Pheochromocytoma and Paraganglioma

**13**

**Chapter 2**

**Abstract**

Pheochromocytomas and

*Diana Loreta Paun and Alexandra Mirica*

Genotype-Phenotype Correlations

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, with genetic background in about 40% of cases, involving more than 30 susceptibility genes. The susceptibility genes can be divided into three main molecular clusters: pseudohypoxic, kinase signaling, and Wnt signaling. Biochemical characterization of these particular tumors should be integrated into the diagnostic algorithm because it can help apply personalized medicine principles and targeted therapy. These tumors can present with very different genotype-phenotype correlations, and their characterization can help the clinical practitioner make optimal clinical management decisions and prioritize genetic testing. This chapter summarizes the most important aspects of genetics and clinical characteristics, together with new

**Keywords:** pheochromocytomas, paragangliomas, genotype-phenotype correlations

Pheochromocytomas (Pheos) and paragangliomas (Pgls) are chromaffin cellderived tumors that can develop from the adrenal medulla or the extra-adrenal paraganglia. There are two types of Pgls: sympathetic and parasympathetic. Both Pheos and sympathetic Pgls are catecholamine-producing tumors. Frequently parasympathetic Pgls are located in the head and neck region, they do not have chromaffin cell phenotypic features, and they are in a vast majority of non-secreting tumors [1, 2]. Pheos are rare tumors, with an annual incidence of 2 to 9.1 per 1 million for

The prevalence of Pheos and Pgls in patients with hypertension is between 0.2

The early detection of Pheos/Pgls is mandatory because if they go undiagnosed and untreated, the cardiovascular morbidity and mortality rates are high. Furthermore, the risk of metastatic disease (the presence of metastases in nonchro-

In the last two decades and especially in the last seven years of medical researches, clinical medical studies showed that 40% of these tumors are associated with underlying germline or somatic mutations in about 30 susceptibility genes. Next-Generation Sequencing (NGS) technology has made the sequencing of the whole exome routinely available, and many clinical research papers reported

maffin tissue) is increased between 10 and 20% [5, 6].

specific genes associated with Pheos and Pgls [2].

Paragangliomas:

genotype-phenotype correlation data.

**1. Introduction**

adults patients [3].

and 0.6% [4].
