Dominik T. Schneider

Ovarian juvenile granulosa cell tumor: A report from the International Ovarian and Testicular Stromal Tumor and International Pleuropulmonary Blastoma/DICER1 Registries

AbstractBackgroundOvarian juvenile granulosa cell tumors (juvGCT) are rare sex cord‐stromal tumors that occur primarily in children and adolescents. This study summarizes the clinical presentation and outcomes of patients with juvGCT.MethodsPatients were enrolled in the International Ovarian and Testicular Stromal Tumor and/or International Pleuropulmonary Blastoma/DICER1 Registries. Available medical records were abstracted, and pathology was centrally reviewed. Surgical staging was classified using the 2014 International Federation of Gynecology and Obstetrics (FIGO) criteria.ResultsIn total, 70 patients with juvGCT enrolled and were diagnosed between 2001 and 2024; most patients (81%, 57 of 70) presented with FIGO stage I disease. Adjuvant chemotherapy was given in 30% (21 of 70); all regimens were platinum‐based. Three‐year event‐free survival among patients with stage IA tumors was 80.2% (95% confidence interval [CI], 62.4%–100.0%), IC1 was 87.4 (95% CI, 72.4%–100.0%), IC2‐IC3 was 63.6% (95% CI, 40.7%–99.5%), and II‐IV was 48% (95% CI, 24.6%–93.8%). Of the patients with recurrent juvGCT with known mitotic index (MI), all had MI greater than 19 mitoses per 10 high power fields (HPF) at diagnosis.ConclusionOutcomes were worse for patients with FIGO stage ≥IC2 disease and for tumors with >19 mitoses per 10 HPF. Given the prognostic significance of MI, the authors strongly recommend the assessment of MI for all juvGCTs. More information about tumor biology is critical to identify which patients may benefit from adjuvant chemotherapy and to facilitate the development of novel therapies.

Bilateral testicular juvenile granulosa cell tumor: Tumor control with conservative, antihormonal therapy

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)

AbstractBackgroundIn 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.MethodsBetween 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.ResultsTesticular 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).ConclusionsTesticular 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.

DICER1-Related Tumor Predisposition: Identification of At-risk Individuals and Recommended Surveillance Strategies

Abstract Purpose: DICER1-related tumor predisposition increases risk for a spectrum of benign and malignant tumors. In 2018, the International Pleuropulmonary Blastoma (PPB)/DICER1 Registry published guidelines for testing- and imaging-based surveillance of individuals with a known or suspected germline DICER1 pathogenic or likely pathogenic (P/LP) variant. One of the goals of the Registry is to continue to refine these guidelines as additional data become available. Experimental Design: Individuals were enrolled in the International PPB/DICER1 Registry, the International Ovarian and Testicular Stromal Tumor Registry, and/or the NCI Natural History of DICER1 Syndrome study. Results: Review of participant records identified 713 participants with a germline DICER1 P/LP variant from 38 countries. To date, 5 cases of type I and 29 cases of type Ir PPB have been diagnosed by surveillance in enrolled individuals. One hundred and three individuals with a germline P/LP variant developed a primary ovarian Sertoli–Leydig cell tumor at a median age of 14 years (range: 11 months–66 years); 13% were diagnosed before 8 years of age, the current age of onset of pelvic surveillance. Additionally, 4% of Sertoli–Leydig cell tumors were diagnosed before 4 years of age. Conclusions: Ongoing data collection highlights the role of lung surveillance in the early detection of PPB and suggests that imaging-based detection and early resection may decrease the risk of advanced PPB. DICER1-related ovarian tumors were detected before 8 years of age, prompting the Registry to recommend earlier initiation of ovarian surveillance with pelvic ultrasound beginning at the time of detection of a germline DICER1 P/LP variant.