Investigation of IgG4‐positive cells in idiopathic multicentric Castleman disease and validation of the 2020 exclusion criteria for IgG4‐related disease

Abstract

Patients with plasma cell type idiopathic multicentric Castleman disease (PC‐iMCD) often show elevated serum IgG4 levels and IgG4‐positive cell infiltration in tissues due to overproduction of interleukin‐6, and may meet the diagnostic criteria for IgG4‐related disease (IgG4‐RD). Although PC‐iMCD has been listed as a major exclusion disease for IgG4‐RD, distinguishing between these diseases is challenging due to a lack of highly specific diagnostic biomarkers. In 2020, we proposed exclusion criteria of IgG4‐RD mimickers. In this paper, we validated the accuracy of the criteria in excluding one of the mimickers, PC‐iMCD, from IgG4‐RD. Validation was performed on 57 PC‐iMCD patients (39 presenting lymph node lesions and 19 with lung lesions) and 29 IgG4‐RD patients (22 presenting lymph node lesions and seven with lung lesions). According to our results, 20.5% of the PC‐iMCD patients with lymph node lesions and 42.1% of those with lung lesions met the diagnostic criteria for IgG4‐RD. All these patients with PC‐iMCD were excluded from a diagnosis of IgG4‐RD by the proposed criteria. Additionally, 6.9% of IgG4‐RD patients met the exclusion criteria. Thus, if the exclusion criteria are met, diagnosis should be made based on a combination of findings including organ distribution of disease, response to steroid therapy, and other pathological findings.

Idiopathic Plasmacytic Lymphadenopathy Forms an Independent Subtype of Idiopathic Multicentric Castleman Disease

“…iMCD is a rare lymphoproliferative disorder that is characterized by multiple lymphadenopathies with unknown etiology [ 17 ]. In particular, iMCD-NOS is a heterogenous entity, likely including undefined disease [ 11 , 18 , 19 , 20 , 21 ]. The present results show that IPL is likely to be a separate subtype of iMCD, along with iMCD-TAFRO and iMCD-NOS, given its unique clinicopathological characteristics.…”

Idiopathic Multicentric Castleman Disease with Strikingly Elevated IgG4 Concentration in the Serum and Abundant IgG4-Positive Cells in the Tissue: A Case Report

“…Additionally, an atopic history, including allergic rhinitis, asthma, and atopic dermatitis, is characteristic for IgG4RD [ 12 ]. Finally, several studies showed that elevated levels of IL-6, IgG, IgA, and IgM, increased CRP, anemia, and hypoalbuminemia are distinctive for iMCD [ 12 , 14 , 15 ]. The persistently elevated levels of serum CRP (≧1.0 mg/dL), IgA, or IgM are proposed as exclusion criteria for IgG4RD by the Japanese Pathology Study Group of IgG4-related disease [ 16 ].…”

Clinicopathological characteristics of gastric IgG4‐related disease: Systematic scoping review

“…48 A thorough workup with serology, including serum immunoglobulin A and M, and C-reactive protein, may help rule out lymphoproliferative diseases, including CD. 49 Currently, it is unclear if gastric IgG4-RD can increase the risk of gastric malignancy. A Japanese observational study reported that 2/8 (25%) gastric IgG4-RD patients had concurrent malignancy, 15 although none of the case reports noted associated malignancy.…”

“…While rare, Castleman disease (CD), an important mimicker of IgG4‐RD, can also present as a gastric mass 48 . A thorough workup with serology, including serum immunoglobulin A and M, and C‐reactive protein, may help rule out lymphoproliferative diseases, including CD 49 …”