Non-seminomatous germ cell tumours

Non-seminomatous germ cell tumours (NSGCTs) are one of the main groups of germ cell tumours (the other being seminoma). Although they are made up of distinct histological entities, in general, they have similar radiographic appearances. They can, however, be found widely in the body, with variable imaging features, pathology, treatment and prognosis. As such they are discussed separately.

This article focuses on a general discussion of non-seminomatous germ cell tumours, as well as providing a structure to individual articles.

Epidemiology

They occur in younger patients than seminoma, with a peak incidence in late teens to twenties. They are the most common primary testicular malignancy, accounting for ~60% of cases.

Some consider testicular microlithiasis to be a risk factor for germ-cell tumours, although this is controversial.

Clinical presentation

They tend to be more aggressive than seminomas, and frequently metastasise.

Serological markers

Approximately 70% of non-seminomatous germ cell tumours produce hormonal markers (tumour markers):

• alpha-fetoprotein (AFP): typically elevated in yolk sac tumour
• beta-human chorionic gonadotropin (β-hCG): typically elevated in choriocarcinoma
• lactate dehydrogenase (LDH)

Pathology

Non-seminomatous germ cell tumours can be divided histologically into:

• embryonal cell carcinoma: rare
• choriocarcinoma: rare (carries worst prognosis)
• yolk sac tumour
• teratoma: accounts for 5-10% of germ cell tumours
  • mature
  • immature
  • teratoma with malignant transformation
• mixed germ cell tumour
  • is the most common type of NSGCT
  • accounts for 40% of all germ cell tumours
  • the most common combination is teratoma and embryonal cell carcinoma

See: classification of germ cell tumours.

Radiographic features

In contrast to seminomas, non-seminomatous germ cell tumours tend to be more heterogeneous on ultrasound and on T2-weighted MR images with frequent cystic areas or calcification. They tend to be more aggressive than seminomas and tunica invasion is common. The appearance of an individual tumour will, of course, vary depending on the location. Please refer to the parent article germ cell tumours for links to specific locations.

Imaging is also essential for the staging of non-seminomatous germ cell tumours which is location dependent. See testicular cancer staging.

Treatment and prognosis

The prognosis of non-seminomatous germ cell tumours is variable and depends on the biological behaviour of individual tumours. Prognosis can be inferred from tumour markers, the location of the primary tumour and the presence of metastases ⁴.

• good prognosis (all of the following must be true)
  • tumour markers
    • alpha-fetoprotein <1000 ng/mL
    • beta HCG <5000 IU/L
    • LDH <1.5x upper limit of normal
  • non-mediastinal location of the primary tumour
  • no nonpulmonary metastases

  These patients are usually treated with orchidectomy followed by chemotherapy (bleomycin, etoposide and cisplatin - BEP regimen).

• intermediate prognosis (all of the following must be true)
  • tumour markers
    • alpha-fetoprotein: 1000-10,000 ng/mL
    • beta-hCG: 5000-50,000 IU/L
    • LDH: 1.5-10x upper limit of normal
  • non-mediastinal location of the primary tumour
  • no nonpulmonary metastases

  These patients are started with chemotherapy cycles and sometimes followed by adjuvant surgery.

• poor prognosis (any of the following):
  • tumour markers
    • alpha-fetoprotein: >10,000 ng/mL
    • beta-hCG: >50,000 IU/L
    • LDH: >10x upper limit of normal
  • mediastinal primary tumour
  • nonpulmonary metastases present

Considering a poor prognosis, surgery is usually precluded, and patients are followed with aggressive chemotherapy.