Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Dec 19;144(25):2593-2603.
doi: 10.1182/blood.2023020911.

Primary large B-cell lymphomas of immune-privileged sites

Affiliations
Review

Primary large B-cell lymphomas of immune-privileged sites

Mark Roschewski et al. Blood. .

Abstract

Diffuse large B-cell lymphoma (DLBCL) encompasses a diverse spectrum of aggressive B-cell lymphomas with remarkable genetic heterogeneity and myriad clinical presentations. Multiplatform genomic analyses of DLBCL have identified oncogenic drivers within genetic subtypes that allow for pathologic subclassification of tumors into discrete entities with shared immunophenotypic, genetic, and clinical features. Robust classification of lymphoid tumors establishes a foundation for precision medicine and enables the identification of novel therapeutic vulnerabilities within biologically homogeneous entities. Most cases of DLBCL involving the central nervous system (CNS), vitreous, and testis exhibit immunophenotypic features suggesting an activated B-cell (ABC) origin. Shared molecular features include frequent comutations of MYD88 (L265P) and CD79B and frequent genetic alterations promoting immune evasion, which are hallmarks of the MCD/C5/MYD88 genetic subtype of DLBCL. Clinically, these lymphomas primarily arise within anatomic sanctuary sites and have a predilection for remaining confined to extranodal sites and strong CNS tropism. Given the shared clinical and molecular features, the umbrella term primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) was proposed. Other extranodal DLBCL involving the breast, adrenal glands, and skin are often ABC DLBCL but are more heterogeneous in their genomic profile and involve anatomic sites that are not considered immune privileged. In this review, we describe the overlapping clinical, pathologic, and molecular features of IP-LBCL and highlight important considerations for diagnosis, staging, and treatment. We also discuss potential therapeutic vulnerabilities of IP-LBCL including sensitivity to inhibitors of Bruton tyrosine kinase, immunomodulatory agents, and immunotherapy.

PubMed Disclaimer

Conflict of interest statement

Conflict-of interest disclosure: The authors declare no competing financial interests.

References

    1. Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of diffuse large B-cell lymphoma. N Engl J Med. 2018;378(15):1396–1407. - PMC - PubMed
    1. Wright GW, Huang DW, Phelan JD, et al. A probabilistic classification tool for genetic subtypes of diffuse large B cell lymphoma with therapeutic implications. Cancer Cell. 2020;37(4):551–568.e14. - PMC - PubMed
    1. Chapuy B, Stewart C, Dunford AJ, et al. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018;24(5):679–690. - PMC - PubMed
    1. Lacy SE, Barrans SL, Beer PA, et al. Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report. Blood. 2020;135(20):1759–1771. - PMC - PubMed
    1. Campo E, Jaffe ES, Cook JR, et al. The International Consensus classification of mature lymphoid neoplasms: a report from the Clinical Advisory Committee. Blood. 2022;140(11):1229–1253. - PMC - PubMed

MeSH terms

LinkOut - more resources