{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:18:22Z","timestamp":1788499102676,"version":"build-2803163510"},"reference-count":12,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2C2010148"],"award-info":[{"award-number":["2022R1A2C2010148"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2022R1A2C2010148"],"award-info":[{"award-number":["2022R1A2C2010148"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Ministry of Health & Welfare","award":["RS-2020-KH088690"],"award-info":[{"award-number":["RS-2020-KH088690"]}]},{"name":"Ministry of Health & Welfare","award":["RS-2024-00440671"],"award-info":[{"award-number":["RS-2024-00440671"]}]},{"name":"Ministry of Health & Welfare","award":["RS-2025-24536373"],"award-info":[{"award-number":["RS-2025-24536373"]}]},{"DOI":"10.13039\/501100002462","name":"Chungnam National University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002462","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0227as991","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background and Clinical Significance: Cutaneous angiosarcoma frequently metastasizes to the lungs, where it may rarely present as diffuse cystic lung disease with recurrent pneumothorax, resulting in substantial diagnostic difficulty. We report a case of pulmonary metastatic cutaneous angiosarcoma in which paired whole-genome sequencing (WGS) of the primary and metastatic lesions was performed to clarify clonal origin and characterize metastatic evolution. Case Presentation: A 65-year-old man with recurrent right-sided pneumothorax and progressive bilateral cystic lung lesions underwent skin and lung biopsies. Histopathological examination and immunohistochemistry established the diagnosis of cutaneous angiosarcoma with pulmonary metastases. Paired WGS was performed on matched scalp and lung tumor specimens to evaluate shared and lesion-specific genomic alterations, pathway enrichment, and copy-number changes. Histopathology confirmed metastatic angiosarcoma involving the lungs. WGS identified 128 shared somatic alterations, supporting a common clonal origin, together with lung-specific and skin-specific mutations indicative of continued genomic divergence. Recurrent alterations involving POT1 and FLT4 were preserved in both lesions, whereas additional POT1 and TP53 alterations were detected only in the pulmonary metastasis. Pathway analysis demonstrated preferential enrichment of IGF1\u2013mTOR, RAS, and WNT\/LRP6 signaling in the metastatic lesion, while Gene Ontology analysis suggested functional divergence associated with metastatic progression. Conclusions: Pulmonary metastatic angiosarcoma should be considered in patients presenting with unexplained diffuse cystic lung disease and recurrent pneumothorax, particularly when pathological findings are inconclusive. Paired WGS complemented conventional histopathology by confirming the metastatic origin and providing insights into clonal evolution and lesion-specific molecular alterations, highlighting its potential value in the investigation of rare metastatic malignancies.<\/jats:p>","DOI":"10.3390\/diagnostics16172824","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:57:23Z","timestamp":1788346643000},"page":"2824","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Paired Whole-Genome Sequencing of Scalp Angiosarcoma and Matched Lung Metastasis Reveals Common Clonal Origin and Lung-Specific Evolution"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9841-2514","authenticated-orcid":false,"given":"Green","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea"},{"name":"Department of Internal Medicine, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1935-2140","authenticated-orcid":false,"given":"Yooyoung","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Thoracic & Cardiovascular Surgery, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-1439","authenticated-orcid":false,"given":"Joo-Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Research Institute, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Yi","family":"Kim","sequence":"additional","affiliation":[{"name":"NGeneS Inc., Sangnok-gu, Asan 15495, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2776-8146","authenticated-orcid":false,"given":"Dahye","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-1785","authenticated-orcid":false,"given":"Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Dermatology, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8873-0021","authenticated-orcid":false,"given":"Min-Kyung","family":"Yeo","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3978-0484","authenticated-orcid":false,"given":"Chaeuk","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, Chungnam National University Hospital, 282 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea"},{"name":"Department of Internal Medicine, College of Medicine, Chungnam National University, 266 Munhwa-ro, Jung-gu, Daejeon 35015, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"200041","DOI":"10.1183\/20734735.0041-2020","article-title":"Investigating cystic lung disease: A respiratory detective approach","volume":"16","author":"Ennis","year":"2020","journal-title":"Breathe"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"bcr2018224648","DOI":"10.1136\/bcr-2018-224648","article-title":"Unusual cystic lung metastasis","volume":"2018","author":"Sagar","year":"2018","journal-title":"BMJ Case Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/COC.0b013e31827e4e7b","article-title":"Angiosarcoma outcomes and prognostic factors: A 25-year single institution experience","volume":"37","author":"Buehler","year":"2014","journal-title":"Am. 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Cancer Netw."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2824\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T04:49:16Z","timestamp":1788497356000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/17\/2824"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":12,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["diagnostics16172824"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16172824","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]}}}