Double-hit lymphoma carrying two distinct c-MYC translocations and the three-way translocation t(3;12;14)(q27;p12;q32) involving BCL6

Abstract

 We describe a 57-year-old woman who presented with a bulky tumor of the iliosacral region. Bone marrow biopsy and computer tomography-assisted needle biopsy of the tumor revealed infiltration of lymphoma cells showing high-grade cytology with a mature B-cell immunophenotype and high proliferation index determined by Ki-67 immunohistochemistry. Cytogenetic studies of bone marrow specimens revealed two distinct karyotypes involving chromosomes 3, 14, and a marker chromosome. A series of fluorescence in situ hybridization studies of metaphase and interphase nuclei revealed a three-way translocation, t(3;12;14)(q27;p12;q32), leading to a BCL6-immunoglobulin heavy chain (IgH) fusion gene, and two distinct c-MYC translocations involving either the IgH or a non-Ig gene as partners. With multiple cycles of chemotherapy, the patient finally achieved complete response. We concluded that this case fulfills the criteria of doublehit lymphoma carrying both c-MYC and BCL6 translocations, and that the lymphoma be placed into the category of the WHO 2008 classification “B-cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma".