Diffuse large B cell lymphoma with chromosomal translocation t(14;19)(q32;q13) occurring in IgG4-related disease

Dear Editor, We report a rare case of diffuse large B cell lymphoma (DLBCL) that likely developed from nodal involvement of IgG4-related disease (IgG4-RD). A 70-year-old Japanese female presented to a primary hospital complaining of asthmatic symptoms. Serological tests identified abnormalities of elevated polyclonal IgG of 7035 mg/dL, IgG4 of 2550 mg/dL, and soluble interleukin-2 receptor (sIL-2R) of 2140 U/mL. A FFDG-PET/CT scan identified lymphadenopathies with mild FDG uptake in the neck, mediastinum, and abdomen. A biopsy specimen of the right supraclavicular fossa lymph node disclosed massive follicular hyperplasia with prominent plasma cell infiltration around follicles and marginal sinuses (Fig. 1a–c). In addition, a small number of plasma cells that were strongly positive for IgG4 had infiltrated into follicles (Fig. 1d). Neither immunohistochemical staining (Fig. 1e, f) nor flow cytometric analysis (Supplemental Fig. 1a) showed light chain restriction in lymphoid cells of the biopsied specimen. Chromosomal analysis by Giemsa-banding showed a normal karyotype. These findings led to a diagnosis of IgG4-related lymphadenopathy. After four years of watch and waiting, the patient showed general malaise with non-infectious pyrexia, mild dyspnea, body weight loss of 10 kg, and systemic lymphadenopathies of the neck, supraclavicular fossa, axillary fossa, and inguinal region. Serological data revealed increases of IgG to 2263mg/ dL, IgG4 to 1010 mg/dL, and sIL-2R to 7730 U/mL. FFDG-PET/CT showed FDG-avid systemic lymphadenopathy and bilateral pleural effusion. Histopathological assessment of the biopsied right axial lymph node identified diffuse infiltration of abnormal large lymphoid cells (Fig. 1g, h) that were positive for CD20 (Fig. 1i) and MUM-1, but negative for CD3, CD5, CD10, BCL-6, and BCL-2, leading to diagnosis of DLBCL. Importantly, most lymphoma cells were IgG4positive (Fig. 1j). Flow cytometric analysis (Supplemental Fig. 1b) identified kappa light chain restriction and Southern blot analysis (Supplemental Fig. 1c) confirmed Ig heavy chain (IgH) rearrangement. A Giemsa-banding study showed a complex abnormality: 47, XX, − 1, add(1)(p11), − 2, add(2)(p11.2), add(4)(q31), +add(5)(q31), del(5)(q?), add(6)(p21), del(6)(q?), add(7)(p11.2), t(14;19)(q32;q13.1), add(18)(q21), − 21, − 22, − 22, +mar1, +mar2, +mar3, +mar4, +mar5 [5/9], and 46, XX [4/9]. Six courses of RCHOP chemotherapy induced only partial response. Complete response was achieved with salvage R-DeVIC chemotherapy (rituximab, carboplatin, etoposide, ifosfamide, dexamethasone) and currently has been maintained for one year. Recent studies have shown an increased risk of malignancy, including malignant lymphoma, in IgG4-RD [1–8]; however, the process of malignant transformation is still poorly understood. The lymphoma cells in our case harbored the reciprocal chromosomal translocation t(14;19)(q32;q13.1) for rearrangements of IgH and BCL3 genes, of which the protein is a member of the IκB family and regulates the nuclear factor (NF)-κB family. DLBCL with BCL3 rearrangement frequently has complex cytogenetic abnormalities [9]. In addition, BCL3 rearrangement is more common in non-GCElectronic supplementary material The online version of this article (https://doi.org/10.1007/s00277-019-03688-w) contains supplementary material, which is available to authorized users.