{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:20:55Z","timestamp":1791991255153,"version":"4.4.0"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,3,10]],"date-time":"2019-03-10T00:00:00Z","timestamp":1552176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The pathological diagnosis of IgG4\u2010related disease (IgG4\u2010<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>) relies on histology, IgG4\u2010positive cells, and an increased IgG4\/IgG ratio. Small biopsies from patients with a presumptive diagnosis of IgG4\u2010<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> often fail to meet consensus histological criteria. The aims of this study were to evaluate consecutive small biopsies from patients with a presumptive diagnosis of IgG4\u2010<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>, and to assess the significance of the pathological findings.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We evaluated 55 small biopsies from patients with a presumptive diagnosis of IgG4\u2010<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>. The retrospective cohort comprised 71 patients with IgG4\u2010<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> and 57 mimics. We performed immunohistochemistry (<jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content>) and <jats:italic>in\u2010situ<\/jats:italic> hybridisation (<jats:styled-content style=\"fixed-case\">ISH<\/jats:styled-content>) for IgG4 and IgG. Twenty\u2010six patients from the prospective cohort met the histological criteria for IgG4\u2010<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> (definite); 29 patients lacked one or more pathological features (borderline). Twenty biopsies (36%) lacked both storiform fibrosis and obliterative phlebitis, and nine (16%) lacked an increase in the number of IgG4\u2010positive plasma cells. Ninety\u2010three per cent of patients showed an IgG4\/total IgG ratio of &gt;40% (&gt;30% by <jats:styled-content style=\"fixed-case\">ISH<\/jats:styled-content>). There were no differences in the incidence of multiorgan disease (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.9), serum IgG4 levels (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.6) and response to therapy between the definite and borderline groups. A strong correlation (Pearson 0.77) between the <jats:styled-content style=\"fixed-case\">IHC<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ISH<\/jats:styled-content> platforms was noted with regard to the IgG4\/total IgG ratio.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Patients with a presumptive diagnosis of IgG4\u2010<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content> but lacking the characteristic pathological features of this disease appear to be clinically similar to those who meet the current pathological criteria. An elevated IgG4\/total IgG ratio is the most sensitive pathological feature, and <jats:styled-content style=\"fixed-case\">ISH<\/jats:styled-content> provides a robust quantification platform. We recommend evaluating tumefactive lymphoplasmacytic infiltrates with an increased IgG4\/IgG ratio, regardless of histological features, for IgG4\u2010<jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13787","type":"journal-article","created":{"date-parts":[[2018,11,8]],"date-time":"2018-11-08T19:42:31Z","timestamp":1541706151000},"page":"688-698","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["The histological diagnosis of IgG4\u2010related disease on small biopsies: challenges and pitfalls"],"prefix":"10.1111","volume":"74","author":[{"given":"Kshitij","family":"Arora","sequence":"first","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T","family":"Ting","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Hematology\/Oncology Massachusetts General Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4230-9308","authenticated-orcid":false,"given":"Vikram","family":"Deshpande","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School Boston MA 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