Three-dimensional reconstruction identifies misaligned pulmonary veins as intrapulmonary shunt vessels in alveolar capillary dysplasia

Abstract

Alveolar capillary dysplasia (ACD) with misalignment of pulmonary veins (MPV) is a lethal neonatal lung disease. Death from ACD/MPV is caused by hypoxia, but the role of the MPV is unknown. Using 3-dimensional reconstruction of ACD/MPV lung tissue, we report that the veins in MPV are intrapulmonary shunt vessels, and speculate that MPV contributes to the poor prognosis.

Keywords: 3-dimensional; 3D; ACD; Alveolar capillary dysplasia; IPSV; Intrapulmonary shunt vessels; MPV; Misalignment of pulmonary veins; PPHN; Persistent pulmonary hypertension of the newborn.

Figure 1

Lung histology from a young infant who died of alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). Hematoxillin and eosin (H&E) stained sections show the typical histologic features of ACD/MPV including large, thin walled vascular channels (MPV) surrounding the broncho-arterial bundle (PA: pulmonary artery; B: airways). Thickened muscular wall of pulmonary arteries (PA) is evident. Serial step sections stained with H&E (a) compared with sections stained with lymphatic endothelium specific immunomarker D2-40 (b) highlights scattered lymphatic channels (L) near the broncho-arterial bundles, but not the MPV confirming that MPVs are not of lymphatic in origin. MPV appears to connect with the pulmonary veins (PV) located in the primary septum (dashed outline, c, d).

Figure 2

Three-dimensional reconstruction of microscopic images from ACD lungs. The pulmonary artery and airway run side-by side with few lymphatics and the pulmonary veins (PV) are clearly separated in the age-matched control (a; pulmonary artery: red; arterial muscular wall: aqua, MPV/shunt vessels: yellow, pulmonary veins: blue; airway: green; lymphatic: pink;). In contrast, extensive vascular network is present surrounding the broncho-arterial bundles of ACD lungs (b–d). These vascular channels appear to course toward the vessels located within the interlobular septa (b) and make contact with the microvessels surrounding the pulmonary arteries and airways (white arrows; b–d).