Signalment:  

3-year old male Boer goat, (Capra circus).Per referring veterinarian: This goat presented with a severe anemia due to parasitism (9% hematocrit), and a fresh, whole blood transfusion was administered. Four hours after transfusion, the goat developed an increased respiratory rate and open-mouthed breathing. Treatments with anti-inflammatory drugs, anti-bacterial drugs, and thoracocentesis for hydrothorax did not ameliorate clinical signs, and the goat died three hours later.

Gross Description:  

Within the thoracic cavity are approximately 700 ml of clear, watery, yellow fluid. Lungs are diffusely rubbery and mottled red and tan with few foci of atelectasis. The pericardial sac contains approximately 70 ml of fibrinous exudate.

The mediastinal lymph nodes are expanded by abundant amounts of caseous material. Scattered throughout the liver and spleen are dozens of variably-sized abscesses. The kidneys are slightly tan to grey, and the subcapsular surface is slightly granular and mottled with pinpoint, tan foci.

Histopathologic Description:

On histology, the majority of hepatic tissue is replaced by multifocal, large abscesses that compress hepatic parenchyma and distort hepatic lobules. Abscesses are composed of large central aggregates of necrotic cellular debris infiltrated by many neutrophils and surrounded by a thick fibrous capsule consisting of well-organized fibroblasts admixed with lymphocytes and occasional bile ducts. In the surrounding hepatic tissue, portal triads are markedly expanded by proliferative bile ducts, admixed with large aggregates of amyloid and many lymphocytes, plasma cells, and macrophages. 

Within the spleen are numerous large abscesses, and surrounding periarteriolar lymphoid aggregates are large aggregates of amyloid. Amyloid distends glomerular tufts. Histochemical staining with Congo red confirms the presence of amyloid as congophilic material that is birefringent and apple green on polarization.

Histologic examination of the lungs revealed an acute, neutrophilic interstitial pneumonia.

Morphologic Diagnosis:  

Liver: Severe, multifocal, chronic hepatic abscesses with marked portal fibrosis, biliary hyperplasia, and portal amyloidosis.

Lab Results:  

Corynebacterium pseudo tuberculosis was cultured from the hepatic and splenic abscesses. Fecal floatation revealed a trichostongyle egg count of 3,400. 

Condition:  

Corynebacterium pseudotuberculosis abscesses in liver; hepatic amyloid

Contributor Comment:  

Multiple abscesses in the liver, spleen, and lymph nodes were due to infection with Corynebacterium pseudo tuberculosis. As a result of chronic inflammatory disease, the goat developed secondary systemic amyloidosis. Death was attributed to the acute pneumonia, possibly due to a transfusion reaction.

Corynebacterium pseudotuberculosis is a gram-positive, pleomorphic, facultative, anaerobic bacillus that commonly causes disease in several domestic species, including goats, sheep, cattle, and horses. In small ruminants, C. pesudotuberculosis is a common cause of lymphadenitis (caseous lymphadenitis), and it may cause pectoral muscle abscesses in horses (pigeon fever) and ulcerative lymphangitis in cattle. In addition, C. pseudotuberculosis may cause subcutaneous abscesses, splenic abscesses, embolic nephritis, and orchitis.(6) As in this case, C. pseudotuberculosis infection is occasionally associated with systemic amyloidosis in small ruminants.(4,7)

Systemic amyloidosis refers to the deposition of amyloid in multiple organs, as opposed to localized amyloidosis, where amyloid is deposited in a single organ. Systemic amyloidosis may result from an immunocyte dyscrasia (primary systemic amyloidosis) or from chronic inflammation (secondary systemic amyloidosis). Amyloid deposited in secondary systemic amyloidosis is composed of AA (amyloid-associated) protein that forms β-pleated sheets. AA protein is derived from serum amyloid-associated (SAA) protein which is produced by the liver as an acute phase reaction to inflammation.(6)

In small ruminants, secondary systemic amyloidosis has been reported to most commonly result from pneumonia,(5,7) though it may also occur in association with nephritis,(5) polyarthritis, urolithaisis, and mastitis.(7) Typically, small ruminants with secondary systemic amyloidosis may have deposits of amyloid in the kidneys, spleen, liver, lymph nodes, gastrointestinal tract, adrenal gland, and vascular tunica media.(2,7)

As in this case, renal glomeruli may be more effected than the renal medulla, and amyloid may form aggregates surrounding splenic periarteriolar lymphoid aggregates.(7) In contrast to this case, hepatic amyloidosis in small ruminants, is more commonly associated with expansion of the sinusoids rather than the portal triads.(4,7)

JPC Diagnosis:  

Liver: Abscesses, multiple, with marked hepatocellular fibrosis, hepatocellular atrophy and loss, biliary hyperplasia, and amyloid formation.

Conference Comment:  

There is some slide variation in this case, and several conference participants described multiple hepatic abscesses while others identified the lesions as pyogranulomas. Participants further noted numerous small, duct-like structures composed of cuboidal cells within the hepatic parenchyma, which prompted a focused exploration of the distinction between bile duct hyperplasia and ductular reaction. Although the liver maintains the ability to regenerate via a tightly controlled process of compensatory hyperplasia, some types of damage, such as toxic injury and massive hepatic necrosis, may render hepatocytes unable to multiply. Instead, there is proliferation of progenitor cells (oval cells), which often form vague, poorly-differentiated ductular structures that are connected to individual canals of Hering and eventually differentiate into hepatocytes or cholangiocytes. This phenomenon, known as ductular reaction, occurs within the hepatic parenchyma.(3) Conversely, bile ductular hyperplasia and proliferation (as seen in cases of bile duct obstruction) are characterized by piling up of epithelium, micropapillary projections, and/or luminal enlargement or distortion, while tortuous bile ducts manifest histopathologically as increased ductular profiles; these changes are generally confined to portal tracts.(8)

Based on the microscopic findings in this case, Fusobacterium necrophorum was suggested as a possible etiologic agent. Hepatic necrobacillosis in ruminants typically occurs when this opportunistic, gram-negative bacterium enters portal circulation as a sequela to toxic rumenitis.(6) Gram-negative septicemia, due to agents such as E. coli or Salmonella spp., could also result in hepatic abscessation. In this case, a Massons trichrome and a Gram stain reveal thick connective tissue capsules surrounding multiple abscesses containing numerous gram-positive bacilli. This, in combination with the culture results as reported by the contributor, identifies C. pseudotuberculosis as the underlying cause.

The contributor provides an excellent summary of both Corynebacterium pseudotuberculosis (which is a potential zoonosis) and systemic amyloidosis in ruminants. Although C. pseudotuberculosis is relatively poorly characterized, some virulence determinants include the following: the leukotoxic phospholipase D exoprotein (PLD) contributes to the destruction of caprine macrophages during infection; the fagABC operon and the fagD gene play a role in virulence and are involved in iron acquisition; the high cell wall concentration of lipids aids in resistance to enzymatic digestion, allowing the bacterium to persist as a facultative intracellular parasite; and CP40, an immunogenic protein that exhibits proteolytic activity as a serine protease.(9) Additionally, recent studies have demonstrated that serum concentrations of haptoglobin (Hp), serum amyloid A and α1 acid glycoprotein are increased in experimental models of ovine caseous lymphadenitis due to C. pseudotuberculosis, which may predispose affected animals to systemic amyloidosis.(1) Readers are urged to review WSC 2013-2014, conference 6, case 4 for a more detailed discussion of amyloidosis.

References:

1. Bastos BL, Loureiro D, Raynal JT, et al. Association between haptoglobin and IgM levels and the clinical progression of caseous lymphadenitis in sheep. BMC Vet Res. 2013;9(1):254-262. 

2. Biescas E, Jiron W, Climent S, Fernandez A, Perez M, Weiss DT, et al. AA amyloidosis induced in sheep principally affects the gastrointestinal tract. J Comp Pathol. 2009;140:238-246.

3. Crawford JM, Burt AD. Anatomy, pathophysiology and basic mechanisms of disease. Burt AD, Portmann BC, Ferrell LD, eds. MacSweens Pathology of the Liver. 6th ed. London, UK: Churchill Livingstone Elesvier; 2012:45-48.

4. Farnsworth GA, Miller S. An unusual morphologic form of hepatic amyloidosis in a goat. Vet Pathol. 1985;22:184-186.

5. Kingston RS, Shih MS, Snyder SP. Secondary amyloidosis in Dall's sheep. J Wildl Dis. 1982;18:381-383.

6. McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 5th ed. St. Louis, MO: Mosby Elsevier; 2012:36-38, 182-189, 284-288, 429-432, 627-628, 758-764, 1031-1032, 1141-1142. 

7. Mensua C, Carrasco L, Bautista MJ, Biescas E, Fernandez A, Murphy CL, et al. Pathology of AA amyloidosis in domestic sheep and goats. Vet Pathol. 2003;40:71-80.

8. Nakanuma Y, Zen Y, Portmann BC. Diseases of the bile ducts. Burt AD, Portmann BC, Ferrell LD, eds. MacSweens Pathology of the Liver. 6th ed. London, UK: Churchill Livingstone Elesvier; 2012:495-497.

9. Pinto AC, de S+�-� PH, Ramos RT, et al. Differential transcriptional profile of Corynebacterium pseudotuberculosis in response to abiotic stresses. BMC Genomics. 2014;15:1-14.

Click the slide to view.

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3-1. Liver

3-2. Spleen

3-3. Kidney

3-4. Liver

3-5. Liver

3-6. Kidney

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