Triple-hit B-cell Lymphoma with MYC, BCL2, and BCL6 translocations/rearrangements: Clinicopathologic Features of 11 Cases

American Journal of Surgical Pathology

Volumn 39, Issue 8, 2015, Pages 1132-1139

  Wang, Wei ^a   Hu, Shimin ^a   Lu, Xinyan ^a   Young, Ken H ^a   Medeiros, L Jeffrey ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

B cell; BCL2; BCL6; lymphoma; MYC; triple hit

Indexed keywords

BCL2 PROTEIN, HUMAN; BCL6 PROTEIN, HUMAN; DNA BINDING PROTEIN; MYC PROTEIN; MYC PROTEIN, HUMAN; PROTEIN BCL 2; TUMOR MARKER;

AGED; CANCER GRADING; CELL PROLIFERATION; CHEMISTRY; FEMALE; FLOW CYTOMETRY; FLUORESCENCE IN SITU HYBRIDIZATION; GENE REARRANGEMENT; GENE TRANSLOCATION; GENETIC PREDISPOSITION; GENETICS; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOLOGY; IMMUNOPHENOTYPING; IMMUNOTHERAPY; LYMPHOMA, B-CELL; MALE; MIDDLE AGED; MORTALITY; PATHOLOGY; PHENOTYPE; PROCEDURES; REMISSION; STEM CELL TRANSPLANTATION; TIME; TREATMENT OUTCOME; VERY ELDERLY;

AGED; AGED, 80 AND OVER; CELL PROLIFERATION; DNA-BINDING PROTEINS; FEMALE; FLOW CYTOMETRY; GENE REARRANGEMENT; GENETIC PREDISPOSITION TO DISEASE; HUMANS; IMMUNOHISTOCHEMISTRY; IMMUNOPHENOTYPING; IMMUNOTHERAPY; IN SITU HYBRIDIZATION, FLUORESCENCE; LYMPHOMA, B-CELL; MALE; MIDDLE AGED; NEOPLASM GRADING; PHENOTYPE; PROTO-ONCOGENE PROTEINS C-BCL-2; PROTO-ONCOGENE PROTEINS C-MYC; REMISSION INDUCTION; STEM CELL TRANSPLANTATION; TIME FACTORS; TRANSLOCATION, GENETIC; TREATMENT OUTCOME; TUMOR MARKERS, BIOLOGICAL;

EID: 84938088646     PISSN: 01475185     EISSN: 15320979     Source Type: Journal    
DOI: 10.1097/PAS.0000000000000434     Document Type: Article

References (41)

1. Basso K, Dalla-Favera R. Roles of BCL6 in normal and transformed germinal center B cells. Immunol Rev. 2012;247: 172-183.
2. Jacobson JO, Wilkes BM, Kwaiatkowski DJ, et al. bcl-2 rearrangements in de novo diffuse large cell lymphoma. Association with distinctive clinical features. Cancer. 1993;72:231-236.
3. Ott G, Rosenwald A, Campo E. Understanding MYC-driven aggressive B-cell lymphomas: pathogenesis and classification. Hematology Am Soc Hematol Educ Program. 2013;2013: 575-583.
4. Klapper W, Stoecklein H, Zeynalova S, et al. Structural aberrations affecting the MYC locus indicate a poor prognosis independent of clinical risk factors in diffuse large B-cell lymphomas treated within randomized trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Leukemia. 2008;22: 2226-2229.
5. Zhou K, Xu D, Cao Y, et al. C-MYC aberrations as prognostic factors in diffuse large B-cell lymphoma: a meta-analysis of epidemiologic studies. PLoS One. 2014;9:e95020.
6. Aukema SM, Siebert R, Schuuring E, et al. Double-hit B-cell lymphomas. Blood. 2011;117:2319-2331.
7. Li S, Lin P, Fayad LE, et al. B-cell lymphomas with MYC/8q24 rearrangements and IGH@BCL2/t(14;18)(q32;q21): an aggressive disease with heterogeneous histology, germinal center B-cell immunophenotype and poor outcome. Mod Pathol. 2012;25: 145-156.
8. Johnson NA, Savage KJ, Ludkovski O, et al. Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival. Blood. 2009;114:2273-2279.
9. Petrich AM, Nabhan C, Smith SM. MYC-associated and double-hit lymphomas: a review of pathobiology, prognosis, and therapeutic approaches. Cancer. 2014;120:3884-3895.
10. Li S, Lin P, Young KH, et al. MYC/BCL2 double-hit high-grade B-cell lymphoma. Adv Anat Pathol. 2013;20:315-326.
11. Kanungo A, Medeiros LJ, Abruzzo LV, et al. Lymphoid neoplasms associated with concurrent t(14;18) and 8q24/c-MYC translocation generally have a poor prognosis. Mod Pathol. 2006;19:25-33.
12. Pillai RK, Sathanoori M, Van Oss SB, et al. Double-hit B-cell lymphomas with BCL6 and MYC translocations are aggressive, frequently extranodal lymphomas distinct from BCL2 double-hit B-cell lymphomas. Am J Surg Pathol. 2013;37:323-332.
13. Aukema SM, Kreuz M, Kohler CW, et al. Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma. Haematologica. 2014; 99:726-735.
14. Tomita N, Tokunaka M, Nakamura N, et al. Clinicopathological features of lymphoma/leukemia patients carrying both BCL2 and MYC translocations. Haematologica. 2009;94:935-943.
15. Motllo C, Grau J, Junca J, et al. Translocation (3;8)(q27;q24) in two cases of triple hit lymphoma. Cancer Genet Cytogenet. 2010;203: 328-332.
16. Bacher U, Haferlach T, Alpermann T, et al. Several lymphomaspecific genetic events in parallel can be found in mature B-cell neoplasms. Genes Chromosomes Cancer. 2011;50:43-50.
17. Xu X, Zhang L, Wang Y, et al. Double-hit and triple-hit lymphomas arising from follicular lymphoma following acquisition of MYC: report of two cases and literature review. Int J Clin Exp Pathol. 2013;6:788-794.
18. Le Gouill S, Talmant P, Touzeau C, et al. The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement. Haematologica. 2007;92: 1335-1342.
19. Stamatoullas A, Buchonnet G, Lepretre S, et al. De novo acute B cell leukemia/lymphoma with t(14;18). Leukemia. 2000;14: 1960-1966.
20. D'Achille P, Seymour JF, Campbell LJ. Translocation (14;18)(q32;q21) in acute lymphoblastic leukemia: a study of 12 cases and review of the literature. Cancer Genet Cytogenet. 2006; 171:52-56.
21. Au WY, Gascoyne RD, Viswanatha DS, et al. Concurrent chromosomal alterations at 3q27, 8q24 and 18q21 in B-cell lymphomas. Br J Haematol. 1999;105:437-440.
22. So CC, Yung KH, Chu ML, et al. Diagnostic challenges in a case of B cell lymphoma unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Int J Hematol. 2013;98:478-482.
23. Magro CM, Wang X, Subramaniyam S, et al. Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination. Am J Dermatopathol. 2014;36:303-310.
24. Benz R, Tchinda J. Double hit, triple hit-look for it. Blood. 2013; 121:2383.
25. Chen D, Ketterling RP. A leukemic presentation of a "triple-hit" lymphoma. Blood. 2014;123:1126.
26. Pemmaraju N, Gill J, Gupta S, et al. Triple-hit lymphoma. Proc (Bayl Univ Med Cent). 2014;27:125-127.
27. Nakayama S, Yokote T, Iwaki K, et al. Multiple cytokine- and multiple cytokine receptor-expressing triple-hit B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma. Pathology. 2013;45: 508-510.
28. Jabbar KJ, Medeiros LJ, Wang SA, et al. Flow cytometric immunophenotypic analysis of systemic mastocytosis involving bone marrow. Arch Pathol Lab Med. 2014;138:1210-1214.
29. Vega F, Chang CC, Medeiros LJ, et al. Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. Mod Pathol. 2005;18:806-815.
30. Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004; 103:275-282.
31. Muris JJ, Meijer CJ, Vos W, et al. Immunohistochemical profiling based on Bcl-2, CD10 and MUM1 expression improves risk stratification in patients with primary nodal diffuse large B cell lymphoma. J Pathol. 2006;208:714-723.
32. Visco C, Li Y, Xu-Monette ZY, et al. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Leukemia. 2012;26:2103-2113.
33. Nyman H, Jerkeman M, Karjalainen-Lindsberg ML, et al. Prognostic impact of activated B-cell focused classification in diffuse large B-cell lymphoma patients treated with R-CHOP. Mod Pathol. 2009;22:1094-1101.
34. Hu H, Wang B, Borde M, et al. Foxp1 is an essential transcriptional regulator of B cell development. Nature Immunol. 2006;7: 819-826.
35. Hoeller S, Schneider A, Haralambieva E, et al. FOXP1 protein overexpression is associated with inferior outcome in nodal diffuse large B-cell lymphomas with non-germinal centre phenotype, independent of gains and structural aberrations at 3p14.1. Histopathology. 2010;57:73-80.
36. Barrans SL, Fenton JA, Banham A, et al. Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome. Blood. 2004;104: 2933-2935.
37. Banham AH, Connors JM, Brown PJ, et al. Expression of the FOXP1 transcription factor is strongly associated with inferior survival in patients with diffuse large B-cell lymphoma. Clin Cancer Res. 2005;11:1065-1072.
38. Sagaert X, de Paepe P, Libbrecht L, et al. Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. J Clin Oncol. 2006;24:2490-2497.
39. Craig VJ, Cogliatti SB, Imig J, et al. Myc-mediated repression of microRNA-34a promotes high-grade transformation of B-cell lymphoma by dysregulation of FoxP1. Blood. 2011;117:6227-6236.
40. van Keimpema M, Gruneberg LJ, Mokry M, et al. FOXP1 directly represses transcription of pro-apoptotic genes and cooperates with NF-kappaB to promote survival of human B-cells. Blood. 2014;124:3431-3440.
41. Glitza IC, Lu G, Shah R, et al. Chromosome 8q24.1/c-MYC abnormality: a marker for high-risk myeloma. Leuk Lymphoma. 2014;1-6.