Germ Cell Tumors (Extracranial)

What are Germ Cell Tumors?

Germ cells are cells of the reproductive system. They are the cells that mature to become egg cells in females or sperm cells in males. Germ cells develop very early as the baby grows inside the mother.

Sometimes, germ cells can form tumors, called germ cell tumors (GCT). Germ cell tumors may be benign (not cancer) or malignant (cancer).

Because germ cells begin to grow so early in fetal development, the cells can sometimes travel to places other than the ovary or testicle. Germ cell tumors can occur in different parts of the body including:

• Ovaries or Testicles (gonadal)
• Neck
• Area between the lungs (mediastinal)
• Back part of the abdomen (retroperitoneal)
• Lower part of the spine or tailbone (sacrum, coccyx)
• Brain (see Intracranial Germ Cell Tumors)

Extracranial germ cell tumors are all germ cell tumors that form outside of the brain. Usually extracranial germ cell tumors form in reproductive organs (ovaries or testicles). These are called gonadal germ cell tumors.

Germ cells can also travel outside of the reproductive system and form tumors. Germ cell tumors that occur outside of the ovaries and testicles are called extragonadal germ cell tumors. About half of germ cell tumors in childhood occur outside the ovaries and testicles. These tumors usually grow along the midline (center) of the body.

Germ cell tumors can occur at any age, newborn through adult. In pediatric patients, they occur most often in young children and teens 15 to 19 years old. These tumors account for about 3% of childhood cancers.

Some children with a germ cell tumor may be treated with surgery alone. Chemotherapy may be used in addition to surgery for more advanced disease or to shrink the tumor before surgery. If the tumor can be completely removed with surgery, children have an excellent chance of recovery.

There are several types of germ cell tumors:

Risk Factors and Causes of Germ Cell Tumors

Germ cell tumors are most common in young children and in teens. An increase in germ cell tumors is seen in adolescents 15-20 years of age.

The cause of germ cell tumors is largely unknown. Certain inherited syndromes can increase the risk of developing a germ cell tumor including Klinefelter syndrome, Swyer syndrome, and Turner syndrome.

In newborns and infants, germ cell tumors occurring in the area of the lower spine or tailbone (sacrococcygeal) tend to occur more often in girls. After infancy, the ovaries are the most common site for a germ cell tumor to develop in girls.

In boys, having an undescended testicle can increase risk for gonadal germ cell tumor in that testicle.

Signs and Symptoms of Germ Cell Tumors

Signs and symptoms of a germ cell tumor depend on the tumor size and location. Symptoms may include:

• Abdominal pain
• Lump or swelling in the abdomen, lower back, or testicle
• Constipation
• Cough or trouble breathing
• Early onset of puberty

Diagnosis of Germ Cell Tumor

Doctors use several types of tests to evaluate germ cell tumors and make a diagnosis. These may include:

• A health history, physical exam, and blood tests to learn about symptoms, general health, past illnesses, and risk factors. 
  • Family history is important to determine whether there might be an inherited risk. 
  • Blood tests are used to evaluate blood counts and liver and kidney function. Blood tests are also used to look for tumor markers, substances released by certain tumors. Tumor markers are monitored throughout treatment and recovery. Tumor markers that are used to diagnose germ cell tumor include alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (β-HCG).
  • Fluid in the abdomen and/or chest may be tested to look for cancer cells. 
• Imaging tests are used to help identify germ cell tumor. The images give information about the size and location of the tumor and help doctors better understand what parts of the body might be affected. Imaging tests include one or more of the following:
  • Ultrasound uses sound waves to create an image of the organs and tissues within the body. Ultrasound may be used to examine the testes or abdomen. 
  • Computed tomography (CT or CAT scan) uses X-rays to create images of the organs and tissues inside the body. 
  • Magnetic resonance imaging (MRI) makes detailed pictures of the body using radio waves and magnets.
  • A bone scan uses a special scanner to take pictures of the body. In this test, the patient receives an injection with small amount of radioactive material that travels throughout the body in the blood. This substance collects in the bones and can highlight areas where cancer has spread.
  • Positron emission tomography (PET) scan uses radioactive glucose (sugar) given through a vein to make computerized images of the body. The glucose travels through the body and is taken up by cells which use sugar for energy. This allows the different tissues and organs to appear as colored pictures on a computer screen. Cancer cells often grow and divide faster than other cells, and they take up more glucose. This can allow the tumor to be seen more clearly on a PET scan. PET can sometimes detect cancer in areas of the body that do not appear on a CT scan or MRI.
• A biopsy is usually performed to diagnose germ cell tumor. In a biopsy, a small sample of the tumor is removed during surgery. A pathologist looks at the tissue sample under a microscope to identify the specific type of germ cell tumor.
  

Staging of Germ Cell Tumor

Staging of pediatric germ cell tumor is based on type of tumor, tumor location, spread of disease, and outcome of surgery. In general, there are 4 stages of germ cell tumor:

Each type of germ cell tumor has specific information used to determine stage. Staging may also depend on the age of the patient. In older adolescents, doctors may use adult criteria to classify the stage of disease.

Prognosis for Germ Cell Tumor

The prognosis is excellent for germ cell tumor when the cancer can be fully removed. Children with stage I or II disease have a greater than 90% cure rate. Survival rates for more advanced disease (stage III or IV) are estimated to be about 80-85%. However, these rates are only estimates because many factors can influence a patient’s chance of cure.

Factors that influence prognosis for germ cell tumor include:

• Type of germ cell tumor
• Location and size of the tumor
• Age of the child
• How the tumor responds to treatment
• If surgery can completely remove the tumor
• Whether there is spread of disease
• Whether the tumor is new or has recurred

About 20% of patients have spread of disease at diagnosis. The most common place for metastasis is the lung, liver, and lymph nodes. Less commonly, germ cell tumor may spread to the brain or bone.

Treatment of Germ Cell Tumor

Treatment for germ cell tumor depends on several factors including the child’s age, type of tumor, location of the tumor, and stage of disease. The main treatments for germ cell tumors are surgery and chemotherapy.

Radiation therapy is not usually used because of the effectiveness of chemotherapy and/or surgery. However, germ cell tumors are sensitive to radiation, and it may be used in cases of recurrent or progressive disease.

Life after Germ Cell Tumor

After treatment, periodic imaging and monitoring of tumor markers are used to watch for recurrence of germ cell tumor.

Long-term problems depend on the specific type of germ cell tumor and the type of treatment received. Children with gonadal germ cell tumors may have problems with fertility (having children) or hormone function.

Late effects of therapy

For general health and disease prevention, all cancer survivors should adopt healthy lifestyle and eating habits, as well as continue to have regular physical checkups and screenings by a primary physician. Childhood cancer survivors treated with systemic chemotherapy or radiation should be monitored at least once a year for acute and late effects of therapy.