{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T17:21:24Z","timestamp":1775496084629,"version":"3.50.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Klinikum der Universit\u00e4t M\u00fcnchen"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>While oral submucous fibrosis (OSMF) in Asia associated to betel nut usage has been extensively characterized both clinically and histologically, the effects of snus (a traditional Scandinavian oral tobacco product) use in Europe are far less well understood. With the growing popularity of snus across Europe, its impact on oral mucosal pathology has become an issue of increasing clinical relevance. In this study, 50 patients were examined, presenting with clinically detectable oral mucosal alterations, associated with habitual snus use. Clinically, the lesions typically appeared as leukoplakic, firm mucosal changes with surface corrugation. In the most severe cases, biopsies were obtained and histopathologically and immunohistochemically analyzed. This evaluation revealed lymphocytic infiltration, epithelial hyperplasia with keratinization, and varying degree of submucosal fibrosis. These findings demonstrate that snus use can induce significant pathohistological manifestations in the oral mucosa, closely analogous to those of the established potentially malignant disorder OSMF. Additional periodontal and dental effects, including gingival recession, erosions, and tooth discoloration, were also recorded. This study provides novel insights into the potential link between snus use and OSMF-like pathology and underscores the importance of vigilant clinical monitoring of affected individuals.<\/jats:p>","DOI":"10.1007\/s00428-026-04414-4","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:11:58Z","timestamp":1769127118000},"page":"879-885","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and histopathological manifestations of snus use in Germany: parallels to betel nut\u2013related oral submucous fibrosis in Asia"],"prefix":"10.1007","volume":"488","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7265-3903","authenticated-orcid":false,"given":"Lukas","family":"Greber","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Otto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Poxleitner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thierbach","family":"Ren\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Ihrler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"4414_CR1","unstructured":"WHO Classification of Tumours Editorial Board (2024) WHO classification of tumours. Head and Neck Tumours, 5th edn, vol 9. International Agency for Research on Cancer, Lyon"},{"key":"4414_CR2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11071793","author":"V Murthy","year":"2022","unstructured":"Murthy V et al (2022) Malignant transformation rate of oral submucous fibrosis: a systematic review and meta-analysis. Int J Cancer  150(6):1043\u20131054","journal-title":"Int J Cancer"},{"key":"4414_CR3","unstructured":"IARC Working Group (2007) IARC monographs on the evaluation of carcinogenic risks to humans. Smokeless tobacco and some tobacco-specific N-nitrosamines, vol 89. International Agency for Research on Cancer, Lyon"},{"issue":"6","key":"4414_CR4","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1002\/ijc.28643","volume":"135","author":"N Guha","year":"2014","unstructured":"Guha N et al (2014) Betel quid chewing and the risk of oral and oropharyngeal cancers: a meta-analysis with implications for cancer control. Int J Cancer 135(6):1433\u20131443","journal-title":"Int J Cancer"},{"key":"4414_CR5","unstructured":"Rumgay H et al (2024) Global burden of oral cancer attributable to smokeless tobacco and areca nut use: a population-attributable fraction analysis.\u00a0Lancet Glob Health\u00a012(6):e889\u2013e899"},{"issue":"1","key":"4414_CR6","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1054\/bjom.1999.0062","volume":"38","author":"SM Haider","year":"2000","unstructured":"Haider SM et al (2000) Clinical and functional staging of oral submucous fibrosis. Br J Oral Maxillofac Surg 38(1):12\u201315","journal-title":"Br J Oral Maxillofac Surg"},{"issue":"1","key":"4414_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s12954-019-0335-1","volume":"16","author":"E Clarke","year":"2019","unstructured":"Clarke E et al (2019) Snus: a compelling harm reduction alternative to cigarettes. Harm Reduct J 16(1):62","journal-title":"Harm Reduct J"},{"issue":"9","key":"4414_CR8","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-050502","volume":"11","author":"M Danielsson","year":"2021","unstructured":"Danielsson M et al (2021) Prevalence, duration of exposure and predicting factors for snus use among young Finnish men: a cross-sectional study. BMJ Open 11(9):e050502","journal-title":"BMJ Open"},{"issue":"1","key":"4414_CR9","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/j.1600-0714.1989.tb00722.x","volume":"18","author":"G Andersson","year":"1989","unstructured":"Andersson G, Ax\u00e9ll T (1989) Clinical appearance of lesions associated with the use of loose and portion-bag packed Swedish moist snuff: a comparative study. J Oral Pathol Med 18(1):2\u20137","journal-title":"J Oral Pathol Med"},{"issue":"4","key":"4414_CR10","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/0964-1955(93)90052-G","volume":"29B","author":"TE Ax\u00e9ll","year":"1993","unstructured":"Ax\u00e9ll TE (1993) Oral mucosal changes related to smokeless tobacco usage: research findings in Scandinavia. Eur J Cancer B Oral Oncol 29B(4):299\u2013302","journal-title":"Eur J Cancer B Oral Oncol"},{"issue":"2","key":"4414_CR11","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1016\/j.oooo.2016.02.020","volume":"122","author":"S Warnakulasuriya","year":"2016","unstructured":"Warnakulasuriya S, Kerr AR (2016) Oral submucous fibrosis: a review of the current management and possible directions for novel therapies. Oral Surg Oral Med Oral Pathol Oral Radiol Oral Endod 122(2):232\u2013241","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol Oral Endod"},{"issue":"9578","key":"4414_CR12","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1016\/S0140-6736(07)60678-3","volume":"369","author":"J Luo","year":"2007","unstructured":"Luo J et al (2007) Oral use of Swedish moist snuff (snus) and risk for cancer of the mouth, lung, and pancreas in male construction workers: a retrospective cohort study. Lancet 369(9578):2015\u201320","journal-title":"Lancet"},{"key":"4414_CR13","unstructured":"German Cancer Society, German Cancer Aid, AWMF (2021) S3 guideline for diagnostics and therapy of oral cavity cancer. Long version 3.0. AWMF registry no. 007\/100OL. German Guideline Program in Oncology, Berlin"},{"issue":"6","key":"4414_CR14","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/jop.12580","volume":"46","author":"PA Brennan","year":"2017","unstructured":"Brennan PA, Arakeri G (2017) Oral submucous fibrosis\u2014an increasing global healthcare problem. J Oral Pathol Med 46(6):405","journal-title":"J Oral Pathol Med"},{"issue":"1","key":"4414_CR15","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s10006-010-0225-x","volume":"15","author":"PV Angadi","year":"2011","unstructured":"Angadi PV, Rekha KP (2011) Oral submucous fibrosis: a clinicopathologic review of 205 cases in Indians. Oral Maxillofac Surg 15(1):15\u201319","journal-title":"Oral Maxillofac Surg"},{"issue":"6","key":"4414_CR16","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/j.1600-0714.1973.tb01848.x","volume":"2","author":"B Roed-Petersen","year":"1973","unstructured":"Roed-Petersen B, Pindborg JJ (1973) A study of Danish snuff-induced oral leukoplakias. J Oral Pathol Med 2(6):301\u2013313","journal-title":"J Oral Pathol Med"},{"issue":"3","key":"4414_CR17","doi-asserted-by":"publisher","first-page":"106","DOI":"10.4103\/0970-9290.33785","volume":"18","author":"K Kiran Kumar","year":"2007","unstructured":"Kiran Kumar K et al (2007) Oral submucous fibrosis: a clinico-histopathological study in Chennai. Indian J Dent Res 18(3):106\u201311","journal-title":"Indian J Dent Res"},{"issue":"2","key":"4414_CR18","first-page":"256","volume":"21","author":"JJ Pindborg","year":"1968","unstructured":"Pindborg JJ et al (1968) Tobacco-induced changes in oral leukoplakic epithelium. Cancer 21(2):256\u2013266","journal-title":"Cancer"},{"key":"4414_CR19","doi-asserted-by":"publisher","DOI":"10.4103\/jcar.JCar_24_20","volume":"20","author":"SS Shetty","year":"2021","unstructured":"Shetty SS et al (2021) Understanding the molecular mechanism associated with reversal of oral submucous fibrosis targeting hydroxylysine aldehyde-derived collagen cross-links. J Carcinog 20:9","journal-title":"J Carcinog"},{"issue":"6","key":"4414_CR20","first-page":"473","volume":"81","author":"SE Kopperud","year":"2023","unstructured":"Kopperud SE et al (2023) Oral lesions associated with daily use of snus, a moist smokeless tobacco product. A cross-sectional study among Norwegian adolescents. Acta Odontol Scand 81(6):473\u2013478","journal-title":"Acta Odontol Scand"},{"issue":"1","key":"4414_CR21","doi-asserted-by":"publisher","first-page":"91","DOI":"10.2334\/josnusd.56.91","volume":"56","author":"M Kharazmi","year":"2014","unstructured":"Kharazmi M et al (2014) Surgical approach to snus-induced injury of the oral mucosa. J Oral Sci 56(1):91\u20134","journal-title":"J Oral Sci"},{"issue":"1","key":"4414_CR22","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1186\/s13000-024-01549-3","volume":"19","author":"S Miluna-Meldere","year":"2024","unstructured":"Miluna-Meldere S et al (2024) Oral mucosal changes caused by nicotine pouches: case series. Diagn Pathol 19(1):127https:\/\/doi.org\/10.1186\/s13000-024-01549-3","journal-title":"Diagn Pathol"},{"issue":"12","key":"4414_CR23","doi-asserted-by":"publisher","first-page":"1942","DOI":"10.1002\/ijc.34643","volume":"153","author":"H Valen","year":"2023","unstructured":"Valen H et al (2023) A systematic review of cancer risk among users of smokeless tobacco (Swedish snus) exclusively, compared with no use of tobacco. Int J Cancer 153(12):1942\u201353","journal-title":"Int J Cancer"},{"issue":"5","key":"4414_CR24","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1001\/archotol.1970.04310050032005","volume":"92","author":"JF Smith","year":"1970","unstructured":"Smith JF et al (1970) Snuff-dipper\u2019s lesion. A cytological and pathological study in a large population. Arch Otolaryngol 92(5):450\u20136","journal-title":"Arch Otolaryngol"},{"issue":"5","key":"4414_CR25","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1001\/archotol.1975.00780340008002","volume":"101","author":"JF Smith","year":"1975","unstructured":"Smith JF (1975) Snuff-dippers lesion. A ten-year follow-up. Arch Otolaryngol Head Neck Surg 101(5):276\u2013277","journal-title":"Arch Otolaryngol Head Neck Surg"},{"issue":"3","key":"4414_CR26","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2105\/AJPH.82.3.351","volume":"82","author":"GN Connolly","year":"1992","unstructured":"Connolly GN, Orleans CT, Blum A (1992) Snuffing tobacco out of sport. Am J Public Health 82(3):351\u2013353","journal-title":"Am J Public Health"},{"issue":"3","key":"4414_CR27","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1177\/08959374970110030101","volume":"11","author":"PB Robertson","year":"1997","unstructured":"Robertson PB, Walsh MM, Greene JC (1997) Oral effects of smokeless tobacco use by professional baseball players. Adv Dent Res 11(3):307\u2013312","journal-title":"Adv Dent Res"},{"issue":"1","key":"4414_CR28","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/S0020-6539(20)34036-3","volume":"60","author":"S Warnakulasuriya","year":"2010","unstructured":"Warnakulasuriya S et al (2010) Oral health risks of tobacco use and effects of cessation. Int Dent J 60(1):7\u201330","journal-title":"Int Dent J"},{"issue":"1","key":"4414_CR29","doi-asserted-by":"publisher","first-page":"35","DOI":"10.4103\/ijmr.IJMR_1793_17","volume":"148","author":"A Muthukrishnan","year":"2018","unstructured":"Muthukrishnan A, Warnakulasuriya S (2018) Oral health consequences of smokeless tobacco use. Indian J Med Res 148(1):35\u201340","journal-title":"Indian J Med Res"},{"issue":"1","key":"4414_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-024-04598-8","volume":"24","author":"D Rungraungrayabkul","year":"2024","unstructured":"Rungraungrayabkul D et al (2024) What is the impact of nicotin","journal-title":"BMC Oral Health"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04414-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-026-04414-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04414-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T15:49:53Z","timestamp":1775490593000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-026-04414-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["4414"],"URL":"https:\/\/doi.org\/10.1007\/s00428-026-04414-4","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,23]]},"assertion":[{"value":"28 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the ethical principles of the Declaration of Helsinki (latest revision) and complied with all applicable institutional and national research ethics guidelines. All procedures involving human participants were carried out with appropriate ethical consideration.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}