title: Erdheim-Chester disease with novel gene mutations discovered as an incidental finding in explanted liver of a patient with hepatitis C cirrhosis: A case report and literature review.
abstract: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by xanthogranulomatous infiltration of foamy histiocytes frequently involving bone and other organ systems. We herein report a unique case of ECD discovered incidentally in an explanted liver in a 65-year-old male with end-stage liver disease secondary to hepatitis C cirrhosis. Histological examination and immunohistochemical studies in the explanted liver revealed prominent foamy histiocytes that were CD68 positive, but CD1a and S100 negative. Mutational hotspot analysis of the explanted liver using a panel of 47 most common cancer-related genes performed by next generation sequencing (NGS) revealed likely somatic mutations in the PDGFRA, PTEN, and HNF1A genes, but no BRAF codon 600 mutations were detected. The bone marrow showed similar findings as in the liver. Whole body PET and bone scans demonstrated increased heterogeneous uptake in bilateral humeral and femoral diaphysis, most compatible with ECD. To our knowledge, this is the first case report of ECD that involves mainly bone marrow and liver with novel genomic alterations. Our case highlights the diversity and complexity of this disease entity and the importance of multi-modality approach integrating clinical and radiologic features with histopathologic and molecular/genomic findings.
authors.affiliation: Department of Pathology, University of California San Diego Health System, La Jolla, CA, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liao
authors.affiliation: Department of Pathology, University of California San Diego Health System, La Jolla, CA, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Thorson
authors.affiliation: Department of Radiology, University of California San Diego Health System, La Jolla, CA, USA.
authors.forename: Tudor
authors.initials: T
authors.lastname: Hughes
authors.affiliation: Department of Pathology, University of California San Diego Health System, La Jolla, CA, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, University of California San Diego Health System, La Jolla, CA, USA. Electronic address: huw003@ucsd.edu.
authors.forename: Huan-You
authors.initials: HY
authors.lastname: Wang
authors.affiliation: Department of Pathology, University of California San Diego Health System, La Jolla, CA, USA. Electronic address: g4lin@ucsd.edu.
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Lin
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D031249:Erdheim-Chester Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D006526:Hepatitis C / Q000150:complications / Q000235:genetics / Q000473:pathology*; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D033162:Incidental Findings; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008297:Male; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics
chemical_list: C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D020796:Receptor, Platelet-Derived Growth Factor alpha; D051059:PTEN Phosphohydrolase
keywords: Cirrhosis; Erdheim-Chester disease; Histiocytosis; Liver transplant