IgG4+ plasma cells in isolated reactive lymphadenopathy.

Abstract

In the study published in this issue, Louzao Martinez et al1 investigate the significance of increased IgG4-positive plasma cells in lymph nodes. The accurate interpretation of this finding is important as awareness of IgG4-related disease (IgG4-RD) is growing among both clinicians and pathologists, and in consequence, IgG4-RD is included in the differential diagnosis of an increasing number of specimens. From a historical perspective, until recently, no common pathophysiologic features were identified among cases diagnosed as Mikulicz syndrome, Riedel thyroiditis, Kuttner tumor, inflammatory pseudotumor, Ormond syndrome, and autoimmune pancreatitis. The discovery of IgG4 and the realization that some cases of sclerosing pancreatitis were associated with local accumulation of IgG4-positive plasma cells, extra-pancreatic involvement,2 and increased serum levels of IgG43 opened a new avenue of investigation that led to the recognition of IgG4-RD as a systemic disease that can involve virtually any organ. This and the fact that treatment with corticosteroids or with rituximab is often effective increased the importance of an accurate diagnosis of IgG4-RD. Confident identification of cases of IgG4-RD led to a better morphologic, immunohistochemical, and serologic characterization of this entity. Indeed, several morphologic features have been consistently described in cases of IgG4-RD: dense lymphoplasmacytic infiltrate, fibrosis with at least a focal storiform pattern, obliterative phlebitis, nonobliterative phlebitis, increased eosinophils, increased numbers of IgG4-positive plasma cells per high-power field (hpf), and increased IgG4/IgG plasma cell ratio (>40%). In addition, most patients have elevated serum IgG4 levels.4 After cases with varying presentations were analyzed, an interesting development was the realization that while features such as fibrosis, dense lymphoplasmacytic infiltrate, obliterative phlebitis, and elevated serum IgG4 are shared by most cases, there is significant variability in the morphologic manifestations of …