Lymphoid neoplasms associated with concurrent t(14;18) and 8q24/c-MYC translocation generally have a poor prognosis

Abstract

We identified 14 B-cell neoplasms with concurrent t(14;18) and chromosome 8q24 or c-MYC translocations shown by conventional cytogenetics or fluorescence in situ hybridization analysis. All cases assessed by conventional cytogenetics had a complex karyotype. There were 10 men and four women, with a median age of 55 years (range, 29-72). None of these patients had a history of follicular lymphoma. The biopsy specimens were obtained from bone marrow, lymph node, and extranodal sites. Morphologically, nine neoplasms had features of Burkitt or atypical Burkitt lymphoma/leukemia and three were diffuse large B-cell lymphoma with high-grade cytologic features. The remaining two cases were plasmablastic myeloma and low-grade B-cell lymphoma, respectively. All cases expressed BCL-2. The proliferation index assessed by using Ki-67 (MIB1) was 5% in the low-grade B-cell lymphoma, 80% in the plasmablastic myeloma, 90-95% in three cases of diffuse large B-cell lymphoma, and ranged from 90 to 499% in most Burkitt and atypical Burkitt neoplasms. The patient with low-grade B-cell lymphoma was treated with rituximab. All other patients received intensive combination chemotherapy. Two of these patients underwent bone marrow transplantation, and one patient received radiation therapy in addition to transplantation. The median follow-up period was 9 months (range, 3-81). In all, 10 patients died with a median survival of 9 months (range, 3-81). We conclude that most B-cell lymphomas with concurrent t(14;18) and 8q24/c-MYC translocations fall within the morphologic spectrum of diffuse large B-cell and Burkitt lymphoma. These neoplasms are high-grade and are associated with a poor prognosis. However, this combination of molecular abnormalities can also rarely occur in other neoplasms, such as the cases of low-grade B-cell lymphoma and plasmablastic myeloma in this study.

Simple karyotype and bcl-6 expression predict a diagnosis of Burkitt lymphoma and better survival in IG-MYC rearranged high-grade B-cell lymphomas

“…The latter likely represent atypical Burkitt lymphoma classified by 2001 WHO classification system, and 'double-hit' lymphomas. 4,6,24 It is interesting to note that all three cases of MYC-rearranged diffuse large B-cell lymphoma in this study were treated with R-CHOP (rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, prednisone), which may not be as effective in these patients compared with those without MYC-rearrangement. 13,25 In multivariate analysis, only bcl-6 expression remained an independent predictor of better overall survival.…”

“…All of these so-called 'double-hit' lymphoma cases were older adults (440 years old) and accounted for 44% of those in patients over 40. Given the unfavorable clinical outcome of these lymphomas, 6,24 conventional and/or molecular cytogenetic testing for BCL-2 and BCL-6 rearrangements in MYC-rearranged lymphomas may be diagnostically and clinically helpful, especially in those patients older than 40.…”

“…Nonetheless, within the subgroup of bcl-6 positive patients, survival could be further stratified by karyotypic complexity, as patients with positive bcl-6 and simple karyotype had the best clinical outcomes. Although unclassifiable and MYC-rearranged diffuse large B-cell lymphomas may benefit from intensified chemotherapeutic regimens used for BL, 6,25,29 future prospective studies in a large number of patients are needed to investigate the optimal therapy for these aggressive lymphomas.…”

“…1 However, these rearrangements are not entirely specific as they are also seen occasionally in other high-grade B-cell lymphomas, [2][3][4][5][6][7] including those in the newly proposed entity 'B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma' (hereafter referred to as unclassifiable B-cell lymphoma) in the 2008 World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissue. 8 Furthermore, MYC rearrangements are often accompanied by varying numbers of additional cytogenetic abnormalities.…”

B-cell lymphomas with concurrent MYC and BCL2 abnormalities other than translocations behave similarly to MYC/BCL2 double-hit lymphomas

“…[4][5][6][7][8][9][10][11][12][13][14] Numerous case series of MYC/BCL2 double-hit lymphoma are reported in the literature. [15][16][17][18][19][20][21][22][23][24] MYC/ BCL2 DHLs represent B10% of all lymphomas that otherwise resemble diffuse large B-cell lymphoma (DLBCL). 10 Although different studies have focused on different aspects or details of double-hit lymphoma, all studies suggest that patients with these lymphomas commonly have an aggressive clinical course characterized by advanced stage disease, extranodal involvement, and high serum lactate dehydrogenase levels.…”