Rosai-Dorfman Disease Represents a Spectrum of IgG4-Related Sclerosing Disease.
Xuefeng Zhang, James Vardiman, Elizabeth Hyjek. University of Chicago Medical Center, IL
Background: Rosai-Dorfman disease (RDD) is a unique clinicopathologic entity of unknown pathogenesis. Although RDD is typically self-limited, aggressive disease and recurrence can occur, often with increasing sclerosis. For patients with aggressive disease, currently available therapeutic options have met with variable success. Emerging evidence indicates that RDD may be due to abnormal immune regulation. Because autoimmune diseases with sclerosis may represent a spectrum of IgG4-related sclerosing disease, we investigated the distribution of IgG4+ plasma cells and FOXP3+ regulatory T cells (Treg), which are major regulators of IgG4 production, in RDD.
Design: Twenty-six specimens (15 nodal, 11 extranodal) from 15 RDD patients, including 4 with recurrent disease, were examined. Eight reactive lymph nodes served as controls. Analysis was performed as described by Shrestha et al (Am J Surg Pathol. 2009;33:1450). Three HPFs in high-density areas in each specimen were photographed under a 40X objective (0.060 mm2) for both IgG4+ plasma cells and FOXP3+ cells. Averages of IgG4+ and FOXP3+ cells in the 3 HPFs were calculated. The degree of sclerosis and histiocyte infiltrate was scored on a scale of 0-3.
Results: Overall, 73.5% of the RDD cases (19/26) showed >10 IgG4+ plasma cells/HPF (median 21, range 0-145), and there were >30 IgG4+ cells/HPF in 46.2% of the cases (12/26). Only one control case exhibited >10 IgG4+ cells/HPF (controls: median 7/HPF, range 1-23/HPF, p<0.05). Nodal (11/15 cases with >10 IgG4+ cells/HPF) and extranodal (8/11 cases with >10 IgG4+ cells/HPF) RDD cases exhibited comparable numbers of IgG4+ cells (p=0.2). There was no significant difference in the number of Tregs between RDD and control cases. Twenty-two cases (84.7%) showed various levels of sclerosis (7 mild, 8 moderate, 7 severe). There was no correlation between the extent of sclerosis or histiocyte infiltrate with the number of IgG4+ cells, except for the specimens taken sequentially from 4 patients with recurrence, which demonstrated a trend toward increased sclerosis with increased number of IgG4+ cells.
Conclusions: More than 70% of RDD (nodal and extranodal) cases showed an increased number of IgG4+ cells, suggesting that some cases of RDD may belong to the spectrum of IgG4-related sclerosing disease. RDD at different stages may have different degrees of sclerosis and numbers of IgG4+ plasma cells. Because IgG4-related sclerosing diseases show promising response to steroid treatment, our results suggest further studies on the therapeutic effects of steroids in RDD cases with increased IgG4+ plasma cells.
Tuesday, March 1, 2011 11:45 AM
Platform Session: Section B, Tuesday Morning