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Journal of Oncology
Volume 2012 (2012), Article ID 872713, 10 pages
http://dx.doi.org/10.1155/2012/872713
Review Article

Updated and New Perspectives on Diagnosis, Prognosis, and Therapy of Malignant Pheochromocytoma/Paraganglioma

1Endocrinology Unit, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50134 Florence, Italy
2Department of Clinical Pathophysiology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy
3Istituto Toscano Tumori, Via Taddeo Alderotti 26N, 50139 Florence, Italy

Received 30 April 2012; Accepted 5 June 2012

Academic Editor: Marialuisa Appetecchia

Copyright © 2012 Gabriele Parenti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Malignant pheochromocytomas/paragangliomas are rare tumors with a poor prognosis. Malignancy is diagnosed by the development of metastases as evidenced by recurrences in sites normally devoid of chromaffin tissue. Histopathological, biochemical, molecular and genetic markers offer only information on potential risk of metastatic spread. Large size, extraadrenal location, dopamine secretion, SDHB mutations, a PASS score higher than 6, a high Ki-67 index are indexes for potential malignancy. Metastases can be present at first diagnosis or occur years after primary surgery. Measurement of plasma and/or urinary metanephrine, normetanephrine and metoxytyramine are recommended for biochemical diagnosis. Anatomical and functional imaging using different radionuclides are necessary for localization of tumor and metastases. Metastatic pheochromocytomas/paragangliomas is incurable. When possible, surgical debulking of primary tumor is recommended as well as surgical or radiosurgical removal of metastases. I-131-MIBG radiotherapy is the treatment of choice although results are limited. Chemotherapy is reserved to more advanced disease stages. Recent genetic studies have highlighted the main pathways involved in pheochromocytomas/paragangliomas pathogenesis thus suggesting the use of targeted therapy which, nevertheless, has still to be validated. Large cooperative studies on tissue specimens and clinical trials in large cohorts of patients are necessary to achieve better therapeutic tools and improve patient prognosis.