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A hydatidiform mole is a proliferation of trophoblastic tissue in pregnant or recently pregnant women. Symptoms may include uterine hyperextension, vomiting, vaginal bleeding, and preeclampsia, especially in early pregnancy. Diagnosis is by beta-hCG and pelvic ultrasonography, and confirmation by biopsy. Tumors are removed by separate diagnostic curettage. If the disease persists after tumor removal, chemotherapy is prescribed.

Epidemiology

Gestational trophoblastic disease usually occurs in women of reproductive age, with only a few cases seen in perimenopausal women. It is extremely rare in postmenopausal women. [ 1 ]

Hydatidiform mole is most common among women under 17 or over 35 years of age. In the United States, these tumors are diagnosed with a frequency of 1 in 2,000 pregnancies. In Asian countries, for unknown reasons, they are detected with a frequency of 2 in 1,000 pregnancies. [ 2 ] More than 80% of cases of hydatidiform mole are benign and regress spontaneously. In other cases, the tumors may persist, have a tendency to invasive growth; in 23% of cases, they can become malignant and form choriocarcinoma.

Choriocarcinoma occurs in approximately 1 in 20,000 to 40,000 pregnancies in the United States and 3 to 9 in 40,000 pregnancies in Southeast Asia and Japan.[ 3 ]

What causes a hydatidiform mole?

Gestational trophoblastic disease is a tumor originating from the trophoblast that surrounds the blastocyst and penetrates the chorion and amnion. This disease can occur during or after intrauterine or ectopic pregnancy. If the disease occurs during pregnancy, spontaneous abortion, then the presence of eclampsia, intrauterine fetal death is characteristic; the fetus rarely survives. Some forms of the tumor are malignant, but benign tumors that behave aggressively are noted. [ 4 ]

Risk factors include late pregnancy, multiple pregnancies, history of spontaneous abortion, high beta-carotene diets, high-fat diets, ethnicity, exposure to environmental toxins, smoking, alcohol consumption, socioeconomic status, herbicide exposure, etc. [ 5 ], [ 6 ]

Pathomorphology

Classification of the disease is based on morphological data. Hydatidiform mole is a pathological pregnancy in which the villi become edematous and trophoblastic tissue proliferates. Destructive chorioadenoma (invasive hydatidiform mole) is a local invasion of the myometrium by a hydatidiform mole.

Choriocarcinoma is an invasive, usually widely metastatic tumor composed of malignant trophoblastic cells and defective edematous villi; most of these tumors develop after a hydatidiform mole. Placental site trophoblastic tumors (the rarest) consist of intermediate trophoblastic cells that persist after pregnancy. They may invade adjacent tissues or metastasize.[ 7 ]

The risk of choriocarcinoma increases in women younger than 20 years and in women older than 39 years. [ 8 ]

Symptoms of hydatidiform mole

Initial symptoms of hydatidiform mole are most often observed in the early stages of pregnancy, the uterus becomes larger than expected and is enlarged to 10-16 weeks of pregnancy. This pathology is characterized by bloody discharge, no fetal movement, no embryonic heart sounds and severe vomiting in the pregnant woman. The detection of grape-like tissue can be used to suspect this disease. Complications such as infectious diseases of the uterus, sepsis, hemorrhagic shock and preeclampsia, which can be observed in the early stages of pregnancy, are encountered. The placental portion of the trophoblastic tumor can cause bleeding.

Choriocarcinoma manifests itself symptomatically as a result of metastasis. Hydatidiform mole does not impair fertility, but predisposes to prenatal or perinatal complications (e.g., congenital malformations, spontaneous abortions).

Diagnostics

If a hydatidiform mole is suspected, serum hCG levels and pelvic ultrasonography are performed. If high hCG levels are detected, the diagnosis can be assumed and confirmed by biopsy. [ 9 ], [ 10 ]

Treatment of hydatidiform mole

Hydatidiform mole, invasive mole, and placental portion of trophoblastic tumor are evacuated by vacuum curettage. If birth is not planned, hysterectomy may be an alternative. Following tumor removal, gestational trophoblastic disease is usually classified clinically to determine the need for additional treatment. Repeat uterine curettage appears to prevent persistent disease and reduce the need for subsequent chemotherapy.[ 11 ]

The clinical classification does not correspond to the morphological classification. A chest X-ray is performed and serum hCG levels are determined. If the hCG level does not normalize within 10 weeks, the disease is classified as persistent. If the disease persists, a CT scan of the brain, chest, abdomen, and pelvis should be performed. Based on the examination data, the hydatidiform mole should be classified as non-metastatic or metastatic. In metastatic disease, the risk of death may be low or high.

NIH (National Institutes of Health) Prognostic Criteria for Metastatic Gestational Trophoblastic Disease

• Urinary excretion of hCG greater than 100,000 IU within 24 hours
• Duration of illness more than 4 months (starting from the previous pregnancy)
• Metastases to the brain or liver
• Illness after pregnancy (postpartum)
• The hCG content in the blood serum is more than 40,000 mIU/ml
• Ineffective previous chemotherapy of more than 8 courses (WHO)

Persistent trophoblastic disease is usually treated with chemotherapy. Treatment of a hydatidiform mole is considered successful if three consecutive serum beta-hCG levels are normal (at weekly intervals). Acceptable oral contraceptives are usually prescribed for 6-12 months; alternatively, any effective method of contraception can be used. Non-metastatic disease can be treated with monochemotherapy using a single chemotherapy drug (methotrexate or dactinomycin). Of the approved drugs, methotrexate (MTX) is the most commonly used with a good therapeutic index. [ 12 ] Alternatively, hysterectomy can be performed in patients over 40 years of age or in patients who desire sterilization, as well as in patients with severe infection or uncontrolled bleeding.

If monochemotherapy is ineffective, then hysterectomy or polychemotherapy is prescribed. In fact, 100% of patients with non-metastatic disease can be cured. [ 13 ]

The most commonly used polychemotherapy regimen is etoposide, methotrexate, and actinomycin D alternating with cyclophosphamide plus vincristine (EMA-CO) as first-line therapy for patients with high-risk disease.[ 14 ],[ 15 ],[ 16 ]

Low-risk metastatic disease is treated with mono- or polychemotherapy. High-risk metastatic disease requires aggressive polychemotherapy. Cure occurs in 90-95% of patients with low-risk disease and in 60-80% with high-risk disease.

What is the prognosis for a hydatidiform mole?

Post-chemotherapy surveillance should include post-treatment ultrasound monitoring. Duplex ultrasonography plays an important role in the surveillance of low-risk disease, and close monitoring of serum β-hCG is essential. Most relapses occur within the first year after completion of chemotherapy. The generally accepted β-hCG surveillance schedule is weekly β-hCG measurement for 6 weeks after chemotherapy, followed by measurements every two weeks for up to 6 months after chemotherapy. Thereafter, β-hCG measurement is performed twice a year for 5 years. [ 17 ]

Hydatidiform mole recurs in approximately 1% of subsequent pregnancies. Patients who have had a hydatidiform mole are given ultrasound early in subsequent pregnancies.