CD5-positive high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements

A 48-year-old man with an unknown medical history presented with fatigue and weakness. His complete blood count revealed a white blood cell count of 221 × 10⁹/L, hemoglobin 8.8 g/dL, and platelet count 110 × 10⁹/L. Peripheral blood smears showed numerous large malignant cells with blastoid features and prominent nucleoli (panel A; Wright-Giemsa stain, 100× lens objective). Flow cytometry of peripheral blood specimen identified 77% abnormal B cells with the following immunophenotype: CD3⁻/CD5⁺/CD10⁻/CD19⁺/CD20⁺/CD22⁺/CD34⁻/CD38⁺/CD45⁺/CD79a⁺/TdT⁻/MPO⁻/kappa⁺/lambda⁻ (panel B). Bone marrow biopsy demonstrated similar malignant cells, involving most of the 90% cellularity (panel C; hematoxylin and eosin stain, 40× lens objective), with positive staining for BCL2, BCL6, CD5, MUM-1, and MYC, and negative staining for CD3, cyclin D1, SOX11, and EBER ISH. Cytogenetic analysis revealed a complex karyotype: 48,XY,+X,−4,t(8;14)(q24.2;q32),+12, t(14;18)(q32;q21.3),−19,del(20)(q11.2q13.3),+2∼4mar[cp4]/46,XY[1]. Optical genome mapping confirmed a complex genome, including MYC, BCL6, and BCL2 fusions with the IGH gene (panel D). Next-generation sequencing identified multiple mutations, including NFKB2 (c.1719_1754del, p.E576_P587del, VAF: 19%), ARID1A (c.1413C>G, p.Y471, VAF: 35%), BCL2 (multiple), IKZF3 (c.485T>G, p.L162R, VAF: 10%), and MYC (multiple).

These findings support a diagnosis of CD5-positive, high-grade B-cell lymphoma with MYC, BCL2, and BCL6 rearrangements. The presence of NFKB2, ARID1A, IKZF3, and BCL2 mutations suggests that high-grade B-cell lymphoma can rarely present as an ABC subtype, driven by mutations affecting the NF-κB pathway, chromatin remodeling, and apoptosis resistance.

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