High-grade B-cell lymphoma (HGBCL) is primarily diagnosed and classified through tissue biopsy. However, in a small subset of cases, the disease predominantly affects peripheral blood and/or bone marrow, necessitating thorough examinations of peripheral blood and bone marrow for a definitive diagnosis. This study aims to investigate the clinicopathological characteristics, diagnostic and differential diagnosis of HGBCL identified through bone marrow evaluation.

Methods and Results: A retrospective analysis was conducted on 23 cases of HGBCL with predominant involvement of peripheral blood and/or bone marrow. The cases were classified according to the 2022 WHO Classification as follows: 10 cases of DLBCL/HGBCL-DH (6 cases of DLBCL/HGBCL-MYC/BCL2 and 4 cases of DLBCL/HGBCL-MYC/BCL2/BCL6), 6 cases of HGBCL,NOS-MYC/BCL6, and 7 cases of HGBCL,NOS. The median age of the patients was 66 years (range, 29-82), with a male-to-female ratio of 1.3:1. All patients presented with de novo disease. With the exception of one case that exhibited extensive involvement of the bone marrow and peripheral blood without organomegaly, all other cases displayed varying degrees of lymphadenopathy or hepatosplenomegaly. Hematologic examinations frequently revealed anemia (65%, 15/23) and thrombocytopenia (91%, 21/23), with median hemoglobin level of 96.5 g/L (range, 43-138 g/L) and median platelet count of 39×10⁹/L (range, 5.0-330×10⁹/L). Leukocytosis was common (57%, 13/23) with a median white blood cell count of 11.50×10⁹/L (range, 3.08-327.84×10⁹/L). Bone marrow involvement predominantly exhibited a diffuse pattern in 91% of cases (21/23), with tumor cells comprising 40% to 90% of cellularity. The majority of cases (83%, 19/23) exhibited blastoid/intermediate morphological features, including 10 with characteristic blastoid morphology. Cytoplasmic vacuoles were evident in 11 cases (48%), while DLBCL morphology in 17% (4/23). Immunophenotypic analysis revealed that 87% (20/23) of cases exhibited a GCB phenotype, with all cases negative for CD34 and TdT expression. Notably, six cases exhibited immature immunophenotypic profiles, manifesting as dim or absent CD20 expression and/or lack of surface immunoglobulin light chain expression, making them difficult to distinguish from B- acute lymphoblastic leukemia (B-ALL). Two distinct cases displayed a Burkitt lymphoma (BL)-like phenotype (CD45dimCD38+CD10+BCL6+BCL2-).The remaining fifteen cases presented features distinct from both B-ALL and BL. Cytogenetic analysis identified complex karyotypes in 55% (11/20) of HGBCL cases. FISH detected MYC (91%), BCL2 (48%), and BCL6 (48%) rearrangements in 23 cases. Isolated MYC-R was observed in 22% (5/23) of cases. Among the two MYC-R-negative cases, one underwent 11q FISH testing with negative results. Additionally, screening for leukemia fusion genes was conducted in eight cases, all of which returned negative results. NGS analysis of 9 HGBCL cases revealed frequent mutations in BCL6 (5/6), CCND3 (4/6), and CREBBP (4/6) among DLBCL/HGBCL-DH cases.

Conclusion: HGBCL with predominant peripheral blood and/or bone marrow involvement typically demonstrates extensive infiltration, frequently exhibiting blastoid/intermediate morphological features with relatively common cytoplasmic vacuoles. The primary differential diagnoses include B-ALL and BL. Given the immature immunophenotype in some cases and the absence of specific architectural patterns in bone marrow, comprehensive diagnostic workup—including conventional karyotyping, FISH (MYC/BCL2/BCL6), and screening for leukemia fusion genes—is critical for definitive diagnosis. NGS may provide additional diagnostic value in challenging cases. For accurate diagnosis of intermediate/blastoid B-cell lymphomas in bone marrow, an integrated MICM (Morphology, Immunophenotyping, Cytogenetics, and Molecular genetics) approach is essential.

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2025
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