Key Points
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A limited number of congenital malformations of the respiratory tract can be identified directly by prenatal sonography.
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These malformations should be described systematically because definitive diagnosis requires histologic examination.
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The identification of subtle lesions that have no detrimental effect on a fetus or postnatal respiratory function is increasingly common.
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A lack of evidence surrounding the natural history of asymptomatic cystic lung lesions has resulted in highly divergent postnatal management strategies.
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A conservative approach to postnatal management of asymptomatic cases is a reasonable option.
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Careful prenatal counselling is recommended.
Congenital Malformations of the Respiratory Tract
Embryologic development of the respiratory tract requires the appropriate growth of the upper airway and the six ‘trees’ that make up the lower respiratory tract – bronchial, arterial (systemic and pulmonary), venous (systemic and pulmonary) and lymphatic – together with a normal thoracic volume, a normal thoracic skeletal structure and normal neuromuscular function.
Defects in any of these elements (except the systemic venous system because there are none known) can affect anatomical organisation resulting in a variety of congenital abnormalities. Whereas some lesions can be detected by direct prenatal sonographic visualisation, other lesions are suspected because of the presence of nonspecific findings (e.g., mediastinal shift) or form part of a more generalised genetic syndrome, for example, the pulmonary hypoplasia seen in skeletal dysplasias such asphyxiating thoracic dystrophy. Other congenital malformations of the lungs only become apparent in the postnatal period when they cause symptoms.
Not all congenital malformations have a detrimental impact on a fetus or postnatal respiratory function. Advances in sonographic technology allow prenatal detection of subtle lesions which may have no immediate clinical impact. A lack of evidence surrounding the natural history of asymptomatic cystic lung lesions has resulted in divergent postnatal management strategies and difficult prenatal counseling.
In this chapter, we will identify thoracic malformations, excluding congenital diaphragmatic hernia (covered in Chapter 31 ), that can be detected directly on prenatal sonography, describe a system to classify these lesions sonographically, define their salient pathological features and discuss the merits of prenatal and postnatal management options.
Thoracic Malformations Detected on Prenatal Ultrasound
Thoracic malformations detectable on prenatal sonography are detailed in Table 30.1 ; however, a definitive diagnosis of these lesions (excluding congenital diaphragmatic hernia (CDH)) requires histologic confirmation. A prenatal or postnatal diagnosis is not possible by radiologic means alone. The imaging appearance of different types of lesions can be identical, rendering specific pathological diagnoses redundant and risking confusion in communication between medical professionals and families. Moreover, it is now apparent that there can be considerable overlap in histologic features within lesions, further highlighting the increasing complexity of diagnosis and the limitations of diagnosis based on imaging modalities alone.
| Macrocystic Lesions |
| Congenital pulmonary airway malformation |
| Bronchogenic cyst or enteric cyst |
| Congenital diaphragmatic hernia |
| Bronchial atresia |
| Congenital lobar emphysema |
| Pleuropulmonary blastoma |
| Microcystic Lesions |
| Congenital pulmonary airway malformation |
| Pulmonary sequestration |
| Pleural effusion |
| Tracheal or laryngeal atresia |
| Pulmonary hypoplasia or agenesis |
| Mediastinal teratoma |
| Rhabdomyoma |
| Ectopia |
In light of these difficulties, a system whereby malformations detected by prenatal sonography are described meticulously in simple language, based on their appearance, and without the presumption of a single pathological diagnosis has been recommended. Within this system, all thoracic malformations are described under the umbrella term congenital thoracic malformation (CTM). Malformations are then defined further using descriptive terms, including the presence and size of cysts, the presence of a feeding vessel, the degree of echogenicity, the presence or absence of mediastinal shift, polyhydramnios and the presence of anomalies in other systems. In practical terms, lesions have been most usefully classified sonographically as either macrocystic or microcystic (see Table 30.1 ).
Detection of CTMs, often at the routine 20-week anomaly scan, allows detailed planning of further prenatal management, including serial sonographic monitoring, delineation of the lesion and intrauterine therapeutic interventions if required. Planning for appropriate neonatal support on delivery can be prepared in advance. The exception to this pattern are pleural effusions, which often present later when scanning is undertaken because of a suspicion of increased amniotic fluid or as an incidental finding on ultrasound (USS) undertaken during the third trimester.
The appeal of enhanced prenatal radiologic definition of lung CTMs has led to the exploration of magnetic resonance imaging (MRI) as an additional modality. MRI has been used in the delineation of fetal lung lesions and the identification of feeding vessels, although this is readily done using Doppler ultrasound. Whether this enhanced imaging provides any additional information of practical value over ultrasound alone has yet to be determined, and in most centres at present, MRI is not part of routine practice.
Macrocystic Lung Lesions
Macrocytic lung lesions include congenital pulmonary airway malformations (CPAMs), bronchogenic cysts, enteric cysts, bronchial atresia and congenital lobar emphysema (see Table 30.1 ). The sonographic appearance includes a cystic lesion(s) of varying size in the thorax with or without mediastinal shift ( Fig. 30.1 ). An essential differential diagnosis to consider on identification of a macrocystic lung lesion is a left-sided diaphragmatic hernia, in which the stomach or bowel herniated into the thorax can be mistaken for a cystic structure. The crucial importance of this differentiation is the subsequent management strategy for CDH, particularly the place of delivery, associations with chromosomal abnormalities and genetic syndromes and general prognosis. Additional sonographic features that assist in the correct identification of a CDH include the absence of a stomach within the abdomen, the visualisation of peristalsis within the thorax, the paradoxical movement of abdominal viscera within the thorax during fetal breathing movements and absence of a diaphragm. However, differentiation can remain difficult on occasion. In a case series of 110 fetuses diagnosed with a CTM, two were later identified as having a diaphragmatic hernia, both after serial prenatal scanning.
Congenital Pulmonary Airway Malformations
Congenital pulmonary airway malformations were previously known as congenital cystic adenomatoid malformations (CCAM). In 2002, Stocker recommended the term CPAM as being preferable to the term congenital cystic adenomatoid malformation because not all types of CPAM are cystic and adenomatoid. The new terminology enables a better description of the entity’s alterations. For example, type 0 is not a cystic lesion, and types 0, 1 and 4 are not adenomatoid lesions.
Congenital pulmonary airway malformations represent the most common cystic lesions diagnosed on prenatal ultrasound. Currently, the best estimate of incidence reported by the European Surveillance of Congenital Anomalies (EUROCAT) is 0.94 in 10 000 live births. Although CPAMs can be defined as macrocystic or microcystic, both types are described in this section.
Opinions vary as to the aetiology of these lesions. Genetic abnormalities that may influence normal lung development or external insults disrupting lung growth have been postulated.
The subclassification of CPAM types remains contentious. Various systems of classification have been proposed with the most widely accepted that of Stocker. Within this system, CPAMs are classified into five types according to the level of the bronchial tree at which the defect is thought to have occurred. The strength of this classification is that specific neoplasms are associated with specific CPAM subgroups; however, these are not distinguishable with prenatal ultrasound, and postnatal histologic examination is required. There can be significant histologic overlap of lesions previously considered distinct (e.g., hybrid forms of CPAM, pulmonary sequestration (PS) and bronchial atresia).
Type 0 or acinar dysplasia
This is a rare type of CPAM and is thought to develop at the level of the bronchus. On histologic examination, bronchial airways are present, but the distal parenchyma is highly unusual and consists mainly of mesenchymal tissue. Macroscopically, the lungs are small, and the condition is not compatible with life. The condition is also termed acinar dysplasia.
Type 1
This is the most common type of CPAM, accounting for approximately 60% to 70% of cases. and thought to develop at the bronchial/bronchiolar level. The cysts range in diameter up to 10 cm, with at least one cyst more than 2 cm in diameter required for diagnosis. They are lined with pseudostratified ciliated columnar epithelium, with mucous cell proliferation also present on occasion.
Type 2
These are less common than type 1 CPAMs, accounting for 15% to 20% of cases, and are thought to arise at the bronchiolar level. Lesions typically consist of multiple small cysts which range in size but must be less than 2 cm in diameter for diagnosis. The cysts are related to dilated bronchiole-like structures and are surrounded by simplified alveolar tissue. These lesions can be associated with other congenital abnormalities such as renal agenesis or dysplasia as well as cardiovascular and neurologic abnormalities.
Type 3 or lung hyperplasia
These are a rare type of CPAM, accounting for 5% to 10% of cases thought to arise at the bronchiolar/alveolar duct level. Their inclusion as a CPAM is controversial because the microscopic features of excess bronchiolar ducts and parenchyma typical of fetal lung is considered by some pathologists to represent lung hyperplasia. The lesions can be large and affect an entire lobe with consequent compression of surrounding lung tissue.
Type 4 or regressed pleuropulmonary blastoma
These are very rare lesions and the most controversial of the CPAM diagnoses. The cysts can be large and are impossible to distinguish radiologically from type 1 CPAMs. On histologic examination, however, the cysts are lined with alveolar or bronchiolar epithelial cells upon mesenchymal tissue. The only difference between this lesion and a pleuropulmonary blastoma (PPB) is the absence of blastema. Some argue that these lesions in fact represent a regressed neoplasm rather than a form of CPAM.
Bronchial Atresia
Bronchial atresia describes interruption of a lobar, segmental or subsegmental bronchus either caused by discontinuity or membranous interruption. It results in the cystic degeneration of the distal lung parenchyma likely caused by accumulation of obstructed fetal lung fluid. As previously stated, CPAMs are also thought to originate from a spectrum of bronchial defects, and bronchial atresia may also lie along this spectrum. Indeed, evidence of bronchial atresia is often identified in hybrid association with CPAMs and PS. Despite complete interruption of the bronchus, the distal lung can fill with air in the postnatal period and even become hyperinflated, although the mechanism is not well understood. Prenatally, there may be a cystic appearance or just mediastinal shift.
Bronchogenic Cysts and Enteric Cysts (Duplication Cysts)
The embryonic lung develops from an outgrowth of the primitive foregut. Disruption of this division can result in the formation of cystic structures broadly termed foregut cysts . Subdivision of these cysts can be made on the basis of their histology.
Bronchogenic cysts have histologic features in keeping with the primitive airway and are commonly identified as single cysts within the mediastinum but may be situated anywhere along the bronchial tree or even in extrathoracic locations. They typically present as a single cyst and are lined with respiratory-type epithelium and contain cartilage in the wall on histologic examination. Clinical manifestations are most commonly attributable to airway compression but cysts may also act as a nidus of infection and bleeding.
In contrast to bronchogenic cysts, enteric cysts have histologic features differentiated towards the gut rather than the bronchus. They can be subdivided according to where they occur along the gastrointestinal (GI) tract. Cysts arising from the oesophagus are termed oesophageal cysts, and cysts arising at a distal point along the GI tract are termed gastroenteric. Malignant change has been described in enteric cysts.
Congenital Lobar Emphysema
This lesion is characterised by hyperinflation of a lobe or segment of the lung and ordinarily presents in a neonate or infant with respiratory distress. Occasionally, it is detected prenatally as an apparent macrocystic lesion on ultrasound or the cause of a profound mediastinal shift. Partial airway obstruction caused by a mucosal flap, twisting of the lobe on its pedicle or a defect in bronchial cartilage results in air trapping. Presumably, the prenatal features, when present, are also a result of partial bronchial obstruction and the accumulation of lung fluid. Histologically, a normal number of distended and sometimes ruptured alveoli are demonstrated. Rarely, there are increased alveolar counts, which has been termed polyalveolar lobe .
Microcystic Lung Lesions
Congenital Pulmonary Airway Malformation
Microcystic CPAMs appear as a uniformly hyperechogenic lesion in the chest on prenatal USS ( Fig. 30.2 ). As with macrocystic lesions, they can be associated with mediastinal shift and hydrops.
Pulmonary Sequestration
Pulmonary sequestrations are defined as isolated areas of lung tissue that do not communicate with the bronchial tree of the normal lung and receive a blood supply from a systemic vessel. They are subdivided into two groups: intralobar, in which the lesion lies within the visceral pleura, and extralobar, in which the sequestration is invested in its own pleura. There can be considerable histologic overlap with features of type 2 CPAMs and bronchial atresia, and in common with these other cystic lesions, the aetiology of PS is not understood.
Many sequestrations present as an echogenic mass in the fetal chest or abdomen at the 20-week anomaly scan. Intralobar sequestrations are typically identified in the left lower lobe, and extralobar lesions are identified beneath the left lower lobe or within the abdomen. Doppler ultrasound can be used to identify the blood supply ( Fig. 30.3 ). Some sequestrations communicate directly with the GI tract, most commonly the lower oesophagus and stomach. Careful monitoring prenatally is required, particularly if there are signs of hydrops as the anomalous blood supply can result in cardiac failure.
Laryngeal or Tracheal Atresia
During embryogenesis, the epithelial lining of both the larynx and trachea is derived from the endoderm. As the endoderm proliferates, occlusion of the lumen of the larynx and trachea occurs followed by recanalization at approximately 10 weeks’ gestation. Failure of recanalization can be partial or complete, with complete failure associated with laryngeal or tracheal atresia and partial failure associated with laryngeal webs.
Laryngeal and tracheal atresia are rare malformations but should be considered if bilateral enlarged and hyperechogenic lungs are present on ultrasound of the fetus. Careful ultrasound examination may reveal a dilated trachea below the level of the obstruction ( Fig. 30.4 ). The mass effect of the distended lungs results in the other typical radiologic features of mediastinal compression and convexity of the diaphragms. Nonspecific features such as polyhydramnios and fetal hydrops may also be evident. Although these lesions can be isolated, they may also be part of a genetic syndrome (e.g., Fraser syndrome), mandating detailed fetal anomaly scanning and genetic investigations if deemed appropriate.
Pulmonary Hypoplasia and Agenesis
Pulmonary hypoplasia and pulmonary agenesis are related malformations characterised by a spectrum of lung parenchymal underdevelopment. Whereas pulmonary agenesis lies at the extreme end of the spectrum with complete absence of lung parenchymal tissue, pulmonary hypoplasia is defined by diminished numbers of airways and alveoli resulting in a reduced lung size. The features for both malformations may be unilateral or bilateral.
The lesions are thought to result from insults during lung embryogenesis, the timing of which relates to the point on the spectrum of the clinical features. Complete agenesis of one or both lungs is exceptionally rare and is often associated with other congenital abnormalities (e.g., scimitar syndrome associated with anomalous pulmonary venous return). The remaining lung in unilateral agenesis is hypertrophied and causes mediastinal shift.
Pulmonary hypoplasia is a more frequent finding and is characterised by reduced lung volume on prenatal ultrasound with the appearance of a small chest or increased heart:lung ratio. Associated congenital abnormalities are present in at least 50% of cases. The pathogenesis might include:
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A deficiency in the thoracic volume inhibiting normal lung growth, such as may be seen in skeletal dysplasias associated with short ribs, in which the rib size restricts pulmonary growth
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A deficiency in fetal breathing movements inhibiting normal lung development, as in the fetal akinesia deformation sequence (e.g., Pena Shokeir syndrome type 1) in which a general lack of movement and minimal or no breathing or swallowing movements inhibits normal lung development ( Fig. 30.5 )
