Clinical and morphological characteristics IgG4-associated retroperitoneal fibrosis

Background: Retroperitoneal fibrosis (RF) is a rare disease with inflammation and fibrosis of the retroperitoneal soft tissues and adjacent organ involvement. At present, a proportion of RF cases are believed to be IgG4-associated. Aim: Clinical and morphological comparison of the IgG4-associated and idiopathic (non-IgG-associated) RF. Materials and methods: The study was based on a comprehensive morphological assessment of surgical and biopsy samples taken from 12 RF patients. In addition to hematoxylin eosin stained specimens, we performed immunohistochemistry (IHC) with determination of absolute CD138⁺ counts, IgG⁺ and IgG4⁺ cells in the inflammatory infiltration, as well as IgG4/IgG and IgG4⁺/CD138⁺ ratios. Results: The proportion the IgG4-associated RF was 66.7% (8/12). The majority of IgG4-associated RF patients were men, with the mean age of 54.9 ± 10.3 years. Idiopathic RF was found without any gender imbalance in the younger patients. In all cases of IgG4-associated RF, the adjacent organs were also involved, whereas in those with idiopathic RF the aortic wall was involved in only half of the cases. Morphological specimen investigation in IgG4-associated RF showed signs characteristic for an IgG4-associated disorder, such as advanced lymphoplasmocytic infiltration, storiform fibrosis, and obliterating phlebitis. IgG4⁺ plasma cells numbers in the infiltrates was at least 25 per high-power field, and the IgG4⁺/IgG⁺ and IgG4⁺/CD138⁺ ratios exceeded 50% in all cases. No signs of an IgG4-associated disease were found in idiopathic RF, with significantly lower numbers of IgG⁺ and IgG4⁺ plasma cells in the infiltrations and the IgG4⁺/IgG⁺ ratio below 10%. Conclusion: A big proportion of RF is IgG4-associated, being an intrinsic feature of a systemic autoimmune IgG4-associated disease. The differential diagnosis should be based on the morphological assessment and immunohistochemistry results with obligatory identification of CD138, IgG, and IgG4 expression in the involved tissues. In some cases, it allows for avoidance of an unnecessary surgery. Reliable and accurate diagnosis would determine the subsequent treatment strategy of these patients.