Malignant pheochromocytoma: predictive factors of malignancy and clinical course in 16 patients at a single tertiary medical center

Abstract

Metastases appear in approximately 10% of patients with pheochromocytoma. There is no predictive marker of malignancy. The aim is to describe clinical course of patients with malignant pheochromocytoma and to identify predictive features of malignancy. The method involves retrospective analysis of patients files diagnosed with malignant pheochromocytoma at our institution between January 1, 1980 and December 31, 2008. We identified 16 patients with malignant pheochromocytoma. There were more men than women (10/6). Mean age of patients at time of diagnosis was 37.75-year-old. Time of occurrence of metastases ranged from 0 to 22 years after first diagnosis of pheochromocytoma. The mean size of the primary tumor was 12.1 cm. High levels of chromogranin A at the time of diagnosis were associated with the presence of metastases. The pheochromocytoma of the adrenal gland scoring scale (PASS) histological evaluation in adrenal primary tumors was above four in all cases but one. All patients had initial surgery, followed in most cases by palliative therapy: chemotherapy (streptozocin, cyclophosphamide-vincristine-dacarbazine, thalidomide, imatinib, everolimus) or (131)I-MIBG; only the latter had replicable encouraging response evaluation criteria in solid tumor response rates. We observed a 10-year survival rate of 50% after initial diagnosis of pheochromocytoma, and 25% after diagnosis of metastasis. Metastasis can occur very late after the initial diagnosis of pheochromocytoma. High chromogranin A levels may be associated with the presence of metastases and poor prognosis. Histological adrenal PASS higher than 4 appears to be suggestive of malignancy. The best therapeutic approach remains to be established.

Lack of Correlations among Histopathological Parameters, Ki-67 Proliferation Index and Prognosis in Pheochromocytoma Patients

“…The study data of Szalat et al (Szalat et al, 2011) supported Thompson's data. Similarly, Strong et al concluded that PASS scoring system was definitely significant in pointing out malignancy, and confirmed with PASS> 4 of their malignant cases, while PASS <4 of benign cases (Strong et al, 2008).…”

“…Yet again, this scoring system was evaluated also by Amit Agarwal et al (Agarwal et al, 2010). Numerous studies reported that the PASS system would be beneficial in differentiating tumors for having a potential to behave biologically aggressive (PASS >or=4) or benign (PASS <4) (Strong et al, 2008;Agarwal et al, 2010;Szalat et al, 2011;de Wailly et al, 2012).…”

“…Again, the relationship between Ki-67 proliferation index and malignancy and recurrence was evaluated separately and insignificant results were found, which was also incompatible with the literature. However, many different results are available in the literature (Agarwal et al, 2010;Szalat et al, 2011;de Wailly et al, 2012).…”

“…Irfan Ocal*, Arzu Avci, Fulya Cakalagaoglu, Huseyin Can to differentiate tumors for having a potential to behave biologically aggressive (PASS >or=4) or benign (PASS <4) (Strong et al, 2008;Agarwal et al, 2010;Szalat et al, 2011;de Wailly et al, 2012).…”

No evidence for increased mortality in SDHD variant carriers compared with the general population

“…[14][15][16] The pooled incidence of malignant PGL, defined as the presence of metastases, [17][18][19] in populations comprising both unaffected SDHD variant carriers and SDHD variant carriers with manifest nonmalignant PGL is about 8%. 20 Prognosis in malignant PGL is poor, with reported 5-year survival rates of 20-55% for malignant sPGL and PCC 21,22 and 60% for malignant HNPGL, 23 although a few cases of survival for 420 years after diagnosis have been described. 24,25 An increasing number of SDHD variant carriers are now being identified through (presymptomatic) testing of family members of SDHD variant carriers with manifest disease, that is, index cases.…”