{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:46:35Z","timestamp":1785890795940,"version":"3.56.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["HT94252410688"],"award-info":[{"award-number":["HT94252410688"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Head and Neck Pathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Upper aerodigestive tract squamous cell carcinoma (UATSCC) is often easy to recognize in its conventional form. However, a subset of tumors loses histologic evidence of squamous differentiation and, instead, become sarcomatoid (spindled). These cases may be difficult or impossible to appropriately classify on biopsy material, even with immunohistochemistry. DNA methylation has emerged as a tool to help in classifying undifferentiated malignancies. We sought to explore whether conventional and sarcomatoid UATSCC harbor the same epigenetic signature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cases of sarcomatoid UATSCC were collected and reviewed. The conventional and sarcomatoid components were documented. Only specimens with concomitant epithelial dysplasia and\/or invasive SCC were included. A panel of keratins (CK AE1\/3, CAM5.2 and CK5\/6) was performed on the sarcomatoid component of each tumor and scored as follows: 0, &lt;\u20091%; 1+, 1\u201325%; 2+, 26\u201350%, 3+, &gt;\u200950%. DNA methylation profiling was performed and compared with profiles from publicly available UATSCC and a control cohort of pleomorphic malignancies including undifferentiated sarcoma, leiomyosarcoma, angiosarcoma, atypical fibroxanthoma\/pleomorphic dermal sarcoma, and melanoma, as well as sarcomatoid carcinoma of cutaneous origin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>21 UATSCC samples from 15 patients were retrieved (9\u00a0M, 6\u00a0F; 47\u201388 years, median 71 years) from sites including tongue (7), larynx (5), pharynx (3), maxillary\/mandibular alveolar ridge (3), \u201cneck\u201d (2), and nasal cavity (1). 12 samples were entirely sarcomatous, while six were conventional SCC and three contained both sarcomatoid and conventional components. Of the sarcomatous components, six were entirely negative (score\u2009=\u20090) for all keratins performed. Using dimensionality reduction analysis of DNA methylation data by Uniform Manifold Approximation and Projection (UMAP) and unsupervised hierarchical clustering, 11 of 12 sarcomatoid UATSCC samples, were positioned with conventional UATSCC. Methylomes of sarcomatoid carcinoma of upper aerodigestive tract and cutaneous origin overlapped. Copy number profile analysis did not show significant differences between conventional and sarcomatoid histologies or tumor time point.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The epigenetic signatures of conventional and sarcomatoid UATSCC are similar, even in cases that lack expression of multiple keratins. DNA methylation profiling may be leveraged in biopsies and entirely sarcomatoid UATSCC to accurately diagnose these cases and differentiate them from pleomorphic sarcomas and melanoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12105-026-01958-4","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T23:52:28Z","timestamp":1785887548000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DNA Methylation Signatures of Upper Aerodigestive Tract Squamous Cell Carcinoma and Sarcomatoid Squamous Cell Carcinoma Are Similar: A Potential Novel Diagnostic Tool for the Diagnosis of Sarcomatoid Squamous Cell Carcinoma"],"prefix":"10.1007","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1139-2914","authenticated-orcid":false,"given":"Josephine K.","family":"Dermawan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Griffith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Starbuck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila","family":"Shurtleff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Travis","family":"Hattery","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Nakitandwe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shauna","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S. A.","family":"Chrisinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Azzato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen J.","family":"Fritchie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"issue":"2","key":"1958_CR1","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1097\/PAS.0000000000000119","volume":"38","author":"JA Bishop","year":"2014","unstructured":"Bishop JA, Montgomery EA, Westra WH (2014) Use of p40 and p63 immunohistochemistry and human papillomavirus testing as ancillary tools for the recognition of head and neck sarcomatoid carcinoma and its distinction from benign and malignant mesenchymal processes. 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For this type of study formal consent is not required. This study was approved by our institutional review board.","order":3,"name":"Ethics","label":"Ethics Approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"For this type of study informed consent is not required.","order":4,"name":"Ethics","label":"Consent to Participate","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"89"}}