The histological diagnosis of IgG4‐related disease on small biopsies: challenges and pitfalls. Issue 5 (10th March 2019)

• Record Type: Journal Article
• Authors: Arora, Kshitij; Rivera, Miguel; Ting, David T; Deshpande, Vikram
• Is Part Of: Histopathology. Volume 74:Issue 5(2019)
• Page Start: 688
• Page End: 698
• Publication Date: 2019-03-10
• Subjects: IgG4‐related disease; Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.13787
• Languages: English
• ISSNs: 0309-0167

Abstract

Abstract : Aims: The pathological diagnosis of IgG4‐related disease (IgG4‐RD) relies on histology, IgG4‐positive cells, and an increased IgG4/IgG ratio. Small biopsies from patients with a presumptive diagnosis of IgG4‐RD 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‐RD, and to assess the significance of the pathological findings. Methods and results: We evaluated 55 small biopsies from patients with a presumptive diagnosis of IgG4‐RD. The retrospective cohort comprised 71 patients with IgG4‐RD and 57 mimics. We performed immunohistochemistry (IHC) and in‐situ hybridisation (ISH) for IgG4 and IgG. Twenty‐six patients from the prospective cohort met the histological criteria for IgG4‐RD (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‐positive plasma cells. Ninety‐three per cent of patients showed an IgG4/total IgG ratio of >40% (>30% by ISH). There were no differences in the incidence of multiorgan disease ( P = 0.9), serum IgG4 levels ( P = 0.6) and response to therapy between the definite and borderline groups. A strong correlation (Pearson 0.77) between the IHC and ISH platforms was noted with regard to the IgG4/total IgG ratio. Conclusion: Patients with a presumptive diagnosis of IgG4‐RD 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 ISH provides a robust quantification platform. We recommend evaluating tumefactive lymphoplasmacytic infiltrates with an increased IgG4/IgG ratio, regardless of histological features, for IgG4‐RD.