Head and Neck Paragangliomas—A Genetic Overview

Abstract

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Head and neck paragangliomas (HNPGL) can be categorized into carotid body tumors, which are the most common, as well as jugular, tympanic, and vagal paraganglioma. A review of the current literature was conducted to consolidate knowledge concerning PGL mutations, familial occurrence, and the practical application of this information. Available scientific databases were searched using the keywords head and neck paraganglioma and genetics, and 274 articles in PubMed and 1183 in ScienceDirect were found. From these articles, those concerning genetic changes in HNPGLs were selected. The aim of this review is to describe the known genetic changes and their practical applications. We found that the etiology of the tumors in question is based on genetic changes in the form of either germinal or somatic mutations. 40% of PCC and PGL have a predisposing germline mutation (including VHL, SDHB, SDHD, RET, NF1, THEM127, MAX, SDHC, SDHA, SDHAF2, HIF2A, HRAS, KIF1B, PHD2, and FH). Approximately 25–30% of cases are due to somatic mutations, such as RET, VHL, NF1, MAX, and HIF2A. The tumors were divided into three main clusters by the Cancer Genome Atlas (TCGA); namely, the pseudohypoxia group, the Wnt signaling group, and the kinase signaling group. The review also discusses genetic syndromes, epigenetic changes, and new testing technologies such as next-generation sequencing (NGS).

Paragangliomas da Cabeça e Pescoço: A Experiência de um Centro Oncológico do Sul da Europa

“…19 Genetic testing is now recommended in all patients presenting with phaeochromocytoma and paraganglioma. [10][11]19,[21][22][23] The increasingly lower costs of gene panel testing combined with the ineffectiveness of family history screening for predicting syndrome risk (due to overall low penetrance) has led to this recommendation. 19 Although it may help predicting tumor behavior and prognosis, the ultimate goal of genetic testing is to identify those patients who should be screened and to diagnose this condition at a presymptomatic stage.…”

“…9 As nearly all germline mutations that lead to hereditary HNPs are attributable to succinate dehydrogenase complex (SDHx) genes, these tumors are extremely rare in neurofibromatosis type 1, Von-Hippel Lindau disease and multiple endocrine neoplasia type 2. [10][11] The surgical management of these lesions is also associated with the possibility of cranial nerve palsies and risk of injury to vital vascular structures, especially in advanced cases, resulting in transient ischemic attacks or major cerebrovascular accidents, leading to permanent neurologic deficits. 2,12 These cardiovascular events may have longstanding cosmetic and/or functional implications.…”

Metformin Treatment Induces Different Response in Pheochromocytoma/Paraganglioma Tumour Cells and in Primary Fibroblasts

“…The first-choice treatment for localized disease is surgery. In contrast, for inoperable metastatic tumours, there is no definitive curative or standard medical therapy, and 40–80% of patients show an overall survival of five years from the diagnosis of the first metastasis [ 6 , 7 ].…”

A Case of Paraganglioma-Induced Adrenergic Shock

“…Paraganglioma (PGL) is a neuroendocrine tumor of chromaffin cells originating from the sympathetic and parasympathetic ganglia located in the nervous plexuses of the autonomic nervous system, from the base of the skull to the pelvis. It represents 15%-20% of chromaffin cell tumors, which are originated mostly in the medulla of the adrenal gland (pheochromocytoma) [ 1 ]. PGL and pheochromocytoma have an annual incidence of 3-8 per 1,000,000 individuals and represent 0.05%-0.1% of cases of resistant hypertension (HT) [ 2 ].…”