Ovarian Granulosa cell Tumor in a Patient with a Pathogenic Variant in the CDC73 Gene (Hyperparathyroidism-Jaw Tumor Syndrome)

Abstract

To report a patient with the hyperparathyroidism-jaw tumor syndrome (HPT-JT) who was found to have a rare ovarian tumor (granulosa cell tumor [GCT]). HPT-JT is caused by pathogenic variants in the CDC73 gene and results in primary hyperparathyroidism (PHPT), benign fibro-osseous jaw tumors, benign or malignant renal tumors and cysts, and benign or malignant uterine tumors. We believe this is the first reported case of HPT-JT and GCT. The patient was a 31-year-old woman with abdominal pain who was found to have adult GCT. Her history was significant for a single gland parathyroidectomy at age 23 for PHPT. Her mother also had PHPT with 1-gland removal, as well as a history of renal cysts. Because of the personal and familial history of PHPT, she underwent germline sequencing of genes associated with PHPT including CASR, CDC73, CDKN1B, MEN1 and RET. Genetic testing revealed a CDC73 gene pathogenic variant (c.687_688dupAG) which creates a premature translational stop signal causing loss-of-function. We report a case of ovarian GCT in a young patient with primary hyperparathyroidism and a CDC73 gene mutation. Ovarian granulosa cell tumor may be another CDC73-related tumor.