title: EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment.
abstract: Few studies have reported Epstein-Barr virus-positive (EBV(+)) large B-cell lymphomas (LBCLs) in young patients without immunodeficiency. We identified 46 such cases in patients ≤45 years of age and analyzed the clinical and pathological characteristics. EBV(+) LBCLs affected predominantly males (male:female = 3.6:1), with a median age of 23 years (range, 4-45 years). All patients presented with lymphadenopathy and 11% also had extranodal disease. Morphologically, 3 patterns were identified: T-cell/histiocyte-rich large B-cell lymphoma-like (n = 36), gray zone lymphoma (n = 7), and diffuse LBCL-not otherwise specified (n = 3). Tumor cells (EBV(+) in >90% of cells) expressed B-cell antigens, were often CD30 and PD-L1 positive, and showed a nongerminal center immunophenotype. A total of 93% expressed EBV latency type II and 7% latency type III. Indoleamine 2,3-dioxygenase was expressed on background accessory cells. The most common treatment regimen was rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (58%), with local radiation therapy added in 21%. With a median follow-up of 22 months, 82% of patients are in clinical remission and only 8% died of disease. Younger patients achieved a significantly higher overall survival than prior series of EBV(+) LBCLs reported in the elderly (P < .0001). In conclusion, EBV(+) LBCLs are not restricted to the elderly. Young patients present with nodal disease and have a good prognosis.
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD;
authors.forename: Alina
authors.initials: A
authors.lastname: Nicolae
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD;
authors.forename: Stefania
authors.identifier: http://orcid.org/0000-0001-7688-1439
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD;
authors.forename: Shahed
authors.initials: S
authors.lastname: Abdullah
authors.affiliation: Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, Bethesda, MD; and.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: Molecular Diagnostics Unit, Laboratory of Pathology, National Cancer Institute, Bethesda, MD.
authors.forename: Thu Anh
authors.initials: TA
authors.lastname: Pham
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD;
authors.forename: Theresa
authors.initials: T
authors.lastname: Davies-Hill
authors.affiliation: Molecular Diagnostics Unit, Laboratory of Pathology, National Cancer Institute, Bethesda, MD.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Xi
authors.affiliation: Molecular Diagnostics Unit, Laboratory of Pathology, National Cancer Institute, Bethesda, MD.
authors.forename: Mark
authors.initials: M
authors.lastname: Raffeld
authors.affiliation: Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD;
authors.forename: Elaine S
authors.identifier: http://orcid.org/0000-0003-4632-0301
authors.initials: ES
authors.lastname: Jaffe
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult