Malignant Paraganglioma of Urinary Bladder 363 Case Report 363 Department of 1 Laboratory Medicine, 2 Urology, and 3 Endocrinology, St. Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada. Address correspondence to Dr. Kalman Kovacs, Department of Laboratory Medicine, 2CC, 30 Bond Street, Toronto, Ontario, M5B 1W8, Canada. E-mail: kovacsk@smh. toronto.on.ca Endocrine Pathology, vol. 16, no. 4, 363–370, Winter 2005 © Copyright 2005 by Humana Press Inc. All rights of any nature whatsoever reserved. 1046–3976/1559-0097 (Online)/ 05/16:363–370/$30.00 Malignant Paraganglioma of the Urinary Bladder: Immunohistochemical Study of Prognostic Indicators Kalman Kovacs, MD, PHD, 1 C. David Bell, MD, 1 Geoffrey W. Gardiner, MD, 1 R. John Honey, MD, 2 Jeannette Goguen, MD, 3 and Fabio Rotondo, BRT 1 Abstract Using various immunohistochemical markers, the objective of our study was to assess whether correlation exists between growth potential of paraganglioma (pheochromo- cytoma) cells and formation of metastasis. The patient was a 28-yr-old man who pre- sented with intermittent episodes of gross hematuria due to a mass in the urinary bladder. He had no constitutional symptoms to suggest paraganglioma. Histologic, immunohis- tochemical, and electron microscopic investigation of the surgically removed tissue proved that the tumor was a malignant paraganglioma with metastases in the regional lymph nodes. The immunohistochemical tests were not supportive of high cell proliferation index, indicating that metastases can develop in the absence of rapid multiplication of the tumor cells. Abnormalities in vascular architecture and marked expression of VEGF in the tumor cells may be regarded as prognostic signs to predict the formation of metastases. Key Words: Extra-adrenal paraganglioma; immunohistochemistry; pathology; progno- sis; urinary bladder neoplasms. to the regional lymph nodes. Elevations of urinary catecholamine levels were demon- strated after a transurethral biopsy was car- ried out and the surgical pathological diagnosis was reached. Several immunohis- tochemical tests were performed to assess whether correlation exists between growth potential of the tumor cells and the for- mation of metastasis. Report of the Case Clinical Findings This 28-yr-old man presented with a 2-yr history of intermittent episodes of severe gross hematuria and difficulties of voiding. Family history was unremarkable and he had no previous medical problems. He was asymptomatic except for hematuria Introduction Pheochromocytomas are neuroendo- crine tumors secreting catecholamines and causing various clinical symptoms such as hypertension, tachycardia, hypermetabo- lism, and, in some cases, heart failure, pul- monary edema, and death [1,2]. They arise most often in the adrenal medulla and less frequently in various extra-adrenal sites including the urinary bladder [3–8]. For these tumors, the term paraganglioma seems to be more appropriate. The sub- stantial majority of pheochromocytomas are benign tumors. Approximately 10% of them, however, are malignant giving rise to metastases [2,6]. We report here a case of malignant paraganglioma (pheochro- mocytoma) in a 28-yr-old man originat- ing in the urinary bladder and spreading