{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T13:51:23Z","timestamp":1777125083498,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The formal pathogenesis of salivary carcinosarcoma (SCS) remained unclear, both with respect to the hypothetical development from either preexisting pleomorphic adenoma (PA) or <jats:italic>de novo<\/jats:italic> and the clonal relationship between highly heterogeneous carcinomatous and sarcomatous components.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We performed clinicopathological and molecular (targeted RNA sequencing) analyses on a large series of 16 cases and combined this with a comprehensive literature search (111 cases). Extensive sampling (average 11.6 blocks), combined with immunohistochemistry and molecular studies (PA\u2010specific translocations including <jats:italic>PLAG1<\/jats:italic> or <jats:italic>HMGA2<\/jats:italic> proven in 6\/16 cases), enabled the morphogenetic identification of PA in 15\/16 cases (93.8%), by far surpassing a reported rate of 49.6%. Furthermore, we demonstrated a multistep (intraductal\/intracapsular\/extracapsular) adenoma\u2010carcinoma\u2010sarcoma\u2010progression, based on two alternative histogenetic pathways (intraductal, 56.3%, versus myoepithelial pathway, 37.5%). Thereby, early intracapsular stages are identical to conventional carcinoma ex PA, while later extracapsular stages are dominated by secondary, frequently heterologous sarcomatous transformation with often large tumour size (&gt;60\u2009mm).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings strongly indicate that SCS (almost) always develops from PA, with a complex multistep adenoma\u2010carcinoma\u2010sarcoma\u2010sequence, based on two alternative histogenetic pathways. The findings from this novel approach strongly suggest that SCS pathogenetically is a rare (3\u20136%), unique, and aggressive variant of carcinoma ex PA with secondary sarcomatous overgrowth. In analogy to changes of terminology in other organs, the term \u201csarcomatoid carcinoma ex PA with\/without heterologous elements\u201d might be more appropriate.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14840","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T03:34:20Z","timestamp":1668483260000},"page":"576-586","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Salivary carcinosarcoma: insight into multistep pathogenesis indicates uniform origin as sarcomatoid variant of carcinoma ex pleomorphic adenoma with frequent heterologous elements"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6183-0249","authenticated-orcid":false,"given":"Stephan","family":"Ihrler","sequence":"first","affiliation":[{"name":"DERMPATH Muenchen  Munich Germany"},{"name":"Institute of Pathology Ludwig\u2010Maximilians\u2010University  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Stiefel","sequence":"additional","affiliation":[{"name":"Dental School Ludwig\u2010Maximilians\u2010University  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Jurmeister","sequence":"additional","affiliation":[{"name":"Institute of Pathology Ludwig\u2010Maximilians\u2010University  Munich Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann","family":"Sandison","sequence":"additional","affiliation":[{"name":"Department of Head Neck Oral Pathology Guy's and St Thomas' NHS Foundation Trust  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Chaston","sequence":"additional","affiliation":[{"name":"Department of Pathology East Kent Hospitals University NHS Foundation Trust  Ashford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Laco","sequence":"additional","affiliation":[{"name":"Fingerland Department of Pathology Charles University Faculty of Medicine and University Hospital Hradec Kralove  Hradec Kr\u00e1lov\u00e9 Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6866-3220","authenticated-orcid":false,"given":"Nina","family":"Zidar","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Faculty of Medicine University of Ljubljana  Ljubljana Slovenia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-8416","authenticated-orcid":false,"given":"Luka","family":"Brcic","sequence":"additional","affiliation":[{"name":"D&amp;R Institute of Pathology Medical University of Graz  Graz Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Stoehr","sequence":"additional","affiliation":[{"name":"Institute of Pathology Friedrich\u2010Alexander University, Erlangen\u2010N\u00fcrnberg, University Hospital Erlangen  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0445-8161","authenticated-orcid":false,"given":"Abbas","family":"Agaimy","sequence":"additional","affiliation":[{"name":"Institute of Pathology Friedrich\u2010Alexander University, Erlangen\u2010N\u00fcrnberg, University Hospital Erlangen  Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0030-4220(86)90102-7"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1984.00800290036008"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tripleo.2006.06.055"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1079-2104(05)80309-9"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348948909800808"},{"key":"e_1_2_12_7_1","first-page":"279","article-title":"Malignant mixed tumors of the salivary glands: a review","volume":"28","author":"Gnepp DR","year":"1993","journal-title":"Pathol. Annu."},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0030-4220(67)90348-9"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.2739\/kurumemedj.47.307"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.2880110104"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00705409"},{"key":"e_1_2_12_12_1","volume-title":"WHO classification of head and neck Tumours","author":"El\u2010Naggar AK","year":"2017"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-012-0385-0"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/aqaa104"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2008.05.009"},{"key":"e_1_2_12_16_1","volume-title":"Head and Neck Tumours","author":"WHO Classification of Tumours Editorial Board","year":"2022"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1309\/5J4008QRY1HWW5W4"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(00)80221-X"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199603000-00003"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2011.03937.x"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2106-2"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2009.12.011"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2005.02058.x"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12454"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.1100"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-015-1887-4"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2007.02736.x"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000980"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001783"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.4103\/2231-0746.175757"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14840","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/his.14840","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14840","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T20:17:18Z","timestamp":1692562638000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.14840"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,7]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["10.1111\/his.14840"],"URL":"https:\/\/doi.org\/10.1111\/his.14840","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,7]]},"assertion":[{"value":"2022-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-12-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}