{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T12:58:43Z","timestamp":1785243523538,"version":"3.55.0"},"reference-count":103,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Chordoma is a rare notochordal malignancy of the axial skeleton, and distant cutaneous metastasis is among its rarest manifestations\u2014an under-recognised mimic of benign and malignant skin tumours that often presents with an incomplete clinical history. Methods: We performed a systematic review and one-stage individual-participant-data (IPD) meta-analysis of all reported cases of distant cutaneous chordoma metastasis, following PRISMA 2020, and complemented it with an illustrative index case of cutaneous poorly differentiated chordoma in a young adult. Missing case-level data were handled by available-case analysis without imputation, with denominators reported throughout. Pooled prevalences were estimated by logistic-normal random-effects models (heterogeneity by I2); latency to cutaneous metastasis was modelled as a time-to-event outcome, and brachyury uptake over time by meta-regression. Results: Forty reports (52 cases) were included; individual data were analysable in 43. Median age was 59 years (range, 2 months\u201388), male-to-female ratio 2.3:1, sacrococcygeal primary 74% (31\/42) and median latency 4.0 years (synchronous to 15). Physaliphorous cells, myxoid stroma and vacuolated cytoplasm dominated, yet brachyury and SMARCB1\/INI1 were documented in only 6\/52 and 1\/52 cases. Pooled prevalences were 74% (95% CI 59\u201385) for a sacrococcygeal primary, 70% (55\u201382) for male sex and 77% (62\u201387) for physaliphorous morphology, with no between-report heterogeneity (I2 = 0%)\u2014expected when almost every report contributes one patient, so these values consolidate rather than extend the descriptive data. Patients younger than 40 years reached cutaneous metastasis far earlier (hazard ratio 17.2, 95% CI 4.7\u201362.9; p &lt; 0.001), and brachyury use rose across eras (\u03c1 = 0.43, p = 0.008). Conclusions: Distant cutaneous chordoma metastasis is a late event that usually signals disseminated disease and a limited life expectancy, commonly months to a few years. Its recognition rests on integrating morphology with nuclear brachyury and, in epithelioid or young presentations, SMARCB1\/INI1. We provide a differential-diagnostic framework and algorithm, distinguishing cohort-supported findings from expert interpretation.<\/jats:p>","DOI":"10.3390\/cells15151348","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T14:08:14Z","timestamp":1785161294000},"page":"1348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distant Cutaneous Metastasis of Chordoma: A Systematic Review and Individual-Participant-Data Meta-Analysis of 52 Cases, with an Illustrative Poorly Differentiated Index Case"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5219-5466","authenticated-orcid":false,"given":"Andreea-Adriana","family":"Neam\u021bu","sequence":"first","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research Centre for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Department of Pathology, Clinical County Emergency Hospital of Arad, Andrenyi Karoly Str., No. 2\u20134, 310037 Arad, Romania"},{"name":"Department of Pathology, \u201cPius Br\u00eenzeu\u201d Clinical County Emergency Hospital Timi\u0219oara, Liviu Rebreanu Boulevard, No. 156, 300723 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Chioiba\u0219","sequence":"additional","affiliation":[{"name":"Department of Surgery I, Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"CBS Medcom Hospital Timi\u0219oara, Popa \u0218apc\u0103 Str., No. 12, 300047 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8088-419X","authenticated-orcid":false,"given":"Alicia","family":"Goldenberg","sequence":"additional","affiliation":[{"name":"Department of Pathology, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY 14263, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8901-8271","authenticated-orcid":false,"given":"Laura","family":"Maghiar","sequence":"additional","affiliation":[{"name":"Department of Psycho-Neurosciences and Rehabilitation, Faculty of Medicine and Pharmacy, University of Oradea, Universit\u0103\u021bii Str., No. 1, 410087 Oradea, Romania"},{"name":"Department of Dermatovenerology, Clinical County Emergency Hospital Bihor, Gheorghe Doja Str., No. 65, 410169 Oradea, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4634-969X","authenticated-orcid":false,"given":"Robert","family":"Barna","sequence":"additional","affiliation":[{"name":"Department of Microscopic Morphology\u2014Anatomic Pathology, ANAPATMOL Research Center, Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrada","family":"Iftode","sequence":"additional","affiliation":[{"name":"Department of Toxicology, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"},{"name":"Research Centre for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-6872","authenticated-orcid":false,"given":"Titus","family":"Grecu","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3971-2756","authenticated-orcid":false,"given":"Sorina","family":"Taban","sequence":"additional","affiliation":[{"name":"Department of Microscopic Morphology\u2014Anatomic Pathology, ANAPATMOL Research Center, Faculty of Medicine, \u201cVictor Babe\u0219\u201d University of Medicine and Pharmacy Timi\u0219oara, Eftimie Murgu Square, No. 2, 300041 Timi\u0219oara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0874-5616","authenticated-orcid":false,"given":"Aleodor","family":"Andea","sequence":"additional","affiliation":[{"name":"Department of Pathology, Roswell Park Comprehensive Cancer Center, Elm and Carlton Streets, Buffalo, NY 14263, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","unstructured":"WHO (2020). 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