(19) Case of complete androgen insensitivity syndrome with gonads containing rudimentary penile tissue and both Mullerian and Wolffian type structures

Background: Complete androgen insensitivity (CAIS) is a disorder of sexual development (DSD). It is caused by a loss of function mutation in a person with a XY genotype, where testosterone has no effect on sexual development. It is inherited in an X-linked recessive pattern, and is typically discovered in amenorrhoeic women, or girls with cryptorchid gonads that come to medical attention. Generally, gonadectomy is recommended post-puberty on an individualized basis to prevent malignancy.

Case: We present a case of a 17 year old phenotypic female with an XY karyotype who was diagnosed with familial CAIS in childhood, as her sister and maternal aunts were also affected. She presented at age 14 and on examination, had unambiguous external genitalia with a vaginal dimple, Tanner stage 4 breast development, and some axillary hair. MRI identified one abdominal and one inguinal gonad. Laboratory findings were typical of CAIS with elevated testosterone and normal FSH. She underwent a laparoscopic bilateral gonadectomy at age 17. Her pathology findings were unusual, showing dysgenetic multinodular testes with Sertoli cell hyperplasia. Additionally, there were both Wolffian and Müllerian structures represented by Walthard remnants and spermatic cord, a fallopian tube and cysts lined by Müllerian-type epithelium respectively. Of note, a nodule of penile-type tissue was also present. There was no malignancy identified.

Comments: To the author’s knowledge this is the first case of ectopic penile tissue identified in an individual with or without CAIS. Additionally, the finding of dysgenetic gonads with both Müllerian and Wolffian structures is unusual. CAIS with the persistence of Müllerian structures (fallopian tube, cervix, uterus) is rare, as the Müllerian system usually regresses due to the anti-Müllerian hormone (AMH) originating from the Sertoli cells of the gonads. Fallopian tube remnants have been reported in up to 35% of CAIS cases. Wolffian remnants in the form of epididymis and vasa deferens have been reported in up to 70% of cases. There has only been one reported case of both Wolffian and Müllerian structures in a CAIS individual with findings of vas deferens, fallopian tube, and a rudimentary uterus. CAIS is generally thought to have lower rates of malignancy than other XY-DSD conditions, as those have a higher incidence of dysgenic gonads. The risk of malignancy with CAIS in the literature is up 22%. Although there was no malignancy identified in our case it poses the question of whether such dysgenetic gonads pose an increased risk for malignant transformation in CAIS patients.