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REVIEW ARTICLE
Prenatal Ultrasound Evaluation and Outcome
of Pregnancy with Fetal Cystic Hygromas and
Lymphangiomas
Yen-Ni Chen
1
, Chih-Ping Chen
1,2,3,4,5,6
*, Chen-Ju Lin
1
,
Shin-Wen Chen
1
1
Department of Obstetrics and Gynecology,
2
Department of Medical Research, Mackay Memorial
Hospital, Taipei, Taiwan,
3
Institute of Clinical and Community Health Nursing,
4
Department of
Obstetrics and Gynecology, School of Medicine, National Yang-Ming University, Taipei, Taiwan,
5
Department of Biotechnology, Asia University, and
6
School of Chinese Medicine, College of Chinese
Medicine, China Medical University, Taichung, Taiwan
Received 17 January 2017; accepted 21 February 2017
Available online ---
KEYWORDS
cystic hygroma,
hydrops fetalis,
lymphangioma,
nuchal translucency
Abstract Cystic hygroma is a type of lymphangioma, which is a vascular anomaly associated
with lymphatic malformations and formed by fluid accumulation mainly located at the cervi-
cofacial and axillary regions. Cystic hygroma is mostly located in the neck (75%), followed
by axilla (20%), retroperitoneum and intra-abdominal organs (2%), limbs and bones (2%), and
mediastinum (1%). It is often associated with chromosome aneuploidies, hydrops fetalis, and
even intrauterine fetal demise. The prognostic factors of the fetal cystic hygroma or lymphan-
gioma are chromosome abnormalities, hydrops fetalis, septations, or thickness of the cystic
hygroma and are associated with other major malformations. Prenatal managements including
ultrasound serial follow-up, magnetic resonance imaging, or even intrauterine injection of
sclerosing agents are suggested. For fetus with the risk of airway obstruction at delivery, ex
utero intrapartum treatment is also indicated. Detailed prenatal counseling is necessary for
better neonatal outcome.
ª2017, Elsevier Taiwan LLC and the Chinese Taipei Society of Ultrasound in Medicine. This is
an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/
by-nc-nd/4.0/).
Conflicts of interest: The authors have no conflicts of interest relevant to this article.
* Correspondence to: Dr Chih-Ping Chen, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan
North Road, Taipei, Taiwan.
E-mail address: cpc_mmh@yahoo.com (C.-P. Chen).
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Please cite this article in press as: Chen Y-N, et al., Prenatal Ultrasound Evaluation and Outcome of Pregnancy with Fetal Cystic Hygromas
and Lymphangiomas, Journal of Medical Ultrasound (2017), http://dx.doi.org/10.1016/j.jmu.2017.02.001
http://dx.doi.org/10.1016/j.jmu.2017.02.001
0929-6441/ª2017, Elsevier Taiwan LLC and the Chinese Taipei Society of Ultrasound in Medicine. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Chinese Taipei Society o
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Ultrasound in Medicine
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Journal of Medical Ultrasound (2017) xx,1e4
Introduction
There are different nomenclatures of cystic hygroma.
Cystic hygroma is a type of lymphangioma, which is also
called nuchal edema or increased nuchal translucency (NT)
during the first trimester. It is a vascular anomaly associ-
ated with lymphatic malformations and formed by fluid
accumulation mainly located at the cervicofacial and axil-
lary regions [1]. It is mainly located in the neck (75%),
followed by axilla (20%), retroperitoneum and intra-
abdominal organs (2%), limbs and bones (2%), and medias-
tinum (1%) [2,3]. The thickness is usually S3 mm. The
incidence of nuchal cystic hygroma is about 1/6000 at birth
and about 1/750 in spontaneous abortion [4].
It is not only associated with lymphatic malformation
but also with chromosome aneuploidies, hydrops fetalis,
and even intrauterine fetal demise (IUFD). The prognosis is
often considered poor. However, cystic hygroma could be
transient in ultrasound findings. It might regress during
pregnancy because of recanalization or the formation of
collaterals [5].
Here, we will review the diagnosis, factors that affect
the prognosis, and the possible management of fetal cystic
hygroma for better perinatal outcome.
Prenatal ultrasound findings
Ultrasound findings of cystic hygroma include thin-walled
and serpiginous or multiseptated intradermal fluid collec-
tions which are often found at cervical regions [6]. Ville
et al [7] defined nuchal cystic hygroma as an area of
sonolucency in the soft tissue of the occipital region, con-
sisted of two symmetrical cavities completed separated by
a midline septum, with or without the internal trabeculae
(multiloculated cysts). NT is the presence of unilocular
collection of nuchal fluid S3mm
3
. The thickness of the
cystic hygroma is measured at its widest part from the
intact skull or skin at the transverse view. Prenatal ultra-
sound of cystic hygroma may show increased nuchal thick-
ness (S3mm), with or without septation at the neck region
or thin-walled, sonolucent, and multilocular structure at
other regions (Figures 1 and 2). Color Doppler may show no
obvious internal flow which can be distinguished from
hemangioma (Figure 3). Besides, the color Doppler ultra-
sound is also effective for the detection of intralesional
hemorrhage. It may show pulsations from the septums to-
ward the cysts [8]. Furthermore, differential diagnosis
should also include encephalocle or cervical teratoma.
Head and spine morphologies should be further evaluated
for suspected neural tubal defects. Polyhydramnios is also
an indicator of neural tube defect but seldom seen in cystic
hygroma.
Cystic hygroma in the anterior triangle of the neck is
often associated with airway compression, which needs
more aggressive intrapartum management. Further image
evaluation using MRI is also recommended prior to birth for
definite tumor size and infiltration pattern.
Common associated ultrasound findings are hydrops
fetalis, cardiac malformations, and skeletal abnormal-
ities. Cardiac malformations are the main anomalies
detected in fetuses with normal karyotype (62.2e72.7%)
[9]. Other major malformations, such as hydrocephalus,
arthrogryposis, agenesis of corpus callosum, pes equi-
novarus, diaphragmatic hernia, amniotic band syndrome,
mesomelia, and bilateral hydronephrosis, were also re-
ported in patients with septated cystic hygroma and
normal karyotype [10].
Figure 1 Neck cystic hygroma with a thickness of 13.9 mm.
Figure 2 Lymphangioma over the abdominal area (arrow).
Figure 3 Color Doppler ultrasounds of cystic hygroma
showed no internal flow.
2 Y.-N. Chen et al.
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Please cite this article in press as: Chen Y-N, et al., Prenatal Ultrasound Evaluation and Outcome of Pregnancy with Fetal Cystic Hygromas
and Lymphangiomas, Journal of Medical Ultrasound (2017), http://dx.doi.org/10.1016/j.jmu.2017.02.001
Outcome
Cystic hygroma is well known with poor outcome because
the fetuses usually have chromosomal abnormalities and
hydrops fetalis or IUFD often occurs during pregnancy. The
unfavorable outcome is 77.8%. However, there are also
patients with cystic hygroma with resolution or survive at
birth without other malformations (16.7e22.2%) [9,11].
There are several factors that can affect and predict the
outcome of cystic hygroma (Table 1).
About 50% of fetal cystic hygromas are found with
chromosomal abnormalities [9,11e13]. The most common
chromosome abnormalities associated with cystic hygroma
are Trisomy 21 and Turner syndrome. Other abnormalities,
such as Trisomy 18, Trisomy 13, and Triploidy, were also
reported. Beside aneuploidies, recent studies showed that
some copy number variants (CNVs) were also associated
with cystic hygroma or increased NT, and it can be detected
by using microarray [14,15]. A meta-analysis showed that
the most common pathologic CNVs are 22q11.2 micro-
deletion syndrome and then 22q11.2 duplication. Others
are 10q26.12q26.3 deletion, 12q21q22 deletion, 1p36
deletion, and Sotos syndrome. Genomic microarray pro-
vides a 5.0% incremental yield of detecting CNVs in fetuses
with increased NT and normal karyotype [14]. Noonan
syndrome is also frequently noted in fetuses with cystic
hygroma. Other genetic disorders, such as Roberts syn-
drome, Cornelia de Lange syndrome, and multiple pteryg-
ium syndrome, are rare; however, they were also reported
in the first-trimester cystic hygroma, and 4p deletion and
unbalanced chromosome 10 were reported at second-
trimester cystic hygroma [9,16] (Table 2).
Although cystic hygroma might be resolved during
pregnancy, whether it would be resolved or not is not
related to the fetal karyotype. However, when it progresses
to hydrops fetalis, the prognosis is not favorable. Several
studies showed that the thickness was also associated with
the prognosis. Tanriverdi et al [12] showed that fetuses
with normal karyotype and nuchal size >6.5 mm had worse
prognosis. Graesslin et al [11] also showed that fetuses with
cystic hygroma <6 mm had good prognosis but not
including those with hydrops fetalis. Scholl et al [17]
showed that the increased thickness of NT is associated
with the increase of the odds of abnormal karyotype, major
congenital anomaly, perinatal loss, and other poor
outcomes.
Rosati and Guariglia [5] reported that 63.2% of non-
septated cystic hygromas and 28.6% of septated cystic
hygromas regressed spontaneously in utero. Compared with
nonseptated cystic hygromas, septated cystic hygromas
have more risk of aneuploidy and worse prognosis, such as
hydrops fetalis [5,16,18]. Turner syndrome was found in
septated hygromas only (30/39), and Trisomy 21 was the
most commonly found abnormal karyotype in nonseptated
hygromas (5/16). Hydrops fetalis was more common in
septated cystic hygromas than in nonseptated cystic
hygromas (60% vs. 19%). Besides, the survival rates were
higher in nonseptated cystic hygromas (27%) than in sep-
tated cystic hygromas (2%).
Nuchal lymphangiomas are likely to be associated with
chromosomal abnormalities. However, when the mass is
located at axilla, the relationship between lymphangioma
and aneuploidies is slightly lower than nuchal lym-
phangioma [8]. It is uncertain that non-nuchal lym-
phangiomas have same risk of chromosome abnormalities
because of the paucity of available data. Lymphangiomas at
the anterior neck have the possibility of airway compres-
sion, which needs airway protection and neonatal resusci-
tative service intrapartum. For those fetuses with
lymphangioma at the trunk region, dystocia and hemor-
rhage secondary to trauma should be alerted and cesarean
section delivery is indicated [19]. Mondal et al [20] reported
a case of congenital fetal lymphangioma causing shoulder
dystocia and uterine rupture without prenatal diagnosis.
IUFD was also noted at laparotomy.
Management
For the management of fetal cystic hygroma or lym-
phangioma, the first common step is cytogenetic study for
suspected aneuploidy, and array comparative genomic hy-
bridization is also recommended for other genetic disor-
ders. Detailed and serial ultrasound examination for follow-
up of the growth of the tumor is necessary. These results
are important for prenatal counseling. For patients with
normal karyotype and favorable prognosis, further consul-
tation with a pediatric surgeon was also needed for post-
natal management. Because huge cystic hygroma may
cause dystocia, neonatal airway compression, or feeding
Table 1 Poor prognostic factors of cystic hygromas and
lymphangiomas.
Chromosome abnormalities
Hydrops fetalis
Thickness of cystic hygroma S6mm
Septated cystic hygromas
Nuchal cystic hygroma
Associated with other major malformations
Table 2 Aneuploidies and genetic disorders associated
with cystic hygromas and lymphangiomas.
Aneuploidies
Trisomy 21
Turner syndrome
Trisomy 18
Trisomy 13
Triploidy
Copy number variants
22q11.2 deletion
22q11.2 duplication
10q26.12q26.3 deletion
1p36 deletion
4p deletion
Others
Roberts syndrome
Cornelia de Lange syndrome
Sotos syndrome
Multiple pterygium
Ultrasound Evaluation of Fetal Lymphangiomas 3
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Please cite this article in press as: Chen Y-N, et al., Prenatal Ultrasound Evaluation and Outcome of Pregnancy with Fetal Cystic Hygromas
and Lymphangiomas, Journal of Medical Ultrasound (2017), http://dx.doi.org/10.1016/j.jmu.2017.02.001
problems. MRI can be used to assess the size and infiltration
of cystic hygroma.
Several studies have suggested that patients with fetal
cystic hygroma and hydrops fetalis without chromosome
abnormalities or other structural abnormalities are candi-
dates for intrauterine sclerotherapy [21e23]. Mikovic et al
[23] reported two patients with fetal neck lymphangiomas
with intrauterine injection of OK-432 at 28 weeks of
gestational age. Aspiration of fluid in cystic hygroma and
injection of same volume of OK-432 were performed.
Increased echogenicity of the cysts was noted after injec-
tion. After the regular follow-up, both the patients were
born without the obvious neck mass and good outcome.
Direct OK-432 injection of the lymphangioma is widely used
in patients with lymphangioma postnatally. However, the
case numbers are sparse in intrauterine injection, and more
case studies are warranted.
After thorough assessment of fetal anatomy, for those
with the risk of airway obstruction at delivery, ex utero
intrapartum treatment is the gold standard strategy. It can
protect the fetuses from neonatal hypoxia and brain injury.
It should be performed under the supervision of a multi-
disciplinary team of obstetricians, anesthesiologists, pedi-
atric surgeons, neonatologists, otolaryngologists, and a
group of operating room nurses and personnel. Therefore,
prenatal counseling is crucial.
Postnatal management includes surgical excision, direct
injection of sclerosing agents, and oral sirolimus. Surgical
excision is one of the treatments, especially for localized
lymphangioma, but local recurrence has been reported after
surgery [24]. Injection of sclerosing agents, such as Bleo-
mycin or OK-432, directly into the mass has been applied for
decreasing the mass size or for total resolution. Oral siroli-
mus was used after birth with decreasing size of axillary
lymphangioma, but the outcome should be followed [25].
Although cystic hygromas or lymphangiomas are common
fetal anomalies during pregnancy and often associated with
poor outcome, in some cases, appropriate counseling and
prenatal evaluation can result in better outcome for the
fetuses.
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4 Y.-N. Chen et al.
+MODEL
Please cite this article in press as: Chen Y-N, et al., Prenatal Ultrasound Evaluation and Outcome of Pregnancy with Fetal Cystic Hygromas
and Lymphangiomas, Journal of Medical Ultrasound (2017), http://dx.doi.org/10.1016/j.jmu.2017.02.001