SAT332 Genetic Characterization Of A Case of Pheochromocytoma In A Pulmonary Transplant Patient
Authors: Perreault Florence , Parisien-Lasalle Stéfanie , Morisset Julie , Poirier Charles , Beauregard Catherine , Agnès Räkel , Ferraro Pasquale , Bourdeau Isabelle 
Published: October 2023

Disclosure: F. Perreault: None. S. Parisien-Lasalle: None. J. Morisset: None. C. Poirier: None. C. Beauregard: None. R. Agnès: None. P. Ferraro: None. I. Bourdeau: None.

Background: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) (PPGLs) are rare tumors arising from the chromaffin cells. Approximately 40% of PPGL patients carry germline mutations in susceptibility genes, including pseudohypoxic related SDHx and VHL genes. An association was described between hypoxemia and PPGLs, notably in higher altitude exposition and cyanotic congenital heart disease. In the latter, a chronic hypoxemic state can lead to gain of function somatic mutations in the EPAS1 gene that encodes for hypoxia-inducible factor 2-alpha (HIF-2) (1). Objective: To describe a rare case of PHEO in a pulmonary transplant patient and characterize the genetic background of the tumor. Clinical Case: A 66 year-old man underwent an unilateral lung transplant at the age of 47 for chronic obstructive pulmonary disease associated with alpha-1 antitrypsin deficiency. He required home oxygen therapy for 3 years prior to transplant and was known for new onset diabetes after transplant, chronic kidney disease, hypertension and paroxysmal atrial tachycardia. His family history was non-contributing. Nineteen years after transplant, a thoracic CT-scan showed a 6.1 cm x 3.9 cm right adrenal mass (HU of 7). Retrospectively, the mass had been present for the last seven years, and increased progressively in size. Diagnosis of PHEO was confirmed by the 24-h urinary catecholamines (norepinephrine 713 nmol/d (N&lt; 650), epinephrine 588 nmol/d (N &lt; 145), normetanephrines 900 nmol/d (N &lt; 600) and metanephrines 1191 nmol/d (N &lt; 370)). Chromogranin A was elevated (3297 ng/mL (N &lt; 104)). The adrenal mass showed no uptake at 18F-FDG PET/CT imaging but fixation at MIBG scintigraphy. The patient received alpha blockers and underwent a laparoscopic right adrenalectomy. The pathology report confirmed a PHEO with a PASS score of 8 to 10. Eighteen months following the surgery, the patient showed no signs of biochemical or radiological recurrence. Genetic studies: 1) Germline PPGL multigene panel: After consent, the patient underwent a panel of 14 susceptibility genes for PPGLs (INVITAE, CA, USA) that revealed no pathogenic variants. 2) Somatic genetic analysis for EPAS1 gene: PHEO DNA was extracted and exons 9, 12 and 16 of the EPAS1 gene were studied by Sanger Sequencing. No pathogenic variants were identified.Conclusion: We report a rare case of PHEO in a pulmonary transplant patient. Our genetic analyses demonstrated the absence of a pathogenic germline variant in known susceptibility PPGL genes and no somatic mutations in the EPAS1 gene. Further work is needed to better understand the genetic and molecular events leading to PHEO in this specific case and determine its possible relationship with hypoxemia.

(1) Vaidya A, Flores SK, Cheng Z-M, Nicolas M, Deng Y, Opotowsky AR, et al. EPAS1 Mutations and Paragangliomas in Cyanotic Congenital Heart Disease. New England Journal of Medicine. 2018;378(13):1259-61.

Presentation: Saturday, June 17, 2023