Parathyroid Carcinoma Workup

  • Author: Lawrence Kim, MD; Chief Editor: Jules E Harris, MD   more...
 
Updated: Dec 7, 2011
 

Laboratory Studies

  • Laboratory workup for parathyroid carcinoma is the same as that for primary hyperparathyroidism. Simultaneous calcium and parathyroid hormone (PTH) levels should be determined.
    • Serum calcium level is usually elevated more markedly than in benign primary hyperparathyroidism.
    • Parathyroid hormone (intact): Parathyroid carcinoma should produce authentic parathyroid hormone; therefore, serum parathyroid hormone levels should be elevated, usually markedly.
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Imaging Studies

  • Imaging studies may be used preoperatively to determine the location of an abnormal parathyroid gland. See Hyperparathyroidism for the rationale of whether to obtain imaging studies for this purpose. Imaging studies may also be used for staging to determine the presence of distant metastases.
  • Radiographs
    • Hand films may show subperiosteal bone resorption of the distal phalanges.
    • Skull films have a characteristic "ground glass" or "salt and pepper" appearance.
    • In severe cases, plain films reveal the classic bone finding, osteitis fibrosa cystica. It consists of bone cysts with or without pathologic fractures. These cysts are also known as brown tumors.
  • CT scanning may be helpful in detecting metastatic disease.
  • Positron emission tomography (PET) scanning may be helpful in staging. False-positive findings due to brown tumors have been reported.[23]
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Other Tests

  • Fine-needle aspiration biopsy is not helpful in establishing a diagnosis and may be harmful by causing tumor dissemination.
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Procedures

  • No preoperative test is currently available to distinguish parathyroid cancer from benign primary hyperparathyroidism reliably.
  • Diagnosis is based on the histologic appearance of the excised parathyroid gland and clinical indicators such as recurrence or metastases.
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Histologic Findings

  • The parathyroid glands are usually large (2-10 g).
  • Tumors are usually encapsulated and often have fibrous septa extending into the gland.
    • The majority of tumors are fibrotic.
    • The parenchyma of the tumor usually has a predominance of chief cells. They are often larger than those typically seen in adenomas and have a bland cytologic appearance.
    • The parenchyma may appear indistinguishable from a benign adenoma.
  • Vascular and extracapsular invasion are common but not universal,[13]
  • Some degree of nuclear atypia is seen commonly, and mitotic figures are usually evident.
  • Proven lymphatic metastases, though uncommon, are a clear indication of malignancy.
  • Molecular or genetic markers may prove useful in distinguishing parathyroid cancer from other lesions. The HRPT2 gene product, parafibromin, is usually absent in parathyroid carcinoma. Increased expression of another marker, PGP9.5, has also been shown to be highly specific for parathyroid carcinoma.[24]
  • Tumors that exhibit some characteristics of carcinoma but are not definitive are referred to as atypical adenoma or adenoma with suspicious features. The clinical behavior of these entities is not known.[25]
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Staging

  • Parathyroid cancer is sufficiently rare that no staging systems have been well established, although some have been proposed.[13]
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Contributor Information and Disclosures
Author

Lawrence Kim, MD  Professor, Departments of Surgery and Medicine, Director of Surgical Endocrinology, University of Arkansas for Medical Sciences; Staff Surgeon, Central Arkansas Veterans Affairs Healthcare System

Lawrence Kim, MD is a member of the following medical societies: 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.

Specialty Editor Board

Sanjiv S Agarwala, MD  Chief of Oncology and Hematology, St Luke's Cancer Center, St Luke's Hospital and Health Network; Professor, Temple University Shool of Medicine

Sanjiv S Agarwala, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Head and Neck Surgery, American Society of Clinical Oncology, Eastern Cooperative Oncology Group, and European Society for Medical Oncology

Disclosure: BMS Honoraria Speaking and teaching; Novartis Consulting fee Consulting; Merck Consulting fee Consulting

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, 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; 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

References

  1. Schaapveld M, Jorna FH, Aben KK, Haak HR, Plukker JT, Links TP. Incidence and prognosis of parathyroid gland carcinoma: A population-based study in The Netherlands estimating the preoperative diagnosis. Am J Surg. Aug 20 2011;[Medline].

  2. Mittendorf EA, McHenry CR. Parathyroid carcinoma. J Surg Oncol. Mar 1 2005;89(3):136-42.

  3. 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].

  4. 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].

  5. Iacobone M, Lumachi F, Favia G. Up-to-date on parathyroid carcinoma: analysis of an experience of 19 cases. J Surg Oncol. Dec 15 2004;88(4):223-8. [Medline].

  6. Douglas L. Fraker. Chapter 44 - Cancer of the Endocrine System, Section 3: Parathyroid Tumors. In: Vincent T. DeVita, Jr., Theodore S. Lawrence, Steven A. Rosenberg. Cancer: Principles & Practice of Oncology. 8th. Philadelphia: Lippincott Williams & Wilkins; 2008:1682-1690.

  7. Wynne AG, van Heerden J, Carney JA. Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine (Baltimore). Jul 1992;71(4):197-205. [Medline].

  8. Busaidy NL, Jimenez C, Habra MA, Schultz PN, El-Naggar AK, Clayman GL, et al. Parathyroid carcinoma: a 22-year experience. Head Neck. Aug 2004;26(8):716-26. [Medline].

  9. Wang CA, Gaz RD. Natural history of parathyroid carcinoma. Diagnosis, treatment, and results. Am J Surg. Apr 1985;149(4):522-7. [Medline].

  10. Hakaim AG, Esselstyn CB Jr. Parathyroid carcinoma: 50-year experience at The Cleveland Clinic Foundation. Cleve Clin J Med. Jul-Aug 1993;60(4):331-5. [Medline].

  11. Favia G, Lumachi F, Polistina F, D'Amico DF. Parathyroid carcinoma: sixteen new cases and suggestions for correct management. World J Surg. Dec 1998;22(12):1225-30. [Medline].

  12. Flye MW, Brennan MF. Surgical resection of metastatic parathyroid carcinoma. Ann Surg. Apr 1981;193(4):425-35. [Medline].

  13. Talat N, Schulte KM. Clinical presentation, staging and long-term evolution of parathyroid cancer. Ann Surg Oncol. Aug 2010;17(8):2156-74. [Medline].

  14. 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].

  15. Lee PK, Jarosek SL, Virnig BA, Evasovich M, Tuttle TM. Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer. May 1 2007;109(9):1736-41. [Medline].

  16. Schaapveld M, Jorna FH, Aben KK, et al. Incidence and prognosis of parathyroid gland carcinoma: a population-based study in The Netherlands estimating the preoperative diagnosis. Am J Surg. Nov 2011;202(5):590-7. [Medline].

  17. 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].

  18. Lim S, Elston MS, Gill AJ, Marsh DJ, Conaglen JV. Metastatic parathyroid carcinoma initially misdiagnosed as parathyroid adenoma: the role of parafibromin in increasing diagnostic accuracy. Intern Med J. Sep 2011;41(9):695-9. [Medline].

  19. 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].

  20. 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].

  21. 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].

  22. 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].

  23. 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].

  24. Howell VM, Gill A, Clarkson A, Nelson AE, Dunne R, Delbridge LW, et al. Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J Clin Endocrinol Metab. Feb 2009;94(2):434-41. [Medline].

  25. Fang SH, Lal G. Parathyroid cancer. Endocr Pract. Mar-Apr 2011;17 Suppl 1:36-43. [Medline].

  26. Schulte KM, Talat N, Miell J, Moniz C, Sinha P, Diaz-Cano S. Lymph node involvement and surgical approach in parathyroid cancer. World J Surg. Nov 2010;34(11):2611-20. [Medline].

  27. 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.

  28. Cetani F, Ambrogini E, Viacava P, Pardi E, Fanelli G, Naccarato AG, et al. Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma?. Eur J Endocrinol. May 2007;156(5):547-54. [Medline].

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

  30. 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].

  31. 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.

  32. 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].

  33. Kleinpeter KP, Lovato JF, Clark PB. Is parathyroid carcinoma indeed a lethal disease?. Ann Surg Oncol. Mar 2005;12(3):260-6.

  34. 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].

  35. Lumachi F, Basso SM, Basso U. Parathyroid cancer: etiology, clinical presentation and treatment. Anticancer Res. Nov-Dec 2006;26(6C):4803-7. [Medline].

  36. Rodgers SE, Perrier ND. Parathyroid carcinoma. Curr Opin Oncol. Jan 2006;18(1):16-22.

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

  38. 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].

  39. 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].

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

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