Ovarian sex cord stromal tumor and malignant mixed germ cell tumor in Constitutional Cancer Mismatch Repair Deficiency Syndrome

Ovarian tumours in children may be associated with cancer predisposition syndromes. We report the case of a 10-year-old girl presenting with acute abdominal pain and hypovolemic shock. She exhibited multiple café-au-lait spots, a tuft of hair on her sacrum, convergent strabismus, microcephaly, and low-set ears with both sensorineural and conductive hearing loss. Diagnosis revealed a large ruptured malignant-mixed germ cell tumour of the left ovary with predominance of yolk sac components and a small sex cord-stromal tumour in the right ovary. Whole exome sequencing detected an MSH6(+) mutation consistent with constitutional-cancer-mismatch-repair-deficiency syndrome. Immunohistochemical analysis showed loss of MSH6 protein expression, indicating presence of both germline and somatic mutations in MSH6. Deficiency of Mismatch Repair (MMR) proteins is known to lead to resistance to conventional chemotherapy, while remaining vulnerable to immunotherapy, as documented in adult studies. However, our patient was treated as per a standard Childrens Oncology Group (COG) protocol with chemotherapy, and has been well till date, 2 years post-completion of treatment. Prevalence of microsatellite instability (MSI) in paediatric germ cell tumours has not been extensively researched and its treatment implications remain unclear.