Usefulness of Histological Studies in Patients with the Androgen Insensitivity Syndrome

Abstract

Androgen receptor (AR) gene mutations are responsible for 15–20 % of disorders of sexual development (DSD). Over 1100 mutations have been described. When the genetic alteration, phenotype, and gonadal histology are compared, a huge discrepancy is observed. This has led in practice to maintaining the clinical classification to which the genetic alteration is ascribed. Three types are distinguished depending on the degree of response of the external genitalia to androgens: complete androgen insensitivity (CAIS), partial androgen insensitivity (PAIS), and mild androgen insensitivity (MAIS). The diagnosis in childhood is difficult; most patients with CAIS consult in adulthood by amenorrhea, patients with PAIS after several interventions for hypospadias repair or testicular descent, and patients with MAIS by gynecomastia and infertility. What can histology contribute? Clearly it will not solve all problems, but in the first place, it is essential to detect the most serious one – is this a patient carrying a germ cell neoplasia in situ (GCNIS) or is it not? And depending on the answer to this question, to which age can the gonadectomy be delayed? Secondly, histology assesses the degree of spermatogenesis in patients with mild or partial insensitivity to androgens, in order to prescribe a treatment that will restore fertility. And thirdly, to show that the pathways by which androgens act on spermatogenesis and the masculinization of the external genitalia are different.