Hydatidiform Mole  

 

Background:

 

Gestational trophoblastic disease encompasses several disease processes that originate in the placenta. These include complete and partial moles, placental site trophoblastic tumors, choriocarcinomas, and invasive moles.

Pathophysiology:

A complete mole contains no fetal tissue. Ninety percent are 46,XX, and 10% are 46,XY. 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 69,XXX or 69,XXY. 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:

  • In Western countries, 1 per 1000-1500 pregnancies is affected. Hydatiform mole is an incidental finding in approximately 1 per 600 therapeutic abortions.
  • In Asian countries, the rate is as much as 15 times higher than in the United States. Japan has a reported rate of 2 cases per 1000 pregnancies. In the Far East, some sources estimate the rate as high as 1 case per 120 pregnancies.

Mortality/Morbidity:

Of patients with hydatidiform mole, 20% develop a trophoblastic malignancy. After a complete mole develops, uterine invasion occurs in 15% of patients, and metastasis occurs in 4%. 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:

Molar pregnancy has no racial or ethnic predilection, although Asian countries show a rate 15 times higher than the US rate. Asian women living in the United States do not appear to have a different rate of molar pregnancies than other ethnic groups.

Age:

Hydatidiform mole is more common at the extremes of reproductive age. Women in the early teens or the perimenopausal years are most at risk. Women older than 35 years have a 2-fold increase in risk. Women older than 40 years experience a 7-fold increase in risk compared to younger women. Parity does not affect the risk.

CLINICAL PRESENTATION

History:

  • Complete mole
    • Vaginal bleeding: The most common symptom of a complete mole is vaginal bleeding. Molar tissue separates from the decidua, causing bleeding. The uterus may become distended by large amounts of blood, and dark fluid may leak into the vagina. This symptom occurs in 97% of cases.
    • Hyperemesis: Patients may also complain of severe nausea and vomiting. This is due to extremely elevated human chorionic gonadotropin (HCG) levels.
    • Hyperthyroidism: Approximately 7% of patients may present with tachycardia, tremor, and warm skin.
  • Partial mole
    • Patients with partial mole do not have the same clinical features as those with complete mole. These patients usually present with signs and symptoms consistent with an incomplete or missed abortion.
    • Vaginal bleeding
    • Absence of fetal heart tone

      Physical Examination:
      • Complete mole
        • Size inconsistent with gestational age: A uterine enlargement greater than expected for gestational age is a classic sign of a complete mole. Unexpected enlargement is caused by excessive trophoblastic growth and retained blood. However, a similar frequency of patients present with size-appropriate enlargement or smaller-than-expected enlargement.
        • Preeclampsia: Approximately 27% of patients with complete mole develop toxemia characterized by hypertension (BP >140/90 mm Hg), proteinuria (>300 mg/d), and edema with hyperreflexia. Convulsions rarely occur.
        • Theca lutein cysts: These are ovarian cysts greater than 6 cm in diameter and accompanying ovarian enlargement. These cysts are usually not palpated on bimanual examination but are identified by ultrasound. Patients may complain of pressure or pelvic pain. Because of the increased ovarian size, there is a risk of torsion. These cysts develop in response to high levels of beta-HCG and spontaneously regress after the mole is evacuated.
      • Partial mole
        • Uterine enlargement and preeclampsia is reported in only 3% of patients.
        • Theca lutein cysts, hyperemesis, and hyperthyroidism are rare.
      • Twinning with a complete mole and a fetus with a normal placenta has been reported. Cases of healthy infants in these circumstances have been reported.

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

      DIFFERENTIAL DIAGNOSIS

      Hyperemesis Gravidarum
      Hypertension
      Hypertension, Malignant
      Hyperthyroidism



 

 

LABORATORY STUDIES

  • Quantitative beta-HCG: HCG levels greater than 100,000 mIU/mL indicates exuberant trophoblastic growth and raises suspicion that a molar pregnancy should be excluded. A molar pregnancy may have a normal HCG level.
  • Complete blood count with platelets: Anemia is a common medical complication, as is the development of a coagulopathy.
  • Test clotting function to exclude the development of a coagulopathy or to treat one if discovered.
  • Liver function tests
  • BUN and creatinine studies
  • Thyroxin: Although women with molar pregnancies are usually clinically euthyroid, plasma thyroxin is usually elevated above normal pregnancy range. Hyperthyroidism may be the presenting complaint.
Imaging Studies:
  • Ultrasound is the criterion standard for identifying both complete and partial molar pregnancies. The classic image is of a snowstorm pattern indicating hydropic chorionic villi.
  • Chest x-ray: Once a molar pregnancy is diagnosed, a baseline chest film should be taken. The lungs are a primary site of metastasis for malignant trophoblastic tumors.

Histologic Findings:

  • Complete mole: Fetal tissue is absent, severe trophoblastic proliferation, hydropic villi, and chromosomes 46,XX or 46,XY are present. Additionally, complete moles show overexpression of several growth factors, including c-myc, epidermal growth factor, and c-erb B-2, compared to normal placenta.

·         Partial mole: Fetal tissue is often present as well as amnion and fetal red blood cells. Hydropic villi and trophoblastic proliferation are also observed.

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 malignant sequelae.
  • Intravenous oxytocin should be started with the dilation of the cervix and continued postoperatively to reduce the likelihood of hemorrhage. Consideration of using other uterotonic formulations (eg, Methergine, Hemabate) is also warranted.
  • Respiratory distress is often observed at the time of surgery. This may be due to trophoblastic embolization, high-output congestive heart failure caused by anemia, or iatrogenic fluid overload. Distress should be aggressively treated with assisted ventilation and monitoring, as required.

Activity:

  • Patients 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 12 months. Adequate contraception is recommended during this period.
  • Monitor serial beta-HCG values 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 are cured by evacuation of the mole.

FOLLOW-UP

Further Outpatient Care:

  • 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 within reference ranges.
    • Levels should consistently drop and should never increase.
    • Once levels have reached reference ranges, check them each month for a year.
    • Any rise in levels should prompt a chest x-ray and pelvic examination to facilitate early detection of metastases.
  • Contraception is recommended for 6 months to a year after evacuation.
  • Patients with a prior complete or partial molar pregnancy have a 10-fold risk of a second mole in a future pregnancy. Evaluate all future pregnancies early with ultrasound.

Complications:

  • 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, intravenous oxytocin should be started prior to beginning the procedure. Methergine and/or Hemabate should also be available. The patient should 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 serially followed for 1 year postevacuation until results are negative.
  • Disseminated intravascular coagulation (DIC): Factors released by the molar tissue have fibrinolytic activity. All patients should be screened for coagulopathy.
  • Trophoblastic embolism is believed to cause acute respiratory insufficiency. The greatest risk factor is a uterus larger than that expected for a gestational age of 16 weeks. The condition may be fatal.

Prognosis:

  • Because of early diagnosis and appropriate treatment, the current mortality from hydatidiform mole is essentially zero. Approximately 20% of women with a complete mole develop a trophoblastic malignancy. Gestational trophoblastic malignancies are 100% curable.
  • The risk of recurrence is 1-2%.

MISCELLANEOUS

MedicalPitfalls:

  • 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 care after evacuation of the mole: Approximately 20% of patients with molar gestations 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 scan of the abdomen, pelvis and brain should be performed, and the patient should be treated based on those findings.
  • Failure to consider the diagnosis in a patient who presents with preeclampsia before 24 weeks' gestation: Twenty-seven percent of patients with a complete mole develop preeclampsia.