title: Diffuse glutamine synthetase overexpression restricted to areas of peliosis in a β-catenin-activated hepatocellular adenoma: a potential pitfall in glutamine synthetase interpretation.
abstract: Hepatocellular adenomas have recently been classified into four subtypes based on molecular findings: hepatocyte nuclear factor 1α (HNF1α) inactivated, inflammatory/telangiectatic, β-catenin activated, and unclassifiable. β-catenin-activated adenomas have the potential for malignant transformation and are thus important to recognize. Diffuse glutamine synthetase immunohistochemical positivity has been shown to be a reliable surrogate marker for β-catenin activation, though variations in staining patterns may be difficult to interpret. We report a case of a peliotic adenoma that was morphologically consistent with a β-catenin wild-type hepatocellular adenoma but harbored a β-catenin mutation by molecular analysis. The tumor lacked nuclear β-catenin positivity and demonstrated a hitherto undescribed pattern of glutamine synthetase overexpression restricted to areas of peliosis with mostly negative staining in non-peliotic areas. This pattern was initially interpreted as physiologic and may represent a potential pitfall in glutamine synthetase interpretation.
authors.affiliation: Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Berry
authors.forename: Rama R
authors.initials: RR
authors.lastname: Gullapalli
authors.forename: Jin
authors.initials: J
authors.lastname: Wu
authors.forename: Katherine
authors.initials: K
authors.lastname: Morris
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Hanson
mesh_terms: D018248:Adenoma, Liver Cell / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015897:Comorbidity; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005974:Glutamate-Ammonia Ligase / Q000096:biosynthesis*; D006498:Hepatectomy; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010382:Peliosis Hepatis / Q000453:epidemiology / Q000378:metabolism*; D015854:Up-Regulation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D051176:beta Catenin; D005974:Glutamate-Ammonia Ligase