Answer: Paraganglioma

Histology: Architecturally, the tumor consists of infiltrating irregular nests associated with a fibroblastic reaction. The tumor cells have abundant amphophilic cytoplasm which in some areas has a granular nature. The tumor shows moderate to marked pleomorphism. However, much of the atypia appears degenerative in nature lacking mitotic figures.

Discussion: The predominant differential diagnosis in this case is infiltrating high grade urothelial carcinoma versus paraganglioma. In contrast to the usual paraganglioma of the bladder or paraganglioma seen in other sites, this case is difficult in that it lacks in many areas of the classic nesting (zellballen) appearance. A clue to the correct diagnosis of paraganglioma is that the cells have abundant amphophilic granular cytoplasm which would be distinctly unusual for urothelial carcinoma. Furthermore, the nature of the atypia is typical for endocrine tumors consisting of nuclei with hyperchromatic, smudgy chromatin lacking mitotic figures. Focally, one can appreciate a nesting appearance separated by fine thin vessels although it is not prominent. It is critical to make a distinction between paraganglioma of the bladder versus urothelial carcinoma as the treatment could differ. With paraganglioma, the lesion lacks multifocality in contrast to urothelial carcinoma such that the goal is just to remove the tumor itself. If the tumor is located in the dome, one can get by with a partial cystectomy as compared to a radical cystectomy for urothelial carcinoma. In many cases, the diagnosis of paraganglioma is known by the clinicians preoperatively due to manifestations of catecholamine secretions. Classically, many patients have hypertension, micturition attacks consisting of palpitation and syncope upon urination. However, a minority of cases may be clinically silent in terms of features relating to catecholamine secretions, where the diagnosis rests on the histopathological examination. Confirmation of the diagnosis of paraganglioma can be made with immunoreactivity to neuroendocrine markers such as synaptophysin and chromogranin with negative immunostaining to various keratins. Immunostaining for S100 variably shows sustentacular cells surrounding tumor nests. One cannot predict the malignant behavior of paragangliomas based on the morphology with approximately 10-15% eventually demonstrating metastases.