Aim: to analyze epidemiological data of patients diagnosed with malignant pheochromocytoma and to distinguish particular features predictive of the occurrence of metastases.
Method: retrospective analysis of all the files of patients who entered our institution between 1980 and 2008, with the diagnosis of pheochromocytoma.
Results: we identified 16 patients (62.5% men) with MP. The age at initial diagnosis of pheochromocytoma ranged between 13 and 56 years, and was before the age of 30 in 31 %. Elapsed time between the initial diagnosis of pheochromocytoma and the first occurrence of metastases ranged from 0 to 22 years. The size of the tumor ranged between 5 and 10 cm in 50% of cases, and was more than 20 cm in 2 cases. Laboratory findings showed that nor-epinephrine was the most frequently elevated catecholamine, whereas very high levels (beyond 200 fold normal range) of chromogranin A predicted a poor prognosis. Histologic findings were not predictive of MP. Metastasis were identified at 2 sites in 40% of patients, and at more than 5 sites in 20%. Patients had various treatments: all had a surgery at the time of the diagnosis of pheochromocytoma; 50% had a second surgery after the diagnosis of metastasis was done, in combination with palliative chemotherapy (cyclophosphamide/vincristine/dacarbazine) or/and l3l1-metaiodobenzylguanidine (MIBG). Two patients had a therapeutic trial with imatinib mesylate, 2 with the experimental drug RADOOl, and one with thalidomide and interferon-alpha. Eight patients continue follow-up within a range of 2 to 18 years after the diagnosis of metastases. The Kaplan-Meier analysis shows a 1 O-year survival rate of 50% after the first diagnosis of pheochromocytoma, and 25% after the diagnosis of metastatic occurrence.
Conclusion: MP is a rare condition, long-term follow-up of patients with so-called benign pheochromocytoma is warranted as metastasis can occur very late in the course ofthe disease. We could not define predictive marker for the development of metastasis. Therapeutic options for inoperable metastatic disease are, unfortunately, very limited.