Molecular Characterization of Ovarian Yolk Sac Tumor in a Postmenopausal Woman: Implications for Pathogenesis

ABSTRACT Ovarian yolk sac tumor is a rare malignant germ cell tumor that typically occurs in young women. In postmenopausal women, yolk sac tumors are extremely rare and have a poor prognosis. These tumors may arise from different biological mechanisms, as germ cells are absent in postmenopausal ovaries. We report a 59‐year‐old woman with pure ovarian yolk sac tumor, without epithelial carcinoma components. Immunohistochemistry showed positive SALL4, AFP, and Glypican‐3 and negative PAX8, confirming germ cell tumor differentiation. The patient developed liver metastasis and peritoneal dissemination resistant to platinum‐based chemotherapy. Comprehensive genomic profiling revealed somatic mutations in ARID1A, CTNNB1 , NFE2L2 , and PIK3CA . These genomic alterations are commonly observed in ovarian clear cell and endometrioid carcinomas, suggesting a somatic, possibly epithelial, origin for postmenopausal yolk sac tumors. These findings suggest that postmenopausal yolk sac tumors may be epithelial carcinomas with yolk sac tumor‐like features, showing genetic and therapeutic similarities to clear cell carcinoma.