Conference 19 - 2014 Case: 01 20150401

Signalment:

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.

Gross Description:

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.

Histopathologic Description:

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.

Morphologic Diagnosis:

Lipid pneumonia (lipogranulomas), subacute-chronic, multifocal and coalescing, mild to moderate (section dependent) consistent morphologically with endogenous lipid pneumonia of ferrets

Lab Results:

PCR evaluation of feces was positive for ferret enteric coronavirus (FECV)

Condition:

Endogenous lipid pneumonia

Contributor Comment:

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)

JPC Diagnosis:

Lung: Pneumonia, granulomatous, subpleural, multifocal, moderate, with intrahistiocytic lipid vacuoles and cholesterol clefts.

Conference Comment:

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.

References:

1. Banjar H. Lipoid Pneumonia: A Review. Bahrain Medical Bulletin 25 (1): 36-39 (2003)

2. Brown CC. Endogenous Lipid Pneumonia in Opossums from Louisiana. Journal of Wildlife Diseases 24(2): 214-219 (1988)

3. Dungworth D. The respiratory system. In: Jubb K, Kennedy P, Palmer N, eds. Pathology of domestic animals. 3rd ed. Orlando, Fla: Academic Press Inc, 1985; 470-474

4. Garner MM et al: Clinicopathologic Features of a Systemic Coronavirus-Associated Disease Resembling Feline Infectious Peritonitis in the Domestic (Mustela putorius). Vet Pathol 45:236-246 (2008)

5. Guarda F, Bollo E, Macchi E. Lipoid Pneumonia in the Red Fox (Vulpes vulpes). JME 4: 13-16 (1997)

6. Himsworth CH, Malek S, Saville K, Allen AL. Endogenous lipid pneumonia and what lies beneath. Can Vet J. 2008;49(8):813-815.

7. Jones DJ, Norris CR, Samii VF, Griffey SM: Endogenous lipid pneumonia in cats: 24 cases (1985-1998). JAVMA 216 (9): 1437-1440 (2000)

8. Lopez A. Respiratory system, mediastinum, and pleurae. In: Zachary JF, McGavin MD, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Elsevier Mosby; 2012:530.

9. Marinez J, Reinacher M, Perpinan D, Ramis A: Identification of Group 1 Coronavirus Antigen in Multisystemic Granulomatous Lesions in Ferrets (mustela putorius furo). J Comp Path 138:54-58, 2008

10. Molina AM, Raya AI, Carrasco L, Blanco A, Monterde JG, Rueda A, Moyano R: Endogenous lipid pneumonia in rats after subacute exposure to CdCl2. Toxicology and Industrial Health 24: 677-681 (2008)

11. Personal communication, Dr. Bruce Williams

12. Raya AI, Fernandez-de Marco M, Nunez A, Afonso JC, Cortade LE, Carrasco L. Endogenous Lipid Pneumonia in a Dog. J Comp Path 135: 153-155 (2006)

13. Sharma A, Ohri S, Bambery P, Singh S: Idiopathic Endogenous Lipoid Pneumonia. Indian J Chest Dis Allied Sci 48: 143-145 (2006)

14. Weller W. Alveolar lipoproteinosis. In Respiratory system, monographs on pathology of laboratory animals, T.C. Jones, U. Mohr and RD Hunt (eds). Springer-Verlag, New York, New York, 171-176

15. Williams BH, Kiupel M, West KH, Raymond JT, Grant CK, Glickman LT: Coronavirus-associated epizootic catarrhal enteritis in ferrets. JAVMA 217 (4): 526-530 (2000)