Giant Seminoma in a Patient With 5α-Reductase Type 2 Deficiency

Abstract

A 49-year-old Japanese phenotypic female was referred for a giant inguinal mass. The parents and maternal half brother were reported to be phenotypically normal, and there was no family history of male pseudohermaphroditism or consanguinity. The parents were divorced shortly after the patient was born, and the patient was reared by her mother. However, at presentation the mother had been deceased for 30 years and, thus, detailed familial information, such as place of parental birth, was not available. Physical examination revealed a giant mass in the left inguinal region and a small testis-like mass in the right inguinal region. The patient had a masculine habitus with no breast development, moderate pubic hair (Tanner stage 3), an enlarged clitoris (5 cm. in stretched length) and a blind ending vagina. The karyotype was 46 XY in all 30 lymphocytes analyzed. Endocrine data were consistent with 5 reductase type 2 deficiency. Basal serum luteinizing hormone was 16.5 IU/l. (adult male normal 1.0 to 8.4), folliclestimulating hormone 56.5 IU/l. (1.0 to 10.5), testosterone 14.7 nmol./l. (11.2 to 50.0), 5 -dihydrotestosterone 0.38 nmol./l. (0.87 to 2.60) and testosterone-to-5 -dihydrotestosterone ratio 39 (12 to 20). She also appeared to manifest abnormal gender role behavior, as has often been reported with this condition.2 Although the patient was raised as a female and recognized herself as a female, she had never sought medical evaluation despite the absence of pubertal development and menarche, and had remained single and was living with another woman. After obtaining informed consent, mutational analysis was performed for the SRD5A2 gene encoding steroid 5 reductase type 2. In brief leukocyte genomic DNA was amplified with the primers for all 5 exons and their flanking introns of SRD5A2 by polymerase chain reaction, and the products were subjected to direct sequencing from both directions.2 Consequently a homozygous C16T transversion resulting in a substitution of the sixth glutamine codon by stop codon (Q6X) was identified. This transversion was absent in a total of 100 normal individuals. The patient underwent surgical exploration for the bilateral masses. Macroscopically the large left mass was an 11 10 8 cm. solid tumor with extensive necrosis and focal hemorrhage, and the small right mass was an atrophic testis 2 to 3 ml. in volume. There was no discernible invasion of adjacent tissues or metastasis to the retroperitoneal lymph nodes. Wolffian structures were well developed, and mullerian structures were absent. Microscopically the solid tumor showed typical findings of seminoma, and the right testis displayed dysgenetic features, such as hyalinized seminiferous tubules, Leydig cell hyperplasia and defective spermatogenesis without carcinoma in situ (see figure). Subsequently the patient received local irradiation therapy. Estrogen supplementation therapy was not started because of her advanced age and refusal. She was healthy at 12-month followup.