Fetal neck masses can have a good or a poor prognosis. Ultrasound and/or magnetic resonance imaging (MRI) can help in the differential diagnosis of fetal neck masses, thus helping to counsel parents carrying fetuses with such an anomaly. In some cases, prenatal treatment is available and can result in the resolution of the neck mass. In others, when the neck mass is large, it can cause airway obstruction with potential fetal demise after delivery. In such cases, it is important to define prenatally the relationship of the neck mass to airway structures indicating the need for pretherapeutic planning of an ex-utero intrapartum treatment (EXIT) procedure, which allows getting access to the fetal airways while fetomaternal circulation is preserved in order to optimize fetal outcome.

In the immediate perinatal period, the most important keys to survival are undoubtedly the pulmonary and cardiovascular systems. Lung development is a meticulous process that starts early in pregnancy, from approximately 26 days after fertilization, with the formation of 2 buds from the ventrolateral wall of the primitive foregut. Throughout pregnancy, the lung becomes a more and more complex and highly specialized organ that allows achieving blood oxygenation in the postnatal period. To be able to do so sufficiently, the lung has to fulfill 5 different stages of maturation.¹ It is only logical that different events during those various stages will end up as a heterogeneous group of lung pathologies. Impairment of the pseudoglandular stage will affect branching or ramification of both bronchial and arterial structures of the lung.² Interference of lung development during the canalicular phase is responsible for decreased complexity of the respiratory acinus and causes impaired lung maturation.

The aim of this chapter is first to describe fetal neck anomalies, and these are divided into the anterocervical or posterocervical pathologies. Second, we describe chest anomalies that primarily relate to fetal lung development and function. Pathologies of the diaphragm, such as congenital diaphragmatic hernia (CDH), lead to an intrathoracic herniation of abdominal organs and, due to a space-occupying effect, can also interfere with normal lung development. Since the emergence of fetal therapy for severe cases of CDH, much research work has been performed in this field and is summarized in this chapter.

Fetal neck anomalies are clinically important because of their potential influence on head position during labor, and also for the possibility of airway obstruction at the time of delivery. These abnormalities can be divided into anterocervical or posterocervical pathologies.

Anterocervical Pathologies

Enlargement of the Thyroid Gland or Goiter

Fetal goiter can be associated with hyperthyroidism, hypothyroidism, or a euthyroid state. Possible causes are intrauterine exposure to antithyroid drugs, congenital metabolic disorders of thyroid synthesis, and iodine excess or deficiency.

Prenatal sonographic studies demonstrate an anterior solid and symmetric mass, which may result in hyperextension of the fetal head. Because of mechanical obstruction of the esophagus, polyhydramnios can often occur. On MRI scan, normal fetal thyroid is easily detected using a T1-weighted image (WI) (Figure 19-1), allowing differential diagnosis from other neck masses.

The prognosis depends on the basic cause of the goiter. Most cases are in women with a history of thyroid disease. Fetal blood sampling can aid in determining fetal thyroid status, especially in women suffering from Grave disease where a transplacental transfer of drugs or thyroid-stimulating antibodies may result in fetal goiter.

Maternal therapy usually corrects fetal hyperthyroidism. Direct fetal therapy in cases of fetal hypothyroidism can be undertaken by amniocentesis or by cordocentesis, and this can result in resolution of the fetal goiter.

Cervical Teratoma

Teratomas are made up of a variety of parenchymal cell types representative of more than a single germ layer. Arising from totipotential cells, these tumors typically are midline or paraxial. They range from benign, well-differentiated cystic lesions to those that are solid and malignant. The most common location of teratomas is sacrococcygeal. In newborns, cervical teratomas represent only 5% of the total.³

Sonographic features include a unilateral and well-demarcated partly solid and cystic or multiloculated mass. Calcifications are present in about 50% of cases. Cervical teratomas may be intimately associated with the thyroid gland and, in addition to tracheal compression, they may cause esophageal compression and polyhydramnios.

MRI is most useful in cases of cervical teratoma for determining the best mode of delivery. This information can be used to guide clinical discussions for the potential need of an EXIT procedure (Figure 19-2).⁴

When fetal hydrops is associated, prognosis is poor with an intrauterine or neonatal mortality rate of about 75%.⁵ This is mainly due to airway compromise associated with the lesions. For those without fetal hydrops, survival after surgery is high, but since these tumors tend to be large, extensive neck dissection and multiple additional procedures are necessary to achieve complete resection of the tumor with acceptable functional and cosmetic results.

Other rare anterocervical masses can include brachial cleft cysts and vascular anomalies such as hemangioma.⁶

Posterocervical Pathology

Second Trimester Nuchal Fold Thickness

Nuchal fold thickness is the second trimester form of nuchal translucency measured at the 11- to 13⁺⁶-week scan. In the measurement of the nuchal skin fold thickness, critical landmarks should include the cavum septum pellucidum, the cerebral peduncles, and the cerebellar hemispheres. Nuchal fold thickness is measured by placing the calipers from the outer skull table to the outer skin surface (Figure 19-3). It is considered to be pathological when the measurement is more than 6 mm. For isolated increased nuchal thickness, the risk for trisomy 21 may be 10 times the background risk. It may be associated with chromosomal defects, cardiac anomalies, infection, or genetic syndromes.^7-11

Encephalocele

Encephalocele is part of the large group of neural tube defects (NTDs). Whereas the group of NTDs have an incidence of about 1 per 1000 births, encephalocele accounts for about 10% of cases in this group.

The precise etiology for more than 90% of these NTDs is unknown. Chromosomal abnormalities, various genetic syndromes, such as Meckel-Gruber, von Voss, Chemke, Roberts, and Knobloch syndromes, and maternal diabetes or ingestion of teratogens, such as warfarin, are implicated. Other associated brain abnormalities that may occur in isolation or as part of genetic or nongenetic syndromes include spina bifida, callosal dysgenesis, Arnold-Chiari II malformation, Dandy-Walker malformation, and brain migrational anomalies. The most common associated chromosomal anomaly is trisomy 18.

Encephaloceles are recognized on ultrasound as cranial defects with herniated fluid-filled or brain-filled cysts (Figure 19-4). They are most commonly found in an occipital location (75% of the cases), but alternative sites include the frontoethmoidal and parietal regions. Differential diagnosis should be made with a benign epidermal scalp cyst (see Figure 19-4) in which case there is no cranial defect.¹²

The prognosis of encephalocele is inversely related to the amount of herniated cerebral tissue. Overall, the neonatal mortality can vary between 10% and 80% depending on whether pediatric or fetal series are looked at, and more than 50% of survivors have mild to severe developmental delay.^12,13

When a parent or previous sibling has had any manifestation of an NTD, the risk of recurrence is about 5%. Periconceptual supplementation of the maternal diet with folate reduces by about half the risk of developing these defects. The dose of folic acid is daily 5 mg for high-risk groups and 0.5 mg for low-risk groups.^14,15

Cystic Hygroma or Lymphangioma

Cystic hygroma or lymphangioma is a cystic lymphatic lesion that can affect any anatomic site in the human body. It usually affects the head and neck with a left-sided predilection.

Cystic hygromas are thought to arise from a combination of the following: a failure of lymphatics to connect to the venous system, abnormal budding of lymphatic tissue, and sequestered lymphatic rests that retain their embryonic growth potential. These lymphatic rests can penetrate adjacent structures or dissect along fascial planes and eventually become canalized.^16,17

Prenatal diagnosis is based on classic sonographic findings that include a complex appearance with multiple fluid-filled cysts and septae (Figure 19-5). The prognosis is often poor, especially if the lesion is associated with hydrops, which is often associated with chromosomal abnormalities such as Turner syndrome, trisomy 21, or Klippel-Trenaunay syndrome.^16,17

Fetal chest anomalies involve pathologies of the fetal lungs and diaphragm as well as those of the fetal heart and mediastinum. In this chapter, only pathologies of the fetal lungs and diaphragm are discussed.

Prenatal lung growth can be interfered with by reduction of the intrathoracic space, oligo- or anhydramnios, and/or impaired fetal breathing movements.¹⁸ Depending on the origin of the malformation, this will result in pathology-specific prognosis.

In most circumstances, ultrasonography will be sufficient to diagnose the thoracic pathology. However, MRI has been proposed as an important complementary examination.^19,20 The potential benefit of MRI for these abnormalities can mainly be explained by its superior tissue contrast, absence of acoustic shadowing, and large field of view. These characteristics provide clinicians with a better idea regarding the extent of the pathology as well as the presence of other associated structural anomalies.²¹ In this chapter, we will discuss how MRI can yield additional information in the prediction of postnatal survival for fetuses with CDH.

Pathologies of the Fetal Lungs

Congenital Cystic Adenomatoid Malformation

Congenital cystic adenomatoid malformation (CCAM) is an uncommon tumor; nonetheless, it represents the majority of all congenital lung lesions detected in utero. A commonly quoted incidence of these lesions is 1 in 25,000 to 1 in 35,000 live births, which likely underestimates their true incidence.²² The exact pathogenesis of this hamartomatous lung tumor is still unknown. The theory is that, due to a vascular insult around the sixth week of gestation, there is a cessation of distal bronchiolar structures, characterized by the lack of alveolar differentiation. The lesion is mostly limited to one single lobe (>95%) and communicates with the normal tracheobronchial tree.²³ The blood supply is maintained by branches of the normal pulmonary artery and veins. Stocker et al first classified the pathology in 3 types ranging from a single cyst to a homogeneous microcystic mass.²⁴

The prenatal sonographic appearance of CCAM will typically demonstrate a hyperechogenic pulmonary tumor, which can be either cystic (type 1), mixed (type 2), or solid—microcystic (type 3) (Figure 19-6). Microcystic disease results in uniform hyperechogenicity of the affected lung tissue. In macrocystic disease, single or multiple cystic spaces may be seen within the thorax. Both microcystic and macrocystic disease may be associated with deviation of the mediastinum, thus including the heart. In contrast, in bilateral disease, the heart may be severely compressed, although not deviated. When there is compression of the heart and major blood vessels in the thorax, fetal hydrops may develop. Polyhydramnios is a common feature, and this may be a consequence of decreased fetal swallowing of amniotic fluid due to esophageal compression, or increased fluid production by the abnormal lung tissue. It is important to search for associated anomalies, because in about 10% of the cases, CCAM is associated with other defects (eg, cardiac and renal anomalies).

Differential diagnosis is often made with CDH. Direct visualisation of the diaphragm and intra-abdominal position of the stomach but also the liver can exclude the diagnosis of CDH. Moreover, the absence of peristaltic movements in the thorax is also helpful to differentiate a CCAM from a CDH. In case of doubt, differential diagnosis can be made easily using MRI.

CCAM has a broad spectrum of MRI findings, especially because this anomaly can present in 3 different ways. The presentation can range from a simple cyst to a homogeneous hyperintense solid mass adjacent to the normal lung parenchyma (Figure 19-7). Types I and III CCAM have image characteristics that can resemble a bronchogenic cyst or pulmonary sequestration, respectively. Hence, the differential diagnosis between these 2 lesions can pose a difficult challenge. The role of MRI in fetuses with CCAM lies mainly in the prognosis of the pathology, which will depend on the amount of lung hypoplasia that can be quantified using MRI. Another strength of MRI can be found in the good spatial resolution of this technique. It is known that a CCAM can diminish or even disappear during pregnancy with typical lower signal intensities on MRI.^21,25 Lower signal intensities can be a problem on sonography to localize the remaining CCAM. MRI has shown to be more accurate in detecting the residual lesion, and this information can be very important for postnatal management.²⁶

Prognosis of CCAM is variable and depends on the degree of impairment of lung development and fetal hemodynamics.²⁷ Isolated unilateral CCAM without hydrops is associated with a good prognosis. In about 60% of cases, the relative size of the fetal tumor remains stable; in 30% of cases there is antenatal shrinkage or resolution; and in 10% of cases there is progressive increase in mediastinal compression. Large intrathoracic cysts can lead to major mediastinal shift and associated hydrops. In affected patients, effective treatment can be carried out by the insertion of thoracoamniotic shunts. In the case of a large solid lesion causing hydrops, the prognosis may be improved by ultrasound-guided laser ablation of the feeding vessel.²⁸

In postnatal life, and in symptomatic neonates, thoracotomy and lobectomy are carried out and survival is about 90%. It is uncertain whether surgery is also needed for asymptomatic neonates.

Sequestration

A pulmonary sequestration represents only a minor part (6%) of congenital lung malformations detected in utero and is found in less than 1 per 50,000 births.^29-31 It is a mass of nonfunctioning lung tissue that has no communication with the normal bronchial tree in contradiction to a CCAM. Its origin can be explained by an accessory lung bud that develops from the ventral aspect of the primitive foregut. Another important difference with a CCAM is the presence of a systemic vascular supply mainly deriving from the abdominal aorta. The lesion is mostly located in the lower lobes and can be divided according to its site. The sequestration can be extralobar (25% of cases) or intralobar (75% of cases). An extralobar sequestration has its own pleural wrapping and venous drainage as opposed to an intralobar sequestration.

Pulmonary sequestrations are sonographically detected as a hyperechogenic mass, most frequently in the posterior part of the left lung. The use of color Doppler ultrasonography to detect the feeding systemic vessel from the thoracic or abdominal aorta permits a more definitive diagnosis (Figure 19-8). Large lung sequestration may form an arteriovenous fistula that causes high-output heart failure and hydrops. Intralobar sequestrations are usually isolated, whereas more than 50% of extralobar sequestrations are associated with other abnormalities, mainly CDH and cardiac defects.^32,33

With T2-weighted MR imaging, a sequestration is specified by a solid, well-defined hyperintense mass, in the same way as a CCAM. Fortunately, visualization of a feeding systemic vessel originating from the thoracic or abdominal aorta can confirm the diagnosis of a sequestration (Figure 19-9). The role of MRI is again in the search for remaining lesions since a sequestration involutes in utero even more frequently than a CCAM.²⁵

The prognosis of a sequestration is, like a CCAM, variable and depends on the degree of impairment of lung development and fetal hemodynamics. It can also give rise to prenatal complications, ie, torsion of the sequestration with secondary pleural effusion, or postnatal complications, ie, infection or rarely an esophago-bronchopulmonary malformation.³⁴ Postnatal outcome also depends on the presence of associated abnormalities. In general, intralobar sequestration has an excellent prognosis, whereas extralobar sequestration has a poor prognosis because of the high incidence of other defects and hydrops.^31,35 In the case of a large lesion with evidence of a hyperdynamic fetal circulation, the prognosis may be improved by ultrasound-guided laser ablation of the feeding vessel.³⁶

Bronchogenic Cyst

Bronchogenic cysts, arising from abnormal budding from the ventral foregut, are seldom diagnosed in utero. These cysts are mostly isolated along the tracheobronchial tree with a predilection for the region of the carina.

A bronchogenic cyst sonographically appears as an anechogenic structure in a normal lung parenchyma.

On the MRI study, it can be easily differentiated thanks to its markedly higher signal than the surrounding lung tissue on T2-weighted imaging (Figure 19-10). However, the value of MRI in these fetuses is limited except in cases when the cyst directly obstructs pulmonary structures.

In utero bronchogenic cysts rarely give rise to symptoms. These cysts can rarely communicate with the tracheobronchial tree and may result in air trapping and/or infection of the infant.³⁷

Congenital High Airway Obstruction

Congenital high airway obstruction (CHAOS) is characterized by an obstruction of the fetal airway involving the higher airways, ie, trachea or larynx. CHAOS is an extremely rare condition, found in about 1 per 50,000 births.^38,39 The obstruction can be due to a variety of causes including cyst(s) in the larynx, malformations that close off the trachea or larynx (atresia), or a narrowing of the glottis. This causes the lungs to enlarge, the tracheobronchial tree to dilate, and eventually may cause congestive heart failure resulting in fetal hydrops and polyhydramnios.

Ultrasound images reveal a hyperechogenic, hyperplastic bilateral lung structure with possible inversion of the diaphragm convexity and, often, fetal hydrops.³⁹

On MRI scan, CHAOS is characterized by enlarged lungs with increased signal intensity on T2-weighted imaging of the gross lung parenchyma (Figure 19-11). The diaphragm will become flattened due to pulmonary expansion. Because of airway obstruction, the trachea and/or bronchi will be filled with fluid (except in the case of a tracheoesophageal fistula) and will allow good contrast with the surrounding isointense mediastinal structures. One must diligently search for associated anomalies that are present in more than 50% of these fetuses.²³

A large type III CCAM can present in a similar way as CHAOS, especially when it only affects a single bronchus. Because MRI has excellent spatial resolution it accurately characterizes this malformation with respect to its anatomical boundaries.

CHAOS may require intervention even before the baby takes a first breath. This abnormality is associated with poor neonatal outcome and increased incidence of stillbirth.^39-41 CHAOS should be differentiated from bronchial atresia affecting only one lung (Figure 19-12).