Pheochromocytomas are rare
neuroendocrine tumors arising from chromaffin cells in the adrenal medulla. They may occur sporadically or in the context of hereditary syndromes. All
pheochromocytomas are considered to have malignant potential (defined as risk of
metastasis, not local invasion). The use of grading systems with incorporated clinical and histopathologic parameters can help but not definitively predict the metastatic potential of
pheochromocytomas. The recent discovery of susceptibility genes provided new insights into the pathogenesis and introduced additional approaches to estimate the metastatic risk of
pheochromocytoma. However, the prevalence of these genetic signatures in
pheochromocytomas has yet to be fully addressed. Therefore, in the present study, we retrospectively reviewed cases of
pheochromocytoma from 1980 to 2018 in the archives of our institution. Three hundred ninety cases were identified, and their clinicopathologic characteristics and genetic statuses were analyzed. About 25% of the cases had
metastases, which were more common in older patients (median, 49 y) than in younger ones. Univariate and multivariate analyses revealed that older age, Hispanic ethnicity,
metastasis, and large primary
tumor size were markedly associated with poor overall survival. In contrast, family history of
pheochromocytoma, lack of symptoms, and bilateral adrenal involvement were associated with better survival. About 37% of the
pheochromocytomas were associated with inherited syndromes. About 52% of tested patients had pathogenic mutations of
pheochromocytoma susceptibility genes. Of these,
succinate dehydrogenase B gene mutation had the strongest association with
metastasis. These data support that genetic testing should be offered to all patients with
pheochromocytoma.