title: Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman's disease.
abstract: IgG4-related disease sometimes involves regional and/or systemic lymph nodes, and often clinically and/or histologically mimics multicentric Castleman's disease or malignant lymphoma. In this study, we examined clinical and pathologic findings of nine patients with systemic IgG4-related lymphadenopathy. None of these cases were associated with human herpes virus-8 or human immunodeficiency virus infection, and there was no T-cell receptor or immunoglobulin gene rearrangement. Histologically, systemic IgG4-related lymphadenopathy was classified into two types by the infiltration pattern of IgG4-positive cells: interfollicular plasmacytosis type and intra-germinal center plasmacytosis type. The interfollicular plasmacytosis type showed either Castleman's disease-like features or atypical lymphoplasmacytic and immunoblastic proliferation-like features. By contrast, the intra-germinal center plasmacytosis type showed marked follicular hyperplasia, and infiltration of IgG4-positive cells mainly into the germinal centers, and some cases exhibited features of progressively transformed germinal centers. Interestingly, eight of our nine (89%) cases showed eosinophil infiltration in the affected lymph nodes, and examined patients showed high elevation of serum IgE. Laboratory examinations revealed elevation of serum IgG4 and soluble interleukin-2 receptors. However, the levels of interleukin-6, C-reactive protein, and lactate dehydrogenase were within normal limits or only slightly elevated in almost all patients. One patient showed a high interleukin-6 level whereas C-reactive protein was within the normal limit. Autoantibodies were examined in five patients and detected in four. Compared with the previously reported cases of multicentric Castleman's disease, our patients with systemic IgG4-related lymphadenopathy were significantly older and had significantly lower C-reactive protein and interleukin-6 levels. In conclusion, in our systemic IgG4-related lymphadenopathy showed pathologic features only partially overlapping those of multicentric Castleman's disease, and serum data (especially C-reactive protein and interleukin-6) are useful for differentiating the two. Our findings of eosinophil infiltration in the affected tissue and elevation of serum IgE may suggest an allergic mechanism in the pathogenesis of systemic IgG4-related lymphadenopathy.
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Sato
authors.forename: Masaru
authors.initials: M
authors.lastname: Kojima
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takata
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Morito
authors.forename: Hideki
authors.initials: H
authors.lastname: Asaoku
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Kohichi
authors.initials: K
authors.lastname: Mizobuchi
authors.forename: Megumu
authors.initials: M
authors.lastname: Fujihara
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kuraoka
authors.forename: Tokiko
authors.initials: T
authors.lastname: Nakai
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ichimura
authors.forename: Takehiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Maiko
authors.initials: M
authors.lastname: Tamura
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis; D005871:Castleman Disease / Q000276:immunology* / Q000473:pathology*; D003937:Diagnosis, Differential; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D008206:Lymphatic Diseases / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
chemical_list: D007074:Immunoglobulin G; D015850:Interleukin-6; D007073:Immunoglobulin E; D002097:C-Reactive Protein