Abstract:
Adult-type ovarian Granulosa Cell Tumor (AGCT) is a rare low-grade malignant sex cord-stromal tumor, accounting for 2–5% of all ovarian malignancies, with 95% of cases occurring in middle-aged women aged 45–55 years. Cases in young patients ≤25 years old are extremely uncommon, accounting for only 5–8% of AGCT cases, but typically exhibit more aggressive biological behavior—characterized by higher recurrence rates, earlier distant metastases, and poorer response to conventional chemotherapy—posing significant challenges to clinical management. We report a 22-year-old nulliparous female who was admitted to Peking University International Hospital in January 2015 due to persistent abdominal distension and intermittent nausea for 10 days. Laparoscopic exploration revealed a large pelvic-abdominal cyst, and pathological examination confirmed right ovarian AGCT with adnexal involvement. She initially received six cycles of BEP adjuvant chemotherapy (etoposide, nedaplatin, bleomycin) after surgery, but suffered the first recurrence in August 2016. Abdominal ultrasound and PET-CT detected lesions in the left adnexa, liver, and splenic capsule, followed by tumor resection at Fudan University Shanghai Cancer Center and six cycles of paclitaxel plus carboplatin chemotherapy. The disease recurred again in April 2019, with pelvic MRI and PET-CT suggesting pancreatic tail metastasis; she underwent radical surgery (total hysterectomy, left adnexectomy, etc.) at Tianjin Medical University Cancer Institute and Hospital, followed by three cycles of doxorubicin liposome plus oxaliplatin chemotherapy. In July 2022, CT confirmed recurrent liver and splenic capsule metastases. Genetic testing identified a CHEK2 p.K373E variant (a key gene in the DNA damage repair pathway) indicating potential sensitivity to PARP inhibitors, while PD-L1 expression was negative (tumor cell positivity 0%, immune cell positivity <1%), suggesting limited efficacy of immunotherapy. Subsequently, the patient was administered oral fuzulopari (150 mg twice daily) combined with apatinib (250 mg once daily). As of August 2025, after 36 months of continuous targeted therapy and regular follow-up, all tumor markers (AFP, CEA, CA-199, HE4, CA-724, CA-153, CA-125) remained within normal ranges, imaging examinations showed stable metastatic lesions, and the patient maintained an ECOG performance status of 0 with no obvious discomfort. This case highlights that for young patients with recurrent AGCT refractory to multiple chemotherapy regimens, genetic testing and PD-L1 assessment are critical to guiding individualized targeted therapy. The combination of fuzulopari (a PARP inhibitor blocking DNA repair) and apatinib (an anti-angiogenic agent inhibiting tumor vascular growth) exerts synergistic anti-tumor effects, serving as a promising treatment strategy to achieve long-term disease control. Given the high risk of late recurrence (5–20 years post-initial treatment) in AGCT, long-term regular follow-up is essential for optimal patient management.
