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Journal of Endocrinological Investigation

Published in:

01-06-2016 | Review

Update on parathyroid carcinoma

Authors: F. Cetani, E. Pardi, C. Marcocci

Published in: Journal of Endocrinological Investigation | Issue 6/2016

Abstract

Introduction

Parathyroid carcinoma (PC) is a rare endocrine disorder, commonly causing severe primary hyperparathyroidism (PHPT). PC is mainly a sporadic disease, but it may occur in familial PHPT. Patients with PC usually present markedly elevated serum calcium and PTH. The clinical features are mostly due to the effects of the excessive secretion of PTH rather than to the spread of tumor. At times, the diagnosis can be difficult.

Purpose

The aim of this work is to review the available data on PC, and focus its molecular pathogenesis and the clinical utility of CDC73 genetic testing and immunostaining of its product, parafibromin. The pathological diagnosis of PC is restricted to lesions showing unequivocal growth into adjacent tissues or metastasis. Inactivating mutations of the cell division cycle 73 (CDC73) gene have been identified in up to 70 % of apparently sporadic PC and in one-third are germline. Loss of parafibromin immunostaining has been shown in most PC. The association of CDC73 mutations and loss of parafibromin predicts a worse clinical outcome and a lower overall 5- and 10-year survival.

Conclusions

The treatment of choice is the en bloc resection of the tumor. The course of PC is variable; most patients have local recurrences or distant metastases and die from unmanageable hypercalcemia.

Marcocci C, Cetani F, Rubin MR, Silverberg SJ, Pinchera A, Bilezikian JP (2008) Parathyroid carcinoma. J Bone Miner Res 23(12):1869–1880CrossRefPubMedPubMedCentral

Cetani F, Marcocci C (2015) Parathyroid carcinoma. In: Bilezikian JP, Marcus R, Levine MA, Marcocci C, Silverberg SJ, J.T. PJ (eds) The parathyroids. Basic and Clinical concepts. vol 1. 3rd edn. Elsevier, Waltham. pp 409–421

Wilkins BJ, Lewis JS Jr (2009) Non-functional parathyroid carcinoma: a review of the literature and report of a case requiring extensive surgery. Head Neck Pathol 3(2):140–149. doi:10.1007/s12105-009-0115-4 CrossRefPubMedPubMedCentral

Harari A, Waring A, Fernandez-Ranvier G, Hwang J, Suh I, Mitmaker E, Shen W, Gosnell J, Duh QY, Clark O (2011) Parathyroid carcinoma: a 43-year outcome and survival analysis. J Clin Endocrinol Metab 96(12):3679–3686CrossRefPubMed

Fernandez-Ranvier GG, Jensen K, Khanafshar E, Quivey JM, Glastonbury C, Kebebew E, Duh QY, Clark OH (2007) Nonfunctioning parathyroid carcinoma: case report and review of literature. Endocr Pract 13(7):750–757 (T813482448232M1H [pii]) CrossRefPubMed

Cetani F, Frustaci G, Torregrossa L, Magno S, Basolo F, Campomori A, Miccoli P, Marcocci C (2015) A nonfunctioning parathyroid carcinoma misdiagnosed as a follicular thyroid nodule. World J Surg Oncol 13:270. doi:10.1186/s12957-015-0672-9 CrossRefPubMedPubMedCentral

Boyle NH, Ogg CS, Hartley RB, Owen WJ (1999) Parathyroid carcinoma secondary to prolonged hyperplasia in chronic renal failure and in coeliac disease. Eur J Surg Oncol 25(1):100–103PubMed

Fallah M, Kharazmi E, Sundquist J, Hemminki K (2011) Nonendocrine cancers associated with benign and malignant parathyroid tumors. J Clin Endocrinol Metab 96(7):E1108–E1114. doi:10.1210/jc.2011-0099 CrossRefPubMed

Marx SJ, Simonds WF, Agarwal SK, Burns AL, Weinstein LS, Cochran C, Skarulis MC, Spiegel AM, Libutti SK, Alexander HR Jr, Chen CC, Chang R, Chandrasekharappa SC, Collins FS (2002) Hyperparathyroidism in hereditary syndromes: special expressions and special managements. J Bone Miner Res 17(Suppl 2):N37–N43PubMed

10.

Newey PJ, Bowl MR, Cranston T, Thakker RV (2010) Cell division cycle protein 73 homolog (CDC73) mutations in the hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid tumors. Hum Mutat 31(3):295–307CrossRefPubMed

11.

Bradley KJ, Hobbs MR, Buley ID, Carpten JD, Cavaco BM, Fares JE, Laidler P, Manek S, Robbins CM, Salti IS, Thompson NW, Jackson CE, Thakker RV (2005) Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome. J Intern Med 257(1):18–26. doi:10.1111/j.1365-2796.2004.01421.x CrossRefPubMed

12.

Wassif WS, Moniz CF, Friedman E, Wong S, Weber G, Nordenskjold M, Peters TJ, Larsson C (1993) Familial isolated hyperparathyroidism: a distinct genetic entity with an increased risk of parathyroid cancer. J Clin Endocrinol Metab 77(6):1485–1489PubMed

13.

Simonds WF, James-Newton LA, Agarwal SK, Yang B, Skarulis MC, Hendy GN, Marx SJ (2002) Familial isolated hyperparathyroidism: clinical and genetic characteristics of 36 kindreds. Medicine (Baltimore) 81(1):1–26CrossRef

14.

del Pozo C, Garcia-Pascual L, Balsells M, Barahona MJ, Veloso E, Gonzalez C, Anglada-Barcelo J (2011) Parathyroid carcinoma in multiple endocrine neoplasia type 1. Case report and review of the literature. Hormones (Athens) 10(4):326–331

15.

Jenkins PJ, Satta MA, Simmgen M, Drake WM, Williamson C, Lowe DG, Britton K, Chew SL, Thakker RV, Besser GM (1997) Metastatic parathyroid carcinoma in the MEN2A syndrome. Clin Endocrinol 47(6):747–751CrossRef

16.

Cetani F, Pardi E, Borsari S, Marcocci C (2011) Molecular pathogenesis of primary hyperparathyroidism. J Endocrinol Invest 34(7 Suppl):35–39 (8004 [pii]) PubMed

17.

Carpten JD, Robbins CM, Villablanca A, Forsberg L, Presciuttini S, Bailey-Wilson J, Simonds WF, Gillanders EM, Kennedy AM, Chen JD, Agarwal SK, Sood R, Jones MP, Moses TY, Haven C, Petillo D, Leotlela PD, Harding B, Cameron D, Pannett AA, Hoog A, Heath H 3rd, James-Newton LA, Robinson B, Zarbo RJ, Cavaco BM, Wassif W, Perrier ND, Rosen IB, Kristoffersson U, Turnpenny PD, Farnebo LO, Besser GM, Jackson CE, Morreau H, Trent JM, Thakker RV, Marx SJ, Teh BT, Larsson C, Hobbs MR (2002) HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 32(4):676–680CrossRefPubMed

18.

Howell VM, Haven CJ, Kahnoski K, Khoo SK, Petillo D, Chen J, Fleuren GJ, Robinson BG, Delbridge LW, Philips J, Nelson AE, Krause U, Hammje K, Dralle H, Hoang-Vu C, Gimm O, Marsh DJ, Morreau H, Teh BT (2003) HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet 40(9):657–663CrossRefPubMedPubMedCentral

19.

Cetani F, Pardi E, Borsari S, Viacava P, Dipollina G, Cianferotti L, Ambrogini E, Gazzerro E, Colussi G, Berti P, Miccoli P, Pinchera A, Marcocci C (2004) Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab 89(11):5583–5591CrossRefPubMed

20.

Simonds WF, Robbins CM, Agarwal SK, Hendy GN, Carpten JD, Marx SJ (2004) Familial isolated hyperparathyroidism is rarely caused by germline mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor syndrome. J Clin Endocrinol Metab 89(1):96–102CrossRefPubMed

21.

Warner J, Epstein M, Sweet A, Singh D, Burgess J, Stranks S, Hill P, Perry-Keene D, Learoyd D, Robinson B, Birdsey P, Mackenzie E, Teh BT, Prins JB, Cardinal J (2004) Genetic testing in familial isolated hyperparathyroidism: unexpected results and their implications. J Med Genet 41(3):155–160CrossRefPubMedPubMedCentral

22.

Villablanca A, Calender A, Forsberg L, Hoog A, Cheng JD, Petillo D, Bauters C, Kahnoski K, Ebeling T, Salmela P, Richardson AL, Delbridge L, Meyrier A, Proye C, Carpten JD, Teh BT, Robinson BG, Larsson C (2004) Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP). J Med Genet 41(3):e32CrossRefPubMedPubMedCentral

23.

Bradley KJ, Cavaco BM, Bowl MR, Harding B, Cranston T, Fratter C, Besser GM, Conceicao Pereira M, Davie MW, Dudley N, Leite V, Sadler GP, Seller A, Thakker RV (2006) Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours. Clin Endocrinol 64(3):299–306. doi:10.1111/j.1365-2265.2006.02460.x CrossRef

24.

Mizusawa N, Uchino S, Iwata T, Tsuyuguchi M, Suzuki Y, Mizukoshi T, Yamashita Y, Sakurai A, Suzuki S, Beniko M, Tahara H, Fujisawa M, Kamata N, Fujisawa K, Yashiro T, Nagao D, Golam HM, Sano T, Noguchi S, Yoshimoto K (2006) Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome. Clin Endocrinol 65(1):9–16. doi:10.1111/j.1365-2265.2006.02534.x CrossRef

25.

Guarnieri V, Scillitani A, Muscarella LA, Battista C, Bonfitto N, Bisceglia M, Minisola S, Mascia ML, D’Agruma L, Cole DE (2006) Diagnosis of parathyroid tumors in familial isolated hyperparathyroidism with HRPT2 mutation: implications for cancer surveillance. J Clin Endocrinol Metab 91(8):2827–2832. doi:10.1210/jc.2005-1239 CrossRefPubMed

26.

Kelly TG, Shattuck TM, Reyes-Mugica M, Stewart AF, Simonds WF, Udelsman R, Arnold A, Carpenter TO (2006) Surveillance for early detection of aggressive parathyroid disease: carcinoma and atypical adenoma in familial isolated hyperparathyroidism associated with a germline HRPT2 mutation. J Bone Miner Res 21(10):1666–1671. doi:10.1359/jbmr.060702 CrossRefPubMed

27.

Korpi-Hyovalti E, Cranston T, Ryhanen E, Arola J, Aittomaki K, Sane T, Thakker RV, Schalin-Jantti C (2014) CDC73 intragenic deletion in familial primary hyperparathyroidism associated with parathyroid carcinoma. J Clin Endocrinol Metab 99(9):3044–3048. doi:10.1210/jc.2014-1481 CrossRefPubMedPubMedCentral

28.

Shattuck TM, Valimaki S, Obara T, Gaz RD, Clark OH, Shoback D, Wierman ME, Tojo K, Robbins CM, Carpten JD, Farnebo LO, Larsson C, Arnold A (2003) Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 349(18):1722–1729CrossRefPubMed

29.

Cetani F, Ambrogini E, Viacava P, Pardi E, Fanelli G, Naccarato AG, Borsari S, Lemmi M, Berti P, Miccoli P, Pinchera A, Marcocci C (2007) Should parafibromin staining replace HRTP2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? Eur J Endocrinol/Eur Feder Endocrine Soc 156(5):547–554CrossRef

30.

Haven CJ, van Puijenbroek M, Tan MH, Teh BT, Fleuren GJ, van Wezel T, Morreau H (2007) Identification of MEN1 and HRPT2 somatic mutations in paraffin-embedded (sporadic) parathyroid carcinomas. Clin Endocrinol 67(3):370–376CrossRef

31.

Cetani F, Pardi E, Ambrogini E, Banti C, Viacava P, Borsari S, Bilezikian JP, Pinchera A, Marcocci C (2008) Hyperparathyroidism 2 gene (HRPT2, CDC73) and parafibromin studies in two patients with primary hyperparathyroidism and uncertain pathological assessment. J Endocrinol Invest 31(10):900–904 (5015 [pii]) CrossRefPubMed

32.

Guarnieri V, Battista C, Muscarella LA, Bisceglia M, de Martino D, Baorda F, Maiello E, D’Agruma L, Chiodini I, Clemente C, Minisola S, Romagnoli E, Corbetta S, Viti R, Eller-Vainicher C, Spada A, Iacobellis M, Malavolta N, Carella M, Canaff L, Hendy GN, Cole DE, Scillitani A (2012) CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort. Cell Oncol (Dordr) 35(6):411–422CrossRefPubMed

33.

Wang O, Wang C, Nie M, Cui Q, Guan H, Jiang Y, Li M, Xia W, Meng X, Xing X (2012) Novel HRPT2/CDC73 gene mutations and loss of expression of parafibromin in Chinese patients with clinically sporadic parathyroid carcinomas. PLoS One 7(9):e45567CrossRefPubMedPubMedCentral

34.

Bricaire L, Odou MF, Cardot-Bauters C, Delemer B, North MO, Salenave S, Vezzosi D, Kuhn JM, Murat A, Caron P, Sadoul JL, Silve C, Chanson P, Barlier A, Clauser E, Porchet N, Groussin L (2013) Frequent large germline HRPT2 deletions in a French National cohort of patients with primary hyperparathyroidism. J Clin Endocrinol Metab 98(2):E403–E408CrossRefPubMed

35.

Cetani F, Banti C, Pardi E, Borsari S, Viacava P, Miccoli P, Torregrossa L, Basolo F, Pelizzo MR, Rugge M, Pennelli G, Gasparri G, Papotti M, Volante M, Vignali E, Saponaro F, Marcocci C (2013) CDC73 mutational status and loss of parafibromin in the outcome of parathyroid cancer. Endocr Connect 2(4):186–195. doi:10.1530/EC-13-0046

36.

Yu W, McPherson JR, Stevenson M, van Eijk R, Heng HL, Newey P, Gan A, Ruano D, Huang D, Poon SL, Ong CK, van Wezel T, Cavaco B, Rozen SG, Tan P, Teh BT, Thakker RV, Morreau H (2015) Whole-exome sequencing studies of parathyroid carcinomas reveal novel PRUNE2 mutations, distinctive mutational spectra related to APOBEC-catalyzed DNA mutagenesis and mutational enrichment in kinases associated with cell migration and invasion. J Clin Endocrinol Metab 100(2):E360–E364. doi:10.1210/jc.2014-3238 CrossRefPubMed

37.

Cavaco BM, Santos R, Felix A, Carvalho D, Lopes JM, Domingues R, Sirgado M, Rei N, Fonseca F, Santos JR, Sobrinho L, Leite V (2011) Identification of de novo germline mutations in the HRPT2 gene in two apparently sporadic cases with challenging parathyroid tumor diagnoses. Endocrine Pathol 22(1):44–52. doi:10.1007/s12022-011-9151-1 CrossRef

38.

Domingues R, Tomaz RA, Martins C, Nunes C, Bugalho MJ, Cavaco BM (2012) Identification of the first germline HRPT2 whole-gene deletion in a patient with primary hyperparathyroidism. Clin Endocrinol 76(1):33–38. doi:10.1111/j.1365-2265.2011.04184.x CrossRef

39.

Enomoto K, Uchino S, Ito A, Watanabe S, Shibuya H, Enomoto Y, Noguchi S (2010) The surgical strategy and the molecular analysis of patients with parathyroid cancer. World J Surg 34(11):2604–2610. doi:10.1007/s00268-010-0618-x CrossRefPubMed

40.

Siu WK, Law CY, Lam CW, Mak CM, Wong GW, Ho AY, Ho KY, Loo KT, Chiu SC, Chow LT, Tong SF, Chan AY (2011) Novel nonsense CDC73 mutations in Chinese patients with parathyroid tumors. Fam Cancer 10(4):695–699. doi:10.1007/s10689-011-9466-6 CrossRefPubMed

41.

Hewitt KM, Sharma PK, Samowitz W, Hobbs M (2007) Aberrant methylation of the HRPT2 gene in parathyroid carcinoma. Ann Otol Rhinol Laryngol 116(12):928–933CrossRefPubMed

42.

Krebs LJ, Shattuck TM, Arnold A (2005) HRPT2 mutational analysis of typical sporadic parathyroid adenomas. J Clin Endocrinol Metab 90(9):5015–5017CrossRefPubMed

43.

Yart A, Gstaiger M, Wirbelauer C, Pecnik M, Anastasiou D, Hess D, Krek W (2005) The HRPT2 tumor suppressor gene product parafibromin associates with human PAF1 and RNA polymerase II. Mol Cell Biol 25(12):5052–5060. doi:10.1128/MCB.25.12.5052-5060.2005 CrossRefPubMedPubMedCentral

44.

Hahn MA, Marsh DJ (2005) Identification of a functional bipartite nuclear localization signal in the tumor suppressor parafibromin. Oncogene 24(41):6241–6248. doi:10.1038/sj.onc.1208778 CrossRefPubMed

45.

Bradley KJ, Bowl MR, Williams SE, Ahmad BN, Partridge CJ, Patmanidi AL, Kennedy AM, Loh NY, Thakker RV (2007) Parafibromin is a nuclear protein with a functional monopartite nuclear localization signal. Oncogene 26(8):1213–1221. doi:10.1038/sj.onc.1209893 CrossRefPubMed

46.

Lin L, Czapiga M, Nini L, Zhang JH, Simonds WF (2007) Nuclear localization of the parafibromin tumor suppressor protein implicated in the hyperparathyroidism-jaw tumor syndrome enhances its proapoptotic function. Mol Cancer Res 5(2):183–193. doi:10.1158/1541-7786.MCR-06-0129 CrossRefPubMed

47.

Hahn MA, Marsh DJ (2007) Nucleolar localization of parafibromin is mediated by three nucleolar localization signals. FEBS Lett 581(26):5070–5074. doi:10.1016/j.febslet.2007.09.050 CrossRefPubMed

48.

Tan MH, Morrison C, Wang P, Yang X, Haven CJ, Zhang C, Zhao P, Tretiakova MS, Korpi-Hyovalti E, Burgess JR, Soo KC, Cheah WK, Cao B, Resau J, Morreau H, Teh BT (2004) Loss of parafibromin immunoreactivity is a distinguishing feature of parathyroid carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res 10(19):6629–6637CrossRef

49.

Juhlin C, Larsson C, Yakoleva T, Leibiger I, Leibiger B, Alimov A, Weber G, Hoog A, Villablanca A (2006) Loss of parafibromin expression in a subset of parathyroid adenomas. Endocr Relat Cancer 13(2):509–523CrossRefPubMed

50.

Juhlin CC, Villablanca A, Sandelin K, Haglund F, Nordenstrom J, Forsberg L, Branstrom R, Obara T, Arnold A, Larsson C, Hoog A (2007) Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification. Endocr Relat Cancer 14(2):501–512CrossRefPubMed

51.

Howell VM, Gill A, Clarkson A, Nelson AE, Dunne R, Delbridge LW, Robinson BG, Teh BT, Gimm O, Marsh DJ (2009) Accuracy of combined protein gene product 9.5 and parafibromin markers for immunohistochemical diagnosis of parathyroid carcinoma. J Clin Endocrinol Metab 94(2):434–441CrossRefPubMed

52.

Kim HK, Oh YL, Kim SH, Lee DY, Kang HC, Lee JI, Jang HW, Hur KY, Kim JH, Min YK, Chung JH, Kim SW (2011) Parafibromin immunohistochemical staining to differentiate parathyroid carcinoma from parathyroid adenoma. Head Neck 34(2):201–206CrossRefPubMed

53.

Witteveen JE, Hamdy NA, Dekkers OM, Kievit J, van Wezel T, Teh BT, Romijn JA, Morreau H (2011) Downregulation of CASR expression and global loss of parafibromin staining are strong negative determinants of prognosis in parathyroid carcinoma. Modern Pathol Off J US Can Acad Pathol Inc 24(5):688–697

54.

Starker LF, Svedlund J, Udelsman R, Dralle H, Akerstrom G, Westin G, Lifton RP, Bjorklund P, Carling T (2011) The DNA methylome of benign and malignant parathyroid tumors. Genes Chromosom Cancer 50(9):735–745CrossRefPubMedPubMedCentral

55.

Costa-Guda J, Imanishi Y, Palanisamy N, Kawamata N, Phillip Koeffler H, Chaganti RS, Arnold A (2013) Allelic imbalance in sporadic parathyroid carcinoma and evidence for its de novo origins. Endocrine. doi:10.1007/s12020-013-9903-4 PubMedPubMedCentral

56.

Verdelli C, Forno I, Vaira V, Corbetta S (2015) MicroRNA deregulation in parathyroid tumours suggests an embryonic signature. J Endocrinol Invest 38(4):383–388. doi:10.1007/s40618-014-0234-y CrossRefPubMed

57.

DeLellis RA (2005) Parathyroid carcinoma: an overview. Adv Anat Pathol 12(2):53–61 00125480-200503000-00003 [pii] CrossRefPubMed

58.

Schantz A, Castleman B (1973) Parathyroid carcinoma. A study of 70 cases. Cancer 31(3):600–605CrossRefPubMed

59.

Bondenson L, Grimelius L, DeLellis RA, Lloyd R, Akerstrom G, Larsson C, Arnold A, Eng C, Shane E, Bilezikian JP (2004) Parathyroid carcinoma. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C (eds) Pathology and genetics. Tumors of Endocrine organs. WHO Classification of Tumours. IARC Press, Lyon, pp 124–127

60.

Delellis RA (2008) Challenging lesions in the differential diagnosis of endocrine tumors: parathyroid carcinoma. Endocrine Pathol 19(4):221–225. doi:10.1007/s12022-008-9050-2 CrossRef

61.

Apel RL (2002) The parathyroid glands. In: LiVolsi VA, Asa SL (eds) Endocrine pathology. Churchill Livingstone, Philadelphia, pp 103–147

62.

Sandelin K, Tullgren O, Farnebo LO (1994) Clinical course of metastatic parathyroid cancer. World J Surg 18(4):594–598CrossRefPubMed

63.

Cetani F, Pardi E, Viacava P, Pollina GD, Fanelli G, Picone A, Borsari S, Gazzerro E, Miccoli P, Berti P, Pinchera A, Marcocci C (2004) A reappraisal of the Rb1 gene abnormalities in the diagnosis of parathyroid cancer. Clin Endocrinol 60(1):99–106 (1954 [pii]) CrossRef

64.

Bergero N, De Pompa R, Sacerdote C, Gasparri G, Volante M, Bussolati G, Papotti M (2005) Galectin-3 expression in parathyroid carcinoma: immunohistochemical study of 26 cases. Hum Pathol 36(8):908–914. doi:10.1016/j.humpath.2005.06.020 CrossRefPubMed

65.

Fernandez-Ranvier GG, Khanafshar E, Tacha D, Wong M, Kebebew E, Duh QY, Clark OH (2009) Defining a molecular phenotype for benign and malignant parathyroid tumors. Cancer 115(2):334–344CrossRefPubMed

66.

Wang O, Wang CY, Shi J, Nie M, Xia WB, Li M, Jiang Y, Guan H, Meng XW, Xing XP (2012) Expression of Ki-67, galectin-3, fragile histidine triad, and parafibromin in malignant and benign parathyroid tumors. Chin Med J (Engl) 125(16):2895–2901

67.

Shifrin A, LiVolsi V, Shifrin-Douglas S, Zheng M, Erler B, Matulewicz T, Davis J (2015) Primary and metastatic parathyroid malignancies: a rare or underdiagnosed condition? J Clin Endocrinol Metab 100(3):E478–E481. doi:10.1210/jc.2014-2760 CrossRefPubMed

68.

Erickson LA, Jin L, Wollan P, Thompson GB, van Heerden JA, Lloyd RV (1999) Parathyroid hyperplasia, adenomas, and carcinomas: differential expression of p27Kip1 protein. Am J Surg Pathol 23(3):288–295CrossRefPubMed

69.

Gill AJ, Clarkson A, Gimm O, Keil J, Dralle H, Howell VM, Marsh DJ (2006) 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 30(9):1140–1149CrossRefPubMed

70.

Marcocci C, Cetani F (2011) Clinical practice. Primary hyperparathyroidism. N Engl J Med 365(25):2389–2397. doi:10.1056/NEJMcp1106636 CrossRefPubMed

71.

Rubin MR, Silverberg SJ, D’Amour P, Brossard JH, Rousseau L, Sliney J Jr, Cantor T, Bilezikian JP (2007) An N-terminal molecular form of parathyroid hormone (PTH) distinct from hPTH(1 84) is overproduced in parathyroid carcinoma. Clin Chem 53(8):1470–1476. doi:10.1373/clinchem.2007.085506 CrossRefPubMed

72.

Cavalier E, Daly AF, Betea D, Pruteanu-Apetrii PN, Delanaye P, Stubbs P, Bradwell AR, Chapelle JP, Beckers A (2010) The ratio of parathyroid hormone as measured by third- and second-generation assays as a marker for parathyroid carcinoma. J Clin Endocrinol Metab 95(8):3745–3749. doi:10.1210/jc.2009-2791 CrossRefPubMed

73.

Caron P, Simonds WF, Maiza JC, Rubin M, Cantor T, Rousseau L, Bilezikian JP, Souberbielle JC, D’Amour P (2011) Nontruncated amino-terminal parathyroid hormone overproduction in two patients with parathyroid carcinoma: a possible link to HRPT2 gene inactivation. Clin Endocrinol 74(6):694–698. doi:10.1111/j.1365-2265.2011.04021.x CrossRef

74.

Rubin MR, Bilezikian JP, Birken S, Silverberg SJ (2008) Human chorionic gonadotropin measurements in parathyroid carcinoma. Eur J Endocrinol/Eur Feder Endocrine Soc 159(4):469–474. doi:10.1530/EJE-08-0169 CrossRef

75.

Talat N, Schulte KM (2010) Clinical presentation, staging and long-term evolution of parathyroid cancer. Ann Surg Oncol 17(8):2156–2174. doi:10.1245/s10434-010-1003-6 CrossRefPubMed

76.

Whitson BA, Broadie TA (2008) Preoperative ultrasound and nuclear medicine studies improve the accuracy in localization of adenoma in hyperparathyroidism. Surg Today 38(3):222–226. doi:10.1007/s00595-007-3612-7 CrossRefPubMed

77.

Kwon JH, Kim EK, Lee HS, Moon HJ, Kwak JY (2013) Neck ultrasonography as preoperative localization of primary hyperparathyroidism with an additional role of detecting thyroid malignancy. Eur J Radiol 82(1):e17–e21. doi:10.1016/j.ejrad.2012.08.003 CrossRefPubMed

78.

Sidhu PS, Talat N, Patel P, Mulholland NJ, Schulte KM (2011) Ultrasound features of malignancy in the preoperative diagnosis of parathyroid cancer: a retrospective analysis of parathyroid tumours larger than 15 mm. Eur Radiol 21(9):1865–1873. doi:10.1007/s00330-011-2141-3 CrossRefPubMed

79.

Hunter GJ, Schellingerhout D, Vu TH, Perrier ND, Hamberg LM (2012) Accuracy of four-dimensional CT for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism. Radiology 264(3):789–795. doi:10.1148/radiol.12110852 CrossRefPubMed

80.

Evangelista L, Sorgato N, Torresan F, Boschin IM, Pennelli G, Saladini G, Piotto A, Rubello D, Pelizzo MR (2011) FDG-PET/CT and parathyroid carcinoma: review of literature and illustrative case series. World J Clin Oncol 2(10):348–354. doi:10.5306/wjco.v2.i10.348 CrossRefPubMedPubMedCentral

81.

Allen ME, Semrad A, Yang AD, Martinez SR (2013) Parathyroid carcinoma survival: improvements in the era of intact parathyroid hormone monitoring? Rare Tumors 5(1):e12. doi:10.4081/rt.2013.e12 CrossRefPubMedPubMedCentral

82.

Busaidy NL, Jimenez C, Habra MA, Schultz PN, El-Naggar AK, Clayman GL, Asper JA, Diaz EM Jr, Evans DB, Gagel RF, Garden A, Hoff AO, Lee JE, Morrison WH, Rosenthal DI, Sherman SI, Sturgis EM, Waguespack SG, Weber RS, Wirfel K, Vassilopoulou-Sellin R (2004) Parathyroid carcinoma: a 22-year experience. Head Neck 26(8):716–726CrossRefPubMed

83.

Lee PK, Jarosek SL, Virnig BA, Evasovich M, Tuttle TM (2007) Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer 109(9):1736–1741. doi:10.1002/cncr.22599 CrossRefPubMed

84.

Sandelin K, Auer G, Bondeson L, Grimelius L, Farnebo LO (1992) Prognostic factors in parathyroid cancer: a review of 95 cases. World J Surg 16(4):724–731CrossRefPubMed

85.

Hundahl SA, Fleming ID, Fremgen AM, Menck HR (1999) Two hundred eighty-six cases of parathyroid carcinoma treated in the US between 1985–1995: a National Cancer Data Base Report. The American College of Surgeons Commission on Cancer and the American Cancer Society. Cancer 86(3):538–544. doi:10.1002/(SICI)1097-0142(19990801)86:3<538:AID-CNCR25>3.0.CO;2-K CrossRefPubMed

86.

Kebebew E (2001) Parathyroid carcinoma. Curr Treat Options Oncol 2(4):347–354CrossRefPubMed

87.

Schulte KM, Talat N, Miell J, Moniz C, Sinha P, Diaz-Cano S (2010) Lymph node involvement and surgical approach in parathyroid cancer. World J Surg 34(11):2611–2620. doi:10.1007/s00268-010-0722-y CrossRefPubMed

88.

Spinelli C, Bonadio AG, Berti P, Materazzi G, Miccoli P (2000) Cutaneous spreading of parathyroid carcinoma after fine needle aspiration cytology. J Endocrinol Invest 23(4):255–257CrossRefPubMed

89.

Rawat N, Khetan N, Williams DW, Baxter JN (2005) Parathyroid carcinoma. Br J Surg 92(11):1345–1353. doi:10.1002/bjs.5182 CrossRefPubMed

90.

Wynne AG, van Heerden J, Carney JA, Fitzpatrick LA (1992) Parathyroid carcinoma: clinical and pathologic features in 43 patients. Medicine (Baltimore) 71(4):197–205CrossRef

91.

Munson ND, Foote RL, Northcutt RC, Tiegs RD, Fitzpatrick LA, Grant CS, van Heerden JA, Thompson GB, Lloyd RV (2003) Parathyroid carcinoma: is there a role for adjuvant radiation therapy? Cancer 98(11):2378–2384. doi:10.1002/cncr.11819 CrossRefPubMed

92.

Clayman GL, Gonzalez HE, El-Naggar A, Vassilopoulou-Sellin R (2004) Parathyroid carcinoma: evaluation and interdisciplinary management. Cancer 100(5):900–905. doi:10.1002/cncr.20089 CrossRefPubMed

93.

Artinyan A, Guzman E, Maghami E, Al-Sayed M, D’Apuzzo M, Wagman L, Kim J (2008) Metastatic parathyroid carcinoma to the liver treated with radiofrequency ablation and transcatheter arterial embolization. J Clin Oncol 26(24):4039–4041. doi:10.1200/JCO.2007.15.9038 CrossRefPubMed

94.

Tochio M, Takaki H, Yamakado K, Uraki J, Kashima M, Nakatsuka A, Takao M, Shimamoto A, Tarukawa T, Shimpo H, Takeda K (2010) A case report of 20 lung radiofrequency ablation sessions for 50 lung metastases from parathyroid carcinoma causing hyperparathyroidism. Cardiovasc Intervent Radiol 33(3):657–659. doi:10.1007/s00270-009-9730-4 CrossRefPubMed

95.

Tong CV, Hussein Z, Noor NM, Mohamad M, Ng WF (2015) Use of denosumab in parathyroid carcinoma with refractory hypercalcemia. QJM Mon J Assoc Physicians 108(1):49–50. doi:10.1093/qjmed/hcu166 CrossRef

96.

Betea D, Bradwell AR, Harvey TC, Mead GP, Schmidt-Gayk H, Ghaye B, Daly AF, Beckers A (2004) Hormonal and biochemical normalization and tumor shrinkage induced by anti-parathyroid hormone immunotherapy in a patient with metastatic parathyroid carcinoma. J Clin Endocrinol Metab 89(7):3413–3420. doi:10.1210/jc.2003-031911 CrossRefPubMed

97.

Horie I, Ando T, Inokuchi N, Mihara Y, Miura S, Imaizumi M, Usa T, Kinoshita N, Sekine I, Kamihara S, Eguchi K (2010) First Japanese patient treated with parathyroid hormone peptide immunization for refractory hypercalcemia caused by metastatic parathyroid carcinoma. Endocr J 57(4):287–292 (JST.JSTAGE/endocrj/K09E−283 [pii]) CrossRefPubMed

98.

Schott M, Feldkamp J, Schattenberg D, Krueger T, Dotzenrath C, Seissler J, Scherbaum WA (2000) Induction of cellular immunity in a parathyroid carcinoma treated with tumor lysate-pulsed dendritic cells. Eur J Endocrinol/Eur Feder Endocrine Soc 142(3):300–306 (1420300 [pii]) CrossRef

99.

Peacock M, Bilezikian JP, Bolognese MA, Borofsky M, Scumpia S, Sterling LR, Cheng S, Shoback D (2011) Cinacalcet HCl reduces hypercalcemia in primary hyperparathyroidism across a wide spectrum of disease severity. J Clin Endocrinol Metab 96(1):E9–E18. doi:10.1210/jc.2010-1221 CrossRefPubMedPubMedCentral

100.

Saponaro F, Faggiano A, Grimaldi F, Borretta G, Brandi ML, Minisola S, Frasoldati A, Papini E, Scillitani A, Banti C, Prete MD, Vescini F, Gianotti L, Cavalli L, Romagnoli E, Colao A, Cetani F, Marcocci C (2013) Cinacalcet in the management of primary hyperparathyroidism: post marketing experience of an Italian multicentre group. Clin Endocrinol 79(1):20–26. doi:10.1111/cen.12108 CrossRef

101.

Silverberg SJ, Rubin MR, Faiman C, Peacock M, Shoback DM, Smallridge RC, Schwanauer LE, Olson KA, Klassen P, Bilezikian JP (2007) Cinacalcet hydrochloride reduces the serum calcium concentration in inoperable parathyroid carcinoma. J Clin Endocrinol Metab 92(10):3803–3808. doi:10.1210/jc.2007-0585 CrossRefPubMed

Title: Update on parathyroid carcinoma
Authors: F. Cetani
E. Pardi
C. Marcocci
Publication date: 01-06-2016
Publisher: Springer International Publishing
Published in: Journal of Endocrinological Investigation / Issue 6/2016
Electronic ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-016-0447-3

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