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Unlike functional parathyroid carcinomas (PC), which typically present with severe hyperparathyroidism (HPT) and are monitored via serum calcium and parathyroid hormone (PTH) levels, NFPC lacks biochemical markers and is monitored solely through imaging. In this study, we present two new cases of primary NFPC and provide a comprehensive review of the literature, including a detailed analysis of immunohistochemical and molecular testing. We also explore potential mechanisms underlying the non-functional state in PC. In one case, the tumor lacked PTH expression by immunohistochemistry, yet low levels of\n                    <jats:italic>PTH<\/jats:italic>\n                    mRNA expression were consistently detected. Differential diagnoses\u2014including medullary and non-medullary thyroid carcinoma, paraganglioma, and other head and neck tumors\u2014were excluded. The second case demonstrated patchy residual PTH immunostaining. Both tumors exhibited extensive whole chromosome losses resulting in a near-haploid genome, with (NFPC 2) or without (NFPC 1) subsequent endoreduplication\/genome doubling. The mutational landscape differed between the two, with neither showing\n                    <jats:italic>CDC73<\/jats:italic>\n                    mutations or loss of parafibromin expression. Diagnosing primary non-functional parathyroid carcinoma can be especially challenging in cases with negative PTH immunohistochemistry.\n                  <\/jats:p>","DOI":"10.1007\/s00428-025-04193-4","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T07:37:40Z","timestamp":1754379460000},"page":"1247-1263","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Diagnosing the silent: the molecular landscape of non-functional parathyroid carcinoma"],"prefix":"10.1007","volume":"487","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5724-7643","authenticated-orcid":false,"given":"Maaia Margo","family":"Jentus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willem E.","family":"Corver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"Snel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke M.","family":"van Haalen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"van Wezel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Ruano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Kapiteijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stijn","family":"Crobach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha M.","family":"Appelman-Dijkstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbey","family":"Schepers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Morreau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"issue":"10","key":"4193_CR1","doi-asserted-by":"publisher","first-page":"3091","DOI":"10.1007\/s00432-021-03576-9","volume":"147","author":"SH Kong","year":"2021","unstructured":"Kong SH, Kim JH, Park MY, Kim SW, Shin CS (2021) Epidemiology and prognosis of parathyroid carcinoma: real-world data using nationwide cohort. 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