{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:51:57Z","timestamp":1789757517363,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T00:00:00Z","timestamp":1746576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HUN-REN OOI-TTK-HCEMM Oncogenomics Research Group","award":["7634"],"award-info":[{"award-number":["7634"]}]},{"DOI":"10.13039\/501100015763","name":"University of Szeged","doi-asserted-by":"publisher","award":["7634"],"award-info":[{"award-number":["7634"]}],"id":[{"id":"10.13039\/501100015763","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The clinicopathological and molecular features of synchronous parathyroid carcinoma (PC) and thyroid carcinoma in a male patient are presented. At 11, he received mantle field radiotherapy for Hodgkin lymphoma. He had a 26-year adulthood history of recurrent nephrolithiasis treated five times with lithotripsy. At 52, he was referred to our clinic for hypercalcemia. Primary hyperparathyroidism was diagnosed (calcium: 3.46 mmol\/L, parathormone: 150 pmol\/L, preserved renal function, nephrolithiasis, and osteoporosis). Neck ultrasound revealed a 41 \u00d7 31 \u00d7 37 mm nodule in the left thyroid and smaller nodules in the right thyroid. Enlarged cervical lymph nodes were not observed. The large nodule was interpreted as parathyroid adenoma on 99Tc-pertechnetate scintigraphy\/99Tc-MIBI scintigraphy with SPECT\/CT. Total left-sided and subtotal right-sided thyroidectomy were performed. Histopathology confirmed locally invasive, low-grade PC (pT2; positive for parafibromin and E-cadherin, negative for galectin-3 and PGP9.5; wild-type expression for p53 and retinoblastoma protein; Ki-67 index 10%) and incidental papillary thyroid carcinoma (pT1b). Genetic profiling revealed no loss in CDC73, MEN1, CCND1, PIK3CA, CDH1, RB1, and TP53 genes. Deletions in CDKN2A, LATS1, ARID1A, ARID1B, RAD54L, and MUTYH genes and monosomies in nine chromosomes were identified. The tumor mutational burden and genomic instability score were low, and the tumor was microsatellite-stable. The thyroid carcinoma exhibited a TRIM24::BRAF fusion. Following surgery, the parathormone and calcium levels had normalized, and the patient underwent radioiodine treatment for thyroid cancer. The follow-up of 14 months was eventless. In summary, the clinical, laboratory, and imaging features of hyperparathyroidism taken together could have suggested malignancy, then confirmed histologically. The synchronous carcinomas were most likely caused by irradiation treatment diagnosed 41 years after exposure. It seems that the radiation injury initially induced parathyroid adenoma in young adulthood, which underwent a malignant transformation around age fifty.<\/jats:p>","DOI":"10.3390\/ijms26094441","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T08:20:53Z","timestamp":1746606053000},"page":"4441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Radiation-Induced Synchronous Parathyroid Carcinoma and Papillary Thyroid Carcinoma: Clinical, Morphological, and Genetic Insights"],"prefix":"10.3390","volume":"26","author":[{"given":"G\u00e1bor","family":"Iv\u00e1nyi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged,  6722 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros","family":"Christofi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged,  6722 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Sipka","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged,  6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Zombori","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9247-6679","authenticated-orcid":false,"given":"Levente","family":"Kuthi","sequence":"additional","affiliation":[{"name":"Department of Surgical and Molecular Pathology, Tumor Pathology Center, National Institute of Oncology, 1122 Budapest, Hungary"},{"name":"Department of Pathology and Experimental Cancer Research, Semmelweis University, 1086 Budapest, Hungary"},{"name":"HUN-REN-ONKOL-TTK-HCEMM Oncogenomics Research Group, National Institute of Oncology, 1122 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Surgical and Molecular Pathology, Tumor Pathology Center, National Institute of Oncology, 1122 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dej\u00e1n","family":"Dobi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, 1091 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"L\u00e1z\u00e1r","sequence":"additional","affiliation":[{"name":"Department of Surgery, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Valkusz","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged,  6722 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4546-6253","authenticated-orcid":false,"given":"B\u00e9la","family":"Iv\u00e1nyi","sequence":"additional","affiliation":[{"name":"Department of Pathology, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e220287","DOI":"10.1530\/ERC-22-0287","article-title":"Diagnosis and management of parathyroid carcinoma: A state-of-the-art review","volume":"30","author":"Roser","year":"2023","journal-title":"Endocr.-Relat. Cancer."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1200\/JOP.19.00540","article-title":"Contemporary evolution and management of parathyroid carcinoma","volume":"17","author":"Fingeret","year":"2020","journal-title":"JCO Oncol. Pract."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1210\/clinem\/dgad455","article-title":"Approach to a patient with parathyroid carcinoma","volume":"109","author":"Cetani","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101966","DOI":"10.1016\/j.beem.2024.101966","article-title":"Parathyroid carcinoma: New insights","volume":"39","author":"Viswanath","year":"2025","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s12022-019-09592-3","article-title":"Using a novel diagnostic nomogram to differentiate malignant from benign parathyroid neoplasms","volume":"30","author":"Bassett","year":"2019","journal-title":"Endocr. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1038\/s41379-019-0252-6","article-title":"Parafibromin immunostaining of parathyroid tumors in clinical routine: A near-decade experience from a tertiary center","volume":"32","author":"Juhlin","year":"2019","journal-title":"Mod. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1007\/s12020-024-03687-6","article-title":"The significance of an immunohistochemical marker-based panel in assisting the diagnosis of parathyroid carcinoma","volume":"84","author":"Hu","year":"2024","journal-title":"Endocrine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6629","DOI":"10.1158\/1078-0432.CCR-04-0493","article-title":"Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma","volume":"10","author":"Tan","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Simescu, R., Pop, M., Piciu, A., Muntean, V., and Piciu, D. (2022). Association of parathyroid and differentiated thyroid carcinomas: A narrative up-to-date review of the literature. Medicina, 58.","DOI":"10.3390\/medicina58091184"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e06369","DOI":"10.1002\/ccr3.6369","article-title":"Synchronous parathyroid carcinoma and papillary thyroid carcinoma","volume":"10","author":"Nacef","year":"2022","journal-title":"Clin. Case Rep."},{"key":"ref_11","first-page":"e24006","article-title":"Synchronous parathyroid carcinoma and nonivasive follicular thyroid neoplasm with papillary-like nuclear features","volume":"14","author":"Alajaimi","year":"2022","journal-title":"Cureus"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1089\/thy.2009.0016","article-title":"Synchronous parathyroid and papillary thyroid carcinomas","volume":"19","author":"Marcy","year":"2009","journal-title":"Thyroid"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1159\/000478927","article-title":"European Thyroid Association guidelines for ultrasound malignancy risk stratification of thyroid nodules in adults: The EU-TIRADS","volume":"6","author":"Russ","year":"2017","journal-title":"Eur. Thyroid. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.humpath.2022.05.014","article-title":"Diagnostic significance of parafibromin expression in parathyroid carcinoma","volume":"127","author":"Gao","year":"2022","journal-title":"Hum. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.juro.2014.05.006","article-title":"Medical management of kidney stones: AUA Guideline","volume":"192","author":"Pearle","year":"2014","journal-title":"J. Urol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"(2019). NICE Guideline\u2014Renal and ureteric stones: Assessment and management. BJU. Int., 123, 220\u2013232.","DOI":"10.1111\/bju.14654"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1080\/003655999750017022","article-title":"Metabolic evaluation and medical management of upper urinary tract stone","volume":"33","author":"Osther","year":"1999","journal-title":"Scand. J. Urol. Nephrol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.jss.2018.07.028","article-title":"Timely evaluation and management of primary hyperparathyroidism in patients with kidney stones","volume":"232","author":"Perez","year":"2018","journal-title":"J. Surg. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/dc.23847","article-title":"Cytological challenges in the diagnosis of intrathyroidal carcinoma: A case report and review of the literature","volume":"46","author":"Balakrishnan","year":"2018","journal-title":"Diagn. Cytopathol."},{"key":"ref_20","first-page":"680876","article-title":"Fine-needle aspiration cytology of parathyroid carcinoma mimic H\u00fcrthle cell thyroid neoplasm","volume":"2014","author":"Sriphrapradang","year":"2014","journal-title":"Case Rep. Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1093\/ajcp\/aqw165.007","article-title":"Fine-needle aspiration of parathyroid carcinoma: A diagnostic pitfall of a rare endocrine malignancy","volume":"146","author":"Adams","year":"2016","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ha, H.J., Kim, E.J., Kim, J.-S., Shin, M.-S., Noh, I., Park, S., Koh, J.S., and Lee, S.-S. (2020). Major clues and pitfalls in the differential diagnosis of parathyroid and thyroid lesions using fine needle aspiration cytology. Medicina, 56.","DOI":"10.3390\/medicina56110558"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"De Falco, N., Santangelo, G., Chirico, F., Cangiano, A., Somella, M.G., Cosenza, A., Ronchi, A., Accardo, M., Pellino, G., and Parmeggiani, D. (2021). Synchronous intrathyroidal parathyroid carcinoma and thyroid carcinoma: Case report and review of the literature. BMC Endocr. Disord., 21.","DOI":"10.1186\/s12902-021-00724-7"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1002\/1097-0142(197903)43:3<1078::AID-CNCR2820430344>3.0.CO;2-R","article-title":"Parathyroid adenomas following irradiation","volume":"43","author":"Russ","year":"1979","journal-title":"Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.ijrobp.2008.06.1487","article-title":"Hyperparathyroidism after irradiation for childhood malignancy","volume":"73","author":"McCullen","year":"2009","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/bjs.1800750914","article-title":"Hyperparathyroidism after neck irradiation","volume":"75","author":"Christmas","year":"1988","journal-title":"Br. J. Surg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1667\/RR14213.1","article-title":"Thyroid cancer after childhood exposure to external radiation: An updated pooled analysis of 12 studies","volume":"185","author":"Veiga","year":"2016","journal-title":"Radiat. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1056\/NEJM198801143180203","article-title":"Risk of second malignancies following Hodgkin\u2019s disease after 15 years","volume":"318","author":"Tucker","year":"1988","journal-title":"N. Eng. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1080\/09553002.2023.2194398","article-title":"Insights into radiation carcinogenesis based on dose-rate effects in tissue stem cells","volume":"99","author":"Otsuka","year":"2023","journal-title":"Int. J. Radiol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"100049","DOI":"10.1016\/j.modpat.2022.100049","article-title":"Homologous recombination repair deficiency: An overview for pathologists","volume":"36","author":"Doig","year":"2023","journal-title":"Mod. Pathol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Suzuki, K., Saenko, V., Yamashita, S., and Mitsutake, N. (2019). Radiation-induced thyroid cancers: Overview of molecular signatures. Cancers, 11.","DOI":"10.3390\/cancers11091290"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41556-018-0243-8","article-title":"The diverse consequences of aneuploidy","volume":"21","author":"Chunduri","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_33","first-page":"3775","article-title":"Alternative genetic pathways in parathyroid tumorigenesis","volume":"84","author":"Farnebo","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Marini, F., Giusti, F., Iantomasi, T., and Brandi, M.L. (2021). Parathyroid tumors: Molecular signatures. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222011206"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s12672-013-0147-9","article-title":"Germline and somatic mutations in cyclin-dependent kinase inhibitor genes CDKN1A, CDKN2B, and CDKN2C in sporadic parathyroid adenomas","volume":"4","author":"Soong","year":"2013","journal-title":"Horm. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"E701","DOI":"10.1210\/jc.2010-1338","article-title":"Somatic mutation and germline sequence abnormalities in CDKN1B, encoding p27Kip1, in sporadic parathyroid adenomas","volume":"96","author":"Marinoni","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e92061","DOI":"10.1172\/jci.insight.92061","article-title":"Genomic profiling reveals mutational landscape in parathyroid carcinomas","volume":"2","author":"Pandya","year":"2017","journal-title":"JCI Insight."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1002\/ijc.33166","article-title":"The genomic profile of parathyroid carcinoma based on whole-genome sequencing","volume":"47","author":"Hu","year":"2020","journal-title":"Int. J. Cancer."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E360","DOI":"10.1210\/jc.2014-3238","article-title":"Whole-exome sequencing studies of parathyroid carcinomas reveal novel PRUNE2 mutations, distinctive mutational spectra related to APOBEC-catalyzed DNA mutagenesis and mutational enrichment in kinases associated with cell migration and invasion","volume":"100","author":"Yu","year":"2015","journal-title":"J. Clin. Endocrin. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/1878-0261.13398","article-title":"Targeted therapy of advanced parathyroid carcinoma guided by genomic and transcriptomic profiling","volume":"17","author":"Teleanu","year":"2023","journal-title":"Mol. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1056\/NEJMoa031237","article-title":"Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma","volume":"349","author":"Shattuck","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1634\/theoncologist.2018-0334","article-title":"Genomic profiling of parathyroid carcinoma reveals genomic alterations suggesting benefit from therapy","volume":"24","author":"Kang","year":"2019","journal-title":"Oncologist"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1097\/JTO.0000000000000493","article-title":"Hippo pathway gene mutations in malignant mesothelioma","volume":"10","author":"Miyanaga","year":"2015","journal-title":"J. Thoracic. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/s43018-020-00109-0","article-title":"Dual ARID1A\/ARID1B loss leads to rapid carcinogenesis and disruptive redistribution of BAF complexes","volume":"1","author":"Wang","year":"2020","journal-title":"Nat. Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.2147\/JIR.S426558","article-title":"Pan-cancer analysis of oncogenic role of RADL4L and experimental validation in hepatocellular carcinoma","volume":"16","author":"Zhou","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"428","DOI":"10.5306\/wjco.v11.i7.428","article-title":"MUTYH: Not just polyposis","volume":"11","author":"Curia","year":"2020","journal-title":"World J. Clin. Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/s41467-021-25288-x","article-title":"System approaches identify the consequences of monosomy in somatic human cells","volume":"12","author":"Chunduri","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1590\/2359-3997000000257","article-title":"Radiation exposure and thyroid cancer: A review","volume":"61","author":"Iglesias","year":"2017","journal-title":"Arch. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1038\/s41379-020-0638-5","article-title":"Clinicopathologic features of kinase fusion-related thyroid carcinomas: An integrative analysis with molecular characterization","volume":"33","author":"Chu","year":"2020","journal-title":"Mod. Pathol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4441\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:28:41Z","timestamp":1760030921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/9\/4441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,7]]},"references-count":49,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ijms26094441"],"URL":"https:\/\/doi.org\/10.3390\/ijms26094441","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,7]]}}}