Testicular and ovarian Juvenile granulosa cell tumors in children and adolescents: Analysis of 113 patients registered to the German Registry for Rare Pediatric Tumors (STEP)

Background

In juvenile granulosa cell tumors (juvGCTs), impaired survival was reported after preoperative tumor rupture, peritoneal metastases, or high mitotic rate (≥20 mitoses per 10 high-power fields). Therefore, a risk stratification was developed to select patients for chemotherapy.

Methods

Between 2001 and 2019, 89 female patients and 24 male patients were prospectively enrolled. Histopathologic classification was according to the World Health Organization classification, and staging was according to Children's Oncology Group and International Federation of Gynecology and Obstetrics classification.

Results

Testicular juvGCTs were detected as scrotal swelling during infancy. No recurrences were reported after orchiectomy. Patients with ovarian juvGCTs presented at a median age of 9.8 years with abdominal discomfort, isosexual precocity, or amenorrhea. After tumor resection, two of 52 patients with stage IA disease, one of 14 with stage IC1 disease (intraoperative rupture), 13 of 18 with stage IC2 or IC3 disease (preoperative rupture), and all five patients with stage II/III disease received chemotherapy. Four recurrences with two deaths were reported. Three recurrent tumors were initially stage IA with a high mitotic rate, and one was a stage II tumor. No recurrences were observed among patients who had stage IC2/IC3 disease, who had unfavorable prognoses in historical cohorts. The 5-year event-free survival was 0.95 ± 0.03 (85 of 89 patients), and overall survival was 0.97 ± 0.02 (87 of 89 patients).

Conclusions

Testicular and ovarian juvGCTs are clinically distinct entities. Although testicular juvGCTs exclusively present during infancy and have an excellent prognosis, ovarian juvGCTs may arise at any age and constitute potentially aggressive tumors. Centralized reference diagnostics and the establishment of counseling structures for the treatment of patients with ovarian juvGCTs improved prognosis compared with historical groups. The mitotic rate and incomplete surgery were identified as important risk factors in addition to tumor stage and should be considered in the risk-stratification of therapy.