PATHOLOGY OF MOLAR PREGNANCY
Department of Pathology, University Medical Centre,
1211 Geneva 4, Switzerland
Hydatidiform mole is a pathologic conceptus characterized by marked enlargement of the placental villi. For unknown reasons, the incidence of moles varies by race (9). Hydatidiform mole occurs at present in approximately 1 in 2000 pregnancies in Europe and the United States, but the rate approaches 1 in 500 in Japan, Singapore and Malaysia (3,9). A significant increase in the incidence of moles has been observed in women after age 40 and in women of 20 years and younger (1,2).
In 1977 (8), it was observed that using a combination of gross, histologic and cytogenetic techniques, it was possible to classify hydatidiform mole into two clinicopathologic entities: the classic complete mole, and the partial mole. This observation was rapidly confirmed (6,7). The exact incidence of molar pregnancy in various populations is not possible to ascertain because most epidemiologic studies have not separated complete from partial moles.
Hydatidiform mole is a part of a generic term: the gestational trophoblastic disease (GTD). This term describes a spectrum of abnormal trophoblastic proliferations associated with villous enlargement (moles) or neoplasms without villi (choriocarcinoma, placental-site trophoblastic tumor). The current classification of GTD is shown in Table 1.
From a clinical point of view, GTD is recognized today as the most curable gynecologic malignancy, for two major reasons:
- Human chorionic gonadotropin (hCG) is produced by the various trophoblastic proliferations, and hCG concentration in the urine or serum is directly related to the number of viable trophoblastic cells. For this reason, hCG is a unique sensitive marker in the management of patients with GTD.
- Proliferating trophoblast is extremely sensitive to certain chemotherapeutic agents, such as methotrexate and actinomycin D.
Complete hydatidiform mole
A complete mole forms often a bulky mass, sometimes consisting of over 500 cc of bloody tissue, and has a classical bunch of grapes appearance. No normal placental tissue is apparent and all villi are enlarged, forming transparent vesicles of variable size (1 to 30 mm). An embryo or fetus is absent.
Histologically, all the villi are distended, edematous and often show central cisterns. Fetal vessels are generally absent. The villous trophoblast shows an irregular proliferation (hyperplasia), often associated with cytologic atypia.
Cytogenetic analysis of complete moles has shown a 46,XX chromosomal constitution. Both X chromosomes are contributed by the father (biandrogenetic) (5). It was found that the androgenetic origin of a complete mole is the result of a duplication of a haploid paternal X sperm (23,X) penetrating an " empty ovum " lacking functional maternal DNA. Nevertheless, a dispermic mechanism (two haploid sperms penetrating an " empty ovum ") (9) is also possible though rare and could account for a 46,XX or 46,XY mole of paternal origin. The monospermic complete mole is called " homozygous " and the dispermic " heterozygous ".
Clinically, complete hydatidiform mole is suspected in a patient whose uterus is larger than expected for gestational age; there is a vaginal bleeding, a repeatedly and markedly elevated hCG level; frequently a first trimester preeclampsia (pregnancy associated hypertension) and, occasionally, a bilateral enlargement of the ovaries, secondary to lutein cysts. Ultrasonography discloses a snowstorm appearance.
A complete hydatidiform mole is at increased risk for the development of persistent gestational trophoblastic disease (PGTD). In this case, following evacuation of the mole, the patient’s hCG levels remain elevated (plateau), or continue to rise, or there is evidence of metastases. Approximately 20% of complete moles may develop PGTD.
Choriocarcinoma, a malignant neoplasm of the trophoblast, occurs in about 2 to 3% of patients with complete mole. In Western countries, 50% of gestational choriocarcinomas follow a complete hydatidiform mole (4).
Partial hydatidiform mole
The partial mole differs from the complete mole in that the volume of the tissue is often less than 300 cc and only a proportion of the villi are vesicular. It is not uncommon for a fetus to be present, and it may be abnormal.
Histologically a proportion of the villi are edematous with sometimes a central cistern. Fetal vessels are usually present. Some enlarged villi may show a degree of trophoblastic hyperplasia but usually less marked than that seen in a complete mole.
Cytogenetic analysis of partial moles has showed that the majority are associated with fetal triploidy, though a few are associated with fetal trisomy or tetraploidy (8). Some partial moles may have a diploid karyotype (8).
The triploid mole is nearly always due to the combination of two sets of chromosomes of paternal origin (diandric), and of a haploid maternal set. The mechanism suggested in triploidy is either the fertilization of a single ovum by two different haploid sperm or by a diploid sperm.
A rapid method for assaying ploidy in molar tissues is DNA cytometric analysis. This technique may serve as a useful complement to the pathologic interpretation.
The biologic behaviour of partial moles is poorly known. It appears that a partial mole can be complicated by PGTD although the risk is much less than that for the complete mole. Fully documented cases of choriocarcinoma have not been reported as complications of partial moles.
Table 2 shows the comparison between complete and partial mole.
Invasive hydatidiform mole
This term is applied to a molar pregnancy in which molar villi grow into the myometrium or its blood vessels, and may extend into the broad ligament and metastasize to the lungs, the vagina or the vulva. All cases of invasive mole are sequelae of hydatidiform moles. Approximately 15% of complete moles are associated with or precede invasive moles. The pathologic diagnosis of invasive mole is rarely made because most cases are treated medically, without hysterectomy.
When high hCG titres persist following evacuation of a mole, the patient is treated with chemotherapy without further pathologic diagnosis. Such a case is diagnosed as PGTD.
When a diagnosis of PGTD is established, proper evaluation must be performed based on certain guidelines. Scientific Committees of the World Health Organization have recently adopted a scoring system which allows identification of risk factors and the appropriate treatment of the disease (9) (Table 3 and Table 4).
- Bandy, L.C., Clarke-Pearson, D.L., and Hammond, C.B. (1984): Obstet. Gynecol., 64:395-399.
- Bracken, M.B. (1987): Br. J. Obstet. Gynaecol., 94:1123-1135.
- Buckley, J.D. (1984): Clin. Obstet. Gynaecol., 27:153-159.
- Elston, C.W. (1978): In: Major Problems in Pathology, edited by J.L. Bennington, Vol. 7., pp. 343-367. Saunders, London.
- Kajii, T., and Ohama, K. (1977): Nature, 268:633-634.
- Szulman, A.E., and Surti, U. (1978): Am. J. Obstet. Gynecol., 131:665-671.
- Szulman, A.E., and Surti, U. (1978): Am. J. Obstet. Gynecol., 132:20-27.
- Vassilakos, P., Riotton, G., and Kajii, T. (1977): Am. J. Obstet. Gynecol., 127:167-170.
- World Health Organization Scientific Group on Gestational Trophoblastic Disease (1983): Technical Report Series Nr 692, Geneva.