Recent Advances in Pheochromocytoma and Paraganglioma: Molecular Pathogenesis, Clinical Impacts, and Therapeutic Perspective volume II

PPGLs are relatively rare neuroendocrine tumors derived from chromaffin cells in the adrenal medulla and/or autonomic nervous system ganglia. Their clinical importance, including various associated complications, is due to catecholamine excess (1,2). Moreover, PPGLs could lead to pheochromocytoma multisystem crisis (PMC), which is a life-threatening endocrine emergency with reported mortality as high as 85-90% (3). Thus, updated knowledge of management of PPGLs, especially based on the molecular mechanisms and genetics, is necessary. Meanwhile, according to the WHO's classification in 2017, all pheochromocytomas could have metastatic potential and no histological system to assess the biological aggressiveness. Hence, "Malignant pheochromocytoma" in the 2004 WHO classification was replaced with "Metastatic pheochromocytoma" in the 2017 WHO classification (4). Considering the above, an updated understanding of clinicopathological advances and the management of PPGLs, mainly based on molecular mechanisms and genetics, is necessary (2,(4)(5)(6)(7).In this Research Topic, Saavedra et al. reviewed the clinical presentation, management, and treatment of patients with PPGLs. In this review article, early diagnosis, combined with an understanding of the genetic landscapes and comprehensive treatment strategies, was described as necessary to improve outcomes for patients with PPGLs. Nevertheless, surgery is the mainstay of treatment for patients with PPGLs. The utilization of Da Vinci robot-assisted laparoscopic surgery contributed to a favorable prognosis for a patient. In addition, Yang et al. reported a case of paraganglioma with a newly detected EPAS1 mutation, which may be the primary driver of the disease. Some therapeutic options in patients who could not receive surgery and/or have metastatic PPGLs have been reported in this collection. For example, Cyclophosphamide-Vincristine-Dacarbazine (CVD) chemotherapy is a conventional therapeutic option and was reported to be the first-line treatment for PPGLs with SDHB-mutation previously ( 8 Besides, Małgorzata et al. investigated a patient with pheochromocytoma, whose ACTH and cortisol values were elevated. Previously, ACTH-producing pheochromocytomas were reported (9,10). However, the patient described by Malgorzata et al. was negative for ACTH (and CRH).Hence, they described that catecholamine excess could activate the hypothalamic-pituitaryadrenal (HPA) axis. Considering the various complications of PPGLs, the phenotype of this case should be taken into consideration.In conclusion, the information presented in this Research Topic provides updated perspectives of the molecular mechanisms and genetics of PPGLs and their unveiled clinicopathological implications. These enrich the perspectives of PPGLs, which could lead to improved clinical outcomes for patients with PPGLs.