The predictive value of immunohistochemistry for MYC, BCL2, and BCL6 in fluorescence in situ hybridization in aggressive mature B-cell lymphomas and re-evaluation according to the 5th edition of the World Health Organization classification: A single-center 9-year experience

Abstract

Background: Diffuse large B-cell lymphoma/High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations (DLBCL/HGBL-MYC/BCL2) represent a distinct and rare diagnostic category in 5(th) Edition World Health Organization (WHO-HAEM5) classification. Aim and Materials and Methods: In this study, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) were used to evaluate the frequency of MYC, BCL2, and BCL6 expression and translocations in DLBCL, HGBL, and Burkitt lymphoma (BL) over a 9-year period at a single center. Results: In our study of 287 aggressive mature B-cell lymphoma (AMBCL) cases, the WHO-HAEM5 classification identified 55.1% as DLBCL, 21.6% as BL, 15.6% as HGBL-NOS, and 7.7% as DLBCL/HGBL-MYC/BCL2. Following molecular analysis, 1.7% of DLBCL cases were reclassified as HGBL-NOS (MYC/BCL6) and 8% as DLBCL/HGBL-MYC/BCL2. AMBCL cases, 38.5% were reclassified as BL, 10.2% DLBCL/HGBL-MYC/BCL2, and 51.3% as HGBL-NOS. Additionally, 5.9% of BL cases were reclassified as HGBL-NOS. Among 287 cases, MYC and BCL2 overexpression significantly correlated with MYC-FISH and BCL2-FISH (P < 0.001). While BCL6-IHC was observed in all rearranged cases, it showed no significant correlation with BCL6-FISH (P = 0.807). In our study, MYC-IHC demonstrated a sensitivity of 88.66%, a specificity of 31.55%, a positive predictive value (PPV) of 42.79%, and a negative predictive value (NPV) of 82.81% for detecting MYC-FISH. BCL2-IHC showed 100% sensitivity, 47.22% specificity, 38.71% PPV, and 100% NPV for BCL2-FISH. Similarly, BCL6-IHC achieved 100% sensitivity, 10% specificity, 19.40% PPV, and 100% NPV for BCL6-FISH. Conclusions: Our study provides a comprehensive assessment of the spectrum of MYC, BCL2, and BCL6 rearrangements based on FISH and IHC analysis results.