{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:04:30Z","timestamp":1791338670641,"version":"4.3.1"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Burkitt lymphoma (BL) is an aggressive B\u2010cell lymphoma that, in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four such cases, two of which regressed spontaneously.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein\u2013Barr virus (EBV)\u2010positive with type I latency. Investigation of the TME showed similar features in all four cases. The analysis revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarised macrophages encircling the neoplastic cells with a peculiar topographic distribution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data provide an <jats:italic>in\u2010vivo<\/jats:italic> picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self\u2010limited state or inducing its regression. These novel results may provide insights into new potential therapeutic avenues in EBV\u2010positive BL patients in the era of cellular immunotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14391","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T09:58:57Z","timestamp":1620208737000},"page":"430-442","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Burkitt lymphoma with a granulomatous reaction: an M1\/Th1\u2010polarised microenvironment is associated with controlled growth and spontaneous regression"],"prefix":"10.1111","volume":"80","author":[{"given":"Massimo","family":"Granai","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"},{"name":"Institute of Pathology University of T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Lazzi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia","family":"Mancini","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse","family":"Akarca","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Santi","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Vergoni","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Guazzo","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Mundo","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"},{"name":"Health Research Institute University of Limerick Limerick Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Cevenini","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Tripodo","sequence":"additional","affiliation":[{"name":"Department of Human Pathology University of Palermo Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioia","family":"Di Stefano","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Puccini","sequence":"additional","affiliation":[{"name":"Department of Haematology University of Florence Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurilio","family":"Ponzoni","sequence":"additional","affiliation":[{"name":"Department of Pathology University Vita\u2010Salute San Raffaele Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-3591","authenticated-orcid":false,"given":"Elena","family":"Sabattini","sequence":"additional","affiliation":[{"name":"Haemolymphopathology Unit \u2010 IRCCS \u2010 Azienda Ospedaliero\u2010Universitaria di Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4945-1422","authenticated-orcid":false,"given":"Claudio","family":"Agostinelli","sequence":"additional","affiliation":[{"name":"Haemolymphopathology Unit \u2010 IRCCS \u2010 Azienda Ospedaliero\u2010Universitaria di Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuray","family":"Bass\u00fcll\u00fc","sequence":"additional","affiliation":[{"name":"Department of Pathology Bilim University \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00fclay","family":"Tecimer","sequence":"additional","affiliation":[{"name":"Department of Pathology Acibadem University \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahu Senem","family":"Demiroz","sequence":"additional","affiliation":[{"name":"Department of Pathology \u0130stanbul University Cerrahpa\u015fa \u0130stanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah","family":"Mnango","sequence":"additional","affiliation":[{"name":"Department of Pathology Muhimbili National Hospital and University for Healthcare and Allied Sciences Dar\u2010es\u2010Salaam Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Dirnhofer","sequence":"additional","affiliation":[{"name":"Institute of Pathology University Hospital Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7156-5365","authenticated-orcid":false,"given":"Leticia","family":"Quintanilla\u2010Martinez","sequence":"additional","affiliation":[{"name":"Institute of Pathology University of T\u00fcbingen T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Marafioti","sequence":"additional","affiliation":[{"name":"Department of Cellular Pathology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Falko","family":"Fend","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7457-300X","authenticated-orcid":false,"given":"Lorenzo","family":"Leoncini","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnologies University of Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199301000-00006"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-200403000-00011"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.pas.0000170350.85798.f4"},{"key":"e_1_2_8_5_1","first-page":"19","article-title":"Burkitt lymphoma with unusual granulomatous reaction. A case report","volume":"47","author":"Janegov\u00e1 A","year":"2011","journal-title":"Cesk. Patol."},{"key":"e_1_2_8_6_1","first-page":"7049","article-title":"HIV\u2010related Burkitt lymphoma with florid granulomatous reaction: an unusual case with good outcome","volume":"7","author":"Li JN","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"e_1_2_8_7_1","volume-title":"World Health Organization classification of tumours of haematopoietic and lymphoid tissues, 4th edn. revised","author":"Swerdlow SH","year":"2017"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2199-7"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.12.6166"},{"key":"e_1_2_8_10_1","first-page":"223","article-title":"Th1\/Th2 balance: the hypothesis, its limitations, and implications for health and disease","volume":"8","author":"Kidd P","year":"2003","journal-title":"Altern. Med. Rev."},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2260"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00614"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.1.97"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0080908"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80397-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/375685a0"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088902"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10209"},{"key":"e_1_2_8_19_1","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.4049\/jimmunol.158.8.3619","article-title":"Class I processing\u2010defective Burkitt\u2019s lymphoma cells are recognized efficiently by CD4+ EBV\u2010specific CTLs","volume":"158","author":"Khanna R","year":"1997","journal-title":"J. Immunol."},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.10.1649"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.18.8649-8659.2001"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.169.3.1593"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8709-2_6"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13027-020-00292-w"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.215053"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4161\/jkst.23820"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.8879"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.09.002"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2015.1008824"},{"key":"e_1_2_8_31_1","first-page":"1070","article-title":"T\u2010bet\u2010positive and IRTA1\u2010positive monocytoid B cells differ from marginal zone B cells and epithelial\u2010associated B cells in their antigen profile and topographical distribution","volume":"90","author":"J\u00f6hrens K","year":"2005","journal-title":"Haematologica"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1500368"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201847722"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2010.023689"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167841"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1086\/491741"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210496"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-05-023663"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-599951"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005158"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/95.6.802"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00194618"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-01-0168"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqv011"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2012.29"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.019"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12997"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12960"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-06-573725"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.39.8495"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14391","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.14391","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14391","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T17:24:51Z","timestamp":1692811491000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.14391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":49,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1111\/his.14391"],"URL":"https:\/\/doi.org\/10.1111\/his.14391","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,5]]},"assertion":[{"value":"2020-09-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}