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International Journal of Endocrinology
Volume 2012, Article ID 671209, 9 pages
Research Article

Delayed Recognition of Disorders of Sex Development (DSD): A Missed Opportunity for Early Diagnosis of Malignant Germ Cell Tumors

1Department of Pathology, Erasmus MC-University Medical Center Rotterdam, Josephine Nefkens Institute, Daniel den Hoed Cancer Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands
2Centre for Reproduction and Development, Monash Institute of Medical Research, Melbourne, VIC, Australia
3Department of Pediatric Endocrinology, Erasmus MC-University Medical Center Rotterdam, Sophia, Rotterdam, The Netherlands
4Department of Radiation Oncology, Erasmus MC-University Medical Center Rotterdam, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
5Department of Pediatric Urology, Erasmus MC-University Medical Center Rotterdam, Sophia, Rotterdam, The Netherlands

Received 11 August 2011; Revised 27 September 2011; Accepted 13 October 2011

Academic Editor: Rodolfo Rey

Copyright © 2012 Remko Hersmus et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Disorders of sex development (DSD) are defined as a congenital condition in which development of chromosomal, gonadal or anatomical sex is atypical. DSD patients with gonadal dysgenesis or hypovirilization, containing part of the Y chromosome (GBY), have an increased risk for malignant type II germ cell tumors (GCTs: seminomas and nonseminomas). DSD may be diagnosed in newborns (e.g., ambiguous genitalia), or later in life, even at or after puberty. Here we describe three independent male patients with a GCT; two were retrospectively recognized as DSD, based on the histological identification of both carcinoma in situ and gonadoblastoma in a single gonad as the cancer precursor. Hypospadias and cryptorchidism in their history are consistent with this conclusion. The power of recognition of these parameters is demonstrated by the third patient, in which the precursor lesion was diagnosed before progression to invasiveness. Early recognition based on these clinical parameters could have prevented development of (metastatic) cancer, to be treated by systemic therapy. All three patients showed a normal male 46,XY karyotype, without obvious genetic rearrangements by high-resolution whole-genome copy number analysis. These cases demonstrate overlap between DSD and the so-called testicular dysgenesis syndrome (TDS), of significant relevance for identification of individuals at increased risk for development of a malignant GCT.