Pathological examination of involved tissue occupies an extremely important place in establishing the diagnosis of IgG4-related disease (IgG4-RD). However, the histological picture in IgG4-RD can vary significantly from organ to organ in this disease even while adhering to basic tenets. Consequently, the pathological diagnosis of this condition is often challenging even in the setting of adequate tissue specimens. This is particularly true with regard to the assessment of lymph nodes in patients who may have IgG4-RD. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity. At least five histological subtypes have already been identified. Lymph node biopsies are often performed because of suspicion that the lymphadenopathy might reflect a malignant lymphoma or other lymphoproliferative disorder.
In general, if the IgG4+/IgG+ plasma cell ratio is ≥40 %, the possibility of IgG4-RD is high, but cases of patients with diagnosis other than IgG4-RD who fulfill this criterion are well described in the literature. In practice, patients with hyper-interleukin (IL)-6 syndromes such as multicentric Castleman’s disease, rheumatoid arthritis, and other immune-mediated conditions frequently show lymph node involvement and often fulfill the diagnostic criteria for IgG4-RD. For this reason, it is important that the diagnosis of IgG4-RD relies not only on the pathological findings, but be the result of a careful clinicopathologic collaboration that considers the overall clinical context and appropriate serologic (in particular, serum IL-6, C-reactive protein, IgG4 concentration) and radiologic data as well.
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