Rearrangements of Immunoglobulin Genes in Tumor Cells of Patients with Primary Mediastinal (Thymic) Large B-Cell Lymphoma

Abstract

Background. Primary mediastinal (thymic) large B-cell lymphoma (PMBCL) is a malignant tumor with large atypical lymphoid cells expressing post-germinal differentiation markers. Rearrangements of immunoglobulin genes in PMBCL are revealed in 30-65 % of cases. Immunoglobulin molecules, however, are expressed neither on the surface, nor in cytoplasm of tumor cells. Aim. To assess cell clonality rate on the basis of rearrangements of immunoglobulin heavy/light chain genes; to determine rearrangement stability at the time of relapse development; to study the range of rearrangements and clonal relationship with primary tumor in metachronous development of mediastinal gray zone lymphoma. Materials & Methods. The assessment of rearrangements of immunoglobulin heavy/light chain genes was based on molecular analysis of 29 primary tumor biopsies and 4 tissue samples with histologically and immunohistochemically verified relapses or metachronous lymphoma development. Results. In 16 (55.2 %) out of 29 cases a rearrangement of immunoglobulin heavy chain genes was reported, in 7 (24.1 %) cases a rearrangement of light chain genes was identified, in 6 (20.7 %) cases no rearrangements of immunoglobulin heavy/light chain genes were found. On the basis of immunoglobulin gene analysis in 2 patients with early relapse a tumor clone was detected that was identical with the one identified at the onset of the disease. In 2 patients with complete remission a metachronous development of mediastinal gray zone lymphoma was reported, whereas molecular genetic analysis revealed a change/disappearance of initial clonal rearrangements of immunoglobulin genes. Conclusion. Total detection rate of B-cell clonality in PMB-CL was 79.3 %. Molecular genetic analysis confirmed that initial clonal rearrangements of immunoglobulin genes were preserved in early relapses, and invalidated tumor clonal relationship in a metachronous development of mediastinal gray zone lymphoma.