Distribution of obstructive intimal lesions and their cellular phenotypes in chronic pulmonary hypertension - A morphometric and immunohistochemical study

We investigated the distribution of pulmonary arteriopathy in chronic pulmo nary hypertension (PH) in a quantitative histopathologic study, using compu ter-assisted image analysis. We also examined the histologic manifestations and cellular phenotypes of various obstructive intimal lesions in PH with an immunohistochemical method. A total of 53 lungs removed at autopsy or ex plantation were obtained for the study from 51 documented cases of moderate to severe PH (15 cases of primary pulmonary hypertension [PPH], eight case s of Eisenmenger's syndrome [EISEN], 22 cases of chronic major-vessel throm boembolic disease [CTED], and three cases of PH associated with other known causes), and two unused donor lungs served as normal controls. Intimal thi ckening in PPH was most prominent in small pulmonary arteries and arteriole s less than 200 mu m in diameter. Plexiform lesions in PPH were associated with significantly smaller arteries than in EISEN. Arteries larger than 400 mu m showed a significant intimal thickening only in CTED. Obstructive int imal lesions in PH comprised a morphologic spectrum with frequent intermedi ate forms between plexiform and thrombotic lesions. Most cells within vario us intimal lesions showed an immunoprofile of myofibroblasts that were posi tive for vimentin and or-smooth muscle actin, but negative for desmin and e ndothelial markers including Factor VIII, clonal designator (CD)31, and CD3 4. Endothelial markers were positive only in the single layer of cells lini ng slitlike lumens, when the latter were present. In conclusion, major type s of PH had characteristic distribution patterns of obstructive intimal les ions, showing mainly a myofibroblastic phenotype and variable endothelial/v ascular differentiation.