Occurrence of Gonadoblastoma in Females with Turner Syndrome and Y Chromosome Material: A Population Study

Abstract

The presence of Y chromosome material in patients with Turner syndrome is a risk factor for the development of gonadoblastoma. However, no cases with gonadoblastoma or other ovarian malignancies have been found in epidemiological studies of cancer, morbidity, or mortality in Turner syndrome. We examined 114 females with Turner syndrome for the presence of Y chromosome material by PCR. Initially, five different primer sets were used. Y Chromosome-positive individuals were further examined with an additional four primer sets. We found 14 (12.2%; 95% confidence interval, 6.9-19.7%) patients who had Y chromosome material. The karyotype in 7 of these patients did not suggest the presence of Y chromosome material. Seven of the patients had been ovariectomized before entering the study due to verified Y chromosome material, whereas three patients were operated upon after the DNA analysis. The histopathological evaluations showed that 1 of the 10 ovariectomized patients actually had a gonadoblastoma. The rest of the patients did not have gonadoblastoma or carcinoma in situ on histopathological evaluation. Three patients (age, >50 yr) positive for Y chromosome material chose not to have ovariectomy performed, and detailed ultrasonographies did not suggest the presence of gonadoblastoma. The frequency of Y chromosome material is high in Turner syndrome (12.2%), but the occurrence of gonadoblastoma among Y-positive patients seems to be low (7-10%), and the risk may have been overestimated in previous studies, perhaps due to problems with selection bias. This study emphasizes the need for prospective unbiased studies.

Distribution of Y-chromosome-bearing cells in gonadoblastoma and dysgenetic testis in 45,X/46,XY infants

“…21 The well-known syndromes associated with a risk for tumor development are: mixed gonadal dysgenesis, some patients with Turner phenotype and in several cases of 46,XY male pseudohermaphroditism. [2][3][4][5][6][7] There is also a reported case of this type of tumor in a 46,XX/46,XY true hermaphrodite. 6 The tumor development in these patients had been associated with the presence of normal or abnormal Y-chromosomes, molecular evidence for Y-derived sequences and intrabdominal location of the abnormal gonads.…”

“…6 The tumor development in these patients had been associated with the presence of normal or abnormal Y-chromosomes, molecular evidence for Y-derived sequences and intrabdominal location of the abnormal gonads. 3,4,7,8,18 The age at diagnosis is variable ranging from birth to the fourth decade; around 94% of cases Distribution of Y-chromosome-bearing cells R Peña-Alonso et al reported in the literature was diagnosed during the second or third decades of life. 22 Data in the literature revealed 10 cases where the tumor developed during childhood, five of them had a 45,X/ 46,XY mixed gonadal dysgenesis and the diagnosis was performed only in one case at 9 months old while the rest were diagnosed around 10 years of age.…”

“…31,32 However, new molecular data indicate that the occurrence of gonadoblastoma among the Y-positive Turner patients is lower than 10% and this risk increases with age. 4 Case 2 was originally diagnosed as 46,XY, but FISH analysis in gonadal tissue showed a 45,X cell line. Recently, hidden mosaicisms for X-and Y-chromosomes were detected by FISH analysis and associated with true hermaphroditism.…”

“…This unique gonadal neoplasm was described by Scully 1 in 1957 as a benign tumor that affects mostly a subset of patients with intersex disorders. The syndromes associated with a clear risk for tumor development are mixed gonadal dysgenesis, 1-3 some patients with Turner phenotype, 4 occasionally in 46,XY male pseudohermaphroditism [2][3][4][5] and there is also a reported case in a 46,XX/46,XY true hermaphrodite. 6 Tumor development in these patients is associated with the presence of either normal or abnormal Y-chromosomes or molecular evidence for Y-derived sequences and intrabdominal location of the abnormal gonad.…”

Analysis of the SRY Gene in Turner Syndrome Patients from the Republic of Macedonia

“…Epidemiological studies in Denmark have questioned the postulated high incidence of gonadoblastoma in Turner syndrome patients [31,32]. Nevertheless, because of the increased risk of gonadoblastoma in Turner syndrome patients with Y-chromosome material [11], the possibility of "low-level hidden" mosaicism for a Y-chromosome-positive cell line in the gonads, the variable age of expression [10], the high malignancy potential of gonado blastoma and the necessity of timely referral for gonadec tomy, analysis of SRY should be offered to all Turner syndrome patients.…”