Double-Expressor Phenotype (BCL-2/c-MYC Co-expression) of Diffuse Large B-Cell Lymphoma and Its Clinicopathological Correlation

Abstract

Introduction Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, the spectrum of which is increasing with time. The 2016 World Health Organization (WHO) update on hematopoietic tumors recognized a prognostic subgroup of DLBCL called double-expressor DLBCL. Double-expressor DLBCL is defined by the coexpression of c-MYC and BCL-2 by using immunohistochemical (IHC) studies. To our knowledge, very few studies have looked into the pathological features of this newly defined prognostic category of DLBCL; therefore, in this study we evaluated the frequency of the double-expressor phenotype of DLBCL and its association with other clinicopathological parameters. Methods We conducted a retrospective observational study in the Department of Histopathology, Liaquat National Hospital and Medical College, from November 2017 till December 2020. Pathological and clinical records were retrieved from departmental archives. All cases diagnosed as DLBCL were included in the study. More than 40% c-MYC expression in the presence of more than 50% BCL-2 expression was defined as doubleexpressor DLBCL. Results The mean age of the patients was 52.1±16.9 years. The mean Ki67 index was 73.0±17.0%. A total of 48.6% cases were of germinal center B-cell-like (GCB) subtype, and 59.6% cases were nodal. Double-expressor phenotype was noted in 35.8% of DLBCL cases. A significant association of double-expressor phenotype was noted with age, gender, Ki67 index and subtype of DLBCL. Double-expressor DLBCL had a higher mean age than non-double-expressor DLBCL. Similarly, double-expressor DLBCL had a higher Ki67 index. Moreover, double-expressor phenotype was associated with non-GCB subtype DLBCL. Conclusion We found a high proportion of double-expressor phenotype DLBCL in our population. Moreover, doubleexpressor phenotype DLBCL was associated with female gender, higher age, higher Ki67 and non-GCB subtype. The association of double-expressor DLBCL with a high Ki67 index and non-GCB subtype confers a poor prognostic significance of this variant of DLBCL, requiring more aggressive therapy.

Comprehensive analysis of the prognostic implication and immune infiltration of CISD2 in diffuse large B-cell lymphoma

“…On the other part, DLBCL cases with low CISD2Risk value were often obtained a curative treatment ( P < 0.05, Figures 5K ). Several studies revealed the poor prognosis of MYC and BCL2 and/or BCL6 overexpression in DLBCL, known as double-expressor DLBCL ( 21 , 42 ). We also reported the overexpression of MYC and BCL2 in DLBCL cases were possiblely associated with CISD2Risk value, and the double-expressor DLBCL exhibited the high CISD2Risk value ( P < 0.05, Figure 5L ).…”

“…In this study, the MHG DLBCL patients exhibited highest CISD2Risk value which indicated a poor prognosis. MHG DLBCL has distinct molecular features with concurrent activation of MYC and BCL2 ( 21 , 42 ). DLBCL patients with double-expressor that defined by the coexpression of MYC and BCL-2 have a poor prognosis after standard chemoimmunotherapy ( 21 , 42 ).…”

Lymph Node Cytology: Morphology and Beyond

“…The non-GCB subtype (including ABC) are either double negative for CD10 and BCL6 or positive for both BCL6 and MUM1. Positivity for both BCL2 and MYC on IHC classifies it as double expressor DLBCL, seen in about 30% of DLBCL, NOS cases [52]. Positivity is defined as >30% cells expressing the marker.…”

“Double expressor” diffuse large B-cell lymphoma: A case report and literature review

“…Inferior and insufficient response to both standard first line therapy [19,21] and in relapsed/refractory settings [9,22] have been observed. In addition, DEL phenotype is associated significantly with the female gender, older age, higher Ki-67 [23], elevated LDH level [24], poor performance status, higher IPI score and higher incidence of extranodal sites [25]. Treatment intensification in first line settings is a matter of debate and controversy, raising questions and confusion between clinicians.…”