S-13-6: RECENT ADVANCES IN THE MANAGEMENT OF PHEOCHROMOCYTOMA AND PARAGANGLIOMA

Abstract

Pheochromocytomas and paragangliomas (PPGL) are rare tumors that cause refractory hypertension and hypertensive crisis. Although metastatic disease accounts for 30% of PPGL, diagnosis of malignant is difficult without the presence of metastatic lesions. We review here several advancements in diagnosis and treatment of PPGL. A nationwide epidemiological survey in Japan revealed that the annual number of patients with PPGL was 3,000, higher than what was reported in previously. While plasma and urine fractionated metanephrines are recommended to be used as specific biochemical testing for diagnosis, creatinine-corrected fractionated metanephrines in spot urine samples which had been widely used in Japan as a convenient screening test was shown to be as useful as 24-hour urine fractionated metanephrines. Regarding imaging studies, a more specific functional imaging for PPGL, 68Ga DOTATATE, was newly developed. 68Ga DOTATATE provides a clear image with high sensitivity and specificity. Currently, PASS or GAPP histological scores and SDHB immunostaining are clinically used to attempt to discriminate benign from malignant tumor. However, since this distinguishing process remains difficult, all cases were classified as malignant with the possibility of metastasis in the WHO classification of endocrine tumor updated in 2017. Approximately 60% of PPGL have germline mutations of PPGL-related genes. Currently the genes are classified into 2 clusters based on their mechanism for etiology of tumorigenesis. Based on the possible mechanisms of tumor development associated with gene mutation, several molecular target drugs are under evaluation to explore more promising treatments for malignant PPGL.