Answer: Paraganglioma

Histology: Diffusely infiltrating the bladder, prostate and seminal vesicles was a nested tumor. The nests are separated by thin fibrovascular stroma. The nests consist of cells with moderately pleomorphic nuclei and abundant eosinophilic cytoplasm.

Discussion: The differential diagnosis in this case rests between infiltrating urothelial carcinoma and paraganglioma. Occasionally infiltrating urothelial carcinoma may have a somewhat nested appearance. However, typically this is relatively focal and lacks the thin fibrovascular anastomosing network typically seen in paraganglioma and other endocrine neoplasms. Often paragangliomas will have more amphophilic granular cytoplasm which was lacking in the current case. The type of atypia seen in paraganglioma is rather classic for an endocrine neoplasm composed of scattered random atypia rather than the diffuse atypia as seen in urothelial carcinoma. One cannot predict benign or malignant behavior solely based on the morphology. Even the presence of paraganglioma invading deeply into the muscle wall is not diagnostic of malignancy. However, in this case, the presence of metastatic disease is diagnostic of a malignant paraganglioma. The majority of paraganglioma of the bladder are preoperatively recognized as such by the clinical findings of secretion of epinephrine. Approximately one half of patients have symptoms of headache, palpitations, hypertension, blurred vision and/or sweating (micturition attack). Approximately 10-50% of bladder paragangliomas are malignant. Localized tumors may be treated with TUR or wedge resection or even partial cystectomy. Yet, typically larger tumors or malignant tumors require radical cystectomy or cystoprostatectomy. If there is a diagnostic dilemma differentiating paraganglioma from high grade urothelial carcinoma, stains for cytokeratin can be performed which are negative in paraganglioma. Neuroendocrine markers (chromogranin, synaptophysin, etc) are positive in these lesions. Stains for S100 protein will often highlight sustentacular cells surrounding the nests of paraganglioma.