Congenital cystic adenomatoid malformation (CCAM) or congenital pulmonary airway malformation (CPAM), the newer term suggested by Stocker to replace CCAM, is a rare developmental anomaly of the lower respiratory tract. These terms encompasses a spectrum of conditions with debatable origins. Affected patients may be completely asymptomatic or present with severe respiratory distress in the newborn period. Some patients become symptomatic later in life with acute respiratory distress, acute infection, or other manifestations.
CPAMs are relatively uncommon, with the reported incidence being between 1/25,000 and 1/35,000. Many cases that previously would not have been detected until complications arose later in life are now detected by routine prenatal ultrasound. Thus the role of the pediatric surgeons has changed from simply dealing with a patient with acute respiratory issues to often providing prenatal consultation for the expectant parents.
CPAM is slightly more common in males and may affect any lobe of the lung (Hernanz-Schulman 1993) and the lesions are equally distributed between the right and the left side. The lesion is unilobar in 80% to 95% of cases and bilateral in fewer than 2% (Stocker et al 1977). Rare cases have been reported of multilobar involvement of 1 lung or bilateral lesions (Rempen et al 1987).
Unlike BPS, CPAMs have a communication with the tracheobronchial tree, albeit via a minute, tortuous passage. In contrast to BPS, CPAMs usually derive their arterial blood supply and venous drainage from normal pulmonary circulation, but anomalous arterial and venous drainage of CPAM has been reported (Rashad et al 1988), as well as so-called “hybrid” CPAMs that have a systemic blood supply (Cass et al 1997).
CPAM is a lesion characterized histologically by a multicystic mass of pulmonary tissue with a proliferation of bronchial structures (Stocker et al 1977; Miller et al 1980). This may represent a failure of bronchiolar structures to mature, which normally occurs at approximately the fifth or sixth 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 (Moerman et al 1992; Langston 2003). The gestational age and location of the airway obstruction may determine whether CPAM, BPS, or lobar emphysema results (Keswani et al 2005; Kunisaki et al 2006).
The pathogenesis is uncertain, but appears to result from an abnormality of the branching morphogenesis of the lung and represents a maturational defect. The different types of CPAMS are thought to originate from different levels of the tracheobronchial tree and at different stages of lung development. CPAM is distinguished from other lesions and normal lung by 5 main criteria: (1) polypoid projections of the mucosa, (2) an increase in smooth muscle and elastic tissue within the cyst walls, (3) an absence of cartilage in the cystic parenchyma, (4) the presence of mucous secreting cells, and (5) the absence of inflammation. While the CPAM portion of the lung does not participate in normal gas exchange, there are connections to the tracheobronchial tree that can lead to air-trapping and respiratory distress in the newborn period.
The exact mechanism resulting in CPAM is unknown, but is thought to include an imbalance between cell proliferation and apoptosis (increased cell proliferation and decreased apoptosis as compared to gestational controls). CPAMs are hamartomatous lesions that comprise both cystic and adenomatous overgrowth of the terminal bronchioles. If large cysts develop in utero, they can compress and compromise the growth of normal surrounding tissue.
In 1977, Stocker et al originally subdivided CCAMs into 3 types: I, II, and III, based on pathologic characteristics (Fig. 29-1). Stocker later revised this classification to CPAM type 0 to IV (Stocker et al 1994). The 5 types were intended to represent the spectrum of malformations of 5 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 duct; and type IV as peripheral. Because of the broad spectrum of malformations covered by this expanded classification system, Stocker (1994) suggested the term CPAM was more appropriate, but CCAM and CPAM are both in common usage. Reported prevalence rates for postnatal cases vary and range from <1% for type 0 lesions, 50% to 65% for type I, 10% to 40% for type II, 5% to 10% for type III, and 10% to 15% for type IV.
Type I lesions 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 are more numerous cysts and smaller (usually less than 1 cm in diameter) and are 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 and the prognosis often depends on the severity of associated anomalies. The most commonly associated anomalies are: 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 type III lesions 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 prognosis in type III CPAMs is variable but can, in severe cases, present with nonimmune hydrops in utero and cardiorespiratory compromise in the newborn (Adzick et al 1985; Harrison et al 1990). Type IV CPAMs 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 of cystic pleuropulmonary blastoma, which may be clinically indistinguishable (McSweeney et al 2003; Hill and Dehner 2004).
The presentation of CPAM is quite variable and can extend from the early prenatal period to late in adult life. The spectrum runs from an incidental finding on a routine chest x-ray in a completely asymptomatic patient, to severe respiratory distress in the newborn period (Fig. 29-4). More and more of these lesions are now picked up in the prenatal period on routine screening ultrasound, allowing for prenatal consultation and planning. Prenatal diagnosis by ultrasonography is generally classified as either microcystic lesions with cysts <5 mm, which appear echogenic and solid, or macrocystic lesions of 1 or more cysts >5 mm, and includes massive pulmonary involvement with the development of hydrops. Hydrops can develop in up to 40% of cases and regression of the lesion is seen in up to 60% during the course of gestation. The need for fetal intervention is rare and limited to those cases with severe hydrops with a predicted mortality of near 100%. MRI is being used more frequently to examine the fetus and can help differentiate CPAM from other thoracic lesions, such as congenital diaphragmatic hernia, foregut duplications, and others (Fig. 29-5).
Antero-postero (A) and lateral (B) views of CCAM in left upper lobe of a 1-month-old male with respiratory distress.
MRI of fetus with CPAM diagnosed in utero. The involved fetal lung is lighter due to the fluid within the cystic structures in the lung parenchyma.
The differential diagnosis of CPAM includes other cystic diseases of the lung including BPS, bronchogenic cyst, and CLE. The primary differentiation between CPAM and BPS is based on 2 anatomic points. BPS has no connection to the tracheobronchial tree and is supplied by an anomalous systemic artery. CPAM is usually not. However, the difference between the 2 lesions is not as discreet as once thought and it is more likely that the 2 are variants of the same abnormal developmental pathway.
In the neonatal period, the diagnosis is usually suspected based on clinical presentation and the initial chest x-ray. A computed tomography (CT) scan is usually definitive, although the exact diagnosis may not be made until surgical exploration is performed (Fig. 29-6). Diagnosis later in life is usually dependent on late symptoms or, in some cases, an incidental finding on a routine chest x-ray. CT scan is still the gold standard.
Chest radiograph (A) and corresponding CT (B) of a 2-day-old tachypneic male showing right lower lobe CPAM.
The infant with type I, II, or IV CPAM may be at significant risk for air trapping in the CPAM, which may acutely worsen the respiratory status (Stocker et al 1977; Bailey et al 1990). In cases of unilateral CPAM, selective intubation of the contralateral bronchus may be a useful temporizing measure until resection of the CPAM can be accomplished. Pneumothorax is an additional concern in CPAM, especially in the type I or II lesions, and may require tube thoracostomy (Bentur et al 1991). The treatment of choice in CPAM is complete resection of the CPAM, usually by lobectomy (Fig. 29-7A-C). In rare cases of extensive involvement of nearly the entire lung, resection of multiple lobes or pneumonectomy may be necessary. There are several reports, however, detailing potentially lethal problems associated with pneumonectomy in newborns resulting from mediastinal shift with vascular compression of the trachea and remaining bronchus (Szarnicki et al 1978). Because of these risks, some groups advocate a nonanatomic resection to preserve as much pulmonary parenchyma as possible to allow postoperative compensatory growth and avoid postpneumonectomy complications (Mentzer et al 1992).
A. Transthoracic inspection of a lobar CPAM at operation. B. Cut section of the operative specimen demonstrating cystic and solid components of the CPAM. C. Histology of a solid CPAM in which the section demonstrates the microcystic disease.
The newborn with a CPAM detected antenatally that subsequently regresses also needs careful postnatal evaluation (MacGillivray et al 1993; Adzick et al 1998). Often subtle abnormalities will be evident on chest radiography, but chest CT scanning may be necessary to detect residual CPAM tissue. Several authors have recommended that as long as these lesions are asymptomatic, they may be observed closely and managed without resection (Adzick et al 1993; MacGillivray et al 1993; Aziz et al 2004; Hsich et al 2005). The argument against this approach includes the reported cases of myxosarcoma, embryonal rhabdomyosarcoma, pleuropulmonary blastoma, and bronchoalveolar carcinoma arising in CPAMs or indistinguishable from them (Stephanopoulos and Catsaros 1963; Wecla et al 1977; Benjamin and Cahill 1991; d'Agostino et al 1997).
Primary lung tumors are rare during the first 2 decades of life, but 4% of those reported were associated with congenital cystic lesions of the lung, including CPAM (Benjamin and Cahill 1991). While CPAM-associated malignancies often arise only after decades, the youngest patient reported with a malignancy was only 13 months of age (Ozcan et al 2001). Because there is an anomalous connection to the tracheobronchial tree, infection is an additional potential complication (Stephanopoulos and Catsaros 1963; Benjamin and Cahill 1991; Ozcan et al 2001; Hasiotou et al 2004; Galadzas et al 2005; Poi et al 2005).
Some have argued that asymptomatic CPAMs should be followed expectantly, and that the risks of surgery in infancy outweigh the potential benefits (Aziz et al 2004). However, the continued presence of CPAM represents a lifelong risk of both infection and malignant transformation. In centers with significant experience in lung resection in infants, CPAMs can be safely resected with virtually no morbidity and mortality (Tsai et al 2007). The authors' approach is to obtain a postnatal CT scan and perform a muscle-sparing thoracotomy or thoracoscopic lobectomy or lung resection when possible to retain normal lung tissue. An added benefit to resection over observation is that the remaining lung undergoes significant compensatory growth within months of the surgery. This does not occur if the CPAM is left in situ. The long-term outcome of infants with CPAM following resection is excellent. If residual CPAM is left behind or the mass is not resected, the child will remain at risk for infectious and potentially malignant complications. The authors recommend prophylaxis against respiratory syncytial virus (RSV) in infancy in those with significant associated pulmonary hypoplasia, pulmonary hypertension, or chronic lung disease. Children who survived open fetal surgery for CPAMs associated with hydrops appear to be still doing well from 1 to 7 years postoperatively.