{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:50:49Z","timestamp":1787028649833,"version":"build-2736575974"},"reference-count":90,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T00:00:00Z","timestamp":1725408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gemelli Policlinic Foundation IRCCS, Rare Diseases Donation","award":["5502162"],"award-info":[{"award-number":["5502162"]}]},{"name":"Research Center of Periodic Fevers of the Catholic University","award":["5502162"],"award-info":[{"award-number":["5502162"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: The relationship between sarcoidosis and the occurrence of neoplasia deserves to be investigated, but this relation has been observed in different and heterogeneous populations, leading to conflicting data. To clarify the causal relationship between these two diseases, different risk factors (e.g., smoking), concurrent comorbidities, corticosteroid therapy, and metastasis development\u2014as an expression of cancer aggressiveness\u2014were investigated. Methods: In a retrospective study on 287 sarcoidosis outpatients at the Pneumological Department of the Gemelli Foundation (Rome, Italy) between 2000 and 2024, the diagnosis of cancer was recorded in 36 subjects (12.5%). Results: The reciprocal timeline of the diseases showed three different scenarios: (1) cancer preceding sarcoidosis or sarcoid-like reactions (63.8%); (2) cancer arising after sarcoidosis diagnosis (8.3%); and (3) sarcoidosis accompanying the onset of malignancy (27.8%). Only two subjects with sarcoidosis and cancer showed metastasis, and one of them was affected by lymphoma. Conclusions: These data suggest that granulomatous inflammation due to sarcoidosis may assume an ambivalent role as a \u201cdouble-edged sword\u201d, according to the M1\/M2 macrophage polarization model: it represents a protective shield, preventing the formation of metastasis through the induction of immune surveillance against cancer while, on the other hand, it can be a risk factor for carcinogenesis due to the persistence of a chronic active inflammatory status. Low-dose steroid treatment was administered in only 31.6% of the cancer\u2013sarcoidosis subjects for less than six months to control inflammation activity, with no promotive effect on carcinogenesis observed.<\/jats:p>","DOI":"10.3390\/jcm13175232","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T04:28:28Z","timestamp":1725424108000},"page":"5232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sarcoidosis and Cancer: The Role of the Granulomatous Reaction as a Double-Edged Sword"],"prefix":"10.3390","volume":"13","author":[{"given":"Angela Maria","family":"Di Francesco","sequence":"first","affiliation":[{"name":"Periodic Fever and Rare Diseases Research Centre, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Pasciuto","sequence":"additional","affiliation":[{"name":"Complex Pneumology Operational Unit, A. Gemelli Policlinic Foundation IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2131-2110","authenticated-orcid":false,"given":"Elena","family":"Verrecchia","sequence":"additional","affiliation":[{"name":"Department of Aging, Orthopaedic and Rheumatological Sciences, A. Gemelli Policlinic Foundation IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovico Luca","family":"Sicignano","sequence":"additional","affiliation":[{"name":"Department of Aging, Orthopaedic and Rheumatological Sciences, A. Gemelli Policlinic Foundation IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Gerardino","sequence":"additional","affiliation":[{"name":"Department of Aging, Orthopaedic and Rheumatological Sciences, A. Gemelli Policlinic Foundation IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Massaro","sequence":"additional","affiliation":[{"name":"Periodic Fever and Rare Diseases Research Centre, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Urbani","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Biochemistry and Molecular Biology, A. Gemelli Policlinic Foundation IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1560-3907","authenticated-orcid":false,"given":"Raffaele","family":"Manna","sequence":"additional","affiliation":[{"name":"Periodic Fever and Rare Diseases Research Centre, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2153","DOI":"10.1056\/NEJMra071714","article-title":"Sarcoidosis","volume":"357","author":"Iannuzzi","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.disamonth.2009.04.008","article-title":"Sarcoidosis: Epidemiology, etiology, pathogenesis, and genetics","volume":"55","author":"Lazarus","year":"2009","journal-title":"Dis. 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