{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T15:04:38Z","timestamp":1785683078428,"version":"3.56.0"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The aim was to gain insight into the biology of primary cutaneous CD4<jats:sup>+<\/jats:sup> small\/medium T\u2010cell lymphoproliferative disorder (PCSM\u2010LPD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We describe the histopathological and clinical characteristics of 177 PCSM\u2010LPD diagnosed at our consultation centre. We performed immunohistochemical multistaining in a subset of cases (<jats:italic>n<\/jats:italic>\u00a0=\u00a046) including PD1, Cyclin D1, and multiple markers of proliferation. We evaluated clonal T\u2010cell\u2010receptor\u2010(TCR) rearrangements and used tissue microdissection to analyse TCR\u2010clonality of PD1(+) cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The cohort of <jats:italic>n<\/jats:italic>\u00a0=\u00a0177 PCSM\u2010LPD included 84 males and 93 females (median age 57, range 13\u201385). Clinical presentation was as a solitary nodule or plaque (head and neck &gt; trunk &gt; extremities). Most patients were treated by local excision or steroids (96%, 69\/72); relapses occurred in 12\/65 (18%) of patients with follow up. Histopathology revealed the predominance of a nodular pattern (75%, 134\/177) and frequent clustering of PD1(+) large cells (70%, 103\/147). We detected Cyclin D1 and PD1 coexpression (&gt;10% of PD1(+)\u2010cells) in 26\/46 (57%), which was not associated with <jats:italic>CCND1<\/jats:italic> breaks or amplifications<jats:italic>.<\/jats:italic> PD1(+)\u2010cells in PCSM\u2010LPDs showed a significantly higher expression of proliferation\u2010associated proteins compared to PD1(\u2212)\u2010cells. A clonal TCR\u2010rearrangement was present in 176\/177 (99%), with a clonal persistence in 7\/8 patients at relapse including distant sites. Tissue\u2010microdissection revealed PD1(+)\u2010cells as the source of clonality, whilst PD1(\u2212)\u2010cells remained polyclonal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PCSM\u2010LPD is a clinically indolent, albeit neoplastic, disease driven by clonal expansion of PD1(+)\u2010cells. We demonstrate Cyclin D1\u2010expression associated with accelerated proliferation as a surprising new biological feature of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14834","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T09:38:10Z","timestamp":1667813890000},"page":"485-494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Cyclin D1 expression, cell proliferation, and clonal persistence characterize primary cutaneous CD4<sup>+<\/sup> small or medium T\u2010cell lymphoproliferative disorder"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4003-6855","authenticated-orcid":false,"given":"Ilske","family":"Oschlies","sequence":"first","affiliation":[{"name":"Department of Pathology, Hematopathology Section University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Kock","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hematopathology Section University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"W\u00fcseke","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hematopathology Section University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hematopathology Section University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hematopathology Section University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Wehkamp","sequence":"additional","affiliation":[{"name":"Department of Dermatology University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-4117","authenticated-orcid":false,"given":"Wolfram","family":"Klapper","sequence":"additional","affiliation":[{"name":"Department of Pathology, Hematopathology Section University Hospital Schleswig\u2010Holstein  Kiel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,18]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"WHO classification of tumors of haematopoietic and lymphoid tissues","author":"Swerdlow SH","year":"2018"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-881268"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.15372"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000511473"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001470"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31818e52fe"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000000987"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000002017"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-643569"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2008.40"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2014.975700"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2403202"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.192435"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/8.suppl_2.S109"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2011.03.006"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2019.04.013"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPW64FFBTTPKFN"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0560.2001.028009448.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-019-02713-7"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.14556"},{"key":"e_1_2_10_22_1","first-page":"123","article-title":"Primary cutaneous CD4+ small\/medium pleomorphic T\u2010cell lymphoproliferative disorder: where do we stand? 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