Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade B-cell lymphoma found in Korea; it manifests with a variety of cellular morphologies and a high proliferation index. It is difficult to differentiate between DLBCL and Burkitt lymphoma (BL) based on immunohistochemistry, histology, and Epstein-Barr virus infection status owing to the overlap in findings. In this study, we performed comparative morphometric analysis to understand the proportional difference in Ki-67 staining between DLBCL and BL. We analyzed Ki-67-stained slides of 103 DLBCLs and 29 BLs that were pathologically confirmed using a three-tier classification system (negative, 1+, 2+, and 3+) to compare Ki-67 expression between BL and activated B-cell and germinal center B-cell subtypes of DLBCL and DLBCL with high proliferation indices (>90% of 2+ and 3+ cells). Patients with DLBCL were older than those with BL (62.1 versus 51.0 years). The number and proportion of negative cells (passenger and true negative cells) were significantly lower in BLs than those in DLBCLs (337.4, 5.9% versus 690.3, 12.4%). The number and proportion of 3+ cells were significantly higher in BLs than those in DLBCLs (5213.6, 96.3% versus 3132.4, 62.0%). BLs and DLBCLs with a high proliferation index showed similar results as those between BLs and overall DLBCLs. We were able to differentiate BLs and DLBCLs with 98.1% sensitivity and 100.0% specificity using an optimal cut-off of 97.9% of 2+/3+ Ki-67-positive cells. Thus, the Ki-67 labeling index may be a good differential biomarker for DLBCLs and BLs.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade B-cell lymphoma (HGBL) comprising morphologically, biologically, and clinically heterogeneous subgroups with various cellular morphologies, molecular characteristics, and a high proliferation index [1,2,3,4,5,6,7,8]
Some types of DLBCLs morphologically resemble features of Burkitt lymphoma (BL) and have a high proliferative index of >95%. The majority of these cases possess translocations of MYC, BCL2, and/or BCL6; these are called “double hit” or “triple hit” lymphomas and sometimes exhibit a blastoid appearance [1,3,10,11,12,13]. These cases were referred to in the 2008 World Health Organization classification as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, and were divided into two categories based on genetic abnormalities in the 2018 classification: HGBL with double/triple hit mutations (HGBL, DH/TH), and HGBL, not otherwise specified (Supplementary Figure S1) [10,14,15]
DLBCLs with a high proliferation index showed an average of 94.3% of 2+/3+ cells among positive cells similar to that of BLs (99.3%), the number and proportion of 3+ cells were higher in BLs than those in DLBCLs (96.3% versus 76.9%, p < 0.001) and those of negative, 1+, and 2+ cells were higher in DLBCLs than those in BLs (11.7%, 5.7%, 17.4% versus 5.9%, 0.7%, and 3.0% for negative, 1+, and 2+ cells, respectively; p = 0.011/p < 0.001)
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common high-grade B-cell lymphoma (HGBL) comprising morphologically, biologically, and clinically heterogeneous subgroups with various cellular morphologies, molecular characteristics, and a high proliferation index [1,2,3,4,5,6,7,8]. The majority of these cases possess translocations of MYC, BCL2, and/or BCL6; these are called “double hit” or “triple hit” lymphomas and sometimes exhibit a blastoid appearance [1,3,10,11,12,13] These cases were referred to in the 2008 World Health Organization classification as B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, and were divided into two categories based on genetic abnormalities in the 2018 classification: HGBL with double/triple hit mutations (HGBL, DH/TH), and HGBL, not otherwise specified (Supplementary Figure S1) [10,14,15]. We designed a comparative morphometric analysis and evaluated the cut-off value for the Ki-67 index in differentiating DLBCLs and BLs
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