PHEOCHROMOCYTOMAS: CAN MALIGNANT POTENTIAL BE PREDICTED? HUBERT JOHN, WALTER H. ZIEGLER, DIETER HAURI, AND PETER JAEGER ABSTRACT Objectives. The presence of metastatic lesions is the only acceptable fact to confirm malignant pheochro- mocytoma. Patients with malignant pheochromocytomas, however, have a very poor survival rate. The aim of our study was to postulate predictive values for malignant pheochromocytomas. Methods. We evaluated symptoms, diagnostic modalities, treatment, and long-term follow-up of 86 patients with 85 benign and 10 malignant pheochromocytomas. Parameters from the benign were compared with those of the malignant pheochromocytomas. Results. Preoperative 24-hour urinary dopamine was in the normal range for benign pheochromocytomas but increased in malignant pheochromocytomas (P 0.0001). Vanillylmandelic acid was elevated in both benign and malignant pheochromocytomas but higher in malignant than in benign tumors (P = 0.01). No differences could be shown in urinary epinephrine and norepinephrine samplings. Tumor location was divided into 77 adrenal (81%) and 18 extra-adrenal (19%) sites. Malignant pheochromocytomas were located more often at extra-adrenal sites (P = 0.03). There was no increased incidence of malignancy in patients with familial bilateral pheochromocytomas or multiple endocrine neoplasia. Tumors greater than 80 g in weight corresponded to malignancy (P 0.0001). Dopamine tumor concentration was higher in malignant than in benign pheochromocytomas (P = 0.01). Persistent arterial hypertension occurred in 9 (13%) of 72 benign and 6 (60%) of 10 malignant pheochromocytomas (P = 0.001). The 10-year survival rate was 94% for benign pheochromocytomas. All patients with malignant pheochromocytomas died within this period (P = 0.0001). Conclusions. High preoperative 24-hour urinary dopamine levels, extra-adrenal tumor location, high tumor weight, elevated tumor dopamine concentration, and postoperative persistent arterial hypertension are all factors that increase the likelihood of malignant pheochromocytoma. Patients with these characteristics should have more frequent follow-up evaluations to identify malignancy at earlier states. UROLOGY 53: 679–683, 1999. © 1999, Elsevier Science Inc. All rights reserved. T he long-term prognosis of patients with malig- nant pheochromocytoma is poor. Histopatho- logic evaluation cannot reliably distinguish malig- nant from benign pheochromocytomas. 1,2 Most investigators rely on the presence of metastases as evidence of malignancy. 3,4 We analyzed a 35-year series to identify possible clinical and biochemical characteristics of malignant pheochromocytoma. MATERIAL AND METHODS During the 35-year period from 1960 to 1995, 86 patients (95 pheochromocytomas) were treated at the Urologic Clinic, University Hospital Zu ¨ rich. There were 42 female and 44 male patients aged 14 to 74 years (median 42). All patients had increased urine concentrations of vanillyl- mandelic acid (VMA) in the 24-hour urine sampling or in spot urine, or both. The method to localize pheochromocytoma has changed with the advent of newer technologies. Tumor local- ization was performed by angiography (plasma catecholamine measurements), computed tomography, or magnetic reso- nance imaging. Patients with suspected extra-adrenal or malignant pheochromocytoma also underwent metaiodoben- zylguanidine-131 (MIBG) scanning. Seventy-eight patients treated after 1965 received preoperative alpha-adrenergic blockade to achieve normal blood pressure, plasma volume, and cardiac rhythm. The 5 patients who did not respond as expected also received additional beta-blockade. All patients underwent adrenalectomy by the thoracolumbar route. Oper- ative complications included cardiac arrest with successful resuscitation (1 patient), lacerations of the inferior vena cava (3 patients), hemopneumothorax (3 patients), splenectomy due to splenic injury (1 patient), and early postoperative pul- monary emboli (3 patients). Two intraoperative deaths oc- From the Urologic Clinic, University Hospital Zu ¨ rich, Zu ¨ rich, Switzerland Reprint requests: Hubert John, M.D., Clinic of Urology, Zurich University Hospital, 809 Zurich, Switzerland Submitted: June 22, 1998, accepted (with revisions): October 8, 1998 ADULT UROLOGY © 1999, ELSEVIER SCIENCE INC. 0090-4295/99/$20.00 ALL RIGHTS RESERVED PII S0090-4295(98)00612-8 679