Grossly, the distribution of lesions involved large regions of the lungs. The pleural surface of the lungs was often irregular and cobblestoned in appearance (Fig 1, top, A). The areas of fibrosis and remodeling formed plaque-like depositions that were discrete from the more normal parenchyma, and extended from the subpleural regions to deep within the organ (Fig 1, middle, B). Grossly discernable honeycombing of the lung was uncommon in the cats, but was a prominent feature in a single cat (Fig 1, bottom, C).
A summary of the relative abundance of the four predominant histologic changes in feline IPF, along with the presence or absence of pulmonary neoplasia, is found in Table 2. Histologically, the disease process in cats, as in human IPF, is multifocal, with relatively normal parenchyma interspersed with the affected tissue. The remodeled lung often was most prominent subpleurally (Fig 2, top left, A, and top right, B). The primary histologic changes in cats, as with humans, included interstitial fibrosis with fibroblast/myofibroblast foci, metaplasia of the alveolar epithelium (honeycomb lung), and interstitial smooth-muscle metaplasia/hyperplasia. Interstitial inflammation was variable but usually not prominent (Table 2). In the most severely affected regions of the lungs, there was extension of the histologic alterations into the deep parenchyma without distinction between subpleural and deeper microenvironments (Fig 2, top left, A, and top right, B). acular medication
Honeycombing was present in all cats, and in these areas the epithelium was composed of low-to-tall columnar cells that often formed well-differentiated mucous cells (Fig 2, middle left, C [human], and middle right, D [feline]); mucous cell metaplasia was the predominant phenotype, being present in 69% of the lung samples analyzed (Fig 2, bottom left, E [human], and bottom right, F [feline]). In the cats without mucous cell metaplasia, the lining cells were well-differentiated type II pneumocytes or columnar cells of unknown phenotype; small foci of squamous metaplasia were less commonly a feature of the epithelium. AB-PAS staining of the lung revealed numerous turquoise interstitial mast cells in the fibrotic and honeycomb lung (Fig 2, bottom right, F). The identity of the mast cells was confirmed using immunohistochemistry against mast cell tryptase (inset, Fig 2, bottom right, F).
Figure 1. Gross pathology of feline IPF. Areas of fibrosis are scattered through the parenchyma, giving the pleural surface a roughened, cobblestone appearance (arrows, top, A). In 3 of the 16 cats, there were primary lung carcinomas in addition to the fibrotic foci (asterisks, top, A). The areas of fibrosis are restricted to the parenchyma, extending from the subpleural region to the deep lung parenchyma (arrows, middle, B), and are interposed with more normal parenchyma (asterisks, middle, B). Grossly apparent honeycomb lung occurs rarely in feline IPF (arrows, bottom, C). Li = liver; Hrt = heart.
Figure 2. Comparative histopathology of feline and human IPF (HE), showing honeycomb lung in human (top left, A) and feline (top right, B) IPF with adjacent relatively normal lung; columnar epithelial cells lining the honeycomb lung of human IPF adjacent to a terminal bronchiole (middle left, C); honeycomb lung in feline (middle right, D) IPF. Bottom right, F: AB-PAS staining of mucous cell metaplasia in honeycomb lung of feline IPF. The mucus is apically oriented in the mucous cells (arrows). Bottom left, E: Mucin in bronchiolar epithelium (BE) of human IPF (AB-PAS stain). Mucosubstances in the human IPF are restricted to the bronchiolar epithelium. Note the turquoise interstitial mast cells in the feline lung. Inset shows immunohistochemistry for mast cell tryptase. Bars in top left, A, and top right, B indicate 400 |j,m; all other bars indicate 50 |j,m.
Table 2—Occurrence and Relative Proportions of the Major Histologic Features in IPF in Cats
|Cat No.||Alveolar Epithelial Metaplasia||Mucous Cell Metaplasia||Smooth-Muscle
|1||+ +||A||+ + +||+||+ + +||P|
|2||+ + + +||P||+ + + +||+||+ + +||A|
|3||+ + + +||P||+ + + +||+ + +||+ + + +||A|
|4||+ + + +||A||+ + + +||+ +||+ + +||A|
|5||+ + + +||P||+ + + +||+ + +||+ + + +||P|
|6||+ + + +||P||+ + + +||+ + +||+ + + +||A|
|7||+ + +||P||+ + + +||+ +||+ + +||A|
|8||+ + +||P||+ + +||+||+ + +||A|
|9||+ + + +||P||+ + + +||+ +||+ + +||A|
|10||+ +||A||+ + + +||+||+ + +||A|
|11||+ +||A||+ + +||+ + +||+ + +||A|
|12||+ +||A||+ + +||+||+ + + +||A|
|13||+ + + +||P||+ + +||+||+ + +||A|
|14||+ + + +||P||+ + + +||+ +||+ + +||P|
|15||+ + + +||P||+ + + +||+ + +||+ + + +||A|
|16||+ + + +||P||+ + + +||+ + +||+ + + +||A|