[1476] Sinus Histiocytosis with Massive Lymphadenopathy (Rosai-Dorfman Disease) Is Not Part of IgG4-Related Sclerosing Disease

Liping Liu, Anamarija Perry, Wenfeng Cao, Lynette Smith, Eric Hsi, Jun Mo, Snjezana Dotlic, Ivan Damjanov, Marina Mosunjac, Geoffrey Talmon, Dennis D Weisenburger, Kai Fu. University of Nebraska Medical Center, Omaha, NE

Background: Sinus histiocytosis with massive lymphadenopathy (SHML) is a rare disorder of unknown etiology characterized by a non-clonal proliferation of distinctive cells of the macrophage/histiocyte lineage. Recent studies have suggested that SHML is part of IgG4-related sclerosing disease (IgG4-RSD). Therefore, we studied 32 cases of SHML and compared the findings to five cases of IgG4-RSD of the pancreas.
Design: The study included 32 biopsy samples (13 nodal, 19 extranodal) from 29 SHML patients with a median age of 17 years (range, 2-70 years). Five cases of IgG4-RSD of the pancreas and 5 reactive lymph nodes were used as positive and negative controls, respectively. Immunohistochemical stains for IgG and IgG4 were performed in all cases. We also performed double stains for CD4 and FOXP3 to evaluate the number of FOXP3+ regulatory T cells (Tregs), which are reported to be increased in IgG4-RSD. The number of IgG and IgG4 positive plasma cells, and FOXP3 positive Tregs was recorded for the three highest density high power fields by three pathologists and the average number of positive cells was calculated, as well as the IgG4/IgG ratio.
Results: There was very good concordance among the three pathologists (r=0.944-0.985) for the three different counts. A comparison of the results (mean ± SD) for SHML, reactive lymph nodes, and IgG4-RSD is given below.

Table 1
 IgG4+ cellsIgG4/IgGTregs
Reactive lymph nodes11.8±5.40.2±0.1140.6±97.7
SHML vs reactive lymph nodesp=1.00p=1.00p=0.0008
SHML vs IgG4-RSDp=0.013p=0.0026p=0.0044

SHML cases exhibited much lower numbers of IgG4+ plasma cells compared to IgG4-RSD (p=0.013), but had similar numbers of IgG4+ cells as reactive lymph nodes (p=1.00). SHML and reactive lymph nodes also had similar IgG4/IgG ratios (p=1.00), but the ratio was much lower than that of IgG4-RSD (p=0.0026). Furthermore, SHML cases had lower numbers of CD4-FOXP3+ Tregs than the reactive lymph nodes (p=0.0008) or IgG4-RSD (p=0.0044). There were no significant differences in IgG4+ plasma cells, IgG4/IgG ratios, or CD4-FOXP3+ Tregs between the nodal and extranodal SHML cases.
Conclusions: There is no significant difference in the number of IgG4+ plasma cells or the IgG4/IgG ratio (two major diagnostic criteria for IgG4-RSD) between SHML cases and reactive lymph nodes, whereas the number of IgG4+ plasma cells and the IgG4/IgG ratio in SHML cases were much lower than in the cases of IgG4-RSD. Thus, our findings indicate that SHML is not part of the spectrum of IgG4-RSD.
Category: Hematopathology

Monday, March 19, 2012 1:00 PM

Poster Session II # 231, Monday Afternoon


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