TESTICULAR TUMOURS IN INTERSEX STATES
Gonadoblastoma is a dysgenetic gonadoma that does not metastasize but which may be associated with dysgerminoma and other malignant germ cell elements. An overwhelming majority (96 %) of gonadoblastomas develop in dysgenetic gonads of 46XY individuals. Most patients with this Tumours are phenotypic females, the rest are phenotypic males with abnormalities of the genitalia and undescended testes. The Tumours is frequently bilateral, usually develops in the second decade, and may secrete estrogens or testosterone.
Germ cell Tumours are rarely seen in individuals with gonadal dysgenesis who do not have any Y-chromosomal material present. Thus, girls with Turner syndrome with the chromosomal constitution 45,X;45,X/46,XX;46,X,del(Xp) or 46,X,del(Xq) are not at an increased risk of this Tumours, but in cases of gonadal dysgenesis due to chromosomal mosaicism such as 45,X/46,XY, or where a Y fragment is present, gonadoblastomas are a significant risk in the dysgenetic gonads, perhaps occurring in up to 20 % of cases. However, in a population-based study of girls with Turner syndrome, analyzed by PCR to detect Y-chromosome material, Gravholt et al. (2000) reported that although the frequency of Y- chromosome material is high in Turner syndrome (12.2 %), the occurrence of gonadoblastoma among Y-positive patients was less than in previous estimates (7–10 %). Gonadal extirpation has been suggested for such patients unless they have an almost normal male phenotype with scrotal testes.
Nevertheless, careful follow-up (perhaps including testicular biopsy) is needed. The report of an infant girl with Turner syndrome, gonadoblastoma and 46XY(del Yp) karyotype indicated that the genes on the Y-chromosome that induce gonadoblastoma are distinct from the sex-determining locus, and detailed mapping of the Y-chromosome gonadoblastoma susceptibility region close to the centromere has been undertaken and candidate genes proposed (Lau 1999).
There is probably no increased risk of gonadoblastoma in Klinefelter syndrome (47, XXY) or in the XYY syndrome. However, gonadoblastoma is associated with sex reversal caused by 9p deletion (Livadas et al. 2003) and WAGR syndrome caused by 11p13 deletion.
Single gene defects can also cause gonadal dysgenesis, and gonadal Tumours are found in at least 30 % of XY cases. The Tumours are gonadoblastomas or dysgerminomas, which arise in the second or third decade. Autosomal recessive forms of XX gonadal dysgenesis are probably not associated with an increased risk for gonadoblastomas, but XY gonadal dysgenesis (Swyer syndrome), is frequently complicated by this Tumours.
Affected individuals are of normal stature and do not have the features of Turner syndrome, but have streak gonads. H-Y antigen may or may not be positive. It has been suggested that the risk of gonadoblastoma and dysgerminoma is confined to the H-Y antigen-positive cases. XY gonadal dysgenesis may also occur as an autosomal recessive condition, and gonadal Tumours frequently complicate the familial testicular dysgenesis syndrome, one of this group of conditions. Again, H-Y antigen-positive cases appear to be the ones susceptible to gonadoblastomas, with a 55 % incidence.
Gonadoblastoma may be associated with renal impairment and gonadal dysgenesis in Frasier syndrome.
The incidence of gonadal neoplasia in true hermaphrodites (individuals with both testicular and ovarian tissue) appears to be low, although both ovarian and testicular Tumours have been reported. Complete testicular feminization (X-linked recessive inheritance) is associated with an increased risk of testicular malignancy (about 5 %), most commonly seminoma. If malignancy develops, it is usually after the age of 25 years, so that orchidectomy can be delayed until after pubertal feminization. The risk of neoplasia in incomplete androgen-insensitivity states, including Reifenstein syndrome, is considered to be low.
In the syndromes of persistent Mullerian duct and pseudovaginal perineoscrotal hypoplasia, the abnormally situated testes are susceptible to the development of seminomas, choriocarcinomas, embryonal carcinomas, gonadoblastomas, or teratocarcinomas. The incidence of gonadal neoplasia may be slightly increased – to up to 4 % in 46XX cases and 10 % in 46XY cases.
In the conditions predisposing to gonadal Tumours, it is advisable to remove the gonads prophylactically in the second decade.