{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:48:44Z","timestamp":1790300924783,"version":"4.1.0"},"reference-count":127,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: IgG4-related disease (IgG4-RD) is a chronic immune-mediated fibroinflammatory disorder characterized by lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, storiform fibrosis, and frequently elevated serum IgG4 levels. Classic forms, such as pancreaticobiliary or retroperitoneal involvement, are often recognized early, whereas atypical manifestations mimic malignancy or inflammatory conditions, leading to delayed or inappropriate treatment. Case Series: A 30-year-old man presented with hyperemesis, proptosis, and gait instability. He was found to have colonic stenosis, stomach thickening, pachymeningitis, and polyserositis. Gastroenteric histology and serology confirmed IgG4-RD. Steroids were ineffective, but rituximab produced sustained clinical and radiologic improvement. A 35-year-old woman developed jaundice and cholestasis with a perihilar mass highly suggestive of cholangiocarcinoma. Histopathology revealed IgG4-RD, and rituximab therapy led to marked clinical and serological improvement. A 64-year-old woman with a submandibular mass underwent sialoadenectomy, with histology confirming IgG4-RD; she remained asymptomatic without systemic treatment. Literature Review: A literature review highlighted the diagnostic challenges of atypical IgG4-RD. Gastrointestinal involvement is rare and often misclassified as inflammatory bowel disease. Isolated biliary disease frequently mimics cholangiocarcinoma, while salivary gland involvement may be misdiagnosed as neoplasia. Serum IgG4 levels &gt;135 mg\/dL and IgG4\/IgG ratio &gt;0.21 may support clinical suspicion, but histopathology remains indispensable for definitive diagnosis and for excluding malignancy. Steroid responsiveness is a hallmark, though relapses after tapering are common, often necessitating B-cell-directed therapy. Conclusions: IgG4-RD should be considered in patients with unexplained, relapsing, or steroid-responsive conditions. Early recognition, multidisciplinary collaboration, and integration of histopathology with clinical features are essential to avoid misdiagnosis and optimize management.<\/jats:p>","DOI":"10.3390\/diagnostics15182299","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T12:04:55Z","timestamp":1757505895000},"page":"2299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinicopathological Pearls and Diagnostic Pitfalls in IgG4-Related Disease: Challenging Case Series and Literature Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3700-6989","authenticated-orcid":false,"given":"Sokol","family":"Sina","sequence":"first","affiliation":[{"name":"Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2485-7557","authenticated-orcid":false,"given":"Giulio Luigi","family":"Bonisoli","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine B, Department of Medicine, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Vitale","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine B, Department of Medicine, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Marzano","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine B, Department of Medicine, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4560-8741","authenticated-orcid":false,"given":"Stefano Francesco","family":"Crin\u00f2","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Endoscopy of Pancreas, The Pancreas Institute, University Hospital of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7813-1583","authenticated-orcid":false,"given":"Maria Cristina","family":"Conti Bellocchi","sequence":"additional","affiliation":[{"name":"Diagnostic and Interventional Endoscopy of Pancreas, The Pancreas Institute, University Hospital of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Boninsegna","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, IRCCS Sacro Cuore Don Calabria Hospital, 37024 Negrar, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Conci","sequence":"additional","affiliation":[{"name":"General and Hepatobiliary Surgery, Department of Surgey, Dentistry, Gynecology and Pediatrics, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9237-7916","authenticated-orcid":false,"given":"Federica","family":"Maiolini","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine B, Department of Medicine, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Nocini","sequence":"additional","affiliation":[{"name":"Unit of Otoryngology-Head and Neck Departement, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Sacchetto","sequence":"additional","affiliation":[{"name":"Unit of Otoryngology-Head and Neck Departement, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1581-0500","authenticated-orcid":false,"given":"Giorgio","family":"Barbera","sequence":"additional","affiliation":[{"name":"Maxillo Facial Surgery Unit, Head and Neck Department, Azienda Ospedaliera Universitaria Integrata Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Fior","sequence":"additional","affiliation":[{"name":"Maxillo Facial Surgery Unit, Head and Neck Department, Azienda Ospedaliera Universitaria Integrata Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikela","family":"Kalaja","sequence":"additional","affiliation":[{"name":"Section of Internal Medicine B, Department of Medicine, University of Verona, Piazzale L.A. 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