Sonographic Appearance of Early Complete Molar Pregnancies
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1 Sonographic Appearance of Early Complete Molar Pregnancies Elizabeth Lazarus, MD, Carol A. Hulka, MD, Bettina Siewert, MD, Deborah Levine, MD Since our anecdotal experience indicates that the classically described snowstorm appearance on ultrasonography of early molar pregnancies is often not present and that theca-lutein cysts are also rare, we examined the ultrasonographic appearance of early complete molar pregnancies. We reviewed the ultrasonographic reports and clinical data of 21 cases of histologically diagnosed complete molar pregnancies with a mean gestational age at sonography of 10.5 weeks (range, 4 to 18 weeks). The diagnosis of molar pregnancy was made on ultrasonography in 12 (57%) cases, was second in the differential diagnosis of one (4.8%) case, and was not considered in eight (38%) cases. No theca-lutein cysts were identified. Five of five (100%) molar pregnancies of 13 weeks or over were diagnosed prospectively, while only eight of 16 (50%) earlier pregnancies were correctly diagnosed prospectively. In a retrospective review of the available images of 16 patients, only nine of 16 (56%) images demonstrated the classic appearance, and no theca-lutein cysts were seen. We conclude that the classic appearance of complete moles on ultrasonography is seen in less than two thirds of cases and even less commonly in the first trimester. The prevalence of theca-lutein cysts is very low. KEY WORDS: Molar pregnancy; First trimester sonography; Thecalutein cysts; Pregnancy, molar. Complete molar pregnancies are difficult to distinguish from normal early pregnancies on the basis of clinical signs and symptoms. β-hcg levels may not become abnormally elevated until the second trimester of pregnancy. Symptoms ABBREVIATIONS HCG, Human chorionic gonadotropin; IU, International unit Received March 8, 1999, from Beth Israel Deaconess Medical Center, Boston, Massachusetts. Revised manuscript accepted for publication June 10, Address correspondence and reprint requests to Deborah Levine, MD, Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA of molar pregnancies such as an enlarged uterus, vaginal bleeding, pregnancy induced hypertension, and absent fetal heartbeat are nonspecific and also may not arise until the second trimester. 1 Ultrasonography is instrumental in the diagnosis of molar pregnancies. The classic ultrasonographic appearance of a complete mole is described as a snowstorm appearance, consisting of a heterogeneous solid collection of echoes within the endometrium. 1 With improved ultrasonographic technology, individual cystic spaces representing hydropic villi have become easier to distinguish within the echogenic mass. However, the size of villi is directly proportional to gestational age, 2 and early molar pregnancies may not demonstrate the archetypal sonographic appearance. Isolated cases 3,4 of unusual appearances of first trimester moles have been reported. However, we found no reports that determine the prevalence of the typical ultrasonographic appearance in early molar pregnancies by the American Institute of Ultrasound in Medicine J Ultrasound Med 18: , /99/$3.50
2 590 EARLY COMPLETE MOLAR PREGNANCIES J Ultrasound Med 18: , 1999 The quoted prevalence 1,5 of concurrent theca-lutein cysts with molar pregnancies is up to 60%. These numbers appear to apply to molar pregnancies at a range of gestational ages. However, the prevalence of theca-lutein cysts in early complete molar pregnancies is unclear. The aim of this study was to examine the ultrasonographic appearance of early complete molar pregnancies and to determine the prevalence of the classic appearance and of theca-lutein cysts in these cases. MATERIALS AND METHODS We performed a retrospective review of all patients with a pathologically proven complete molar pregnancy diagnosed at our institution from October 11, 1990, to July 31, Cases were obtained from a search of the pathology department database. We performed a chart review to document the age of the patient, menstrual age at the time of the earliest ultrasonogram performed, β-hcg levels at the time of the ultrasonogram, indication for ultrasonography, and prospective sonographic diagnosis. Two reviewers (D.L., E.L.) reviewed all available images to examine the appearance of the uterus and ovaries and to offer a retrospective interpretation. A classic complete mole appearance was considered as a uterine cavity distended with echogenic tissue containing small cystic spaces (Fig. 1). The appearance of a possible mole was that of echogenic material Figure 1 Sagittal transabdominal image obtained at 18 weeks of gestation for vaginal bleeding. A complex echogenic mass containing multiple discrete cystic spaces expands the endometrium. This appearance is archetypal of complete moles. Both ovaries were normal without cysts. within a distended endometrium with or without large cysts. A molar pregnancy was not considered when any or all of these findings were absent. Thecalutein cysts were defined as multiple cysts enlarging the ovary. All ultrasonography was performed on Acuson 128 or 128XP (Mountain View, CA) and ATL UM9 or HDI3000 (Bothell, WA) machines. β-hcg levels were determined by the AxSYM total HCG assay (Abbott Laboratories, Abbott Park, IL). Standard normal ranges were provided by the manufacturer. RESULTS Of 25 patients with histologically proven molar pregnancies, 21 patients underwent ultrasonographic examinations at our institution. The mean age of the patients was 31 years (range, 20 to 46 years). Mean gestational age at sonography was 10.5 weeks (range, 4 to 18 weeks). The indication for ultrasonography included vaginal bleeding (13 patients), determine dates or fetal survey (two patients), question spontaneous or threatened abortion (three patients), question living or nonliving status (one patient), pain (one patient), and rule out ectopic pregnancy (one patient). The diagnosis of molar pregnancy was made prospectively on ultrasonography in 12 cases (57%), was second in the differential diagnosis of one case (4.8%), and was not considered in eight cases (38%). Five of five (100%) molar pregnancies of 13 weeks or over were prospectively diagnosed, while only eight of 16 (50%) earlier pregnancies were correctly diagnosed prospectively (Table 1). The other ultrasonographic diagnoses offered included spontaneous abortion (five cases) (Figs. 2, 3), thickened endometrium (two cases), retained products of conception (one case), and early intrauterine gestation (one case). No theca-lutein cysts were identified prospectively. Of the 21 cases, 16 had images available for retrospective review. Only nine of 16 (56%) cases demon- Table 1: Prospective Diagnoses Menstrual Age Prospective Diagnosis < 13 weeks 13 weeks Totals Classic mole (57%) Possible mole 1 1 (5%) Mole not considered 8 8 (38%) Totals 16 (76%) 5 (23%) 21
3 J Ultrasound Med 18: , 1999 LAZARUS ET AL 591 A B Figure 2 Sagittal (A) and transverse (B) endovaginal images of an early complete molar pregnancy obtained at 7 weeks of gestation for vaginal bleeding. An anechoic ovoid fluid collection with a mean diameter of 13 mm was prospectively diagnosed as an anembryonic incomplete abortion. Histologic examination yielded complete molar pregnancy. strated the classic appearance of molar pregnancy (Table 2). All nine cases were correctly diagnosed prospectively. Of the remaining seven cases, molar Figure 3 Transabdominal image obtained at 10 weeks 5 days of gestation for vaginal bleeding. An irregular fluid collection containing a circular mass is suggestive of an abnormal yolk sac within a gestational sac. Irregular hypoechoic soft tissue surrounds the fluid collection. Prospective diagnosis was spontaneous abortion. The retrospective review suggested mole as a possible diagnosis, since the echogenic material surrounding the endometrial fluid could potentially represent hydropic decidua. Histologic examination yielded complete molar pregnancy. pregnancy was considered in the retrospective differential diagnosis in five cases. Of these five cases, the prospective diagnoses were molar pregnancy (N = 2), differential diagnosis including molar pregnancy (N = 1), and mole not considered (N = 2). In two cases, molar pregnancy was not considered either retrospectively or prospectively. We encountered a spectrum of unusual sonographic appearances of complete molar pregnancy, including an intrauterine anechoic fluid collection similar to a gestational sac (Fig. 2), a fluid collection with a complex echogenic mass similar to an edematous placenta (Fig. 4), a heterogeneously thickened endometrium, and echogenic fluid-fluid levels within the endometrium (Fig. 5). Of the 16 cases imaged in the first trimester, β- HCG levels of 13 were determined within 48 h of the ultrasonography. Of these, seven cases were within the normal range, four cases were elevated, and one case was below the normal range. Of the five cases imaged during the second trimester, four had β-hcg levels determined. One case was in the normal range, and three cases were elevated. No association was seen between elevated β-hcg levels and the Table 2: Retrospective Diagnoses Menstrual Age Retrospective Diagnosis < 13 weeks 13 weeks Totals Classic mole (56%) Possible mole 5 5 (31%) Mole not considered 2 2 (13%) Totals 11 (69%) 5 (31%) 16
4 592 EARLY COMPLETE MOLAR PREGNANCIES J Ultrasound Med 18: , 1999 A B Figure 4 Sagittal (A) and transverse (B) endovaginal images obtained at 12 weeks 6 days of gestation for vaginal bleeding. A complex echogenic mass containing small irregular cystic spaces is partially surrounded by a crescentic fluid collection within the endometrium. This appearance is highly suggestive of complete molar pregnancy, but not classic. correct diagnosis of mole in either the prospective or the retrospective review. In only two of 16 cases was molar pregnancy not considered in the diagnosis retrospectively. In one of these cases imaged at 7 menstrual weeks, the β-hcg level was determined 48 h after the ultrasonography to be at a level 14,000 miu/ml (international reference preparation). In the other cases in which a molar pregnancy was considered, β-hcg values were available in 13 of 14 cases, with a mean of 251,238 miu/ml (range, 70,448 to 522,251 miu/ml). The mean β-hcg level in cases at gestational age 13 weeks and above (260,730 miu/ml) was not significantly different from those at less than 13 weeks (249,638 miu/ml). In the retrospective review of 16 cases, 27 of 32 possible ovaries were visualized. The largest ovarian cyst identified retrospectively in our series was 3.5 cm. No theca-lutein cysts were seen. Reports from the original 21 cases similarly did not identify any theca-lutein cysts. Statistical methods used were the chi-square test and Student t-test. diagnosis. β-hcg levels typically do not rise until late in the first trimester or early second trimester and may be well within the expected range during the first trimester. 7 In the case that was misdiagnosed on ultrasonography both prospectively and retrospectively for which the β-hcg level was available, Figure 5 Transverse transabdominal image obtained at 8 weeks 5 days of gestation demonstrates an unusual configuration of echogenic fluid-fluid levels (arrows) within the endometrium, consistent with layering blood products. Prospective diagnosis of molar pregnancy was made. Histologic examination yielded complete molar pregnancy. DISCUSSION Complete molar pregnancies occur in approximately one per 1200 to 2000 pregnancies in the United States. 6 Symptoms of moles include vaginal bleeding, enlarged uterus, absent fetal heartbeat, pregnancy induced hypertension, hyperemesis, and anemia. 1,5 As these symptoms are nonspecific, β- HCG levels that exceed those of normal pregnancies and ultrasonography are necessary to establish the
5 J Ultrasound Med 18: , 1999 LAZARUS ET AL 593 the low level (14,000 miu/ml) did not lead clinicians to suspect a molar pregnancy. Because of nonspecific symptoms, ultrasonography is crucial in the diagnosis of molar pregnancy. The classic sonographic appearance of a snowstorm image of complete moles is due to hydropic villi packed into the endometrial canal. However, in early pregnancy, ultrasonography may not be able to distinguish the villi, as the vesicles are too small and the interfaces too numerous. 8 As the pregnancy continues, the villi swell, giving rise to the classic appearance. In our study, molar pregnancy was diagnosed prospectively in 57% of cases. Retrospective review showed classic mole in 56% of cases. Sixteen of 21 (76%) ultrasonograms were performed prior to 13 weeks of gestational age, and only 50% of these early cases were correctly diagnosed prospectively. This relatively low accuracy exemplifies the difficulty of diagnosing molar pregnancy during early pregnancy. Two case reports describe examples of early molar pregnancies with atypical appearances, including an endometrial fluid collection containing a hyperechoic ovoid mass 3 and a cluster of hypoechoic structures surrounded by an echogenic rim. 4 Neither of these appearances was duplicated in our series, again indicating that a range of ultrasonographic presentations exists in the first trimester. We saw no theca-lutein cysts, suggesting that the quoted prevalence ranging from 20 to 60% is an overestimation. The development of theca-lutein cysts is due to stimulation of the ovaries from the increased production of β-hcg in molar pregnancies. As these levels often do not rise until early in the second trimester, 7 thecalutein cysts probably form rarely in early molar pregnancies. The review of images was biased in that we were evaluating a group of histologically proven molar pregnancies. However, our findings suggest that a high index of suspicion will allow for improved first trimester diagnosis of molar pregnancies. Even with knowledge of the diagnosis, two of our early cases of molar pregnancy did not provide any sonographic signs of molar pregnancies. Our results show that it is not always possible to make a diagnosis of early molar pregnancies by ultrasonography, and therefore histologic examination of specimens remains important. REFERENCES 1. Green CL, Angtuaco TL, Shah HR, et al: Gestational trophoblastic disease: A spectrum of radiologic diagnosis. RadioGraphics 16:1371, Szulman AE, Surti U: Linear relationship between gestational age and size of villi. Am J Obstet Gynecol 132:20, Bronson RA, van de Vegte GL: An unusual first-trimester sonographic finding associated with development of hydatidiform mole: The hyperechoic ovoid mass. AJR 160:137, Crade M, Weber PR: Appearance of molar pregnancy 9.5 weeks after conception. J Ultrasound Med 10:473, Jauniaux E: Ultrasound diagnosis and follow-up of gestational trophoblastic disease. Ultrasound Obstet Gynecol 11:367, Callen PW: Ultrasonography in Obstetrics and Gynecology. 3rd Ed. Philadelphia, WB Saunders, 1994, p Wagner BJ, Woodward PJ, Dickey GE: Gestational trophoblastic disease: Radiologic-pathologic correlation. RadioGraphics 16:131, DeBaz BP, Lewis TJ: Imaging of gestational trophoblastic disease. Semin Oncol 22:130, 1995
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