Genetics of High-Grade Endometrioid Adenocarcinoma of the Ovary With Yolk Sac Differentiation: A Case Report

TL;DR

This case report describes a rare ovarian tumor in a perimenopausal woman with yolk sac differentiation and highlights the importance of genetic testing for accurate diagnosis.

Contribution

The study presents a rare case with molecular profiling revealing mutations supporting an endometrioid origin in a mixed ovarian tumor.

Findings

The tumor showed pathogenic mutations in CTNNB1, ARID1A, and PIK3CA, indicating an endometrioid lineage.

Molecular profiling helped clarify the tumor's phenotype and origin despite overlapping morphological features.

The case underscores the diagnostic challenges and the need for genetic testing in rare ovarian tumors.

Abstract

Yolk sac tumors (YST) are relatively rare ovarian neoplasms that typically occur in young women, whereas yolk sac differentiation in ovarian epithelial tumors represents an exceedingly rare malignancy of perimenopausal and postmenopausal women. The latter is usually associated with Müllerian epithelial neoplasms and is somatically derived. Accurate identification of tumor lineage is essential for proper classification and treatment, especially in mixed tumors with overlapping morphological and immunohistochemical features and shared mutations. Most of the reported cases have lacked genetic testing. Here, we present a case of high-grade endometrioid adenocarcinoma with yolk sac tumor differentiation in a perimenopausal woman. The tumor demonstrated an unusual morphology and immunohistochemical profile, raising the possibility of either a common early precursor or divergent differentiation. Genomic analysis revealed pathogenic mutations in CTNNB1, ARID1A, and PIK3CA, supporting an endometrioid origin. This case highlights the diagnostic challenges posed by rare ovarian tumors and emphasizes the role of molecular profiling in clarifying tumor phenotype. Pathologists should be aware of the potential association between epithelial tumors and yolk sac tumor differentiation, particularly in older patients, to avoid misdiagnosis and to ensure appropriate therapeutic strategies.

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