Introduction

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

Pathophysiology
A complete mole contains no fetal tissue. Ninety percent are 46,XX, and 10% are 46,XY.1,2
Complete moles can be divided into 2 types:

Androgenetic complete mole

o Homozygous

These account for 80% of complete moles.

Two identical paternal chromosome complements, derived from

duplication of the paternal haploid chromosomes.

Always female; 46,YY has never been observed.

o Heterozygous

These account for 20% of complete moles.

May be male or female.

All chromosomes are of parental origin, most likely due to dispermy.

Biparental complete mole: Maternal and paternal genes are present but failure of maternal
imprinting causes only the paternal genome to be expressed.3
o The biparental complete mole is rare.

o A recurrent form of biparental mole, which is familial and appears to be inherited

as an autosomal recessive trait, has been described. Al-Hussaini describes a series
of 5 women with as many as 9 consecutive molar pregnancies.4,5
o Mutations in NLRP7 at 19q13.4 have been identified as causative in recurrent
molar pregnancies.6,7,8
With a partial mole, fetal tissue is often present. Fetal erythrocytes and vessels in the villi are a
common finding. The chromosomal complement is 69,XXX or 69,XXY.9 This results from
fertilization of a haploid ovum and duplication of the paternal haploid chromosomes or from
dispermy. Tetraploidy may also be encountered. As in a complete mole, hyperplastic
trophoblastic tissue and swelling of the chorionic villi occur.

Frequency
United States
By studying elective pregnancy terminations, hydatidiform moles were determined to occur in
approximately 1 in 1200 pregnancies.10
International
The reported frequency of hydatidiform mole varies greatly. Some of this variability can be
explained by differences in methodology (eg, single hospital vs population studies, identification
of cases). The reported frequencies range from 1 in 100 pregnancies in Indonesia to 1 in 200
pregnancies in Mexico to 1 in 5000 pregnancies in Paraguay.11 The study of pathologic material
from first- and second-trimester abortions established a frequency of complete and partial
hydatidiform moles in Ireland of 1 per 1945 pregnancies and 1 per 695 pregnancies,
respectively.12

Mortality/Morbidity
A hydatidiform mole is considered malignant if metastases or destructive invasion of the
myometrium (ie, invasive mole) occurs, or when the serum hCG levels plateau or rise during the
period of follow-up and an intervening pregnancy is excluded. Malignancy (see eMedicine's
article Gestational Trophoblastic Neoplasia) is diagnosed in 15-20% of patients with a complete
hydatidiform mole and 2-3% of partial moles.13,14 Lung metastases are found in 4-5% of patients
with a complete hydatidiform mole and rarely in cases of partial hydatidiform moles.15,16

Race
Differences in the frequency of hydatidiform moles between ethnic groups have been reported
internationally.11,17 In the United States, comparison of frequency of hydatidiform moles in
African Americans and Caucasians have yielded conflicting results.17 If differences exist, whether
they are due to genetic differences or environmental factors is not clear.

Sex
Hydatidiform mole is a disease of pregnancy and therefore a disease of women.
See Medscape's Pregnancy Resource Center.

Age
Hydatidiform mole is more common at the extremes of reproductive age. Women in their early
teenage or perimenopausal years are most at risk.18,19,20,11,17 Women older than 35 years have a 2fold increase in risk. Women older than 40 years experience a 5- to 10-fold increase in risk
compared to younger women. Parity does not affect the risk.

Clinical
History

Complete mole: The typical clinical presentation of complete molar pregnancies has
changed with the advent of high-resolution ultrasonography. Most moles are now
diagnosed in the first trimester before the onset of the classic signs and symptoms.21,22
o Vaginal bleeding: The most common classic 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 50% of cases.
o Hyperemesis: Patients may also report severe nausea and vomiting. This is due to
extremely high levels of human chorionic gonadotropin (hCG).
o Hyperthyroidism: Signs and symptoms of hyperthyroidism can be present due to
stimulation of the thyroid gland by the high levels of circulating hCG or by a
thyroid stimulating substance (ie, thyrotropin) produced by the trophoblasts.23

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.
o Vaginal bleeding
o Absence of fetal heart tones

Physical

Complete mole (See images below.)

o 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, patients present with size-appropriate enlargement or smaller-thanexpected enlargement at a similar frequency.
o Preeclampsia: Pelvic ultrasonography has resulted in the early diagnosis of most
cases of hydatidiform mole and preeclampsia is seen in less than 2% of cases.22
o Theca lutein cysts: These are ovarian cysts greater than 6 cm in diameter and
accompanying ovarian enlargement. These cysts are not usually palpated on
bimanual examination but are identified by ultrasonography. Patients may report
pressure or pelvic pain. Because of the increased ovarian size, torsion is a risk.
These cysts develop in response to high levels of beta-hCG. They spontaneously
regress after the mole is evacuated, but it may take up to 12 weeks for complete
regression.
o

Theca lutein cysts.

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Theca lutein cysts.

o

Complete mole.
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Complete mole.
o

Complete mole with an area of clot near cervix consistent with

bleeding.
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Complete mole with an area of clot near cervix consistent with bleeding.

Partial mole
o Uterine enlargement and preeclampsia is reported in only 5% of patients.24
o Theca lutein cysts, hyperemesis, and hyperthyroidism are extremely rare.

Twinning (See image below.)

o Twinning with a complete mole and a fetus with a normal placenta has been
reported (see image below). Cases of healthy infants in these circumstances have
been reported.25,9
o Women with coexistent molar and normal gestations are at higher risk for
developing persistent disease and metastasis26 . Termination of pregnancy is a
recommended option.
o The pregnancy may be continued as long as the maternal status is stable, without
hemorrhage, thyrotoxicosis, or severe hypertension. The patient should be
informed of the risk of severe maternal morbidity from these complications.27
o Prenatal genetic diagnosis by chorionic villus sampling or amniocentesis is
recommended to evaluate the karyotype of the fetus.
o

Twin gestation. Complete mole and normal twin.

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Twin gestation. Complete mole and normal twin.

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

http://emedicine.medscape.com/article/254657-overview