Multicentric Castleman's disease with abundant IgG4-positive cells: a clinical and pathological analysis of six cases.
BACKGROUND
Differentiation between multicentric Castleman's disease and systemic immunoglobulin (Ig) G4-related lymphadenopathy is sometimes difficult. It has been suggested that measurement of the IgG4-/IgG-positive cell ratio is useful for the differential diagnosis of the two diseases. However, the authors present a detailed report of six patients with multicentric Castleman's disease with abundant IgG4-positive cells (IgG4-/IgG-positive cell ratio, >40%).


RESULTS
In the present series, the patients showed systemic lymphadenopathy, polyclonal hypergammaglobulinaemia and elevated serum interleukin-6 (IL-6) and C-reactive protein levels. Further, anaemia, hypoalbuminaemia, hypocholesterolaemia and thrombocytosis were observed. These findings were consistent with those of multicentric Castleman's disease. Although five patients showed elevated serum IgG4 levels, only two patients showed an increased serum IgG4/IgG ratio. However, the two patients showed highly elevated serum IgG4 levels, but the serum IgG4/IgG ratios were, although increased, not very high. Also, a patient with increased serum IgG4/IgG ratio showed a good response to antihuman IL-6 receptor monoclonal antibody (tocilizumab). Histologically, the germinal centres were mostly small and regressive, and frequently penetrated by hyalinised blood vessels, and there was no eosinophil infiltration. These findings were different from those of IgG4-related lymphadenopathy.


CONCLUSIONS
The authors conclude that multicentric Castleman's disease sometimes occurs with abundant IgG4-positive cells and elevated serum IgG4 levels. Therefore, the two diseases cannot be differentially diagnosed by immunohistochemical staining alone. Laboratory findings, especially IL-6 level, C-reactive protein level and platelet count, are important for the differential diagnosis of the two diseases.
Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yasuharu
Y
Sato
Masaru
M
Kojima
Katsuyoshi
K
Takata
Toshiaki
T
Morito
Kohichi
K
Mizobuchi
Takehiro
T
Tanaka
Dai
D
Inoue
Hideyuki
H
Shiomi
Haruka
H
Iwao
Tadashi
T
Yoshino
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001706:Biopsy; D002097:C-Reactive Protein / Q000032:analysis; D005871:Castleman Disease / Q000175:diagnosis* / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis* / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis; D008198:Lymph Nodes / Q000473:pathology; D008206:Lymphatic Diseases / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged
D015415:Biomarkers; D007074:Immunoglobulin G; D015850:Interleukin-6; D002097:C-Reactive Protein