Pre-germ cell neoplasia in-situ in a patient with complete androgen insensitivity syndrome

Abstract

Abstract Introduction/Objective Complete androgen insensitivity syndrome is a disorder of sex development in 46, XY individuals with external female genitalia and undescended testes, often presenting with inguinal hernia in infancy and/or primary amenorrhea in adolescents. Given the increased risk for the development of germ cell neoplasms in the ectopic testis, early gonadectomy or orchidopexy may be indicated. Methods/Case Report We report a 21-year-old patient assigned female at birth (46, XY) with a history of bilateral inguinal hernia repairs (age 2) and later with lack of menarche (age 16). Additional work-up showed an elevated testosterone level (394 ng/mL) and normal luteinizing and follicle stimulating hormone values. On pelvic ultrasound, retained intraabdominal gonads were identified, but female sex organs were absent. During a gonadal relocation procedure, the gonads appeared irregular in shape with multiple cysts and small nodules, and bilateral gonadectomy was performed. Grossly, the gonads measured 4.9 and 4.3 cm with a smooth external surface and a lobulated cut surface with multiple cysts, up to 1.6 cm, containing clear, serous fluid. Histologic sections showed most seminiferous tubules were lined only by Sertoli cells with only occasional spermatogonia. Leydig cell hyperplasia and areas of ovarian-like stroma were seen. OCT4 immunostain highlighted the nuclei of individually disposed germ cells in the base of tubules (singly dispersed, non-linear pattern), raising concern for germ-cell neoplasia in-situ (GCNIS). However, the histology and staining pattern were better interpreted as diagnostic of germ cells with delayed maturation and pre-GCNIS. Additionally, OCT4 showed rare single cells within the stroma and considered to represent residual undifferentiated gonadal tissue. After gonadectomy, the patient was started on hormone replacement therapy. Results (if a Case Study enter NA) NA Conclusion This case highlights the potential pitfalls in the interpretation of OCT4 immunostain to avoid misdiagnosis of germ cell neoplasia.