Pathogenesis and evolution of plexiform lesions in pulmonary hypertension associated with scleroderma and human...

Patients with primary pulmonary hypertension develop vascular lesions characterized by proliferated blood channels, the so-called plexiform lesions. These lesions are often associated with concentric intimal obliteration of pulmonary vessels. We report that the lungs of three patients with scleroderma-associated pulmonary hypertension showed a predominance of obliterative-concentric lesions, with relatively few plexiform or combined lesions. In contrast, plexiform lesions predominated in the lungs obtained from three patients with human immunodeficiency virus (HIV)-associated pulmonary hypertension; pure obliterative-concentric lesions were infrequent. Both plexiform and concentric obliterative lesions stained strongly positive for the endothelial cell marker factor VIII-related antigen. Muscle-specific actin immunostaining highlighted the smooth muscle cells of the tunica media of plexiform vessels, but not the luminal layers of the concentric-obliterative lesions. Proliferating cells, as determined by immunostaining with the MIB-1 antibody, were only detected in the plexiform vascular lesions. We postulate that concentric-obliterative lesions and plexiform lesions are temporally and etiologically related. A scaffolding of proliferating endothelial cells could be the common denominator of both lesions. Our hypothesis that there exists a chronological continuum, proceeding from early, proliferative plexiform lesions to late, nonproliferative concentric-obliterative lesions in primary and secondary pulmonary hypertension, may lead to better targeted treatment strategies and disease classification.