{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T08:06:59Z","timestamp":1788336419596,"version":"build-2803163510"},"reference-count":104,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T00:00:00Z","timestamp":1731628800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Kyowa Kirin International plc"},{"DOI":"10.13039\/501100013362","name":"Swiss Cancer Research Foundation","doi-asserted-by":"publisher","award":["KFS-4243-08-2017"],"award-info":[{"award-number":["KFS-4243-08-2017"]}],"id":[{"id":"10.13039\/501100013362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["IZLIZ3_200253\/1"],"award-info":[{"award-number":["IZLIZ3_200253\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["320030-232320"],"award-info":[{"award-number":["320030-232320"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006390","name":"University of Lausanne","doi-asserted-by":"publisher","award":["CCP 10-3224-9"],"award-info":[{"award-number":["CCP 10-3224-9"]}],"id":[{"id":"10.13039\/501100006390","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of diseases characterized by abnormal neoplastic T-cell growth in the skin. Mycosis fungoides (MF), the most common CTCL, manifests as erythematous skin patches and\/or plaques, tumours or erythroderma. The disease may involve blood, lymph nodes and rarely viscera. S\u00e9zary syndrome (SS) is a unique leukaemia\/lymphoma syndrome related to MF, which presents with blood and skin involvement at diagnosis.<\/jats:p>\n                  <jats:p>The pathogenesis of MF\/SS is not fully elucidated. The presence of skin lesions at distant sites underpins a hypothesis that MF\/SS lesions may develop through haematogenous seeding. Phenotypic similarities between malignant and normal T cells led to the notion that disease-initiating mutations occur in specific subtypes of mature T cells, which are responsible for most CTCLs. However, this mature T-cell precursor model is not always consistent with clinical observations and research on MF\/SS pathogenesis.<\/jats:p>\n                  <jats:p>Here, we review evidence supporting an alternative model of pathogenesis for MF\/SS involving haematogenous seeding as a key process responsible for the initiation and progression of the disease. According to this hypothesis, malignant transformation occurs at an early stage of T-cell development (probably in bone marrow or thymus), yielding circulating neoplastic T cells which colonize the skin where the microenvironment is most permissive for proliferation and evolution. These mutated precursor cells seed the skin where they find a suitable niche to develop into clinically perceptible disease. Subsequently, malignant T cells can re-enter the bloodstream, re-seed pre-existing lesions and seed new areas of the skin, causing synchronous and convergent changes in the transcriptomic profile of lesions and tumours, and clinical disease progression \u2013 \u2018consecutive haematogenous seeding\u2019 captures this temporal phenomenon.<\/jats:p>\n                  <jats:p>This model radically changes the current understanding of CTCL pathogenesis, transforming it from a primarily cutaneous disease with secondary involvement of blood, to a systemic disease, where the spread of malignant cells through the blood to the skin is not a phenomenon of advanced disease but is an essential component of pathogenesis.<\/jats:p>\n                  <jats:p>This understanding of MF\/SS could have several clinical implications, including standardizing our approach to assessing blood tumour burden, potential advances in prognosis and monitoring, and investigating combination treatments to improve patient outcomes.<\/jats:p>","DOI":"10.1093\/bjd\/ljae441","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T15:23:20Z","timestamp":1731597800000},"page":"381-389","source":"Crossref","is-referenced-by-count":15,"title":["Haematogenous seeding in mycosis fungoides and S\u00e9zary syndrome: current evidence and clinical implications"],"prefix":"10.1093","volume":"192","author":[{"given":"Robert","family":"Gniadecki","sequence":"first","affiliation":[{"name":"Division of Dermatology, University of Alberta , Edmonton, AB ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5478-8735","authenticated-orcid":false,"given":"Emmanuella","family":"Guenova","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Lausanne University Hospital and Faculty of Biology and Medicine, University of Lausanne , Lausanne ,","place":["Switzerland"]},{"name":"University Institute and Clinic for Immunodermatology, Medical Faculty, Johannes Kepler University Linz , Linz ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9698-5809","authenticated-orcid":false,"given":"Christiane","family":"Querfeld","sequence":"additional","affiliation":[{"name":"Department of Pathology and Division of Dermatology, City of Hope Medical Center and Beckman Research Institute , Duarte, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan P","family":"Nicolay","sequence":"additional","affiliation":[{"name":"University Medical Center Mannheim\/Ruprecht Karls University of Heidelberg , Mannheim ,","place":["Germany"]},{"name":"Skin Cancer Unit, German Cancer Research Center , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Scarisbrick","sequence":"additional","affiliation":[{"name":"University Hospital Birmingham , Birmingham ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubomir","family":"Sokol","sequence":"additional","affiliation":[{"name":"Moffitt Cancer Center , Tampa, FL ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,15]]},"reference":[{"key":"2025021810042592300_ljae441-B1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.3389\/fonc.2018.00198","article-title":"New therapies and immunological findings in cutaneous T-cell lymphoma","volume":"8","author":"Fujii","year":"2018","journal-title":"Front Oncol"},{"key":"2025021810042592300_ljae441-B2","first-page":"61","article-title":"Cutaneous T cell lymphoma","volume-title":"Nat Rev Dis Primers","author":"Dummer","year":"2021"},{"issue":"Suppl. 4","key":"2025021810042592300_ljae441-B3","doi-asserted-by":"crossref","first-page":"iv30","DOI":"10.1093\/annonc\/mdy133","article-title":"Primary cutaneous lymphomas: ESMO 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