{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T12:14:11Z","timestamp":1781871251555,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000871","name":"Mayo Clinic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Adamantinoma\u2010like Ewing sarcoma (ALES) is a rare aggressive malignancy occasionally diagnosed in the thyroid gland. ALES shows basaloid cytomorphology, expresses keratins, p63, p40, frequently CD99, and harbours the t(11;22) <jats:italic>EWSR1::FLI1<\/jats:italic> translocation. There is debate on whether ALES resembles more sarcoma or carcinoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed RNA sequencing from two ALES cases and compared findings with skeletal Ewing's sarcomas and nonneoplastic thyroid tissue. ALES was investigated by <jats:italic>in situ<\/jats:italic> hybridization (ISH) for high\u2010risk human papillomavirus (HPV) DNA and immunohistochemistry for the following antigens: keratin 7, keratin 20, keratin 5, keratins (AE1\/AE3 and CAM5.2), CD45, CD20, CD5, CD99, chromogranin, synaptophysin, calcitonin, thyroglobulin, PAX8, TTF1, S100, p40, p63, p16, NUT, desmin, ER, FLI1, INI1, and myogenin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>An uncommon <jats:italic>EWSR1::FLI<\/jats:italic> transcript with\u00a0retained <jats:italic>EWSR1<\/jats:italic> exon 8 was detected in both ALES cases. Regulators of <jats:italic>EWSR1::FLI1<\/jats:italic> splicing (<jats:italic>HNRNPH1<\/jats:italic>, <jats:italic>SUPT6H<\/jats:italic>, <jats:italic>SF3B1)<\/jats:italic> necessary for production of a functional fusion oncoprotein, as well as 53 genes (including <jats:italic>TNNT1<\/jats:italic>, <jats:italic>NKX2.2<\/jats:italic>) activated downstream to the <jats:italic>EWSR1::FLI1<\/jats:italic> cascade, were overexpressed. Eighty\u2010six genes were uniquely overexpressed in ALES, most of which were related to squamous differentiation. Immunohistochemically, ALES strongly expressed keratins 5, AE1\/AE3 and CAM5.2, p63, p40, p16, and focally CD99. INI1 was retained. The remaining immunostains and HPV DNA ISH were negative.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Comparative transcriptomic profiling reveals overlapping features of ALES with skeletal Ewing's sarcoma and an epithelial carcinoma, as evidenced by immunohistochemical expression of keratin 5, p63, p40, CD99, the transcriptome profile, and detection of <jats:italic>EWSR1::FLI1<\/jats:italic> fusion transcript by RNA sequencing.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.14961","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T15:10:43Z","timestamp":1684336243000},"page":"426-434","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptomic and immunophenotypic characterization of two cases of adamantinoma\u2010like Ewing sarcoma of the thyroid gland"],"prefix":"10.1111","volume":"83","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-6952","authenticated-orcid":false,"given":"Kyriakos","family":"Chatzopoulos","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"},{"name":"Department of General and Anatomic Pathology, Faculty of Medicine Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime I.","family":"Davila","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Numrah","family":"Fadra","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory A.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"},{"name":"NeoGenomics Laboratories  Aliso Viejo CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay T.","family":"Minn","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotiris","family":"Sotiriou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"},{"name":"Department of General and Anatomic Pathology, Faculty of Medicine Aristotle University of Thessaloniki  Thessaloniki Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre M.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3666-2546","authenticated-orcid":false,"given":"Lori A.","family":"Erickson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin C.","family":"Halling","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kandelaria M.","family":"Rumilla","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000000460"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199902000-00004"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-019-01098-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2095-1"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-15-224"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-4-r36"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2011-12-8-r72"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0506580102"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr260"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan2507"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.072454.119"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.12.063"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-1761"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-017-0830-1"},{"key":"e_1_2_9_18_1","first-page":"6431","article-title":"Slow skeletal muscle troponin T, titin and myosin light chain 3 are candidate prognostic biomarkers for Ewing's sarcoma","volume":"18","author":"Deng Y","year":"2019","journal-title":"Oncol. Lett."},{"key":"e_1_2_9_19_1","unstructured":"Gene Ontology (Gene Ontology Consortium) [Internet]. Skin development. Accessed August 25 2020. Available at:http:\/\/amigo.geneontology.org\/amigo\/term\/GO:0043588."},{"key":"e_1_2_9_20_1","unstructured":"Gene Ontology (Gene Ontology Consortium) [Internet]. Epidermis development. Accessed August 25 2020. Available at:http:\/\/amigo.geneontology.org\/amigo\/term\/GO:008544."},{"key":"e_1_2_9_21_1","unstructured":"Gene Ontology (Gene Ontology Consortium) [Internet]. Keratinocyte differentiation. Accessed August 25 2020. at:http:\/\/amigo.geneontology.org\/amigo\/term\/GO:0030216."},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1434"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000345245"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-019-01021-5"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-022-01412-1"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001171"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12105-014-0558-0"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/cyt.12817"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2019.04.008"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-017-2148-5"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001064"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/1066896911405320"},{"key":"e_1_2_9_33_1","first-page":"54","article-title":"EWSR1 rearrangement in papillary thyroid microcarcinoma is related to classic morphology and the presence of small\u2010cell phenotype","volume":"22","author":"Kovacevic B","year":"2022","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/1066896913486696"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2011.01.004"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2011.07.008"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056408"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08014-w"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.07.034"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2013.11.003"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0434-18.2019"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-018-0212-9"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0888-7543(03)00149-6"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.3233\/CBM-191200"},{"key":"e_1_2_9_45_1","first-page":"615","article-title":"Plasmacytoid dendritic cell subpopulations in head and neck squamous cell carcinoma","volume":"26","author":"Thiel A","year":"2011","journal-title":"Oncol. Rep."},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.06.107"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i10.1562"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601120"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.14961","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T05:26:34Z","timestamp":1691645194000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.14961"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,17]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1111\/his.14961"],"URL":"https:\/\/doi.org\/10.1111\/his.14961","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,17]]}}}