Ovarian Germ Cell Tumors: Evaluation and Management in Adolescents and Women Under 30
Overview and Prognosis
Ovarian germ cell tumors in young women should be managed with fertility-sparing surgery followed by risk-stratified chemotherapy, as these tumors are highly chemosensitive with 5-year survival rates exceeding 85%. 1
Malignant germ cell tumors represent 5% of all ovarian cancers but account for 80% of preadolescent malignant ovarian tumors, with median age at diagnosis of 16-20 years. 1, 2 These tumors are almost always unilateral and exquisitely chemosensitive, making conservative surgical approaches highly effective. 3
Initial Evaluation and Workup
Imaging Studies
- Pelvic ultrasound is the initial imaging modality for suspected ovarian masses 1
- Abdomino-pelvic CT scan is required for staging 1
- Chest X-ray to evaluate for pulmonary metastases 1
- MRI may demonstrate characteristic features such as fatty and calciferous content in dermoid cysts 1
- PET scan should be considered in selected cases of germ cell tumors 1
Tumor Markers
Measure the following serum markers before surgery, as they guide diagnosis, treatment decisions, and surveillance: 1
- Alpha-fetoprotein (AFP) – elevated in yolk sac tumors and embryonal carcinoma
- Beta-hCG – elevated in choriocarcinoma and embryonal carcinoma 2
- Lactate dehydrogenase (LDH) – elevated in dysgerminoma
In women under 35 years with a pelvic mass, AFP levels are particularly useful for identifying germ cell tumors. 1
Pulmonary Function Testing
Obtain baseline pulmonary function tests if bleomycin chemotherapy is being considered, as bleomycin carries risk of pulmonary toxicity. 1
Genetic Considerations
Screen for gonadal dysgenesis, as this is a risk factor for germ cell tumors. 1
Surgical Management: Fertility-Sparing Approach
Primary Surgical Principles
Fertility-sparing surgery should be performed regardless of stage in all patients desiring future fertility. 1 This approach consists of:
- Unilateral salpingo-oophorectomy (removal of affected ovary and fallopian tube only) 1, 3
- Preservation of contralateral ovary, fallopian tube, and uterus 1, 3
- Surgical staging when appropriate (see below for staging considerations)
Staging Considerations
For adolescents and children with early-stage germ cell tumors, comprehensive surgical staging may be omitted. 1 This represents a departure from adult protocols and reflects the excellent salvage rates with chemotherapy. 1
For patients who undergo comprehensive staging, the procedure includes: 1
- Peritoneal washings
- Inspection and palpation of peritoneal surfaces
- Omental sampling
- Lymph node assessment (though full lymphadenectomy is not required)
Critical Pitfall: Avoid radical surgery and full staging procedures in young patients, as these are usually unnecessary and inappropriate given the efficacy of salvage chemotherapy. 1 Removal of both ovaries does not improve outcomes in advanced disease. 3
Incomplete Staging Management
If a patient has undergone incomplete surgical staging, management decisions depend on: 1
- Tumor histology
- Imaging results
- Tumor marker levels (AFP, beta-hCG)
- Patient age
- Fertility preservation desires
Completion surgery is not routinely required if imaging and tumor markers are reassuring. 1
Post-Childbearing Considerations
After childbearing is complete, completion surgery (removal of remaining ovary and uterus) may be considered but is category 2B recommendation, meaning it is not strongly endorsed. 1
Adjuvant Chemotherapy: Risk-Stratified Approach
Observation Without Chemotherapy (Low-Risk Disease)
Observation with surveillance alone is recommended for: 1
- Stage I dysgerminoma
- Stage I, grade 1 immature teratoma
This recommendation is based on European and pediatric data showing excellent outcomes with surveillance alone. 1
For select children or adolescents with stage IA or IB tumors, observation or chemotherapy may be considered on a case-by-case basis. 1
Chemotherapy Indications (High-Risk Disease)
BEP chemotherapy (bleomycin, etoposide, cisplatin) for 3-4 cycles is recommended for: 1
- Any stage embryonal tumors or endodermal sinus (yolk sac) tumors
- Stage II-IV dysgerminoma
- Stage I, grade 2-3 immature teratoma
- Stage II-IV immature teratoma
BEP Regimen Details
The 4-cycle BEP regimen is the standard (category 2A recommendation). 1 However, there is nuance regarding cycle number:
- 4 cycles is preferred for most patients
- 3 cycles of 3-week BEP may be considered for low-risk or stage I disease (category 2B), though most clinicians avoid this abbreviated approach 1
- Memorial Sloan Kettering Cancer Center criteria can identify low-risk tumors suitable for 3 cycles 1
Important: Dose reductions or delays are not recommended even in the setting of neutropenia. 1
Alternative Regimen for Dysgerminoma
For select patients with stage IB-III dysgerminoma where minimizing toxicity is critical, 3 courses of etoposide/carboplatin may be used: 1
- Carboplatin 400 mg/m² (AUC 5-6) on day 1
- Etoposide 120 mg/m² on days 1-3
- Every 4 weeks for 3 courses
This regimen avoids bleomycin-related pulmonary toxicity but is reserved for specific clinical scenarios.
Surveillance and Follow-Up
Surveillance Schedule
For patients in complete clinical response after treatment, follow-up includes: 1
- Clinical examination every 2-4 months for 2 years
- Tumor markers (AFP and beta-hCG if initially elevated) every 2-4 months for 2 years
- Imaging (CT or MRI) as clinically indicated
MRI is increasingly preferred over CT to avoid excess radiation exposure in this young patient population. 1
Timing of Relapses
Most relapses occur within 12-18 months, typically in the peritoneal cavity or retroperitoneal lymph nodes. 1 Tumor markers often provide early warning of relapse before imaging changes are apparent. 1
Fertility Monitoring
Patients who underwent fertility-sparing surgery should be monitored with ultrasound examinations as necessary to assess the remaining ovary. 1
Management of Recurrent Disease
Treatment Options for Recurrence
For patients with abnormal markers and definitive recurrent disease, options include (both category 2B): 1
- High-dose chemotherapy with stem cell transplant
- Additional standard chemotherapy regimens
Critical Recommendation: Refer patients with recurrent disease to a tertiary care center for stem cell transplant consultation, as this offers potentially curative therapy. 1
Prognosis in Recurrence
Unlike male germ cell tumors, relapsed ovarian germ cell tumors in previously treated females are more difficult to cure. 1 However, salvage chemotherapy remains highly effective in chemotherapy-naïve patients. 1
Fertility Outcomes After Treatment
Studies consistently demonstrate excellent fertility outcomes after conservative surgery and chemotherapy for malignant ovarian germ cell tumors: 3
- Normal menstrual function returns in the vast majority of patients
- Fertility rates are preserved
- No increased risk of teratogenicity in offspring
This data strongly supports the fertility-sparing surgical approach even in advanced disease. 3
Pathology Considerations
Histologic Subtypes
Malignant germ cell tumors include: 1, 2
- Dysgerminoma (most common pure malignant type)
- Immature teratoma (graded 1-3 based on immature neuroepithelial tissue)
- Yolk sac tumor (endodermal sinus tumor)
- Embryonal carcinoma
- Choriocarcinoma
- Mixed germ cell tumors (combination of above elements)
Grading of Immature Teratomas
A two-tiered grading system (low-grade vs. high-grade) is now more commonly used than the traditional three-tier system: 1
- Low-grade (grade 1): Rare foci of immature neuroepithelial tissue occupying <1 low power field (40×)
- High-grade (grades 2-3): Immature neuroepithelial tissue occupying ≥1 low power field (40×)
Pathology Review
Because of the chemosensitivity of these tumors and the increasing adoption of fertility-sparing surgery, correct pathological diagnosis is essential and cases should be examined by gynecological pathologists. 1
Key Clinical Pitfalls to Avoid
Do not perform bilateral oophorectomy or hysterectomy in young women with germ cell tumors, even in advanced disease – removal of both ovaries does not improve outcomes 3
Do not omit tumor marker measurement (AFP, beta-hCG, LDH) before surgery – these guide treatment and surveillance 1
Do not delay pulmonary function testing if bleomycin is planned – baseline assessment is essential 1
Do not reduce chemotherapy doses in the setting of neutropenia – maintain full doses 1
Do not assume comprehensive staging is always necessary in adolescents with early-stage disease – it may be safely omitted 1
Do not treat stage I dysgerminoma or stage I grade 1 immature teratoma with chemotherapy – observation is the standard of care 1