Key Terms: Cryptorchidism, Chemotherapy, Hematologist, Germ Cell, Gonads, Oncologist, Teratoma.
Definition
Extracranial germ cell tumors are reproductive cells that have developed into a rare form of malignancy within the reproductive system or within another part of the body, outside of the brain.
Description
Germ cells are cells that develop into the reproductive organs (gonads) during a child's embryonic stage; the testicles in males, the ovaries in females. Germ, meaning "seed," refers to directly to these cells' role in production of the sperm and the ovums. On rare occasions, these calls can experience an abnormal transformation and growth, and develop into a germ cell tumor.
After normal embryonic development, germ cells travel down through the midline path of the body and enter the pelvis to form the gonads. For this reason, most germ cells tumors develop in the testes or ovaries and are referred to as gonadal germ cell tumors. However, germ cells can also migrate during the embryonic development and travel to other regions of the body. Also known as extragonadal germ cell tumors, these tumors can develop inside the chest, coccyx, abdomen, and pelvis. Because they grow outside the cranium (another location of possible germ cell tumor growth), these types of germ cells are commonly referred to as extracranial germ cell tumors.
Malignant extracranial germ cell tumors can also spread (metastasize) to other parts of the body. The liver, lungs, and the lymph nodes can be commonly affected by metastasis, but in rare cases the central nervous system and skeletal structure (bones and marrow) can also be affected. Benign extracranial germ cell tumors do not metastasize, but the increased pressure caused by their growth can damage and/or hinder the function of nearby organs and structures.
Extracranial germ cell tumors are divided into certain types, depending on their characteristics. The four most common forms of extracranial germ cell tumors include:
- Mature teratoma—The most common subtype of extracranical germ cell tumor and generally benign in nature. Mature teratomas are cysts that contain germ cell layers from the ectoderm (skin and nervous tissue), mesoderm (muscle, bone, cartilage, and connective tissue), and endoderm (the lining of the digestive and respiratory systems). As such, any type of tissue can grow within these cysts, usually of a type far different from the surrounding tissue; i.e. hair and teeth growing in the testes. Some mature tertomas can even secrete enzymes and hormones, such as insulin, androgens, and growth hormones.
- Immature teratoma—Similar to mature tertomas, but the tissues are more immature. Immature teratomas may also contain neuroepithelium tissues (associated with the development of the nevrous system). Germ cell tumors of this classification are more likely to be malignant in nature.
- Yolk Sac tumor—The most common malignant extracranial germ cell tumor in young children. Yolk sac tumors are also the most common germ cell tumor, benign or malignant, to develop in the testes of infants and young boys. Tumors are soft and brittle with a yellow and/or grayish cystic exterior. Necrosis and extensive hemorrhaging are common experienced with yolk sac tumors.
- Germinoma—Depending on the location of tumor, germinomas are known as dysgerminoas (ovaries) and seminomas (testes). They are most common malignancy to affect the central nervous system of children.
Demographics
Approximately half of all extracranial germ cell tumors are benign in nature. Of these tumors, almost 50% of them will develop in the gonads, 25% in the coccyx, and roughly 5% in miscellaneous extragonadal locations, such as chest, stomach, liver, and central nervous system.
Extracranial germ cells tumors are particularly rare amongst young children, only accounting for approximately 3% of cancer cases for children 15 years of age and younger. However, this incidence rate rises dramatically in adolescents (aged 15 to 19 years of age) accounting for approximately 14% of cancer cases. However, in both categories, the incidence rate of extracranial germ cell tumors has been rising over the last few decades.
Causes & Symptoms
The underlying cause behind the development of extracranial germ cell tumors is not fully understood. However, a number of inherited defects of the central nervous system, spine, and genitourinary (genital and urinary organs) tract have been associated with an increased risk of development. Cryptorchidism, for example, has been identified as a possible risk factor for the development of testicular germ cell tumors. Patients with Klinefelter's syndrome (a chromosomal anomaly in males) and Swyer's syndrome (a developmental problem of the gonads) are also at risk of developing extragonadal germ cell tumors in the chest and central nervous system, respectively.
Symptoms
Symptoms of extracranial germ cell tumors will great depend on the type and location of the tumor, as well as the age and gender of the patient. However, general symptoms will include:
- A growth, swelling, or mass that can be felt and/or seen
- Constipation and/or urinary retention
- Incontinence
- Leg weakness
- Abnormal testicular shape or size, sometimes painful, in boys
- Abdominal pain in girls
- Abnormal shortness of breath
- Chest pain
Diagnosis
Patients presenting with the various symptoms of extracranial germ cell tumors should be given a thorough history and careful physical examination. This examination should include blood testing and complete blood count. Germ cell tumors often produce proteins in the blood that can be used as markers. In particular, elevated levels of alpha-fetoprotein and human chorionic gonadotropin may indicate the presence of extracranial germ cell tumors. If indicated, this examination should be followed by either a computed tomography (CT) scan or magnetic resonance imaging (MRI) scan. This will provide the physician with a better picture of where the tumor is located. Chest x-rays can determine if there is tumor growth in the lungs.
If this initial examination indicated the presence of a tumor, a biopsy must be conducted to confirm whether or not the tumor is malignant. If the cancer cells are malignant, a pathologist can determine what grade the tumor is and estimate its growth rate. There are three grades of cell malignancy: Low (almost normal appearance, slow growth, unlikely to spread), Intermediate (average appearance and growth, may spread), and High (highly abnormal in appearance, quick growth rate, and likely to spread).
Treatment Team
Children and adolescents are the most common patients to be afftected by extracranial germ cell tumors. Unlike adults, they may not always understand what is happening to them and are likely to become upset and scared by both their disease and the various stages of the diagnostic and therapeutic process. As such, children with cancer should always be treated by a multidisciplinary team of cancer specialists. In addition to their family health provider, primary care should be provided by specialists trained in treating children and adolescents, including surgical subspecialists, oncologists, hematologists, and nursing specialists. In addition, social workers and therapists, as well as rehabilitation specialists, can provide the young patient with the effective supportive care they will require during and after treatment. Quality of life should be the focus of any therapeutic regimen for child patients.
Clinical Staging, Treatments, and Prognosis
Initial diagnosis of the germ cell tumor will help determine whether or not it is malignant or benign in nature. If a malignancy is detected, further diagnostic studies will be required to determine if the tumor has spread to other areas of the body. Staging of the tumor depends on its size and whether it has metastasized. There are four stages commonly associated with all extracranial germ cell tumors:
- Stage 1—Cancer has not spread to surrounding tissues and lymph nodes. Surgical removal of tumor will eliminate all cancer cells.
- Stage 2—Cancer has metastasized to surrounding tissues and/or lymph nodes. Surgical removal of tumor cannot eliminate all cancer cells.
- Stage 3—Cancer has metastasized to surrounding tissue, to several lymph nodes, and is present in the fluid of the abdomen. Surgical removal of tumor cannot eliminate all cancer cells.
- Stage 4—The cancer has spread to other organs of the bod Tumor has spread to other areas
Treatment
Treatment will depend greatly on the stage, grade, and position of the extracranial germ cell tumor. Other factors will include the child's age, general health, medical history, and their tolerance for specific procedures and medications. Generally, treatment will involve the surgical removal of the tumor and, if required, the surrounding tissue. This is followed by either chemotherapy (drugs used to kill the tumor cells) and/or radiotherapy (killing the cancerous cells with radiation). To what lengths these procedures will be employed will depend on the size of the tumor and to what extent it has spread throughout the body.
Effective treatment of extracranial germ cell tumors may require the use of other modalities, including bone marrow transplantation, hormonal replacement, antibiotics and supportive and follow-up care.
Questions to Ask Your Doctor
- Is the tumor benign or malignant, and where is it located? How will that affect the prognosis?
- What risks and side effects my child could face undergoing the different treatments for this type of cancer?
- Has the malignancy spread any further than the original tumor and, if so, what parts of the body are affected?
- WHat is the likelihood the tumor will return?
- Do you know of any support groups my child and I can contact?
Prognosis
Recent advances in treatment modalities, such as the use of Cisplatin-based chemotherapy, have provided a high five-year survival rate; between 75% and 90%. However, some types of germ cells tumors may respond differently to treatment, thus increasing or worsening the patient's prognosis. For example, germ cell tumors in the lower back have a very low survival rate (approximately 28%) even if the malignancy is localized. Extracranial germ cell tumors can also be recurrent in nature, returning after surgical removal. The tumor may occur in the original location or another area of the body. These can occur in 20% to 30% of all high risk patients. Unfortunately, the presence of recurrent extracranial germ cell tumors offers a poor prognosis. It is important to ask the physician regarding the prognosis of each type of germ cell tumor.
Coping With Cancer Treatment
Special considerations should be taken with coping with the treatment of extracranial germ cell tumors, as the majority of patients will be adolescents and young children. Some adolescents may find discussing these tumors to be embarrassing. Even so, if possible, older children should be involved in all the details of their treatment. The patient will rely heavily upon family and friends for support during this difficult time. Counselors, therapists, and local support groups may also be of assistance. The goal must be to prevent fear and confusion, as well as to maintain the child's quality of life as much as possible.
Clinical Trials
Due to the rarity of childhood cancers, all child patients should be considered for entrance into clinical trials. New treatments are being researched constantly. Details of current and future clinical trials can be found at the National Cancer Institute's website:
Prevention
As these cancerous cells begin very early during pregnancy, there are no known preventive measures against extracranial germ cell tumors.
Resources
Books
Barrett A. "Gene Cell Tumors." In Cancer in Children: Clinical Management., edited by P.A. Voute, C. Kalifa, and A. Barrett. New York, NY: Oxford University Press, 1998, pp. 292-307.
Cushing B, E Perlman, N Marina, and R Castleberry. "Gene Cell Tumors." In Principles and Practice of Pediatric Oncology (4th ed)., edited by Phillip Pizzo and David Poplack. Philadelphia, PA: Lippincott Williams & Wilkins, 2002, pp. 1091-1113.
Periodicals
Hawkins E. "Germ Cell Tumors." American Journal of Clinical Pathology 109 (#4, Suppl 1998): S82-S88.
Other
"Childhood Extracranial Germ Cell Tumors."National Cancer Institute
Javeed M."Gern Cell Tumors."eMedicine Journal
—Jason Fryer
