Key Points
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Fetal tumours are rare and should be managed by an experienced multidisciplinary team.
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Magnetic resonance imaging is an important imaging modality in the diagnosis and management of fetal tumours.
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Fetal neck masses may result in airway obstruction and the ex utero intrapartum treatment (EXIT) procedure may need to be planned for delivery.
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In utero treatment of sacrococcygeal teratomas can be performed in fetuses showing signs of compromise.
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Good outcomes can be achieved in many cases of fetal tumours.
Introduction
Fetal tumours are a rare and heterogeneous group of fetal malformations, ranging from benign lesions that may cause fatal airway obstruction without appropriate management, through those with mass effect and low malignant potential, to very rare fetal malignancies. The unifying feature is that they are rare and require complex antenatal, intrapartum and postnatal management from highly specialist services. With improvements in antenatal detection and assessment, involvement of the multidisciplinary team (MDT) and individualised care planning and management from the point of diagnosis, devastating and fatal outcomes such as unexpected airway obstruction or massive fetal or neonatal haemorrhage can be avoided, and potentially, the outcomes for these infants can be improved.
Neck Masses
Introduction
Neck masses are most commonly noted in the second trimester at the time of the detailed anatomy scan, although they may present as an incidental finding on later scans or be referred due to polyhydramnios and measuring large for gestational age. The majority of neck masses detected at this gestational age are mixed cystic and solid in nature and arise in the anterior triangle. Posterior cystic neck lesions and those evident in the first trimester commonly have a different aetiology as outlined later and in Chapter 19 .
The two most common neck masses are lymphangiomas and teratomas. A lymphangioma will be a well-circumscribed, predominantly avascular mass consisting of thin walled cystic areas. Lymphangiomas arise laterally but often crosses the midline, and although not invasive, they can extend into the mediastinum and thoracic cavity and can obstruct the airway ( Fig. 37.1 ).
A teratoma has a heterogeneous appearance with varying degrees of cystic and solid components ( Fig. 37.2 ). They are often well vascularised. There is no pathognomonic ultrasound appearance, and teratomas can be difficult to differentiate from lymphangiomas. However, areas of calcification on ultrasound (or fat signal on magnetic resonance imaging (MRI)) make the diagnosis of teratoma more likely. As with lymphangiomas, fetal teratomas are rarely invasive but can cause oropharyngeal obstruction and deviation. Compressive effects can also cause significant disruption to the bony skull and the skull base; ultrasound (US) and MRI should be used to detect signs of this. Care should be taken to differentiate a cervical teratoma from an epignathus, a rare teratoma arising from the palate-pharyngeal region around the basisphenoid (Rathke pouch), which fills the buccal cavity. This is associated with poor prognosis because of the location and potential for invasion into the skull base and brain tissue.
Differential Diagnoses
Before confirmation of a cystic neck mass, other differentials must be considered. Posteriorly, this would primarily be gross nuchal oedema. Careful US examination of the skull and brain structure should be performed to exclude encephalocele or cervical myelomeningocele. Anteriorly, cervical teratoma is a primary differential. Anomalies of thyroid development, including tumours and goitres can present similarly. Masses with a more cystic appearance may represent thyroid or branchial cleft cysts or thyroglossal duct cysts.
Cystic Lymphangioma
Embryologically, the lymphatic system develops after the formation of blood vessels. The most widely accepted model of lymphatic development to date was developed more than a century ago. It proposes that the endothelial cells bud from the veins to form primary lymphatic sacs. These then sprout towards the periphery. The two main lymphatic sacs develop near the junction of the subclavian and anterior cardinal veins, and the lymphatic capillaries spread from these towards the head, neck, arm and thorax. The failure of these jugular lymph sacs to drain into the developing lymphatic system is thought to cause abnormal lymphatic sprouting, lymph accumulation and the development of lymphangiomas.
The terms cystic hygroma and lymphangioma are synonymous and have been used to describe congenital dilated cystic malformations, predominantly in the region of the neck. However, it should be recognised that these masses may arise from or extend into the thorax and mediastinum or axilla. Less commonly, lymphangiomas have been reported elsewhere in fetuses, including the extremities and abdominal wall.
In the first trimester, the term cystic hygroma is used to describe a significantly increased nuchal translucency, often with internal septations (see Chapter 19 ). Such cases are more frequently associated with underlying chromosomal aneuploidies, particularly monosomy X (Turner syndrome), trisomy 18 and trisomy 21. In the absence of aneuploidy, there is a higher incidence of underlying genetic disorders that may not be detected antenatally. However, in the era of microarray and improved targeted testing for Noonan syndrome (in which >80% can be diagnosed), the antenatal detection rate is improving. A detailed first trimester anomaly scan, including cardiac anatomy, should be performed in such cases and further investigations offered. In the event of a normal karyotype or microarray, if the findings do not resolve, and particularly if there is a further anomaly found on ultrasound, genetic counselling should be considered. If antenatal testing is declined, careful assessment of the infant should be performed in the neonatal period.
Increased nuchal translucency is also associated with cardiac abnormalities, and in some cases, ultrasound signs of fluid in other fetal compartments such as the thorax, abdomen and generalised skin oedema may be noted; this is known as fetal hydrops or hydrops fetalis. In cases of hydrops, investigations as described earlier should be performed, as well as consideration of other causes such as red cell alloimmunisation or nonimmune causes, including viral infection and metabolic disease (see Chapter 36 ). In cases of persistent hydrops presenting in the first trimester, the outlook is very poor with few fetuses surviving to delivery.
In cases of first trimester cystic hygromas that have been appropriately investigated and no genetic abnormality found, particularly in those cases that resolve, the prognosis is very good.
The development of a cystic neck mass in the second trimester is likely to have a different aetiology ( Table 37.1 ) from those seen in the first trimester and may carry a better prognosis unless associated with hydrops or generalised oedema, in which cases the prognosis remains poor.
| Diagnosis | Ultrasound features | Incidence | Outcome |
|---|---|---|---|
| Cervical lymphangiomas | Well-circumscribed or diffuse cystic mass, laterally located, and often arising from cervical area, floor of mouth or the tongue | 1 in 1775 live births | Can cause complex airway obstruction; referral to ENT and consideration of EXIT procedure recommended; presence in the first trimester is associated with chromosomal abnormalities |
| Cervical teratomas | Can be massive, usually solid with some cystic areas, and well defined; may have internal calcifications, positioned in the anterior neck; 3:1 female:male ratio | 1 in 40,000 live births | Can cause complex airway obstruction; referral to ENT and consideration of EXIT procedure are recommended |
| Haemangioma | Typically posterolateral, well-defined, solid masses with slow vascular flow | Rare | May be associated with cortical malformations; brain MRI indicated, can be part of PHACES syndrome |
| Cervical thymic cyst | Commonly multiloculated but can be uniloculated, most commonly to the left, splaying the carotid artery and jugular vein | Very rare | |
| Congenital goitre | Symmetric thyroid enlargement; associated with maternal propylthiouracil use (for Graves’ disease) and maternal thyroid stimulation-blocking antibody | Rare | Unlikely to cause airway obstruction; when present, intubation is usually successful |
| Brachial cleft cysts | Unilateral, uniloculated anterolateral thin-walled cyst | Rare | Not reported to cause airway obstruction |
| Vascular malformations | Multiloculated cystic structure often laterally located | Rare | |
| Neuroblastoma | Retropharyngeal, solid mass, with or without calcification, extending into mediastinum or skull | Very rare |
Teratomas
Fetal teratomas are rare tumours with an incidence of 1 in 40,000 live births. Although most commonly found in the region of the lower spine and pelvis (sacrococcygeal teratomas (SCTs); discussed in detail later), 6% are related to the neck. Teratomas are (almost always) formed of tissues derived from the three germ cell layers: endoderm, mesoderm and ectoderm. Although teratomas are predominantly (>80%) benign tumours with well-differentiated tissues, the rapid growth and the mass effect can cause significant complications; primarily by obstruction or deviation of the trachea and oesophagus. In cases of immature teratoma, with more poorly differentiated tissues, there in increased risk for invasion and metastases; however, the prognosis remains good with a greater than 80% 5-year survival rate.
The origin of fetal teratomas remains poorly understood. The most widely accepted hypothesis is that aberrant pluripotent cells are sequestered during embryogenesis, in the fourth to fifth week of gestation, that are able to proliferate to form disorganised structures comprising tissue types derived from the three embryonic germ layers.
Antenatal Management
Tertiary-level ultrasound assessment and multidisciplinary counselling are important in any neck mass. The ultrasound assessment should include details of the site and size of the mass, solid or cystic components, calcification, associated vascularity and assessment of invasion into or deviation of adjacent structures. Attempts should be made to determine the nature of the mass to aid counselling regarding postnatal management, likelihood of complications and long-term outcomes.
A routine element of ultrasound assessment of fetal neck masses should be assessment for evidence of tracheal deviation or oesophageal occlusion. Indirect markers of these include polyhydramnios or a small or nonvisible stomach bubble. In some cases, the oropharynx may be fluid filled and readily visible, indicating significant partial or total occlusion. Ultrasound assessment is also important in the determination of fetal well-being, particularly in identifying development of cardiac compromise or hydrops, and to regularly assess the growth and size of the mass. The utility of three-dimensional (3D) US imaging in neck masses is unclear and becomes difficult to achieve in larger tumours at later gestations, particularly in the absence of polyhydramnios. Although its clinical benefit may be limited in such cases, we have found that it is useful to the parents ( Fig. 37.3 ).
After 24 weeks’ gestation, ultrasound assessment should be performed every 2 weeks. These assessments should focus on assessing the size of the mass, any changes in characteristics including vascularity, fetal neck extension, amniotic fluid volume and signs of cardiac compromise. To aid delivery planning, fetal presentation and placental site should be carefully mapped.
Increasing polyhydramnios and features of cardiac compromise, including hydrops or Doppler abnormalities, are indications for more frequent assessment. In cases of significant polyhydramnios, particularly associated with maternal discomfort, amniodrainage may be indicated, although this is associated with rupture of membranes and preterm labour. In view of the anticipated airway difficulties and the advantages of a planned delivery, amniodrainage should be kept to a minimum and performed in a centre where ex utero intrapartum treatment (EXIT) is possible.
Magnetic resonance imaging
Fetal MRI is generally accepted to be safe up to 3 Tesla and is being increasingly exploited. The advantages of the technique are its excellent soft tissue definition and the large field of view it provides, allowing global imaging of the fetal head and neck at any gestation. In addition, it is a useful adjuvant to ultrasound when imaging is limited, for example, in cases of oligohydramnios, poor fetal position or maternal obesity. The difficulty with fetal MRI is in imaging an unpredictably mobile fetus. To overcome this, fast MRI sequences are used to obtain single-slice acquisitions, producing a motion frozen stack of images, free from artefact. A variety of fast MRI sequences are used to obtain T1- and T2-weighted images (depending on the manufacturer of the hardware), which acquire 15 to 20 3-mm slices in less than 25 seconds.
The most common and important indication for fetal MRI in the context of neck masses is to assess airway patency to inform decisions on mode of delivery ( Fig. 37.4 ). Because the fetal airway is fluid filled, it appears bright on T2-weighted sequences. This allows the trachea to be traced through the neck using imaging in three orthogonal planes. This may confirm patency or conversely assist surgeons in planning the best approach for tracheostomy.
After patency is confirmed, the passage of the trachea can be mapped and displacement assessed. As an aid to determining the degree of airway displacement, the tracheoesophageal displacement index (TEDI) has been developed, which is defined as the sum of the lateral and ventral displacement of the tracheoesophageal complex from its normal anatomical location. A TEDI score greater than 12 mm has been reported to be predictive of a complicated airway (100% vs 46%; P = .04) 10 ( Fig. 37.5 ).
As well as assessing airway patency, fetal MRI can help identifying the underlying cause of neck masses, as the improved soft tissue definition and differences in signal from T1- and T2-weighted imaging can help distinguish pathologies. MRI can also help describe the relationship among the mass, airway and other structures of the neck, head and thorax and help assess for neck extension secondary to the tumour, which may necessitate delivery by caesarean section. Additional information on the depth of invasion and structures involved can aid surgical planning. MRI has been reported to obtain additional findings or make an alternative diagnosis to ultrasound in 83% of cases of fetal neck masses.
Magnetic resonance imaging is also useful for assessing the fetal lungs, which are clearly visualised in T2-weighted imaging. They can be collapsed, hypoplastic or hyperinflated in cases of fetal neck masses. There is potential for MRI derived total lung volume measurements to help predict lethal pulmonary hypoplasia.
Determining airway patency remains challenging with MRI because of the relative thickness of the slices compared with the size of the fetal airway structures. There is ongoing research in reconstructing the two-dimensional stacks of slices in three orthogonal planes into anatomically relevant 3D volumes. This would improve spatial resolution and therefore the diagnostic ability of imaging in the future. Reconstructing virtual bronchoscopies as an aid in evaluating airway patency is an exciting future possibility.
Prognosis
The antenatal prognosis for a fetus with a cystic hygroma and normal karyotype and cardiac structure is good with few cases dying in utero . The in utero mortality rate in cases of teratoma is higher because of increased vascularity and associated cardiac demands. At present (because of limited worldwide cases), there is no predictive model for adverse in utero outcomes.
In utero therapies
There are a few reports of in utero therapy, including sclerotherapy, for cystic hygroma and fetal surgery for teratoma. The numbers are very limited, and these therapies are not routinely practised, although they may have a role in the case of the previable hydropic fetus, in which the mortality rate is close to 100% if delivered or left untreated.
Fetoscopy is used in some centres to assess the patency of the fetal airway; however, there are only currently two reports in the literature of operative intervention for neck masses. One report details the in utero removal of a pedunculated nasopharyngeal tumour using YAG (yttrium aluminum garnet) laser excision. A second report details a fetal endoscopic tracheal intubation technique (FETI). In this case, a fetus with a giant cervical teratoma was successfully intubated at 35 weeks’ gestation. This allowed a standard elective lower segment caesarean section to be performed with immediate use of the endotracheal tube at birth for ventilation.
Intrapartum Management: The EXIT Procedure
The EXIT procedure is performed to secure the fetal airway before stopping placental circulation. By maintaining the fetus on placental circulation, oxygenation is assured, allowing additional time to establish an airway. The first successful case was described in 1990 for the insertion of a tracheostomy in a fetus with an epignathus. However, the term EXIT was coined, and the procedure was first routinely used for management of pregnancies complicated with congenital diaphragmatic hernia treated with fetoscopic endotracheal balloon occlusion (FETO) (see Chapter 31 ). The EXIT procedure is now a widely used technique in centres managing the delivery of fetuses with neck masses with a high suspicion of airway complications. Although developed from the routinely performed lower segment caesarean section, an EXIT procedure should not be regarded as such and comes with its unique complexities and risks to both the mother and fetus.
The EXIT procedure is used for a variety of fetal anomalies which obstruct the fetal airway, preventing spontaneous respiration and making intubation of the airway either very difficult or impossible. The anomalies can be extrinsic, including teratomas and lymphangiomas, or intrinsic, such as laryngeal atresia, congenital upper airway obstruction, obstructive malformations of the upper airways and intrathoracic lesions such as congenital hydrothorax. It is also sometimes used in cases of FETO in which the balloon has not been electively removed before delivery. Interventions performed with the EXIT procedure include intratracheal intubation, tracheotomy and tracheoplasty.
It remains difficult to predict which fetuses will have a complicated airway. Ultrasound and MRI may be unable to demonstrate airway patency throughout its course, and in such cases, it is sensible to assume EXIT is required. A large mass, a suspected diagnosis of teratoma or signs of obstruction such as polyhydramnios or a small or absent stomach bubble all increase the chance of airway obstruction; therefore, if any of these are present, an EXIT should be planned. When the airway is visible but deviates from its normal course, the TEDI (see earlier) provides a guide to when EXIT may be appropriate. In masses that are not teratomas, a TEDI of greater than 12 mm has 100% sensitivity and 86% specificity for a complicated airway.
However, all cases should be evaluated on a case-by-case basis by an experienced multi-MDT. In our experience, neck masses can change rapidly after delivery, with sudden postpartum increases in vascularity and size, so even in cases in which antenatal imaging suggests a patent airway, careful consideration should be given by an MDT on the possible benefits of an EXIT procedure to safely establish a secure airway in the early neonatal period.
Detailed antenatal planning with an MDT, which should include the obstetricians; neonatologists; anaesthetists (both maternal and neonatal); paediatric ear, nose and throat surgeons; radiologists; theatre scrub teams; and critically the parents, is essential for each case. The theatre space itself should be sufficient to accommodate the various teams and ‘zones’ established for each specialty. A detailed brief and ‘talk through’ of the procedure, including plans for foreseeable complications and confirmation that all necessary equipment and drugs are available, should be performed immediately before the procedure. Ideally, delivery should be as close to term gestation as possible; however, because of increasing polyhydramnios, up to 76% of cases are delivered at a late preterm gestation (median, 35weeks).
The parents of the baby should be involved in the antenatal planning process and a nominated midwife assigned to the case. Discussion should be undertaken antenatally with the parents and plans made for cases in which it is not possible to gain airway access and other worst-case scenarios such as severe hypoxia or prolonged fetal bradycardia. Psychological support for the parents should be offered.
To provide adequate fetal perfusion, maternal anaesthesia should aim to provide optimal uterine relaxation and suitable maternal blood pressure. EXIT procedures are usually performed under deep maternal general anaesthesia because volatile anaesthetics assist in uterine relaxation. Regional anaesthesia has been reported but requires intravenous infusion of glyceryl trinitrate (GTN) and remifentanil. Rapid-sequence induction and general endotracheal anaesthesia with maternal paralysis and epidural for postoperative analgesia is a standard technique. After delivery of the fetus, the concentration of volatile agents is reduced and/or converted to intravenous anaesthesia, and oxytocin is given to establish uterine tone. More recently, the SIVA (supplemental intravenous anaesthesia) technique has been used. This exploits the tocolytic effects of propofol and allows a reduction in the use of volatile anaesthetic agents. This reduced exposure to volatile agents may reduce fetal myocardial suppression and may also be a more suitable technique in cases in which prolonged maternal exposure to volatile agents is not desirable.
Before uterine incision, particularly in cases of extensive anterior placentation, intraoperative sterile ultrasound mapping of the placenta should be performed to avoid inadvertent placenta incision. The head, neck and upper torso of the fetus are delivered along with the fetal right arm ( Fig. 37.6 ). The fetus should have 10 μg/kg fentanyl and 0.1 mg/kg of vecuronium immediately into the deltoid muscle. Monitoring of the fetal saturations and heart rate should be performed with sterile monitoring equipment. Atropine should be available and usage determined by a senior neonatologist. After this, attempts should be made to secure the airway with direct laryngoscopy. If this is not successful, examination of the airway with a rigid bronchoscope, flexible bronchoscopy, or both should be performed and guided intubation attempted. If this is unsuccessful, an attempt at tracheostomy should be considered. After the airway is secured, the baby can be delivered and transferred to the neonatal unit for further assessment. If there are prolonged episodes of desaturation or bradycardia or compromise to the maternal health (bleeding, hypotension), the baby should be delivered immediately even if a definitive airway has not been secured.
