Congenital cystic adenomatoid malformation (CCAM) of the lung is a lesion characterized by a multicystic mass of pulmonary tissue with a proliferation of bronchial structures (Stocker et al., 1977; Miller et al., 1980). It may represent a failure of maturation of bronchiolar structures, occurring at approximately the 5th or 6th week of gestation during the pseudoglandular stage of lung development (Stocker et al., 1977; Miller et al., 1980; Shanji et al., 1988). Alternatively, it may represent focal pulmonary dysplasia, since skeletal muscle has been identified within the cyst walls (Leninger and Haight, 1973). Others have suggested that it may be the result of airway obstruction (Demos and Teresi, 1975; Cochia and Sobonya, 1981; Moerman et al., 1992; Langston, 2003). The gestational age and location of the airway obstruction may determine whether CCAM, bronchopulmonary sequestration, or lobar emphysema results (Keswani et al., 2005; Kunisaki et al., 2006).

CCAM is slightly more common in males and may affect any lobe of the lung (Hernanz-Schulman, 1993). The lesion is unilobar in 80% to 95% of cases and bilateral in fewer than 2% (Stocker et al., 1977). Unlike bronchopulmonary sequestration (BPS), CCAMs have a communication with the tracheobronchial tree, albeit via a minute tortuous passage. In contrast to BPS, CCAMs derive their arterial blood supply and venous drainage from normal pulmonary circulation, but anomalous arterial and venous drainage of CCAM have also been reported (Rashad et al., 1988) as well as the so-called “hybrid” CCAMs that have a systemic blood supply (Cass et al., 1997).

Stocker et al., (1977) originally subdivided CCAM into three types based on their pathologic characteristics (Figure 35-1). More recently, Stocker revised this classification to include five types. Stocker initially recommended that CCAM be classified as type I, II, and III and later added type 0 and IV (Stocker et al., 1977; Stocker, 2002). The five types were intended to represent the spectrum of malformations of five successive groups of airways. Type 0, a condition previously described as acinar dysplasia (Davidson et al., 1998) is described as bronchial; type I as bronchial/bronchiolar; type II as bronchiolar; type III as bronchiolar/alveolar dust; and type IV as peripheral. Because of the broad spectrum of malformations covered by this expanded classification system, Stocker (1994) suggested the term congenital pulmonary airway malformation (CPAM), and both CCAM and CPAM are in common usage. Stocker’s classification is a histologic one, although commonly applied to sonographic appearance.

Type I lesions account for 50% of postnatal cases of CCAM, and consist of single or multiple cysts lined by ciliated pseudostratified epithelium. These cysts are usually quite large (3–10 cm) and few in number (1–4). Type I lesions are usually associated with a favorable outcome. Type II lesions account for 40% of postnatal cases of CCAM and consist of more numerous cysts of smaller diameter (usually less than 1 cm) lined by ciliated, cuboidal, or columnar epithelium. Respiratory bronchioles and distended alveoli may be present between these cysts. There is a high frequency of associated congenital anomalies with type II lesions. The prognosis for type II lesions often depends on the severity of associated anomalies. The most commonly associated anomalies include genitourinary, such as renal agenesis or dysgenesis; cardiac, including truncus arteriosus and tetralogy of Fallot; jejunal atresia; diaphragmatic hernia; hydrocephalus; and skeletal anomalies (Stocker et al., 1977). The high incidence of associated anomalies has led to speculation that this type of CCAM may occur as a result of events occurring prior to 31 days of gestation (Walker and Cudmore, 1990). The type III lesions account for only 10% of cases and are usually large homogeneous microcystic masses that cause mediastinal shift. These lesions have bronchiole-like structures lined by ciliated cuboidal epithelium, separated by masses of alveolar-sized structures lined by nonciliated cuboidal epithelium. The mixture of epithelial and mesenchymal structures in type III lesions has led to speculation that its development is related to events occurring prior to 28 days of gestation, after the formation of the lung buds (Walker and Cudmore, 1990). The prognosis in type III CCAMs is variable but can in severe cases present with nonimmune hydrops in utero and cardiorespiratory compromise in the newborn (Adzick et al., 1985b; Harrison et al., 1990a). Type IV CCAMs account for approximately 15% of cases and are characterized by very large cysts up to 10 cm lined by flattened epithelium resting on loose mesenchyme. These lesions can have areas of focal stromal hypercellularity with histologic overlap with grade I pleuropulmonary blastoma (McSweeney et al., 2003; Hill and Dehner, 2004).

Adzick et al., (1985b) have proposed a modification of Stocker’s classification of CCAMs based on anatomy and sonographic appearance to assist in predicting prenatal outcome. In this classification, macrocystic CCAMs have single or multiple cysts >5 mm in diameter. Microcystic CCAMs are more solid and bulky, with cysts that are <5 mm in diameter. This distinction can easily be made sonographically in the fetus. Macrocystic lesions appear sonographically as fluid-filled cysts, while microcystic lesions appear solid with an almost homogeneous appearance (Adzick et al., 1985b). This is a useful sonographic distinction, because microcystic lesions are at increased risk for the development of hydrops. The high mortality rate of microcystic lesions is due to the large size these lesions attain and secondary sequelae, including mediastinal shift, pulmonary hypoplasia, polyhydramnios, and nonimmune hydrops (Adzick et al., 1985b, 1993, 1998; Harrison et al., 1990a).

CCAM has been considered a relatively rare lesion, although in more recent years, with the widespread use of obstetrical ultrasound, there has been a rapid increase in the number of cases detected prenatally (Nicolaides et al., 1987; Adzick et al., 1998). A commonly quoted incidence of CCAM lesions is between 1:25,000 and 1:35,000 livebirths (Laberge et al., 2001).

CCAM is diagnosed by prenatal ultrasound demonstrating a lung tumor that may be solid or cystic, and with an absence of systemic vascular flow (Figure 35-2) (Dann et al., 1981; Bezzuti and Isler, 1983; Diwan et al., 1983; Cone and Adam, 1984; Johnson et al., 1984; Morcos and Lobb, 1986; Mendoza et al., 1986; Deacon et al., 1990). Types I and II CCAM appear as cystic or echolucent pulmonary masses, and may appear similar to diaphragmatic hernia, cystic hygroma, and other cystic lesions, such as bronchogenic or enteric cysts, and pericardial cysts (Boulot et al., 1991). In contrast, type III CCAM typically appears as a large hyperechogenic mass, often associated with mediastinal shift and, in advanced cases, hydrops (Adzick et al., 1985b).

The sonographic appearance of CCAMs can range from solid echodense mass filling the chest to a lesion with a single dominant cyst with a compressive effect on the mediastinum. The vast majority of CCAMs derive their blood supply from the pulmonary circulation and drain via the pulmonary veins. However, color Doppler should be used to search for the presence of a systemic feeding vessel. This may be observed in most BPSs (the main differential diagnosis in CCAMs) and in “hybrid” CCAM lesions (Cass et al., 1997). The systemic feeding vessel in hybrid CCAM lesions usually comes directly off the descending aorta; however, transdiaphragmatic systemic feeding vessels have also been observed in CCAMs.

A change in the echogenicity of type III CCAMs may occur between 30 and 34 weeks in which they become isoechogenic with adjacent normal lung. Although sonographically invisible, such cases of CCAM are still readily apparent on MRI. Occasionally, postnatal imaging with CT scanning reveals no evidence of CCAM, which may be due to the presence of lobar emphysema instead.

The differential diagnosis of fetal thoracic masses includes congenital diaphragmatic hernia (CDH) (see Chapter 37), bronchogenic or enteric cysts, BPS (see Chapter 34), mediastinal cystic hygroma (see Chapter 32), bronchial atresia or stenosis, neuroblastoma, and brain heterotopia (Adzick et al., 1985a; Hobbins et al., 1979; Gonzalez-Cuezzi et al., 1980; Romero et al., 1982; Chinn et al., 1983). The sonographic appearance of CCAM will influence the differential diagnosis. Type I CCAMs are more likely to be confused with a CDH. Observing peristalsis in the loops of herniated intestine or emptying of the stomach herniated through the diaphragm may help to differentiate the two (May et al., 1993). Fetal magnetic resonance imaging (MRI) may be helpful in evaluating fetal chest masses and distinguishing them from diaphragmatic hernia (Figure 35-3) (Hubbard and Crombleholme, 1998). It is also worth noting that CCAM can coexist with CDH (Stocker et al., 1977). The microcystic type III CCAMs are highly echogenic. This is helpful in distinguishing CCAM from solid tumors such as neuroblastoma. Bronchogenic cysts are unilocular and are usually adjacent to major bronchi, which may be confused with a type I CCAM. However, the main differential diagnosis in type III CCAM is usually BPS. Unlike most CCAMs, BPS derives its blood supply from the systemic circulation (Carter, 1959). This systemic blood supply to BPS can often be demonstrated with the use of color flow Doppler studies (Figure 35-4) (Hernanz-Schulman et al., 1991; Morin et al., 1994). There has been an anecdotal report of CCAM associated with anomalous blood supply (Rashad et al., 1988). With the exception of this case, the demonstration of systemic blood supply to a thoracic mass has been thought to be pathognomonic of BPS. More recently, Cass et al., (1997) described six cases of cystic adenomatoid malformation that had systemic blood supply. These lesions were called “hybrid” lesions as they had features of both CCAMs and BPSs and their natural history was also a mixture of the two lesions. The prognosis in hybrid CCAM is much more favorable than “pure” CCAM (Crombleholme et al., 2002).

The postnatal natural history of CCAM can be quite variable (Adzick, 1993, 1998). The lesion can be completely asymptomatic and come to medical attention only when chest radiography is performed for other reasons, such as a history of mild respiratory complaints with recurrent infections in infancy or childhood. However, most postnatal patients will present at birth with severe cardiorespiratory compromise due to severe pulmonary hypoplasia (Atkinson et al., 1972; Stocker et al., 1977; Nishibayashi et al., 1981; Pulpeiro et al., 1987; Heij et al., 1990; Hernanz-Schulman et al., 1991; Neilson et al., 1991; Kuller et al., 1992; Cloutier et al., 1993). Even before the advent of obstetrical sonography, it was recognized that up to 14% of cases of CCAM result in stillbirths (Stocker et al., 1977). This observation hinted at the different prenatal natural history of CCAM.

Our understanding of the natural history of CCAM is still evolving. The worst outcome is observed in fetuses in which hydrops develops (Adzick et al., 1985b, 1998; Harrison et al., 1990a; Adzick, 1993). Hydrops is usually seen in very large lesions, often type III lesions, which cause mediastinal shift and vena caval obstruction (Figure 35-5). Hydrops may also be exacerbated by the loss of protein from the CCAM into the amniotic fluid, thus reducing the fetal colloid oncotic pressure from hypoproteinemia (Hernanz-Schulman et al., 1991). Anecdotal reports exist of fetuses with CCAM surviving after the onset of hydrops (Golladay and Mollitt, 1984; Graham et al., 1982; Glaves and Baker, 1983; Heydanus et al., 1993; Meagher et al., 1993; Etches et al., 1994; Dommergues et al., 1997; Higby et al., 1998; Bunduki et al., 2000; Diamond et al., 2003). Diamond et al., (2003) suggested that resolution by 30 weeks’ gestation may be more common than is appreciated. The reason for this unexpected resolution of hydrops in CCAM was not apparent until the natural history of CCAM was defined by Crombleholme (Crombleholme et al., 2002). CCAMs plateau in their growth at an average of 26 weeks’ gestation after which the fetus grows around the CCAM allowing hydrops to resolve (Crombleholme et al., 2002).

The overall prognosis depends primarily on the size of the lesion, as well as whether it is predominantly macrocystic or microcystic. Polyhydramnios is seen in up to 70% of CCAMs diagnosed antenatally (Adzick et al., 1998). The pathogenesis of polyhydramnios is not completely understood but is thought to relate to esophageal obstruction from mediastinal shift and interference with fetal swallowing of amniotic fluid (Miller et al., 1980; Murayama et al., 1987). This is supported by the absence of fluid in the fetal stomach in such cases.

The diagnosis of CCAM may also have implications for the health of the mother. The mother with a fetus with CCAM may develop the “mirror syndrome,” a hyperdynamic pre-eclamptic state that may be life-threatening. The “mirror syndrome” has also been seen in molar pregnancies, sacrococcygeal teratoma, and in fetal conditions that result in poor placental perfusion, which leads to endothelial cell injury (Creasy, 1979; Roberts et al., 1989). The only treatment for this syndrome is immediate delivery of the baby and placenta.