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LYMPHOMA

High-grade B-cell lymphoma (HGBL)-NOS is clinicopathologically and genetically more similar to DLBCL/HGBL-DH than DLBCL

Leukemia volume 37, pages 422–432 (2023)Cite this article

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Abstract

High-grade B-cell lymphoma, not otherwise specified (HGBL-NOS) is rare and data focused on these neoplasms is lacking. We studied the clinicopathologic and genetic features of 136 HGBL-NOS patients and compared them to patients with DLBCL/HGBL-DH (n = 224, defined by 5th Edition WHO) and DLBCL (n = 217). HGBL-NOS patients had clinical features similar to DLBCL/HGBL-DH patients. MYC rearrangement (MYC-R) was present in 43% of HGBL-NOS. With induction regimen similar to DLBCL/HGBL-DH patients, HGBL-NOS patients had a median overall survival (OS) of 28.9 months, similar to DLBCL/HGBL-DH (p = 0.48) but inferior to DLBCL patients (p = 0.03). R-EPOCH induction was associated with improved OS compared with R-CHOP. MYC-R, history of lymphoma, and high IPI were independent adverse prognostic factors in HGBL-NOS patients. Whole transcriptome profiling performed on a subset of HGBL-NOS cases showed a profile more similar to DLBCL/HGBL-DH than to DLBCL; 53% of HGBL-NOS had a DH-like signature (DH-like-Sig) and were enriched for MYC-R. DH-like-Sig+ HGBL-NOS patients had a poorer OS than DH-like-Sig-negative patients (p = 0.04). In conclusion, HGBL-NOS has clinicopathologic features and a gene expression profile more similar to DLBCL/HGBL-DH than to DLBCL. Cases of HGBL-NOS frequently carry MYC-R and have a DH-like-Sig+. R-EPOCH induction in HGBL-NOS appears associated with improved OS compared with standard R-CHOP.

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Fig. 1: The study case selection process.
Fig. 2: Representative case of HGBL-NOS.
Fig. 3: Gene rearrangement frequency.
Fig. 4: Overall survival.
Fig. 5: Transcriptome profiling showed differentially expressed genes and pathways in HGBL-NOS.
Fig. 6: Double hit gene signature defined by the top 30 significantly differentially expressed genes between DLBCL/HGBL-DH and DLBCL-GCB (left).
Fig. 7: A double hit gene signature defined by 38 genes from a previously reported DH signature [15] is included and significantly differentially expressed between DLBCL/HGBL-DH (D/THL) and DLBCL-GCB in the current panel (left).

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Data availability

The datasets of the current study are available from the corresponding author on reasonable request.

Change history

  • 23 January 2023

    The name L. Jeffrey Medeiros has been tagged correctly.

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Acknowledgements

The study was partially supported by Faculty Startup Fund (SL) and Research Grant (LQ and SL) from the Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center.

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  1. Department of Hematopathology, UT MD Anderson Cancer Center, Houston, TX, United States

    Shaoying Li, Lianqun Qiu, Jie Xu, Pei Lin, Chi Young Ok, Guilin Tang, Timothy J. McDonnell, M. James You, Mahsa Khanlari, Roberto N. Miranda & L. Jeffrey Medeiros

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Contributions

SL designed the study, collected data, analyzed data, and wrote the paper; LQ collected data, analyzed data, and wrote the paper; JX, PL, CYO, GT, TJM, MJY, MK, and RNM contributed data and edited the paper; LJM contributed data, analyzed data and wrote the paper. All authors edited and approved the final version of the paper.

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Correspondence to Shaoying Li.

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Li, S., Qiu, L., Xu, J. et al. High-grade B-cell lymphoma (HGBL)-NOS is clinicopathologically and genetically more similar to DLBCL/HGBL-DH than DLBCL. Leukemia 37, 422–432 (2023). https://doi.org/10.1038/s41375-022-01778-9

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