Original ArticlesPheochromocytoma A Clinicopathologic and Molecular Study of 390 Cases From a Single CenterLiu, Zhonghua MD, PhD*; Ma, Junsheng PhD†; Jimenez, Camilo MD‡; Zhang, Miao MD, PhD* Author Information Departments of *Pathology †Biostatistics ‡Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, TX A portion of this data was presented in abstract form at the 2020 USCAP Annual Meeting in Los Angeles, CA. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Miao Zhang, MD, PhD, Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030 (e-mail: [email protected]). The American Journal of Surgical Pathology: September 2021 - Volume 45 - Issue 9 - p 1155-1165 doi: 10.1097/PAS.0000000000001768 Buy Metrics Abstract 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. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.