{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T23:28:28Z","timestamp":1779233308900,"version":"3.51.4"},"reference-count":95,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Max Lindemann Memorial Foundation Miami"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Parathyroid cancer (PC) is rare, but its pre-operative recognition is important to choose appropriate access strategies and achieve oncological clearance. This study characterizes features of mediastinal parathyroid cancer (MPC) and explores criteria aiding in the pre-operative recognition of malignancy. We assembled data from 502 patients with mediastinal parathyroid neoplasms (MPNs) from a systematic review of the literature 1968\u20132020 (n = 467) and our own patient cohort (n = 35). Thirty-two of the 502 MPNs (6.4%) exhibited malignancy. Only 23% of MPC patients underwent oncological surgery. Local persistence and early recurrence at a median delay of 24 months were frequent (45.8%), and associated with a 21.7-fold (95%CI 1.3\u2013351.4; p = 0.03) higher risk of death due to disease. MPCs (n = 30) were significantly larger than cervical PC (n = 330), at 54 \u00b1 36 mm vs. 35 \u00b1 18 mm (\u03c72 = 20; p &lt; 0.0001), and larger than mediastinal parathyroid adenomas (MPA; n = 226) at 22 \u00b1 15 mm (\u03c72 = 33; p &lt; 0.01). MPC occurred more commonly in males (60%; p &lt; 0.01), with higher calcium (p &lt; 0.01) and parathyroid hormone (PTH) levels (p &lt; 0.01) than MPA. Mediastinal lesions larger than 3.0 cm and associated with a corrected calcium \u2265 3.0 mM are associated with a more than 100-fold higher odds ratio of being malignant (OR 109.2; 95%CI 1.1\u2013346; p &lt; 0.05). The composite 3 + 3 criterion recognized 74% of all MPC with an accuracy of 83%. Inversely, no MPN presenting with a calcium &lt; 3.0 mM and size &lt; 3.0 cm was malignant. When faced with pHPT in mediastinal location, consideration of the 3 + 3 rule may trigger an oncological team approach based on simple, available criteria.<\/jats:p>","DOI":"10.3390\/cancers14235852","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T07:01:30Z","timestamp":1669618890000},"page":"5852","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mediastinal Parathyroid Cancer"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9091-0512","authenticated-orcid":false,"given":"Klaus-Martin","family":"Schulte","sequence":"first","affiliation":[{"name":"Academic Department of Surgery, School of Medicine and Psychology, College of Health and Medicine, Australian National University, Canberra, ACT 2601, Australia"},{"name":"Department of Endocrine Surgery, King\u2019s College Hospital Foundation Trust, London SE5 9RS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1450-044X","authenticated-orcid":false,"given":"Gabriele","family":"Galat\u00e1","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, King\u2019s College Hospital Foundation Trust, London SE5 9RS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Talat","sequence":"additional","affiliation":[{"name":"Department of Endocrine Surgery, King\u2019s College Hospital Foundation Trust, London SE5 9RS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.coemr.2018.03.003","article-title":"Primary hyperparathyroidism\u2014Hypercalcemic and normocalcemic variants","volume":"3","author":"Bilezikian","year":"2018","journal-title":"Curr. 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