Inflammatory hepatocellular adenomas developed in the setting of chronic liver disease and cirrhosis.

Abstract

Hepatocellular adenoma is considered to occur exclusively in non-fibrotic livers. It is a heterogeneous entity and a molecular classification is now widely accepted. The most frequent hepatocellular adenoma subtype, namely inflammatory adenoma, harbor somatic activating mutations of genes involved in the interleukin-6 pathway that lead to high C-reactive protein and serum amyloid A expression. The aim of our study was to investigate a series of benign hepatocellular neoplasms developed on cirrhotic livers and characterized by an unequivocal histological diagnosis. We performed a clinical, pathological, and molecular study of 10 benign hepatocellular neoplasms developed in three patients with cirrhosis. Markers allowing hepatocellular adenoma classification were assessed by quantitative real-time PCR and immunohistochemistry. Samples were sequenced for CTNNB1, HNF1A, IL6ST, GNAS, STAT3, and TERT (promoter) mutations. A control series of 32 classical macronodules developed in cirrhosis related to various etiologies was screened by immunohistochemistry and gene sequencing. The three patients had cirrhosis related to metabolic syndrome and/or alcohol intake; two had a single tumor, while the third developed more than 30 lesions. Microscopic examination showed well-differentiated neoplasms sharing features with inflammatory adenoma including inflammatory infiltrates, sinusoidal dilatation, and dystrophic vessels. Sequencing revealed classical hotspot somatic mutations (IL6ST, n=8; STAT3, n=1; and GNAS, n=1) known to be responsible for IL-6/JAK/STAT pathway activation. Two classical high-grade macronodules demonstrated high serum amyloid A and/or C-reactive protein expression, without gene mutations. Altogether, our findings support the existence of rare inflammatory adenoma developed in cirrhosis.

• Authors: Julien Calderaro, Jean C Nault, Charles Balabaud, Gabrielle Couchy, Marie-Christine Saint-Paul, Daniel Azoulay, Dalila Mehdaoui, Alain Luciani, Elie S Zafrani, Paulette Bioulac-Sage, Jessica Zucman-Rossi
• Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc (Mod Pathol) Vol. 29 Issue 1 Pg. 43-50 (Jan 2016) ISSN: 1530-0285 [Electronic] United States
• PMID: 26516697 (Publication Type: Journal Article)

Chemical References

• CTNNB1 protein, human
• Chromogranins
• HNF1A protein, human
• Hepatocyte Nuclear Factor 1-alpha
• IL6ST protein, human
• STAT3 Transcription Factor
• beta Catenin
• Cytokine Receptor gp130
• TERT protein, human
• Telomerase
• GNAS protein, human
• GTP-Binding Protein alpha Subunits, Gs

Topics

• Adenoma, Liver Cell (complications, genetics, pathology)
• Adult
• Chromogranins
• Cytokine Receptor gp130 (genetics, metabolism)
• End Stage Liver Disease (complications, genetics, pathology)
• Female
• GTP-Binding Protein alpha Subunits, Gs (genetics, metabolism)
• Hepatocyte Nuclear Factor 1-alpha (genetics, metabolism)
• Humans
• Liver (metabolism, pathology)
• Liver Cirrhosis (complications, genetics, pathology)
• Liver Neoplasms (complications, genetics, pathology)
• Male
• Middle Aged
• Mutation
• Promoter Regions, Genetic
• STAT3 Transcription Factor (genetics, metabolism)
• Telomerase (genetics, metabolism)
• beta Catenin (genetics, metabolism)