title: Clinicopathological categorization of Epstein-Barr virus-positive T/NK-cell lymphoproliferative disease: an analysis of 42 cases with an emphasis on prognostic implications.
abstract: Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases (EBV-T/NK-LPDs) include several overlapping EBV-related conditions with variably aggressive courses. For prognostic categorization, we retrospectively analyzed 42 EBV-T/NK-LPD cases. Male (79% [33/42]), young (≤40 years; 83% [35/42]) patients and T-cell lineage (81% [34/42]; CD8/CD4 = 1.8) were predominant. Clinicopathologically, three systemic and one cutaneous category were developed: hemophagocytic lymphohistiocytosis (HLH; 26% [11/42]), chronic active EBV infection (CAEBV; 31% [13/42]), systemic unclassifiable disease (24% [10/42]), and hydroa vacciniforme/hydroa vacciniforme-like lymphoma (HV/HVL; 19% [8/42]). Prognostically, cutaneous disease (HV/HVL) was better than systemic disease (p = 0.014; median, 285 vs. 10 months). In systemic diseases, HLH was worst (p = 0.002; 3[HLH] vs. 4[unclassifiable] vs. not reached [CAEBV]). Univariate survival analysis (n = 42) revealed cytopenia (≥one lineage; p < 0.001), onset age (>40 years; p = 0.001), T-cell lineage (p = 0.041), hemophagocytic histiocytes (p = 0.031), elevated lactate dehydrogenase (p = 0.020), and liver dysfunction (p = 0.023) predicted shorter survival. In multivariate analysis, T-cell lineage (p = 0.025 [HR =11.3]) and cytopenia (p = 0.028 [HR =5.4]) were independent prognostic factors. Therefore, EBV-T/NK-LPD could be classified into four prognostic categories.
authors.affiliation: a Department of Pathology , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , South Korea.|b Tumor Immunity Medical Research Center and Tumor Microenvironment Global Core Research Center, Seoul National University , Seoul , South Korea.|c Department of Pathology , Seoul National University Bundang Hospital, Seoul National University College of Medicine , Seongnam , South Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Paik
authors.affiliation: a Department of Pathology , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , South Korea.|c Department of Pathology , Seoul National University Bundang Hospital, Seoul National University College of Medicine , Seongnam , South Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Choe
authors.affiliation: c Department of Pathology , Seoul National University Bundang Hospital, Seoul National University College of Medicine , Seongnam , South Korea.
authors.forename: Hyojin
authors.initials: H
authors.lastname: Kim
authors.affiliation: d Department of Internal Medicine , Seoul National University Bundang Hospital, Seoul National University College of Medicine , Seongnam , South Korea.
authors.forename: Jeong-Ok
authors.initials: JO
authors.lastname: Lee
authors.affiliation: e Department of Pediatrics , Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Children's Hospital , Seoul , South Korea.
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: e Department of Pediatrics , Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Children's Hospital , Seoul , South Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: f Department of Laboratory Medicine , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , South Korea.
authors.forename: Dong Soon
authors.initials: DS
authors.lastname: Lee
authors.affiliation: g Department of Internal Medicine , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , South Korea.
authors.forename: Dae Seog
authors.initials: DS
authors.lastname: Heo
authors.affiliation: a Department of Pathology , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , South Korea.|b Tumor Immunity Medical Research Center and Tumor Microenvironment Global Core Research Center, Seoul National University , Seoul , South Korea.
authors.forename: Chul-Woo
authors.initials: CW
authors.lastname: Kim
authors.affiliation: h Department of Dermatology , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , South Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Cho
authors.affiliation: g Department of Internal Medicine , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , South Korea.
authors.forename: Tae Min
authors.initials: TM
authors.lastname: Kim
authors.affiliation: a Department of Pathology , Seoul National University Hospital, Seoul National University College of Medicine , Seoul , South Korea.|b Tumor Immunity Medical Research Center and Tumor Microenvironment Global Core Research Center, Seoul National University , Seoul , South Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D019070:Cell Lineage / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D060965:Clonal Evolution; D020031:Epstein-Barr Virus Infections / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D063189:Symptom Assessment; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: Chronic active EBV infection; EBV-positive T/NK-cell lymphoproliferative disorder; Epstein–Barr virus; hydroa vacciniforme-like lymphoma; systemic EBV-positive T-cell lymphoproliferative disease of childhood