Volume 281, May 2026, 156426Author links open overlay panelFan Yang a 1, Jinhua Zheng a 1, Xiaoqian Wang b, Longkuan Xu a, Hui Wei a, Jing Lin aShow moreAbstract

Adult Granulosa Cell Tumors (AGCTs) are uncommon ovarian neoplasms typically characterized by low-grade malignant behavior. However, AGCTs can occasionally undergo high-grade transformation, which may substantially impact clinical outcomes. In this study, we report the first documented instance of AGCT with high-grade hepatoid transformation (AGCT-HGHT) and perform a review of previously reported cases of AGCT with high-grade/sarcomatoid transformation (AGCT-HST). This case expands the spectrum of AGCT-HST and ovarian tumors with hepatoid morphology and emphasizes the need for further research into the molecular mechanisms and clinical significance of these genetic alterations as potential prognostic markers and therapeutic targets in AGCTs.

Introduction

Adult Granulosa Cell Tumor (AGCT) is an infrequent ovarian neoplasm that typically demonstrates low malignant potential. These tumors account for approximately 2–4% of all ovarian tumors and are the most common form of malignant ovarian sex cord-stromal tumors [1]. Despite generally having a favorable prognosis, AGCTs have the potential for high-grade transformation, which can significantly impact their clinical course and prognosis [2], [3], [4], [5], [6], [7], [8], [9]. The high-grade transformed component of AGCT often manifests as a sarcoma or exhibits a pattern resembling that of Juvenile Granulosa Cell Tumor (JGCT), characterized by pronounced nuclear atypia and pleomorphism and increased mitotic activity [2], [6]. The Forkhead Box L2 (FOXL2) c.402 C>G, p.(Cys134Trp) mutation, a hallmark of AGCTs, is present in both low-grade and high-grade components of AGCT with high-grade/sarcomatoid transformation (AGCT-HST). Additionally, AGCT-HST may display unique molecular alterations that differentiate it from classic AGCT. In this study, we present the first documented case of AGCT with high-grade hepatoid transformation (AGCT-HGHT), and review the existing literature on AGCT-HST.

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This report describes the case of a 51-year-old female patient (gravida 5 para 3) who presented to the hospital with a two-year history of menopause and abnormal vaginal bleeding persisting for more than two weeks. Imaging studies identified a substantial solid mass measuring 15 × 9.8 × 14 cm in the right adnexal region (Fig. 1A). Laboratory evaluations revealed elevated tumor marker levels, with a serum alpha-fetoprotein (AFP) level of 1210 ng/mL and cancer antigen 125 (CA125) level of

Discussion

Adult type granulosa cell tumor (AGCT) is an uncommon, slow-growing sex cord neoplasm that accounts for roughly 2–5% of all ovarian malignancies. It is overwhelmingly post-menopausal, with a sharp incidence peak between 50 and 55 years [14]. Every practicing pathologist recognizes its archetypal hallmarks: microfollicular Call–Exner bodies, coffee-bean nuclear grooves, scant cytoplasm, and crucially the canonical somatic mutation c.402 C>G in the FOXL2 gene (p.C134W). Yet three major knowledge

CRediT authorship contribution statement

Longkuan Xu: Formal analysis, Data curation. Hui Wei: Formal analysis, Data curation. Jinhua Zheng: Project administration, Conceptualization. Xiaoqian Wang: Formal analysis, Data curation. Fan Yang: Writing – original draft, Formal analysis, Data curation. Jing Lin: Writing – review & editing, Methodology.

Ethics approval

The study was approved by the Institutional Review Board of the First Affiliated Hospital of Guilin Medical University. The patient gave written informed consent for the use of tissue specimens.

Funding

No funding.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

The authors would like to thank the Geneseeq (Nanjing, China) for generous technical support of NGS related to this work.

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These authors contributed equally.

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