Gonadoblastoma in patients with 45,X/46,XY mosaicism: A 16-year experience

Background It is recognised that individuals with a 45, X/46, XY karyotype, known as Turner mosaic syndrome with Y chromosome material (TMSY), have an increased risk of developing gonadoblastoma (GB), which may then devolve into one of a number of germ cell malignancies. Hence, children with TMSY are usually recommended to undergo prophylactic gonadectomy. Objective We designed this study to describe the phenotypic features of our series of children with TMSY who underwent prophylactic gonadectomy in order to evaluate the prevalence of GB and germ cell malignancies in their resected specimens. Study design This is a retrospective case series wherein we comprehensively reviewed the clinical, histological, and cytogenetic features of all patients who underwent prophylactic gonadectomy at three tertiary paediatric referral centres over 16 years. Cases were identified from surgical logbooks and through the institutional histopathology database. Data were collected with particular reference to clinical phenotype, predominant karyotype cell line, operative management, anatomical findings and the presence of neoplastic changes. Results Fourteen children ranging in age at the time of surgery from 2 weeks to 17 years were included in the series. Eleven children were reared as females. The three children who were reared as males had severe penoscrotal hypospadias. The 46, XY cell line was the predominant cell line in seven (50%) cases in blood lymphocytes. The resected specimens from four patients (28.6%) contained GB, with three patients having bilateral GB. This sub-group of patients with GB were aged 5 months, 48 months, 71 months, and 13 years. GB arose in one patient with and three patients without genital virilisation. There was no focus of invasive germ cell tumour in any specimen. Discussion GB may be present in infants with TMSY as young as 5 months, even with low levels of Y chromosome material. The prevalence of GB in prophylactic gonadectomy specimens is similar to many previously reported series, although the absence of dysgerminoma in our series is reassuring. The exclusive presence of GB in intra-abdominal gonads is in keeping with the findings of several other series. Conclusion Owing to the presence of gonadoblastoma in the gonads of children with TMSY as young as 5 months, we recommend that all patients with intra-abdominal gonads in the context of TMSY should duly undergo prophylactic gonadectomy, although the timing of such surgery can be discussed with parents during counselling regarding the risk of malignancy.