Clonal heterogeneity of polymorphic B-cell lymphoproliferative disease, EBV-positive, iatrogenic/immune senescence: implications on pathogenesis and treatment.
Hematology
; 27(1): 684-690, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-35666668
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 × 104 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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Infecções por Vírus Epstein-Barr
/
Transtornos Linfoproliferativos
Tipo de estudo:
Etiology_studies
Limite:
Aged
/
Female
/
Humans
Idioma:
En
Revista:
Hematology
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article