SAT329 Case Series Of Patients With FGFR-1 Related Pheochromocytoma With A Focus On Biochemical And Imaging Signatures

Abstract

Abstract Disclosure: S. Jhawar: None. J. Del Rivero: None. K. Pacak: None. Introduction: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal gland and neural crest, respectively. 40% of cases are associated with germline mutations and 30-40% somatic driver mutations. Here, we present two patients with PCC who were found to have somatic FGFR1 mutation. FGFR signaling is involved in regulation of tissue repair, angiogenesis, and inflammation. Patient 1: A 70-year-old female with a history of resistant hypertension, episodic palpitations and sweating presented with diffuse abdominal pain and chest tightness. She was noted to have a blood pressure of 220/160 mm Hg. CT scan showed a 4.2 x 3.9 cm left adrenal mass, suspicious for malignancy and a <1 cm retroperitoneal mass. Blood work revealed elevated plasma normetanephrine (NM) 3543 pg/mL (normal 0- 145) and metanephrine (MN) 871 pg/mL (normal 0-62). 18F-FDG PET/CT showed a left adrenal mass without abnormal FDG activity. 68Ga-DOTATATE PET/CT was compatible with left PCC (SUVmax 28). 18F-DOPA PET/CT showed left PCC and a small retroperitoneal PGL. Two weeks after initiating phenoxybenzamine, she underwent total left adrenalectomy. Pathology was consistent with PCC. Molecular testing revealed FGFR1 pathogenic somatic mutation (c.1638C>G p.Asn546Lys). Patient 2: A 73-year-old male with known left renal cell carcinoma presented to our institution for management of recurrent right PCC. He was found to have a 3.8 cm right adrenal incidentaloma eight years ago and elevated plasma NM 6.3 nmol/L (normal <0.9), MN 1.5 nmol/L (normal <0.5). He underwent total right adrenalectomy, and the diagnosis of PCC was confirmed on histopathology. Two years later, he developed a 5.1 x 4.7 cm nodular mass in the right adrenal fossa and a <1 cm liver lesion on CT scan. The adrenal lesion showed intense avidity on 68Ga-DOTATATE PET/CT and 18F-DOPA PET/CT and mild avidity on 18FDG-PET/CT. 18F-DOPA PET/CT also showed avidity towards the liver lesion. He was started on doxazosin and underwent laparoscopic right adrenalectomy. Pathology demonstrated PCC. Whole exome sequencing of the tumor showed pathogenic FGFR1 mutation (c.1638C>G, p.Asn546Lys). Discussion: Activating FGFR1 mutations are associated with sporadic PCC. The biochemical phenotype of our patients showed higher levels of NM than MN. The imaging profile revealed that 18F-DOPA PET/CT was more sensitive than 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT as it showed avidity towards other extra-adrenal lesions. Further studies in larger cohorts are needed to enhance understanding of pathogenesis, biochemical and imaging phenotype, which will help tailor the treatment and potential development of novel targeted therapies. Presentation: Saturday, June 17, 2023