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

Li, Shaoying; Seegmiller, Adam C.; Lin, Pei; Wang, Xuan J.; Miranda, Roberto N.; Bhagavathi, Sharathkumar; Medeiros, L. Jeffrey

doi:10.1038/modpathol.2014.95

Cited by 78 publications

(70 citation statements)

References 37 publications

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“…Furthermore, genomic and gene expression profiling have landscaped DLBCLs in adults as a heterogenous entity, while in children, they are predominantly homogenous, with a germinal centre immunophenotype and a lack of t (14;18). HGBL, with MYC and BCL2 or BCL6 rearrangements are reported rarely in young adults, adolescents and children [3][4][5]. Two children, aged 9 and 11 years, with HGBL with MYC/BCL6 aberrations are documented but HGBL with MYC and BCL2 translocations, are unreported in children, to date [5,[14][15][16][17].…”

Section: • Dual Expression But Not Dual Rearrangements Of Myc and Bcl2mentioning

confidence: 99%

“…The aggressive clinical course of DHL is typified by advanced disease stage with a high-intermediate or high International Prognostic Index, extranodal spread, including frequent bone marrow and CNS involvement and elevated serum lactate dehydrogenase levels [3,4,10]. Some studies have identified heightened gastrointestinal tract involvement [3,10,11].…”

Section: • Dual Expression But Not Dual Rearrangements Of Myc and Bcl2mentioning

confidence: 99%

“…Originally regarded as an uncommon malignancy that accounted for <1% of all lymphomas, more recent systematic investigations of MYC and BCL2 abnormalities have demonstrated that DHL/HGBCL with MYC and BCL2 translocations is an underestimated malignancy. Currently DHL/HGBCL with MYC and BCL2 translocations accounts for approximately 10% of all lymphomas with the phenotypic and immunophenotypic features of diffuse large B-cell lymphoma (DLBCL) [3,4]. Demographically, DHL/HGBCL with MYC and BCL2 translocations occurs in older patients, with a predominant age range of 51 to 65 years and a slight male bias [1,3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Currently DHL/HGBCL with MYC and BCL2 translocations accounts for approximately 10% of all lymphomas with the phenotypic and immunophenotypic features of diffuse large B-cell lymphoma (DLBCL) [3,4]. Demographically, DHL/HGBCL with MYC and BCL2 translocations occurs in older patients, with a predominant age range of 51 to 65 years and a slight male bias [1,3,4]. They are rare in children, adolescents and young adults [5].…”

Section: Introductionmentioning

confidence: 99%

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AIDS-Associated Pediatric High Grade B-cell Lymphoma with MYC and BCL2 Translocations

Mz¹,

Ramdial²,

Jb³

et al. 2017

J AIDS Clin Res

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Abstract"Double hit" lymphomas (DHLs) are now included as a distinct entity in the 2016 revised World Health Classification of lymphoid neoplasms under the rubric "High-grade B-cell lymphoma (HGBCL), with MYC and BCL2 and/or BCL6 translocations". While DHL/HGBCL with MYC and BCL2 translocations accounts for approximately 10% of all lymphomas with the phenotypic and immunophenotypic features of diffuse large B-cell lymphoma (DLBCL), to date, the entity is unreported in children <12 years and in patients with AIDS. In reporting a DHL/HGBCL with MYC and BCL2 translocations in a 10 year old boy, we contextualize, for the first time, its occurrence and clinicopathological profile in the context of pediatric HIV infection and AIDS. In so doing, the defining features of DHL/ HGBCL with MYC and BCL2 translocations in the updated 2016 WHO classification are discussed. In addition, the clinicopathological features and therapeutic approaches in children and adults and related challenges thereof, are highlighted. Finally, the spectrum of AIDS-associated lymphomas in children and adults are tabulated and the associated diagnostic and therapeutic challenges are addressed briefly.Citation: Msimang MZ, Ramdial PK, Kuppusamy JB, Nargan K, Sheik-Gafoor MH (2017) anterior colonic resection with colo-anal anastomosis and covering ileostomy was successfully undertaken, but the patient developed sepsis and required a relaparotomy for resection of necrotic colonic tissue. On recovery he received radiotherapy and further chemotherapy, but responded poorly and demised from multi-organ failure. Pathological featuresGross features: The lower anterior resection specimen measured 38 × 8 cm ( Figure 1A) and contained a 14 × 9 × 7 cm exophytic, creamwhite, fleshy tumor ( Figure 1B) with hemorrhagic foci, 12 cm and 3 cm from the proximal and distal excision margins, respectively. The proximal and circumferential resection margins were tumor-free. The microscopic findings confirmed an ulcerative, invasive malignancy with transmural involvement and a diffusely infiltrative pattern ( Figure 1C). The pleomorphic tumor cells were large with scant eosinophilic cytoplasm, indistinct cell borders and large, vesicular nuclei with distinctive nuclear membranes and prominent nucleoli ( Figure 1D). Brisk mitotic activity was evident. Immunohistochemically, there was bright and diffuse CD45 (Figure 2A), CD20 ( Figure 2B), BCL2 ( Figure 2C), BCL6 ( Figure 2D) and CD10 ( Figure 2E) immunopositivity. In addition, there was patchy MUM-1 ( Figure 3A) and approximately 60%, variable nuclear and cytoplasmic C-MYC immunopositivity ( Figure 3B) and a Ki-67 proliferation index of >90% ( Figure 3C). T-lymphocyte and terminal deoxynucleotidyl transferase immunomarkers were negative. Epstein Barr virus (EBV)-encoded small RNA (EBER) positivity ( Figure 3D) was confirmed on chromogen in-situ hybridization investigation.

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Section: • Dual Expression But Not Dual Rearrangements Of Myc and Bcl2mentioning

confidence: 99%

Section: • Dual Expression But Not Dual Rearrangements Of Myc and Bcl2mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

AIDS-Associated Pediatric High Grade B-cell Lymphoma with MYC and BCL2 Translocations

Mz¹,

Ramdial²,

Jb³

et al. 2017

J AIDS Clin Res

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show abstract

“…88,113,114,117,[126][127][128] To further confound the issue of definition of DH, one study has suggested that so-called "atypical DH lymphomas" (those with single translocations of MYC or BCL2 with copy number alterations of the other gene, or copy number alterations of both genes) have similar poor outcome to conventional DH lymphomas. 87,129,130 In addition to potential clinical importance associated with MYC partner genes, there may be histologic associations as well. A non-IG partner gene was associated with DLBCL morphology.…”

Section: B-cell Lymphomamentioning

confidence: 99%

Update in large cell lymphoma: understanding the pathology report

Hsi

2015

Hematology

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The diffuse aggressive large B-cell lymphomas are a heterogeneous group of B-cell malignancies. Although many are readily recognized due to characteristic clinical and pathologic features, several problematic areas still exist in diagnosis of these lymphomas due to a variety of reasons that include imprecise or difficult-to-apply diagnostic criteria, gaps in our understanding of lymphoma biology, and limitations in technologies available in the clinical laboratory compared to the research laboratory. This may result in some degree of confusion in the pathology report, particularly if the issues are not clearly explained, leading to frustration or misinterpretation on the part of the reader. In this review, I will discuss the pathologic features of a subset of the WHO 2008 classification diffuse aggressive large B-cell lymphomas, focusing on areas in which difficulties exist in diagnosis and/or biomarker marker assessment. A deeper understanding of the issues and areas of uncertainty due to limitations in our knowledge about the biology of these diseases should lead to better communication between pathologists and clinicians.

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Alternative genetic alterations of MYC, BCL2, and/or BCL6 in high‐grade B‐cell lymphoma (HGBL) and diffuse large B‐cell lymphoma (DLBCL): Can we identify different prognostic subgroups?

Blomme,

De Paepe,

Devos

et al. 2023

Genes Chromosomes & Cancer

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High‐grade B‐cell lymphoma (HGBL)/diffuse large B‐cell lymphoma (DLBCL) with rearrangements (R) in MYC and BCL2 and/or BCL6 are correlated with poor prognosis. Little is known about the impact of other genetic alterations (gain (G) or amplification (A)) of these genes. The aim of the study was to investigate whether we can identify new prognostic subgroups. Fluorescence in situ hybridization (FISH) results from 169 HGBL/DLBCL were retrospectively categorized into: (1) concurrent MYC‐R and BCL2‐R and/or BCL6‐R—samples with MYC‐R and BCL2‐R (+/− BCL6‐R); n = 21, and HGBL/DLBCL with MYC‐R and BCL6‐R; n = 11; (2) concurrent R and G/A in MYC and BCL2 and/or BCL6 called “alternative HGBL/DLBCL”—samples with (n = 16) or without (n = 6) BCL2 involvement; (3) BCL2 and/or BCL6 alterations without MYC involvement (n = 35); (4) concurrent G/A in MYC and BCL2 and/or BCL6 without R (n = 25); and (5) “No alterations” (n = 55). Patients with HGBL/DLBCL‐MYC/BCL2 and “alternative” HGBL/DLBCL (with BCL2 involvement) had significantly worse survival rates compared to the “no alterations” group. G/A of these genes in the absence of rearrangements did not show any prognostic significance. HGBL/DLBCL with MYC‐R and BCL6‐R without BCL2 involvement showed a better survival rate compared to HGBL/DLBCL‐MYC/BCL2. According to immunohistochemistry, “double/triple” expression (DEL/TEL) did not show a significantly worse outcome compared to absent DEL/TEL. This study highlights the continued value of FISH assessment of MYC, BCL2, and BCL6 in the initial evaluation of HGBL/DLBCL with different survival rates between several genetic subgroups.

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

Cited by 78 publications

References 37 publications

AIDS-Associated Pediatric High Grade B-cell Lymphoma with MYC and BCL2 Translocations

AIDS-Associated Pediatric High Grade B-cell Lymphoma with MYC and BCL2 Translocations

Update in large cell lymphoma: understanding the pathology report

Alternative genetic alterations of MYC, BCL2, and/or BCL6 in high‐grade B‐cell lymphoma (HGBL) and diffuse large B‐cell lymphoma (DLBCL): Can we identify different prognostic subgroups?

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