AFIP Wednesday Slide Conference - No. 12
December 1, 1999

Conference Moderator:
Dr. F.M. Garner, Diplomate, ACVP
4416 Oak Hill Road
Rockville, MD 20853

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Case I - Y10628-8 (AFIP 2688902 )
Signalment: 8-week-old, Labrador retriever, male, canine, Canis familiaris.
History: The puppy was presented for whining, listlessness, anorexia, and circling of 1-2 day's duration. The puppy's temperature was 100 degree F. An abdominal radiograph appeared normal. Blood and serum were collected and submitted for a CBC and serum chemistries, respectively. At 6 weeks-of-age, the puppy had received vaccinations for canine distemper and canine parvovirus. Treatment was initiated at 8 am the morning of presentation and consisted of IV fluids (LRS) and IM antibiotics (PenG). Fluids and antibiotics were repeated throughout the day. The puppy's condition had worsened by 8 pm, and he died later that night. The puppy was necropsied the next day.
Gross Pathology: The brain exhibited moderate, diffuse malacia, and numerous petechiae were scattered throughout the midbrain and brain stem. Lymph nodes throughout the body were moderately enlarged and very hemorrhagic. Numerous ecchymoses were scattered over the epicardium and endocardium. The liver was slightly swollen and congested, and the gallbladder was edematous. The spleen was slightly enlarged and contained prominent lymphoid foci. A few petechia were scattered over the serosal surfaces of the stomach and urinary bladder. A small to moderate amount of mucoid to hemorrhagic fluid was in the stomach and small intestine.
Laboratory Results: The CBC and serum chemistries revealed anemia (HCT=22.3%), thrombocytopenia (PLT=23,000/uL), mild neutrophilia (78%), lymphopenia (10%), elevated liver enzymes [ALKP=287 (normal range=5-56U/L)], hypoproteinemia (TP=4; normal range=6-8.4 g/dL), and hypoalbuminemia (ALB=2; normal range=3.5-5.3 g/dL).

Contributor's Diagnosis and Comments: Moderate to severe, acute, periacinar to midzonal and bridging, necrotizing hepatitis with hepatocellular intranuclear adenovirus inclusions.
Etiology: canine adenovirus-1
Disease: Infectious Canine Hepatitis
Microscopically, the liver is characterized by moderate to severe, acute periacinar to midzonal and bridging, coagulative and lytic, hepatocellular necrosis associated with numerous hepatocellular intranuclear magenta inclusions consistent with canine adenovirus-1 infection (infectious canine hepatitis). The lesions of infectious canine hepatitis (ICH) result from the tropism of canine adenovirus-1 for endothelium, mesothelium, and hepatic parenchyma. The reason for the increased susceptibility of periacinar hepatocytes to necrosis is unknown. Widespread hemorrhages occur due to leakage from damaged vascular endothelium, inability of damaged liver to replace clotting factors, and exhaustion of clotting factors resulting from accelerated consumption initiated by endothelial damage (DIC). Vaccination has greatly reduced the frequency of clinical disease and death due the ICH.
AFIP Diagnosis: Liver: Hepatitis, necrotizing, acute, multifocal to coalescing, severe, with hepatocellular eosinophilic intranuclear inclusion bodies, Labrador retriever, canine.
Conference Note: Canine adenovirus-1 (CAV1)(Genus Mastadenovirus, Family Adenoviridae) also known as infectious canine hepatitis (ICH) virus. Adenoviruses are icosohedral, 80-100 nm, double stranded DNA virus. Most adenoviruses cause enteric or respiratory diseases that are acute, mild and rarely produce clinical disease except in the immunocompromised host. CAV1 is uncommon among adenoviruses in that it can produce severe generalized disease, including hepatitis, respiratory disease, ocular disease (blue eye), encephalopathy and interstitial nephritis. CAV1 is also an important pathogen of foxes, wolves, coyotes, skunks, raccoons, and bears. This virus was recognized as the cause of fox encephalitis and was proven to cause ICH-like symptoms experimentally many years before it was realized that the same virus caused both conditions.
Clinically, ICH is often associated with corneal opacity. Before enzyme immunoassay, hemagglutination-inhibition, neutralization or polymerase chain reaction tests were available to diagnose ICH, this was considered an important clinical sign to differentiate ICH from other acute viral diseases. Although ICH produces relatively distinctive histologic lesions, clinically it may be difficult to differentiate from canine distemper, toxoplasmosis, coccidiomycosis, and ehrlichiosis.
Contributor: Diagnostic Laboratory Services, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762.
1. Greene CE: Infectious Diseases of the Dog and Cat, 2nd ed., pp 22-27. WB Saunders, Philadelphia, PA, 1998
2. Kelly WR. The liver and biliary system. In: Pathology of Domestic Animals, eds. K.V.F. Jubb, P.C. Kennedy, and N. Palmer, 4th ed., Vol 2, pp. 319-406, Academic Press, Inc., San Diego, California, 1993
Case II - 98-9138 (AFIP 2694721)
Signalment: Six-year-old castrated male Labrador retriever (Canis familiaris)
History: The dog was diagnosed with pemphigus foliaceus via biopsy and treated for one month with Triamcinolone and 10 days with Imuran. The dog developed diarrhea two weeks after Triamcinolone therapy began and became anorexic and lethargic 3 days after Imuran treatment began. The dog presented with weakness, icterus, generalized lymphadenopathy, and bilateral harsh respiratory sounds. Clinical signs progressed despite supportive care, and the animal died while in the hospital.
Gross Pathology: There was cutaneous ulceration over the bridge of the nose and ulceration of the hard palate. There were multifocal raised, granular yellow 0.1 cm coalescent perivascular foci on the pericardial surface of the heart. The myocardium of the left ventricular free wall had poorly delineated yellow/red foci. The lung contained randomly scattered 0.2-0.3 cm red rimmed target lesions in all lobes. The parietal pleura was granular and reddened. There was focal softening and yellow/red discoloration of the left renal crest and yellow radial streaks in the medulla and cortex of both kidneys. The liver was enlarged and friable with multifocal 0.1-0.3 cm soft red foci.
Laboratory Results:
CBC abnormalities included: macrocytic (1+), hypochromic (1+) anemia (HCT 26.6%, normal 37.0-56.0%) with polychromasia (1+) anisocytosis (1+) and poikilocytosis (1+). Mild neutrophilic leukocytosis (10.4x103/mm3, normal 3.0-9.5) with a left shift (bands- 3.5x103/mm3, normal 0) was also present.
Serum chemistry abnormalities included markedly elevated alkaline phosphatase (>3750 u/l, normal 11-174), alanine aminotransferase (2326 u/l, normal 19-136), aspartate aminotransferase (636 u/l, normal 21-41) and total bilirubin (10.3 mg/dl, normal 0.1-0.6). There was also hypoproteinemia (5.2 g/dl, normal 5.7-7.3) and hypoalbuminemia (2.8 g/dl, normal 3.1-4.3).
Urinalysis abnormalities included low specific gravity (1.010, normal 1.015-1.045), high pH (8.0, normal 6.0-7.0), proteinuria (2+), bilirubinuria (3+), hematuria (3+), and many yeast forms within the sediment. Urine culture yielded a pure culture of Candida albicans (>100,00 colonies/ml).

Contributor's Diagnosis and Comments: Heart: Severe acute multifocal necrosuppurative myocarditis and fibrinosuppurative epicarditis with intralesional fungal spores and pseudohyphae consistent with Candida spp. Etiology: Candida albicans.
Candida albicans is a commensal organism commonly found as part of the normal flora of the gastrointestinal tract. Candida albicans can cause superficial infections of the skin and mucous membranes and, less commonly, systemic infections in hosts whose resistance has been lowered due to prolonged antibiotic therapy, chronic illness, or immune suppression. Systemic candidiasis is very rare and has been reported in humans, nonhuman primates, mice, cetaceans, birds, pigs, foals, calves, cats and dogs.
AFIP Diagnosis: Heart: Myocarditis and epicarditis, necrotizing, acute, multifocal, moderate, with numerous yeast, hyphae and pseudohyphae, Labrador retriever, canine, etiology consistent with Candida sp.
Conference Note: The presence of budding, 3-5 mm diameter yeast cells (blastospores), pseudohyphae and hyphae in tissue is diagnostic of candidiasis, but the particular species cannot be identified by histologic examination. Although conference participants readily identified the etiologic agent in the H&E stained sections, the organisms were also strongly positive by the GMS method for fungi.
Candida infections must be differentiated from Aspergillus sp., Histoplasma capsulatum, and Torulopsis glabrata. Aspergillus in tissues is identified by its septate, uniform width (3-4 mm) hyphae with acute angle dichotomous branching and occasionally conidia or fruiting bodies. Histoplasma capsulatum does not form pseudohyphae and hyphae are rarely encountered in tissue. Torulopsis glabrata is very similar to Candida but does not produce hyphae.
Most cases of systemic fungal infection are the result of a compromised immune system, as in this case in which the dog was treated with immunosuppressive drugs.
Contributor: Department of Pathology, Angell Memorial Hospital, 350 S. Huntington Avenue, Boston, MA 02130.

1. Bartram PA, Smith BP, Holmberg C, Mandell CP: Combined immunodeficiency in a calf. JAVMA 195(3):347-350, 1989
2. Chandler FW, Watts JC: Candidiasis. In: Pathologic Diagnosis of Fungal Infections, eds. Chandler, Watts, pp. 97-99. American Society of Clinical Pathologists, Chicago, IL, 1987
3. Clercx C, McEntee K, Snaps F, Jacquinet E, Coignoul F: Bronchopulmonary and disseminated granulomatous disease associated with Aspergillus fumigatus and Candida species Infection in a golden retriever. JAAHA 32:139-145, 1996
4. Dunn JL, Buck JD, Spotte S: Candidiasis in captive pinnipeds. JAVMA 185(11):1328-1330, 1984
5. Foley GL, Schlafer DH: Candida abortion in cattle. Vet Pathol 24:532-536, 1987
6. Fulton RB, Walker RD: Candida albicans urocystitis in a cat. JAVMA 200(4):524-526, 1992
7. Gerding PA, Morton LD, Dye JA: Ocular and disseminated candidiasis in an immunosuppressed cat. JAVMA 204(10):1635-1638, 1994
8. Jones TC, Hunt RD, King NW: Veterinary Pathology, 6th ed., pp. 238. Williams and Wilkins, Baltimore, MD, 1997
9. Jubb KVF, Kennedy PC, Palmer N: Pathology of Domestic Animals, Vol. 2, 4th edition, pp. 256-257. Academic Press Inc., San Diego, CA, 1993
10. Merlin TL, Gibson DW, Connor DH: Infectious and Parasitic Diseases. In: Pathology, eds. Rubin E, Farber JL, pp. 408-409. JB Lippincott Co, Philadelphia, PA, 1994
11. Reilly L, Palmer J: Systemic candidiasis in four foals. JAVMA 205(3): 464-466, 1994
Case III - P8-306 (AFIP 2683851)
Signalment: 22-month-old female New Zealand white rabbit (Oryctolagus cuniculus)
History: The rabbit was transgenic for the EJras oncogene, which had been targeted to epidermal keratinocytes by the upstream regulatory region of the cottontail rabbit papilloma virus. The transgene causes development of keratoacanthomas and squamous cell carcinomas in rabbits, and the model is used to study the multistep progression of cancer. The doe had been used successfully as a breeder during the past year and had produced multiple litters. However, most of the young in the last two litters died before weaning.
Gross Pathology: Hair had been pulled from around the neck. The fur on the dewlap was green/blue. The underlying skin was slightly red. The mammary tissue was engorged with milk.
Laboratory Results: Pseudomonas aeruginosa was isolated from the cutaneous lesions.

Contributor's Diagnoses and Comments: Moderate acute purulent dermatitis and hemorrhage - Pseudomonas aeruginosa
Pseudomonas aeruginosa has been associated with blue/green discoloration of rabbit fur, exudative moist dermatitis, abscesses, septicemia, pneumonia, and diarrhea. The organism is commonly found in soil and is known to contaminate water and aqueous solutions including alkaline disinfectants. It is of comparatively low virulence and has been found frequently in suppurative processes in domestic animals. It also causes severe epidemics of respiratory disease in mink and chinchillas, and green wool condition in sheep. It produces a pyocyanin pigment, which is bluish green and oxidizes to brown. The organism produces lecithinase and protease, which appear to be responsible for edema and induration of the skin and for the hemorrhagic and necrotizing skin lesions. Rabbits are less susceptible to experimental infection than guinea pigs.
AFIP Diagnosis: Haired skin: Dermatitis, subacute, diffuse, severe, with intracorneal pustules, folliculitis, acanthosis, and numerous intracorneal bacteria.
Conference Note: Gram stains performed at the AFIP demonstrated large numbers of Gram negative bacilli within the superficial epidermis.
Other causes of bacterial dermatitis in rabbits include Pasteurella multocida, Stapylococcus aureus, Fusobacterium necrophorum, Arcanobacterium (Corynebacterium) pyogenes, Streptococcus sp., and Treponema cuniculi.

Contributor: Department of Comparative Medicine, H054, M.S. Hershey Medical Center, Penn State University, 500 University Drive, Box 850, Hershey, PA 17033
1. DeLong D, Manning PJ: Bacterial diseases. In: The Biology of the Laboratory Rabbit, eds., Manning PJ, Ringler DH, Newcomer CE, p. 162. Academic Press, San Diego, CA, 1994
2. Peng X, Griffith JW, Han R, Lang CM, Kreider JW: Development of keratoacanthoma and squamous cell carcinoma in transgenic rabbits with targeted expression of EJras oncogene in epidermis. Am J Pathol 155:1-10, 1999
3. Samuelson J: Infectious Diseases. In: Robbin's Pathologic Basis of Disease, eds., Cotran RS, Kumar V, Collins T, 6th ed., pp. 376-377. WB Saunders Company, Philadelphia, PA, 1999
4. Schoenbaum M: Pseudomonas aeruginosa in rabbit fur. Lab Ani 15:5, 1981
Case IV - 1794/98 (AFIP 2681371)
Signalment: Guinea pig (Cavia aperea porcellus), adult male.
History: This animal originated from a colony of guinea pigs held at the department of food hygiene of the Leipzig University. No clinical signs were observed. The animal died unexpectedly after having been experimentally infected with Trichinella spiralis six weeks earlier.
Gross Pathology: Necropsy findings revealed loss of weight. The cecum contained a red-brown liquid.
Laboratory Results: Histologically, the animal showed a mild to moderate granulomatous myositis with only very few eosinophilic granulocytes, affecting many diverse skeletal muscles and the diaphragm. Within these lesions encysted larvae of Trichinella spiralis were detectable. Additionally a severe necrotizing typhlitis, a moderate mononuclear interstitial myocarditis and a moderate necrotizing hepatitis were diagnosed (slides not submitted).

Contributor's Diagnosis and Comments: Skeletal muscle (masticatory muscle): focal granulomatous myositis, minimal infiltration with eosinophilic granulocytes, encysted nematode larvae; guinea pig (Cavia aperea porcellus). Cavioidea, Rodentia, Mammalia; Cause: Infection with Trichinella spiralis.
Trichinellosis is a zoonotic disease. Trichinella spiralis belongs to a genus of nematode parasites in the family Trichinellidae. Humans become infected after consumption of uncooked or incompletely cooked meat of infected pigs, bears, and aquatic mammals. These animals are the natural sources of infection for human beings. The parasitic life cycle begins with the ingestion of infected meat. The activity of digestive juice leads to release of the encysted larvae, which undergo four molts and mature into adults. The male parasites die after copulation, while the females penetrate the crypts of Lieberkuhn, enter the submucosal lymphatics and deposit large numbers of larvae within the lymphatic spaces. These larvae migrate into the blood vessels and reach the striated muscles via the blood stream. They invade muscle bundles, where they become encysted and stay throughout the life of the host. The infected muscle cell becomes a "nurse cell". In this case, the larvae occurred in many striated muscles, including the humeral and femoral musculature, the diaphragm, and the masticatory muscles, while the cardiac muscle was not affected. The cause of the sudden death of this guinea pig is interpreted as a sequela of the severe necrotizing typhlitis, the moderate mononuclear interstitial myocarditis, and the moderate necrotizing hepatitis; no parasites were detectable within these organs.
AFIP Diagnosis: Skeletal muscle: Myositis, lymphoplasmacytic and eosinophilic, multifocal, mild, with encysted nematode larvae, guinea pig (Cavia aperea porcellus), rodent, etiology consistent with Trichinella spiralis.
Conference Note: Identification of parasites in tissue sections requires detailed knowledge of the microanatomy of the various parasite groups. Nematodes have a cuticle, musculature, pseudocoelom and gastrointestinal tract. Trichinella sp. belongs to a group of nematodes classified as aphasmids. Key anatomic features of aphasmids are the presence of bacillary bands and stichosomes.
In the United States, trichinosis was maintained in swine through the practice of garbage feeding. The institution of garbage cooking in the mid-1950's, as part of the vesicular exanthema eradication program, greatly reduced the incidence of the disease in the United States.
Special thanks to Dr. Chris Gardiner (Captain, USN) for his consultation on this case.
Contributor: Institut für Veterinär-Pathologie, Universität Leipzig, An den Tierliniken 33, 04103 Leipzig, Germany
1. Hulland TJ: Muscle and tendon. In: Pathology of Domestic Animals, Vol. 1, eds. Jubb KVF, Kennedy PC, Palmer N, 4th ed., pp. 253-255. Academic Press, San Diego, CA, 1993
2. Jones TC, Hunt RD, King NW: Veterinary Pathology, 6th ed., p. 629. Williams and Wilkins, Baltimore, MD, 1997
J Scot Estep, DVM
Captain, 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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