SUN-294 Urinary Bladder Paraganglioma With POT1 and RECQL4 Mutations Almost Missed by Ga-68 DOTATATE PET/CT

Abstract Disclosure: V. Vadini: None. A. Matoso: None. N. Singla: None. R.R. Banerjee: None. A.H. Hamrahian: None. S.M. Chen Cardenas: None. Background: Urinary bladder paragangliomas (UBPGL) are exceedingly rare, constituting <1% of all paragangliomas (PGL). Clinical presentation ranges from asymptomatic to hyperadrenergic symptoms in relation to voiding. Despite the high sensitivity of Ga68-DOTATATE PET/CT, bladder PGL may be missed due to the accumulation and excretion of the tracer in the urinary system. We present a case of a urinary bladder PGL which was clinically and biochemically suspected but initially missed on Ga68 imaging. We also identified two previously unreported variants of unknown significance in this context.Clinical Case: 65-year-old woman with history of multiple (>20) colonic polyps, Hodgkin lymphoma, follicular thyroid carcinoma presented with resistant hypertension for 8 years. Prior lab evaluation was notable for: PRA 0.15 ng/ml/h, aldosterone 10 ng/dl, and normokalemia. Aldosterone was 5 ng/dl, 2 hours after saline infusion. Normal 24-hour urinary metanephrines 156ug/day (36-209ug/day) and elevated normetanephrines 1,254 ug/24 hour (131-512ug/day). Abdominal CT did not reveal adrenal lesions; AVS did not lateralize. Spironolactone therapy improved blood pressure (BP) control; however, BP spikes continued along with headaches occasionally associated with voiding/bowel movements. Medications were amlodipine 10 mg/day, eplerenone 50 mg BID, nebivolol 5 mg/day, doxazosin 2 mg nightly. Repeat labs showed normal free metanephrines 48 pg/ml (≤57pg/ml), but elevated normetanephrine 531 pg/ml (≤148pg/ml). Ga68-DOTATATE PET/CT was obtained due to suspicion of PGL, tracer avid lesion was not identified. However, a pelvic MRI revealed a 2.5 cm well defined anterior bladder dome mass. Retrospective review of the Ga-68 DOTATE PET/CT revealed well-defined uptake in the region corresponding to the mass. She underwent partial cystectomy with complete resolution of symptoms, and improved BP control requiring 2 agents rather than the 4 preoperatively, plasma normetanephrines normalized. Tumor IHC was positive for synaptophysin, chromogranin A and S100 indicating neuroendocrine origin. Tumor marker p63 was negative and SDHB expression was retained. Genetic testing showed variants of uncertain significance for POT1(p.Asp632Glu)and RECQL4 (p. Arg1004Gln). Repeat evaluation for primary aldosteronism was negative. POT1 or RECQL4 variants have not been described in relation to PGL. Germline variants in the POT1 gene have been implicated in other solid tumors (lymphomas, thyroid cancer).Conclusions: Bladder paragangliomas pose a diagnostic challenge. As illustrated in this case, Ga68-DOTATATE PET/CT initially missed this lesion due to the urinary excretion of the tracer highlighting the need for other imaging modalities when considering bladder PGLs. Further studies examining whether POT1 or REQL4 mutations might be pathogenic for (urinary) PGLs are warranted. Presentation: Sunday, July 13, 2025