Functional imaging for pheochromocytoma-paraganglioma: a step closer to understanding its place in clinical practice.

Abstract

Pheochromocytomas–paragangliomas (PPG) are rare tumors that, when originating in the adrenal medulla or sympathetic paraganglia, are characterized by increased synthesis and secretion of catecholamines and expression of catecholamine reuptake transporters. Furthermore, as neuroendocrine tumors, PPG may express cell membrane somatostatin receptors. These characteristics make PPG amenable to various functional imaging (FI) modalities that, in conjunction with anatomic imaging (AI) such as computed tomography (CT) and magnetic resonance imaging (MRI), can assist with the localization and characterization of these unique neoplasms. Several FI modalities are currently available, including (i) target catecholamine physiology [Ior I-meta-iodobenzylguanidine (MIBG); F-fluoro-dihydroxyphenylalanine (F-DOPA) positron emission tomography (PET); Ffluorodopamine (F-FDA) PET], (ii) identify somatostatin receptor expression [In-DTPA-pentetreotide (octreotide); Ga-DOTATATE PET], or (iii) target increased tumoral glucose uptake [F-fluorodeoxyglucose (FDG) PET]. The role of FI in the routine evaluation of PPG remains poorly studied, partly due to the rarity of these tumors and the fact that few centers see large numbers of such patients, which makes prospective hypothesis-driven studies difficult to achieve. Additionally, although some FI studies (such as MIBG and FDG-PET scans) are widely available for clinical use, other modalities remain experimental and difficult to obtain outside of a clinical research setting. Furthermore, all FI technologies are expensive, and the cost-effectiveness of FI as part of routine clinical practice has not been studied. The current study by Brito and colleagues [1] was commissioned by the Endocrine Society as it developed its inaugural PPG guideline [2], and the goal of the study was to describe the additive benefit of FI in PPG patients who had undergone routine AI with CT/MRI. Brito et al. [1] conducted a systematic literature review of 32 studies published from 1983 to 2012 that evaluated FI in patients with biochemically proven PPG. The systematic review included data from 1264 patients and used a clearly defined methodology. The authors found that FI testing incrementally aided in PPG localization in only 21/1445 (1.5 %) primary tumors and 28/805 (3.5 %) of metastases, leading them to conclude that FI tests have a limited role in the routine diagnostic evaluation of PPG. In fact, in more than 95 % of patients with resectable disease, CT/MRI scans were sufficient for determining appropriate treatment. Furthermore, in malignant PPG, F-DOPA PET, and FFDA PET were the most successful at identifying lesions not detected via AI, providing additional benefit in 6/60 (10 %) and 5/78 (6.4 %) cases, respectively. Although a good first step in better understanding the utility of FI in the diagnosis of PPG, the current study has some unavoidable limitations. All of the studies examined lacked a control group, and most of these were retrospective in nature. Furthermore, some studies evaluated PET without simultaneous CT likely reducing the PET performance for localizing PPG. In addition, many of the primary studies did not include relevant information on the clinical and genetic aspects of PPG that have been delineated over the last decade (e.g., genotype analysis, biochemical phenotype, and clinical factors that help predict malignant & Camilo Jimenez cjimenez@mdanderson.org