The incidence of pheochromocytoma and paraganglioma (PPGL) in the pediatric population is estimated to be 0.2 - 0.3 cases per million children, whereas the incidence of malignant PPGLs is about 0.02 cases per million children. The recent study of Pamporaki et al. included 748 patients with PPGLs, in which 95 patients had first presentation during childhood (18 years of age or younger). Children showed statistically higher prevalence than adults of hereditary (80.4% vs 52.6%), extra-adrenal (66.3% vs 35.1%), multifocal (32.6% vs 13.5%), metastatic (49.5% vs 29.1%), and recurrent (29.5% vs 14.2%) PPGLs. Tumors due to cluster 1 mutations were more prevalent among children than adults (76.1% vs 39.3%; P < 0.0001) and this paralleled a higher prevalence of noradrenergic tumors in children than in adults (93.2% vs 57.3%). This and other studies also showed that extra-adrenal PGLs were mainly located in the abdomen. Previously, we have also showed a higher rate of SDHB-related metastatic and primary PPGL in children than in adults. This data suggested that all pediatric patients with PPGLs should undergo genetic testing and appropriate imaging as a guide for further treatment and follow-up. This also applies to HIF2A-related pediatric PPGLs, where recurrence, multiplicity, and metastasis is very common and often multiple surgeries are needed to control tumor growth and polycythemia.
Imaging algorithm for pediatric PPGL should be carefully considered due to several factors: 1. it is expected that in children with hereditary PPGLs, these tumors will recur and present as multiple/metastatic; 2. life-long follow-up is necessary; 3. radiation using CT should be limited to avoid radiation overexposure; 4. follow-up guidelines for children with hereditary PPGLs are not available. Therefore, appropriate effort must be initiated to establish such guidelines that will also include appropriate biochemical surveillance and other aspects. Recent data has suggested that at least in patients with metastatic and head and neck PPGLs, DOTA-analogs with 68Ga can be very useful and should be coupled with anatomical imaging, especially when surgery is planned. Regarding new unpublished data on pediatric patients, it is noted that 68Ga-DOTATATE PET/CT is also very useful in SDHB-related pediatric patients but it can be inferior to detect abdominal PGLs, where the correct detection of these tumors must be coupled with anatomical imaging and/or ultrasound. For HIF2A-related PPGLs in pediatric patients, we have recently shown that 18F-FDOPA is the functional imaging modality of choice.
Finally, new data on the pediatric population of patients with PPGLs showed that a prevalence of attention deficit hyperactivity disorder (ADHD) was 21% in our patients, which was significantly higher than 7.2% seen in the general pediatric population.
Acknowledgements
This research was supported by the Intramural Research Program of the NICHD/NIH.
Pamporaki et al. JCEM 2017; 102:1122.