Germ Cell Tumors



Germ cell tumors (GCTs) are a heterogeneous group with a suspected common cell of origin, the primordial germ cell.

  • Their location can be gonadal or extragonadal.
  • The numerous histologic subtypes are broadly classified as mature or immature teratomas and malignant GCTs.
  • See “Brain Tumor” chapter for primary CNS GCT.


The incidence has a bimodal distribution with a smaller peak in early infancy and a larger peak in adolescence.

  • In children younger than 15 years of age, GCTs occur at a rate of 2.4 cases per million children, and they account for 2–3% of all malignancies.
  • Between 15 and 19 years of age, extracranial GCTs account for approximately 14% of cancer diagnoses.
  • Teratomas and germinomas are the predominant histologic subtypes of early infancy and adolescence respectively.
  • Sacrococcygeal teratomas account for 50% of childhood teratomas. They are most prevalent in infants (1:40,000 live births); with a female predominance (4:1)

Risk Factors

  • Sex chromosome abnormalities are associated with an increased risk for GCTs.
  • Klinefelter syndrome is associated with an increased risk of mediastinal GCTs.
    • Approximately 50% of adolescent mediastinal GCTs are associated with a cytogenetic diagnosis of Klinefelter syndrome.
  • Turner syndrome with any portion of Y chromosome material, Swyer syndrome, nonscrotal partial androgen insensitivity, Frasier syndrome, and males with Denys-Drash syndrome are all associated with streak gonads at increased risk for developing GCTs.
  • History of cryptorchidism is associated with an increased risk of testicular GCT.


Familial GCT has been described in 1.5–2% of adult GCTs and a similar contribution to adolescent GCTs is presumed.

General Prevention

  • Prophylactic gonadectomy is recommended for streak gonads in the specific syndromes mentioned above because of the increased risk of developing GCTs.
  • Guidelines on the management of cryptorchidism recommend the following to decrease the future risk of testicular GCT:
    • Orchidopexy by 18 months of age
    • Consideration of orchiectomy of an undescended testis in all boys with a normal contralateral testis when orchidopexy is not feasible
    • Consider orchiectomy or biopsy in a post pubertal boy with cryptorchidism.
    • Counsel all men with a history of cryptorchidism and/or their parents regarding the long-term risk of testicular cancer.


  • GCTs are hypothesized to originate from primordial germ cells containing neoplastic genetic aberrations.
  • Arrested migration of primordial germ cells is presumed to explain the midline location of extragonadal GCTs.
  • The postpubertal peak in the incidence of GCTs suggests hormonal factors are involved in their growth.
  • Isochromosome 12p or i(12)p is present in more than 80% of postpubertal GCTs. GCTs without the i(12)p typically have gain of 12p chromosomal material.
    • Mature and immature ovarian tumors are biologically distinct in their lack of association with the i(12)p.
    • A number of other genetic mutations have been observed in testicular GCTs.
  • Malignant GCTs in children younger than age 4 years typically contain cytogenetic abnormalities of chromosomes 1, 3, 6, and others.
    • The i(12)p is rarely seen in this group.
    • Deletion of 1q36 is present in 80–100% of infantile malignant GCTs in testicular and extragonadal sites.
    • Recurrent genetic changes of infantile yolk sac tumors include loss of 6q24-qter, gain of 20q and 1q, loss of 1p, and c-myc or n-myc amplification.

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