B-cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations

Abstract

To identify and investigate clinicopathological features of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 translocations ("double-hit" lymphoma). Tissue microarray was constructed from formalin-fixed and paraffin-embedded tissue samples of aggressive B cell lymphomas diagnosed between 2009 and 2012, including 129 cases of diffuse large B cell lymphoma (DLBCL), 5 cases of B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (BCLU), 7 cases of Burkitt lymphoma and 4 cases of high-grade follicular lymphoma with diffuse large B cell lymphoma component. Interphase fluorescence in-situ hybridization (FISH) was performed with a panel of probes including myc, bcl-2/IgH and bcl-6 to document related gene translocation and copy number changes. Medical record review was performed and follow-up data was recorded. Among 145 cases, 5 cases (3.4%) of B cell lymphomas with concurrent myc and bcl-2/IgH or bcl-6 rearrangements (double-hit lymphomas) were identified, including 2 cases involving myc and bcl-2 translocations (1 DLBCL and 1 BCLU), and 3 cases involving myc and bcl-6 translocations (all DLBCLs). Three cases with concurrent bcl-2/IgH and bcl-6 translocations were found. Single gene translocations or increase of copy numbers were found in 66 cases, representing 51.2% (66/129) of all de novo DLBCLs. Ki-67 index of the 5 "double-hit" lymphomas ranged from 60% to 100%. Clinical follow-up data were available in 4 of the 5 "double-hit" lymphoma patients, three of whom died within 2 years and 1 patient was alive after 36 months of follow-up. "Double-hit" B-cell lymphomas are rare and can only be identified by molecular detection. They should not be considered synonymous with BCLU morphologically, and may present entities within other morphological spectra. Most of the patients have a poor prognosis. Further in-depth studies of larger case numbers are required to determine the pathologic and genetic variables of the lesion.