Molar pregnancy and choriocarcinoma: Diseases of Reproduction

Molar pregnancy and gestational choriocarcinoma are abnormalities in the development of the fertilized egg. Molar pregnancy and has an incidence in the United States of 1 in 1000 to 1 in 1500 pregnancies. Older women have higher rates than younger women. Hydatidiform mole, another name for molar pregnancy is a condition occurring as a result of alterations in fertilization. In normal pregnancy fertilization results in the formation of a zygote that has 2 sets of genes, one set of 23 from the mother and one set of 23 from the father. A complete hydatidiform molar pregnancy occurs when the zygote has 2 sets of genes, both from the father. In this situation there is no fetus. A partial molar pregnancy has 3 sets of genes, one set from the mother and two from the father due to the fact that two sperm fertilized the egg. In this situation there is a non-viable fetus. They are non-cancerous growths made up of trophoblast tissue (tissue that forms the placenta). Molar tissue looks like a bunch of grapes. Vaginal ultrasound studies show the uterine cavity with a snow storm appearance. Symptoms are irregular vaginal bleeding, tiredness and weakness. Blood pressure may be elevated and there maybe symptoms of hyperthyroidism. The treatment is dilatation and curettage to remove the abnormal tissue from the uterus. Since this is a disease of trophoblastic tissue the cells make the hormone, human chorionic gonadotropin. Human chorionic gonadotropin is similar in structure to thyroid stimulating hormone. The beta subunit of the hormone β-hcg can be detected in the maternal blood stream, at high levels of 100,000 m IU/mL which is much higher than the levels in normal pregnancy. They may be as high as 200,000 m IU/mL. These high levels will mimic TSH because of the similarity in structure of the two enzymes causing the hyperthyroid symptoms. Blood levels of this hormone are monitored after a D&C to be certain that β-hcg is no longer detected. Monitoring may need to be done for weeks or months. By 6 and certainly by 12 months β-hcg should be undetected. If the β-hcg levels persist or rise chemotherapy is given.

Gestational choriocarcinoma is a trophoblastic and very aggressive cancer. It is rare with an incidence in the United States of 1 in 20,000 to 1 in 40,000 pregnancies. It is a cancer that is made up of the two cells of the trophoblast, syncytiotrophoblast and cytotrophoblast but they do not form villi that are characteristic of placental tissue. While rare this tumor is preceded by a hydatidiform mole 50% of the time, 20% to 30% of the time it is preceded by a normal pregnancy. About 20% of choriocarcinomas are preceded by a spontaneous abortion (miscarriage). Ectopic pregnancy precedes this cancer in 2% of the cases. Choriocarcinoma may occur with Hyperemesis Gravidarum- a condition where the mother has severe nausea. The severe nausea occurs because there are high levels of the β-hcg produced by the tumor cells. The tumor tissue is made up of syncytiotrophoblasts and cytotrophoblasts without the formation of villi. Choriocarcinoma is a rapidly growing cancer and spreads to other parts of the body through the blood stream. Common sites for metastatic tumor growth are the lungs and brain and it is not uncommon for the first symptoms to be due to these metastases. Choriocarcinoma in the lung will present with coughing, often coughing that produces blood, chest pain and difficultly in breathing. If the tumor has spread to the brain headaches, muscle weakness on one side of the body, difficulty in maintaining balance vision and speech changes and other neurological signs and symptoms are often noted. Β-hcg is seen in the spinal fluid. Β-hcg blood levels are very high and can be higher than 200,000 m IU/ml. Cure rates are very good and are in the range of 85-95 %. The treatment consists of methotrexate or actinomycin D. If the cancer is high-risk or persistent it is treated with etoposide, methotrexate, actinomycin D and cyclophosphamide and vincristine.

Choriocarcinoma has a non-gestational form that arises from germ cells of the ovary or testes and thus can affect children and adults of both sexes. It is sometimes associated with other somatic high-grade malignancies. In females it is roughly 0.6% of ovarian cancers and it males it is 0.19% of testicular choriocarcinoma. The non-gestational form is highly aggressive but is not easily treated. High levels of β-hcg are also seen in this form of choriocarcinoma. It is differentiated from gestational choriocarcinoma by DNA polymorphism analysis. Non-gestational choriocarcinoma will contain the only the patient’s DNA, while gestational choriocarcinoma contains both maternal and paternal DNA. The treatment of non-gestational choriocarcinoma differs from than that of gestational choriocarcinoma and thus it is important in women to make a clear diagnosis of one or the other in order to prescribe the correct treatment regimen. This is especially important since gestational choriocarcinoma can occur years after the index pregnancy. Treatment of non-gestational choriocarcinoma is surgery and bleomycin, etoposide, and cisplatin. It is not as successful as treatment of gestational choriocarcinoma and depends on the stage of the disease. Stage IV survival has been 25% in three years while the early stages are better. However newer treatment regimens are evolving and are more successful.

While the gestational tumors of hydatidiform mole and choriocarcinoma are rare, their etiology stems from genetic aberrations of fertilization and are examples of abnormal gestation. Non-gestational choriocarcinoma arises from germ cells in the ovary or testes and are thus reproductive tract diseases.