Pulmonary sarcoid granulomas are characterised by their elective distribution along collecting lymphatics. However, relationships between granulomas and intralobular lymphatics or blood microvascularisation have not been investigated. Therefore, we undertook a specific analysis of blood capillaries and lymphatics supplying sarcoid granulomas to identify additional clues to understanding the pathophysiogenesis of these lesions.Six pulmonary samples were immunolabelled with D2-40, anti-CD34 and anti-CD31 antibodies, paying particular attention to the relationships between lymphatics and granulomas, and the pattern of blood microvessels supplying sarcoid lesions. A morphometric study of granulomas included their distance to lymphatics and a three-dimensional reconstruction of a granuloma in its lymphatic context. Intralobular granulomas were closely associated with lymphatics; apart from a few granulomas, blood capillaries stopped at the outer border of the fibrous ring surrounding granulomas, and perigranuloma capillaries were particularly scarce.Our observations of the lymphatic and blood microvascular environment of intralobular pulmonary sarcoid granulomas provide evidence for the critical role of lymphatics in the emergence of these lesions. Moreover, pulmonary sarcoid lesions could be considered avascular structures, thereby providing new insights into the understanding of the granuloma physiology and the distribution of blood-borne therapeutic agents.KEYWORDS: Fibrosis, lymphatics, microvessels, sarcoid granulomas S arcoidosis is a multisystem disorder of unknown cause with thoracic involvement in up to 90% of patients [1]. Sarcoid granulomas are comprised of clusters of epithelioid and giant cells surrounded by a rim of lymphocytes and fibroblasts. A peripheral fibrous ring of varied thickness surrounds the lesions that have a tendency to coalesce, resulting in typical fibrotic nodules. The characteristic distribution of granulomas along the pulmonary collecting lymphatics, i.e. peribronchovascular spaces, interlobular septa and subpleural connective tissue, is a major diagnostic criterion [2]. Moreover, their tropism for the outer wall of pulmonary arteries or veins is well known [3].In addition to these features, the relationships between pulmonary sarcoid granulomas and the intralobular lymphatic network or the pulmonary blood capillaries have not yet been adequately examined. Investigating these close relationships might help improve our understanding the biology of granulomas and also orient therapeutic drug research to achieve better targeted distribution. To address this issue, we systematically analysed the interface between granulomas and the lymphatic network by means of D2-40 immunohistochemical labelling or their blood microvessels with CD34 and CD31 immunolabelling [4,5]. To better discriminate their blood and lymphatic vascular supplies we specifically focused our study on selected isolated granulomas, whose location is predominantly intralobular.
MATERIALS AND METHODS
Surgical lung ...