Sex chromosome disorders, including sex chromosome mosaicism, result in a large clinical spectrum. There is scarce information about the histological pattern of these gonads.
Aim: to characterize the histology and cell markers pattern in gonads of patients with chromosomal mosaicism.
Gonadal biopsies from thirteen patients with chromosomal mosaicism, including chromosome Y were studied. Six were rearing as male and seven as female .
Patients were divided in two subgroups (G), according to external genitalia. G1, with atypical genitalia:n=7, chronological age(CA) at biopsy, was 1.75, 0.25-12 years(y) expressed as median and range. Five patients were rearing as males and two as females. G2, Turner syndrome,n=6,CA at biopsy was 13.8, 3.5-18.8 y, all patients were reared as females.
H&E sections from gonadal biopsies were observed by two specialists. Immunohistochemical studies for the detection of pluripotential marker OCT 3/4, Sertoli cell marker SOX9 and granulosa cell marker FOXL2 were done.
A total of 24 samples were studied, 13 from G1 and 11 from G2. Dysgenetic testicular parenchyma was found in 8/13 of G1 (62%) and 3/11 of G2 (27%). Only one sample with ovarian structures was found in G2. Histological structures compatible with streak were observed in 4/13 in G1(31%) and in 5/11(45%) in G2. Mullerian structures were found in 6/13 of G1(46%) and in 2/11(18%) in G2. In 4 samples of 2 patients gonadoblastoma, embryonic carcinoma and dysgerminoma were found, both corresponding to G2. Of the samples that presented testicular parenchyma, 43% had structures compatible with Mullerian remnants. OCT 3/4 was expressed in 42.8% of G1, all of them corresponding to testicular parenchyma, and in 66.7% of G2. All the patients were older than 3 months. SOX9 was present in 75% of G1, in the nucleus of Sertoli cells inside the seminiferous cords. Positive expression of SOX9 was found in isolated nuclei of tissues of G2(50%) without seminiferous cords. FOXL2 expression was found in 33.3 % of G1 and in 100% of G2.
In conclusion, the complexity of the tissues corresponding to patients with chromosomal mosaicism requires a deep histological and immunohistochemical analysis that allow the characterization of cell types and cell cancer risk. Samples of G1(2/7) showed testicular parenchyma and Mullerian remnants, which might indicate an early alteration in the function of the Sertoli cell. The expression of Sertoli cell marker SOX9 in streak tissues of G2, suggests an increased risk of gonadoblastoma development.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology