Abstract
Turner syndrome (TS) patients with Y chromosome material face an increased risk of gonadal germ cell tumors (GCTs). This case report discusses the challenges in decision-making regarding prophylactic gonadectomy, considering the risk of malignancy and the desire to preserve fertility. We report a case of a 12-year-old female with mosaic TS and Y chromosome material who initially presented with short stature and obesity. Karyotype analysis showed a mixed cell line (45X and 46XY). Counseling about the increased risk of developing GCT and preservation of gonadal function was provided, and we decided to delay gonadectomy until the age of 12. Prophylactic bilateral gonadectomy revealed dysgerminoma associated with GB at the age of 12. Fortunately, the patient was asymptomatic, with no additional therapy required due to the early stage of the disease. The case highlights the dilemma in managing TS patients with Y chromosome material, where the risk of GCT varies depending on the type of difference in sex development and gonadal function. The decision to delay gonadectomy reflects the emphasis on preservation of ovarian, although it poses a risk of malignancy. This case underscores the importance of individualized care in TS patients with Y chromosome material, balancing the risk of malignancy against preservation of ovarian. It emphasizes the need for timely and personalized decision-making in prophylactic gonadectomy.
Keywords: Germ cell tumor, Gonadoblastoma, Gonadectomy, Turner syndrome, Y chromosome
Introduction
Turner syndrome (TS) is a genetic condition characterized by the 45,X genotype with or without identifiable mosaicism, often involving differences in sex development (DSDs). Some DSDs predispose patients to gonadal germ cell tumors (GCTs). The risk of developing GCTs varies based on the type of DSD and the degree of androgen receptor loss of function [1]. Approximately 12% of patients with TS have Y chromosome material, including the testes-specific protein Y-linked region (TSPY) [2]. The presence of TSPY is associated with a high risk of developing gonadoblastoma (GB) and germ cell neoplasia in situ (GCNIS), and GB/GCNIS can develop into malignant tumors, such as germ cell tumors (GCTs) [3]. TS patients with Y chromosome material have a 12–40% risk of developing GCNIS/GB [1].
Conversely, the increased risk of GCNIS in patients with certain DSDs is not well understood. This uncertainty has shifted clinical practice regarding gonadal preservation. Previously, prophylactic gonadectomy was the standard approach, but this is no longer the case, especially considering the potential advantages of maintaining gonadal function until at least puberty [4].
Herein, we report a case of TS with Y chromosome material in a patient who underwent prophylactic gonadectomy, which revealed that she had already developed dysgerminoma associated with GB.
Case report
The patient was a 12-year-old girl. At the age of 9 years, she was referred to our hospital because of her short stature and obesity. Her height, weight, and body mass index were 118.5 cm [–2.03 standard deviation], 33.9 kg, and 24.14 kg/m2, respectively. The genitalia appeared normal. Follicle-stimulating hormone levels were elevated (44.1 U/L; normal range 1.2–19.0 U/L) at the age of 10 years. During evaluations for short stature, karyotype analysis of peripheral blood lymphocytes revealed two cell lines: 25 of 30 metaphases analyzed indicated a single X chromosome (45X), while five cells were positive for a Y chromosome (46XY). Based on these results, we diagnosed TS with Y chromosome material. The patient and family were counseled about the increased risk of GB with the potential for GCT development.
We performed laparoscopic bilateral prophylactic gonadectomy 2 years after the TS diagnosis when the patient was 12 years of age. Histopathological examination of the left ovary confirmed dysgerminoma associated with GB (Fig. 1). The full metastatic work-up was negative, and serum alpha-fetoprotein and β-human chorionic gonadotropin levels were within the normal range. No additional therapy was required since the patient was diagnosed with stage IA dysgerminoma. There has been no recurrence in the 6 months since the surgery at the time of writing this report.
Fig. 1.
Pathological findings. A Macroscopic findings of the left ovary; two nodular lesions are observed in a row. B H&E stain × 40 magnification. C H&E stain × 100 magnification; histopathological findings of the left ovary. Most of the ovarian parenchyma is replaced by nests and sheets of neoplastic cells with round nuclei and clear cytoplasm. D H&E stain, × 200 magnification; minor evidence of residual gonadoblastoma, characterized by eosinophilic basement membrane material and sex cord cells, is identified. H&E hematoxylin and eosin
Discussion
We described the presence of dysgerminoma in a 12-year-old female patient with mosaic TS with a Y chromosome, revealed during bilateral prophylactic ovary removal. The patient was asymptomatic, and prophylactic bilateral gonadectomy was successfully performed before the development of symptomatic and metastatic disease due to dysgerminoma. The risk of developing GCT varies depending on the type of DSD and the gonadal function of the patient [4]. It is recognized that patients with TS who have a Y chromosome have an increased risk of developing gonadal tumors, with potential for malignant transformation [5].
However, perspectives on gonadectomy differ, particularly regarding the preservation of fertility [2]. Practical guidelines emphasize an increased risk of malignant GCT with advancing age, recommending early gonadectomy at the onset of puberty [1]. The International Turner Syndrome Consensus Group recommends that female individuals with TS and Y chromosome material undergo gonadectomy at the time of diagnosis, regardless of age [2]. However, these recommendations are based on analyses that include cases prior to the year 2000, and not all of them are amenable to the present era with the development of chemotherapy and preservation of ovarian function. Therefore, gonadectomy is no longer considered the default or automatic treatment approach. This shift is supported by data indicating that 42% of girls with TS with Y chromosome material entered puberty spontaneously, and 11% achieved spontaneous menarche, indicative of gonadal function [2].
Dysgerminoma often develops into a large abdominal mass and causes acute abdominal pain due to torsion of the ovarian tumor pedicle or intertumoral hemorrhage [6]. In addition, the development of dysgerminoma poses risks, including chemotherapy side effects and late complications. Based on this discussion, it is crucial to carefully evaluate the risks associated with GCT in TS patients with Y chromosome material. These risks include acute abdominal complications due to the ovarian tumor pedicle and potential long-term complications from chemotherapy. Equally important is the consideration of ovarian function preservation prior to deciding on prophylactic gonadectomy.
A limitation of this case report was the delayed gonadectomy following the initial diagnosis at the age of 9 years. Initially, our focus was on the potential for ovarian function and fertility rather than on the risk of malignancy. This approach stemmed from deliberations that gave precedence to ovarian preservation. However, ovarian preservation was ultimately not realized due to the gynecologist’s decision.
In conclusion, we present a case of a patient with TS with Y chromosome material who underwent prophylactic gonadectomy that revealed the presence of dysgerminoma with a background of GB. Our case highlights the importance of individualized consideration in balancing the risk of tumorigenesis with the preservation of ovarian function in TS patients with Y chromosome material.
Acknowledgements
We thank all the Shiga University of Medical Science medical staff involved in treating this patient.
Author contributions
AT and YM collected and interpreted the data and wrote the manuscript. KS and KM designed the study, interpreted the data, wrote the manuscript, and provided medical care for the patient. YM collected data, evaluated the patient, performed the surgery, and provided medical care for the patient. S.M performed the pathological diagnosis and collected data. All authors have discussed the results and critically reviewed the manuscript.
Data availability
All data generated or analyzed during this study are included in this published article.
Declarations
Conflict of interest
The authors declare no competing financial interests.
Ethical approval
Formal approval is not required for this type of study.
Informed consent
Informed consent was obtained from the patient included in this study.
Footnotes
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Data Availability Statement
All data generated or analyzed during this study are included in this published article.