Lymphadenopathy of IgG4-related disease: an underdiagnosed and overdiagnosed entity
Section snippets
Occurrence of lymphadenopathy in IgG4-related disease
A mere 10 years ago, Kamisawa et al1, 2 proposed the existence of a new disease entity characterized by tumefactive sclerosing inflammation of multiple organs, tissue infiltration by IgG4+ plasma cells, elevated serum IgG4 levels, and favorable response to steroid therapy. This disease has now come to be known as “IgG4-related disease,” after multiple revisions in terminology over the years.3, 4, 5, 6, 7 Although IgG4-related disease affects predominantly extranodal sites, in particular
Clinical features of IgG4-related lymphadenopathy
As depicted in Figure 1, there are 4 scenarios whereby lymphadenopathy occurs in IgG4-related disease (Figure 1).9, 10, 11, 12, 15, 16, 17
In scenario A, regional lymph nodes are found in excision specimens of involved organs (such as pancreas or submandibular gland). The lymph nodes may or may not be enlarged, and they rarely produce symptoms.
In scenario B, systemic lymphadenopathy represents part of the initial presentation of IgG4-related disease, or is discovered on work-up of the patients
Should IgG4 immunostain be performed routinely on all reactive lymph nodes so as not to miss IgG4-related lymphadenopathy?
The more we learn about IgG4-related disease, the more we realize that an increase in IgG4+ cells and IgG4/IgG ratio is not all that specific when taken in isolation. With widespread application of IgG4 and IgG immunostains on reactive lymph nodes in recent years, many other diseases and even nonspecific reactive lymphadenopathies have occasionally been found to show high IgG4+ cell count and high IgG4/IgG ratio, but the significance of the IgG4+ cell infiltrate in such cases is unclear.
Conclusions
Our understanding of IgG4-related disease is still evolving. It is likely that the diagnostic approach to IgG4-related lymphadenopathy will have to be modified in future with the availability of new data.
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