Extracranial Germ Cell Tumors in Children: Ten Years of Experience in Three Children’s Medical Centers in Shanghai

SIMPLE SUMMARY: A few large series of cases of extracranial germ cell tumors (GCTs) are reported in Asian children. We present a retrospective analysis of extensive scale data of pediatric extracranial GCTs from multiple centers in China. The pathological subtypes and primary sites of tumors showed a preference for occurrence at different ages. For example, sacrococcygeal tumors mostly occur in infants, while mediastinal tumors are common in adolescents. In the context of treatment strategies including platinum-based various chemotherapy regimens, the 5-year overall survival rate and event-free survival rates were 94.13% and 82.33%, respectively. There is no difference in overall survival rate among different chemotherapy regimens for children. The independent clinical factors associated with poor prognosis were that the primary tumor is located in the mediastinum and alpha-fetoprotein levels greater than 10,000 ng/L. In conclusion, the incidence rate and clinical features of extracranial GCTs in children in China are similar to those reported in Europe and the United States. The age distribution of various pathological types and primary sites reflect the characteristics of tumor cell origin of primordial germ cell (PGC) mismigration. For the malignant germ cell tumor with the primary site of mediastinum, more effective treatment regiments should be explored. ABSTRACT: Objective: The aim was to describe the clinical features of extracranial germ cell tumors (GCTs) in pediatrics and study the clinical risk factors related to survival for malignant germ cell tumors (MGCTs) in order to optimize therapeutic options. Methods: The clinical data of children with extracranial GCTs in three children’s medical centers in Shanghai were retrospectively analyzed. Results: In total, 1007 cases of extracranial GCTs diagnosed between 2010 and 2019 were included in this study, including teratomas (TERs) 706 (70.11%) and MGCTs 301 (29.89%). There were twice as many TER cases as MGCT cases. Approximately 50% of children with GCTs were <3 years old (43.39% for TERs, 67.13% for MGCTs). GCTs in children of different ages show differences in tumor anatomical locations and pathological subtypes. The 5-year event-free survival (EFS) and overall survival (OS) of all patients with MGCTs were 82.33% (95% CI, 77.32%, 86.62%) and 94.13% (95% CI, 90.02%, 96.69%), respectively. The multivariate Cox regression analysis identified a primary site in the mediastinum and alpha fetoprotein (AFP) levels ≥10,000 ng/mL as independent adverse prognostic factors (p < 0.0.0001, χ(2) = 23.6638, p = 0.0225, χ(2) = 5.2072.). There were no significant differences in OS among children receiving various chemotherapy regimens, such as the BEP, PEB, JEB and other regimens (VBP/VIP and AVCP/IEV) (p < 0.05). Conclusions: The clinical features of GCTs in Chinese pediatrics are similar to those reported in children in Europe and America. The age distribution of pathological types and primary sites in GCTs reflect the developmental origin of type I and type II GCTs transformed from mismigration primordial germ cells (PGCs). Optimizing the current platinum-based chemotherapy regimens and exploring the treatment strategies for MGCTs of the mediastinum are future research directions.