Parathyroid carcinoma
Parathyroid carcinoma is a very rare cancer of the glands that control blood calcium, and most of its harm comes from extremely high calcium rather than from spread. Removing the tumour intact in one piece at the first operation gives the best chance of cure, and calcium-lowering drugs control the disease when it cannot be removed.
Overview
Parathyroid carcinoma is a malignant neoplasm of parathyroid chief cells that presents with severe primary hyperparathyroidism: very high calcium and parathyroid hormone, 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.
State of the art today
- 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.
Show survival figures (1)
Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
- Cinacalcet and denosumab have turned uncontrollable hypercalcaemia, historically the cause of death, into a manageable problem for most patients.
Where it starts and where it drains
Site decides cause and behaviour: HPV drives oropharyngeal cancer, EBV drives nasopharyngeal cancer, tobacco drives oral and laryngeal cancer; all drain into the neck node levels that surgeons and radiotherapists map.
- Oral cavity and tongue
- Oropharynx: tonsil, base of tongue (HPV)
- Nasopharynx (EBV)
- Larynx and hypopharynx
- Parotid and other salivary glands
- ThyroidSporadic parathyroid carcinoma · Hyperparathyroidism-jaw tumour syndrome associated (germline CDC73) · Non-functioning parathyroid carcinoma (rare)
- level I (submandibular)
- level II (upper jugular)
- level III-IV (jugular)
- level V (posterior)
- level VI (central, thyroid)
- retropharyngeal (nasopharynx)
Same organ: Head and neck squamous cell carcinoma, Nasopharyngeal carcinoma, Salivary gland cancers, Thyroid cancer, Nasal cavity and paranasal sinus cancers (including esthesioneuroblastoma), NUT carcinoma (midline carcinoma with NUTM1 rearrangement), Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)
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.
- AI in radiologyEstablished
- cfDNA fragmentomicsEstablished
- Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)Standard of care
- DNA methylation profilingEstablished
- HCC surveillance in cirrhosis (ultrasound + AFP)Standard of care
- High-risk pancreatic surveillance (CAPS / PRECEDE)Established
- A 28-day national pathway for people with a positive multi-cancer blood test
- A breath test to rule out cancer in people with vague symptoms
- A cancer blood test for older people arriving at A&E with unexplained symptoms
- A legislated, publicly reported 28-day standard from urgent referral to diagnosis
- A live national dashboard of stage at diagnosis as the scorecard for early detection
- A single 'cancer check at 60' appointment bundling all screening tests
Background: Alpha-fetoprotein (AFP), Barrett's oesophagus, CA 19-9, Early detection, Faecal immunochemical test (FIT). Also on OnCo: Symptoms and red flags · Early detection roadmap.
Where the cases are
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
En bloc resection with ipsilateral thyroid lobectomy and removal of adherent tissue, avoiding capsule rupture; re-resection for loco-regional recurrence.
Cinacalcet titrated to calcium, denosumab or intravenous bisphosphonate, hydration; palliative resection or ablation of metastases to reduce PTH burden.
Germline CDC73 testing and family counselling; surveillance for jaw and renal tumours in carriers.
Subtypes & biomarkers
top- Sporadic parathyroid carcinoma
- Hyperparathyroidism-jaw tumour syndrome associated (germline CDC73)
- Non-functioning parathyroid carcinoma (rare)
- 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)
Target prevalence in this cancer
- 1933First clear description of parathyroid carcinoma (Sainton and Millot)
- 2002HRPT2 (CDC73) identified as the hyperparathyroidism-jaw tumour syndrome gene
Carpten and colleagues, Nat Genet.
- 2003Somatic and germline CDC73 mutations in sporadic parathyroid carcinoma
Shattuck and colleagues, NEJM.
- 2004Cinacalcet approved
Including hypercalcaemia of parathyroid carcinoma (FDA).
- 2022WHO classification refines carcinoma criteria
Fifth edition endocrine tumours.
Open problems, and what is being done about each
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.
and how the field plans to fix it →What is being done about thisAdvanced and metastatic diseaseAvailable now- Bone-modifying agents (bisphosphonates, denosumab)Standard of care
- DordaviproneApproved
- HIPEC / PIPAC (intraperitoneal chemotherapy)Established
- Laser interstitial thermal therapy (LITT)Established
- Liquid biopsy (ctDNA)Standard of care
- Lutetium-177 vipivotide tetraxetanApproved
In trials- ACTIONRecruiting
- CAR-T for glioma (IL13Rα2, GD2, EGFRvIII, multi-target)Phase 1
- CIRCULATE-Japan (GALAXY / VEGA / ALTAIR)Active
- DESTINY-Breast12Positive
- DYNAMICPositive
- EF-14Positive
Ideas and roadmaps- A billion-dollar prize for the first durable cure of a lethal metastatic cancer
- A blood test for the pre-metastatic niche
- A global rapid tissue donation network for metastatic disease
- A national rapid research autopsy network for end-stage cancer
- A regulatory endpoint for drugs that block spread, not tumours
- A ring-fenced metastasis programme with metastasis-specific endpoints
Background: Blood-brain barrier (BBB), Circulating tumour DNA (ctDNA), EGFRvIII, Epithelial–mesenchymal transition & drug efflux, H3 K27M (diffuse midline glioma). Also on OnCo: Atlas: what treats advanced disease · Mechanics: invasion and metastasis.
Rarity precludes randomised trials; international registries are the evidence base.
and how the field plans to fix it →What is being done about thisRare cancers and small trialsAvailable now- AI trial matching & clinical decision supportEstablished
- Comprehensive genomic profilingStandard of care
- Dinutuximab (ch14.18) / dinutuximab betaApproved
- Eflornithine (DFMO)Approved
- LarotrectinibApproved
- Limb-salvage surgery and endoprosthetic reconstructionStandard of care
In trials- ACTIONRecruiting
- COG AALL1731Positive
- COG ANBL0032Positive
- DeFiPositive
- Euro Ewing 2012Positive
- Functional (ex vivo) drug testingEmerging
Ideas and roadmaps- A digital second-opinion network answering community oncologists within 72 hours
- A DRUP-style protocol for off-label generic targeted drugs in rare tumours
- A funded expert second opinion for every new high-stakes or rare cancer diagnosis
- A global first-in-human network for academic cancer trials with single ethics review
- A global open trials operating system any hospital can plug into
- A live 'seats available' feed for trial slots, like airline inventory
Background: Basket, umbrella, and platform trials, Centralisation and high-volume centres, FNCLCC grade (soft-tissue sarcoma), Histotype-tailored therapy, INRG staging and risk groups. Also on OnCo: Find a trial · Expert centres.
Trials
topRecruiting now (live from ClinicalTrials.gov)
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Expert centres
topCentres linked to this cancer in OnCo
- via Thyroid cancer
- via Thyroid cancer
- via Thyroid cancer
- via Immune checkpoint inhibitors
- A.C. Camargo Cancer CenterSão Paulo, BRvia Germline (hereditary) testing, Hereditary cancer syndromes
- Hadassah Medical CenterJerusalem, ILvia Immune checkpoint inhibitors, Germline (hereditary) testing
- Hospital de Clínicas de Porto AlegrePorto Alegre, BRvia Germline (hereditary) testing, Hereditary cancer syndromes
- via Thyroid cancer, Germline (hereditary) testing
- Peking Union Medical College HospitalBeijing, CNvia Thyroid cancer, Germline (hereditary) testing
- The Hospital for Sick Children (SickKids)Toronto, ON, CAvia Immune checkpoint inhibitors, Germline (hereditary) testing
- ASST Spedali Civili di BresciaBrescia, ITvia Thyroid cancer
- via Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- Cancer Research UKLondon, GBvia Thyroid cancer
- Catalan Institute of Oncology (ICO)L'Hospitalet de Llobregat, ESvia Germline (hereditary) testing
- Cedars-Sinai CancerLos Angeles, CA, USvia Immune checkpoint inhibitors
- Centre hospitalier de l'Université de Montréal (CHUM)Montréal, QC, CAvia Immune checkpoint inhibitors
- Centre Léon BérardLyon, FRvia Immune checkpoint inhibitors
- Children's Hospital of PhiladelphiaPhiladelphia, PA, USvia Germline (hereditary) testing
- Chinese Society of Clinical OncologyBeijing, CNvia Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- Edinburgh Cancer Centre / CRUK Scotland CentreEdinburgh, GBvia Germline (hereditary) testing
- ETOP IBCSG Partners FoundationBern, CHvia Immune checkpoint inhibitors
- First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou, CNvia Thyroid cancer
- via Germline (hereditary) testing
- Geneva University Hospitals (HUG)Geneva, CHvia Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- GOG FoundationPhiladelphia, PA, USvia Immune checkpoint inhibitors
- via Germline (hereditary) testing
- Groote Schuur Hospital / University of Cape TownCape Town, ZAvia Germline (hereditary) testing
- Guangdong Provincial People's HospitalGuangzhou, CNvia Immune checkpoint inhibitors
- via Germline (hereditary) testing
- Henan Cancer HospitalZhengzhou, CNvia Immune checkpoint inhibitors
- Hospital Universitari i Politècnic La FeValencia, ESvia Germline (hereditary) testing
- Hospital Universitario 12 de OctubreMadrid, ESvia Immune checkpoint inhibitors
- Hunan Cancer HospitalChangsha, CNvia Immune checkpoint inhibitors
- via Germline (hereditary) testing
- via Germline (hereditary) testing
- via Germline (hereditary) testing
- via Immune checkpoint inhibitors
- International Association for the Study of Lung CancerDenver, CO, USvia Immune checkpoint inhibitors
- IRCCS Humanitas Research HospitalRozzano (Milan), ITvia Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- Istituto Oncologico Veneto IRCCSPadua, ITvia Immune checkpoint inhibitors
- King Hussein Cancer CenterAmman, JOvia Germline (hereditary) testing
- Korle Bu Teaching HospitalAccra, GHvia Germline (hereditary) testing
- Kyoto University HospitalKyoto, JPvia Immune checkpoint inhibitors
- Lagos University Teaching HospitalLagos, NGvia Germline (hereditary) testing
- via Immune checkpoint inhibitors
- Leiden University Medical CenterLeiden, NLvia Immune checkpoint inhibitors
- Ludwig Cancer ResearchNew York, USvia Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- Melanoma Research AllianceWashington, DC, USvia Immune checkpoint inhibitors
- MovemberMelbourne, AUvia Germline (hereditary) testing
- National Cancer Center KoreaGoyang, KRvia Thyroid cancer
- via Immune checkpoint inhibitors
- Parker Institute for Cancer ImmunotherapySan Francisco, USvia Immune checkpoint inhibitors
- Peking University Cancer HospitalBeijing, CNvia Immune checkpoint inhibitors
- QIMR Berghofer Medical Research InstituteBrisbane, AUvia Germline (hereditary) testing
- Ramathibodi Hospital, Mahidol UniversityBangkok, THvia Germline (hereditary) testing
- Shaare Zedek Medical CenterJerusalem, ILvia Germline (hereditary) testing
- via Immune checkpoint inhibitors
- Shanghai Pulmonary HospitalShanghai, CNvia Immune checkpoint inhibitors
- Sheba Medical CenterRamat Gan, ILvia Immune checkpoint inhibitors
- Shizuoka Cancer CenterNagaizumi, Shizuoka, JPvia Germline (hereditary) testing
- via Germline (hereditary) testing
- Society for Immunotherapy of CancerMilwaukee, WI, USvia Immune checkpoint inhibitors
- Society of Gynecologic OncologyChicago, IL, USvia Immune checkpoint inhibitors
- Taipei Veterans General HospitalTaipei, TWvia Immune checkpoint inhibitors
- Tawam HospitalAl Ain, AEvia Thyroid cancer
- Tel Aviv Sourasky Medical CenterTel Aviv, ILvia Immune checkpoint inhibitors
- Tohoku University HospitalSendai, JPvia Germline (hereditary) testing
- via Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- University of Malaya Medical CentreKuala Lumpur, MYvia Germline (hereditary) testing
- via Immune checkpoint inhibitors
- West Japan Oncology GroupOsaka, JPvia Immune checkpoint inhibitors
- via Immune checkpoint inhibitors
- Zhejiang Cancer HospitalHangzhou, CNvia Immune checkpoint inhibitors
Questions to ask
topQuestions to ask your oncologist about Parathyroid carcinoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Serum calcium and PTH, CDC73mutation and parafibromin loss, PGP9.5 and galectin-3 immunostaining, Ki-67 and capsular or vascular invasion), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Sporadic parathyroid carcinoma, Hyperparathyroidism-jaw tumour syndrome associated, Non-functioning parathyroid carcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Suspected or confirmed carcinoma, resectable
- For my situation (suspected or confirmed carcinoma, resectable), which of the standard options do you recommend and why?Why: Guideline options include: En bloc resection with ipsilateral thyroid lobectomy and removal of adherent tissue, avoiding capsule rupture; re-resection for loco-regional recurrence.
Hypercalcaemia, unresectable or metastatic disease
- For my situation (hypercalcaemia, unresectable or metastatic disease), which of the standard options do you recommend and why?Why: Guideline options include: Cinacalcet titrated to calcium, denosumab or intravenous bisphosphonate, hydration; palliative resection or ablation of metastases to reduce PTH burden.
All patients
- For my situation (all patients), which of the standard options do you recommend and why?Why: Guideline options include: Germline CDC73 testing and family counselling; surveillance for jaw and renal tumours in carriers.
Any stage
- Are there clinical trials I could join, for example of Bone-modifying agents (bisphosphonates, denosumab), Immune checkpoint inhibitors?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Preoperative diagnosis: no reliable imaging or biochemical threshold, so many patients have inadequate first surgery”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “No effective systemic anticancer therapy for metastatic disease; genomic profiling for actionable alterations and immunotherapy case series are the current approach”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
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Direct links plus the targets, companies, and technologies of this cancer's products.
Latest papers
topQuery for this cancer: (TITLE:"Parathyroid carcinoma" OR ABSTRACT:"Parathyroid carcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Parathyroid carcinoma, not a curated reading list.
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