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.