Figure 2. Claudin10-positive cells with marked pleomorphism are widely distributed in various patterns in IPF lungs.

Paraffin-embedded lung sections from patients with IPF and COPD were immunohistochemically labeled for Cldn10. Brown signals correspond to Cldn10. (A, B, C) Representative photomicrographs of normal-looking alveoli with slightly remodeled bronchiolar region (A) and bronchiolar regions (B, C) from COPD lungs are shown. Despite the variation of subcellular localization of Cldn10, Cldn10-positive cells mostly displayed organized cell arrangements. Arrow in (A) denotes cytoplasmic and/or nuclear expression of Cldn10 in the cells at terminal (or respiratory) bronchiole. Dashed-line in (B) encompasses bronchiolar epithelium in which Cldn10 signals are confined to the uppermost portion of the lateral membrane between the epithelial cells, apparently corresponding to tight junctions. Cldn10 expression was occasionally spotted at luminal end of the bronchiolar epithelium (C). (D-O) Representative photomicrographs with different arrangements of Cldn10-positive cells are shown. (D) Asterisks denote Cldn10-positive epithelial monolayers in a moderately fibrotic region. Arrow denotes a cellular mass in the airspace containing Cldn10-positive cells. (E) Area circled by dotted line denotes mosaic cell mass in the airspace containing Cldn10-positive and negative cells. (F) Two different arrangements of club cells were juxtaposed with each other; one with organized columnar cells expressing Cldn10 at the uppermost portion of the lateral membrane between the epithelial cells (area circled by dashed line) and the other with mosaic mixtures of Cldn10-positive and negative cells (area circled by dotdashed line). (G) Asterisks denote Cldn10-positive epithelial monolayers. Luminal side of fibroblastic foci (FF) is lined by Cldn10-positive and negative cells with round-to-oval shape. (H) Area circled by dotted line denotes a mosaic cell mass containing Cldn10-positive and negative cells. Highly fibrotic area is located to the right of the mass, where Cldn10 signals are barely observed at the luminal edge. I: Area circled by dot-dashed line denotes a polypoid cell mass containing Cldn10-positive and negative cells. (J) Area with honeycomb change display multiple cysts lined by Cldn10-positive club cell monolayers. (K) Magnified view of the boxed region in (J) display a mosaic cell mass in the airspace containing Cldn10-positive and negative cells (area surrounded by dotted line) and Cldn10-positive monolayer that partially line the cyst wall (area surrounded by dashed line). (L) Area surrounded by dashed line denotes columnar club cells forming organized monolayer. The expression of Cldn10 is confined to the uppermost portion of the lateral membrane between the epithelial cells, apparently at tight junctions. Adjacent bronchiolar epithelium to the left is lined by cuboidal epithelial cells negative or weakly positive for Cldn10. (M) Fibrotic interstitium with Cldn10-positive club cells randomly distributed therein. Numerous Cldn10-negative cuboidal cells are also spotted in the vicinity of Cldn10-positive cells. (N) Cldn10-positive club cells with oval-to-columnar shape populate the alveolar wall in a monolayer arrangement. (O) Area circled by dot-dashed line denotes a mosaic cell mass containing Cldn10-positive and negative cells. The mass barely attaches to the lung structure located to the right. Original magnifications: x100 (A, J); x200 (B, C, D, E, H, N); x400 (F, G, I, K, L, M, O).