Cystic Hygroma in the Fetus and Newborn

Patrick G. Gallagher, Maurice J. Mahoney, and John R. Gosche

Cystic hygromas are developmental abnormalities of the lymphoid system that occur at sites of
lymphatic-venous connection, most commonly in the posterior neck. They are frequently associated
with karyotypic abnormalities, various malformation syndromes, and several teratogenic agents. The
disease course of an infant with cystic hygroma is unpredictable. When diagnosed prenatally, the
overall prognosis is poor. Cystic hygroma diagnosed after birth is usually associated with a good
prognosis. This article reviews the embryologic, genetic, and pathologic correlates of these lymphatic
system abnormalities, as well as the clinical course and outcome of the fetus and newborn with a cystic
hygroma. Management strategies are reviewed, including newer nonsurgical therapies for the neonate
with a cystic hygroma.
Copyright 9 1999 by W.B. Saunders Company

Ystic hygromas are congenital malforma- Embryology

C tions of the lymphatic system, a complex
network of thin-walled vessels that carry tissue
fluid to the venous system. They are character-
ized by single or multiple fluid-filled lesions that
occur at sites of lymphatic-venous connection,
most commonly in the posterior neck. Typically,
cystic hygromas develop late in the first trimester
to early in the second trimester, becoming less
common as pregnancy progresses. Fluid accu-
mulation in dilated lymphatics and surrounding
connective tissue leads to progressive lymph-
edema and nonimmune hydrops often occurs.l.2
Overall, the long-term prognosis for a fetus with
a cystic hygroma is poor.
Once considered diagnostic of Turner syn-
drome, s cystic hygromas are now known to be
associated with other karyotypic abnormalities
and several malformation syndromes. ~,2 The
true incidence of cystic hygroma is unknown
(Table 1). 4-~1 In miscarried fetuses greater than
3 cm in crown-rump length, the incidence of
cystic hygroma is 1 in 200. 8 Rates as high as 1 in
100 unselected pregnancies have been report-
ed. 5 An increase in the detection of cystic hy-
groma in the past 25 years4,8,1~ has been attrib-
uted to the increased use of prenatal ultrasound,
improved sonographic equipment, and more ex-
perienced sonographers. ~
This report reviews the embryologic, genetic,
and pathologic correlates of these lymphatic sys-
tem abnormalities, as well as the clinical course
and outcome of the fetus and newborn with a
cystic hygroma. Management strategies are re-
viewed, including newer nonsurgical therapies
for the neonate with a cystic hygroma.
The lymphatic system develops at the end of the
fifth week as endothelial outgrowths from the
venous system. Six lymphatic sacs, two jugular
sacs draining the head, neck, and arms, two iliac
sacs draining the legs and lower trunk, and two
sacs draining the gut, which are called the ret-
roperitoneal sac and the cisterna chyli, develop
in close proximity to large veins. The lymphatic
vessels develop from these lymphatic sacs in a
process of centrifugal extension and branching.
To complete formation of the lymphatic system,
the major lymphatic vessels, the right and left
thoracic ducts, connect with the venous system
at the junction of the internal jugular and sub-
clavian veins near the end of the sixth week.
Developmental anomalies of the lymphatic ves-
sels are due to either a defect in the connection
of the lymphatics with the venous system or ab-
normal development of lymphatic vessels/,2,1a
Failure of the jugular sacs to connect to and
drain into the jugular veins leads to lymphatic
fluid stasis and a series of events termed the
jugular lymphatic obstruction sequence (Fig
1). 14.15 The jugular lymphatic sacs enlarge and
fluid accumulates in lymphatic vessels and sur-
From the Departments of Pediatrics, Genetics, Obstetrics and Gyne-
cology, and Su~tery, Yale University School of Medicine, New
Haven, CT.
Address ~Orint requests to Patrick G. Gallagher, MD, Department of
Pediatrics, Yale University School of Medicine, 333 Cedar Street,PO
Box 208064, New Haven, CT 06520-8064; e-mail: patrick.
gallagher@yale,edu
Copyright 9 1999 by W.B. Saunders Company
0146-0005/99/2304-0009510. 00/0

Seminars in Perinatology, Vol 23, No 4 (August), 1999: pp 341-356 341

342 Gallagher, Mahoney, and Gosche
Table 1. Incidence of Fetal Posterior Nuchal Cystic Hygroma
Group
Unselected pregnancies, 10-15.9 weeks
Unselected pregnancies, 9-15 weeks
Liveborn, stillborn, terminations at one hospital
Fetuses scanned with anomalies
Miscarriages
Miscarried fetuses >3 cm in crown-rump length
Prenatal diagnosis unit
Scanned for suspected anomalies
Fetal/neonatal autopsies
r o u n d i n g connective tissue leading to the devel-
o p m e n t o f cystic hygromas o f the posterior neck,
excess nuchal skin, alterations in hair growth
and patterning, and protrusion of the lower ear.
Peripheral l y m p h e d e m a fills the subcutaneous
tissues leading to relative overgrowth of the over-
lying skin, p r o m i n e n c e o f the pads of the fin-
gers, and narrow, hyperconvex nails. T h e lack of
lymphatic drainage leads to an increased volume
of flow in the venous system, resulting in large
veins. T h e r e is a high incidence o f flow-related
cardiac defects t h o u g h t to be related to disten-
tion o f the lymphatics at the level o f the ascend-
ing aorta. 14,16,17
If connection between the jugular lymphatic
and the venous system is not established, the
lymphatics continue to dilate and effusions of
the thoracic, pericardial, and abdominal cavities
result. If this c o n n e c t i o n is established or an
alternate route o f lymphatic flow is established,
the distended lymphatic sac collapses and the
hygromas resolve, leaving a wide, thickened
neck and p r o m i n e n t nuchal skin folds. Subse-
q u e n t drainage o f the subcutaneous tissues re-
sults in r e d u n d a n t skin, which is particularly
p r o m i n e n t in the face. Frequently, the hands
and feet have not completely drained and are
still edematous at the time o f birth. T h e descrip-
tion o f a fetus with a left-sided cystic hygroma
and e d e m a o f the entire body except the
right arm, suggesting that the left jugular sac
and thoracic duct, but not the right were ob-
structed 18 supports the jugular lymphatic ob-
struction theory.
Abnormalities o f the connection of the iliac
lymphatic sacs and the venous system are analo-
gous to abnormalities of the jugular systems. T h e
iliac lymphatic sacs enlarge and lymph fluid ac-
cumulates in the lower extremities and genital
Incidence Reference No.
1:132 4
1:100 5
1:332 6
1:18 7
1:875 8
1:200 8
1:667 9
1:106 10
1:43 11
region. If there is marked enlargement of the
iliac sacs, the a b d o m e n becomes distended. The
establishment o f lymphatic-venous connection
and subsequent decompression of the iliac sac
leads to r e d u n d a n t abdominal skin, making this
series of events o n e cause o f the so-called prune
belly syndrome.
Anomalous d e v e l o p m e n t of the lymphatic sys-
tem results from either abnormal embryonic se-
questration of lymphatic tissue or from abnor-
mal budding of lymphatic e n d o t h e l i u m between
6 to 9 weeks' gestation. T h e result is decreased,
defective, or absent lymphatic vessels. The estab-
lishment of alternate routes o f lymphatic drain-
age, like c o n n e c t i o n of the lymphatic and ve-
nous systems, may lead to the resolution of cystic
hygromas and lymphedema. In T u r n e r syn-
drome, the peripheral lymphatic vessels have
b e e n shown to be absent or hypoplastic, 19-2~sug-
gesting that in these patients, alternate lymph
drainage into the venous system is established
while the lymph is still in the extremities.
Genetics
Cystic hygroma is frequently a c o m p o n e n t of
other malformation syndromes and is com-
monly associated with o t h e r coexisting anoma-
lies. T h e most c o m m o n abnormality associated
with cystic hygroma is T u r n e r syndrome, which
is f o u n d in approximately 50% to 70% o f cases.
T u r n e r syndrome occurs in 1 o f 5,000 to 10,000
births and is usually due to a 45,X karyotype
resulting from chromosomal nondysjunction.
Many fetuses with cystic hygromas and T u r n e r
syndrome have coexisting abnormalities of car-
diac development including aortic valve defects,
hypoplasia of the third part o f the aortic arch,
anomalous origin o f the branches of the aortic
 CysticHygroma 343

B
Figure 1. Jugular lym-
phatic-venous connection LAG IN JUGULAR LYMPHSAC
DRAINAGE INTO JUGULAR VEIN
and the jugular lymphatic
obstruction sequence. (A)
Left. The lymphatic system 1
ACCUMULATION OF LYMPHFLUID
in a normal fetus with a WITHIN LYMPHATICSYSTEM
patent connection between
the jugular lymphatic sac
and the internal jugular
vein. Right. A fetus with
OISTENDED JUGULAR LYMPH
I
DISTENDED TRIBUTARY LYMPHATICS

failed lymphatic-venous con-

nection with a cystic hy-
/ I ",,, 1
PERIPHERAL LYMPHEDEMA
groma and hydrops fetalis. oovednfl J r iludde hairline

L
u ~ hair
(Reprinted with permis- directional
sion. l Copyright 9 1983 Patter.
Massachusetts Medical So-
Redundant Puffy hands
ciety. All rights reserved.) htclal sldn and feet
(B) The presumed genesis
of the jugular lymphatic ob- Dee >set Predomlrmrce
struction sequence. (Re- nanow of digital
printed with permission, it ) nails whorls

arch, and septal defectsA 7.21-2s Thus, the classic
fetal p h e n o t y p e for 45,X includes large cystic
hygromas o f the posterior neck and trunk, gen-
eralized subcutaneous lymphedema, particularly
on the dorsa o f the hands and feet, and aortic
preductal coarctation s,16a4.94 (Fig 2). However,
this p h e n o t y p e is not f o u n d in the majority o f
T u r n e r syndrome fetuses and it has b e e n associ-
ated with karyotypic abnormalities o t h e r than
45,X. la
In utero fetal demise is c o m m o n in 45,X fe-
ruses. 9 Over 95% o f nonmosaic 45,X fetuses are
spontaneously aborted. However, o f liveborn ne-
onates with T u r n e r syndrome, approximately
40% are mosaic or have variant chromosomal
patterns; only 7% o f these fetuses are spontane-
ously aborted, suggesting that survivors with less
severe features of T u r n e r syndrome have lesser
degrees o f chromosomal abnormalities, includ-
ing mosaicism and structural X c h r o m o s o m e
abnormalities, is
O t h e r chromosomal abnormalities have also
344 GaUagher, Mahoney, and Gosche

Figure 2. Turner syndrome. (A) A fetus with Turner

syndrome showing huge, bilateral cystic hygromas
and marked, diffuse lymphedema. In the same fetus,
there is marked edema of the dorsa of the (B) hands
and (C) feet. (Reprinted with permission? z)

b e e n associated with cystic hygroma including tal ultrasound was cystic hygroma and increased
autosomal trisomies, particularly trisomy 21 (Ta- nuchal thickness, 25 O t h e r karyotypic a b n o r m a l
ble 2). In a series of 187 fetuses with Down ities associated with cystic hygroma include
syndrome, the most c o m m o n finding on prena- Klinefelter syndrome, partial trisomies, par-
 Cystic Hygro~ 345

Table 2. Chromosomal Constitution of 900 Karyot~ed Fetuses with Cystic Hygroma

All Fetuses (%) First Trimester ( % ) Second Trimester ( % )
45,X 282 (31.3) 41 (12.1) 241 (42.7)
Trisomy 21 136 (15) 72 (21.4) 64 (11.3)
Trismoy 18 66 (7.3) 46 (13.7) 20 (3.5)
Trisomy 13 23 (2.5) 10 (3) 13 (2.3)
Other abnormal karyotype 35 (3.9) 16 (4.8) 19 (3.4)
Normal 358 (40) 151 (45) 207 (36.8)
Total 900 (100) 336 (100) 564 (100)
Reprinted with permission,as

tial monosomies, translocations, and mosa-
icism. 1,4,26-al When fetuses with a cystic hygroma
are classified by gestational age, autosomal tri-
somies are most commonly observed in the first
trimester, whereas Turner syndrome is the most
common abnormality detected in the second
trimester (Table 2).
Cystic hygromas have been associated with a
number of inherited disorders and malforma-
tion syndromes associated with a normal karyo-
type (Table 8). These include Noonan syn-
drome, Roberts syndrome, and the multiple
pterygium syndromes. Cystic hygromas have also
been associated with teratogen exposure includ-
ing alcohol, aminopterin, and trimethadioneA
There are reports of fetal nuchal cystic hy-
groma with a normal karyotype occurring in
Table 3. Genetic and Malformation Syndromes with
Cystic Hygroma a Reported Component
Noonan syndrome
Roberts syndrome
Brachmann-de Lange syndrome
Fryns syndrome
Achondrogenesis type II
Multiple pterygium syndromes
Distichiasis-lymphedema syndrome
Cumming syndrome
Cowchock syndrome
Cowden disease
Achondroplasia
Pena-Shokeir syndrome
Fraser syndrome
Proteus syndrome
Thrombocytopenia-absent radii
Polysplenia syndrome
Zellweger syndrome
Williams syndrome
OculoMental digital syndrome
Opitz-Frias syndrome
Beckwith-Wiedemann syndrome
Hereditary lymphedema
Data from references 1, 10, 16, 28, and 32-41.
multiple siblings of a family suggesting an auto-
somal recessive pattern of inheritance. 9,4~
Typically, the hygromas are unilocular and re-
solve spontaneously; long-term prognosis ap-
pears good. In a few cases, recurrent cystic hy-
gromas have been coinherited with various
malformations 4~ or have been associated
with nonimmune hydrops and perinatal lethal-
ity. 42,48,4sA different pathobiology has been sug-
gested for these cases.
Pathology
The anatomic distribution and severity of lym-
phatic vessel anomalies varies with the underly-
ing disorder (see later in article). Cystic hygro-
mas range from the size of a small pouch to giant
collections of fluid extending from the vertex
and down to the shoulders and back. ~9 The
masses may have either smooth or irregular con-
tours, the latter suggesting a multilocular collec-
tion of fluid. Incision of the mass releases free
tissue fluid. Cystic hygromas are poorly defined
and are not easily dissected from the overlying
skin. Hygroma spaces are lined by endothelial
cells and contain serous lymphatic fluid (Fig
3). lsa5 The hygromas contain thick-walled ves-
sels with smooth muscle in their wall and lym-
phoid aggregates within the connective tissue
component. Progressive lymphedema may lead
to fluid collections in surrounding connective
tissues.
In Turner syndrome, unique pathological fea-
tures are present. There are very distended cer-
vical and lumbar hygromas composed of hypo-
cellular connective tissue dividing fluid-filled
connective tissue spaces that lack an endothelial
cell lining. In contrast to non-Turner syndrome
fetuses who have generalized dilatation of pe-
ripheral lymphatics, peripheral lymphatics are
346 Gallagher, Mahoney, and Gosche
deficient or absent in 45,X fetuses. 2~176 These
observations have led to the suggestion that
there are differences in the pathogenesis o f the
clinical features observed in T u r n e r and non-
T u r n e r syndrome fetuses with lymphatic abnor-
malities.20,s2
Presentation and Course
Cystic hygromas are the most c o m m o n prena-
tally diagnosed anomaly o f the posterior neck.
Typical ultrasound appearance is a mass with
multiple e c h o l u c e n t cysts of varying size in the
posterior and lateral aspect o f the neck 49 (Fig 4).
They are quite variable in size, but frequently
the hygromas are as large or larger than the fetal
head. Nuchal hygromas are frequently bilateral,
and they may grow so large as to lie adjacent to
each o t h e r separated by the nuchal ligament,
creating the appearance of a single mass with
one or m o r e septa in the center. Over time, as
Figure 3. Pathology of
lymphatic vascular defects.
(A) Dilated, endothelial-
lined lymphatics from a
euploid fetus with cystic
hygroma. (B) Transverse
section at the level of the
humeral heads from a 45,X
fetus. Numerous dilated,
cystic lymphatic channels
are present, extending pos-
terolaterally. (Reprinted
with permission. 13)
l y m p h e d e m a of the u p p e r back, neck, and base
of the skull accumulates, fluid filled regions with
septa are f o u n d inside the skin. 49
Continued l y m p h e d e m a leads to effusions in
the serous cavities, including the pleura, pericar-
dium, and abdomen. These dilated cavities may
impede venous return leading to heart failure. 13
Progressive hydrops fetalis develops in up to
75% o f cases and usually results in fetal demise
in the ensuing weeks. 2As,2s,5~ High protein con-
centration in the hygroma fluid has been sug-
gested to contribute to the hypoproteinemia
and resulting generalized edema. 52
Several studies have analyzed the prognostic
significance of classifying hygromas into sep-
tated and nonseptated categories based on
prenatal ultrasound findings. Although some
studies have suggested that the presence of sep-
tations predicts an increased likelihood o f aneu-
ploidy and p o o r fetal prognosis, 5,26,3~ this
has not been a universal finding. 4,a~176 It has
 Cystic Hygroma
Figure 4. Prenatal ultrasound of cystic hygroma. A
typical, bilateral, asymetric cystic hygroma (CH) is
seen in the fetal neck, posterior to the fetal head
(FH). Septations (S) are seen within the hygroma.
(Reprinted with permission. 49)
been suggested that nonseptated lesions are
temporary lymph fluid collections due to incom-
plete lymphatic obstruction and that increased
pressure in the lymphatic system may overcome
the obstruction and lead to a higher rate o f
resolution in nonseptated lesions. 5,2a,54
The differential diagnosis of a posterior jux-
tacranial mass includes cephalocele, meningo-
cele, hemangioma, and teratoma (Table 4). T h e
predominantly cystic appearance, the lack o f ev-
idence o f a calvarial defect or a gyral pattern,
lack of distortion o f intracranial anatomy, the
absence o f spinal dysraphism, and the constant
position of the mass relative to the fetal head are
helpful diagnostic characteristics3, 49,5a O t h e r ul-
trasonic characteristics to aid in the differentia-
tion of these lesions are listed in Table 5. Trans-
vaginal ultrasound has been f o u n d to allow
more detailed and earlier detection of fetal nu-
chal cystic hygroma 54,57-59 and the finding o f
increased nuchal translucency on transvaginal
ultrasound has been shown to be a sensitive test
for fetal aneuploidy. 4
Pregnancy complications include oligohy-
dramnios in about two thirds of cases. T h e cause
o f the oligohydramnios is thought to be fetal
hypovolemia and hypoperfusion with secondary
347
p o o r renal perfusion and output. In the remain-
ing cases, amniotic fluid volume is normal or
increased. Polyhydramnios has been attributed
to a manifestation of hydrops fetalis; however,
most cases of cystic hygroma and hydrops fetalis
occur in pregnancies complicated by oligohy-
dramnios. Highly variable maternal serum and
amniotic fluid alpha-fetoprotein levels, from ex-
tremely high to normal levels, have b e e n ob-
served in pregnancies complicated by cystic hy-
groma.X,60
Prenatal Course
T h e variable presentation and course of the fe-
tus diagnosed with a cystic hygroma depends o n
a variety o f factors including gestational age at
diagnosis, associated aneuploidy or structural
abnormalities, and location o f the hygroma.
When a nuchal cystic hygroma is detected in
the first trimester, the earliest sign is a simple
elevation of a membrane-like thickening in the
posterior triangles of the neck. In hygromas de-
tected in the first trimester, the degree o f cystic
change is not as well developed and septations
are less likely. ~ A fetal c h r o m o s o m e abnormality
is f o u n d in approximately 50% o f fetuses, typi-
cally an autosomal trisomy. 4,s,s~
Recently, the finding o f increased nuchal
translucency during the first trimester has been
associated with fetal chromosomal abnormali-
ties, particularly autosomal trisomies. 4.12.62When
increased nuchal translucency is c o m b i n e d with
maternal age, crown-rump measurements, or
maternal serum h u m a n chorionic gonadotro-
pin, screening for fetal trisomy in the first tri-
mester can effectively be done. 63-66 Increased
nuchal translucency at 10 to 13 weeks' gestation
has not only been associated with fetal trisomy,
but also with o t h e r serious structural malforma-
Table 4. Differential Diagnosis of Fetal Neck Mass
with a Cystic Component
Encephalocele (occipital)
Meningocele
Branchial cyst
Hemangioma
Lymphangioma (lateral neck)
Lipoma
Laryngocele
Thyroglossal duct cyst (midline)
Dermoid cyst (midline)
Teratoma (rare)
34~ Gallagher, Mahoney, and Gosche

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o
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0

8
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0

o
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9
 Cystic Hygroma
tions, particularly congenital heart disease and
omphalocele, and various single gene disorders,
even in the absence of aneuploidy. 63,67-7~ The
precise relationship, if any, between increased
nuchal translucency and cystic hygroma has yet
to be determined. ~6
In the fetus with an isolated nuchal cystic
hygroma detected in the first trimester, a normal
karyotype and no other detectable congenital
anomalies ( - 1 0 % to 20% of cases), the progno-
sis appears good. These hygromas are typically
small, unilateral, and lack septa. 2s The hygroma
may resolve by 20 weeks' gestation with no evi-
dence of the hygroma apparent at birth, sl This
improvement in prognosis has been related to
an early partial lymphatic obstruction or a delay
in jugular lymphatic connection that results in
transient fluid collection that resolves and is of
minimal effect. Lesions that persist into the sec-
ond trimester represent either complete ob-
struction or failure of jugular lymphatic connec-
tion or a different etiopathobiology.
Diagnosis of a cystic hygroma in the second
trimester has been associated with a poor prog-
nosis. 1,2 Poor prognosis has been associated with
very large hygromas, severe lymphedema or hy-
drops fetalis, and the presence of coexisting
chromosomal abnormalities or malformation
syndromes. Approximately two thirds of fetuses
diagnosed with cystic hygroma in the second
trimester have aneuploidy, most commonly
Turner syndrome. In fetuses with a cystic hy-
groma and a normal karyotype, the risk for a
second major malformation has been estimated
to be approximately 30%. 6 Some of these mal-
formations, such as persistent left superior vena
cava, intestinal malrotation, duodenal atresia,
and imperforate anus cannot always be identi-
fied by prenatal ultrasonography. 6,28 Nondiag-
nostic anomalies indicative of a poor prognosis
include growth retardation, polyhydramnios, or
fetal akinesiaA Fetal death is likely if there is
aneuploidy, severe lymphedema and hydrops fe-
talis, or if the cystic hygroma is part of a severe
malformation syndrome. ~
Although u n c o m m o n , fetuses with cervical
cystic hygromas that are diagnosed after 30
weeks of gestation appear to have a good prog-
nosis, approaching that of infants with postna-
tally diagnosed lesions. These pregnancies are
not complicated by amniotic fluid abnormali-
ties; the fetuses usually do not develop hydrops
349
and seldom have associated structural malforma-
tions or abnormal karyotypes. 71 Occasionally, fe-
tuses with a normal karyotype, an isolated cystic
hygroma at a location other than the posterior
neck, and no associated malformations are iden-
tified in the third trimester. These fetuses also
have a good prognosis, which has been related
to a different developmental pathobiology than
posterior nuchal cystic hygromas 72-76 (Fig 5).
Management
Prenatal Considerations
The finding of a cystic hygroma on prenatal
ultrasound should prompt a detailed ultrasono-
graphic review of fetal anatomy to detect struc-
tural malformations and signs of fetal hydrops.
Particular attention should be directed to the
anatomy of the fetal cardiovascular and genito-
urinary systems and toward detection of signs of
hydrops fetalis such as fetal skin edema, ascites,
or pleural or pericardial effusions. 4~
The presence of a cystic hygroma is an indi-
cation for invasive diagnosis to obtain a fetal
karyotype as this prenatal diagnosis yields a
higher proportion of abnormal karyotypes than
any other fetal anomaly. Karyotype may be ob-
tained by amniocentesis, chorionic villus sam-
pling, or umbilical blood sampling. In some
cases, karyotype has been obtained from aspi-
rates of the cystic hygroma, ascites, or pleural
fluid. 77-a~ These alternative sources are appeal-
ing in cases complicated by very large cystic hy-
gromas a n d / o r hydrops fetalis in which obtain-
ing amniotic fluid or fetal blood may be difficult
because of obstructions from large hygromas or
oligohydramnios.
The disease course of a fetus with a cystic
hygroma is unpredictable. There is no reliable
method for predicting which hygromas will re-
gress and which hygromas are associated with
aneuploidy and other anomalies. Prognosis de-
pends on a variety of factors including gesta-
tional age at detection, fetal karyotype, and
other findings on ultrasound, such as additional
congenital anomalies or n o n i m m u n e hydrops
fetalis. For instance, the presence of hydrops
fetalis has been associated with fetal death within
a few weeks of diagnosis in all but a few
c a s e s . 1,2,4,99,81-a4 These factors should be taken
into consideration in the m a n a g e m e n t of these
350 Gallagher, Mahoney, and Gosche

Figure 5. Cystic hygroma outside the posterior neck. (A) Neonate with an anterior or "bearded" cystic hygroma.
(B) A neonate with a cystic hygroma of the axilla. (Photograph courtesy of Dr Robert Hertzlinger, Bridgeport,
CT). In both cases, the hygromas were detected late in pregnancy, karyotypes were normal, and there were no
other associated anomalies.

fetuses. It is i m p o r t a n t to note that the natural
history o f the fetus with a cystic h y g r o m a is in-
complete. T h e n u m b e r of pregnancies that have
c o n t i n u e d to delivery is too small to m a k e defin-
itive conclusions a b o u t the course a n d o u t c o m e
in all diagnostic categories. 1 Overall, the prog-
nosis is p o o r a n d m a n y pregnancies have b e e n
terminated. 60
In the p r e g n a n c y in which an a b n o r m a l
karyotype or a second significant m a l f o r m a t i o n
is detected, p r e g n a n c y termination may be con-
sidered. H y d r o p s fetalis is c o m m o n in these
pregnancies a n d the associated mortality ap-
proaches 100%. 83,84
If the karyotype a n d ultrasound are normal,
the parents should still be counseled a b o u t an
uncertain prognosis. If the p r e g n a n c y is contin-
ued, the fetus should be followed closely with
detailed, serial ultrasounds. 3~ If an isolated cystic
h y g r o m a not associated with aneuploidy or any
malformations has resolved by 20 weeks, it is
likely that the infant will be normal. However,
resolution of the hygroma, p e r se, does n o t im-
ply g o o d prognosis, as resolution has b e e n doc-
u m e n t e d in fetuses with Turner, 71,sl Down, s5
Noonan, 32,7a and Roberts 33 syndromes. Also, it is
i m p o r t a n t to note w h e n counseling the parents
of a fetus with a cystic hygroma, a n o r m a l karyo-
type, a n d o t h e r associated anomalies, that the
fetus may suffer f r o m a syndrome or malforma-
tion that is difficult to diagnose prenatally or
there may be tissue mosaicism or a c h r o m o s o m a l
defect. 29 It is also i m p o r t a n t to note that the
long-term developmental follow-up of infants
with a resolved h y g r o m a is not available. T h e
prognosis for infants with a n o r m a l karyotype
and no detectable malformations whose cystic
h y g r o m a does not resolve by 20 weeks' gestation
is unknown. 86
Large cystic hygromas in fetuses that survive
to term can complicate obstetric a n d perinatal
m a n a g e m e n t . Infants with large prenatally diag-
nosed cystic hygromas may require delivery via
cesarean section to decrease the risk of dystocia
and birth injury. T h e r e are reports of successful
vaginal delivery after intrauterine cyst decom-
pression, s7,ss T h e r e also are reports of serial as-
piration o f large cystic hygromas to prevent the
d e v e l o p m e n t of polyhydramnios, irreversible fe-
tal facial deformity, a n d hydrops fetalis, ss and
 CysticHygroma
one group has observed regression of a large
cystic hygroma after intrauterine aspiration and
injection of a sclerosing agent, s9
In some infants, very large hygromas of the
head and neck region make airway access diffi-
cult and may lead to death or permanent disabil-
ity because of neonatal asphyxia and anoxic
brain injury. For these infants, prenatal imaging
with magnetic resonance imaging9~ and the es-
tablishment of airway access while placental per-
fusion to the fetus is maintained during planned
cesarean section has proved successful.91,92
Neonatal Considerations
Over half of cystic hygromas diagnosed postna-
tally are detected in the neonatal period and
90% have become apparent by the end of the
second year of life.9s The most common site of
involvement is the neck (75%), typically in the
posterior triangle, followed in frequency by the
axilla (20%), and less commonly in the medias-
tinum, abdomen, retroperitoneum, and other
rare sites. 94 Cervical cystic hygromas occur in the
left side of the neck approximately twice as often
as on the right. 95 Hygromas rarely regress spon-
taneously after birth, 94 although resolution after
an episode of infection has been described. The
growth of cystic hygromas is generally propor-
tional to the growth of the child. These lesions
have the potential for rapid enlargement as a
result of trauma, hemorrhage, or infection. The
incidence of spontaneous infection has been re-
ported between 7% and 30% and secondary bac-
teremia may occur. 96 In addition, infection in-
creases the difficulty and risks associated with
subsequent excision. Therefore, treatment
should be instituted at an early age, before the
onset of infection. Early excision is particularly
important when the anatomic location of the
lesion poses a risk of airway obstruction in the
event of rapid enlargement of the hygroma as a
result of hemorrhage or infection.
Diagnostic evaluation in the newborn period
should include ultrasound examination of the
heart and the genitourinary system, in addition
to imaging of the lesion, and a karyotype. Be-
cause tissue mosaicism has been described in
infants with cystic hygroma, karyotypic analysis
of more than one tissue after delivery has been
suggested, eg, skin, peripheral blood, or hy-
groma fluid. This is particularly important in
351
cases when a postnatal karyotype is necessary to
resolve discordant clinical features and prenatal
karyotype.1 Neonates with Turner syndrome
present with a short, webbed neck, a low hair-
line, prominent ears, lymphedema of the hands
and feet, and in many cases, cardiac or renal
abnormalities. Although no intervention is nec-
essary for the peripheral edema, peripheral in-
vasive procedures should be minimized to de-
crease the risk of infection. It has been
suggested that infants with significant webbing
of the neck have cardiac examination as approx-
imately two thirds of these infants have congen-
ital heart disease. 16 Interestingly, when infants
with Turner, Noonan, or Down syndrome with
or without web neck were compared, there was a
significantly increased risk of flow-related con-
genital heart defects in those infants with
webbed necks. 16
Surgical Therapy
Before attempting excision of a cystic hygroma,
the extent of the lesion and its relationship to
surrounding structures must be clearly defined.
For superficial lesions, ultrasound, with or with-
out Doppler, may adequately define the extent
of the lesion and rule out involvement of under-
lying structures. 97 For more complex lesions,
computed tomography or magnetic resonance
imaging may be required to adequately assess
the extent of the lesion. Magnetic resonance
imaging (especially T2-weighted images) has
been reported to be particularly useful for eval-
uating extension of lymphatic abnormalities into
the deep structures of the neck and mediasti-
num and for defining the relationship of the
anomaly to neurovascular bundles and soft-tis-
sue s t r u c t u r e s . 9 a - l ~ 1 7 6
At present, complete excision remains the
treatment of choice for cystic hygromas. For su-
perficial lesions, complete excision can usually
be accomplished with litde difficulty. Not infre-
quently, cystic hygromas involve adjacent vital
structures, including cranial nerves, major vascu-
lar structures, or soft tissues such as the hypo-
pharynx, parotid gland, or trachea. They may
also extend from one anatomic region into an-
other; as many as 10% of cervical lesions will
extend into the chest or mediastinum. For these
complex cystic hygromas, complete removal may
require multiple operations and may not be pos-
352 Gallagher, Mahoney, and Gosche
sible without damaging adjacent vital structures.
In one large series, only three fourths of the
cystic hygromas were able to be completely ex-
cised.101
There are several important technical points
that should be followed when excising a cystic
hygromal02:
1. The incision must be large e n o u g h to ade-
quately expose the lesion. A simple transverse
cervical incision may be adequate for many
cervical cystic hygromas, but incision may
need to be extended onto the chest as a
median sternotomy for hygromas that extend
into the mediastinum.
2. The dissection must be meticulous. Bleeding
must be diligently controlled. Every attempt
should be made not to rupture the wall of the
cyst, because the fluid within the cyst will
frequently aid in defining the correct plane
for dissection.
3. All vital structures must be carefully identi-
fied and preserved. Cystic hygroma is a be-
nign disease; it is not acceptable to sacrifice
vital structures to completely excise the le-
sion.
4. An attempt should be made to identify and
ligate all draining lymphatic channels. This is
usually not possible. Thus, to prevent postop-
erative accumulation of lymphatic fluid, a
drain should be left in the bed of the lesion
postoperatively. If the above points are fol-
lowed, most cystic hygromas can be excised
with minimal morbidity.
The mortality rate associated with excision of
a cystic hygroma should approach zero. Postop-
erative complications, including recurrence,
wound seromas, infection, and nerve damage
occurs in 30% or more of cases. 101,103 Recur-
rence rates vary depending on the complexity of
the lesion and the completeness of excision.
Simple hygromas that are completely excised
seldom recur. Complex lesions that are com-
pletely excised recur in 10% to 27% of cases;
those that are only partially resected, recur in
50% to 100% of cases. 97 Histological examina-
tion of resected lesions frequently shows evi-
dence of microscopic residual tumor; however,
if all gross tumor has been removed, a low re-
currence rate can be expected.
Nonsurgical Therapies
In the past, the mortality rate for surgical exci-
sion of a cystic hygroma was high. As a result,
multitudes of nonsurgical treatments were at-
tempted. Some of these therapies have included
serial aspiration, incision and drainage, radio-
therapy, and the injection of a variety of scleros-
ing agents. T M None of these treatments proved
particularly effective. In the m o d e r n era, non-
surgical therapies have principally been used as
a treatment for either recurrent or unresectable
lesions. However, recent experience suggests
that at least two agents may have some efficacy as
a primary treatment for cystic hygroma, bleomy-
cin, and OK-432.
The sclerosing agent bleomycin has been
used to treat cystic hygromas via intralesional
injection, either in saline or as a fat emul-
sion, usually after aspiration of the hygroma
fluid. 1~176 Doses of bleomycin have ranged
from 1 to 9 mg and repeated doses have been
administered at intervals ranging from 1 week to
6 weeks. After bleomycin administration, most
patients develop fever, redness, and painful
swelling at the site of the injection, which per-
sists for up to 2 weeks. The reported experience
with bleomycin injections indicates that approx-
imately 40% to 50% of patients have had com-
plete or near complete regression of their hy-
groma, and another 30% to 40% of patients
have had at least a 50% reduction in the size of
their lesions. However, 12% to 18% of patients
have experienced either no response or a poor
response (<50% reduction in size) to therapy.
The authors of these reports suggest that the
results with bleomycin therapy are comparable
with the results obtained with surgical excision
of cystic hygromas. There are significant con-
cerns about this therapy because pulmonary fi-
brosis has developed as a side effect of bleomy-
cin exposure when it has been used as an
anticancer agent.
OK-452, a lyophilized mixture of a low viru-
lence Su strain of Streptococcus pyogenes of h u m a n
origin, which has been incubated with penicillin
G, has showed promise as a nonsurgical treat-
ment for cystic hygroma, i~ OK-432 has been
used as both primary therapy for cystic hygroma
and as a treatment for recurrent and unresect-
able lesions. Like bleomycin, OK-432 requires
direct intralesional injection after hygroma fluid
 Cystic Hygroma
aspiration o n o n e o r m o r e occasions at intervals
that vary f r o m 3 weeks to 3 m o n t h s . After OK-
432 treatment, m o s t patients e x p e r i e n c e m o d e r -
ate to h i g h fevers that last for several days a n d
local i n f l a m m a t o r y reactions with tenderness, er-
y t h e m a , a n d swelling o f their lesions that last u p
to 1 week. Reportedly, w h e n OK-432 is used as
p r i m a r y therapy, c o m p l e t e resolution m a y o c c u r
in 50% o r m o r e o f cases, a l t h o u g h fewer t h a n
10% o f patients will have m i n i m a l o r n o c h a n g e
in the size o f their lesions. However, w h e n OK-
432 is used as a t r e a t m e n t for r e c u r r e n t o r un-
resectable cystic hygromas, generally less t h a n
50% o f patients have c o m p l e t e resolution o f
their lesions, a n d as m a n y as 20% o f patients
have h a d m i n i m a l o r n o r e s p o n s e to therapy.
Unlike m a n y o t h e r s c l e r o t h e r a p e u t i c agents,
OK-432 i n d u c e s less fibrosis o f the overlying skin
a n d s u b c u t a n e o u s tissue. Thus, the cosmetic re-
suits have b e e n excellent in patients w h o have
h a d c o m p l e t e resolution o f their cystic hygro-
mas, a n d there has b e e n m i n i m a l fibrosis a n d a
decrease in postoperative l y m p h o r r h e a in pa-
tients w h o have residual lesions that have re-
q u i r e d s u b s e q u e n t surgical r e s e c t i o n ) l 0
T h e s e r e c e n t reports o f n o n o p e r a t i v e treat-
m e n t for cystic h y g r o m a s have certainly b e e n
m o r e p r o m i s i n g t h a n the n o n o p e r a t i v e thera-
pies that have b e e n a t t e m p t e d in the past. How-
ever, the r e p o r t e d trials o f b l e o m y c i n a n d OK-
432 t h e r a p y have c o m e f r o m a small n u m b e r o f
centers a n d have n o t b e e n r a n d o m i z e d . T h e r e -
fore, at present, surgical excision r e m a i n s the
p r e f e r r e d t r e a t m e n t for m o s t cystic hygromas.
This m a y be particularly true for cystic h y g r o m a s
that have the potential to c o m p r o m i s e the pa-
tient's airway as a result o f the swelling that
occurs after injection o f e i t h e r b l e o m y c i n o r
OK-432.
Future Pregnancies
C o u n s e l i n g for parents with a previously affected
fetus with cystic h y g r o m a begins with review o f
the history o f the earlier p r e g n a n c y . This in-
cludes detailed review o f the physical e x a m i n a -
tion a n d diagnostic studies o f the affected fetus.
If history o r e x a m i n a t i o n identifies a teratogenic
risk factor, the parents s h o u l d be c o u n s e l e d to
avoid the particular item. If a genetic s y n d r o m e
has b e e n identified, the parents s h o u l d be pro-
vided the a p p r o p r i a t e r e c u r r e n c e risks. W h e n a
353
c o n d i t i o n with variable expression a n d autoso-
mal d o m i n a n t i n h e r i t a n c e is suspected, first de-
gree relatives i n c l u d i n g the p a r e n t s a n d siblings
s h o u l d be e x a m i n e d f o r mild f o r m s o f expres-
sion.
A l t h o u g h the r e c u r r e n c e risk f o r isolated cys-
tic h y g r o m a has b e e n q u o t e d as quite low, 7 the
true r e c u r r e n c e risk f o r isolated cystic h y g r o m a
is u n k n o w n . Prenatal u l t r a s o u n d s c r e e n i n g
s h o u l d be offered. I n cases in which karyotype
abnormalities were identified in previously af-
fected fetuses, cytogenetic analyses s h o u l d be
considered.
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