title: IgG4 plasma cell myeloma: new insights into the pathogenesis of IgG4-related disease.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Julia T
authors.initials: JT
authors.lastname: Geyer
authors.affiliation: Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Niesvizky
authors.affiliation: Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Jayabalan
authors.affiliation: Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Mathew
authors.affiliation: Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Shivakumar
authors.initials: S
authors.lastname: Subramaniyam
authors.affiliation: Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Geyer
authors.affiliation: Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.affiliation: Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medical Center, New York, NY, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Ely
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology* / Q000473:pathology*
chemical_list: D007074:Immunoglobulin G