Case 3: Cancer predisposition associated with polycythemia and multiple functional paragangliomas (Pacak-Zhuang syndrome).
A 16-year-old female with somatic mosaicism for an activating mutation in the EPAS1 (HIF2A ) gene leading to polycythemia and paraganglioma (Pacak-Zhuang syndrome) was found to have a right suprarenal mass and 3 additional retroperitoneal masses. These were resected and identified as paragangliomas16. Surveillance whole-body MRI (wbMRI) obtained almost 2 years later identified a 1.5 cm left suprarenal mass. Plasma normetanephrine levels were slowly rising, and re-staging 18F-FDG PET demonstrated an FDG-avid suprarenal mass, as well as additional small FDG-avid retroperitoneal nodules concerning for paragangliomas which had not been identified on the earlier MRI exams (Fig. 3A-D).18F-FDG PET/CT obtained 6 months later for continued clinical progression (worsening hypertension along with progressive elevations in normetanephrine and chromogranin A levels) was limited secondary to a marked increase in hypermetabolic brown fat activity that presumably resulted from the elevated serum catecholamines (Fig. 3E), a phenomenon that has been described in adult PGL patients with elevated catecholamines17. This degree of intense brown fat uptake, in addition to obscuring primary tumor sites along the sympathetic chain, has a “sink effect”, with the marked increase in FDG uptake in brown fat FDG uptake limiting availability of tracer for detecting disease elsewhere. Tracers targeting somatostatin receptors are unaffected by elevated catecholamines and a subsequent68Ga-DOTATATE PET, performed 2 weeks after the patient started systemic targeted therapy16, clearly demonstrated the left suprarenal lesion and the para-aortic paraganglioma (Fig. 3F-K), with no other sites of disease seen.