Clonal heterogeneity of polymorphic B-cell lymphoproliferative disease, EBV-positive, iatrogenic/immune senescence: implications on pathogenesis and treatment. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Hwang, Yu-Yan; Au-Yeung, Rex; Leung, Rock Y.Y.; Tse, Eric; Kwong, Yok-Lam
• Is Part Of: Hematology. Volume 27:Issue 1(2022)
• Page Start: 684
• Page End: 690
• Publication Date: 2022-12-31
• Subjects: EBV-positive -- EBV-negative -- lymphoproliferative disease -- clonal heterogeneity; Blood -- Diseases -- Periodicals; Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; 616.15005
• DOI: 10.1080/16078454.2022.2081299
• Languages: English
• ISSNs: 1024-5332

Abstract

ABSTRACT: Background: Epstein Barr virus positive (EBV+) immunodeficiency-associated lymphoproliferative disorders (IA-LPD) are heterogeneous diseases with variable treatment strategies that are not well-defined. Case presentation: A 68-year-old woman with systemic lupus erythematosus developed EBV+ B-cell polymorphic lymphoproliferative disease (LPD). Positron emission tomography computed tomography (PET/CT) showed a large nasopharyngeal mass, multiple pulmonary lesions, splenomegaly and disseminated lymphadenopathy. Plasma EBV DNA was grossly elevated to 1.5 × 10 4 IU/mL. There were three paraproteins. Treatment with O-CHOP (obinutuzumab, cyclophosphamide, adriamycin, vincristine, prednisolone) led to undetectable plasma EBV DNA, suggesting eradiation of the EBV-positive malignant clone. However, radiologic abnormalities were still present on PET/CT, and paraprotein persisted. A nasopharyngeal re-biopsy showed infiltration with EBV-negative plasma cells. On treatment with lenalidomide, she finally achieved complete metabolic response. Molecular analysis showed that the EBV+ B-cell LPD and the EBV– plasma cell lesion exhibited identical immunoglobulin gene rearrangements. Next generation sequencing revealed that the EBV+ B-LPD showed mutation in only one gene ( TP53 ), a profile typical of EBV-driven lymphoid neoplasms. However, the EBV– plasma cell lesion showed mutations in five genes ( TP53, SF3B1, STAT5B, CD79B and CRKL ), suggesting that these mutations instead of EBV infection were the oncogenic driver. Conclusion: The presence of both EBV+ and EBV– lesions, which showed different mutational profiles, indicated clonal heterogeneity that might be of biologic and therapeutic significance.