Malformations

Prenatal diagnosis and fetal therapy for congenital lung malformations have evolved significantly since Adzick et al. described the near universal mortality of congenital pulmonary airway malformation (CPAM)-induced fetal hydrops almost three decades ago.⁴ Congenital BPMs represent 90% of lung lesions seen in clinical practice and include CPAMs, (formally called congenital cystic adenomatoid malformation or CCAM), bronchopulmonary sequestration (BPS), and congenital lobar emphysema (CLE).⁵ Other less common malformations are varied and are included in the classification system described by Langston et al.⁶ (Box 22-1), but will not be discussed in this chapter.

Prenatal ultrasonography (US) functions as a window into fetal development and is the most common mode of prenatal diagnosis of congenital thoracic abnormalities (Box 22-2). We routinely supplement ultrasound with magnetic resonance imaging (MRI) as a complementary method to further define the anatomy of the lesion and overall fetal morphology.^7,8 In combination, the two modalities allow accurate prenatal diagnosis of the different types of BPMs and exclude other anatomic anomalies.

Congenital Pulmonary Airway Malformation

CPAMs are the most commonly diagnosed BPM. The best estimate of the incidence of CPAM is 0.66 per 10,000 live births, but better studies are needed based on high quality prenatal imaging of all pregnancies in a study population.⁹ This heterogeneous group of congenital cystic and noncystic lung masses is characterized by an extensive overgrowth of immature primary bronchioles localized to a segment of the bronchial tree (Fig. 22-2).¹⁰ The current classification system defined by Stocker classifies CPAMs into five types that differ by location, cystic structure, size, and epithelial lining (Table 22-1). However, from a practical perspective, the prenatal classification of CPAMs is divided into two categories based on prenatal ultrasound findings: (1) macrocystic lesions containing a single or multiple cysts that are 5.0 mm in diameter or greater; and (2) microcystic lesions presenting as a solid echogenic mass on prenatal ultrasound (Fig. 22-3).⁴

In the prenatal period, ultrasound will usually demonstrate an area of hyperechogenic tissue with or without hypoechoic cysts that vary in number and size. Signs of mass effect may be seen, such as mediastinal shift, diaphragmatic eversion, and polyhydramnios. With very large lesions, heart failure (hydrops) due to mediastinal shift and cardiac compression can occur.¹¹ CPAMs receive their blood supply from the pulmonary artery and have pulmonary venous drainage. However, there is a subset of CPAMs, known as hybrid lesions, where the blood supply also includes an anomalous systemic artery.¹² These lesions demonstrate anatomic and histologic features of both CPAMs and BPS.

The diagnosis of CPAMs by an experienced sonographer is usually straightforward. However, there are specific entities that are commonly misdiagnosed (Table 22-2). A skilled sonographer can usually easily differentiate these lesions by understanding the blood supply (congenital diaphragmatic hernia [CDH], lung agenesis, BPS), observation of bowel peristalsis (CDH), documentation of the absence of one lung (lung agenesis), or visualization of bronchial dilation (bronchial atresia, congenital high airway obstruction syndrome [CHAOS]). MRI is also a useful adjunct for differentiating these entities. In our opinion, it should be applied routinely in fetal diagnostic centers.

Bronchopulmonary Sequestration

Bronchopulmonary sequestrations comprise approximately 10% of prenatally diagnosed BPMs, and are characterized by a portion of the lung that does not connect to the tracheobronchial tree. These lesions have a systemic arterial supply that can arise from the aorta or various systemic arterial branches above or below the diaphragm, and may have systemic or pulmonary venous return. Two different types of sequestration are described: intralobar (ILS) and extralobar (ELS) which differ in their prenatal and postnatal characteristics. An ILS shares visceral pleural investment with normal lung and drains into the pulmonary venous system while an ELS has a separate pleural investment and may have either systemic or pulmonary venous drainage.13,14

ELS is seen as a homogeneous hyperechoic mass in a paraspinal location, most often in the left lower thorax (Fig. 22-4). The pathogenesis is related to a supernumerary lobe developing from abnormal budding early in foregut embryogenesis.¹⁵ If the bud arises before the development of the pleura, it is invested with the adjacent lung and becomes an ILS. If the bud develops after visceral pleural formation, it grows separately and acquires its own pleural covering.¹⁴ It is important to appreciate that ELS can be found at any level in the pleural space and are also found within or beneath the diaphragm (see Fig. 22-4B).¹⁵ The major feature that helps discriminate an ELS from a CPAM is the blood supply derived from the systemic circulation with systemic venous drainage identified by Doppler ultrasound or MRI. However, it is important to appreciate that some anatomic ELSs can contain visible cysts that ultimately are shown to have CPAM histology (Fig. 22-5). In addition, an ELS can occasionally have venous drainage via a large venous channel draining directly into a pulmonary vein that is usually identified as aberrant venous drainage by imaging studies.

In contrast to ELS, ILS routinely has pulmonary venous drainage and has variable degrees of hyperechogenicity by ultrasound or MRI. They are uniformly associated with the lower lobes and are distinguishable from the microcystic hybrid lesions described previously only by the absence of pulmonary arterial inflow. Careful Doppler ultrasound identification of the arterial inflow to these lesions is required to definitively distinguish between a microcystic hybrid CPAM and an ILS prenatally. Finally, an ILS can be difficult to distinguish from a systemic to pulmonary vascular malformation where the bronchial anatomy and pulmonary parenchyma are relatively normal, but there is an aberrant systemic blood supply coursing through a vascular network within normal parenchyma with venous drainage into the pulmonary vein. The subtleties of prenatal diagnosis of these lesions are consistent with a continuum of developmental pathogenesis. It should be emphasized that postnatal computed tomography (CT) should be obtained in all patients to confirm the anatomy and to aid in management. The final diagnosis will depend on the anatomy found at postnatal resection as well as the histologic analysis, and is frequently a combination of the classifications previously described.

Congenital Lobar Emphysema

CLE is a condition characterized by overinflation and distension of one or more pulmonary lobes with compression of the adjacent lung. In 50% of cases, the cause is unknown. In the remaining 50%, it may result from dysplastic bronchial cartilage, endobronchial obstruction, extrinsic compression from aberrant cardiopulmonary vasculature, or diffuse bronchial abnormalities related to infection.¹⁶ In the fetus, amniotic fluid trapping is analogous to air trapping and can lead to lobar expansion. The left upper lobe is the most frequently affected, followed by right middle and upper lobes, with rare bilateral or multifocal involvement. CLE is most commonly diagnosed in the neonate or infant presenting with respiratory distress.

Prenatal discrimination between CLE and CPAM or bronchial atresia may be difficult, but the absence of a systemic vascular supply differentiates this lesion from an ELS. Although complications such as polyhydramnios and hydrops have not been reported with CLE, perinatal respiratory distress correlates with the prenatal size of the lesion as manifest by mediastinal shift or compression of adjacent lung parenchyma.¹⁷

Bronchogenic Cysts and Bronchial Atresia/Stenosis

Bronchogenic cysts develop from abnormal budding of the tracheal diverticulum or the ventral aspect of the primitive foregut, which is not followed by bronchial development or branching. The result is a cavity that may or may not communicate with the airway and can be found in a variety of locations depending on the location of abnormal budding during foregut development. Histologically, these lesions are thin walled and have a bronchial epithelial lining, and are filled with mucus.¹⁸ Prenatal diagnosis of these lesions is usually made by ultrasound where they may be seen as an isolated cystic structure in the mediastinum, or causing bronchial obstruction with findings of bronchial dilation and lung hyperplasia distal to the point of obstruction. Bronchial atresia without a bronchogenic cyst also results in hyperplasia distal to the level of obstruction and is frequently associated with mucocele formation. The presence of dilated bronchi indicates a diagnosis of atresia rather than microcystic CPAM. The more proximal the atresia, the greater the potential for mass effect manifest by mediastinal shift, and ultimately, fetal hydrops. Segmental bronchial stenosis/atresia is a relatively recently recognized abnormality characterized by an echogenic segment of lung on ultrasound that is indistinguishable from and usually diagnosed as a microcystic CPAM.¹⁹

Congenital Pulmonary Airway Malformation

Experience with serial imaging of large numbers of fetuses with CPAMs has clarified the pre- and perinatal natural history of this anomaly. There is a typical pattern of growth of a CPAM with a period of growth relative to the size of the fetus until approximately 26 weeks gestation at which time growth plateaus. After 28 weeks, the CPAM typically gets smaller relative to the size of the fetus as measured by the CPAM volume ratio or CVR. The CVR is calculated by dividing the volume of the CPAM (length × height × width × 0.52) by the head circumference. In addition, the CVR has proven on retrospective and prospective assessment to be the most useful predictor for the development of hydrops.²⁰