Parathyroid cancer
Parathyroid cancer, also known as parathyroid carcinoma, is a rare endocrine malignancy that arises from the parathyroid glands, which are responsible for regulating calcium levels in the body. This cancer often leads to hyperparathyroidism, characterized by elevated levels of parathyroid hormone and calcium in the blood, resulting in various metabolic complications. Risk factors include hereditary conditions like hyperparathyroidism-jaw tumor syndrome and prior radiation treatment to the neck. While the exact causes remain unknown, genetic mutations, particularly in the CDC73 gene, have been implicated in its development.
The disease is slow-growing and typically metastasizes late, with common sites including the lungs, bones, and other tissues. Symptoms often reflect severe hyperparathyroidism, and diagnosis usually involves imaging studies such as CT scans and ultrasounds, along with blood tests for calcium and parathyroid hormone levels. Treatment primarily consists of surgical removal of the tumor, although radiation and chemotherapy are options for inoperable cases, albeit with limited success. Prognosis significantly improves with early detection and complete resection, though recurrence is possible. Overall, parathyroid cancer is one of the rarest forms of cancer, affecting a small number of individuals each year.
On this Page
Subject Terms
Parathyroid cancer
ALSO KNOWN AS: Parathyroid carcinoma
RELATED CONDITIONS: Primary hyperparathyroidism, hypercalcemia
DEFINITION: Parathyroid cancer is an uncommon endocrine malignancy of the parathyroid glands. The parathyroid glands, at the upper and lower poles of the thyroid gland, are usually distinguishable as four distinct glands; however, more or less than four have been found during surgeries.
The parathyroid glands help normalize the body’s metabolism by regulating calcium concentrations in the blood. The hormone released by the parathyroid gland acts on bones, kidney structures, and tissues of the intestines. Parathyroid cancer has been known to cause increased production and activity of the glands, or hyperparathyroidism.
Risk factors: Increased risk of parathyroid cancer is associated with hereditary hyperparathyroidism, and a related condition called hyperparathyroidism-jaw tumor syndrome (HPT-JT). Previous radiation to the neck is known to be a slight for head and neck cancer. No association between gender and parathyroid cancer has been reported.
Etiology and the disease process: What causes parathyroid cancer is unknown. However, a related cancer-producing gene (oncogene) has been located on chromosome 11. Also, some cases of parathyroid cancer in patients under twenty years of age indicate a genetic factor as a potential causative factor in this form of cancer. As the disease progresses, parathyroid hormone levels become elevated and as high as 10.2 times the upper limit of normal. Even a very small metastatic deposit may produce significant parathyroid hormone release and cause severe calcium level increases. Parathyroid cancer grows slowly and metastasizes late, with the lungs being a common (one third of all cases) area of involvement. Other sites that may be affected include bones, the pleura, the pericardial tissue surrounding the heart, and the pancreas. Because the disease is usually slow-growing, most patients die of metabolic complications rather than the cancer itself.
Incidence: Parathyroid cancer is one of the rarest of all human cancers, with an estimated incidence of between 1.25 and 5.7 cases per 10,000,000 people. It constitutes 0.005 percent of all cancers and affects around 100 people in the United States each year. The incidence of hyperparathyroidism has increased since 1974, yet studies show that the incidence of parathyroid cancer among patients with primary hyperparathyroidism is around 1 percent.
Symptoms: Parathyroid cancer usually manifests with symptoms consistent with severe hyperparathyroidism. Because most parathyroid cancer tumors preserve the ability to produce active parathyroid hormone, hypercalcemia is a common feature. There is a greater incidence of renal and bone disease compared with patients with hyperparathyroidism. Hoarseness with recurrent laryngeal nerve involvement is rare. However, its presence in a patient with primary hyperparathyroidism who has not had prior neck surgery is very suggestive of parathyroid cancer.
Screening and diagnosis: Diagnosis of parathyroid cancer is considered with a palpable neck mass, significantly elevated calcium and parathyroid hormone (PTH) levels, and combined renal and bone disease. Hypercalcemia, the hallmark of hyperparathyroidism, is usually severe in patients with parathyroid cancer. For patients suspected to have this form of cancer, computed (CT) scanning is thought to be the most useful for detecting the primary tumor, its local extent, and metastases. Ultrasonography, in conjunction with CT scans and (MRI), may be useful in evaluating the disease in the neck and better detects distant metastases in the chest or abdomen. If any of these noninvasive tests are unsuccessful in localizing the tumor, specific venous sampling or arteriography is useful. Other options include the parathyroid hormone test, the Sestamibi scan, and the SPECT scan (single photon emission computed tomography scan).
Below is the staging system for these relatively rare tumors, with subgroups based on tumor size and metastases.
Tumor size:
- T1 = Primary tumor less than 3 centimeters (cm) in size
- T2 = Primary tumor greater than 3 cm
- T3 = Primary tumor of any size with invasion of the surrounding soft tissues
- T4 = Massive central compartment disease invading the trachea and esophagus or recurrent parathyroid cancer
Metastases:
- N0 = No regional lymph node metastases
- N1 = Regional lymph node metastases
- M0 = No evidence of distant metastases
- M1 = Evidence of distant metastases
Stage grouping:
- Stage I: T1N0M0
- Stage II: T2N0M0
- Stage IIIA: T3N0M0
- Stage IIIB: T4N0M0
- Stage IIIC: Any T, N1, M0
- Stage IV: Any T, any N, M1
Genetics has come to play an increasingly important role in parathyroid cancers, as doctors discovered the CDC73 gene mutation plays a pivotal role in the molecular pathogenesis of parathyroid carcinoma. CDC73 encodes parafibromin, a tumor-suppressor, whose absence is apparent in parathyroid carcinoma cases. Mutations in other genes, including the PRUNE2 gene, have also been found to play a role in parathyroid cancers.
Treatment and therapy: Initial therapeutic treatment for parathyroid cancer involves surgical of the entire tumor. Patients who are not surgical candidates, such as those in whom the tumor has invaded neck structures, undergo radiation therapy or chemotherapy; however, these therapies have met with limited success.
Prognosis, prevention, and outcomes: The prognosis for individuals with parathyroid cancer varies. The best prognosis results from early detection and complete removal of the tumor during the initial surgery. The average time between the initial surgery and the first potential recurrence is around two to three years. Recurrence earlier than this is an unfavorable factor regarding prognosis. The recurrence-free five-year survival rate is over 86 percent. Complete cure is reported unlikely once the tumor has recurred, yet lengthened survival can be possible with surgery or or both. Radiation therapy for inoperable parathyroid carcinoma is usually ineffective. In cases of recurrence of the tumor, the five-year overall survival rate is reported to be about 78 percent and the ten-year survival rate varies below that percentage.
Bibliography
Copstead, Lee-Ellen C., and Jacquelyn Banasik. Pathophysiology: Biological and Behavioral Perspectives. 5th ed., Philadelphia: Saunders, 2013.
Harrison, Louis B., Roy B. Sessions, and Merrill S. Kies. Head and Neck Cancer: A Multidisciplinary Approach. 4th ed., Philadelphia: Wolters, 2014.
Jung, Chan K., et al. "Update from the 2022 World Health Organization Classification of Thyroid Tumors: A Standardized Diagnostic Approach." Endocrinology and Metabolism, vol. 37, no. 5, 2022, pp. 703-718, doi.org/10.3803/EnM.2022.1553. Accessed 4 July 2024.
Kim, Lawrence T. “Parathyroid Carcinoma.” Medscape, 3 Aug. 2021, emedicine.medscape.com/article/280908-overview?form=fpf. Accessed 4 July 2024.
Kulkarni, P. S., and Purvish M. Parikh. “The Carcinoma of Parathyroid Gland.” Indian Journal of Cancer, vol. 41, 2004, pp. 51–59.
Licata, Angelo A., and Edgar V. Lerma. Diseases of the Parathyroid Glands. New York: Springer, 2012.
Oertli, Daniel, and Robert Udelsman. Surgery of the Thyroid and Parathyroid Glands. 2nd ed., New York: Springer, 2012.
“Parathyroid Cancer.” MedlinePlus, 1 Sept. 2017, medlineplus.gov/genetics/condition/parathyroid-cancer/. Accessed 4 July 2024.
“Parathyroid Cancer: Causes, Symptoms, Diagnosis & Treatment.” Cleveland Clinic, 5 Jan. 2022, my.clevelandclinic.org/health/diseases/6182-parathyroid-cancer. Accessed 4 July 2024.
Raghavan, Derek. Textbook of Uncommon Cancer. 4th ed., Hoboken: Wiley, 2012.
Schulte, Martin, et al. "Margin Free Resection Achieves Excellent Long Term Outcomes in Parathyroid Cancer." Cancers, vol. 15, no. 1, 2023, doi.org/10.3390/cancers15010199. Accessed 4 July 2024.
Wiseman, Sam M., et al. “Parathyroid Carcinoma: A Multicenter Review of Clinicopathologic Features and Treatment Outcomes.” Ear, Nose and Throat Journal, vol. 83.7, 2004, pp. 491–94.
Zhao, Liwei, and Xianghui He. "Advances in the Molecular Genetics of Parathyroid Tumors." Chinese Medical Journal, vol. 137, no. 3, 5 Feb. 2024, pp. 376-378, doi: 10.1097/CM9.0000000000002935.