Adult (age unspecified) female ferret, Mustela putorius euroThis was one of several ferrets in this colony suffering from debilitation due to watery diarrhea. The animal died despite supportive care and a necropsy was performed by the overseeing clinical veterinarian.
No gross lesions were reported in the gastrointestinal tract. Lungs appeared collapsed and atelectatic, with multifocal pale, plaque like areas of discoloration noted throughout all lobes.
Multiple slides were submitted from different blocks in this case and there is some variation in the appearance and distribution of lesions between cuts.
Multifocal, often coalescing areas of lipid pneumonia are present. These are often (correlative to the gross distribution of lesions seen) present in subpleural locations, although foci deep within pulmonary parenchyma are often noted. Some areas consist solely of homogeneous alveolar aggregates of foamy macrophages. Others are comprised of more dense mixed inflammatory infiltrates including histiocytes, lymphocytes, scattered neutrophils and occasional multinucleated giant cells. Cholesterol clefts and crystals are often seen in association with these latter areas. Infrequent focal areas of alveolar thickening and mild interstitial fibrosis are also noted in some lesions.
In general, most other adjacent lung tissue is atelectatic due to post-mortem collapse, but evidence of other concurrent chronic or active pulmonary disease processes (e.g. foreign body material, observable organisms, neoplasia, etc.) was not noted.
Lipid pneumonia (lipogranulomas), subacute-chronic, multifocal and coalescing, mild to moderate (section dependent) consistent morphologically with endogenous lipid pneumonia of ferrets
PCR evaluation of feces was positive for ferret enteric coronavirus (FECV)
Endogenous lipid pneumonia
Endogenous lipid pneumonia is seen commonly as an incidental finding in ferrets(9,11) and was not thought to be related to the cause of death or of clinical significance in this animal. Although the specific cause of lipid pneumonia in general is often unknown, the entity has been reported widely over a large spectrum of species, both wild and domestic, (2, 3,7, 12,14) as well as in humans.(1,13) In general, such disease (i.e. lipid pneumonia) is often categorized as exogenous or endogenous (EnLP). The former is usually associated with aspiration from oral or nasal administration of mineral oil or petroleum-based compounds due to a failure to provoke either airway (glottic closure or cough) or mucociliary transport response mechanisms.(1) EnLP has a variety of both known and suspected causes as well as numerous other observed associations. Despite this, in many cases the exact underlying pathogenesis remains undetermined and is probably multifactorial.(3,7) In general, either bronchial obstruction or direct pneumocyte injury leads to overproduction of surfactant with high cholesterol content. Phagocytosis of this lipid leads to accumulations of foamy macrophages which may subsequently incite other inflammatory responses.(7) Other factors altering lipid mobilization and metabolism may also play a role. For example, the rapid mobilization of body fat by some mustelids has led to speculation that the lung could possibly act as a route for excretion of lipids.(5) A correlation with pulmonary nematode parasitic infestation has been made in several species. (2,7) EnLP has been previously reported in rats, where it was described with high spontaneous frequency under varying descriptive designations, including alveolar lipoproteinosis, multifocal histiocytosis, and alveolar proteinosis.(14) It is also well described in this species as a consequence of oral cadmium exposure (as well as other toxins), with subsequent type II pneumocyte hyperplasia and club (Clara) cell activation.(10)
In most cases when present, EnLP is an incidental finding secondary to some (often prior & undetermined) direct pneumocyte injury or bronchial obstructive process, and effort should be made to detect either resolved or active concurrent pulmonary disease. However, caution should be exercised in ascribing a major primary role in morbidity and mortality to these lesions alone.
The cause of death in this animal was thought to be debilitation and dehydration secondary to ferret enteric coronavirus infection (as suggested by a typical clinical presentation(15) and confirmed by PCR evaluation of feces). Microscopic assessment of the GI tract was of little additional benefit due to the degree of autolytic change present. Although the clinical presentation and other gross and histopathologic findings are distinctly different, the lesions of EnLP should not be mistaken for those associated with multisystemic coronavirus infection (resembling FIP) in ferrets.(4)
Lung: Pneumonia, granulomatous, subpleural, multifocal, moderate, with intrahistiocytic lipid vacuoles and cholesterol clefts.
Endogenous lipid pneumonia (EnLP) is a common but obscure entity with an elusive pathogenesis that is diagnosed routinely in ferrets usually as an incidental finding. Its occurrence in cats and occasionally in dogs is less frequent and also of unknown significance; however, it is frequently reported in the vicinity of cancerous lesions in dogs, cats and people, possibly due to the accumulation of lipid breakdown products of neoplastic cells.(8) This finding, in addition to other reports of EnLPs association with a variety of intrapulmonary and extrapulmonary conditions, indicates it may occur secondarily to underlying disease, equating its discovery as evidence supporting further pursuit of a primary illness.(6)
This case illustrates EnLPs classic histologic presentation as subpleural accumulations of histiocytes, lipid, and cholesterol. This distinctive subpleural location is curious given the proposed pathogenesis of pneumocyte damage and subsequent cholesterol release from disintegrating cell membranes.(7) Conference participants could not determine how such alveolar accumulations routinely end up forming subpleural nodules, and most agree with the contributors suspicions of a multifactorial pathogenesis in the formation of EnLP.
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11. Personal communication, Dr. Bruce Williams
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