Acquisition of a t(11;14)(q13;q32) in clonal evolution in a follicular lymphoma with a t(14;18)(q32;q21) and t(3;22)(q27;q11.2).

Chromosome translocations involving an immunoglobulin (IG) locus and another gene, either BCL or MYC, are common events in B-cell lymphoma. Occasionally, two IG loci, one with BCL and the other with MYC, are simultaneously involved; such cases are classified as double-hit (DH) lymphomas. These tumors often show intermediate histologic features between those of diffuse large B-cell lymphoma and those of Burkitt lymphoma. Patients with DH lymphoma have a poor prognosis. Rarely, lymphomas in which three IG loci are simultaneously involved with two different BCL genes and MYC have been reported. These cases are classified as triple-hit lymphomas; virtually all these are aggressive tumors with an even worse prognosis. We present here a unique case of follicular lymphoma (FL) with rearranged BCL2, BCL6, and BCL1 (also known as CCND1) genes. Lymphoma cells at first clinical relapse had a complex karyotype that included a t(3;22)(q27;q11) and t(14;18)(q32;q21). About 15 years after initial diagnosis, the lymphoma cells showed clonal cytogenetic evolution and acquired a t(11;14)(q13;q32). This article is the first case report of a low grade B-cell lymphoma that had three lymphoma-associated reciprocal translocations not involving MYC and that had a long indolent clinical course.