Clinical care of pheochromocytoma/paraganglioma (PPGL) has greatly improved over the last decades due to tremendous advances in biochemistry, imaging, genetics and therapeutics. From the historical perspective the names of Manger, Gifford, Crout and Sjoerdsma deserve recognition for their seminal work on PPGLs. Prior to 1964 two thirds of all cases were discovered at autopsy. While most patients now are diagnosed while living, some still die with an undiscovered PPGL despite the availability of highly effective diagnostic and therapeutic modalities. Lack of awareness, ignorance of clinical clues, and poor post-surgical follow-up are to blame for this.
In recent years improved analytical technologies, enabling a more detailed understanding of catecholamine metabolism, has resulted in a paradigm shift in laboratory testing from catecholamines to metanephrines. The precise diagnostic and theranostic role of promising new functional imaging agents beyond conventional MIBG need to be defined. Modern surgical and sophisticated anesthetic management of PPGLs has resulted in a near zero perioperative mortality but reliable post-surgical prediction of metastatic disease is currently still impossible despite the availability of several risk stratification scores.
Revolutionary advances in molecular biology and genetics have made it clear that PPGLs have the richest hereditary background of all tumors with more than one third due to a germline mutation. The evolving role of somatic mutations in apparent sporadic PPGLs for clinical practice will be established. Growing evidence shows that hereditary PPGLs are characterized by distinct clinical presentations with differences in biological behavior reflecting underlying mutations. Advanced integration of genomics and metabolomics will further contribute to improved personalized diagnostics, treatment and surveillance.
A major outstanding clinical problem continues to be the lack of effective curative treatment of metastatic PPGLs. A concerted multidisciplinary approach of basic and clinical research, using relevant in vitro en in vivo models for identification of therapeutic targets for development of new drugs to be evaluated in well-designed multicenter clinical trials, is crucial for improving the prognosis of these patients.