The pathology of IgG4-related disease: critical issues and challenges.
IgG4-related disease (IgG4-RD) is a chronic and relapsing disease. The diagnosis of IgG4-RD is based on a combination of features that include clinical, imaging, serologic, histology, and immunohistochemistry. Nonetheless, histopathology has emerged as the gold standard for the diagnosis of IgG4-RD. Guidelines for the pathologic diagnosis of this condition have been published by an international group of experts: a triumvirate of histologic features allows for a confident diagnosis of IgG4-RD to be made in most cases: (1) a dense lymphoplasmacytic infiltrate, (2) storiform-type fibrosis, and (3) obliterative phlebitis. Elevated numbers of IgG4-positive plasma cells are essential for the diagnosis, but this feature is not sufficient in, and of, itself. IgG4-positive plasma cells are also seen in a variety of inflammatory and neoplastic diseases. An elevated IgG4 to IgG ratio, more than 40%, improves the specificity of this stain. A wide range of inflammatory and neoplastic diseases including antineutrophil cytoplasmic antibody (ANCA)-related vasculitis, chronic infections, mesenchymal neoplasms, carcinoma, and lymphoma should be excluded before arriving at a diagnosis of IgG4-RD. This review aims to provide the histopathologist with a set of practical guidelines for the diagnosis of IgG4-RD, and also addresses the many controversies associated with the diagnostic aspects of this disease.
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, 02114 USA. vdeshpande@partners.org
Vikram
V
Deshpande
D000465:Algorithms; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000175:diagnosis; D001327:Autoimmune Diseases / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002908:Chronic Disease; D003937:Diagnosis, Differential; D005355:Fibrosis; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007239:Infections / Q000175:diagnosis; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000175:diagnosis; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D017410:Practice Guidelines as Topic; D012008:Recurrence
D015415:Biomarkers; D007074:Immunoglobulin G