Risk Stratification on Pheochromocytoma and Paraganglioma from Laboratory and Clinical Medicine
Department of Clinical Research Pathology Division, Department of Diagnostic Pathology, National Hospital Organization Hakodate Hospital, Hakodate 041-8512, Hokkaido, Japan
Division of Sports Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan
Department of Endocrinology, Metabolism and Hypertension, National Hospital Organization, Kyoto Medical Center, Kyoto 612-8555, Japan
Author to whom correspondence should be addressed.
J. Clin. Med. 2018, 7(9), 242; https://doi.org/10.3390/jcm7090242
Received: 25 July 2018 / Revised: 21 August 2018 / Accepted: 23 August 2018 / Published: 27 August 2018
(This article belongs to the Special Issue Pheochromocytoma and Paraganglioma: Research Update)
Pheochromocytoma (PCC) and sympathetic paraganglioma (PGL) are rare neuroendocrine tumors characterized by catecholamine production in the adrenal medulla and extra-adrenal paraganglia. PCC and PGL (PPGL) with metastasis was termed malignant PPGL. However, the distinction between “benign” and “malignant” PPGLs has been debated. Currently, all PPGLs are believed to have some metastatic potential and are assigned malignant tumors (ICD-O/3) by the WHO Classification of Endocrine Organs (2017, 4th edition). Therefore, the previous categories benign and malignant PPGL have been eliminated in favor of risk stratification approach. The Grading of Adrenal Pheochromocytoma and Paraganglioma (GAPP) is a tool for risk stratification for predicting metastasis and the prognosis of patients. At least 30% of PPGLs are hereditary, with 20 genes identified and genotype-phenotype correlations clarified. Of these genes, VHL, RET and NF1 have been well investigated and are the primary cause of bilateral PCC. In addition, mutation of succinate dehydrogenase gene subunits SDHB and SDHD are strongly correlated with extra-adrenal location, younger age, multiple tumors, metastasis and poor prognosis. Disease stratification by catecholamine phenotype and molecular profiling correlates with histological grading by GAPP. PPGLs should be understood comprehensively based on clinical, biochemical, molecular and pathological data for patient care. A flow chart for pathological diagnosis is included.