Introduction: Bladder Paragangliomas (PGLs) are rare neuroendocrine tumors derived from sympathetic paraganglionic tissue within the bladder wall, accounting for <1% of all Pheochromocytomas and Paragangliomas (PPGLs). >40% of PPGLs are associated with inherited syndromes through mutations affecting citric acid cycle enzymes (commonly SDH). Susceptibility gene identification has important implications for long-term care and facilitates targeted cascade genetic screening. Functional imaging using MIBG, Gallium DOTATATE and FDG-PET have become important tools in both diagnosis and treatment (Peptide Receptor Radionuclide Therapy).
Clinical Cases: We report the demographics, clinical characteristics and novel features of 7 patients with bladder PGLs. The series includes 2 females and 5 males, median age 38 years (range 14-68). 5 presented with hematuria and 2 were detected incidentally (1 found on radiological imaging and the other during cystoscopy surveillance). Other symptoms reported were headaches, sweating and palpitations which were relieved by urination. Only 1/7 had a known family history of PGLs. 5/7 patients had elevated plasma normetadrenaline levels and 2 had non-elevated catecholamine metabolites (these 2 patients were asymptomatic).
6/7 patients had genetic testing performed and pathogenic variants were identified in 4 (Fumarate hydratase (FH), SDHA, SDHB*2 genes) and no pathogenic variant identified in 2 patients in our genetic panel of 10 PPGL genes. All primary tumors demonstrated MIBG avidity and in 2 patients assessed there was PGL FDG-PET avidity. Metastatic disease was present in 2 patients (2 SDHB mutations; with 1 MIBG avid bone and 1 FDG-PET avid nodal metastasis). SDHB immunostaining on resected histology was available for 3 cases - absent SDHB immunostaining in the patient with SDHA mutation and strongly positivity in 2 patients (1 with no genetic mutation and in 1 with FH mutation).
Conclusions: The majority (>65%) of patients with bladder PGL have a germ line mutation in a susceptibility gene involving the citric acid cycle. An extended gene panel should be performed in all patients diagnosed with bladder PGLs including SDHA and FH gene mutations. SDH immunostaining of tumour can indicate SDHx gene defects but can be normal in FH mutations. SDHB is associated with increased risk of malignant/metastatic behavior. All 3 modalities of functional imaging (Ga DOTATATE, FDG PET, & MIBG) have a role in the assessment and treatment decision making in the management of bladder PGLs.