Clinical Implications of Idiopathic Multicentric Castleman Disease Among Japanese: A Report of 28 Cases

Abstract

To clarify the clinicopathologic findings of idiopathic multicentric Castleman disease among Japanese, 28 cases were studied. Two variants were delineated by the clinicopathologic findings (1) idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (n = 18) and (2) nonidiopathic plasmacytic lymphadenopathy type (n= 10). Clinicopathologically, idiopathic plasmacytic lymphadenopathy was defined by the prominent polyclonal hyperimmunoglobulinemia, normal germinal centers, and sheet-like infiltration of plasma cells in the interfollicular area of the lymph node. Histologically, the nonidiopathic plasmacytic lymphadenopathy type was characterized by hyaline-vascular germinal centers of the lymph node lesion. In comparison with idiopathic plasmacytic lymphadenopathy, patients with nonidiopathic plasmacytic lymphadenopathy showed infrequent prominent polyclonal hyperimmunoglobulinemia and frequent association with autoimmune disease. However, there was no difference in the overall 5-year survival between the 2 subtypes. Compared with idiopathic multicentric Castleman disease in Western countries, the chronic course of the disease of idiopathic multicentric Castleman disease in Japan appears to be related to negativity for human herpesvirus 8 infection.

Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman's disease

“…The clinical findings of systemic lymphadenopathy and hypergammaglobulinemia, which are characteristic of systemic IgG4-related lymphadenopathy, are also highly reminiscent of multicentric Castleman's disease. [15][16][17][18] However, none of our patients had anemia, hypoalbuminemia, or hypocholesterolemia, and elevated interleukin-6 and C-reactive protein were the exceptions. These findings are quite different from those of multicentric Castleman's disease.…”

“…These findings are quite different from those of multicentric Castleman's disease. [15][16][17][18] Interleukin-6 is a multifunction cytokine that has various biological activities in target cells and regulates immune responses, acute phase reactions, hematopoiesis, and bone metabolism. 25 Dysregulated overproduction of interleukin-6 is found in autoimmune diseases, such as rheumatoid arthritis, multicentric Castleman's disease, and Crohn's disease.…”

“…25 Dysregulated overproduction of interleukin-6 is found in autoimmune diseases, such as rheumatoid arthritis, multicentric Castleman's disease, and Crohn's disease. [16][17][18]26,27 C-reactive protein is a pentamer of 23-kd subunits that is synthesized and secreted by hepatocytes upon stimulation by a variety of inflammatory cytokines, including tumor necrosis factor-a, interleukin-1, and especially interleukin-6. Therefore, interleukin-6 is closely related to the production of C-reactive protein.…”

“…Idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia is considered identical to multicentric Castleman's disease in Western countries. 17,18 Idiopathic plasmacytic lymphadenopathy and multicentric Castleman's disease show similar clinicopathology. However, idiopathic plasmacytic lymphadenopathy has a significantly better 5-year survival rate than multicentric Castleman's disease.…”

“…17,18 Multicentric Castleman's disease exhibits an aggressive and usually fatal disease course associated with infectious complications and risk of malignant tumors; one-third of such patients develop Kaposi sarcoma or B-cell lymphoma. 17,18 IgG4-related disease sometimes involves regional and/or systemic lymph nodes, 3,4,11 and is often clinically and/or histologically suspected to be multicentric Castleman's disease and/or malignant lymphoma. 5,6,11 However, systemic IgG4-related lymphadenopathy is either not mentioned or only briefly alluded to in previous reports.…”