Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival

Johnson, Nathalie A.; Savage, Kerry J.; Ludkovski, Olga; Ben-Neriah, Susana; Woods, Ryan; Steidl, Christian; Dyer, Martin J. S.; Siebert, Reiner; Kuruvilla, John; Klasa, Richard; Connors, Joseph M.; Gascoyne, Randy D.; Horsman, Douglas E.

doi:10.1182/blood-2009-03-212191

Cited by 526 publications

(570 citation statements)

References 41 publications

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“…4,7,24 Three of six unclassifiable cases in this study harbored such dual translocations. The fourth such case was a diffuse large B-cell lymphoma.…”

Section: Discussionmentioning

confidence: 66%

“…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.…”

Section: Discussionmentioning

confidence: 92%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2010

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Rearrangement of MYC with immunoglobulin genes is a hallmark of Burkitt lymphoma. However, this rearrangement is not entirely specific and is often accompanied by varying numbers of additional cytogenetic abnormalities. This study aimed to assess the impact of karyotypic complexity, in correlation with comprehensive immunophenotypic analyses on the diagnosis and clinical outcomes of 34 cases of MYC-IG rearranged lymphomas that included Burkitt lymphoma (twenty-two cases), diffuse large B-cell lymphoma (three cases), unclassifiable B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (six cases), and plasmablastic lymphoma (three cases). Additional cytogenetic abnormalities were observed in 26 of 34 cases (76%), including four cases (12%) that harbored dual translocations involving BCL-2 or BCl-6. Burkitt lymphoma cases had a significantly lower number of additional abnormalities (mean of 1.7), compared with unclassified B-cell lymphoma (3.3), diffuse large B-cell lymphoma (21.7), and plasmablastic lymphoma (6.7). Cases with simple karyotype (p2 additional abnormalities) were more likely to have a diagnosis of Burkitt lymphoma (89 versus 33% in patients with 42 additional abnormalities, Po0.01) and express bcl-6 (95 versus 47%, Po0.01). In addition, Burkitt lymphoma, bcl-6 expression, and simple karyotype were individual predictors of better overall survival. However, in multivariate analyses, only bcl-6 expression remained an independent predictor, although survival could be further stratified by karyotypic complexity in bcl-6( þ ) patients. We conclude that simple karyotype and bcl-6 expression suggest a diagnosis of Burkitt lymphoma and may portend better overall survival. These results may be very useful in the diagnosis and stratification of MYC-IG rearranged high-grade B-cell lymphomas.

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“…4,7,24 Three of six unclassifiable cases in this study harbored such dual translocations. The fourth such case was a diffuse large B-cell lymphoma.…”

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2010

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“…[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.…”

mentioning

confidence: 99%

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

Seegmiller

Lin

et al. 2015

Modern Pathology

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Large B-cell lymphomas with IGH@BCL2 and MYC rearrangement, known as double-hit lymphoma (DHL), are clinically aggressive neoplasms with a poor prognosis. Some large B-cell lymphomas have concurrent abnormalities of MYC and BCL2 other than coexistent translocations. Little is known about patients with these lymphomas designated here as atypical DHL. We studied 40 patients of atypical DHL including 21 men and 19 women, with a median age of 60 years. Nine (23%) patients had a history of B-cell non-Hodgkin lymphoma. There were 30 diffuse large B-cell lymphoma (DLBCL), 7 B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma, and 3 DLBCL with coexistent follicular lymphoma. CD10, BCL2, and MYC were expressed in 28/39 (72%), 33/35 (94%), and 14/20 (70%) cases, respectively. Patients were treated with standard (n ¼ 14) or more aggressive chemotherapy regimens (n ¼ 17). We compared the atypical DHL group with 76 patients with DHLand 35 patients with DLBCL lacking MYC and BCL2 abnormalities. The clinicopathologic features and therapies were similar between patients with atypical and typical DHL. The overall survival of patients with atypical double-hit lymphoma was similar to that of patients with double-hit lymphoma (P ¼ 0.47) and significantly worse than that of patients with DLBCL with normal MYC and BCL2 (P ¼ 0.02). There were some minor differences. Cases of atypical double-hit lymphoma more often have DLBCL morphology (Po0.01), less frequently expressed CD10 (Po0.01), and patients less often had an elevated serum lactate dehydrogenase level (P ¼ 0.01). In aggregate, these results support expanding the category of MYC/ BCL2 DHL to include large B-cell lymphomas with coexistent MYC and BCL2 abnormalities other than concurrent translocations.

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“…3,4 In particular, the so-called 'double-hit' lymphomas that are characterized by MYC rearrangement and a concurrent rearrangement of other B-cell lymphomaassociated genes such as BCL2 or BCL6 are associated with poor response to therapy, aggressive clinical course and dismal prognosis. [5][6][7] These lymphomas are classified as 'B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma' in the current 2008 WHO classification of hematopoietic neoplasms. 8 Evaluation for MYC alterations in diffuse large B-cell lymphoma is typically performed by fluorescence in situ hybridization (FISH).…”

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confidence: 99%

Scoring of MYC protein expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists

et al. 2015

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Recent studies have shown that immunohistochemical evaluation of MYC protein expression in diffuse large B-cell lymphoma is a useful prognostic tool with high concordance rate among pathologists. Concordance in these studies was assessed among few pathologists from one institution by scoring tissue microarrays. In daily practice, MYC evaluation is performed on entire tumor sections by a diverse group of pathologists. In our study, nine hematopathologists from two institutions scored whole-tissue sections of two sets of cases. The training set included 13 cases of diffuse large B-cell lymphoma and 4 cases of Burkitt lymphoma. The validation set included 18 cases of diffuse large B-cell lymphoma and 1 case of Burkitt lymphoma. MYC positivity was defined as Z40% of tumor cells demonstrating nuclear staining similar to prior studies. The mean score for each case was used to determine MYC status with discrepant cases defined as having any score causing a different MYC status designation. Discrepant cases from the training set were characterized by staining heterogeneity, extensive necrosis or crush artifact and had mean scores within 15 percentage points of 40%. Cases from the validation set that demonstrated any of these features were scored twice on two different days. Overall concordance was moderate (Kappa score: 0.68, P-valueo0.001) with no significant change between the two sets (Kappa scores: 0.69 vs 0.67). Thirty-nine percent of cases were discrepant. The findings indicate that a significant number of diffuse large B-cell lymphomas are inherently difficult to score due to staining heterogeneity. The effect of heterogeneity can be under-represented when concordance is measured among few pathologists scoring tissue microarrays. Careful scoring strategy in our study failed to improve concordance. In the absence of specific instructions on how to deal with heterogeneity, caution is advised when evaluating MYC expression in diffuse large B-cell lymphoma.

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Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival

Cited by 526 publications

References 41 publications

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

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

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

Scoring of MYC protein expression in diffuse large B-cell lymphomas: concordance rate among hematopathologists

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