Etiology of Congenital Pulmonary Airway Malformation (CPAM)
CPAM occurs due to abnormal embryonic development of the airways during fetal lung development, though the exact molecular mechanisms remain incompletely understood.
Developmental Pathogenesis
CPAM results from anomalous development of the airways during fetal life, leading to cystic and/or adenomatous pulmonary areas. 1, 2 The malformation represents a failure of normal bronchial tree maturation, creating disorganized tissue that can range from microscopic to macroscopic cystic structures. 1
Molecular and Genetic Factors
Recent research has identified specific genetic abnormalities associated with CPAM development:
- KRAS somatic mutations have been confirmed in CPAM tissue, representing the first concrete molecular pathway identified in these malformations. 1
- Other genetic susceptibilities linked to tumor development are currently under investigation, though specific pathways remain to be fully elucidated. 1
- These molecular findings suggest CPAM may arise from localized genetic events during lung morphogenesis rather than inherited germline mutations. 1
Clinical Context for Young Adults
When CPAM presents in young adults (as opposed to prenatal or neonatal diagnosis), it indicates the lesion remained asymptomatic throughout childhood:
- The malformation was present since fetal development but did not cause sufficient symptoms to prompt earlier diagnosis. 3, 2
- Adult presentation typically occurs with complications such as recurrent pneumonia, spontaneous pneumothorax, breathlessness, fever, or hemoptysis. 3, 2
- A 24-year-old case series documented presentation after three episodes of pneumonia over 6 months, illustrating how previously silent lesions can become symptomatic. 2
Important Clinical Caveat
The prevalence of CPAM may be higher than currently reported because many cases remain asymptomatic and symptomatic cases in adults are often missed or misdiagnosed. 2 This underscores that the developmental anomaly occurs during fetal life in all cases, but clinical recognition may be delayed for years or decades. 4