{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T01:12:39Z","timestamp":1747185159437,"version":"3.40.5"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,11,19]],"date-time":"2020-11-19T00:00:00Z","timestamp":1605744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004528","name":"Maastricht Universitair Medisch Centrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004528","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The role of inflammation in conventional cutaneous melanoma has been extensively studied, whereas only little is known about the inflammatory microenvironment and immunogenic properties of spitzoid melanocytic neoplasms. The composition of infiltrating immune cells and the architectural distribution of the inflammation, in particular, are still obscure. This is the first study, to our knowledge, to systematically characterise the inflammatory patterns and the leucocyte subsets in spitzoid melanocytic lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We examined 79 spitzoid neoplasms including banal Spitz naevi (SN, <jats:italic>n<\/jats:italic>\u00a0=\u00a050), atypical Spitz tumours (AST, <jats:italic>n<\/jats:italic>\u00a0=\u00a017) and malignant Spitz tumours (MST, <jats:italic>n<\/jats:italic>\u00a0=\u00a012) using histopathological analysis and immunohistochemistry. Spitzoid melanocytic lesions showed a high frequency (67.1%, <jats:italic>n<\/jats:italic>\u00a0=\u00a053 of 79) of inflammation. Four inflammatory patterns were identified according to architectural composition, distribution and intensity of inflammation. The majority of the inflammatory infiltrate corresponded to CD3<jats:sup>+<\/jats:sup>\/CD8<jats:sup>+<\/jats:sup> T lymphocytes (56.1%), followed by CD3<jats:sup>+<\/jats:sup>\/CD4<jats:sup>+<\/jats:sup> T cells (35.7%) and CD68<jats:sup>+<\/jats:sup> histiocytes (20.3%). CD3<jats:sup>+<\/jats:sup>\/TIA\u20101<jats:sup>+<\/jats:sup> cytotoxic T lymphocytes constituted 3.7% of inflammatory cells. Rarely, CD3<jats:sup>+<\/jats:sup>\/ granzyme B<jats:sup>+<\/jats:sup> cytotoxic T lymphocytes (2.7%) and CD138<jats:sup>+<\/jats:sup> plasma cells (0.5%) were detected in the infiltrating immune cells. There was no significant difference in the inflammatory cellular composition among the spitzoid melanocytic subgroups (SN versus AST versus MST).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings demonstrate that Spitz tumours are highly immunogenic lesions. Inflammation with the presence of lymphocytic aggregates predominated in SN, but was not distinctive for this melanocytic category. A strong and intense inflammation was suggestive of an underlying malignancy. The infiltrating cytotoxic T lymphocyte subsets in Spitz tumours deserve further investigation in larger study cohorts to elucidate prognostic and immuno\u2010oncological therapeutic relevance.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14259","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T19:49:05Z","timestamp":1600976945000},"page":"607-626","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Integrative histopathological and immunophenotypical characterisation of the inflammatory microenvironment in spitzoid melanocytic neoplasms"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8808-4952","authenticated-orcid":false,"given":"Lisa M","family":"Hillen","sequence":"first","affiliation":[{"name":"Department of Pathology GROW School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik L D","family":"Vandyck","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daphne J G","family":"Leunissen","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca T A","family":"de Greef","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology and Medical Technology Assessment Maastricht University Medical Center Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca M","family":"Bosisio","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Cell and Tissue Research (TCTR) University of Leuven KUL Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"zur Hausen","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost","family":"van den Oord","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Cell and Tissue Research (TCTR) University of Leuven KUL Leuven Belgium"},{"name":"Department of Pathology University Hospitals Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Winnepenninckx","sequence":"additional","affiliation":[{"name":"Department of Pathology GROW School for Oncology and Developmental Biology Maastricht University Medical Center Maastricht the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e3181934218"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197707)40:1<217::AID-CNCR2820400134>3.0.CO;2-2"},{"key":"e_1_2_11_4_1","first-page":"591","article-title":"Melanomas of childhood","volume":"24","author":"Spitz S","year":"1948","journal-title":"Am. 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