Signalment:  

9-year-old, female neutered, Persian cross-bred, feline (Felis domesticus)The cat was referred to the Royal (Dick) School of Veterinary Studies with a 4 month history of intermittent coughing and retching, which was unresponsive to furosemide (diuretic) and Synulox (antibiotic). Broncho-alveolar lavage fluid prior to referral contained very large numbers of monomorphic epithelial cells but was otherwise non-diagnostic. The cat presented with a severe tachypnoea (100-160 bpm). Thoracic radiographs were performed and revealed a mixed alveolar, interstitial, nodular and bronchial pattern with bullous change in the caudo-dorsal lung lobes. PCR for Mycoplasma sp. was negative. A clinical diagnosis of Idiopathic Pulmonary Fibrosis was made. The cat was prescribed steroids, Sildenafil (Viagra), Colchicine and Salbutamol (Ventolin). Some response to the steroid treatment was observed but this was limited. Over the following 9 months the cat deteriorated with several episodes of hospitalization.

Gross Description:  

The cat was in obese body condition (4.2kg). The lungs were diffusely mottled dark and light pink with numerous multifocal to coalescing firm, yellow-brown to yellow-green, depressed areas over the surface. These ranged from 2-12 mm diameter and extended into the parenchyma. This was more pronounced in the caudal right lung lobe. The airways were clear. Mild, multifocal bilateral chronic renal cortical infarcts were also noted, characterized by firm, depressed, tan foci. 

Histopathologic Description:

Lung Right caudal lung lobe 1 section

Approximately 70-80% of the lung parenchyma is remodeled by multifocal to coalescing areas of increased cellularity, predominantly located subpleurally, but also extending into the central parenchyma. In these areas, the pulmonary interstitium is markedly expanded by fusiform and plump mesenchymal cells (fibrocytes and fibroblasts), and thick bundles of plump spindloid cells with moderate amounts of eosinophilic cytoplasm, and a medium sized oval to elongated nucleus with a reticular chromatin pattern (myofibroblasts) (Fig. 4-1). Where present, alveolar spaces are lined by a single to occasionally multiple layers of low columnar to cuboidal epithelial cells with indistinct cell borders, a moderate amount of pale eosinophilic, finely granular cytoplasm and a basally located, round to oval nucleus with a finely stippled chromatin pattern, and one to two medium sized nucleoli consistent with type II pneumocytes (honeycomb lung). 

Within the alveolar lumen are numerous, plump, polyhedral to round cells with abundant, highly vacuolated, pale eosinophilic cytoplasm and a medium sized oval nucleus with a finely stippled chromatin pattern and a single, medium sized nucleolus (alveolar macrophages). These cells are occasionally binucleated and multinucleated. Small aggregates of lymphocytes and plasma cells are scattered throughout the remaining pulmonary parenchyma. 

Small to medium sized bronchi contain numerous alveolar macrophages interspersed with abundant pale amphophilic to basophilic, lightly fibrillar, acellular material (mucus), small areas of deeply basophilic, cracked acellular material (mineral) and acicular (cholesterol) clefts. At the periphery of the large bronchi are numerous, small peri-bronchiolar glands. In less severely affected areas, the alveolar lumens are multifocally enlarged by non-staining spaces (emphysema). 

Special stains/Immunohistochemistry: The cuboidal cells lining the alveolae are strongly positive for cytokeratin, confirming their epithelial nature. The interstitial mesenchymal proliferation stained variably blue and pink (collagen and smooth muscle, respectively) (Fig. 4-2) and large areas stained strongly with smooth muscle actin confirming the presence of smooth muscle (Fig. 4-3).

Morphologic Diagnosis:  

Lung Right cranial lung lobe - Severe, multifocal to coalescing interstitial fibrosis with fibroblast and myofibroblast foci, type II pneumocyte hyperplasia (honeycomb lung) and alveolar interstitial smooth muscle proliferation

Condition:  

Idiopathic pulmonary fibrosis

Contributor Comment:  

The severe, multifocal to coalescing interstitial fibrosis, interstitial smooth muscle proliferation, alveolar macrophages and excess mucus production are consistent with the clinical diagnosis of feline idiopathic pulmonary fibrosis (FIPF). The lesions were similar in nature throughout the lung but were more severe in the right caudal lung lobe than the left cranial lung lobe. There was also squamous metaplasia in sections of the cranial lung lobe, which is also a feature of this condition.

FIPF is an uncommon condition, first described in 2000 by Rhind and Gunn-Moore(2). The average age of onset is approximately 8.7 years and the average time between onset clinical signs to death is 5.5 months.(1) This case has many features characteristic of this condition: sub-plural and caudo-dorsal distribution, persistent progressive fibrosis with temporal heterogeneity of lesions, alveolar type II pneumocyte hyperplasia and small foci of alveolar epithelial squamous metaplasia in some sections. This condition has been associated with the development of bronchoalveolar carcinoma, which was not a feature of this case. The aetiology is not currently known. Toxic, hypersensitivity, inflammatory and genetic origins have been investigated. 

Parallels have been drawn between FIPF and Usual Interstitial Pneumonia (UIP) in man.(3) Salient features of UIP in man include interstitial fibrosis with fibroblast/ myofibroblast proliferation, temporal heterogeneity of lung remodeling, subpleural orientation, honeycomb change, interstitial smooth muscle proliferation and scant inflammation.

A type II pneumocyte defect has been described in a familial form of human interstitial pulmonary fibrosis (IPF), with abnormal cytoplasmic lamellar body-like inclusions seen on electron microscopy.(3) Similar ultrastructural changes were observed in type II pneumocytes of affected cats by Williams et al. The authors suggested that FIPF may be due to a defect in the type II pneumocyte and that cats potentially represent a spontaneous model of IPF in humans. 

JPC Diagnosis:  

Lung: Interstitial fibrosis, multifocally extensive, severe with fibroblast and smooth muscle proliferation, type II pneumocyte hyperplasia, and alveolar histiocytosis

Conference Comment:  

Idiopathic pulmonary fibrosis is a respiratory disease of humans that affects 11 male and 8 female patients per 100,000 individuals per year. Consequently, a representative animal model to study this malady is highly coveted and bleomycin-treated rodents have not proved to be adequate subjects to date.(3) The contributor did an excellent job of outlining what is currently known about this disease in cats. 

References:

1. Cohn L, Norris E, Hawkins E, Dye J, Johnson C and Williams K: Identification and characterization of an Idiopathic Pulmonary Fibrosis-like condition in cats. J Vet Intern Med 18:623-641, 2004
2. Rhind S and Gunn-Moore D: Desquamative form of Cryptogenic Fibrosing Alveolitis in a cat. J Comp Path 123:226-229, 2000
3. Williams K, Malarkey D, Cohn L, Patrick D, Dye J and Toews G: Identification of Spontaneous Feline Idiopathic Pulmonary Fibrosis. Chest 125:2278-2288, 2004

Click the slide to view.

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4-1. Lung, cat

4-2. Lung, cat.

4-3. Lung, cat.

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