Age-Dependent Presentation and Clinical Course of 1465 Patients Aged 0 to Less than 18 Years with Ovarian or Testicular Germ Cell Tumors; Data of the MAKEI 96 Protocol Revisited in the Light of Prenatal Germ Cell Biology.

Gabriele Calaminus,Angelika Eggert,Dietrich Von Schweinitz,Jalid Sehouli,Thomas Klingebiel,Raimund Stein,Christian P Kratz,Thomas A Olson,Heribert Jürgens,Michael Dworzak,Peter Albers,Nicolas U Gerber,Alexander Claviez,Birgit Fröhlich,Leendert Looijenga,Jörg Faber,Dominik T Schneider,Nacera Infed,Stefan Schönberger,Christian Vokuhl,Martin L Metzelder ,D Harms ,U Göbel

doi:10.3390/cancers12030611

Abstract

Objective: To evaluate prognostic factors in pediatric patients with gonadal germ cell tumors (GCT). Methods: Patients <18 years with ovarian and testicular GCT (respectively OGCT and TGCT) were prospectively registered according to the guidelines of MAKEI 96. After resection of the primary tumor, patients staged ≥II received risk-stratified cisplatin-based combination chemotherapy. Patients were analyzed in respect to age (six age groups divided into 3-year intervals), histology, stage, and therapy. The primary end point was overall survival. Results: Between January 1996 and March 2016, the following patients were registered: 1047 OGCT, of those, 630 had ovarian teratoma (OTER) and 417 had malignant OGCT (MOGCT); and 418 TGCT, of those, 106 had testicular teratoma (TTER) and 312 had malignant TGCT (MTGCT). Only in MTGCT, older age correlated with a higher proportion of advanced tumors. All 736 teratomas and 240/415 stage I malignant gonadal GCT underwent surgery and close observation alone. In case of watchful waiting, the progression rate of OGCT was higher than that of TGCT. However, death from disease was reported in 8/417 (1.9%) MOGCT and 8/312 (2.6%) MTGCT irrespective of adjuvant chemotherapy and repeated surgery. Conclusions: The different pathogenesis and histogenesis of gonadal GCT reflects sex- and age-specific patterns that define clinically relevant risk groups. Therefore, gender and age should be considered in further research on the biology and clinical practice of pediatric gonadal GCT.

Highlights

Teratomas (TER) and malignant germ cell tumors (MGCT) constitute a heterogeneous group of germ cell tumors (GCT)
Of boys aged 3–12 years, only one out of 10 was identified as type II GCT [20]. These findings indicate that the presentation of gonadal and extragonadal GCT in infants, children, and adolescents may reflect different developmental pathways, which still have to be elucidated [21,22,23]
Our data, representing the largest series of TER to date, show a distinct difference in behavior between ovarian teratoma (OTER) and testicular teratoma (TTER), which underlines the influence of sex in the development and presentation of this disease

Summary

Introduction

Teratomas (TER) and malignant germ cell tumors (MGCT) constitute a heterogeneous group of germ cell tumors (GCT). Malignant testicular gonadal germ cell tumors (MTGCT) are the most frequent solid cancer of men aged 18 to 45 years and encompass about 92.5% of all MGCT. Malignant ovarian GCT (MOGCT) and malignant extragonadal GCT (MEGCT) are rare and account for only 3.9% and 3.6% of all MGCT, respectively [1,2,3]. MGCT develop at extragonadal sites, demonstrating the difference in clinical presentation of the various entities; among gonadal GCT in children and adolescents, 60% are MOGCT and 40% are MTGCT. Detailed analysis of epidemiological GCT data has demonstrated characteristic patterns and a significant correlation between gender and age in respect to tumor histology, site, and stage [4]. The prognosis of GCT correlates with therapy, in particular with the completeness of tumor resection [5,6,7]

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