A Three-dimensional Analysis of Blood Vessels in Bronchioloalveolar Carcinoma

Abstract

The three-dimensional architecture of blood vessels within lung adenocarcinomas has not been well studied. In 19 cases with bronchioloalveolar carcinoma with central fibrosis, we three-dimensionally examined blood vessel architecture in 150 microm thick sections stained with elastin staining and anti-CD34 antibody. We examined four regions: normal alveoli and three regions within the tumor including an area adjacent to the normal alveoli (external area), an area in which tumor cells were replacing epithelial cells (replacement area), and a central fibrotic area (fibrotic area). Elastin staining showed that elastic fibers formed the framework of the alveoli, and the alveolar structure shrank more strongly to the center of the tumor due to folding of alveolar walls invaded by adenocarcinoma cells. We also measured three vessel parameters in these four regions. The vessel diameters were 4.08+/-1.10 microm, 3.95+/-1.02 microm, 5.04+/-1.56 microm, and 6.11+/-2.23 microm, the circumferences of those vessels seen as complete circles were 43.11+/-12.78 microm, 43.71+/-12.87 microm, 95.21+/-39.32 microm, and 126.77+/-54.65 microm; the lengths between vessel bifurcations were 13.28+/-3.08 microm, 13.47+/-4.58 microm, 24.91+/-9.66 microm, and 41.82+/-28.08 microm in the normal alveoli, and the external, replacement, and fibrotic areas, respectively. Blood vessel architecture changed such that the vessels became larger and coarser towards the center of the tumor. Our three-dimensional analysis suggests continuous remodeling of alveolar capillaries rather than angiogenesis within bronchioloalveolar carcinoma.