Congenital lung lesions—underlying molecular mechanisms

https://doi.org/10.1053/j.sempedsurg.2010.03.003Get rights and content

Congenital lung lesions comprise a broad spectrum of rare but clinically significant developmental abnormalities, including congenital cystic adenomatoid malformation, bronchopulmonary sequestrations, congenital lobar emphysema, and bronchogenic cysts, which are commonly surgically treated. Although the terms congenital cystic adenomatoid malformation, bronchopulmonary sequestrations, congenital lobar emphysema, and bronchogenic cysts are entrenched in clinical usage and comfortably correspond to rigid pathologic definitions, there is a considerable overlap in the findings. Disregarding the controversy about lesion nomenclature and classification, it is widely accepted that congenital lung lesions result from perturbations in lung and airway embryogenesis. It is generally accepted that both place (level in the tracheobronchial tree) and timing (gestational age) of the embryologic insult correlates with the type of lesion and histopathology that is manifested. The objective of this review is to briefly review normal lung development and to analyze the known molecular mechanisms underlying those diseases.

Section snippets

Normal lung development

The bronchial tree of the human lung has more than 105 conducting and 107 respiratory airways arrayed in an intricate pattern crucial for oxygen flow. Lung development is a highly orchestrated process directed by mesenchymal(vessels)-epithelial interactions, which control and coordinate the temporal and spatial expression of multiple regulatory factors required for proper lung formation. Many endogenous and exogenous biophysical and biochemical factors may disturb this delicate process leading

Congenital cystic adenomatoid malformation

CCAMs are relatively rare developmental abnormalities of the lung that can cause significant morbidity and mortality in infants as the result of associated fetal hydrops, lung hypoplasia, and respiratory distress. The lesions are described as hamartomatous lesions, ie, normal lung tissues in a disorganized spatial arrangement. The result of this process is a multicystic mass that replaces the normal lung structure. Human CCAMs are unilateral and usually confined to a single lobe. The exact

Bronchopulmonary sequestration

BPS are microscopic cystic masses of nonfunctioning pulmonary tissue that lack an obvious communication with the tracheobronchial tree. Typically, the lung tissue in BPS receives all or most of its blood supply from an anomalous systemic artery, with the origin of this artery being variable. Two forms of sequestration are recognized: intralobar and extralobar. Although rare, both forms can occur simultaneously. Intralobar sequestrations (ILS) are incorporated into the normal surrounding lung,

Congenital lobar emphysema

CLE is a term used to describe a distended, hyperlucent lobe on plain radiographs, usually the left upper or the right middle lobe.60 Pathologically, a distinction is made between a polyalveolar lobe, in which the number of alveoli is greatly increased, and congenital lobar overinflation, in which the alveoli are markedly distended. CLE is rarely diagnosed prenatally, possibly because of its low prevalence in utero or the increased echogenicity of the lungs, which could be too subtle to be

Bronchogenic cysts

BC result from abnormal budding of the foregut. As foregut duplication cysts, they share common features with esophageal duplication cysts but are characterized by the presence of cartilage, smooth muscle and glands in their wall. The majority is located in the mediastinum, usually adjacent to the distal trachea or proximal main stem bronchi, but they can also be found within the parenchyma of the lung.66 They are usually unilocular, filled with fluid or mucus and generally do not communicate

Concluding remark

The spectrum of congenital lung lesions likely results from disordered embryologic interactions, which occur during the course of fetal lung development. Although some molecular links are being suggested, it is still too early to establish any molecular pathway as the cause of these congenital lesions.

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    S.G. was supported by FCT grant ref. SFRH/BD/15,260/2004; Y.H. is supported by the Sophia Foundation (SSWO project 482).

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