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

J Clin Endocrinol Metab. 2011 Mar;96(3):717-25. doi: 10.1210/jc.2010-1946. Epub 2010 Dec 29.


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.

MeSH terms

  • Adolescent
  • Adrenal Gland Neoplasms / mortality
  • Adrenal Gland Neoplasms / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Autonomic Nervous System Diseases / mortality
  • Autonomic Nervous System Diseases / pathology*
  • Child
  • Child, Preschool
  • Chromaffin System / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis / pathology
  • Paraganglioma / mortality
  • Paraganglioma / pathology*
  • Pheochromocytoma / mortality
  • Pheochromocytoma / pathology*
  • Prognosis
  • Proportional Hazards Models
  • Regression Analysis
  • Retrospective Studies
  • Risk Factors
  • Survival
  • Survival Analysis
  • Young Adult