Malignant Pheochromocytomas/Paragangliomas and Ectopic Hormonal Secretion: A Case Series and Review of the Literature.

Anna Angelousi,Annabel Berthon,Melpomeni Peppa,Krystallenia Alexandraki,Eva Kassi,Fabio Rueda Faucz,Alexandra Chrisoulidou,Gregory Kaltsas

doi:10.3390/cancers11050724

Abstract

Malignant pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine neoplasms defined by the presence of distant metastases. There is currently a relatively paucity of data regarding the natural history of PCs/PGLs and the optimal approach to their treatment. We retrospectively analyzed the clinical, biochemical, imaging, genetic and histopathological characteristics of fourteen patients with metastatic PCs/PGLs diagnosed over 15 years, along with their response to treatment. Patients were followed-up for a median of six years (range: 1–14 years). Six patients had synchronous metastases and the remaining developed metastases after a median of four years (range 2–10 years). Genetic analysis of seven patients revealed that three harbored succinate dehydrogenase subunit B/D gene (SDHB/D) mutations. Hormonal hypersecretion occurred in 70% of patients; normetanephrine, either alone or with other concomitant hormones, was the most frequent secretory component. Patients were administered multiple first and subsequent treatments including surgery (n = 12), chemotherapy (n = 7), radionuclide therapy (n = 2) and radiopeptides (n = 5). Seven patients had stable disease, four had progressive disease and three died. Ectopic hormonal secretion is rare and commonly encountered in benign PCs. Ectopic secretion of interleukin-6 in one of our patients, prompted a literature review of ectopic hormonal secretion, particularly from metastatic PCs/PGLs. Only four cases of metastatic PC/PGLs with confirmed ectopic secretion of hormones or peptides have been described so far.

Highlights

Malignant pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine tumors with an incidence of less than 1/1,000,000, defined by the presence of metastatic disease in non-chromaffin tissues without considering recurrent or locally invasive tumors [1,2,3]
A number of histopathological scores have been developed to denote the malignant potential of these neoplasms such as the Adrenal Pheochromocytoma and Paraganglioma (GAPP) Score used to evaluate the malignant potential of both PCs and sympathetic PGLs, and the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) used to evaluate the malignant potential of PCs only, it exhibits a relatively low predictive value [11,12]
In one patient with a bladder PGL, metastases were found in the aortopulmonary window and the heart (substantiated by dedicated cardiac magnetic resonance imaging (MRI))

Summary

Introduction

Malignant pheochromocytomas (PCs) and paragangliomas (PGLs) are rare neuroendocrine tumors with an incidence of less than 1/1,000,000, defined by the presence of metastatic disease in non-chromaffin tissues without considering recurrent or locally invasive tumors [1,2,3]. A number of histopathological scores have been developed to denote the malignant potential of these neoplasms such as the Adrenal Pheochromocytoma and Paraganglioma (GAPP) Score used to evaluate the malignant potential of both PCs and sympathetic PGLs, and the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) used to evaluate the malignant potential of PCs only, it exhibits a relatively low predictive value (sensitivity 50% and specificity 45%) [11,12]. The presence of inactivating mutations of the succinate dehydrogenase subunit B (SDHB) gene is strongly associated with the development of metastatic PCs and PGLs [17]

Results

Discussion

Conclusion