{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T09:05:44Z","timestamp":1765098344423,"version":"3.37.3"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K15693; 19K10101"],"award-info":[{"award-number":["15K15693; 19K10101"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although emergence of keratin 17 (K17) and reciprocal loss of K13 are immunohistochemical hallmarks for oral mucosal malignancy, we report here findings of K17-positive (+) speckles, possibly equivalent to Civatte bodies, in benign oral lichen planus. Sixty-two biopsy samples from oral lichen planus cases were subjected to immunohistochemical examinations to analyze the distribution as well as histopathogenesis of Civatte bodies. K17 was irregularly positive among oral lichen planus-affected epithelial cells, and K17-positive (+) filamentous structures were irregularly distributed within the cytoplasm in confocal images. K17+\u2009speckles were identified as Civatte bodies, and they were mainly distributed in the interface between epithelial cells and lymphocytic infiltrates (type A, 52.8%), followed by distribution within the epithelial layer (type B, 24.7%) or within the lamina propria with lymphocytic infiltration (type C, 22.5%). Apoptotic figures were often engulfed by macrophages and clearly distinguished from Civatte bodies by the presence TUNEL signals. These results indicate that K17 is a sensitive immunohistochemical marker for Civatte bodies and useful for differential diagnosis of oral lichen planus from other oral mucosal lesions. Civatte bodies are generated from denucleation of K17+\u2009epithelial cells during the process of cell death via dyskeratosis, which is possibly related to blood capillary collapse.<\/jats:p>","DOI":"10.1038\/s41598-020-71496-8","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T10:04:10Z","timestamp":1599127450000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Keratin 17-positive Civatte bodies in oral lichen planus\u2014distribution variety, diagnostic significance and histopathogenesis"],"prefix":"10.1038","volume":"10","author":[{"given":"Tatsuya","family":"Ab\u00e9","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norio","family":"Kitagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shohei","family":"Yoshimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manabu","family":"Yamazaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuichiro","family":"Inai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuichi","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7108-8391","authenticated-orcid":false,"given":"Takashi","family":"Saku","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"71496_CR1","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.oraloncology.2011.03.015","volume":"47","author":"T Mikami","year":"2011","unstructured":"Mikami, T. et al. Emergence of keratin 17 vs. loss of keratin 13: their reciprocal immunohistochemical profiles in oral carcinoma in situ. Oral Oncol. 47, 497\u2013503 (2011).","journal-title":"Oral Oncol."},{"key":"71496_CR2","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/j.1440-1827.2009.02499.x","volume":"60","author":"T Kobayashi","year":"2010","unstructured":"Kobayashi, T. et al. Histopathological varieties of oral carcinoma in situ: diagnosis aided by immunohistochemistry dealing with the second basal cell layer as the proliferating center of oral mucosal epithelia. Pathol. Int. 60, 156\u2013166 (2010).","journal-title":"Pathol. Int."},{"key":"71496_CR3","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s00428-015-1735-6","volume":"466","author":"T Mikami","year":"2015","unstructured":"Mikami, T. et al. Keratin 17 is co-expressed with 14-3-3 sigma in oral carcinoma in situ and squamous cell carcinoma and modulates cell proliferation and size but not cell migration. Virchows Arch. 466, 559\u2013569 (2015).","journal-title":"Virchows Arch."},{"key":"71496_CR4","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.yexmp.2017.02.018","volume":"102","author":"T Ab\u00e9","year":"2017","unstructured":"Ab\u00e9, T. et al. Proteomic and histopathological characterization of the interface between oral squamous cell carcinoma invasion fronts and non-cancerous epithelia. Exp. Mol. Pathol. 102, 327\u2013336 (2017).","journal-title":"Exp. Mol. Pathol."},{"key":"71496_CR5","first-page":"808","volume-title":"A Textbook of Oral Pathology","author":"WG Shafer","year":"1980","unstructured":"Shafer, W. G., Hine, M. K. & Levy, B. M. A Textbook of Oral Pathology 4th edn, 808\u2013814 (W. B. Saunders Co., Philadelphia, 1980).","edition":"4"},{"key":"71496_CR6","first-page":"166","volume-title":"Atlas d\u2019Histopathologie Cutan\u00e9e","author":"A Civatte","year":"1957","unstructured":"Civatte, A. Atlas d\u2019Histopathologie Cutan\u00e9e 166 (Masson, Paris, 1957)."},{"key":"71496_CR7","unstructured":"Sabouraud, R. Sur quelques points de l'anatomie pathologique du lichen plan de Wilson. Ann. Dermatol. Syphiligr. 5e s\u00e9rie (Tome I), 491\u2013505 (1910)."},{"key":"71496_CR8","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1111\/cup.12294","volume":"41","author":"WHC Burgdorf","year":"2014","unstructured":"Burgdorf, W. H. C. & Plewig, G. Who described Civatte bodies?. J. Cutan. Pathol. 41, 340\u2013346 (2014).","journal-title":"J. Cutan. Pathol."},{"key":"71496_CR9","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S1079-2104(99)70033-8","volume":"88","author":"EH van der Meij","year":"1999","unstructured":"van der Meij, E. H. et al. A review of the recent literature regarding malignant transformation of oral lichen planus. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 88, 307\u2013310 (1999).","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod."},{"key":"71496_CR10","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1034\/j.1600-0714.2003.00125.x","volume":"32","author":"EH van der Meij","year":"2003","unstructured":"van der Meij, E. H. & van der Waal, I. Lack of clinicopathologic correlation in the diagnosis of oral lichen planus based on the presently available diagnostic criteria and suggestions for modifications. J. Oral Pathol. Med. 32, 507\u2013512 (2003).","journal-title":"J. Oral Pathol. Med."},{"key":"71496_CR11","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.oooo.2016.05.004","volume":"122","author":"YSL Cheng","year":"2016","unstructured":"Cheng, Y. S. L., Gould, A., Kurago, Z., Fantasia, J. & Muller, S. Diagnosis of oral lichen planus: a position paper of the American Academy of Oral and Maxillofacial Pathology. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 122, 332\u2013354 (2016).","journal-title":"Oral Surg. Oral Med. Oral Pathol. Oral Radiol."},{"key":"71496_CR12","first-page":"120","volume-title":"Dermatopathology","author":"H Montogomery","year":"1967","unstructured":"Montogomery, H. Dermatopathology Vol. 1, 120 (Hoeber-Harper & Row, New York, 1967)."},{"key":"71496_CR13","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1007\/BF00595563","volume":"242","author":"H Ebner","year":"1972","unstructured":"Ebner, H. & Gebhart, W. Beitrag zur Histochmie und Ultrastructur der sogenannten hyalinen bzw. Kolloiden K\u00f6rperchen. Arch. Derm. Forsch. 242, 153\u2013164 (1972).","journal-title":"Arch. Derm. Forsch."},{"key":"71496_CR14","first-page":"162","volume-title":"Histopathologie Cutan\u00e9e","author":"J Civatte","year":"1982","unstructured":"Civatte, J. Histopathologie Cutan\u00e9e 2nd edn, 162\u2013167 (Flammarion, Paris, 1982).","edition":"2"},{"key":"71496_CR15","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1046\/j.1468-3083.2003.00577_7.x","volume":"17","author":"Y G\u00fcrb\u00fcz","year":"2003","unstructured":"G\u00fcrb\u00fcz, Y., Apaydin, R., M\u00fcezzino\u01e7lu, B., Bilen, N. & \u00d6zkara, S. K. Altered cytokeratin expression in lichen planus. J. Eur. Acad. Dermatol. Venereol. 17, 235\u2013236 (2003).","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"71496_CR16","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1111\/j.1600-0560.1998.tb01687.x","volume":"25","author":"H Biermann","year":"2006","unstructured":"Biermann, H. & Rauterberg, E. W. Expression of fetal cytokeratins in epidermal cells and colloid bodies in lichen planus. J. Cutan. Pathol. 25, 35\u201343 (2006).","journal-title":"J. Cutan. Pathol."},{"key":"71496_CR17","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1097\/DAD.0000000000000503","volume":"38","author":"J Lanoue","year":"2016","unstructured":"Lanoue, J., Yanofsky, V. R., Mercer, S. E. & Phelps, R. G. The use of anti-keratin 903 antibodies to visualize colloid bodies and diagnose lichen planopilaris. Am. J. Dermatopathol. 38, 353\u2013343 (2016).","journal-title":"Am. J. Dermatopathol."},{"key":"71496_CR18","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/0030-4220(81)90124-9","volume":"51","author":"TE Daniels","year":"1981","unstructured":"Daniels, T. E. & Quadra-White, C. Direct immunofluorescence in oral mucosal disese: a diagnostic analysis of 130 cases. Oral Surg. 51, 38\u201347 (1981).","journal-title":"Oral Surg."},{"key":"71496_CR19","first-page":"336","volume":"93","author":"K Pihlman","year":"1985","unstructured":"Pihlman, K., Hietanen, J., Linder, E. & Reunala, T. Immunologic findings of oral lichen planus. Scand. J. Dent. Res. 93, 336\u2013342 (1985).","journal-title":"Scand. J. Dent. Res."},{"key":"71496_CR20","first-page":"536","volume":"94","author":"J Reibel","year":"1986","unstructured":"Reibel, J. & Schi\u00f6dt, M. Immunohistochemical studies on colloid bodies (Civatte bodies) in oral lesions of discoid lupus erythematosus. Scand. J. Dent. Res. 94, 536\u2013544 (1986).","journal-title":"Scand. J. Dent. Res."},{"key":"71496_CR21","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1111\/j.1365-2559.2012.04283.x","volume":"61","author":"T Kobayashi","year":"2012","unstructured":"Kobayashi, T. et al. Keratin 10-positive orthokeratotic dysplasia: a new leucoplakia-type precancerous entity of the oral mucosa. Histopathology 61, 910\u2013920 (2012).","journal-title":"Histopathology"},{"key":"71496_CR22","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s12565-018-0462-x","volume":"94","author":"N Kitagawa","year":"2019","unstructured":"Kitagawa, N., Otani, T. & Inai, T. Nisin, a food preservative produced by Lactococcus lactis, affects the localization pattern of intermediate filament protein in HaCaT cells. Anat. Sci. Int. 94, 163\u2013171 (2019).","journal-title":"Anat. Sci. Int."},{"key":"71496_CR23","doi-asserted-by":"publisher","first-page":"1977","DOI":"10.1002\/jcp.24364","volume":"228","author":"K Al-Eryani","year":"2013","unstructured":"Al-Eryani, K. et al. Hemophagocytosis-mediated keratinization in oral carcinoma in-situ and squamous cell carcinoma: a possible histopathogenesis of keratin pearls. J. Cell. Physiol. 228, 1977\u20131988 (2013).","journal-title":"J. Cell. Physiol."},{"key":"71496_CR24","first-page":"153","volume-title":"Histopathology of the Skin","author":"WF Lever","year":"1967","unstructured":"Lever, W. F. Histopathology of the Skin 4th edn, 153\u2013158 (J. B. Lippoincott Co., Philadelphia, 1967).","edition":"4"},{"key":"71496_CR25","first-page":"5","volume":"80","author":"H Gourgerot","year":"1953","unstructured":"Gourgerot, H. & Civatte, A. Crit\u00e9res cliniques et histologiques des lichens plans cutan\u00e9s et muquex: D\u00e9limitation. Ann. Dermatol. 80, 5\u201329 (1953).","journal-title":"Ann. Dermatol."},{"key":"71496_CR26","first-page":"355","volume":"14","author":"VRW Golttz","year":"1963","unstructured":"Golttz, V. R. W. & Hult, A.-M. Zur histochemischen Natur der Kolloidk\u00f6rper beim Lichen ruber planus. Hautarzt 14, 355\u2013358 (1963).","journal-title":"Hautarzt"},{"key":"71496_CR27","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1834-7819.1980.tb03657.x","volume":"25","author":"CJ Griffin","year":"1980","unstructured":"Griffin, C. J., Jolly, M. & Smythe, J. D. The fine structure of epithelial cells in normal and pathological buccal mucosa. II. Colloid body formation. Aust. Dent. J. 25, 12\u201319 (1980).","journal-title":"Aust. Dent. J."},{"key":"71496_CR28","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/j.1600-0765.1970.tb00733.x","volume":"5","author":"NG El-Labban","year":"1970","unstructured":"El-Labban, N. G. Light and electron microscopic studies of colloid bodies in lichen planus. J. Periodont. Res. 5, 315\u2013324 (1970).","journal-title":"J. Periodont. Res."},{"key":"71496_CR29","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/0030-4220(69)90231-X","volume":"28","author":"PA Pullon","year":"1969","unstructured":"Pullon, P. A. Ultrastructure of oral lichen planus. Oral Surg. Oral Med. Oral Pathol. 28, 365\u2013371 (1969).","journal-title":"Oral Surg. Oral Med. Oral Pathol."},{"key":"71496_CR30","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1365-2133.1974.tb06357.x","volume":"90","author":"NG El-Labban","year":"1974","unstructured":"El-Labban, N. G. & Kramer, I. R. H. Civatte bodies and the actively dividing epithelial cells in oral lichen planus. Br. J. Dermatol. 90, 13\u201323 (1974).","journal-title":"Br. J. Dermatol."},{"key":"71496_CR31","doi-asserted-by":"publisher","first-page":"e704","DOI":"10.1097\/MD.0000000000000704","volume":"94","author":"T Maehara","year":"2015","unstructured":"Maehara, T. et al. Cytokine profiles contribute to understanding the pathogenic difference between Good syndrome and oral lichen planus: two case reports and literature review. Medicine (Baltimore) 94, e704 (2015).","journal-title":"Medicine (Baltimore)"},{"key":"71496_CR32","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1111\/j.0022-202X.2004.22709.x","volume":"123","author":"DA Jones","year":"2004","unstructured":"Jones, D. A. et al. Identification of autoantigens in psoriatic plaques using expression cloning. J. Invest. Dermatol. 123, 93\u2013100 (2004).","journal-title":"J. Invest. Dermatol."},{"key":"71496_CR33","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1002\/med.21291","volume":"34","author":"L Jin","year":"2014","unstructured":"Jin, L. & Wang, G. Keratin 17: a critical player in the pathogenesis of psoriasis. Med. Res. Rev. 34, 438\u2013454 (2014).","journal-title":"Med. Res. Rev."},{"key":"71496_CR34","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1111\/j.1600-0714.2010.00946.x","volume":"39","author":"MR Roopashree","year":"2010","unstructured":"Roopashree, M. R. et al. Pathogenesis of oral lichen planus\u2014a review. J. Oral Pathol. Med. 39, 729\u2013734 (2010).","journal-title":"J. Oral Pathol. Med."},{"key":"71496_CR35","doi-asserted-by":"publisher","first-page":"304","DOI":"10.3855\/jidc.7049","volume":"10","author":"A Karaaslan","year":"2016","unstructured":"Karaaslan, A. et al. Lactococcus lactis spp lactis infection in infants with chronic diarrhea: two cases report and literature review in children. J. Infect. Dev. Ctries. 10, 304\u2013307 (2016).","journal-title":"J. Infect. Dev. Ctries."},{"key":"71496_CR36","doi-asserted-by":"publisher","first-page":"112013","DOI":"10.1016\/j.yexcr.2020.112013","volume":"392","author":"M Yamazaki","year":"2020","unstructured":"Yamazaki, M. et al. Rac1-dependent phagocytosis of apoptotic cells by oral squamous cell carcinoma cells: a possible driving force for tumor progression. Exp. Cell Res. 392, 112013 (2020).","journal-title":"Exp. Cell Res."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71496-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71496-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71496-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T18:00:42Z","timestamp":1670349642000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-71496-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,3]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["71496"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-71496-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2020,9,3]]},"assertion":[{"value":"24 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14586"}}