IgG4-related disease

IgG4-related disease (IgG4-RD) is considered a fibro-inflammatory condition with a marked propensity to form mass forming lesions, characterized by a dense lymphoplasmacytic infiltrate, the presence of abundant IgG4+ plasma cells, frequent elevation of serum IgG4 and a dramatic initial response to glucocorticoid. Nowadays, IgG4-RD has been described in almost every organ system: the pancreatobiliary tract, liver, salivary glands, nasopharynx, bone marrow, lacrimal gland, extra-ocular muscles and retrobulbar space, kidneys, lungs, lymph nodes, meninges, aorta and arteries, skin, breast, prostate, thyroid gland and pericardium. Although the common diagnostic features of all these regional involvements cannot be defined with certainty, and slight differences have been noted in different organs, many histopathological features are shared. Consensus has not yet been reached regarding criteria that have to be fulfilled for a new IgG4-RD. The proposed criteria include appropriate clinical and histopathological findings, presence of abundant tissueinfiltrating IgG4+ plasma cells, high serum IgG4 concentrations, response to steroid therapy, other autoimmune diseases or other organ involvement. The two hallmark features for diagnosis are histopathological characteristics and the presence of infiltrating IgG4+ plasma cells. In this review, we will focus on the histopathological features of IgG4-RD in specific organs and discuss the relationship with inflammatory pseudotumour and malignancy, IgG4 counting methods, and diagnosis using biopsy specimens. • IgG4-related disease (IgG4-RD) is a multi-organ system disease that has been recognized in the last 10 years. • IgG4-RD has a marked propensity to present as mass-forming lesions. • The two hallmark features for diagnosis are histopathological characteristics and the presence of infiltrating IgG4+ plasma cells. • Correct identification is crucial to avoid unnecessary major surgical procedures and initiate corticosteroid therapy.