Fetal lung development can be categorized into the embryonic, pseudoglandular, canalicular, and saccular phases.¹ Embryonic development begins at 24 to 26 days gestation when a diverticulum arises from the ventral wall of the foregut. Over the next 2 days, the right and left lung buds arise from this diverticulum. The developing airways become separated from the esophageal portion of the foregut by ingrowths of adjacent mesoderm that form the tracheoesophageal septum. The lung buds elongate into primary lung sacs, and the 5 secondary bronchi develop as outgrowths of the primary bronchi. This completes the embryonic period, at approximately the end of the fifth week.

The pseudoglandular phase predominantly consists of development of the bronchial tree. During this phase, the airways are blind tubules lined with columnar or cuboidal epithelium. The pseudoglandular phase occurs between the fifth and 16th weeks of gestation. Nearly all of the conducting airways are present by the end of the pseudoglandular phase.

The canalicular phase represents the early stage of development of transitional airways. There is decrease in mesenchymal tissue within the developing lungs, and newly formed capillaries and air spaces approximate one another. The canalicular phase occurs between the 17th week and the 25th to 28th weeks.

The saccular (or alveolar) phase relates to development of the alveoli. Defined acinar morphology is present by the 28th week of gestation. During the final weeks of fetal development, there is prolific development of alveoli. Alveolar development continues in postnatal life to approximately the age of 8 years.

Tracheal cartilage development predominantly occurs during the pseudoglandular and canalicular periods. Initial cartilage development occurs during the seventh to eighth weeks of gestation. Bronchial cartilage development occurs in a centrifugal direction.

Anomalies of the lung related to abnormal bronchopulmonary (lung bud) development include agenesis, bronchial atresia, tracheal atresia, some instances of congenital lobar emphysema, congenital cystic adenomatoid malformation, pulmonary bronchogenic cyst, tracheal bronchus, and accessory cardiac bronchus. The pathogenesis of bronchogenic cysts apparently involves abnormal epithelial budding caused by local defects in the mesenchymal substrate.² The faulty development that results in cystic adenomatoid malformation occurs later in gestation, and is characterized by disordered development of the bronchioles and failure of differentiation of the epithelium into a mature form. This may be related to faulty signaling between the bronchioles and peribronchial mesenchyme during the period of active bronchial development, which occurs between the fifth and eighth weeks.³ The developmental mechanism of pulmonary sequestration involves both abnormal bronchial budding (supernumerary budding from the foregut, or pinching off from the developing bronchial tree) and failure of normal mesenchymal maturation (persistent systemic arterial supply).^4,5 Congenital lobar emphysema can be caused by any developmental abnormality that results in lobar air trapping, such as a focal anomaly of airway cartilage, intrinsic or extrinsic bronchial obstruction, or abnormal supporting stroma of the alveolar wall.^6,7

A spectrum of anomalies results from arrested development of lung; this is termed the agenesis-hypoplasia complex. The temporal stage of the arrested development is an important determining factor in the nature of the resultant anomaly. The patterns include agenesis (absence of bronchus and lung), aplasia (absence of lung, but preserved bronchus), and hypoplasia (rudimentary bronchus and lung). The agenesis-hypoplasia complex most often involves an entire lung or lobe (hypogenetic lung syndrome). Developmental arrest occasionally occurs at the segmental level. Segmental bronchial agenesis most often involves the right upper lobe.^8,9

The pulmonary arteries develop from the sixth aortic arch. The proximal part of the sixth aortic arch becomes the proximal segments of the right and left pulmonary arteries. On the left, the connection with the arch is maintained as the ductus arteriosus. Pulmonary arterial development parallels that of the airways during fetal development. Postnatal development results in increase in peripheral vessel branching commensurate with alveolar development until approximately 8 years of age. Anomalies of pulmonary artery development include agenesis, hypoplasia, anomalous systemic connection, and arteriovenous malformation.

During the embryonic phase of fetal development, pulmonary venous blood drains from the splanchnic plexus into the primordium of the systemic venous system. Pulmonary venous development begins with caudal and cranial outpouchings of the sinoatrial regions of the heart. These extend toward the lung buds. The caudal outpouching regresses. The cranial portion develops as the common pulmonary vein. Eventually, the common pulmonary vein incorporates into the left atrial wall. Residual splanchnic pulmonary connections regress. This leaves 4 independent pulmonary veins entering the left atrium. Potential pulmonary venous anomalies include pulmonary varix, systemic connection, and agenesis.

Congenital lung malformations comprise a heterogeneous and overlapping group of anomalies (Table 1-1). The terminology applied to these lesions is often imprecise. There is overlap of the embryological, pathological, clinical, and radiological features of these various lesions. A number of classification schemes have been proposed in an attempt to provide order to the sometimes confusing array of anomalies. Many investigators consider lung anomalies to represent a spectrum of pulmonary and vascular mal-development.¹⁰ Bush proposed simplified nomenclature based on the gross anatomy and imaging appearance. The 5 major categories in this system consist of a congenitally enlarged hyperlucent lobe, congenital thoracic malformations, a congenitally small lung, absent lung, absent trachea, and absent bronchus.¹¹ Langston has developed a classification system based on the pathologic features and presumed embryogenesis. Table 1-1 is adapted from this system. Langston emphasizes the importance of developmental airway obstruction in the pathogenesis of multiple seemingly unrelated lung malformations.¹²

Pulmonary Agenesis and Aplasia

Pulmonary agenesis is the complete absence of lung parenchyma, vessels, and bronchial structures in a lung, a lobe, or (rarely) both lungs. Pulmonary aplasia represents the same constellation of findings except that a rudimentary bronchus is present. Pulmonary agenesis and aplasia result from a developmental abnormality at approximately 4 weeks of gestational age. The anomaly usually involves an entire lung. The left upper lobe is the most common site of lobar agenesis/aplasia. The contralateral lung typically has compensatory enlargement, but is otherwise normal. Morbidity and mortality are greater in those patients with right lung agenesis than in those with involvement of the left lung, presumably as a result of more pronounced mediastinal shift and concomitant torsion of the great vessels and major airways.

More than 50% of children with pulmonary agenesis or aplasia have coexistent congenital anomalies of the cardiovascular, gastrointestinal, skeletal, or genitourinary systems. Patent ductus arteriosus and patent foramen ovale are the most common cardiovascular anomalies in these children. The associated skeletal anomalies of the limbs and spine tend to be ipsilateral to the lung abnormality. Ipsilateral radial ray defects and hemifacial microsomia can occur in association with pulmonary agenesis. Severe cardiac anomalies are more common in patients with agenesis of the right lung than with agenesis of the left lung.^13,14

Symptomatic children with agenesis of a lung often have anatomic distortion of the airway and vascular compression. In some patients, there is intrinsic airway stenosis. Symptomatic newborns exhibit manifestations of respiratory distress: tachypnea, cyanosis, and impaired gas exchange.

Imaging studies demonstrate shift of normal lung to fill the void created by agenesis or aplasia. There is marked mediastinal shift and the contralateral lung bulges across the midline (Figure 1-1). The severity of contralateral lung herniation varies between patients. If the left lung is absent, the right cardiomediastinal border sometimes produces a sharp perpendicular line adjacent to the left margin of the sternum as viewed on a frontal radiograph. With agenesis of the right lung, the left cardiomediastinal border is shifted to the right of the sternum and the entire cardiac silhouette is contiguous with that of the liver (Figure 1-2). The ribs are crowded together on the side of the absent lung. Bronchography and bronchoscopy demonstrate absence of the main bronchus in patients with agenesis. Cross-sectional imaging with MR or helical CT shows absence of lung parenchyma, bronchial structures, and pulmonary and bronchial vessels on the affected side. These studies are also valuable for documenting secondary effects on the airway and mediastinal vessels. The imaging appearance of pulmonary aplasia is identical to that of agenesis except that a rudimentary bronchus is present.^15,16

The radiographic findings of lobar agenesis/aplasia are subtle. Most often, the ipsilateral lung is small and the remaining lobes are hyperinflated. There may be an abnormal density in the region of the involved lobe that mimics atelectasis. Agenesis of the right middle lobe and right upper lobe or of the left upper lobe results in a retrosternal density that parallels the anterior chest wall on lateral radiographs. At times, the radiographic appearance of lobar agenesis mimics that of lobar collapse. If the standard radiographic findings are inconclusive, computed tomography is diagnostic. MR can be helpful to demonstrate secondary airway abnormalities, and to define the mediastinal vascular anatomy.^15,16

Pulmonary Hypoplasia

The definition of pulmonary hypoplasia is deficient or incomplete development of the lung, such that there is decreased size of the lung and a diminished number of functioning pulmonary units (i.e., cells, airways, and alveoli). Both lungs are involved in most patients with pulmonary hypoplasia. Unilateral or lobar forms also occur, usually associated with anomalies of the ipsilateral pulmonary artery and pulmonary veins. Bilateral pulmonary hypoplasia typically causes severe, often fatal, neonatal respiratory distress.^17,18

Pulmonary hypoplasia occurs as a primary lesion in 10% to 15% of cases. The more common secondary form is associated with one or more other conditions that directly or indirectly interfere with lung development, usually by compromising the thoracic space available for lung growth. Intrathoracic lesions are most common; these include congenital diaphragmatic hernia, extralobar sequestration, agenesis of the diaphragm, and a large fetal pleural effusion or chylothorax. Asphyxiating thoracic dystrophy (Jeune syndrome) is an example of a thoracic cage anomaly that compromises fetal lung development. Others include short-rib polydactyly syndromes, metatrophic dysplasia, Ellis-van Creveld syndrome, achondrogenesis, and severe forms of osteogenesis imperfecta. Extrathoracic causes of pulmonary hypoplasia include oligohydramnios (e.g., renal agenesis, severe urinary tract obstruction) and abdominal distention (e.g., ascites, polycystic kidney disease). Diminished pulmonary vascular perfusion as a result of a cardiac or vascular anomaly can also lead to pulmonary hypoplasia.¹⁴

The clinical presentation of pulmonary hypoplasia varies according to the severity of the anomaly. Most often, there are manifestations of respiratory distress in the newborn, with cyanosis, tachypnea, hypoxia, hypercapnia, and acidosis. With severe bilateral involvement, there may be rapid progression to death from severe hypoxemia. The small lungs are difficult to ventilate, and complications of mechanical ventilation are common; these include pulmonary interstitial emphysema, pneumothorax, pneumomediastinum, and pneumopericardium. Pneumothorax can also develop spontaneously in these infants.

The radiographic diagnosis of bilateral pulmonary hypoplasia is sometimes difficult. Lung aeration can initially appear normal on chest radiographs. The small size of the lungs may not be appreciated until serial radiographs show that the appearance is persistent. The thoracic cage is usually small and the diaphragm is elevated (Figure 1-3).

Unilateral pulmonary hypoplasia appears radiographically as a small, but well aerated, lung. The ipsilateral pulmonary artery is small or absent. Occasionally, an anomalous draining pulmonary vein is visible (e.g., scimitar syndrome). The hypoplastic lung is oligemic, and blood flow to the contralateral lung may be increased. The mediastinum is deviated toward the side of the hypoplasia; this is accentuated during inspiration (Figure 1-4). The radiographic differential diagnosis includes hypogenetic lung syndrome, Swyer-James McLeod syndrome, and unilateral absence of the pulmonary artery. Occasionally, there is cystic distention of the hypoplastic lung (possibly as a result of a developmental defect at the bronchial-alveolar junction), resulting in an appearance that overlaps that of congenital cystic adenomatoid malformation.

The early prenatal detection of clinically significant pulmonary hypoplasia is helpful for parental counseling and planning for optimal perinatal management. Techniques for assessing the fetus with suspected pulmonary hypoplasia include various measurements based on sonography and MRI. Sonographic measurements that can be useful include the ratio of fetal lung area to thoracic area, the ratio of thoracic circumference to abdominal circumference, and the ratio of lung area to thoracic area. MR allows estimation of the fetal lung volume, which can be compared to the expected values for the gestational age or evaluated as a ratio of lung volume to estimated body weight.^19–21

Potter syndrome refers to a constellation of findings that occur with bilateral renal agenesis and other conditions that cause severely diminished urine excretion in utero. The findings include severe pulmonary hypoplasia, oligohydramnios, and dysmorphic features. The bilateral pulmonary hypoplasia in these infants usually results in death soon after birth. Potter syndrome occurs in approximately 1 in 3000 livebirths. The newborn with Potter syndrome has characteristic features that include hypertelorism, epicanthic folds, low-set ears, a flattened nose, micrognathia, and limb anomalies; the facial appearance in these children is termed Potter facies.²²

Many clinicians also use the term Potter syndrome to refer to similar, but not necessarily lethal, features of infants who are the products of pregnancies in which there is severe oligohydramnios from causes other than bilateral renal agenesis. A more proper term in this situation is Potter phenotype. These mimicking conditions account for approximately 80% of newborns with manifestations of the Potter phenotype. These abnormalities include cystic renal dysplasia, severe obstructive uropathy, autosomal recessive polycystic kidney disease, renal hypoplasia, medullary dysplasia, and Denys-Drash syndrome.^23–25

Bronchial Atresia

Bronchial atresia is a focal obliteration of a proximal segmental or subsegmental bronchus. The pathogenesis of bronchial atresia is unknown, but apparently involves an insult to a formed bronchus rather than a primary developmental failure. One potential mechanism is an interruption of the arterial supply of a developing fetal bronchus, with subsequent ischemia and scarring or discontinuity between the cells at the tip of the bronchial bud and the more proximal aspect of the developing bronchus. Despite the presence of an atretic bronchial segment, the distal branches can develop normally. Typically, the abnormality involves segmental bronchi at or near their origins; however, lobar or subsegmental bronchi can also be involved. The most common site is the apical posterior bronchus of the left upper lobe. Other potential sites include the segmental bronchi of the right upper lobe, right middle lobe, and right lower lobe.^12,26

At the parahilar margin of the affected portion of the lung, a segment of the bronchus immediately distal to the atresia is dilated and filled with mucous; this is the bronchocele (mucocele) that is a characteristic feature of bronchial atresia. The cystic, blindly terminating, mucus-filled bronchocele does not connect to the main bronchial tree. The more distal bronchi are filled with mucous, but otherwise are relatively normal. The alveoli in the lobe or segment distal to the atretic bronchus are ventilated by collateral pathways, and this portion of the lung becomes hyperinflated and noncollapsible. Occasionally, there is associated microcystic parenchymal maldevelopment.

Most patients with bronchial atresia are asymptomatic. Recurrent lung infections can occur. Other potential clinical findings include dyspnea and manifestations of bronchial asthma. Pectus excavatum is sometimes associated with bronchial atresia, possibly because of costosternal retraction during the efforts to overcome the airway obstruction caused by encroachment on normal lung tissue by the hyperinflated segments. Spontaneous pneumothorax occasionally occurs as a complication of bronchial atresia.²⁷

Chest radiographs of children with bronchial atresia show a hyperinflated lobe or segment, and a round or lobulated parahilar mass (the bronchocele) (Figure 1-5). The parahilar mass may appear solid or cystic, and it sometimes has a branching character. The mass represents dilated mucous-filled bronchi distal to the obstruction. The appearance of the parahilar mass is termed the mucoid impaction sign. The portion of lung distal to the mass is hyperinflated. The involved lung is also oligemic, a result of intrapulmonary vascular compression and hypoxic vasoconstriction. Expiratory CT is particularly useful for demonstrating the hyperinflated portion of involved lung, as well as the central branching bronchocele that has attenuation characteristics of soft tissue or fluid. With MRI, the bronchocele appears as a branching structure radiating from the hilum, with high signal intensity on both T1-weighted and T2-weighted images.^14,28–32

On prenatal sonography, the portion of lung involved with bronchial atresia appears enlarged and hyperechoic. Enlarged branching central bronchi may be visible. There is sometimes a cystic character. The pathologic anatomy can also be demonstrated with fetal MR. In the neonate, bronchial atresia appears as a radiographically opaque segment or lobe, due to retention of fetal alveolar fluid.^33–35

The radiographic differential diagnosis of bronchial atresia includes allergic bronchopulmonary aspergillosis, cystic bronchiectasis, bronchogenic cyst, and intrapulmonary sequestration (bronchial atresia with systemic vascular connection). Any acquired lesion that causes proximal airway obstruction and focal air trapping can have a radiographic appearance that is similar to that of congenital bronchial atresia; examples include foreign body, tumor, and inflammatory stricture. CT usually allows accurate exclusion of a hilar mass in these children, and aids in the distinction between mucoid impaction and nodular lesions. Contrast-enhanced spiral CT allows exclusion of an anomalous vascular component, as occurs with sequestration.

Bronchopulmonary Sequestration

Bronchopulmonary sequestration is a mass composed of lung tissue that receives its blood supply from an anomalous systemic artery and does not communicate with the bronchial tree via anatomically normal bronchial structures. Bronchopulmonary sequestration, like hypogenetic lung syndrome, is a combined anomaly of tracheobronchial development and pulmonary vascular development. There are 2 main types: intralobar and extralobar (Table 1-2). An intralobar sequestration is within the visceral pleura. The arterial supply is by one or more anomalous systemic arteries, and drainage is usually via the pulmonary veins. An extralobar sequestration is contained in a pleural envelope separate from that of the normal lung, is supplied by one or more anomalous systemic arteries, and can have various pathways of venous drainage.^36,37

The typical treatment for bronchopulmonary sequestrations is surgical resection. The intralobar type usually requires a formal lobectomy.⁵ Because some extralobar sequestrations regress or disappear spontaneously, nonoperative management is appropriate for selected asymptomatic patients.³⁸ Transcatheter embolization is an additional nonsurgical therapeutic option that frequently results in complete disappearance of the lesion.^39–41

Extralobar Sequestration

An extralobar sequestration results from aberrantly located mesenchyme that develops apart from the normal lung. The pathogenesis likely involves abnormal budding of the primitive foregut (i.e., an anomalous or supernumerary lung bud). Therefore, this is a type of noncommunicating bronchopulmonary foregut malformation, as is bronchogenic cyst. Although there is no communication with the tracheobronchial tree, bronchial atresia is not the primary embryonic event in this anomaly. Persistence of primitive splanchnic arteries that supply the foregut during fetal development leads to systemic arterial supply of the sequestration. The mass contains dilated bronchioles, alveoli and subpleural lymphatic vessels. The original connection with the foregut disappears or regresses to form a fibrous pedicle. Occasionally, a patent communication (esophageal bronchus) with the gastrointestinal tract persists; the lesion may then be termed a bronchopulmonary foregut malformation.^5,42

Extralobar sequestration occurs with a 4:1 male-to-female ratio. More than half of children with extralobar sequestration have an associated anomaly, such as congenital diaphragmatic hernia, diaphragmatic eventration, diaphragmatic paralysis, cystic adenomatoid malformation, bronchogenic cyst, foregut duplication, pericardial defect, vertebral anomalies, ectopic pancreas, or pectus excavatum. Extralobar sequestration is supradiaphragmatic in 90% of patients; usually located between the left lower lobe and the left hemidiaphragm. Other potential locations include the mediastinum, within the diaphragm, and, rarely, below the diaphragm. The arterial supply is from the aorta or a primary branch of the aorta; 15% are supplied by an artery that arises below the diaphragm. One-fifth of these lesions are fed by multiple arteries. The venous drainage is most often via a systemic vein, typically in the azygos or hemiazygos systems; portal or pulmonary venous connections can also occur.^5,43

Extralobar sequestration is typically asymptomatic. Most are detected on routine prenatal sonography or on a chest radiograph obtained of an infant or child for an unrelated indication. A large lesion can cause respiratory distress in the neonate. The radiographic appearance is easily confused with that of pneumonic consolidation, and the diagnosis is sometimes first established when CT is performed to evaluate a “recurrent” or “nonclearing” pneumonia in an older infant or child. In other patients, the lesion is detected during the diagnostic workup of an associated thoracic or cardiac anomaly. Rarely, the lesion produces a symptomatic left-to-right shunt. Congenital tension hydrothorax caused by torsion of a sequestration has been reported.^44,45

Extralobar sequestration can be detected prenatally with sonography or MR as a solid well-defined triangular mass in the lower aspect of the thorax, usually on the left. The complex character of the lesion results in a hyperechoic appearance on sonography. The differential diagnosis includes various other congenital lung lesions (Table 1-3). With MR, the lesion produces greater signal intensity than lung on T2-weighted images. Cystic areas are sometimes visible. If a systemic feeding artery can be visualized, this finding is helpful in confirming the diagnosis. In 6% to 10% of cases, a pleural effusion accompanies the lesion; this may be a result of dilated subpleural lymphatics or torsion around the connecting vasculature. Rarely, a large pleural effusion leads to compression of the vena cava and heart, causing fetal hydrops; this can be treated with in utero drainage. Partial or complete spontaneous regression of extralobar sequestrations is common during fetal life; approximately three-quarters of these lesions undergo relative decrease in size in utero. The fetus with suspected sequestration should be carefully evaluated for potential accompanying anomalies.^34,46,47

In the neonate, the sonographic appearance of an extralobar sequestration is that of an echogenic mass, usually located adjacent to the diaphragm. The degree of sonographic heterogeneity of the lesion varies between patients. Rarely, small hyperechoic foci are present because of collateral air drift. An additional rare pattern is that of multiple, small, fluid-filled cysts. Sonography of the affected neonate sometimes allows visualization of an anomalous supplying artery arising from the aorta. An attempt should also be made to demonstrate the pattern of venous drainage. Enlargement of the azygos and hemiazygos vessels can occur in these infants.

The pathologic anatomy of extralobar sequestration is optimally demonstrated with helical CT or MRI. The hallmark feature is at least one large systemic artery supplying the lung “mass.” With CT, the lesion is typically homogeneous; occasionally, there are internal cysts. The margins are relatively well defined, and may be lobulated. Adjacent atelectatic lung sometimes obscures the borders, however. No air is present within the mass unless there is superimposed infection or a connection with the gastrointestinal system.^42,49

In those unusual instances of sequestration in which there is a patent communication with the gastrointestinal system, air bronchograms may be visible within the lesion. CT shows the communication as an air-filled tubular structure extending toward the esophagus. An upper GI contrast study usually allows definitive demonstration of an esophageal bronchus.⁵⁰

Intralobar Sequestration

Intralobar sequestration is a form of bronchial atresia in which there is systemic arterial supply to the involved portion of the lung. Langston terms this as bronchial atresia with systemic vascular connection. The blood supply of an intralobar sequestration is from the thoracic or abdominal segments of the aorta in 75% of instances, and other thoracic systemic vessels in 25%. Potential supplying arteries include the celiac, splenic, intercostal, subclavian, and coronary arteries. Venous drainage is often through the pulmonary veins. As with isolated bronchial atresia, parenchymal maldevelopment similar to the small cyst type of cystic adenomatoid malformation can occur with intralobar sequestration.^12,51–54

As compared to the extralobar type, intralobar sequestration usually presents later in childhood. Most patients have manifestations of recurrent or persistent pulmonary infection. Infection is much more common with intralobar sequestration than with the extralobar type. Hemoptysis may occur. Rarely, there are signs of congestive failure because of shunting through the lesion. Hemothorax caused by infarction of an intralobar sequestration has been reported.

An intralobar sequestration is usually visualized on standard chest radiographs as a soft-tissue density lung mass with smooth or lobulated margins. It is most often located in the basilar portion of the lower lobe (Figure 1-6). Other potential imaging findings include bronchiectasis, atelectasis, mediastinal shift, and prominence of the ipsilateral pulmonary hilum. In some patients, suggestive findings of a sequestration are recurrent lower-lobe pneumonias or the presence of a rounded consolidation that does not clear completely with antibiotic therapy.^51,55

The computed tomographic appearance of intralobar sequestration is variable. Potential findings include a homogeneous soft-tissue mass, a cystic lesion containing air or fluid, focal emphysema with surrounding solid tissue, or a hypervascular focus of lung tissue (Figure 1-7). Calcifications are occasionally present. The anomalous systemic vascular supply and the pathway of venous drainage are demonstrable with helical CT, MR angiography, or catheter angiography (Figure 1-8). The characteristic venous drainage of an intralobar sequestration is via pulmonary veins rather than systemic veins; however, this finding alone does not provide accurate distinction from an extralobar sequestration.^51,54–57

Congenital Cystic Adenomatoid Malformation

Congenital cystic adenomatoid malformation (congenital pulmonary airway malformation) is a complex developmental lesion composed of cystic and solid dysplastic pulmonary tissue. The lesion has hamartomatous characteristics pathologically. It consists of immature lung tissue, with proliferation of bronchioles that form cysts rather than normal alveoli. The lesion usually contains both cystic and solid tissue. The pathogenesis likely involves a maturation defect in lung embryogenesis, with failure of the pulmonary mesenchyme to induce normal bronchoalveolar differentiation during the fifth through seventh weeks of gestation. Discordant development of the vascular and mesenchymal components of the developing lung leads to an abnormal proliferation of these structures. Immunohistochemical analysis of the cellular components of congenital cystic adenomatoid malformation suggests that there is an arrest or disruption of normal branching morphogenesis, which causes an overgrowth of respiratory epithelium. The solid adenomatoid form apparently is embryologically distinct from the more common cystic variety.^3,58,59

Congenital cystic adenomatoid malformation accounts for approximately 25% of all congenital lung abnormalities. The prevalence is slightly higher in males than in females. There is equal frequency of occurrence in both lungs. There is a slight predilection for location in the upper lobes; it is uncommon in the right middle lobe. Congenital cystic adenomatoid malformation can occur in association with a pulmonary sequestration; this is sometimes termed a hybrid lesion.^60–62 Congenital cystic adenomatoid malformation can also be associated with congenital bronchial atresia.⁶³

Congenital cystic adenomatoid malformation is classically divided into 3 types, based on the gross and microscopic features.³ Although there is substantial overlap in the clinical and pathological features of cystic adenomatoid malformation in individual patients, there is utility in considering the 3 basic types as separate entities. Type I (large cyst type) is most common, accounting for approximately 70% of cases. This lesion contains one or more cysts that are at least 2 cm in diameter. The cysts communicate with adjacent airways, and have some pathologic features of dilated bronchi. There are often adjacent smaller cysts and solid components. Type II (small cyst type) cystic adenomatoid malformation contains numerous cysts between 0.5 and 2 cm diameter. The cysts are lined by cuboidal to columnar epithelium, and histologically resemble dilated terminal and respiratory bronchioles. This lesion sometimes occurs as a secondary phenomenon because of a localized embryonic airway obstruction; that is, bronchial atresia. The rare type III cystic adenomatoid malformation (solid type) is a grossly solid-appearing lesion that contains tiny cysts ( o.5 cm) on histologic examination. This adenomatoid or solid form of congenital pulmonary airway malformation may represent localized pulmonary hyperplasia in response to fetal airway obstruction.^3,12,64

The most common clinical presentation of congenital cystic adenomatoid malformation is acute progressive respiratory distress, which develops shortly after birth. The infant may have cyanosis, grunting, retractions, and tachypnea. Rarely, there is sudden onset of symptoms caused by a pneumothorax. Physical examination demonstrates diminished breath sounds at the site of the lesion, hyper-resonance, and shifted cardiac sounds. If the lesion is small, the clinical presentation may occur beyond the perinatal period, with respiratory distress, failure to thrive, or recurrent pneumonia. Fetal lung compression by a large cystic adenomatoid malformation can cause symptomatic pulmonary hypoplasia. Nonimmune fetal hydrops can also occur with a large lesion, as a result of impaired cardiac contractility and impaired venous return to the heart; this finding indicates a grave prognosis.⁶⁵

In some patients, the clinical presentation of congenital cystic adenomatoid malformation does not occur until adulthood or late childhood. These patients often present with recurrent pneumonia localized to the involved lobe.⁶⁶ Diagnosis of the underlying congenital malformation may be difficult in these patients, as inflammation, abscess formation, and fibrosis can result in the formation of epithelial-lined pulmonary cysts that are radiographically and pathologically similar to the cysts of congenital cystic adenomatoid malformation.⁶⁴ In addition to recurrent infection, late-onset congenital cystic adenomatoid malformation may come to clinical attention because of a pneumothorax or as an incidental finding on an imaging study performed for another indication.⁶⁷

The macrocystic forms of cystic adenomatoid malformation are generally considered to carry a more favorable prognosis than the microcystic variety, although the medical literature does not uniformly support this concept. Approximately 50% ofinfants with the type II malformation have other anomalies, some of which adversely affect the prognosis. These associated anomalies include renal agenesis, extralobar sequestration, and sirenomelia. Associated anomalies occur in only approximately 10% of infants with type I congenital cystic adenomatoid malformation. Type III congenital cystic adenomatoid malformation is usually a large lesion that produces marked respiratory distress. Cardiovascular compromise is a potential complication of mediastinal displacement. Any type of cystic adenomatoid malformation that occupies a substantial portion of the chest cavity during fetal development can cause compression and hypoplasia of the ipsilateral lung.

On prenatal sonography, type I congenital cystic adenomatoid malformation appears as a simple or complex fluid-filled mass that contains one or more large cysts. The type II lesion consists of multiple small cysts with interspersed echogenic parenchyma. The type III lesion is a homogeneous echogenic mass.^48,54 Occasionally, differentiation between congenital cystic adenomatoid malformation and congenital diaphragmatic hernia is difficult on prenatal ultrasound; MRI may be helpful in this situation (Figure 1-9).⁶⁸ In addition, the prenatal imaging appearance of the type III adenomatoid variant often is identical to other solid pulmonary lesions, such as sequestration.

Approximately three-fourths of fetuses with cystic adenomatoid malformation survive. Some authors report lower survival rates with type III lesions, but other studies have not confirmed this pattern. A poor outcome is likely if prenatal sonography shows nonimmune hydrops. Polyhydramnios, caused by esophageal compression by the lung mass or increased fluid production from the abnormal lung tissue, is associated with a guarded prognosis.⁴⁸ Spontaneous in utero regression of congenital cystic adenomatoid malformation occurs in a substantial minority of cases. Regression is demonstrated on prenatal sonography as temporal decrease in size of the lesion relative to the remainder of the fetus, or (rarely) complete disappearance.^69,70 This is most common with a type II lesion. However, CT imaging of the newborn with prenatal sonographic evidence of complete spontaneous resolution of a mass frequently detects residual abnormalities, even if chest radiographs are normal.⁷¹

The radiographic findings of infants with congenital cystic adenomatoid malformation are variable. The most characteristic appearance is that of multiple rounded, air-filled, thin-walled cysts of variable size (Figure 1-10). In the newborn, the cysts often contain fluid, resulting in the radiographic appearance of a solid intrapulmonary mass. As fluid clears and is replaced by air in the macrocystic forms of this lesion, the cystic character becomes evident radiographically (Figure 1-11). The air-filled cysts may progressively enlarge with time and compress adjacent mediastinal structures and normal lung tissue (Figure 1-12). Pneumothorax can occur. Because the type III lesion contains cysts that are too small to be resolved radiographically, the imaging appearance is that of a solid mass that displaces adjacent structures. A large congenital cystic adenomatoid malformation, regardless of type, produces mediastinal shift, displacement of the hemidiaphragm, and atelectasis or hypoplasia in adjacent lung. At the other extreme, a small congenital cystic adenomatoid malformation can be radiographically occult.^64,71

Postnatal sonography can be useful if radiographs show a solid-appearing intrathoracic mass in the newborn. The cystic nature of the type I and type II lesions can be effectively demonstrated by this technique. Typically, there is a complex internal appearance that includes multiple cysts, internal septations, and solid elements. The type III lesion has an echogenic, solid-appearing character on sonography.⁷²

CT is the optimal technique for demonstrating the pathologic anatomy in many children with congenital cystic adenomatoid malformation. A type I lesion has one or more large air-filled cysts, usually surrounded by smaller cysts and a variable amount of soft tissue (Figure 1-13). The soft-tissue attenuation areas correspond histologically to glandular tissue or bronchiolar structures. Occasionally, areas surrounding the macroscopic cysts have attenuation values intermediate between those of air and soft tissue (lower than normal lung); this tissue corresponds histologically to microscopic cysts and thin-walled structures resembling small bronchioles. If there is superimposed infection, cystic adenomatoid malformation appears as a complex lesion on CT, with combined cystic and solid components, air-fluid levels, and ill-defined margins (Figures 1-14 and 1-15). A Type II lesion has a heterogeneous appearance on CT, with small variably-sized cysts, often with intermixed soft tissue (Figure 1-16). As on standard radiographs, a type III congenital cystic adenomatoid malformation appears as a solid pulmonary mass on CT (Figure 1-17).^54,73,74