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Evolution in the definition and diagnosis of the Hodgkin lymphomas and related entities

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Abstract

Hodgkin lymphoma was the first of the lymphomas to be recognized as a specific disease entity. However, recent studies have highlighted the heterogeneity of the diseases associated with this eponym warranting clarification and refinement of diagnostic terminology. While classic Hodgkin lymphoma (CHL) remains an essentially unchanged diagnostic entity in the 2022 International Consensus Classification of Mature Lymphoid Neoplasms (2022 ICC), nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is now renamed nodular lymphocyte predominant B cell lymphoma (NLPBL) in recognition of the distinct pathologic, biologic, and clinical differences. Fan patterns A, B, and C (sharing the presence of evident follicular structures, and retention of a B cell rich background) will be combined in “typical” or grade 1, while the other “variant” patterns, D, E, and F, are considered grade 2. T-cell/histiocyte-rich large B cell lymphoma (THRBCL) is considered part of the “variant” NLPHL continuum.

The entity previously known as “B cell lymphoma, unclassifiable (BCLU), with features intermediate between diffuse large B cell lymphoma (DLBCL) and CHL” has been renamed “mediastinal gray zone lymphoma” (MGZL) in recognition of the importance of the thymic niche in the biology of this tumor. The diagnostic criteria for MGZL have been refined and require both a high tumor cell density and a strongly preserved B cell program.

This article will describe updates on CHL, NLPBL, and MGZL in the recently published 2022 ICC and provide some useful differential diagnostic clues in cases with atypical morphology or immunophenotype.

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Acknowledgements

TAT holds a Mandate for Fundamental and Translational Research from the “Stichting tegen Kanker” (2019-091) and is a co-founder of the Fund “Me To You” supporting research in lymphoma/leukemia (https://www.kuleuven.be/mecenaat/fondsen/geneeskunde/fonds-me-to-you).

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Authors and Affiliations

  1. Department of Pathology, UZ Leuven, University Hospitals, Herestraat 49, B-3000, Leuven, Belgium

    Thomas A. Tousseyn

  2. Translational Cell and Tissue Research Laboratory, KU Leuven, Leuven, Belgium

    Thomas A. Tousseyn

  3. Division of Hematopathology, Mayo Clinic, Rochester, MN, USA

    Rebecca L. King & Andrew L. Feldman

  4. Institute of Pathology and Neuropathology and Comprehensive Cancer Center, Tübingen University Hospital, Tübingen, Germany

    Falko Fend

  5. Department of Pathology, IUCT-Oncopole, Labex TOUCAN, Toulouse, France

    Pierre Brousset

  6. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Elaine S. Jaffe

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Contributions

All the authors are members of the Clinical Advisory Committee that prepared the 2022 ICC classification of lymphoid neoplasms. TAT and RLK contributed equally to the writing of this review and preparation of the tables. FF, ALF, PB, and ESJ reviewed and corrected the manuscript.

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Correspondence to Thomas A. Tousseyn.

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Key messages

- “Hodgkin” terminology will be reserved for the classic HL; the 4 major subtypes of CHL remain unchanged.

- Nodular LP B cell lymphoma is the new terminology for the formerly known nodular LP Hodgkin lymphoma, and “typical” Fan patterns (A, B, and C) will be combined in grade 1, while the other “variant” patterns (D, E, and F) are considered grade 2.

- THRLBCL is considered part of the “variant” NLPHL continuum.

- Mediastinal gray zone lymphoma requires both (1) strongly preserved B cell program and (2) high tumor cell density.

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Tousseyn, T.A., King, R.L., Fend, F. et al. Evolution in the definition and diagnosis of the Hodgkin lymphomas and related entities. Virchows Arch 482, 207–226 (2023). https://doi.org/10.1007/s00428-022-03427-z

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