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IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease.

TitleIgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease.
Publication TypeJournal Article
Year of Publication2014
AuthorsGeyer JT, Niesvizky R, Jayabalan DS, Mathew S, Subramaniyam S, Geyer AI, Orazi A, Ely SA
JournalMod Pathol
Volume27
Issue3
Pagination375-81
Date Published2014 Mar
ISSN1530-0285
KeywordsAged, Aged, 80 and over, Female, Humans, Immunoglobulin G, Male, Middle Aged, Multiple Myeloma
Abstract

IgG4-related disease is a newly described systemic fibroinflammatory process, characterized by increase in IgG4-positive plasma cells. Its pathogenesis, including the role of IgG4, remains poorly understood. Plasma cell myeloma is typically associated with a large monoclonal serum spike, which is frequently of IgG isotype. We sought to identify and characterize a subset of IgG4-secreting myeloma, as it may provide a biological model of disease with high serum levels of IgG4. Six out of 158 bone marrow biopsies (4%) from patients with IgG myeloma expressed IgG4. Four patients were men and two were women, with a mean age of 64 (range 53-87) years. Imaging showed fullness of pancreatic head (1), small non-metabolic lymphadenopathy (1), and bone lytic lesions (6). Two patients developed necrotizing fasciitis. All had elevated serum M-protein (mean 2.4, range 0.5-4.2 g/dl), and none had definite signs or symptoms of IgG4-related disease. Four myelomas had plasmablastic morphology. Four had kappa and two had lambda light chain expression. Three cases expressed CD56. Two patients had a complex karyotype. In conclusion, the frequency of IgG4 myeloma correlates with the normal distribution of IgG4 isoform. The patients with IgG4 myeloma appear to have a high rate of plasmablastic morphology and could be predisposed to necrotizing fasciitis. Despite high serum levels of IgG4, none had evidence of IgG4-related disease. These findings suggest that the increased number of IgG4-positive plasma cells is not the primary etiologic agent in IgG4-related disease. Elevated serum levels of IgG4 is not sufficient to produce the typical disease presentation and should not be considered diagnostic of IgG4-related disease.

DOI10.1038/modpathol.2013.159
Alternate JournalMod. Pathol.
PubMed ID24030741