A unique rearrangement involving the BCL6, MYC, IGH and BCL2 loci in diffuse large cell lymphoma. L. Richmond, C. Aguilar, G.S. Bezzegh, J. Skierkowski, G. Hart, C. Berger, T.C. Brown. Genzyme Genetics, Phoenix, AZ.
   Chromosomal abnormalities involving t(14;18)(q32.3;q21) and 3q27 (BCL6) are common in B-cell non-Hodgkin lymphoma of germinal center cell origin. B-cell lymphoma with concurrent t(14;18) and 8q24 (c-Myc) translocations fall within the morphologic spectrum of diffuse large B-cell (DLCL) and Burkitt lymphoma. These cases are extremely rare and are associated with an aggressive clinical course and poor prognosis. It has been suggested that t(14;18) and 3q27 rearrangements are mutually exclusive in lymphoma, however, our case not only has this combination but also involves c-MYC. We believe this to be the first study to report such a combination. Cytogenetic and fluorescence in situ hybridization (FISH) studies were performed on a bone marrow sample from a 90-year old female patient who was diagnosed as having diffuse large cell lymphoma. Chromosome analysis of metaphase cells revealed an abnormal karyotype: 47,XX,t(2;3)(q11.2;q27),add(14)(q32)x2,del(18)(q22q23),+mar[20]. Metaphase FISH analysis using whole chromosome paints for chromosomes 8, 14 and 18 showed chromosome 18 material on 3q, while 8q and 14q had additional unknown material. To further identify the unknown material, FISH was performed using the IGH/BCL2 (14;18), MYC/IGH (8;14), CCND1/IGH (11;14) and MALT1(18q) probes. The interphase FISH results were positive for both the IGH/BCL2 (76% of cells) and MYC/IGH probes (77% of cells). The CCND1/IGH probe revealed no evidence of a translocation, however 68% of the cells had an extra IGH signal. The MALT1 probe results were normal, allowing localization of the breakpoint on chromosome 18 at q21.32, between the MALT1 and BCL2 genes. The BCL6 break-apart probe at 3q27 confirmed this locus was disrupted by the 18q;2q material. The combination of both chromosomal analysis and FISH were essential in identifying the complex rearrangements in this lymphoma. FISH results enabled us to further clarify the cytogenetic findings and identify the following derivative chromosomes in this patient's bone marrow sample: der(3)t(2;18;3),der(8)t(18;14;8),der(14)t(8;14)x2 and der(18)t(14;18).