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

Patients can present in the newborn period or early infancy with respiratory distress, recurrent respiratory infection, and pneumothorax. The lesion may be confused with a diaphragmatic hernia (Chapter 95.8). Patients with smaller lesions are usually asymptomatic until mid-childhood, when episodes of recurrent or persistent pulmonary infection or chest pain occur. Breath sounds may be diminished, with mediastinal shift away from the lesion on physical examination. Chest radiographs reveal a cystic mass, sometimes with mediastinal shift (Fig. 387-2). Occasionally, an air-fluid level suggests a lung abscess.

Figure 387-2 Neonatal chest x-ray showing large multicystic mass in the left hemithorax with mediastinal shift due to congenital cystic adenomatoid malformation (CCAM).

(From Williams HJ, Johnson KJ: Imaging of congenital cystic lung lesions, Paediatr Resp Rev 3:120–127, 2002.)

Treatment

Antenatal intervention in severely affected infants is controversial but can include excision of the affected lobe for microcystic lesions, aspiration of macrocystic lesions, and, rarely, open fetal surgery. In the postnatal period, surgery is indicated for symptomatic patients. Although surgery may be delayed for asymptomatic infants because postnatal resolution has been reported, true resolution appears to be very rare in that abnormalities usually remain detectable on CT or MRI. Sarcomatous and carcinomatous differentiation has been described in patients with CCAM, so surgical resection by 1 yr of age is recommended to limit malignant potential. The mortality rate is <10%. Another indication for surgery is to rule out pleuropulmonary blastoma, a malignancy that can appear radiolographically similar to type I CCAM.

Pathophysiology

The lung tissue in a sequestration does not connect to a bronchus and receives its arterial supply from the systemic arteries (commonly off the aorta) and returns its venous blood to the right side of the heart through the inferior vena cava (extralobar) or pulmonary veins (intralobar). The sequestration functions as a space-occupying lesion within the chest; it does not participate in gas exchange and does not lead to a left-to-right shunt or alveolar dead space. Communication with the airway can occur as the result of rupture of infected material into an adjacent airway. Collateral ventilation within intrapulmonary lesions via pores of Kohn can occur. Pulmonary sequestrations can arise through the same pathoembryologic mechanism as a remnant of a diverticular outgrowth of the esophagus. Some propose that intrapulmonary sequestration is an acquired lesion primarily caused by infection and inflammation; inflammation leads to cystic changes and hypertrophy of a feeding systemic artery. This is consistent with the rarity of this lesion in autopsy series of newborns. Gastric or pancreatic tissue may be found within the sequestration. Cysts also may be present. Other associated congenital anomalies, including CCAM (Chapter 387.3), diaphragmatic hernia (Chapter 95.8), and esophageal cysts, are not uncommon. Some believe that intrapulmonary sequestration is often a manifestation of cystic adenomatoid malformation and have questioned the existence of intrapulmonary sequestration as a separate entity.

Clinical Manifestations and Diagnosis

Physical findings in patients with sequestration include an area of dullness to percussion and decreased breath sounds over the lesion. During infection, crackles may also be present. A continuous or purely systolic murmur may be heard over the back. If findings on routine chest radiographs are consistent with the diagnosis, further delineation is indicated before surgical intervention (Fig. 387-3). CT with contrast can demonstrate both the extent of the lesion and its vascular supply. Magnetic resonance angiography (MRA) is also useful. Ultrasonography can help rule out a diaphragmatic hernia and demonstrate the systemic artery. Surgical removal is recommended. Identifying the blood supply before surgery avoids inadvertently severing its systemic artery.

Figure 387-3 A, Plain chest x-ray showing changes in the region of the right lower/middle lobe of the lung. B, CT showing parenchymal changes in the right lower lobe of the lung in keeping with a sequestration.

(From Corbett HJ, Humphrey GME: Pulmonary sequestration, Paediatr Resp Rev 5:59–68, 2004.)

Intrapulmonary sequestration is generally found in a lower lobe and does not have its own pleura. Patients usually present with infection. In older patients, hemoptysis is common. A chest radiograph during a period when there is no active infection reveals a mass lesion; an air-fluid level may be present. During infection, the margins of the lesion may be blurred. There is no difference in the incidence of this lesion in each lung.

Extrapulmonary sequestration is much more common in boys and almost always involves the left lung. This lesion is enveloped by a pleural covering and is associated with diaphragmatic hernia and other abnormalities such as colonic duplication, vertebral abnormalities, and pulmonary hypoplasia. Many of these patients are asymptomatic when the mass is discovered by routine chest radiography. Other patients present with respiratory symptoms or heart failure. Subdiaphragmatic extrapulmonary sequestration can manifest as an abdominal mass on prenatal ultrasonography. The advent of prenatal ultrasonography has also enabled evidence that fetal pulmonary sequestrations can spontaneously regress.

Treatment

Treatment of intrapulmonary sequestration is surgical removal of the lesion, a procedure that usually requires excision of the entire involved lobe. Segmental resection occasionally suffices. Surgical resection of the involved area is recommended for extrapulmonary sequestration.

Etiology and Pathology

Bronchogenic cysts arise from abnormal budding of the tracheal diverticulum of the foregut before the 16th wk of gestation and are originally lined with ciliated epithelium. They are more commonly found on the right and near a midline structure (trachea, esophagus, carina), but peripheral lower lobe and perihilar intrapulmonary cysts are not infrequent. Diagnosis may be precipitated by enlargement of the cyst, which causes symptoms by pressure on an adjacent airway. When the diagnosis is delayed until an infection occurs, the ciliated epithelium may be lost, and accurate pathologic diagnosis is then impossible. Cysts are rarely demonstrable at birth. Later, some cysts become symptomatic by becoming infected or by enlarging and compromising the function of an adjacent airway.

Clinical Manifestations and Treatment

Fever, chest pain, and productive cough are the most common presenting symptoms. Dysphagia may be present; some bronchogenic cysts are asymptomatic. A chest radiograph reveals the cyst, which can contain an air-fluid level (Fig. 387-4). CT scan or MRI is obtained in most cases to better demonstrate anatomy and extent of lesion before surgical resection. Treatment of symptomatic cysts is surgical excision after appropriate antibiotic management. Asymptomatic cysts are generally excised in view of the high rate of infection.

Figure 387-4 Chest x-ray showing an ovoid, well-defined, soft-tissue density causing splaying of the carina due to bronchogenic cyst.

(From Williams HJ, Johnson KJ: Imaging of congenital cystic lung lesions, Paediatr Resp Rev 3:120–127, 2002.)

Etiology and Pathology

Congenital pulmonary lymphangiectasia is characterized by greatly dilated lymphatic ducts throughout the lung. It can occur in 3 pathologic circumstances: pulmonary venous obstruction that produces an elevated transvascular pressure and engorges the pulmonary lymphatics; generalized lymphangiectasia, as a generalized disease of several organ systems, including lungs and the intestines (can be associated with Noonan syndrome); and primary lymphangiectasia limited to the lung as a manifestation of an abnormality in lymphatic development.

Clinical Manifestations and Treatment

Children with pulmonary venous obstruction or severe pulmonary lymphangiectasia present with dyspnea and cyanosis in the newborn period. Hydrops fetalis may be diagnosed antenatally. Chest radiographs reveal diffuse, dense, reticular densities with prominence of Kerley B lines. Pleural effusions are common; thoracentesis will reveal chylothorax in this setting. If the lung is not completely involved, the spared areas appear hyperlucent. Respiration is compromised because of impaired diffusion and decreased pulmonary compliance. The diagnosis can be suggested by CT scan and/or cardiac catheterization; definitive diagnosis requires lung biopsy (either thoracoscopic or open).

Treatment is supportive and includes administration of oxygen, mechanical ventilation, nutritional support (including gastrostomy placement and use of feedings containing medium-chain triglycerides), and careful fluid management with diuretics. Primary pulmonary lymphangiectasia can produce severe pulmonary dysfunction that can require long-term mechanical ventilation; long-term survival and resolution of respiratory insufficiency is possible even in severe cases. Occasionally, the pulmonary venous obstruction is secondary to left-sided cardiac lesions; relief of the latter can produce improvement in pulmonary dysfunction. Generalized lymphangiectasia generally produces milder pulmonary dysfunction, and survival to mid-childhood and beyond is not unusual.

Etiology and Pathology

A lung hernia is a protrusion of the lung beyond its normal thoracic boundaries. About 20% are congenital, with the remainder being noted after chest trauma or thoracic surgery or in patients with pulmonary diseases such as cystic fibrosis (Chapter 395) or asthma (Chapter 138), which cause frequent cough and generate high intrathoracic pressure. A congenital weakness of the suprapleural membrane (Sibson’s fascia) or musculature of the neck can play a role in the appearance of a lung hernia. More than half of congenital lung hernias and almost all acquired hernias are cervical. Congenital cervical hernias usually occur anteriorly through a gap between the scalenus anterior and sternocleidomastoid muscles. Cervical herniation is usually prevented by the trapezius muscle (posteriorly, at the thoracic inlet) and by the three scalene muscles (laterally).

Clinical Manifestations and Treatment

The presenting sign of a cervical hernia (Sibson hernia) is usually a neck mass noticed while straining or coughing. Some lesions are asymptomatic and detected only when a chest film is taken for another reason. Findings on physical examination are normal except during Valsalva maneuver, when a soft bulge may be noticed in the neck. In most cases, no treatment is necessary, although these hernias can cause problems during attempts to place a central venous catheter through the jugular or subclavian veins. They can resolve spontaneously.

Paravertebral or parasternal hernias are usually associated with rib anomalies. Intercostal hernias usually occur parasternally, where the external intercostal muscle is absent. Posteriorly, despite the seemingly inadequate internal intercostal muscle, the paraspinal muscles usually prevent herniation. Straining, coughing, or playing a musical instrument can have a role in causing intercostal hernias, but in most cases, there is probably a pre-existing defect in the thoracic wall.

Surgical treatment for lung hernia is occasionally justified for cosmetic reasons. In patients with severe chronic pulmonary disease and chronic cough and for whom cough suppression is contraindicated, permanent correction might not be achieved.