MYC/BCL2 double- and MYC/BCL2/BCL6 triple-hit follicular lymphomas associated with t(8;14;18)(q24;q32;q21)

We describe two follicular lymphoma (FL) patients with MYC/BCL2 double- and MYC/BCL2/BCL6 triple-hit translocations. The first patient (case 1) was a man in his 30s who presented with stage IV disease with leukemic manifestation. The second patient (case 2) was a man in his 60s who presented with relapsed FL, but his disease was in a limited stage. Histopathology of the lymph node biopsies revealed grade 3A FL in both cases. MYC positivity and the Ki-67-labeling index were 60-70 and 20% in case 1 and 30 and 50% in case 2, respectively. G-banding revealed t(8;14;18)(q24;q32;q21) in both cases and fluorescence in situ hybridization using MYC, IGH, and BCL2 break-apart probes confirmed t(8;14;18)(+5'BCL2,-3'MYC;+3'MYC,-5'IGH;+5'IGH,-5'BCL2). In case 2, additional materials of der(8)t(8;14;18) were duplicated and translocated to chromosome Y, and t(3;16)(q27;p13)/BCL6::CIITA was identified. We obtained BCL2-major breakpoint region::IGHJ5::IGHG1 and MYC exon 2::IGHA2 fusion sequences by long-distance polymerase chain reaction in case 1, and proposed that t(8;14;18) was generated by two-step translocations and that BCL2::IGH and MYC::IGH involved the same IGH allele. Both patients responded to the standard chemotherapy for FL. We suggest that the presence of t(8;14;18) in FL does not immediately indicate high-grade transformation and aggressive clinical behavior requiring intensive chemotherapy.