# Parathyroid carcinoma

Source: https://onco.cc/cancers/parathyroid-carcinoma/  
OnCo record `parathyroid-carcinoma` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

The 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.

Open 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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Tags: nci-coverage; rare; endocrine
- 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)

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/parathyroid-carcinoma/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/parathyroid-carcinoma/#overview [1 subtype, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/parathyroid-carcinoma/#what-it-is [4 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/parathyroid-carcinoma/#finding-it [4 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/parathyroid-carcinoma/#treating-it [3 settings, 1 decision with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/parathyroid-carcinoma/#evidence [1 key paper, 5 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/parathyroid-carcinoma/#science
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/parathyroid-carcinoma/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/parathyroid-carcinoma/#living-with-it [13 questions]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/parathyroid-carcinoma/coming/ [1 medicine, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/parathyroid-carcinoma/data/ [9 connected records]

## Standard of care

- Suspected or confirmed carcinoma, resectable: En bloc resection with ipsilateral thyroid lobectomy and removal of adherent tissue, avoiding capsule rupture; re-resection for loco-regional recurrence. ([Thyroid cancer](https://onco.cc/cancers/thyroid/))
- Hypercalcaemia, unresectable or metastatic disease: Cinacalcet titrated to calcium, denosumab or intravenous bisphosphonate, hydration; palliative resection or ablation of metastases to reduce PTH burden. ([Bone-modifying agents (bisphosphonates, denosumab)](https://onco.cc/technologies/bone-modifying-agents/), [Cinacalcet](https://onco.cc/drugs/cinacalcet/))
- All patients: Germline CDC73 testing and family counselling; surveillance for jaw and renal tumours in carriers. ([Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/))

## State of the art

- 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, but no drug is approved for the cancer itself.
- The WHO 2022 classification tightened histological criteria, separating carcinoma from atypical parathyroid tumours.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Parathyroid_carcinoma
- NCI PDQ: parathyroid cancer: https://www.cancer.gov/types/parathyroid
- NCCN Neuroendocrine and Adrenal Tumors: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1448
- CDC73 in parathyroid carcinoma (NEJM 2003): https://doi.org/10.1056/NEJMoa031237

## Connected records

- technologies: [Bone-modifying agents (bisphosphonates, denosumab)](https://onco.cc/technologies/bone-modifying-agents/), [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- terms: [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Rare cancers](https://onco.cc/terms/rare-cancers/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)
- key papers: [Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma](https://onco.cc/key-papers/paper-shattuck-n-engl-j-med/)
- cancers: [Hyperparathyroidism-jaw tumour syndrome (CDC73-related parathyroid carcinoma)](https://onco.cc/cancers/hyperparathyroidism-jaw-tumour-syndrome/), [Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)](https://onco.cc/cancers/multiple-endocrine-neoplasia/), [Multiple endocrine neoplasia type 1 (MEN1)](https://onco.cc/cancers/men1-syndrome/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- drugs: [Cinacalcet](https://onco.cc/drugs/cinacalcet/)

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JSON: https://onco.cc/api/v1/entities/parathyroid-carcinoma.json