Predictive Characteristics of Malignant Pheochromocytoma

Abstract

Purpose:The prognosis of patients with malignant pheochromocytoma is poor, but the predictive factors are not well understood. We aimed to identify the clinical characteristics predictive of malignancy after initial surgical removal in patients with pheochromocytoma. Materials and Methods:We retrospectively reviewed the records of 152 patients diagnosed with pheochromocytoma, including 5 (3.3%) with metastasis at the time of the initial surgical excision and 12 (7.9%) who developed metastasis during follow-up. To determine the factors predictive of malignancy, we compared clinical, radiographical, and urinary chemical findings between patients with benign and malignant disease. Mean follow-up was 41.5 months (range, 0.9-298 months) after surgery. Results: Malignant tumors were significantly larger than benign tumors (11.1±4.0 cm vs. 6.2±3.4 cm, p＜0.001), and postoperative persistence of arterial hypertension was more frequent after removal of malignant than benign tumors (p=0.001). Among the 147 patients without metastatic disease at diagnosis, those who developed metastasis had significantly lower concentrations of urinary catecholamine metabolites per unit of tumor, including vanillylmandelic acid (1.2 vs. 3.7 mg/day/cm, p=0.049), epinephrine (4.5 vs. 168.9 μg/day/cm, p=0.008), and norepinephrine (13.1 vs. 121.8 mg/day/cm, p ＜0.001). The overall 5-year metastasis-free survival rate was 84.4% and was significantly higher in patients with smaller tumors (≤5.5 vs. ＞5.5 cm; 90.6% vs. 81.2%, p=0.025) and higher 24-hour secretion of vanillylmandelic acid (＞2.1 vs. ≤2.1 mg/ day/cm; 94.9% vs. 70.9%, p=0.019). Conclusions: Large tumor size (＞5.5 cm) and minimally elevated 24-hour urinary vanillylmandelic acid (≤2.1 mg/day/cm) were significantly associated with a higher probability of a malignant pheochromocytoma portending a lower metastasis-free survival and mandating more rigorous follow-up after surgery.

Pheochromocytomas and paragangliomas: assessment of malignant potential

“…They found elevations in 6/11 malignant compared to 3/35 benign tumors, with respective median levels of 61 pg/ml (15.6-330.8) and 30 pg/ml [30]. The metabolite VMA is produced in the later stages of catecholamine metabolism, and some studies have noted a significant difference in VMA excretion between benign and malignant tumors [11,22,23]. However, VMA is elevated in both benign and malignant, is not elevated in EPI-secreting PPGLs [39], and was found to correlate with both NE (r = 0.64; P B 0.01) and DA (r = 0.67; P B 0.01), but not with EPI [30].…”

ERBB‐2 overexpression as a risk factor for malignant phaeochromocytomas and paraganglinomas

“…Many malignant PPGLs may be initially classified as benign. An extra‐adrenal location and primary tumour size larger than 5 cm have been recognized as risk factors associated with malignant PPGLs . germline mutation in the succinate dehydrogenase B ( SDHB ) gene may also be associated with an increased frequency of malignancy and poor survival in PPGLs …”

Total 18F-FDG PET/CT Metabolic Tumor Volume Is Associated With Postoperative Biochemical Response in Patients With Metastatic Pheochromocytomas and Paragangliomas

“…2 Patients with metastatic PCCs/PGLs are often associated with a primary tumor greater than 6 cm, necrosis, hemorrhage, and high mitotic index. 5,6 SDHB mutation has been associated with metastatic disease, as well as a poor prognosis in both children and adults. 7,8 Currently, there is no cure for metastatic PCCs and PGLs once metastases have developed if the tumor sites are not resectable.…”