Updating on the Management of Germ-Cell Tumors in Disorders of Sex Development: Intratubular Germ-Cell Neoplasia, Unclassified Type in a 46,XY DSD Patient with Persistent Müllerian Duct Syndrome

Introduction

The significantly increased risk for developing specific types of malignancies is clinically and biologically relevant in patients with disorders of sex development (DSD). Moreover, those patients who bear Y chromosome material in their karyotype are at increased risk for the development of type II germ-cell tumors (GCTs), arising from early fetal germ cells.[1] Intratubular germ-cell neoplasia of unclassified type (ITGCNU) in testicular tissue and gonadoblastoma in the gonads without an obvious testicular differentiation represent the precursor lesions of most GCTs.[2] ITGCNU is characterized by the presence of germ cells in the seminiferous tubules, located on their basement membrane.[3] Clinically asymptomatic, usually constitutes a microscopic finding when a testicular biopsy is performed. Small atrophic testis, family history for testicular cancer, history of infertility, and cryptorchidism are considered the other risk factors for ITGCNU. An early diagnosis of precursor lesions of GCTs is nowadays possible and advisable, thanks to the use of immunohistochemical methods. OCT ¾,[4] [5] NANOG,[6] and AP-2γ[7] are transcription factors critically involved with self-renewal of undifferentiated embryonic stem cells whose positivity on immunohistochemistry is highly predictive of malignancy in GCTs. Considering that ~50% of patients with a testicular biopsy positive for ITGCNU have developed invasive tumor at 5 years follow-up,[8] an early diagnosis and a prompt treatment according to the guidelines for type II GCTs are mandatory. In this case report, we describe a case of ITGCNU in a 46,XY DSD patient with a persistent müllerian duct syndrome (PMDS). The literature review on the association between ITGCNU and DSD and its current management is also performed showing a well-known correlation between ITGCNU and testicular microlithiasis,[9] but the description of ITGCNU in DSD patients as a remarkable point has not yet been described.

• References

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