This 47-year-old woman with history of labile hypertension was found to have a 6 cm. diameter lobulated mass arising from the posterior bladder wall. On cystoscopic exam, the tumor appeared to have ruptured through the urothelium forming a polypoid intravesical mass measuring 2.5 cm in diameter. A biopsy was followed by radical cystectomy.

Note the large round tumor with a knob-like projection in the center protruding into the bladder lumen (Fig. 8.1). The tumor has a variegated surface with areas of hemorrhage. It consists of round or polygonal epithelioid cells arranged in nests separated by vascular septa (Fig. 8.2). The tumor cells have abundant cytoplasm with an eosinophilic granular or amphophilic appearance, vesicular nuclei with fine granular chromatin, and rare punctate nucleoli (Fig. 8.3).

The differential diagnosis includes paraganglioma (Fig. 8.4), nested variant of urothelial carcinoma (Fig. 8.5), granular cell tumor (Fig. 8.6), malignant melanoma (Fig. 8.7), and metastatic carcinoma.

Paraganglioma of the Bladder

Key Features:

• Usually occurs in young women (mean age 45 years; M:F = 1:3)
• Presents with hematuria and hypertension; may cause headaches, flushing, diaphoresis related to micturition in some cases
• Cells arranged in zellballen; immunoreactive for chromogranin, synaptophysin, NSE, and S-100 protein (sustentacular cells only); negative for cytokerain AE1/3, CK7, and CK20
• No reliable histologic criteria to predict behavior; mitotic figures, necrosis, vascular invasion, DNA ploidy, p53 status, and MIB-1 labelling index are unhelpful in predicting outcome
• Tumor stage and completeness of resection are most important prognostic indicators; no recurrence or metastasis in stage T1 and T2 tumors
• About 20% of cases are malignant based on the presence of regional or distant metastases
• Cystectomy is the treatment of choice

The history of labile hypertension, the presence of a bladder mass, and the histologic features in combination are diagnostic of paraganglioma. In fact, the correct diagnosis in this case was made preoperatively. A series of tests on her urine sample showed 24-hour urinary vanillyl mandelic acid of 44.8 (ref. Range 20), urine epinephrine of 27.5 (ref. Range <15), and urine norepinephrine of 1124 (ref. Range <100). The histologic features, including the zellballen pattern, are characteristic. The tumor cells are strongly immunoreactive for chromogranin (Fig. 8.8) and synaptophysin. Sustentacular cells are highlighted on immunostaining for S-100 protein (Fig. 8.9). The tumor invaded through the muscularis propria but did not involve the vaginal mucosa.

Follow-up: The patient was last seen for arthritis 6 years after surgery. She had no evidence of recurrent or residual tumor.