Beware of the umbilical cord ‘cyst’

In two articles published in this issue1, 2, attention has been drawn to anechoic masses of the umbilical cord as a prominent prenatal feature of fetal aneuploidy, allowing the opportunity to remind those involved in prenatal diagnosis of the association between cord ‘cysts’ and poor pregnancy outcome. Umbilical cord cysts, although rare, represent the second most common anomaly of the umbilical cord3-6. In the 1980s, the time when most fetal anomalies were characterized, reports on umbilical cord cysts were scarce7-11. Nowadays, with modern ultrasound image technology, these fluid-filled masses are increasingly detected prenatally, so their clinical significance can be delineated more accurately3-6. Prenatal diagnosis and management of anechoic lesions of the umbilical cord require basic knowledge of their pathophysiology and natural history. From the pathological point of view, the vast majority represents cysts and pseudocysts, with only a minority corresponding to vascular lesions. True cysts have similar ultrasound appearances to pseudocysts, so prenatal differentiation is difficult. True cysts originate from embryonic remnants, such as the allantois or omphalomesenteric duct, and their characteristic histological feature is the presence of an epithelial lining. Omphalomesenteric cysts are extremely rare, with diagnosis being reported only once prenatally9. Allantoic cysts have been detected prenatally more often12, 13, frequently in association with anomalies of the urinary tract, mainly patent urachus, although they can also coexist with an omphalocele8. They frequently resolve spontaneously in utero. However, cyst resolution does not necessarily imply that the urachus has been obliterated and postnatal review is indicated14. The opposite, namely rapid increase in size, may lead to acute fetal distress by progressive compression of the umbilical vessels15. Umbilical cord pseudocysts are far more common than true cysts. They are due to local degeneration or focal edema of the Wharton's jelly and, therefore, lack such an epithelium. Their prenatal ultrasound appearance, number and size vary widely and they can be located in any portion of the cord but mainly occur close to the fetal insertion16-19. They are strongly associated with chromosomal defects and other congenital anomalies, especially omphalocele and hydrops16-19. The original observation that cord pseudocysts are a prominent feature of trisomy 18 was made by Jauniaux et al.16 almost 15 years ago, a finding that has been confirmed extensively by others17-19. Indeed, among the 13 histologically proven cases of pseudocyst reviewed by Smith et al.18, eight were associated with aneuploidy and two with other anomalies. In our own series of 13 cases of umbilical cord pseudocysts, we noted chromosomal abnormalities in seven, mainly trisomy 18 and trisomy 13, with three additional euploid fetuses having structural defects19. Special consideration should also be given to pseudocysts arising from an angiomyxoma of the cord. In these cases, the pseudocyst is always located close to the tumor and sometimes is the most prominent prenatal ultrasound finding5, 6. Occasionally it can reach massive proportions, leading to fetal hypoproteinemia, dystocia during labor or fetal death as a result of twisting of the pseudocyst around the cord5, 6, 20, 21. The possibility of compression of the adjacent umbilical vessels and fetal hydrops leading to fetal death should also be considered6. From the currently available literature, therefore, it seems that the implications of prenatal identification of umbilical cord cysts in the second and third trimesters are well established. However, the clinical significance when detected in the first trimester remains controversial. Two series involving a total of 18 cases of first-trimester umbilical cord cysts showed that they are more frequently detected between 8 and 9 weeks of gestation with spontaneous resolution and no effect on pregnancy outcome in all cases22, 23. In another report, however, Ross et al.24 reported 29 cases of first-trimester umbilical cord cysts in a high-risk population, with associated fetal structural anomalies and chromosomal defects noted in about 25% of cases. Because the formation of cysts is coincidental with both the onset of umbilical cord coiling and formation of the physiological midgut hernia, it has been hypothesized that these developmental phenomena could increase hydrostatic pressure within the umbilical vessels, favoring exudation of water into the Wharton's jelly and formation of pseudocysts24. The rapid resolution of the cysts may support the view that they probably represent a normal developmental variant rather than a pathological condition. These uncertainties highlight the paucity of available data on the prenatal ultrasound evaluation of the umbilical cord in the first trimester. Hill et al.25 stated that the cord is approximately the same length as the crown–rump length, and found a shorter cord in cases associated with early miscarriage. Ghezzi et al.26 investigated cord thickness in the first trimester and found a close correlation with fetal growth, lean cords being associated with miscarriage and pre-eclampsia. In a subsequent study, they also found an association between increased cord diameter and chromosomal defects, suggesting that this could be an early marker of fetal aneuploidy27. This same group now reports one of the largest series on first-trimester umbilical cord cysts published so far1. They found striking differences in pregnancy outcome between those pregnancies with simple cysts and those with complex cysts, the former being transient with no clinical significance and the latter almost invariably being associated with aneuploidy and early miscarriage. Their findings could explain, at least in part, discrepancies regarding outcomes noted by different authors in previous series22-24. Another lesion presenting as an umbilical cord anechoic mass is focal dilatation of umbilical vein or artery28, 29. Most of these anomalies are overlooked at the time of delivery as they frequently mimic cord hematomas. With color Doppler ultrasound, the differential diagnosis between these vascular conditions and cord fluid-filled lesions is straightforward. However, they also present initially as a ‘cyst’ in the cord; the implications are worth considering here, especially regarding their association with fetal distress and death28, 29. Recently, an association with trisomy 18 has also become evident30. I invite the readers of this Journal to take a look at these papers and, more importantly, to pay closer attention to the umbilical cord when performing obstetric ultrasound.