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Diagnostic utility of lymphocyte enhancer factor 1 in aggressive B-cell lymphoma with MYC rearrangement
Xin Wang1, Maria Faraz1, Anne Chen1
1Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA.
Insights
Lymphocyte enhancer factor 1 (LEF1) expression patterns can help diagnose aggressive B-cell lymphomas (BCL) with MYC rearrangement. Strong LEF1 staining suggests EBV-negative Burkitt lymphoma, while negative staining indicates DLBCL-MYC-R/DH/TH.
Area of Science:
- Hematology
- Oncology
- Molecular Pathology
Background:
- Aggressive B-cell lymphomas (BCL) with MYC gene rearrangement (MYC-R) present diagnostic challenges.
- Accurate subtyping is crucial for appropriate treatment and prognosis.
Purpose of the Study:
- To evaluate the diagnostic utility of lymphocyte enhancer factor 1 (LEF1) expression in aggressive BCL with MYC-R.
- To differentiate between subtypes of aggressive BCL based on LEF1 staining patterns.
Main Methods:
- Studied 67 BCL cases including Burkitt lymphoma (BL), DLBCL-NOS with MYC-R, and double-hit/triple-hit (DH/TH) lymphomas.
- Used immunohistochemical stains to assess LEF1 expression in three patterns: negative (pattern 0), weak/heterogeneous (pattern 1), and moderate/strong uniform (pattern 2).
- Included DLBCL-NOS without MYC-R as a control group.
Main Results:
- Pattern 1 (weak/heterogeneous LEF1) was observed in all studied BCLs with MYC-R and in DLBCL without MYC-R.
- Pattern 2 (strong/uniform LEF1) was characteristic (86% PPV) for Epstein-Barr virus (EBV)-negative BL.
- Pattern 0 (negative LEF1) was prevalent in DLBCL-MYC-R/DH/TH (76%) and EBV-positive BL (7/8 cases).
Conclusions:
- LEF1 expression patterns offer diagnostic value in aggressive BCL with MYC-R.
- Strong LEF1 staining (pattern 2) is indicative of EBV-negative BL.
- Negative LEF1 staining (pattern 0) suggests DLBCL-MYC-R/DH/TH, aiding differentiation in limited specimens.
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.
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