Endocrine Pathology

, Volume 22, Issue 1, pp 44–52

Identification of De Novo Germline Mutations in the HRPT2 Gene in Two Apparently Sporadic Cases with Challenging Parathyroid Tumor Diagnoses

  • Branca Maria Cavaco
  • Rita Santos
  • Ana Félix
  • Davide Carvalho
  • José Manuel Lopes
  • Rita Domingues
  • Marta Sirgado
  • Nádia Rei
  • Fernando Fonseca
  • Jorge Rosa Santos
  • Luís Sobrinho
  • Valeriano Leite
Article

DOI: 10.1007/s12022-011-9151-1

Cite this article as:
Cavaco, B.M., Santos, R., Félix, A. et al. Endocr Pathol (2011) 22: 44. doi:10.1007/s12022-011-9151-1

Abstract

The diagnosis of parathyroid carcinomas is often difficult. HRPT2 mutations have been identified in familial [hyperparathyroidism-jaw tumor (HPT–JT) syndrome] and sporadic parathyroid carcinomas, supporting that HRPT2 mutations may confer a malignant potential to parathyroid tumors. In this study, we report the clinical, histopathological, and genetic investigation of two unrelated cases, whom had apparently sporadic malignant parathyroid tumors, initially diagnosed as adenomas. In one case, the differential diagnosis was complicated by cervical seeding of parathyroid tumor cells. Genetic studies identified de novo HRPT2 germline mutations in cases 1 (c.518_521delTGTC [p.Ser174LysfsX27]) and 2 (c.226 C > T [p.Arg76X]), unveiling the hereditary HPT-JT syndrome in both patients. Furthermore, the identification of somatic mutations in the patients‟ parathyroid tumors provided evidence for complete inactivation of the HRPT2 gene, which was consistent with the tumor malignant features. The sensitivity of parafibromin immunostaining to detect HRPT2 mutations was limited. The present data suggests that patients with apparently sporadic parathyroid carcinomas, or parathyroid tumors with atypical histological features, should undergo molecular genetic testing, as it may detect germline HRPT2 mutations. Establishing the diagnosis of hereditary HPT-JT syndrome is relevant for clinical counseling and management of the carriers and their relatives.

Keywords

Parathyroid carcinoma Tumor seeding Hyperparathyroidism-jaw tumor syndrome (HPT-JT) HRPT2 gene Parafibromin De novo mutation 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Branca Maria Cavaco
    • 1
    • 5
  • Rita Santos
    • 2
  • Ana Félix
    • 3
    • 5
  • Davide Carvalho
    • 6
    • 8
  • José Manuel Lopes
    • 7
    • 8
    • 9
  • Rita Domingues
    • 1
    • 5
  • Marta Sirgado
    • 3
  • Nádia Rei
    • 1
  • Fernando Fonseca
    • 10
  • Jorge Rosa Santos
    • 4
  • Luís Sobrinho
    • 1
    • 2
  • Valeriano Leite
    • 1
    • 2
    • 5
  1. 1.Centro de Investigação de Patobiologia Molecular (CIPM)Instituto Português de Oncologia de Lisboa Francisco GentilLisboaPortugal
  2. 2.Serviço de EndocrinologiaInstituto Português de Oncologia de Lisboa Francisco GentilLisboaPortugal
  3. 3.Serviço de Anatomia PatológicaInstituto Português de Oncologia de Lisboa Francisco GentilLisboaPortugal
  4. 4.Serviço de Cirurgia de Cabeça e PescoçoInstituto Português de Oncologia de Lisboa Francisco GentilLisboaPortugal
  5. 5.Centro de Estudos de Doenças Crónicas (CEDOC), Faculdade de Ciências Médicas (FCM)Universidade Nova de LisboaLisboaPortugal
  6. 6.Serviço de Endocrinologia, Diabetes e MetabolismoHospital de São JoãoPortoPortugal
  7. 7.Serviço de Anatomia PatológicaHospital de São JoãoPortoPortugal
  8. 8.Faculdade de MedicinaUniversidade do PortoPortoPortugal
  9. 9.Instituto de Patologia e ImunologiaUniversidade do PortoPortoPortugal
  10. 10.Serviço de EndocrinologiaHospital Curry CabralLisboaPortugal