A 64-year-old man with well-controlled systemic arterial hypertension and type 2 diabetes mellitus was referred to our institution for a single episode of gross painless hematuria in the absence of other lower urinary tract symptoms. His personal and family histories were negative for urologic pathology, neurofibromatosis and multiple endocrine neoplasia syndrome. His baseline blood pressure (120/65 mm Hg) and pulse rate (65 to 75 bpm) were within normal limits.
Initial urine cytology revealed only a few red blood cells and urine culture was negative for microorganisms. Abdominal ultrasound revealed a partial cystic mass of the anterior bladder wall that measured 5 × 4 × 3 cm. Adjacent structures, including the prostate, were not involved. Cystoscopy confirmed the presence of a well-circumscribed non-obstructive submucosal mass covered by smooth urothelium at the anterior bladder neck. This mass lacked the typical exophytic or ulcerative appearance of a urothelial carcinoma and the cytoscopic differential diagnosis included lymphoma and leiomyoma. During transurethral resection of the tumour under spinal anaesthesia, the patient manifested extreme blood pressure fluctuations (systolic 150/215 mm Hg; diastolic 80/125 mm Hg) with one episode of severe sinus bradycardia (heart rate dropped from 70 to 37 bpm). The patient’s heart rate normalized with atropine but labile blood pressure persisted throughout the procedure. The tumour resection was incomplete due to tumour bulk and hemorrhage at resection. Post-tumour resection, the patient was monitored by telemetry for 24 hours and his vital signs returned to baseline values.
Histopathologic examination of the resected tumour revealed a paraganglioma composed of nests of mitotically quiescent polygonal cells with pink granular cytoplasm that were arranged in a characteristic Zellballen organoid growth pattern (). The tumour demonstrated a prominent vascular network typical of paraganglioma. The neoplasm extensively infiltrated the lamina propria and muscularis propria of the bladder. In addition, the tumour contained a large component of ganglioneuroma consisting of mature ganglion and spindle cells () that had merged with the paraganglioma component. The paraganglioma tumour cells were strongly immunoreactive for chromogranin and synaptophysin and were negative for keratin immunostains, including high and low molecular weight cytokeratins and cytokeratins AE1/AE3. The ganglion cells within the ganglioneuroma component were immunoreactive for S-100 protein as were the sustentacular cells within the paraganglioma component. There was no evidence of a primitive neural component within the tumour. The patient was diagnosed with a CPG of the urinary bladder.
Paraganglioma component of the composite paraganglioma-ganglioneuroma showing the typical Zellballen growth pattern of paraganglioma (hematoxylin-phloxine-saffron stain, 100× magnification).
Ganglioneuroma component of the composite paraganglioma-ganglioneuroma containing occasional and prominent ganglion cells (hematoxylin-phloxine-saffron stain, 100× magnification).
Further staging with computerized tomography and magnetic resonance imaging delineated a focus of residual tumour 1.8 × 1.1 × 3 cm anterior to the prostatic urethra within the bladder wall. There was no evidence of extravesical tumour extension and 131I-metaiodobenzylguanidine (MIBG) scintigraphy demonstrated no evidence of metastatic disease. Most interestingly, serum levels of catecholamines and 24-h urinary excretion of catecholamines, vanillylmandelic acid and metanephrines at postcytoscopic resection were all within normal limits. Preoperative serum and urine catecholamine/catecholamine metabolites were not measured. The patient underwent partial cystectomy under alpha1-receptor blockade; the surgical specimen revealed residual paraganglioma-ganglioneuroma and appeared to be completely excised. He remains symptom-free 12 months after surgery with no evidence of tumour recurrence or metastatic disease.