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Germ Cell Tumors (Extracranial)

Other names / types: Embryonal carcinoma, yolk sac tumor, germinoma, teratoma, mixed germ cell tumor, endodermal sinus tumor

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.

The human body has two main types of cells: somatic cells and germ cells. A somatic cell is any cell in the body that is not a reproductive cell. A germ cell is a cell involved in reproduction. “Germ” comes from the Latin “germen” which means sprout or offshoot.

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:

  1. Mature teratomas are benign tumors. The cells of the tumor look much like normal cells. They are the most common type of extracranial germ cell tumor. They usually form in the sacrum or coccyx in newborns. They also occur in the ovaries of girls as they enter puberty

  2. Immature teratomas are malignant tumors. The cells of the tumor look very different from normal cells. They are most often found in the sacrum or coccyx in newborns and in the ovaries of girls during puberty.

  3. Germinomas are cancerous germ cell tumors. These tumors make a hormone called beta-human chorionic gonadotropin (β-HCG). This hormone may be used as a tumor marker and can help in the diagnosis and monitoring of disease.

    Types of germinomas include: dysgerminomas (ovary), seminomas (testicle), and extragonadal germinomas. These tend to be slow growing tumors.

    Nongerminomas are cancerous germ cell tumors that tend to grow more quickly. Types of nongerminoma tumors include yolk sac tumor, choriocarcinomas, embryonal carcinoma, and mixed germ cell tumor. A nongerminoma that is found in the testes is called a nonseminoma.

    • Yolk sac tumors (also known as endodermal sinus tumor) can be gonadal or extragonadal. They most often occur in the ovaries or testes and make up about 25% of germ cell tumors. Although rare, yolk sac tumor is the most common testicular cancer in boys under 3 years of age. Yolk sac tumors make the hormone alpha-fetoprotein (AFP). The survival rate for childhood yolk sac tumor is over 90%.
    • Choriocarcinomas can be gonadal or extragonadal. They make the hormone beta-human chorionic gonadotropin (β-HCG).
    • Embryonal carcinomas can produce β-HCG and/or AFP. They do not form in the ovary, but can occur in the testicle or other parts of the body.
    • Mixed germ cell tumors can be gonadal or extragonadal. They are made up of malignant germ cell tumor and teratoma.

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.
  1. Germ cell tumors are classified by how the cells look under a microscope. Subtypes include:

    • Germinoma
      • Germinoma
      • Dysgerminoma (ovary)
      • Seminoma (testis)
    • Nongerminoma (somtimes called Nonseminoma)
      • Teratoma (mature and immature)
      • Yolk Sac Tumor (endodermal sinus tumor)
      • Choriocarcinoma
      • Embryonal carcinoma
      • Mixed GCT
  2. Tumors in newborns and young children can occur throughout the body. Extragonadal tumors in young children most often occur in the sacrum or coccyx. In some cases, part of the tumor may be seen externally. When germ cell tumors are present before birth, there is a risk for preterm delivery or problems during birth including tumor rupture causing infant blood loss. Some tumors may be found on routine ultrasound imaging of the fetus during pregnancy.

    Germ cell tumors in young children are usually benign (noncancerous) teratomas. Malignant tumors are less common in younger children.

    Malignant Tumor Subtype Location
    Yolk Sac Tumor Extragonadal, Ovary, Testicle
    Dysgerminoma
    Ovary
  3. Germ cell tumors in teens and young adults are usually gonadal, occurring within the testes or ovary. They may be benign teratomas or have malignant components. Extragonadal tumors in older children and adolescents frequently occur in the mediastinum (chest).

    Malignant Tumor Subtype
    Location
    Seminoma
    Testicle
    Dysgerminoma
    Ovary
    Germinoma
    Extragonadal
    Yolk Sac Tumor
    Extragonadal, Ovary, Testicle
    Choriocarcinoma
    Extragonadal, Ovary, Testicle
    Embryonal Carcinoma
    Extragonadal, Ovary, Testicle
    Mixed germ cell tumors
    Extragonadal, Ovary, Testicle

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:

Stage Tumor treatment
Stage I The tumor is completely removed with surgery
Stage II The tumor is removed by surgery, but there are microscopic cells left behind
Stage III Surgery could not completely remove the tumor, or there is spread of disease to nearby tissues or lymph nodes
Stage IV The tumor has spread to other parts of the body such as liver or lungs

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.

Nonseminoma Testicular GCT
Stage I Limited to testis; complete removal by surgery; no evidence of disease.
Stage II Some rupture of the tumor before or during surgery; spread of disease to nearby tissue; tumor markers do not return to normal.
Stage III Incomplete removal of the tumor with surgery; spread of disease to lymph nodes.
Stage IV
Distant spread of disease to liver, brain, bone, or lung.
Ovarian GCT
Stage I Limited to ovary; complete removal by surgery; no evidence of disease.
Stage II Limited microscopic disease after surgery or the cancer has spread to the outer covering of the ovary.
Stage III Incomplete removal of the tumor with surgery; spread of disease to lymph nodes.
Stage IV
Distant spread of disease: liver, brain, bone, or lung.

The following stages are from the International Federation of Gynecology and Obstetrics (FIGO):

  • Stage I: In stage I, cancer is found in one or both of the ovaries and has not spread
    • Stage IA: Cancer is found in one ovary.
    • Stage IB: Cancer is found in both ovaries.
    • Stage IC: Cancer is found in one or both ovaries and one of the following is true:
      • Cancer is found on the outside surface of one or both ovaries; or
      • The capsule (outer covering) of the tumor has ruptured (broken open); or
      • Cancer cells are found in fluid that has collected in the abdomen; or
      • Cancer cells are found in washings of the peritoneal cavity (the body cavity that contains most of the organs in the abdomen).
  • Stage II: In stage II, cancer is found in one or both ovaries and has spread into other areas of the pelvis.
    • Stage IIA: Cancer has spread to the uterus and/or the fallopian tubes (the long slender tubes through which eggs pass from the ovaries to the uterus).
    • Stage IIB: Cancer has spread to other tissue within the pelvis such as the bladder, rectum, or vagina.
    • Stage IIC: Cancer has spread to the uterus and/or fallopian tubes and/or other tissue within the pelvis and one of the following is true:
      • Cancer is found on the outside surface of one or both ovaries; or
      • The capsule (outer covering) of the tumor has ruptured (broken open); or
      • Cancer cells are found in fluid that has collected in the abdomen; or
      • Cancer cells are found in washings of the peritoneal cavity (the body cavity that contains most of the organs in the abdomen).
  • Stage III: In stage III, cancer is found in one or both ovaries and has spread to other parts of the abdomen. Cancer that has spread to the surface of the liver is also stage III disease.
    • Stage IIIA: The tumor is found in the pelvis only, but cancer cells that can only be seen with a microscope have spread to the surface of the peritoneum (tissue that lines the abdominal wall and covers most of the organs in the abdomen) or to the small bowel.
    • Stage IIIB: Cancer has spread to the peritoneum and is 2 centimeters or smaller in diameter.
    • Stage IIIC: Cancer has spread to the peritoneum and is larger than 2 centimeters in diameter and/or has spread to lymph nodes in the abdomen.
  • Stage IV: In stage IV, cancer is found in one or both ovaries and has metastasized (spread) beyond the abdomen to other parts of the body. Cancer that has spread to tissues in the liver is also stage IV disease.
Germ Cell Tumor Outside the Reproductive System (Extragonadal)
Stage I Limited to one location; complete removal by surgery; no evidence of disease; normal tumor markers after surgery.
Stage II Limited microscopic disease after surgery including nearby tissue and/or lymph nodes; tumor markers do not return to normal.
Stage III Incomplete removal of the tumor with surgery or spread of disease to lymph nodes.
Stage IV
Distant spread of disease: liver, brain, bone, or lung.

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.

  1. Surgery to remove the tumor is a main treatment for germ cell tumors. When possible, the goal of treatment is complete removal (resection) of the tumor. For early stage disease, if the tumor can be fully removed, no other treatment may be needed.

    This type of tumor often requires special care during surgery. Germ cell tumors can grow near vital organs, and they can break apart easily. If parts of the tumor break off (tumor spill), then the cancer is considered to be higher stage.

  2. Chemotherapy may be used alone or in combination with surgery to treat germ cell tumors. Type of chemotherapy will depend on several factors including the child’s age, type of tumor, location of the tumor, and response to therapy. Germ cell tumors usually respond well to platinum-based chemotherapy. Chemotherapy for pediatric germ cell tumor usually includes bleomycin, etoposide, and cisplatin.

    Chemotherapy may be given before surgery to shrink the tumor so that it is easier to remove. Chemotherapy also may be given after surgery to kill any remaining cancer cells.

    High-dose chemotherapy with stem cell rescue may be a treatment option for recurrent 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. 

Patients treated with etoposide have an increased risk of future leukemia. Patients who receive bleomycin are at risk for developing respiratory disease.

Survivors of testicular cancer in adulthood have been shown to have an increased risk of second cancer. It is not yet known how these risks might be similar or different for survivors of childhood testicular cancer.

Long term follow up by a medical provider familiar with late effects and survivorship issues is important for all survivors of pediatric cancer.


Reviewed: June 2018