Ovarian Germ Cell Tumor: Pathogenesis, Classification, Epidemiology, Symptoms, Diagnosis, Pathology, Staging, Management and Prognosis

Ovarian Germ Cell Tumor

~Introduction

Ovarian germ cell tumors (OGCTs) are a diverse group of neoplasms that originate from primitive germ cells of the ovary. Although they constitute only about 15–20% of all ovarian tumors, they are the most common ovarian malignancies in children and adolescents. Unlike epithelial ovarian cancers, which typically affect postmenopausal women, ovarian germ cell tumors occur predominantly in young females, often during the first three decades of life.

These tumors exhibit a wide spectrum of biological behavior, ranging from benign lesions such as mature cystic teratomas to highly malignant tumors like dysgerminoma, yolk sac tumor, and choriocarcinoma. Advances in chemotherapy and fertility-sparing surgery have dramatically improved survival rates, making ovarian germ cell tumors one of the most curable forms of ovarian cancer.

~Embryology and Pathogenesis

Primordial germ cells originate in the yolk sac endoderm and migrate to the developing gonads during early embryogenesis. Disruption in their differentiation or genetic regulation can result in neoplastic transformation.

Key pathogenetic mechanisms include:

• Abnormal germ cell maturation

• Chromosomal abnormalities, especially involving chromosome 12p

• Activation of oncogenes and loss of tumor suppressor genes

The tumors are typically unilateral, reflecting the localized nature of germ cell transformation in the ovary.

~Classification of Ovarian Germ Cell Tumors

According to the World Health Organization (WHO), ovarian germ cell tumors are classified as follows:

1. Dysgerminoma

• Ovarian counterpart of testicular seminoma

• Most common malignant OGCT

• Occurs in adolescents and young women

• Highly radiosensitive and chemosensitive

2. Yolk Sac Tumor (Endodermal Sinus Tumor)

• Highly malignant

• Rapid growth

• Most common malignant OGCT in children

3. Teratomas

• Mature cystic teratoma (dermoid cyst) – benign

• Immature teratoma – malignant, graded based on neuroectodermal tissue

4. Embryonal Carcinoma

• Rare

• Highly aggressive

• Often produces multiple tumor markers

5. Choriocarcinoma (Non-gestational)

• Extremely rare

• Highly malignant

• Produces very high β-hCG levels

6. Mixed Germ Cell Tumors

• Combination of two or more germ cell components

• Most commonly dysgerminoma + yolk sac tumor

~Epidemiology

• Age: Peak incidence between 10–30 years

• Gender: Occurs exclusively in females

• Malignancy rate: Higher in younger age groups

• Bilaterality: Rare (except dysgerminoma, ~10–15%)

~Clinical Presentation

Common Symptoms

• Abdominal pain or discomfort

• Abdominal distension

• Palpable pelvic or abdominal mass

• Menstrual irregularities

Acute Presentation

• Torsion of ovarian mass

• Rupture causing acute abdomen

Hormonal Manifestations

• Precocious puberty (β-hCG secretion)

• Amenorrhea

• Virilization (rare)

~Tumor Markers

Tumor markers are crucial for diagnosis, staging, and follow-up.

Tumor Marker	Associated Tumors
AFP	Yolk sac tumor, embryonal carcinoma
β-hCG	Choriocarcinoma, embryonal carcinoma
LDH	Dysgerminoma
CA-125	May be mildly elevated

Key Point:
Elevated AFP excludes pure dysgerminoma.

~Diagnostic Evaluation

1. Imaging

• Ultrasound (Pelvis): First-line investigation

• CT / MRI: Defines tumor extent and metastasis

2. Laboratory Investigations

• Serum AFP, β-hCG, LDH

• Complete blood count

• Liver and renal function tests

3. Surgical Staging

• Required for definitive diagnosis

• Includes peritoneal washings, omental biopsy, lymph node assessment

~Gross Pathology

• Large, unilateral ovarian mass

• Solid or mixed solid-cystic appearance

• Areas of hemorrhage and necrosis in malignant tumors

~Histopathology

Dysgerminoma

• Sheets of large polygonal cells

• Clear cytoplasm

• Central nuclei with prominent nucleoli

• Lymphocytic infiltration

Yolk Sac Tumor

• Schiller-Duval bodies

• Reticular or microcystic pattern

• AFP positivity

Immature Teratoma

• Neuroectodermal tissue

• Graded I–III based on immaturity

~Staging

Ovarian germ cell tumors are staged according to the FIGO staging system used for ovarian cancers.

• Stage I: Tumor confined to ovaries

• Stage II: Pelvic extension

• Stage III: Peritoneal metastasis

• Stage IV: Distant metastasis

~Management

Surgical Treatment

• Fertility-sparing surgery is preferred

  • Unilateral salpingo-oophorectomy

  • Preservation of uterus and contralateral ovary

Chemotherapy

• Indicated in most malignant OGCTs

• BEP regimen (Bleomycin, Etoposide, Cisplatin)

• Highly effective with excellent outcomes

Radiotherapy

• Limited role

• Mainly used in dysgerminoma when chemotherapy is contraindicated

~Prognosis

• Overall survival exceeds 90% with appropriate treatment

• Dysgerminoma: Excellent prognosis

• Yolk sac tumor: Good response to chemotherapy

• Immature teratoma: Prognosis depends on grade

~Follow-Up and Surveillance

• Regular pelvic examination

• Serial tumor marker evaluation

• Imaging at defined intervals

• Monitoring of fertility and menstrual function

~Complications

• Chemotherapy-induced toxicity

• Infertility (rare with modern regimens)

• Recurrence

• Adhesions and surgical complications

~Differential Diagnosis

• Epithelial ovarian tumors

• Sex cord-stromal tumors

• Metastatic ovarian tumors

• Functional ovarian cysts

~Conclusion

Ovarian germ cell tumors represent a unique and highly curable group of ovarian neoplasms that predominantly affect children, adolescents, and young women. Early diagnosis, accurate histological classification, use of tumor markers, and fertility-preserving treatment strategies have significantly improved patient outcomes.

With modern chemotherapy protocols, even advanced-stage disease carries an excellent prognosis. A multidisciplinary approach involving gynecologic oncologists, pathologists, radiologists, and fertility specialists is essential for optimal care and long-term survival.