Head and neck paragangliomas: Genetic spectrum and clinical variability in 79 consecutive patients

Valentina Piccini, Elena Rapizzi, Alessandra Bacca, Giuseppe Di Trapani, Raffaele Pulli, Valentino Giachè, Benedetta Zampetti, Emanuela Lucci-Cordisco, Letizia Canu, Elisa Corsini, Antongiulio Faggiano, Luca Deiana, Davide Carrara, Valeria Tantardini, Stefano Mariotti, Maria Rosaria Ambrosio, Maria Chiara Zatelli, Gabriele Parenti, Annamaria Colao, Carlo PratesiGiampaolo Bernini, Tonino Ercolino, Massimo Mannelli

Research output: Contribution to journalArticlepeer-review


Head and neck paragangliomas (HNPGLs) are neural crest-derived tumors. In comparison with paragangliomas located in the abdomen and the chest, which are generally catecholamine secreting (sPGLs) and sympathetic in origin, HNPGLs are, in fact, parasympathetic in origin and are generally nonsecreting. Overall, 79 consecutive patients with HNPGL were examined for mutations in SDHA, SDHB, SDHC, SDHD, SDHAF2, VHL, MAX, and TMEM127 genes by PCR/sequencing. According to a detailed family history (FH) and clinical, laboratory (including metanephrines), and instrumental examinations, patients were divided into three groups: a) patients with a positive FH for HNPGL (index cases only), b) patients with a negative FH and multiple HNPGLs (synchronous or metachronous) or HNPGL associated with an sPGL, and c) patients with negative FH and single HNPGL. The ten patients in group a) proved to be SDHD mutation carriers. The 16 patients in group b) proved to be SDHD mutation carriers. Among the 53 patients in group c), ten presented with germ-line mutations (three SDHB, three SDHD, two VHL, and two SDHAF2). An sPGL was found at diagnosis or followed up in five patients (6.3%), all were SDHD mutation carriers. No SDHC, SDHA, MAX, and TMEM127 mutations were found. In SDHD mutation carriers, none of the patients affected by HNPGL associated with sPGL presented missense mutations. In conclusion, a positive FH or the presence of multiple HNPGLs is a strong predictor for germ-line mutations, which are also present in 18.8% of patients carefully classified as sporadic. The most frequently mutated gene so far is SDHD but others, including SDHB, SDHAF2, and VHL, may also be affected.

Original languageEnglish
Pages (from-to)149-155
Number of pages7
JournalEndocrine-Related Cancer
Issue number2
Publication statusPublished - Apr 2012

ASJC Scopus subject areas

  • Endocrinology
  • Oncology
  • Cancer Research
  • Endocrinology, Diabetes and Metabolism


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