Ovarian Gynandroblastoma: A Rare Sex Cord-Stromal Tumor with Unique Morphological,Genetic,and Clinical Features—A Series of Two Patients with Clinicopathological and Molecular Analysis,and a Review of the Literature

Abstract

Background

Gynandroblastoma is an exceptionally rare ovarian sex cord-stromal tumor containing both male and female components. Due to its rarity, molecular data are limited, and its clinical behavior remains incompletely understood.

Methods

We retrospectively analyzed 2 tumors of gynandroblastoma diagnosed at 2 teaching hospitals. Clinicopathological data, including patient demographics, tumor characteristics, and outcomes, were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed on both tumors to evaluate for the presence of FOXL2 (Forkhead Box L2) and/or DICER1 (dicer 1, ribonuclease III) mutations.

Results

Both tumors were FIGO stage IA . Microscopically, tumor #1 contained well-differentiated Sertoli cell tumor (SCT) and adult-type granulosa cell tumor (AGCT) components, while tumor #2 comprised moderately differentiated Sertoli-Leydig cell tumor (SLCT) and AGCT components. Immunophenotypically, both tumors were positive for the sex cord-stromal markers calretinin and inhibin. NGS revealed the absence of FOXL2 c.402C>G (p.Cys134Trp) in both tumors. DICER1 mutations were absent in both tumors. Both patients remained disease-free during follow-up periods of 6 and 62 months, respectively.

Conclusion

Gynandroblastoma remains a distinct and rare entity with characteristic histopathological and molecular features. Our findings align with previous studies, emphasizing the rarity of FOXL2 mutation and the absence of DICER1 mutations in tumors with an AGCT component, regardless of the male sex cord component. Further studies are needed to better understand its molecular pathogenesis and long-term outcomes.