{"product_id":"understanding-parathyroid-carcinoma-a-patient-rsquo-s-guide-to-diagnosis-treatment-and-life-after-surgery","title":"Understanding Parathyroid Carcinoma: A Patient\u0026rsquo;s Guide to Diagnosis, Treatment, and Life After Surgery","description":"\u003cp\u003eParathyroid carcinoma (PC) is an extremely rare cancer of the parathyroid glands — the tiny glands in the neck that regulate calcium in the blood. It accounts for less than 1% of all cases of primary hyperparathyroidism and approximately 0.005% of all cancers, but it can cause dangerously high calcium levels and severe damage to the kidneys and bones. This article translates a 2024 clinical review from The Journal of Clinical Endocrinology \u0026amp; Metabolism, which uses the story of a 50-year-old patient to walk through how doctors diagnose and treat this challenging disease — from first symptoms through surgery, recurrence, and long-term management.\u003c\/p\u003e\n\n\u003ch1\u003eUnderstanding Parathyroid Carcinoma: A Patient’s Guide to Diagnosis, Treatment, and Life After Surgery\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#one-patients-story\"\u003eOne Patient’s Story: A 50-Year-Old Man with Severe Symptoms\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#background\"\u003eBackground: What Is Parathyroid Carcinoma?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#clinical-presentation\"\u003eClinical Presentation: How Doctors Suspect Parathyroid Carcinoma\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#perioperative-management\"\u003ePerioperative Management: Preparing Patients with Dangerous Calcium Levels for Surgery\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#surgical-approach\"\u003eSurgical Approach: Why the First Operation Matters Most\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#pathological-diagnosis\"\u003ePathological Diagnosis: How the Lab Confirms Cancer\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#germline-testing\"\u003eGermline Mutation Testing: The Genetics of Parathyroid Carcinoma\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#red-flags\"\u003eKey Red Flags: Factors That Raise Suspicion of Parathyroid Carcinoma\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eLimitations: What the Medical Community Still Doesn’t Know\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations: What Patients Should Do\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eParathyroid carcinoma is very rare, causing severe hypercalcemia and organ damage, but can be managed with the right team and vigilant follow-up.\u003c\/li\u003e\n\u003cli\u003eRecognize red flags: calcium above 14 mg\/dL, very high PTH, kidney stones, bone disease, neck mass, or vocal cord paralysis.\u003c\/li\u003e\n\u003cli\u003eGermline CDC73 testing is recommended for all patients with parathyroid carcinoma to guide follow-up and family screening.\u003c\/li\u003e\n\u003cli\u003eAvoid fine-needle biopsy of suspected parathyroid masses due to unreliable results and risk of tumor seeding.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"one-patients-story\"\u003eOne Patient’s Story: A 50-Year-Old Man with Severe Symptoms\u003c\/h2\u003e\n\u003cp\u003eThe case begins in September 2009, when a 50-year-old man was admitted to the hospital after a full year of distressing symptoms: nausea, constipation, increased thirst, severe pain in his knees and shins, and marked fatigue.\u003c\/p\u003e\n\u003cp\u003eHis medical history provided important clues. Since age 34, he had suffered from recurrent kidney stones in both kidneys (bilateral nephrolithiasis). More recently, he had experienced multiple fragility fractures — broken bones from minimal trauma — in his hip and both upper arm bones (humeri). His past medical history and family history were otherwise unremarkable.\u003c\/p\u003e\n\u003cp\u003eBlood tests revealed a striking picture. His serum calcium was severely elevated at 18 mg\/dL (normal range: 8.1–10.4 mg\/dL), and his parathyroid hormone (PTH) level was extraordinarily high at 2058 ng\/L (normal range: 15–65 ng\/L). These results confirmed a diagnosis of \u003cstrong\u003eprimary hyperparathyroidism\u003c\/strong\u003e (PHPT), a condition in which one or more parathyroid glands overproduce PTH, pulling calcium out of the bones and into the bloodstream.\u003c\/p\u003e\n\u003cp\u003eHe was initially treated with intravenous fluids, a diuretic called furosemide, and bisphosphonates (medications that slow bone breakdown). This treatment progressively brought his calcium down to 13 mg\/dL — still above normal, but safer.\u003c\/p\u003e\n\u003cp\u003eImaging studies came next. A 99mTc-sestamibi scan (a specialized nuclear medicine scan for parathyroid tissue) showed an enlarged parathyroid gland at the lower pole of the right thyroid lobe. A total-body contrast-enhanced computed tomography (CT) scan revealed an 8-centimeter parathyroid mass tightly adhered to the thyroid lobe, as well as multiple \u003cstrong\u003ebrown tumors\u003c\/strong\u003e — bone lesions caused by long-standing excess PTH — in his long bones, vertebrae, ribs, and scapulae (shoulder blades).\u003c\/p\u003e\n\u003cp\u003eIn October 2009, surgeons removed the right inferior parathyroid gland along with the ipsilateral thyroid lobe (the thyroid lobe on the same side). Because the tumor was strongly adherent to surrounding tissue, the inferior laryngeal nerve was partially resected (cut away) as well. Interestingly, the surgical report made no mention of local invasion — a detail that would matter later.\u003c\/p\u003e\n\u003cp\u003eSoon after surgery, the patient developed \u003cstrong\u003ehungry bone syndrome\u003c\/strong\u003e, a condition where bones rapidly absorb calcium from the blood after years of being depleted. He required treatment with calcium and calcitriol (the active form of vitamin D) for 8 months to keep his blood calcium stable.\u003c\/p\u003e\n\u003cp\u003eIn November 2010, roughly a year after his surgery, he was referred to the outpatient clinic at the University of Pisa for further consultation. He felt generally well, and no masses were felt in his neck. His serum calcium was normal at 9.3 mg\/dL (normal range: 8.6–10.2 mg\/dL), but his PTH was slightly elevated at 121 ng\/L (normal range: 10–75 ng\/L). His estimated glomerular filtration rate (eGFR), a measure of kidney function, was reduced at 61 mL\/min\/1.73 m², indicating early kidney impairment.\u003c\/p\u003e\n\u003cp\u003eAn abdominal ultrasound showed calcium deposits inside both kidneys (bilateral nephrocalcinosis). A bone density test (dual-energy x-ray absorptiometry, or DXA) revealed marked bone loss in the lumbar spine (T-score −3.1), femoral neck (T-score −2.9), and the distal third of the radius in the forearm (T-score −6.6) — the last being a profound level of bone thinning. X-rays of the skeleton showed that his previously identified bone lesions had fully healed.\u003c\/p\u003e\n\u003cp\u003eOver the next 18 months, his serum calcium and PTH levels gradually climbed — calcium up to 14 mg\/dL and PTH up to 393 ng\/L. An ultrasound found two lesions in the neck at the site of his prior surgery (measuring 10 and 18 mm), and a 99mTc-sestamibi scan showed increased uptake on the right side of the neck. Two additional neck lesions were identified, the largest reaching 20 mm.\u003c\/p\u003e\n\u003cp\u003eLooking at the whole picture — his relatively young age, male sex, extremely high calcium and PTH at diagnosis, bone and kidney involvement, and the size of the original tumor — doctors strongly suspected \u003cstrong\u003eparathyroid carcinoma\u003c\/strong\u003e (PC), a rare but serious cancer of the parathyroid gland.\u003c\/p\u003e\n\u003cp\u003eFurther imaging with total-body CT and positron emission tomography (PET)\/CT using 18F-FDG confirmed the disease had returned in the neck, with no evidence of spread (metastases) elsewhere in the body.\u003c\/p\u003e\n\u003cp\u003eThis patient’s journey — from severe symptoms, to surgery, to recurrence — illustrates the core challenge of parathyroid carcinoma: it can be difficult to diagnose before surgery, tends to recur, and requires a coordinated, experienced medical team to manage at every step.\u003c\/p\u003e\n\n\u003ch2 id=\"background\"\u003eBackground: What Is Parathyroid Carcinoma?\u003c\/h2\u003e\n\u003cp\u003eParathyroid carcinoma is a very rare malignancy. It accounts for less than 1% of all cases of primary hyperparathyroidism and approximately 0.005% of all cancers. It is usually associated with severe, symptomatic primary hyperparathyroidism — meaning patients often have strikingly high calcium levels and related symptoms.\u003c\/p\u003e\n\u003cp\u003eRecent reports from several countries (the United States, Australia, Finland, China, and South Korea) indicate that the incidence of PC is rising. The authors note this increase may be partly explained by better diagnostic accuracy, but it may also reflect a true increase in how often the disease occurs.\u003c\/p\u003e\n\u003cp\u003eHere are the key numbers from international registries:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eThe largest U.S. series, from the \u003cstrong\u003eSurveillance, Epidemiology and End Results (SEER)\u003c\/strong\u003e database, included \u003cstrong\u003e609 cases\u003c\/strong\u003e of PC diagnosed between 1975 and 2016.\u003c\/li\u003e\n  \u003cli\u003eThe largest Asian series came from South Korea (\u003cstrong\u003e255 cases\u003c\/strong\u003e, 2003–2017) and China (\u003cstrong\u003e234 cases\u003c\/strong\u003e, 1984–2015).\u003c\/li\u003e\n  \u003cli\u003eChinese data showed a marked increase in diagnosed cases: from \u003cstrong\u003e13 cases between 1996 and 2000\u003c\/strong\u003e to \u003cstrong\u003emore than 100 cases between 2011 and 2015\u003c\/strong\u003e.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003ePC is generally diagnosed in the fifth decade of life (typically in a person’s 40s or 50s) — usually about 10 years earlier than benign parathyroid adenoma. Unlike benign parathyroid tumors, in which women outnumber men by a ratio of 3–4:1, PC shows no sex preference.\u003c\/p\u003e\n\u003cp\u003ePC most commonly occurs as a sporadic disease affecting a single gland. \u003cstrong\u003eSomatic mutations\u003c\/strong\u003e (genetic changes that occur in a person’s lifetime, not inherited) in a gene called \u003cstrong\u003eCDC73\u003c\/strong\u003e are found in up to \u003cstrong\u003e80%\u003c\/strong\u003e of patients with apparently sporadic PC. Approximately \u003cstrong\u003e30%\u003c\/strong\u003e of cases harbor a \u003cstrong\u003egermline\u003c\/strong\u003e (inherited) CDC73 mutation, suggesting that a genetic predisposition plays an important role in many patients.\u003c\/p\u003e\n\u003cp\u003eThe CDC73 gene codes for a 531-amino acid protein called \u003cstrong\u003eparafibromin\u003c\/strong\u003e. This protein is primarily found in the nucleus of cells and is a component of a complex called PAF1 that regulates gene transcription and affects how DNA is packaged (chromatin organization). When parafibromin is chemically modified by tyrosine phosphorylation, it acts as a tumor suppressor — it inhibits cell growth by suppressing Cyclin D1 and the MYC proto-oncogene. When it is dephosphorylated, however, it can act as an oncogene, forming a complex with β-catenin and activating signaling pathways (Wnt, Hedgehog, and Notch) involved in development and tissue maintenance. Outside the nucleus, parafibromin also regulates the cell’s internal skeleton (actin cytoskeleton) and inhibits p53-mediated cell death (apoptosis).\u003c\/p\u003e\n\u003cp\u003eFor diagnosing PC, the loss of parafibromin immunoreactivity in the nucleus of tumor cells is considered a reliable marker of CDC73 alterations.\u003c\/p\u003e\n\u003cp\u003eMutations in other genes — including \u003cstrong\u003ePRUNE2, KMT2D, CDKN2C, PIK3CA\u003c\/strong\u003e, and key genes in the PI3K\/AKT\/mTOR pathway — have also been reported in PC.\u003c\/p\u003e\n\u003cp\u003ePC may also occur as part of \u003cstrong\u003ehyperparathyroidism–jaw tumor syndrome (HPT-JT)\u003c\/strong\u003e, a rare autosomal dominant inherited disorder in which \u003cstrong\u003e37%\u003c\/strong\u003e of affected patients develop parathyroid carcinoma. HPT-JT is characterized by primary hyperparathyroidism, jaw tumors (ossifying fibromas), and, in some cases, kidney lesions and uterine tumors.\u003c\/p\u003e\n\u003cp\u003eA small minority of PC patients — about \u003cstrong\u003e2%\u003c\/strong\u003e, mostly in their seventh decade of life — have \u003cstrong\u003enonfunctioning PC\u003c\/strong\u003e, meaning their calcium and PTH levels are normal. In these cases, the diagnosis is made only after a surgeon removes a neck lump that was found incidentally on imaging or because it was causing compression symptoms.\u003c\/p\u003e\n\n\u003ch2 id=\"clinical-presentation\"\u003eClinical Presentation: How Doctors Suspect Parathyroid Carcinoma\u003c\/h2\u003e\n\u003cp\u003eDistinguishing parathyroid carcinoma from the far more common benign parathyroid adenoma is genuinely difficult before surgery. The typical clinical picture of PC includes symptoms related to moderate or severe hypercalcemia:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eNausea, vomiting, dehydration, and constipation\u003c\/li\u003e\n  \u003cli\u003eSigns of target organ damage — nephrocalcinosis (calcium deposits in the kidneys), kidney stones, and impaired kidney function in up to \u003cstrong\u003e80%\u003c\/strong\u003e of patients\u003c\/li\u003e\n  \u003cli\u003eManifestations of very high PTH levels: osteitis fibrosa cystica (bone disease with cysts), subperiosteal bone resorption, a “salt-and-pepper” appearance on skull x-rays, and bone loss of up to \u003cstrong\u003e90%\u003c\/strong\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eAt the physical examination, a doctor might feel a neck lump, or a patient might have laryngeal nerve palsy (hoarseness or voice changes). Distant metastases — most commonly to the lungs, bone, liver, and cervical lymph nodes — occur late in the disease course and are responsible for the intractable hypercalcemia that ultimately becomes life-threatening.\u003c\/p\u003e\n\u003cp\u003eSeveral clinical and laboratory findings should raise suspicion of PC, including:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eMale sex\u003c\/li\u003e\n  \u003cli\u003eA palpable neck mass and\/or laryngeal nerve palsy\u003c\/li\u003e\n  \u003cli\u003eModerate-to-severe hypercalcemia — serum calcium generally above \u003cstrong\u003e14 mg\/dL\u003c\/strong\u003e and\/or ionized calcium above \u003cstrong\u003e1.77 mmol\/L\u003c\/strong\u003e\n\u003c\/li\u003e\n  \u003cli\u003eVery high PTH levels — more than \u003cstrong\u003e3 to 10 times\u003c\/strong\u003e the upper limit of normal\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eUltrasound features that suggest PC include:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eParathyroid gland size greater than \u003cstrong\u003e3 cm\u003c\/strong\u003e\n\u003c\/li\u003e\n  \u003cli\u003eA heterogeneous cystic structure\u003c\/li\u003e\n  \u003cli\u003eIrregular borders and calcifications\u003c\/li\u003e\n  \u003cli\u003eSigns of infiltration and suspicious vascularity\u003c\/li\u003e\n  \u003cli\u003eMarked adhesion to (or infiltration of) adjacent structures at surgical exploration\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eOne retrospective ultrasound study of 69 PHPT cases (8 PC and 61 benign parathyroid lesions larger than 15 mm) found that local infiltration and calcification each had a \u003cstrong\u003e100% positive predictive value\u003c\/strong\u003e for PC — meaning when either feature was present, the lesion was always malignant. A more recent similar study found that a tumor size above \u003cstrong\u003e2.05 cm\u003c\/strong\u003e and tumor infiltration were independent markers of PC.\u003c\/p\u003e\n\u003cp\u003eConventional parathyroid imaging is otherwise of limited value for the preoperative diagnosis of PC unless there is clear evidence of local invasion or metastases. For example, 99mTc-sestamibi scans are not very helpful, though PC does tend to retain the tracer longer than benign lesions. When doctors strongly suspect PC, they may use \u003cstrong\u003e4-dimensional computed tomography (4DCT)\u003c\/strong\u003e or magnetic resonance imaging (MRI) with gadolinium contrast to look for invasion into surrounding structures.\u003c\/p\u003e\n\u003cp\u003eA retrospective study of 20 patients with PC found that the sensitivity of any single imaging technique — neck ultrasound, 4DCT, or 99mTc-sestamibi SPECT-CT — was approximately \u003cstrong\u003e80%\u003c\/strong\u003e. Combining all three techniques raised sensitivity to \u003cstrong\u003e95% or higher\u003c\/strong\u003e.\u003c\/p\u003e\n\u003cp\u003ePET\/CT with 18F-FDG is useful for staging, monitoring treatment response, and detecting recurrences in many cancers, but published experience in PC is limited. One important warning: \u003cstrong\u003ebrown tumors\u003c\/strong\u003e (the bone lesions caused by severe hyperparathyroidism) are very metabolically active and show up strongly on 18F-FDG-PET\/CT. They can easily be misdiagnosed as bone metastases, so doctors must interpret these scans carefully.\u003c\/p\u003e\n\u003cp\u003eIn recent years, 18F-choline PET\/CT has become an increasingly useful tool for finding hyperfunctioning parathyroid glands. Experience in PC is still limited to case reports, but it has successfully detected recurrent disease in several published cases.\u003c\/p\u003e\n\u003cp\u003eFinally, the authors strongly advise against \u003cstrong\u003epreoperative fine-needle aspiration (FNA)\u003c\/strong\u003e of a suspected parathyroid lesion. FNA cannot reliably distinguish a benign from a malignant tumor, and — most importantly — it can cause tumor rupture and \u003cstrong\u003eseeding\u003c\/strong\u003e, meaning cancer cells can spread along the needle track and contaminate surrounding tissues.\u003c\/p\u003e\n\n\u003ch2 id=\"perioperative-management\"\u003ePerioperative Management: Preparing Patients with Dangerous Calcium Levels for Surgery\u003c\/h2\u003e\n\u003cp\u003ePatients with mild hypercalcemia — serum calcium below \u003cstrong\u003e12 mg\/dL\u003c\/strong\u003e — do not need specific preoperative treatment. The situation is different for patients with severe hypercalcemia, which is often accompanied by anorexia, nausea, vomiting, and nephrogenic diabetes insipidus (a condition where high calcium prevents the kidneys from concentrating urine, leading to extreme dehydration and reduced kidney function).\u003c\/p\u003e\n\u003cp\u003eThe first goal is to correct volume depletion. Doctors typically start with intravenous saline, possibly combined with subcutaneous calcitonin (a hormone that quickly lowers calcium). The rate of fluid administration depends on how severe the hypercalcemia is. Loop diuretics (such as furosemide) may be added in patients at risk of fluid overload once their volume status has been restored.\u003c\/p\u003e\n\u003cp\u003eThese measures — intravenous fluid with or without diuretics — typically reduce serum calcium by \u003cstrong\u003e1 to 2 mg\/dL within a few hours\u003c\/strong\u003e. However, this effect is only temporary unless stronger medications are started. Potent intravenous bisphosphonates (pamidronate or zoledronate) or \u003cstrong\u003edenosumab\u003c\/strong\u003e (a monoclonal antibody that blocks bone breakdown) are used to get more sustained calcium lowering.\u003c\/p\u003e\n\u003cp\u003eAnesthesiologists also need to be aware of the complications of moderate-to-severe hypercalcemia during surgery. High calcium levels can affect the blood clotting system, trigger heart arrhythmias, and interfere with non-depolarizing muscle relaxants (medications used to temporarily paralyze muscles during anesthesia).\u003c\/p\u003e\n\n\u003ch2 id=\"surgical-approach\"\u003eSurgical Approach: Why the First Operation Matters Most\u003c\/h2\u003e\n\u003cp\u003eComplete surgical removal of the tumor at the initial operation offers the best chance of cure. The gold standard procedure is \u003cstrong\u003een bloc resection\u003c\/strong\u003e — removing the tumor in one piece along with the ipsilateral thyroid lobe (the thyroid on the same side), the surrounding involved structures, and clear margins, all without spilling tumor cells.\u003c\/p\u003e\n\u003cp\u003eDuring surgery, certain findings may alert an experienced endocrine surgeon to cancer:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eA firm, gray-white lesion (as opposed to the soft, reddish-brown appearance of a benign adenoma)\u003c\/li\u003e\n  \u003cli\u003eA thick fibrous capsule and dense adhesions to surrounding structures\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThe following principles guide surgical decision-making:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eEn bloc resection reduces recurrence and metastasis risk.\u003c\/strong\u003e This approach generally has a higher success rate, although some studies have not shown a clear mortality or recurrence benefit from wider resections.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eThe recurrent laryngeal nerve\u003c\/strong\u003e (the nerve that controls the vocal cords) should be preserved unless the tumor has grown completely around it.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLymph node metastases\u003c\/strong\u003e are found in up to \u003cstrong\u003e19%\u003c\/strong\u003e of PC cases, and are more common when the tumor is larger than 3 cm. Removing lymph nodes that are visibly involved is justified, but there is not enough evidence to recommend routine preventive (prophylactic) removal of all nearby lymph nodes.\u003c\/li\u003e\n\u003c\/ol\u003e\n\u003cp\u003eWhen a patient has already had a more limited first surgery and the pathology report later reveals parathyroid carcinoma, the question is whether to go back. If there was extensive vascular and capsular invasion and\/or persistent hypercalcemia after surgery, further surgery should be performed as soon as possible. If calcium and PTH levels are normal after the initial surgery, the decision is more personalized. A test called \u003cstrong\u003eparafibromin immunohistochemistry\u003c\/strong\u003e (staining the tumor tissue to see whether the parafibromin protein is present) can help guide this decision:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eIf parafibromin staining is \u003cstrong\u003enegative\u003c\/strong\u003e (the protein is absent), this suggests a more aggressive tumor, and revision surgery with en bloc resection should be considered.\u003c\/li\u003e\n  \u003cli\u003eIf parafibromin staining is \u003cstrong\u003epositive\u003c\/strong\u003e (the protein is present), further surgery might be avoided — though the authors note that long-term studies are needed to confirm that this more conservative approach is safe.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThere is also a specific question about how to manage family members of a patient who has PC with a germline CDC73 mutation. The current expert recommendation is \u003cstrong\u003enot\u003c\/strong\u003e to perform prophylactic parathyroidectomy (removing the glands before disease develops) in healthy gene carriers. Instead, the recommended approach is:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003ePerform a bilateral neck exploration to identify all four parathyroid glands.\u003c\/li\u003e\n  \u003cli\u003eRemove only the glands that look macroscopically abnormal.\u003c\/li\u003e\n  \u003cli\u003eMonitor gene carriers regularly for the development of parathyroid, kidney, jaw, and uterine problems.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003ch2 id=\"pathological-diagnosis\"\u003ePathological Diagnosis: How the Lab Confirms Cancer\u003c\/h2\u003e\n\u003cp\u003eA definitive diagnosis of parathyroid carcinoma requires at least one of the following definite signs of malignancy, as established by the \u003cstrong\u003eWorld Health Organization (WHO)\u003c\/strong\u003e:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eUnequivocal neoplastic infiltration of adjacent tissues\u003c\/li\u003e\n  \u003cli\u003eLymphovascular invasion (cancer cells inside lymphatic or blood vessels attached to the vessel wall, usually with associated blood clots)\u003c\/li\u003e\n  \u003cli\u003ePerineural invasion (cancer cells around or into nerves)\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eOther findings — strict adherence to surrounding structures, marked fibrosis with collagenous septa, or increased mitotic activity — may also be seen in PC, but these are \u003cem\u003enot\u003c\/em\u003e specific to malignancy. They can also appear in benign lesions and in \u003cstrong\u003eatypical parathyroid tumors\u003c\/strong\u003e (lesions with concerning features but no definite signs of invasion), which the 2022 WHO classification now calls “atypical parathyroid tumors.”\u003c\/p\u003e\n\u003cp\u003eFoci of coagulative necrosis (areas of dead tumor tissue) are more commonly seen in high-grade tumors, but necrosis alone is not considered a hallmark of malignancy in parathyroid pathology. It must be distinguished from harmless causes of dead tissue, such as spontaneous infarction (loss of blood supply) or changes after a fine-needle aspiration.\u003c\/p\u003e\n\u003cp\u003eMost PCs show solid or trabecular growth patterns, though follicular, spindle cell, and even carcinosarcomatous patterns occasionally occur. Nuclear atypia — enlarged, hyperchromatic (darkly stained), or bizarre-looking nuclei — can also be seen in benign adenomas and is not diagnostic of cancer on its own.\u003c\/p\u003e\n\u003cp\u003ePathologists use features like cellular pleomorphism (cells looking very different from one another), necrosis, and mitotic activity to classify PC as \u003cstrong\u003elow-grade\u003c\/strong\u003e or \u003cstrong\u003ehigh-grade\u003c\/strong\u003e:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eHigh-grade PC\u003c\/strong\u003e typically shows pleomorphic nuclei, prominent nucleoli, coagulative necrosis, abnormal mitoses, and\/or an increased proliferative index.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMild nuclear enlargement\u003c\/strong\u003e without necrosis or elevated mitotic activity is not enough to diagnose PC.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThe \u003cstrong\u003eKi-67 index\u003c\/strong\u003e (a measure of how quickly cells are dividing) is a useful test. A Ki-67 index above \u003cstrong\u003e5%\u003c\/strong\u003e is usually found in parathyroid carcinoma, while a lower score is common in both adenomas and atypical parathyroid tumors. Because of this overlap, the 2022 WHO classification strongly encourages the routine use of Ki-67 staining in parathyroid pathology.\u003c\/p\u003e\n\u003cp\u003eThe WHO also emphasizes the use of \u003cstrong\u003eparafibromin immunohistochemistry\u003c\/strong\u003e. This test is less expensive than gene sequencing and helps predict CDC73 mutations. When there is a complete loss of parafibromin staining in the nucleus, the tumor is classified as “\u003cstrong\u003eparafibromin-deficient\u003c\/strong\u003e.”\u003c\/p\u003e\n\u003cp\u003eTo standardize reporting and improve patient care, the \u003cstrong\u003eInternational Collaboration on Cancer Reporting (ICCR)\u003c\/strong\u003e has proposed a uniform pathology report. Core elements include the parathyroid gland’s weight, size, and tumor grade — including whether there is necrosis, the mitotic count, and whether there is perineural or lymphovascular invasion. The ICCR also recommends Ki-67 and parafibromin staining on all cases.\u003c\/p\u003e\n\u003cp\u003eFinally, the \u003cstrong\u003eAmerican Joint Committee on Cancer (AJCC) eighth edition\u003c\/strong\u003e of cancer staging classifies PC based on local extension (how far the tumor has grown into surrounding tissues) and the presence of distant metastases.\u003c\/p\u003e\n\n\u003ch2 id=\"germline-testing\"\u003eGermline Mutation Testing: The Genetics of Parathyroid Carcinoma\u003c\/h2\u003e\n\u003cp\u003eBecause up to \u003cstrong\u003e30%\u003c\/strong\u003e of apparently sporadic PCs are actually associated with inherited germline CDC73 mutations, the authors recommend that \u003cstrong\u003eall individuals diagnosed with PC be offered germline genetic testing\u003c\/strong\u003e, wherever possible.\u003c\/p\u003e\n\u003cp\u003eMost CDC73 mutations are point mutations or small insertions\/deletions spread throughout the gene; large deletions or insertions are rare.\u003c\/p\u003e\n\u003cp\u003eWhy does this matter for patients?\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003ePatients with a confirmed germline CDC73 mutation should be monitored closely after surgery for early detection of local recurrence, new distant metastases, and the possible development of disease in other parathyroid glands.\u003c\/li\u003e\n  \u003cli\u003eRegular surveillance is also recommended for other HPT-JT-related conditions, including kidney lesions, jaw tumors, and uterine tumors.\u003c\/li\u003e\n  \u003cli\u003eGenetic testing of first-degree family members (parents, siblings, children) is recommended. Family members who carry the mutation should be monitored to catch disease early, while those who test negative can be reassured and spared unnecessary medical surveillance.\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eFor patients who have persistent or recurrent disease that cannot be surgically removed and who test negative for CDC73 mutations, the authors suggest considering \u003cstrong\u003enext-generation sequencing\u003c\/strong\u003e of the tumor. This approach looks for mutations in other genes that might be targeted by newer, specific therapies.\u003c\/p\u003e\n\n\u003ch2 id=\"red-flags\"\u003eKey Red Flags: Factors That Raise Suspicion of Parathyroid Carcinoma\u003c\/h2\u003e\n\u003cp\u003eFor endocrinologists and endocrine surgeons, certain findings in a patient with primary hyperparathyroidism should immediately raise concern for parathyroid carcinoma. These include:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eThe patient is \u003cstrong\u003emale\u003c\/strong\u003e (since benign PHPT is far more common in women).\u003c\/li\u003e\n  \u003cli\u003eThe patient is relatively \u003cstrong\u003eyoung\u003c\/strong\u003e (under 50).\u003c\/li\u003e\n  \u003cli\u003eSerum calcium is very high (\u003cstrong\u003eabove 14 mg\/dL\u003c\/strong\u003e).\u003c\/li\u003e\n  \u003cli\u003ePTH levels are extremely elevated (\u003cstrong\u003emore than 3–10 times\u003c\/strong\u003e the upper limit of normal).\u003c\/li\u003e\n  \u003cli\u003eThe patient has had \u003cstrong\u003ekidney stones, kidney calcification, or impaired kidney function\u003c\/strong\u003e.\u003c\/li\u003e\n  \u003cli\u003eThe patient has significant \u003cstrong\u003ebone disease\u003c\/strong\u003e, including brown tumors or severe bone loss.\u003c\/li\u003e\n  \u003cli\u003eThere is a \u003cstrong\u003epalpable neck mass\u003c\/strong\u003e or vocal cord paralysis.\u003c\/li\u003e\n  \u003cli\u003eUltrasound shows a \u003cstrong\u003elarge tumor (over 2–3 cm)\u003c\/strong\u003e, with irregular borders, calcifications, or signs of invasion into surrounding tissue.\u003c\/li\u003e\n  \u003cli\u003eAt the time of surgery, the lesion is \u003cstrong\u003efirm, gray, and densely adherent\u003c\/strong\u003e to the thyroid gland and other neck structures.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"limitations\"\u003eLimitations: What the Medical Community Still Doesn’t Know\u003c\/h2\u003e\n\u003cp\u003eIt is important for patients to understand that parathyroid carcinoma remains a poorly understood disease in many respects.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eFirst, there is no reliable preoperative test.\u003c\/strong\u003e No blood marker, imaging finding, or biopsy result can definitively diagnose PC before surgery in most cases. The diagnosis often only becomes clear after a pathologist examines the removed tissue and finds definitive invasion.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecond, many features of the disease overlap with benign conditions.\u003c\/strong\u003e Atypical parathyroid tumors can look similar under the microscope, and even experienced pathologists can struggle to classify them. The Ki-67 index helps, but there is overlap between benign and malignant tumors.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eThird, the genetic picture is incomplete.\u003c\/strong\u003e While CDC73 mutations explain most cases, mutations in other genes are only beginning to be understood. The long-term behavior of tumors with different genetic profiles is still being studied.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eFourth, treatment for recurrent disease is limited.\u003c\/strong\u003e Surgery is the mainstay of treatment, and repeated operations are often needed, but when the disease is no longer operable, medical therapy mainly focuses on managing hypercalcemia — the dangerous high calcium levels — rather than curing the cancer itself. Targeted therapies have shown promise in only a few reported cases.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eFifth, the benefit of wider surgery is debated.\u003c\/strong\u003e Although en bloc resection is generally recommended, some studies have not found a clear survival advantage compared with more limited resection. This reflects the rarity of the disease and the difficulty of conducting large clinical trials.\u003c\/p\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations: What Patients Should Do\u003c\/h2\u003e\n\u003cp\u003eBased on this review, here is what patients and their families should keep in mind:\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSeek an experienced surgical team.\u003c\/strong\u003e Parathyroid carcinoma is so rare that outcomes are significantly better when the initial surgery is performed by a surgeon experienced in parathyroid disease. The first operation offers the best chance of cure.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about genetic testing.\u003c\/strong\u003e If you have been diagnosed with PC, talk to your doctor about germline CDC73 testing. The results can guide your follow-up, your family’s screening, and even treatment decisions.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eStay consistent with follow-up.\u003c\/strong\u003e Even after successful surgery, the recurrence rate is \u003cstrong\u003e40% to 60%\u003c\/strong\u003e. Regular monitoring of serum calcium and PTH levels, along with neck imaging when needed, can catch recurrences early when surgery is still possible.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eProtect your kidneys and bones.\u003c\/strong\u003e High calcium and PTH levels take a serious toll on these organs. Treating hypercalcemia aggressively, staying well hydrated, and monitoring kidney function and bone density are all essential parts of long-term care.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eInvolve family members in genetic counseling.\u003c\/strong\u003e If a CDC73 mutation is found, first-degree relatives (parents, siblings, children) should be offered testing. Carriers need monitoring; non-carriers can be reassured.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eBe wary of biopsy.\u003c\/strong\u003e Fine-needle aspiration of a suspected parathyroid mass is not recommended because it cannot reliably distinguish benign from malignant disease and may spread cancer cells.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eConsider a multidisciplinary team.\u003c\/strong\u003e Given its rarity, PC should be managed in a center with expertise in endocrinology, endocrine surgery, pathology, and genetics working together.\u003c\/li\u003e\n\u003c\/ol\u003e\n\u003cp\u003eThe story of the 50-year-old patient in this review illustrates both the challenges and the possibilities. Despite a recurrence after his first surgery, he was able to undergo multiple surgeries over more than a decade, with his serum calcium levels tracked carefully from November 2010 through March 2022. Each time the disease returned, imaging — including CT, 18F-FDG PET\/CT, and 18F-choline PET\/CT — helped locate the lesions, and surgical removal helped bring his calcium levels back under control.\u003c\/p\u003e\n\u003cp\u003eParathyroid carcinoma is a serious and challenging disease, but it is manageable with the right team, the right timing, and a vigilant approach to follow-up. Knowledge is part of the treatment — and this patient’s story shows how far the medical field has come in understanding and treating this rare cancer.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is parathyroid carcinoma?\u003c\/h3\u003e\n\u003cp\u003eParathyroid carcinoma is an extremely rare cancer of the parathyroid glands, which regulate blood calcium. It accounts for less than 1% of primary hyperparathyroidism cases. It usually causes severe high calcium levels, leading to kidney stones, kidney damage, and bone disease. It can be difficult to diagnose before surgery.\u003c\/p\u003e\n\u003ch3\u003eWhat symptoms should make me suspect parathyroid carcinoma?\u003c\/h3\u003e\n\u003cp\u003eRed flags include severe hypercalcemia (calcium above 14 mg\/dL), extremely high PTH levels, kidney stones or impaired kidney function, significant bone disease, a palpable neck mass, or vocal cord paralysis. Ultrasound may show a tumor larger than 2–3 cm with irregular borders, calcifications, or signs of invasion. Male sex and younger age also raise concern.\u003c\/p\u003e\n\u003ch3\u003eShould I have genetic testing if I am diagnosed with parathyroid carcinoma?\u003c\/h3\u003e\n\u003cp\u003eYes. Up to 30% of apparently sporadic parathyroid carcinomas are linked to inherited CDC73 mutations. The authors recommend offering germline genetic testing to all patients with parathyroid carcinoma. Results guide your follow-up, your family's screening, and treatment decisions. First-degree relatives should also be offered testing if a mutation is found.\u003c\/p\u003e\n\u003ch3\u003eIs a biopsy safe for suspected parathyroid cancer?\u003c\/h3\u003e\n\u003cp\u003eNo. The authors strongly advise against fine-needle aspiration (FNA) of suspected parathyroid lesions. FNA cannot reliably distinguish benign from malignant tumors and may cause tumor rupture and seeding, spreading cancer cells along the needle track. Diagnosis usually requires examination of the surgically removed tissue.\u003c\/p\u003e\n\u003ch3\u003eWhat follow-up is needed after surgery for parathyroid carcinoma?\u003c\/h3\u003e\n\u003cp\u003eEven after successful surgery, recurrence rates are 40% to 60%. Regular monitoring of serum calcium and PTH levels, along with neck imaging when needed, is essential to catch recurrences early. Protect your kidneys with hydration and monitor kidney function and bone density. A multidisciplinary team is recommended.\u003c\/p\u003e\n\u003ch3\u003eWhat is hungry bone syndrome after parathyroid surgery?\u003c\/h3\u003e\n\u003cp\u003eHungry bone syndrome occurs when bones rapidly absorb calcium from the blood after being depleted by long-standing high PTH levels. It can cause dangerously low blood calcium. Treatment requires calcium and calcitriol (active vitamin D) for months. In one patient, this treatment was needed for 8 months to keep calcium stable.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\u003cp\u003eThis patient-friendly article is based on peer-reviewed research published in \u003cem\u003eThe Journal of Clinical Endocrinology \u0026amp; Metabolism\u003c\/em\u003e (JCEM), 2024, Volume 109, pages 256–268.\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eOriginal title:\u003c\/strong\u003e “Approach to the Patient With Parathyroid Carcinoma”\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAuthors:\u003c\/strong\u003e Filomena Cetani, Elena Pardi, Liborio Torregrossa, Simona Borsari, Laura Pierotti, Elisa Dinoi, and Claudio Marcocci\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAffiliations:\u003c\/strong\u003e Unit of Endocrinology, University Hospital of Pisa, Pisa, Italy; Department of Clinical and Experimental Medicine, University of Pisa; Department of Surgical, Medical, Molecular Pathology and Clinical Area, University of Pisa\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePublication details:\u003c\/strong\u003e The Journal of Clinical Endocrinology \u0026amp; Metabolism, 2024, Vol. 109, No. 1, pp. 256–268. DOI: \u003ca href=\"https:\/\/doi.org\/10.1210\/clinem\/dgad455\"\u003e10.1210\/clinem\/dgad455\u003c\/a\u003e\n\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAdvance access publication:\u003c\/strong\u003e August 2, 2023\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp\u003eThis patient-friendly article was created by a medical writer to translate the original scientific publication into accessible language for patients and caregivers. It is not a substitute for professional medical advice, diagnosis, or treatment. Always consult your doctor or endocrinologist with questions about your specific medical situation.\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47423020236956,"sku":null,"price":0.0,"currency_code":"RUB","in_stock":true}],"url":"https:\/\/diagnosticdetectives.ru\/products\/understanding-parathyroid-carcinoma-a-patient-rsquo-s-guide-to-diagnosis-treatment-and-life-after-surgery","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}