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

Figure 1

Immunohistochemical staining and fluorescent in situ hybridization (FISH) of the gonadoblastoma and carcinoma in situ lesions of patient 1. (a) Representative hematoxylin and eosin staining. The germ cells present in the GB and CIS stain positive for (b) OCT3/4 (brown), (c) TSPY (red), and (d) SCF (brown). (e) The supportive cells in the CIS lesion are SOX9 positive (brown staining) and are negative for FOXL2. (f) In the GB, the supportive cells stain positive for FOXL2 (brown staining) and are negative for SOX9. (a–f) In every image the GB lesion is shown on the left side (embryonic germ cells intermixed with granulose-like supportive cells), CIS containing seminiferous tubules on the right side (CIS cells associated with Sertoli cells on the basal lamina). Magnification 200x and 400x for all. Slides (b)–(f) are counterstained with hematoxylin. (g) Representative FISH with Y-centromere-specific probe (shown in red) and X-centomere-specific probe (shown in green). Magnification 630x. (h) Schematic representation of the different moments in time of clinical intervention, blue arrow, identification of a malignant type II germ cell tumor, together with GB and CIS as precursor lesions at the age of 26 years. Review of the clinical history showed hypospadias and cryptorchid testes, signs of TDS/DSD which were not recognized at an early age. Grey-dashed arrows; early recognition of TDS/DSD could have allowed early detection and treatment of the malignancy, thereby, preventing the need for additional systemic treatment.