Anatomy of the intralobular and interlobular lymphatics in the human lung with special references to its topographical relation to lymph nodules and nodular composite cells

BACKGROUND The intra- and inter-lobular configuration of pulmonary lymph vessels and nodules remains obscure. CD169-positive macrophages and dendritic cells (DCs) cross-present cancer antigens to T lymphocytes. METHODS We examined 40 tissue blocks from 20 surgically obtained lung lobes immunohistochemically and morphometrically. All 20 patients with lung cancer survived more than five years without metastasis. RESULTS Podoplanin-positive lymph vessels (LVs) with or without concomitant arteriole arose from interalveolar septa, where lymph vessel endothelia adjoined alveolar epithelia. In contrast, we did not find LVs along the terminal bronchiole within 0.5mm from the end at alveoli. Lymph nodules were rare in alveolar tissue 60-80mm from the cancer lesion; if present, they were 0.1-0.3mm across, attached to a lymph vessel, and largely composed of T lymphocytes. By contrast, alveolar tissue near the cancer (5-10mm) often contained larger nodules 0.2-1.0mm thick. These nodules had no polarization in architecture and consistently accompanied LVs. Arteriole-associated nodules and subpleural nodules were predominant, while bronchiole-associated nodules were fewer in all specimens. The subpleural nodule, receiving LVs along interlobular veins, was sometimes large. The nodule near the cancer always contained DC-SIGN-positive DCs, CD169-positive macrophages, and B cell-dominant lymphocytes; CD1a- or CD83-positive DCs were occasionally present. Nodules from smokers contained significantly more DCs and CD169-positive macrophages. CONCLUSION Lymph nodules seemed to obtain cancer antigens from "afferent LVs" along intralobular arterioles and interlobular veins and they might play a critical role for providing activated or suppressed DCs and macrophages to the regional node. 250.