Pheochromocytomas and paragangliomas: assessment of malignant potential

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting tumors which arise from the adrenal glands or sympathetic neuronal tissue. Malignant transformation of these tumors occurs in a significant proportion and may therefore lower overall survival rates. In patients with PPGLs it is impossible to identify malignant disease without the presence of metastatic disease, something which can occur as long as 20 years after initial surgery. Early identification of malignant disease would necessitate a more aggressive treatment approach, something which may result in better disease outcome. We have therefore reviewed possible predictors of malignancy and current developments in order to help clinicians to swiftly assess malignant potential in patients with PPGLs. Currently, there is no absolute marker which can objectively reflect malignant potential. Tumor size is the most reliable predictor and should therefore be used as the baseline characteristic. The combination of various clinical markers (extra-adrenal disease and post-operative hypertension), biochemical markers (high dopamine, high norepinephrine and epinephrine to total catecholamine ratio) and/or histological markers (SNAIL, microRNAs and/or microarray results) can raise or lower the suspicion of malignancy. Furthermore, we discuss how clinical markers may affect biochemical results linked to malignancy, how biochemical results may distinguish hereditary syndromes, the role of imaging in determining malignant potential and tumor detection, and recent results of proposed histological markers.

Diagnostic Performance of 68Ga-DOTATATE PET/CT, 18F-FDG PET/CT and 131I-MIBG Scintigraphy in Mapping Metastatic Pheochromocytoma and Paraganglioma

“…Despite the recent discovery of certain germline mutations, such as succinate dehydrogenase subunit B (SDHB) in an aggressive tumour [3,4], at present there is no single marker that can objectively distinguish between benign and malignant PCC/PGL [5][6][7][8]. The diagnosis of malignancy is solely based on the presence of distant metastasis.…”

The management of head-and-neck paragangliomas

“…None of the markers in a large set of putative markers of malignancy can reliably predict malignancy, and tumour size is still the major indicator of risk, as it is for phaeochromocytomas (Korevaar & Grossman 2011). The risk of malignancy is higher in SDHB mutation carriers, while multifocality is more frequent in SDHD germline mutations (Burnichon et al 2009).…”

Metabolomic profile of the adrenal gland: from physiology to pathological conditions

“…The presence of metastases is indispensable to identify patients with malignant disease who require a more aggressive therapeutic approach. Finally, the combination of various clinical, biochemical, and/or histological markers can indicate an aggressive tumor behavior (Korevaar & Grossman 2011).…”