{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:46:19Z","timestamp":1776235579181,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1816493","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:44:44Z","timestamp":1776231884000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Serum IgG4-negative multifocal IgG4-related hepatic inflammatory pseudotumor: dissociation between circulating IgG4 and local immune activation"],"prefix":"10.3389","volume":"17","author":[{"given":"Wei","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Radiology, Beijing YouAn Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dawei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiology, Beijing YouAn Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruichen","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Radiology, Beijing YouAn Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongkai","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Radiology, Beijing YouAn Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing YouAn Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Shao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beijing YouAn Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songtao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Beijing YouAn Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2012.72","article-title":"Consensus statement on the pathology of Igg4-related disease","volume":"25","author":"Deshpande","year":"2012","journal-title":"Mod Pathol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2020.1859710","article-title":"The 2020 revised comprehensive diagnostic (Rcd) criteria for Igg4-Rd","volume":"31","author":"Umehara","year":"2021","journal-title":"Mod Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26115325","article-title":"Igg4-related disease: Current and future insights into pathological diagnosis","volume":"26","author":"Arias-Intriago","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1053\/j.semdp.2019.07.007","article-title":"Immunoglobulin G4-related hepatobiliary disease","volume":"36","author":"Lee","year":"2019","journal-title":"Semin Diagn Pathol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12061497","article-title":"A case of hepatic immunoglobulin G4-related disease presenting as an inflammatory pseudotumor and sclerosing cholangitis","volume":"12","author":"Jang","year":"2022","journal-title":"Diagnostics (Basel)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800836","article-title":"Pathological classification of hepatic inflammatory pseudotumor with respect to Igg4-related disease","volume":"20","author":"Zen","year":"2007","journal-title":"Mod Pathol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.205526","article-title":"Igg4-related disease: What a hematologist needs to know","volume":"104","author":"Chen","year":"2019","journal-title":"Haematologica"},{"key":"B8","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1136\/annrheumdis-2019-216561","article-title":"The 2019 American College of Rheumatology\/European League against Rheumatism classification criteria for Igg4-related disease","volume":"79","author":"Wallace","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/art.34593","article-title":"Recommendations for the nomenclature of Igg4-related disease and its individual organ system manifestations","volume":"64","author":"Stone","year":"2012","journal-title":"Arthritis Rheum"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.44066","article-title":"Incidental finding of hepatic inflammatory pseudotumor immunoglobulin G4-related disease with underlying chronic hepatitis C","volume":"15","author":"Delbrune","year":"2023","journal-title":"Cureus"},{"key":"B11","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/s12876-016-0504-6","article-title":"A case of Igg4-related hepatic inflammatory pseudotumor replaced by an abscess after steroid treatment","volume":"16","author":"Shibata","year":"2016","journal-title":"BMC Gastroenterol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1007\/s12328-023-01861-3","article-title":"Igg4-Related Hepatic Inflammatory Pseudotumor in a Patient with Serum Igg4-Negative Type 1 Autoimmune Pancreatitis","volume":"16","author":"Hideshima","year":"2023","journal-title":"Clin J Gastroenterol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.pan.2024.11.018","article-title":"Serum Igg4-negative and Igg4-positive type 1 autoimmune pancreatitis present with different clinicopathological features: An analysis of a nationwide survey in Japan","volume":"25","author":"Sano","year":"2025","journal-title":"Pancreatology"},{"key":"B14","article-title":"Igg4-related disease of the hepatobiliary tract: 2 case reports and review of the literature","volume":"81","author":"Spapen","year":"2018","journal-title":"Acta Gastroenterol Belg"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/his.15357","article-title":"Clinicopathologic features and outcomes of hepatic inflammatory pseudotumour (Ipt) and hepatic Ipt-like lesions","volume":"86","author":"Nguyen","year":"2025","journal-title":"Histopathology"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v16.i5.667","article-title":"Hepatic pseudotumor: A diagnostic challenge","volume":"16","author":"Samanta","year":"2024","journal-title":"World J Hepatol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/s2665-9913(24)00022-5","article-title":"Proliferative features of Igg4-related disease","volume":"6","author":"Katz","year":"2024","journal-title":"Lancet Rheumatol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1002\/art.41120","article-title":"The 2019 American College of Rheumatology\/European League against Rheumatism classification criteria for Igg4-related disease","volume":"72","author":"Wallace","year":"2020","journal-title":"Arthritis Rheumatol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1413860","article-title":"Pathogenic roles of follicular helper T cells in Igg4-related disease and implications for potential therapy","volume":"15","author":"Xu","year":"2024","journal-title":"Front Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1080\/25785826.2024.2407224","article-title":"The immunological pathogenesis of Igg4-related disease categorized by clinical characteristics","volume":"48","author":"Akiyama","year":"2025","journal-title":"Immunol Med"},{"key":"B21","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.alit.2024.07.005","article-title":"Human T follicular helper cells and their impact on Ige and Igg4 production across allergy, Malignancy, and Igg4-related disease","volume":"74","author":"Akiyama","year":"2025","journal-title":"Allergol Int"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s40266-024-01172-3","article-title":"Pharmacological management of Igg4-related disease: From traditional to mechanism-based targeted therapies","volume":"42","author":"Akiyama","year":"2025","journal-title":"Drugs Aging"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.24040","article-title":"Activation of fibroblasts by plasma cells via Pdgf\/Pdgfr signaling in Igg4-related sialadenitis","volume":"64","author":"Kitaoka","year":"2024","journal-title":"J Clin Exp Hematop"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1172\/jci183396","article-title":"Rare genetic variants provide a mechanistic basis for immune imbalance in Igg4-related disease","volume":"134","author":"Ciavatta","year":"2024","journal-title":"J Clin Invest"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29913","article-title":"Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American Association for the Study of Liver Diseases","volume":"68","author":"Marrero","year":"2018","journal-title":"Hepatology"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v29.i36.5180","article-title":"Liver metastases: The role of magnetic resonance imaging","volume":"29","author":"Maino","year":"2023","journal-title":"World J Gastroenterol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.190.2.8284394","article-title":"Hepatic abscesses: Mr imaging findings","volume":"190","author":"M\u00e9ndez","year":"1994","journal-title":"Radiology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s12328-020-01245-x","article-title":"Difficulty in differentiating between Igg4-related hepatic inflammatory pseudotumor and intrahepatic cholangiocarcinoma","volume":"14","author":"Hamano","year":"2021","journal-title":"Clin J Gastroenterol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2021-244572","article-title":"Igg4-related hepatic inflammatory pseudotumour: Could Mri suggest the correct diagnosis","volume":"14","author":"Primitivo","year":"2021","journal-title":"BMJ Case Rep"},{"key":"B30","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s13244-024-01782-w","article-title":"Characteristics of imaging in hepatic inflammatory pseudotumors: A comparison between Igg4-related and Igg4-unrelated cases","volume":"15","author":"Lin","year":"2024","journal-title":"Insights Imaging"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/s1499-3872(17)60062-6","article-title":"Role of Mr in the differentiation of Igg4-related from non-Igg4-related hepatic inflammatory pseudotumor","volume":"16","author":"Sheng","year":"2017","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1104650","article-title":"Igg4-related disease","volume":"366","author":"Stone","year":"2012","journal-title":"N Engl J Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16081537","article-title":"Recent advances in pathology of intrahepatic cholangiocarcinoma","volume":"16","author":"Choi","year":"2024","journal-title":"Cancers (Basel)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1148\/rg.2016150196","article-title":"Multimodality imaging of liver infections: Differential diagnosis and potential pitfalls","volume":"36","author":"B\u00e4chler","year":"2016","journal-title":"Radiographics"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1102\/1470-7330.2007.0002","article-title":"Imaging of liver metastases: Mri","volume":"7","author":"Namasivayam","year":"2007","journal-title":"Cancer Imaging"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00261-022-03555-9","article-title":"Magnetic resonance imaging of inflammatory pseudotumor of the liver: A 2021 systematic literature update and series presentation","volume":"47","author":"Calistri","year":"2022","journal-title":"Abdom Radiol (NY)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1816493\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:44:48Z","timestamp":1776231888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1816493\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2026.1816493"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1816493","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]},"article-number":"1816493"}}