ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P427 | DOI: 10.1530/endoabs.63.P427

Genetic mutations in bladder paragangliomas - not just SDHB-related disease

Samantha Anandappa, Louise Breen, Ramesh Thurairaja, Dimitra Christodoulou, Audrey Jacques, Anand Velusamy, Barbara McGowan, Louise Izatt & Paul Carroll


Guys and St Thomas’ Hospital NHS Foundation Trust, London, UK.


Bladder Paragangliomas (PGLs) are rare forms of neuroendocrine tumours arising from sympathetic paraganglionic tissue. They account for <1% of all Pheochromocytomas and Paragangliomas (PPGLs) and < 0.06% of all bladder tumours. All patients with PPGLs are recommended to be considered for genetic testing as ~ 40% of PPGLs are associated with a germline mutation, even if there is no prior family history of disease. Identifying an inherited PPGL predisposition has important implications for ongoing care and surveillance of the index case and provides the opportunity for cascade targeted genetic screening in the family. Bladder PGLs often display aggressive phenotypes with metastatic disease particularly if a germline SDHx mutation is identified thus requiring closer long term follow-up. Bladder PGLs can either be secretory or non-secretory and elevated normetadrenaline levels are often found in those with inherited SDHx mutations. We report six cases of bladder PGLs - 2 female and 4 male patients. Patients were aged 14–64 at the time of diagnosis, with a mean age of 36. Five presented with haematuria and 1 PGL was found incidentally following radiological imaging. Other reported symptoms were headaches, sweating and palpitations which were relieved by passing urine. Only 1 patient reported a family history of PGLs. Five patients had elevated plasma normetadrenaline levels and one patient was asymptomatic with plasma metanephrines within the reference range. Metastatic disease has been detected in two patients so far, one of whom had elevated Dopamine metabolites. Five patients had genetic testing. Pathogenic mutations were identified in four patients (FH, SDHA, SDHB*2 genes) and no mutation was identified in one patient from our genetic panel. All tumours demonstrated MIBG avidity. SDHB immunostaining on resected histology was available for two cases - absent staining in the patient with SDHA mutation and strongly positive SDHB immunoreactivity in the patient with FH mutation. Elevated plasma normetadrenaline together with negative SDHB immunostaining is a strong predictor of mutations affecting the SDHx genes. Elevated Dopamine and its metabolites in the context of Bladder PGLs (as in any sympathetic PGLs) should raise suspicion of metastatic disease warranting rigorous surveillance with multi-modal imaging. Hence it is important to undertake genetic testing in all patients diagnosed with bladder PGL with an extended panel as we have identified FH and SDHA mutations in our cohort. The genetic panel may need to involve further genes in the citric acid cycle to guide better surveillance strategy for this particular tumour group.

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