Functional Imaging Signature of Patients Presenting with Polycythemia/Paraganglioma Syndromes

Abstract

Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau gene. Recently, mutations in the prolyl hydroxylase gene (PHD) 1 and 2 and in the hypoxiainducible factor 2 a (HIF2A) were also found to be associated with multiple and recurrent PPGL. Such patients also presented with PPGL and polycythemia, and later on, some presented with duodenal somatostatinoma. In additional patients presenting with PPGL and polycythemia, no further mutations have been discovered. Because the functional imaging signature of patients with PPGLpolycythemia syndromes is still unknown, and because these tumors (in most patients) are multiple, recurrent, and metastatic, the goal of our study was to assess the optimal imaging approach using 4 different PET radiopharmaceuticals and CT/MRI in these patients. Methods: Fourteen patients (10 women, 4 men) with confirmed PPGL and polycythemia prospectively underwent 68 Ga-DOTATATE (13 patients), 18 F-FDG (13 patients), 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) (14 patients), 18 F-fluorodopamine ( 18 F-FDA) (11 patients), and CT/MRI (14 patients). Detection rates of PPGL lesions were compared between all imaging studies and stratified between the underlying mutations. Results: 18 F-FDOPA and 18 F-FDA PET/CT showed similar combined lesion-based detection rates of 98.7% (95% confidence interval [CI], 92.7%-99.8%) and 98.3% (95% CI, 90.9%-99.7%), respectively. The detection rates for 68 Ga-DOTATATE (35.3%; 95% CI, 25.0%-47.2%), 18 F-FDG (42.3; 95% CI, 29.9%-55.8%), and CT/MRI (60.3%; 95% CI, 48.8%-70.7%) were significantly lower (P , 0.01), irrespective of the mutation status. Conclusion: 18 F-FDOPA and 18 F-FDA are superior to 18 F-FDG, 68 Ga-DOTATATE, and CT/MRI and should be the radiopharmaceuticals of choice in this rare group of patients.

Performance of 68Ga-DOTA–Conjugated Somatostatin Receptor–Targeting Peptide PET in Detection of Pheochromocytoma and Paraganglioma: A Systematic Review and Metaanalysis

“…The detection rates of 68 Ga-DOTA-SST PET and other imaging modalities ( 18 F-FDOPA PET, 18 F-FDG PET, and 123/131 I-MIBG scanning) are illustrated in Figure 3. 68 Ga-DOTA-SST PET consistently showed a higher detection rate than 18 F-FDOPA PET, 18 F-FDG PET, and 123/131 I-MIBG scintigraphy, with the exception of one study regarding polycythemia/paraganglioma syndrome (45). In that study, 68 Ga-DOTA-SST PET showed the lowest detection rate of 35% (95% confidence interval [CI], 24%-48%), whereas the detection rate for 18 F-FDOPA PET was 99% (95% CI, 93%-100%).…”

“…Thus, 13 studies were included in the qualitative synthesis. We further excluded 4 studies that had exclusive patient populations: SDHB mutation (22), SDHx mutation in pediatric patients (24), sporadic type (23), and polycythemia/paraganglioma syndrome (45); inclusion of those studies might hinder generalization of the results. Therefore, 9 studies (215 patients) with no specific inclusion criteria for subtype were included in the metaanalysis (13)(14)(15)(16)(17)(18)(19)(20)(21), with the assumption that this pooled population might reflect patients with unknown genetic status in clinical practice.…”

“…Study and clinicopathologic characteristics are described in Tables 1 and 2, respectively. Seven studies used histopathology and BVC as the reference standard (13,(17)(18)(19)(20)(21)45), whereas 6 used only BVC (14)(15)(16)(22)(23)(24). The imaging modalities used for BVC included CT, MRI, 18 F-FDG PET, 18 F-FDOPA PET, and MIBG scintigraphy.…”

“…The imaging modalities used for BVC included CT, MRI, 18 F-FDG PET, 18 F-FDOPA PET, and MIBG scintigraphy. 68 Ga-DOTA-SST PET was performed for primary staging in 4 (15,(18)(19)(20), restaging in 2 (22,45), and staging or restaging in 7 studies (13,14,16,17,21,23,24). Radioligands were DOTATATE in 9 (13-15,18,21-24,45), DOTATOC in 2 (16,17), and DOTANOC in 2 studies (19,20).…”

“…Regarding the patient selection domain, 3 studies had an unclear risk of bias because they were retrospective, and it was not reported whether patients were consecutively enrolled (16)(17)(18). There was a high concern of applicability in 4 studies, as they only included patients with a specific genetic status or phenotypic subtype (15,22,24,45). Regarding the index test domain, there was an unclear risk of bias in 3 studies, as it was unclear whether the index test was interpreted without knowledge of the reference standard (14,18,21).…”