Bladder Mass in an Elderly Man

Specimen Type:



A 68 year old man underwent bladder biopsy. Clinical information is unavailable. Submitted are multiple ovoid fragments of light tan tissue measuring 1.2x1.2x0.5cm in aggregate.

Pathologic Features:

The tumor is composed of cells arranged in nests separated by a prominent vascular network (Fig 1). The cells have abundant amphophilic or eosinophilic or clear cytoplasm; the nuclei display finely dispersed chromatin with enlarged nucleoli (Fig 2, 3). Nuclear atypia including nuclear enlargement, pleomorohism and hyperchromasia is seen in some areas (Fig 4); mitotic activity is absent. The tumor is diffusely positive for chromogranin (Fig 5) and scattered cells are positive for S100 (Fig 6).

Differential Diagnosis:

  • Urothelial carcinoma, nested variant (Fig 7)
  • Pheochromocytoma (Paraganglioma)

Urothelial carcinoma, nested variant: This rare pattern of urothelial carcinoma was first described as a tumor with a “deceptively benign” appearance that closely resembles Brunn’s nests infiltrating the lamina propria. Nuclei generally show little or no atypia, but the tumor invariably contains foci of unequivocal cancer with cells exhibiting enlarged nuclei and coarse nuclear chromatin. Useful features in recognizing this lesion as malignant are the tendency for increasing cellular anaplasia in the deeper aspects of the cancer; it’s infiltrating nature, and the frequent presence of muscle wall invasion.

Paraganglioma: These tumors comprise less than 0.1% of all bladder neoplasms. The most characteristic symptom complex is the “micturation attack,” consisting of bursting headache, anxiety, tremulousness, pounding sensation, blurred vision, sweating, and even syncopy. Hypertension is observed in most individuals. Grossly, most are single lesions measuring only a few millimeters in greatest dimention. Histologically, this tumor almost always assumes the characteristic “zellballen” pattern. Cells tend to be round with amphophilic to acidophilic cytoplasm and ovoid nuclei. Occasional bizarre nuclei, such as seen in other neuroendocrine neoplasms, may be present. Mitoses are uncommon. Characteristically, pheochromocytomas contain a combination of neuroendocrine and sustentacular cells which react with NSE and S100 protein respectively. The behavior of this tumor cannot be accurately predicted from pathologic examination alone.



Key Features:

  • Grossly, usually a small mass lesion
  • Microscopically, “zellballen” pattern, round cells with amphophilic to acidophilic cytoplasm and round to ovoid nuclei, occasional bizarre nuclei; uncommon mitosis
  • Immunohistochemically, diffusely positive for chromogranin; there are scattered positive cells for S100

Comment: Pheochromocytoma of the urinary bladder is rare and approximately 20 cases have been reported in literature. Herein, we present a typical case of pheochromocytoma; no difficulty is encountered when it comes to the diagnosis. However, a nested variant of urothelial carcinoma should always be kept in mind in your differential. An immunohistochemical study will help clinch the diagnosis. Surgical resection is the treatment of choice in the majority of cases. For metastatic tumors, chemotherapy and radiotherapy may be effective.


  1. Siatelis A, Konstantinidis C, Volanis D, et al. Pheochromocytoma of the urinary bladder: report of 2 cases and review of literature. Minerva Urol Nefrol. 2008 Jun;60(2):137-40.
  2. Safwat AS, Bissada NK. Pheochromocytoma of the urinary bladder. Can J Urol. 2007 Dec;14 (6):3757-60.