Journal Article

Personalized Management of Pheochromocytoma and Paraganglioma

Kroiss, Matthias, Grossman, Ashley, Beuschlein, Felix, Eisenhofer, Graeme, Bechmann, Nicole, Nölting, Svenja, Taieb, David, Pacak, Karel, Fassnacht, Martin

2022

Overview

Abstract Pheochromocytomas/paragangliomas are characterized by a unique molecular landscape that allows their assignment to clusters based on underlying genetic alterations. With around 30% to 35% of Caucasian patients (a lower percentage in the Chinese population) showing germline mutations in susceptibility genes, pheochromocytomas/paragangliomas have the highest rate of heritability among all tumors. A further 35% to 40% of Caucasian patients (a higher percentage in the Chinese population) are affected by somatic driver mutations. Thus, around 70% of all patients with pheochromocytoma/paraganglioma can be assigned to 1 of 3 main molecular clusters with different phenotypes and clinical behavior. Krebs cycle/VHL/EPAS1-related cluster 1 tumors tend to a noradrenergic biochemical phenotype and require very close follow-up due to the risk of metastasis and recurrence. In contrast, kinase signaling–related cluster 2 tumors are characterized by an adrenergic phenotype and episodic symptoms, with generally a less aggressive course. The clinical correlates of patients with Wnt signaling–related cluster 3 tumors are currently poorly described, but aggressive behavior seems likely. In this review, we explore and explain why cluster-specific (personalized) management of pheochromocytoma/paraganglioma is essential to ascertain clinical behavior and prognosis, guide individual diagnostic procedures (biochemical interpretation, choice of the most sensitive imaging modalities), and provide personalized management and follow-up. Although cluster-specific therapy of inoperable/metastatic disease has not yet entered routine clinical practice, we suggest that informed personalized genetic-driven treatment should be implemented as a logical next step. This review amalgamates published guidelines and expert views within each cluster for a coherent individualized patient management plan. Graphical Abstract Graphical Abstract

• Publisher: Oxford University Press
• Subject: Adrenal Gland Neoplasms - diagnosis / Adrenal Gland Neoplasms - genetics / Adrenal Gland Neoplasms - therapy / Customization / Development and progression / Disease susceptibility / Droperidol / Gene mutations / Germ-Line Mutation / Heritability / Humans / Kinases / Krebs cycle / Metastases / Metastasis / Molecular clusters / Mutation / Neuroendocrine tumors / Paraganglioma / Paraganglioma - diagnosis / Paraganglioma - genetics / Paraganglioma - therapy / Patients / Phenotypes / Pheochromocytoma / Pheochromocytoma - diagnosis / Pheochromocytoma - genetics / Pheochromocytoma - therapy / Review / Sibutramine / Signs and symptoms / Tricarboxylic acid cycle / Tumors / White people / Wnt protein