What is a germ cell tumor?

What is a Germ Cell Tumour

Germ cell tumours are neoplasms arising from primordial germ cells—the cells destined to become eggs or sperm—that can occur in gonadal (testicular or ovarian) or extragonadal sites along the body's midline. 1, 2

Origin and Biological Basis

• Germ cell tumours originate from the germline cells that migrate during embryonic development from the yolk sac wall to the primitive gonad 3
• Their intrinsic pluripotency—the ability to differentiate into any cell type—explains why these tumours display such diverse histological patterns and biological behaviors 2, 4
• The developmental potential of each tumour is determined by the maturation stage and imprinting status of the originating germ cell 4

Anatomical Distribution

Gonadal locations:

• Testicular germ cell tumours represent 95% of all testicular malignancies and are the most common solid tumour in men aged 15-40 years 5, 6
• Ovarian germ cell tumours account for approximately 2.9% of all ovarian tumours, with an incidence of 0.7 per million per year in Europe 1

Extragonadal locations:

• Extracranial sites include mediastinum, retroperitoneum, and sacrococcygeal regions (0.7 per million per year in Europe) 1, 3
• Intracranial sites primarily involve the suprasellar region and pineal gland (0.4-0.6 per million per year) 1
• These midline locations reflect the embryonic migration pathway of primordial germ cells 3

Histological Classification

According to WHO classification, germ cell tumours include: 1

Seminomatous tumours:

• Seminoma (most common testicular malignancy in young adults) 6
• Spermatocytic seminoma 1

Non-seminomatous tumours:

• Embryonal carcinoma 1
• Yolk sac tumour (endodermal sinus tumour) 1
• Choriocarcinoma 1
• Teratoma (mature, immature, or with malignant transformation) 1
• Polyembryoma 1

Mixed germ cell tumours:

• Tumours with multiple histological components, where each component and its relative proportion must be documented 1

Clinical Significance and Prognosis

• Germ cell tumours are among the most curable solid cancers, with cure rates exceeding 95% in localized disease and over 80% in metastatic disease 7, 8
• Prognosis is stratified using the International Germ Cell Cancer Collaborative Group (IGCCCG) classification, which categorizes patients into good (90% 5-year survival), intermediate (80%), and poor (50%) prognosis groups based on histology, primary site, metastatic location, and tumour markers (AFP, β-HCG, LDH) 1
• Testicular germ cell tumours show marked racial and geographical variation, being much more common in Western Europe (especially Scandinavia) and rare in Africa and among Black populations 3

Tumour Markers

Critical diagnostic and prognostic markers include: 1, 5

• AFP (alpha-fetoprotein): Elevated in yolk sac tumours and some embryonal carcinomas; always indicates non-seminomatous component even if histology shows "pure seminoma" 5
• β-HCG (beta-human chorionic gonadotropin): Produced by choriocarcinoma and syncytiotrophoblasts; elevated in 40% of advanced non-seminomas and 15-20% of advanced seminomas 5
• LDH (lactate dehydrogenase): Non-specific marker used in prognostic stratification 1

Age and Presentation Patterns

• In fetuses and neonates, germ cell tumours are predominantly mature and immature teratomas, usually curable with surgery alone 2
• Malignant germ cell tumours occur mainly in children and young adults, representing one of the most important neoplasm groups in this age range 3
• Peak incidence for seminoma is in the third decade of life 6