Pathogenesis and Evolution of Plexiform Lesions in Pulmonary Hypertension Associated with Scleroderma and Human Immunodeficiency Virus Infection

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.