Clinical Risk Factors for Malignancy and Overall Survival in Patients with Pheochromocytomas and Sympathetic Paragangliomas: Primary Tumor Size and Primary Tumor Location as Prognostic Indicators

Abstract

CONTEXT: Pheochromocytomas and sympathetic paragangliomas are rare neuroendocrine tumors for which no precise histological or molecular markers have been identified to differentiate benign from malignant tumors. OBJECTIVE: The aim was to determine whether primary tumor location and size are associated with malignancy and decreased survival. DESIGN AND SETTING: We performed a retrospective chart review of patients with either pheochromocytoma or sympathetic paraganglioma. PATIENTS: The study group comprised 371 patients. MAIN OUTCOME MEASURES: Overall survival and disease-specific survival were analyzed according to tumor size and location. RESULTS: Sixty percent of patients with sympathetic paragangliomas and 25% of patients with pheochromocytomas had metastatic disease. Metastasis was more commonly associated with primary tumors located in the mediastinum (69%) and the infradiaphragmatic paraaortic area, including the organ of Zuckerkandl (66%). The primary tumor was larger in patients with metastases than in patients without metastatic disease (P < 0.0001). Patients with sympathetic paragangliomas had a shorter overall survival than patients with pheochromocytomas (P < 0.0001); increased tumor size was associated with shorter overall survival (P < 0.001). Patients with sympathetic paragangliomas were twice as likely to die of disease than patients with pheochromocytomas (hazard ratio = 1.93; 95% confidence interval = 1.20-3.12; P = 0.007). As per multivariate analysis, the location of the primary tumor was a stronger predictor of metastases than was the size of the primary tumor. CONCLUSIONS: The size and location of the primary tumor were significant clinical risk factors for metastasis and decreased overall survival duration. These findings delineate the follow-up and treatment for these tumors.