Testicular feminization syndrome.

Clinical History

Amenorrhea.

Imaging Findings

The phenotypical female patient was referred to our department for amenorrhea. Physical examination revealed normal weight and height, decreased pubic hair and normal breast development for her age. External genitalia (labia major, labia minor and clitoris) were normal in appearance, in addition with the vagina which was short and ended blindly. No cervix, uterus or ovaries were identified. Biochemical analysis showed markedly high testosterone levels (11,35ng/ml with normal values for female individuals 0,2-1,2 ng/ml), while gonadotropic hormones and estradiol levels were normal.
Ultrasound examination showed ovoid masses in both inguinal canals, with echogenicity and vascularity similar to these of a testis but with a slightly smaller size (Fig. 1). No uterus or ovaries were identified. Both kidneys were also normal.
On MRI examination testes were homogenous and showed low signal intensity in T1-weighted images and intermediate signal intensity in T2-weighted images (Fig. 2). The absence of uterus (Fig. 3) and ovaries was confirmed.
Karyotype analysis revealed a 46XY genotype and the patient underwent for surgical removal of both testes (due to high risk for malignant transformation) and reconstruction of the vagina. Hormonal replacement therapy with estrogens was started. Testosterone concentration in the blood felt to 3,50 ng/ml after the operation.
Pathologic evaluation of specimens showed testes with epididimys and elements of the spermatic cord. The efferent ductules lining was only Sertoli cells, while an increased number of Leydig cells were found in the stroma of each testis. Extensive fibrosis of each testis was identified.

Discussion

Testicular feminization syndrome or Swyer syndrome is a cause of male pseudohermaphrodism (1). It primarily presents with amenorrhea. The incidence of the syndrome is 1/20000 births to 1/64000 births (2). It is an X-linked syndrome and occurs due to a mutation to the Tfm gene, responsible for the formation of androgen receptors in the cells (3). Patients with this syndrome have the external sex characteristics of normal females, as their cells are unresponsive to androgens produced by the testes and differentiate under the influence of estrogens. The production of Mullerian inhibiting substance (MIS) or antimullerian hormone (AMH) from the Sertoli cells suppresses the paramesonephric ducts which are responsible for the formation of the uterus, uterus tubes and the upper third of the vagina.
Testes are frequently found in the inguinal canal or labial regions, but they can be found anywhere in the abdomen. There is an increased risk of malignant transformation in ectopic testes (3,6% until the age of 25 and 33% until the age of 50) (4) which usually induces surgical removal of these structures.
Ultrasound examination can easily identify the ectopic testes if they are in the inguinal canals or in the labial region. It presents however low sensitivity when the testes are intrabdominal (5).
Computed Tomography (CT) can easily localize the undescended testis from its intrabdominal position, through the inguinal canal, to its final position in the scrotum. It can also reveal any focal lesion of the testes, due to tumor formation or inflammation.
MRI examination has specific advantages over CT. It is noninvasive, lacks any ionizing radiation and obtains multiplanar images of the abdominal cavity and inguinal regions. Normal testis is high signal intensity on T2-weighted images. Undescended testis is hypointense with respect to fat on T1-weighted sequences and isointense or hyperintense with respect to fat on T2-weighted sequences.
When a testis is not seen on ultrasound, CT or MRI, Digital Subtraction Angiography (DSA) or laparoscopic or surgical exploration are performed to allow for a mandatory removal.

Differential Diagnosis List

Final Diagnosis

Testicular feminization syndrome

URL:	https://www.eurorad.org/case/2581
DOI:	10.1594/EURORAD/CASE.2581
ISSN:	1563-4086