Rare case of Turner syndrome patient with metastatic dysgerminoma and no Y-chromosomal material with pathogenic variants found in KIT and MTOR

Abstract

Introduction: The presence of Y-chromosomal material in females with Turner syndrome (TS) is a well-established risk factor for developing gonadoblastoma and malignant transformations hereof. However, these events are rarely seen in TS patients with no Y-chromosomal material. Thus, it is the current understanding that parts of the Y-chromosome are essential for malignant transformation of gonadoblastoma in the dysgenetic gonad.

Methods: We report a case of a TS female with an apparent 46,X,idic(Xq) karyotype, who was diagnosed with a metastatic dysgerminoma. Whole exome sequencing of tumor and blood, along with RNA sequencing of the tumor, was performed to comprehensively search for cryptic Y-chromosomal material and pathogenic variants.

Results: No Y-chromosomal material was detected in neither tumor nor blood. Whole exome sequencing of DNA and RNA revealed a pathogenic somatic gain-of-function mutation in KIT and a pathogenic missense mutation in MTOR. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, followed by adjuvant chemotherapy. Unfortunately, she died due to chemotherapy-induced pneumonitis seven months after initial diagnosis.

Conclusion: Females with TS can develop metastatic dysgerminoma even in the absence of Y-chromosomal material. This questions the current understanding of Y-chromosomal material being essential for the malignant transformation of a gonadoblastoma in the dysgenetic gonad.