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 0.5 mm from the end at alveoli. Lymph nodules were rare in alveolar tissue 60-80 mm from the cancer lesion; if present, they were 0.1-0.3 mm across, attached to a lymph vessel, and largely composed of T lymphocytes. By contrast, alveolar tissue near the cancer (5-10 mm) often contained larger nodules 0.2-1.0 mm 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.