B cells behaving badly: a better basis to behold belligerence in B-cell lymphomas

A plethora of genetic abnormalities has been described in B-cell lymphomas, some of which arise when physiologic mechanisms involved in the generation of immunologic diversity go awry. Several different lymphoma types, such as follicular lymphoma (FL), mantle cell lymphoma (MCL), and Burkitt lymphoma (BL), are associated with hallmark translocations that occur as a consequence of these errors (t(14;18)(q32;q21), t(11;14)(q13;q32), and t(8;14)(q24;q32), respectively); however, none of these associations is absolute and none is completely diagnostically specific or sensitive. The advantages and limitations of a variety of different testing strategies in the 2 most common lymphomas, FL and diffuse large B-cell lymphoma (DLBCL), are reviewed herein, including an evaluation of the role of PCR-based approaches, FISH, and more nascent genomic technologies. The use of immunophenotypic strategies that may potentially provide, albeit imperfectly, more user-friendly surrogates for underlying genetic aberrations and cell-of-origin designations derived from gene-expression profiling analyses are also discussed. Finally, a newly designated category of lymphoma with features intermediate between DLBCL and BL is appraised, highlighting the central role of genetic analysis in this diagnostic gray zone.