AUTHOR=Cortez Briana N. , Kuo Mickey J. M. , Jha Abhishek , Patel Mayank , Carrasquillo Jorge A. , Prodanov Tamara , Charles Kailah M. , Talvacchio Sara , Derkyi Alberta , Lin Frank I. , Taïeb David , Del Rivero Jaydira , Pacak Karel 

TITLE=Case Series: ATRX Variants in Four Patients with Metastatic Pheochromocytoma

JOURNAL=Frontiers in Endocrinology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1399847

DOI=10.3389/fendo.2024.1399847

ISSN=1664-2392

ABSTRACT=<p>Few reports have highlighted the rare presence of somatic <italic>ATRX</italic> variants in clinically aggressive, metastatic pheochromocytoma/paraganglioma (PCC/PGL); however, none have addressed detailed clinical presentation (including biochemistry and imaging) and management of these patients. Here, we address these clinical features and management based on four PCC patients with somatic <italic>ATRX</italic> variants from our National Institutes of Health PCC/PGL cohort. A total of 192 patients underwent exome sequencing (germline, somatic, or both), and four males were found to have somatic <italic>ATRX</italic> variants (with additional somatic <italic>VHL</italic> and <italic>FH</italic> oncogenic variants in patients 2 and 4, respectively). Per-lesion and per-patient comparisons were performed among functional imaging scans performed at the NIH. Biochemical phenotype and response to systemic treatment were evaluated. This mini-series supports prior studies showing aggressive/metastatic PCC in patients with somatic <italic>ATRX</italic> variants, as all developed widespread metastatic disease. All four PCC patients presented with noradrenergic biochemical phenotype, and some with significant elevation in 3-methoxytyramine. <sup>18</sup>F-FDOPA PET/CT was found to be the superior functional imaging modality, with 100% lesion detection rate when compared to that of <sup>68</sup>Ga-DOTATATE, <sup>18</sup>F-FDG, <sup>18</sup>F-FDA, and <sup>123</sup>I-MIBG scans. While patients did not respond to chemotherapy or tyrosine kinase inhibitors, they responded to targeted radiotherapy using high-specific-activity <sup>131</sup>I-MIBG (Azedra<sup>®</sup>) or <sup>177</sup>Lu-DOTATATE (Lutathera<sup>®</sup>).</p>