Discussion:

Paraganglioma of the urinary bladder is very rare and account for 0.06% of all bladder tumors and 6% of extra-adrenal pheochromocytomas. However, in the genitourinary tract, the urinary bladder is the most common site (79.2%), followed by the urethra (12.7%), pelvis (4.9%), and ureter (3.2%).These tumors originate from chromaffin tissue of the sympathetic nervous system associated with the urinary bladder wall and are most commonly situated at the dome or the trigone of the bladder and may be nonfunctional or functional. They remain usually benign, but 15–20% tumors may show malignant behavior. Bladder paraganglioma occur more frequently in women than in men, and clinical presentation occur mainly during the third decade of life.

On cystoscopy appearance of a yellow, submucosal tumor should raise the suspicion of a bladder paraganglioma.  Placing the tumour in a Zenker’s fixative will turn the tumour black; a positive chromaffin reaction. On histopathology, tumor cells are seen as large polygonal cells with abundant granular cytoplasm arranged in a Zellballen pattern and are surrounded by a fibrous network rich in blood vessels.

Bladder paraganglioma can be confused histologically with urothelial carcinomas, especially the nested variant of urothelial carcinoma, and other tumors including bladder granular cell tumors, metastatic large cell neuroendocrine carcinoma and malignant melanoma. Presence of diffuse growth pattern, focal clear cells, necrosis, and muscularis propria invasion, with significant cautery artefact, and failure of pathologists to include it in their differential diagnosis may lead to their misdiagnosis as urothelial cancer. Immunohistochemistry is usually positive for neuron specific enolase (NSE), chromogranin and synaptophysin and negative for cytokeratin.

There are no definitive characteristics which reliably distinguish benign from malignant tumour, and desmoplastic reaction is often absent. The distinction between benign and malignant paraganglioma has long been contentious, with the only widely accepted and definitive proof of malignancy being metastasis to other organs. Some histological features such as tumour necrosis, a mitotic rate greater than 3/30 high power field, capsular invasion, large nests with central degeneration, a lack of hyaline globules, a high nuclear/cytoplasmic ration, monotony of a cytological pattern and spindle cells patters are suggestive of increased malignant predilection

Surgery is the mainstay of the treatment that requires total excision. If diagnosed preoperatively, a partial cystectomy is preferred over trans-urethral resection as majority of these tumors extend in the deep layers of the detrusor muscle. Chance of recurrence is high following resection and should not be considered as evidence of malignancy. Total cystectomy is reserved for large lesions when bladder preservation is impossible or in the presence of lymph node metastasis. Bladder paraganglioma is a chemo-resistant and radioresistant tumor, though radiation and chemotherapy, either in the neoadjuvant or adjuvant setting, has been used in a few cases.

Because bladder paragangliomas are likely to recur and to metastasize, lifelong follow-up with appropriate history, annual measurement of plasma and urinary catecholamine levels and cystoscopy is essential. Imaging study (CT scan and 123 I-MIBG scintiscan) should be done to locate recurrence and metastasis sites if reappearance of symptoms or resurgence of catecholamines occurs.