{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:11:16Z","timestamp":1779192676868,"version":"3.51.4"},"reference-count":88,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-053"],"award-info":[{"award-number":["2021-I2M-1-053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parathyroid carcinoma (PC) is a rare endocrine malignancy characterized by aggressive clinical behavior driven primarily by parathyroid hormone (PTH) overproduction. Standard morphological assessments frequently struggle to definitively distinguish true carcinomas from atypical benign lesions, presenting significant diagnostic challenges and a risk of overdiagnosis. Recent advances emphasize the genetic and epigenetic foundations of PC tumor biology. A central oncogenic mechanism involves the CDC73 gene, where the biallelic inactivation of CDC73 and the gain of function of mutant parafibromin\u2014which destabilizes p53 mRNA\u2014facilitate apoptosis evasion. Additionally, alterations in parallel pathways, such as the PI3K\/AKT\/mTOR cascade, and epigenetic dysregulation further contribute to disease progression. To address morphological limitations, contemporary diagnostic approaches increasingly utilize adjunctive multimarker immunohistochemical panels (including parafibromin, Ki-67, and Galectin-3) and explore emerging non-coding RNA liquid biopsy signatures. Finally, this review discusses the development of preclinical models and the application of genotype-guided targeted therapies, aiming to improve the clinical management and precision medicine strategies for PC.<\/jats:p>","DOI":"10.3390\/ijms27104549","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:53:10Z","timestamp":1779191590000},"page":"4549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Parathyroid Carcinoma: From Molecular Pathogenesis and Diagnostic Biomarkers to Targeted Therapeutics"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1368-4387","authenticated-orcid":false,"given":"Chunlong","family":"Wang","sequence":"first","affiliation":[{"name":"Cell Resource Center, Department of Pathology, Institute of Basic Medical Sciences, School of Basic Medicine, Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing 100005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Geriatric Department, Peking University People\u2019s Hospital, Beijing 100044, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqin","family":"Liu","sequence":"additional","affiliation":[{"name":"Cell Resource Center, Department of Pathology, Institute of Basic Medical Sciences, School of Basic Medicine, Chinese Academy of Medical Sciences (CAMS), Peking Union Medical College (PUMC), Beijing 100005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.beem.2018.11.002","article-title":"Parathyroid carcinoma","volume":"32","author":"Salcuni","year":"2018","journal-title":"Best Pract. 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