Monique E De Paepe, Merline Kocheekkaran V Benny, Lauren Priolo, Francois I Luks, Svetlana Shapiro

The cellular mechanisms underlying the microvascular dysangiogenesis of bronchopulmonary dysplasia (chronic lung disease of the newborn) remain largely undetermined. We report unusual pulmonary vascular findings in a 27-week-gestation male newborn who died on the second day of life from intractable respiratory failure, following a pregnancy complicated by prolonged membrane rupture and persistent severe oligohydramnios. As expected, postmortem examination revealed pulmonary hypoplasia (lung/body weight ratio: 2.23%; 10th percentile for 27 weeks: 2.59%). In addition, lung microscopy revealed complex networks of non-sprouting, tortuous, and bulbously dilated capillaries, randomly distributed in widened airspace septa. Anti-smooth muscle actin immunohistochemistry demonstrated immunoreactive central densities within capillary lumina, suggestive of intravascular pillar formation. The plexus-forming, non-sprouting type of angiogenesis and apparent transluminal pillar formation are consistent with intussusceptive ("longitudinal splitting") angiogenesis. In concordance with previous observations made in human fetal lung xenografts, these findings support the notion that human postcanalicular lungs have the capacity to switch from sprouting to non-sprouting, intussusceptive-like angiogenesis, possibly representing an adaptive response activated by hemodynamic flow alterations and/or hypoxia. The possible relationship between the intussusceptive-like vascular changes observed in this case and the microvascular dysangiogenesis characteristic of bronchopulmonary dysplasia remains to be determined.