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.

Epidemiology
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 2-fold 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.