Pheochromocytomas and paragangliomas

Abstract

Purpose of review Great progress has been made in understanding the genetic and molecular basis of pheochromocytoma and paragangliomas (PPGLs). This review highlights the new standards in the diagnosis and management of pediatric PPGLs. Recent findings The vast majority of pediatric PPGLs have an associated germline mutation, making genetic studies imperative in the work up of these tumors. Somatostatin receptor-based imaging modalities such as 68Ga-DOTATATE and 64Cu-DOTATATE are shown to have the greatest sensitivity in pediatric PPGLs. Peptide receptor radionuclide therapies (PRRTs) such as 177Lu-DOTATATE are shown to have efficacy for treating PPGLs. Summary Genetics play an important role in pediatric PPGLs. Advances in somatostatin receptor-based technology have led to use of 68Ga-DOTATATE and 64Cu-DOTATATE as preferred imaging modalities. While surgery remains the mainstay for management of PPGLs, PRRT is emerging as a treatment option for PPGLs

Metastatic sporadic paraganglioma with EWSR1::CREM gene fusion: A unique molecular profile that expands the phenotypic diversity of the molecular landscape of the EWSR1::CREM gene fusion positive tumors

“…The mutations are classified into three different clusters based on the mutations in genes regulating pseudohypoxia pathway, WNT and kinase signaling pathway. Most pediatric paraganglioma harbor mutations in the genes regulating pseudohypoxia pathway such as SDHB , SDHD , and VHL 34 . In the case of our patient, no mutations in the known pathways were identified.…”

“…Most pediatric paraganglioma harbor mutations in the genes regulating pseudohypoxia pathway such as SDHB , SDHD , and VHL . 34 In the case of our patient, no mutations in the known pathways were identified. It is also interesting to note that most of the studies into the genetics of paragangliomas have identified mutations but very few translocations have been reported.…”

Complex roles of nicotinamide N-methyltransferase in cancer progression

“…Pheochromocytoma and paragangliomas (PCPGs) are rare and unique tumors originating from the neural crest-derived chromaffin cells in the adrenal medulla or paraganglia [ 113 ]. Chromaffin cell tumors within the adrenal glands are termed pheochromocytomas while tumors arising from extra-adrenal chromaffin cells are defined as paragangliomas [ 114 ]. The most distinct feature of PCPGs is they often produce and secrete catecholamines including adrenaline, noradrenaline, and dopamine, among which the synthesis of adrenaline is catalyzed by phenylethanolamine N -methyltransferase (PNMT) and needs SAM as a co-substrate [ 115 ].…”

“…The most distinct feature of PCPGs is they often produce and secrete catecholamines including adrenaline, noradrenaline, and dopamine, among which the synthesis of adrenaline is catalyzed by phenylethanolamine N -methyltransferase (PNMT) and needs SAM as a co-substrate [ 115 ]. Intriguingly, the transcriptional profiling of tumors showed that PCPGs can be divided into two clusters: a “pseudohypoxic” cluster that includes tumors with von Hippel–Lindau tumor suppressor (VHL) and succinate dehydrogenase (SDHx) mutations and an “activated tyrosine kinase” cluster, mainly associated with aberrations in ret proto-oncogene(RET) and neurofibromatosis type-1 (NF1) [ 114 ]. PCPGs manifest a strong hypoxic-like signaling, abnormal mitochondrial morphology as well as DNA hypermethylation, which is increasingly recognized in SDHx-mutated PCPG [ 116 ].…”

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

“…The symptoms experienced by PPGL patients include, but are not limited to, secretion of excess catecholamines, which can manifest as various cardiovascular-related indications such as hypertension via increased total peripheral resistance, heart attack without previous history, shock (non-cardiogenic pulmonary), arrhythmias, and oedemas (2). Also, pseudo-bowel obstructions, diabetic ketoacidosis, and multisystem crises involving lactic acidosis have been associated with PPGL patients (3). Since PPGLs are rare and symptoms are non-specific, they have potential for underdiagnosis.…”