Cystic Hygroma of the Neck: Prognostic Factors and Therapeutic Implications

The cystic hygroma (CH) of the neck is a rare congenital malformation that is due to an abnormal development of lymphatic system. Its gravity is due to the high frequency of chromosomic anomaly and/ or fetal malformations whom are associated to it. Objective of the study: To precise the prognostic features, as well as to bring forward therapeutic strategy. Study design: It is a retrospective study taking place in Kairouan’s hospital at gynecologic department lasting two years, from January 2011 to December 2012. During this period we collected nine cases of CH of the neck diagnosed in antenatality thanks to the obstetrical ultrasonography performed in the second trimester and the diagnosis of which is confirmed by the foetopathological examination. Results: Thanks to ultrasonography, the antenatal diagnosis of CH became easy and possible since the tenth week of pregnancy at 22% of cases. The CH is associated with foetal hydrops in 34% of cases and with a malformative syndrome in 22%. Three fetuses were already dead in uteru when diagnosing the CH. Karyotype was realized only in six cases in which 66% had chromosomal abnormalities. On the therapeutic plan, an uterine evacuation was performed to three patients who present already an in utero fetal death. The medical interruption of the pregnancy was indicated for the other cases. A fetopathological xam was systematicly performed and had confirmed the diagnosis . Besides, this exam showed a fetal hydrops in 3 cases and a polymalformatif syndrom in two cases. Conclusion: Cystic hygroma is an early suggestive sign of chromosomal aberration or malformative abnormalities. Prognostic features are well established: hydrops, malformative syndrome and karyotype abnormalities. Once one or several bad prognosis factors are identified, this justify a medical interruption of pregnancy. Gy ne col ogy & Obetrics ISSN: 2161-0932 Gynecology & Obstetrics


Introduction
The cystic hygroma (CH) of the neck is defined as a unique liquid tumour, most commonly bilateral and behind the neck. It is due to abnormalities in the development of the lymphatic system [1][2][3][4].
It is a rare malformation which can be isolated or associated either with other lymphatic system abnormalities or with chromosomal aberrations or malformative syndromes. This abnormality can be transitory or persistent [2]. Thanks to the fetal ultrasonography, the antenatal diagnosis of this malformation is already possible in the first trimester of pregnancy.
It is particularly important to discover this abnormality because it can alert early of chromosomal aberrations or foetal structural anomalies [2,3].
This malformation has often a dark prognosis, particularly when it is associated with a foetal hydrops. However in some cases, it resolves spontaneously and the pregnancy evolves until term. This evolutionary disparity and the lack of knowledge of prognosis factors explain the difficulties of menagement of this affection.
The aim of our study is to identify the pronostic elements and propose a pragmatic therapeutic approach.

Study Design
It is a retrospective analytic study based on patients' files taking place in Kairouan's hospital at gynecologic department, lasting two years, from January 2011 to December 2012.
During this period we collected nine cases of CH of the neck diagnosed thanks to the ultrasonography in the first two trimesters of pregnancy.
All our patients performed an ultrasonography in the first trimester (between 10 and 14 weeks of amenorrhea) and a morphological ultrasound between 20 and 24 weeks of amenorrhea.we have adopted in our study only the foeti who carry a cystic malformation with septa and retrocervical localization, that is isolated or associated with other anomalies. The highlighting of a cystic hygroma imposes a specialized ultrasound and a fetal karyotype.

Exclusion's criteria
• Other cervical tumours such as cystic lymphangioma, increased nuchal translucency • Malformations in the central neural system such as meningocelis and myelomeningocelis Contrasting with chromosomal abnormalities, older women are not at a higher risk of CH. In our series, 78% of the patients were young (under 35 years old). By the way, no risk features for CH have been identified in literature.
CH of the neck results from developing abnormalities in the lymphatic system. This system develops from five primitive cistern resulting from budding of the venous system [6].
These cisterns are made of: • Two bags flanking the internal jugular vein.
• A retroperitoneal bag on the bases of the mesenteric vein.
• Two iliac bags behind the sciatic vein.
These primitive bags connect with eleven other cisterns and undergo budding centrifugal lymphatic system to the device. These lymphatic cisterns are drained by the adjacent venous system. The only constant connection is the lymphatic-jugular one.
The CH occurs by partitioning of these cisterns or lack of communication with the adjacent venous system, in this case the internal jugular. Dilated jugular cisterns lead to fluid cavities. When the blockage is total, CH gradually increases in volume and can lead to compression of the foetal venous return, causing foetal hydrops. At the contrary, when the blockage is partial or if a secondary connection is established with the lymphatic system, the anomaly may regress ( Figure 3).
We aim to analyse the elements of the diagnosis and the prognosis of the CH of the neck in order to propose a practical attitude to have facing a CH of the neck.

Results
The mean age of our patients was 27,1 years with extremes from 19 to 40 years. Most of our patients were pauciparus and 44 % were nulliparus. No women had anterior CH of the neck and only one patient had a former new born suffering from Down's syndrome who died in two days. The CH of the neck was discovered by chance in 6 women and because of decrease in the foetal moves in the other 3 patients. The diagnosis took place in pregnancy of less than 20 weeks of amenorrhea in 7 cases. It was possible from the twelfth week of amenorrhea in 22% of the patients. The diagnosis was late in two cases in the second trimester of pregnancy.
The ultrasonographic aspect was suggestive in all patients with bi or multi parted off liquid retro cervical formation with a waving size (Figure 1a and 1b).
A foetal hydrops was seen in 34 % of the cases. 3 foetuses were already dead in utero when the diagnosis of the CH of the neck was made. The karyotype analysis using amniocentesis was performed in only 5 cases. It was abnormal in 66% of cases: a Down syndrome in two cases and a Turner syndrome in one.
Concerning the outcomes of the pregnancy, the 3 patients with intra uterine foetal death had a uterine evacuation; the other patients were proposed a pregnancy therapeutic interruption. Only one woman refused because of the normality of the karyotype, but the pregnancy prospect was an intra uterine foetal death at 24 weeks of pregnancy. A foetopathological examination was performed in all the cases. It confirmed the diagnosis of CH of the neck in all cases ( Figure 2).
A foetal hydrops was associated in 3 foetuses, multiple foetal structural anomalies were diagnosed in 2 cases and a suggestive aspect of monosomy X in one foetus (Table 1).

Discussion
The CH of the neck is the most screened anomaly during the first trimester of pregnancy. Its prevalence is about 1 % of all the ultrasonographic exams during the first trimester and it represents 10% of all the malformations diagnosed during the second trimester of pregnancy. On term, its frequency is about 17/100 000 births [5]. This decrease in frequency is due to the high rate of spontaneous abortion, inta uterine foetal deaths and of therapeutic pregnancy interruption.   In humans, the formation of these cisterns is usually complete in 8 WP. The progress of ultrasonography are that CH can be diagnosed from the seventh or eighth week of pregnancy [1,2,4].
In addition, 95% of foetal CH develop in the neck [1], their antenatal diagnosis by ultrasonography is easy and fundamental. In fact, CH is an important and early sign of chromosomal anomalies, polymalformative syndromes and genetic anomalies. Antenatal diagnosis of CH of the neck is only ultrasonographic.
The usual aspect is that of a rounded bi parted off cyst, located bilaterally at the back of the neck region. This fluid image often includes a floating partition featured by being bifid at its posterior [7].
The diagnosis is sometimes less obvious because of the volume or the ultra sonic structure of the cyst.a multi parted aspect is rarely reported.
The differential diagnosis arises mainly with occipital meningocele characterized by a lack of continuity in the brain's contour [2,8]. At the opposite, the differential diagnosis with the lymphangiomas, the paraxial teratomas and the hemangiomas arises rarely because of their, generally, heterogeneous ultra sonographic structure and especially by their front cervical or thoracic localization [9,10]. In our study, ultrasonographic images were very suggestive in 8 cases for CH. The 9th case was misdiagnosed as an amniotic band while it was an enormous CH.
The retro cervical CH may be isolated or associated with other malformative anomalies affecting the bones, the heart and the kidneys. In literature, this combination is estimated at 60% of cases [3,11,12]. Thus, CH record imposes a repeated and deepened morphological check up searching for a possible underlying abnormality. In our study, the ultrasound examination found a polymalformative syndrome in 22% of cases and a generalized hydrops in 3 cases.
The discovery of a CH always imposes a foetal karyotype . This allows to intervene early in cases of chromosomal abnormalities. At the contrary, the normality of karyotype allows for careful ultrasound morphological monitoring in a referral center. Indeed, even with a normal chromosome formula, the CH of the neck can reveal in 30% of the cases [3,2,13] either a genetic anomaly or a malformative syndrome as the disease of multiple pterygia, Roberts' syndrome or Noonan's syndrome, that is a male Turner's syndrome. In our study, 60 % of the performed karyotypes were abnormal and a malformative syndrome was found in 2 cases. Our study confirm the data of the literature concerning the high rate of chromosomic aberrations and congenital foetal malformations associated to the cystic hygroma.This justify the utility of an etiological evaluation including necessarily a karyotype and a detailed morphological utrasound.
The prognosis of this malformation is usually dark [3,4,8,14]. It is based on a number of factors: chromosomal abnormalities, associated malformations, foetal hydrops and the regressive nature of the CH. A Bernard P et al. study [3] based on 190 cases of CH of the neck has largely demonstrated the prognostic value of each criteria cited above:  The karyotype was performed in 149 cases and a chromosomal abnormality was found in 66 % of cases. These anomalies were Turner's syndrome in 66%.Other chromosomal abnormalities are also found: Down's syndrome (15%), trisomy 18 (7.5%), trisomy 13 (13%) [3].
 The foetal hydrops has a very dark prognosis. Indeed, the survival rate is only 3.5% of cases without any associated chromosomal  The spontaneous regression of the CH of the neck is generally regarded as a good prognosis criteria if associated with a normal karyotype [4]. This regression can occur regardless to the size and to the initial presentation of the CH. It does not exclude neither associated chromosomal abnormalities nor severe malformations nor foetal hydrops [3,4].
 Besides, it seems that the size and fragmentation of the Hygroma had no prognostic value. Because the size of our sample is reduced, it would thus be impossible to have conclusions nor to confirm or counter the data of the literature in this subject.
The study of the spontaneous evolution of fetuses with CH of the neck is skewed by the high rate (69%) of pregnancy therapeutic interruption [1,4]. In the same study of Bernard [3], he found a rate of 52% of pregnancy therapeutic interruption, 36.5% of spontaneous miscarriages and 4% of neonatal deaths. In our study, a pregnancy therapeutic interruption was performed in 55% cases and in 45% of cases the evolution was to in utero foetal deaths.
The practical attitude to be taken when discovering a CH of the neck during an ultrasound examination depends on the prognosis criteria ( Figure 4).
• A normal karyotype is a good prognosis factor. In such cases,it is necessary to insist on the importance of an ultrasound follow-up to look for associated abnormalities.
• A foetal hydrops darkens the prognosis. It requires a deep etiological inquiry.In our series, the diagnosis of an associated foetal hydrops or chromosomal abnormality justified pregnancy therapeutic interruption in 5 cases.

Conclusion
The CH of the neck is a rare malformation with a dark prognosis. Thanks the progress of the techniques and the machines in the field of ultrasonography, the antenatal diagnosis of CH is easily possible since 10 WP. Because CH of the neck is a very early and suggestive sign of chromosomal or congenital abnormalities, its screening is imperative while performing any ultrasonographic examination. The prognosis factors are clearly established: foetal hydrops, structural in born malformation or chromosomal abnormalities. When present, any of these features, leads most commonly to the therapeutic pregnancy interruption.