eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs

Parathyroid Carcinoma

Author: Lawrence Kim, MD, Chief of Surgical Services, Central Arkansas Veterans Affairs Healthcare System; Director of Surgical Endocrinology, Professor, Department of Surgery, University of Arkansas for Medical Sciences
Contributor Information and Disclosures

Updated: May 4, 2009

Introduction

Background

Parathyroid carcinoma is a rare malignancy of the parathyroid glands. These tumors usually secrete parathyroid hormone, thereby producing hyperparathyroidism, which is usually severe. Parathyroid carcinoma may be suspected, but it usually cannot be confirmed prior to operation. This complicates the treatment strategy.

Photomicrograph of parathyroid carcinoma showing ...

Photomicrograph of parathyroid carcinoma showing typical fibrotic septae. Histologic diagnosis can be difficult.

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Photomicrograph of parathyroid carcinoma showing ...

Photomicrograph of parathyroid carcinoma showing typical fibrotic septae. Histologic diagnosis can be difficult.


Pathophysiology

Parathyroid carcinomas cause hyperparathyroidism (for a more complete discussion see Hyperparathyroidism). Hyperparathyroidism is caused by overproduction of parathyroid hormone. In most cases, hyperparathyroidism is caused by a single benign adenoma (approximately 85%). The vast majority of the remaining cases are caused by parathyroid hyperplasia or multiple adenomas. In less than 1% of cases of hyperparathyroidism, the etiology is parathyroid carcinoma. 

The hyperparathyroidism seen in parathyroid carcinoma is usually severe, with high serum calcium levels, severe bone disease, and renal stones. Rarely, parathyroid cancer can be nonfunctional, that is, it may cause a tumor but not produce parathyroid hormone and the sequelae of hyperparathyroidism. Overproduction of authentic parathyroid hormone from nonparathyroid sources is extremely rare but has been reported. Modern assays for parathyroid hormone measure the intact, authentic molecule and do not detect similar molecules produced by other tumors. Therefore, an elevated parathyroid hormone level is virtually always parathyroid in origin.

Untreated, parathyroid carcinoma leads to severe symptoms of hyperparathyroidism and may cause renal stones, nephrocalcinosis, pathologic fractures, and neuropsychiatric symptoms. The diagnosis is often not made prior to parathyroidectomy. This results in inadequate tumor excision and a propensity to local recurrence. Regional lymph node and distant metastases are usually not present at initial diagnosis. Recurrences may be treated by local excision or ablative treatments such as radiofrequency ablation. Death is usually caused by medically refractory hypercalcemia and seldom tumor burden alone.

Frequency

United States

Parathyroid cancer occurs in less than 1% of all cases of hyperparathyroidism.1,2

International

A slightly higher prevalence has been reported from referral centers in Japan and Italy.3,4

Mortality/Morbidity

  • Survival has varied widely in the literature, with 5-year survival ranging from 20-85% and 10-year survival from approximately 15-80%.5,6,7,8,9,10,11 The best data come from the National Cancer Data Base. In this series, 5-year survival was 88.5% and 10-year survival was 49.1%.12
  • A significant number of patients continue to die of recurrent disease many years after the initial treatment.
  • Permanent cure is achieved in the minority of patients.

Race

No known racial predilection exists.

Sex

Parathyroid cancer occurs equally in males and females.12

Age

Parathyroid cancer usually occurs in patients older than 30 years. After that, no predominant age association has been noted.

Clinical

History

The history should focus on symptoms of hypercalcemia plus the other symptoms of hyperparathyroidism. The onset is usually more abrupt, and the symptoms more severe than hyperparathyroidism due to benign disease.

  • Bone pain, pathologic fracture, or other evidence of bone disease (approximately 90% of patients)
  • Renal stones (50-80% of patients)
  • Symptoms of hypercalcemia - Fatigue, weakness, confusion, depression, constipation

Physical

  • Palpable mass in the neck (approximately 50% of patients)
    • A palpable mass is virtually never present with benign parathyroid adenomas or hyperplasia.
    • If a mass is palpated, parathyroid carcinoma should be suspected.
  • Signs of hypercalcemia

Causes

The etiology is unknown in most cases. Parathyroid cancer may be associated with the genetic disease hyperparathyroidism jaw tumor syndrome. It also may be associated with a history of neck irradiation.

  • Several genetic defects have been reported to be associated with parathyroid cancer. Mutations of the HRPT2 gene (1q25-31) cause hyperparathyroidism jaw tumor syndrome, and a relatively high proportion (approximately 15%) of these patients develop parathyroid cancer. However, many sporadic parathyroid carcinomas exhibit defects in this gene.13 The gene codes for a tumor suppressor protein called parafibromin. 
  • Cyclin D1 overexpression has been associated with parathyroid carcinoma.14 Parafibromin can negatively regulate cyclin D1 and may be responsible at least in part for this observation.15
  • Allelic loss of the retinoblastoma protein has been shown to be associated with parathyroid carcinoma.16
  • Mutations of the MEN1 gene can occasionally be seen in parathyroid carcinomas.17

More on Parathyroid Carcinoma

Overview: Parathyroid Carcinoma
Differential Diagnoses & Workup: Parathyroid Carcinoma
Treatment & Medication: Parathyroid Carcinoma
Follow-up: Parathyroid Carcinoma
Multimedia: Parathyroid Carcinoma
References
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References

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  2. Yip L, Seethala RR, Nikiforova MN, Nikiforov YE, Ogilvie JB, Carty SE, et al. Loss of heterozygosity of selected tumor suppressor genes in parathyroid carcinoma. Surgery. Dec 2008;144(6):949-55; discussion 954-5. [Medline].

  3. Obara T, Fujimoto Y. Diagnosis and treatment of patients with parathyroid carcinoma: an update and review. World J Surg. Nov-Dec 1991;15(6):738-44. [Medline].

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  12. Hundahl SA, Fleming ID, Fremgen AM, Menck HR. Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985-1995: a National Cancer Data Base Report. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer. Aug 1 1999;86(3):538-44. [Medline].

  13. Shattuck TM, Valimaki S, Obara T. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med. Oct 30 2003;349(18):1722-9. [Medline].

  14. Vasef MA, Brynes RK, Sturm M, Bromley C, Robinson RA. Expression of cyclin D1 in parathyroid carcinomas, adenomas, and hyperplasias: a paraffin immunohistochemical study. Mod Pathol. Apr 1999;12(4):412-6. [Medline].

  15. Woodard GE, Lin L, Zhang JH, Agarwal SK, Marx SJ, Simonds WF. Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene. Feb 10 2005;24(7):1272-6. [Medline].

  16. Cryns VL, Thor A, Xu HJ. Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med. Mar 17 1994;330(11):757-61. [Medline].

  17. Haven CJ, van Puijenbroek M, Tan MH, Teh BT, Fleuren GJ, van Wezel T, et al. Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clin Endocrinol (Oxf). Sep 2007;67(3):370-6. [Medline].

  18. van Baardwijk A, de Jong J, Arens A, Thimister P, Verseput G, Kremer B, et al. False-positive FDG-PET scan due to brown tumours. Eur J Nucl Med Mol Imaging. Mar 2006;33(3):393-4. [Medline].

  19. Bergero N, De Pompa R, Sacerdote C. Galectin-3 expression in parathyroid carcinoma: immunohistochemical study of 26 cases. Hum Pathol. Aug 2005;36(8):908-14.

  20. DeLellis RA. Parathyroid carcinoma: an overview. Adv Anat Pathol. Mar 2005;12(2):53-61.

  21. Fernandez-Ranvier GG, Jensen K, Khanafshar E, Quivey JM, Glastonbury C, Kebebew E, et al. Nonfunctioning parathyroid carcinoma: case report and review of literature. Endocr Pract. Nov-Dec 2007;13(7):750-7. [Medline].

  22. Hunt JL, Carty SE, Yim JH. Allelic loss in parathyroid neoplasia can help characterize malignancy. Am J Surg Pathol. Aug 2005;29(8):1049-55.

  23. Iihara M, Okamoto T, Suzuki R, Kawamata A, Nishikawa T, Kobayashi M, et al. Functional parathyroid carcinoma: Long-term treatment outcome and risk factor analysis. Surgery. Dec 2007;142(6):936-43; discussion 943.e1. [Medline].

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  25. Lin L, Czapiga M, Nini L, Zhang JH, Simonds WF. Nuclear localization of the parafibromin tumor suppressor protein implicated in the hyperparathyroidism-jaw tumor syndrome enhances its proapoptotic function. Mol Cancer Res. Feb 2007;5(2):183-93. [Medline].

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  28. Sandelin K, Thompson NW, Bondeson L. Metastatic parathyroid carcinoma: dilemmas in management. Surgery. Dec 1991;110(6):978-86; discussion 986-8. [Medline].

  29. Sandelin K, Tullgren O, Farnebo LO. Clinical course of metastatic parathyroid cancer. World J Surg. Jul-Aug 1994;18(4):594-8; discussion 599. [Medline].

  30. van Heerden JA, Weiland LH, ReMine WH, Walls JT, Purnell DC. Cancer of the parathyroid glands. Arch Surg. Apr 1979;114(4):475-80. [Medline].

  31. Vetto JT, Brennan MF, Woodruf J. Parathyroid carcinoma: diagnosis and clinical history. Surgery. Nov 1993;114(5):882-92. [Medline].

  32. Yart A, Gstaiger M, Wirbelauer C. The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Mol Cell Biol. Jun 2005;25(12):5052-60.

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Further Reading

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Keywords

parathyroid cancer, parathyroid gland, parathyroid carcinoma, parathyroid malignancy, parathyroid gland malignancy, hyperparathyroidism, bone disease, high serum calcium level, renal stones, hypercalcemia

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Contributor Information and Disclosures

Author

Lawrence Kim, MD, Chief of Surgical Services, Central Arkansas Veterans Affairs Healthcare System; Director of Surgical Endocrinology, Professor, Department of Surgery, University of Arkansas for Medical Sciences
Lawrence Kim, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Clinical Endocrinologists, American Association of Endocrine Surgeons, American College of Surgeons, Association for Academic Surgery, Association of VA Surgeons, International Association of Endocrine Surgeons, Society of Surgical Oncology, Society of University Surgeons, and Southwestern Surgical Congress
Disclosure: Nothing to disclose.

Medical Editor

Sanjiv S Agarwala, MD, Chief of Oncology and Hematology, St Luke's Cancer Center, St Luke's Hospital and Health Network; Associate Professor of Cancer Biology, University of Pennsylvania
Sanjiv S Agarwala, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Head and Neck Surgery, Eastern Cooperative Oncology Group, and European Society for Medical Oncology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Wendy Hu, MD, Consulting Staff, Department of Hematology/Oncology and Bone Marrow Transplantation, Huntington Memorial Medical Center
Wendy Hu, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Blood and Marrow Transplantation, American Society of Hematology, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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