Pulmonary Medicine

Congenital Abnormalities of the Lower Airways and Lungs

What every physician needs to know:

Congenital abnormalities of the lower airways (CALA) are relatively rare and may affect the central airways, peripheral airways and/or lung parenchyma. Current convention classifies for primary types of abnormality; congenital pulmonary airway malformation (CPAM), bronchopulmonary sequestration (BPS; intralobar (IPS) and extralobar (EPS), bronchogenic cyst (BC) and congenital lobar overinflation (CLO), formerly known as congenital lobar emphysema (CLE).

Initial presentation of CALA can vary, depending on the type, location and degree of pulmonary compromise. Some lesions present in infancy and early childhood while others can present in later childhood through adulthood. Symptoms may include hypoxemia and respiratory distress at birth or persistent cough and wheeze or recurrent infections later in life.

Most abnormalities are identified with prenatal ultrasound but advanced postpartum imaging (computed tomography of the chest or magnetic resonance imaging) is needed for definitive diagnosis. Imaging is also necessary in order to develop long-term management plans and define anatomy for possible surgical resection. Most lesions require urgent or elective resection as they may be associated with severe respiratory distress at birth, significant complications later in life, or the potential for future malignancy. Some asymptomatic abnormalities, such as small EPS or CLO, may be observed.

Classification:

CPAM

Congenital Pulmonary Airway Malformation (CPAM), formerly referred to as congenital cystic adenomatoid malformation, is a mass of abnormal lung tissue historically described as Stocker type I-III, based on the size of the cysts. Additional types, 0 and IV, have been added. CPAM occurs in approximately one in 10,000 live births and is distributed equally between both sexes.

Type 0 CPAM represents 1-3% of cases and is thought to occur very early in gestation. Cysts are very small and comprise of tracheal/bronchial tissue. These lesions are incompatible with life as they cause central airway obstruction.

Type I CPAM is most frequently seen, accounting for 60-70% of all CPAM. They consist of bronchiolar tissue and are thought to occur later in gestation. Radiographically, type I CPAM typically consist of a single, dominant cyst but may include a few cysts 2-10 cm in diameter. Cysts are generally limited to one lobe, but multilobar involvement has been reported in up to 5% of cases. Large cysts often cause mediastinal shift and diaphragmatic compromise leading to respiratory distress at birth. However, many type I CPAM are diagnosed later in life. All CPAM should be resected as there is an association between CPAM and bronchioloalveolar carcinoma (BAC).

Type II CPAM represent 15-20% of all CPAM and are comprised of multiple small cysts 0.5-2 cm in diameter lined with bronchiolar tissue and are believed to develop in mid-gestation. Type II CPAM are seen in association with other congenital anomalies in up to 60% of patients. The presence of other anomalies often leads to early diagnosis, even in the absence of early respiratory signs and symptoms. Resection is recommended if associated abnormalities are consistent with a good long-term prognosis.

Type III CPAM account for 5-10% of all CPAM. Lesions are often very large, involving most of the involved hemithorax, and consist of small, variable-sized cysts and solid elements. They are of acinar origin and are thought to develop relatively early in gestation. Type III CPAM are generally diagnosed at birth secondary to marked respiratory distress. Prognosis is more guarded compared to other types of CPAM as complications can include pulmonary hypoplasia and secondary pulmonary hypertension.

Type IV CPAM represent 1-10% of CPAM. Cysts are up to 7 cm in diameter, comprised of alveolar tissue, and occur late in gestation. Presentation is similar to type I CPAM, with some infants being symptomatic immediately and others exhibiting no symptoms until later in life. Large cysts can resemble a pneumothorax and this type for CPAM should be suspected in newborns and older children with unexplained pneumothoraces. There is a strong association between type IV CPAM and pleuropulmonary blastoma (PPB). For this reason, large cyst CPAM all require resection.

See Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, and Figure 7.

Figure 1.

Chest radiograph of CPAM - Notice the subtlety of findings on CXR, necessitating further imaging.

Figure 2.

Lateral chest radiograph of CPAM. Again, further imaging is required as this malformation is difficult to view on chest radiograph.

Figure 3.

Axial CT of the Chest showing a CPAM. Note the large, single cyst Stocker type I CPAM causing mediastinal shift resulting in left lung compromise.

Figure 4.

Another Stocker Type I CPAM. Note the numerous large cysts.

Figure 5.

Smaller Stocker Type I CPAM.

Figure 6.

Smaller Stocker Type I CPAM

Figure 7.

Pathologically, this was diagnosed as CPAM Stocker Type II due to the smaller satellite cysts, but the larger cyst could be confused with Stocker Type I CPAM

Bronchopulmonary Sequestration

Bronchopulmonary sequestrations (BPS) is divided into extralobar sequestrations (ELS) and intralobar sequestrations (ILS), both of which are characterized by a lack of connection to the airways and the presence of a systemic arterial blood supply. Extralobar sequestrations occur in one out of 800,000 live births, has a male predominance of 3:1, and is usually identified prenatally on ultrasound. Pathology shows abnormal microcystic lung tissue contained within its own separate pleura. ELS typically occur in the lower lobes and are associated with other congenital anomalies in up to 40% of cases. ELS are often symptomatic at birth though they can be identified later in life as incidental findings, particularly smaller lesions.

ILS is more common than ELS, occurring in approximately one out of 200,000 live births. Unlike ELS, ILS is equally divided between sexes and is much more commonly diagnosed postnatally. It also contains abnormal microcystic lung tissue but is contained within the pleura of a normal lobe. Like ELS, ILS is most frequently located in the lower lobes and often on the left side. ILS is generally diagnosed in older children who present with recurrent pneumonia.

See Figure 8, Figure 9, Figure 10 and Figure 11.

Figure 8.

Extralobar sequestration on chest radiograph. Notice the increased density along the right heart border.

Figure 9.

Coronal chest tomography showing a extrapulmonary sequestration in the right lower lobe with a feeding systemic artery

Figure 10.

The feeding vessel can be seen more clearly on the axial view.

Figure 11.

Computed tomography angiography with 3-dimensional reconstruction showing an extralobar sequestration in a two-month old infant. The study demonstrates the large thoracic feeding artery.

Bronchogenic Cysts

Bronchogenic cyst (BC) occurs in one out of 20,000 live births, with an equal distribution between sexes. BC can be diagnosed prenatally, but symptoms may develop at any age. Radiographically, BC may be located in the mediastinum, lung parenchyma, or extra-thoracic locations and are characterized by thin-walled cysts, often with an air-fluid level. The cysts vary in size and are comprised of respiratory epithelium, cartilage plates, and often, gastric mucosa. When not identified on prenatal ultrasound, patients often present with recurrent cough or wheeze. Because BC often contain gastric mucosa, serious complications, such as hemorrhage, may develop and resection is recommended in all cases.

See Figure 12, Figure 13, Figure 14 and Figure 15.

Figure 12.

Chest radiograph of a toddler with chronic cough and wheezing on exam demonstrated course rhonchi on exam. Notice the increased density and thickness of the mediastinum.

Figure 13.

Note the compression of the esophagus in an esophagram of the same patient with a bronchogenic cyst. While chest radiograph and esophagram show mediastinal and esophageal shift and compression, anatomical definition requires computed tomography of the chest.

Figure 14.

Initial axial (Figure 1) and coronal (Figure 2) chest computed tomography showing a mediastinal mass with homogenous soft tissue density with anterior displacement of the trachea and posterior displacement of the esophagus. Surgical removal of all BC is recommended to decrease the risk of recurrent pneumonias, mass effect and hemorrhage.

Figure 15.

Initial axial (Figure 1) and coronal (Figure 2) chest computed tomography showing a mediastinal mass with homogenous soft tissue density with anterior displacement of the trachea and posterior displacement of the esophagus. Surgical removal of all BC is recommended to decrease the risk of recurrent pneumonias, mass effect and hemorrhage.

Congenital Lobar Overinflation

Congenital lobar overinflation (CLO) occurs in one out of 20,000-30,000 live births and has a male predominance of 3:1. Diagnosis is invariably made postnatally, as prenatal ultrasound may show a cyst-like structure similar to other congenital abnormalities and progressive overinflation only occurs postnatally. CLO is, by definition, connected to the tracheobronchial tree. There is often airway stenosis or other abnormalities which lead to airway obstruction with subsequent air trapping and enlargement of airways and alveoli. The histology of the air spaces is actually normal rather than emphysematous, hence the change in nomenclature. Among children with CLO, 1/4 - 1/3 are symptomatic at birth, 1/2 are symptomatic by six months of age and nearly all are symptomatic by one year of age. Chest radiographs are often diagnostic. Although asymptomatic CLO may be observed, most are symptomatic and require resection.

See Figure 16, Figure 17, Figure 18, Figure 19 and Figure 20.

Figure 16.

Chest radiograph showing increased hyperinflation of the left upper lobe causing mediastinal shift typical of congenital lobar overinflation.

Figure 17.

A coronal view of the anterior chest showing a hyperinflated left upper lobe from congenital lobar overinflation. Also note the mediastinal shift and corresponding atelectasis of the right lung.

Figure 18.

Coronal chest tomography showing the mid-thorax and left upper lobe hyperinflation with compensatory mediastinal shift and atelectasis of the right lung as well as the left lower lobe.

Figure 19.

Chest tomography axial view of the mid-thorax showing mediastinal shift and right lung atelectasis from congenital overinflation of the left upper lobe.

Figure 20.

Chest tomography axial view of the lower-thorax showing mediastinal shift and right lung atelectasis from congenital overinflation of the left upper lobe.

Are you sure your patient has a congenital abnormality of the lower airways?

Many congenital abnormalities of the lower airway are identified on prenatal ultrasound. They often demonstrate some degree of regression prior to birth but natural history can be quite variable and complete resolution is exceedingly rare. Advanced imaging (computed tomography of the chest or magnetic resonance imaging) is always required by six months of age for definitive diagnosis of most abnormalities. Radiographic findings vary by the type of abnormality and are discussed above. Advanced imaging is generally sufficient for presumptive diagnosis.

Children with CALA may present immediately after birth with hypoxemia and respiratory distress or later in life with persistent cough or wheeze or recurrent infection. Roughly 1/4 of patients are symptomatic at birth with 3/4 developing symptoms through adulthood. The symptoms should prompt imaging as above.

Beware: There are other diseases that can mimic congenital pulmonary vascular anomalies

Neonatal respiratory distress can be caused by more common disease processes, such as transient tachypnea of the newborn, respiratory distress syndrome and persistent pulmonary hypertension of the newborn. Other causes include neonatal pneumonia, congenital heart disease, pneumothorax as well as congenital diaphragmatic hernia. Most of these illnesses can be discerned by history, imaging and other laboratory analyses.

Patients with chronic cough and wheeze may have asthma, cystic fibrosis, primary ciliary dyskinesia, protracted bacterial bronchitis, infection, foreign body, aspiration or interstitial lung disease. A thorough history as to the quality and timing of cough and wheezing may help rule out certain etiologies. Physical exam and imaging will also narrow the differential, along with imaging.

Why did the patient develop a congenital abnormality of the lower airways?

The embryogenesis of CALA is poorly understood. In utero, normal lung development relies on temporal and spatial tissue interactions regulated by a variety of signals from transcription factors, growth factors, and cell adhesion factors. Any abnormalities in the timing, location and intensity of signals produced during any stage of lung development may result in the development of CALA.

Which individuals are at greatest risk of developing congenital abnormalities of the lower airways?

CALA appear to be sporadic occurrences. No definitive familial inheritance pattern or specific genetic abnormalities have been found in association with most CALA. The exception to this is Stocker Type IV CPAM which have a close association with pleuropulmonary blastoma and DICER1 genetic mutations.

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

No laboratory studies are necessary to diagnose CALA. Most CALA have characteristic imaging findings and can be presumptively diagnosed based on imaging alone. As above, prenatal ultrasound findings must be confirmed on postnatal imaging studies.

Certain types of CPAM can be associated with malignancy such as bronchioloalveolar carcinoma and pleuropulmonary blastoma. Genetic testing for DICER1 mutations, which is positive in 2/3 of patients with PPB, is recommended for patients suspected of type IV CPAM.

What imaging studies will be helpful in making or excluding the diagnosis of congenital abnormalities of the lower airways?

CALA are often identified on prenatal ultrasound. Lesions are usually seen as echogenic masses with or without cystic and solid components. Hydrops associated with congenital abnormalities may be identified as well. Doppler imaging may be useful in identifying associated vascular anomalies. As previously discussed, the natural history of these lesions is unpredictable, with many showing regression, but postnatal advanced imaging is required for all infants with a history of CALA on prenatal ultrasound.

Simple chest radiographs are warranted on all infants with a history of CALA on prenatal ultrasound. Infants who have significant abnormalities on simple imaging requiring immediate advanced imaging. Those with minor or "normal" plain films can have elective advanced imaging at six months of age. Many CALA can presumptively be diagnosed based on CT or MRI findings.

CLO present in an atypical fashion, as prenatal ultrasound is often normal and overinflation only becomes evident on subsequent chest radiographs postnatally. The appearance of CLO on plain imaging is often characteristic enough to make a presumptive diagnosis.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis?

Prenatal ultrasound often identify CALA prior to birth. As already stated, any infant with history of CALA on prenatal ultrasound requires advanced thoracic imaging.

Postnatal chest radiographs may demonstrate hyperlucent or multicystic regions or radiopaque solid components characterizing CPAM. Further characterization of these lesions is obtained with computed tomography of the chest, particularly if there is diagnostic uncertainty on plain radiography. BPS may be identified by subtle lower lobe densities on plain chest radiographs and persistent densities are suggestive of such. Characteristics of BPS on chest CT may include a heterogenous mass including solid and cystic components with or without cavitation and air-fluid levels. Contrast studies or Doppler ultrasound are often applied to define the vascular supply of these lesions. BC are generally characterized as thin-walled, smooth, round cysts, commonly with air-fluid levels, on plain films or CT imaging. Thoracic imaging, as described above, is generally sufficient to presumptively diagnose most CALA.

CLO present differently than other as CALA. Prenatal ultrasound is often normal and immediate postnasal plain chest radiographs demonstrate a fluid or air-filled lobe or lobes. Progressive hyperinflation of the affected lobe causing mediastinal shift and atelectasis of contralateral lobes is present on subsequent imaging. Chest CT may confirm these features but often is not necessary.

What diagnostic procedures will be helpful in making or excluding the diagnosis?

Thoracic imaging is generally sufficient to make presumptive diagnosis of most CALA. Surgical resection is typically necessary and provides histologic confirmation of diagnoses. Other diagnostic procedures are usually not needed.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis?

As stated previously, thoracic imaging is often sufficient for presumptive diagnosis of most CALA and surgical resection with histologic examination generally confirms diagnoses. Specific histologic findings of CALA were discussed under "classification".

If you decide the patient has congenital abnormalities of the lower airways, how should the patient be managed?

All symptomatic CALA require surgical resection. There is significant debate regarding the management of asymptomatic CALA. Some authorities recommend surgical resection for all CALA while others allow for observation of some lesions. Asymptomatic lesions such as small ELS or CLO may be conservatively managed with routine clinical follow-up and serial imaging studies. These lesions have not been associated with serious, life-threatening complications or malignancy later in life. Concerns have been raised, however, regarding repeated exposure to ionizing radiation and the potential loss of anatomic and physiologic lung development during the first 4-6 years of life.

There is general agreement that other CALA require resection. There is a clear association between CPAM and the future development of malignancy, which is particularly true for Type IV CPAM and pleuropulmonary blastoma. Additional arguments for surgical removal include improved compensatory lung growth and decreased radiation exposure as above. BC are generally removed secondary to symptoms caused by mass effect and airway obstruction as well as recurrent infections and potential for pulmonary hemorrhage. As previously stated, CLO almost always becomes symptomatic by one year of age and require resection.

What is the prognosis for patients managed in the recommended ways?

Most patients do well after surgical removal of CALA and long-term prognosis is good. Prognosis is, however, particularly related to the extent of lung resection and possible related congenital abnormalities. Infants with large lesions requiring multi-lobe resection often have some degree of pulmonary hypoplasia and secondary pulmonary hypertension. These issues may negatively impact long-term prognosis. Lesions associated with other congenital abnormalities (Type II CPAM and ELS) may have a more guarded prognosis as well.

What other considerations exist for patients with congenital abnormalities of the lower airways?

The pathogenesis and radiology of CALA are poorly understood and warrant additional investigation. Long-term observational studies comparing surgical resection of CALA versus observation would also be of value in developing evidence-based guidelines for care. Such studies would also provide insight into the true risk of malignant degeneration among some of these abnormalities.

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