A registry-based study of thyroid paraganglioma: Histological and genetic characteristics

Ernst Von Dobschuetz, Helena Leijon, Camilla Schalin-Jäntti, Francesca Schiavi, Michael Brauckhoff, Mariola Peczkowska, Giovanna Spiazzi, Serena Demattè, Maria Enrica Cecchini, Paola Sartorato, Jolanta Krajewska, Kornelia Hasse-Lazar, Katarzyna Roszkowska-Purska, Elisa Taschin, Angelica Malinoc, Lars A. Akslen, Johanna Arola, Dariusz Lange, Ambrogio Fassina, Gianmaria PennelliMattia Barbareschi, Jutta Luettges, Aleksander Prejbisz, Andrzej Januszewicz, Tim Strate, Birke Bausch, Frederic Castinetti, Barbara Jarzab, Giuseppe Opocher, Charis Eng, Hartmut P H Neumann

Research output: Contribution to journalArticle

Abstract

The precise diagnosis of thyroid neoplasias will guide surgical management. Primary thyroid paraganglioma has been rarely reported. Data on prevalence, immunohistochemistry (IHC), and molecular genetics in a systematic series of such patients are pending. We performed a multinational population-based study on thyroid paraganglioma and analyzed prevalence, IHC, and molecular genetics. Patients with thyroid paraganglioma were recruited from the European-American-Head-and-Neck-Paraganglioma-Registry. Demographic and clinical data were registered. Histopathology and IHC were re-investigated. All patients with thyroid paraganglioma underwent molecular genetic analyses of the SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, RET, TMEM127, and MAX genes. Analyses included Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) for detection of large rearrangements. Of 947 registrants, eight candidates were initially identified. After immunohistochemical analyses of these eight subjects, 5 (0.5%) were confirmed to have thyroid paraganglioma. IHC was positive for chromogranin, synaptophysin, and S-100 and negative for calcitonin in all five thyroid paragangliomas, whereas the three excluded candidate tumors stained positive for pan-cytokeratin, a marker excluding endocrine tumors. Germline variants, probably representing mutations, were found in four of the five confirmed thyroid paraganglioma cases, two each in SDHA and SDHB, whereas the excluded cases had no mutations in the tested genes. Thyroid paraganglioma is a finite entity, which must be differentiated from medullary thyroid carcinoma, because medical, surgical, and genetic management for each is different. Notably, approximately 80% of thyroid paragangliomas are associated with germline variants, with implications for additional tumors and a potential risk for the family. As opposed to sporadic tumors, surgical management and extent of resection are different for heritable tumors, each guided by the precise gene involved.

Original languageEnglish
Pages (from-to)191-204
Number of pages14
JournalEndocrine-Related Cancer
Volume22
Issue number2
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • Molecular genetics
  • Neuroendocrinology
  • Thyroid

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

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    Von Dobschuetz, E., Leijon, H., Schalin-Jäntti, C., Schiavi, F., Brauckhoff, M., Peczkowska, M., Spiazzi, G., Demattè, S., Cecchini, M. E., Sartorato, P., Krajewska, J., Hasse-Lazar, K., Roszkowska-Purska, K., Taschin, E., Malinoc, A., Akslen, L. A., Arola, J., Lange, D., Fassina, A., ... Neumann, H. P. H. (2015). A registry-based study of thyroid paraganglioma: Histological and genetic characteristics. Endocrine-Related Cancer, 22(2), 191-204. https://doi.org/10.1530/ERC-14-0558