{"entity":{"id":"parathyroid-carcinoma","kind":"cancer","name":"Parathyroid carcinoma","aka":[],"tldr":"Parathyroid carcinoma is a cancer of the glands that control blood calcium, seen in a few people per ten million a year; most of its harm comes from dangerously high calcium rather than spread. Removing the tumour intact at the first operation gives the best chance of cure, and cinacalcet and bone-protecting drugs control calcium when it cannot be removed.","summary":"Parathyroid carcinoma is a malignant neoplasm of parathyroid chief cells that presents with severe primary hyperparathyroidism: calcium and parathyroid hormone far above adenoma levels, bone disease, kidney stones and renal impairment, and often a palpable neck mass, in contrast to the mild disease of parathyroid adenoma. About a quarter of sporadic cases and nearly all cases in the hyperparathyroidism-jaw tumour syndrome carry inactivating mutations in CDC73 (HRPT2), whose product parafibromin is lost on immunohistochemistry; germline testing is recommended for all patients because of the syndromic association. Preoperative distinction from adenoma is unreliable, so the diagnosis is often made at surgery or pathology.\n\nThe only curative treatment is en bloc resection of the tumour with the ipsilateral thyroid lobe and any adherent tissue, avoiding capsular rupture; incomplete initial surgery is the main cause of recurrence, which is usually loco-regional and can be re-resected repeatedly. Radiotherapy and chemotherapy have little proven activity. Because morbidity and death come from hypercalcaemia rather than tumour mass, medical control matters: cinacalcet (a calcimimetic, approved for hypercalcaemia of parathyroid carcinoma), denosumab or bisphosphonates for bone resorption, hydration and, in crisis, dialysis. Rare durable responses to PD-1 inhibitors have been reported in tumours with high mutation burden, and case series describe activity of multikinase inhibitors, but there is no approved systemic anticancer therapy.\n\nOpen problems are pre-operative recognition (parafibromin and PGP9.5 staining, calcium and PTH thresholds), the lack of trials, and effective therapy for metastatic disease beyond calcium control.","asOf":"2026-09-10","wikipedia":"https://en.wikipedia.org/wiki/Parathyroid_carcinoma","links":[{"label":"NCI PDQ: parathyroid cancer","url":"https://www.cancer.gov/types/parathyroid"},{"label":"NCCN Neuroendocrine and Adrenal Tumors","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"},{"label":"CDC73 in parathyroid carcinoma (NEJM 2003)","url":"https://doi.org/10.1056/NEJMoa031237"}],"tags":["nci-coverage","rare","endocrine"],"related":[],"cancers":[],"sections":[],"technologies":["bone-modifying-agents","germline-testing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["hereditary-cancer-syndromes","rare-cancers"],"trials":[],"people":[],"bottlenecks":["b-rare-cancers"],"keyPapers":["paper-shattuck-n-engl-j-med"],"journals":[],"dependsOn":[],"notes":[],"group":"endocrine","burden":"Under one percent of primary hyperparathyroidism; a few cases per ten million people per year, with equal sex distribution and a median age around 50.","subtypes":["Sporadic parathyroid carcinoma","Hyperparathyroidism-jaw tumour syndrome associated (germline CDC73)","Non-functioning parathyroid carcinoma (rare)"],"biomarkers":["Serum calcium and PTH (typically far above adenoma levels)","CDC73 (HRPT2) mutation and parafibromin loss","PGP9.5 and galectin-3 immunostaining","Ki-67 and capsular or vascular invasion (WHO 2022 criteria)"],"standardOfCare":[{"setting":"Suspected or confirmed carcinoma, resectable","approach":"En bloc resection with ipsilateral thyroid lobectomy and removal of adherent tissue, avoiding capsule rupture; re-resection for loco-regional recurrence.","refs":["thyroid"],"guideline":{"nccn":"Category 2A","version":"NCCN Neuroendocrine and Adrenal Tumors (parathyroid carcinoma); American Association of Endocrine Surgeons guideline 2016","url":"https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448"}},{"setting":"Hypercalcaemia, unresectable or metastatic disease","approach":"Cinacalcet titrated to calcium, denosumab or intravenous bisphosphonate, hydration; palliative resection or ablation of metastases to reduce PTH burden.","refs":["bone-modifying-agents","cinacalcet"],"guideline":{"version":"NCCN Neuroendocrine and Adrenal Tumors"}},{"setting":"All patients","approach":"Germline CDC73 testing and family counselling; surveillance for jaw and renal tumours in carriers.","refs":["germline-testing","hereditary-cancer-syndromes"]}],"stateOfArt":["Cinacalcet and denosumab have turned uncontrollable hypercalcaemia, historically the cause of death, into a manageable problem for most patients.","CDC73 testing identifies the hereditary syndrome and allows surveillance of relatives.","Reports of checkpoint inhibitor response in high-mutation-burden tumours and of multikinase inhibitor activity point towards genomically guided treatment, no drug is approved for the carcinoma itself, so tumour sequencing and a tumour-agnostic or basket trial are the route to one.","The WHO 2022 classification tightened histological criteria, separating carcinoma from atypical parathyroid tumours."],"history":[{"year":1933,"title":"First clear description of parathyroid carcinoma (Sainton and Millot)","refs":[]},{"year":2002,"title":"HRPT2 (CDC73) identified as the hyperparathyroidism-jaw tumour syndrome gene","note":"Carpten and colleagues, Nat Genet.","refs":[]},{"year":2003,"title":"Somatic and germline CDC73 mutations in sporadic parathyroid carcinoma","note":"Shattuck and colleagues, NEJM.","refs":[]},{"year":2004,"title":"Cinacalcet approved","note":"Including hypercalcaemia of parathyroid carcinoma (FDA).","refs":[]},{"year":2022,"title":"WHO classification refines carcinoma criteria","note":"Fifth edition endocrine tumours.","refs":[]}],"pipeline":["bone-modifying-agents","checkpoint-inhibitor"],"openProblems":["Preoperative diagnosis: no reliable imaging or biochemical threshold, so many patients have inadequate first surgery.","No effective systemic anticancer therapy for metastatic disease; genomic profiling for actionable alterations and immunotherapy case series are the current approach.","Rarity precludes randomised trials; international registries are the evidence base."]},"route":"/cancers/parathyroid-carcinoma/","neighbours":{"technology":[{"id":"bone-modifying-agents","kind":"technology","name":"Bone-modifying agents (bisphosphonates, denosumab)","route":"/technologies/bone-modifying-agents/"},{"id":"germline-testing","kind":"technology","name":"Germline (hereditary) testing","route":"/technologies/germline-testing/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"term":[{"id":"hereditary-cancer-syndromes","kind":"term","name":"Hereditary cancer syndromes","route":"/terms/hereditary-cancer-syndromes/"},{"id":"rare-cancers","kind":"term","name":"Rare cancers","route":"/terms/rare-cancers/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"}],"paper":[{"id":"paper-shattuck-n-engl-j-med","kind":"paper","name":"Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma","route":"/key-papers/paper-shattuck-n-engl-j-med/"}],"cancer":[{"id":"hyperparathyroidism-jaw-tumour-syndrome","kind":"cancer","name":"Hyperparathyroidism-jaw tumour syndrome (CDC73-related parathyroid carcinoma)","route":"/cancers/hyperparathyroidism-jaw-tumour-syndrome/"},{"id":"multiple-endocrine-neoplasia","kind":"cancer","name":"Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)","route":"/cancers/multiple-endocrine-neoplasia/"},{"id":"men1-syndrome","kind":"cancer","name":"Multiple endocrine neoplasia type 1 (MEN1)","route":"/cancers/men1-syndrome/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"drug":[{"id":"cinacalcet","kind":"drug","name":"Cinacalcet","route":"/drugs/cinacalcet/"}]}}