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Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics

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Abstract

Rare cases of human herpesvirus 8 (HHV8)-negative effusion-based large B-cell lymphoma (EB-LBCL) occur in body cavities without antecedent or concurrent solid mass formation. In contrast to HHV8 + primary effusion lymphoma (PEL), EB-LBCL has no known association with HIV or HHV8 infection. However, the small sample sizes of case reports and series worldwide, especially from non-Japanese regions, have precluded diagnostic uniformity. Therefore, we conducted a retrospective, multi-institutional study of 55 cases of EB-LBCL and performed a comprehensive review of an additional 147 cases from the literature to identify distinct clinicopathologic characteristics. In our study, EB-LBCL primarily affected elderly (median age 80 years), immunocompetent patients and manifested as lymphomatous effusion without a solid component. The lymphomatous effusions mostly occurred in the pleural cavity (40/55, 73%), followed by the pericardial cavity (17/55, 31%). EB-LBCL expressed CD20 (53/54, 98%) and PAX5 (23/23, 100%). Most cases (30/36, 83%) were of non-germinal center B-cell subtype per the Hans algorithm. HHV8 infection was absent (0/55, 0%), while Epstein-Barr virus was detected in 6% (3/47). Clinically, some patients were managed with drainage alone (15/34, 44%), while others received rituximab alone (4/34, 12%) or chemotherapy (15/34, 44%). Eventually, 56% (22/39) died with a median overall survival (OS) of 14.9 months. Our findings were similar to those from the literature; however, compared to the non-Japanese cases, the Japanese cases had a significantly higher incidence of pericardial involvement, a higher rate of chemotherapy administration, and longer median OS. Particularly, we have found that Japanese residence, presence of pericardial effusion, and absence of MYC rearrangement are all favorable prognostic factors. Our data suggest that EB-LBCL portends a worse prognosis than previously reported, although select patients may be managed conservatively. Overall, EB-LBCL has distinct clinicopathologic characteristics, necessitating the establishment of separate diagnostic criteria and consensus nomenclature.

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Fig. 1: Clinical imaging studies of EB-LBCL.
Fig. 2: Cytologic features of EB-LBCL.
Fig. 3: Immunophenotype of EB-LBCL.
Fig. 4: Statistical analyses of the overall survival (OS) of our cohort and different groups in the literature.
Fig. 5: Statistical analyses of the overall survival (OS) based on effusion sites and therapy.
Fig. 6: Survival analyses of multiple factors of EB-LBCL.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The authors thank Richard Bouffard, Susan Bell, Pei Hui, Lorraine Savoca, Cynthia DeRiso, and Mary Helie (Department of Pathology, Yale University School of Medicine) for their technical insight and assistance. The authors also thank Dr. Koji Izutsu (Department of Hematology, National Cancer Center Hospital, Tokyo, Japan) for providing additional survival data for our review.

Funding

This work was partially supported by the NIH/NCI grant 1R01CA233490-01A1.

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Z.P. and S.D.G. performed study concept and design, acquisition of data, analysis and interpretation of data, and preparation, review, and revision of the paper; J.Y. and M.L.X. provided study concept and design, acquisition of data, and review and revision of the paper; R.C.B., D.L.V.M., X.C., X.W., J.M., M.C., Y.X., L.E.B., P.L., Y.Z., E.D.H., E.W., Q.Z., and K.H.Y. provided acquisition and interpretation of data, and review and revision of the paper; S.D.G., H.T., A.M., R.G.H., and N.P. provided statistical analyses, and review and revision of the paper. T.S. provided advice on clinical data analyses. All authors read and approved the final paper.

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Correspondence to Zenggang Pan.

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E.D.H. has received sponsored research from Eli-Lilly and served in the advisory board (Honoria) for Cytomx and Astellas. M.C. has served as a consultant for ALAB. M.L.X. has served in the Seattle Genetics lymphoma advisory board and as a consultant for Pure Marrow and Blueprint Medicines. All other authors declare no competing interests.

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Gisriel, S.D., Yuan, J., Braunberger, R.C. et al. Human herpesvirus 8-negative effusion-based large B-cell lymphoma: a distinct entity with unique clinicopathologic characteristics. Mod Pathol (2022). https://doi.org/10.1038/s41379-022-01091-x

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