Germ cell tumors develop from primitive cells that normally mature into ova (eggs) in the ovaries of women and sperm in the testicles of men. Ninety percent of all germ cell tumors develop in the ovaries and testes. In females, these are called gonadal tumors. In males, these are referred to as germ cell tumors of the testis. The remaining 10% develop outside of the gonads. These are called extragonadal germ cell tumors. Extragonadal germ cell tumors typically form in the chest, back portion of the abdomen (the retroperitoneum), lower back and central portion of the brain.

Many researchers believe that extragonadal germ cell tumors are related to developmental problems that occur before birth. In the growing embryo, germ cells typically move from a site near the middle of the body to their permanent home in the ovaries or testes. Sometimes, however, there is a problem, and the germ cells never reach their final destination. Instead, the misplaced germ cells settle in the mid-chest area between the lungs, in the lower back just above the buttocks or in the head near the pea-sized pineal gland located in the middle of the brain. When misplaced germ cells grow in these sites, they sometimes develop into tumors, which can be noncancerous (benign) or cancerous (malignant).

Extragonadal germ cell tumors account for 2% to 3% of all childhood cancers. In young children, these tumors tend to occur in the lower back. Most of these tumors are not cancerous. In adults, extragonadal germ cell tumors tend to occur in the mid-chest area. About 40% of these tumors are cancerous. Cancerous extragonadal germ cell tumors are rare. Only one new case is diagnosed each year for every 2 million to 3 million people in the United States. Cancerous extragonadal germ cell tumors occur equally in young boys and girls, but in adults, they are nine times more common in men than in women.

Recently, some specific genetic abnormalities have been associated with extragonadal germ cell tumors. In addition, these are also associated with cancers of the blood system, specifically a cancer of the platelet forming organs of the bone marrow. The association of these two rare cancers raises the possibilities that they may be derived from a common cell which upon becoming abnormal, may develop into a germ cell cancer or a blood type of cancer.

There are several types of cancerous extragonadal germ cell tumors. They are initially classified as seminomas or nonseminomas. Nonseminomas can be further classified as embryonal carcinomas, malignant teratomas, endodermal sinus tumors, choriocarcinomas or mixed germ cell tumors. The specific type of germ cell tumor influences both treatment and prognosis. There are several reasons for making a distinction between seminomas and nonseminomas, principally related to the responsiveness to radiation treatments. Seminomas tend to be very responsive to radiation, and radiation is the mainstay for treatment. Chemotherapy is often used for nonseminomas and in certain circumstances, seminomas as well.

Symptoms depend on the location of the tumor:

• Mid-chest area (mediastinum) – Cancerous germ cell tumors can cause chest pain, breathing problems, cough and fever. They most commonly are diagnosed in men aged 20 to 30. Patients may also have bulging veins on their chest and neck as initial manifestation of an abnormal growth in the middle of the chest.



• Lower-back area (presacral area) – A cancerous germ cell tumor usually appears as a mass in the lower abdomen or buttocks of an infant or young child. Because of its size and location, the mass may cause difficulty in walking, urinating or having a bowel movement. Noncancerous and cancerous germ cell tumors are much more common in children than in adults. Tumors in children younger than 6 months old are noncancerous in 98% of cases. Tumors in children older than 6 months are cancerous in about 65% of cases.



• Retroperitoneal area – Tumors that arise from the back of the abdomen (the retroperitoneal) may present with back pain, an abdominal mass that can be felt during a physical examination, or blockage of the kidneys due to pressure on the tubes that drain the kidney to the bladder. This is one of the most common presenting features of extragonadal germ cell tumors.



• Head (pineal area) – Cancerous germ cell tumors cause symptoms by pressing directly on parts of the brain or by interfering with the normal flow of the fluid that circulates around the brain and spinal cord. Symptoms can include headache, nausea, vomiting, memory loss, lethargy, difficulty walking, inability to look upward, uncontrolled eye movements or double vision. A child with a tumor that begins to produce hormones may show physical signs of puberty at an abnormally young age. Almost all pineal germ cell tumors occur in people younger than 40.

Because cancerous extragonadal germ cell tumors are rare, your doctor probably will ask about common medical conditions that could be causing your symptoms. For example, if you have a cough, fever and difficulty breathing, your doctor may suspect a respiratory-tract infection. The true cause of your condition may not be known until your doctor orders X-rays or scans of the area of the body where you are having symptoms.

Your doctor will thoroughly examine you, paying special attention to the area where you have symptoms. If you have symptoms of a lower-back tumor, the exam may include a rectal examination and, in women, a pelvic examination. If you have symptoms of a pineal tumor, the physical exam will include a neurological examination.

Your doctor will order different diagnostic tests depending on where the tumor is located:

• Mid-chest area (mediastinum) – A standard chest X-ray shows the tumor's location in 95% of cases. Computed tomography (CT) of the chest can reveal the extent of the tumor. CT of the abdomen can check to see if the tumor has spread to the liver or other sites. To confirm the diagnosis, doctors usually examine a piece of the tumor, which is removed with a needle (aspiration) or by cutting open the tumor. This is called a biopsy. However, some patients with nonseminomas can be diagnosed through blood tests that look for abnormal blood levels of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG).



• Lower-back area (presacral area) – Ultrasound or magnetic resonance imaging (MRI) will be used to assess the size of the tumor. To check for tumor cells that have spread, your doctor probably will order a bone scan, chest X-ray, CT scan of the lungs and a bone-marrow biopsy or aspirate. A biopsy of the tumor confirms the diagnosis.



• Head (pineal area) – Although a CT scan of the head usually will show a pineal tumor, an MRI provides more information. To make a definitive diagnosis, the tumor is removed surgically and examined in a laboratory.

Because of the association of cancers of the blood-forming cells, a careful examination of the blood counts and sometimes an evaluation of the bone marrow may be a part of the diagnostic workup.

In most patients with suspected germ cell tumors, blood tests of the levels of AFP and beta-hCG can help to determine the specific type of tumor (seminoma or nonseminoma). In people with pineal tumors, AFP and beta-hCG levels also may be measured in the spinal fluid. The fluid is removed from the spinal cord for testing in a procedure known as a spinal tap or lumbar puncture.

Unless treated, a cancerous extragonadal germ-cell tumor will continue to grow. Depending on its location, this cancer eventually may spread to the lungs, bones (especially the spine), liver or other sites.

There is no way to prevent cancerous extragonadal germ cell tumors.

Treatment depends on the location and type of tumor. In general, small seminomas are treated with radiation and larger ones are treated with chemotherapy followed by radiation. Nonseminomatous tumors almost always are treated with chemotherapy followed by surgical removal of any larger tumors that remains after chemotherapy.

• Mid-chest area (mediastinum) – Seminomas usually are treated with high-dose radiation and sometimes with chemotherapy. Nonseminomas are treated with chemotherapy.



• Lower-back area (presacral area) and retroperitoneal tumors – Chemotherapy is used to shrink the tumor as much as possible before it is removed surgically. If the entire tumor is not removed during surgery, a second course of chemotherapy may be given, followed by a second surgery to get the rest of the tumor.



• Head (pineal area) – The tumor is removed surgically. Both non-seminomas and seminomas may be treated with radiation. However, because high-dose radiation can damage parts of the brain, some hospitals try a combination of chemotherapy and a lower dose of radiation, especially for non-seminomas.

Because doctors always are eager to determine the best treatment for rare types of cancer, your doctor may talk with you about the possibility of enrolling in a clinical trial. This is an experimental treatment program.

Call your doctor whenever you or someone in your family has any symptoms of a cancerous extragonadal germ cell tumor. Because these tumors are rare, many cancer specialists have limited experience in treating them. If an extragonadal germ cell tumor is diagnosed, ask your doctor about the availability of consultation at a cancer center that has sufficient expertise.

Noncancerous tumors outside the brain rarely pose any threat to survival. Survival for people with cancerous tumors depends on the location:

• Mid-chest area (mediastinum) – For seminomas, long-term survival is roughly 80% in people treated with radiation alone. Some studies show that survival may increase when chemotherapy is added. For nonseminomas, long-term survival is about 50% after chemotherapy, especially if the tumor has not invaded the surrounding lung areas in the central portion of the chest.



• Lower-back area (presacral area) – Even for patients with localized cancer, the survival rate is only about 28%. It decreases to 4% for those with disease that has spread to other organs.



• Head (pineal area) – After treatment, long-term survival is more than 80%.

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