Residency · Residency · Pathology
Testicular and Ovarian Germ Cell Tumors
Introduction
Germ cell tumors (GCTs) arise from primordial germ cells and represent a diverse group of neoplasms occurring in gonadal and extragonadal sites. They are the most common solid malignancy in males aged 15 to 35 and account for approximately 20 to 25 percent of ovarian neoplasms. Understanding their classification, morphology, and immunohistochemical profiles is essential for accurate diagnosis.
Embryology and Pathogenesis
Primordial germ cells migrate from the yolk sac to the gonadal ridge during embryogenesis. Germ cell neoplasia in situ (GCNIS) is the precursor lesion in the testis, found in nearly all adult-type GCTs. Isochromosome 12p, designated i(12p), is a hallmark cytogenetic abnormality in testicular GCTs. Risk factors include cryptorchidism, disorders of sex development, and prior contralateral GCT.
Classification of Testicular Germ Cell Tumors
Seminoma
Seminoma is the most common pure testicular GCT, accounting for approximately 50 percent. It consists of sheets of uniform cells with clear cytoplasm and prominent nucleoli, accompanied by a lymphocytic infiltrate. The immunoprofile is positive for OCT3/4, PLAP, D2-40, SALL4, and c-KIT, while CD30 is negative. A granulomatous reaction is common.
Non-Seminomatous Germ Cell Tumors (NSGCTs)
Embryonal carcinoma is composed of primitive epithelial cells with marked pleomorphism and is positive for OCT3/4, CD30, and SALL4. Yolk sac tumor characteristically shows Schiller-Duval bodies along with reticular and microcystic patterns, and is positive for AFP, glypican-3, and SALL4. Choriocarcinoma displays a biphasic pattern of syncytiotrophoblast and cytotrophoblast with markedly elevated beta-hCG. Teratoma contains mature or immature elements from all three germ layers; in the postpubertal testis, teratoma is considered malignant regardless of the degree of maturity.
Classification of Ovarian Germ Cell Tumors
Dysgerminoma
Dysgerminoma is the ovarian counterpart of seminoma and represents the most common malignant ovarian GCT. It has identical morphology and immunophenotype to seminoma. Prognosis is excellent due to high chemosensitivity.
Immature Teratoma
Immature teratoma of the ovary is graded 1 through 3 based on the amount of immature neuroepithelium. The grade correlates directly with prognosis and the need for adjuvant chemotherapy.
Yolk Sac Tumor
Yolk sac tumor is the most common ovarian GCT in children. Elevated serum alpha-fetoprotein (AFP) is a reliable tumor marker for diagnosis and monitoring.
Staging and Serum Tumor Markers
AFP is elevated in yolk sac tumor and some embryonal carcinomas, with a half-life of approximately 5 days. Beta-hCG is elevated in choriocarcinoma and some seminomas, with a half-life of 24 to 36 hours. LDH is non-specific but correlates with tumor burden. Staging follows the AJCC TNM system, which includes an S category for serum markers in testicular tumors.
Mixed Germ Cell Tumors
Approximately 30 to 40 percent of testicular GCTs are mixed, containing more than one histologic component. Each component must be reported with its percentage. The presence of even small amounts of non-seminomatous elements changes management from seminoma-directed to NSGCT-directed therapy.
Immunohistochemistry Summary
| Marker | Seminoma | Embryonal CA | Yolk Sac | Choriocarcinoma |
|---|---|---|---|---|
| OCT3/4 | + | + | - | - |
| SALL4 | + | + | + | + |
| CD30 | - | + | - | - |
| AFP | - | - | + | - |
| Beta-hCG | +/- | - | - | + |
| Glypican-3 | - | - | + | + |
Clinical Pearls
All components and their percentages must be reported in mixed GCTs because the presence of any non-seminomatous element dictates therapy. GCNIS identified in a testicular biopsy warrants close surveillance or treatment of the contralateral testis given the high risk of subsequent tumor development. Post-chemotherapy retroperitoneal lymph node dissection specimens should be carefully sampled to quantify viable tumor, teratoma, and necrosis, as each carries different prognostic and therapeutic implications. Serum markers that fail to decline appropriately after orchiectomy suggest residual or metastatic disease and should prompt further investigation.
References
- Moch H, et al. WHO Classification of Tumours: Urinary System and Male Genital Organs. 5th ed. Lyon: IARC Press; 2022.
- Ulbright TM. Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol. 2005;18(Suppl 2):S61-S79.
- Nogales FF, et al. Germ cell tumours of the ovary: an update. Adv Anat Pathol. 2014;21(3):178-192.
- Williamson SR, et al. The World Health Organization 2016 classification of testicular germ cell tumours: a review and update. Histopathology. 2017;70(3):335-346.