Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of lymphomas that accounts for 30 %–40 % of all non-Hodgkin lymphoma (NHL) cases. It is characterized by different clinicopathological features, immunophenotypes, morphologic variants, and genetic alterations [[1], [2], [3]]. According to gene expression signatures, DLBCL can be classified into two subtypes: germinal center B-cell-like (GCB-DLBCL) and activated B-cell-like (ABC-DLBCL). These subtypes are associated with distinct biological and clinical features. Currently, the front-line chemoimmunotherapy for DLBCL is the addition of the anti-CD20 monoclonal antibody rituximab® to the standard CHOP regimen, which consists of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). This treatment method contributes to cure rates of 60–70 % [[4], [5], [6]]. However, approximately one-third of patients with DLBCL experience relapse or become refractory.

To improve risk stratification and ultimately prognostication, some subgroups of DLBCL with poor outcomes after R-CHOP treatment have been proposed. These include double-expressor lymphoma (DEL) and double-hit lymphoma (DHL). DEL is characterized by the co-expression of C-Myc and Bcl2 proteins, as determined by immunohistochemical (IHC) analysis. This lymphoma subtype comprises approximately 14 %–44 % of all DLBCL cases [1,2,[7], [8], [9], [10]] and is associated with a poor prognosis, with a five-year overall survival (OS) rate ranging from 30 % to 50 % after R-CHOP chemotherapy when compared to other DLBCL cases [[11], [12], [13]]. DEL cases are usually categorized using a cutoff of ≥40 % and ≥50 % for C-Myc and Bcl2 expression, respectively. However, recent studies have suggested that a cutoff of ≥70 % for C-Myc expression is more optimal than the ≥40 % cutoff, with higher reproducibility and predictive value [14,15]. Using the ≥70 % cutoff for C-Myc high expression (C-Mychigh), DEL cases can be further subdivided into DEL with high C-Myc expression (DEL-C-Mychigh) and DEL with intermediate (range from 40 % to 69 %) C-Myc expression (DEL-C-Mycinter) [[14], [15], [16]]. DHL is defined as a subset of DLBCL harboring Myc rearrangement coincided with other concurrent translocations of either Bcl2 or Bcl6 in the 4th revised edition of the World Health Organization (WHO) classification [17]. However, in the 5th edition of the WHO classification of haematolymphoid tumours (WHO-HAEM5), DHL has been reframed conceptually and redefined as high-grade B-cell lymphoma with Myc and Bcl2 rearrangements (HGBL-Myc/Bcl2) due to variable gene expression profiles and mutational spectra [1]. Patients with HGBCL-Myc/Bcl2 have a poor prognosis, with a five-year OS rate ranging from 15 % to 27 % [11,12,18]. Myc gene rearrangement and C-Myc protein overexpression are also involved in the pathogenesis of lymphomas and are thought to be correlated with a significantly poor prognosis in patients with DLBCL. However, the clinical significance of Myc gene rearrangement and C-Myc protein overexpression in DLBCL is controversial [19].

In this study we aimed to undertake a comparative analysis of the clinicopathologic features observed in patients with DEL and Non-DEL. In addition, we sought to evaluate the prognostic significance of Myc gene rearrangement, as well as the impact of varying cutoffs for C-Myc expression, in cases of C-Myc/Bcl2 double-expressor lymphoma.