Review ArticlesPheochromocytomas and Paragangliomas An Update on Recent Molecular Genetic Advances and Criteria for MalignancyGuo, Zhenying MD*,†; Lloyd, Ricardo V. MD, PhD*Author Information *University of Wisconsin School of Medicine and Public Health, Madison, WI †Zhejiang Cancer Hospital, Hangzhou, China The authors have no funding or conflicts of interest to disclose. Reprints: Ricardo V. Lloyd, MD, PhD, Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792 (e-mail: [email protected]). Advances In Anatomic Pathology: September 2015 - Volume 22 - Issue 5 - p 283-293 doi: 10.1097/PAP.0000000000000086 Buy Metrics Abstract Pheochromocytomas are uncommon neuroendocrine tumors arising in the adrenal medulla, whereas paragangliomas arise from chromaffin cells in sympathetic and parasympathetic locations outside of the adrenal gland. Molecular genetic studies in the past few years have identified >10 genes involved in the pathogenesis of pheochromocytomas and paragangliomas, including RET oncogene, involved in the pathogenesis of multiple endocrine neoplasia (MEN) 2A and 2B, von Hippel-Lindau tumor-suppressor gene, neurofibromatosis type 1 gene, succinate dehydrogenase, THEM127, and several others. The presence of genetic alterations in some of these genes such as in MEN 2A and 2B can be used to diagnose these disorders clinically, and other mutations such as succinate dehydrogenase can be used in the pathologic prediction of benign and malignant pheochromocytomas and paragangliomas. Although it has been difficult to separate benign and malignant pheochromocytomas and paragangliomas, recent studies that may predict the behavior of these chromaffin-derived neoplasms have been reported. The Pheochromocytoma of the Adrenal Scale Score and the Grading system for Adrenal Pheochromocytoma and Paraganglioma scoring system are also discussed. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.