ArticleFrontiers in immunology2026
Case Report: Serum IgG4-negative multifocal IgG4-related hepatic inflammatory pseudotumor: dissociation between circulating IgG4 and local immune activation.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disorder characterized by aberrant immune regulation and progressive stromal remodeling. Hepatic involvement in the form of IgG4-related hepatic inflammatory pseudotumor (IgG4-HIPT) is uncommon and may radiologically resemble malignant or infectious liver disease. Although elevated serum IgG4 levels are often considered supportive for diagnosis, normal serum IgG4 concentrations do not exclude the disease and may obscure timely recognition. We describe a 60-year-old man presenting with multifocal hepatic lesions, mild inflammatory symptoms, and normal serum IgG4 levels. Imaging revealed arterial phase enhancement, peripheral rim enhancement, diffusion restriction, and increased metabolic activity on ^18F-FDG PET/CT, raising strong suspicion for metastatic disease or hepatic abscess. Histopathological analysis demonstrated dense IgG4-positive lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis, establishing the diagnosis of IgG4-HIPT. Marked radiologic regression was observed following corticosteroid therapy. This case illustrates a serum IgG4-negative phenotype of IgG4-HIPT and highlights the potential dissociation between circulating immunoglobulin levels and localized immune-driven fibroinflammatory activity. These findings support the concept that IgG4-RD represents an immune-mediated stromal remodeling disorder rather than a purely antibody-dependent condition. Early tissue confirmation is essential to guide immunomodulatory therapy and prevent unnecessary oncologic intervention. Recognition of this entity broadens the understanding of immune-mediated liver disease and underscores the importance of mechanism-based treatment approaches.
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