CD20-Negative Large B-Cell Lymphomas: The Diagnostic Challenge of Tumors with Downregulation of Mature B-Cell Marker Expression
CD20-negative aggressive B-cell lymphomas are a rare and heterogeneous group of lymphomas representing a diagnostic challenge for pathologists and a therapeutic issue for clinicians, because the outcome of these patients is poor with the current therapeutic approaches. CD20-negative aggressive lymphomas include plasmablastic lymphoma, primary effusion lymphoma, ALK-positive large B-cell lymphoma and HHV8-positive diffuse large B-cell lymphoma. Conditions of immunosuppression and viral infections, such as Epstein-Barr virus and Human Herpes virus 8, are associated with all of these lymphomas with the exclusion of ALK-positive large B-cell lymphoma, which occurs in immunocompetent hosts and is not associated with viral infections. Common features of these aggressive tumors are high-grade histology with immunoblastic or plasmablastic differentiation, the absence or weak expression of mature B-cell markers such as CD20 and the frequent expression of plasma cell-associated markers. The aim of this review is to highlight the diagnostic challenges associated with the group of CD20-negative aggressive B-cell lymphomas, emphasizing key morphologic and molecular features, which are critical in the diagnosis of the different entities belonging to this rare group of diseases.
Authors
- Alessia Cavazza (ORCID: https://orcid.org/0000-0002-4735-2121)
- Massimiliano Fabozzi (ORCID: https://orcid.org/0000-0001-5102-0210)
- Maurizio Zizzo (ORCID: https://orcid.org/0000-0001-9841-7856)
- Nektarios Koufopoulos (ORCID: https://orcid.org/0000-0001-9502-7916)
- Stefano Ricci (ORCID: https://orcid.org/0000-0002-4289-954X)
- Paola Parente (ORCID: https://orcid.org/0000-0003-0591-6723)
- Francesca Sanguedolce
- Valentina Fragliasso (ORCID: https://orcid.org/0000-0002-4189-0316)
- Antonino Neri (ORCID: https://orcid.org/0000-0001-9047-5912)
- Alessandra Bisagni (ORCID: https://orcid.org/0000-0001-8484-7871)
- Giuseppe Broggi (ORCID: https://orcid.org/0000-0003-2576-6523)
- Ione Tamagnini
- Rosario Caltabiano (ORCID: https://orcid.org/0000-0001-8591-8010)
- Stefano Ascani (ORCID: https://orcid.org/0000-0002-4516-9040)
- Lucìa Mangone (ORCID: https://orcid.org/0000-0002-5089-5178)
- Magda Zanelli (ORCID: https://orcid.org/0000-0002-8733-9933)
- Luca Cimino (ORCID: https://orcid.org/0000-0001-7956-9950)
- Andrea Palicelli (ORCID: https://orcid.org/0000-0003-2299-5160)
- Andrea Morini (ORCID: https://orcid.org/0000-0001-9140-0488)
- Serena Salzano (ORCID: https://orcid.org/0009-0005-3669-8759)
- Claudia Camposeo
Institutions
- University of Foggia (IT)
- University of Modena and Reggio Emilia (IT)
- National and Kapodistrian University of Athens (GR)
- University of Perugia (IT)
- Casa Sollievo della Sofferenza (IT)
- University of Catania (IT)
- Azienda Sanitaria Unità Locale di Reggio Emilia (IT)
- Azienda Ospedaliera S.Maria (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
Publication Details
- Journal
- International Journal of Molecular Sciences
- Published
- 2025-08-14
- DOI
- https://doi.org/10.3390/ijms26167843
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministero della Salute