Institutional members access full text with Ovid®

Share this article on:

Recent Advances in Understanding the Etiology and Pathogenesis of Pediatric Germ Cell Tumors

Mosbech, Christiane H. BSc; Rechnitzer, Catherine MD, DMSc; Brok, Jesper S. MD, PhD; Rajpert-De Meyts, Ewa MD, DMSc; Hoei-Hansen, Christina E. MD, DMSc

Journal of Pediatric Hematology/Oncology: May 2014 - Volume 36 - Issue 4 - p 263–270
doi: 10.1097/MPH.0000000000000125
Medical Progress

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.

*Department of Growth and Reproduction

Department of Pediatrics, University Hospital of Rigshospitalet, Copenhagen

Department of Pediatrics, University Hospital of Hilleroed, Hilleroed, Denmark

Supported by The Danish Cancer Society, The Danish Child Cancer Foundation.

The authors declare no conflict of interest.

Reprints: Christina E. Hoei-Hansen, MD, DMSc, Department of Pediatrics, University Hospital of Hilleroed, Dyrehavevej 29, DK—3400 Hilleroed, Denmark (e-mail:

Received November 16, 2013

Accepted January 15, 2014

Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.