{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:07:26Z","timestamp":1785150446871,"version":"3.55.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Human T-lymphotropic virus type-1 (HTLV-1) is endemic in some countries, including Brazil. HTLV-1 is the etiological agent of adult T-cell leukemia-lymphoma (ATLL), a rare and aggressive CD4+ T-lymphocyte malignancy. ATLL affects 1\u20135% of virus carriers. Dermatological involvement occurs in 40\u201370%. Diagnosis is based on clinicopathologic correlation and HTLV-1 serology. There are few therapeutic options so far.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is an observational retrospective cohort study with ATLL patients followed in a tertiary hospital in S\u00e3o Paulo, Brazil. Data were collected at diagnosis. Survival curves using the Kaplan\u2013Meier method were analyzed with log-rank test, univariate and multivariate analyses were performed with the Cox proportional hazards model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Forty-four patients were studied, 24 females (54.5%), and 20 males (45.5%). The median age at diagnosis was 59.4\u202fyears. Classification at diagnosis was: 16 (36.4%) chronic (93.7% unfavorable, 6.2% favorable), 14 (31.8%) acute, 10 (22.7%) smoldering, four (9.1%) lymphoma, and none with primary cutaneous tumoral. Regarding skin lesions, 18 (40.9%) had plaques; 15 (34.1%) nodules\/tumors; 11 (25.0%) papules; 10 (22.7%) erythroderma; seven (15.9%) patches; two (4.5%) ichthyosis; one (2.3%) purpuric lesions. Epidermotropism\/exocytosis of lymphocytes was observed in 25 patients (62.5%), and Pautrier microabscesses in three (7.3%). Four patients (10.0%) had subcutaneous involvement, two (5.0%) folliculotropism, two (5.0%) angiocentrism, and one (2.5%) perineural involvement. Ten patients (25.0%) presented a lichenoid pattern. Thirty-four patients (79.1%) had increased lactate dehydrogenase; 20 (45.5%) lymphocytosis; six (13.6%) flower cells in peripheral blood; six (14.6%) hypercalcemia; five (12.2%) hypoalbuminemia. Beta-2 microglobulin was increased in all 24 cases investigated. Monoclonal T-lymphocytes were observed in the blood of 23 patients (76.7%) and the skin of 19 (76.0%). Thirty patients (68.2%) died. Median overall survival was 32.3\u202fmonths. Acute and chronic unfavorable forms had worse prognoses, with median overall survival of 23.3 and 34.1\u202fmonths, respectively (<jats:italic>p<\/jats:italic>\u202f=\u202f0.0011). After multivariate analysis, Shimoyama classification (acute) and urea levels were associated with poorer prognoses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We described a large Brazilian cohort of ATLL with cutaneous involvement. Description of clinical, pathology, laboratory, and follow-up data, and factors associated with poorer survival is essential to provide better care and to improve the quality of life of these patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1505865","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T08:59:58Z","timestamp":1738918798000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Characterization of adult T-cell leukemia\/lymphoma patients with specific skin lesions in a tertiary dermatological service in Brazil"],"prefix":"10.3389","volume":"12","author":[{"given":"Mariana","family":"Valente","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Sanches","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youko","family":"Nukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade","family":"Cury-Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno Castro","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Miyashiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1089\/aid.1993.9.381","article-title":"An HTLV-I vaccine: why, how, for whom?","volume":"9","author":"de The","year":"1993","journal-title":"AIDS Res Hum Retrovir"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"388","DOI":"10.3389\/fmicb.2012.00388","article-title":"Epidemiological aspects and world distribution of HTLV-1 infection","volume":"3","author":"Gessain","year":"2012","journal-title":"Front Microbiol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1128\/JVI.01522-06","article-title":"GLUT1 is not the primary binding receptor but is associated with cell-to-cell transmission of human T-cell leukemia virus type 1","volume":"81","author":"Takenouchi","year":"2007","journal-title":"J Virol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"931","DOI":"10.4049\/jimmunol.180.2.931","article-title":"Tax-inducible production of CC chemokine ligand 22 by human T cell leukemia virus type 1 (HTLV-1)-infected T cells promotes preferential transmission of HTLV-1 to CCR4-expressing CD4+ T cells","volume":"180","author":"Hieshima","year":"2008","journal-title":"J Immunol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"404","DOI":"10.4269\/ajtmh.2002.66.404","article-title":"Molecular epidemiology of human T lymphotropic virus type 1 transmission in Okinawa, Japan","volume":"66","author":"Kakuda","year":"2002","journal-title":"Am J Trop Med Hyg"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1126\/science.2992082","article-title":"The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats","volume":"229","author":"Felber","year":"1985","journal-title":"Science"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1126\/science.6330891","article-title":"Trans-acting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells","volume":"225","author":"Sodroski","year":"1984","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1146\/annurev.immunol.15.1.15","article-title":"Human T cell leukemia virus type I (HTLV-I) and human diseases","volume":"15","author":"Uchiyama","year":"1997","journal-title":"Annu Rev Immunol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1182\/blood.V50.3.481.481","article-title":"Adult T-cell leukemia: clinical and hematologic features of 16 cases","volume":"50","author":"Uchiyama","year":"1977","journal-title":"Blood"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1182\/blood-2018-11-881268","article-title":"The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas","volume":"133","author":"Willemze","year":"2019","journal-title":"Blood"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s11864-014-0321-5","article-title":"Incidence of adult T-cell leukemia\/lymphoma in nonendemic areas","volume":"16","author":"Yoshida","year":"2015","journal-title":"Curr Treat Options in Oncol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1097\/00126334-200312150-00013","article-title":"HTLV-I in the general population of Salvador, Brazil: a city with African ethnic and sociodemographic characteristics","volume":"34","author":"Dourado","year":"2003","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e0171303","DOI":"10.1371\/journal.pone.0171303","article-title":"HTLV-1 is predominantly sexually transmitted in Salvador, the city with the highest HTLV-1 prevalence in Brazil","volume":"12","author":"Nunes","year":"2017","journal-title":"PLoS One"},{"key":"ref15","first-page":"25","article-title":"Secretaria de Vigil\u00e2ncia em Sa\u00fade. Preval\u00eancia da infec\u00e7\u00e3o por HTLV-1\/2 no Brasil","volume":"51","year":"2020","journal-title":"Boletim Epidemiol\u00f3gico"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/0140-6736(90)92432-H","article-title":"Adult T-cell leukaemia\/lymphoma in Brazil and its relation to HTLV-I","volume":"336","author":"de Oliveira","year":"1990","journal-title":"Lancet"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1002\/ijc.2910430214","article-title":"Modelling the risk of adult T-cell leukemia\/lymphoma in persons infected with human T-lymphotropic virus type I","volume":"43","author":"Murphy","year":"1989","journal-title":"Int J Cancer"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1182\/blood.V74.1.388.388","article-title":"Infection of human T-cell leukemia virus type I and development of human T-cell leukemia lymphoma in patients with hematologic neoplasms: a possible linkage to blood transfusion","volume":"74","author":"Chen","year":"1989","journal-title":"Blood"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1080\/02841860802657235","article-title":"Adult T-cell leukemia\/lymphoma (ATL) presenting in the skin: clinical, histological and immunohistochemical features of 52 cases","volume":"48","author":"Bittencourt","year":"2009","journal-title":"Acta Oncol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1111\/j.1365-2141.1991.tb08051.x","article-title":"Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma. A report from the lymphoma study group (1984-87)","volume":"79","author":"Shimoyama","year":"1991","journal-title":"Br J Haematol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/1346-8138.12374","article-title":"Meeting report on the possible proposal of an extranodal primary cutaneous variant in the lymphoma type of adult T-cell leukemia-lymphoma","volume":"41","author":"Tsukasaki","year":"2014","journal-title":"J Dermatol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"2570","DOI":"10.1182\/blood-2015-03-632489","article-title":"Treatment and survival among 1594 patients with ATL","volume":"126","author":"Katsuya","year":"2015","journal-title":"Blood"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1056\/NEJM198308043090501","article-title":"Clinical course of retrovirus-associated adult T-cell lymphoma in the United States","volume":"309","author":"Bunn","year":"1983","journal-title":"N Engl J Med"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"761","DOI":"10.2214\/ajr.182.3.1820761","article-title":"Thoracic CT findings of adult T-cell leukemia or lymphoma","volume":"182","author":"Okada","year":"2004","journal-title":"AJR Am J Roentgenol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0925-5710(95)00350-2","article-title":"Cerebral mass lesions associated with adult T-cell leukemia\/lymphoma","volume":"61","author":"Kawasaki","year":"1995","journal-title":"Int J Hematol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"4337","DOI":"10.1182\/blood-2009-09-242347","article-title":"Long-term study of indolent adult T-cell leukemia-lymphoma","volume":"115","author":"Takasaki","year":"2010","journal-title":"Blood"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/S0140-6736(87)92752-8","article-title":"Strongyloides stercoralis as candidate co-factor for HTLV-I-induced leukaemogenesis","volume":"2","author":"Yamaguchi","year":"1987","journal-title":"Lancet"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1053\/j.semdp.2019.07.010","article-title":"Cutaneous manifestations of adult T-cell leukemia\/lymphoma","volume":"37","author":"Miyashiro","year":"2020","journal-title":"Semin Diagn Pathol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.jaad.2014.10.006","article-title":"Cutaneous manifestations of human T-cell lymphotrophic virus type-1-associated adult T-cell leukemia\/lymphoma: a single-center, retrospective study","volume":"72","author":"Marchetti","year":"2015","journal-title":"J Am Acad Dermatol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"3961","DOI":"10.1182\/blood-2010-11-316794","article-title":"Type of skin eruption is an independent prognostic indicator for adult T-cell leukemia\/lymphoma","volume":"117","author":"Sawada","year":"2011","journal-title":"Blood"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1002\/hon.2900040109","article-title":"Virus associated adult T-cell leukemia (ATL) in Japan: clinical, histological and immunological studies","volume":"4","author":"Kikuchi","year":"1986","journal-title":"Hematol Oncol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1097\/00000478-198404000-00003","article-title":"The pathologic spectrum of adult T-cell leukemia\/lymphoma in the United States. Human T-cell leukemia\/lymphoma virus-associated lymphoid malignancies","volume":"8","author":"Jaffe","year":"1984","journal-title":"Am J Surg Pathol"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1200\/JCO.2008.18.2428","article-title":"Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting","volume":"27","author":"Tsukasaki","year":"2009","journal-title":"J Clin Oncol"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"S15","DOI":"10.1097\/00042560-199600001-00004","article-title":"Adult T-cell leukemia in Japan","volume":"13","author":"Takatsuki","year":"1996","journal-title":"J Acquir Immune Defic Syndr Hum Retrovirol"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1200\/JCO.18.00501","article-title":"Revised adult T-cell leukemia-lymphoma international consensus meeting report","volume":"37","author":"Cook","year":"2019","journal-title":"J Clin Oncol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"5458","DOI":"10.1200\/JCO.2007.11.9958","article-title":"VCAP-AMP-VECP compared with biweekly CHOP for adult T-cell leukemia-lymphoma: Japan clinical oncology group study JCOG9801","volume":"25","author":"Tsukasaki","year":"2007","journal-title":"J Clin Oncol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1111\/1346-8138.12419","article-title":"Effect of anti-CCR4 monoclonal antibody (mogamulizumab) on adult T-cell leukemia-lymphoma: cutaneous adverse reactions may predict the prognosis","volume":"41","author":"Yonekura","year":"2014","journal-title":"J Dermatol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.clml.2019.03.004","article-title":"Mogamulizumab for the treatment of adult T-cell leukemia\/lymphoma","volume":"19","author":"Ureshino","year":"2019","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/S0140-6736(18)32984-2","article-title":"Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial","volume":"393","author":"Horwitz","year":"2019","journal-title":"Lancet"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"4086","DOI":"10.1200\/JCO.2016.67.7732","article-title":"Multicenter phase II study of Lenalidomide in relapsed or recurrent adult T-cell leukemia\/lymphoma: ATLL-002","volume":"34","author":"Ishida","year":"2016","journal-title":"J Clin Oncol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"4021","DOI":"10.3324\/haematol.2024.285233","article-title":"Distinctive genomic features of human T-lymphotropic virus type 1-related adult T-cell leukemia-lymphoma in Western populations","volume":"109","author":"Myers","year":"2024","journal-title":"Haematologica"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1309\/2YGD1P0QCVCWBLDX","article-title":"Adult T-cell leukemia\/lymphoma in Bahia, Brazil: analysis of prognostic factors in a group of 70 patients","volume":"128","author":"Bittencourt","year":"2007","journal-title":"Am J Clin Pathol"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.annder.2018.01.049","article-title":"Cutaneous presentation of adult T-cell leukemia\/lymphoma (ATLL). Single-center study on 37 patients in metropolitan France between 1996 and 2016","volume":"145","author":"Hurabielle","year":"2018","journal-title":"Ann Dermatol Venereol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"4124","DOI":"10.1200\/JCO.2008.16.4558","article-title":"International peripheral T-cell and natural killer\/T-cell lymphoma study: pathology findings and clinical outcomes","volume":"26","year":"2008","journal-title":"J Clin Oncol"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1097\/00126334-199905010-00009","article-title":"Adult T-cell leukemia\/lymphoma in northeastern Brazil: a clinical, histopathologic, and molecular study","volume":"21","author":"Barbosa","year":"1999","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.1097\/00042560-199600001-00005","article-title":"Adult T-cell leukemia\/lymphoma in Jamaica: 1986-1995","volume":"13","author":"Hanchard","year":"1996","journal-title":"J Acquir Immune Defic Syndr Hum Retrovirol"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1309\/AJCPL52QGQPZWFHE","article-title":"Analysis of cutaneous lymphomas in a medical center in bahia, Brazil","volume":"140","author":"Bittencourt","year":"2013","journal-title":"Pathol Patterns"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"4346","DOI":"10.1111\/cas.15097","article-title":"Epidemiology of adult T-cell leukemia-lymphoma in Japan: an updated analysis, 2012-2013","volume":"112","author":"Ito","year":"2021","journal-title":"Cancer Sci"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.prp.2018.10.001","article-title":"Clinical and histopathological significance of PD-1 expression in cutaneous lesions of adult T-cell leukemia-lymphoma","volume":"215","author":"Higuchi","year":"2018","journal-title":"Pathol Res Pract"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1111\/j.1365-4632.2008.03526.x","article-title":"Specific cutaneous manifestations in adult T-cell leukemia\/lymphoma","volume":"47","author":"Pezeshkpoor","year":"2008","journal-title":"Int J Dermatol"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"5051","DOI":"10.1158\/1078-0432.CCR-12-0604","article-title":"Long-term outcomes of 1,263 patients with mycosis fungoides and Sezary syndrome from 1982 to 2009","volume":"18","author":"Talpur","year":"2012","journal-title":"Clin Cancer Res"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1182\/blood-2007-03-055749","article-title":"Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC)","volume":"110","author":"Olsen","year":"2007","journal-title":"Blood"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1505865\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T09:00:02Z","timestamp":1738918802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1505865\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":52,"alternative-id":["10.3389\/fmed.2025.1505865"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1505865","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]},"article-number":"1505865"}}