Diagnostic utility of lymphocyte enhancer factor 1 in aggressive B-cell lymphoma with MYC rearrangement

Objectives We sought to investigate the diagnostic value of lymphocyte enhancer factor 1 (LEF1) expression in aggressive B-cell lymphomas (BCL) with MYC gene rearrangement (MYC-R). Methods Sixty-seven cases of BCL were studied and included Burkitt lymphoma (BL) (23 cases); diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) with MYC-R (13 cases); and DLBCL/high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (double-hit [DH] or triple-hit [TH], 17 cases). Random DLBCL-NOS (14 cases) without MYC-R was recruited as a control group. By immunohistochemical stains, 3 patterns of LEF1 staining were recorded as pattern 0 (negative), pattern 1 (weak and heterogeneous staining, <80%), and pattern 2 (moderate/strong and uniform staining, ≥80%). Results Pattern 1 can be seen in all BCLs with MYC-R included in this study and more commonly seen in DLBCL without MYC-R (8/14 cases). Pattern 2 is characteristic (positive predictive value = 86%) for Epstein-Barr virus (EBV)-negative BL, while pattern 0 was seen in 22 (76%) of 29 cases of DLBCL-MYC-R/DH/TH (P <. 001). Seven of 8 EBV-positive BL cases showed pattern 0, which was completely opposite to the common pattern 2 in EBV-negative BL (12/15 cases). Pattern 2 was not detected in all DH/TH cases. Conclusions Weak and heterogeneous staining of LEF1 can be seen in all the BCLs with and without MYC-R. Strong and uniform staining of LEF1 is highly characteristic of EBV-negative BL among all aggressive BCLs with MYC-R, while the negative staining of LEF1 is mostly suggestive of DLBCL-MYC-R/DH/TH. Lymphocyte enhancer factor 1 provides additional diagnostic value in the differentiation of BL from other aggressive BCLs with MYC-R, especially in a limited specimen. The Author(s) 2025.