Hydatidiform Mole

INTRODUCTION @

Background: Gestational trophoblastic disease includes several disease processes that originate in the placenta. This includes complete and partial moles, placental site trophoblastic tumors, choriocarcinomas and invasive moles.

Almost all women with malignant gestational trophoblastic disease can be cured with preservation of reproductive function. The following discussion will be limited to hydatidiform moles, complete and partial.

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Pathophysiology: A complete mole contains no fetal tissue. 90% are 46XX and 10% are 46XY. All chromosomes are of paternal origin. An enucleate egg is fertilized by a haploid sperm, which then duplicates its chromosomes, or the egg is fertilized by 2 sperm. In a complete mole the chorionic villi have grapelike (hydatidiform) swelling, and there is trophoblastic hyperplasia.

With a partial mole, fetal tissue is often present. The chromosomal complement is 69XXX or 69XXY. This results from fertilization of a haploid ovum and duplication of the paternal haploid chromosomes, or from dispermy. As in a complete mole, there is hyperplastic trophoblastic tissue and swelling of the chorionic villi.

Frequency:
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Mortality/Morbidity: Of patients with hydatidiform mole, 20% will develop a trophoblastic malignancy. After a complete mole, uterine invasion occurs in 15% of patients, and metastasis occurs in 4% of patients. No cases of choriocarcinoma have been reported after a partial mole, although 4% of patients with partial moles develop persistent nonmetastatic trophoblastic disease requiring chemotherapy.

Race: There is no racial/ethnic predilection for molar pregnancy. However, as discussed in the section on frequency, Asian countries show a rate 15 times higher than the US. Asian women living in the US do not appear to have a different rate of molar pregnancies than other ethnic groups.

Sex: Hydatidiform mole is a disease of pregnancy, and therefore a disease of women.

Age: Hydatidiform mole is more common at the extremes of reproductive age. The early teens and the perimenopause years are most at risk. Women over age 35 have a twofold increase in risk. Women over 40 experience a risk that is 7 times higher than in younger women. Parity does not affect the risk.

CLINICAL @

History:

Physical:

Causes: A diet deficient in animal fat and carotene may be a risk factor.

DIFFERENTIALS @

Hyperemesis Gravidarum
Hypertension
Hypertension, Malignant
Hyperthyroidism
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WORKUP @

Lab Studies:
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Imaging Studies:
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Histologic Findings:

  • Complete mole: Absent fetal tissue, severe trophoblastic proliferation, hydropic villi, chromosomes 46XX or 46XY. Additionally, complete moles show overexpression of several growth factors, including c-myc, epidermal growth factor, and c-erbB-2 as compared to normal placenta.

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  • Partial mole - Fetal tissue often present as well as amnion and fetal red blood cells. Hydropic villi and trophoblastic proliferation is also seen.
    TREATMENT @

    Medical Care:

    • Stabilize the patient
    • Transfuse for anemia
    • Correct any coagulopathy
    • Treat hypertension

    Surgical Care:

    • Evacuation of the uterus by dilation and curettage is always necessary.
    • Prostaglandin or oxytocin induction is not recommended because of the increased risk of bleeding and of malignant sequelae.
    • Intravenous Pitocin should be started with the dilation of the cervix and continued postoperatively to reduce the likelihood of hemorrhage. Consideration of using other uterotonic formulations such as methargin and Hemabate is also warranted.
    • At the time of surgery respiratory distress is often observed. This may be due to trophoblastic embolization, high output congestive hear failure due to anemia, or iatrogenic fluid overload. This should be treated aggressively with assisted ventilation and monitoring, as required.

    Consultations: Gynecologic oncology should be consulted if it is believed that patient is at risk for or has developed malignant disease.

    Diet: No special diet is required.

    Activity:

    • Patient may resume activity as tolerated.
    • Pelvic rest is recommended for 4-6 weeks after evacuation of the uterus and the patient is instructed not to become pregnant for twelve months. Adequate contraception is recommended during this time period.
    • Serial Beta hCG values will be followed to identify the rare patient who develops malignant disease. Should a pregnancy occur, the elevation in Beta hCG would be confused with development of malignant disease.
    MEDICATION @

    Prophylactic chemotherapy for hydatidiform mole is controversial. Most women will be cured by evacuation of the mole.
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    FOLLOW-UP @

    Further Outpatient Care:
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    • Serial quantitative beta hCG levels should be determined.
      • Draw the first level 48 hours after evacuation, and then every 2 weeks until the levels are normal.
      • Levels should consistently drop and should never increase.
      • Once levels have reached normal, check each month for 1 year.
      • Any rise in levels should prompt a chest x-ray and pelvic exam to facilitate early detection of metastases.
    • Contraception is recommended for six months to a year after evacuation.
    • Patients with a prior complete or partial molar pregnancy have a ten-fold risk of a second mole in a future pregnancy. Evaluate all future pregnancies early with ultrasound.

    Complications:
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    • Perforation of the uterus during suction curettage sometimes occurs because the uterus is large and boggy. If perforation is noted, the procedure should be completed under laparoscopic guidance.
    • Hemorrhage is a frequent complication during the evacuation of a molar pregnancy. For this reason IV Pitocin should be started prior to beginning the procedure. Methergine and/or Hemabate should also be available. The patient should also be typed and crossed and have blood readily available.
    • Malignant trophoblastic disease develops in 20% of molar pregnancies. For this reason, quantitative HCG should be followed serially until negative, and for 1-year post evacuation.
    • DIC - Factors released by the molar tissue have fibrinolytic activity. All patients should be screened for coagulopathy.
    • Trophoblastic embolism is believed to be the cause of acute respiratory insufficiency. The greatest risk factor is a uterus larger than 16 weeks. The condition may be fatal.

    Prognosis:
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    • Currently, because of early diagnosis and appropriate treatment, the mortality from hydatidiform mole is essentially zero. Approximately 20% of women with a complete mole will develop a trophoblastic malignancy. Gestational trophoblastic malignancies are 100% curable.

    Patient Education:
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    • Because of the small but real potential for development of malignant disease, and because these malignancies are absolutely curable, the importance of consistent followup must be emphasized.
    • It is important that the patient avoid pregnancy for 1 year to avoid any confusion about the development of malignant disease. Effective contraception should be used. If a pregnancy were to occur, the elevation in Beta hCG levels could not be differentiated from the disease process.
    • Future pregnancies should undergo sonographic evaluation early because of the increased risk of recurrence of a molar gestation.
    • The risk of recurrence is 1-2%.
    MISCELLANEOUS @

    Medical/Legal Pitfalls:
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    • Failure to consider the diagnosis in a patient who presents with hyperemesis. Many patients with molar gestations develop intractable nausea and vomiting due to the high levels of circulating HCG.
    • Failure to explain the importance of close follow up after evacuation of the mole. Approximately 20% of patients with molar gestations will develop trophoblastic malignancy.
    • Failure to recognize the significance of plateauing Beta HCG levels. If Beta HCG levels plateau, serious consideration must be given to the possibility of persistent or malignant disease. A chest x-ray should be performed for metastasis. If metastatic disease is found, staging by CT of the abdomen, pelvis and brain should be performed, and the patient treated based on what those tests reveal.
    • Failure to consider the diagnosis in a patient who presents with preeclampsia before 24-weeks gestation. Of those with a complete mole, 27% develop preeclampsia.
    PICTURES @

    Caption: Picture 1. Theca Lutein cysts
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    Picture Type: Photo
    Caption: Picture 2. Complete Mole
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    Picture Type: Photo
    Caption: Picture 3. Complete mole with an area of clot near cervix consistent with bleeding.
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    Picture Type: Photo
    BIBLIOGRAPHY @