Ovarian germ cell tumors originate from primitive germ cells and account for approximately 20–40% of ovarian tumors. These tumors predominantly occur in young females and represent the most common gynecological tumors in adolescents. Apart from mature teratomas, most histological types are malignant.
Pathology
Teratoma
Teratoma is the most common germ cell tumor, typically composed of tissue from 2–3 germ layers (ectoderm, mesoderm, and/or endoderm), though occasionally consisting of a single germ layer. The benign or malignant nature of the tumor depends on the degree of tissue differentiation.
Mature Teratoma
A benign tumor, mature teratomas account for 10–20% of all ovarian tumors, 60% of ovarian tumors in patients under 20 years old, 85–97% of germ cell tumors, and over 95% of ovarian teratomas. Most are unilateral, with bilateral cases occurring in 10% of patients. The majority of tumors are cystic, often unilocular, of moderate size, with smooth and firm walls. The cavity frequently contains greasy material and hair, and teeth or bone are occasionally observed. A small protuberance protruding into the cavity is often seen on the wall, referred to as the "Rokitansky nodule." The tumor consists of multiple germ layer elements, and the inner lining of the cyst wall is often covered by stratified squamous epithelium. Differentiation into a single germ layer is also possible, such as struma ovarii, which secretes thyroid hormone and may even cause hyperthyroidism. Any component of a mature teratoma can undergo malignant transformation, with a malignancy rate of 2–4%. Squamous cell carcinoma is the most common type of malignancy, followed by adenocarcinoma and carcinoid tumors, typically occurring near the thickened wall of the "Rokitansky nodule."
Immature Teratoma
A malignant tumor, immature teratomas represent 1–3% of ovarian teratomas and are most frequently observed before the age of 30, particularly among individuals aged 11–19. These tumors are often solid, with a fleshy appearance, though they may contain cystic regions. They are comprised of embryonic tissues with varying degrees of immaturity, predominantly primitive neural tissue. Microscopically, most cases exhibit primitive neural tubules and rosettes, mixed with various ectodermal or endodermal components. The histological grading is classified into 1–3 levels based on the amount of immature neural epithelial tissue present, which directly correlates with the likelihood of recurrence and metastasis. The recurrence and metastasis rates of this tumor are high. However, some patients who undergo subsequent surgeries for recurrences may show evidence of transformation from immature to mature tumor tissue, indicating a reversal of malignancy.
Dysgerminoma
Dysgerminoma is a primitive germ cell tumor that accounts for 1–2% of malignant ovarian tumors. It almost exclusively occurs in children and young women, predominantly affecting one ovary. Tumors are typically round or oval, usually greater than 10 cm in size, rubbery to the touch, with a smooth or lobulated surface. Sections are solid and light brown in color. Microscopically, the tumor is composed of large round or polygonal cells with prominent nuclei and abundant cytoplasm. Tumor cells are arranged in sheets or cords, separated by small amounts of fibrous stroma, which often contains lymphocytic infiltration. Dysgerminomas exhibit good sensitivity to chemotherapy and radiotherapy, resulting in favorable prognoses.
Yolk Sac Tumor
This tumor originates from extra-embryonic structures such as the yolk sac, with a histological structure resembling the unique perivascular formations (Schiller-Duval bodies) of the rat placenta. It was previously referred to as an endodermal sinus tumor. As the second most common ovarian germ cell tumor, yolk sac tumors account for approximately 20% of cases and are primarily seen in girls and young women. Most tumors are unilateral, round or oval, and exhibit regions of hemorrhage and necrosis on cross-section. The tumor tissue is friable and prone to rupture. Microscopically, a variety of structures can coexist, with a loose reticular pattern being the most common, alongside endodermal sinus-like, papillary, solid, and glandular structures. The stroma is typically mucoid and loose. Tumor cells exhibit diverse morphology and can secrete alpha-fetoprotein (AFP), making elevated serum AFP levels an important diagnostic and therapeutic monitoring marker. The tumor is highly malignant, grows rapidly, is prone to early metastasis, and responds well to chemotherapy.
Embryonal Carcinoma
Embryonal carcinoma is a rare, undifferentiated malignant germ cell tumor with a potential for multiple differentiation pathways. It accounts for less than 5% of malignant ovarian germ cell tumors. These tumors are encapsulated, soft, and often accompanied by hemorrhage, necrosis, and capsular rupture. They are solid, grayish-white, and resemble fish flesh on cross-section. Microscopically, tumor cells display a relatively homogeneous or pleomorphic appearance, growing in sheets or nests, often with focal glandular differentiation. The stroma is composed of primitive and mucinous tissue. The tumor cells may exhibit various patterns, including solid, nested, glandular, and papillary structures. Pure embryonal carcinoma is rare and often coexists with other germ cell tumors. This tumor is highly invasive, exhibits wide dissemination, and metastasizes early. Early metastases occur via lymphatic spread, with later stages involving hematogenous dissemination. Prognoses are poor, although chemotherapy offers sensitivity.
Choriocarcinoma
Choriocarcinoma, also known as chorioepithelioma, includes primary ovarian choriocarcinomas, which are referred to as non-gestational choriocarcinomas. These tumors are derived from multipotent germ cells differentiating into extra-embryonic structures such as trophoblasts or yolk sac. They are characterized by extreme malignancy and can be classified as mixed or pure types. Primary ovarian choriocarcinomas are typically of the mixed type, with choriocarcinoma components coexisting with other malignant germ cell tumors. Microscopically, the morphology of primary ovarian choriocarcinoma resembles gestational choriocarcinoma and consists of cytotrophoblasts and syncytiotrophoblasts. A definitive diagnosis requires the presence of both trophoblastic cell types. The tumor exhibits early hematogenous metastasis and has a worse prognosis compared to gestational choriocarcinomas.
Diagnosis
Benign ovarian germ cell tumors often lack specific symptoms and are typically identified during routine physical examinations or when patients present with complications such as torsion or rupture. Malignant ovarian germ cell tumors frequently exhibit characteristic clinical features, including younger onset, large tumor size, and rapid disease progression. Yolk sac tumors and primary ovarian choriocarcinomas may secrete serum AFP and hCG, respectively, which can aid in diagnosis, though definitive confirmation requires histopathological examination.
Treatment
Benign Germ Cell Tumors
The treatment of benign germ cell tumors follows the same principles as those for benign ovarian epithelial tumors.
Malignant Germ Cell Tumors
Surgical Treatment
For patients with no fertility preservation requirements, comprehensive staging surgery is recommended. For young patients wishing to preserve fertility, fertility-sparing surgery is feasible regardless of disease stage. Surgical intervention remains the preferred approach for recurrent ovarian germ cell tumors.
Chemotherapy
Malignant germ cell tumors are highly sensitive to chemotherapy. Except for stage I dysgerminomas and low-grade immature teratomas, adjuvant chemotherapy is recommended post-surgery. The BEP (bleomycin + etoposide + cisplatin) regimen is the first choice, with four cycles for high-risk patients and three cycles for low-risk patients. To minimize toxic side effects, especially neurotoxicity, the carboplatin + etoposide regimen can be used for three cycles in patients with stage II–III dysgerminomas. Given the pulmonary toxicity of bleomycin, dose reductions are necessary for pediatric patients (0–14 years).
Radiotherapy
Although dysgerminomas are radiosensitive, radiotherapy is rarely used in initial treatment due to its detrimental effects on ovarian function. For recurrent dysgerminomas, radiotherapy remains effective after chemotherapy resistance has developed.