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Latour S. Human Immune Responses to Epstein-Barr Virus Highlighted by Immunodeficiencies. Annu Rev Immunol 2025; 43:723-749. [PMID: 40279309 DOI: 10.1146/annurev-immunol-082323-035455] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/27/2025]
Abstract
Inborn errors of immunity (IEIs) represent unique in natura models that uncover key components of immunity in humans, in particular those that predispose to infections. Epstein-Barr virus (EBV) is one of the most common opportunistic infectious agents in humans and is responsible for several diseases, including infectious mononucleosis, nonmalignant and malignant lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, and smooth muscle and epithelial tumors. For most individuals, EBV infection persists for life without pathological consequences. IEIs that do not predispose to EBV infection suggest that innate and humoral responses are not necessary or redundant for the immune response to EBV. IEIs associated with high susceptibility to EBV infection provide unequivocal genetic proof of the central role of CD8+ T cell responses in immunity to EBV. They also highlight the distinct steps and pathways required for, on the one hand, the effector cytotoxic functions of CD8+ T cells and, on the other hand, the expansion and maturation of cytotoxic CD8+ T cells.
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Affiliation(s)
- Sylvain Latour
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, INSERM UMR 1163, Paris, France;
- Institut Imagine, Université Paris Cité, Paris, France
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2
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Zhang Y, Xie J, Zheng Y, Zhou X. Infectious mononucleosis complicated by transitory Epstein-Barr virus infection of T and natural killer cells. J Hematop 2024; 17:129-137. [PMID: 38967898 PMCID: PMC11324775 DOI: 10.1007/s12308-024-00595-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 06/27/2024] [Indexed: 07/06/2024] Open
Abstract
Epstein-Barr virus (EBV) typically infects B cells in infectious mononucleosis (IM), but a rare case shows EBV infection in T cells. Seven cases of lymphoproliferative disorder caused by EBV-positive cytotoxic T/natural killer (NK) cell proliferation in the lymph nodes, termed IM with transient EBV infection of T and NK cells (EBV + T/NK cells in IM), are reported here. The purpose of the study is to describe clinicopathological features of EBV + T/natural killer (NK) cells in IM of the lymph node. We retrospectively analysed seven cases of Chinese children and young people adults with EBV + T/NK cells in IM. We used morphological observation, immunohistochemical staining, EB virus in situ hybridisation detection, and analysis of T-cell receptor gene rearrangement. The patients were healthy prior to illness, experiencing sudden onset occurring in all the patients, with high fever as the first symptom, followed by lymphadenopathy and hepatosplenomegaly. Diagnosis occurred < 1.5 months of symptom onset. Most lymphocytes in lesions expressed CD3 and Granzyme B or TIA-1 and lacked CD5. CD56 was expressed in numerous cells in 5 of the 7 cases. EBV-encoded RNA (EBER) was detected in medium-to-large-sized cells (50-100 cells per cell/high-power field). T-cell receptor (TCR) gene rearrangement was seen in six cases, with monoclonal rearrangement in four cases. Treatment was conservative treatment but not chemotherapy. Four received anti-HLH therapy and others anti-inflammatory treatment. All patients survived with relapse after long-term clinical observation and follow-up. EBV + T/NK cells in IM can elicit malignant features that mimic T/NK-cell lymphoma pathologically and benign features mimicking IM clinically. These findings indicate that EBV + T/NK cells in IM could serve as valuable diagnosis. Additional clinical information, including age of onset (children and young people), nature of onset (sudden), disease course (short), symptoms (systemic), EBV infection status (acute), and lymph node involvement, is crucial for accurate diagnosis and prognostic evaluation.
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Affiliation(s)
- Yanlin Zhang
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
| | - JianLan Xie
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - Yuanyuan Zheng
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
| | - XiaoGe Zhou
- Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China
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3
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Tralongo P, Bakacs A, Larocca LM. EBV-Related Lymphoproliferative Diseases: A Review in Light of New Classifications. Mediterr J Hematol Infect Dis 2024; 16:e2024042. [PMID: 38882456 PMCID: PMC11178045 DOI: 10.4084/mjhid.2024.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Accepted: 04/16/2024] [Indexed: 06/18/2024] Open
Abstract
Epstein-Barr virus (EBV) is a prevalent virus that can be detected in the vast majority of the population. Most people are asymptomatic and remain chronically infected throughout their lifetimes. However, in some populations, EBV has been linked to a variety of B-cell lymphoproliferative disorders (LPDs), such as Burkitt lymphoma, classic Hodgkin lymphoma, and other LPDs. T-cell LPDs have been linked to EBV in part of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other uncommon histotypes. This article summarizes the current evidence for EBV-associated LPDs in light of the upcoming World Health Organization classification and the 2022 ICC classification.
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Affiliation(s)
- Pietro Tralongo
- Division of Anatomic Pathology and Histology - Fondazione Policlinico Universitario "Agostino Gemelli"- IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Arianna Bakacs
- Division of Anatomic Pathology and Histology - Fondazione Policlinico Universitario "Agostino Gemelli"- IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Luigi Maria Larocca
- Division of Anatomic Pathology and Histology - Fondazione Policlinico Universitario "Agostino Gemelli"- IRCCS, Università Cattolica del Sacro Cuore, Largo Francesco Vito, 1, 00168, Rome, Italy
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4
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Ono S, Yoshimoto K, Matsubara M, Nishimura N, Kawashima H, Yoneima R, Yada N, Nishio K. Report of Two Contrasting Cases of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis: Comparison to Infectious Mononucleosis and Flow Cytometric Analysis of Bone Marrow. Int Med Case Rep J 2024; 17:43-49. [PMID: 38269069 PMCID: PMC10807454 DOI: 10.2147/imcrj.s443996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 12/24/2023] [Indexed: 01/26/2024] Open
Abstract
Purpose This study aims to investigate the characteristics of Epstein-Barr virus associated-hemophagocytic lymphohistiocytosis (EBV-HLH) and HLH caused by a severe form of infectious mononucleosis (IM-HLH) compared to IM by EBV, and thus also to assist in early diagnosis and providing appropriate treatment. Methods Data for this analysis were collected from patients at the Department of General Medicine, Nara Medical University, between April 1, 2012, and August 1, 2020. EBV infection was diagnosed using clinical presentation and laboratory tests. HLH diagnosis followed the HLH-2004 protocol, supplemented by plasma EBV DNA detection. A range of clinical and laboratory parameters were collected, including age, sex, clinical outcomes, blood cell counts, hemoglobin, platelets, and various serum values. Plasma EBV DNA levels and flow cytometric analysis (FCM) of bone marrow were performed for HLH cases. Results Among 1850 hospitalized patients, 14 cases were identified, including 2 HLH cases and 12 IM cases. Comparative analysis revealed distinctive features of HLH, including lower lymphocyte and platelet counts and higher levels of ferritin, soluble interleukin 2 receptor (sIL-2R), and D dimer compared to IM. Notably, one HLH case responded well to corticosteroid monotherapy, while the other case did not, resulting in a fatal outcome. Detection of a cluster of CD5-CD7 lymphocytes in bone marrow is a hallmark of EBV-HLH and useful to distinguish from IM-HLH. Conclusion This study underscores the importance of early differentiation among EBV-HLH, IM-HLH, and IM in adults to guide appropriate treatment strategies. While specific laboratory markers help distinguish HLH from IM, a more detailed analysis of FCM is crucial for precise diagnosis of HLH cases and tailored therapeutic interventions.
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Affiliation(s)
- Shiro Ono
- Department of General Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Kiyomi Yoshimoto
- Department of General Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Masaki Matsubara
- Department of General Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Nobushiro Nishimura
- Department of General Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Hiromasa Kawashima
- Department of General Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Ryo Yoneima
- Department of General Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Noritaka Yada
- Department of General Medicine, Nara Medical University, Kashihara, Nara, Japan
| | - Kenji Nishio
- Department of General Medicine, Nara Medical University, Kashihara, Nara, Japan
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5
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Egorova ON, Kharlamova EN, Tarasova GM. Differential diagnosis of a local form of granulomatosis with polyangiitis: nasal cavity and paranasal sinuses lesions (part 1). MODERN RHEUMATOLOGY JOURNAL 2023. [DOI: 10.14412/1996-7012-2023-1-7-15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/19/2023]
Abstract
Granulomatosis with polyangiitis (GPA) is a primary vasculitis associated with antineutrophil cytoplasmic antibodies, characterized by necrotizing vasculitis with predominant involvement of small vessels of various localizations and necrotizing granulomatous inflammation with multiple clinical manifestations. GPA remains one of the most severe systemic vasculitis with unfavorable prognosis. When analyzing the course of the disease, there are two variants of GPA, local (with lesions of the upper respiratory tract, URT, organs of vision and hearing) and generalized (with lesions of the URT, organs of vision and hearing in combination with the lungs and/or kidneys, gastrointestinal tract, nervous systems, skin involvement).The article discusses the differential diagnosis of the disease with the nasal cavity and paranasal sinuses lesions onset, which requires an interdisciplinary approach and interaction of doctors of different specialties.
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6
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Comprehensive analysis of the differential cellular and EBV miRNA expression profiles in Mature T and NK cell lymphomas. Pathol Res Pract 2022; 233:153846. [DOI: 10.1016/j.prp.2022.153846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 03/03/2022] [Accepted: 03/17/2022] [Indexed: 11/19/2022]
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Skin diseases in Asian individuals that you do not want to miss: A selection of unique or relatively more common conditions in Asian populations. Clin Dermatol 2021; 39:879-886. [PMID: 34785016 DOI: 10.1016/j.clindermatol.2021.05.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The Asian population currently constitutes a simple majority of the global population, comprising nearly 60%. The percentage of the US population that identifies as Asian is expected to grow to 41 million by the year 2050, making up an eventual 9% of the US population. As the world and US populations of Asian individuals increase, the demand for dermatologic care from this population will increase, requiring dermatologists to become more familiar with the diagnosis and treatment of Asian-specific skin characteristics and diseases. In this contribution, we review skin conditions specific to or relatively more common in Asian patients to help recognition and management of diseases in an increasing Asian patient population. We discuss prurigo pigmentosa, primary cutaneous plasmacytosis, lipodystrophia centrifugalis abdominalis infantilis, Epstein-Barr viru-positive T- and natural killer-cell lymphoproliferative disorders, acquired bilateral nevus of Ota-like macules, and Behҫet disease.
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8
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Chen Q, Liu S, Zhang K, Yu B, Zhang W, Zhang H, Chen X. Hsa-miR-372-5p regulates the NIMA related kinase 7 and IL-1β release in NK/T-cell lymphoma. Leuk Lymphoma 2021; 62:2648-2656. [PMID: 34080953 DOI: 10.1080/10428194.2021.1933472] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Epstein-Barr virus (EBV) infection is prevalent and associated with distinct diseases including infectious mononucleosis (IM), chronic active EBV infection (CAEBV) and NK/T-cell lymphoma (NKTL). However, the specific roles of EBV in these diseases remain unclear. Here, the whole miRNA expression datasets derived from 7 IM, 6 CAEBV, and 3 NKTL biopsies were obtained. Homo sapiens microRNA-372-5p (Hsa-miR-372-5p) was upregulated in both CAEBV and NKTL patients. Overexpression of hsa-miR-372-5p altered the expression of over 100 proteins. In addition, hsa-miR-372-5p may target NIMA related kinase 7 to regulate NLRP3 inflammasome activation in host cell. Taken together, we reported different miRNA expression profiles in distinct EBV associated diseases, which provided novel insights to understand how host miRNAs contribute to the mechanism of EBV associated diseases. Hsa-miR-372-5p, as well as other differential expressed miRNA, might serve as potential targets in the therapy of various EBV associated diseases.
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Affiliation(s)
- Qi Chen
- Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, China.,Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
| | - Shenglin Liu
- College of Biological and Food Engineering, Huaihua University, Huaihua, China.,Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Kaoyuan Zhang
- Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Bo Yu
- Department of Dermatology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Wei Zhang
- Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
| | - Hongyu Zhang
- Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, China
| | - Xiaofan Chen
- Shenzhen Key Laboratory for Translational Medicine of Dermatology, Biomedical Research Institute, Shenzhen Peking University - The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
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9
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Oh SJ, Lee J, Park JH, Lee JH, Cho J, Ko YH, Lee D. Hydroa Vacciniforme-Like Lymphoproliferative Disorder in Korea: Prognostic Implication of Clinical Signs and Whole Blood Epstein-Barr Virus DNA. Ann Dermatol 2021; 33:222-227. [PMID: 34079181 PMCID: PMC8137328 DOI: 10.5021/ad.2021.33.3.222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 09/03/2020] [Accepted: 10/07/2020] [Indexed: 11/08/2022] Open
Abstract
Background Hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) is rare Epstein-Barr virus (EBV)-associated disease. The classic form of HVLPD is a self-resolving disease, whereas the systemic form can progress to malignant lymphoma, resulting in fatal outcomes. However, the prognostic factors remain unclear. Objective This study aimed to evaluate the clinical characteristics of HVLPD and the association between whole blood EBV DNA and clinical outcomes. Methods We retrospectively reviewed our 25-year experience involving 11 patients with HVLPD from a single tertiary center in South Korea and evaluated the clinical characteristics of HVLPD and the correlation between whole blood EBV DNA and clinical outcomes. Results Of the total 11 patients, 54.5% (6/11) manifested classic HVLPD that resolved with conservative treatment, while 45.5% (5/11) patients had systemic HVLPD, four of whom died of progressive disease or hemophagocytic syndrome. Five patients with systemic HVLPD manifested severe skin lesions such as prominent facial edema, deep ulcers and necrotic skin lesions involving sun-protected areas. Median EBV DNA levels at initial diagnosis were higher in three dead patients than in those alive (2,290 vs. 186.62 copies/µl). Conclusion When EBV DNA levels were high, patients showed severe skin lesions and when EBV DNA levels were low, skin lesions tended to improve. Thus, patients with high EBV DNA levels showed an increased risk of severe skin lesions and disease progression.
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Affiliation(s)
- Se Jin Oh
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jongeun Lee
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji-Hye Park
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Hee Lee
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Junhun Cho
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Young-Hyeh Ko
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dongyoun Lee
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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10
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Affiliation(s)
- Young Hyeh Ko
- Department of Pathology, Korea University Guro Hospital, Seoul, Korea
- Department of Pathology, Hanyang University Hospital, Seoul, Korea
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11
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Dieudonne Y, Martin M, Korganow AS, Boutboul D, Guffroy A. [EBV and immunodeficiency]. Rev Med Interne 2021; 42:832-843. [PMID: 33867195 DOI: 10.1016/j.revmed.2021.03.324] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2020] [Revised: 03/18/2021] [Accepted: 03/21/2021] [Indexed: 11/30/2022]
Abstract
Epstein-Barr virus (EBV), discovered in 1964, is a double-stranded DNA virus belonging to the Herpesviridae family. EBV has a lymphoid tropism with transforming capacities using different oncogenic viral proteins. This virus has two replication cycles: a lytic cycle mainly occuring during primary infection and a latent cycle allowing viral persistence into host memory B cells. More than 90% of adults are seropositive for EBV worldwide, with a past history of asymptomatic or mild primary infection. EBV infection can sometimes cause life-threatening complications such as hemophagocytic lymphohistiocytosis, and lead to the development of lymphoproliferative disorders or cancers. Risk factors associated with these phenotypes have been recently described through the study of monogenic primary immune deficiencies with EBV susceptibility. We here review the virological and immunological aspects of EBV infection and EBV-related complications with an overview of current available treatments.
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Affiliation(s)
- Y Dieudonne
- Université de Strasbourg, Inserm UMR - S1109, 67000 Strasbourg, France; Hôpitaux universitaires de Strasbourg, service d'immunologie clinique et de médecine interne, centre national de référence des maladies auto-immunes et systémiques rares, Est/Sud-Ouest (RESO), centre de compétence pour les déficits immunitaires primitifs de l'adulte, 67000 Strasbourg, France; Université de Strasbourg, faculté de médecine, 67000 Strasbourg, France
| | - M Martin
- Service de médecine interne, maladies infectieuses et tropicales, centre hospitalier universitaire de Poitiers, 86021 Poitiers, France; Université de Poitiers, 86021 Poitiers, France
| | - A-S Korganow
- Université de Strasbourg, Inserm UMR - S1109, 67000 Strasbourg, France; Hôpitaux universitaires de Strasbourg, service d'immunologie clinique et de médecine interne, centre national de référence des maladies auto-immunes et systémiques rares, Est/Sud-Ouest (RESO), centre de compétence pour les déficits immunitaires primitifs de l'adulte, 67000 Strasbourg, France; Université de Strasbourg, faculté de médecine, 67000 Strasbourg, France
| | - D Boutboul
- Service d'immunopathologie clinique, U976 HIPI, hôpital Saint-Louis, université de Paris, Paris, France.
| | - A Guffroy
- Université de Strasbourg, Inserm UMR - S1109, 67000 Strasbourg, France; Hôpitaux universitaires de Strasbourg, service d'immunologie clinique et de médecine interne, centre national de référence des maladies auto-immunes et systémiques rares, Est/Sud-Ouest (RESO), centre de compétence pour les déficits immunitaires primitifs de l'adulte, 67000 Strasbourg, France; Université de Strasbourg, faculté de médecine, 67000 Strasbourg, France.
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12
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Li X, Zhang W. Expression of PD-L1 in EBV-associated malignancies. Int Immunopharmacol 2021; 95:107553. [PMID: 33765613 DOI: 10.1016/j.intimp.2021.107553] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/22/2021] [Accepted: 02/28/2021] [Indexed: 02/06/2023]
Abstract
Epstein-Barr virus infection is closely related to the occurrence and development of a variety of malignant tumors. Tumor immunotherapy has been combined with modern biological high-tech technology, and has become the fourth cancer treatment mode after surgery, chemotherapy and radiotherapy. In 2013, immunotherapy was named the first of ten scientific breakthroughs by science. It aims to control and destroy tumor cells by stimulating and enhancing autoimmune function. In recent years, immune checkpoint inhibitors (ICIs) targeting PD-L1 have become a research hotspot in the field of cancer. Recent studies have shown that EBV infection can upregulate PD-L1 through complex mechanisms. Further understanding of these mechanisms and prevention of hyperprogressive disease (HPD) can make PD-L1 immune checkpoint inhibitors an effective way of immunotherapy for EBV related malignant tumors.
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Affiliation(s)
- Xiaoxu Li
- Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China; Clinical Laboratory, The Second People's Hospital of Wuhu City, Wuhu 241001, Anhui, People's Republic of China
| | - Wenling Zhang
- Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China; Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China.
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13
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Lungu M, Telehuz A, Voinescu DC, Sapira V, Trifan A, Elkan EM, Fătu A, Creangă VZ, Polinschi M, Stoleriu G, Niculet E. NK/T-cell non-Hodgkin lymphoma: Case report and review of the literature. Exp Ther Med 2020; 21:91. [PMID: 33363602 PMCID: PMC7725024 DOI: 10.3892/etm.2020.9523] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 10/26/2020] [Indexed: 11/25/2022] Open
Abstract
Natural killer (NK)/T-cell lymphomas represent a rare type of lymphoid malignancy with mostly extranodal involvement, having NK cell or (rare) T cell lineage, classified by the World Health Organization into several subtypes which can involve the head and neck region, with the most frequent one being the nasal type. This article presents the case of a 31-year-old patient who presented at the Emergency Unit of Saint Andrew Emergency Clinical Hospital of Galati suffering from mycosis fungoides-like cutaneous lesions, associated with partial left eyelid ptosis of unknown etiology, as well as a poor health status with fever and respiratory failure. The final diagnosis was NK/T-cell non-Hodgkin lymphoma, possibly nasal type with medium sized T cells. The complexity of the rare diagnosis, associated with the unusual rapid patient evolution towards exitus 3 months after diagnosis, the intra-orbital metastatic involvement and the absence of a standardized treatment are case peculiarities, some of which are consistent with current literature data.
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Affiliation(s)
- Mihaiela Lungu
- Clinical Department, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Anca Telehuz
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Doina Carina Voinescu
- Clinical Department, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Violeta Sapira
- Clinical Department, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Angel Trifan
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Eva Maria Elkan
- Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Ana Fătu
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Valerica Zărnescu Creangă
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Mihai Polinschi
- Research Center of Medical and Pharmaceutical Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Gabriela Stoleriu
- Clinical Department, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
| | - Elena Niculet
- Department of Morphological and Functional Sciences, Faculty of Medicine and Pharmacy, 'Dunarea de Jos' University of Galati, 800008 Galati, Romania
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14
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Li N, Wang YZ, Zhang Y, Zhang WL, Zhou Y, Huang DS. Natural killer/T-cell lymphoma with intracranial infiltration and Epstein-Barr virus infection: A case report. World J Clin Cases 2020; 8:3284-3290. [PMID: 32874983 PMCID: PMC7441250 DOI: 10.12998/wjcc.v8.i15.3284] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Revised: 05/15/2020] [Accepted: 07/21/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Because of atypical clinical symptoms, lymphoma is easily confused with infectious diseases. Extranodal nasal-type natural killer/T-cell lymphoma (NKTL) is more common, and there are few cases of eyelid site onset and intracranial infiltration, which increases the difficulty of diagnosis. This disease usually has a very poor prognosis and there are few reports of recovery.
CASE SUMMARY A 3-year-old boy was admitted to our hospital due to an initial misdiagnosis of "eyelid cellulitis" and failed antibiotic treatment. He was characterized by fever, right eyeball bulging, convulsions, and abnormal liver function. His blood Epstein-Barr virus (EBV) DNA was positive (8.798 × 104 copies/mL), and remained positive for about half a year. The cranial imaging examination suggested a space-occupying lesion in the right eyelid, with the right temporal lobe and meninges involved. The boy underwent ocular mass resection. The pathological diagnosis was NKTL. He was diagnosed as having NKTL with intracranial infiltration, combined with chronic active EBV infection (CAEBV). Then he underwent systemic chemotherapy and intrathecal injection. The boy suffered from abnormal blood coagulation, oral mucositis, diarrhea, liver damage, and severe bone marrow suppression but survived. Finally, the tumor was completely relieved and his blood EBV-DNA level turned negative. The current follow-up has been more than 2 years and his condition is stable.
CONCLUSION This case suggests that chemotherapy combined with intrathecal injection may have a good effect on intracranial infiltrating lymphoma and CAEBV, which deserves further study and discussion.
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Affiliation(s)
- Nan Li
- Pediatric Department, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100176, China
| | - Yi-Zhuo Wang
- Pediatric Department, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100176, China
| | - Yi Zhang
- Pediatric Department, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100176, China
| | - Wei-Ling Zhang
- Pediatric Department, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100176, China
| | - Yan Zhou
- Pediatric Department, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100176, China
| | - Dong-Sheng Huang
- Pediatric Department, Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100176, China
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15
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CD21 (Complement Receptor 2) Is the Receptor for Epstein-Barr Virus Entry into T Cells. J Virol 2020; 94:JVI.00428-20. [PMID: 32238579 DOI: 10.1128/jvi.00428-20] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Accepted: 03/14/2020] [Indexed: 12/13/2022] Open
Abstract
Epstein-Barr virus (EBV) is associated with a number of T-cell diseases, including some peripheral T-cell lymphomas, hemophagocytic lymphohistiocytosis, and chronic active EBV disease. The tropism of EBV for B cells and epithelial cell infection has been well characterized, but infection of T cells has been minimally explored. We have recently shown that the EBV type 2 (EBV-2) strain has the unique ability to infect mature T cells. Utilizing an ex vivo infection model, we sought to understand the viral glycoprotein and cellular receptor required for EBV-2 infection of T cells. Here, using a neutralizing-antibody assay, we found that viral gp350 and complement receptor 2 (CD21) are required for CD3+ T-cell infection. Using the HB5 anti-CD21 antibody clone but not the Bly-4 anti-CD21 antibody clone, we detected expression of CD21 on both CD4+ and CD8+ T cells, with the highest expression on naive CD4 and CD8+ T-cell subsets. Using CRISPR to knock out CD21, we demonstrated that CD21 is necessary for EBV entry into the Jurkat T-cell line. Together, these results indicate that EBV uses the same viral glycoprotein and cellular receptor for both T- and B-cell infection.IMPORTANCE Epstein-Barr virus (EBV) has a well-described tropism for B cells and epithelial cells. Recently, we described the ability of a second strain of EBV, EBV type 2, to infect mature peripheral T cells. Using a neutralizing antibody assay, we determined that EBV uses the viral glycoprotein gp350 and the cellular protein CD21 to gain entry into mature peripheral T cells. CRISPR-Cas9 deletion of CD21 on the Jurkat T-cell line confirmed that CD21 is required for EBV infection. This study has broad implications, as we have defined a function for CD21 on mature peripheral T cells, i.e., as a receptor for EBV. In addition, the requirement for gp350 for T-cell entry has implications for EBV vaccine studies currently targeting the gp350 glycoprotein to prevent EBV-associated diseases.
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16
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Lymphoma Mimicking Chronic Active Epstein-Barr Virus: A Case Report. Head Neck Pathol 2020; 14:1028-1031. [PMID: 32350807 PMCID: PMC7669935 DOI: 10.1007/s12105-020-01154-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Revised: 03/05/2020] [Accepted: 03/17/2020] [Indexed: 12/26/2022]
Abstract
Epstein-Barr virus (EBV) is the main cause of infectious mononucleosis (IM), a self-limiting infection among immunocompetent patients. EBV is also implicated in the development of several malignancies. We describe a case of a previously healthy 34-year-old man who presented with non-tender, enlarging, right cervical lymphadenopathy for over a year that was associated with significant weight loss, fevers, and night sweats. Two fine needle core biopsies showed inconclusive then reactive tissue, respectively. A third excisional biopsy demonstrated a reactive lymph node with EBV-positive IM. There was no evidence of lymphoma by histologic examination or flow cytometry. A diagnosis of chronic active EBV (CAEBV) was rendered. Subsequent lymph node debulking six months later showed classic Hodgkin lymphoma (CHL) positive for EBV. The patient underwent chemotherapy with full treatment response. This is an unusual presentation of EBV infection that led to either a delayed onset or delayed diagnosis of CHL.
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17
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Xue R, Elbendary A, Liu H, Chen Y, Cleaver N, Elston DM. Hydroa vacciniforme-like lymphoma: Clinicopathologic description, treatment, and outcome. J Am Acad Dermatol 2019; 85:752-755. [PMID: 31759090 DOI: 10.1016/j.jaad.2019.11.031] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Revised: 11/11/2019] [Accepted: 11/13/2019] [Indexed: 11/25/2022]
Affiliation(s)
- Ruzeng Xue
- Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong, China.
| | - Amira Elbendary
- Department of Dermatology, Kasr Alainy Faculty of Medicine, Cairo University, Egypt
| | - Hongfang Liu
- Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yongfeng Chen
- Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | | | - Dirk M Elston
- Department of Dermatology & Dermatological Surgery, Medical University of South Carolina, Charleston
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18
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Rodriguez R, Fournier B, Cordeiro DJ, Winter S, Izawa K, Martin E, Boutboul D, Lenoir C, Fraitag S, Kracker S, Watts TH, Picard C, Bruneau J, Callebaut I, Fischer A, Neven B, Latour S. Concomitant PIK3CD and TNFRSF9 deficiencies cause chronic active Epstein-Barr virus infection of T cells. J Exp Med 2019; 216:2800-2818. [PMID: 31537641 PMCID: PMC6888974 DOI: 10.1084/jem.20190678] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 07/23/2019] [Accepted: 08/29/2019] [Indexed: 12/13/2022] Open
Abstract
Identification of biallelic loss-of-function mutations in TNFRSF9 and PIK3CD in a kindred with chronic active Epstein-Barr virus infection of T cells (CAEBV) suggests that CAEBV is the consequence of factors providing growth advantage to EBV-infected T cells combined with defective cell immunity toward EBV-infected cells. Infection of T cells by Epstein-Barr virus (EBV) causes chronic active EBV infection (CAEBV) characterized by T cell lymphoproliferative disorders (T-LPD) of unclear etiology. Here, we identified two homozygous biallelic loss-of-function mutations in PIK3CD and TNFRSF9 in a patient who developed a fatal CAEBV. The mutation in TNFRSF9 gene coding CD137/4-1BB, a costimulatory molecule expressed by antigen-specific activated T cells, resulted in a complete loss of CD137 expression and impaired T cell expansion toward CD137 ligand–expressing cells. Isolated as observed in one sibling, CD137 deficiency resulted in persistent EBV-infected T cells but without clinical manifestations. The mutation in PIK3CD gene that encodes the catalytic subunit p110δ of the PI3K significantly reduced its kinase activity. Deficient T cells for PIK3CD exhibited reduced AKT signaling, while calcium flux, RAS-MAPK activation, and proliferation were increased, suggestive of an imbalance between the PLCγ1 and PI3K pathways. These skewed signals in T cells may sustain accumulation of EBV-infected T cells, a process controlled by the CD137–CD137L pathway, highlighting its critical role in immunity to EBV.
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Affiliation(s)
- Rémy Rodriguez
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France.,University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France
| | - Benjamin Fournier
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France.,University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France
| | - Debora Jorge Cordeiro
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France.,University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France
| | - Sarah Winter
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France.,University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France
| | - Kazushi Izawa
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France
| | - Emmanuel Martin
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France
| | - David Boutboul
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France.,University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France
| | - Christelle Lenoir
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France
| | - Sylvie Fraitag
- Department of Pathology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Sven Kracker
- University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France.,Laboratory of Human Lymphohematopoiesis, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France
| | - Tania H Watts
- Department of Immunology, University of Toronto, Toronto, Canada
| | - Capucine Picard
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France.,University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France.,Centre d'Etude des Déficits Immunitaires, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.,Department of Pediatric Immunology, Hematology and Rheumatology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Julie Bruneau
- University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France.,Department of Pathology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Isabelle Callebaut
- Sorbonne Université, Muséum National d'Histoire Naturelle, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7590, Institut de Minéralogie, de Physique des Matériaux et de Cosmochimie, Paris, France
| | - Alain Fischer
- University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France.,Department of Pediatric Immunology, Hematology and Rheumatology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.,Collège de France, Paris, France.,Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France
| | - Bénédicte Neven
- University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France.,Department of Pediatric Immunology, Hematology and Rheumatology, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Sylvain Latour
- Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Institut National de la Santé et la Recherche Médicale, Unité Mixte de Recherche 1163, Paris, France .,University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, France
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19
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Gammaherpesvirus entry and fusion: A tale how two human pathogenic viruses enter their host cells. Adv Virus Res 2019; 104:313-343. [PMID: 31439152 DOI: 10.1016/bs.aivir.2019.05.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The prototypical human γ-herpesviruses Epstein-Barr virus (EBV) and Kaposi Sarcoma-associated herpesvirus (KSHV) are involved in the development of malignancies. Like all herpesviruses, they share the establishment of latency, the typical architecture, and the conserved fusion machinery to initiate infection. The fusion machinery reflects virus-specific adaptations due to the requirements of the respective herpesvirus. For example, EBV evolved a tropism switch involving either the B- or epithelial cell-tropism complexes to activate fusion driven by gB. Most of the EBV entry proteins and their cellular receptors have been crystallized providing molecular details of the initial steps of infection. For KSHV, a variety of entry and binding receptors has also been reported but the mechanism how receptor binding activates gB-driven fusion is not as well understood as that for EBV. However, the downstream signaling pathways that promote the early steps of KSHV entry are well described. This review summarizes the current knowledge of the key players involved in EBV and KSHV entry and the cell-type specific mechanisms that allow infection of a wide variety of cell types.
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20
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Gao LM, Zhao S, Zhang WY, Wang M, Li HF, Lizaso A, Liu WP. Somatic mutations in KMT2D and TET2 associated with worse prognosis in Epstein-Barr virus-associated T or natural killer-cell lymphoproliferative disorders. Cancer Biol Ther 2019; 20:1319-1327. [PMID: 31311407 DOI: 10.1080/15384047.2019.1638670] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Affiliation(s)
- Li-Min Gao
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Sha Zhao
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Wen-Yan Zhang
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Mi Wang
- Department of Dermatology and Venerology, West China Hospital of Sichuan University, Chengdu, China
| | - Hui-Fang Li
- Cellular Biology Laboratory of Core Facility, West China Hospital of Sichuan University, Chengdu, China
| | - Anle Lizaso
- Department of Medicine, Burning Rock Biotech, Shanghai, China
| | - Wei-Ping Liu
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
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21
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Epstein-Barr virus incidental expression in bone marrow cells: a study of 230 consecutive bone marrow biopsy samples. Hum Pathol 2019; 88:60-65. [PMID: 30946931 DOI: 10.1016/j.humpath.2018.11.034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Revised: 11/19/2018] [Accepted: 11/30/2018] [Indexed: 11/20/2022]
Abstract
Epstein-Barr virus (EBV) is associated with many neoplastic hematologic conditions, but scattered EBV-positive cells can be detected in lymph nodes of healthy individuals and they usually represent latently infected lymphocytes. The incidence of EBV detection in normal bone marrow samples has not been studied and is largely unknown. The lack of knowledge regarding the true incidence of encountering bystander latent EBV-positive cells in the bone marrow may potentially lead to a diagnostic dilemma when assessing a staging bone marrow for a patient with an EBV-positive B or T/NK-cell lymphoma. The aim of our study was to investigate the rate of detection of EBV expression in bone marrow samples and correlate any positive findings with various clinical parameters including patient's age, sex, clinical history, immune status, and any neoplastic transformation if follow-up data are available. We retrospectively studied 230 consecutive bone marrow biopsies performed in 2013 and found 5 cases (2.17%) with scattered EBV-positive cells by in situ hybridization. The observed scattered EBV-positive cells are largely small in size and likely represent bystander, latently infected cells. The rate of detection of EBV-positive cells in the bone marrow appears to be slightly higher in immunodeficient individuals (3%) than in immunocompetent patients (1%).
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22
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Guan P, Chen Z, Chu L, Zhen L, Zhang L, Pan L, Liu W, Liu R. Extranodal NK/T-cell lymphoma in adolescents: imaging findings of a consecutive 7-year case series. J Int Med Res 2019; 47:1210-1220. [PMID: 30727780 PMCID: PMC6421368 DOI: 10.1177/0300060518822406] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Objectives Extranodal NK/T-cell lymphoma is reportedly a rare but emerging type of
lymphoma in adolescents. The present study was performed to specify its
imaging characteristics. Methods Our hospital’s picture archiving and communication systems were searched from
January 2009 to December 2016. We identified 13 patients aged <18 years
with pathologically confirmed extranodal NK/T-cell lymphoma in the head and
neck region. The computed tomography and magnetic resonance images were
reviewed to summarize the imaging characteristics of extranodal NK/T-cell
lymphoma in adolescents. Results The mean age at onset was 15.2 ± 1.46 years (range, 12–17 years) with a
male:female ratio of 1.17:1.00. Most of the patients (n = 10) displayed
nasal cavity and/or paranasal involvement. The tumor was homogeneous in both
computed tomography and magnetic resonance images and showed slight
enhancement. No calcification or liquefactive necrosis was observed.
Adjacent structures were usually involved. Conclusion Suggestive imaging characteristics could acquaint specialists with extranodal
NK/T-cell lymphoma in adolescents, facilitating improved early recognition
of the diagnosis and helping to improve the patient’s outcome.
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Affiliation(s)
- Pujun Guan
- 1 Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.,*These authors contributed equally to this work
| | - Zihang Chen
- 2 Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.,3 Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.,*These authors contributed equally to this work
| | - Lei Chu
- 1 Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Li Zhen
- 4 Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Li Zhang
- 3 Department of Hematology, West China Hospital, Sichuan University, Chengdu, China
| | - Ling Pan
- 3 Department of Hematology, West China Hospital, Sichuan University, Chengdu, China
| | - Weiping Liu
- 2 Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
| | - Rongbo Liu
- 1 Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
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23
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Kim WY, Montes-Mojarro IA, Fend F, Quintanilla-Martinez L. Epstein-Barr Virus-Associated T and NK-Cell Lymphoproliferative Diseases. Front Pediatr 2019; 7:71. [PMID: 30931288 PMCID: PMC6428722 DOI: 10.3389/fped.2019.00071] [Citation(s) in RCA: 90] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 02/21/2019] [Indexed: 12/14/2022] Open
Abstract
EBV-associated T and NK-cell lymphoproliferative diseases (EBV-T/NK LPDs) are characterized by the transformation and proliferation of EBV-infected T or NK cells. The 2016 revised World Health Organization classification recognizes the following EBV-positive lymphoproliferative disorders (LPD): chronic active EBV infection (CAEBV) of T- and NK-cell type (cutaneous and systemic forms), systemic EBV-positive T-cell lymphoma of childhood, aggressive NK-cell leukemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity primary EBV-positive nodal T/NK-cell lymphoma. EBV-associated hemophagocytic lymphohistiocytosis (HLH), although not included in the WHO classification because it is a reactive, inflammatory disease, is included in this review because it can be life-threatening and may have overlapping features with other EBV+ T/NK LPDs. EBV+ T/NK LPDs are rare diseases difficult to diagnose and manage properly, because some LPDs have unusual presentations, and discrepancies between clinical and histological findings might be encountered. Furthermore, EBV+ T/NK disorders share some clinico-pathological features, and may evolve into other categories during the clinical course, including malignant transformation of CAEBV. Here, we review the EBV+ T/NK LPDs in terms of their definitions, clinical features, histology, immunophenotype, molecular findings, and pathogenesis. This review aims to increase our understanding and awareness of the differential diagnosis among the different EBV+ T/NK LPDs. New insights into the genetic characteristics of these disorders will also be discussed.
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Affiliation(s)
- Wook Youn Kim
- Institute of Pathology and Neuropathology and Comprehensive Cancer Center Tübingen, University Hospital Tübingen, Eberhard-Karls-University, Tübingen, Germany.,Department of Pathology, Konkuk University School of Medicine, Seoul, South Korea
| | - Ivonne A Montes-Mojarro
- Institute of Pathology and Neuropathology and Comprehensive Cancer Center Tübingen, University Hospital Tübingen, Eberhard-Karls-University, Tübingen, Germany
| | - Falko Fend
- Institute of Pathology and Neuropathology and Comprehensive Cancer Center Tübingen, University Hospital Tübingen, Eberhard-Karls-University, Tübingen, Germany
| | - Leticia Quintanilla-Martinez
- Institute of Pathology and Neuropathology and Comprehensive Cancer Center Tübingen, University Hospital Tübingen, Eberhard-Karls-University, Tübingen, Germany
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24
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Wang YD, Wu LL, Ma LY, Shang XB, Li ZY, Wang W, Shen C, Yang JJ, Sun LX, Zhao CY. Chronic active EBV infection associated with NK cell lymphoma and hemophagocytic lymphohistiocytosis in a 27-year-old woman: A case report. Medicine (Baltimore) 2019; 98:e14032. [PMID: 30633196 PMCID: PMC6336602 DOI: 10.1097/md.0000000000014032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
RATIONALE Chronic active Epstein-Barr virus infection (CAEBV) is a common infectious disease that often affects multiple organs or systems. However, it is liable to be neglected and misdiagnosed owing to its insidious onset, lack of specific findings in the early phase, and a general lack of awareness among clinicians. PATIENT CONCERNS:: a 27-year-old woman case has been described who was initially misdiagnosed as drug-induced liver injury due to onset presentation of mild splenomegaly, recurrent liver dysfunction, and disputable pathological evidence of liver biopsy. DIAGNOSES CAEBV complicated with natural killer (NK) cell lymphoma and hemophagocytic lymphohistiocytosis (HLH) was diagnosed by in situ hybridization of liver tissue section with EBV-encoded RNA -1 probe and flow cytometry of bone marrow. INTERVENTIONS After admission, the patient received symptomatic treatment and antiviral therapy (combination of acyclovir and foscarnet sodium) as well as adjuvant treatment (thymosin alpha 1 and methylprednisolone); later, the patient received etoposide and dexamethasone for diagnosis of EBV associated HLH. Subsequently, the disease progressed to NK cell lymphoma and the patient received the revised EPOCH chemotherapy regimen [etoposide (100 mg/d, d1-5), dexamethasone (7.5 mg/d, d1-5; 5 mg/d, d6-14), cyclophosphamide (0.8 g/d, d1-2), and pegaspargase (3750 u/d, tid, d1-2)]. OUTCOMES Although the patient received a series of therapies and other comprehensive measures, finally she died of gastrointestinal hemorrhage and multiple organ failure. LESSONS Liver is one of the main target organs of EBV infection. In the clinical setting of unexplained fever and liver injury, it is necessary to be aware of CAEBV, as well as its fatal complication such as EBV associated NK cell lymphoma and HLH.
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Affiliation(s)
- Ya-Dong Wang
- Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang
| | - Ling-Ling Wu
- Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang
| | - Lu-Yuan Ma
- Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang
| | - Xiao-Bo Shang
- Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang
| | - Zi-Yue Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang
| | - Wei Wang
- Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang
| | - Chuan Shen
- Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang
| | - Jing-Jing Yang
- Department of Infectious Diseases, Nanpi County Hospital, Cangzhou
| | - Li-Xia Sun
- Department of Hematopathology, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China
| | - Cai-Yan Zhao
- Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang
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25
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Acute Epstein-Barr virus-positive cytotoxic T cell lymphoid hyperplasia in the upper aerodigestive tract, mimicking extranodal natural killer/T cell lymphoma, nasal type. Virchows Arch 2018; 474:219-226. [PMID: 30488123 DOI: 10.1007/s00428-018-2498-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 10/29/2018] [Accepted: 11/21/2018] [Indexed: 10/27/2022]
Abstract
To describe the clinicopathological features of nine patients with acute Epstein-Barr virus (EBV)-positive cytotoxic T cell lymphoid hyperplasia (EBV+TLH) in the upper aerodigestive tract, in which initial findings led to a preliminary misdiagnosis of extranodal NK/T cell lymphoma, nasal type (ENKTL). A series of nine cases of EBV+TLH in one Chinese institution over a 9-year interval was retrospectively analyzed. Median age was 16 years (range 5-29 years) with a M:F ratio of 5:4. All patients were previously healthy with an acute onset period of < 1 month. Six patients (66%) presented with masses or polypoid protrusions in the upper aerodigestive tract. Nasopharyngeal symptoms, cervical lymphadenopathy, and fever were found in 89%, 78%, and 56% of patients, respectively. In seven cases, morphology mainly showed small-sized irregular cells and in two cases medium-to-large cells. In all cases, the cells diffusely expressed cytoplasmic CD3 and at least one marker for cytotoxic granules, but were negative for CD56. CD5 expression was detected in eight cases (8/9, 89%). In all cases, double staining for CD3 and EBER indicated that most T cells were infected with EBV. T cell receptor gene rearrangement was performed in five cases and all showed polyclonal results. All patients achieved complete remission within 1 month after diagnosis without any chemoradiotherapy and were followed up 19-124 months without recurrent disease. EBV+TLH in the upper aerodigestive tract is occasionally observed in China. The histopathologic features of EBV+TLH can mimic ENKTL. EBV+TLH should be taken into consideration as a potential diagnosis when the disease duration is short, spontaneous remission is achieved without intervention, and when histology shows infiltration with EBV-infected T lymphocytes.
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26
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Fatal Septic Shock in a Patient with Hemophagocytic Lymphohistiocytosis Associated with an Infectious Mononucleosis. Case Rep Crit Care 2018; 2018:9756050. [PMID: 30356381 PMCID: PMC6176343 DOI: 10.1155/2018/9756050] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Accepted: 09/09/2018] [Indexed: 11/24/2022] Open
Abstract
The authors describe the case of a young woman who developed a clinical pictures resembling a septic shock-related multiple organ dysfunction syndrome a couple of months after having been diagnosed suffering from a hemophagocytic lymphohistiocytosis associated with an infectious mononucleosis. Despite the aggressive treatment, which included antibiotics, vasopressors, IV immunoglobulins, and the use of an extracorporeal device aimed to remove mediators released both during sepsis and the cytokine storm determined by the hemophagocytic lymphohistiocytosis, the patient died. At the autopsy, an extremely uncommon aggressive lymphoma of Epstein-Barr virus-positive T-lymphocytes with systemic involvement was discovered.
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27
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Epstein-Barr Virus Type 2 Infects T Cells and Induces B Cell Lymphomagenesis in Humanized Mice. J Virol 2018; 92:JVI.00813-18. [PMID: 30089703 DOI: 10.1128/jvi.00813-18] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 08/05/2018] [Indexed: 12/14/2022] Open
Abstract
Epstein-Barr virus (EBV) has been classified into two strains, EBV type 1 (EBV-1) and EBV type 2 (EBV-2) based on genetic variances and differences in transforming capacity. EBV-1 readily transforms B cells in culture while EBV-2 is poorly transforming. The differing abilities to immortalize B cells in vitro suggest that in vivo these viruses likely use alternative approaches to establish latency. Indeed, we recently reported that EBV-2 has a unique cell tropism for T cells, infecting T cells in culture and in healthy Kenyan infants, strongly suggesting that EBV-2 infection of T cells is a natural part of the EBV-2 life cycle. However, limitations of human studies hamper further investigation into how EBV-2 utilizes T cells. Therefore, BALB/c Rag2null IL2rγnull SIRPα humanized mice were utilized to develop an EBV-2 in vivo model. Infection of humanized mice with EBV-2 led to infection of both T and B cells, unlike infection with EBV-1, in which only B cells were infected. Gene expression analysis demonstrated that EBV-2 established a latency III infection with evidence of ongoing viral reactivation in both B and T cells. Importantly, EBV-2-infected mice developed tumors resembling diffuse large B cell lymphoma (DLBCL). These lymphomas had morphological features comparable to those of EBV-1-induced DLBCLs, developed at similar rates with equivalent frequencies, and expressed a latency III gene profile. Thus, despite the impaired ability of EBV-2 to immortalize B cells in vitro, EBV-2 efficiently induces lymphomagenesis in humanized mice. Further research utilizing this model will enhance our understanding of EBV-2 biology, the consequence of EBV infection of T cells, and the capacity of EBV-2 to drive lymphomagenesis.IMPORTANCE EBV is a well-established B cell-tropic virus. However, we have recently shown that the EBV type 2 (EBV-2) strain also infects primary T cells in culture and in healthy Kenyan children. This finding suggests that EBV-2, unlike the well-studied EBV-1 strain, utilizes the T cell compartment to persist. As EBV is human specific, studies to understand the role of T cells in EBV-2 persistence require an in vivo model. Thus, we developed an EBV-2 humanized mouse model, utilizing immunodeficient mice engrafted with human cord blood CD34+ stem cells. Characterization of the EBV-2-infected humanized mice established that both T cells and B cells are infected by EBV-2 and that the majority of infected mice develop a B cell lymphoma resembling diffuse large B cell lymphoma. This new in vivo model can be utilized for studies to enhance our understanding of how EBV-2 infection of T cells contributes to persistence and lymphomagenesis.
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Abstract
The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification. In this article, we review the definitions, morphology, pathogenesis, and evolving concepts of the various EBV-associated disorders including EBV+ diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), EBV+ mucocutaneous ulcer, DLBCL associated with chronic inflammation, fibrin-associated DLBCL, lymphomatoid granulomatosis, the EBV+ T and NK-cell LPD of childhood, aggressive NK leukaemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity of primary EBV+ nodal T- or NK-cell lymphoma. The current knowledge regarding the pathogenesis of B-cell lymphomas that can be EBV-associated including Burkitt lymphoma, plasmablastic lymphoma and classic Hodgkin lymphoma will be also explored.
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Tokoro S, Namiki T, Miura K, Watanabe K, Arai A, Imadome K, Yokozeki H. Chronic active Epstein-Barr virus infection with cutaneous lymphoproliferation: haemophagocytosis in the skin and haemophagocytic syndrome. J Eur Acad Dermatol Venereol 2017; 32:e116-e117. [PMID: 29024023 DOI: 10.1111/jdv.14640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- S Tokoro
- Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - T Namiki
- Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - K Miura
- Department of Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - K Watanabe
- Department of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - A Arai
- Department of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.,Department of Laboratory Molecular Genetics of Hematology, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
| | - K Imadome
- Department of Advanced Medicine for Infections, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo, 157-8535, Japan
| | - H Yokozeki
- Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan
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31
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Levoska MA, Cohen JI, Manoli I, Richard Lee CC, Ching SST, Shand J, Tamura D, Kraemer KH, DiGiovanna JJ. Recurrent scarring papulovesicular lesions on sun-exposed skin in a 22-year-old man. J Am Acad Dermatol 2017; 78:637-642. [PMID: 28964535 DOI: 10.1016/j.jaad.2017.08.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2017] [Revised: 07/28/2017] [Accepted: 08/03/2017] [Indexed: 12/12/2022]
Abstract
KEY TEACHING POINTS.
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Affiliation(s)
- Melissa A Levoska
- Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland; Medical Research Scholars Program, National Institutes of Health, Bethesda, Maryland
| | - Jeffrey I Cohen
- Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
| | - Irini Manoli
- Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
| | - Chyi-Chia Richard Lee
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Steven S T Ching
- Flaum Eye Institute, University of Rochester, Rochester, New York
| | - Jessica Shand
- Division of Pediatric Hematology-Oncology and Wilmot Cancer Center, University of Rochester, Rochester, New York
| | - Deborah Tamura
- Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Kenneth H Kraemer
- Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - John J DiGiovanna
- Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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Kim HJ, Ko YH, Kim JE, Lee SS, Lee H, Park G, Paik JH, Cha HJ, Choi YD, Han JH, Huh J. Epstein-Barr Virus-Associated Lymphoproliferative Disorders: Review and Update on 2016 WHO Classification. J Pathol Transl Med 2017; 51:352-358. [PMID: 28592786 PMCID: PMC5525035 DOI: 10.4132/jptm.2017.03.15] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 03/11/2017] [Accepted: 03/14/2017] [Indexed: 01/25/2023] Open
Abstract
Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.
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Affiliation(s)
- Hyun-Jung Kim
- Department of Pathology, Inje University, Sanggye Paik Hospital, Seoul, Korea
| | - Young Hyeh Ko
- Sungkyunkwan University, School of Medicine, Samsung Medical Center, Seoul, Korea
| | - Ji Eun Kim
- SMG-SNU Boramae Medical Center, Seoul National University, Seoul, Korea
| | | | - Hyekyung Lee
- Eulji University Hospital, Eulji University School of Medicine, Daejeon, Korea
| | - Gyeongsin Park
- Gangnam St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jin Ho Paik
- Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hee Jeong Cha
- Ulsan University Hospital, Ulsan University School of Medicine, Ulsan, Korea
| | - Yoo-Duk Choi
- Chonnam National University Hospital, Chonnam National University, Gwangju, Korea
| | | | - Jooryung Huh
- Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea
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Yang H, Fu G, Liu J, Da Z, Cheng X, Chen C, Li Y, Fu B, Li X. Clinical analysis of 42 cases of EBV-positive mature T/NK-cell neoplasms. Exp Ther Med 2017; 14:567-574. [PMID: 28672968 PMCID: PMC5488386 DOI: 10.3892/etm.2017.4531] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2015] [Accepted: 03/31/2017] [Indexed: 12/22/2022] Open
Abstract
The pathogenesis of Epstein-Barr virus-positive (EBV+) mature T-cell and natural killer (NK)-cell neoplasms is challenging to understand. The clinical features are diverse, with no typical manifestation. Therefore, it is important to analyze the association of the clinical characteristics and prognoses of patients with various factors associated with EBV+ T/NK-cell neoplasms, particularly extranodal NK/T cell lymphoma, systemic EBV+ T/NK cell lymphoproliferative disorders, aggressive NK cell leukemia and EBV+ peripheral T-cell lymphoma. Therefore, 42 cases of EBV+ T/NK-cell neoplasms with information on age, gender, fever, LDH level, complete blood count (CBC) and immunophenotype (CD5/CD20) were retrospectively analyzed to examine the clinical features, prognoses and related factors. It was found that patients ≤60 years old accounted for 86% of cases. The frequency of stage III/IV disease was higher in groups with pancytopenia (P=0.005), high LDH level (P=0.020), CD5-expression status (P=0.031) and fever (P=0.024). There were significant differences in the mean International Prognostic Index (IPI) scores according to the presence or absence of fever (P=0.022), elevated or normal lactose dehydrogenase (LDH) levels (P=0.001), and pancytopenia or normal complete blood count (CBC; P=0.046). Analysis of overall survival showed that CD5 expression, CBC, IPI scores and LDH levels were factors associated with OS. CD5 expression (P=0.003), CBC (P=0.003) and IPI scores (P=0.017) were identified to be important risk factors on the basis of Cox regression analysis. The mean survival time was longer in the CD5+, CD20+ and normal CBC groups, and there was no clear difference in survival time according to LDH level or fever. In summary, CD5 and CD20 may be prognostic factors in EBV+ T/NK lymphoid neoplasms, and CBC and fever are most likely to influence the IPI score and Ann Arbor stage.
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Affiliation(s)
- Haiyan Yang
- Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
| | - Gan Fu
- Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
| | - Jia Liu
- Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
| | - Zhenzhen Da
- Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
| | - Xiaoye Cheng
- Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
| | - Cong Chen
- Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
| | - Yan Li
- Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
| | - Bin Fu
- Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
| | - Xiaolin Li
- Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China
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Kim YJ, Choi SY, Lee WJ, Won CH, Chang SE, Choi JH, Lee MW. Two cases of hydroa vacciniforme-like lymphoproliferative disease controlled by anti-inflammatory agents. PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE 2017; 33:287-290. [PMID: 28543883 DOI: 10.1111/phpp.12318] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/18/2017] [Indexed: 11/28/2022]
Affiliation(s)
- Young Jae Kim
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sun Young Choi
- Department of Dermatology, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Woo Jin Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chong Hyun Won
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Eun Chang
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jee Ho Choi
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Mi Woo Lee
- Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Kyriakidis I, Vasileiou E, Karastrati S, Tragiannidis A, Gompakis N, Hatzistilianou M. Primary EBV infection and hypersensitivity to mosquito bites: a case report. Virol Sin 2017; 31:517-520. [PMID: 27900557 DOI: 10.1007/s12250-016-3868-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Ioannis Kyriakidis
- 2nd Department of Pediatrics, Medical School, Aristotle University of Thessaloniki, AHEPA General Hospital, Thessaloniki, 54636, Greece.
| | - Eleni Vasileiou
- 2nd Department of Pediatrics, Medical School, Aristotle University of Thessaloniki, AHEPA General Hospital, Thessaloniki, 54636, Greece
| | - Sofia Karastrati
- 2nd Department of Pediatrics, Medical School, Aristotle University of Thessaloniki, AHEPA General Hospital, Thessaloniki, 54636, Greece
| | - Athanasios Tragiannidis
- 2nd Department of Pediatrics, Medical School, Aristotle University of Thessaloniki, AHEPA General Hospital, Thessaloniki, 54636, Greece
| | - Nikolaos Gompakis
- 2nd Department of Pediatrics, Medical School, Aristotle University of Thessaloniki, AHEPA General Hospital, Thessaloniki, 54636, Greece
| | - Maria Hatzistilianou
- 2nd Department of Pediatrics, Medical School, Aristotle University of Thessaloniki, AHEPA General Hospital, Thessaloniki, 54636, Greece
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Xing Y, Yang J, Lian G, Chen S, Chen L, Li F. Chronic active Epstein-Barr virus infection associated with hemophagocytic syndrome and extra-nodal natural killer/T-cell lymphoma in an 18-year-old girl: A case report. Medicine (Baltimore) 2017; 96:e6845. [PMID: 28489771 PMCID: PMC5428605 DOI: 10.1097/md.0000000000006845] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Revised: 04/13/2017] [Accepted: 04/17/2017] [Indexed: 12/11/2022] Open
Abstract
RATIONALE Chronic active Epstein-Barr virus infection (CAEBV) associated with hemophagocytic syndrome (HPS) and extra-nodal natural killer (NK)/T-cell lymphoma (ENKL) is a rare life-threatening disorder. This disease is easily misdiagnosed because of its varied presentations. PATIENT CONCERNS An 18-year-old girl was admitted to our hospital with a history of edema in the lower limbs and intermittent fever lasting for more than 1 month. At admission, she had severe liver injury of unknown etiology. Laboratory test results revealed pancytopenia, hyperferritinemia, hypertriglyceridemia, and hypofibrinogenemia. Results of serologic tests for EBV were positive. Results of a skin biopsy indicated EBV-positive NK/T-cell lymphoma, and bone marrow aspiration revealed focal hemophagocytosis and atypical lymphoid cells. DIAGNOSIS On the basis of these findings, we diagnosed the case as extra-nodal NK/T-cell lymphoma-associated HPS (natural killer/T-cell lymphoma-associated hemophagocytic syndrome), which is commonly induced by CAEBV. INTERVENTIONS Treatment consisted of general management of hepatitis, supplemented with albumin and empirical antibiotic therapy. OUTCOMES The patient died from massive gastrointestinal hemorrhage a week after she was discharged from the hospital. LESSONS ENKL and HPS present with varied features and are generally fatal; therefore, clinicians should proceed with caution in suspected cases. HPS should be considered when the patient presents with fever, hepatosplenomegaly, pancytopenia, and liver failure. When HPS is suspected, clinicians should determine the underlying cause, such as severe infection, including infection with viruses such as EBV; genetic predisposition; or underlying malignancies, especially lymphoma because of its strong association with HPS.
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Washio K, Oka T, Abdalkader L, Muraoka M, Shimada A, Oda M, Sato H, Takata K, Kagami Y, Shimizu N, Kato S, Kimura H, Nishizaki K, Yoshino T, Tsukahara H. Gene expression analysis of hypersensitivity to mosquito bite, chronic active EBV infection and NK/T-lymphoma/leukemia. Leuk Lymphoma 2017; 58:2683-2694. [PMID: 28367723 DOI: 10.1080/10428194.2017.1304762] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
The human herpes virus, Epstein-Barr virus (EBV), is a known oncogenic virus and plays important roles in life-threatening T/NK-cell lymphoproliferative disorders (T/NK-cell LPD) such as hypersensitivity to mosquito bite (HMB), chronic active EBV infection (CAEBV), and NK/T-cell lymphoma/leukemia. During the clinical courses of HMB and CAEBV, patients frequently develop malignant lymphomas and the diseases passively progress sequentially. In the present study, gene expression of CD16(-)CD56(+)-, EBV(+) HMB, CAEBV, NK-lymphoma, and NK-leukemia cell lines, which were established from patients, was analyzed using oligonucleotide microarrays and compared to that of CD56brightCD16dim/- NK cells from healthy donors. Principal components analysis showed that CAEBV and NK-lymphoma cells were relatively closely located, indicating that they had similar expression profiles. Unsupervised hierarchal clustering analyses of microarray data and gene ontology analysis revealed specific gene clusters and identified several candidate genes responsible for disease that can be used to discriminate each category of NK-LPD and NK-cell lymphoma/leukemia.
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Affiliation(s)
- Kana Washio
- a Department of Pediatrics , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.,b Department of Pathology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Takashi Oka
- b Department of Pathology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Lamia Abdalkader
- b Department of Pathology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan.,c Department of Pathology, Faculty of Medicine , Mansoura University , Egypt
| | - Michiko Muraoka
- a Department of Pediatrics , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Akira Shimada
- a Department of Pediatrics , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Megumi Oda
- a Department of Pediatrics , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Hiaki Sato
- b Department of Pathology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Katsuyoshi Takata
- b Department of Pathology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Yoshitoyo Kagami
- d Division of Molecular Medicine , Aichi Cancer Center Research Institute , Nagoya , Japan
| | - Norio Shimizu
- e Department of Virology, Division of Virology & Immunology , Medical Research Institute, Tokyo Medical and Dental University , Tokyo , Japan
| | - Seiichi Kato
- f Department of Pathology and Laboratory Medicine , Nagoya University Hospital , Nagoya , Japan
| | - Hiroshi Kimura
- g Department of Virology , Nagoya University Graduate School of Medicine , Nagoya , Japan
| | - Kazunori Nishizaki
- h Department of Otorhinolaryngology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Tadashi Yoshino
- b Department of Pathology , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
| | - Hirokazu Tsukahara
- a Department of Pediatrics , Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences , Okayama , Japan
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Comprehensive assessment of peripheral blood TCRβ repertoire in infectious mononucleosis and chronic active EBV infection patients. Ann Hematol 2017; 96:665-680. [PMID: 28091735 DOI: 10.1007/s00277-016-2911-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Accepted: 12/22/2016] [Indexed: 10/20/2022]
Abstract
Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV+ LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection. Recently, high-throughput sequencing of the hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (T cell receptor β (TCRβ)) has emerged as a sensitive approach to assess the T cell repertoire. In this study, we fully characterized the diversity of peripheral blood TCRβ repertoire in IM (n = 6) and CAEBV patients (n = 5) and EBV-seropositive controls (n = 5). Compared with the healthy EBV-seropositive controls, both IM and CAEBV patients demonstrate a significant decrease in peripheral blood TCRβ repertoire diversity, basically, including narrowed repertoire breadth, highly expanded clones, and skewed CDR3 length distribution. However, there is no significant difference between IM and CAEBV patients. Furthermore, we observed some disease-related preferences in TRBV/TRBJ usage and combinations, as well as lots of T cell clones shared by different groups (unique or overlapped) involved in public T cell responses, which provide more detailed insights into the divergent disease evolution.
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Tamoto Y, Ishida R, Shiogama K, Kado H, Kamezaki M, Chinen Y, Matsumoto Y, Kusaba T, Konishi E, Tsutsumi Y, Tamagaki K. Extranodal NK/T-cell Lymphoma, Nasal Type Accompanied by PR3-ANCA-associated Glomerulonephritis. Intern Med 2017; 56:2007-2012. [PMID: 28768972 PMCID: PMC5577078 DOI: 10.2169/internalmedicine.56.8365] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
A 62-year-old man exhibiting nasal obstruction and glomerulonephritis with proteinase 3-antineutrophil cytoplasmic antibodies (PR3-ANCAs) was diagnosed with extranodal NK/T-cell lymphoma, nasal type (ENKL) with infiltration of neutrophils with apoptosis. Chemoradiotherapy reduced the tumor, improved the renal function, and decreased the PR3-ANCA levels. ANCA-positivity is observed in immunoinsufficient diseases, in which neutrophils lead to apoptosis and translocate intracellular granules, such as PR3, to the cell surface, triggering the production of ANCAs. In our case, the PR3-ANCA production was derived from the expression of PR3 on the cell surface of apoptotic neutrophils. This is the first report on ENKL describing the mechanism of ANCA development.
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Affiliation(s)
- Yuta Tamoto
- Division of Nephrology, Department of Medicine, Kyoto Prefectural University of Medicine, Japan
| | - Ryo Ishida
- Division of Nephrology, Department of Medicine, Kyoto Prefectural University of Medicine, Japan
| | - Kazuya Shiogama
- Department of Pathology, Fujita Health University School of Medicine, Japan
| | - Hiroshi Kado
- Division of Nephrology, Department of Medicine, Kyoto Prefectural University of Medicine, Japan
| | - Michitsugu Kamezaki
- Division of Nephrology, Department of Medicine, Kyoto Prefectural University of Medicine, Japan
| | - Yoshiaki Chinen
- Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Japan
| | - Yosuke Matsumoto
- Departments of Hematology and Laboratory Medicine, Aiseikai Yamashina Hospital, Japan
| | - Tetsuro Kusaba
- Division of Nephrology, Department of Medicine, Kyoto Prefectural University of Medicine, Japan
| | - Eiichi Konishi
- Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Japan
| | - Yutaka Tsutsumi
- Department of Pathology, Fujita Health University School of Medicine, Japan
| | - Keiichi Tamagaki
- Division of Nephrology, Department of Medicine, Kyoto Prefectural University of Medicine, Japan
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Ariizumi H, Sasaki Y, Harada H, Uto Y, Azuma R, Isobe T, Kishimoto K, Shiozawa E, Takimoto M, Ohike N, Mori H. Post-cytokine-release Salt Wasting as Inverse Tumor Lysis Syndrome in a Non-cerebral Natural Killer-cell Neoplasm. Intern Med 2017; 56:1855-1861. [PMID: 28717082 PMCID: PMC5548679 DOI: 10.2169/internalmedicine.56.8125] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The pathogenesis of cerebral/renal salt-wasting syndrome remains unknown. We herein present a case of salt-wasting syndrome with a natural killer-cell neoplasm without cerebral invasion. A 78-year-old man with hemophagocytic syndrome received two cycles of chemotherapy that did not induce tumor lysis syndrome, but repeatedly caused polyuria and natriuresis. The expression of tumor necrosis factor-α in the neoplasm led us to hypothesize that an oncolysis-induced cytokine storm may have caused renal tubular damage and salt wasting. Our theory may explain the pathogenic mechanism of cerebral/renal salt-wasting syndrome associated with other entities, including cerebral disorders, owing to the elevation of cytokine levels after subarachnoid hemorrhage.
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Affiliation(s)
| | - Yosuke Sasaki
- Department of Pathology, Showa University School of Medicine, Japan
| | - Hiroshi Harada
- Department of Hematology, Showa University Fujigaoka Hospital, Japan
| | - Yui Uto
- Department of Hematology, Showa University Fujigaoka Hospital, Japan
| | - Remi Azuma
- Department of Hematology, Showa University Fujigaoka Hospital, Japan
| | - Tomohide Isobe
- Department of Pathology, Showa University Fujigaoka Hospital, Japan
| | - Koji Kishimoto
- Department of Pathology, Showa University Fujigaoka Hospital, Japan
| | - Eisuke Shiozawa
- Department of Pathology, Showa University School of Medicine, Japan
| | | | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Japan
| | - Hiraku Mori
- Department of Hematology, Showa University Fujigaoka Hospital, Japan
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Abstract
This article will focus on the cutaneous lymphoproliferative disorders associated with EBV, with an emphasis on the upcoming changes in the revised 4th Edition of the WHO classification of tumors of the hematopoietic system, many of which deal with cutaneous disorders derived from NK-cells or T-cells. Extranodal NK/T-cell lymphoma usually presents in the upper aerodigestive tract, but can involve the skin secondarily. EBV-associated T- and NK-cell lymphoproliferative disorders (LPD) in the pediatric age group include the systemic diseases, chronic active EBV infection (CAEBV) and systemic EBV+ T-cell lymphoma of childhood. Hydroa vacciniforme (HV)-like LPD is a primarily cutaneous form of CAEBV and encompasses the lesions previously referred to as HV and HV-like lymphoma (HVLL). All the T/NK-cell-EBV-associated diseases occur with higher frequency in Asians, and indigenous populations from Central and South America and Mexico. Among the B-cell EBV-associated LPD two major changes have been introduced in the WHO. The previously designated EBV-positive diffuse large B-cell lymphoma (EBV-DLBCL) of the elderly, has been changed to EBV-DLBCL with 'not otherwise specified' as a modifier (NOS). A new addition to the WHO system is the more recently identified EBV+ mucocutaneous ulcer, which involves skin and mucosal-associated sites.
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Affiliation(s)
- Alejandro A Gru
- Pathology & Dermatology, Hematopathology and Dermatopathology Sections, University of Virginia, Charlottesville, VA, USA.
| | - Elaine S Jaffe
- Hematopathology, National Cancer Institute (NCI), Bethesda, MD, USA
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Chen CC, Chang KC, Medeiros LJ, Lee JYY. Hydroa vacciniforme and hydroa vacciniforme-like T-cell lymphoma: an uncommon event for transformation. J Cutan Pathol 2016; 43:1102-1111. [DOI: 10.1111/cup.12801] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Revised: 05/02/2016] [Accepted: 08/08/2016] [Indexed: 01/06/2023]
Affiliation(s)
- Chien-Chin Chen
- Department of Pathology; Chia-Yi Christian Hospital; Chia-Yi Taiwan
- Department of Cosmetic Science; Chia Nan University of Pharmacy and Science; Tainan Taiwan
| | - Kung-Chao Chang
- Department of Pathology, College of Medicine; National Cheng Kung University and Hospital; Tainan Taiwan
| | - L. Jeffrey Medeiros
- Department of Hematopathology; The University of Texas MD Anderson Cancer Center; Houston TX USA
| | - Julia Yu-Yun Lee
- Department of Dermatology, College of Medicine; National Cheng Kung University and Hospital; Tainan Taiwan
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Cytotoxic Molecule-positive Epstein-Barr Virus-associated Peripheral T-cell Lymphoma in a 20-Month-old Child: A Case Report and Review of the Literature. J Pediatr Hematol Oncol 2015; 37:e475-80. [PMID: 26056791 DOI: 10.1097/mph.0000000000000368] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Peripheral T-cell lymphoma (PTCL) is rare in children. Expression of cytotoxic molecules (CM) in nodal PTCL has unique clinicopathologic features, including an Epstein-Barr virus (EBV) association. However, CM+, EBV-associated PTCL is extremely rare in the childhood, with only 1 study having been reported to date, including both pediatric and adult patients. We report a case of CM+ PTCL in a 20-month-old boy with left neck lymphadenopathy as well as multiple visceral lesions. A biopsied lymph node was diffusely infiltrated by atypical lymphoid cells with a CD4/CD8, granzyme B+, perforin+, and TIA-1+ phenotype, and EBV positivity by in situ hybridization. Rearrangements of the TCR γ-chain and β-chain genes were demonstrated by polymerase chain reaction. Ancillary genetic studies detected trisomy 2, trisomy 10, a structurally abnormal 6p, and additional copies of the IRF4 gene. Multiple bone marrow biopsies failed to show any evidence of tumor, histiocytic hyperplasia, or hemophagocytosis. This lesion was therefore diagnosed as "CM+, EBV-associated high-grade peripheral T-cell lymphoma." After 5 cycles of chemotherapy, the patient was in remission 8 months following initial diagnosis. To our knowledge, this represents the youngest child with this rare tumor in the published literature, and showing an unusually favorable initial response to therapy.
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Hong M, Ko YH. CD30-Positive T-Cell Lymphoproliferative Disease of the Oral Mucosa in Children: A Manifestation of Epstein-Barr Virus-Associated T-Lymphoproliferative Disorder. J Pathol Transl Med 2015; 49:525-30. [PMID: 26420252 PMCID: PMC4696526 DOI: 10.4132/jptm.2015.07.13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2015] [Revised: 07/10/2015] [Accepted: 07/13/2015] [Indexed: 12/24/2022] Open
Abstract
Eosinophilic ulcer of the oral mucosa (EUOM) is a very rare, benign, self-limiting ulcerative lesion of the oral cavity of unknown pathogenesis, and belongs to the same spectrum of CD30+ T-cell lymphoproliferative disease (LPD) of the oral mucosa. The etiology and pathogenesis of the disease are unknown. We report two cases in children who were initially diagnosed with EUOM and CD30+ T-cell LPD, respectively. However, retrospective analysis revealed that a majority of infiltrated atypical T cells were positive for Epstein-Barr virus (EBV). The present cases suggest that the pathogenesis and etiology of EUOM or CD30+ T-cell LPD occurring in children are different from those in adults. EUOM or CD30+ T-cell LPD in children is a manifestation of EBV-positive T-cell LPD, and should therefore be distinguished from the disease in adults.
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Affiliation(s)
- Mineui Hong
- Department of Pathology, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Young Hyeh Ko
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Sakakibara Y, Wada T, Muraoka M, Matsuda Y, Toma T, Yachie A. Basophil activation by mosquito extracts in patients with hypersensitivity to mosquito bites. Cancer Sci 2015; 106:965-71. [PMID: 25990049 PMCID: PMC4556384 DOI: 10.1111/cas.12696] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 05/10/2015] [Accepted: 05/14/2015] [Indexed: 01/09/2023] Open
Abstract
Hypersensitivity to mosquito bites (HMB) is a cutaneous disorder belonging to the group of Epstein-Barr virus (EBV)-associated T/natural killer (NK)-cell lymphoproliferative diseases, and is primarily mediated by EBV-infected NK cells. It is characterized by intense local skin reactions accompanied by general symptoms after mosquito bites, and infiltration of EBV-infected NK cells into the bite sites. However, the mechanisms underlying these reactions have not been fully examined. We recently described the activation of circulating basophils by mosquito extracts in vitro in a patient with HMB. To further investigate this finding, we studied four additional patients with HMB. All patients showed typical clinical features of HMB after mosquito bites and they had NK lymphocytosis and high peripheral blood EBV DNA loads. We found evidence of EBV infection in NK cells through in situ hybridization that detected EBV-encoded small RNA-1, and flow cytometry showed HLA-DR expression on almost all NK cells. Basophil activation tests with the extracts of epidemic mosquitoes Culex pipiens pallens and Aedes albopictus showed positive responses to one or both extracts in all samples from patients with HMB, suggesting the presence of mosquito antigen-specific IgE and its binding to basophils. In particular, the extract of Aedes albopictus was able to activate basophils in all available patient samples. These results indicate that basophils and/or mast cells activated by mosquito bites may be involved in initiation and development of severe skin reactions to mosquito bites in HMB.
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Affiliation(s)
- Yasuhisa Sakakibara
- Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
| | - Taizo Wada
- Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
| | - Masahiro Muraoka
- Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
| | - Yusuke Matsuda
- Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
| | - Tomoko Toma
- Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
| | - Akihiro Yachie
- Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan
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Serrão T, Dias A, Nunes P, Figueiredo A. An uncommon presentation of EBV-driven HLH. Primary or secondary? An ongoing dilemma. BMJ Case Rep 2015; 2015:bcr-2015-209615. [PMID: 25948855 DOI: 10.1136/bcr-2015-209615] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Abstract
Haemophagocytic lymphohistiocytosis (HLH) is a potentially fatal syndrome, mainly characterised by dysregulated immune activation. The syndrome is related to a genetic cause, in the classic primary form, or to identified triggers such as infections, malignancy or rheumatological processes, in the classic secondary form. Epstein-Barr virus (EBV) is the most common agent implicated in hereditary and non-hereditary conditions. We describe a 23-month-old girl who experienced severe clinical deterioration with respiratory distress due a bilateral pleural effusion within the first week of primary EBV infection. Fever, generalised oedema and hepatosplenomegaly, along with a pruritic morbilliform erythematous rash, were the first clinical signs. Respiratory impairment followed with hypoxaemia and the patient was admitted to the intensive care unit for thoracocentesis. Further investigation showed persistent bicytopaenia, hypertriglyceridaemia, hyperferritinaemia and elevated α chain of interleukin-2 receptor (sCD25). Diagnostic criteria for HLH were fulfilled. Therapy was instituted with dexamethasone, ciclosporin A and intravenous immunoglobulin 6 days after admission with progressive clinical recovery.
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Affiliation(s)
- Tânia Serrão
- Hospital Dona Estefânia. Centro Hospitalar Lisboa Central, Lisbon, Portugal
| | - Alexandra Dias
- Department of Paediatric Unit, Hospital Fernando Fonseca, Amadora, Portugal
| | - Pedro Nunes
- Department of Intensive Care Unit, Hospital Fernando Fonseca, Amadora, Portugal
| | - António Figueiredo
- Department of Paediatric Unit, Hospital Fernando Fonseca, Amadora, Portugal
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47
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Affiliation(s)
- Young-Hyeh Ko
- Samsung Medical Center, Department of Pathology, Sungkyunkwan University School of Medicine, Seoul, Korea
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48
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Epstein-Barr virus type 2 latently infects T cells, inducing an atypical activation characterized by expression of lymphotactic cytokines. J Virol 2014; 89:2301-12. [PMID: 25505080 DOI: 10.1128/jvi.03001-14] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
UNLABELLED Epstein-Barr virus (EBV) is a well-established B-cell-tropic virus associated with various lymphoproliferative diseases of both B-cell and non-B-cell origin. EBV is associated with a number of T-cell lymphomas; however, in vitro studies utilizing prototypical EBV type 1 (EBV-1) laboratory strains have generally failed to readily infect mature T cells in culture. The difficulties in performing in vitro T-cell experiments have left questions regarding the role of EBV in the pathogenesis of EBV-positive T-cell lymphoproliferative diseases largely unresolved. We report here that the EBV type 2 (EBV-2) strain displays a unique cell tropism for T cells. In remarkable contrast to EBV-1, EBV-2 readily infects primary T cells in vitro, demonstrating a propensity for CD8(+) T cells. EBV-2 infection of purified T cells results in expression of latency genes and ultimately leads to T-cell activation, substantial proliferation, and profound alteration of cytokine expression. The pattern of cytokine production is strikingly skewed toward chemokines with roles in lymphocyte migration, demonstrating that EBV-2 has the ability to modulate normal T-cell processes. Collectively, these novel findings identify a previously unknown cell population potentially utilized by EBV-2 to establish latency and lay the foundation for further studies to elucidate the role of EBV in the pathogenesis of T-cell lymphoproliferative diseases. IMPORTANCE The ability of EBV to infect T cells is made apparent by its association with a variety of T-cell lymphoproliferative disorders. However, studies to elucidate the pathogenic role of EBV in these diseases have been limited by the inability to conduct in vitro T-cell infection experiments. Here, we report that EBV-2 isolates, compromised in the capacity to immortalize B cells, infect CD3(+) T cells ex vivo and propose a working model of EBV-2 persistence where alteration of T-cell functions resulting from EBV-2 infection enhances the establishment of latency in B cells. If indeed EBV-2 utilizes T cells to establish a persistent infection, this could provide one mechanism for the association of EBV with T-cell lymphomas. The novel finding that EBV-2 infects T cells in culture will provide a model to understand the role EBV plays in the development of T-cell lymphomas.
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49
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Iwatsuki K, Hamada T. Current therapy of choice for cutaneous lymphomas: Complementary to the Japanese Dermatological Association/Japanese Skin Cancer Society guidelines. J Dermatol 2014; 41:43-9. [DOI: 10.1111/1346-8138.12346] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2013] [Accepted: 10/21/2013] [Indexed: 11/26/2022]
Affiliation(s)
- Keiji Iwatsuki
- Departments of Dermatology; Okayama University Graduate; School of Medicine, Dentistry and Pharmaceutical Sciences; Okayama Japan
| | - Toshihisa Hamada
- Departments of Dermatology; Okayama University Graduate; School of Medicine, Dentistry and Pharmaceutical Sciences; Okayama Japan
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