Chromosomal analysis of clonally related B‐cell lymphomas with discordant immunoglobulin light‐chain restrictions at different anatomical sites

To the Editor, Detection of immunoglobulin light‐chain restriction is important in the diagnosis of B‐cell non‐Hodgkin lymphoma. Clonally related B‐cell lymphomas with discordant immunoglobulin light‐chain restrictions at different anatomic sites, are rare. To the best of our knowledge, only three cases have been reported to date (Supporting Information: Table 1), and the underlying mechanisms remain largely unknown. Human immunoglobulin kappa (IGK) and lambda (IGL) light‐ chain genes are located on chromosome 2 (2p11.2) and chromosome 22 (22q11), respectively. Associations between chromosomal abnormalities in neoplastic cells and discordant immunoglobulin light‐chain restrictions have not been reported to date. Here, we report a case of B‐cell lymphomas with discordant immunoglobulin light‐chain restrictions at different anatomical sites, and discuss a potential mechanism underlying this discordance. A 72‐year‐old man, with a 2‐month history of swelling in the left inguinal lymph node, presented to our hospital. Computed tomography of the neck, chest, abdomen, and pelvis showed enlargement of the abdominal and pelvic lymph nodes. Flow cytometric evaluation of the inguinal lymph nodes revealed a monotypic B‐cell population with an immunophenotype of CD19+, CD20+, CD10+, and surface IGK light‐chain restriction (Figure 1a−c). Hematoxylin and eosin (H&E)‐stained histological sections of lymph node tissue showed diffuse sheets of relatively large lymphoid cells, with scattered lymphoid follicles (Supporting Information: Figure 1a). Immunohistochemically, these atypical lymphoid cells were positive for CD20, CD10, BCL2, and BCL6 and negative for CD3 and CD5 (Supporting Information: Figure 1b,c). The Ki‐67 proliferation index in atypical lymphoid cells was high (52.39%) (Supporting Information: Figure 1d). Capillary electrophoresis of polymerase chain reaction (PCR) products, amplified from DNA extracted from the lymph node tissue, showed a monoclonal peak for VH(FR1)/JH and VH(FR2)/JH immunoglobulin heavy chain (IGH) gene rearrangement (Supporting Information: Figure 2a). Monoclonal peaks corresponding to VH(FR3)/JH, DH1‐6/JH, and DH7/JH were not observed. Cytogenetic studies using fluorescence in situ hybridization (FISH) identified a BCL2‐IGH translocation, t(14;18). No IGH‐MYC translocation, t (8;14), was identified. Giemsa banding (G‐banding) analysis of the neoplastic cells in the lymph node revealed complex chromosomal abnormalities, including add(1)(p13), add(3)(q27), der(4)t(1;4)(q21;q31), add(9) (p13), and t(14;18)(q32;q21) (Supporting Information: Figure 3a). Diffuse large B‐cell lymphoma (DLBCL) and follicular lymphoma (FL) (grade 3 A) were diagnosed (DLBCL, 50%; FL, 50%). Three weeks after the inguinal lymph node examination, bone marrow aspiration and biopsy were performed for staging of the malignant lymphoma. Flow cytometry of the bone marrow revealed a monotypic B‐cell population with an immunophenotype that resembled inguinal lymph node cells (CD19+, CD20+, CD10+), but with surface IGL light‐ chain restriction (Figure 1d−f). H&E‐stained bone marrow tissue revealed atypical lymphoid cells that were morphologically similar to the lymphoma cells of the inguinal lymph node (Supporting Information: Figure 1e). Immunohistochemically, these atypical lymphoid cells were positive for CD20, CD10, and BCL2 but negative for CD3 (Supporting Information: Figure 1f,g). The Ki‐67 proliferation index in these lymphoma cells was high (86.43%) (Supporting Information: Figure 1h). Capillary electrophoresis of PCR products, amplified from DNA extracted from 10% formalin‐fixed and paraffin‐embedded bone marrow samples, showed a monoclonal peak for VH (FR1)/JH and VH(FR2)/JH IGH gene rearrangement (Supporting Information: Figure 2b). Monoclonal