SAT-LB313 A Unicorn With Double Horns - Metastatic Paraganglioma in a Patient With Beckwith-Wiedemann Syndrome and Hereditary Paraganglioma Syndrome Iv

• Published in: Journal of the Endocrine Society Vol. 4; no. Supplement_1
• Main Authors: Narayanan, Anand, Soe, Myat, Wheeler, Amber L, Fitzgerald, Paul A
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 08-05-2020
• Subjects: Tumor Biology
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/jendso/bvaa046.2066

Introduction: Beckwith-Wiedemann syndrome (BWS), a multisystem genomic imprinting disorder in chromosome 11p15.5 region, is an overgrowth syndrome often presenting with macroglossia, abdominal wall defects, hemihyperplasia, enlarged abdominal organs and an increased risk of tumors including neuroblastoma, rhabdomyosarcoma, unilateral Wilm’s tumor, hepatoblastoma, adrenal cortical carcinoma and pheochromocytoma. Six cases of benign bilateral pheochromocytomas and one case of pheochromocytoma with lymph node metastasis in BWS have been described in the literature. We describe the first case of BWS with distant metastatic paraganglioma harboring an SDHB (succinate dehydrogenase subunit B) mutation.
Presentation: A 28-year-old male with BWS whose history included an omphalocele and diaphragmatic hernia in infancy, neuroblastoma resected at age 2, and left carotid paraganglioma (PGL) resected at age 22 presented with abdominal pain. CT A/P with contrast revealed a 3.3 x 4.4 cm hypervascular mass and multiple bone metastases. Workup revealed normal plasma/urine metanephrines, elevated plasma dopamine of 178 pg/ml (normal <20) and elevated chromogranin A of 190 ng/ml (normal <90). 68Ga-dotatate PET CT showed hypermetabolic 4.4 cm mass (SUV 83), right hypopharynx mass (SUV 49), and many dota avid areas throughout the skeleton. The abdominal mass was resected and pathology was consistent with PGL. Due to unusual presentation, patient underwent hereditary cancer genetic testing (67 gene panel) and pathogenic mutation (c.713delT) in the SDHB gene was identified, consistent with hereditary PGL syndrome IV.
Conclusion: While pheochromocytomas and other tumors are commonly found in association with BWS, PGLs are not. This is the first documented case of a patient with BWS having distant metastatic PGL. Malignant transformation of hereditary and sporadic pheochromocytomas and paraganglioma (PPGLs) is more common in SDHx associated PPGLs (>40% of metastatic PPGLs are related to an SDHB mutation). Hereditary PGL syndromes should be suspected in the case of PGLs that are recurrent, early onset (<45 years), extra-adrenal and/or metastatic. With additional genetic testing, our patient with an already rare growth disorder was found to have hereditary PGL syndrome IV caused by a pathogenic mutation in the SDHB gene. This unique case highlights the rationale and importance of systematic genetic cancer screening in the diagnostic evaluation of PPGLs.