Congenital Pulmonary Airway Malformation

Congenital pulmonary airway malformation (CPAM) (Fig. 1) affects between 1/8,000 and 1/35,000 livebirths¹.

CPAM results from the disordered development of the lower respiratory tract. The current theory of pathogenesis favors a maturational arrest in bronchopulmonary development, resulting in dysplastic tissue distal to this segment¹,²,³. CPAM appears to consist of two major subtypes: type I consists of lesions due to an arrest at the pseudoglandular stage of development (5-17 weeks post-conception); and type II lesions that occur during the saccular period (3rd trimester)⁵. The aberrant cysts in CPAM have intracystic communication⁴.

Figure 1. Left-sided CPAM (arrow); heart compressed against ribs on the right. Normal right lung behind the heart.

Figure 2. Left-sided CPAM (straight arrow) with hydrops (curved arrow).

Stocker⁵ initially subdivided congenital cystic adenomatoid malformation (CCAM) into three subtypes based upon postnatal cystic size and histology: type I, cysts between 30-100 mm; type II, cysts < 10 mm (Fig. 2); type III, microcystic. When Stocker added two additional types to his categories of congenital cystic adenomatoid malformation (type O, acinar dysplasia and type IV, peripheral), he suggested a change in the name of this lesion from CCAM to CPAM⁶. This nomenclature has, generally, carried over to the prenatal diagnosis of CPAM. The classification of Adzick et al⁷ based on the size of cysts > 5 mm and < 5 mm differs from this pathologic criteria.

CPAMs are evenly distributed between the left and right lung. Lesions are unilobar in 80% to 95% of cases⁵,⁸. CPAM may affect more than one lobe, but bilateral lesions are rare⁹,¹⁰.

Because of its abnormal development, the CPAM portion of the lung does not assist with gas exchange.

Microcystic lesions tend to have a rapid growth phase between 20 and 26 weeks’ gestation. The volume of the lesion then plateaus and may regress¹¹,¹²,¹³. Microcystic lesions have an increased risk to develop hydrops. Microcystic CPAMs may become isoechoic with adjacent normal lung between 30-34 weeks’ gestation. Although they may not be detectable sonographically, these lesions remain visible on MRI.

Macrocystic lesions do not have a characteristic mid-pregnancy growth spurt and generally do not regress in volume as pregnancy advances.

Since the defect in CPAM is at the bronchiolar level, the vascular supply to the normal and abnormal lung segments is usually unaffected.

Large microcystic or macrocystic lesions have the potential to compress the esophagus and inferior vena cava. Polyhydramnios may result from impairment of fetal swallowing¹⁴. When intrathoracic pressure is sufficient to impair venous return to the heart, hydrops (Fig.3) may result¹⁵. In the presence of incipient or frank hydrops, fetal intervention may be considered¹⁶. Compression of the contralateral lung by a large CPAM can result in pulmonary hypoplasia⁴,¹³.

Figure 3. CPAM. Complete involvement right lung (straight arrow) with secondary hydrops (scalp edema [curved arrow] and ascites [short arrow]).

Figure 4. Right-sided CPAM (arrow); heart compressed against ribs on the left.

Increasing mediastinal shift as gestation advances is associated with decreased survival. A severe shift has been defined as complete displacement of the heart across the thorax with no visible contralateral lung (Fig. 4)¹¹.

The degree of lung involvement is associated with survival – involvement of a single lobe suggests a better outcome than if the entire lung is involved¹⁴. Bilateral lung involvement has a poor prognosis¹⁷.

CPAM is characteristically diagnosed after 16 weeks’ gestation¹⁴. The ability to correctly diagnosis lung lesions by prenatal ultrasound is limited¹⁰. Achiron et al¹⁸ reported four cases of fetal hyperechogenic lung with subsequent resolution. In one case, retained mucoid lung secretions was confirmed as the etiology for the echogenic lobe.

In cases of segmental lung echogenicity without a mediastinal shift and signs of hydrops, there is a possibility of spontaneous resolution.

Differential Diagnosis

The differential diagnosis for CPAM is outlined in Table I.

Table I. Differential diagnosis of an echogenic chest mass⁵⁵

Bronchopulmonary sequestration
Bronchial atresia/stenosis
Lobar emphysema
Lobar mucus plug
Neuroblastoma
Mediastinal teratoma
Congenital diaphragmatic hernia

Bronchopulmonary Sequestration

An echogenic lung mass, generally in the left lower lobe, with a systemic arterial supply is characteristic of a pulmonary sequestration. However, hybrid lesions with features of both congenital pulmonary airway malformation and pulmonary sequestration may occur¹⁷,¹⁹,²⁰.

Bronchial Atresia

Bronchial atresia is a rare echogenic lung lesion with a prevalence of 1/100,000²¹. It is due to either a malformed dysplastic section of the main stem, lobar or segmental bronchus, or a bronchial atresia secondary to a traumatic fetal event²². As would be expected, there is a poor perinatal prognosis with main stem, in contrast to lobar or segmental bronchial atresia. Bronchial atresia and CPAM frequently co-exist²³.

A diagnosis of bronchial atresia is rarely made antenatally.

The characteristic sonographic finding with bronchial atresia is a dilated tubular structure within an echogenic lung mass. Three-dimensional sonography is helpful in attempting to delineate a central hypoechoic structure within an echogenic lung mass as a bronchus²⁴. The occlusion of the bronchus leads to accumulation of lung fluid distal to the obstruction. The subsequent enlargement of the lung results in an eversion of the diaphragm, a contralateral medialstinal shift and compression of the normal lung, resulting in pulmonary hypoplasia.

In the neonate with mild bronchial atresia, CT is the imaging modality of choice. Characteristic findings include: occlusion of a bronchus central to a mucocele and emphysematous changes in the peripheral lung fields²⁵.

Congenital Lobar Emphysema

Lobar emphysema (Fig. 5) is generally a postnatal diagnosis due to an obstruction that permits inflation, but not deflation, of a lung segment. An intrinsic obstruction is due to defective bronchial cartilage or a mucus plug. An extrinsic mass (teratoma, CPAM) compressing a bronchus may produce the same effect. While seldom diagnosed in-utero, the neonatal incidence of congenital lobar emphysema is the same as for pulmonary sequestration and it is only slightly less frequent than CPAM²⁶.

Figure 5. Congenital lobar emphysema (arrow).

The increased lung echogenicity with congenital lobar emphysema is due an excessive accumulation of lung fluid in the alveoli. A sufficient amount of pressure may build up behind the obstruction to permit the fluid to escape and thereby reduce the echogenicity of the lung²⁷.

Frequently, a postnatal diagnosis, including histology, is required to clearly distinguish between the above diagnoses. It has, therefore, been suggested that the generic term – Congenital Lung Lesion – be used prenatally. Many, if not all, of the lung malformations may represent a continuum with airway obstruction as the primary etiology²⁸. Specific descriptions of the lung mass would include its architecture (cystic or solid), location, size, presence or absence of a medialstinal shift, and signs of hydrops²⁰,²⁹.

Adrenal Neuroblastoma

Neuroblastomas are the most common solid tumor in children under one year, with an incidence of 1/17,000 infants³⁰. A family history has been identified in 1-2% of cases³¹,³².

In-utero, neuroblastomas are characteristically diagnosed in the 3rd trimester. However, a neuroblastoma has been diagnosed as early as 20 weeks’ gestation³².

90% of neuroblastomas identified prenatally are adrenal in origin³².

When a large suprarenal mass is first detected, CPAM is generally the first diagnosis that is considered. Sonographically, a neuroblastoma may be cystic, solid (Fig. 6) or mixed cystic/solid in appearance³².

Figure 6. Neuroblastoma (arrow).

Serial ultrasound examinations every two weeks should be obtained in order to monitor the size of the mass and to assess the fetus for possible metastases, specifically to the placenta³³.

Cystic neuroblastomas generally have a better prognosis³⁴. When the diagnosis is in doubt fetal MRI is helpful³⁵.

Mediastinal Teratoma

Congenital teratomas occur in approximately 1/30,000 births, with 40% located in the sacrococcygeal area; 7% of cases occur in the mediastinum³⁶,³⁷.

Sonographically, mediastinal teratomas are large cystic and solid masses. When the tumor has achieved a sufficient size, cardiac compression, hydrops and polyhydramnios may result. If the teratoma has calcifications with acoustic shadowing, it is more easily distinguished from CPAM³⁸. A predominantly cystic mediastinal teratoma with hydrops can be aspirated to reduce the intrathoracic pressure and successfully manage the hydrops³⁹.

CPAM may occur in association with a congenital diaphragmatic hernia⁵,⁶.

Sonographic Assessment

An extended fetal anatomic survey is required when CPAM is suspected to rule out associated cardiac anomalies⁵, as well as to evaluate the fetus for possible sonographic stigmata of a karyotypic abnormality. In general, an isolated CPAM has not been associated with an increased risk of karyotypic malformations⁷.

In cases of possible microcystic CPAM and a mediastinal shift, weekly ultrasound examinations until the plateau of microcystic growth (26–28 weeks) can look for potential signs of hydrops¹¹,¹². After 26–28 weeks’ gestation, the fetus increases in size relative to the CPAM, allowing hydrops to resolve⁴⁰. Ultrasonic surveillance can then be individualized based upon the size of the lesion. If CPAM has dominant cysts, serial ultrasound examinations until delivery are required to look for hydrops.

The CPAM volume is calculated using the formula for an elipse (height x width x length x 0.52). The CPAM volume is divided by the head circumference in centimeters to correct for gestational age. In one study a CPAM volume ratio(CVR) > 1.6 was associated with a hydrops rate of 80% versus 2% for a CVR < 1.640. Even with a CVR < 1.6, acute enlargement of a dominant cyst could result in hydrops.

The overall prognosis with a CPAM depends, not on its type, but on the size of the lesion. Approximately 6-11% of CPAM will undergo spontaneous regression⁷,⁴¹.

Fetal Therapy

CPAM with hydrops is almost invariably fatal⁴².

The current therapy of choice for microcystic CPAM with hydrops prior to 32 weeks’ gestation is one course, or if there is no response, a second course, of two doses of 12 mg of betamethasone. Steroid treatment is believed to arrest the growth of CPAM, resulting in an earlier plateau in its growth rate. Fetuses with non-hydropic and hydropic microcystic CPAM have survival rates of 85% and 49%, respectively, after a course of steroids⁴³,⁴⁴.

Type I or type II fetal CPAMs have significantly lower response rates to a course of maternal betamethasone, in contrast to microcystic CPAMs.

For hydrops that develops or recurs after 32 weeks’ gestation, an EXIT procedure followed by neonatal surgery should be considered⁴⁵.

Macrocystic lesions that have resulted in hydrops can be treated with initial aspiration of the largest cysts (Fig. 7)⁴,⁴⁶. If there are multiple large cysts, shunting of one cyst will decompress the other cysts due to their intercommuncation⁴. Reaccumulation of fluid may occur in a multicystic CPAM and, therefore, require a cyst-amniotic fluid catheter for permanent drainage and to reduce the mass effect of the cyst or cysts⁴⁷. If there is a dominant cyst, even with a CVR < 1.6, acute enlargement of the cyst may result in hydrops. Twice weekly sonographic surveillance is, therefore, required to assess the fetus for the earliest signs of hydrops. Even after decompression and resolution of hydrops, surviving neonates often have respiratory insufficiency.

Figure 7. Right CPAM (19 weeks).

Contraindications to cyst drainage would include an abnormal fetal karyotype, a predominantly solid CPAM, or major fetal cardiac abnormality. The overall survival after a thoracoamniotic shunt is in the vicinity of 60%⁴⁸.

The reported complications with catheter placement are the common complications associated with in utero procedures – structural and/or vascular fetal trauma, chorioamnionitis, preterm labor, and preterm premature rupture of the membranes⁴.

Neonatal Therapy

The postnatal history of CPAM is highly variable. The lesion may be completely asymptomatic or a child may have recurrent respiratory infections⁵. Occasionally, postnatal CT may not reveal any evidence for a previously detected echogenic fetal lung mass. These cases are likely secondary to segmental or lobar mucous plugs that subsequently resolved¹⁸.

80% of symptomatic postnatal patients with CPAM present at birth with cardiac or respiratory compromise⁵.

In the absence of hydrops, neonatal survival approaches 100%. However, many of the neonates with large lesions require significant ventilatory support⁷. With a type I CPAM there is a risk of air trapping in the CPAM, resulting in respiratory compromise. Pneumothorax may also occur⁴⁹.

The presence of CPAM (Fig. 8) is a lifelong risk for both infection and malignant transformation. The malignant transformation of CPAM has been estimated between 1%⁵⁰ and 4%⁵¹. The bronchioloalveolar carcinomas associated with CPAM generally appear between 6 years of age and young adulthood⁵². As a result, some groups recommend the removal of CPAMs even in asymptomatic neonates. An additional benefit of resection is the compensatory growth of the normal lung that occurs after surgery⁵³.

Figure 8. CPAM (arrow) neonatal CT.

Complications from pediatric surgery range between 6-9%; mortality is rare. Most infants have normal pulmonary function on follow–up examination⁵⁰,⁵¹.

There is lack of consensus with respect to the appropriate course of action in asymptomatic children with a presumptive diagnosis of CPAM. In one study 33% of pediatric surgeons recommended observation with a highly variable frequency of follow-up. The cost of expectant observation must factor in, not only office visits and periodic chest CTs, but also the intangible cost of radiation exposure²,⁵⁴. The use of MRI for surveillance in asymptomatic neonatal CPAM has not been evaluated. However, MRI is generally less effective than CT in the evaluation of cystic lesions.

In general, surgical intervention in the asymptomatic patient is associated with shorter hospital stays, fewer complications and decreased medical costs when compared to surgical intervention only with the advent of symptoms².

Congenital Pulmonary Airway Malformation

Chapter 1