Congenital cystic adenomatoid malformation of the lung insights into the pathogenesis utilizing quantitative analysis of vascular marker CD34 (QBEND-10) and cell proliferation marker MIB-1

Congenital cystic adenomatoid malformation (CCAM) encompasses a spectrum of variably cystic developmental anomalies of the lung histologically characterized by immature lung tissue. The pathogenesis is uncertain, but many investigators favor a maturation arrest in bronchopulmonary development. To investigate this hypothesis, the vascular development and proliferation capacity of lung tissue with CCAM type I from nine infants ranging in age from 20 weeks gestation to 42 days old were studied immunohistochemically utilizing CD34 for the former and MIB-1 for the latter. Both markers were quantitated on an image analysis system. CCAM was hypovascular with a mean vascular index of 20.05% ± 6.58 compared to 40.06% ± 4.19 for the age-matched controls (P < 0.000001). The proliferation index of both epithelial and mesenchymal components was higher in CCAM (10.46 ± 3.48) than in control tissue (7.14 ± 1.88; P < 0.012). In contrast to the control lung tissue which showed a remarkable synchrony between the vascular development and proliferation throughout the parenchyma, focal asynchrony between the proliferation of the epithelial and stromal components was noted in CCAM. The vascularity in CCAM corresponds to that seen in early gestation. The cellular proliferation in CCAM is higher than in full-term infants and corresponds to late second trimester or early third trimester fetuses. These findings support the proposed pathogenesis of a maturation defect in lung embryogenesis.