Our Health Library information does not replace the advice of a doctor. Please be advised that this information is made available to assist our patients to learn more about their health. Our providers may not see and/or treat all topics found herein. This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER. Most ovarian masses in children are not malignant.[1] The most common malignant neoplasms are germ cell tumors, followed by epithelial tumors, stromal tumors, and then other tumors such as Burkitt lymphoma.[2,3,4,5] Most malignant ovarian tumors occur in girls aged 15 to 19 years.[6] References: The Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) staging system has been used for ovarian cancers (see Table 1). References: Clinical Presentation, Histology, and Prognosis The most common presenting symptoms of ovarian tumors in children are dysmenorrhea and abdominal pain. Ovarian tumors derived from malignant epithelial elements include the following types: There are subtypes within each tumor type. The subtypes include benign tumors, tumors with low malignant potential or borderline tumors, and adenocarcinomas. Most ovarian tumors in pediatric patients are benign and borderline,[1] with rare malignant lesions in adolescent patients.[2] Studies have reported the following: Girls with ovarian carcinoma (epithelial ovarian neoplasia) fare better than do adults with similar histology, probably because girls usually present with low-stage disease.[4,5] The potential association with genetic predisposition (e.g., BRCA variant) in pediatric patients has not yet been studied. Treatment of Childhood Epithelial Ovarian Neoplasia Treatment options for nonmalignant childhood epithelial ovarian neoplasia include the following: Treatment of epithelial ovarian neoplasia is based on stage and histology. Most pediatric and adolescent patients have stage I disease. In the TREP study,[3] of the eight patients with benign tumors, seven patients had stage I disease, and one patient had stage III disease. Of the eight patients with borderline tumors, three patients had stage I disease, and five patients had stage III disease (based on washings and omental implants). All 16 patients were treated with surgery alone. At the time of the report, 15 patients were alive without disease; the one death was not from ovarian cancer. Treatment options for childhood malignant ovarian epithelial cancer include the following: Treatment of malignant ovarian epithelial cancer is stage-related and follows adult protocols, which may include surgery and chemotherapy. For more information, see Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment. References: General Information About Sex Cord–Stromal Tumors Clinical presentation The clinical presentation and prognosis of patients with sex cord–stromal tumors vary by histology. In all entities, metastatic spread occurs rarely and, if present, is usually limited to the peritoneal cavity.[1] Distant metastases mostly occur in patients whose disease has relapsed. Some tumors may be associated with hormone secretion—for example, estrogen in granulosa cell tumors or androgens in Sertoli-Leydig cell tumors.[2] Diagnostic evaluation In the United States, these tumors may be registered in the International Testicular and Ovarian Stromal Tumor Registry.[3] In Europe, patients are prospectively registered in the national rare tumor groups.[3,4] The recommendations regarding diagnostic work-up, staging, and therapeutic strategy have been harmonized between these registries.[3] The European Cooperative Study Group for Pediatric Rare Tumors within the PARTNER project (Paediatric Rare Tumours Network - European Registry) has published comprehensive recommendations for the diagnosis and treatment of sex cord–stromal tumors in children and adolescents.[5] Histology and molecular features Ovarian sex cord–stromal tumors are a heterogeneous group of rare tumors that derive from the gonadal non–germ cell component.[1] Histological subtypes display some areas of gonadal differentiation and include juvenile (and, rarely, adult) granulosa cell tumors, Sertoli-Leydig cell tumors, and sclerosing stromal tumors. Other histological subtypes, such as steroid cell tumor, sex cord tumor with annular tubules, or thecoma, are exceedingly rare. Ovarian Sertoli-Leydig cell tumors in children and adolescents are commonly associated with the presence of germline DICER1 pathogenic variants and may be a manifestation of familial pleuropulmonary blastoma syndrome.[6] A two-institution study analyzed eight children aged 4 to 16 years who were diagnosed with Sertoli-Leydig cell tumors. All eight tumors were found to harbor somatic hotspot DICER1 variants, and five patients carried germline DICER1 pathogenic variants (two of them had the phenotype of DICER1 syndrome).[7] Individuals with Sertoli-Leydig cell tumor were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry.[8] In total, 191 participants with ovarian Sertoli-Leydig cell tumor were enrolled, with most presenting with Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I disease (92%, 175 of 191 patients). Germline DICER1 variant testing results were available for 156 patients; 58% of these patients had a pathogenic or likely pathogenic germline variant. Somatic DICER1 variant testing showed RNase IIIB hotspot variants in 97% (88 of 91) of intermediate- and poorly differentiated tumors. Prognostic factors Prognostic factors related to stage and high mitotic count have been identified. In a report from the German Maligne Keimzelltumoren (MAKEI) study, 54 children and adolescents with prospectively registered sex cord–stromal tumors were analyzed. Forty-eight patients presented with stage I tumors, and six patients had peritoneal metastases. While overall prognosis was favorable, patients at risk could be identified by stage (stage IC, preoperative rupture, stages II and III) and histological criteria such as high mitotic count.[9] A study of 44 patients from the European Cooperative Study Group on Pediatric Rare Tumors showed that stage and histopathologic differentiation determined the prognosis of patients with Sertoli-Leydig cell tumors.[10] Individuals with Sertoli-Leydig cell tumor were enrolled in the International Pleuropulmonary Blastoma/DICER1 Registry and/or the International Ovarian and Testicular Stromal Tumor Registry.[8] In total, 191 participants with ovarian Sertoli-Leydig cell tumor were enrolled. Adjuvant chemotherapy was administered to 40% of patients (77 of 191). Among these patients, nearly all received platinum-based regimens (95%, 73 of 77), and 30% (23 of 77) received regimens that included an alkylating agent. The 3-year recurrence-free survival rate was 93.6% (95% confidence interval [CI], 88.2%–99.3%) for patients with stage IA tumors, compared with 67.1% (95% CI, 55.2%–81.6%) for patients with stage IC tumors and 60.6% (95% CI, 40.3%–91.0%) for patients with stage II to stage IV tumors (P < .001). Among patients with FIGO stage I tumors, those with mesenchymal heterologous elements who were treated with surgery alone were at higher risk of recurrence (hazard ratio [HR], 74.18; 95% CI, 17.99–305.85). Treatment of childhood sex cord–stromal tumors Treatment options for childhood sex cord–stromal tumors include the following: A French registry identified 38 girls younger than 18 years with ovarian sex cord–stromal tumors.[2] Childhood Juvenile Granulosa Cell Tumors The most common histological subtype of sex cord–stromal tumors in girls younger than 18 years is juvenile granulosa cell tumor (median age, 7.6 years; range, birth to 17.5 years).[11,12] Juvenile granulosa cell tumors represent about 5% of ovarian tumors in children and adolescents and are distinct from the granulosa cell tumors seen in adults.[1,13] Risk factors Juvenile granulosa cell tumors have been reported in children with Ollier disease and Maffucci syndrome.[14,15,16] Clinical presentation Patients with juvenile granulosa cell tumors present with the following symptoms:[17,18] Treatment of childhood juvenile granulosa cell tumors Treatment options for childhood juvenile granulosa cell tumors include the following: Surgery As many as 90% of children with juvenile granulosa cell tumors will have low-stage disease (stage I) by FIGO criteria. These patients are usually curable with unilateral salpingo-oophorectomy alone. In one series, 15 of 17 patients underwent fertility-sparing surgery, and only two patients received adjuvant chemotherapy. No recurrences were reported.[19] Chemotherapy Patients with spontaneous tumor rupture or malignant ascites (FIGO stage IC2, IC3), advanced disease (FIGO stages II–IV), or tumors with high mitotic activity have a poorer prognosis and require chemotherapy.[2,4,13] Cisplatin-based chemotherapy regimens have been used with some success in both the adjuvant and recurrent disease settings.[4,11,20,21,22] Childhood Sertoli-Leydig Cell Tumors Clinical presentation and risk factors Sertoli-Leydig cell tumor is a common histological subtype of sex cord–stromal tumors. It is rare in young girls and more frequently seen in adolescents. The tumor may secrete androgens and, thus, present with virilization, secondary amenorrhea,[23] or precocious puberty.[24] These tumors may be associated with Peutz-Jeghers syndrome, but more frequently are a part of the DICER1-tumor spectrum.[6,25,26] Patients with Sertoli-Leydig cell tumors should be evaluated for germline DICER1 pathogenic variants. If a germline DICER1 pathogenic variant is found, regular follow-up for ovarian and other tumors such as thyroid disease (multinodular goiter, carcinoma) should be considered. Genetic counseling should also be considered.[26,27] Treatment and outcome of childhood Sertoli-Leydig cell tumors Treatment options for childhood Sertoli-Leydig cell tumors include the following: Surgery Surgery is the primary treatment for Sertoli-Leydig cell tumors and is the only treatment for low-stage disease (FIGO stage IA). The event-free survival rate for these patients is approximately 100%.[2][Level of evidence C1] However, up to 10% of patients may develop metachronous contralateral tumors, particularly in the context of underlying DICER1 germline pathogenic variants.[28] Chemotherapy Patients with Sertoli-Leydig cell tumors with abdominal spillage during surgery, spontaneous tumor rupture, or metastatic disease (FIGO stages IC, II, III, and IV) are treated with cisplatin-based combination chemotherapy, although the impact of chemotherapy has not been studied in clinical trials in children.[2,10] One study reported on 40 women (average age, 28 years) with FIGO stage I or IC Sertoli-Leydig cell tumors of the ovary.[29][Level of evidence C1] References: Small cell carcinomas of the ovary are exceedingly rare and aggressive.[1] The prognosis is poor for these patients. This cancer may be associated with hypercalcemia.[2] Molecular Features Somatic and germline SMARCA4 variants have been reported in small cell carcinoma of the ovary, hypercalcemia-type. This finding suggests potential molecular and biological similarities to rhabdoid tumors.[3,4,5] However, one study of children with small cell carcinoma of the ovary, hypercalcemia-type, revealed that this tumor appears molecularly distinct from extracranial rhabdoid tumors with either SMARCA4 or SMARCB1 alterations. In this study, tumors underwent genomic analysis that included RNA sequencing (n = 11) and methylation profiling (n = 9). These findings support their continued classification as different tumor types.[6] Treatment of Childhood Small Cell Carcinoma of the Ovary, Hypercalcemia-Type Treatment options for childhood small cell carcinoma of the ovary, hypercalcemia-type, include the following: Aggressive multimodality therapy Successful treatment has been reported in a few cases using aggressive therapy, including surgery and high-dose chemotherapy with stem cell rescue.[2,7,8,9][Level of evidence C1] Tazemetostat Tazemetostat is an EZH2 inhibitor that demonstrates activity against preclinical models of small cell carcinoma of the ovary with SMARCA4 loss.[10] Evidence (tazemetostat): References: Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, see the ClinicalTrials.gov website. The following is an example of a national and/or institutional clinical trial that is currently being conducted: Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of the following pediatric specialists and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life: For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care. The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website. Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2020, childhood cancer mortality decreased by more than 50%.[3,4,5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer. Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people in the United States. Therefore, all pediatric cancers are considered rare. The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows: Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers diagnosed in children aged 0 to 14 years and 9.3% of the cancers diagnosed in adolescents aged 15 to 19 years. These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers. Information about these tumors may also be found in sources relevant to adults with cancer, such as Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment. References: The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above. This summary was comprehensively reviewed. This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages. Purpose of This Summary This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pediatric ovarian cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions. Reviewers and Updates This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH). Board members review recently published articles each month to determine whether an article should: Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary. The lead reviewers for Childhood Ovarian Cancer Treatment are: Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries. Levels of Evidence Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Permission to Use This Summary PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]." The preferred citation for this PDQ summary is: PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Ovarian Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/ovarian/hp/child-ovarian-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 31846269] Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images. Disclaimer Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page. Contact Us More information about contacting us or receiving help with the Cancer.gov website can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the website's Email Us. Last Revised: 2024-09-11 This information does not replace the advice of a doctor. Ignite Healthwise, LLC disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use and Privacy Policy. Learn how we develop our content. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Ignite Healthwise, LLC.Topic Contents
Childhood Ovarian Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]
General Information About Childhood Ovarian Cancer
Stage Information for Ovarian Cancer
Stage Description FIGO = Fédération Internationale de Gynécologie et d'Obstétrique. a Adapted from Berek et al.[1] I Tumor confined to the ovary. IA Tumor limited to one ovary (capsule intact); no tumor on surface of the ovary; no malignant cells in the ascites or peritoneal washings. IB Tumor limited to both ovaries (capsules intact); no tumor on surface of the ovary; no malignant cells in the ascites or peritoneal washings. IC Tumor limited to one or both ovaries, with any of the following: IC1 Surgical spill. IC2 Capsule ruptured before surgery or tumor on the surface of the ovary. IC3 Malignant cells in the ascites or peritoneal washings. II Tumor involves one or both ovaries with pelvic extension (below pelvic brim) or primary peritoneal cancer. IIA Extension and/or implants on uterus and/or fallopian tubes. IIB Extension to other pelvic intraperitoneal tissues. III Tumor involves one or both ovaries or primary peritoneal cancer, with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes. IIIA1 Positive retroperitoneal lymph nodes only (cytologically or histologically proven): IIIA1(i) Lymph nodes ≤10 mm in greatest dimension. IIIA1(ii) Lymph nodes >10 mm in greatest dimension. IIIA2 Microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes. IIIB Macroscopic peritoneal metastasis beyond the pelvis ≤2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes. IIIC Macroscopic peritoneal metastasis beyond the pelvis >2 cm in greatest dimension, with or without metastasis to the retroperitoneal lymph nodes (includes extension of tumor to capsule of liver and spleen without parenchymal involvement of either organ). IV Distant metastasis excluding peritoneal metastases. IVA Pleural effusion with positive cytology. IVB Parenchymal metastases and metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of the abdominal cavity). Childhood Epithelial Ovarian Neoplasia
Childhood Sex Cord–Stromal Tumors
Childhood Small Cell Carcinoma of the Ovary, Hypercalcemia-Type
Treatment Options Under Clinical Evaluation for Childhood Ovarian Cancer
Special Considerations for the Treatment of Children With Cancer
Latest Updates to This Summary (09 / 11 / 2024)
About This PDQ Summary
Our Health Library information does not replace the advice of a doctor. Please be advised that this information is made available to assist our patients to learn more about their health. Our providers may not see and/or treat all topics found herein. This information does not replace the advice of a doctor. Ignite Healthwise, LLC disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use and Privacy Policy. Learn how we develop our content. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Ignite Healthwise, LLC.Childhood Ovarian Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]