Journal of Endocrinological Investigation

, Volume 31, Issue 10, pp 900–904 | Cite as

Hyperparathyroidism 2 gene (HRPT2, CDC73) and parafibromin studies in two patients with primary hyperparathyroidism and uncertain pathological assessment

  • F. Cetani
  • E. Pardi
  • E. Ambrogini
  • C. Banti
  • P. Viacava
  • S. Borsari
  • J. P. Bilezikian
  • A. Pinchera
  • C. Marcocci
Original Article

Abstract

HRPT2 and parafibromin studies improved the diagnostic accuracy in two patients with primary hyperparathyroidism (PHPT) referred to us after surgery, in whom the clinical data were at variance with the pathological diagnosis of adenoma and carcinoma, respectively. Patients were referred to us after parathyroidectomy. Patient #1 had had a 1.5-cm tumor easily removed with a histological diagnosis of parathyroid carcinoma and normocalcemia for 2 years. Re-examination of the histology showed no cardinal signs of parathyroid cancer. Patient #2, with severe PHPT, had had the removal of a 3.5-cm tumor described histologically as adenoma. Ten years later PHPT recurred and persisted despite removal of two mildly enlarged parathyroid glands that were histologically normal. Re-review of the initial histology showed a trabecular pattern, fibrous bands, and atypical mitoses, suggesting an atypical adenoma. Because of the suspicion that case #1 could be an atypical adenoma and case #2 a carcinoma further molecular studies were performed. No HRPT2 and parafibromin abnormalities were identified in patient #1, strongly indicating a benign lesion. In patient #2, an HRPT2 germline mutation was found (E115X in exon 4) and associated with no parafibromin staining. These data, together with the clinical features, supported the suspicion of a parathyroid carcinoma that was confirmed by histological examination of further slides of the tumor, showing capsular and vascular invasion. A lung 1.5-cm nodule detected by computed tomography was excised. Histology showed a metastasis of parathyroid carcinoma. HRPT2 gene studies improved the diagnostic accuracy in 2 parathyroid tumors that are of uncertain type.

Key-words

Atypical parathyroid adenoma HRPT2 parafibromin parathyroid carcinoma primary hyperparathyroidism 

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References

  1. 1.
    Shane E. Clinical Review 122: Parathyroid carcinoma. J Clin Endocrinol Metab 2001, 2: 485–93.CrossRefGoogle Scholar
  2. 2.
    DeLellis RA. Parathyroid carcinoma: an overview. Adv Anat Pathol 2005, 12: 53–61.PubMedCrossRefGoogle Scholar
  3. 3.
    Bondenson L, Grimelius L, DeLellis RA, et al. Parathyroid carcinoma. In DeLellis RA, Lloyd RV, Heitz PU, Eng C eds. Pathology and genetics of tumours of endocrine organs. WHO Classification of Tumour. Lyon, FR: IARC Press. 2004, 124–7.Google Scholar
  4. 4.
    Grimelius L, DeLellis RA, Bondenson L, et al. Parathyroid adenoma. In DeLellis RA, Lloyd RV, Heitz PU, Eng C eds. Pathology and genetics of tumours of endocrine organs. WHO Classification of Tumour. Lyon, FR: IARC Press. 2004, 128–32.Google Scholar
  5. 5.
    Schantz A, Castleman B. Parathyroid carcinoma. A study of 70 cases. Cancer 1973, 31: 600–5.Google Scholar
  6. 6.
    Cryns VL, Thor A, Xu HJ, et al. Loss of the retinoblastoma tumor-suppressor gene in parathyroid carcinoma. N Engl J Med 1994, 330: 757–61.PubMedCrossRefGoogle Scholar
  7. 7.
    Naccarato AG, Marcocci C, Miccoli P, et al. Bcl-2, p53 and MIB-1 expression in normal and neoplastic parathyroid tissues. J Endocrinol Invest 1998, 213: 136–41.CrossRefGoogle Scholar
  8. 8.
    Farnebo F, Auer G, Farnebo LO, et al. Evaluation of retinoblastoma and Ki-67 immunostaining as diagnostic markers of benign and malignant parathyroid disease. World J Surg 1999, 23: 68–74.PubMedCrossRefGoogle Scholar
  9. 9.
    Cetani F, Pardi E, Viacava P, et al. A reappraisal of the Rb1 gene abnormalities in the diagnosis of parathyroid cancer. Clin Endocrinol (Oxf) 2004, 60: 99–106.CrossRefGoogle Scholar
  10. 10.
    Howell VM, Haven CJ, Kahnoski K, et al. HRPT2 mutations are associated with malignancy in sporadic parathyroid tumours. J Med Genet 2003, 40: 657–63.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Shattuck TM, Välimäki S, Obara T, et al. Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma. N Engl J Med 2003, 349: 1722–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Cetani F, Pardi E, Borsari S, et al. Genetic analyses of the HRPT2 gene in primary hyperparathyroidism: germline and somatic mutations in familial and sporadic parathyroid tumors. J Clin Endocrinol Metab 2004, 89: 5583–91.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    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.PubMedCrossRefGoogle Scholar
  15. 15.
    Cetani F, Ambrogini E, Viacava P, et al. Should parafibromin staining replace HRPT2 gene analysis as an additional tool for histologic diagnosis of parathyroid carcinoma? Eur J Endocrinol 2007, 156: 547–54.PubMedCrossRefGoogle Scholar
  16. 16.
    Juhlin CC, Villablanca A, Sandelin K, et al. Parafibromin immunoreactivity: its use as an additional diagnostic marker for parathyroid tumor classification. Endocr Relat Cancer 2007, 14: 501–12.PubMedCrossRefGoogle Scholar
  17. 17.
    Guarnieri V, Scillitani A, Muscarella LA, et al. Diagnosis of parathyroid tumors in familial isolated hyperparathyroidism with HRPT2 mutation: implications for cancer surveillance. J Clin Endocrinol Metab 2006, 91: 2827–32.PubMedCrossRefGoogle Scholar
  18. 18.
    Kelly TG, Shattuck TM, Reyes-Mugica M, et al. 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 2006, 21: 1666–71.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2008

Authors and Affiliations

  • F. Cetani
    • 1
  • E. Pardi
    • 1
  • E. Ambrogini
    • 1
  • C. Banti
    • 1
  • P. Viacava
    • 2
  • S. Borsari
    • 1
  • J. P. Bilezikian
    • 3
  • A. Pinchera
    • 1
  • C. Marcocci
    • 1
  1. 1.Departments of EndocrinologyUniversity of PisaPisaItaly
  2. 2.Oncology (Section of Pathology)University of PisaPisaItaly
  3. 3.Department of Medicine and PharmacologyColumbia University College of Physicians & SurgeonsNew YorkUSA

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