title: Spectrum of Epstein-Barr virus-associated T-cell lymphoproliferative disorder in adolescents and young adults in Taiwan.
abstract: Epstein-Barr Virus (EBV) is a herpesvirus usually infecting B-cells but may occasionally infect T- or natural killer (NK)-cells. EBV-associated T- or NK-cell lymphoproliferations represent a continuous spectrum of diseases ranging from asymptomatic infection, infectious mononucleosis (IM), to clonal and malignant lymphoproliferations including systemic EBV-positive T/NK-cell lymphoproliferative disease (EBV-T/NK-LPD) of childhood and hydroa-vacciniforme-like lymphoma of the skin. The clonal diseases are more prevalent in East Asia and exhibit overlapping clinical and pathological features with chronic active EBV infection. Here we report our experience on 10 cases of EBV-associated T-cell lymphoproliferation from Taiwan including five males and five females with a median age of 18 years old (range, 15-28). The most common clinical symptoms were fever, neck mass and hepatosplenomegaly. Eight of these patients showed elevated lactate dehydrogenase level and half of the patients had cytopenia. All patients had either elevated EBV antibody titers or increased serum EBV DNA levels. Five cases were clinically IM-like with polyclonal (3 cases) or clonal (2 cases) T-cell lymphoproliferation. Two patients each had chronic active EBV infection (CAEBV) and hemophagocytic lymphohistiocytosis (HLH). One patient had both CAEBV and HLH. One of the HLH patients with marrow infiltration by intra-sinusoidal large atypical lymphocytes experienced a fulminant course. In a median follow-up time of 21.5 months, seven patients were free of disease, one was alive with disease, and two died of disease in 31 and 3 months, respectively, despite chemotherapy. We confirmed a wide clinicopathological range of EVB-associated T-cell lymphoproliferation in Taiwan. Furthermore, monomorphic LPD and the single case with fulminant course as defined by Ohshima et al (Pathol Int 2018) as categories A3 and B, respectively, died of disease despite chemotherapy. Our report, the largest series in the recent decade from Taiwan, adds to the understanding of these rare diseases with variable clinical and histopathological presentations.
authors: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital Taichung, Taiwan.
authors: Ren-Ching
authors: RC
authors: Wang
authors: Department of Pathology, Chi-Mei Medical Center, and Department of Nursing, National Tainan Institute of Nursing Tainan, Taiwan.
authors: Sheng-Tsung
authors: ST
authors: Chang
authors: Department of Pathology, Chi-Mei Medical Center, and Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology Tainan, Taiwan.
authors: Yen-Chuan
authors: YC
authors: Hsieh
authors: Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors: Wan-Ting
authors: WT
authors: Huang
authors: Department of Pathology, Chung Shan Medical University Hospital and School of Medicine, Chung Shan Medical University Taichung, Taiwan.
authors: Jeng-Dong
authors: JD
authors: Hsu
authors: Department of Anatomic Pathology, Buddhist Dalin Tzu Chi Hospital Chiayi, Taiwan ; School of Medicine, Buddhist Tzu Chi University Hualien, Taiwan.
authors: Chih-En
authors: CE
authors: Tseng
authors: Division of Hematology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, and Chang Gung University College of Medicine Kaohsiung, Taiwan.
authors: Ming-Chung
authors: MC
authors: Wang
authors: Division of Hematology and Oncology, Department of Internal Medicine, Chung-Shan Medical University Hospital and School of Medicine, Chung-Shan Medical University Taichung, Taiwan.
authors: Wei-Shou
authors: WS
authors: Hwang
authors: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital Taichung, Taiwan.
authors: John
authors: J
authors: Wang
authors: Department of Pathology, Chi-Mei Medical Center Tainan, Taiwan ; Taipei Medical University and National Taiwan University Taipei, Taiwan.
authors: Shih-Sung
authors: SS
authors: Chuang
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000628:therapy / Q000821:virology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008232:Lymphoproliferative Disorders / Q000175:diagnosis / Q000276:immunology / Q000401:mortality / Q000628:therapy / Q000821:virology*; D008297:Male; D010641:Phenotype; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology / Q000821:virology*; D013624:Taiwan; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D015415:Biomarkers; D004279:DNA, Viral; D007770:L-Lactate Dehydrogenase
keywords: Epstein-Barr virus; T/natural killer-cell lymphoproliferation; Taiwan; hemophagocytic lymphohistiocytosis; infectious mononucleosis; systemic T/natural killer-cell lymphoproliferative disease