Long-Term Outcomes of Parathyroidectomy in Hyperparathyroidism-Jaw Tumor Syndrome: Analysis of Five Families with CDC73 Mutations

  • Maurizio IacoboneEmail author
  • Valentina Camozzi
  • Caterina Mian
  • Gianmaria Pennelli
  • Costantino Pagetta
  • Eric Casal Ide
  • Giulia Masi
  • Stefania Zovato
  • Francesca Torresan
Original Scientific Report



Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare disease caused by CDC73 germline mutations, with familial primary hyperparathyroidism (pHPT), ossifying jaw tumors, genito-urinary neoplasms. The present study was aimed at determining the long-term postoperative outcome of parathyroidectomy in HPT-JT.


A retrospective analysis of a single-center series of 20 patients from five unrelated HPT-JT families undergoing parathyroid surgery was performed.


Pathology confirmed a single-gland involvement in 95% of cases at onset. Parathyroid carcinoma occurred in three patients undergoing en-bloc parathyroidectomy and thyroid lobectomy: parathyroid benign lesions in 17 patients undergoing subtotal parathyroidectomy for evident multiglandular involvement (n = 1) or selective parathyroidectomy for single-gland involvement (n = 16), during bilateral (n = 13) or targeted unilateral neck exploration (n = 7). At a median overall follow-up of 16 years (range 2.5–42), patients with parathyroid carcinoma had a persistent/recurrent disease in 66.6%; patients with benign lesions had recurrent pHPT in 23.5% after a prolonged disease-free period; recurrent benign pHPT occurred slightly more often in cases of discordant preoperative localization (60% vs 9%; p = 0.06).


pHPT in HPT-JT is generally characterized by a benign and single-gland involvement, with a relatively increased risk of malignancy (15%). Parathyroid carcinoma needs extensive surgery because of high risk of permanent/recurrent disease (66.6%). In benign involvement, targeted unilateral exploration with selective parathyroidectomy may be effective in cases of concordant single-gland localization at preoperative localization imaging techniques. Bilateral neck exploration with subtotal parathyroidectomy might be preferred in cases of negative or discordant preoperative localization, because of the increased risk of multiglandular involvement and long-term recurrences (23.5%).



The study was supported by a Grant from University of Padua to Maurizio Iacobone (BIRD172205).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study has been approved by the Institution review board.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Carling T, Udelsman R (2005) Parathyroid surgery in familial hyperparathyroid disorders. J Intern Med 257:27–37CrossRefGoogle Scholar
  2. 2.
    Bradley KJ, Hobbs MR, Buley ID et al (2005) Uterine tumours are a phenotypic manifestation of the hyperparathyroidism-jaw tumour syndrome. J Intern Med 257:18–26CrossRefGoogle Scholar
  3. 3.
    Iacobone M, Barzon L, Porzionato A et al (2007) Parafibromin expression, single-gland involvement, and limited parathyroidectomy in familial isolated hyperparathyroidism. Surgery 142(6):984–991CrossRefGoogle Scholar
  4. 4.
    Iacobone M, Masi G, Barzon L et al (2009) Hyperparathyroidism jaw tumor syndrome: a report of three large kindred. Langenbecks Arch Surg 394:817–825CrossRefGoogle Scholar
  5. 5.
    Masi G, Barzon L, Iacobone M et al (2008) Clinical, genetic, and histopathologic investigation of CDC73-related familial hyperparathyroidism. Endocr Relat Cancer 15:1115–1126CrossRefGoogle Scholar
  6. 6.
    Masi G, Iacobone M, Sinigaglia A et al (2014) Characterization of a new CDC73 missense mutation that impairs Parafibromin expression and nucleolar localization. PLoS One 9(5):e97994CrossRefGoogle Scholar
  7. 7.
    Iacobone M, Barzon L, Porzionato A et al (2009) The extent of parathyroidectomy for HRPT2-related hyperparathyroidism. Surgery 145:250–251CrossRefGoogle Scholar
  8. 8.
    Sarquis MS, Silveira LG, Pimenta FJ et al (2008) Familial hyperparathyroidism: surgical outcome after 30 years of follow up in three families with germline HRPT2 mutations. Surgery 143:630–640CrossRefGoogle Scholar
  9. 9.
    Mehta A, Patel D, Rosenberg A et al (2014) Hyperparathyroidism-jaw tumor syndrome: results of operative management. Surgery 156:1315–1325CrossRefGoogle Scholar
  10. 10.
    Li Y, Simonds WF (2015) Endocrine neoplasms in familial syndromes of hyperparathyroidism. Endocr Relat Cancer 23(6):R229–R247CrossRefGoogle Scholar
  11. 11.
    Lloyd RV, Osamura RY, Klőpper G, Rosai J (2017) WHO classification of tumours of endocrine organs, 4th edn. IARC Press, LyonGoogle Scholar
  12. 12.
    Iacobone M, Lumachi F, Favia G (2004) Up-to-date on parathyroid carcinoma: analysis of an experience of 19 cases. J Surg Oncol 88:223–228CrossRefGoogle Scholar
  13. 13.
    Iacobone M, Ruffolo C, Lumachi F, Favia G (2005) Results of iterative surgery for persistent and recurrent parathyroid carcinoma. Langenbecks Arch Surg 390:385–390CrossRefGoogle Scholar
  14. 14.
    Iacobone M, Carnaille B, Palazzo F, Vriens M (2015) Hereditary hyperparathyroidism—a consensus report of the European Society of Endocrine Surgeons (ESES). Langenbecks Arch Surg 400:867–886CrossRefGoogle Scholar
  15. 15.
    Carpten JD, Robbins CM, Villablanca A et al (2002) HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw tumor syndrome. Nat Genet 32:676–680CrossRefGoogle Scholar
  16. 16.
    Shattuck TM, Valimaki S, Obara T et al (2003) Somatic and germline mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 349:1722–1729CrossRefGoogle Scholar
  17. 17.
    Howell VM, Haven CJ, Kahnoski K et al (2003) HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet 40:657–663CrossRefGoogle Scholar
  18. 18.
    Bradley KJ, Cavaco BM, Bowl MR et al (2006) Parafibromin mutations in hereditary hyperparathyroidism syndromes and parathyroid tumours. Clin Endocrinol (Oxf) 64(3):299–306CrossRefGoogle Scholar
  19. 19.
    Juhlin C, Larsson C, Yakoleva T et al (2006) Loss of parafibromin expression in a subset of parathyroid adenomas. Endocr Relat Cancer 13:509–523CrossRefGoogle Scholar
  20. 20.
    Guarnieri V, Scillitani A, Muscarella LA et al (2006) Diagnosis of parathyroid tumors in familial isolated hyperparathyroidism with HRPT2 mutation: implications for cancer surveillance. J Clin Endocrinol Metab 91:2827–2832CrossRefGoogle Scholar
  21. 21.
    Porzionato A, Macchi V, Barzon L et al (2006) Immunohistochemical assessment of parafibromin in mouse and human tissues. J Anat 209:817–827CrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2019

Authors and Affiliations

  • Maurizio Iacobone
    • 1
    Email author
  • Valentina Camozzi
    • 2
  • Caterina Mian
    • 2
  • Gianmaria Pennelli
    • 3
  • Costantino Pagetta
    • 1
  • Eric Casal Ide
    • 1
  • Giulia Masi
    • 4
  • Stefania Zovato
    • 5
  • Francesca Torresan
    • 1
  1. 1.Endocrine Surgery Unit, Department of Surgery, Oncology and GastroenterologyUniversity of PaduaPaduaItaly
  2. 2.Endocrinogy Unit, Department of MedicineUniversity of PaduaPaduaItaly
  3. 3.Pathology Unit, Department of MedicineUniversity of PaduaPaduaItaly
  4. 4.Department of Molecular MedicineUniversity of PaduaPaduaItaly
  5. 5.Familial Tumor UnitVeneto Institute of Oncology, (IOV)-IRCCSPaduaItaly

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