Abstract

Background: Ovarian germ cell tumors (OGCTs) are the most common type of ovarian tumor, encompassing mature and immature teratoma and malignant tumors. The standard treatment for mature teratoma is surgery, traditionally involving oophorectomy or salpingo-oophorectomy. However, these procedures reduce ovarian tissue reserve and carry a high risk of bilateral tumor development. Therefore, ovarian tissue-sparing tumorectomy has emerged as a popular alternative. This procedure aims to remove the tumor while preserving as much healthy ovarian tissue as possible, mitigating the risk of bilateral tumor development and preserving future fertility. The primary treatment approach for malignant OGCTs is surgery followed by postoperative chemotherapy. This combined treatment strategy aims to achieve complete resection and increase the likelihood of a long-term cure. There are very few studies on pediatric OGCTs within the Asian population. Therefore, this study aimed to comprehensively review the clinical presentation, treatment modalities, and outcomes of pediatric OGCTs at a tertiary hospital in Vietnam.

Methods: This retrospective study examined patients aged 1 month to 15 years treated for OGCTs at Children's Hospital No.2 between January 2016 and January 2021. Their symptoms, age at diagnosis, imaging, tumor markers, treatment methods, and complications were recorded. The long-term outcomes were the rate of recurrence and mortality.

Results: This study comprised 162 patients with a mean age of 9.1 +/- 3.6 years. Most had mature teratomas (n = 137), followed by immature teratomas (n = 11), yolk sac tumors (n = 7), dysgerminomas (n = 5), and mixed germ cell tumors (n = 2). At admission, their most common complaint was abdominal pain (73.5%), followed by abdominal mass (20.4%). Alpha-fetoprotein (AFP) levels were elevated in nine patients with immature teratomas, all with yolk sac tumors, all with malignant mixed germ cell tumors, and one with dysgerminoma. Beta human chorionic gonadotrophin (b hCG) levels were elevated in two patients with dysgerminomas and all with malignant mixed germ cell tumors. The mean tumor size was 9.1 +/- 5.1 cm (2.8–32 cm). Our study identified size tumor 8 cm, solid mass, and positive tumor markers as important predictors of malignancy. The median follow-up was 3.3 years (3 months to 6.5 years). Among patients with mature teratomas, three (2.2%) experienced recurrence, and none died. Among patients with immature teratomas and malignant OGCTs, one (4%) experienced relapse and died.

Conclusions: Both benign and malignant OGCTs have a good prognosis. Imaging and tumor markers are important for initial diagnosis and treatment planning. Ovarian-sparing tumorectomy is a safe and effective management option for mature teratomas. Surgical resection combined with platinum-based chemotherapy achieves good outcomes for malignant OGCTs.

Introduction

Ovarian tumors are uncommon in childhood, with an estimated overall incidence of 2.6 per 100,000 prepubertal females. However, their incidence can vary by patient age and histological diagnosis1. Ovarian germ cell tumors (OGCTs) are the most common type of ovarian tumor, accounting for 47.3–87.7%2. Mature teratoma is the most frequent OGCT. Immature teratoma and malignant OGCTs, including yolk sac tumors, dysgerminoma, gonadoblastoma, embryonal carcinoma, and mixed germ cell tumors, are relatively rare.

The standard treatment for mature teratoma is surgery, often involving oophorectomy or salpingo-oophorectomy. However, these procedures can reduce ovarian tissue reserve and may lead to bilateral tumor development. Consequently, there is a growing preference for ovarian tissue-sparing tumorectomy. This procedure aims to remove the tumor while preserving as much healthy ovarian tissue as possible, minimizing the risk of bilateral tumor development and preserving future fertility3. The primary treatment approach for malignant OGCTs is surgery combined with adjuvant chemotherapy. Complete resection is essential to provide patients with a possible long-term cure4, 5.

Despite the significance of understanding and managing OGCTs in children, limited research is available, especially in the Asian population. Over the past decade, our center has made changes to treatment approaches. This study aimed to comprehensively review the clinical presentation, treatment modalities, and outcomes of pediatric OGCTs at a tertiary hospital in Viet Nam.

Methods Setting and study design

We retrospectively reviewed all pediatric patients (aged ≤15 years at diagnosis) with OGCTs treated between January 2016 and January 2021 at Children’s Hospital No.2 in Ho Chi Minh City, Vietnam. We recorded their symptoms, age at diagnosis, imaging, tumor markers, treatment methods, and complications.

The OGCT diagnosis was based on a combination of clinical presentation, tumor markers (alpha-fetoprotein [AFP] and beta human chorionic gonadotrophin [βhCG]), and imaging characteristics. In cases where preoperative and intraoperative features suggested a benign tumor and its macroscopic appearance allowed for separating the ovarian tissue from the tumor, an ovarian tissue-sparing tumorectomy was performed. However, if there was any uncertainty about the benign nature of the tumor before surgery, a complete unilateral spingo-oophorectomy was performed. In situations where complete tumor resection risked injury to adjacent organs, resection was canceled, and neoadjuvant chemotherapy was administered. In such cases, a second surgery was performed to remove residual tumors and/or lymph nodes. Our study used the Children’s Oncology Group (COG) staging system. Immature teratomas were graded according to the Norris classification. The median follow-up was 3.3 years (3 months to 6.5 years).

This study was approved by the ethics committee of Children’s Hospital No.2 (225/QĐ-BVNĐ2) and accepted by The University of Medicine and Pharmacy at Ho Chi Minh City6.

Statistical analysis

All statistical analyses were performed using SPSS software (version 25.0; IBM, United States). Discrete variables are described as percentages. Continuous variables are described as means and standard deviations when normally distributed or medians with ranges when non-normally distributed. Normally distributed continuous variables were compared between groups using Student’s t-test, and non-normally distributed continuous variables were compared using the nonparametric Mann–Whitney U test. Discrete variables were compared between groups using Fisher’s exact test. A 95% confidence interval was used, and a p

Overall survival (OS) was calculated as the time from the date of diagnosis to death from any cause. Event-free survival (EFS) was calculated as the time between diagnosis and any event (e.g., malignant germ cell recurrence and death). The last follow-up was censored for patients who remained alive. Survival was analyzed using the Kaplan–Meier method.

Results Patient characteristics

Our study enrolled all 162 patients with a mean age of 9.1 ± 3.6 years (1–15 years). At admission, their most common complaint was abdominal pain (73.5%), followed by abdominal mass (20.4%). Among them, 23 (13%) were discovered incidentally with ultrasound. No patient with mature teratomas had elevated AFP or βhCG levels. However, AFP levels were elevated in 19 (11.7%) patients (47–105,031 ng/mL): nine with immature teratomas, seven with yolk sac tumors, one with dysgerminoma, and two with malignant mixed germ cell tumors. Four (2.5%) patients had elevated βhCG levels (60–16,638 mIU/mL): two with dysgerminomas and two with malignant mixed germ cell tumors (Table 1).

Cell surface-associated mucin 16 (MUC16/CA-125) levels were measured at diagnosis in 68 patients. They were elevated in 17 patients: seven with mature teratomas, five with immature teratomas, four with yolk sac tumors, and one with dysgerminoma.

Table 1.

The patients clinical characteristics

Parameters Number (%) Mean (range) 9.1 (1-15 years) Presenting symptoms Abdominal pain 119 (73.5%) Abdominal mass 33 (20.4%) Vomitting 21 (13.0%) Valginal bleeding 5 (3.1%) Urinary symptoms 1 (0.6%) Constipation 1 (0.6%) Prepubertal 105 (64.8%) Postpubertal 57 (35.2%) Presenting signs Palpable mass 119 (73.5%) Tumor markers Elevated AFP 19 (11.7%) hCG 4 (2.5%) AFP and bhCG 3 (1.9%) Normal 142 (87.7%) Imaging US 162 (100%) CT 108 (66.7%)

Table 2.

Histopathologic subtypes

Histopathology n (%) Mature teratoma 137 (84.6%) Immature teratoma 11 (6.8%) Grade 1 6 Grade 2 1 Grade 3 4 Yolk sac 7 (4.3%) Dysgerminoma 5 (3.1%) Mixed germ cell 2 (1.2%) Total 162

Table 3.

Surgical management of malignant ovarian germ cell tumors

Surgical procedure n (%) Malignant No. Collection of ascites