title: Triple-hit B-cell Lymphoma With MYC, BCL2, and BCL6 Translocations/Rearrangements: Clinicopathologic Features of 11 Cases.
abstract: Lymphomas with translocations/rearrangements of MYC, BCL2, and BCL6, so-called triple-hit B-cell lymphoma, are rare, and few studies on these tumors are available in the literature. We report 11 cases of triple-hit B-cell lymphoma and characterize their clinicopathologic findings. All patients were men, with a median age of 64 years (range, 45 to 80 y), and 4 patients had antecedent or concurrent follicular lymphoma. Using the 2008 World Health Organization classification, these cases were classified as: 5 B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma; 4 DLBCL; 1 DLBCL with concurrent follicular lymphoma; and 1 low-grade follicular lymphoma. All cases were positive for CD10, BCL2, and FOXP1. Ten of 11 cases were positive for CD20. MYC expression was high in 10/11 (91%), BCL6 was positive in 8/11 (73%), and MUM1/IRF4 was positive in 6/11 (55%) cases. T-cell antigens, TdT, and Epstein-Barr virus-encoded RNA were negative in all cases. Ten of 11 cases showed a high proliferation index-70% to 100%, and the follicular lymphoma had a 30% proliferation rate. Using most algorithms, all cases belonged to germinal center B-cell-like group. All patients received standard or more aggressive immunochemotherapy regimens. Three patients had no response to chemotherapy; 4 patients showed a partial response; 2 patients had complete remission after chemotherapy; and 2 patients had just begun chemotherapy. Three patients underwent a stem cell transplant. The median follow-up time was 5.3 months. Five patients died, and 6 patients were alive at last follow-up. Two patients who underwent stem cell transplant after complete response to chemotherapy were in remission with 16 to 19 months of clinical follow-up. In summary, triple-hit lymphomas are clinically aggressive tumors associated with a poor prognosis. Patients often respond poorly to chemotherapy, but a subset may completely respond to chemotherapy followed by stem cell transplant.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shimin
authors.initials: S
authors.lastname: Hu
authors.forename: Xinyan
authors.initials: X
authors.lastname: Lu
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D016393:Lymphoma, B-Cell / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010641:Phenotype; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012074:Remission Induction; D033581:Stem Cell Transplantation; D013997:Time Factors; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: C000595707:BCL2 protein, human; C084103:BCL6 protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C489427:MYC protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D016271:Proto-Oncogene Proteins c-myc