Germ cell tumors

Definition

Germ cell tumors are tumors that begin in cells that, in a developing fetus, become sperm or egg cells. Because of the way a baby develops in the womb, these kinds of tumors are found in the ovaries and testes, and in other sites along the midline of the body, such as the brain, the center of the chest, and the center back wall of the abdominal cavity. They can also be found in the center parts of the pelvis, cervix, and uterus, in the vagina or prostate, in the oral or nasal cavities, or on the lips. These tumors are usually discovered either during the first few years of life, or shortly after puberty (when an increase in hormone levels may initiate cancer formation).

Description

Germ cell tumors are a diverse group of tumors that all begin in germ cells, the cells in the developing fetus that become sperm or egg cells. Incidence in the United States is 2-3 cases/million live births. They can occur in the ovaries or testes or outside the reproductive organs in many other locations along the middle of the body. Some are very malignant and some are almost always benign; most require surgery, although some kinds are also treated with additional radiation or chemotherapy . Some typically appear in infancy, others are more common in adolescents. The treatment and prognosis will depend on the kinds of tissues present in the tumor and on the location.

Germ cell tumors are divided into two types: germinomas, which contain only immature germ cells; and embryonic tumors, which contain some cells that have started to develop into other tissues (as would happen in normal development of a fetus). Embryonic types of tumor commonly include endodermal sinus tumors, embryonal carcinoma , choriocarcinoma and teratoma. Gonadoblastoma and polyembryoma are rare types of embryonic germ cell tumors. Many tumors are mixed, containing more than one cell type.

Generally, any kind of germ cell tumor can appear at any germ cell tumor site, although some types are significantly more common at some locations. For example, about 40% of all germ cell tumors are teratomas in the area of the tailbone, which are typically diagnosed in the first month or two of life. Germinomas and endodermal sinus tumors are most common in the ovaries. Embryonal carcinomas are most common in the testes, usually mixed with endodermal sinus tumors or choriocarcinoma.

Demographics

Like other features of this diverse group of tumors, demographics of this cancer vary with the site and type. The peak in incidence of germ cell tumors during the first few years of life is primarily due to the high numbers of teratomas in the tailbone area, which are about 4 times more common in girls than in boys. The second peak, however, in adolescents reflects a significant number of testicular cancers in teenage and young adult males. Other common childhood germ cell tumors are tumors of the abdomen, vagina and testicles in infants, brain tumors in childhood, and ovarian tumors in early teens. Adult germ cell tumors in adults are usually in the testes or ovaries. Germ cell tumors are found in all populations of the world in approximately equal numbers.

Causes and symptoms

The causes of germ cell tumors are not well understood, although events at puberty—probably increases in certain hormone level—are thought to play a role in tumors of the ovaries and testicles that occur in adolescents or early teens. Some germ cell tumors have a high percentage of certain genetic sequences, thought to be a possible cause of those types of cancers, while some have a high frequency of abnormal chromosome numbers. Some types of germ cell tumors do tend to run in families. Since germ cell tumors are made up of several different types of cancers, there are probably at least several different causes.

The most common symptom of germ cell tumors is a mass along the midline of the body. This mass may be accompanied by abdominal pain or bloating. Other possible symptoms include:

• constipation
• enuresis (involuntary discharge of urine)
• early entry into puberty
• vaginal bleeding
• late onset of menstruation
• menstrual problems
• excessive hair growth
• weakness in legs
• need to urinate often
• shortness of breath, other breathing problems
• diabetes
• hormonal abnormalities
• stunted growth
• headaches or vision problems

Diagnosis

Most germ cell cancers are initially identified by the discovery of lump in the testicles or somewhere else along the midline of the body. When a lump is identified, often the person's physician will arrange for a biopsy of the lump. During a biopsy, a small piece of the lump is removed and cut into thin sections. A specialist examines these sections under a microscope, looking for abnormal kinds of cells. How much the biopsied tissue is different from healthy tissue is a good indication of how severe the disease will probably be, and the results of biopsies are used to give tumors a grade that indicates the patient's chances of survival.

Tests that give a doctor pictures of the tumor are also used, such as x rays, computed tomography (CT) scans, or ultrasound. X rays can show the doctors where calcium deposits have occurred in normally soft tissues (an indication of disease). Ultrasound and CT scanning give more details with regard to a specific tumor, such as its site of origin, whether it is solid or cystic, and how well defined its borders are. Well-defined borders have a better chance of complete surgical removal.

Another type of useful test which is specific to germ cell tumors is the measurement of several tumor markers . Tumor markers are proteins, often identified in blood samples, that are produced by tumor cells. Two main tumor markers are commonly seen to suggest a germ cell tumor, alpha-fetoprotein (AFP) and ß-Human Chorionic Gonadotropin (ß-HCG). Germ cell tumors which produce elevated levels of AFP include endodermal sinus tumors and teratoma, although high levels of AFP are also produced by normal infants. ß-HCG is usually associated with tumors which contain elements of the choriocarinoma or embryonic carcinoma types of germ cell tumors. These markers are also used as a measure of the success of surgery or other therapies, and to monitor patients for a recurrence of the disease.

Treatment team

As the understanding of cancer grows and new treatment approach are developed, the complexity of cancer treatment also increases. Today, a multi-disciplinary approach to cancer treatment is considered necessary for effective patient care. People involved in the treatment of a germ cell cancer will typically include the referring physician (often a gynecologist or pediatrician), a gynecological oncologist, a pathologist, and a nurse. If radiation therapy is pursued, a radiation oncologist, radiation therapist, radiation nurse, radiation physicist, and a dosimetrist will also be involved. Treatment may also include a psychologist, nutritionist, social worker and chaplain.

Clinical staging, treatments, and prognosis

Staging

Staging and grading tumors is a way of predicting the severity of the disease. Tumor grades are based on the types of tissues present in the tumor; stages indicate the cancer's spread. Separate staging systems exist for both adult and childhood ovarian cancers and adult and childhood testicular cancers. These are developed separately by groups of pediatric and adult oncologists.

OVARIAN CANCERS.

Pediatric ovarian cancers are usually graded according to the following scheme: Grade 0 contains only mature tissues (tissues which have already become specific kinds of tissues, rather than primitive developing cells. Grade 1 contains mostly mature tissues, with some immature cells present. Grade 2 contains a moderate amount of immature cells, and in Grade 3, numerous immature cells are present.

Adult ovarian cancer is usually staged, with Stage I being found only in the ovaries. Stage II in adult ovarian cancer means that the cancer has spread to the uterus or the fallopian tubes, or other structures in the pelvic area. Stage III tumors are those which have spread to the lymph nodes or outer parts of abdominal organs. Stage IV tumors have spread to the interior of abdominalorgans such as the liver or the intestines.

TESTICULAR CANCERS.

Pediatric testicular cancers are typically staged in a manner similar to adult ovarian cancers: Stage I tumors are limited to the testes, with normal postoperative tumor markers. Stage II tumors have spread to the abdominal lymph nodes and have elevated tumor markers; Stage III have greater involvement of the abdominal lymph nodes. Stage IV tumors have spread to other organs such as the lung.

Adult testicular cancers are commonly staged according to a simplified TNM system. Stage T (with several levels described) indicates a tumor that is localized, N means a tumor that has spread to local lymph nodes, and M means a tumor that has spread to distant lymph nodes and organs.

Treatment

The treatment choice in any specific germ cell tumor depends mainly on the type of tumor and the stage at diagnosis, although the age of the patient and whether or not future childbearing is an issue will also influence treatment choices. Treatment of most germ cell tumors involves surgical removal of the tumor. Advanced cancers normally will be followed by chemotherapy. For some tumors, it may not be possible to completely remove the cancerous tissues. In those cancers, "debulking" surgery will be performed in order to reduce the size of the tumor in order for chemotherapy (or radiation) to be most effective.

Chemotherapy can be given through pills taken by mouth, by injections or through IVs. Chemotherapy works by killing cancerous cells, and can kill cancer cells that have traveled away from the initial site. Therefore, in more advanced stages of disease, chemotherapy will sometimes be the primary treatment. Possibly another surgery will be performed after radiation therapy or chemotherapy is finished. This surgery (second-look surgery) allows the doctor to confirm that cancerous tissues have been eradicated.

Chemotherapy usually involves a platinum-based drug such as cisplatin in combination with one or two other anti-cancer medications. These drugs are used in combination because, since they each have different side effects, high doses can be given without increasing the risk of a serious drug reaction. Using combinations also decreases the chance that a cancer will develop resistance to any particular drug. Different combinations of drugs are used to treat different types of tumors.

The treatment of some types of germ cell cancers may follow a slightly different pattern. Germinomas are especially sensitive to radiation. This may be the primary treatment mode for those kinds of tumors. Radiation is used to shrink the size of tumors, and even in ovarian cancers usually involves only external irradiation. The only type of germ cell tumor in children in which radiation is regularly used is germinomas occurring in the brain.

When first-line treatments fail, stronger combinations of drugs may be given, or different, sometimes experimental therapies may be tried. These kinds of therapies includes immune system products like interferons that have been shown to destroy cancerous cells and new drugs being developed that decrease blood flow to tumors. Therapies like immunotoxins, which include anti-cancer drugs attached to antibodies specific to tumor cells, and other ways of making drugs more specific for tumor cells, are also being investigated. Many clinical trials for germ cell cancers are evaluating a therapy called "peripheral stem cell rescue, " in which the patient's red blood cells are removed before high-dose chemotherapy is given, then replaced after the chemotherapy is complete. This decreases the side effects of the medications and improves the patient's chances of successful treatment.

The prognosis for germ cell tumors depends greatly on the type of germ cell tumor involved and the location in which it is found. Generally, about 90% of patients diagnosed with only localized tumors survive, compared to 50-70% of those who are diagnosed with tumors which have already spread. There is wide variation in the cure rates, depending on the tumor types involved. Mature teratomas of the ovaries, which are by far the most common type of ovarian tumor, are almost always benign, unless mixed with other, more malignant germ cell tumor types. Choriocarcinomas and embryonal carcinomas, on the other hand, are especially malignant, with an average survival time without treatment of only a few months. Since ovarian cancers are the most difficult to catch early, ovarian cancers of types more malignant than the mature teratoma have the worst prognosis among the germ cell tumors. With modern treatment methods, most often including chemotherapy after surgical removal, survival rates have greatly improved. If caught early, most germ cell tumors have good cure rates.

Alternative and complementary therapies

Alternative and complementary therapies are therapies which fall outside the scope of traditional, first-line therapies like surgery, chemotherapy and radiation. Complementary therapies are meant to supplement those traditional therapies with the objective of relieving symptoms. Alternative therapies are nontraditional, unproven attempts to cure the disease.

Common complementary therapies in germ cell disease include aromatherapy, art therapy, massage, meditation, music therapy, prayer, t'ai chi, yoga, and other forms of exercise. These therapies have the objective of reducing anxiety and increasing a patient's feeling of well-being.

Numerous alternative therapies exist in cancer treatment. Laetril, a product of apricot seeds, is probably one of the most well known. Laetril contains a form of cyanide that may be released by tumor enzymes and may act to kill cancerous cells. However, the product is not approved for use in the United States, and the National Cancer Institute sponsored two clinical trials for the drug in the late 1970s and early 1980s, and decided that no further investigation into the drug was necessary. Vitamins and other nutritional elements like vitamins A, C, and E, and selenium are thought to act as antioxidants . Vitamin E, melatonin, aloe vera, and a compound called beta-1, 3-glucan are thought to stimulate the immune system. Natural substances like garlic, ginger, and shark cartilage are also commonly held to shrink tumors, with less defined modes of action. Antineoplastons are believed by some to be another alternative approach to a cancer cure. Antineoplastons are small proteins which may act as molecular messengers and which may be absent from the urine and blood of many cancer patients. Replacing these proteins may have beneficial effects. After some proposed clinical trials were not completed, the National Cancer Institute draws no definitive conclusions about the effectiveness of antineoplaston therapy. Patients should discuss any supplements with their treating physicians.

Coping with cancer treatment

The use of chemotherapy and radiation therapy in addition to surgery has greatly increased the numbers of germ cell tumor patients that survive; but both of these treatments unavoidably result in damage to some healthy tissues and other undesirable side effects. Some of the more common side effects of chemotherapy include:

• hair loss (alopecia )
• fatigue and weakness
• nausea and vomiting
• bed wetting

Hair loss is a very common side effect of many drugs used to treat cancer. Getting a sample of hair before hair loss begins is desirable in case a wig is desired after hair loss begins. The patient's hair color and texture could then be more closely matched. Hair may thin out gradually or it may come out in big clumps. To slow down the rate of hair loss, avoid any unnecessary sources of damage to the hair, like curling, blow-drying, or chemical treatments.

Hair loss is a difficult part of dealing with cancer for all patients past infancy, especially for teenage patients. Children should be given the right to choose their own way of coping and their choices should be supported. Children may choose to remain bald, or may want to choose hats or scarves instead of wigs. Schools may need to be persuaded to allow a child to wear some kind of head covering. It is important to assure the child that loss of hair is a sign that the medication is doing its job, and that hair loss is temporary.

Hair usually begins regrowth within a few months of the end of intensive chemotherapy, although it may begin to thin out again during the course of maintenance drugs. Sometimes hair comes in a different color or texture than the original hair. It may be a good idea to prepare a child for that possibility.

Fatigue and weakness are other common side effects of chemotherapy. Side effects of the chemotherapy medications, along with the natural depletion of the body's resources as it fights off the disease and normal psychological consequences of the disease such as depression combine to make fatigue a very significant part of coping with cancer treatment.

The best way to deal with these symptoms is to cut back on activities and allow plenty of time for resting to let the body heal. Patients should avoid as much extra stress as possible, limiting visitors if necessary in order to avoid being overtired. Children should not be forced into the role of invalid. Children must be allowed to pursue normal activities and hobbies as much as possible. Parents can best manage this by helping to select those activities that the child considers most important, and by providing a backup plan for times when the child does become too fatigued, such as alternate means of mobility (for example, a stroller, wheel chair or other acceptable and safe vehicle). It is also important to make sure that a well-balanced diet is provided.

Nausea and vomiting are also fairly common side effects of many chemotherapy drugs. Radiation to the brain or the GI tract can also cause nause and vomiting. After a few courses of chemotherapy drugs, some patients will become nauseated just from the thought of an upcoming treatment, or from smelling certain odors that act as nausea triggers. Drugs that combat nausea and vomiting can be prescribed, but are often not effective for anticipatory nausea. There are self-help measures that can be tried. If nausea and vomiting are a problem, heavy, regular meals should be avoided in favor of small, frequent snacks made up of light but nourishing foods like soup. Avoiding food smells and other strong odors may help.

Desensitization, hypnosis, guided imagery, and relaxation techniques may be used if nausea and vomiting are severe. These techniques help to identify the causes which trigger the nausea and vomiting, decrease patient anxiety, and distract the patient from thinking about getting sick. In children, activities like playing video games can be offered as very effective means of distraction.

Bedwetting is another common side effect of anticancer drugs, and one which can be especially distressing for older children. A child who experiences this problem should be reassured that the problem is temporary and will go away when the drug treatment is over. Parents can help the child cope by keeping extra linens ready or covering the wet spot with towels kept handy and most of all, by conveying an attitude that wetting the bed is not a big deal. Children should never be punished. It may also help to limit drinks for a couple of hours before bedtime, or to wake the child at regular intervals overnight to use the bathroom.

The biggest problem for those undergoing radiation therapy is the development of dry, sore, "burned" skin in the area being treated. Radiation does not hurt during treatment and does not make the person radioactive. Skin in the treatment area will become red, get itchy and sore, and may blister and peel, becoming painful. Patients with fair skin, or those who have undergone previous chemotherapy have a greater risk of more serious reactions. Dry, itchy or sore skin is temporary; but affected skin may be more sensitive to sun exposure for the rest of the patient's lifetime, so a good sunscreen should be used whenever affected skin is exposed to sunlight.

Fear and anxiety are major factors in coping with cancer, including cancer treatments. The feelings are completely normal. Some patients find that concentrating on restful, pleasurable activities like hobbies, prayer, or meditation is helpful in decreasing negative emotions. Support groups are another useful tool, since they provide an environment where fears can be freely expressed and understood.

Clinical trials

Nearly a hundred clinical trials testing new treatments for germ cell tumors are ongoing. New approaches being evaluated emphasize new combinations of existing chemotherapy drugs, peripheral stem cell therapies to supplement chemotherapy, alternative therapies like anti-neoplastons, and new drug delivery approaches such as immunotoxins.

Therapies being evaluated in clinical trials are usually considered experimental and some, like peripheral stem cell rescue, can be very expensive. Most insurance companies do not cover the costs of experimental therapies.

To find an ongoing clinical trial for a specific kind of germ cell tumor, call the National Cancer Institute at 1-800-4-CANCER.

Prevention

Since the causes of germ cell tumors are not well understood, few identified risk factors exist, thus providing little information on the possibility of preventing these kinds of cancers. However, there are ways of improving prognosis with regards to germ cell tumors. Ovarian cancers are difficult to catch in early stages; women who get regular gynecological check-ups are more likely to have ovarian cancer diagnosed in more treatable stages. Males who have had testicular cancer can improve their chances of catching recurrences in early stages by doing regular self-exams.

Special concerns

A special concern in germ cell tumor patients, especially since most patients are children or young adults, is maintaining these patients' ability to bear children. Unfortunately, all of the common treatments can have a negative effect on future fertility. Radiation, especially, destroys fertility and is avoided in children except for germinomas of the brain. Patients whose reproductive organs must be removed suffer major psychological consequences of the loss of childbearing potential and often, as well, suffer from altered feelings of sexuality . The treatment team will attempt to choose treatment options that will preserve the patient's childbearing ability to the best of medical capabilities.

See Also Ovarian cancer; Testicular cancer; Extragondal germ cell tumors; Gynecological cancers; Childhood cancers

Resources

BOOKS

Cook, Allan R., ed. The New Cancer Sourcebook. New York:Omnigraphics, Inc., 1996.

Pizzo and Poplack, ed. Principles and Practice of Pediatric Oncology. Philadelphia: Lippincott-Raven, 1997.

Buckman, R. What You Really Need to Know About Cancer. Baltimore: Johns Hopkins University Press, 1999

Pinkerton, C.R., and P.N. Plowman. ed. Pediatric Oncology. Chapman and Hall Medical, 1998.

ORGANIZATIONS

American Cancer Society, 1599 Clifton Road, NE, Atlanta, GA30329-4251. (800)586-4872 <http://www.cancer.org> 29 June 2001.

National Cancer Institute, 9000 rockville Pike, Bethesda, Maryland, 20892. (800)422-6237. <http:www.nci.nih.gov.> 29 June 2001.

The Wellness Community, 10921 Reed Harman Highway, Cincinnati, Ohio, 45242 (888)793-9355. "A free program of emotional support, education and hope for people with cancer and their loved ones." <http://www.wellnesscommunity.org> 29 June 2001.

OTHER

QUACKWATCH "Your Guide to Health Fraud, Quackery and Intelligent Decisions." <http://www.quackwatch.com>

Wendy Wippel, M.S.

KEY TERMS

Choriocarcinoma

—A highly aggressive malignant germ cell tumor made up of tissue derived from the outer membrane which covers the fetus.

Embryonic carcinoma

—A highly malignant germ cell tumor made up of tissues derived from the embryo.

Endodermal sinus tumor

—A more aggressive germ cell tumor made up of tissue originating in the nutrient sac of the embryo.

Germinoma

—A tumor that develops purely from primitive germ cells.

Gonadoblastoma

—A rare and almost always benign form of cancer highly associated with abnormal development of reproductive organs.

Polyembryoma

—A very rare, aggressive form of germ cell tumor usually found in the ovaries.

QUESTIONS TO ASK THE DOCTOR

• Can you explain what kind of cancer I have?
• Is it a benign or aggressive form of germ cell tumor? Can you explain the grade and stage of my cancer? What are the chances that it will come back?
• How was this cancer diagnosed?
• What is my prognosis?
• What treatments are we going to pursue? What happens if these don't work?
• Do you have experience in treating this type of cancer?
• Is there anything I can do to optimize treatment? Are there any particular side effects I should expect?
• Are there complementary therapies that you would recommend? Any other things that would help me cope with the diagnosis or treatment?