Although patients with pulmonary arterial hypertension (PAH) carrying a bone morphogenetic protein receptor type 2 (BMPR2) mutation present approximately 10years earlier than noncarriers and have a more severe hemodynamic compromise at diagnosis, their histological features have never been investigated in detail and compared with noncarriers.

The aim of this study was to explore and compare the histology and morphology of pulmonary vascular lesions between BMPR2 mutation carriers and noncarriers.

Five random sections of lung parenchyma from 27 PAH patients, including 15 BMPR2 mutation carriers and 12 noncarriers, have been histological reevaluated blindly by two experienced pathologists. Plexiform lesions (Pls) density (n/cm²), inflammation score and arterial thickening were evaluated in the two patient groups. We found a positive trend of Pls density in BMPR2 mutation carriers as compared to noncarriers. We found no difference in the artery inflammation evaluated according to a semiquantitative score system. There was also no difference in the arterial thickening (i.e. intimal, medial and total wall thickening) evaluated in 5 transversal artery sections using the Nikon NIS-Elements morphometrical software. Bronchial artery thickening was evaluated by measuring the bronchial artery surface and by comparing it to the bronchial surface (bronchial artery surface/bronchus surface). Major bronchial artery thickening was associated with BMPR2 mutation status. It is noteworthy that most patients with a high bronchial artery surface/bronchus surface ratio presented haemoptysis. In addition, bronchial microvascularization evaluated by immunohistochemistry evidenced a much more prominent bronchial capillary network in BMPR2 mutated group. We noticed also that “atypical Pls” (histologically identified as larger angiodysplastic and fibrotic lesions) have almost exclusively been found in the group of BMPR2 mutation carriers.

Our results reveal, for the first time, distinctive morphologic patterns between lungs of patients with BMPR2 mutation carriers and noncarriers. A better knowledge of these specific histological features will lead to a better understanding of the PAH pathogenesis.