Pediatric patients with pheochromocytoma and paraganglioma should have routine preoperative genetic testing for common susceptibility genes in addition to imaging to detect extra-adrenal and metastatic tumors

Abstract

Background Pediatric pheochromocytomas and paragangliomas (PC/PGLs) are rare with limited data as to what the optimal management approach is. The aim of this study was to determine the role of genetic testing and imaging to detect extra-adrenal and/or metastatic tumors in pediatric PC/PGLs. Methods A retrospective study of 55 patients diagnosed at ≤ 21 years of age with PC/PGLs was performed with analysis of data on genetic testing and multimodal imaging. Results Eighty percent of patients (n=44/55) had a germline mutation. The majority were found to have either VHL (38%) or SDHB (25.4%) mutation. PC was present in 67% (n=37/55) of patients and was bilateral in 51.3% (n=19/37). The majority of patients with bilateral PC had VHL (79%). Abdominal PGL was present in 21.8% (n=12/55), head and neck PGL in 11% (n=6/55) and thoracic PGL in 3.6% (n=2/55) of patients. For PGL, SDHx accounted for 72% (n=13/18) of mutations. The rate of malignancy was 16.4% (n=9/55), 55.5% had SDHB mutations. In two-thirds of patients, functional imaging identified either extra-adrenal PGL and/or metastatic disease. Conclusions The majority of pediatric patients with PC/PGL have germline mutations. Therefore, all pediatric patients with PC/PGLs require genetic testing and imaging to detect extra-adrenal PGL and metastatic disease to guide treatment and follow up.

Characteristics of pediatric pheochromocytoma/paraganglioma

“…[3456] Similar percentages of extra-adrenal PCC/PGL are also reported by Stackpole et al . (31%) and Ross (28%).…”

“…[7] However, lower prevalence (31%–64%) of hypertension in other studies, may suggest even lower prevalence of sustained hypertension in those studies. [39] Considering the data from above-mentioned studies, it is likely that the prevalence of hypertension is not very high as previously thought and approximately only 70% of pediatric PCC/PGL may have sustained hypertension.…”

Preoperative selective vs non-selective α-blockade in PPGL patients undergoing adrenalectomy

“…Surgical resection, the only curative therapy, still carries a high intraoperative risk of causing massive catecholamine release into the circulation ( 6 ). This leads to a complex series of intraoperative hemodynamic instability issues during adrenalectomy for pheochromocytomas, including rapid and severe blood pressure fluctuations that greatly increase the risk of major morbidity ( 7 ). Anesthetic induction, intraoperative tumor handling and accidental squeezing of the tumor can instantly increase catecholamine release, resulting in severe intraoperative hypertensive crisis and potentially stroke, myocardial infarction and other severe complications ( 8 ).…”

Nationwide study of patients with head and neck paragangliomas carrying SDHB germline mutations

“…A later start for tumour screening has been proposed based on statistical models of the age‐dependent penetrance of SDHB mutations and, although the mean age in this cohort was relatively high, the youngest patient developed an HNPGL at age 11 years, and an 18‐year‐old patient had already developed PGL metastases. The optimal age to start screening for PGLs in SDHB mutation carriers thus remains a subject of debate19, 20, 21.…”