**4. Peculiarities of pediatric pheochromocytoma**

The subgroup of pediatric Pheos and Pgls is still poorly studied, but the latest data stated that they have peculiarities compared to the adult population.

Pediatric Pheos and Pgls have a prevalence of 8–9% in recent studies [47], with a median age between 12 and 14 years, the youngest age reported to date is four years, and a preponderance of boys between 52.7% to 65.5% [48].

In terms of diagnosing algorithms, The European practice guidelines recommend diagnosing Pheos/Pgls plasmatic metanephrines and normetanephrine, 24-hour urinary fractionated metanephrines, and optionally chromogranin A dosing [24].

In the study of [49], the authors reported a high incidence of 70% of genetic causes of Pheos/Pgls, with pathogenic mutation, detected preferably with the use of NGS.

Considering the clinical spectrum of pediatric Pheos, the prevalence of sustained hypertension is more common in children 70% than adults (50%) [50].

Furthermore, a large majority of 70–80% of pediatric catecholamine secreting tumors are functional, making the clinical diagnosis more approachable. Moreover, 10% of the tumors can be malignant, with about 20% found at multifocal sites [50–52]. Subsequently, an increased incidence of extra-adrenal tumors of about 30% was reported in recent studies [48, 49, 53].

In terms of the genetic landscape of pediatric Pheos, to date, ten genes have been described in the medical literature in association with Pheos at a pediatric age: RET, VHL, NF1, SDHD, SDHB, SDHA, FH, MAX, HIF2A, and PHD1 [24]. Thus, clinicians should always bear in mind the high frequency of the next implicated genes: VHL mutations as the most prevalent in pediatric patients ranging from 28.0% to 49.0% of cases, followed by SDHB and SDHD, RET mutations (1.0–5.4% of cases), and NF1 gene mutations (3.0% of cases) [24, 54].

Another important aspect is that about 50% of pediatric Pheos/Pgls can recur, compared with the 15–20% proportion reported in the adult population as a 10-year probability of recurrence [3]. Subsequently, in the pediatric population, a secondary tumor can be diagnosed by 30 years, underling the necessity of proper lifelong monitoring [49, 51].
