Delayed Recognition of Disorders of Sex Development (DSD): A Missed Opportunity for Early Diagnosis of Malignant Germ Cell Tumors. (19th January 2012)

• Record Type: Journal Article
• Authors: Hersmus, Remko; Stoop, Hans; White, Stefan J.; Drop, Stenvert L. S.; Oosterhuis, J. Wolter; Incrocci, Luca; Wolffenbuttel, Katja P.; Looijenga, Leendert H. J.
• Other Names: Rey Rodolfo Academic Editor.
• Is Part Of: International journal of endocrinology. Volume 2012(2012)
• Publication Date: 2012-01-19
• Subjects: Endocrinology -- Periodicals; Endocrinology; Endocrinology -- Periodicals; Endocrine System Diseases -- Periodicals; Periodicals; 616.4
• DOI: 10.1155/2012/671209
• Languages: English
• ISSNs: 1687-8337

Abstract

Abstract : 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.