Diagnostic guidelines for IgG4-related disease with a focus on histopathological criteria

IgG4-related disease (IgG4-RD) is an under recognized, protean, multiorgan fibro-inflammatory condition of unknown aetiology that is defined by its unique histopathological features, that are fairly similar regardless of the affected organ. Patients with IgG4-RD also share certain clinical features: a tendency for formation of mass lesion(s), frequent elevations in their serum IgG4 concentration, as well as an excellent response to glucocorticoid treatment. The 3 key histologic features of IgG4-RD are: 1) dense lymphoplasmacytic infiltrate, 2) fibrosis, arranged at least focally in a storiform pattern, and 3) obliterative phlebitis. The diagnosis of IgG4-RD requires both these characteristic histologic features as well as elevated numbers of IgG4 positive plasma cells. Neither elevations in serum IgG4 concentrations nor increased tissue IgG4-plasma cells are in themselves sufficient for the diagnosis, and histopathology remains the key to the accurate diagnosis of IgG4-RD.