IgG4-Related Lymphadenopathy

Abstract

Lymphadenopathy is frequently observed in patients with immunoglobulin G4-related disease (IgG4-RD) and sometimes appears as the first manifestation of the disease. The diagnosis of IgG4-related lymphadenopathy is complicated owing to a great histological diversity, with at least 5 histological subtypes. Indeed, lymph node biopsy may be performed under the suspicion that the lymphadenopathy is a malignant lymphoma or other lymphoproliferative disorder. The diagnosis of IgG4-RD is characterized by both elevated serum IgG4 (>135 mg/dL) and histopathological features, including a dense lymphoplasmacytic infiltrate rich in IgG4+ plasma cells (IgG4+/IgG+ plasma cell ratio >40%). However, 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. Owing to these factors, IgG4-RD cannot be differentiated from hyper-IL-6 syndromes on the basis of histological findings alone. Laboratory analyses are crucial to differentiate between the 2 diseases. Hyper-IL-6 syndromes are characterized by elevated serum levels of IgG, IgA, IgM, and C-reactive protein (CRP); thrombocytosis; anemia; hypoalbuminemia; hypocholesterolemia. In contrast, IgG4-RD does not share any of these characteristics. Therefore, the diagnosis of IgG4-RD requires not only pathological findings but also clinical and laboratory analyses.

Clinicopathologic analysis of IgG4-related skin disease

“…In contrast, IgG4-related disease does not have any of these characteristics. 3,5,9,10 In conclusion, patients with IgG4-related skin disease had uniform clinicopathology, with lesions frequently found on the skin of the face, head, and neck, particularly the periauricular, cheek, and mandible regions; these were frequently accompanied by progressively transformed germinal centerstype IgG4-related lymphadenopathy. …”

“…3 Hyper-IL-6 syndromes, such as multicentric Castleman's disease, rheumatoid arthritis, and immunemediated conditions, sometimes fulfill the diagnostic criteria for IgG4-related disease. 9,10 Recently, we encountered a case of cutaneous involvement of multicentric Castleman's disease that fulfilled the diagnostic criteria for IgG4-related disease. 11 Therefore, it is important to differentiate between IgG4-related skin disease and cutaneous involvement of multicentric Castleman's disease.…”

Elevated Serum IgG4 Complicated by Pericardial Involvement with a Patchy ¹⁸F-FDG Uptake in PET/CT: Atypical Presentation of IgG4-related Disease

“…A histological and immunohistochemical examination of the biopsy specimen revealed an increase in the number of IgG4-positive plasma cells (>100 per highpower field), an IgG4 + /IgG + plasma cells ratio >50%, similar to IgG4-related lymphadenopathy type II (follicular hyperplasia) (Fig. 3) (19,20). However, storiform fibrosis, obliterative phlebitis, eosinophilic infiltration and immunoglobulin light-chain restriction were not observed.…”

A case of IgG4-related disease seemingly presenting as a T-cell lymphoma

“…[15] Meanwhile, when imaging or even pathological biopsy cannot exclude the possibility of lymphoma for patients with lymph node enlargement, the examination of serum IgG4 level should be performed. To prevent harmful misdiagnosis and unnecessary chemotherapy, pathologists and clinicians should collaborate closely to evaluate each possibility of diseases.…”