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Value and limits of routine histology alone or combined with glutamine synthetase immunostaining in the diagnosis of hepatocellular adenoma subtypes on surgical specimens.

ABSTRACT: Immunohistochemistry is a valid method to classify hepatocellular adenoma (HCA). The aim was to test the performance of routine histology combined to glutamine synthetase (GS) staining to identify the 2 major HCA subtypes: HNF1 ? inactivated (H-HCA) and inflammatory HCA (IHCA). 114 surgical cases, previously classified by immunohistochemistry, were analysed. Group A comprised 45 H-HCAs, 44 IHCAs, and 9 ? -catenin-activated IHCAs (b-IHCA), and group B, 16 b-HCA and unclassified HCA (UHCA). Steatosis was the hallmark of H-HCA. IHCA and b-IHCA were mainly characterized by inflammation, thick arteries, and sinusoidal dilatation; b-IHCA could not be differentiated from IHCA by routine histology. Group B was identified by default. A control set (91 cases) was analyzed using routine and GS stainings (without knowing immunohistochemical results). Among the 45 H-HCAs and 27 IHCAs, 40 and 24 were correctly classified, respectively. Among the 10 b-IHCAs, 4 were identified as such using additional GS. Eight of the 9 HCAs that were neither H-HCA nor IHCA were correctly classified. Conclusion. Routine histology allows to diagnose >85% of the 2 major HCA subtypes. GS is essential to identify b-HCA. This study demonstrates that a "palliative" diagnostic approach can be proposed, when the panel of specific antibodies is not available.

SUBMITTER: Bioulac-Sage P

PROVIDER: S-EPMC3590632 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Value and limits of routine histology alone or combined with glutamine synthetase immunostaining in the diagnosis of hepatocellular adenoma subtypes on surgical specimens.

Bioulac-Sage Paulette P Taouji Saïd S Le Bail Brigitte B Possenti Laurent L Balabaud Charles C

International journal of hepatology 20130219

Immunohistochemistry is a valid method to classify hepatocellular adenoma (HCA). The aim was to test the performance of routine histology combined to glutamine synthetase (GS) staining to identify the 2 major HCA subtypes: HNF1 α inactivated (H-HCA) and inflammatory HCA (IHCA). 114 surgical cases, previously classified by immunohistochemistry, were analysed. Group A comprised 45 H-HCAs, 44 IHCAs, and 9 β -catenin-activated IHCAs (b-IHCA), and group B, 16 b-HCA and unclassified HCA (UHCA). Steato ...[more]

PMID: 23509631

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Project description:The current clinical practice is based on the assumption of strong correlation between diffuse glutamine synthetase expression and ?-catenin activation in hepatocellular adenoma and hepatocellular carcinoma. This high correlation is based on limited data and may represent an oversimplification as glutamine synthetase staining patterns show wide variability in clinical practice. Standardized criteria for interpreting diverse glutamine synthetase patterns, and the association between each pattern and ?-catenin mutations is not clearly established. This study examines the correlation between glutamine synthetase staining patterns and ?-catenin mutations in 15 typical hepatocellular adenomas, 5 atypical hepatocellular neoplasms and 60 hepatocellular carcinomas. Glutamine synthetase staining was classified into one of the three patterns: (a) diffuse homogeneous: moderate-to-strong cytoplasmic staining in >90% of lesional cells, without a map-like pattern, (b) diffuse heterogeneous: moderate-to-strong staining in 50-90% of lesional cells, without a map-like pattern, and (c) patchy: moderate-to-strong staining in <50% of lesional cells (often perivascular), or weak staining irrespective of the extent, and all other staining patterns (including negative cases). Sanger sequencing of CTNNB1 exon 3 was performed in all cases. Of hepatocellular tumors with diffuse glutamine synthetase staining (homogeneous or heterogeneous), an exon 3 ?-catenin mutation was detected in 33% (2/6) of typical hepatocellular adenoma, 75% (3/4) of atypical hepatocellular neoplasm and 17% (8/47) of hepatocellular carcinomas. An exon 3 mutation was also observed in 15% (2/13) of hepatocellular carcinomas with patchy glutamine synthetase staining. The results show a modest correlation between diffuse glutamine synthetase immunostaining and exon 3 ?-catenin mutations in hepatocellular adenoma and hepatocellular carcinoma with discrepancy rates >50% in both hepatocellular adenoma and hepatocellular carcinoma. The interpretation of ?-catenin activation based on glutamine synthetase staining should be performed with caution, and the undetermined significance of various glutamine synthetase patterns should be highlighted in pathology reports.

Dataset Information

Value and limits of routine histology alone or combined with glutamine synthetase immunostaining in the diagnosis of hepatocellular adenoma subtypes on surgical specimens.

Publications

Value and limits of routine histology alone or combined with glutamine synthetase immunostaining in the diagnosis of hepatocellular adenoma subtypes on surgical specimens.

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