{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T07:35:02Z","timestamp":1768548902967,"version":"3.49.0"},"reference-count":25,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"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>Diagnostic work-up of IgG4-related disease (IgG4-RD) pleural involvement is a complex task, as there is a broad spectrum of differential diagnoses to consider. We report the case of a patient presenting with relapsing pleural effusion, discussing the main challenges for achievement of a definite diagnosis. A 63-year-old man was admitted for pleural effusion prevalent on the ride side, initially labeled as idiopathic non-specific pleuritis, based on tissue evaluation after a medical thoracoscopy. He was started on steroids with initial improvement, but a later CT scan showed a relapse of pleural effusion associated with diffuse pleural thickening; a subsequent surgical pleural biopsy revealed features suggestive for IgG4-RD, with a marked increase of IgG4 positive plasma cells. High IgG4 serum levels were also found. The present case underlines the importance of increasing awareness of this potential condition among physicians in order to properly guide the diagnostic work-up, as it is likely that IgG4-RD accounts for a proportion of patients with pleural effusions, labeled as idiopathic. In particular, in patients with unexplained pleural effusion, IgG4-RD should be included among differential diagnoses when lymphoplasmacytic infiltration is observed, and a multidisciplinary interaction between clinicians and pathologists appears crucial for an accurate diagnosis and an appropriate management.<\/jats:p>","DOI":"10.3390\/diagnostics11122177","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T02:46:08Z","timestamp":1637721968000},"page":"2177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Pleural Involvement in IgG4-Related Disease: Case Report and Review of the Literature"],"prefix":"10.3390","volume":"11","author":[{"given":"Federico","family":"Mei","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"},{"name":"Respiratory Diseases Unit, Azienda Ospedaliero-Universitaria \u201cOspedali Riuniti\u201d, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7465-2229","authenticated-orcid":false,"given":"Massimiliano","family":"Mancini","sequence":"additional","affiliation":[{"name":"Morphological and Molecolar Pathology Unit, Ospedale Sant\u2019Andrea, 00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulio","family":"Maurizi","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit, Ospedale Sant\u2019Andrea, 00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5497-6856","authenticated-orcid":false,"given":"Andrea","family":"Vecchione","sequence":"additional","affiliation":[{"name":"Morphological and Molecolar Pathology Unit, Ospedale Sant\u2019Andrea, 00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Zuccatosta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erino Angelo","family":"Rendina","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unit, Ospedale Sant\u2019Andrea, 00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Gasparini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Public Health, Universit\u00e0 Politecnica delle Marche, 60126 Ancona, Italy"},{"name":"Respiratory Diseases Unit, Azienda Ospedaliero-Universitaria \u201cOspedali Riuniti\u201d, 60126 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1056\/NEJM200103083441005","article-title":"High serum IgG4 concentrations in patients with sclerosing pancreatitis","volume":"344","author":"Hamano","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1056\/NEJMra1104650","article-title":"IgG4-related disease","volume":"366","author":"Stone","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1183\/09031936.00025211","article-title":"Pulmonary manifestations of immunoglobulin G4- related sclerosing disease","volume":"39","author":"Ryu","year":"2012","journal-title":"Eur. Respir. J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.rmed.2017.10.005","article-title":"Thoracic involvement in IgG4-related disease in a UK-based patient cohort","volume":"132","author":"Corcoran","year":"2017","journal-title":"Respir. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2150","DOI":"10.1097\/MD.0000000000002150","article-title":"Intrathoracic involvements of immunoglobulin G4- related sclerosing disease","volume":"94","author":"Fei","year":"2015","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1097\/MCP.0000000000000581","article-title":"Pleural effusion related to IgG4","volume":"25","author":"Murata","year":"2019","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1097\/PAS.0b013e3181f7266b","article-title":"IgG4-related disease: A cross- sectional study of 114 cases","volume":"34","author":"Zen","year":"2010","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1002\/art.39205","article-title":"IgG4-related disease: Clinical and laboratory features in one hundred twenty-five patients","volume":"67","author":"Wallace","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1181","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":"ref_10","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1097\/PAS.0b013e3181bd535b","article-title":"IgG4-related lung and pleural disease: A clinico-pathologic study of 21 cases","volume":"33","author":"Zen","year":"2009","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1707","DOI":"10.1097\/MD.0000000000001707","article-title":"Diagnostic Performance of Serum IgG4 Levels in Patients With IgG4-Related Disease","volume":"94","author":"Yu","year":"2015","journal-title":"Medicine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1097\/MCP.0000000000000374","article-title":"Pleural diseases","volume":"23","author":"Gasparini","year":"2017","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1159\/000511626","article-title":"Diagnostic Yield and Safety of Image-Guided Pleural Biopsy: A Systematic Review and Meta-Analysis","volume":"100","author":"Mei","year":"2021","journal-title":"Respiration"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1183\/16000617.0020-2016","article-title":"Advanced medical interventions in pleural disease","volume":"25","author":"Bhatnagar","year":"2016","journal-title":"Eur. Respir. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"893","DOI":"10.2169\/internalmedicine.50.4726","article-title":"IgG4-related pleural disease diagnosed by a re-evaluation of chronic bilateral pleuritis in a patient who experienced occasional acute left bacterial pleuritis","volume":"50","author":"Yamamoto","year":"2011","journal-title":"Intern. Med."},{"key":"ref_16","first-page":"18","article-title":"ImmunoglobulinG4- related pleuritis\u2013a case report","volume":"19","author":"Marta","year":"2016","journal-title":"Respir. Med. Case Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.amjms.2018.05.004","article-title":"IgG4-related pleuritis with no other organ involvement","volume":"356","author":"Kita","year":"2018","journal-title":"Am. J. Med. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/cyt.12641","article-title":"Clinicopathological features of immunoglobulin G4-related pleural lesions and diagnostic utility of pleural effusion cytology","volume":"30","author":"Kasashima","year":"2018","journal-title":"Cytopathology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/cei.12999","article-title":"Association of immunoglobulin G4 and free light chain with idiopathic pleural effusion","volume":"190","author":"Murata","year":"2017","journal-title":"Clin. Exp. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","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":"ref_21","first-page":"101019","article-title":"Characteristics of pleural effusion in IgG4-related pleuritis","volume":"29","author":"Saito","year":"2020","journal-title":"Respir. Med. Case Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1136\/jcp.2010.085613","article-title":"Numerous IgG4-positive plasma cells are ubiquitous in diverse localized non-specific chronic inflammatory conditions and need to be distinguished from IgG4-related systemic disorders","volume":"64","author":"Strehl","year":"2011","journal-title":"J. Clin. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"257","DOI":"10.2169\/internalmedicine.3031-19","article-title":"Thoracoscopic Findings in IgG4-related Pleuritis","volume":"59","author":"Yasokawa","year":"2020","journal-title":"Intern Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.humpath.2005.05.011","article-title":"IgG4-positive plasma cells in inflammatory pseudotumor (plasma cell granuloma) of the lung","volume":"36","author":"Zen","year":"2005","journal-title":"Human Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41584-020-0500-7","article-title":"IgG4-related disease: An update on pathophysiology and implications for clinical care","volume":"16","author":"Perugino","year":"2020","journal-title":"Nat. Rev. Heumatol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/12\/2177\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:34:51Z","timestamp":1760168091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/12\/2177"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,23]]},"references-count":25,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["diagnostics11122177"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11122177","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,23]]}}}