Between 1% and 3% of all mid-trimester sonograms reveal a choroid plexus cyst (CPC).1 Because they have been linked with aneuploidy, and because they are located in the brain, these cysts usually make expecting
parents quite anxious. In this review, we will discuss when these abnormalities are cause for concern and when they can be
ignored. In the process, we'll describe the embryology of the choroid plexus, the diagnosis of CPC, and when invasive testing
is warranted.
Figure 1. Normal choroid plexus at midgestation.
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Visualizing the choroid plexus The choroid plexus is a highly vascular structure derived from the pia mater lining of the brain. It occupies the bulk of
the lateral ventricles, except for the frontal horns.2 Its primary function is to synthesize cerebrospinal fluid.3 It can be identified on an ultrasound as early as 6 weeks of gestation when it appears as a highly echogenic structure (Figure
1). The choroid plexus remains prominent throughout early fetal life and may be visualized with either transvaginal or transabdominal
sonography. It's best observed by first obtaining the standard biparietal diameter (BPD) image, and then rotating the transducer
rostrally in the same axial plane. This will bring the lateral ventricles into view. The oval-shaped, intensely echogenic
area within the lateral ventricles is the choroid plexus. Similarly, in the parasagittal and coronal views, you can see the
choroid plexus as you scan through the ventricular spaces. The choroid plexus appears to touch the lateral walls of the lateral
ventricle. In pregnancies complicated by ventriculomegaly, however, the choroids will appear to be dangling in the fluid-filled
ventricle.
Figure 2. Right-sided choroid plexus cyst seen on routine sonogram. The cyst is outlined by the calipers within the choroid
plexus..
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How dangerous are choroid plexus cysts? Cysts in the choroid plexus may be found during routine sonography of the fetal brain as early as 14 weeks of gestation.
These cysts are usually less than 1 cm in diameter and may be unilateral or bilateral. They appear as echolucent structures
within the body of the choroid plexus (Figure 2). They represent epithelial aberrations that become filled with cerebrospinal
fluid and cellular debris.4 The appearance of these cysts is related to the stage of development of the neuroepithelium.5 Rapid growth of the neuroepithelial cells overlying the immature loose mesenchymal cells, combined with increased glycogen
deposition, leads to the formation of fluid-filled spaces.
Under normal circumstances, as these cysts mature and brain tissue undergoes organizational changes, they resolve within 24
weeks of gestation. But a small number of cysts persist into the early neonatal period.
Between 1% and 3% of chromosomally normal fetuses will have an isolated CPC in the mid-trimester.1,6,8,12,13 They rarely have any effect on cerebral function. To date, there have been no reports of developmental or neurological deficiencies
in chromosomally normal infants with isolated CPC.7
The differential diagnosis of CPC includes arachnoid cysts, hydrocephalus, and neoplasms. Initial hemorrhagic cysts and neoplasms
are typically more echogenic and may vary more widely in size. CPCs are typically regular, small echolucent areas that do
not distort the brain parenchyma. On rare occasions the cysts may be large enough to mimic hydrocephalus. During hydrocephalus,
a generalized enlargement of the lateral ventricles, the ventricles become filled with fluid, and often the choroid plexus
will appear to be dangling within this fluid. So in hydrocephalus, the choroid plexus should be visible and distinct from
the lateral wall of the ventricle. A CPC should appear as a fluid-filled cavity within the body of the choroid plexus and
will have a distinct cyst wall. As we mentioned earlier, cysts should gradually resolve as brain tissue matures and the accumulated
fluid is reabsorbed.
Prior to 1985, the finding of a CPC was generally believed to be a normal variant. However, over the last 18 years, several
studies have found a link between trisomy 18 (Edwards syndrome) and these cysts. Therefore, more significance is now being
placed upon this sonographic finding. There has been much debate over the meaning of these cysts, and whether invasive prenatal
testing is warranted. A number of studies have attempted to determine if certain characteristics of the cysts—such as number,
size, bilaterality, and location—increase the risk of aneuploidy. Most researchers believe that none of these characteristics
confers a substantially increased risk.8,9
Table: 1 Midtrimester sonographic findings seen in trisomy 18
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Although trisomy 18 is the chromosomal anomaly most commonly associated with CPC, there are a few case reports of trisomy
21. However, in a comprehensive review, Gupta and associates, showed that the risk of trisomy 21 in a fetus with isolated
CPC is not increased above that of the general population.7 The association between trisomy 18 and CPC remains much more controversial. After Down syndrome, trisomy 18 is the most common
autosomal trisomy. Even so, its rarity in the population requires that large cohorts be studied to draw meaningful conclusions
about the association between Edwards syndrome and sonographic findings. Like Down syndrome, trisomy 18 is usually related
to meiotic nondysjunction; however up to 15% of cases are due to translocation and mosaicism.10 The greatest risk factor for trisomy 18 is advanced maternal age. There are numerous malformations associated with trisomy
18 that may be detected by routine sonography (Table 1). As many as 30% of fetuses affected by trisomy 18 will have CPC.11,12 But 50% to 80% of trisomy 18 fetuses will have major structural abnormalities identified on a targeted sonogram.1,11,12 The major clinical question is how to assign the risk of aneuploidy in fetuses with isolated CPC. Risk calculations have
been difficult to standardize because trisomy 18 is so rare. In a low-risk population, the incidence is 1/8,000, and increases
with advancing maternal age.2 Ghidini and colleagues pooled data over an 11-year period in a low-risk population in which they found 199 cases of isolated
CPC.14 They compared the incidence of trisomy 18 and CPC in an Italian population to data in the English language literature to
arrive at likelihood ratios for trisomy 18 in fetuses with isolated CPC, concluding that there was a sevenfold increase above
the age-related risk of trisomy 18 in fetuses with isolated CPC. Other investigators have used similar methods to derive likelihood
ratios. One team arrived at a relative risk of 8.6 at mid-gestation (Table 2).21 This patient population was a mixture of high- and low-risk patients including women of all ages and patients referred for
suspected anomalies.15,16
Gratton and colleagues have proposed a modification of the age-related risk of trisomy 18 based upon both the sonographic
finding of CPC and maternal serum analyte screening.9 In their analysis, they used a trisomy 18 analyte detection rate of 60% and then modified the risks based upon normal or
abnormal maternal serum markers. In pregnancies complicated by isolated CPC where the serum screening predicts less than a
1 in 270 chance of trisomy 18, clinicians do not need to offer amniocentesis. According to their data, the risk of trisomy
18 approaches the loss rate from amniocentesis only in women older than 37.
Several other studies question the link between CPC and trisomy 18. Reinsch surveyed 16,059 obstetric patients over a 3-year
period. He found CPC in 1.9% of a mixed population and no cases of trisomy 18 in fetuses with isolated CPC.6 The two fetuses affected by trisomy 18 had additional anomalies. He concluded that an amniocentesis need not be offered to patients with CPC unless there are additional major structural abnormalities.
Another literature review of eight prospective trials that included perinatal and neonatal outcomes concluded that there was
no increase in the risk of trisomy 18 among fetuses with isolated CPC in a low-risk population.17
Finally, a research team designed a cost/benefit and cost-effectiveness strategy to determine the economic impact of screening
versus invasive testing in routine prenatal care. From an economic standpoint, they concluded that neither isolated CPC nor
abnormal analyte screen results were justification for invasive testing.16 Therefore, most experts only advocate invasive testing when the fetus has additional anomalies and/or the mother is over
35 years of age.
Conclusions CPCs are a relatively common sonographic finding, occurring in 1% to 3% of fetuses in a low-risk population. The significance
of these cysts remains controversial. Several studies have shown that isolated cysts don't justify invasive prenatal testing
in such low-risk patients. However, there are few data integrating the sonographic findings with maternal serum analyte screening
to provide a truly individualized risk assessment of trisomy 18 for each patient. Currently, there is little consensus as
to the recommendations in these settings.
Our practice is to do a risk assessment based upon maternal age, sonographic findings, and serum analyte results and to apply
the likelihood ratio concept.9
With this approach, the a priori risk is adjusted based upon the sonographic findings. Given the presence of an isolated CPC,
we multiply the trisomy 18 risk ratio derived from maternal age and serum screening result by a factor of eight. For example,
if the patient's a priori risk is 1/8,000 and we find an isolated CPC at 17 weeks, her revised risk for fetal trisomy 18 would
be 1/1,000. At that point, we provide in-depth patient counseling, using data derived from the literature. The patient is
made aware of the implications of isolated CPC as well as her assigned risk of aneuploidy. This is predicated on the performance
of a detailed survey of the fetal anatomy and the absence of any other markers suggestive of trisomy 18. When CPC cysts are
noted on routine antenatal sonography, we pay particular attention to the cardiac outflow tracts, hands, and feet.
There has been some debate as to whether or not clinicians should even tell patients about the presence of an isolated CPC.
A recent editorial proposed that patients should not be made aware of the CPC.18 The authors suggest that if a woman is at "low risk" for aneuploidy because she is younger than 35, or preferably because
of her biochemical screening results, and there are no other sonographic anomalies, the finding of CPCs should be considered
a normal variant and there is no reason to discuss the risk of aneuploidy. This recommendation hinges upon the classification
of patients as "low risk" by their age and/or biochemical screening results, and the completion of a detailed sonogram to
exclude other markers of aneuploidy.
A separate editorial, offered in response to the previous opinion, suggests that we classify CPCs as sonographic findings
rather than simply normal variants.19 The authors believe that sonographic findings that have been correlated with aneuploidy cannot be considered normal variants
without karyotype confirmation. They propose that a "low-risk" patient with a CPC on routine sonogram may be at higher risk
when her a priori risk and sonographic findings are factored into her overall aneuploidy risk assessment regardless of normal
biochemical screening results. Additionally, according to the authors, we should not assume that all pregnant patients accept
the same risk threshold for invasive testing, or that these women will be unduly worried to the point where withholding medical
information becomes an acceptable alternative to involving the patient in her medical care and decision-making.
Our approach is to fully involve the patient in her care, based upon the ethical principle of autonomy. In our view, the patient
has the right to be informed of findings that have clinical relevance. Although a discussion of the findings may be distressing
to an expecting parent, we feel obligated to disclose these findings and are fully prepared to counsel the patient regarding
the implications and management. We do not routinely recommend amniocentesis to low-risk patients in the setting of isolated
CPC. But patient autonomy ultimately guides further testing, and amniocentesis is performed upon patient request once the
risks, benefits, and alternatives of the procedure have been discussed.
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