CD5-positive B-cell acute lymphoblastic leukemia/lymphoma with MEF2D::BCL9 mimicking aggressive mature B-cell lymphoma: a case report of a newly described entity and potential diagnostic pitfall.

Here, we present a challenging diagnostic case of a B-cell acute lymphoblastic leukemia (B-ALL) presenting as a rare extramedullary and extranodal presentation without bone marrow or peripheral blood involvement, also classified as B-cell lymphoblastic lymphoma (B-LBL). Our case demonstrated a lack of expression for typical immature B-ALL markers CD34, TdT, and CD99 and instead showed positive expression for CD5, SOX11, BCL-6, and c-MYC, which are markers more often seen in mature aggressive B-cell lymphomas. A distinction between B-ALL and the aggressive B-cell lymphomas, high-grade B-cell Lymphoma (HGBL), and mantle cell lymphoma (MCL), which can show a blastoid morphology, could not be made based on our immunohistochemistry (IHC), flow cytometry, and FISH studies. The diagnosis of B-ALL in our case eventually required extensive molecular methods, with next generation sequencing (NGS)-based DNA and RNA fusion genomic profiling studies to achieve an accurate diagnosis and classification. The molecular studies identified a positive MEF2D::BCL9 gene fusion, a recently described rare abnormality in high-risk B-ALL. These rare B-ALL cases with a MEF2D::BCL9 gene fusion have been categorized as specific B-ALL subtypes in the newest World Health Organization (WHO) 5th edition classification of hematolymphoid tumors and lymphoid neoplasms. We want to share the challenges we faced in making this new diagnosis and the results of our studies, since complete expression profiles for this rare entity have not yet been extensively described.