Association of urinary bladder paragangliomas with germline mutations in the SDHB and VHL genes

Abstract

Objective Our primary goal was to examine the clinical characteristics of a series of patients with urinary bladder paragangliomas (UBPGLs), focusing particularly on their genetic backgrounds. Materials and methods We analyzed the medical records of patients who presented to the National Institutes of Health with UBPGL from 2000 to 2013 to determine their clinical characteristics and outcomes, biochemical phenotype, tumor size, and genetic background. Results Of the 27 patients with UBPGLs who were identified, 17 (63%) had underlying genetic mutations. Overall, 14 (51.9%) patients had a germline mutation in the succinate dehydrogenase subunit B gene (SDHB), and 3 (11.1%) had in the von Hippel-Lindau gene (VHL). Of the 21 patients who had biochemical data available before their first operation, 19 (90.5%) presented with a noradrenergic biochemical phenotype; 7 (33.3%) patients had tumors that also secreted dopamine. In addition, 1 patient (4.8%) had elevated metanephrine levels, and 2 (9.5%) had normal biochemical data. In total, 13 (48.1%) patients in the series were diagnosed with metastatic disease, at either first presentation or follow-up; 6 of these patients (46.1%) had SDHB mutations. Conclusions UBPGLs typically present with a noradrenergic phenotype and are frequently associated with underlying germline mutations. Patients presenting with these rare neuroendocrine tumors should be screened for these mutations. In addition, patients with UBPGLs should be followed up closely for metastatic development regardless of genetic background, as almost half of the patients in this series presented with metastatic disease and less than half of them had SDHB mutations.

Genitourinary paraganglioma: Demographic, pathologic, and clinical characteristics in the surveillance, epidemiology, and end results database (2000–2012)

“…Martucci et al found patients with bladder PGLs to have a mean age of 29.4 years at diagnosis 9 . The patients in this study were followed closely due to inherited conditions associated with mutations of genes including von Hippel-Lindau and succinate dehydrogenase.…”

“…To determine if paraganglioma resection is complete, the patient should have a 24-hour urinary catecholamine and catecholamine metabolite test two weeks after their surgery; if the levels are normal, the resection is complete 9,16 . Lastly, because recurrence is possible, periodic follow-up is recommended for all cases of PGLs with plasma metanephrines, and CT or MRI as indicated 13,14,16 .…”

“…SEER 18, as a database, represents 27.8% of the US population and does not capture all the cases of PGLs in the US as evidenced by the 27 cases of bladder PGLs described in the study by Martucci et al 9 . In addition, SEER only roughly characterizes the US population because most cancers reported likely represent patients who live in urban areas and are foreign-born because SEER has a higher proportion of US Native Hawaiian, Pacific Islander, Asian, American Indian, Alaskan native, and Hispanic populations as compared to the white and black populations 22 .…”

“…Of these sites, the bladder is the most common (79.2%) 10,12 . Regardless, bladder PGLs remain extremely rare, accounting for less than 0.06% of all bladder neoplasms and 6% of paragangliomas 4,9,12–19 . About 17% of bladder PGLs are nonfunctional, while the majority cause paroxysmal symptoms such as headache, diaphoresis, and palpitations 10 .…”

“…Most bladder PGLs are benign but 13–20% have been reported as malignant, when malignancy is defined as metastases in areas where chromaffin tissue is uncommon 3,9–11 . Most PGLs are treated conservatively, with surgery 1–20 which is typically curative in non-metastatic disease 12 .…”