Sporadic Burkitt Lymphoma Lacking MYC Protein Expression: A Rare Entity With Diagnostic Pitfalls and Dismal Prognosis.

Abstract

The pathognomonic genetic alteration in Burkitt lymphoma (BL) is the immunoglobulin (IG)-MYC translocation, causing intense nuclear MYC expression in almost all cases. Rare cases harbor MYC rearrangements yet lack detectable MYC protein expression. In this study, we report 8 cases of MYC protein-negative sporadic BL (MYC⁻ sBL). These cases accounted for 1.4% (8/574) of all sporadic BL cases. The median age was 10 years (range: 5 to 77 y), with a male-to-female ratio of 3:1. The majority (62.5%, 5/8) presented with advanced-stage disease (III/IV), and 25.0% (2/8) had bone marrow involvement. Morphologically, all cases met the World Health Organization (WHO) diagnostic criteria for BL, characterized by monotonous medium-sized cells with a typical "starry sky" pattern. Immunophenotypically, all cases exhibited a germinal center B-cell phenotype with nearly 100% Ki-67 positivity. Notably, MUM1 was positive in 50.0% (4/8) of cases, while Epstein-Barr virus (EBV)-encoded RNA (EBER) was positive in only 25.0% (2/8). Despite fluorescence in situ hybridization (FISH)-confirmed MYC rearrangement and the absence of BCL2 or BCL6 abnormalities, MYC protein expression was undetectable. Furthermore, patients with MYC⁻ sBL exhibited significantly inferior overall survival (OS) compared with those with MYC protein-positive sporadic BL (MYC+ sBL) (P<0.0001, HR=404.1). These findings confirm that MYC⁻ sBL is a rare but distinct clinicopathological entity associated with poor clinical outcomes, despite lacking unique histologic features. The molecular mechanisms underlying the absence of MYC protein expression remain to be investigated.