Persistent Müllerian Duct Syndrome and Concurrent Pre-Germ Cell Neoplasia In Situ

Persistent Müllerian duct syndrome (PMDS) is a rare disorder of sex development in 46,XY individuals, characterized by the presence of Müllerian duct structures and typically associated with cryptorchidism and an elevated risk of testicular malignancy. Germ cell neoplasia in situ (GCNIS) is a known precursor to testicular germ cell tumors, but the earlier stage of pre-GCNIS remains poorly characterized, particularly in the context of PMDS. We report the first known case of pre-GCNIS identified in a patient with PMDS. A male infant presented with a non-palpable right testis and was found to have intra-abdominal gonads with Müllerian remnants. Histopathology revealed centrally located gonocytes with OCT3/4 expression but without the morphological features of GCNIS, consistent with pre-GCNIS. Management included right orchiectomy and left orchiopexy. This case highlights the underrecognized early stages of germ cell dysregulation in PMDS and raises important considerations about the timing of gonadectomy, fertility preservation, and long-term surveillance. Further research is needed to clarify the malignant potential of pre-GCNIS in DSD populations and to inform individualized, risk-based management strategies.