Genetic insights into pediatric congenital pulmonary airway malformations: a 13-year single-center experience

With advancements in antenatal imaging techniques, congenital lung lesions are increasingly being diagnosed prenatally, resulting in a growing population of asymptomatic patients encountered by clinicians. However, the etiopathogenesis of these lesions remains unclear, and their malignant potential is not fully understood. In this study, we aimed to investigate the genetic alterations in congenital pulmonary airway malformations (CPAM) and assess their potential for malignant transformation.

This study included patients under 18 years of age who underwent surgery for congenital pulmonary airway malformation at our institution between 2010 and 2023. Demographic and clinical characteristics were retrospectively analyzed. Lung resection specimens of patients diagnosed with CPAM were re-evaluated, and tissue sections were obtained. For patients operated before 2018, real-time PCR was performed using paraffin-embedded tissue blocks, while targeted next-generation sequencing was employed for cases after 2018 to detect variants in the KRAS gene. The collected data were analyzed using SPSS version 22.0.

Among 35 patients operated for CPAM, variants in the KRAS gene were detected in 8 patients (22.8%). The majority of cases with variants were diagnosed with type 1 CPAM (p < 0.05). The mean age at surgery was significantly lower in KRAS-positive patients (3.75 ± 2.66 months) compared with KRAS-negative patients (29.89 ± 53.68 months; p < 0.05). No evidence of malignant transformation was observed in any case.

KRAS variants can be detected in a subset of pediatric CPAM cases, particularly in type 1 CPAM lesions. KRAS-positive patients underwent surgery at a significantly younger age, likely due to lesion characteristics and antenatal diagnosis. Although no malignant transformation was observed in our series, the presence of KRAS variants indicates a potential molecular predisposition to malignancy. Combining routine histopathological evaluation with targeted molecular analysis can improve risk stratification and guide clinical management. Larger prospective studies are needed to clarify the prognostic and therapeutic implications of KRAS positivity in CPAM.