Congenital cystic lung disease covers a spectrum of lung malformations that include congenital cystic adenomatoid malformation (CCAM; which is also defined by the term congenital pulmonary airway malformation or CPAM), bronchopulmonary sequestration (BPS), congenital lobar emphysema (CLE), and bronchogenic cysts. The intricate process of lung development begins at about 4 weeks’ gestation and consists of 6 discrete phases: (1) the embryonic stage (4–7 weeks’ gestation); (2) the pseudoglandular stage (5–17 weeks’ gestation); (3) the canalicular stage (16- to 26-weeks’ gestation); (4) the saccular stage (24- to 38-weeks’ gestation); (5) the alveolar stage (36-weeks’ gestation to 2 years of age); and (6) microvascular maturation (birth to 2–3 years of age).1
A key stage in the development of congenital cystic lung disease appears to be the pseudoglandular stage, when branching morphogenesis occurs. Branching morphogenesis results in the formation of the conductive airway system, which is an essential prerequisite to alveolization. Lung development is influenced at all stages by the spatial and temporal distribution of a variety of signaling molecules and their receptors and by the positive and negative control of signaling by paracrine, autocrine, and endocrine mechanisms. It is likely that a developmental arrest or maturation disorder in the pseudoglandular stage is responsible for the vast majority of developmental lung anomalies, and although many of the responsible genes and gene products have been identified, the precise mechanisms involved are unknown.2, 3, 4, and 5 Analysis of resected fetal lung lesions have shown an imbalance between cellular proliferation and apoptosis, suggesting a loss of growth regulation.6
Although there is a tendency to compartmentalize congenital cystic lung disease into discrete pathological conditions, there is considerable overlap between conditions. An example is the shared features of CCAM and BPS within so-called hybrid lesions, which exhibit the histological features of CCAM combined with the anomalous vascular anatomy of BPS.
Epidemiology of Neonatal Cystic Lung Lesions
There are few data on the epidemiology of cystic lung lesions. One frequently quoted study using population-based data estimated the incidence of CCAM to be 1 per 25,000 to 35,000 pregnancies.7 Most cystic lung lesions occur with equal frequency in the right and left lungs and have a slight preponderance for males.8
The differential diagnosis of cystic lung lesions in an infant include CPAM, BPS, CLE, bronchogenic cysts, as well as congenital diaphragmatic hernia (CDH) and a variety of congenital and acquired cystic lesions of the lung and mediastinum. Some of the acquired cystic lung conditions include pulmonary interstitial emphysema, postinfectious pulmonary cysts, lung abscesses, and rare tumors, including bronchioloalveolar carcinoma (BAC) and pleuropulmonary blastoma (PPB).
CONGENITAL CYSTIC ADENOMATOID MALFORMATION AND CONGENITAL PULMONARY AIRWAY MALFORMATION
The CCAM and CPAM cystic lung hamartomas are associated with a proliferative increase in terminal bronchioles relative to alveoli. The result ...