AFIP Wednesday Slide Conference - No. 7
29 October 1997

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Conference Moderator: LTC Catherine Wilhelmsen
Diplomate, ACVP
Armed Forces Radiobiology Research Institute
8901 Wisconsin Avenue
Bethesda, MD 20889-5603

Case I - CT96-4055 (AFIP 2593329)

Signalment: 14-day-old, female, kitten (Felis catus).

History: Approximately two weeks after birth, two previously healthy female kittens housed in a biomedical research facility had acute onset of respiratory distress. On auscultation, the veterinarian detected moist rales and crackling throughout the lungs. Treatment with antibiotics proved ineffective. The kittens became depressed; the kitten used in this case died within 24 hrs of the onset of clinical signs. The other kitten died the following day.

This litter of two kittens was born to a primipara queen used in a study of fetal alcohol syndrome. The queen was purchased for the study 11 months previously from a Class A vendor. She had been born in the vendor's colony (which was advertised as ‘disease-free') and had been vaccinated against feline calicivirus, feline parvovirus (panleukopenia), feline herpesvirus type 1 (Feline Viral Rhinotracheitis), Chlamydia psittaci , and rabies. While on study, she was fed a fatty acid (docosahexaenoic acid) deficient diet, received alcohol-filled capsules, and was bred to one of the research facility's toms. After parturition, she and her kittens were housed in a separate room and had no contact with other cats. At no time during the study did the queen manifest any clinical abnormalities, and no other cats in the colony exhibited similar disease.

Gross Pathology: At necropsy, the kitten was found to be in good flesh, with an empty stomach, and yellow, pasty feces in the colon. The cranial lung lobes were congested and consolidated.

Laboratory Results: Bacterial culture of the lung was negative.

Contributor's Diagnosis and Comments: Lung: Pneumonia, broncho- interstitial, multifocal, acute, severe, necrotizing, with intranuclear viral inclusions.
Etiology: feline herpesvirus-1 (feline rhinotracheitis virus)

The kittens died of severe necrotizing pneumonia caused by feline herpes- virus (FHV-1) infection. Significant microscopic changes were confined to the lungs. Multifocally, bronchi and bronchioles were necrotic and filled with fibrin, neutrophils and cellular debris. There was multifocal patchy necrosis of alveoli, with flooding of lumina with fibrin and cellular debris. In less affected areas, alveolar septa were thickened by neutrophils, fibrin and edema, with numerous microthrombi within alveolar capillaries. Alveolar lumina contained small to moderate numbers of neutrophils and fibrin. The stroma surrounding arteries and arterioles was edematous and infiltrated by lymphocytes, macrophages and neutrophils. The pleura was multifocally thickened by macrophages, neutrophils and fibrin. Nuclei of remaining airway epithelial cells were occasionally cleared, with margination of the chromatin and smudgy to discrete eosinophilic inclusions. Indistinct, smudgy eosinophilic inclusions were also found in scattered alveolar septal cells, surrounded by a dark rim of marginated chromatin. Necrotizing bronchitis, bronchiolitis and pneumonia with intranuclear eosinophilic viral inclusion bodies are diagnostic of that agent. Transmission electron microscopy on formalin fixed tissue was used to confirm the diagnosis; typical 100-105 nm unenveloped icosahedral viral particles were readily demonstrated in bronchial epithelial cell nuclei. In some of the sections, typical type A Cowdry inclusions were difficult to identify, due to the extensive necrosis of the bronchial/bronchiolar epithelium.

The differential diagnosis for feline pneumonia should include other viral agents, bacteria, chlamydia, fungi, protozoan and metazoan parasites, and foreign body/aspiration pneumonia. Toxoplasma gondii can cause necrotizing pneumonia; microscopic diagnosis is based on finding typical clusters of basophilic round zoites within cells. Calicivirus infection is usually limited to the upper respiratory tract; however, some strains have a strong tropism for alveolar type I pneumocytes, and result in interstitial pneumonia. However, bronchial and bronchiolar epithelium is generally spared, and intranuclear inclusions are not present. Primary bacterial pneumonia is encountered uncommonly in the cat. Chlamydia psittaci, generally a cause of feline conjunctivitis, can cause a mild bronchointerstitial pneumonia which, in the absence of secondary bacterial infection, is self-limiting. It does not cause severe necrosis or intranuclear inclusions. In mycotic or parasitic pneumonia, the etiologic agent is readily identified in section. In pneumonia caused by either aspiration of stomach contents or inadvertent administration of material into the lungs via a misplaced stomach tube, the inflammatory infiltrate would contain a significant population of macrophages and foreign material may be visible grossly or microscopically. In the case of agents with a high lipid content (milk or mineral oil, for example), macrophages would contain prominent empty vacuoles, representing lipid removed during processing of the tissue. Lipid can be demonstrated with frozen sections stained with Sudan black or oil red O histochemical stains.
FHV-1 infection in cats generally results in rhinotracheitis, an upper respiratory tract disease with virus replication occurring primarily in the epithelium of the nasal passages, pharynx, soft palate, conjunctiva, tonsils, and trachea. After an incubation period of 2 to 6 days, the virus replicates in and lyses permissive cells, resulting in epithelial necrosis and formation of intranuclear inclusion bodies. Clinically, the disease is characterized by fever, salivation, sneezing, coughing, oral respiration, and serous to mucopurulent nasal and ocular discharges. Virus is shed in these secretions, and is the usual route of transmission via nose to nose contact or sneezed droplets. Most cats recover in 7 to 14 days, but mortality can occur in infants or immunosuppressed older animals. In kittens, ocular involvement (conjunctivitis neonatorum) can result in ulcerative keratitis, panopthalmitis, and blindness. Rarely the virus can cause severe fatal pulmonary disease, characterized by necrotizing bronchitis, bronchiolitis, and pneumonia, with serofibrinous flooding of alveoli and airways in young kittens and other susceptible animals. Experimental infections can cause systemic disease, fatal encephalitis, and abortions; these complications occur rarely in natural infections. Like other herpesviruses, FHV-1 can cause a latent infection, with the virus residing in the trigeminal ganglia, optic nerves, olfactory bulbs, and corneas. Stress and other factors, including corticosteroid injections, can trigger intermittent viral shedding by these carrier animals.

Although the queen in this case had a history of FHV-1 vaccination, she was likely a carrier. The vendor colony had experienced an outbreak of feline herpesvirus disease in 1994, which had not been fully eradicated. The queen was probably infected prior to vaccination, and subsequent vaccination would be ineffectual in eliminating the latent infection. The stress of pregnancy and lactation likely resulted in recrudescence and viral shedding. Shedding queens can infect their litters via grooming, nose to nose contact, sneezed nasal secretions, or through the milk. The severe pneumonia and absence of lesions in the upper respiratory tract suggest these kittens may have been infected via inhalation of aerosolized viral particles released by the queen by sneezing.

Screening for latent FHV-1 infection can help to prevent its inadvertent introduction into research colonies or catteries. Serology is the easiest, least expensive method, but it cannot discriminate between vaccination and prior infection. Virus culture of oral and ocular secretions can detect the small percentage of clinically healthy cats who are actively shedding virus at the time of the test. In one study, 15% of clinically healthy, latently infected cats were found to be spontaneously shedding virus. Pretreatment with corticosteroids significantly increased the sensitivity of this test by inducing viral shedding 8 to 10 days later. Polymerase chain reaction, using primers directed against the thymidine kinase gene of FHV-1, is more sensitive than virus culture, and a nested PCR technique was found to be significantly more sensitive than the single PCR.
Case 7-1. Lung. Necrosis of bronchiole and surrounding septae and a nuclear inclusion (above the center). 40X

AFIP Diagnosis: Lung: Pneumonia, bronchointerstitial, necrotizing, subacute, diffuse, moderate to severe, with intranuclear inclusion bodies, breed unspecified, feline, etiology consistent with feline herpesvirus 1.

Conference Note: In addition to cats, several domestic animal species are susceptible to respiratory infections caused by alphaherpesviruses. Canine herpesvirus 1 causes a highly fatal systemic disease in neonatal dogs, characterized by necrotizing vasculitis in multiple organs, especially lung, liver, and kidney. Equine herpesvirus 1, which is an important cause of abortion, encephalomyelitis, and neonatal foal mortality, causes an acute necrotizing interstitial pneumonia in neonatal foals. Equine herpesvirus 4 (rhinopneumonitis virus) causes predominantly respiratory disease that is independent of abortions and is seen mostly in weanling foals during autumn. This disease is characterized by slight fever, serous or catarrhal rhinitis, and conjunctivitis. Bovine herpesvirus 1 causes infectious bovine rhinotracheitis in cattle, characterized by inflammatory lesions in the upper respiratory tract, trachea, and conjunctiva. Certain strains of porcine herpesvirus 1 (pseudorabies, Aujeszky's disease) can cause rhinitis and pneumonia in swine, characterized by hemorrhagic consolidation of cranioventral regions of the lung, with necrosis in bronchioles and adjacent alveoli as the principal histologic feature.

Feline herpesvirus 2, also known as feline cell-associated herpesvirus (FeCAHV), has been implicated along with other viruses as a causative agent in the etiopathogenesis of some forms of feline lower urinary tract disease. Kruger et al7demonstrated through genetic and serologic studies that FeCAHV is a strain of bovine herpesvirus 4.

Contributor: Veterinary Resources Program, National Center for Research Resources, National Institutes of Health, Bethesda, MD 20892-5230.


1. Dungworth D L. The Respiratory System, In Pathology of Domestic Animals, 4th Edition, Vol 2., P. V. F. Jubb, P. C. Kennedy, and N. Palmer (ed.), Academic Press, Inc., p. 558-559, 1993.
2. Scott FW. Feline Viral Diseases, In Textbook of Veterinary Internal Medicine, Vol.1, S.E. Ettinger, and E.C Feldman (ed.) W.B. Saunders, p. 425-429. 1995.
3. Gaskell RM and Povey RC. Feline viral rhinotracheitis: sites of virus replication and persistence in acutely and persistently infected cats. Research in Veterinary Science 27:167-174, 1979.
4. Reubel, GH, Ramos, RA, Hickman, MA , et al. Detection of active and latent feline herpesvirus 1 infections using the polymerase chain reaction. Arch. Virol. 132: 409-420, 1993.
5. Hara M, Fukuyama M, Suzuki Y, et al. Detection of feline herpesvirus 1 DNA by the nested polymerase chain reaction. Veterinary Microbiology 48: 345-352, 1996.
6. Gaskell, R.M. Transmission of feline viral rhinotracheitis. Veterinary Record. 111, pp. 359-362, 1982.
7. Kruger JM, Osborne CA, Whetstone CA, Goyal SM, Semlak RA: Genetic and serologic analysis of feline cell-associated herpesvirus-induced infection of the urinary tract in conventionally reared cats. Am J Vet Res 1989 Dec;50(12):2023,2027.

International Veterinary Pathology Slide Bank:
Laser disc frame #15417.

Case II - 97-1251 (AFIP 2593990)

Signalment: 13-year-old, 2.65 kg, female, spayed, Domestic Shorthair cat.

History: The cat presented to the veterinarian with a 2-week history of icterus and a longer history of polyphagia and weight loss. Physical exam revealed a large abdominal mass and ascites. Radiographically, the mass appeared to be in the area of the kidneys and ultrasound revealed a cystic mass extending from the liver to the kidneys. The cat was taken to surgery, the mass was deemed unresectable, and the cat was euthanatized.

Gross Pathology: At necropsy, the mucous membranes, subcutaneous fat deposits, abdominal fat and pericardial fat were markedly icteric. The liver was diffusely red-orange and weighed 120 grams (4.5% of body weight). There was a diffuse, slightly enhanced reticular pattern. The pancreas was largely replaced by a 10.5 cm-long, 1.0-2.5 cm-diameter, firm, tan mass composed of multiple tubular cystic loci (consistent with antemortem ultrasound). This lesion was removed at surgery and submitted separately.

Laboratory Results:

Alk Phos 274 (N=15-55) IU/L
ALT 710 (N=20-75) IU/L
AST 237 (N=0-100) IU/L
T. BiL 9.8 (N=0-0.1) mg/dL
Glob 6.0 (N=2.1-5.1) g/dL
T. prot 8.8 (N=6-8) g/dL

Cytology: Aspiration of the mass was inconclusive, showing nondegenerate PMN's, occasional small lymphocytes, few monocytes and eosinophils as well as sheets of uniform epithelium characterized by oval nuclei, 1-2 nucleoli and moderate amounts of basophilic cytoplasm with numerous small vacuoles.

Contributor's Diagnosis and Comments: Liver: Severe chronic diffuse bridging lymphocytic pericholangitis and hepatitis. Pancreas (sections not submitted): Severe chronic diffuse sclerosing lymphoplasmacytic pancreatitis with marked multifocal ductular ectasia.

The findings in this case are consistent with feline progressive cholangitis. According to Lucke and Davies (1984), cats usually present with ascites, jaundice, polyphagia and weight loss; some cats are anorexic. In the same study, cats had unremarkable serum biochemistries with the exception of mildly to moderately increased alkaline phosphatase activities in 12 of 21 cats, and mild to marked increases in conjugated bilirubin in 6 cases.

Gross findings of feline progressive cholangitis consist of a normal to enlarged liver, an enhanced reticular pattern and variably present hepatic nodular change. Histologically, there is prominent lymphocytic infiltration and fewer numbers of other leukocytes. Other changes can include bile duct destruction and/or proliferation, and fibrosis with vascular changes similar to those seen in cirrhosis.

Due to the normal anatomic fusion of the feline pancreatic and biliary ducts proximal to the duodenum, feline hepatobiliary disease may be seen in conjunction with chronic pancreatitis and obstruction. The cat in this case had a severe sclerosing pancreatitis of unknown etiology.

This particular lesion was thought to be somewhat unusual due to the relatively monomorphic population of lymphocytes present. Published reports indicate that in most cases there is usually a small plasmacytic or suppurative component to the lesion. For this reason a differential diagnosis of lymphosarcoma was considered. However, lymphoid pseudofollicles in the infiltrate (visible in some fields/sections), the presence of small numbers of plasma cells, the absence of cytological atypia within the infiltrating lymphocytes, and the presence of chronic pancreatitis led to the final diagnosis of lymphocytic pericholangitis and hepatitis.
Case 7-2. Liver. Severe lymphocytic periportal inflammation. 10X
AFIP Diagnosis: Liver: Cholangiohepatitis, lymphofollicular, bridging, diffuse, moderate, with multifocal random necrotizing hepatitis, Domestic Shorthair cat, feline.

Conference Note: Feline cholangitis/cholangiohepatitis has been described as a disease complex including three characteristic histologic lesions, each presumably reflecting progressive stages of one disease.4 In this report, suppurative cholangitis/cholangiohepatitis, characterized by periportal and hepatic parenchymal infiltration of neutrophils with bile duct hyperplasia, mild fibrosis, and filling of bile ducts with inflammatory cellular debris, was considered the earliest of the three lesions. Long-term inflammation associated with progression of this condition reportedly led to nonsuppurative cholangitis/cholangiohepatitis, with the characteristic histologic findings of lymphocytic and plasmacytic periportal inflammation, bile duct hyperplasia, and periportal fibrosis. Biliary cirrhosis, with severe portal fibrosis, bile duct hyperplasia, nodular hepatic hyperplasia, and a variable degree of chronic inflammation, was presumed to be the end-stage result of long-term cholangiohepatitis in some cats.

In a recent retrospective study, Gagne et al5 described three subclassifications of feline inflammatory liver disease based on the predominant cell type within portal areas, i.e. lymphocytic-plasmacytic, neutrophilic, and mixed. Lymphocytic portal hepatitis was characterized by portal infiltration of lymphocytes and plasma cells, without neutrophils or macrophages. Inflammation was restricted to the portal area and did not extend into hepatic parenchyma. Lymphoid follicles were occasionally found. Bile duct proliferation and portal or portal-bridging fibrosis were present in most cases, but neither biliary epithelial degeneration nor inflammatory cells in bile ducts was seen. Cats with neutrophilic portal hepatitis had primarily neutrophils, with varying numbers of lymphocytes and plasma cells, present within portal areas. Periportal hepatocellular necrosis was a common finding, as was bile duct epithelial degeneration, necrosis, inflammatory cell infiltrate, and duct proliferation. Portal and portal bridging fibrosis was common. Cats with mixed portal hepatitis had approximately equal numbers of lymphocytes/plasma cells and neutrophils. In this third group of cats, associated histologic changes were similar to those with predominantly neutrophilic portal infiltrates. The authors propose using the term lymphocytic portal hepatitis for those cases characterized by lymphocytic/plasmacytic inflammation confined to the portal areas, and that hepatitis characterized by cholangitis and portal neutrophilic infiltrates with or without lymphocytes and plasma cells be termed cholangiohepatitis.

Contributor: University of Tennessee Veterinary Teaching Hospital, 2407 River Drive, Room A201, Knoxville, TN 37996-4500.


1. Kelly WR: The liver and biliary system. In: Pathology of Domestic Animals, 4th edition, Academic Press, Inc., New York; Jubb KVF, Kennedy PC, Nigel P, eds., Volume 2, pp. 360-361, 1993.
2. Lucke VM, Davies JD: Progressive lymphocytic cholangitis in the cat. Journal of Small Animal Practice 25:249-260, 1984.
3. Prasse KW, Mahaffy EA, DeNovo R, Cornelius L: Chronic lymphocytic cholangitis in three cats. Vet Pathol 19:99-108, 1982.
4. Day DG: Feline cholangiohepatitis complex. In: Veterinary Clinics of North America: Small Animal Practice 25(2):375-385, 1995.
5. Gagne JM, Weiss DJ, Armstrong PJ: Histopathologic evaluation of feline inflammatory liver disease. Vet Pathol 33:521-526, 1996.

International Veterinary Pathology Slide Bank:
Laser disc frame #5433-7, 13096, 16360, 16361


Case III - 97-255 (AFIP 2593987)

Signalment: 16-year-old, female, spayed, Dachshund, canine.

History: This animal was presented for bilateral serous nasal discharge and open-mouthed breathing. Thoracic radiographs revealed left heart enlargement with severe bilateral pulmonary edema and generalized hepatomegaly. She was treated with furosemide, nitroglycerin, and supplemental oxygen. She subsequently went into respiratory arrest and died.

Gross Pathology: A cosmetic necropsy was performed. The heart was enlarged, globoid, and had two apices. Both ventricles were markedly dilated and there was moderate nodular thickening of the mitral valve leaflets. All lung lobes were red, with irregular, 1-3 mm diameter, pale, patchy areas, and oozed serosanguineous fluid from cut surfaces. Intestinal vessels were prominent and congested. The liver was enlarged and weighed 500 grams (8.3% of body weight). The gall bladder contained an 8 mm3 spiny black concretion. There was a
15 x 6 x 6 mm, pale, firm, well-circumscribed mass in the pylorus.

Laboratory Results:

ALP - 718 IU/L (N=12-72)
serum cholesterol - 432 mg/dL (N=125-210)
serum T4 - normal

Contributor's Diagnoses and Comments:

1) Moderate to marked, multifocal pulmonary vascular and interstitial amyloidosis.
2) Mild to moderate, multifocal, acute, suppurative pneumonia.
3) Mild to moderate, multifocal, interstitial fibrosis.
Pulmonary vascular amyloid deposition, although seldom reported, is estimated to occur in over 22% of the aging canine population (>10 years of age). There are no known sex, breed, or concurrent disease predispositions. Amyloid deposits are most frequently confined to the intima and media of pulmonary arteries, and are not demonstrated in other tissues.
Case 7-3. Lung. The wall of a pulmonary artery and the interstitium are thickened by amyloid deposits with a focal influx of neutrophils and macrophages. 20X
AFIP Diagnoses:
1. Lung: Amyloidosis, vascular and interstitial, multifocal, moderate, with interstitial fibrosis and type II pneumocyte hyperplasia, Dachshund, canine.
2. Lung: Pneumonia, neutrophilic, acute, diffuse, mild, with intra-alveolar hemorrhage.

Conference Note: Conference participants discussed the interesting histologic findings which, along with the history, suggest the superimposition of an acute infectious process upon the chronic secondary pulmonary effects of cardiac insufficiency in this dog. The predominantly neutrophilic inflammation suggests bacterial infection. Interstitial fibrosis is likely a result of long-term pulmonary congestion. It is unclear as to what type of amyloid is involved in the vascular amyloid deposits of the dog. Some believe it may be reactive amyloidosis; however, recent articles state that the amyloid deposits are a senile form of amyloidosis. The precise pathogenesis is unclear. Recent articles describe this amyloid as apolipoprotein A1-derived vascular amyloidosis. Mild pulmonary vascular amyloidosis is frequently observed in aged dogs. Participants agreed that the severity of the lesion in this case is unusual.

Chronic left-sided heart failure causes congestion of alveolar capillaries. There is transudation of fluid, initially limited to perivascular interstitial spaces, causing thickening of the alveolar septa. In time, the transudate overflows into the alveoli. With persistently elevated pulmonary venous pressure, the alveolar capillaries may become tortuous, and may rupture to produce small hemorrhages into the alveolar spaces. Alveolar macrophages phagocytose erythrocytes and eventually become filled with hemosiderin, leading to the classic appearance of "heart failure cells". Long-term persistence of septal edema often induces fibrosis within the alveolar walls, which, together with the accumulation of hemosiderin, is characteristic of chronic venous congestion of the lung.

Contributor: University of Tennessee, Department of Pathology, P.O. Box 1071, Knoxville, TN 37901-1071.
1. Roertgen KE, et al: Apolipoprotein A1-derived pulmonary vascular amyloid in aged dogs. Am J Pathol 147(5):1311-1317, 1995.
2. Johnson KH, et al: Pulmonary vascular amyloidosis in aged dogs. Am J Pathol 141(5):1013-1019, 1992.
3. Maxie MG, Prescott JF: The urinary system. In: Pathology of Domestic Animals, 4th ed., Jubb KVF, Kennedy PC, Palmer N, editors, Academic Press, Inc.
New York; volume 2, pp. 484-486, 1993.
4. Kumar V, Cotran RS, Robbins SL: Basic Pathology, 6th ed., W.B. Saunders Company, p. 310, 1997.

International Veterinary Pathology Slide Bank:
Laser disc frame #6996


Case IV - W1082/97 (AFIP 2597452)
Signalment: Adult Merino cross, ovine, sex unknown.

History: Abattoir specimen taken for routine screening of flocks for Johne's disease.

Gross Pathology: The distal ileum and proximal colon were thickened and edematous and the ileocecal lymph node was enlarged.

Laboratory Results: None.

Contributor's Diagnosis and Comments: Enteritis, granulomatous, diffuse, chronic, severe, with diffuse granulomatous lymphadenitis and multifocal lymphogranulomatous phlebitis, lymphangitis and arteritis, mixed breed, adult ovine, caused by acid-fast bacilli, Mycobacterium avium var paratuberculosis, Johne's Disease.

In this case, there is extensive atrophy of normal mucosal components, which are replaced by an extensive infiltrate of macrophages into the lamina propria and submucosa, and also with variable numbers of lymphocytes, plasma cells, neutrophils and eosinophils, and generally low numbers of Langhans giant cells and epithelioid macrophages. Peyer's patches are hyperplastic, and mesenteric attachments are edematous. There are nodular areas of vasculitis and lymphangitis (not present in all sections). Although the surface epithelium is absent in most areas, this is interpreted as an artifact associated with autolysis and not an ulcerative process. The macrophages throughout the intestinal lesions are distended with mycobacteria, confirmed by Ziehl Nielsen stains, but apparent as fine basophilic cytoplasmic stippling in H&E-stained sections. The lesions are typical for the so-called lepromatous or multibacillary form of ovine Johne's disease (JD). A second form of the disease in small ruminants, the paucibacillary form, has few organisms, few infected macrophages and the inflammatory lesions are predominantly lymphocytic rather than granulomatous. In this second form, the diagnosis may be difficult to confirm, either by histopathology or by culture.

JD was initially recognized as an important disease of cattle, and more recently of small ruminants, including sheep, goats, alpacas and deer. In sheep, early lesions are rarely associated with diarrhea and intestinal lesions may be multifocal and irregular rather than the diffuse terminal ileitis seen in cattle. In advanced cases in small ruminants, weight loss and decreased milk and meat production are more common than diarrhea.

There are strain difference in M. paratuberculosis between the bovine and small ruminant isolates, and ovine isolates are more difficult to culture, making confirmation, particularly of paucibacillary cases, diagnostically challenging. Because of the similarity of histologic lesions between JD of ruminants and Crohn's disease of humans, a possible causal relationship has long been suspected but is as yet unproven. The disease can be transmitted experimentally to rabbits, but whether this species serves as a natural reservoir to maintain and disseminate the disease amongst ruminant species is not yet clear. In many countries, JD is endemic amongst sheep flocks and eradication is considered impractical. In Australia, the incidence of JD in sheep flocks is low, and recently eradication programs have been introduced. This animal was identified at slaughter as a probable JD case and came from a flock known to be infected. Obviously, the role rabbits potentially play in acting as reservoir hosts for JD is of significance to recently instituted eradication programs in Australia.

The pathogenesis of JD in sheep is not well understood. Lesions are thought to arise primarily in the ileocecal Peyer's patches and, depending on immune response, develop into lepromatous or paucibacillary forms of the disease. In the multibacillary form of the disease, a range of cytokines are generated but appear ineffective at controlling proliferation of the organism, whereas there is a limited response in the paucibacillary forms, and TNF- is the dominant cytokine present. With either form, JD is thought to acquired as young lambs, and older stock are more resistant to infection. It has been speculated that the larger Peyer's patches in young stock facilitate this susceptibility to infection, and with the atrophy of Peyer's patches with maturity, resistance to infection with M. paratuberculosis develops.

Case 7-4. Intestine. The lamina propria is expanded by a sheet of epitheloid macrophages. 20X
Case 7-4. Intestine. A myriad of acid-fast bacilli is present within the macrophages. Acid-fast, 40X

AFIP Diagnoses: 1. Small intestine: Enteritis, granulomatous, diffuse, severe, with granulomatous lymphangitis, villous fusion, and numerous intrahistiocytic bacilli, Merino cross, ovine, etiology consistent with Mycobacterium avium subspecies paratuberculosis. 2. Mesenteric adipose tissue: Atrophy, diffuse, severe.

Conference Note: Some sections viewed in conference contain small numbers of coccidia with morphology consistent with Eimeria spp.

The intestinal macrophage is the target cell for infection by M. a. paratuberculosis. After the organisms are ingested, they undergo endocytosis by intestinal M cells. Intact and degraded mycobacteria are transported in vacuoles across the M cells to macrophages in subepithelial areas. Specific macrophage receptors for this organism have not been identified, although other mycobacteria use complement receptor types 1 and 3 on macrophages. After uptake by macrophages, the bacteria often resist the degradative and killing mechanisms of the macrophage via sulphatide production, which prevents phagosome-lysosome fusion, escape from the phagosome into the cytoplasm, glycolipid-mediated inhibition of nitric oxide production, and inhibition of the respiratory burst and oxidative killing mechanisms by superoxide dismutase and glycolipid production.

In paratuberculosis, as in other mycobacterioses, cell-mediated immunity is considered to be the principle mechanism for clearing infection. Antibody is regarded to be of little use against intracellular mycobacteria, and high serum antibody concentrations are often seen in the presence of advanced clinical disease.3

Contributor: School of Veterinary Science, The University of Melbourne, 250 Princes Highway, Werribee Vic 3030, Australia


1. Aduriz JJ, Juste RA, Cortabarria N: Lack of mycobactin dependence of mycobacteria isolated on Middlebrook 7H11 from clinical cases of ovine paratuberculosis. Vet Microbiol 45(2-3):211-217, 1995.
2. Alzuherri HM, Woodall CJ, Clarke CJ: Increased intestinal TNF-alpha, IL-1beta and IL-6 expression in ovine paratuberculosis. Vet Immunol-Immunopathol 49(4):331-345, 1996.
3. Clarke CJ: The pathology and pathogenesis of paratuberculosis in ruminants and other species. J Comp Path 116:217-261, 1997.
4. Clarke CJ, Little D: The pathology of ovine paratuberculosis: gross and histological changes in the intestine and other tissues. J Comp Path 114:419-437, 1996.
5. Dukes TW, Blover GJ, Brooks BW, Duncan JR, Swendrowski M: Paratuberculosis in Saiga antelope (Saiga tatarica) and experimental transmission to domestic sheep. Journ of Wildlife Diseases 28(2):161-170, 1992.
6. Barker IK, Van Dreumel AA, Palmer N: The alimentary system. In: Pathology of Domestic Animals, 4th ed., Jubb KVF, Kennedy PC, Palmer N, editors, Academic Press, Inc. New York; volume 2, pp. 247-252, 1993.
7. Navarro JA, Sanchez J, Bernabe A, Gomez MA, Gomez S, Seva J: Detection of Mycobacterium paratuberculosis antigen with colloidal immunogold in naturally infected sheep. J Vet Med B 39:421-427, 1992.
8. Perez V, Garcia-Marin JF, Badiola JJ: Description and classification of different types of lesions associated with natural paratuberculosis infection in sheep. J Comp Path 114:107-122, 1996.
9. Stehman SM: Paratuberculosis in small ruminants, deer, and South American camelids. Vet Clin North Am Food Anim Pract 12(2):441-55, 1996.

International Veterinary Pathology Slide Bank:
Laser disc frame #5012-3, 7112, 18606, 18689.

Terrell W. Blanchard
Major, VC, USA
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615

* The American Veterinary Medical Association and the American College of Veterinary Pathologists are co-sponsors of the Registry of Veterinary Pathology. The C.L. Davis Foundation also provides substantial support for the Registry.

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