Etiology and Pathology

Pulmonary agenesis differs from hypoplasia in that agenesis entails the complete absence of a lung. Agenesis differs from aplasia by the absence of a bronchial stump or carina that is seen in aplasia. Bilateral pulmonary agenesis is incompatible with life, manifesting as severe respiratory distress and failure. Based on reports of patients with parental consanguinity, pulmonary agenesis is thought to be an autosomal recessive trait. The incidence is estimated to be 1 in 10,000-15,000 births.

Clinical Manifestations and Prognosis

Unilateral agenesis or hypoplasia can have few symptoms and nonspecific findings, resulting in only 33% of the cases being diagnosed while the patient is living. Symptoms tend to be related to associated central airway complications of compression, stenosis, and/or tracheobronchomalacia. In patients in whom the right lung is absent, the aorta can compress the trachea and lead to symptoms of central airway compression. Right lung agenesis has a higher morbidity and mortality than left lung agenesis. Pulmonary agenesis is often seen in association with other congenital anomalies such as the VACTERL sequence (vertebral anomalies, anal atresia, congenital heart disease, tracheoesophageal fistula, renal anomalies, and limb anomalies), ipsilateral facial and skeletal malformations, and central nervous system and cardiac malformations. Compensatory growth of the remaining lung allows improved gas exchange, but the mediastinal shift can lead to scoliosis and airway compression. Scoliosis can result from unequal thoracic growth.

Diagnosis and Treatment

Chest radiographic findings of unilateral lung or lobar collapse with a shift of mediastinal structures toward the affected side can prompt referral for suspected foreign body aspiration, mucous plug occlusion, or other bronchial mass lesions. The diagnosis requires a high index of suspicion to avoid the unnecessary risks of bronchoscopy, including potential perforation of the rudimentary bronchus. CT of the chest is diagnostic, although the diagnosis may be suggested by chronic changes in the contralateral aspect of the chest wall and lung expansion on chest radiographs. Conservative treatment is usually recommended, although surgery has offered benefit in selected cases.

Pathology

Congenital cystic adenomatoid malformation (CCAM) consists of hamartomatous or dysplastic lung tissue mixed with more normal lung, generally confined to one lobe. This congenital pulmonary disorder occurs in ∼1-4/100,000 births. Three histologic patterns have been described. Type 1 (50%) is macrocystic and consists of a single or several large (>2 cm in diameter) cysts lined with ciliated pseudostratified epithelium. The wall of the cyst contains smooth muscle cells and elastic tissue. One third of cases have mucus-secreting cells. Cartilage is rarely seen in the wall of the cyst. This type has a good prognosis for survival. Type 2 (40%) is microcystic and consists of multiple small cysts with histology similar to that of the type 1 lesion. Type 2 is associated with other congenital anomalies and carries a poor prognosis. In type 3 (<10%), the lesion is solid with bronchiole-like structures lined with cuboidal ciliated epithelium and separated by areas of nonciliated cuboidal epithelium. This lesion carries the poorest prognosis and can be fatal. Prenatal ultrasonographic findings are classified as macrocystic (single or multiple cysts >5 mm) or microcystic (echogenic cysts <5 mm).

Etiology

The lesion probably results from an embryologic insult before the 35th day of gestation, with maldevelopment of terminal bronchiolar structures. Histologic examination reveals little normal lung and many glandular elements. Cysts are very common; cartilage is rare. The presence of cartilage might indicate a somewhat later embryologic insult, perhaps extending into the 10th-24th wk. Although growth factor interactions and signaling mechanisms have been implicated in altered lung-branching morphogenesis, the exact roles in the maldevelopment seen here remain obscure.

Diagnosis

Cystic adenomatoid malformations can be diagnosed in utero by ultrasonography (Fig. 387-1). Fetal cystic lung abnormalities can include cystic adenomatoid malformations (40%), pulmonary sequestration (14%) (Chapter 387.4), or both (26%); the median age at diagnosis is usually 21 wk gestation. In 1 series, only 7% had severe signs of fetal distress including hydrops, pleural effusion, polyhydramnios, ascites, or severe facial edema; 96% of the fetuses were born alive, 2 of whom died in the neonatal period. Lesions causing fetal hydrops have a poor prognosis. Large lesions, by compressing adjacent lung, can produce pulmonary hypoplasia in nonaffected lobes (Chapter 387.2). Even lesions that appear large in early gestation can regress considerably or decrease in relative size and be associated with good pulmonary function in childhood. CT allows accurate diagnosis and sizing of the lesion.

Figure 387-1 Imaging of congenital cystic adenomatous malformation of the lung (CCAM) on the same patient with prenatal ultrasound scan (A), chest radiograph (B), and CT scan (C). Note that the lesion is not visible on the chest radiograph.

(From Lakhoo K: Management of congenital cystic adenomatous malformations of the lung, Arch Dis Child Fetal Neonatal Ed 94:F73–F76, 2009.)

Clinical Manifestations