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.

Bibliography

Bentsianov BL, Goldstein NA, Giuste R, et al. Unilateral pulmonary agenesis presenting as an airway lesion. Arch Otolaryngol Head Neck Surg. 2001;126:1386-1389.

Greenough A, Ahmed T, Broughton S. Unilateral pulmonary agenesis. J Perinat Med. 2006;34:80-81.

Krivchenya DU, Dubrovin AG, Krivchenya TD, et al. Aplasia of the right lung in a 4-year-old child: surgical stabilization of the mediastinum by diaphragm translocation leading to complete recovery from respiratory distress syndrome. J Pediatr Surg. 2000;35:1499-1502.

387.2 Pulmonary Hypoplasia

Jonathan D. Finder

Etiology and Pathology

Pulmonary hypoplasia involves a decrease in both the number of alveoli and the number of airway generations. The hypoplasia may be bilateral in the setting of bilateral lung constraint, as in oligohydramnios or thoracic dystrophy. Pulmonary hypoplasia is usually secondary to other intrauterine disorders that produce an impairment of normal lung development (Chapter 95). Conditions such as deformities of the thoracic spine and rib cage (thoracic dystrophy), pleural effusions with fetal hydrops, cystic adenomatoid malformation, and congenital diaphragmatic hernia physically constrain the developing lung. Any condition that produces oligohydramnios (fetal renal insufficiency or prolonged premature rupture of membranes) can also lead to diminished lung growth. In these conditions, airway and arterial branching are inhibited, thereby limiting the capillary surface area. Large unilateral lesions, such as congenital diaphragmatic hernia and cystic adenomatoid malformation, can displace the mediastinum and thereby produce a contralateral hypoplasia, although usually not as severe as that seen on the ipsilateral side.

Clinical Manifestations

Pulmonary hypoplasia is usually recognized in the newborn period, owing to either the respiratory insufficiency or the presentation of persistent pulmonary hypertension. Later presentation (tachypnea) with stress or respiratory viral infection can be seen in infants with mild pulmonary hypoplasia.

Treatment

Mechanical ventilation and oxygen may be required to support gas exchange. Specific therapy to control associated pulmonary hypertension, such as inhaled nitric oxide, may be useful. In cases of severe hypoplasia, the limited capacity of the lung for gas exchange may be inadequate to sustain life. Extracorporeal membrane oxygenation can provide gas exchange for a critical period of time and permit survival. Rib-expanding devices (vertically expansible prosthetic titanium ribs) can improve the survival of patients with thoracic dystrophies (Chapter 671).

387.3 Cystic Adenomatoid Malformation

Jonathan D. Finder

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.