Pheochromocytoma and Paraganglioma in Children and Adolescents: Experience of the French Society of Pediatric Oncology (SFCE)

Abstract

Purpose The purpose of this work is to assess the clinical outcome of pediatric patients diagnosed with pheochromocytoma and paraganglioma (PPGL) detected in France since 2000. Methods A retrospective multicenter study was conducted that included all patients younger than 18 years with PPGL diagnosed in France between 2000 and 2016. Patients were identified from 4 different sources: the National Registry of Childhood Solid Tumors, the French Pediatric Rare Tumors Database, the French registry of succinate dehydrogenase (SDH)-related hereditary paraganglioma, and the nationwide TenGen network. Results Among 113 eligible patients, 81 children with available data were enrolled (41 with adrenal and 40 with extra-adrenal PPGL). At diagnosis, 11 had synchronous metastases. After a median follow-up of 53 months, 27 patients experienced a new event (n = 7 second PPGL, n = 1 second paraganglioma [PGL], n = 8 local recurrences, n = 10 metastatic relapses, n = 1 new tumor) and 2 patients died of their disease. The 3- and 10-year event-free survival rates were 80% (71%-90%) and 39% (20%-57%),respectively, whereas the overall survival rate was 97% (93%-100%)at 3 and 10 years. A germline mutation in one PPGL-susceptibility gene was identified in 53 of the 68 (77%) patients who underwent genetic testing (SDHB [n = 25], VHL [n = 21], RET [n = 2], HIF2A [n = 2], SDHC [n = 1], SDHD [n = 1], NF1 [n = 1]). Incomplete resection and synchronous metastases were associated with higher risk of events (P = .011, P = .004), but presence of a germline mutation was not (P = .11). Conclusions Most pediatric PPGLs are associated with germline mutations and require specific follow-up because of the high risk of tumor recurrence.

Pseudohypoxic pheochromocytomas and paragangliomas dominate in children

“…This may account for the lower number of patients with extra-adrenal (35%), multifocal (15%), and recurrent (11%) PPGLs. 3,21 22 This is confirmed by our data. In the Tumori Rari in Etá Pediatrica (TREP) study, however, completeness of surgery showed no statistically significant differences in EFS.…”

“…The French Pediatric Rare Tumors Database on children with PPGLs demonstrated incomplete tumor resection as significant adverse prognostic factor for events 22 . This is confirmed by our data.…”

Pheochromocytoma and paraganglioma: germline genetics and hereditary syndromes

“…Risk estimates for metastatic PCC/PGL in the pediatric population vary from 10-50% (Bausch et al, 2014, Pamporaki et al, 2017, de Tersant et al, 2020. However, there is great variation in the length of follow-up in studies, which makes exact estimates difficult to make.…”

High‐risk abdominal pediatric paraganglioma

“…Paragangliomas are extra-adrenal benign (90%) and neoplastic (10%) neuroendocrine tumors affecting neural crest derivatives, 1,2 extremely rare in pediatric practice, with only 113 children in France from 2000 to 2016 3 and a worldwide incidence of less than 0.1% of pediatric cancers. 4 Given its rarity, no standard protocol is validated and most therapeutics are discussed in national multidisciplinary meetings.…”