Extragonadal germ cell tumors

Definition

Germ cells are primitive cells within the body that normally mature into ova (egg) or sperm cells. More than 90% of all germ cell tumors are gonadal; that is, they develop in the ovaries or the testes (the gonads). The remaining 5-10% of germ cell tumors arise outside of the gonads: these are the extragonadal germ cell tumors. These tumors occur mostly in the chest, lower back, and head.

Description

Extragonadal germ cell tumors are related to developmental problems that occur prior to birth. In the growing embryo, germ cells migrate to the immature ovaries or testes. In some instances, these cells fail to move to the gonads and end up in the midchest area between the lungs (mediastinum), the lowest part of the back (presacral area), or near the pea-sized gland between the two hemispheres of the brain (pineal gland). When these germ cells grow in these extragonadal sites, they sometimes develop into tumors. These tumors can be benign (noncancerous) or malignant (cancerous).

Benign extragonadal germ cell tumors are called benign teratomas. Malignant extragonadal germ cell tumors are subdivided into seminoma and nonseminoma. The nonseminoma germ cell tumors include: embryonal carcinoma , malignant teratoma, endodermal sinus tumor, choriocarcinoma, and mixed germ cell tumors. The specific category of extragonadal germ cell tumor that is present has a major influence on both treatment and prognosis.

Demographics

Extragonadal germ cell tumors are quite rare. One new case is diagnosed annually for every 1 million people in the United States.

In young children, extragonadal germ cell tumors tend to occur primarily in the presacral area. The majority of these tumors are benign.

In adults, extragonadal germ cell tumors tend to be in the mediastinum. Of these, approximately 40% are malignant.

Malignant extragonadal germ cell tumors occur with equal frequency in boys and girls. But, they are approximately nine times more likely to occur in men than in women.

Extragonadal germ cell tumors occur with equal frequency in members of all races and ethnic groups. There does not appear to be any relationship of extragonadal germ cell tumors to any geographic region.

Causes and symptoms

The cause, or causes, of extragonadal germ cell tumors are not known.

The symptoms of an extragonadal germ cell tumor depend on the type and location of the tumor.

Mediastinum

Germ cell tumors of the mediastinum are primarily diagnosed in men between the ages of 20 and 30. Symptoms include:

• chest pain
• breathing problems
• cough
• fever

Presacral area

Presacral germ cell tumors are primarily diagnosed in children under the age of six. These are generally seen as a mass in the lower abdomen or buttocks. Because of the size and location of the tumor, the patient may have difficulty passing urine or having a bowel movement. Tumors detected in children under the age of six months are benign in 98% of cases. Tumors detected in children over the age of six months are malignant in approximately 65% of cases.

Pineal area

Almost all pineal germ cell tumors occur in people under the age of 40. Symptoms include:

• headache
• nausea
• vomiting
• lethargy
• difficulty walking
• memory loss
• an inability to look upward
• uncontrolled eye movement
• double vision

In some cases, a pineal germ cell tumor can begin to produce hormones that can cause a child to enter puberty at an abnormally young age (precocious puberty).

Diagnosis

The diagnosis of an extragonadal germ cell tumor usually begins with a thorough physical examination. In cases where a presacral tumor is suspected, this will include a rectal examination and a pelvic examination in women. In cases where a germ cell tumor of the pineal area is suspected, a complete neurological examination will be performed.

Mediastinum

The first test for a tumor of the mediastinum is a standard chest x ray . This will detect the tumor and show its location in 95% of cases. This will be followed by a computed tomography (CT) scan of the chest to determine the size of the tumor and by a CT scan of the abdomen to see if there has been a spread (metastasis ) to the liver or other abdominal sites.

Diagnosis is generally confirmed by taking a needle biopsy of the tumor. In this procedure, a needle is injected directly into the tumor and a sample is removed.

Certain types of nonseminomas can be detected via blood tests for levels of alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG).

Presacral area

Germ cell tumors of the presacral area are diagnosed by either magnetic resonance imaging (MRI) or ultrasound imaging techniques. These techniques allow for the determination of both the location and the precise size of the tumor. To check for metastases, a bone scan, chest x rays, and a CT scan of the lungs should be performed. Sometimes a bone marrow biopsy is also ordered.

Diagnosis of a presacral germ cell tumor is confirmed by a direct biopsy of the tumor. This may be either an excisional biopsy, in which the tumor is first removed, then examined; or, a needle biopsy, in which only a sample of the tumor is removed for examination.

Pineal area

A CT scan of the head will usually show a pineal tumor. An MRI scan, using gadolinium as a tracer chemical, may also be ordered.

Blood tests for AFP and beta-hCG may help to diagnose pineal area germ cell tumors. Tests for these chemicals on the cerebrospinal fluid (lumbar puncture ) may also be ordered.

The diagnosis of a pineal area germ cell tumor is usually confirmed upon biopsy of the tumor after it has been removed from the patient.

Treatment team

Treatment of an extragonadal germ cell tumor depends on the location of the tumor. Most tumors are treated with a combination of surgery, chemotherapy , and radiation treatments.

Germ cell tumors of the mediastinum are generally not surgically removed. They are treated with high-dose radiation and sometimes with chemotherapy. Germ cell tumors of the presacral area are treated with chemotherapy to shrink the tumor, then surgery to remove the tumor. This surgery is generally performed by a physician who specializes in tumor removal surgery of the lower abdomen and pelvis. Germ cell tumors of the pineal area are generally removed by a brain surgeon and then the patient is treated with radiation and/or chemotherapy.

Chemotherapy is administered under the direction of a physician who specializes in cancer (oncologist). Radiation therapies are generally administered by radiological technicians under the direction of an oncologist, a radiologist, a health physicist, and/or a medical radiation dosimetrist.

Clinical staging, treatments, and prognosis

The prognosis for patients with benign extragonadal germ cell tumors is excellent after surgery to remove the tumor is completed.

In the cases of malignant extragonadal germ cell tumors, the prognosis depends on the type and size of the tumor that is found.

Fifty-six percent of nonseminomas and 90% of seminomas have a good prognosis. Another 28% of nonseminomas and the remaining 10% of seminomas have an intermediate prognosis. While 16% of nonseminomas have a poor prognosis. A good prognosis is defined as a five-year survival rate above 85%. An intermediate prognosis is defined as a five-year survival rate between 50% and 85%. A poor prognosis is defined as a five year survival rate lower than 50%.

For both seminomas and nonseminomas, the prognosis is better if the tumors have not metastasized to other tissues. This is particularly true in the case of mediastinal tumors : those that have metastasized outside the general region of the lungs lead to particularly poor prognoses.

The prognosis for nonseminomas is based primarily on AFP and hCG concentrations found in the blood. The lower the levels of these two chemicals in the blood, the better the prognosis.

Alternative and complementary therapies

There are no effective alternative treatments for extragonadal germ cell tumors other than surgery, chemotherapy, and radiation.

Coping with cancer treatment

Most patients who undergo surgery to remove their tumors can resume their normal activities within a few days of the operation.

In some cases of presacral area germ cell tumors, it is difficult to remove the entire tumor in a single operation. In these cases, it is necessary for the patient to undergo a second course of chemotherapy prior to a second surgery to remove the remaining tumor.

When extensive chemotherapy is necessary, the patient may require counseling to help cope with the side effects of these treatments, such as loss of head and body hair, weight loss , nausea, fatigue , and changes in psychological well-being.

Clinical trials

There were 12 clinical trials underway, in early 2001, aimed at the treatment of extragonadal germ cell tumors. More information on these trials, including contact information, may be found by conducting a clinical trial search at the web site of the National Cancer Institute, CancerNet (<http://cancernet.nci.nih.gov>).

Prevention

Because the causes of extragonadal germ cell tumors are not known, there are no known preventions.

Special concerns

Repeat surgery may be necessary for extragonadal germ cell tumors, particularly those of the presacral area because these tumors are often difficult to remove completely. Careful monitoring by the medical team will be required.

See Also Bone marrow aspiration and biopsy; Nuclear medicine scan; Testicular cancer

Resources

BOOKS

Jones, W.G., I. Appleyard, P. Harnden, and J.K. Joffe, eds. Germ Cell Tumors IV. London: John Libbey & Company, Ltd., 1998.

PERIODICALS

Hainsworth, J.D., and F.A. Greco. "Extragonadal Germ Cell Tumors and Unrecognized Germ Gell Tumors." Seminars in Oncology (April 1992), 119-127.

ORGANIZATIONS

National Cancer Institute. Building 31, Room 10A03, 31 Center Dr., MSC 2580, Bethesda, MD 20892-2590. (800) 4-CANCER. <http://www.nci.nih.gov>.

OTHER

Extragonadal Germ Cell Cancer Articles and Links. 15 April 2001. 2 July 2001 <http://www.acor.org/TCRC/egc_links.html>.

Paul A. Johnson, Ed.M.

KEY TERMS

Germ cells

—Cells that are involved in reproduction. These cells are usually located in the gonads. Sometimes they fail to move to the gonads during embryonic development and cause tumors in other parts of the body.

Gonads

—The reproductive organs: the testes and ovaries.

Mediastinum

—The mid-chest area between the lungs.

Pineal gland

—A pea-sized gland just below the brain.

Presacral area

—The lowest part of the back.

QUESTIONS TO ASK THE DOCTOR

• Which type of extragonadal germ cell tumor do I have?
• Is my tumor operable?
• What are my treatment options?
• What is the likelihood of my type of tumor being successfully removed with a single surgery?
• What is the prognosis for my tumor type?
• How often should I seek follow-up examinations?