Epstein-Barr virus-related lymphoproliferative disorders of the skin
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Epstein Barr Virus (EBV) is associated both solid (nasopharyngeal carcinoma, non-nasopharyngeal lymphoepithelioma- like carcinoma, gastric carcinoma, leiomyosarcoma) and hematolymphoid malignancies, some of the latter, however, spanning over a spectrum ranging from reactive and self-limiting to severe and life-threatening conditions. This review will focus on the disorder most commonly involving the skin, namely: EBVpositive mucocutaneous ulcer; lymphomatoid granulomatosis; EBV-positive diffuse large B cell lymphoma; plasmablastic lymphoma; post-transplant lymphoproliferative disorder; extranodal NK/T cell lymphoma, nasal type; angoimmunoblastic T cell lymphoma; severe mosquito bite allergy; hydroa vacciniformelike lymphoproliferative disorder. Given the uncommon occurrence of all these infiltrates in the skin, multidisciplinary approach, as well as referral to tertiary care centers are always advisable.
Plaza JA, Gru AA, Sangueza OP, et al. An update on viralinduced cutaneous lymphoproliferative disorders. CME Part I. J Am Acad Dermatol 2023;88:965-80. DOI: https://doi.org/10.1016/j.jaad.2021.11.068
Dunmire SK, Hogquist KA, Balfour HH. Infectious Mononucleosis. Curr Top Microbiol Immunol 2015;390:211-40. DOI: https://doi.org/10.1007/978-3-319-22822-8_9
Smith NA, Coleman CB, Gewurz BE, Rochford R. CD21 (complement receptor 2) is the receptor for Epstein-Barr virus entry into T Cells. J Virol 2020;94:e00428-20. DOI: https://doi.org/10.1128/JVI.00428-20
Murata T, Sugimoto A, Inagaki T, et al. Molecular basis of Epstein-Barr Virus latency establishment and lytic reactivation. Viruses 2021;23:13:2344. DOI: https://doi.org/10.3390/v13122344
Yin H, Qu J, Peng Q, Gan R. Molecular mechanisms of EBVdriven cell cycle progression and oncogenesis. Med Microbiol Immunol 2019;208:573-83. DOI: https://doi.org/10.1007/s00430-018-0570-1
Gru AA, Jaffe ES. Cutaneous EBV-related lymphoproliferative disorders. Semin Diagn Pathol 2017;34:60-75. DOI: https://doi.org/10.1053/j.semdp.2016.11.003
Jaffe ES. Navigating the cutaneous B-cell lymphomas: avoiding the rocky shoals. Mod Pathol 2020;33:96-106. DOI: https://doi.org/10.1038/s41379-019-0385-7
Gulley ML, Tang W. Laboratory assays for Epstein-Barr virus-related disease. J Mol Diagn 2008; 10:279-92. DOI: https://doi.org/10.2353/jmoldx.2008.080023
Roe CJ, Siddiqui MT, Lawson D, Cohen C. RNA in situ hybridization for Epstein-Barr virus and cytomegalovirus: comparison with in situ hybridization and immunohistochemistry. Appl Immunohistochem Mol Morphol 2019;27:155-9. DOI: https://doi.org/10.1097/PAI.0000000000000568
Quintanilla-Martinez L, Swerdlow SH, Tousseyn T, et al. New concepts in EBV-associated B, T, and NK cell lymphoproliferative disorders. Virchows Arc. 2023;482:227-44. DOI: https://doi.org/10.1007/s00428-022-03414-4
Dojcinov SD, Quintanilla-Martinez L. How I diagnose EBVpositive B- and T-cell lymphoproliferative disorders. Am J Clin Pathol 2023;159:14-33. DOI: https://doi.org/10.1093/ajcp/aqac105
Giraldo CN, Lynch DT. EBV positive mucocutaneous ulcer. In: StatPearls. Treasure Island (FL): StatPearls Publishing.
Ikeda T, Gion Y, Nishimura Y, et al. Epstein-Barr virus-positive mucocutaneous ulcer: a unique and curious disease entity. Int J Mol Sci 2021;22:1053. DOI: https://doi.org/10.3390/ijms22031053
Ikeda T, Gion Y, Sakamoto M, et al. Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer. Mod Pathol 2020;33:2437-48. DOI: https://doi.org/10.1038/s41379-020-0599-8
Ohata Y, Tatsuzawa A, Ohyama Y, et al. A distinctive subgroup of oral EBV+ B-cell neoplasm with polymorphous features is potentially identical to EBV+ mucocutaneous ulcer. Hum Pathol 2017;69:129-39. DOI: https://doi.org/10.1016/j.humpath.2017.09.013
Melani C, Jaffe ES, Wilson WH. Pathobiology and treatment of lymphomatoid granulomatosis, a rare EBV-driven disorder. Blood 2020;135:1344-52. DOI: https://doi.org/10.1182/blood.2019000933
Beaty MW, Toro J, Sorbara L, et al. Cutaneous lymphomatoid granulomatosis: correlation of clinical and biologic features. Am J Surg Pathol 2001;25:1111-20. DOI: https://doi.org/10.1097/00000478-200109000-00001
Colby TV. Current histological diagnosis of lymphomatoid granulomatosis. Mod Pathol 2012; 25:S39-42. DOI: https://doi.org/10.1038/modpathol.2011.149
Frances C, Du LT, Piette JC, et al. Wegener’s granulomatosis. Dermatological manifestations in 75 cases with clinicopathologic correlation. Arch Dermatol 1994;130:861-7. DOI: https://doi.org/10.1001/archderm.130.7.861
Vermeesch J, Ramirez J, Lafond A. Primary cutaneous Epstein-Barr virus-positive diffuse large B-cell lymphoma: a rare and aggressive cutaneous lymphoma. Cutis 2018;102:421-4.
Ross AM, Leahy CI, Neylon F, et al. Epstein-Barr virus and the pathogenesis of diffuse large B-cell lymphoma. Life (Basel) 2023;13:521. DOI: https://doi.org/10.3390/life13020521
Frontzek F, Staiger AM, Wullenkord R, et al. Molecular profiling of EBV associated diffuse large B-cell lymphoma. Leukemia 2023;37:670-9. DOI: https://doi.org/10.1038/s41375-022-01804-w
Bourbon E, Maucort-Boulch D, Fontaine J, et al. Clinicopathological features and survival in EBV-positive diffuse large B-cell lymphoma not otherwise specified. Blood Adv 2021;5:3227-39. DOI: https://doi.org/10.1182/bloodadvances.2021004515
Chikeka I, Grossman M, Deng C, et al. Plasmablastic lymphoma in an HIV patient with cutaneous presentation: a case of remarkable remission in a typically refractory disease. JAAD Case Rep 2020;6:161-5. DOI: https://doi.org/10.1016/j.jdcr.2019.11.007
Bailly J, Jenkins N, Chetty D, et al. Plasmablastic lymphoma: an update. Int J Lab Hematol 2022;44:54-63. Erratum in: Int J Lab Hematol 2022;44:1121. DOI: https://doi.org/10.1111/ijlh.13863
Castillo JJ, Bibas M, Miranda RN. The biology and treatment of plasmablastic lymphoma. Blood 2015;125:2323-30. DOI: https://doi.org/10.1182/blood-2014-10-567479
Ferreira MCC, Arai Seque C, Enokihara MMSES, et al. Posttransplant lymphoproliferative disorder with cutaneous involvement: a series of four cases. Clin Transplant 2021;35:e14162. DOI: https://doi.org/10.1111/ctr.14162
Burns DM, Chaganti S. Epstein-Barr virus-associated lymphoproliferative disorders in immunosuppressed patients. Ann Lymphoma 2021;5:24. DOI: https://doi.org/10.21037/aol-20-42
Hue SS, Oon ML, Wang S, et al. Epstein-Barr virus-associated T- and NK-cell lymphoproliferative diseases: an update and diagnostic approach. Pathology 2020;52:111-27. DOI: https://doi.org/10.1016/j.pathol.2019.09.011
King RL, Khurana A, Mwangi R, et al. Clinicopathologic characteristics, treatment, and outcomes of post-transplant lymphoproliferative disorders: a single-institution experience using 2017 WHO diagnostic criteria. Hemasphere 2021;5:e640. DOI: https://doi.org/10.1097/HS9.0000000000000640
Kimura H, de Leval L, Cai Q, Kim WS. EBV-associated NK and T-cell lymphoid neoplasms. Curr Opin Oncol 2022;34:422-31. DOI: https://doi.org/10.1097/CCO.0000000000000889
Vasconcelos Pd, Ferreira C, Soares-Almeida L, Filipe P. Multifocal primary cutaneous extranodal NK/T lymphoma nasal type. An Bras Dermatol 2016;91:219-21. DOI: https://doi.org/10.1590/abd1806-4841.20164090
Ngamdamrongkiat P, Sukpanichnant S, Chairatchaneeboon M, et al. Cutaneous involvement of extranodal NK/T cell lymphoma, nasal type, a clinical and histopathological mimicker of various skin diseases. Dermatopathology (Basel) 2022;9:307-20. DOI: https://doi.org/10.3390/dermatopathology9030037
Kim H, Ko YH. The Pathologic and genetic characteristics of extranodal NK/T-Cell Lymphoma. Life (Basel). 2022;12:73. DOI: https://doi.org/10.3390/life12010073
Chiba S, Sakata-Yanagimoto M. Advances in understanding of angioimmunoblastic T-cell lymphoma. Leukemia 2020;34:2592-606. DOI: https://doi.org/10.1038/s41375-020-0990-y
Oishi N, Sartori-Valinotti JC, Bennani NN, et al. Cutaneous lesions of angioimmunoblastic T-cell lymphoma: clinical, pathological, and immunophenotypic features. J Cutan Pathol 2019;46:637-44. DOI: https://doi.org/10.1111/cup.13475
Advani RH, Skrypets T, Civallero M, et al. Outcomes and prognostic factors in angioimmunoblastic T-cell lymphoma: final report from the international T-cell Project. Blood 2021;138:213-20. DOI: https://doi.org/10.1182/blood.2020010387
Yamada M, Ishikawa Y, Imadome KI. Hypersensitivity to mosquito bites: a versatile Epstein-Barr virus disease with allergy, inflammation, and malignancy. Allergol Int 2021;70:430-8. DOI: https://doi.org/10.1016/j.alit.2021.07.002
Kondo M, Mizutani M, Yamanaka K. Mosquito bite-induced localized NK/T-cell lymphoma relapsed in a patient with complete remission of extranodal NK/T-cell lymphoma, nasal type. Case Rep Dermatol 2019;11:194-7. DOI: https://doi.org/10.1159/000501358
Ordoñez-Parra J, Mejía Cortes M, Tamayo-Buendía MM, Infante Gómez AM. Hydroa vacciniforme-like lymphoproliferative disorder (HV-LPD) is an Epstein-Barr virus (EBV) associated disease. An Bras Dermatol 2021;96:388-90. DOI: https://doi.org/10.1016/j.abd.2020.06.023
Chen CC, Chang KC, Medeiros LJ, Lee JY. Hydroa vacciniforme and hydroa vacciniforme-like lymphoproliferative disorder: a spectrum of disease phenotypes associated with ultraviolet irradiation and chronic Epstein-Barr virus infection. Int J Mol Sci 2020;21:9314. DOI: https://doi.org/10.3390/ijms21239314
Rice AS, Bermudez R. Hydroa Vacciniforme. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023.
Chang L, Zhang C, Lu J, et al. Clinical and pathological features of hydroa vacciniforme-like lymphoproliferative disorder along with risk factors indicating poor prognosis. Infect Drug Resist 2023;16:1545-59. DOI: https://doi.org/10.2147/IDR.S402040
Copyright (c) 2024 the Author(s)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.