Journal of Comparative Pathology 2008

Porcine

Multifocal Granulomatous Hepatitis Caused by Actinobacillus

pleuropneumoniae Serotype 2 in Slaughter Pigs: APP occurs in all
pigs of all ages characterized by necrotizing, hemorrhagic bronchopneumonia and
serofibrinous pleuritis. Other rare manifestations of APP are meningitis, osteomyelitis,
arthritis, endocarditis, otits media and granulomatous hepatitis. The granulomas
have asteroid bodies formation (Bodies with splendore hoeppli material)

Detection by In-situ Hybridization of Pasteurella multocida Toxin (toxA) Gene in

the Lungs of Naturally Infected Pigs – PMT (ToxA gene product) produced by P
multocida Types A and D are associated with pulmonary abscessation. PMT causes
increased vascular permeability and is toxic to neutrophils.

Histopathological Distinction and Evaluation of Biliary and Peribiliary Cysts in Pig

Liver. J. Comp. Path. 2008, Vol. 139, 202e207. Most intrahepatic cysts are derived from
bile ducts (biliary cysts), but are usually not clinically significant. Peribiliary cysts are
derived from the peribiliary glands located in fibrous tissue of large portal areas and can
cause local compression and circulatory disturbance

Capillary Haemangiomas of the Scrotum and Testicle in Boars. J. Comp. Path. 2008,
Vol. 139, 177e186. Scrotal hemangiomas occur frequently, but testicular hemangiomas
are rare, and they rarely occur together. The authors suggest an inherited basis since all
pigs in the study group were related and of a large white breed. The authors suggest a
UV component to the development of scrotal tumors.
 Left-scrotal/ right testicular

Vascular-associated Lymphoid Tissue in Swine (Sus scrofa).

Vol 58, No 2 April 2008. mononuclear cells were noted in the intima
and occasionally the inner portion of the tunica media and adventitia
at branching sites. The infiltrating cells were primarily CD3+CD4+ T
cells, with some macrophages. Focal accumulations of mononuclear
cells in the arterial wall of healthy humans at predilection sites for
atherosclerotic lesions.

A prospective, case control study evaluating the association between Clostridium

difficile toxins in the colon of neonatal swine and gross and microscopic lesions. J
Vet Diagn Invest 19:52–59 2007). Clostridium difficile --suckling pigs with
mesocolonic edema and typhlocolitis.

Brain lesions in pigs affected with postweaning multisystemic wasting syndrome. J

Vet Diagn Invest 19:109–112 (2007). Cerebellar lymphohistiocytic vasculitis and
fibrinoid degeneration combined with hemorrhages or with lymphohistiocytic meningitis
in pigs with PMWS.

Association of myocarditis with high viral load of porcine circovirus

type 2 in several tissues in cases of fetal death and high mortality in
piglets. A case study. J Vet Diagn Invest 19:368–375 (2007). High number of
mummifications and stillbirths, a high neonatal mortality rate, and many piglets with
congenital tremors or hind leg ataxia. A high load of PCV2 DNA was observed in
myocardium, liver, and spleen from mummified or stillborn piglets, lower in piglets with
myocarditis, and even further lower in pigs without myocarditis. Neither porcine
parvovirus nor encepaholomyocarditis virus was detected.

Paramyxovirus infection in pigs with interstitial pneumonia and encephalitis in the

United States. J Vet Diagn Invest 13:428–433 (2001). In the last few years, newly
recognized paramyxoviruses have been associated with severe disease in several animal
species, including swine, as well as in human beings. Recently, a paramyxovirus was
isolated from a swine herd in the northcentral United States that experienced an epizootic
of respiratory and central nervous system disease. Affected pigs had interstitial
pneumonia with necrotizing bronchiolitis and encephalitis characterized by lymphocytic
perivasculitis and diffuse gliosis. Other pig respiratory viruses are PRRS, porcine
respiratory coronavirus (PRCV), porcine circovirus (PCV) type 2, antigenically variant
H1N1 strains of swine influenza virus (SIV), as well as H1N2 SIV in England and H3N2
SIV in the United States have been identified. Historically, only a few viruses had been
associated with respiratory disease in swine, and, in field situations, only swine influenza
virus (SIV) and pseudorabies virus (PRV) were detected with any frequency.
Cytomegalovirus, adenovirus, and enterovirus also have been reported to cause
pneumonia in swine but are rarely encountered.

Fibroepithelial Hamartoma in a Domestic Pig. Vet Pathol 44:411–413 (2007).

Histologic examination revealed a moderate orthokeratotic hyperkeratosis with variable
degrees of epithelial proliferation. The main body of the dysplasia consisted of
collagenous fibers. In addition, some proliferating small blood vessels as well as focally
gathered dilated apocrine glands were evident.

Porcine Circovirus Type 2-Associated Cerebellar Vasculitis in Postweaning

Multisystemic Wasting Syndrome
(PMWS)-Affected Pigs. Vet Pathol 44:621–634 (2007). Acute hemorrhages and edema
of cerebellar meninges and parenchyma due to a necrotizing vasculitis resulted in
degeneration and necrosis of the gray and white matter. Few to numerous PCV2 DNA
and antigenbearing endothelial cells were detected. Detection of caspase 3 activity and
DNA strand breaks showed numerous apoptotic endothelial cells in the vascular lesions
observed. Lesions in PDNS are characterized primarily by a cutaneous and
subcutaneous necrotizing vasculitis and glomerulonephritis and are likely mediated by
immune complex deposition.
Multiple Hepatic Peribiliary Cysts in a Young Pig. Vet Pathol 44:707–709 (2007). All
lobes of the liver contained numerous cysts of varying size containing serous fluid in all
lobes. Histopathologically, the cysts were located mainly around the large bile duct and
in the connective tissue of the portal tracts. The cysts were lined by a single layer of
columnar, cuboidal, and flattened epithelial cells. Occasionally, goblet cells were
observed. The epithelial cells were stained with periodic acid–Schiff/alcian blue and
high-iron diamine/alcian blue, indicating the presence of neutral mucin, sialomucin, and
sulfomucin.

The Distribution and Density of Clostridium difficile Toxin Receptors on the

Intestinal Mucosa of Neonatal Pigs. Vet Pathol 44:814–822 (2007). The most
important virulence factors of C. difficile are 2 large exotoxins, toxin A (TcdA) and
toxin B (TcdB). TcdA is a potent enterotoxin with effects on host tissues that are
dependent upon receptor-mediated endocytosis of the intact toxin. TcdB is an effective
cytotoxin, but it apparently does not bind receptors on intact mucosal epithelium. TcdB is
much less toxic in vivo unless there is underlying damage to the mucosa, and it is not
essential for the virulence of C. difficile. The receptors for TcdA in the pig remain to be
identified, but a-galactosyl does not seem to be significant to its binding.

Histopathological and Immunohistochemical Findings in the Lungs of

Pigs Infected Experimentally with Mycoplasma hyopneumoniae
Histopathological changes consisted of exudates in airways and alveolar
lumina, peribronchial and peribronchiolar lymphoid hyperplasia, and
enlargement of alveolar septa. These changes coincided with significant
increases in the expression of cytokines (IL-1a, IL-1b, IL-8, TNF-a and INF-g)
and lymphoid markers (CD4+, CD8+, muramidase, IgG+, IgA+).

Characterization of Interstitial Nephritis in Pigs with Naturally Occurring Postweaning

Multisystemic Wasting Syndrome Vet Path 2008 Jan: types of tubulointerstitial inflammation seen
were: lymphoplasmacytic, granulomatous and mixed. The epithelium of renal tubules was the consistently
positive with in situ hybridization. Unlike in lymphoid tissue, the amount of PCV-2 was not associated with
severity of granulomatous inflammation, but did for lymphoplasmacytic inflam.

Metritis, Valvular Endocarditis, and Septicemia by Actinobacillus equuli in a Gilt in the United
States. Vet Pathol 45:495–499 (2008). Gross findings included metritis, splenomegaly, and valvular
endocarditis. Bacterial endocarditis (in the mitral and tricuspid valves) and metritis with dissemination
to multiple organs was diagnosed by using histologic examination. Gram-negative coccobacillary
organisms present in the valvular lesions were characterized as Actinobacillus equuli.

Porcine Circovirus 2 Inclusion Bodies in Pulmonary and Renal Epithelial Cells. Vet Pathol 45:640–
644 (2008). The most common lesions of PMWS are lymphohistiocytic to granulomatous lymphadenitis,
interstitial pneumonia and interstitial nephritis, with intracytoplasmic amphophilic botryoid inclusion
bodies in macrophages. Intracytoplasmic botryoid inclusion bodies were observed in bronchial, bronchial
glandular, and renal tubular epithelium of several pigs from 4 different farms in Western and Eastern
Canada

Reproduction of Postweaning Multisystemic Wasting Syndrome in Pigs by Prenatal Porcine

Circovirus 2 Infection and Postnatal Porcine Parvovirus Infection or Immunostimulation. Vet
Pathol 45:842–848 (2008). Postweaning multisystemic wasting syndrome (PMWS) was reproduced in
prenatally porcine circovirus 2 (PCV2)-infected pigs by either postnatal infection with porcine parvovirus
(PPV) or by immunostimulation. Prenatal infection Plus Postnatal PArvo or immunostimulation or any
Post natal PCV-2 infection. But not PCV-2 in utero with no subsequent infection or immunostimulation.

Naturally occurring sheep-associated malignant catarrhal fever in North American

pigs. J Vet Diagn Invest 21:250–253 (2009). typical lymphoproliferative vasculitis in
multiple tissues of the affected pigs. Ovine herpesvirus 2 (OvHV-2) DNA was detected
by polymerase chain reaction in the tissues of affected pigs in both cases. The amplified
sequences were identical between the clinically affected pigs and the OvHV-2–infected
sheep. Additional virological and bacteriological examination showed that the affected
pigs were negative for agents that cause Aujeszky’s disease, classical swine fever,
porcine enterovirus, and rabies.

Acquired Melanosis Caused by Acorn Ingestion in the Nero Siciliano Pig: Diffuse black discoloration
of lymph node cortex and medulla and melanosis of fat. Acorns have high total phenolic compounds.
Hypothesized that swine tyrosinase could act on phenolic substances found in acorns and increase the
biosynthesis and the anomalous storage of melanin.

Multifocal Granulomatous Hepatitis Caused by Actinobacillus pleuropneumoniae

Serotype 2 in Slaughter Pigs APP occurs in all pigs of all ages characterized by
necrotizing, hemorrhagic bronchopneumonia and serofibrinous pleuritis. Other rare
manifestations of APP are meningitis, osteomyelitis, arthritis, endocarditis, otits media
and granulomatous hepatitis. The granulomas have asteroid bodies formation (Bodies
with splendore hoeppli material)

Reproductive Failure Experimentally Induced in Sows via Artificial Insemination

with Semen Spiked with Porcine Circovirus Type 2. Vet Pathol 46:707–716 (2009).
All live-born piglets -PCV2 viremic at birth. Stillborn fetuses-congestive heart failure.
Mummified fetuses - crown-rump length from 7 to 27 cm, indicating fetal death between
42 and 105 days of gestation. PCV2 antigen was detected in the myocardium by
immunohistochemistry of 7/8 (88%) live-born piglets, 2/2 (100%) of the stillborn
fetuses, and 25/25 (100%) of the mummified fetuses. In addition, 4/25 mummified
fetuses had PCV2 antigen associated with smooth muscle cells and fibroblasts. The
results of this study indicate that intrauterine administration of PCV2 causes reproductive
failure in naıve sows

Swine
Expression of Mx protein & interferon-α (IFN-α) in pigs experimentally infected
with swine influenza virus. pp161-67. March 2006 NW
- Mx protein and IFN-α antigen were expressed in the lung from pigs experimentally
infected with swine influenza virus
- Simultaneous detection of viral RNA, Mx protein, and IFN-α in the
bronchial and bronchiolar epithelial cells and macrophages in lung
- Probably, the cells infected virus produce Mx protein and IFN-α
- Mx proteins mediate antiviral activity of IFN-α
- Antiviral activity of IFN-α in swine influenza is mediated by all of the following:
- 2’5’oligoadenylate synthetase, Protein kinase R, Mx1 protein
Mx proteins inhibit synthesis of viral protein

Evidence of breed-dependent differences in susceptibility to porcine circovirus type-

2(PCV2)-associated disease & lesions. pp281-93. May 2006 AR
• Predisposition of Landrace pigs to PCV-2 induced disease and lesions (PMWS)
• Low levels of passively acquired antibodies are protective

Pathogenicity of Vietnamese enterotoxigenic Escherichia coli strains in colostrum-

deprived 1-day-old piglets. pp150-160, Mar 2006 AR
• preweaning colibacillosis is major cause of death in Vietnam
o isolates belonging to serotype O8
o produced heat stabile and heat labile enterotoxins; did NOT produce any
of the recognized fimbriae
o hemagglutination: unique mannose-resistant hemagglutination activity
with guinea pig, sheep, human, & chicken red blood cells at 37°C, but not
18°C
o enterocyte brush border attachment - unidentified colonization factor
• inoculation into colostrum-deprived 1 day old piglets:
F- strain: acute watery diarrhea w/in 4 hrs; up to 20% weight loss
attached exclusively to ileum
EM demonstrated presence of fimbriae
Conclusion: new pathogenic ETEC fimbrial type in piggeries in Vietnam, with a unique
hemagglutination property and attachment characteristics similar to ETEC bearing F5
fimbriae.

Brain Lesions Induced by Experimental Intranasal Infection of Japanese Encephalitis Virus

in Piglets: J Comp Path 141 vol 2-3:JE experimentally induced in 3 week-old piglets by a single
intranasal inoculation of Japanese encephalitis virus (JEV). The lesions consisted of glial cell
aggregates and lymphocytic perivascular cuffing throughout the olfactory tract and pyriform
cortex. JEV antigens were detected in the cytoplasm and neuronal processes of small nerve cells
in the granule cell layer of the olfactory bulb, in the neuronal processes of the olfactory tract and
in the cytoplasm of neurons in the pyriform cortex. JEV is one of 4 major encephalitic
flaviviruses of public health importance, the other 3 being West Nile virus, St. Louis encephalitis
virus in America, and Murray Valley encephalitis virus in Australasia

Investigation into the pathology of shoulder ulcerations in

sows. Veterinary Record (2009) 165, 171-174. Stage 1-
epidermal necrosis, thrombosis of dermal blood vessels, multiple
colonies of bacteria. Stage 2 Dermal necrosis, and multiple colonies of
bacteria. Stage 3 – Subcutis necrosis, the periosteum of the tuber spina
scapula was reactive and thickened. Stage 4 - Exposed bone of the
tuber spina scapula was covered with a thin layer of granulation tissue
that was superficially necrotic. tuber spina scapula was extremely
deformed and had developed into a mushroom-like shape due to the
formation of an excessive volume of osseous tissue (no osteitis or
osteomyelitis). The initial lesions were due to thrombosis (failures of
the blood supply) and secondary infection. Similar to pressure sores in
humans.

REVIEW PAPER: Host-Pathogen Interactions in the Kidney during Chronic

Leptospirosis. Vet Pathol 46:792–799 (2009). During chronic infection, renal
colonization and leptospiruria persist despite cellular and humoral responses by the
host. Tubulointerstitial nephritis is the most common lesion associated with chronic
infection, and this may progress to fibrosis and subsequent renal failure. For leptospires
to disseminate within the host, leptospiral invasion is likely mediated by enzyme
secretion, hemolysins, sphingomyelinases. Tubulointerstitial nephritis is a primary
lesion during acute renal injury in leptospirosis, with characteristic lesions, such as
interstitial edema and lymphocytic infiltrates. proteins called Len (leptospiral endostatin-
like) proteins, some of which were shown to bind complement regulatory proteins,
e.g., plasma factor H. Pathogenic Leptospira spp. can also bind the human
complement regulator C4BP, which can provide added resistance against host
complement.5 LPS from Leptospira is atypical in that it activates human cells
through TLR2 and not the conventional TLR4 pathway. Leptospiruria persists
despite active immune processes, such as interstitial nephritis characterized by
lymphocyte infiltration, anti-leptospiral immunoglobulin production, MHC II
expression, and TLR activation.

Expression of Major Histocompatibility Complex Class II Antigens in Porcine

Leptospiral Nephritis. Vet Pathol 46:800–809 (2009). cytokine-stimulated tubular
epithelial cells express MHCII. Leptospirosis in fattening pigs is characterized by
several degrees of nephritis, from absence of lesions to severe multifocal tubulo-
interstitial inflammation. Nephritic lesions were classified histologically into
perivascular lymphocytic (4 pigs), lymphofollicular (6 pigs), lymphohistiocytic (8 pigs),
and neutrophilic (2 pigs) pattern. MHCII expression by histiocytes and lymphocytes
was observed in all lesions. Prominent MHCII expression in regenerating tubular
epithelium was observed in lymphofollicular and lymphohistiocytic nephritis. MHCII
contributes to the intensity of the inflammatory response.

Brain lesions induced by Experimental Intranasal infection of Japanese Encephalitis

virus in piglets. Glial aggregates, lymphocyte cuffs, Olfactory bulb granular cell layer,
and neurons of and pyriform cortex. JEV is flavivirus- WNV, St Louis Encephalitis,
Murray Valley encephalitis in Australia.

Lymphocyte Apoptosis and Thrombocytopenia in Spleen during Classical Swine Fever: Role of
Macrophages and Cytokines: Results showed a progressive depletion of splenic lymphoid structures and
evidence of platelet aggregation processes. Lymphoid depletion was due to lymphocyte apoptosis, which
could not be ascribed to the direct action of the virus on these cells; direct virus action could play only a
secondary role in the death of these cells. Absence of severe tissue and endothelial damage, together with
moderate procoagulant cytokine levels in the serum, suggest that hemorrhage in CSF is due to
thrombocytopenia. Monocyte/macrophages were the main target cells for the CSF virus, TNF- and, to a
lesser extent, IL-1 and IL-6 appear to be the major cytokines involved in the pathogenesis of
lymphocytopenia and thrombocytopenia.

Melamine- and Cyanuric Acid–Associated Renal Failure in Pigs in Thailand. Vet

Pathol 46:1156–1159 (2009). kidneys of all 5 pigs were yellowish and slightly swollen,
with precipitation of crystalline material on the cut surface. Histologically, epithelial
degeneration and necrosis were evident in proximal and distal tubules and
collecting ducts. Round, yellow-brown crystals with radiating striations were
diffusely distributed through the lumen of proximal and distal tubules and collecting
ducts. Blood urea nitrogen and creatinine levels were elevated. Melamine and analogs,
including cyanuric acid, were detected by gas chromatography mass spectrometry.