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

ABSTRACT Objective: 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. Methods: 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. Results: Genetic testing revealed a CDC73 gene pathogenic variant (c.687_688dupAG) which creates a premature translational stop signal causing loss-of-function. Conclusion: 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. Abbreviations: GCT = granulosa cell tumor HPT-JT = hyperparathyroidism-jaw tumor syndrome IHC = immunohistochemistry PHPT = primary hyperparathyroidism