Background IgG4-related disease (IgG4-RD) is a distinct entity, characterized by tumefactive fibro-inflammatory lesions rich in polyclonal IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis and often elevated serum IgG4 concentrations. There is evolving data that IgG4-RD is associated with lymphomas.
Objectives To evaluate the prevalence of B-cell clonalityand malignant lymphoproliferationin patients with IgG4-RD.
Methods Single – center retrospective study. We reviewed medical records of patients treated in Nasonova Research Institute of rheumatology from 2010 to 2014. 15 patients with biopsy proven IgG4-RD were included (10 pts with definite IgG4-RD, 5pts with possible/probable IgG4 according to comprehensive diagnostic criteria of IgG4-RD (Umehara H et al., 2011). B-cell clonality was detected in PCR analysis of immunoglobulin (Ig) V-D-J genes heavy chain rearrangements (FR1, FR2, FR3) (on frozen tissue section or paraffin embedded).
Results 15 patients were included. The mean age was 39.5 years (range 19-67), mean duration of the disease before the diagnosis of IgG4-RD 55.9 months (range 5-204). The mean number of organs involved was 2.6 (range 1-4): orbit 10, salivary glands 9, lymph nodes 7, biliary tract 1, breast 1, bones 1, soft tissues of the neck 1 and nasal cavity or paranasal sinuses 8. Thirteen patients (86.7%) had elevated serum IgG4 levels >135 mg/dl at baseline (mean 919.4 mg/dl, range 81-3990 mg/dl). In 8 patients serum protein electrophoresis with immunofixation was performed and in 2 cases (25%) paraproteinemia was detected (tracer IgGκ - 1, monoclonal IgMκ 3.2 g/l - 1). These 2 patients demonstrated B-cell clonality in the tissue specimens as well (in bone marrow and submandibular salivary gland respectively). However, pathological and immunohystochemical examination didn't prove the existence of lymphoma. Altogether B-cell clonality was detected in 3 patients (20%): by PCR analysis of Ig heavy chain rearrangements in 2 cases (in submandibular salivary gland-1 and in bone marrow – 1), by PCR analysis of Ig kappa chain rearrangements (Vκ-Jk and Vκ-KDE/Intron RSS-KDE) in 1 case. The latter patient didn't have monoclonal secretion in the serum, however she exhibited pathological characteristics of MALT-lymphoma of the lacrimal gland with κ chain restriction. The diagnosis of IgG4-RD and MALT lymphoma in this patient was made simultaneously. In 1 patient clonality was uncertain (clonal variant exceeded polyclonal background three times).
Conclusions It seems that IgG4-RD can act as a background for lymphoma formation. In our research 3 pts (20%) had B-cell clonality in the affected tissues and 1 patient (6.7%) developed IgG4-related MALT-lymphoma of lacrimal gland. B-cell clonality does not necessarily constitute lymphoma, but these patients require very close follow-up. Serum electrophoresis with immunofixation and PCR analysis of B-cell IgH/L chain rearrangements is strongly recommended in patients with IgG4-RD.
Disclosure of Interest None declared