Abstract

INTRODUCTION

Androgen insensitivity syndrome (AIS), also called testicular feminization syndrome, is a form of X-linked male pseudohermaphroditism that is clinically recognized in patients with a female phenotype. The incidence of this syndrome has been reported in 1: 20,400 newborns.

CASE REPORT

Miss AB, a 20-year-old female, attended our outpatients’ department (OPD) on 16 August 2007 with complaints of lump lower abdomen for last two months [Figure 1]. She also complained of nausea and vomiting for the last few days. She had history of primary amenorrhea and poorly developed secondary sexual characteristics. There was no history of cyclic abdominal pain, hormonal intake, radiation exposure or any chemotherapy. There was no history of significant trauma and medical or surgical illness. There was no history of any major disease in the family. She is the second child of her mother being delivered vaginally at the age of 29 years. The mother reported that the pediatrician after examining the baby told the parents that the external genitalia of the baby were inadequately developed and advised the mother to return after one year if there was no adequate development. Over time they did not turn up and she started growing up as a female although with very poor development of her secondary sex characters. She has one brother and one sister. All of them attained puberty normally and are enjoying good health.

Postoperatively she received two more cycles of adjuvant chemotherapy of the same regime.

On 25 February 2008 repeat total S. testosterone was 120 ng/dl and free testosterone 940 ng/dl.

Over four months after operation she was doing well and her secondary sexual characters were developing (breast development Tanner Stage III) after taking hormonal supplementation advised by the endocrinologist. She is on regular follow-up, she attended our OPD for checkup on 20 October 2009 with no evidence of disease clinically, USG was within normal limits and normal S. AFP.

DISCUSSION

In androgen insensitivity syndrome (AIS), there is failure of normal masculinisation of the external genitalia in chromosomally male individuals. This failure of virilisation can be either complete androgen insensitivity syndrome (CAIS), or partial androgen insensitivity syndrome (PAIS), depending on the amount of residual receptor function. In post-pubertal patients, the most frequent cause for consultation is primary amenorrhea; however, in pre-pubertal patients, inguinal hernia may be the only symptom. The diagnosis of CAIS /male pseudohermaphroditism (46, XY) can be difficult in the neonate period, sometimes the only clue to suggest the diagnosis is an inguinal hernia in these females, who display a normal phenotype. Newborn girls with inguinal hernias have a 1.6% incidence of being male pseudohermaphrodites (46, XY) and should undergo a prompt karyotype analysis.

The karyotype is 46 XY, although cases with chromosomal mosaicism have also been reported.[1] Individuals with CAIS have female external genitalia with normal labia, clitoris and vaginal introitus. The phenotype of individuals with PAIS may range from mildly virilized female external genitalia, clitorimegaly without other external anomalies to mildly undervirilized male external genitalia (hypospadias and/or diminished penile size).[2–4]

The basic etiology of AIS is a loss of function mutation in the androgen receptor (AR) gene. This AR gene has been localized to the long arm of the X chromosome (i.e. Xq11-13). Over 200 such mutations have been described, including complete and partial gene deletions, point mutations, and small insertions/deletions.[5]

In patients with CAIS, the testes should be removed after pubertal development is complete to prevent malignant transformation. In patients with cryptorchidism, the risk of developing germ cell tumor is increased fourfold to eightfold. The risk is 1% if the testis is retained in the inguinal canal. The risk of developing germ cell tumor when a cryptorchid testis is intra-abdominal is about 5%. Almost half of the testicular neoplasms are malignant (dysgerminoma), but transformation usually does not occur until after puberty. In patients who develop virilisation and have an XY karyotype, the testes should be removed immediately to preserve the female phenotype and female gender identity. Bilateral laparoscopic gonadectomy is the preferred procedure for removal of intra-abdominal testes.[6–7]

The histology in our case was typical of non-seminomatous germ cell tumor embryonal carcinoma, which mostly occurs in the 20-30 years age group. These tumors are more aggressive than seminomas. Although pure embryonal cell carcinoma constitutes about 3% of testicular germ cell tumor, if one includes the mixed tumors, then embryonal carcinoma cells is present in about 45% of testicular germ cell tumors.[8]

Our patient had omental metastasis which is very rare with few reported cases but at the same time it is difficult to explain if it is due to seedling or due to prior FNAC.[9] Management of non-seminomatous germ cell tumor Stage III constitutes neoadjuvant chemotherapy with BEP regime followed by surgery and the overall cure rate is around 50–70%, depending on risk factors.

Footnotes