Mediastinal paragangliomas: Association with mutations in the succinate dehydrogenase genes and aggressive behavior

Department of Internal Medicine, University of Texas, Dallas, Texas 75390-8857, USA.
Endocrine Related Cancer (Impact Factor: 4.81). 03/2009; 16(1):291-9. DOI: 10.1677/ERC-08-0214
Source: PubMed


Extra-adrenal pheochromocytomas, otherwise known as paragangliomas (PGLs), account for about 20% of catecholamine-producing tumors. Catecholamine excess and mutations in the genes encoding succinate dehydrogenase subunits (SDHx) are frequently found in patients with PGLs. Only 2% of PGLs are found in the mediastinum, and little is known about genetic alterations in patients with mediastinal PGLs, catecholamine production by these tumors, or their clinical behavior. We hypothesized that most mediastinal PGLs are associated with germ line SDHx mutations, norepinephrine and/or dopamine excess, and aggressive behavior. The objective of this study was to characterize genetic, biochemical, and clinical data in a series of ten patients with mediastinal PGLs. All ten primary mediastinal PGL patients had germ line SDHx mutations, six in SDHB, and four in SDHD genes. Chest or back pain were the most common presenting symptoms (five patients), and catecholamines and/or their metabolites were elevated in seven patients. Additional tumors included head and neck PGLs in four patients, pheochromocytoma in one patient, and bladder PGL in another. Metastatic disease was documented in six patients (60%), and a concurrent abdominal mass was found in one patient. We conclude that mediastinal PGLs are strongly associated with SDHB and SDHD gene mutations, noradrenergic phenotype, and aggressive behavior. The present data suggest that all patients with mediastinal PGLs should be screened for SDHx gene mutations, regardless of age.

Full-text preview

Available from:
  • Source
    • "PGLs may occur sporadically or as part of a hereditary syndrome. 60 % can develop metastatic disease, indicating that these tumors are often aggressive and need follow up (Ghayee et al. 2009). Only 2 % of PGLs are found in the mediastinum and are associated with germ line mutations in either SDHB or SDHD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Head and neck paragangliomas are rare tumours and can arise as a part of inherited syndromes. Their association with thymic tumour is not well known. Case description: This report describes a female patient who presented with right sided neck paragangliomas. The histology of the tumour was consistent with paraganlioma. Few years later her MRI scan of the chest revealed presence of an anterior mediastinal mass that corresponded to the location of the thymus. Review of her previous scans showed that the mass was present all along and had gradually increased in size. Patient developed symptoms including fatigue, dyspnoea, migratory polyarthritis, Raynaud's phenomenon and erythema nodosum. She had sternotomy and excision of mediastinal mass. The histology was consistent with cortical thymoma (WHO type B2) and she had radiotherapy. After treatment her constitutional symptoms improved. Her paraganglioma susceptibility genes are negative. Discussion and evaluation: To our knowledge this is only the second case report in the literature of coexistence of carotid body tumour and thymoma. The first case reported was bilateral carotid body tumour, thyroid gland adenoma and thymoma. This case also highlights the importance of long term surveillance, multidisciplinary management and being aware of associated pathologies in patients with isolated paraganglioma.
    Full-text · Article · Dec 2015 · SpringerPlus

  • No preview · Article · Oct 1957 · A.M.A. archives of ophthalmology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent Alcator C-Mod experimental campaigns have focused upon the study of the Advanced Tokamak regimes, which includes characterization of the RF heating, the formation and dynamics of internal barriers, H-mode edge pedestal, and divertor and scrape-off physics. The ICRF system has been recently upgraded with the improved performance of the 4-strap antenna. Total ICRF power in excess of 5 MW has been launched successfully into the plasma during this campaign. Due to the compact nature of C-Mod, the power feeds for the antenna are vacuum strip lines. Their orientation, to the tokamak B-field, is governed by maintaining E<15 kV/cm in locations where the RF E-field is parallel to tokamak B-field. Other modifications included improved protection tile grounding and installation of protective shields for Faraday screen ceramic isolators. The antennas also make use of BN protection tiles to eliminate high Z impurities from the antennas. The present empirical power limit results from arcing in a region of the antenna strap where E∼15 kV/cm and parallel to B and injections from the metallic fasteners used to attach the BN tiles to the antenna.
    No preview · Conference Paper · Feb 2002
Show more