P-057 BILATERAL PHEOCHROMOCYTOMA DIAGNOSED BY ADRENAL BIOPSY IN A PATIENT WITH AN ASSOCIATED GASTROINTESTINAL TUMOR (GIST)

Abstract Introduction Paragangliomas (PGL) are rare neuroendocrine tumors of paraganglia derived from neural crest cells. When they arise from the adrenal medulla, they are named pheochromocytomas (PCC). The diagnosis of PCC typically relies on the demonstration of increased metanephrines (in plasma or in a 24-hour urine sample) along with a concerning adrenal mass. Adrenal biopsies are generally contraindicated if a catecholamine secreting tumor is suspected, because it might trigger a hypertensive/cardiovascular crisis. PCC and PGL are often associated with pathogenic germline variants (up to 40%), particularly in individuals with multiple, multifocal, early onset cases or a family history of PPGL, and in the presence of other tumors. Clinical Case A 75-year-old woman with bilateral adrenal incidentaloma underwent a bilateral adrenal biopsy at an outside hospital. The biopsy was uneventful and the histological analysis was suspicious for bilateral PCCs. Subsequently, she was referred to endocrinology. She reported repeated episodes of symptomatic palpitations, very high blood pressure (systolic BP > 200 mmHg) and weight loss with occasionally orthostatic dizziness. She denied any suggestive family history of PCC or tumor related. A Ga68 DOTATOC PET-CT showed uptake in bilateral adrenal masses without any distant lesions. There was an exophytic lesion in the lesser curvature of the stomach with a biopsy consistent with a gastrointestinal stromal tumor (GIST). The adrenals were removed laparoscopically and confirmed the diagnosis of bilateral PCC. Immunohistochemistry showed low expression of SDHB, but cytoplasmic and granular. The GIST also showed a low, heterogenous SDHB expression with granular cytoplasmic staining with somatic KIT/ PDGFRA mutation, a well-known alteration in sporadic tumors. Genetic germline analysis of the tumor was negative for all the expanded pannel and somatic genetic testing was negative for EPAS/HIF, VHL. We only found a loss of function mutation at a mosaic level in DNMT3A, which was absent in the tumor tissue and it is therefore unlikely to be associated with its pathogenesis. Conclusion there is no role for adrenal biopsy which can potentially trigger a hypertensive crisis. Even though germline mutations are prevalent, some patients are negative for variants in the currently known genes associated with PCC/PGL. However, the spectrum of affected genes keeps expanding (locus heterogeneity). In selected patients, a search for epigenetic alterations, although technically more demanding, should be considered. In highly suspicious clinical scenario, for example with a familial or/and a syndromic presentation, such as in this patient with a concomitant GIST, family counseling remains particularly complex in the instance of negative genetic analyses. Direct relatives should be counseled about a potential risk of transmission of an unknown variant and screened for the presence of PCC/PGL and associated tumors.Figure 1:Proportion of origin of the underlying mutational mechanism in PGL/PCC Table 1:Plasma values before and after bilateral adrenalectomy and partial gastrectomy