Delayed recognition of disorders of sex development (DSD): A missed opportunity for early diagnosis of malignant germ cell tumors

Remko Hersmus, Hans Stoop, Stefan White, Stenvert Drop, Jan Oosterhuis, Luca Incrocci, Katja Wolffenbuttel, Leendert Looijenga

    Research output: Contribution to journalArticleResearchpeer-review

    25 Citations (Scopus)

    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.
    Original languageEnglish
    Article number671209
    Pages (from-to)1 - 9
    Number of pages9
    JournalInternational Journal of Endocrinology
    Volume2012
    DOIs
    Publication statusPublished - 2012

    Cite this

    Hersmus, Remko ; Stoop, Hans ; White, Stefan ; Drop, Stenvert ; Oosterhuis, Jan ; Incrocci, Luca ; Wolffenbuttel, Katja ; Looijenga, Leendert. / Delayed recognition of disorders of sex development (DSD): A missed opportunity for early diagnosis of malignant germ cell tumors. In: International Journal of Endocrinology. 2012 ; Vol. 2012. pp. 1 - 9.
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    title = "Delayed recognition of disorders of sex development (DSD): A missed opportunity for early diagnosis of malignant germ cell tumors",
    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.",
    author = "Remko Hersmus and Hans Stoop and Stefan White and Stenvert Drop and Jan Oosterhuis and Luca Incrocci and Katja Wolffenbuttel and Leendert Looijenga",
    year = "2012",
    doi = "10.1155/2012/671209",
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    Hersmus, R, Stoop, H, White, S, Drop, S, Oosterhuis, J, Incrocci, L, Wolffenbuttel, K & Looijenga, L 2012, 'Delayed recognition of disorders of sex development (DSD): A missed opportunity for early diagnosis of malignant germ cell tumors', International Journal of Endocrinology, vol. 2012, 671209, pp. 1 - 9. https://doi.org/10.1155/2012/671209

    Delayed recognition of disorders of sex development (DSD): A missed opportunity for early diagnosis of malignant germ cell tumors. / Hersmus, Remko; Stoop, Hans; White, Stefan; Drop, Stenvert; Oosterhuis, Jan; Incrocci, Luca; Wolffenbuttel, Katja; Looijenga, Leendert.

    In: International Journal of Endocrinology, Vol. 2012, 671209, 2012, p. 1 - 9.

    Research output: Contribution to journalArticleResearchpeer-review

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    T1 - Delayed recognition of disorders of sex development (DSD): A missed opportunity for early diagnosis of malignant germ cell tumors

    AU - Hersmus, Remko

    AU - Stoop, Hans

    AU - White, Stefan

    AU - Drop, Stenvert

    AU - Oosterhuis, Jan

    AU - Incrocci, Luca

    AU - Wolffenbuttel, Katja

    AU - Looijenga, Leendert

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