- What is CPAM?
CPAM is a rare congenital birth defect that includes a non-cancerous cystic mass of abnormal lung tissue. At birth, some babies born with CPAM will not be able to breathe effectively due to the large mass in their chest. If a baby is unable to breathe effectively on his or her own, the situation becomes life-threatening and immediate care is needed to stabilize the baby until surgery can be performed.
In most cases, CPAM appears in only one of the lungs. In about 80 to 95 percent of cases, it is only present in one lobe of the affected lung. The right lung has three lobes, and the left lung has two lobes. CPAM can affect any of these lobes.
- Types of CPAM
Type I Lesions: Most CPAM lesions are considered type I. These lesions are usually quite large and few in number (1 to 4). This type has a very favorable outcome.
Type II Lesions: This type consists of more numerous smaller cysts. It is more commonly associated with other congenital anomalies, including those of the cardiac and skeletal systems, as well as hydrocephalus and diaphragmatic hernia. The prognosis for type II depends upon the severity of the associated anomalies.
Type III Lesions: These are usually large lesions that cause shifting of the organs that are normally found in the chest. This means that the windpipe, heart and unaffected lung are shifted and compressed. For this reason, the heart may not be able to function well.
This can lead to the development of hydrops. Hydrops is an abnormal accumulation of fluid in at least two fetal cavities, such as in the abdomen, around the heart or lungs or under the skin. This is the most serious type of CPAM.
At birth, if the size of the CPAM requires immediate assistance, a tube will be placed into your baby’s airway to help him or her breathe.
- How We Treat CPAM
The main type of treatment for CPAM is a lobectomy. This means that the lobe in the lung that contains the cyst(s) is completely removed.
The timing of surgery depends on whether your infant has breathing problems or not. If there are no breathing problems, your baby will go home with you from the newborn nursery and will be given time to grow. Surgery will need to be performed at about 2 to 6 months of age.
If the mass is so large that it interferes with your baby’s ability to breathe without help, we will perform surgery within the first week after birth. Before surgery, we will stabilize your baby and give him or her some time to adjust to life outside of your uterus. One of our physicians will assess the mass and perform a general evaluation of your baby to check for any associated anomalies.
If there are no breathing problems, your baby will go home with you from the newborn nursery and will be given time to grow. Surgery may be performed at about 2 to 6 months of age. In severe cases of CPAM, a lobectomy is the treatment of choice. This means that the lobe in the lung that contains the cyst(s) will be completely removed.
The Fetal Care Center Dallas team has evaluated several babies with CPAM. We know that a diagnosis of CPAM can be a very emotional experience for a family and, in some cases, difficult treatment decisions must be made quickly. We are with you every step of the way to provide a thorough, compassionate approach to your baby’s care.
For Healthcare Providers
Congenital Pulmonary Airway Malformation (CPAM) is one of the congenital cystic lung lesions that can be diagnosed prenatally. It is a congenital malformation of the pulmonary tissue that occurs during the pseudoglandular stage of lung development (5th-16th week of gestation) and is characterized by proliferation of bronchial structures. Initially they were referred to as Congenital Cystic Adenomatoid Malformation (CCAM) but are preferentially called CPAMs now as not all lesions are cystic. Hallmarks of prenatal diagnosis on ultrasonography include a lung mass that may be solid or cystic and an absence of systemic vascular flow.
- Differential Diagnosis
The differential diagnosis of fetal thoracic masses includes congenital diaphragmatic hernia (CDH), Bronchopulmonary sequestration (BPS), Bronchopulmonary foregut malformations, congenital hyperinflation syndromes, mediastinal cystic hygroma, bronchial atresia or stenosis, neuroblastoma and brain heterotopia. The sonographic appearance of CPAM will influence the differential diagnosis.
The sonographic appearance of CPAMs can range from solid echodense mass filling the chest to a lesion with a single dominant cyst with a mass effect on the heart and mediastinum. The vast majority of CPAMs derive their blood supply from the pulmonary artery 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 CPAMs) and in “hybrid” CPAM lesions (Cass et al., 1997). The systemic feeding vessel in hybrid CPAM lesions usually comes directly off the descending aorta; however, trans diaphragmatic systemic feeding vessels have also been observed in CPAMs.
CPAMs were originally pathologically classified by Stocker into 3 types (I, II, and II) and subsequently type 0 and type IV were added (MacSweeney, 2003). Types I and II CPAM appear as cystic or echolucent pulmonary masses and may appear similar to diaphragmatic hernia, cystic hygroma, and other cystic lesions, such as bronchopulmonary foregut malformation or enteric or pericardial cysts. In contrast, type III CPAM typically appears as a large hyperechogenic mass, often associated with mediastinal shift and, in advanced cases, hydrops.
Type I CPAMs 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). In rare cases in the past, amniography and computed tomographic (CT) scanning were employed to distinguish CDH from other thoracic lesions (Adzick, 1993). More recently, fetal magnetic resonance imaging (MRI) has proved extremely helpful in evaluating fetal chest masses and distinguishing them from diaphragmatic hernia (Hubbard and Crombleholme, 1998). It is also worth noting that there have been cases of CPAM occurring in association with CDH (Stocker et al., 1977). The microcystic type III CPAMs are highly echogenic. This is helpful in distinguishing CPAM 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 CPAM.
However, the main differential diagnosis in CPAM is usually BPS. Unlike most CPAMs, 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 (Hernanz-Schulman et al., 1991; Morin et al., 1994). 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 older literature, there is an anecdotal report of CPAM 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 had been thought to be pathognomonic of BPS. However, 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 CPAMs and BPSs and their natural history was also a mixture of the two lesions. The prognosis in hybrid CPAM is more favorable than CPAMs without a systemic feeding vessel (Crombleholme et al., 2002).
- Prenatal Natural History
The outcome of fetuses diagnosed prenatally with CPAM has only recently been reported and our understanding of the natural history of CPAM is still evolving. We know that the worst outcome is observed in fetuses in which hydrops develops (Adzick, 1993; Adzick et al., 1985B, 1998; Harrison et al., 1990A). Hydrops is usually seen in very large lesions, often type III lesions, which cause mediastinal shift and vena caval obstruction. Hydrops may also be exacerbated by the loss of protein from the CPAM into the amniotic fluid, thus reducing the fetal colloid oncotic pressure from hypoproteinemia (Hernanz-Schulman et al., 1991). There are only anecdotal reports of a fetus with CPAM surviving after the onset of hydrops. Diamond et al. suggested that resolution by 30 weeks’ gestation may be more common than is appreciated. The reason for this unexpected resolution of hydrops in CPAM was not apparent until the natural history of CPAM was better defined by Crombleholme et al. (2002). CPAMs plateau in their growth at an average of 26 weeks’ gestation after which the fetus grows around the CPAM allowing hydrops to resolve (Crombleholme et al., 2002).
Adzick et al. proposed a modification of Stocker’s classification of CPAMs based on anatomy and sonographic appearance to assist in predicting outcome in cases detected in utero (Adzick et al., 1985B). In this classification, macrocystic CPAMs have single or multiple cysts >5 mm in diameter. Microcystic CPAMs 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 due to fine interfaces with the ultrasound beam creating an almost homogeneous appearance (Adzick et al., 1985B). This is a useful sonographic distinction because microcystic lesions may be 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). Despite the type of lesions, however, the overall prognosis depends primarily on the size of the lesion. Polyhydramnios is seen in up to 70% of CPAMs 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 stomachs of many of these fetuses.
The diagnosis of CPAM may also have implications for the health of the mother. Adzick et al. (1993) reported a mother with a fetus with CPAM that developed the “mirror syndrome,” a hyperdynamic pre-eclamptic state that may be life-threatening. The “mirror syndrome” has been seen in molar pregnancies, sacrococcygeal teratoma and in fetal conditions that result in poor placental perfusion which leads to endothelial cell injury (Roberts et al., 1989; Creasy, 1979). The only treatment for this syndrome is immediate delivery of the baby and placenta.
The antenatal diagnosis of a large CPAM might at first appear to be an ominous finding; however, several reports have described disappearing fetal lung masses (Adzick and Harrison, 1993; Adzick et al., 1993; Budorick et al., 1992; Fine et al., 1988; MacGillivray et al., 1993; Saltzman et al., 1988). MacGillivray et al. (1993) have reported six cases of large CPAMs with associated mediastinal shift that progressively decreased in size over the course of gestation. These lesions were all of the microcystic or type III variety, but none were associated with nonimmune hydrops. The percentage of cases that will undergo spontaneous regression is not known for certain but the experience at two tertiary-care centers was between 6 and 11% of evaluated cases (Adzick et al., 1998; MacGillivray et al., 1993). The reason for regression of fetal CPAM is not understood. Decompression of the fluid from the CPAM into the tracheobronchial tree or outgrowing its blood supply has been suggested as possible mechanisms (Adzick et al., 1993). There has been no biochemical or sonographic marker that allows us to distinguish between CPAM that will regress and one that will progress to hydrops. There is a change in the echogenicity of type III CPAMs between 30 and 34 weeks in which they become isoechogenic with adjacent normal lung. Although sonographically invisible, CPAMs are readily apparent on MRI. This likely accounts for the so called “disappearing CPAMs” which may become isoecogenic and regress in size but do not disappear. Occasionally, postnatal imaging with CT scanning reveals no evidence of type III CPAMs. It is likely that the diagnosis in these cases is not CPAM but segmental or lobar hyperinflation.
Crombleholme et al. (2002) reported the use of CPAM volume and the CPAM volume ratio at presentation as a predictor of the development of hydrops. The CPAM volume is calculated using the formula for the volume of an ellipse (h × w × l × 0.52) in cm3 with the measurement of the greatest length in the sagittal section and the width and height taken at 90 degrees to the sagittal measurement. The CPAM volume ratio (CVR) is obtained by dividing the CPAM volume by the head circumference (in cm) to correct for any differences in gestational age. Based on 32 fetuses with CPAM, the CPAM volume and the CVR were found to be significantly higher in fetuses who had or would develop hydrops. In addition, when the mean of the group that did not develop hydrops plus two standard deviations were added a cutoff value of 1.6 was obtained. In a prospective study of 42 fetuses with CPAM, only 2% of fetuses with CVR <1.6 (and no dominant cyst) developed hydrops. Of those fetuses with CVRs >1.6, 80% developed hydrops (Crombleholme et al., 2002). The CVR is a useful criterion to select fetuses at greatest risk for the development of hydrops and those at low risk for development of hydrops.
One of the largest experiences with prenatally diagnosed CPAM was reported by Adzick, Harrison and Crombleholme (1998). This series reflected the combined experience of the Center for Fetal Diagnosis and Treatment at the Children’s Hospital of Philadelphia and the Fetal Treatment Center at the University of California San Francisco, comprising a 12–year retrospective study at the two centers and 175 fetal lung lesions. There were 134 fetuses with CPAM in this group. Of these, 14 pregnancies were terminated, 101 cases were managed expectantly, 13 women underwent open fetal surgery and 6 fetuses underwent thoracoamniotic shunt placement. In the fetuses that did not develop nonimmune hydrops, the postnatal survival was 100%. In contrast, of 25 large CPAMs that developed hydrops and were managed expectantly, there was 100% mortality, with death in utero or immediately after birth. Among the 76 fetuses with CPAMs that were not associated with hydrops, the uniform survival was, in part, due to planned near-term delivery at a tertiary-care center. Many of the babies with large lesions required substantial ventilatory support and four needed the support of extracorporeal membrane oxygenation (ECMO).
Fifteen CPAM lesions appeared large at 20–26 weeks of gestation with an associated contralateral mediastinal shift, but then clearly decreased in size during the third trimester with return of the position of the heart toward midline. Although four of these shrinking lesions were associated with polyhydramnios, including one case with fetal ascites, these phenomena resolved as the masses decreased in size.
- Clinical Picture
The postnatal natural history of CPAM can be quite variable. 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 (Stocker et al., 1977). However, fewer than 10% of CPAMs present after the first year of life. Eighty percent of symptomatic postnatal patients present at birth with severe cardiorespiratory compromise due to severe pulmonary hypoplasia (Atkinson et al., 1972; Cloutier et al., 1993; Heij et al., 1990; Hernanz-Schulman et al., 1991; Kuller et al., 1992; Neilson et al., 1991; Nishibayashi et al., 1981; Pulpeiro et al., 1987; Stocker et al., 1977). Even before the advent of obstetrical sonography, it was recognized that up to 14% of cases of CPAM result in stillbirths (Stocker et al., 1977). This observation hinted at the different prenatal natural history of CPAM.
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. More and more of these lesions are now picked up in the prenatal period on routine screening ultrasound, allowing for prenatal consultation and planning. A CT scan is usually definitive, although the exact diagnosis may not be made until surgical exploration and pathological confirmation. Diagnosis later in life is usually dependent on late symptoms or in some cases an incidental finding on a routine CXR. CT scan is still the gold standard.
- Fetal Intervention
The management of CPAM depends on the CVR value that is obtained at presentation. If the CVR is less than 1.6 and there is no evidence of a dominant cyst, the CPAM has only a 2% risk for the development of hydrops (Crombleholme et al., 2002). The fetus should have weekly sonograms to measure the CPAM volume and CVR in order to identify early signs of hydrops or more likely that the plateau in growth had been reached. Once the growth plateau is reached, the pregnancy is no longer at risk for the development of hydrops. The surveillance of the fetus can be reduced but one should continue to assess the size of the CPAM, as well as the risk of pulmonary hypoplasia or air trapping which would influence delivery management.
If there is a dominant cyst, even if the CVR is <1.6, the fetus remains at significant risk for acute enlargement of the cyst and development of hydrops. The CPAMs with a dominant cyst behave differently because of fluid secretion into the cyst causing acute enlargement whch because of the abrupt change in size causes hydrops. A thoracoamniotic shunt may be considered in these cases at the very earliest sign of hydrops. We favor the use of fetal thoracosopy for placement of thoracoamniotic shunts in cystic CPAMs so that laser fenestration can be performed to connect all of the major cysts prior to placing a thoracoamniotic shunt.
If the CVR is >1.6 at presentation, with or without a dominant cyst, there is up to an 80% chance of hydrops developing. Twice weekly sonographic surveillance should be started to help detect the earliest signs of hydrops in which case fetal surgery may be considered. Also, with a CVR of >1.6, a course of maternal steroids (betamethasone) should be considered. There are several small series documenting resolution of hydrops in patients with CPAMs that were not candidates for open fetal surgery who were treated with steroids (Tsao et al., 2003; Parenteau et al., 2006). It is thought that steroids may arrest the growth of the solid component of the CPAM inducing an early growth plateau allowing the fetus to grow around the CPAM and hydrops to resolve. It is not proven that steroids truly affect the growth of CPAMs and the observations reported may be due to the CPAMs naturally entering the plateau phase independent of the steroids. Not all CPAMs respond to steroids, however. We have treated 42 cases with maternal steroids with significant progression in two cases despite initial improvement. Both went on to open fetal surgery. If steroids are to be administered for hydropic CPAM, it is prudent to do so in conjunction with consultation with a fetal surgery center.
Fetuses with CPAM and a dominant cyst in which hydrops develops prior to 32 weeks can be considered for treatment in utero. Nicolaides et al. (1987) reported the first case of CPAM treated in utero. Decompression of a very large cystic lung lesion in a 20-week-old fetus by percutaneous placement of thoracoamniotic catheter shunt was reported by Clark et al. in 1987. This procedure resulted in resolution of both mediastinal shift and hydrops and successful delivery at 37 weeks of gestation. Postnatally, the infant underwent uneventful resection of the CPAM. Six subsequent cases have been reported by Adzick et al., with favorable outcome in five of the six fetuses treated (Adzick et al., 1993, 1998). Wilson et al. reported 10 cases treated with thoracoamniotic shunting with 70% survival (Wilson et al., 2004) and Szaflik et al in 2017 reported 12 cases with macrocystic CPAMs resulting in10 live births. A literature search identified a total of 98 fetuses with CCAM treated with thoracoamniotic shunting between 1987 and 2016 (Szaflik et al., 2017). In the combined data the survival rate was 77% (53 of 69) for hydropic and 90% (37 of 41) for nonhydropic fetuses.
It is important to note that despite successful decompression by thoracoamniotic shunting, survivors often have marked respiratory insufficiency, and some have required ECMO or high-frequency ventilation. These cases are unusual in that hydrops developed in macrocystic lesions. The most worrisome antenatal presentation is a large microcystic CPAM with hydrops that does not lend itself to catheter decompression.
Open fetal surgery remains a treatment option for type III CPAMs associated with hydrops refractory to maternal steroids. Fetal surgical resection of massively enlarged microcystic CPAM with associated hydrops has been performed in 25 patients at 21 to 29 weeks of gestation (Adzick et al., 1993, 1998; Harrison et al., 1990B). In one case, a multicystic lesion underwent thoracoamniotic shunt placement which failed to adequately decompress the mass effect prior to fetal surgery. In the 16 fetuses that survived, fetal CPAM resection led to hydrops resolution in 1 to 2 weeks, return of the mediastinum to the midline within 3 weeks and impressive in utero lung growth. There were nine fetal deaths in the cases of fetal surgery resection. In one case, the “mirror syndrome” had already developed in the mother (Creasy, 1979). The fetal operation was successful, and the hydrops improved but the placentomegaly and maternal hyperdynamic state remained and the fetus was delivered 1 week later. In one case, the fetus had bradycardia and died 8 hours postoperatively. In another case, uncontrolled uterine contractions were the cause of intraoperative fetal death. In the remaining deaths, massive hydrops was present, and the fetuses died intraoperatively, one during induction of anesthesia and the others immediately after the fetal thoracotomy was performed with terminal bradycardia after delivery of the CPAM from the chest.
In some instances, the size of the CPAM remains substantial with significant mediastinal shift and cardiac compression. In these cases, delivery by EXIT-to-Resection may be indicated (Hedrick et al., 2005). The rationale for this approach is that the mediastinal shift and compression by the CPAM will make ventilation difficult if not impossible and will similarly impair venous return if ECMO was attempted. During EXIT-to-Resection, a thoracotomy for resection of the CPAM usually by formal lobectomy is performed on placental support. In this approach, when the infant is born, the trachea is decompressed facilitating ventilation and, if ECMO is needed, venous return to the cannula will be unobstructed. We have performed 13 EXIT-to-Resection procedures for CPAMs with significant intrathoracic airway compromise. In this small series all but one patient survived, but 3 required ECMO support.
- Steroids in the Treatment of CPAM
Some patients either won’t be candidates for open fetal surgery because of medical or psychosocial contraindications or due to reservations regarding maternal risks of the procedure. In these cases, one or more courses of maternal steroids (betamethasone) may be effective in arresting the growth of the CPAM.
We reported a series of CPAMs of varying types (Morris et al. 2008) and found a 50% response rate among 4 cases of high risk CPAMs. In collaboration with UCSF and CHOP, we pooled our cases and determined that in type III or microcystic CPAMs, there was an 85% response rate but type I or II CPAMs had a significantly lower response rate. We have experience with 54 CPAMs treated prospectively with betamethasone for CPAMs with CVR > 1.6 and/or hydrops. In patients with CPAMs with CVR > 1.6 but no hydrops, survival was 100%. Even in hydropic CPAMs, 49% responded to steroids with resolution of hydrops and survival. In the 6 cases that did not respond to one course of steroids a second course was successful in 2 of 6. If the CPAM does not respond to 2 courses of steroids the best alternative is open fetal surgery.
At the Fetal Care Center Dallas, we treat all CPAMs with a CVR > 1.6 or evidence of hydrops with a course of 2 doses of 12 mg of betamethasone. These high risk CPAMs are followed 2 to 3 times a week. Response is defined as plateau in growth of CPAM, and usually occurs at a mean gestational age of 26 weeks but can range from 24 to 32 weeks. We believe that steroids induce arrest of CPAM growth, resulting in a plateau earlier than might otherwise occur. The fetus then grows around the CPAM and gradually the hydrops resolves.
We have observed that, while CPAMs may stop growing, some large lesions don’t regress as readily as less high risk CPAMs. For this reason, we have seen more CPAMs remain quite large with compromise of the intrathoracic airway requiring delivery by EXIT-to-Resection. It is essential that these CPAMs having responded to steroids be followed very closely and reassessed for the compromise of the intrathoracic airway and need for delivery by EXIT.
- Management of Pregnancy
The initial evaluation of the patient with a suspected fetal CPAM should include a detailed ultrasound examination to confirm the diagnosis, including color flow Doppler studies to demonstrate or exclude systemic blood supply as seen in hybrid lesions or BPS. The size of the cysts within the lesion should be noted, as well as the size and location of the CPAM. Evidence of mediastinal shift and subtle signs of hydrops should be sought. The incidence of chromosomal anomalies in CPAM is uncertain. In the report by Adzick et al. (1998) among 134 prenatally diagnosed CPAMs at a tertiary-care center, there was only one fetus with a chromosomal abnormality (trisomy 21), for an incidence of only 0.7%. We recommend amniocentesis for karyotype analysis if fetal treatment is anticipated (D’Alton et al., 1993).
Often, a patient may present with a large CPAM and hydrops in which case there isn’t time for karyotype analysis, in these cases we proceed without a karyotype as long as there are no other sonographic abnormalities. Fetal echocardiography should be performed in all cases of suspected CPAM because of an increased incidence of associated cardiac anomalies, particularly truncus arteriosus and tetralogy of Fallot (Miller et al., 1980; Stocker et al., 1977). In addition, there is impaired cardiac function in large CPAMs that shift the mediastinum causing compression of the ventricles, elevated central filling pressures, altered ventricular inflow patterns and reversal of IVC flow with atrial contractions. This pattern of restrictive ventricular filling associated with flow reversals in the IVC with atrial contractions may be a harbinger of the development of hydrops. At a minimum, prenatal consultation should be obtained from a pediatric surgeon, a neonatologist and a pediatric cardiologist.
If there are associated life-threatening congenital anomalies, the family can be counseled and may choose not to continue the pregnancy. The development of the maternal “mirror syndrome” warrants immediate delivery. A fetus with an isolated CPAM but no hydrops should be followed closely by at least weekly serial sonography until plateau in CPAM growth is observed. Occasionally, these lesions will regress during gestation and CPAMs should be observed for signs of hydrops. All fetuses with CPAMs should be referred for delivery at a tertiary-care center, preferably with ECMO capability, where a planned delivery with appropriate resuscitation and surgery can be performed. There is usually no need for cesarean delivery of a baby with CPAM except for standard obstetrical indications and for cases which require EXIT-to-Resection.
- Management of the Newborn
The fetus with CPAM should be referred for delivery at a center with an intensive care nursery and appropriate staff available to resuscitate a newborn with potentially severe pulmonary hypoplasia. The newborn should be evaluated in the nursery to confirm the prenatal diagnosis and exclude other associated anomalies. The infant with type I or II CPAM may be at significant risk for air trapping in the CPAM, which may acutely worsen the respiratory status within hours of birth. 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.
- Surgical Treatment
CPAM is usually confined to a single lobe. Rare cases have been reported of multilobar involvement of one lung or bilateral lesions (Rempen et al., 1987). Complete resection of the CPAM, usually by lobectomy, is the treatment of choice in CPAM. In 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 non-anatomic resection to preserve as much pulmonary parenchyma as possible to allow postoperative compensatory growth and avoid postpneumonectomy complications (Mentzer et al., 1992).
The newborn with a CPAM detected antenatally that subsequently regressed needs postnatal evaluation. Chest radiographs are not often helpful but subtle abnormalities may be evident, but chest CT scanning may be necessary to detect residual CPAM. Several authors have recommended that, as long as these lesions are asymptomatic, they be observed closely and managed without resection (Aziz et al., 2004; Hsich et al., 2005; Adzick et al., 1993; MacGillivray et al., 1993). The argument against this approach includes the reported cases of myxosarcoma, embryonal rhabdomyosarcoma, pleuropulmonary blastoma and bronchoalveolar carcinoma arising in CPAMs. While primary lung tumors are rare during the first two decades of life, 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 complication for which these infants remain at risk.
Some have argued that asymptomatic CPAMs should only be followed and the risks of surgery in infancy outweighs the potential benefits (Aziz et al., 2004). However, CPAMs represent a life-long risk of both infection and malignant transformation. There are no means available to follow these patients and identify a problem before infection has occurred or malignant transformation has taken place. In centers with significant experience in lung resection in infants, CPAMs can be safely resected with no mortality and virtually no morbidity (Tsai et al., 2007).
Our approach is to obtain a postnatal CT scan and use minimally invasive surgical approaches including thoracoscopic lobectomy, muscle sparing thoracotomy, and non-anatomic resection when possible to retain as much normal lung tissue as possible. 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.
- Minimally Invasive Techniques
A formal posterolateral thoracotomy in neonates and infants can have unintended morbidity related to decreased shoulder mobility, scoliosis and the development of chest wall deformities on long-term follow-up. As a consequence, the use of minimally invasive techniques, such as thoracoscopic lobectomies and muscle sparing thoracotomy, have become the preferred approaches in neonates and children.
The technique for a muscle sparing thoracotomy utilizes a 4 to 5cm transverse incision in the mid-axilla at about the level of the nipple. The serratus anterior and latissimus dorsi are spared by retraction allowing exposure of the ribs. Patience is required with the use of this technique as initial exposure will be limited until relaxation of the latissimus and serratus occurs with time.
- Thoracoscopic lobectomy
For the last decade, we have preferred to use minimally invasive techniques to perform lobectomies in all of these infants with congenital cystic lesions. The benefits of avoiding a formal thoracotomy and the morbidity associated with it greatly out way the disadvantages of the increased technical difficulty and operative time. In fact, with experience the operative times have equaled or are faster than with a standard thoracotomy.
Potter et al in 2012 reported that thoracoscopic resection was used in 39.4% of 1120 children who underwent resection of cystic lung disease. Utilization of the thoracoscopic approach increased from 32.2% in 2008 to 48.2% in 2012. After stratifying by magnitude of resection and adjusting for patient complexity, complication rates and postoperative length of stay were similar between thoracoscopic and open approaches.
- Long-Term Outcome
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 be at risk for complications. As noted above, these include air trapping with gradual enlargement over time, infection and malignancy arising within the CPAM. Also, as noted above, the infants usually have remarkable compensatory growth of the residual lung following resection, with continued alveorization for several years. Even in cases with severe pulmonary hypoplasia due to the CPAM, these children appear to have no limitations on their activities and are no more at risk for respiratory infections than other children. There is some data to suggest an increased predisposition to reactive airway disease in these children. We do recommend prophylaxis with Synagis in infancy in children with significant pulmonary hypoplasia, pulmonary hypertension or chronic lung disease as they are not likely to tolerate RSV infection as well as children with normal lung development. The children who survived open fetal surgery for CPAMs associated with hydrops appear to be still doing well from 5-15 years postoperatively.
- Genetics and Recurrence Risk
CPAM has no known genetic defect responsible for its development and is thought to be an early developmental anomaly of uncertain cause. CPAM is not known to be specifically associated with chromosomal abnormalities, although one case of the 134 CPAMs reported by Adzick et al. (1998) had trisomy 21. No cases of recurrence of CPAM in a sibling or offspring have been reported.
Adzick NS, Harrison MR, Glick PL, et al. Fetal cystic adenomatoid malformation: prenatal diagnosis and natural history. J Pediatr Surg. 1985b;20:483-488.
Adzick NS, Harrison MR. Management of the fetus with a cystic adenomatoid malformation. World J Surg. 1993;17:342-349.
Adzick NS, Harrison MR, Crombleholme TM. Fetal lung lesions: management and outcome. Am J Obstet Gynecol. 1998;179:884-889.
Atkinson JB, Ford EG, Ketagawa H. Persistent pulmonary hypertension complicating cystic adenomatoid malformations in a neonate. J Pediatr Surg 1972; 27: 54-6.
Bailey PV, Tracy T Jr, Connors RH, et al. Congenital bronchopulmonary malformations: diagnostic and therapeutic considerations. J Thorac Cardiovasc Surg. 1990;99:597-603.
Benjamin DR, Cahill JL. Bronchioloalveolar carcinoma of the lung and congenital cystic adenomatoid malformation. Am J Clin Pathol. 1991;95:889-892.
Bentur L, Canny G, Thoener P, et al. Spontaneous pneumothorax in cystic adenomatoid malformation: unusual clinical and histologic features. Chest. 1991;99:1292-1293.
Bezzuti RT, Isler RJ. Antenatal ultrasound detection of cystic adenomatoid malformation of lung: report of a case and review of the recent literature. Clin Ultrasound. 1983;11:342-346.
Bianchi DW, Crombleholme TM, D’Alton ME, Malone FA, second edition – Fetology: Diagnosis and Management of the Fetal Patient McGraw Hill, New York, NY. 2010
Boulot P, Pages A, Deschamps F, et al. Early prenatal diagnosis of congenital cystic adenomatoid malformation of the lung (Stocker’s type I): a case report. Eur J Obstet Gynecol Reprod Biol. 1991;41:159-162.
Carter R. Pulmonary sequestration. Ann Thorac Surg. 1959;7:68-68.
Cass DL, Crombleholme TM, Howello LJ, et al. Cystic lung lesions with systemic arterial blood supply: a hybrid of congenital cystic adenomatoid malformation and bronchopulmonary sequestration. J Pediatr Surg. 1997;32:986-990.
Chinn DH, Filly RA, Callen PW, et al. Congenital diaphragmatic hernia diagnosed prenatally by ultrasound. Radiology. 1983;148:119-123.
Clements BS, Warner JO. Pulmonary sequestration and related congenital bronchopulmonary vascular malformations: nomenclature and classification based on anatomical and embryological considerations. Thorax. 1987;42:401-408.
Clements BS. Congenital malformations of the lungs and airways. In: Tausig LM, Land a u LI, eds. Pedialr Respiratory Medicine. St Louis: Mosby; 1999:I 106- 1122.
Cloutier MM, Schaeffer DA, Hight D. Congenital cystic adenomatoid malformation. Chest 1993; 103: 761-4.
Cochia R, Sobonya RE. Congenital cystic adenomatoid malformation of the lung and bronchial atresia. Hum Pathol. 1981;12:947-950.
Collin P, Desjardins JG, Khan AH. Pulmonary sequestration. J Pediatr Surg. 1987;22:750-753.
Cone APD, Adam AE. Cystic adenomatoid malformation of the lung (Stocker type III) found on antenatal ultrasound examination. Br J Radiol. 1984;57:176-178.
Coran Ri\1, Stocker JT. Extralobar sequestration with frequently associ ated congenital cystic adenomatoid malformatio,n type 2: a repo rt of 50 cases. Pediatr Dev Palhol l 999;2: 454- •162.
Crombleholme TM, Leichtly KW, Howell LJ, et al. Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung. JPediatr Surg. 2002;37:331-338.
Dann SM,Martin JN,White SJ. Antenatal ultrasound findings in cystic adenomatoid malformation. Pediatr Radiol. 1981;10:180-182.
Davidson LA, Batman P, Fagan DG. Congenital acinar dysplasia: a rare cause of pulmonary hypoplasia. Histopathology. 1998;32:57-59
Deacon CS, Smart PJ, Rimmer S. The antenatal diagnosis of congenital cystic adenomatoid malformation of the lung. Br J Radiol. 1990;63:968-970.
Deluca FG, Wesselhoelft CW. Surgically treatable cause of neonatal respira tory lung distress. Clin Peri11a101 1978;5:37-•17.
Demos NJ, Teresi A. Congenital lung malformations: a unified concept and a case report. J Thorac Cardiovasc Surg. 1975:70:260-264.
Diwan RV, Brennan JN, Phillipson EH, et al. Ultrasonic prenatal diagnosis of Type III congenital cystic adenomatoid malformation of lung. J Clin Ultrasound. 1983;11:218-221.
DeParedes CG, Pierce WS, Johnson DG, Waldcnhauscn JA. Pulmonary sequestration in infants and children; a 20-ycar experience and review of the literature. / Pediatr Surg I970:5:136- 141.
De Santis M, Masini L, Noia G, el al. Congeni tal cystic malformation of the lung: antenatal ultrasound findin gs and fetal-neo natal outcome. Fiftee n years’ experience. Fetal Diagn Tiier 2001:15:246-248.
Dolkhart L, Reimer F, Helmuth W, et al. Antenatal diagnosis of pulmonary sequestration: a review. Obstet Gynecol Surg. 1992;47:515-520.
Duncombe GI, Dickeson JE, Kikiros CS. Prenatal diagnosis and manage ment of congenital cystic adenomatoid malformation of the lung. Am J Obstet Gyn 2002:187:950-954.
Elias K, Aufses AH. Squamous cell carcinoma occurring in an intralobar pulmonary sequestration. Exp Med Surg. 1960;18:36-46.
Gerle RD, Jaretski A, Ashley CA, et al. Congenital bronchopulmonary malformation: pulmonary sequestration communicating with the gastrointestinal tract. N Engl J Med. 1968;278:1413-1419.
Gonzalez-Cuezzi F, Boggs JD, Raffensberger JG. Brain heterotopia in the lungs: a rare case of respirator disease in the newborn. Am J Clin Pathol. 1980;73:281-285
Gottrup F, Lund C. Intralobar pulmonary sequestration: a report of 12 cases. Scand J Respir Dis. 1978;59:21-29.
Harrison MR, Adzick NS, Jennings RW, et al. Antenatal intervention for congenital cystic adenomatoid cystic malformation. Lancet. 1990a;336:965-967
Hazebrock FWJ, Pattenier JW, Tibboel D, et al. Congenital diaphragmatic hernia: the impact of preoperative stabilization. J Pediatr Surg. 1989;24:678-684.
Heithoff KB, Sane SM, Williams HJ, et al. Bronchopulmonary foregut malformations. A unifying etiological concept. AJR AmJ Roentgenol. 1976;126:46-55.
Hernanz-Schulman M. Cysts and cystlike lesions of the lung. Radiol Clin North Am. 1993;31:631-649.
Hernanz-Schulman M, Stein IM, Neblett WW, et al. Pulmonary sequestration: diagnosis with color flow sonography and a new theory of associated hydrothorax. Radiology. 1991;180:817-821.
Hobbins JC, Grannum PAT, Berkowitz RL, et al. Ultrasound in the diagnosis of congenital anomalies. Am J Obstet Gynecol. 1979;134: 331-345
Hubbard AM, Crombleholme TM. Prenatal and neonatal lung lesions. Semin Roentgenol. 1998;33:117-125.
Johnson JA, Rumack CM, Johnson ML, et al. Cystic adenomatoid malformation: antenatal demonstration. AJR Am J Roentgenol. 1984;142:483-484.
Juettner FM, Pinter HH, Hammer G, et al. Bilateral intralobar pulmonary sequestrations: therapeutic implications. Ann Thorac Surg. 1987;43:660-662.
Keswani SG, Crombleholme TM, Pawel BR, et al. Prenatal diagnosis and management of mainstem bronchial atresia. Fetal Diagn Ther. 2005;20:74-78.
Kravitz RM. Con gen ital malformations of the lung. C/in Nori/, Am l994;41:453-472.
Kuller JA1, Yankowitz J, Goldberg JD, Harrison MR, Adzick NS, Filly RA, Callen PW, Golbus MS. Outcome of antenatally diagnosed cystic adenomatoid malformations. Am J Obstet Gynecol. 1992 Oct;167(4 Pt 1):1038-41.
Kunisaki SM, Fauza DO, Nemes LP, et al. Bronchial atresia: the hidden pathology within a spectrum of prenatally diagnosed lung masses. J Pediatr Surg. 2006;41:61-65.
Laberge JM, Flageole H, Pugash D, et al. Outcome of the prenatally diagnosed congenital cystic adenomatoid lung malformation: a Canadian experience. Fetal Diagn Ther. 2001;16:178-186.
Langer JC, Filler RM, Bohn DJ, et al. Timing of surgery for congenital diaphragmatic hernia: is emergency operation necessary? J Pediatr Surg. 1989;23:731-738.
Landing BH, Dixon LG. Congeni tal malformations and genetic d isorde rs of the respiratory tract. Am Rev Rcspir Dis 1979:120: 151- 158.
Langston C. New concepts in the pathology of congenital lung malformations. Semin Pediatr Surg. 2003;12:17-37.
Leninger BJ, Haight C. Congenital cystic adenomatoid malformation of the left lobe lower lobe with compression of remaining lung. ClinPediatr. 1973;12:182-186
Miller JA, Corteville JE, Lange r JC . Congen ita l cystic adenoma toid malfor mation in the fetus: natural history and predictors of outcome. / Pedialr S11rg l996;31:805-808.
MacSweeney F1, Papagiannopoulos K, Goldstraw P, Sheppard MN, Corrin B, Nicholson AG; An assessment of the expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation. Am J Surg Pathol. 2003 Aug;27(8):1139-46.
MacGillivray TE,Adzick NS,Harrison MR, et al. Disappearing fetal lung lesions. J Pediatr Surg. 1993;28:1321-1325.
Marcus SF, Lobb MO. The antenatal diagnosis by ultrasonography of type III congenital cystic adenomatoid malformation of the lung: case report. Br J Obstet Gynaecol. 1986;93:1002-1005
May DA, Barth RA, Yeager S, et al. Perinatal and postnatal chest sonography. Radiol Clin North Am. 1993;31:499-516.
Mendoza A, Wolf P, Edwards DK, et al. Prenatal ultrasonographic diagnosis of congenital adenomatoid malformation of the lung. Arch Pathol Lab Med. 1986;110:402-404.
Mentzer SJ, Filler RM, Phillips J. Limited pulmonary resections for congenital cystic adenomatoid malformation of the lung. J Pediatr Surg. 1992;27:1410-1413.
Miller RK, Sieber WK, Yunis EJ. Congenital cystic adenomatoid malformation of the lung: a report of 17 cases and review of the literature. Pathol Annu. 1980;1:387-407.
Moerman P, Fryns JP, Vandenberghe K, et al. Pathogenesis of congenital cystic adenomatoid malformation of the lung. Histopathology. 1992;21:315-321.
Morin C, Fillatrault P, Russo P. Pulmonary sequestration with histologic changes of cystic adenomatoid malformation. Pediatr Radiol. 1989;19:130-133.
Morin L, Crombleholme TM, Lewis F, et al. Bronchopulmonary sequestration: prenatal diagnosis with clinicopathologic correlation. Curr Opin Obstet Gynecol. 1994;6:479-481.
Morris LM, Lim FY, Livingston JC, Polzin WJ, Crombleholme TM. High risk fetal congenital pulmonary airway malformations have a variable response to steroids. J Pediatr Surgery. 2009. Jan;44(1):60-5.
Moulik D, Robinson L, Daily DK, et al. Perinatal sonographic depiction of intralobar pulmonary sequestration. J Ultrasound Med. 1987;6:703-706.
Nicolaides KH, Blatt AJ, Greenough A. Chronic drainage of fetal pulmonary cysts. Lancet. 1987;1:618-619.
O’Mara CS, Baker RR, Jeyasingham K. Pulmonary sequestration. Surg Gynecol Obstet. 1978;147:609-616.
Ozcan C, Celik A, Ural Z, et al. Primary pulmonary rhabdomyosarcoma arising within cystic adenomatoid malformation: a case report and review of the literature. J Pediatr Surg. 2001;36:1062-1065.
Rashad F, Gaisoni E, Gaglione S. Aberrant arterial supply in congenital cystic adenomatoid malformation of the lung. J Pediatr Surg. 1988;23:107-108
Rempen A, Feige A, Wunsch P. Prenatal diagnosis of bilateral cystic adenomatoid malformation of the lung. J Clin Ultrasound. 1987;15:3-8.
Romero R, Chernenak FA,Katzen J, et al. Antenatal sonographic findings of extralobar pulmonary sequestration. J Ultrasound Med. 1982;1:131-132.
Savic B, Birtel FJ, Thalen W, et al. Lung sequestration: report of seven cases and review of 540 published cases. Thorax. 1979;34:96.
Shanji FM, Sachs JH, Perkins DG. Cystic diseases of the lungs. Surg Clin North Am. 1988;68:581-618.
Stephanopoulos C, Catsaros H. Myxosarcoma complicating a cystic hamartoma. Thorax. 1963;18:144-145.
Stocker JT, Madewell JER, Drake RM. Congenital cystic adenomatoid malformation of the lung: classification and morphologic spectrum. Hum Pathol. 1977;8:155-171.
Szarnicki R, Maurseth K, deLoval M, et al. Tracheal compression by the aortic arch following right pneumonectomy. Ann Thorac Surg. 1978;25:321-324.
Taguchi ‘I; Suita S, Yamanouchi T, et al. Antenatal diagnosis and surgical
management or congenital cystic adenomatoicl malforma tion o r the lung. Fetal Diag11 ·n ier 1995;10:400- 405.
Takeda S, Miyoshi S. Inoue M, et al. Clinical spect ru m or congeni tal cystic disease or the lung in children. EurJ Cardiot/rorac Surg 1999;15:11- 18.
Taneler B, Valcin M. Yilmaz B. Congeni tal Lobar emphysema: a clinicopathologic evaluation of 14 cases. Eur J Pediatr Surg 2003;13:108- 111.
Thilenius OG, Ruschhaupt DG, Replogh RL, et al. Spectrum of pulmonary sequestration: association with anomalous pulmonary venous drainage in infants. Pediatr Cardiol. 1983;4:97-100.
Ueda K,Grippo R,Unger R, et al. Rhabdomyosarcoma of lung arising in a congenital cystic adenomatoid malformation. Cancer. 1977;40:383-388.
Walker J, Cudmore RE. Respiratory problems and cystic adenomatoid malformation of the lung. Arch Dis Child. 1990;65:649-659.
Warner CL, Britt RL, Riley HD Jr. Bronchopulmonary sequestration in infancy or childhood. J Pediatr. 1958;53:521-528.
Wecla K, Grippo R, Unger R, et al. Rhab do myosa rcoma o r lung arising in a congenital cystic adenomatoid malformation. Cancer 1977;40:383-388.
MacSweeney F1, Papagiannopoulos K, Goldstraw P, Sheppard MN, Corrin B, Nicholson AG. An assessment of the expanded classification of congenital cystic adenomatoid malformations and their relationship to malignant transformation. Am J Surg Pathol. 2003 Aug;27(8):1139-46.