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.
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
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
- In the US: In western countries, 1:1000-1:1500
pregnancies are affected. It is an incidental finding in approximately 1 in
600 therapeutic abortions.
- Internationally: In Asian countries the rate is as much
as 15 times higher than in the US. Japan has a reported rate of 2 per 1000
pregnancies. In the Far East, some sources estimate the rate as high as 1:120
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
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
- 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 hCG.
- Hyperthyroidism - Approximately 7% of patients may present with
tachycardia, tremor, and warm skin.
- Patients with partial mole do not have the same clinical features as
complete mole. These patients usually present with signs and symptoms
consistent with an incomplete or missed abortion.
- Absence of fetal heart tones
- Size greater than dates - Uterine enlargement greater than expected for
dates is a classic sign of a complete mole. This is due both to excessive
trophoblastic growth and retained blood. However, a similar frequency of
cases present as size appropriate for or smaller than expected for dates.
- Preeclampsia - Approximately 27% of patients with complete mole develop
toxemia characterized by hypertension (BP>140/90), proteinuria (>300 mg/24h)
and edema with hyperreflexia. Convulsions rarely occur.
- Theca lutein cysts - Ovarian cysts greater than 6 cm in size and
accompanying ovarian enlargement. These cysts are usually not palpated on
bimanual exam, but are identified by ultrasound. Patients may complain of
pressure or pelvic pain, and because of the increased ovarian size, there is
a risk of torsion. These cysts develop in response to high levels of Beta
hCG, and regress spontaneously after the mole is evacuated.
- 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. There have been case reports of healthy infants in these
Causes: A diet deficient in animal fat and carotene may be a
- Quantitative beta hCG - hCG levels greater than 100,000 mIU/mL indicates
exuberant trophoblastic growth and should raise suspicion that a molar
pregnancy should be ruled out. 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 of clotting function to rule out the development of a coagulopathy,
or to treat if one is discovered
- Thyroxin - Although women with molar pregnancies are usually clinically
euthyroid, plasma thyroxin is usually elevated above normal pregnancy range.
Also, hyperthyroidism may be the presenting complaint.
- Ultrasound is the gold 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
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.
Partial mole - Fetal tissue often present as well as amnion and fetal red
blood cells. Hydropic villi and trophoblastic proliferation is also seen.
- 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.
- 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.
Prophylactic chemotherapy for hydatidiform mole is
controversial. Most women will be cured by evacuation of the mole.
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 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.
- 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.
- 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.
- 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%.
- 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
- 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%
|Caption: Picture 1. Theca Lutein cysts
|Picture Type: Photo
|Caption: Picture 2. Complete Mole
|Picture Type: Photo
|Caption: Picture 3. Complete mole with
an area of clot near cervix consistent with bleeding.
|Picture Type: Photo
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