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 neonates, most extracranial GCTs are benign midline teratomas.
    • Despite being nonmalignant, they confer high morbidity secondary to hydrops fetalis and premature delivery.
  • In children <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.
  • In children 15 to 19 years, extracranial GCTs account for approximately 14% of cancer diagnoses; most GCTs in this age group are germinomas.
  • 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

  • GCTs are thought to result from altered intrauterine events; potential risk factors include fetal chemical or hormone exposures or congenital abnormalities, primarily of sex chromosomes or sexual differentiation.
  • In boys, increased risk of testicular or mediastinal GCT with cryptorchidism and Klinefelter syndrome respectively
  • Approximately 50% of adolescent mediastinal GCTs are associated with Klinefelter syndrome.
  • Disorders of sexual differentiation including Turner syndrome with any portion of Y chromosomal material, Frasier syndrome, Swyer syndrome, other androgen insensitivity syndromes, Denys-Drash syndrome are all associated with increased GCT in streak gonads.
  • Streak gonads particularly associated with gonadoblastoma


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 postpubertal boy with cryptorchidism.
    • Counsel all men with a history of cryptorchidism and/or their parents regarding the long-term risk of testicular cancer.


  • GCTs arise from primordial germ cells with molecular defects.
    • Germinomas (testicular seminomas and ovarian dysgerminomas) originate directly from undifferentiated primordial germ cells.
    • Embryonal carcinomas have early embryonic differentiation, so produce teratomas with all three germ layers (endoderm, ectoderm, mesoderm).
    • Yolk sac tumors and choriocarcinomas originate from primordial germ cells with extra-embryonic differentiation.
    • Mixed malignant GCTs contain various histologies.
  • Primordial germs cells migrate through the midline from the yolk sac to the gonadal ridge; disruption of this migration likely explains the midline propensity of extragonadal GCTs.
  • Certain oncogenic miRNAs (miR-371-373 and miR-302/367 clusters) are overexpressed in all malignant GCTs.
    • These are detectable in serum at time of diagnosis and should respond to treatment; this is more sensitive and specific than traditional biomarkers.
  • Genetic profiles are different in children than adults, even for same histologic subtypes, suggesting gene expression may be driven, at least partially, by pubertal hormonal changes.
  • Gain of short arm of chromosome 12, isochromosome 12p [or i(12)p] is present in >80% postpubertal GCTs.
  • Malignant GCTs in children <4 years often contain cytogenetic abnormalities in chromosomes 1, 3, 6, 11 and others.
    • Deletion of 1q36 is present in 80–100% of infantile malignant GCTs in testicular as well as extragonadal sites.
    • Infantile yolk sack tumors include alterations including loss of 6q24-qter or 1p, gain of 20q and 1q, and c-myc or n-myc amplification.
  • Single nucleotide polymorphisms (SNPs) in genes involved in KIT/ KITLG signaling, male germ cell development, increased telomerase activity, defective microtubules, and DNA damage repair pathways are implicated in GCT development.
  • Epigenetics may also contribute to GCT development.
    • Yolk sac tumors have increased methylation.

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