Skip to main content
Log in

Non-Functional Parathyroid Carcinoma: A Review of the Literature and Report of a Case Requiring Extensive Surgery

  • Case Reports
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

Abstract

Parathyroid carcinoma is a rare malignancy, and only accounts for 0.5–2% of cases of primary hyperparathyroidism. Less than 10% of parathyroid carcinomas are non-functional, and as such, they have been rarely reported in the literature. Importantly, margin status at resection is related to prognosis, and only a handful of case reports of non-functional carcinoma note this important parameter. Here we report the first case of non-functional parathyroid carcinoma with negative margins, and review the literature on this rare entity. Whether functional or non-functional, parathyroid carcinoma can often be difficult to differentiate from benign parathyroid adenoma. While diagnosis has been based on clinical and histological criteria, recent data concerning the molecular underpinnings of parathyroid carcinoma may allow for improved accuracy in distinguishing benign and malignant parathyroid tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Hundahl SA, Fleming ID, Fremgen AM, et al. Two hundred eighty-six cases of parathyroid carcinoma treated in the U.S. between 1985–1995: a National Cancer Data Base Report. Cancer. 1999;86:538–44. doi:10.1002/(SICI)1097-0142(19990801)86:3<538::AID-CNCR25>3.0.CO;2-K.

    Article  PubMed  CAS  Google Scholar 

  2. Rawat N, Khetan N, Williams DW, et al. Parathyroid carcinoma. Br J Surg. 2005;92:1345–53. doi:10.1002/bjs.5182.

    Article  PubMed  CAS  Google Scholar 

  3. Munson ND, Foote RL, Northcutt RC, et al. Parathyroid carcinoma: is there a role for adjuvant radiation therapy? Cancer. 2003;98:2378–84. doi:10.1002/cncr.11819.

    Article  PubMed  Google Scholar 

  4. Chow E, Tsang RW, Brierley JD, et al. Parathyroid carcinoma—the Princess Margaret Hospital experience. Int J Radiat Oncol Biol Phys. 1998;41:569–72. doi:10.1016/S0360-3016(98)00098-4.

    Article  PubMed  CAS  Google Scholar 

  5. Busaidy NL, Jimenez C, Habra MA, et al. Parathyroid carcinoma: a 22-year experience. Head Neck. 2004;26:716–26. doi:10.1002/hed.20049.

    Article  PubMed  Google Scholar 

  6. Iacobone M, Ruffolo C, Lumachi F, et al. Results of iterative surgery for persistent and recurrent parathyroid carcinoma. Langenbecks Arch Surg. 2005;390:385–90. doi:10.1007/s00423-005-0555-6.

    Article  PubMed  Google Scholar 

  7. Peacock M, Bilezikian JP, Klassen PS, et al. Cinacalcet hydrochloride maintains long-term normocalcemia in patients with primary hyperparathyroidism. J Clin Endocrinol Metab. 2005;90:135–41. doi:10.1210/jc.2004-0842.

    Article  PubMed  CAS  Google Scholar 

  8. Fernandez-Ranvier GG, Jensen K, Khanafshar E, et al. Nonfunctioning parathyroid carcinoma: case report and review of the literature. Endocr Pract. 2007;13:750–7.

    PubMed  Google Scholar 

  9. Kirkby-Bott J, Lewis P, Harmer CL, et al. One stage treatment of parathyroid carcinoma. Eur J Surg Oncol. 2005;31:78–83. doi:10.1016/j.ejso.2004.06.014.

    Article  PubMed  CAS  Google Scholar 

  10. Yamashita H, Noguchi S, Murakami N, et al. Immunohistological study of nonfunctional parathyroid carcinoma: review of a case. Acta Pathol Jpn. 1992;42:279–85.

    PubMed  CAS  Google Scholar 

  11. Klink BK, Karulf RE, Maimon WN, et al. Nonfunctioning parathyroid carcinoma. Am Surg. 1991;7:463–7.

    Google Scholar 

  12. Collins FD, Warren MC, Palmer FJ, et al. Nonfunctioning parathyroid carcinoma: a case history. J Surg Oncol. 1986;31:60–1. doi:10.1002/jso.2930310114.

    Article  PubMed  CAS  Google Scholar 

  13. Murphy MN, Glennon PG, Diocee MS, et al. Nonsecretory parathyroid carcinoma of the mediastinum: light microscopic, immunocytochemical, and ultrastructural features of a case, and review of the literature. Cancer. 1986;58:2468–76. doi:10.1002/1097-0142(19861201)58:11<2468::AID-CNCR2820581120>3.0.CO;2-M.

    Article  PubMed  CAS  Google Scholar 

  14. Merlano M, Conte P, Scarsi P, et al. Non-functioning parathyroid carcinoma: a case report. Tumori. 1985;71:193–6.

    PubMed  CAS  Google Scholar 

  15. Yamashita H, Noguchi S, Nakayama I, et al. Light and electron microscopic study of nonfunctioning parathyroid carcinoma: report of a case with a review of the literature. Acta Pathol Jpn. 1984;34:123–32.

    PubMed  CAS  Google Scholar 

  16. Anderson BJ, Samaan NA, Vassilopoulou-Sellin R, et al. Parathyroid carcinoma: features and difficulties in diagnosis and management. Surgery. 1983;94:906–15.

    PubMed  CAS  Google Scholar 

  17. Ordoñez NG, Ibanez ML, Samaan NA, et al. Immunoperoxidase study of uncommon parathyroid tumors. Am J Surg Pathol. 1983;7:535–42.

    Article  PubMed  Google Scholar 

  18. Aldinger KA, Hickey RC, Ibanez ML, et al. Parathyroid carcinoma: a clinical study of seven cases of functioning and two cases of nonfunctioning parathyroid cancer. Cancer. 1982;49:388–97. doi:10.1002/1097-0142(19820115)49:2<388::AID-CNCR2820490230>3.0.CO;2-F.

    Article  PubMed  CAS  Google Scholar 

  19. Chahinian AP, Holland JF, Nieburgs HE, et al. Metastatic nonfunctioning parathyroid carcinoma: ultrastructural evidence of secretory granules and response to chemotherapy. Am J Med Sci. 1981;282:80–4. doi:10.1097/00000441-198109000-00005.

    Article  PubMed  CAS  Google Scholar 

  20. Dhom G, Hohbach C. Case 12. Ultrastruct Pathol. 1980;1:141–50. doi:10.3109/01913128009141410.

    Article  PubMed  CAS  Google Scholar 

  21. Altenähr E, Saeger W. Light and electron microscopy of parathyroid carcinoma: report of three cases. Virchows Arch A Pathol Anat. 1973;360:107–22.

    Article  PubMed  Google Scholar 

  22. Pachter MR, Lattes R. Uncommon mediastinal tumors: report of two parathyroid adenomas, one nonfunctional parathyroid carcinoma and one “bronchial-type-adenoma”. Chest. 1963;43:519–28. doi:10.1378/chest.43.5.519.

    Article  CAS  Google Scholar 

  23. Sieracki JC, Horn RC. Nonfunctional carcinoma of the parathyroid. Cancer. 1960;13:502–6. doi:10.1002/1097-0142(196005/06)13:3<502::AID-CNCR2820130312>3.0.CO;2-R.

    Article  PubMed  CAS  Google Scholar 

  24. McQuillan AS. Parathyroid tumor: report of two cases. Ann Surg. 1938;108:464–8. doi:10.1097/00000658-193809000-00008.

    Article  Google Scholar 

  25. Armstrong HG. Primary carcinoma of the parathyroid gland with report of a case. Bull Acad Med Tor. 1938;11:105–10.

    Google Scholar 

  26. Guy CC. Tumors of the parathyroid glands. Surg Gynecol Obstet. 1929;149:522–7.

    Google Scholar 

  27. Baba H, Kishihara M, Tohmon M, et al. Identification of parathyroid hormone messenger ribonucleic acid in an apparently nonfunctioning parathyroid carcinoma transformed from a parathyroid carcinoma with hyperparathyroidism. J Clin Endocrinol Metab. 1986;62:247–52.

    Article  PubMed  CAS  Google Scholar 

  28. Rodgers SE, Perrier ND. Parathyroid carcinoma. Curr Opin Oncol. 2006;18:16–22. doi:10.1097/01.cco.0000198019.53606.2b.

    Article  PubMed  Google Scholar 

  29. Schantz A, Castleman B. Parathyroid carcinoma: a study of 70 cases. Cancer. 1973;31:600–5. doi:10.1002/1097-0142(197303)31:3<600::AID-CNCR2820310316>3.0.CO;2-0.

    Article  PubMed  CAS  Google Scholar 

  30. Ippolito G, Palazzo FF, Sebag F, et al. Intraoperative diagnosis and treatment of parathyroid cancer and atypical parathyroid adenoma. Br J Surg. 2007;94:566–70. doi:10.1002/bjs.5570.

    Article  PubMed  CAS  Google Scholar 

  31. Carpten JD, Robbins CD, Villablanca A, et al. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet. 2002;32:676–80. doi:10.1038/ng1048.

    Article  PubMed  CAS  Google Scholar 

  32. Shattuck TM, Välimäki S, Obara T, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinomas. N Engl J Med. 2003;349:1722–9. doi:10.1056/NEJMoa031237.

    Article  PubMed  CAS  Google Scholar 

  33. Howell VM, Haven CJ, Kahnoski K, et al. HRPT2 mutations are associated with malignancy in sporadic parathyroid tumors. J Med Genet. 2003;40:657–63. doi:10.1136/jmg.40.9.657.

    Article  PubMed  CAS  Google Scholar 

  34. Tan MH, Morrison C, Wang P, et al. Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma. Clin Cancer Res. 2004;10:6629–37. doi:10.1158/1078-0432.CCR-04-0493.

    Article  PubMed  CAS  Google Scholar 

  35. Gill AJ, Clarkson A, Gimm O, et al. Loss of nuclear expression of parafibromin distinguishes parathyroid carcinomas and hyperparathyroidism-jaw tumor (HPT-JT) syndrome-related adenomas from sporadic parathyroid adenomas and hyperplasias. Am J Surg Pathol. 2006;30:1140–9. doi:10.1097/01.pas.0000209827.39477.4f.

    PubMed  Google Scholar 

  36. Rozenblatt-Rosen O, Hughes CM, Nannepaga SJ, et al. The parafibromin tumor suppressor protein is part of a human Paf1 complex. Mol Cell Biol. 2005;25:612–20. doi:10.1128/MCB.25.2.612-620.2005.

    Article  PubMed  CAS  Google Scholar 

  37. Woodard GE, Lin L, Zhang JH, et al. Parafibromin, product of the hyperparathyroidism-jaw tumor syndrome gene HRPT2, regulates cyclin D1/PRAD1 expression. Oncogene. 2005;24:1272–6. doi:10.1038/sj.onc.1208274.

    Article  PubMed  CAS  Google Scholar 

  38. Yart A, Gstaiger M, Wirbelauer C, et al. The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Mol Cell Biol. 2005;25:5052–60. doi:10.1128/MCB.25.12.5052-5060.2005.

    Article  PubMed  CAS  Google Scholar 

  39. Mosimann C, Hausmann G, Basler K. Parafibromin/Hyrax activates Wnt/Wg target gene transcription by direct association with beta-catenin/Armadillo. Cell. 2006;125:327–41. doi:10.1016/j.cell.2006.01.053.

    Article  PubMed  CAS  Google Scholar 

  40. Wang P, Bowl MR, Bender S, et al. Parafibromin, a component of the human PAF complex, regulates growth factors and is required for embryonic development and survival in adult mice. Mol Cell Biol. 2008;28:2930–40. doi:10.1128/MCB.00654-07.

    Article  PubMed  CAS  Google Scholar 

  41. Hunt JL, Carty SE, Yim JH, et al. Allelic loss in parathyroid neoplasia can help characterize malignancy. Am J Surg Pathol. 2005;29:1049–55.

    PubMed  Google Scholar 

Download references

Acknowledgments

We thank Dr. Rebecca Chernock for help with processing of the gross resection specimen, Dr. Samir El-Mofty and Dr. Brian Nussenbaum for helpful discussions on the case, and Mary Madden for assistance with manuscript preparation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to James S. Lewis Jr..

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wilkins, B.J., Lewis, J.S. Non-Functional Parathyroid Carcinoma: A Review of the Literature and Report of a Case Requiring Extensive Surgery. Head and Neck Pathol 3, 140–149 (2009). https://doi.org/10.1007/s12105-009-0115-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-009-0115-4

Keywords

Navigation