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Chronic inflammation elicited by the implant has been implicated in its pathogenesis. Infection or implant rupture may also be responsible for late seromas. Cytomorphological examination coupled with CD30 immunostaining and eventual T-cell clonality assessment are essential for BI-ALCL diagnosis. However, some benign effusions may also contain an oligo\/monoclonal expansion of CD30\u2009+\u2009cells that can make the diagnosis challenging. Since cytokines are key mediators of inflammation, we applied a multiplexed immuno-based assay to BI-ALCL seromas and to different types of reactive seromas to look for a potential diagnostic BI-ALCL-associated cytokine profile. We found that BI-ALCL is characterized by a Th2-type cytokine milieu associated with significant high levels of IL-10, IL-13 and Eotaxin which discriminate BI-ALCL from all types of reactive seroma. Moreover, we found a cutoff of IL10\/IL-6 ratio of 0.104 is associated with specificity of 100% and sensitivity of 83% in recognizing BI-ALCL effusions. This study identifies promising biomarkers for initial screening of late seromas that can facilitate early diagnosis of BI-ALCL.<\/jats:p>","DOI":"10.1007\/s00262-020-02778-3","type":"journal-article","created":{"date-parts":[[2020,11,4]],"date-time":"2020-11-04T11:03:01Z","timestamp":1604487781000},"page":"1379-1392","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["IL-10, IL-13, Eotaxin and IL-10\/IL-6 ratio distinguish breast implant-associated anaplastic large-cell lymphoma from all types of benign late seromas"],"prefix":"10.1007","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3159-5380","authenticated-orcid":false,"given":"Arianna","family":"Di Napoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Greco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Scafetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ascenzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Gulino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Aurisicchio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Santanelli Di Pompeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Bonifacino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Giarnieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Mancini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marshall E.","family":"Kadin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,11,4]]},"reference":[{"key":"2778_CR1","unstructured":"Feldman AL, Harris NL, et al (2017) Breast implant-associated anaplastic large cell lymphoma. 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The Animal Welfare Committee of the University of Rome Sapienza (Rome) in accordance with the European Guidelines for Animal Care and Use of Laboratory Animals approved all experiments with rodents (Project Authorization # A69A0.2.EXT.12). All the procedures have been performed in accordance with \u201cDirective 2010\/63\/EU on the protection of Animals used for scientific purposes\u201d and made effective in Italy by the Legislative Decree DLGS 26\/2014.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from patients upon sample collection. Patients consented to the use of their specimens and data for research and publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"Six-week-old female NOD.Cg-Prkdcscid Il2rgtm1Wjl\/SzJ mice (NSG) obtained from Charles River were used in this work.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Animal source"}},{"value":"Primary tumor cells derived from seromas of three patients diagnosed with BI-ALCL at Sant\u2019Andrea Hospital, Roma, Italy were used in this work. Two out of 3 primary cultured cells were successfully authenticated using Short Tandem Repeat (STR) analysis by ATCC (n. STRA11550 and STRA11552). TLBR-1,-2,-3,-4 are cell lines derived from clinical cases of BIA-ALCL and were kindly provided by Dr. Alan L. Epstein, MD PhD (Keck School of Medicine, University of Southern California). Mac-1, Mac-2A are cutaneous T cell lymphoma lines established by MEK and, Karpas 299 are an ALK-positive systemic ALCL line obtained from the DSMZ German Collection of Microorganisms and cell cultures GmbH. No cell line authentication was necessary.","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Cell line authentication"}}]}}