Placental Surface Cysts Detected on Sonography
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1 Article Placental Surface Cysts Detected on Sonography Histologic and Clinical Correlation Douglas L. Brown, MD, Donald N. DiSalvo, MD, Mary C. Frates, MD, Karen M. Davidson, MD, David R. Genest, MD Objective. To evaluate the clinical outcome and histologic findings of pregnancies in which placental surface cysts were detected on prenatal sonography. Methods. A computerized search of our obstetric sonographic database from 1988 through 2000 identified 34 cases. Results of pathologic examinations, when performed, were obtained. Sonographic features were correlated with histologic findings and clinical parameters. Results. On review of available microscopic slides, in all cases in which the cyst was seen at pathologic examination, there was subchorionic fibrin with central cyst formation. All pregnancies resulted in live births, although intrauterine growth restriction occurred in 4 (12%) of 34. Three (11%) of 28 cases with placental pathologic findings had maternal floor infarction. Only 2 significant associations between sonographic features and postnatal findings were found. In all cases of intrauterine growth restriction, average cyst size was larger than 4.5 cm. Of 12 cysts larger than 4.5 cm, 4 (33%) had intrauterine growth restriction. Of 22 cysts smaller than 4.5 cm, there were no instances of intrauterine growth restriction (P =.01). Of 32 cases with 3 or fewer cysts, only 2 had intrauterine growth restriction, whereas in 2 cases with more than 3 cysts, both had intrauterine growth restriction (P =.01). Conclusions. Most placental surface cysts are associated with a normal pregnancy outcome. Most such cysts are related to cystic change in an area of subchorionic fibrin. Cysts larger than 4.5 cm or more than 3 in number are more frequently associated with intrauterine growth restriction. Key words: intrauterine growth restriction; maternal floor infarction; placental cysts; subchorionic fibrin. Abbreviations IUGR, intrauterine growth restriction; MFI, maternal floor infarction; PCIS, placental cord insertion site Received December 19, 2001, from the Departments of Radiology (D.L.B., D.N.D., M.C.F.), Obstetrics and Gynecology (K.M.D.), and Pathology (D.R.G.), Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts. Revision requested December 27, Revised manuscript accepted for publication January 9, Address correspondence and reprint requests to Douglas L. Brown, MD, Department of Radiology, Brigham and Women s Hospital, 75 Francis St, Boston, MA Cystic masses arising from the fetal surface of the placenta have been referred to by different terms, including subchorionic cysts, chorionic cysts, membranous cysts, and subamniotic hematomas. 1 5 Their etiology remains controversial, 5 and there are contradictory opinions as to their clinical importance. These cysts have been reported to be of no clinical importance. 4 6 Conversely, others have reported an association with intrauterine growth restriction (IUGR) 1,2,4 and have suggested the need for follow-up studies. Most of the reports thus far have been case reports with fewer than 5 cases in each report. The purpose of this study was to evaluate these cystic masses in a larger series of patients. For pregnancies in which cystic masses were seen protruding from the fetal surface of the placenta, we sought to evaluate the sonographic findings, clinical importance, and histologic correlates by the American Institute of Ultrasound in Medicine J Ultrasound Med 21: , /02/$3.50
2 Placental Surface Cysts Detected on Sonography Materials and Methods We performed a retrospective search of the computerized database of all obstetric sonograms obtained at our institution from 1988 through 2000, searching for all cases of cystic placental lesions. The sonographic reports and images, when available, were reviewed to be sure the cyst arose from the fetal surface of the placenta and protruded into the amniotic cavity. If the images were unavailable, the report had to state the cyst location adequately before that case was included. Cases were excluded if the cyst did not arise from the fetal surface of the placenta and protrude into the amniotic cavity. Therefore, this study does not consider cystic areas within the placenta. Vascular spaces on the fetal surface of the placenta were also excluded. Additionally, cases were excluded if delivery was not performed at our institution. From review of the sonographic report and images, we recorded the following information: gestational age when the cyst was first seen, number of cysts, size of the cyst (based on average of 3 dimensions), change in size when multiple sonograms were available, appearance of the cyst, and location of the cyst with respect to the placental cord insertion site (PCIS). When more than 1 study was available, the largest size on any of the sonograms was recorded, and when there were multiple cysts, the size of the largest cyst was recorded. The appearance of the cyst was categorized as simple if it was anechoic or complex if there were any echoes within it. Cyst location was listed as near the placental cord insertion, not near the placental cord insertion, or unknown. There was no strict definition of near or not near, because this determination was generally made from the report of the sonogram. The perinatal and neonatal records were reviewed to determine the outcome. The outcome was categorized as live born without morbidity, live born with morbidity, or death. Morbidity was arbitrarily defined as hospitalization of the neonate for 1 week or more for any reason. Intrauterine growth restriction was defined as birth weight below the 10th percentile. 7 Preterm delivery was defined as delivery before 37 weeks, based on the best estimate of gestational age. If the placenta was examined histologically, those results were obtained. For the cystic mass itself, the type of cyst as stated in the original pathologic report was recorded. Additionally, because there seemed to be some variability in terminology, we retrieved as many of the original microscopic slides as possible and reviewed those. We also recorded any associated placental pathologic findings, particularly trying to assess for extensive fibrin deposition in the placenta and maternal floor infarction (MFI). The sonographic features of cyst appearance, number of cysts, and cyst size were compared with several clinical and histologic parameters: clinical outcome (morbidity or no morbidity), IUGR, preterm delivery, extensive subchorionic fibrin in the placenta, and MFI. Statistical analysis was done with contingency tables using χ 2 analysis or the Fisher exact test as appropriate and the Mann-Whitney U test (StatView; SAS Institute Inc, Cary, NC). P <.05 was considered significant. Results Thirty-four cases in 33 patients constituted the study group. In 1 patient, placental surface cysts occurred in 2 different pregnancies; MFI occurred in both pregnancies. The gestational age when the cyst was first shown on sonography was 27.1 ± 6.7 weeks (mean ± SD; range, weeks). Single cysts (Fig. 1) were present in 22 cases, 2 cysts in 9 cases, 3 cysts in 1 case, 4 cysts in 1 case, and at least 6 cysts in 1 case (Fig. 2). Cyst size ranged from 1.8 to 8.0 cm (mean ± SD, 4.0 ± 1.8 cm). In 26 cases there was at least 1 follow-up sonogram after initial identification of the cyst. In 11 cases there was no change; in 5 cases the cyst enlarged; in 1 case the cyst shrank; and in 2 cases the cyst initially enlarged and then shrank. In 7 of these 26 cases, the size change could not be determined. The cysts were simple (Fig. 1) in 15 cases and complex (Fig. 3) in 13 cases. Two patients with multiple cysts had both simple and complex cysts. In 4 cases the cyst appearance was unknown, because the images could not be found and the cyst appearance was not described in the report for those examinations. The cyst was near the PCIS in 22 cases, and the cyst location was unknown in 12. In a few cases of cysts near the PCIS, it was not clear on the original sonogram whether the cyst actually arose from the placenta or from the adjacent umbilical cord. 642 J Ultrasound Med 21: , 2002
3 Brown et al All pregnancies resulted in live births. There was no neonatal morbidity in 24 (71%) of the 34 cases; in 10 cases (29%) there was neonatal morbidity. Of the 10 cases of morbidity, 9 were related to respiratory or feeding difficulties, or both, whereas 1 neonate had tetralogy of Fallot, which had been diagnosed prenatally. Preterm delivery occurred in 14 cases (41%). Of the 14 preterm deliveries, 7 had unstoppable preterm labor, 6 were for IUGR, nonreassuring fetal test results, or both, and 1 was for severe preeclampsia. Intrauterine growth restriction, based on birth weights, occurred in 4 cases (12%). The mean birth weight in the 12 full-term fetuses was 3104 ± 554 g. Macrosomia (birth weight >90th percentile) occurred in 2 cases (6%). In 2 of the 4 cases with IUGR, the estimated fetal weight at the time of the sonography when the cyst(s) was first seen was below the 10th percentile and suggested IUGR. The initial sonographic examinations in these 2 cases occurred at 24 and 34 weeks. In both of these cases, sonography was done because of size less than dates. In the other 2 cases with IUGR, the fetal measurements and estimated fetal weight were appropriate initially (at 18 and 24 weeks), and IUGR was not suggested until follow-up sonography later in the pregnancy. In both of these latter 2 cases, IUGR had occurred in a prior pregnancy. Pathologic examination of the placenta (Fig. 4) was performed in 28 cases. Results of the initial pathologic findings were a chorionic cyst in 7 cases, an amniotic cyst in 6, and a hematoma in 4. One cyst was reported as a fibrin-lined pseudocyst, and 1 was reported as focal separation of the amnion and chorion. In 4 cases the type of cyst was not reported, and in 5 cases the cyst was not seen at pathologic examination. We speculate that the cyst may have ruptured in these latter 5 cases. The original histologic slides were available in 15 cases. Review of those slides showed that in 14 cases the cyst appeared to be due to subchorionic fibrin with central cyst formation (Fig. 5). In these 14, the cyst was never subamniotic, although the chorion was stretched and thinned. Extravillous trophoblasts (i.e., X cells) were always present within the fibrin layer, which surrounded a central cyst. In 1 case, the cyst could not be identified on the available microscopic slides. Of the 28 cases with placental histologic findings available, extensive subchorionic fibrin deposition had been reported in 14 cases (50%). Maternal floor infarction occurred in 3 (11%) of these 28 cases. In the 6 cases without placental histologic findings available, MFI seemed unlikely, because all 6 had normal outcomes with no instances of IUGR or preterm delivery. Therefore, the frequency of MFI in the study population was likely 3 (9%) of 34. Statistical comparison of the sonographic features (cyst size, cyst appearance, and number of cysts) versus clinical outcome (morbidity or no morbidity), IUGR, preterm delivery, extensive subchorionic fibrin, and MFI revealed only 2 sig- Figure 1. Sonogram showing a single simple cyst. A single anechoic cyst (c) is shown along the fetal surface of the placenta. It is adjacent to the PCIS (arrow). The echoes in the amniotic fluid in the near field are artifacts. Figure 2. Sonogram showing multiple cysts. Numerous cysts extend away from the fetal surface of the placenta (arrow). J Ultrasound Med 21: ,
4 Placental Surface Cysts Detected on Sonography Figure 3. Sonogram showing a complex cyst. This cyst (indicated by cursors) on the fetal surface of the placenta contains a focal area of internal echoes (arrow). Figure 4. Gross photograph of the placenta showing a single cyst. The large cyst (C) protrudes from the placental surface. It can be difficult to determine in some cases if the cyst arises from the placenta or the umbilical cord, but this was shown to arise from the placenta. nificant associations. The number of cysts and cyst size (when considered as a categoric variable) were each significant in relation to IUGR. In all cases of IUGR, the average cyst size was larger than 4.5 cm. Of 12 cysts larger than 4.5 cm, 4 (33%) had IUGR, and 8 (67%) did not have IUGR; of 22 cysts smaller than 4.5 cm, there were no instances of IUGR (P =.01). Regarding the number of cysts, of 32 cases with 3 or fewer cysts, only 2 had IUGR, whereas of 2 cases with more than 3 cysts, both had IUGR (P =.01). Discussion Evaluating the prior experience with cystic masses arising from the fetal surface of the placenta is difficult because of the variable terminology that has been used. The type of lesion we report here seems to be the same as what has been described as a membranous cyst, 2 subchorionic cyst, 4,5 chorionic cyst, 3 and subamniotic hematoma. 1 However, the term subamniotic hematoma also appears to have been used to describe a different lesion. 8 It is uncertain whether cases of massive Figure 5. Photomicrographs of the fetal placental surface showing a large, thin-walled subchorionic cyst. A, Low-power magnification of the fetal surface of the placenta showing a large subchorionic cyst (arrow) adjacent to a fetal vessel (arrowhead). B, High-power magnification of the cyst wall showing amnion (A), chorion (C), and fibrin (F) infiltrated by intermediate trophoblasts (white arrows). A B 644 J Ultrasound Med 21: , 2002
5 Brown et al subchorionic thrombohematomas 9,10 might be part of the spectrum of the same lesion we describe here. Our study is limited to cystic masses protruding from the fetal surface of the placenta into the amniotic cavity. Variable clinical importance has been ascribed to the lesions we describe. Some authors consider them to be of no clinical importance, whereas others warn of associated IUGR and the need for clinical and sonographic follow-up. Our results encompass the variable clinical importance reported in these prior studies, which included smaller numbers of cases. In most of our cases, pregnancy outcome was normal. Intrauterine growth restriction occurred in approximately 10% of cases, and MFI also occurred in approximately 10% of cases. Only cyst size and number were significantly associated with IUGR. In all cases of IUGR the cyst was larger than 4.5 cm in mean diameter at some point in the pregnancy. Although cysts larger than 4.5 cm were more frequently associated with IUGR, most (67%) cysts larger than 4.5 cm were not associated with IUGR. Regarding the number of cysts, IUGR was present whenever there were more than 3 cysts; however, this only occurred in 2 cases. Half of the cases of IUGR had 3 or fewer cysts. Thus, our data suggest that cyst size and number may be useful to predict IUGR; however, one cannot rely fully on either parameter to predict IUGR. Admittedly, however, in our 4 cases of IUGR, the IUGR may have been detected regardless of the cysts, because in 2 cases sonography was done for size less than dates, and in 2 cases there had been IUGR in prior pregnancies (which may have prompted further sonography). Also, in 2 of our 4 cases of IUGR, the IUGR was evident at the time the cyst was first seen. The location of these cysts close to the PCIS has been noted previously. 1,3,10 The retrospective nature of our study did not allow us to determine cyst location in all our cases, but in most cases the cyst did appear to be close to the PCIS. The reason for this is unclear. Perhaps it could be related to fetal traction on this fixed portion of the cord, weakening the adjacent chorionic surface of the placenta. It has been suggested that large subchorionic cysts near the PCIS should be followed for possible IUGR. 4 On the basis of our data, although admittedly incomplete, location near the PCIS is probably not a factor predictive for IUGR, because this location seems typical of most such cysts. Maternal floor infarction is an uncommon disorder and is somewhat of a misnomer, because the lesion is not really an infarction but consists of massive fibrinoid deposition in the maternal floor or basal plate of the placenta With MFI, there is an increased frequency of fetal growth restriction and fetal death MFI may recur in subsequent pregnancies. Cysts such as those described here have been associated with MFI or massive perivillous fibrin deposition. 1,13 It has been suggested that X cells (i.e., trophoblasts outside the villi) may be associated with formation of these cysts. 4,11,13,14 These X cells occur with increased frequency in MFI, and the X cells have been found in the walls of these cysts. It has also been suggested that subchorionic intervillous thrombi may undergo cystic degeneration, leading to cysts on the surface of the placenta. 14 Eddy currents in the intervillous space in this location have been postulated to lead to increased fibrin deposition. 14 Indeed, half of our cases in which placental pathologic findings were obtained had extensive subchorionic fibrin in the placenta. The importance of this fibrin is uncertain, however, because the determination was made subjectively, and the amount of fibrin considered normal in a placenta is variable and difficult to quantify. On the basis of our results and the proposals of others, 13,14 we suspect that these cysts form in an area of subchorionic fibrin deposition. Perhaps related to X cells in or at the edge of the fibrin, cystic change occurs in the area of the fibrin. The chorion becomes thinned by the cyst and balloons outward along with the amnion. There are several limitations of our study, including its retrospective nature, which limits evaluation of the sonographic features. The number of cases was still relatively small, limiting statistical analysis. Also, we used the 10th percentile to define IUGR; others have suggested using a lower percentile. Variable terminology, variable assessment of the amount of fibrin in the placenta, and lack of a strict definition of MFI all limit the histologic portion of our study. 15 In summary, most placental surface cysts are single and occur near the PCIS. They can be simple or complex. In most cases, the pregnancy outcome is normal. We think that these cysts are related to cyst formation in subchorionic fibrin deposits. Intrauterine growth restriction or MFI occurs in about 10% of cases. Cysts that are larger than 4.5 cm or that are more than 3 in number seem to have a higher frequency of IUGR. J Ultrasound Med 21: ,
6 Placental Surface Cysts Detected on Sonography References 1. Deans A, Jauniaux E. Prenatal diagnosis and outcome of subamniotic hematomas. Ultrasound Obstet Gynecol 1998; 11: Kirkinen P, Jouppila P. Intrauterine membranous cyst: a report of antenatal diagnosis and obstetric aspects in 2 cases. Obstet Gynecol 1986; 67:26S 30S. 3. Gray SE, Lettieri L, Salafia CM, Vintzileos AM. Placenta, chorionic cyst, recurrent. Fetus 1993; 3: Raga F, Ballester M, Osborne N, Bonilla-Musoles F. Subchorionic placental cyst: a cause of fetal growth retardation: ultrasound and color-flow Doppler diagnosis and follow-up. J Natl Med Assoc 1996; 88: Vernof KK, Benirschke K, Kephart GM, Wasmoen TL, Gleich GJ. Maternal floor infarction: relationship to X cells, major basic protein, and adverse perinatal outcome. Am J Obstet Gynecol 1992; 167: Benirschke K, Kaufmann P. Nonvillous parts of the placenta. In: Pathology of the Human Placenta. 2nd ed. New York, NY: Springer-Verlag; 1990: Katzman P, Genest DR. Maternal floor infarction and massive perivillous fibrin deposition: histological definitions, association with intrauterine fetal growth restriction, and risk of recurrence. Pediatr Dev Pathol 2002; 5: Ferrara N, Menditto C, DiMarino M, Ciccarelli A, Gerosolima G, Menditto V. Subchorionic placental cyst: histopathological and clinical aspects in 2 cases. Pathologica 1996; 88: Harris R, Alexander R. Ultrasound of the placenta and umbilical cord. In: Callen P (ed). Ultrasonography in Obstetrics and Gynecology. 4th ed. Philadelphia, PA: WB Saunders Co; 2000: Lubchenco LO, Hansman C, Dressler M, Boyd E. Intrauterine growth as estimated from liveborn birth-weight data at 24 to 42 weeks gestation. Pediatrics 1963; 32: Van den Bosch T, Van Schoubroeck D, Cornelis A, Dubin M. Prenatal diagnosis of a subamniotic hematoma. Fetal Diagn Ther 2000; 15: Richards DS, Bennett BB. Prenatal ultrasound diagnosis of massive subchorionic thrombohematoma. Ultrasound Obstet Gynecol 1998; 11: Tam W, Fung H, Fung T, Lau T, To K. Intra-uterine growth retardation and transverse lie due to massive subchorionic thrombohematoma and overlying large subchorionic cyst. Acta Obstet Gynecol Scand 1997; 76: Benirschke K, Kaufmann P. Pathology of maternal floor infarction. In: Pathology of the Human Placenta. 2nd ed. New York, NY: Springer-Verlag; 1990: Andres RL, Kuyper W, Resnik R, Piacquadio KM, Benirschke K. The association of maternal floor infarction of the placenta with adverse perinatal outcome. Am J Obstet Gynecol 1990; 163: J Ultrasound Med 21: , 2002
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