Fibroblast foci, small foci of ongoing mesenchymal cell proliferation with fibroblasts/myofibroblasts and collagen, similar to the foci seen in UIP of humans were observed at the periphery of the honeycomb lung (Fig 3, top left, A [human], and top right, B [feline]). As with human IPF, the epithelial cells overlying the fibroblast foci in feline IPF were often attenuated or cuboidal type II pneumocytes (Fig 3, top left, A [human], and top right, B [feline]).
Interstitial smooth-muscle metaplasia/hyperplasia was present in all of the cats. The smooth-muscle cells were interspersed with the metaplastic epithelium and fibrous connective tissue, forming discrete, thick bundles; similar smooth-muscle changes are found in human IPF (Fig 3, bottom left, C [human], and bottom right, D [feline]).
In addition to the above changes, scattered large foci of alveolar macrophages were found in all of the cats. These regions of alveolar histiocytes were often associated with hyperplastic type II pneumocytes; the macrophages were not as abundant in areas of chronic remodeling and honeycomb lung. In addition to the chronic lung remodeling of IPF, three of the cats had primary pulmonary neoplasms consistent with bronchioloalveolar carcinomas. buy alphagan
a-SMA: In normal cat lung, a-SMA was restricted to the smooth muscle of the pulmonary vasculature, airway walls, and openings to the respiratory bronchioles; there was little SMA evident in the alveolar septa (Fig 4, bottom left, E). In IPF cats, there was abundant SMA in the bundles of well-differentiated metaplastic smooth muscle. SMA-positive myofibroblasts were found subjacent to the metaplastic epithelium of the honeycomb lung, as well as in the myofibroblast foci; a similar distribution of SMA was seen in the human IPF lung (Fig 4, top left, A [human], and top right, B [feline]). Many myofibroblasts were localized to the areas of acute, ongoing alveolar septal injury, as well as septa in the areas of minimal injury and remodeling (Fig 4, middle left, C, and middle right, D).
Figure 3. Comparative histopathology of feline and human IPF (HE), showing fibroblast/myofibroblast foci in human (top left, A) and feline (top right, B) IPF. The foci are comprised of proliferating mesenchymal cells (arrows) overlain by epithelial cells (EC) that vary from attenuated cells to type II pneumocytes and columnar epithelial cells. Smooth-muscle metaplasia (arrows) is shown in areas of fibrosis in human (bottom left, C) and feline (bottom right, D) IPF. Bars indicate 50 |j,m.
Figure 4. Immunohistochemical localization of a-SMA in human and feline IPF, showing a-SMA immunohistochemistry for myofibroblast metaplasia in human (top left, A) and feline (top right, B) honeycomb lung (arrows indicate subepithelial myofibroblasts; arrowhead indicates smooth-muscle bundle); early myofibroblast metaplasia (arrow) in the alveolar septa of active epithelial injury (middle left, C) [note the sloughed cells, morphologically consistent with hypertrophied type II pneumocytes, shown by asterisks]; myofibroblast metaplasia in histologically normal alveolar septa (middle right, D); normal feline lung (bottom left, E) [SMA signal in smooth muscle around terminal bronchiole (TB) and respiratory bronchiole (RB)]. Bars indicate 50 |j,m.