INTRODUCTION. Hydatidiform moles are characterized by parental disomy, which leads to maldevelopment of the fetus and consequent placental malformation.
Perinatal/Neonatal Casebooks &
&
&
&
&
&
&
&
&
&
&
&
&
&
Placental Pathology Casebook Kurt Benirschke, Section Editor Contributed by Elizabeth Albers Sean Daneshmand Andrew Hull A case of twin pregnancy consisting of a complete hydatidiform mole with a coexistent, viable fetus is presented. The case is distinctive for its presentation on ultrasound, its unusually low levels of serum hCG, its remarkable histology, and its term delivery. Journal of Perinatology 2001; 21:72 ± 75.
following case describes a patient with CHM and a viable, normal fetus delivered at term with no persistent trophoblastic disease 3 months after delivery. CASE REPORT A 21-year-old, G2P1001, Hispanic woman presented for late prenatal care at a gestational age of 25 weeks. She had one previous
INTRODUCTION Hydatidiform moles are characterized by parental disomy, which leads to maldevelopment of the fetus and consequent placental malformation. The placenta is diffusely edematous with massive fluid accumulation in some or all of the villi. In 1977, Kajii and Ohama 1 showed that all complete hydatidiform moles (CHMs) are derived from paternal chromosomes. A spermatozoon fertilizes an ``empty egg,'' devoid of maternal chromosomes. Subsequent chromosomal duplication results in a 46,XX karyotype. A 46,YY karyotype would result from fertilization with a male-determining spermatozoon and is incompatible with life. In 1978, Szulman and Surti 2 divided moles into two distinct clinical, genetic and histologic entities. CHMs are usually 46,XX and of paternal origin, which precludes embryonic or fetal development. All of the villi are markedly hydropic and avascular. Partial hydatidiform moles (PHM) are often triploid with 23 of the chromosomes of maternal origin and 46 of paternal origin, resulting in a 69,XXX or 69,XXY karyotype. Although feto-placental development occurs, long-term survival is rare. The incidence of CHMs is estimated at 1/2000 in the United States, although there is vast geographic variability elsewhere.3 The incidence of CHMs with a coexistent fetus is much rarer, with an estimated incidence of 1/22,000 to 1/100,000.4 ± 8,17 PHM with a complete fetus is also uncommon, occurring in only 0.005% to 0.01% of pregnancies. Less than 30 cases of complete mole with coexistent fetus have been reported in the literature since 1978 and only 16 cases of complete mole with a viable fetus have been reported.3 ± 8,10 ± 16 The Departments of Pathology and Obstetrics and Gynecology, University of California, San Diego Medical Center, San Diego, CA. Address correspondence and reprint requests to Elizabeth Albers, MD, UCD Medical Center, 200 West Arbor Drive, San Diego, CA 92103.
Figure 1 A. (top) Ultrasound examination of the patient at 28 weeks showing a normal-appearing placenta (single arrow) with an adjacent large tissue mass with multiple sonolucent areas (double arrow). B. (bottom) Ultrasound examination at 28 weeks showing sonolucent tissue mass. Journal of Perinatology 2001; 21:72 ± 75
# 2001 Nature Publishing Group All rights reserved. 0743-8346/00 $17
72
www.nature.com/jp
Complete Hydatidiform Mole with Coexistent Term Twin Pregnancy
pregnancy, 1 year prior, which resulted in the normal, spontaneous vaginal delivery of a healthy, term infant. The pregnancy was without complications. Family history was negative for fetal anomalies or congenital defects. Her prenatal laboratory studies were unremarkable except for a microcytic anemia. She denied vaginal bleeding or hyperemesis and her blood pressure was normal. A routine ultrasound examination at 28 weeks showed a normal-appearing fetus, which was appropriately sized for dates. The placenta appeared to consist of two distinct components, a normal looking placenta, into which the umbilical cord inserted, and an adjacent tissue mass, which contained multiple, large, sonolucent areas. There was no apparent separating membrane between the normal placenta and the tissue mass (Figure 1A and B). Differential diagnosis included a degenerating uterine leiomyoma, a large subchorionic hematoma, and a partial or complete hydatidiform mole. Ultrasound examination of the maternal liver and adnexae was unremarkable. Amniocentesis yielded a 46,XX karyotype and normal amniotic fluid alpha fetoprotein. Maternal chest X-ray, liver, and thyroid function tests were normal. Subsequent ultrasound examinations at 30, 34, and 37 weeks' gestation showed appropriate fetal growth and no change in the placental mass. The patient remained well with no
Albers et al.
signs of pre-eclampsia or thyroid disease. At 40 weeks and 5 days, the patient had a spontaneous vaginal delivery of a healthy, female infant, weighing 2965 g with 1- and 5-minute Apgar scores of 9 and 9. An intact, 410-g placenta, measuring 20.517.02.0 cm, was then delivered, which had attached hydropic villi (Figure 2). A postpartum ultrasound revealed a retained, grape-like mass within the uterus. Molar tissue (890 g) was then manually extracted (Figure 2). The serum hCG at the time of delivery was 53,953 IU/l. The expected level of serum hCG at delivery is between 10,000 and 40,000 IU/l.9 Microscopic examination of the placenta revealed predominantly unremarkable, mature villous tissue. However, a small area of markedly dilated and edematous villi was directly opposed to the rest of the normal, placental disc (Figure 3A). There was a clear delineation between the two tissues without any evidence of intervening decidual tissue. Examination of the molar tissue that was not attached to the placenta showed hydropic and avascular villi with hyperplastic trophoblast in the scalloped pattern typical of hydatidiform moles (Figure 3B). There was no evidence of any embryonic remnant; however, an extensive amount of degenerated trophoblast was noted.
Figure 2. Gross photograph of the normal placenta and the adjacent complete hydatidiform mole. Journal of Perinatology 2001; 21:72 ± 75
73
Albers et al.
Complete Hydatidiform Mole with Coexistent Term Twin Pregnancy
month postpartum. A follow-up chest X-ray remained negative for metastatic disease 1 month after delivery.
Figure 3 A. (top) Photomicrograph showing the juxtaposition of the mature, villous tissue (single arrow) with the hydropic, avascular molar tissue (double arrow). B. (bottom) Photomicrograph of the complete hydatidiform mole with typical features: hydropic, avascular villi and hyperplastic trophoblast.
Cytogenetic analysis of the molar tissue revealed it to have a normal, female karyotype (46,XX). Levels of serum hCG were followed and declined steadily from a peak of 53,953 IU/l at birth to 322 IU/l 1 week postpartum to less than 2 IU/l 1 74
DENOUEMENT AND DISCUSSION Complete Hydatidiform Mole with Coexistent Term Twin Pregnancy Although the incidence of CHM with coexisting twin is exceedingly low, it is of value to assess the outcome of all cases because of the attendant risk of persistent trophoblastic disease (PTD). The risk of PTD after CHM and PHM is reported to be between 8% and 20% and 1% and 5%, respectively.4 However, the risk of PTD after a CHM with a coexisting twin is reported to be much higher. Stellar et al.5 found the risk of PTD after a complete mole with a coexisting fetus to be 55% as opposed to a single molar pregnancy where the risk was 14%. A greater incidence of PTD with metastatic disease was also reported for women with a CHM and a coexisting twin versus women with a singleton molar pregnancy. It is also worth considering that the incidence of CHM with a coexisting twin may be climbing secondary to an increase in the use of infertility pharmacotherapy. The four patients reported on by Shahabi et al.4 and by Bristow et al.10 employed infertility drugs to become pregnant. It may be that the induced ovulation of more than one ovum that results from drugs such as clomiphene citrate leads to an increased number of abnormal ova, such as the chromosomally ``empty'' ovum. Whether or not a woman can carry a normal fetus with a coexisting complete mole to term without the sequelae of persistent trophoblastic disease has become an important question. The current case of dizygotic twin pregnancy is unique in its presentation on ultrasound, with its low levels of serum hCG and the unusual juxtaposition of the normal placenta with portions of the molar tissue. The ultrasound diagnosis of complete molar pregnancy is often not as clear as it was in this case. The peak level of serum hCG that was available is the delivery level of 53,953 IU/l. Levels of serum hCG can reach as high as 900,000 to 1,000,000 in singleton molar pregnancies and the values can be even greater in complete moles with a coexisting fetus.4 Stellar et al.5 reported a mean high level of serum hCG of 799,590 IU/l in a study of eight patients with a complete mole and a coexisting twin. The low level of serum hCG in this case may be due to the extensive amount of degenerated trophoblast. The sharp division between the normal placenta and the attached molar placenta is also unusual. The two tissues did not intermingle despite the lack of any intervening decidual tissue. It is also rare that a patient with a complete hydatidiform mole and a coexisting twin carries that pregnancy to term with no complications. Patients with a complete hydatidiform mole and a coexisting fetus are at risk for a number of complications, including hyperemesis gravidarum, hyperthyroidism, the sudden onset of pre-eclampsia before the 20th week of gestation, hemorrhage and persistent gestational trophoblastic disease, which may require multiple cycles of chemotherapy. This is only the ninth case reported in the literature in which a patient with a complete hydatidiform mole and a Journal of Perinatology 2001; 21:72 ± 75
Complete Hydatidiform Mole with Coexistent Term Twin Pregnancy
coexistent, viable fetus has delivered at term (defined as date of delivery after the 36th week of gestation). Of the eight other term cases in the literature, only three had persistent trophoblastic disease. Certainly more cases need to be evaluated, but the early evidence may suggest that there is no increased risk for persistent trophoblastic disease in carrying an uncomplicated complete mole with a coexistent viable fetus to term. References
1. Kajii T, Ohama K. Androgenetic origin of hydatidiform mole. Nature 1977;268:633 ± 634. 2. Szulman AE, Surti U. The syndromes of hydatidiform mole: I. Cytogenetic and morphologic correlations. Am J Obstet Gynecol 1978;131:665 ± 671. 3. Anderson CK, Deiter RW, Motz MJ, Goldstein J. Complete hydatidiform mole with a coexistent healthy, viable fetus near term. J Reprod Med 1996;41:55 ± 58. 4. Shahabi S, Naome G, Cobin L, et al. Complete hydatidiform mole and coexisting normal fetuses. J Reprod Med 1997;42:756 ± 760. 5. Stellar MA, Genest DR, Bernstein MR, Lage JM, Goldstein DP, Berkowitz R. Natural history of twin pregnancy with complete hydatidiform mole and coexisting fetus. Obstet Gynecol 1994;83:35 ± 42. 6. Bruchim I, Kidron D, Amiel A, Altaras M, Fejgin MD. Complete hydatidiform mole and a coexistent viable fetus: report of 2 cases and review of the literature. Gynecol Oncol 2000;77:197 ± 202. 7. Choi - hong SR, Genest DR, Crum CP, Berkowitz R, Goldstein DP, Schofield D. Twin pregnancies with complete hydatidiform mole and coexisting fetus. Hum Pathol 1995;26:1175 ± 1180.
Journal of Perinatology 2001; 21:72 ± 75
Albers et al.
8. Block MF, Merrill JA. Hydatidiform mole with coexistent fetus. Obstet Gynecol 1982;60:129 ± 134. 9. Bakerman S. ABC's of Interpretive Laboratory Data. 3rd ed. Myrtle Beach, SC: Interpretive Laboratory Data; 1994. p. 288 ± 289. 10. Bristow RE, Shumway JB, Khouzami AN, Witter FR. Complete hydatidiform mole and surviving coexistent twin. Obstet Gynecol Surv 1996;51:705 ± 709. 11. Fishman DA, Padilla LA, Keh P, Cohen L, Frederiksen M, Lurain JR. Management of twin pregnancies consisting of a complete hydatidiform mole and normal fetus. Obstet Gynecol 1998;91:546 ± 550. 12. Hurteau JA, Roth LM, Schilder JM, Sumners J. Complete hydatidiform mole coexisting with a twin live fetus: clinical course. Gynecol Oncol 1997;66:156 ± 159. 13. Suzuki M, Matsunobu A, Wakita K, Nishijima M, Osanai K. Hydatidiform mole with a surviving coexisting fetus. Obstet Gynecol 1980;56: 384 ± 388. 14. Miller D, Jackson R, Ehlen T, McMurtrie E. Complete hydatidiform mole coexistent with a twin live fetus: clinical course of 4 cases with complete cytogenetic analysis. Gynecol Oncol 1993;50:119 ± 123. 15. Chen FP. Molar pregnancy and living normal fetus coexistent until term: prenatal biochemical and sonographic diagnosis. Hum Reprod 1997;12:853 ± 856. 16. Jinno M, Ubukata Y, Hanyu I, Satou M, Yoshimura Y, Nakamura Y. Hydatidiform mole with a surviving coexistent fetus following in - vitro fertilization. Hum Reprod 1994;9:1770 ± 1772. 17. Benirschke K, Kaufmann P. The Pathology of the Human Placenta. 4th ed. Springer - Verlag, NY, 2000, pp. 718 ± 753.
75
