Fellow University of Florida Gainesville, Florida, United States
Introduction: Paragangliomas (PGLs) are rare neuroendocrine tumors derived from paraganglia of autonomic nervous system with strong genetic associations. Urinary bladder PGLs originate from the sympathetic neurons of the urinary bladder wall, which represent 0.7% of all PGLs and <0.05% of all bladder tumors. We report a case of a 42-year-old woman who presented with hematuria and further work up revealed a bladder PGL. Removal of the tumor showed a somatic succinate dehydrogenase B (SDHB) gene mutation and germline testing showed a Mesenchymal Epithelial Transition (MET) mutation.
Case Description: 42-year-old female presented with new onset hematuria. As part of her evaluation, she underwent cystoscopy and CT intravenous pyelogram which revealed a 3.7 cm bladder mass centered near the left uretero-vesical junction, as well as a hyper dense cardiac mass on the atrial septum. Transurethral biopsy of the bladder tumor revealed a PGL, grade 1. Immunohistochemistry showed loss of SDHB protein expression in tumor cells. Metanephrine level was 74 pg/mL and 57 pg/mL on repeat testing (normal <57 pg/mL), but normetanephrine and total metanephrine were within normal limits. Chromogranin A was also normal. On 24-hour urine studies, metanephrines were 305 mcg/24h (normal 58- 203 mcg/24h), normetanephrines were 109 pg/mL (normal <148 pg/mL) and dopamine was 564 (normal 52-480 mcg/24h). PET DOTATATE scan indicated no evidence of metastatic disease and a hyper dense cardiac mass that had no uptake. Cardiac MRI showed a well-circumscribed mass in the interatrial septum measuring 2 x 1.7 cm concerning for either myxoma or PGL. In addition, there was a suspicious breast nodule and axillary lymph node concerning breast cancer. Breast biopsy is pending. The patient received doxazosin and successfully underwent transurethral resection of bladder PGL. Germline testing showed heterozygosity for the pQ272H (c.816G >C) variant in the MET gene.
Discussion: Bladder PGLs are rare neuroendocrine neoplasms. Like in our case, a common presentation of bladder PGLs is hematuria and often discovered after a tissue biopsy or surgical procedure. Patients with PGLs particularly having SDHB pathogenic variants have increased risk of metastatic disease. The germline MET variant mutation found is of interest as hotspot mutations in this gene can be seen in up to 2.5% of tumor pheochromocytoma/PGL in some studies. Further studies are underway on the tumor sample to better define the role of MET in this case. Interestingly, germline MET mutations have been associated with papillary renal cancers demanding an increasing appreciation of an overlap of genes associated with PGL and renal cancers. This case illustrates the important clinical point that both germline and genetic testing of a tumor is paramount as it may have an impact on patient follow-up and neoplasia screening.
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