sml2179@cumc.columbia.edu.
6
Department of Pathology and Cell Biology, Columbia University Medical Center, 630 W 168th Street, VC14-238, New York, NY, 10032, USA. ans2133@cumc.columbia.edu.
7
Department of Pathology and Cell Biology, Columbia University Medical Center, 630 W 168th Street, VC14-238, New York, NY, 10032, USA. as4400@cumc.columbia.edu.
8
Department of Pathology and Cell Biology, Columbia University Medical Center, 630 W 168th Street, VC14-238, New York, NY, 10032, USA. her2007@cumc.columbia.edu.
9
Department of Pathology and Cell Biology, Columbia University Medical Center, 630 W 168th Street, VC14-238, New York, NY, 10032, USA. jhl3@cumc.columbia.edu.
10
Department of Pathology and Cell Biology, Columbia University Medical Center, 630 W 168th Street, VC14-238, New York, NY, 10032, USA. marcelafa@hotmail.com.

Abstract

BACKGROUND:

Four subtypes of hepatocellular adenomas (HCA) are recognized: hepatocyte-nuclear-factor-1α mutated (H-HCA), β-catenin-mutated type with upregulation of glutamine synthetase (b-HCA), inflammatory type (IHCA) with serum-amyloid-A overexpression, and unclassified type. Subtyping may be useful since b-HCA appear to have higher risk of malignant transformation. We sought to apply subtype analysis and assess histological atypia, correlating these with next-generation sequencing analysis.

METHODS:

Twenty-six HCA were stained with serum amyloid A (SAA), liver fatty acid-binding protein (LFABP), glutamine synthetase (GS), and β-catenin IHC, followed by analysis with a targeted multiplex sequencing panel.

RESULTS:

By IHC, 4 HCA (15.4 %) were classified as b-HCA, 11 (42.3 %) as IHCA, 9 (34.6 %) as H-HCA, and two (7.7 %) unclassifiable. Eight HCA (30.8 %) showed atypia (3 b-HCA, 4 IHCA and 1 H-HCA). Targeted sequencing confirmed HNF1A mutations in all H-HCA, confirming reliability of LFABP IHC in identifying these lesions. CTNNB1 mutations were detected in 1 of 4 (25 %) of GS/β-catenin-positive cases, suggesting that positive GS stain does not always correlate with CTNNB1 mutations.

CONCLUSIONS:

Immunohistochemistry does not consistently identify b-HCA. Mutational analysis improves the diagnostic accuracy of β-catenin-mutated HCA and is an important tool to assess risk of malignancy in HCA.

PMID:
26961851
PMCID:
PMC4784347
DOI:
10.1186/s13000-016-0475-5
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center