title: Recent advances in understanding the etiology and pathogenesis of pediatric germ cell tumors.
abstract: Pediatric germ cell tumors (GCTs) are rare neoplasms arising predominantly in the gonads and sacrococcygeal, mediastinal, and intracranial localizations. In this article, we review current knowledge of pathogenesis of pediatric GCTs, which differs from adult/adolescent GCTs. One distinctive feature is the absence of a progenitor stage, such as carcinoma in situ or gonadoblastoma, which are seen in adult/adolescent GCTs, except spermatocytic seminoma. The primordial germ cell (PGC) is the suggested origin of all GCTs, with variations in histology reflecting differentiation stage. Expression of pluripotency transcription factors OCT-3/4, NANOG, and AP-2γ in germinomas/seminomas/dysgerminomas is consistent with retaining a germ cell phenotype. Teratomas, in contrast, develop through a pathway of aberrant somatic differentiation of immature germ cells, and the yolk sac tumors and choriocarcinomas result from abnormal extraembryonic differentiation. In pediatric GCTs, origin is suggested at an earlier developmental stage because of predisposing genetic factors, although responsible genes remain largely unknown. Some extragonadal GCTs have been linked to overexpression of the KIT/KITLG system, allowing for survival of aberrantly migrated ectopic PGCs. Infant gonadal/sacrococcygeal GCTs may be caused by apoptosis-related pathways, consistent with an association with polymorphisms in BAK1. Although recent advances have identified candidate pathways, further effort is needed to answer central questions of pathogenesis of these fascinating tumors.
authors.affiliation: *Department of Growth and Reproduction †Department of Pediatrics, University Hospital of Rigshospitalet, Copenhagen ‡Department of Pediatrics, University Hospital of Hilleroed, Hilleroed, Denmark.
authors.forename: Christiane H
authors.initials: CH
authors.lastname: Mosbech
authors.forename: Catherine
authors.initials: C
authors.lastname: Rechnitzer
authors.forename: Jesper S
authors.initials: JS
authors.lastname: Brok
authors.forename: Ewa
authors.initials: E
authors.lastname: Rajpert-De Meyts
authors.forename: Christina E
authors.initials: CE
authors.lastname: Hoei-Hansen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005833:Genital Neoplasms, Female / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005834:Genital Neoplasms, Male / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D009373:Neoplasms, Germ Cell and Embryonal / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012445:Sacrococcygeal Region / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins