High-grade B-cell lymphoma/leukemia associated with t(14;18) and 8q24/MYC rearrangement: a neoplasm of germinal center immunophenotype with poor prognosis

Aug 28, 2026

The editorial discusses high-grade B-cell lymphoma/leukemia characterized by germinal center immunophenotype and poor prognosis, focusing on the co-occurrence of t(14;18)/BCL-2 and 8q24/MYC rearrangement. It reviews how IG gene translocations define follicular lymphoma and Burkitt’s lymphoma, while noting that these genetic events also appear in subsets of diffuse large B-cell lymphoma and other lymphoid neoplasms. The text summarizes clinicopathologic patterns, including adult predominance, frequent extranodal involvement, and rapidly progressive, refractory disease with survival often under one year, and explains the classification challenges across overlapping morphologic spectra.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages5

Reading Time13 min

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Introduction

Genetic hallmarks and lack of absolute specificity

Rationale and study focus

MYC/BCL2 high-grade B-cell lymphoma/leukemia

Extent of reported cases

Clinicopathologic features and clinical course

Adult demographics and disease presentation

Extranodal involvement and survival

Classification challenges

EDITORIALS & PERSPECTIVES High-grade B-cell lymphoma/leukemia associated with t(14;18) and 8q24/MYC rearrangement: a neoplasm of germinal center immunophenotype with poor prognosis Pei Lin, L. Jeffrey Medeiros Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA 77030. [E-mail: Peilin@mdanderson.org. DOI:](E-mail: Peilin@mdanderson.org. DOI:) 10.3324/haematol.11263 Chromosomal translocations involving the immu noglobulin genes (IG) are common in malignant lymphomas. 1,2 The t(14;18)(q32;q21), which juxtaposes the BCL-2 gene, normally located at 18q21, with the IG heavy-chain locus on 14q32, is the genetic hallmark of follicular lymphoma (FL) . Similarly, the t(8;14)(q24;q32), which juxtaposes the MYC (previously known as c-MYC) gene normally located at 8q24 with the IG heavy-chain locus, as well as the so-called variant translocations, t(2;8)(p12;q24) and t(8;22)(q24;q11), involving the IG light chain genes, are considered genetic hallmarks of Burkitt’s lymphoma (BL). However, these translocations are not specific. The t(14;18)(q32;q21) also occurs in about 25-30% of cases of de novo diffuse large B-cell lymphoma (DLBCL) and has been rarely described in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) . Likewise, the 8q24/MYC rearrangement can be observed in a small subset of DLBCL and up to 40-50% of high grade B-cell lymphomas other than BL.3 Furthermore, the 8q24/MYC rearrangement has been reported in a variety of other lymphoma or leukemia types including CLL/SLL, B-cell prolymphocytic leukemia, mantle cell lymphoma and FL, and usually these tumors are in transformation to higher-grade lymphoma.4-6 It is believed, therefore, that the 8q24/MYC rearrangement may exist either as a primary initiating event in classical BL or as a secondary event (that is, acquired during clonal evolution) in other lymphoma types. Rarely, MYC deregulation can also result from 8q24/MYC rearrangement with non-IG partners, such as the t(8;9)(q24;p13), as described by Le Gouill and colleagues7 as well as others. In adults, the 8q24/MYC rearrangement is most commonly encountered in B-cell lymphomas other than BL. This is because DLBCL, which can carry the 8q24/MYC rearrangement in 10-15% of cases, is a very common type of lymphoma, representing 30-40% of all lymphomas, whereas BL represents only 1-2% of lymphomas in adults. The frequency of the 8q24/MYC rearrangement is even higher when lymphoid neoplasms with morphologic and immunophenotypic features intermediate between BL and DLBCL, or cases of DLBCL with a high proliferation rate (>80%) are selectively analyzed. In this subgroup up to 60% of the neoplasms carry 8q24/MYC rearrangements.3 In a subset of these lymphomas, both 8q24/MYC rearrangement and the t(14;18)/BCL2-IgH can be detected and this is the subgroup that is the focus of the paper by Le Gouill and colleagues in this issue of the journal.7 There are approx- imately 100 such cases reported in the literature; most as single case reports or as small series. From this point forward, we will refer to these neoplasms as MYC/BCL2 (M/B) high-grade B-cell lymphoma/leukemia for convenience. Alternative terms used by others for these neoplasms include dual fusion or double hit lymphomas although we believe these terms are less specific. Table 1 summarizes the results of selected reports presenting four cases or more. The series studied by LeGouill and colleagues is the largest reported to date.7 Subsequent to our previous publication of patients with M/B highgrade B-cell lymphoma/leukemia,8 we have identified 11 additional cases at our institution for a total of 23 cases. The key clinicopathologic features of these cases of M/B high-grade B-cell lymphoma/leukemia are summarized in Table 2. We also have identified this combination of molecular abnormalities in rare cases of plasmablastic myeloma and low-grade B-cell lymphoma, but these cases are not included in th

FAQs

What clinical pattern and prognosis are described for patients with MYC/BCL2 high-grade disease?

Patients are usually adults and often present at an advanced stage with extranodal involvement, especially gastrointestinal tract and central nervous system. The course is described as rapidly progressive, refractory, and associated with short survival typically under one year despite aggressive therapy.

Aug 28, 2026

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